Pyogenic granuloma is thought to represent an exuberant tissue reaction to local irritation. It occurs in second decade of life in young females. Clinically, oral pyogenic granuloma is a smooth or lobulated exophytic growth, pedunculated or sessile, which usually bleeds on provocation. Oral pyogenic granuloma preferentially affects the gingiva. On rare occasion, it can be found extragingivally on lips, tongue, buccal mucosa, and palate which may mimic more serious pathological conditions such as malignancies. This article reports an unusual case of extra gingival pyogenic granuloma occurring on the right buccal mucosa in a female patient and discusses the features that distinguish this lesion from other similar oral mucosal lesions.  Pyogenic granuloma is a benign, soft tissue, non-neoplastic lesion of the oral cavity, thought to represent a reactive exuberant tissue-reaction to local irritation or trauma. The termA 45-year-old female patient reported with the chief complaint of growth on the inner aspect of right cheek with one-year duration. History of presenting illness revealed that the growth was gradual in onset, initially small in size now increased to attain the present size. There was also a history of occasional bleeding from the growth during chewing. The patient’s medical history and family was insignificant. Extra oral examination showed no swelling or facial asymmetry. Intraoral examination revealed a solitary exophytic, pedunculated growth on the right side of buccal mucosa at the level of occlusal plane .The exophytic growth appears erythematous with grayish white borders with lobulated surface. The growth measured of about 2cm×1cm in diameter, which was soft to firm in consistency and bled on provocation. The cusp of the right upper premolars had sharp buccal edge corresponding to about the center of the swelling. There was no evidence of pus discharge from the lesion. Regional lymph nodes were not palpable. Based on the history and clinical appearance of the lesion, provisional diagnosis of benign exophytic growth of right buccal mucosa was considered. And the differential diagnosis included traumatic fibroma, pyogenic granuloma, and capillary hemangioma. The lesion was excised under local anesthesia and sent for histopathological examination. The wound healing was completed and no recurrence was noted on 3-year follow up period .Hullihen (1844) was first to define pyogenic granuloma in the English literature. In 1897, pyogenic granuloma in man was designated as botryomycosis hominis. Hartzell (1904) is credited with giving the current term of pyogenic granuloma or granuloma pyogenicum. It was also called as Crocker and Hartzell's disease. Angelopoulos histologically defined it as hemangiomatous granuloma due to the presence of frequent blood vessels and the inflammatory nature of the lesion.et al.(This lesion is formed as a result of exaggerated localized tissue reaction to a trauma or any irritation like calculus, poor oral hygiene, nonspecific infection, over hanging restorations, cheek biting, previous dental extractions, exfoliating primary teeth, bone spicules, root remnants, tooth brush trauma. Pyogenicet al. reportedThe incidence of pyogenic granuloma is 26.8 to 32% of all reactive lesions. In the oClinically, the appearance of pyogenic granuloma is red/pink to purple, and can be smooth or lobulated mass which may be pedunculated or sessile. Younger lesions are more likely to be red because of the high number of blood vessels. Older lesions begin to change into a pink color. Pyogenic granuloma grows in size up to several centimeters in size but is usually less than 2.5cm. It can b2 and flash lamp pulsed dye lasers. Lasers have advantage of minimum pain and invasiveness and the lack of need for suturing or packing.(et al.(et al.(Management of pyogenic granuloma is conservative surgical excision, after thorough oral prophylaxis. If the lesion is small, painless and free of bleeding, oral prophylaxis and removal of causative irritants is advised. If the lesion is of large size, a thorough oral prophylaxis followed by surgical excision using gingivectomy or flap surgery procedures is done. Other tr packing. Moon et g.(et al. reportedl.(et al. used a sl.(et al. After exAs the occurrence of pyogenic granuloma in extra gingival sites is unusual, this case report emphasizes the importance of the correct diagnosis of this lesion and differentiating this from other benign and malignant oral mucosal lesion which have similar characteristics. Subsequently, the oral physicians should be aware of occurrence of these type of lesions on uncommon sites and there proper management.


