Evolution of mammals

The evolution of mammals has passed through many stages since the first appearance of their synapsid ancestors in the Pennsylvanian sub-period of the late Carboniferous period. By the mid-Triassic, there were many synapsid species that looked like mammals. The lineage leading to today's mammals split up in the Jurassic; synapsids from this period include "Dryolestes", more closely related to extant placentals and marsupials than to monotremes, as well as "Ambondro", more closely related to monotremes. Later on, the eutherian and metatherian lineages separated; the metatherians are the animals more closely related to the marsupials, while the eutherians are those more closely related to the placentals. Since "Juramaia", the earliest known eutherian, lived 160 million years ago in the Jurassic, this divergence must have occurred in the same period.
After the Cretaceous–Paleogene extinction event wiped out the non-avian dinosaurs (birds being the only surviving dinosaurs) and several mammalian groups, placental and marsupial mammals diversified into many new forms and ecological niches throughout the Paleogene and Neogene, by the end of which all modern orders had appeared.
Mammals are the only living synapsids. The synapsid lineage became distinct from the sauropsid lineage in the late Carboniferous period, between 320 and 315 million years ago. The sauropsids are today's reptiles and birds along with all the extinct amniotes more closely related to them than to mammals. This does not include the mammal-like reptiles, a group more closely related to the mammals.
Throughout the Permian period, the synapsids included the dominant carnivores and several important herbivores. In the subsequent Triassic period, however, a previously obscure group of sauropsids, the archosaurs, became the dominant vertebrates. The mammaliaforms appeared during this period; their superior sense of smell, backed up by a large brain, facilitated entry into nocturnal niches with less exposure to archosaur predation. The nocturnal lifestyle may have contributed greatly to the development of mammalian traits such as endothermy and hair. Later in the Mesozoic, after theropod dinosaurs replaced rauisuchians as the dominant carnivores, mammals spread into other ecological niches. For example, some became aquatic, some were gliders, and some even fed on juvenile dinosaurs.
Most of the evidence consists of fossils. For many years, fossils of Mesozoic mammals and their immediate ancestors were very rare and fragmentary; but, since the mid-1990s, there have been many important new finds, especially in China. The relatively new techniques of molecular phylogenetics have also shed light on some aspects of mammalian evolution by estimating the timing of important divergence points for modern species. When used carefully, these techniques often, but not always, agree with the fossil record.
Although mammary glands are a signature feature of modern mammals, little is known about the evolution of lactation as these soft tissues are not often preserved in the fossil record. Most research concerning the evolution of mammals centers on the shapes of the teeth, the hardest parts of the tetrapod body. Other important research characteristics include the evolution of the middle ear bones, erect limb posture, a bony secondary palate, fur, hair, and warm-bloodedness.
Definition of "mammal".
While living mammal species can be identified by the presence of milk-producing mammary glands in the females, other features are required when classifying fossils, because mammary glands and other soft-tissue features are not visible in fossils.
One such feature available for paleontology, shared by all living mammals (including monotremes), but not present in any of the early Triassic therapsids, is shown in Figure 1 (on the right), namely: mammals use two bones for hearing that all other amniotes use for eating. The earliest amniotes had a jaw joint composed of the articular (a small bone at the back of the lower jaw) and the quadrate (a small bone at the back of the upper jaw). All non-mammalian tetrapods use this system including amphibians, turtles, lizards, snakes, crocodilians, dinosaurs (including the birds), ichthyosaurs, pterosaurs and therapsids. But mammals have a different jaw joint, composed only of the dentary (the lower jaw bone, which carries the teeth) and the squamosal (another small skull bone). In the Jurassic, their quadrate and articular bones evolved into the incus and malleus bones in the middle ear. Mammals also have a double occipital condyle; they have two knobs at the base of the skull that fit into the topmost neck vertebra, while other tetrapods have a single occipital condyle.
In a 1981 article, Kenneth A. Kermack and his co-authors argued for drawing the line between mammals and earlier synapsids at the point where the mammalian pattern of molar occlusion was being acquired and the dentary-squamosal joint had appeared. The criterion chosen, they noted, is merely a matter of convenience; their choice was based on the fact that "the lower jaw is the most likely skeletal element of a Mesozoic mammal to be preserved." Today, most paleontologists consider that animals are mammals if they satisfy this criterion.
The ancestry of mammals.
Amniotes.
The first fully terrestrial vertebrates were amniotes — their eggs had internal membranes that allowed the developing embryo to breathe but kept water in. This allowed amniotes to lay eggs on dry land, while amphibians generally need to lay their eggs in water (a few amphibians, such as the common Suriname toad, have evolved other ways of getting around this limitation). The first amniotes apparently arose in the middle Carboniferous from the ancestral reptiliomorphs.
Within a few million years, two important amniote lineages became distinct: mammals' synapsid ancestors and the sauropsids, from which lizards, snakes, turtles/tortoises, crocodilians, dinosaurs, and birds are descended. The earliest known fossils of synapsids and sauropsids (such as "Archaeothyris" and "Hylonomus", respectively) date from about 320 to 315 million years ago. The times of origin are difficult to know, because vertebrate fossils from the late Carboniferous are very rare, and therefore the actual first occurrences of each of these types of animal might have been considerably earlier than the first fossil.
Synapsids.
Synapsid skulls are identified by the distinctive pattern of the holes behind each eye, which served the following purposes:
The synapsid pelycosaurs included the largest land vertebrates of the Early Permian, such as the 6 m (20 ft) long "Cotylorhynchus hancocki". Among the other large pelycosaurs were "Dimetrodon grandis" and "Edaphosaurus cruciger".
Therapsids.
Therapsids descended from pelycosaurs in the middle Permian and took over their position as the dominant land vertebrates. They differ from pelycosaurs in several features of the skull and jaws, including larger temporal fenestrae and incisors that are equal in size.
The therapsid lineage that led to mammals went through a series of stages, beginning with animals that were very like their pelycosaur ancestors and ending with some that could easily be mistaken for mammals:
Therapsid family tree.
Only the dicynodonts, therocephalians, and cynodonts survived into the Triassic.
Biarmosuchia.
The Biarmosuchia were the most primitive and pelycosaur-like of the therapsids.
Dinocephalians.
Dinocephalians ("terrible heads") included both carnivores and herbivores. They were large; "Anteosaurus" was up to 6 m (20 ft) long. Some of the carnivores had semi-erect hindlimbs, but all dinocephalians had sprawling forelimbs. In many ways they were very primitive therapsids; for example, they had no secondary palate and their jaws were rather "reptilian".
Anomodonts.
The anomodonts ("anomalous teeth") were among the most successful of the herbivorous therapsids — one sub-group, the dicynodonts, survived almost to the end of the Triassic. But anomodonts were very different from modern herbivorous mammals, as their only teeth were a pair of fangs in the upper jaw and it is generally agreed that they had beaks like those of birds or ceratopsians.
Theriodonts.
The theriodonts ("beast teeth") and their descendants had jaw joints in which the lower jaw's articular bone tightly gripped the skull's very small quadrate bone. This allowed a much wider gape, and one group, the carnivorous gorgonopsians ("gorgon faces"), took advantage of this to develop "sabre teeth". But the theriodont's jaw hinge had a longer term significance — the much reduced size of the quadrate bone was an important step in the development of the mammalian jaw joint and middle ear.
The gorgonopsians still had some primitive features: no bony secondary palate (but other bones in the right places to perform the same functions); sprawling forelimbs; hindlimbs that could operate in both sprawling and erect postures. But the therocephalians ("beast heads"), which appear to have arisen at about the same time as the gorgonopsians, had additional mammal-like features, e.g. their finger and toe bones had the same number of phalanges (segments) as in early mammals (and the same number that primates have, including humans).
Cynodonts.
 The cynodonts, a theriodont group that also arose in the late Permian, include the ancestors of all mammals. Cynodonts' mammal-like features include further reduction in the number of bones in the lower jaw, a secondary bony palate, cheek teeth with a complex pattern in the crowns, and a brain which filled the endocranial cavity.
Multi-chambered burrows have been found, containing as many as 20 skeletons of the Early Triassic cynodont "Trirachodon"; the animals are thought to have been drowned by a flash flood. The extensive shared burrows indicate that these animals were capable of complex social behaviors.
Triassic takeover.
The catastrophic mass extinction at the end of the Permian, around 252 million years ago, killed off about 70 percent of terrestrial vertebrate species and the majority of land plants.
As a result, ecosystems and food chains collapsed, and the establishment of new stable ecosystems took about 30 million years. With the disappearance of the gorgonopsians, which were dominant predators in the late Permian, the cynodonts' principal competitors for dominance of the carnivorous niches were a previously obscure sauropsid group, the archosaurs, which includes the ancestors of crocodilians and dinosaurs.
The archosaurs quickly became the dominant carnivores, a development often called the "Triassic takeover". Their success may have been due to the fact that the early Triassic was predominantly arid and therefore archosaurs' superior water conservation gave them a decisive advantage. All known archosaurs have glandless skins and eliminate nitrogenous waste in a uric acid paste containing little water, while the cynodonts probably excreted most such waste in a solution of urea, as mammals do today; considerable water is required to keep urea dissolved.
However, this theory has been questioned, since it implies synapsids were necessarily less advantaged in water retention, that synapsid decline coincides with climate changes or archosaur diversity (neither of which has been tested) and the fact that desert-dwelling mammals are as well adapted in this department as archosaurs, and some cynodonts like "Trucidocynodon" were large-sized predators.
The Triassic takeover was probably a vital factor in the evolution of the mammals. Two groups stemming from the early cynodonts were successful in niches that had minimal competition from the archosaurs: the tritylodonts, which were herbivores, and the mammals, most of which were small nocturnal insectivores (although some, like "Sinoconodon", were carnivores that fed on vertebrate prey, while still others were herbivores or omnivores). As a result:
This retreat to a nocturnal role is called a nocturnal bottleneck, and is thought to explain many of the features of mammals.
From cynodonts to crown mammals.
Fossil record.
Mesozoic synapsids that had evolved to the point of having a jaw joint composed of the dentary and squamosal bones are preserved in few good fossils, mainly because they were mostly smaller than rats:
In the past years, however, the number of Mesozoic fossil mammals has increased decisively; only 116 genera were known in 1979, for example, but about 310 in 2007, with an increase in quality such that "at least 18 Mesozoic mammals are represented by nearly complete skeletons".
Mammals or mammaliaforms.