Anorexia nervosa is a severe psychiatric disorder most commonly starting during the teenage-years and associated with food refusal and low body weight. Typically there is a loss of menses, intense fear of gaining weight, and an often delusional quality of altered body perception. Anorexia nervosa is also associated with a pattern of high cognitive rigidity, which may contribute to treatment resistance and relapse. The complex interplay of state and trait biological, psychological, and social factors has complicated identifying neurobiological mechanisms that contribute to the illness. The dopamine D1 and D2 neurotransmitter receptors are involved in motivational aspects of food approach, fear extinction, and cognitive flexibility. They could therefore be important targets to improve core and associated behaviors in anorexia nervosa. Treatment with dopamine antagonists has shown little benefit, and it is possible that antagonists over time increase an already hypersensitive dopamine pathway activity in anorexia nervosa. On the contrary, application of dopamine receptor agonists could reduce circuit responsiveness, facilitate fear extinction, and improve cognitive flexibility in anorexia nervosa, as they may be particularly effective during underweight and low gonadal hormone states. This article provides evidence that the dopamine receptor system could be a key factor in the pathophysiology of anorexia nervosa and dopamine agonists could be helpful in reducing core symptoms of the disorder. This review is a theoretical approach that primarily focuses on dopamine receptor function as this system has been mechanistically better described than other neurotransmitters that are altered in anorexia nervosa. However, those proposed dopamine mechanisms in anorexia nervosa also warrant further study with respect to their interaction with other neurotransmitter systems, such as serotonin pathways. The eating disorder anorexia nervosa is a severe psychiatric disorder with high mortality. Anorexia nervosa usually begins during adolescence  with a lThe hallmark sign of anorexia nervosa is the restriction of energy intake relative to requirements leading to a significantly low body weight . This seThe causes for developing anorexia nervosa are considered complex interactions between psychosocial and neurobiological abnormalities . This haFor a long time, the brain serotonin system was the primary focus of neurobiological research in anorexia nervosa, but this system is very complex and difficult to model in terms of distinct receptor-stimulus-behavior associations. More recently research suggested that brain dopamine circuitry could be a potential key player in the pathophysiology of altered food intake in anorexia nervosa , 11, 12.This article will review research on dopamine in anorexia nervosa and then provide evidence that brain dopamine function is tied to a variety of core and associated symptoms of anorexia nervosa. Targeting this system pharmacologically especially with dopamine agonists could be a promising approach to ameliorate this illness and facilitate recovery.The main dopamine releasing neurons arise from the midbrain ventral tegmental area and substantia nigra and project to caudate and putamen, the medial prefrontal, cingulate, and entorhinal cortex , as well as to the limbic system with nucleus accumbens, amygdala, septum, and piriform cortex (mesolimbic projections) . The besA variety of studies indicated altered dopamine function in anorexia nervosa. In a group ill with anorexia nervosa, cerebrospinal fluid homovanillic acid, the major dopamine metabolite, was reduced by about 30% compared to controls , and recFood intake is driven by a complex interplay between cognitive, emotional, and energy homeostasis maintaining mechanisms between brain and body . This printake has been associated with reduced caudate dopamine receptor availability in rodents, after they were fed with a high caloric “cafeteria food” diet  used in reinforcement learning paradigms are necessarily a reward in the sense of positive reinforcer or pleasant experience for individuals with anorexia nervosa. Rather brain dopamine circuits in anorexia nervosa could be hypersensitive to salient stimuli in general. Salient stimuli (conditioned and unconditioned) activate brain dopamine circuits , and higOne might argue that if the dopamine system is hypersensitive in anorexia nervosa, it should promote food seeking instead of avoidance. There is little research that investigated those phenomena in humans, but starvation in non-eating disordered healthy individuals lead to difficulties with the modulation of how much food to eat , a phenoO-methyltransferase val/val genotype, a genotype that has been associated with lower dopamine tone in the frontal cortex (Previous research has shown that anorexia nervosa is associated with high premorbid and comorbid anxiety disorders . Typicall cortex . This suAn increasing body of literature is now describing how dopamine neuron activation across the amygdala, ventral tegmental area, striatum, and hippocampus is important for fear extinction acquisition, whereas fear extinction consolidation requires prefrontal cortical dopamine D1 and D2 receptor stimulation , 62, 63.Other studies have implicated the dopamine D2 receptor in conditioned fear response. For instance, the dopamine D2 agonist quinpirol applied to the midbrain ventral tegmental area reduced expression of conditioned fear response in rodents and it was hypothesized that this was mediated by presynaptic dopamine release modulation and specifically via the dopamine D2 receptor, as dopamine D1 stimulation did not produce this effect . HoweverTaken together, the dopamine D1 and D2 receptors appear to be potential targets for treatment of anxiety and modulation of conditioned fear. Receptor stimulation could be promising although systemic application of dopamine D2 blockade facilitated fear extinction as well . Most stOne of the most puzzling symptoms in anorexia nervosa is body image distortion, which drives pathologic eating behavior as well as suicide . The disSet-shifting is a neurocognitive concept that refers to the ability to switch between tasks and behaviors flexibly. In other words, set-shifting is the mental ability to change behavior in relation to changing rules and demands. Several studies found that adults with anorexia nervosa have set-shifting deficits in that they tend to perseverate on previously applicable rules , 80. SucThe literature on dopamine receptor manipulation and its effects on set-shifting and cognitive flexibility in humans are small, but available studies suggest that D1 and D2 manipulation affects cognitive flexibility . CognitiThe above-described research suggests that there are distinct dopamine functions that are associated with feeding, reward processing, body perception, as well as learning and cognitive functions, which suggests that this system may be involved in the pathophysiology of anorexia nervosa.Various dopaminergic drugs have been shown to affect eating and body weight. For instance stimulants such as the dopamine reuptake inhibitor methylphenidate or the dopamine reuptake inhibiting antidepressant bupropion frequently attenuate food intake and promote weight loss . RelevanVarious studies investigated in anorexia nervosa dopaminergic drugs, typically neuroleptics, but the results yielded mixed results at best, and especially controlled studies are rare . The medA recent study showed that a dopaminergic challenge using the drug amphetamine lead to anxiety in anorexia nervosa as opposed to euphoria in healthy controls . This fuThis review is primarily focused on dopamine function and its role in anorexia nervosa. However, brain neurotransmitter systems obviously do not act independently, which may have direct impact on eating disorder pathology. For instance, one study found that the interaction between serotonin transporter and dopamine D2/3 receptor binding was related to anxiety in anorexia nervosa . Above IAnorexia nervosa continues to be an incredibly difficult-to-treat disorder with high mortality and limited treatment options. This review presents a theoretical approach to this problem and provides evidence that the dopamine D1 and D2 receptors could be involved in core and associated symptoms of anorexia nervosa. Figure Several dopaminergic medications have been tested in treating anorexia nervosa but they were for the most part dopamine receptor antagonists, which could in fact make a hyper-sensitivity of the system worse. On the contrary, as described above dopamine receptor stimulation could reduce such receptor sensitivity and promote behavior change. It is unlikely that such medication reduces core symptoms such as drive for thinness and body image distortion “by itself” as for instance an antidepressant resolves depressed mood and anhedonia in major depression. Much rather dopamine receptor stimulation may aid in fear extinction in the context of psychotherapy and learning, as well as reduce a hypersensitive or hyperactive dopamine receptor system over time. Further, dopamine receptor manipulation might also work best in conjunction with a serotonin system specific agent, as both systems interact and are altered in anorexia nervosa. It may also be necessary to develop pharmacological strategies that are specific for the underweight state and such a regimen may then need to be adjusted when the individual with anorexia nervosa reaches normal weight and normalization of gonadal hormones.In summary, there is evidence from basic science and some indication from human studies that dopamine D1 and D2 receptor stimulation could be a helpful pharmacological intervention for anorexia nervosa. Future research will need to test those hypotheses and also whether there is a difference in effectiveness in children and adolescents compared to adults, or whether the effects may be generalizable to the majority of anorexia nervosa patients.The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


C. elegans utilizes a relatively simple neural circuit to mediate avoidance responses to noxious stimuli such as the volatile odorant octanol. This avoidance behavior is modulated by dopamine. cat-2 mutant animals that are deficient in dopamine biosynthesis have an increased response latency to octanol compared to wild type animals, and this defect can be fully restored with the application of exogenous dopamine. Because this avoidance behavior is mediated by glutamatergic signaling between sensory neurons and premotor interneurons, we investigated the genetic interactions between dopaminergic signaling and ionotropic glutamate receptors. cat-2 mutant animals lacking either the GLR-1 or GLR-2 AMPA/kainate receptors displayed an increased response latency to octanol, which could be restored via exogenous dopamine. However, whereas cat-2 mutant animals lacking the NMR-1 NMDA receptor had increased response latency to octanol they were insensitive to exogenous dopamine. Mutants that lacked both AMPA/kainate and NMDA receptors were also insensitive to exogenous dopamine. Our results indicate that dopamine modulation of octanol avoidance requires NMR-1, consistent with NMR-1 as a potential downstream signaling target for dopamine.The nematode  A basic function of the nervous system is to confer the ability to detect external stimuli and to generate appropriate behavioral and physiological responses. These responses can be modulated when parallel streams of information are provided to the nervous system and neural activity is appropriately altered. A classic example of this is the effect of addictive narcotics such as cocaine via a dopaminergic pathway on glutamatergic synapses in the ventral tegmental area Caenorhabditis elegans, the presence of food has a strong modulatory influence on many behaviors. For instance, the physical sensation of bacterial food stimulates C. elegans mechanosensory neurons to release dopamine 2+) C. elegans avoidance response to the noxious stimulant 1-octanol is also modulated by dopamine.In the nematode C. elegans avoidance response has been well studied. Under laboratory conditions C. elegans are typically raised on agar plates and spend most of their time crawling forward. When they detect various types of noxious stimuli, they respond by rapidly initiating backward locomotion. These stimuli include toxic volatile odorants such as octanol The glr-1 result in animals that are defective for response to nose touch eat-4, which codes for a vesicular glutamate transporter expressed in ASH and other glutamatergic neurons nlp-3 likely play a role in the primary pathway for octanol response The ASH neurons make glutamatergic and neuropeptidergic synapses with five pairs of premotor interneurons  2+/PKC In mammals, interactions between dopamine signaling and NMDA signaling have been well characterized eat-4 (ky5)glr-1 (n2461)glr-1 (ky176)nmr-1 (ak4)glr-2 (ak10)dop-1 (vs100), dop-2 (vs105), dop-3(vs106)dat-1 (ok157). Strains containing mutant alleles were obtained from the Caenorhabditis Genetics Center , and strains harboring multiple mutations were generated using standard genetic crosses and PCR genotyping (see below). glr-1 (ky176) glr-2 (ak10) and nmr-1; lin-15 akEx118 All strains were maintained on standard NGM agar with OP50 cat-2 (e1112) and glr-1 (n2461) alleles were genotyped on the basis of DdeI and BsrI RFLPs, respectively. All other alleles are deletion alleles and were genotyped using triplex PCR. Primer sequences, PCR conditions, and RFLP genotyping details are all available upon request.Genotyping of all mutant alleles was performed using PCR or RFLPs. The C. elegans behavior (data not shown). Therefore, we performed pilot control experiments for the N2 and cat-2 strains