Some writers restrict the term "mammal" to the crown group mammals, the group consisting of the most recent common ancestor of the monotremes, marsupials, and placentals, together with all the descendants of that ancestor. In an influential 1988 paper, Timothy Rowe advocated this restriction, arguing that "ancestry... provides the only means of properly defining taxa" and, in particular, that the divergence of the monotremes from the animals more closely related to marsupials and placentals "is of central interest to any study of Mammalia as a whole." To accommodate some related taxa falling outside the crown group, he defined the Mammaliaformes as comprising "the last common ancestor of Morganucodontidae and Mammalia [as he had defined the latter term] and all its descendants." Besides Morganucodontidae, the newly defined taxon includes Docodonta and Kuehneotheriidae. Though haramiyids have been referred to the mammals since the 1860s, Rowe excluded them from the Mammaliaformes as falling outside his definition, putting them in a larger clade, the Mammaliamorpha.
Some writers have adopted this terminology noting, to avoid misunderstanding, that they have done so. Most paleontologists, however, still think that animals with the dentary-squamosal jaw joint and the sort of molars characteristic of modern mammals should formally be members of Mammalia.
Where the ambiguity in the term "mammal" may be confusing, this article uses "mammaliaform" and "crown mammal".
Morganucodontidae.
The Morganucodontidae first appeared in the late Triassic, about 205M years ago. They are an excellent example of transitional fossils, since they have both the dentary-squamosal and articular-quadrate jaw joints. They were also one of the first discovered and most thoroughly studied of the mammaliaforms outside of the crown-group mammals, since an unusually large number of morganucodont fossils have been found.
Docodonts.
Docodonts, among the most common Jurassic mammaliaforms, are noted for the sophistication of their molars. They are thought to have had general semi-aquatic tendencies, with the fish-eating "Castorocauda" ("beaver tail"), which lived in the mid-Jurassic about 164M years ago and was first discovered in 2004 and described in 2006, being the most well-understood example. "Castorocauda" was not a crown group mammal, but it is extremely important in the study of the evolution of mammals because the first find was an almost complete skeleton (a real luxury in paleontology) and it breaks the "small nocturnal insectivore" stereotype:
"Hadrocodium".
The family tree above shows "Hadrocodium" as an "aunt" of crown mammals. This mammaliaform, dated about 195M years ago in the very early Jurassic, exhibits some important features:
Earliest crown mammals.
The crown group mammals, sometimes called 'true mammals', are the extant mammals and their relatives back to their last common ancestor. Since this group has living members, DNA analysis can be applied in an attempt to explain the evolution of features that do not appear in fossils. This endeavor often involves molecular phylogenetics, a technique that has become popular since the mid-1980s.
Family tree of early crown mammals.
Cladogram after Z.-X Luo. († marks extinct groups)
Color vision.
Early amniotes had four opsins in the cones of their retinas to use for distinguishing colours: one sensitive to red, one to green, and two corresponding to different shades of blue. The green opsin was not inherited by any crown mammals, but all normal individuals did inherit the red one. Early crown mammals thus had three cone opsins, the red one and both of the blues. All their extant descendants have lost one of the blue-sensitive opsins but not always the same one: monotremes retain one blue-sensitive opsin, while marsupials and placentals retain the other (except cetaceans, which later lost the other blue opsin as well). Some placentals and marsupials, including higher primates, subsequently evolved green-sensitive opsins; like early crown mammals, therefore, their vision is trichromatic.
Australosphenida and Ausktribosphenidae.
Ausktribosphenidae is a group name that has been given to some rather puzzling finds that:
Australosphenida is a group that has been defined in order to include the Ausktribosphenidae and monotremes. "Asfaltomylos" (mid- to late Jurassic, from Patagonia) has been interpreted as a basal australosphenid (animal that has features shared with both Ausktribosphenidae and monotremes; lacks features that are peculiar to Ausktribosphenidae or monotremes; also lacks features that are absent in Ausktribosphenidae and monotremes) and as showing that australosphenids were widespread throughout Gondwanaland (the old Southern Hemisphere super-continent).
Recent analysis of "Teinolophos", which lived somewhere between 121 and 112.5 million years ago, suggests that it was a "crown group" (advanced and relatively specialised) monotreme. This was taken as evidence that the basal (most primitive) monotremes must have appeared considerably earlier, but this has been disputed (see the following section). The study also indicated that some alleged Australosphenids were also "crown group" monotremes (e.g. "Steropodon") and that other alleged Australosphenids (e.g. "Ausktribosphenos", "Bishops", "Ambondro", "Asfaltomylos") are more closely related to and possibly members of the Therian mammals (group that includes marsupials and placentals, see below).
Monotremes.
"Teinolophos", from Australia, is the earliest known monotreme. A 2007 study (published 2008) suggests that it was not a basal (primitive, ancestral) monotreme but a full-fledged platypus, and therefore that the platypus and echidna lineages diverged considerably earlier. A more recent study (2009), however, has suggested that, while "Teinolophos" was a type of platypus, it was also a basal monotreme and predated the radiation of modern monotremes. The semi-aquatic lifestyle of platypuses prevented them from being outcompeted by the marsupials that migrated to Australia millions of years ago, since joeys need to remain attached to their mothers and would drown if their mothers ventured into water (though there are exceptions like the water opossum and the lutrine opossum; however, they both live in South America and thus don't come into contact with monotremes). Genetic evidence has determined that echidnas diverged from the platypus lineage as recently as 19-48M, when they made their transition from semi-aquatic to terrestrial lifestyle.
Monotremes have some features that may be inherited from the cynodont ancestors:
Unlike other mammals, female monotremes do not have nipples and feed their young by "sweating" milk from patches on their bellies.
These features are not visible in fossils, and the main characteristics from paleontologists' point of view are:
Multituberculates.
Multituberculates (named for the multiple tubercles on their "molars") are often called the "rodents of the Mesozoic", but this is an example of convergent evolution rather than meaning that they are closely related to the Rodentia. They existed for approximately 120 million years—the longest fossil history of any mammal lineage—but were eventually outcompeted by rodents, becoming extinct during the early Oligocene.
Some authors have challenged the phylogeny represented by the cladogram above. They exclude the multituberculates from the mammalian crown group, holding that multituberculates are more distantly related to extant mammals than even the Morganucodontidae. Multituberculates are like undisputed crown mammals in that their jaw joints consist of only the dentary and squamosal bones-whereas the quadrate and articular bones are part of the middle ear; their teeth are differentiated, occlude, and have mammal-like cusps; they have a zygomatic arch; and the structure of the pelvis suggests that they gave birth to tiny helpless young, like modern marsupials. On the other hand, they differ from modern mammals:
Theria.
Theria ("beasts") is the clade originating with the last common ancestor of the Eutheria (including placentals) and Metatheria (including marsupials). Common features include:
Metatheria.
The living Metatheria are all marsupials (animals with pouches). A few fossil genera, such as the Mongolian late Cretaceous "Asiatherium", may be marsupials or members of some other metatherian group(s).
The oldest known metatherian is "Sinodelphys", found in 125M-year-old early Cretaceous shale in China's northeastern Liaoning Province. The fossil is nearly complete and includes tufts of fur and imprints of soft tissues.
Didelphimorphia (common opossums of the Western Hemisphere) first appeared in the late Cretaceous and still have living representatives, probably because they are mostly semi-arboreal unspecialized omnivores.
Tracks from the Early Cretaceous of Angola show the existence of raccoon-size mammals 118 million years ago.
The best-known feature of marsupials is their method of reproduction:
Although some marsupials look very like some placentals (the thylacine, "marsupial tiger" or "marsupial wolf" is a good example), marsupial skeletons have some features that distinguish them from placentals:
Marsupials also have a pair of marsupial bones (sometimes called "epipubic bones"), which support the pouch in females. But these are not unique to marsupials, since they have been found in fossils of multituberculates, monotremes, and even eutherians — so they are probably a common ancestral feature that disappeared at some point after the ancestry of living placental mammals diverged from that of marsupials.
Some researchers think the epipubic bones' original function was to assist locomotion by supporting some of the muscles that pull the thigh forwards.
Eutheria.
The time of appearance of the earliest eutherians has been a matter of controversy. On one hand, recently discovered fossils of "Juramaia" have been dated to 160 million years ago and classified as eutherian. Fossils of "Eomaia" from 125 million years ago in the Early Cretaceous have also been classified as eutherian. A recent analysis of phenomic characters, however, classified "Eomaia" as pre-eutherian and reported that the earliest clearly eutherian specimens came from "Maelestes", dated to 91 million years ago. That study also reported that eutherians did not significantly diversify until after the catastrophic extinction at the Cretaceous–Paleogene boundary, about 66 million years ago.
"Eomaia" was found to have some features that are more like those of marsupials and earlier metatherians:
"Eomaia" also has a Meckelian groove, a primitive feature of the lower jaw that is not found in modern placental mammals.
These intermediate features are consistent with molecular phylogenetics estimates that the placentals diversified about 110M years ago, 15M years after the date of the "Eomaia" fossil.
"Eomaia" also has many features that strongly suggest it was a climber, including several features of the feet and toes; well-developed attachment points for muscles that are used a lot in climbing; and a tail that is twice as long as the rest of the spine.
Placentals' best-known feature is their method of reproduction:
It has been suggested that the evolution of placental reproduction was made possible by retroviruses that:
From a paleontologist's point of view, eutherians are mainly distinguished by various features of their teeth, ankles and feet.
Expansion of ecological niches in the Mesozoic.
Generally speaking, most species of mammaliaforms did occupy the niche of small, nocturnal insectivores, but recent finds, mainly in China, show that some species and especially crown group mammals were larger and that there was a larger variety of lifestyles than previously thought. For example:
A study on Mesozoic mammaliaforms suggests that they were a primary factor in constraining mammalian body size, rather than solely competion from dinosaurs.
Evolution of major groups of living mammals.
There are currently vigorous debates between traditional paleontologists and molecular phylogeneticists about how and when the modern groups of mammals diversified, especially the placentals. Generally, the traditional paleontologists date the appearance of a particular group by the earliest known fossil whose features make it likely to be a member of that group, while the molecular phylogeneticists suggest that each lineage diverged earlier (usually in the Cretaceous) and that the earliest members of each group were anatomically very similar to early members of other groups and differed only in their genetics. These debates extend to the definition of and relationships between the major groups of placentals.
Molecular phylogenetics-based family tree of placental mammals.
Molecular phylogenetics uses features of organisms' genes to work out family trees in much the same way as paleontologists do with features of fossils — if two organisms' genes are more similar to each other than to those of a third organism, the two organisms are more closely related to each other than to the third.
Molecular phylogeneticists have proposed a family tree that is both broadly similar to but has notable differences from that of the paleontologists. Like paleontologists, molecular phylogeneticists have differing ideas about various details, but here is a typical family tree according to molecular phylogenetics: Note that the diagram shown here omits extinct groups, as one cannot extract DNA from fossils.
Here are the most significant of the differences between this family tree and the one familiar to paleontologists:
The grouping together of the Afrotheria has some geological justification. All surviving members of the Afrotheria originate from South American or (mainly) African lineages — even the Indian elephant, which diverged from an African lineage about . As Pangaea broke up, Africa and South America separated from the other continents less than 150M years ago, and from each other between 100M and 80M years ago. So it would not be surprising if the earliest eutherian immigrants into Africa and South America were isolated there and radiated into all the available ecological niches.
Nevertheless, these proposals have been controversial. Paleontologists naturally insist that fossil evidence must take priority over deductions from samples of the DNA of modern animals. More surprisingly, these new family trees have been criticised by other molecular phylogeneticists, sometimes quite harshly:
Timing of placental evolution.
Recent molecular phylogenetic studies suggest that most placental orders diverged late in the Cretaceous period, about 100 to 85 million years ago, but that modern families first appeared later, in the late Eocene and early Miocene epochs of the Cenozoic period. Fossil-based analyses, on the contrary, limit the placentals to the Cenozoic. Many Cretaceous fossil sites contain well-preserved lizards, salamanders, birds, and mammals, but not the modern forms of mammals. It is likely that they simply did not exist, and that the molecular clock runs fast during major evolutionary radiations. On the other hand, there is fossil evidence from of hoofed mammals that may be ancestors of modern ungulates.
Fossils of the earliest members of most modern groups date from the Paleocene, a few date from later and very few from the Cretaceous, before the extinction of the dinosaurs. But some paleontologists, influenced by molecular phylogenetic studies, have used statistical methods to extrapolate "backwards" from fossils of members of modern groups and concluded that primates arose in the late Cretaceous. However, statistical studies of the fossil record confirm that mammals were restricted in size and diversity right to the end of the Cretaceous, and rapidly grew in size and diversity during the Early Paleocene.
Evolution of mammalian features.
Jaws and middle ears.
"Hadrocodium", whose fossils date from the early Jurassic, provides the first clear evidence of fully mammalian jaw joints and middle ears, in which the jaw joint is formed by the dentary and squamosal bones while the articular and quadrate move to the middle ear, where they are known as the incus and malleus.
One analysis of the monotreme "Teinolophos" suggested that this animal had a pre-mammalian jaw joint formed by the angular and quadrate bones and that the definitive mammalian middle ear evolved twice independently, in monotremes and in therian mammals, but this idea has been disputed. In fact, two of the suggestion's authors co-authored a later paper that reinterpreted the same features as evidence that "Teinolophos" was a full-fledged platypus, which means it would have had a mammalian jaw joint and middle ear.
Lactation.
It has been suggested that lactation's original function was to keep eggs moist. Much of the argument is based on monotremes (egg-laying mammals):
Later research demonstrated that caseins already appeared in the common mammalian ancestor approximately 200–310 million years ago. The question of whether secretions of a substance to keep eggs moist translated into actual lactation in therapsids is open. A small mammaliomorph called "Sinocodon", generally assumed to be the sister group of all later mammals, had front teeth in even the smallest individuals. Combined with a poorly ossified jaw, they very probably did not suckle. Thus suckling may have evolved right at the pre-mammal/mammal transition. However, tritylodontids, generally assumed to be more basal, show evidence of suckling. Morganucodontans, also assumed to be basal Mammaliaformes, also show evidence of lactation.
Digestive system.
The evolution of the digestive system has formed a significant influence in mammal evolution. With the emergence of mammals, the digestive system was modified in a variety of ways depending on the animal's diet.  For example, cats and most carnivores have simple large intestines, while the horse as a herbivore has a voluminous large intestine. An ancestral feature of ruminants is their multi-chambered (usually four-chambered) stomach, which evolved about 50 million years ago. Along with morphology of the gut, gastric acidity has been proposed as a key factor shaping the diversity and composition of microbial communities found in the vertebrate gut. Comparisons of stomach acidity across trophic groups in mammal and bird taxa show that scavengers and carnivores have significantly higher stomach acidities compared to herbivores or carnivores feeding on phylogenetically distant prey such as insects or fish.
Despite the lack of fossilization of the gut, microbial evolution of the gut can be inferred from the interrelationships of existing animals, microbes and probable foodstuffs. Mammals are metagenomic, in that they are composed of not only their own genes, but also those of all of their associated microbes. Gut microbiota has co-diversified as mammalian species have evolved. Recent studies indicate that adaptive divergence between mammalian species is shaped in part by changes in the gut microbiota. The house mouse may have evolved not only with, but also in response to, the unique bacteria inhabiting its gut.
Hair and fur.
The first clear evidence of hair or fur is in fossils of "Castorocauda" and "Megaconus", from 164M years ago in the mid-Jurassic. As both mammals "Megaconus" and "Castorocauda" have a double coat of hair, with both guard hairs and an undercoat, it may be assumed that their last common ancestor did as well. This animal must have been Triassic as it was an ancestor of the Triassic "Tikitherium". More recently, the discovery of hair remnants in Permian coprolites pushes back the origin of mammalian hair much further back in the synapsid line to Paleozoic therapsids.
In the mid-1950s, some scientists interpreted the foramina (passages) in the maxillae (upper jaws) and premaxillae (small bones in front of the maxillae) of cynodonts as channels that supplied blood vessels and nerves to vibrissae (whiskers) and suggested that this was evidence of hair or fur. It was soon pointed out, however, that foramina do not necessarily show that an animal had vibrissae; the modern lizard "Tupinambis" has foramina that are almost identical to those found in the non-mammalian cynodont "Thrinaxodon". Popular sources, nevertheless, continue to attribute whiskers to "Thrinaxodon". A trace fossil from the Lower Triassic had been erroneously regarded as a cynodont footprint showing hair, but this interpretation has been refuted. A study of cranial openings for facial nerves connected whiskers in extant mammals indicate the Prozostrodontia, small immediate ancestors of mammals, presented whiskers similar to mammals, but that less advanced therapsids would either have immobile whiskers or no whisker at all. Fur may have evolved from whiskers. Whiskers themselves may have evolved as a response to nocturnal and/or burrowing lifestyle.
Ruben & Jones (2000) note that the Harderian glands, which secrete lipids for coating the fur, were present in the earliest mammals like "Morganucodon", but were absent in near-mammalian therapsids like "Thrinaxodon". The Msx2 gene associated with hair follicle maintenance is also linked to the closure of the parietal eye in mammals, indicating that fur and lack of pineal eye is linked. The pineal eye is present in "Thrinaxodon", but absent in more advanced cynognaths (the Probainognathia).
Insulation is the "cheapest" way to maintain a fairly constant body temperature, without consuming energy to produce more body heat. Therefore, the possession of hair or fur would be good evidence of homeothermy, but would not be such strong evidence of a high metabolic rate.
Erect limbs.
Understanding of the evolution of erect limbs in mammals is incomplete — living and fossil monotremes have sprawling limbs. Some scientists think that the parasagittal (non-sprawling) limb posture is limited to the Boreosphenida, a group that contains the therians but not, for example, the multituberculates. In particular, they attribute a parasagittal stance to the therians "Sinodelphys" and "Eomaia", which means that the stance had arisen by 125 million years ago, in the Early Cretaceous. However, they also discuss that earlier mammals had more erect forelimbs as opposed to the more sprawling hindlimbs, a trend still continued to some extent in modern placentals and marsupials.
Warm-bloodedness.
"Warm-bloodedness" is a complex and rather ambiguous term, because it includes some or all of the following:
Since scientists cannot know much about the internal mechanisms of extinct creatures, most discussion focuses on homeothermy and tachymetabolism. However, it is generally agreed that endothermy first evolved in non-mammalian synapsids such as dicynodonts, which possess body proportions associated with heat retention, high vascularised bones with Haversian canals, and possibly hair. More recently, it has been suggested that endothermy evolved as far back as "Ophiacodon".
Modern monotremes have a low body temperature compared to marsupials and placental mammals, around . Phylogenetic bracketing suggests that the body temperatures of early crown-group mammals were not less than that of extant monotremes. There is cytological evidence that the low metabolism of monotremes is a secondarily evolved trait.
Respiratory turbinates.
Modern mammals have respiratory turbinates, convoluted structures of thin bone in the nasal cavity. These are lined with mucous membranes that warm and moisten inhaled air and extract heat and moisture from exhaled air. An animal with respiratory turbinates can maintain a high rate of breathing without the danger of drying its lungs out, and therefore may have a fast metabolism. Unfortunately these bones are very delicate and therefore have not yet been found in fossils. But rudimentary ridges like those that support respiratory turbinates have been found in advanced Triassic cynodonts, such as "Thrinaxodon" and "Diademodon", which suggests that they may have had fairly high metabolic rates.
Bony secondary palate.
Mammals have a secondary bony palate, which separates the respiratory passage from the mouth, allowing them to eat and breathe at the same time. Secondary bony palates have been found in the more advanced cynodonts and have been used as evidence of high metabolic rates. But some cold-blooded vertebrates have secondary bony palates (crocodilians and some lizards), while birds, which are warm-blooded, do not.
Diaphragm.
A muscular diaphragm helps mammals to breathe, especially during strenuous activity. For a diaphragm to work, the ribs must not restrict the abdomen, so that expansion of the chest can be compensated for by reduction in the volume of the abdomen and "vice versa". Diaphragms are known in caseid pelycosaurs, indicating an early origin within synapsids, though they were still fairly inefficient and likely required support from other muscle groups and limb motion.
The advanced cynodonts have very mammal-like rib cages, with greatly reduced lumbar ribs. This suggests that these animals had more developed diaphragms, were capable of strenuous activity for fairly long periods and therefore had high metabolic rates. On the other hand, these mammal-like rib cages may have evolved to increase agility. However, the movement of even advanced therapsids was "like a wheelbarrow", with the hindlimbs providing all the thrust while the forelimbs only steered the animal, in other words advanced therapsids were not as agile as either modern mammals or the early dinosaurs. So the idea that the main function of these mammal-like rib cages was to increase agility is doubtful.
Limb posture.
The therapsids had sprawling forelimbs and semi-erect hindlimbs. This suggests that Carrier's constraint would have made it rather difficult for them to move and breathe at the same time, but not as difficult as it is for animals such as lizards, which have completely sprawling limbs. Advanced therapsids may therefore have been significantly less active than modern mammals of similar size and so may have had slower metabolisms overall or else been bradymetabolic (lower metabolism when at rest).
Brain.
Mammals are noted for their large brain size relative to body size, compared to other animal groups. Recent findings suggest that the first brain area to expand was that involved in smell. Scientists scanned the skulls of early mammal species dating back to 190–200 million years ago and compared the brain case shapes to earlier pre-mammal species; they found that the brain area involved in the sense of smell was the first to enlarge. This change may have allowed these early mammals to hunt insects at night when dinosaurs were not active.