at the start of each day when behavioral tests for other strains were planned. If these two control strains did not display the modulatory behavior as shown in cat-2 control data for each experiment. Results are typically pooled from several experiments conducted on different days to control for environmental variability, and are presented as mean ± S.E.M.; statistical significance was measured using an unpaired Student's t-test. For brevity in the figures, statistical analysis for the wild type and cat-2 control experiments are only shown in The Sos ("smell-on-a-stick") assay was performed on standard nematode growth medium (NGM) plates with no food, essentially as described Basal locomotion rate was visually scored by manually counting body bends of freely moving animals on NGM agar plates with no food in 10 sec. bins. The data were then normalized to body bends per minute.To treat animals with exogenous dopamine, 40 µL of a freshly prepared 1 M dopamine solution in distilled water was spread onto a standard NGM plate and allowed to briefly dry in a laminar flow hood. The plates were shielded from ambient light and used within 5-10 minutes. An equal volume of distilled water was used for vehicle only controls.cat-2 mutant animals. cat-2 codes for tyrosine hydroxylase, an enzyme essential for dopamine biosynthesis cat-2 should in principle not affect the levels of any other catecholamines or serotonin cat-2 (e1112) mutant allele we used is a nonsense mutation predicted to truncate the protein coding sequence prior to the active site of the enzyme and is thus likely to be a null allele, this strain still has 30–40% of wild type levels of dopamine To determine whether dopamine plays a role in modulating octanol response, we tested dopamine-deficient C. elegans respond to octanol on average within about 2 seconds, whereas cat-2 mutant animals responded around 4 seconds  was used as a control. Exogenous dopamine fully restored normal response to cat-2 animals, but had no effect on wild type or eat-4 animals . These results suggest that dopamine modulates the octanol avoidance behavior in C. elegans, likely by potentiating neural activity in the octanol sensing neurons (ASH and others), premotor interneurons, or other cells that provide or receive input from these neurons.To determine if the behavioral deficit observed in  animals . It is tglr-1, and glr-2 animals  the aforementioned premotor interneurons that regulate forward and backward locomotion. Based on GFP reporter studies, GLR-1 is expressed in all five pairs of premotor interneurons, whereas GLR-2 is co-expressed with GLR-1 in all the premotor interneurons except AVB  animals .glr-1. glr-1 (ky176) is a Tc1 transposon excision allele and is partially dominant negative in a nose touch reversal assay glr-1 (n2461) is a nonsense mutation that functions as a genetic null glr-1 mutants was close to (or just slightly faster than) eat-4 mutants, indicating that the deficit in octanol response in glr-1 mutants can largely be accounted for by a loss in glutamatergic signaling. Exogenous dopamine did not improve response latency for either mutant. These results are consistent with glutamatergic signaling from ASH neurons to the premotor interneurons playing a role in the octanol avoidance response.We tested two different alleles of glr-1 and cat-2 mutations. cat-2; glr-1 double mutant animals had increased response latency to octanol  is a deletion allele that is a predicted molecular null glr-1 mutants, glr-2 mutant animals also showed a similar increase in response latency as glr-1 mutant animals that was comparable to eat-4 mutants, indicating that behavioral defect in glr-2 mutants could largely be accounted for by a deficit in glutamatergic signaling. glr-2 mutant animals showed a slight but significant improvement when tested in the presence of exogenous dopamine  alleles by using a preexisting glr-1 (ky176) glr-2 (ak10) double mutant strain. We decided not to carry out a cross between the n2461 and ak10 alleles because the glr-1 and glr-2 genes are only about 0.5 map units apart on chromosome III. We found that glr-1 glr-2 double mutant animals behaved similarly to that of glr-2 single mutants; that is, glr-1 glr-2 double mutant animals were weakly sensitive to exogenous dopamine, but exogenous dopamine significantly decreased the response latency of cat-2; glr-1 glr-2 mutant animals  mutation, a deletion that is a predicted molecular null nmr-1 animals were not significantly different than wild type animals  the activity of which is modulated by dopamine, and that this modulation requires NMR-1.We have found that the avoidance behavior to octanol in C. elegans responded robustly to dilute octanol off food. . However, it is also interesting to note that for response to dilute octanol simultaneous loss of dop-1, dop-2, and dop-3 phenocopied cat-2 mutants C. elegans head neurons reliably. For instance, the dopamine receptor DOP-3, acting cell autonomously in ASH neurons, may be involved in this attenuation to dilute octanol 2+, wherein dopamine potentiates Ca2+ currents in ASH neurons in a DOP-4 dependent fashion Some prior studies have explored the role of dopamine in octanol avoidance, albeit in somewhat different behavioral paradigms. Dopamine appears to attenuate response to dilute octanol  2+ transients in ASH neurons are altered in cat-2 mutants compared to wild type when animals are stimulated by high osmolarity − channels have been reported in C. elegansWhat is the site of action for dopamine in modulating octanol response? The studies referenced above suggest that the obvious location is the ASH neurons. Consistent with this, we and others have found that Canlp-3-encoded neuropeptides released from ASH neurons promote avoidance to dilute octanol in the presence of food via a GSA-1 Gsα dependent mechanism. This also requires the putative neuropeptide receptor NPR-17 eat-4 mutants still have a significant residual response to octanol. However, our experiments with undiluted octanol were performed off food, which may not involve GSA-1 but rather EGL-30/Gqα, which is the case for response to dilute octanol 2+-dependent events via NMR-1 mediated conductances, perhaps through direct phosphorylation of NMDA receptor subunits via cAMP/PKA dependent mechanisms as seen in mammalian neurons C. elegans behaviors. The emerging picture is that the modulation of even a relatively simple behavior such as the avoidance response involves a complex, multicellular pathway involving multiple neurotransmitter systems, of which nmr-1 is just one component.Depending on the site of action, dopamine may exert its modulatory effect on the response circuit in different ways. Data S1Excel spreadsheet containing raw data for all behavioral assays. Mean response latency, S.E.M., sample size, and p values (where applicable) are given.(XLSX)Click here for additional data file.


Compelling evidence indicates the participation of polyamines in abiotic and biotic stress responses in plants. Indeed, genetic engineering of polyamine levels in plants has successfully improved biotic and abiotic stress resistance in model plants and crops. We anticipate that many of the current challenges in agriculture to cope with climate change and maintain nutritional quality of fruits and vegetables can be approached by considering the polyamine pathway.The polyamine field is very dynamic as demonstrated in the large number of monthly publications in all disciplines studying polyamines . It is composed by a broad spectrum of research laboratories spread around the world, which have provided important contributions into mechanistic processes, present and future practical applications. Still, some areas remain to be explored which makes this a fascinating topic in plant sciences. In this topic, the Editors aimed at establishing a broad perspective of polyamine action in plant stress and development by inviting key researchers in the field. We would like to thank all contributors for joining us in this special topic in Frontiers in Plant Science and we hope that authors have enjoyed the interactions and discussions with editors and reviewers around their excellent works.SAMDC1 enhances the expression of defense-related genes in Arabidopsis and promotes disease resistance against bacterial and oomycete pathogens. Another complementary perspective, Valdés-Santiago and Ruiz-Herrera (This topic contains five reviews, five original research studies and one hypothesis and theory article. Minocha et al.  provides-Herrera  provide -Herrera  provide -Herrera  summariz-Herrera  in an or-Herrera  provide -Herrera  report t-Herrera  propose The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Mikania micrantha H.B.K. in Yunnan, China, the influence of sweet potato [Ipomoea batatas (L.) Lam.] on its reproductive characteristics was studied. The trial utilized a de Wit replacement series incorporating six ratios of sweet potato and M. micrantha plants in 25 m2 plots over 2 years.As a means of biologically controlling M. micrantha occurred at the end of September; flowering and fruiting occurred from October to February. Flowering phenology of M. micrantha was delayed (P < 0.05), duration of flowering and fruiting was reduced (P < 0.05) and duration of bud formation was increased (P < 0.05) with increasing proportions of sweet potato. Reproductive allocation, reproductive investment and reproductive index of M. micrantha were significantly reduced (P < 0.05) with increasing sweet potato densities. Apidae bees, and Calliphoridae or Syrphidae flies were the most abundant visitors to M. micrantha flowers. Overall flower visits decreased (P < 0.05) as sweet potato increased. Thus the mechanism by which sweet potato suppressed sexual reproduction in M. micrantha was essentially two-fold: causing a delay in flowering phenology and reducing pollinator visits. The number, biomass, length, set rate, germination rate, and 1000-grain dry weight of M. micrantha seeds were suppressed (P < 0.05) by sweet potato competition. With proportional increases in sweet potato, sexual and asexual seedling populations of M. micrantha were significantly reduced (P < 0.05). The mortality of both seedling types increased (P < 0.05) with proportional increases in sweet potato.Budding of M. micrantha, and is a promising alternative to traditional biological control and other methods of control. Planting sweet potato in conjunction with other control methods could provide a comprehensive strategy for managing M. micrantha. The scenario of controlling M. micrantha by utilizing a crop with a similar growth form may provide a useful model for similar management strategies in other systems.These results suggest that sweet potato significantly suppresses the reproductive ability of the invasive species  Plant invasions have received attention on a global scale. Invasive plants have caused great economic harm, biodiversity loss, environmental problems, and even human and animal health issues , 2. CurrMikania micrantha H.B.K. is a rapidly-growing perennial creeping vine belonging to the family Asteraceae native to Central and South America , an important locally grown cash crop native to the American tropics, was observed to inhibit M. micrantha growth in Longchuan County of Yunnan Province, China in sweet potato fields where M. micrantha occurred [M. micrantha growth and soil nutrients [M. micrantha, with plant height, branch, leaf, stem node, adventitious root, and biomass of M. micrantha suppressed significantly; furthermore sweet potato also demonstrated higher levels of nutrient uptake than M. micrantha. Moreover, flowering of M. micrantha was significantly suppressed in mixed culture with sweet potato and with decreasing proportions of M. micrantha, the competitiveness of sweet potato increased at a rate exceeding what would be predicted by the increase in relative density [M. micrantha.To explore ecological methods for managing stigated , 28–31. occurred . Subsequutrients . Sweet p density . HoweverM. micrantha in Yunnan Province, China. Previous reports did not refer to impacts on reproductive characteristics, so this is the first report of how sweet potato competition affects characteristics such as flowering and seed production in M. micrantha. These findings are important to further elucidate the competitive interaction and mechanisms between sweet potato and M. micrantha and provide insights for similar ecological control methods that could be applied to other invasive alien species.Building on our former studies , 30, 31,M. micrantha has