Arene oxide

In chemistry, an arene oxide is an epoxide of an arene. Two important families of arene oxides are benzene oxides and naphthalene oxides as these are intermediates in the oxidative degradation of benzene and naphthalene, two common pollutants. Benzopyrene is also converted to an epoxide, (+)-benzo[a]pyrene-7,8-epoxide.
Selected reactions.
Benzene oxide (C6H6O) exists as an equilibrium mixture with the seven-membered ring oxepin, which has three double bonds. They are valence isomers and in equilibrium via disrotatory 6π ring closing and opening.
Arene oxides are highly reactive. Benzene oxide and naphthalene-1,2-oxide hydrate to give dihydroxydihydrobenzene and 1,2-dihydroxydihydronaphthalene, respectively. The hydration is catalyzed by epoxide hydrolase enzymes. Dehydration of these diols, which is driven by rearomatization, gives phenol and 1-naphthol. Oxidation of 1,2-dihydroxydihydronaphthalene, catalyzed by dihydrodiol dehydrogenase, gives the 1,2-naphthoquinone.


Ranbir Chander Sobti

Ranbir Chander Sobti is an Indian educationist, cell biologist. He is a former vice chancellor of the Panjab University, Chandigarh and Babasaheb Bhimrao Ambedkar University, Lucknow. He is known to have involved in advanced research in plant genetic studies and has written over 240 articles, and 22 books including "Essentials of Biotechnology" and "Emerging Trends in Biomedical Science and Health". He is an elected Fellow of several major science academies such as Indian National Science Academy, National Academy of Agricultural Sciences, National Academy of Medical Sciences, National Academy of Sciences, India, and Punjab Academy of Sciences. The Government of India awarded him the fourth highest civilian honour of the Padma Shri, in 2009, for his contributions to Literature and Education.
Biography.
Ranbir Chander Sobti was born to S. D. Sobti and Sheela Sobti in Taran Taran district of Punjab on 19 August 1948 and graduated in Science (BSc) with honours from Panjab University in 1969. He continued his studies at the same institution to secure his master's degree (MSc) in 1970 and a doctoral degree (PhD) in 1974. While doing his doctoral research, he also passed a certificate course in German language in 1971. His career started as a teaching assistant in 1974 at his alma mater where he worked for 28 years. He served the institution in various capacities such as Curator (1975–1976), Lecturer (1976–1985), Reader (1985–1994) and Professor in Cell Biology (1994–2006) when he was appointed as the vice chancellor of the university. In between, he took a hiatus and worked at the University of Miami, Florida as a resident associate professor during two periods, 1976–1980 and 1983–1985. During his stay at Miami, he successfully completed the course of Master of Science in Public Health (MSPH) in 1983.
In 2006, Sobti assumed the responsibility as the vice chancellor of Panjab University and continued in the post till 2012. He also worked as the Dean of the Alumni Relations (1998–1999) and Foreign Students (2001–2004), as the honorary director of the Honorary Director of the UGC Academic Staff College (2004–2006) and as the Chairman, Board of Examiners of the Department of Electronics and Accreditation of Computer Classes (DOAECC). In 2012, he moved to Babasaheb Bhimrao Ambedkar University (BBAU) as its vice chancellor and held the position till 2018. When the Indian Science Congress Association conducted their 101st annual session at Jammu, he chaired the session as its general president. He has also served as the director of the National Research Development Corporation (NRDC) and as a member of the executive council of the National Assessment and Accreditation Council (NAAC), Bangalore. He headed the panel of NAAC which conducted an appraisal on the Tripura University in 2015. He is a member of "Zaheer Science Foundation", a New Delhi-based non government organization promoting scientific research and educational reforms, in coordination with government agencies.
Sobti is married to Vipin Khindagi; the marriage took place on 8 October 1975, while he was working as a curator at Panjab University.
Legacy.
The Centre of Biotechnology of the Panjab University was established during Sobti's tenure as the Reader of the Department of Zoology at the university and he worked as the founder coordinator of the Centre from 1989 to 1995. His efforts are reported behind the elevation of the Centre into a department in 1995 and he chaired the department till 2005, except for a period from February 2001 to September 2002. While he served as the vice chancellor, the university started 65 industry-oriented courses, established a dedicated post of Dean for the research department, established chairs for contemporary and traditional thought and introduced semester system for all academic courses. It was during this period, the university received over 800 million in research grants and 3 billion in government funding. With the funding, he helped establish regional centres and colleges in rural areas and initiated programs to provide preferential admission to AIDS/Thalassemia patients and single girl child families at the affiliated colleges and university campus and provided free education to orphans and differently abled students. The university also took up the responsibility to adopt 8 nearby villages and set up facilities there for computer literacy, community health and language learning. In 2011, a community radio service under the name, "Jyotirgmaya 91.2 MHz", was launched for exchange of knowledge and information among the participating communities and to provide a dialogue platform for them. It was under his vice chancellorship at the Babasaheb Bhimrao Ambedkar University, the institution started its collaboration with Uttar Pradesh Council for Science and Technology (UPCST) and North Eastern Railway (NER), Lucknow Division for innovations in the public sector services. He established the "Centre for Industry Institution Partnership Program" (CIIPP), a forum for dialogue between industry representatives and academicians, and also contributed in making the University campus, a smoke-free and polythene-free green campus.
Sobti's early researches were linked to cancer biology and some of his writings, which comprise 22 books and 246 articles, were based on his cancer researches. ResearchGate, an online repository of scientific articles, has listed 156 of his articles and they are reported to have been cited over 2000 times, with an h-index of 18. He has handled several projects for University Grants Commission, Council of Scientific and Industrial Research, Indian Council of Medical Research, Department of Biotechnology and the Ministry of Human Resource Development and has been a member of the Editorial Boards of journals such as "Molecular and Cellular Biochemistry", "Cytology and Genetics", and the "Indian Journal of Human Genetics". He has participated in several seminars and conferences for delivering keynote addresses; his oration, "Universities and the innovation cycle", at the centenary conference of the Association of Commonwealth Universities in 2015, was one among them. The 12th Dr. J. C. Bose Memorial Lecture of Institution of Electronics and Telecommunication Engineers (2006), Sir Shri Ram Memorial Oration (2007), D. D. Jain Oration (2007) and Dr. G. S. Randhawa Oration (2009) are some of the other lectures delivered by him.
Awards and honours.
The National Academy of Sciences, India (NASI) elected Sobdi as its Fellow in 1992 and the National Academy of Medical Sciences (NAMS) and the National Academy of Agricultural Sciences (NAAS) followed suit by electing him as their Fellow in 2003 and 2011 respectively. He has also been inducted into the elected Fellows list by the Indian National Science Academy (2012), Punjab Academy of Sciences, Zoological Society, Institution of Chemical Engineers, International Academy of Cardiovascular Sciences, Union for International Cancer Control, and the Comprehensive Cancer Centre for State of Florida.
Sobti received the "INSA Young Scientist Medal" of the Indian National Science Academy and the "Science Award" of the Kothari Scientific and Research Commission in 1977. A year later, he was awarded the "Indo-UK Young Scientist Exchange Program Award", followed by the Indo-France Exchange Program Award in 1986, INSA-Royal Society Exchange Program Award in 1988 and INSA–Japan Society Exchange Program Award in 1994. He received four awards in 2008, Career Award of the University Grants Commission, B. C. Guha Memorial Award, Amity Academic Excellence Award, Punjab Sarkar Parman Patra, and four more awards in 2009, Life Time Achievement Award of the National Open and Distance Education Board, Yokohama National University International Exchange Foundation Award, Jai Prakash Memorial Education Award, and the fourth highest Indian civilian award of the Padma Shri. Chaudhary Devi Lal Manch Educational Award and the Prof. P. N. Mehra Memorial Award reached him in 2010 and he received the General President's Gold Medal of the Indian Science Congress Association and Swami Vivekananda National Award in 2011. He was awarded the PMA Excellence in Education Award in 2012 and the Punjab Academy of Sciences honoured him with the Lifetime Achievement Award in 2013. He is also a recipient of the Ranbaxy Research Award and Punjab Rattan Award.