been expanding rapidly within Longchuan County, as the plant has invaded agricultural areas and forest margins [The study site was located in Longchuan County , in the western end of Yunnan Province, Southwest China. This area is characterized by a typical tropical climate, having a rainy season featuring heavy rainfall with 90 % relative humidity alternating with a dry season . RainfalMikania micrantha is one of the most serious invasive species in Longchuan County where this study took place. This perennial weed exhibits a climbing growth form in forests, orchards and shrublands, but on roadsides, in open wasteland areas without crops, and other areas without woody vegetation, it takes on a prostrate form. It has infested sugarcane, orange, banana, coffee, pineapple, bamboo, sweet potato, maize crops, as well as artificial pasture and secondary forest in the study area [M. micrantha can invade disturbed environments via light weight wind-dispersed seeds that are produced in great numbers, as high as 170,000 m−2 [udy area . M. micr,000 m−2 . At a lo,000 m−2 .M. micrantha. Because of its purple root, it is also known as purple sweet potato. The aboveground parts of the plant are used for livestock fodder and its roots are used for human eating. It is propagated by seed or by clonal means, with 20–50 cm fragments with 3–5 nodes typically planted [Sweet potato, native to the American tropics, is one of the main food and cash crops in tropical and subtropical regions of Yunnan Province. It is also grown in many other regions of China and other subtropical or warm-temperate regions of the world as a food source. In Longchuan County, local villagers have grown it for over 100 years . This he planted .M. micrantha plants (including roots) were collected from a M. micrantha population located in a nearby forest margin and whole sweet potato plants were collected from farmland, respectively. To ensure relative uniformity among the experimental stock, one-node segments  were taken from central stem portions of relatively young plants of similar size from both species. The segments were placed in Hoagland’s solution [M. micrantha plants were utilized  while maintaining a constant planting density of 20 plants m−2 (0.25 × 0.20 m spacing). All plots were arranged in a complete randomized design with 4 replicates utilizing 25 m2 plots (5 × 5 m). All sweet potato and M. micrantha plants were distributed evenly within the plot. During the experiment, the two species exhibited prostrate growth. The plots were not weeded and no fertilizers were used.The experiments were conducted during the May, 2014-October, 2015 growing season within maize and sweet potato intercropping land in the vicinity of Zhangfeng Town, Longchuan County, utilizing a de Wit replacement series method . On 7 Masolution  and growM. micrantha, including the dates of initial and last budding, flowering, fruiting and seed set. During peak flowering times, we marked 20 inflorescences of M. micrantha in each plot and recorded the number of flower visits per insect visitor on each inflorescence between 9:00 and 18:00 (time of maximum pollinator activity) for two continuous days with all plots monitored simultaneously over the same two days. According to [M. micrantha), or another pollinator group beyond these three taxa. At the same time, twenty plants of each species were selected randomly and harvested within the middle region of each plot. M. micrantha plants were carefully removed and separated, and number of inflorescences and flowers were recorded. The fresh weight of inflorescences and flowers and total biomass of each M. micrantha plant were measured. On 28 January 2015, seed production of M. micrantha was measured in the study plots after flowering had waned, but prior to seed dispersal. Another twenty plants of each species were selected randomly and harvested within the middle region of each plot. The number, size (length) and dry weight of M. micrantha seeds were measured. Sixty days later, germination rates of M. micrantha seeds from each plot were tested in the laboratory.From October 2014 to February 2015, flowering and fruiting phenology were recorded at 3 days intervals for rding to  each floM. micrantha seedlings was monitored in each quadrat monthly. We did not remove the seedlings that were counted but rather kept track of the total that emerged through the season, month by month. Seedling mortality was also recorded for the M. micrantha that emerged.During the spring, summer and fall of 2015 (March–October), four small quadrats (1 × 1 m) were selected randomly and marked in each plot. Seedlings were identified as either produced from germinating seeds  or vegetative growth . The number of new sexual and asexual M. micrantha [−1) = inflorescence biomass/total biomass of each plant, (2) Reproductive investment (g·g−1) = flower biomass/total biomass of each plant, (3) Reproductive index (g·g−1) = flower biomass/inflorescence biomass of each plant, (4) Reproductive ratio (flower·mg−1) = flower number/inflorescence biomass of each plant and (5) Reproductive efficiency index (flower·mg−1) = flower number/total biomass of each plant.Reproductive characteristics of icrantha , 38 wereM. micrantha plants were analyzed by analysis of variance (one-way ANOVA) using IBM SPSS 22.0 software. If significant differences were detected with the ANOVA, Tukey’s HSD, Post Hoc Multiple Comparisons, Homogeneity of Variance tests were used to detect differences among treatments at a 5 % level of significance.All growth variables  of M. micrantha occurred at the end of September, and flowering and fruiting occurred from October to February in our study area .Budding of ea Table . The peaM. micrantha were observed for each inflorescence per day, with Apidae (bees), Calliphoridae (flies), Syrphidae (flies) and other pollinators accounting for 61.2, 22.0, 12.4, and 4.4 % of total visits, respectively, in monoculture  suppressed with decreasing proportions of M. micrantha (Table M. micrantha were significantly lower (P < 0.05). The reproductive ratio of M. micrantha did not differ significantly among treatments  with decreasing proportions of M. micrantha.For a ratio of sweet potato to M. micrantha germinated for 6 months (March–August), primarily occurring between May–June. Asexual seedling populations first arose in March, and then increased in density monthly from March to October. In monoculture, sexual population and asexual population densities were 89.25 ± 4.35 m−2 and 134.75 ± 4.99 m−2, respectively (Table M. micrantha significantly declined (P < 0.05); higher seedling mortality rates were also associated with greater proportions of sweet potato.Sexual seedling populations of M. micrantha were reduced when grown in association with sweet potato. A previous study showed that plant height, branch, leaf, stem node, adventitious root, and biomass of M. micrantha were suppressed significantly by sweet potato competition [M. micrantha were also significantly suppressed with increasing proportions of sweet potato. Moreover, with decreasing number and biomass of inflorescences and flowers, the reproductive allocation, reproductive investment and reproductive index of M. micrantha were also significantly reduced. The net result of the presence of sweet potato was reduced reproductive potential of M. micrantha and like other invasive species, its reproductive ability, including flowering characteristics, seed dispersal and seed germination parameters, is associated with its invasiveness [Our research showed that the biomass, flowering, seed and seedling characteristics of petition . The presiveness –43.M. micrantha was significantly delayed, duration of flowering and fruiting was significantly reduced and duration of bud formation was markedly increased with increased sweet potato proportions.Flowering phenology is affected by number, timing and duration of flowers . These fM. micrantha observed in our study was the negative impact of sweet potato on pollinator visitation. M. micrantha depends on insects for sexual reproduction as it is self-incompatible [M. micrantha flowers and were observed to have the longest foraging time of all floral visitors, which is consistent with the results of other studies [M. micrantha corresponded with reduced insect activity. Moreover, in mixed culture, 70–90 % of M. micrantha stems and leaves were covered by sweet potato [M. micrantha flowers. Because flowering in both sweet potato and M. micrantha occurs at virtually the same time, pollinators visited both species during the monitoring period; however, because the number of flowers per shoot was at least 15 times greater for M. micrantha than sweet potato [M. micrantha flower number. M. micrantha can produce a large number of flowers and small, light, and wind-dispersed seeds [M. micrantha is consistent with the commonly observed link between pollinator visitation rate and seed set [Along with reduced biomass and delayed flowering, another major factor reducing reproductive output in mpatible . For insmpatible –48 and c studies , 49. Ovet potato , thus ret potato , the maied seeds . The negseed set .M. micrantha, with fewer flowers, lower seed setting percentage, lower 1000-grain weight and shorter flowering duration observed in plants growing in nutrient-deficient soils with suboptimal fertility, but soils with an overabundance of nutrients  also resulted in fewer flowers and low seed set [M. micrantha seeds was significantly suppressed with decreasing proportions of M. micrantha. This is because M. micrantha plants covered by dense carpets of sweet potato received fewer pollinator visits and produced fewer seeds. Furthermore, sweet potato exhibited greater absorption of soil nutrients than M. micrantha [M. micrantha in the presence of sweet potato.Nutrient availability also influences reproductive output by seed set . Meanwhiseed set , 52. Ligseed set . The preicrantha ; the resM. micrantha is formidable [M. micrantha were concentrated primarily in the 0–5 cm soil layer, which contained 98 % of the total seeds present in the soil [M. micrantha from stem fragments that root easily at the nodes and from vegetative ramets arising from rosettes can be considered at least as important as reproduction by seeds [M. micrantha and seedlings suffer a high level of mortality under natural conditions [M. micrantha were significantly suppressed, corresponding to increased mortality with increasing levels of sweet potato competition. Thus, the best time to control M. micrantha is during the seedling period and control measures should be comprehensive involving both herbicides and appropriate cultural techniques [The potential for high levels of sexual and/or vegetative reproduction by rmidable . It has rmidable , 55. Larby seeds , 56. Thenditions . The prechniques .M. micrantha could be used to reduce M. micrantha growth and reproductive ability in tropical and subtropical agricultural regions suitable for cultivation of sweet potato. Both plants have similar growth forms and climatic requirements, and sweet potato is a high value crop, and thus we recommend planting sweet potato in areas infested by M. micrantha, perhaps as part of a rotation involving more vulnerable crops. Sweet potato could even be planted in habitats such as waste areas not currently cultivated in order to reduce M. micrantha