Alpha,N,O-TMS

Alpha,N,O-TMS, or α,N-dimethyl-5-methoxytryptamine, is a lesser-known psychedelic drug. Its abbreviated nomenclature is derived from its structure, as it is α,N,O-trimethyl serotonin. α,N,O-TMS was first synthesized by Alexander Shulgin. In his book "TiHKAL" ("Tryptamines I Have Known and Loved"), Shulgin lists the dosage as 10-20 mg when taken orally, and the duration as 6–8 hours.


Safety syringe

A safety syringe is a syringe with a built-in safety mechanism to reduce the risk of needlestick injuries to healthcare workers and others. The needle on a safety syringe can be detachable or permanently attached. On some models, a sheath is placed over the needle, whereas in others the needle retracts into the barrel. Safety needles serve the same functions as safety syringes, but the protective mechanism is a part of the needle rather than the syringe. Legislation requiring safety syringes or equivalents has been introduced in many nations since needlestick injuries and re-use prevention became the focus of governments and safety bodies.
Types.
There are many types of safety syringes available on the market. Auto Disable (AD) syringes are designed as a single use syringe, with an internal mechanism blocking the barrel once depressed so it cannot be depressed again. The other type of syringe with a re-use prevention feature is the breaking plunger syringe. An internal mechanism cracks the syringe when the plunger is fully depressed to prevent further use. These syringes are only effectively disabled with a full depression of the plunger; users can avoid activating the re-use prevention feature and re-use the syringe.
The more effective safety syringes have reuse and needlestick prevention features. A sheath or hood slides over the needle after the injection is completed with a Needlestick Prevention Syringe, which also has a re-use prevention feature (either an auto disable mechanism or breaking plunger). Retractable syringes use either manual or spring-loaded retraction to withdraw the needle into the barrel of the syringe. Some brands of spring-loaded syringes can have a splatter effect, where blood and fluids are sprayed off the cannula from the force of the retraction. Manual retraction syringes are generally easier to depress because there is no resistance from a spring.
Alternatives.
Traditional glass syringes can be re-used once disinfected. Plastic body syringes have become more popular in recent years because they are disposable. Unfortunately, improper disposal methods and re-use are responsible for transferring blood borne diseases.
Importance.
Of the 55 cases documented by the CDC of (non-sex work) occupational transmission of HIV, 90% were from contaminated needles that pierced the skin. The direct cost of needlestick injuries was calculated in a recent study to be between $539 and $672 million US dollars. That includes only lab tests, treatment, service and "other"; it does not take into account lost time and wages for employers and individuals.
Legislation.
United States.
Two lawyers, Mike Weiss and Paul Danzinger, were approached in 1998 by an inventor, Thomas Shaw, who was having trouble selling a safety syringe developed to protect health care workers from accidentally being infected by dirty needles. The problems were due to monopolistic actions of a major industry needle maker and hospital group purchasing organizations. The case was settled before trial for $150 million. This was portrayed by the 2011 movie "Puncture". Shaw's attempts to get his retractable needle accepted by health care facilities were covered in a 2010 "Washington Monthly" article.
External links.
• Washington Monthly, Jul/Aug 2010, "Dirty Medicine"


Telemedicine and Advanced Technology Research Center (United States Army)

The Telemedicine and Advanced Technology Research Center (TATRC) performs medical reconnaissance and special operations to address critical gaps that are underrepresented in DoD medical research programs. TATRC is an office of the headquarters of the US Army Medical Research and Materiel Command (USAMRMC).
History.
The need for a TATRC- like organization was recognized as early as 1990, when the Army and Air Force medical departments wanted to jointly develop, procure, and deploy a filmless medical diagnostic imaging system (MDIS), at a time when such a system did not exist. On 1 November 1991, Lieutenant Colonel Fred Goeringer was assigned as the MDIS project officer, and by 1993 under his leadership the Navy had also joined this effort and a formal organization, the Medical Advanced Technology Management Office (MATMO) was established. MATMO, as it was referred to, became better known as the DOD “Telemedicine Test Bed” after the Assistant Secretary of Defense for Health Affairs designated the Army as Executive Agent for telemedicine in 1994.
During the mid-1990s a broad array of advanced and developing technologies were used to meet military medicine requirements including biomedical science, a secure global positioning system, wireless networking, data compression, and adaptable tactical and mobile networks. In March 1996, COL Gary Gilbert, PhD, US Army Medical Service Corps succeeded COL Goeringer as Director. In 1997, Col Jeffrey Roller, MD, US Air Force Medical Corps was assigned to serve as Clinical Director and subsequently succeeded COL Gilbert who became the MRMC Deputy for IM/IT until his retirement in June 1998. In 1998, MATMO was re-organized and renamed the Telemedicine and Advanced Technology Research Center (TATRC). Colonel Roller continued as Director until his retirement in October 2006, at which time Colonel Karl Friedl Ph.D., US Army Medical Service Corps, assumed the directorship.
Since its inception, TATRC has played a prominent role in developing advanced technologies in areas such as: health informatics; medical imaging; mobile computing and remote monitoring; and simulation and training. TATRC also played an important role in championing organizations such as The American Telemedicine Association (ATA) during its early years, and has continued to be an important thought leader in areas such as the use of virtual reality tools, biomaterials and hospital-of-the-future concepts. The use of advanced technologies to support deployed forces has been a common theme as far back as 1993, when LTC Ronald Poropatich, MD, with dual appointments at Walter Reed Army Medical Center and MATMO deployed to Somalia during Operation Restore Hope.
Between 1993 and 1996 tertiary care telemedicine was supported from the Walter Reed Telemedicine Directorate and was deployed for military medical missions in 12 countries.
Currently, TATRC manages more than $250 million annually, primarily through congressional special interest funding, and has expanded from its original office at Fort Detrick, Maryland, to a more global presence with offices in Georgia, California, Hawaii and Europe. Equally important has been TATRC's partnership with numerous universities, commercial enterprises, and other federal agencies, supporting approximately 500 ongoing research projects.


Ottilie Lundgren


5-Benzyloxytryptamine

5-Benzyloxytryptamine (5-BT), is a tryptamine derivative which acts as an agonist at the 5-HT1D, 5-HT2 and 5-HT6 serotonin receptors, and an antagonist of TRPM8.
Legality.
5-Benzyloxytryptamine is illegal in Singapore.


KAHA Ligation

The α-Ketoacid-Hydroxylamine (KAHA) Amide-Forming Ligation is a chemical reaction that is used to join two unprotected fragments in peptide synthesis. It is an alternative to the Native Chemical Ligation (NCL).
KAHA Ligation was developed by Jeffrey W. Bode group at ETH Zürich (previously University of Pennsylvania).
Overview.
An α-ketoacid at the C-terminus of one peptide fragment reacts with a hydroxylamine at the N-terminus of another to form a peptide bond (amide bond).
The reaction can happen in the presence of unprotected side chains, and it does not require any coupling reagents or catalysts. The only byproducts are water and CO2.
The first reported protein synthesized by KAHA ligation was human GLP-1 (7-36). Since then, a variety of small proteins (up to 200 residues) have been synthesized, including ubiquitin and other similar modifier proteins, hormone proteins, nitrophorin 4, S100A4 and cyclic proteins.
C-terminal ketoacid monomers are pre-loaded on resin via a linker for Fmoc-SPPS (Fmoc-based solid phase peptide synthesis). Initial research utilised sulfur ylide linkers, but more recently the group developed acid- and photo-labile ketoacid monomers that can be loaded directly on Rink Amide resin.
The most commonly used N-terminal hydroxylamine is the 5-oxaproline, which results in a homoserine residue after ligation and O-N rearrangement.


Claudio Luchinat

Claudio Luchinat (February 15, 1952 in Florence - ) is an Italian chemist. He is author of about 550 publications in Bioinorganic Chemistry, NMR and Structural Biology, and of four books. At the moment his h-index is 70 and his papers have been quoted more than 19,000 times.
He earned a PhD in Chemistry from the University of Florence. He has been full professor of Chemistry at the University of Bologna (1986–96).
He is currently a researcher at the University of Florence and full professor of Chemistry at the same university (1996-, CERM and Department of Chemistry). He is member of the Italian Chemical Society, New York Academy of Sciences, American Association for the Advancement of Science.


Prostate evolution in monotreme mammals

The monotremes (egg laying mammals) represent the order of extant mammals most distantly related to humans. The platypus ("Ornithorhynchus anatinus") is indigenous to eastern Australia; the short-beaked echidna ("Tachyglossus aculeatus") is indigenous to Australia and Papua New Guinea; whereas the long-beaked echidna ("Zaglossus bruijni") is restricted to Papua New Guinea and Irian Jaya. Since monotremes exhibit characteristics common with both reptiles (e.g. presence of a cloaca) and therian mammals (e.g. mammary glands), they are of great interest for the study of mammalian evolution.
Monotremes exhibit a combination of reptilian and mammalian characteristics.
Male monotremes are testicond (have intraabdominal testes) with the testes undergoing seasonal emergence during winter. The fully developed seminiferous tubules exhibit distinctly small stages of spermatogenesis in that more than one stage is often observed in a cross section of the tubule, a characteristic of spermatogenesis that has also been observed in a reptile, common in birds and man.
The monotreme paired excurrent ducts (ductuli efferentes, epididymides and vas deferens) empty into a single urethra. Glandular tissue surrounds the urethra into which a pair of bulbourethral glands (Cowper's glands) empty at the base of the penis. The intraabdominal testes and excurrent ducts, along with the presence of a cloaca exhibit homology to the reptilian male reproductive tract.
The combination of reptilian and mammalian structures within the monotreme reproductive tract has informed the evolution of the male reproductive tract in mammals. For example, the intraabdominal low sperm storage capacity of the echidna epididymis informed the role of the epididymis as a prime mover in the evolution of descended testes in mammals as it relates to lower extragonadal temperatures enhancing epididymal sperm storage in scrotal mammals.
The glandular designation of periurethral tissue within the monotreme male reproductive tract has been a matter of scientific discussion for approximately two centuries. Examination of the monotreme periurethral tissue has been limited by the availability of these protected and relatively rare mammals, hence, the long time line for scientific research of reproductive tissue between studies.
Structure of the monotreme prostate.
The glandular tissue surrounding the monotreme urethra most likely represents a rudimentary prostate. There are no periurethral glands in reptiles. Hence, the evolution of the prostate gland is unique to mammals. Primordial periurethral glands have been described in the platypus as secretory glandular tissue surrounding the length of the urethra. The periurethral tissue exhibits regional swelling, being widest immediately beneath the bladder and progressively reducing in thickness along the length of the urethra. Surrounding the periurethral glands is a urethral muscularis. Observations in the platypus of the periurethral glands were non-committal as to homology with the prostate. Subsequently, the periurethral tissue in the echidna was definitively identified as a rudimentary prostate. This is supported by:
In aggregate, these characteristics of glandular tissue surrounding the urethra identify a rudimentary disseminate prostate in monotremes.


Lymphokine-activated killer cell

In cell biology, a lymphokine-activated killer cell (also known as a LAK cell) is a white blood cell that has been stimulated to kill tumor cells. If lymphocytes are cultured in the presence of Interleukin 2, it results in the development of effector cells which are cytotoxic to tumor cells.
Mechanism.
It has been shown that lymphocytes, when exposed to Interleukin 2, are capable of lysing fresh, non-cultured cancer cells, both primary and metastatic. LAK cells respond to these lymphokines, particularly IL-2, by lysing tumor cells that were already known to be resistant to NK cell activity.
The mechanism of LAK cells is distinctive from that of natural killer cells because they can lyse cells that NK cells cannot. LAK cells are also capable of acting against cells that do not display the major histocompatibility complex, as has been shown by the ability to cause lysis in non-immunogenic, allogeneic and syngeneic tumors. LAK cells are specific to tumor cells and do not display activity against normal cells.
Cancer Treatment.
LAK cells, along with the administration of IL-2 have been experimentally used to treat cancer in mice and humans, but there is very high toxicity with this treatment - Severe fluid retention was the major side effect of therapy, although all side effects resolved after interleukin-2 administration was stopped.


Tonaja


FLP-FRT recombination

In genetics, Flp-"FRT" recombination is a site-directed recombination technology, increasingly used to manipulate an organism's DNA under controlled conditions "in vivo". It is analogous to Cre-"lox" recombination but involves the recombination of sequences between short flippase recognition target ("FRT") sites by the recombinase flippase ("Flp") derived from the 2 µ plasmid of baker's yeast "Saccharomyces cerevisiae".
The 34bp minimal FRT site sequence has the sequence
for which flippase (Flp) binds to both 13-bp 5'-GAAGTTCCTATTC-3' arms flanking the 8 bp spacer, i.e. the site-specific recombination (region of crossover) in reverse orientation. "FRT"-mediated cleavage occurs just ahead from the asymmetric 8bp core region (5'""3') on the top strand and behind this sequence on the bottom strand. Several variant "FRT" sites exist, but recombination can usually occur only between two "identical" "FRT"s but generally not among "non-identical" ("heterospecific") "FRT"s.
Biological function.
In yeast, this enzyme corrects decreases in 2 µ plasmid copy number caused by rare missegregation events. It does so by causing recombination between the two inverted repetitions on the 2 µ plasmid during DNA replication. This changes the direction of one replication fork, causing multiple rounds of copying in a single initiation.
Mutations of the FRT site sequence.
Senecoff "et al." (1987) investigated how nucleotide substitutions within the FRT affected the efficacy of the FLP-mediated recombination. The authors induced base substitutions in either one or both of the FRT sites and tested the concentration of FLP required to observe site-specific recombinations. Every base substitution was performed on each of the thirteen nucleotides within the FRT site (example G to A, T, and C). First, the authors showed that most mutations within the FRT sequence cause minimal effects if present within only one of the two sites. If mutations occurred within both sites, the efficiency of FLP is dramatically reduced. Second, the authors provided data for which nucleotides are most crucial for the binding of FLP and efficacy of the site-specific recombination. If the first nucleotide in both FRT sites is substituted to a cytosine (G to C), the third nucleotide is substituted for a thymine (A to T), or the seventh nucleotide is substituted for an adenosine (G to A), then the efficacy of the FLP-mediated site-specific recombination is reduced more than 100-fold. While a base substitution of any of the aforementioned nucleotides in only one of the FRT sites led to a ten-fold, ten-fold, and five-fold reduction of efficacy, respectively.
Base Substitutions in the capitalized nucleotides led to the greatest reduction in FLP-mediated site-specific recombination (Wildtype x mutant and mutant x mutant):
Many available constructs include an additional arm sequences (5'--3') one base pair away from the upstream element and in the same orientation:
This segment is dispensable for excision but essential for integration, including Recombinase-mediated cassette exchange.
Because the recombination activity can be targeted to a selected organ, or a low level of recombination activity can be used to consistently alter the DNA of only a subset of cells, Flp-"FRT" can be used to construct genetic mosaics in multicellular organisms. Using this technology, the loss or alteration of a gene can be studied in a given target organ of interest, even in cases where experimental animals would not survive the loss of this gene in other organs ("spatial control"). The effect of altering a gene can also be studied over time, by using an inducible promoter to trigger the recombination activity late in development ("temporal control") - this prevents the alteration.
Biochemical structure of Flp and mechanism of action.
Biochemically relevant structure and active site.
The Flp protein, much like Cre, is a tyrosine family site-specific recombinase. This family of recombinases performs its function via a type IB topoisomerase mechanism causing the recombination of two separate strands of DNA. Recombination is carried out by a repeated two-step process. The initial step causes the creation of a Holliday junction intermediate. The second step promotes the resulting recombination of the two complementary strands. As their family name suggests, a highly conserved tyrosine nucleophile cleaves the DNA strands. The nucleophilic properties of the tyrosine attack and bind to the 3'-phosphate at the point of DNA cleavage. The resulting 5'-hydroxyl group of the cleaved DNA acts as the nucleophile and attacks the 3'-phosphate on the complementarily cleaved DNA strand, resulting in successful recombination. Outside of the tyrosine residue, there is a conserved catalytic pentad. This pentad is made up of a lysine (Lysβ), two arginines (Arg I and II), a histidine (His-II), and a histidine/tryptophan (His/Trp-III) that comprises a mandatory and highly conserved constellation of residues for the active site of Flp and Cre (along with other IB topiosomerases). These other residues are crucial to the correct orientation of Flp binding and positioning on the DNA strands.
Application of FLP-mediated site-specific recombination.
Initial problems.
Thermolability.
Initial application of the FLP-FRT recombinase did not work in mammals. The FLP protein was thermolabile (denatured at elevated temperatures) and therefore was not useful in the mammalian model due to elevated body temperatures of these model systems. However, due to patents and restrictions on the use of Cre-Lox recombination, great interest was taken to produce a more thermostable FLP-FRT cassette. Some of the first results were produced by Buchholz "et al." (1997) by utilizing cycling mutagenesis in "Escherichia coli" . In their research, the authors transfected "E. coli c"ells with two plasmids: one coding for randomly mutated FLP proteins downstream of an arabinose promoter and another containing a lacZ gene promoter within a FRT cassette. The "E. coli" were grown on arabinose plates at 37 °C and 40 °C, and if recombination occurred, the lacZ expression would be attenuated, and the colonies would appear white. White colonies were selected from each generation and grown on a new arabinose plates at same previous temperatures for eight generations. After recombination was confirmed by western-blotting and the mutated FLP genes were sequenced, this eighth generation FLP protein (FLPe) was transfected into mammalian cell culture, and recombination in mammalian cells was confirmed. This variant of FLP only has 4 amino acid substitutions: P2S, L33S, Y108N, and S294P.
Generation of genetic mosaics.
Genetic mosaicism occurs within an organism when similar cell types express different phenotypes due to dissimilar genotypes at specific loci. Simply put, this occurs when one organism contains different genotypes, which is usually rare in nature. However, this can be easily (and problematically) produced using FLP-FRT recombination. If two different FRT sites are present within a cell, and FLP is present in appropriate concentrations, the FRT cassette will continue to be excised and inserted between the two FRT sites. This process will continue until the FLP proteins fall below the required concentrations resulting in cells within an organism possessing different genotypes. This has been seen from fruit flies to mice and is indiscriminate against specific chromosomes (somatic and sex) or cell types (somatic and germline).
Determination of cell lineages.
Before the publication of Dymecki "et al". (1998), Cre recombinase had been used for cell-fate mapping of neuronal progenitors in mice using the "En2" promoter. Thus, the authors of Dymecki "et al". (1998) theorized that FLP recombinase could be utilized in a similar fashion with a similar efficacy as Cre recombinase in mice. The authors created a two transgenic mouse lines: a neuronal Wnt1::Flp fusion line and a line that possessed the FRT cassette flanking the 18th exon of "tm1Cwr". The authors chose this exon for excision because if it is excised, its results in a null phenotype. The authors mated the two lines and allowed the progeny to reach adulthood before the progeny were sacrificed. RNA extraction was performed on neuronal, muscular, enteric, and tail tissue. Reverse-transcription PCR and northern blotting confirmed the excision of the 18th exon of "tm1Cwr" abundantly in the brain tissue and moderately in muscular tissue (due to Scwhann cells within the muscle). As expected, excision was not seen in other tissues. The authors saw equal, if not better, efficiency of the FLP recombinase in cell-fate determination than Cre recombinase.
In "Drosophila melanogaster" (Fruit Fly).
To date, Flp recombinase has been utilized many times in "D. melanogaster." A comparison of Flp recombinase to Cre recombinase in "D. melanogaster" was published by Frickenhaus "et al." (2015)"." The authors of Frickenhaus "et al." (2015) had a two-fold objective: characterize and compare the efficacy of Flp recombinase "knock-out" to Cre recombinase "knock-out" and RNAi knockdown and reveal the function of "cabeza" (caz), the fly ortholog to "FUS", in the neurons and muscle tissue of "D. melanogaster". "FUS" has been strongly implicated in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia in humans "." The authors used an "elav"-Gal4/UAS-Flp or Cre system to express the recombinase specifically in neurons and a "Mef2"-Gal4/UAS-Flp or Cre system to express it specifically in muscles. The authors conclude that the Flp recombinase "knock-out" tool is more effective than both RNAi and Cre recombinase for the purpose of knocking out specific genes in specific tissues or cell lines due to the lack of the leaky expression seen in both the Cre protein and the RNAi transcript. Also, the authors witnessed a toxicity to the Cre protein that is not seen with the Flp protein.
In "Danio rerio" (Zebrafish).
The efficacy of the FLPe recombinase system was evaluated in zebrafish by Wong "et al". (2009). Embryos, that were hemizygous for a FRT-flanked enhanced green fluorescent protein (EGFP) downstream of a muscle-specific promoter, were injected with the FLPe protein. Without FLPe, these embryoes should express EGFP in all muscle tissue, and if crossed with a wild type strand, 50% of the resulting progeny should also express EGFP in muscle tissue. Embryoes, injected with FLPe, had significantly reduced expression of EGFP in muscle tissue, and mosaicism was seen also. When these embryoes reached adulthood, they were mated with a wild type strain, and the resulting clutches had significantly less progeny that expressed the EGFP in the muscle tissue (0-4%). These results show, that not only is FLPe highly effective in somatic cells, it is highly effective in the germline of zebrafish, also,
In plants.
Creation of "phytosensors" or "sentinels" in "Arabidopsis thaliana" and Tobacco.
Phytosensors are genetically modified plants that can report the presence of biotic or abiotic contaminants. Obviously, the production of these engineered plants have great agricultural and laboratory promise. However, creating an appropriate reporter vector has shown to be problematic. "cis"-regulatory elements play a major role in the transcriptional activation of genes in plants, and many are not well understood. Many phytosensors either under express their reporter genes or report false-positives due to synthetic promoters. The authors of Rao "et al." (2010) utilized the FLP recombinase tool for the production of a highly efficient phytosensors. The authors used a heat shock promoter to induce the production of FLP while a FRT-flanked vector separated the CaMV 35S promoter from the beta-glucuronidase gene (GUS). When the plants were exposed to heat-shock, FLP-induction led to the excision of the FRT-flanked vector, effectively moving the GUS gene directly downstream of the CaMV 35S promoter. The activation of GUS led to the leaves of the plants to change from green to blue; thus, the phytosensor effectively reported stress to the model system!
With Cre-recombinase.
Production of the gate-way-ready inducible MiRNA (GRIM) expression system.
RNA interference (RNAi) has caused a paradigm shift in the expression of genes and potential gene knockouts in Eukaryotes. Before the production of the GRIM expression system, the creation of RNAi vectors was expensive and time consuming. The vectors were produced by the traditional copy-and-paste molecular cloning method. Garwick-Coppens "et al". (2011) developed a much more efficient method for the production of RNAi vectors in which expression of the RNAi can be knocked-in using Cre-recombinase and knocked-out using Flp-recombinase. The novel GRIM Expression System allows for the much faster generation of expression vectors containing artificial RNAi constructs. The authors went on to show that their expression system works quite effectively in human embryonic kidneys (HEK) cells, a common human immortalized cell line in molecular research.


Megan Valentine

Megan T. Valentine is an American engineer. She is a professor of mechanical engineering at the University of California, Santa Barbara and associate director of the California NanoSystems Institute. Valentine’s research focuses on understanding how forces are generated and transmitted in living materials and how they control cellular outcomes.
In 2019, Valentine was elected a Fellow of the American Physical Society for her "pioneering research in the development of microrheology and the applications of biomechanics at multiple length scales to diverse biological systems." Two years later, she was also elected a Fellow of the American Institute for Medical and Biological Engineering.
Early life and education.
Valentine was born to parents Jonathan and Margaret Valentine in Tamaqua, Pennsylvania and attended St. Jerome's Regional School and Marian High School. While in high school, she was named a National Science Scholars Program Semi-Finalist and was chosen to attend the 1991 Central Pennsylvania Leadership Seminar. In 1993, her article "His Girls" was published in The High School Writer newspaper, a national student newspaper.
Upon graduating from high school, she became the first in her family to graduate with a bachelor’s degree, having receiving her degree in physics from Lehigh University in 1997. She then earned a master’s degree in physics from the University of Pennsylvania in 1999, followed by her PhD in physics from Harvard University in 2003.
Career.
In 2007, Valentine accepted an assistant professor position at the University of California, Santa Barbara (UCSB), but deferred her start date to 2008 so that she could build "sophisticated microscopy rooms that provided temperature control in a low noise (acoustic, electromagnetic, vibration) environment." Upon accepting her placement at the school, Valentine began working as the co-principal investigator for the Nanosystems Science, Engineering and Technology (INSET) program. In recognition of her research, Valentine was the recipient of the 2013 National Science Foundation CAREER Award for her proposal "An Integrated Approach to Neuron Mechanics: Deciphering the Functional, Mechanical, and Structural Interactions between Microtubules and Actin." In 2015, Valentine received a Fulbright Scholarship to collaborate with Professor Creton at ESPCI ParisTech to study the strength, toughness and self-healing properties of living materials in synthetic system.
In 2019, Valentine was elected a Fellow of the American Physical Society for her "pioneering research in the development of microrheology and the applications of biomechanics at multiple length scales to diverse biological systems." Two years later, she was also elected a Fellow of the American Institute for Medical and Biological Engineering for "outstanding contributions to the microscale analysis of biomaterials, fundamental science of cellular mechanics, and generation of novel bioinspired materials.' In the same month, Valentine agreed to serve as Co-Director of the California NanoSystems Institute.


As-Saffah

Abu al-‘Abbās ‘Abdu'llāh ibn Muhammad al-Saffāḥ, or Abul ‘Abbas as-Saffaḥ (; 721/722 – 10 June 754) was the first caliph of the Abbasid caliphate, one of the longest and most important caliphates (Islamic dynasties) in Islamic history. (Due to different methods of romanising Arabic names, the spellings As-Saffah and Al-Saffah may both be found.)
Abū'l ‘Abbās' laqab or caliphal title was "As-Saffāḥ" (), meaning "the Blood-Shedder" for his ruthless tactics and perhaps also to instill fear in his enemies.
Family origins and earlier history.
As-Saffāḥ, born in Humeima (modern-day Jordan), was head of one branch of the Banu Hāshim from Arabia, a subclan of the Quraysh tribe who traced its lineage to Hāshim, a great-grandfather of Muhammad via 'Abbās, an uncle of Muhammad, hence the title "Abbasid" for his descendants' caliphate. This indirect link to Muhammad's larger clan formed sufficient basis for As-Saffah's claim to the title "caliph".
As narrated in many hadith, many believed that in the end times a great leader or "mahdi" would appear from the family of Muhammad, to which Ali belonged, who would deliver Islam from corrupt leadership. The half-hearted policies of the late Umayyads to tolerate non-Arab Muslims and Shi'as had failed to quell unrest among these minorities.
During the reign of late Umayyad Caliph Hisham ibn Abd al-Malik this unrest led to a revolt in Kufa in southern Iraq, mainly by the town's slaves. Shi'ites revolted in 736 and held the city until 740, led by Zayd ibn Ali, a grandson of Husayn and another member of the Banu Hashim. Zayd's rebellion was put down by Umayyad armies in 740. The revolt in Kufa indicated both the strength of the Umayyads and the growing unrest in the Muslim world.
During the last days of the Umayyad caliphate, Abu al-‘Abbās and his clan chose to begin their rebellion in Khurasān, an important, but remote military region comprising eastern Iran, southern parts of the modern Central Asian republics of Turkmenistan, Uzbekistan, Tajikistan, Kyrgyzstan and northern Afghanistan. In 743, the death of the Umayyad Caliph Hishām provoked a rebellion in the east. Abu al-`Abbās, supported by Shi'as and the residents of Khurasān, led his forces to victory over the Umayyads. The civil war was marked by millennial prophecies encouraged by the beliefs of some Shi'as that As-Saffāḥ was the "mahdi." In Shi'ite works such as the "Al-Jafr" faithful Muslims were told that the brutal civil war was the great conflict between good and evil. The choice of the Umayyads to enter battle with white flags and the Abbasids to enter with black encouraged such theories. The color white, however, was regarded in much of Persia as a sign of mourning.
As-Saffah's Caliphate.
In early October 749 (132 AH), Abu al-'Abbās as-Saffāh's rebel army entered Kufa, a major Muslim center in Southern Iraq. As-Saffah had not been yet declared caliph. One of his priorities was to eliminate his Umayyad rival, caliph Marwan II. The latter was defeated in February 750 at a battle on the (Great) Zab river north of Baghdad, effectively ending the Umayyad caliphate, which had ruled since 661 AD. Marwan II fled back to Damascus, which didn't welcome him, and was ultimately killed on the run in Egypt that August.
In one far-reaching, historic decision, as-Saffāh established Kufa as the new capital of the caliphate, ending the dominance of Damascus in the Islamic political world, and Iraq would now become the seat of 'Abbassid power for many centuries.
Later tales recount that, concerned that there would be a return of rival Umayyad power, as-Saffāh invited all of the remaining members of the Umayyad family to a dinner party where he had them clubbed to death before the first course, which was then served to the hosts. The only survivor, Abd al-Rahman ibn Mu'awiya, escaped to the province of al-Andalus (Spain), where the Umayyad caliphate would endure for three centuries in the west in the Emirate of Córdoba. Another version is that as-Saffāḥ's new governor to Syria, 'Abd Allāh ibn 'Ali, hunted down the last of the family dynasty, with only Abd al-Rahmān escaping. Ultimately, 'Abbasid rule was accepted even in Syria, and the beginning of the new Islamic dynasty was considered "free from major internal dissensions."
As-Saffāh's four-year reign was marked with efforts to consolidate and rebuild the caliphate. His supporters were represented in the new government, but apart from his policy toward the Umayyad family, as-Saffāh is widely viewed by historians as having been a mild victor. Jews, Nestorian Christians, and Persians were well represented in his government and in succeeding Abbasid administrations. Education was also encouraged, and the first paper mills, staffed by skilled Chinese prisoners captured at the Battle of Talas, were set up in Samarkand.
Equally revolutionary was as-Saffāh's reform of the army, which came to include non-Muslims and non-Arabs in sharp contrast to the Umayyads who refused any soldiers of either type. As-Saffāh selected the gifted Abu Muslim as his military commander, an officer who would serve until 755 in the Abbasid army.
Not all Muslims accept the legitimacy of his caliphate, however. According to later Shi'ites, as-Saffāh turned back on his promises to the partisans of the Alids in claiming the title caliph for himself. The Shi'a had hoped that their "imam" would be named head of the caliphate, inaugurating the era of peace and prosperity the millennialists had believed would come. The betrayal alienated as-Saffāh's Shi'a supporters, although the continued amity of other groups made Abbasid rule markedly more solvent than that of the Umayyads.
Caliph Abu al-`Abbās `Abdu’llāh as-Saffāḥ died of smallpox on June 10, 754 (136 AH), only four years after taking the title of caliph. Before he died, as-Saffah appointed his brother Abu Ja'far al-Mansur and, following him, the caliph's nephew Isa ibn Musa as his successors; ibn Musa, however, never filled the position.
Abbasid Military Activities.
During his reign a great battle took place in 751 known as the Battle of Talas or "Battle of Artlakh" was a military engagement between the Abbasid Caliphate along with their ally the Tibetan Empire against the Chinese Tang dynasty. In July 751 AD, Tang and Abbasid forces met in the valley of the Talas River to vie for control over the Syr Darya region of central Asia. After several days of stalemate, the Karluk Turks originally allied to the Tang defected to the Abbasids and tipped the balance of power, resulting in a Tang rout.
The defeat marked the end of Tang westward expansion and resulted in Muslim control of Transoxiana for the next 400 years. Control of this region was economically beneficial for the Abbasids because it was on the Silk Road. Historians debate whether or not Chinese prisoners captured in the aftermath of the battle brought paper-making technology to the Middle East, where it eventually spread to Europe.
The numbers of combatants involved in the Battle of Talas are not known with certainty; however, various estimates exist. The Abbasid army (200,000 Muslim troops according to Chinese estimates, though these numbers may be greatly exaggerated) which included contingents from their Tibetan ally met the combined army of 10,000 Tang Chinese and 20,000 Karluk mercenaries (Arab records put the Chinese forces at 100,000 which also may be greatly exaggerated).
In the month of July 751, the Abbasid forces joined in combat with the Tang Chinese force (the combined army of Tang Chinese and Karluk mercenaries) on the banks of the Talas river.
The Tang army was subjected to a devastating defeat. The Tang dynasty's defeat was due to the defection of Karluk mercenaries and the retreat of Ferghana allies who originally supported the Chinese. The Karluk mercenaries, two-thirds of the Tang army, defected to the Abbasids during the battle; Karluk troops attacked the Tang army from close quarters while the main Abbasid forces attacked from the front. The Tang troops were unable to hold their positions, and the commander of the Tang forces, Gao Xianzhi, recognized that defeat was imminent and managed to escape with some of his Tang regulars with the help of Li Siye. Out of an estimated 10,000 Tang troops, only 2,000 managed to return from Talas to their territory in Central Asia. Despite losing the battle, Li did inflict heavy losses on the pursuing Arab army after being reproached by Duan Xiushi. After the battle, Gao was prepared to organize another Tang army against the Arabs when the devastating An Shi Rebellion broke out in 755. When the Tang capital was taken by rebels, all Chinese armies stationed in Central Asia were ordered back to China proper to crush the rebellion.
Also in 751, the Byzantine Emperor Constantine V led an invasion across the frontier of the Caliphate. The Byzantines captured Theodosiopolis (Erzurum) and Melitene (Malatya), which was demolished. There was no serious attempt to retain control of the captured cities, except for Camachum (modern Kemah, Erzincan), which was garrisoned.
Succession.
As-Saffah died after a five year reign and Al-Mansur took on the responsibility of establishing the Abbasid caliphate by holding on to power for nearly 22 years, from Dhu al-Hijjah 136 AH until Dhu al-Hijjah 158 AH (754 – 775). Al-Mansur was proclaimed Caliph on his way to Mecca in the year 753 (136 AH) and was inaugurated the following year. Abu Ja'far Abdallah ibn Muhammad took the name Al-Mansur ("the victorious") and agreed to make his nephew Isa ibn Musa his Heir to the Abbasid caliphate. This agreement was supposed to resolve rivalries in the Abbasid family, but Al-Mansur's right to accession was particularly challenged by his uncle Abdullah ibn Ali. Once in power, caliph Al-Mansur had his uncle imprisoned in 754 and killed in 764.


Gray treefrog

The gray treefrog ("Dryophytes versicolor") is a species of small arboreal holarctic tree frog native to much of the eastern United States and southeastern Canada.
It is sometimes referred to as the eastern gray treefrog, northern gray treefrog, common gray treefrog, or tetraploid gray treefrog to distinguish it from its more southern, genetically disparate relative, Cope's gray treefrog.
Description.
As the scientific name implies, gray treefrogs are variable in color owing to their ability to camouflage themselves from gray to green or brown, depending on the substrate where they are sitting. The degree of mottling varies. They can change from nearly black to nearly white. They change color at a slower rate than a chameleon. One aspect that is unique to this frog appearance is that its legs feature a dark bandish pattern which then contrast sharply with the black-marked bright yellow or orange under the sides of its legs and arms. Dead gray treefrogs and ones in unnatural surroundings are predominantly gray. The female does not call and has a white throat; however, the male does call and can show a black/gray/brown throat during the breeding season. The female is usually larger than the male. It is important to know when trying to identify this frog that the appearance at a younger age is similar to others of the same species, but as the frog increases in age the appearance varies. They are relatively small compared to other North American frog species, typically attaining no more than . Their skin has a lumpy texture to it, giving them a warty appearance.
This species is virtually indistinguishable from Cope's gray treefrog, the only readily noticeable difference being that Cope's Gray treefrog has a shorter, faster call. However, the call rates of both gray treefrogs are temperature dependent and at lower temperatures Cope's gray treefrog can have a call rate approximating that of the gray treefrog. The difference in call can be heard, but it is best quantified by counting the number of pulses per second in their whistled trills. The gray treefrog has a pulse rate of 16 to 34 pulses per second while Cope's gray treefrog has a pulse rate of 34 to 60 pulses per second. Even though there is potential for overlap, because of the temperature dependence of the pulse frequency the two species are easily distinguished where they occur together. At a given temperature, the pulse frequency for the gray treefrog is approximately 1/2 that of Cope's gray treefrog.
The gray treefrog also has 48 chromosomes (4n), and is called the tetraploid gray treefrog in scientific literature. Cope's gray treefrog, or diploid gray treefrog, retained its 2n (24) original chromosome count. Hybridization between these species results in early mortality of many larvae, but some individuals survive to adulthood though they have reduced fertility.
Both of these similar species have bright-yellow patches on their hind legs, which distinguishes them from other treefrogs, such as the bird-voiced tree frog. The bright patches are normally only visible while the frog is jumping. Both species of gray treefrogs are slightly sexually dimorphic. Males have black or gray throats, while the throats of the females are lighter.
Tadpoles have rounded bodies (as opposed to the more elongated bodies of stream species) with high, wide tails that can be colored red if predators are in the system. Metamorphosis can occur as quickly as two months with optimal conditions. At metamorphosis, the new froglets will almost always turn green for a day or two before changing to the more common gray. Young frogs will also sometimes maintain a light green color and turn gray or darker green after reaching adulthood.
Distribution and habitat.
Gray treefrogs inhabit a wide range, and can be found in most of the eastern half of the United States, as far west as central Texas and Oklahoma. They also range into Canada in the provinces of Quebec, Ontario, and Manitoba, with an isolated population in New Brunswick.
The gray treefrog is capable of surviving freezing of its internal body fluids to temperatures as low as -8 °C.
The gray treefrog is most common in forested areas, as it is highly arboreal. Its calls are often heard in rural residential areas of the East Coast and the Midwest. It prefers to breed in semipermanent woodland ponds without fish, but it also lays eggs in swamps, vernal pools, man-made fountains and water gardens, and even in rainwater-filled swimming pool covers.
Behavior.
These frogs rarely ever descend from high treetops except for breeding. They are strictly nocturnal. Male gray treefrogs rarely have large choruses, as they are mostly solitary animals, but might vocalize competitively at the height of breeding periods. Gray treefrogs may congregate around windows and porch lights to eat insects that are attracted to the light. During the day they often rest on horizontal tree branches or leaves out in the open, even in the sun. Evidently they are less prone to overheating and desiccation than other amphibians and rely on their superb camouflage to hide them from predators.
Breeding.
Mating calls and chorusing are most frequent at night, but individuals often call during daytime in response to thunder or other loud noises. Males produce advertisement calls for females as well as aggressive calls to counter other males. Females are able to discriminate between these.
In captivity.
Needs are similar to that of the American green treefrog.


Nicotinate dehydrogenase

In enzymology, a nicotinate dehydrogenase () is an enzyme that catalyzes the chemical reaction
The 3 substrates of this enzyme are nicotinate, H2O, and NADP+, whereas its 3 products are 6-hydroxynicotinate, NADPH, and H+.
Classification.
This enzyme belongs to the family of oxidoreductases, specifically those acting on CH or CH2 groups with NAD+ or NADP+ as acceptor.
Nomenclature.
The systematic name of this enzyme class is nicotinate:NADP+ 6-oxidoreductase (hydroxylating). Other names in common use include nicotinic acid hydroxylase, and nicotinate hydroxylase.
Biological role.
This enzyme participates in nicotinate and nicotinamide metabolism. It has 2 cofactors: FAD, and Iron.


Ecastolol

Ecastolol is a beta blocker.