populations. Our results showed that various components of reproduction for M. micrantha were significantly reduced by suppression of plant growth; the original data is available online [M. micrantha. Finally, high cover of sweet potato shading M. micrantha plants also reduced pollinator visits, seeds number, and seedling populations of M. micrantha. Thus the mechanism by which sweet potato reduced sexual reproduction in M. micrantha was essentially twofold: causing a delay in flowering phenology and reducing pollinator visits. In addition to utilizing sweet potato, research in this study and other recent studies revealed that control of M. micrantha ideally should take place during the seedling period when M. micrantha is most vulnerable and should be comprehensive for optimal results, employing both chemical and cultural control. Thus in the case of our study region in southern Asia, the most effective timing of control is in the peak of sexual seedling emergence in May–June. The potential for utilizing a crop like sweet potato to compete with an invasive plant may well apply to many other agronomic settings where other management techniques  are unreliable or are associated with environmental concerns. The scenario of controlling M. micrantha by utilizing a crop with a similar growth form may provide a useful model for similar management strategies in other systems.The competitive advantage of sweet potato over e online . Floweri


Kaposi’s sarcoma-associated herpesvirus  is the cause of Kaposi sarcoma (KS), the most common malignancy in HIV-infected individuals worldwide, primary effusion lymphoma (PEL) and multicentric Castleman disease (MCD). KSHV is a double-stranded DNA virus that encodes several homologues of cellular proteins. The structural similarity between viral and host proteins explains why some viral homologues function as their host counterparts, but sometimes at unusual anatomical sites and inappropriate times. In other cases, structural modification in the viral proteins can suppress or override the function of the host homologue, contributing to KSHV-related diseases. For example, viral IL-6 (vIL-6) is sufficiently different from human IL-6 to activate gp130 signaling independent of the α subunit. As a consequence, vIL-6 can activate many cell types that are unresponsive to cellular IL-6, contributing to MCD disease manifestations. Here, we discuss the molecular biology of KSHV homologues of cellular products as conduits of virus/host interaction with a focus on identifying new strategies for therapy of KS and other KSHV-related diseases. Kaposi’s sarcoma-associated herpesvirus (KSHV) was identified in 1994 as a novel human herpesvirus that was shown to be the cause of Kaposi sarcoma (KS) ,3,4,5. MThe disclosure of the entire DNA sequence of KSHV prompted investigation on several viral gene homologues of cellular genes, presumably pirated by the virus during evolution . Since tThe Hungarian dermatologist Moritz Kaposi first described KS in the 1970s, before HIV and KSHV were discovered. Since the worldwide spread of HIV/AIDS, KS has been recognized as one of the AIDS-related diseases. Several epidemiologic types of KS are recognized; these include classic KS , endemic KS , epidemic KS  and post-transplant KS (in transplant recipients). All these KS types are the same disease.ORF K13) protein  and kaposin (ORF K12), and lytic genes, including vGPCR (ORF 74) and vCyclin (ORF72) [GM-CSF, IL-6 and IL-1β), chemokines  and interferon-responsive genes, which are likely critical contributors to the prominent proinflammatory phenotype of KS [KSHV-infected cells in KS lesions, the “KS cells” show a characteristic spindle cell shape. KS cells express latency-related genes, including LANA, vFLIP ( (ORF72) . Intrigu (ORF72) ,18,19. v (ORF72) . vFLIP ape of KS . Furtherpe of KS . A20, a pe of KS . When TNpe of KS . Insteadpe of KS . High-lepe of KS .Another function of vFLIP is regulation of cell death by autophagy, a tightly regulated process of cell degradation leading to the removal of cytoplasmic cell components . vFLIP iORF K6), vMIP-II (ORF K4) that share extensive sequence identity  to the cellular cytokine MIP1α (macrophage inflammatory protein/CCL3), and vMIPIII (ORF K4.1), which is more distantly related to MIP1α [2+ ion-dependent signaling [KSHV encodes the proteins vMIP-I , which aligns in the middle of viral genome [Other than vIL-6 and vFLIP, there are several viral inflammatory factors encoded by the KSHV genome . vIRF1 (l genome , inhibitl genome . vIRF3/Ll genome . An impol genome , and inhl genome . Transgel genome . Other tl genome . The oncl genome . Thus, il genome . Nutlin-l genome ,98.We have described KSHV-pirated genes and their functions in KSHV-related diseases. It is clear that viral homologues of cellular genes that have been captured during virus-host co-evolution play important roles in KSHV life cycle and pathogenicity. Therefore, a clear understanding of the function of these factors can provide precise therapeutic targets directed at the pathogen. Precision medicine is a current goal in cancer therapy, as it ideally targets important unique tumor targets while sparing the normal cell counterparts. Targeting KSHV-specific factors is in line with current efforts.


The prevalence of bovine tuberculosis (BTB) in dairy cattle in the three major milk producing regions of Eritrea was assessed by subjecting 15,354 dairy cattle, 50 % of Eritrea’s dairy cattle population, to the single intradermal comparative tuberculin test (SICTT). Skin test results were interpreted according to guidelines of the World Organization for Animal Health (OIE) with >4 mm as cutoff in skin thickness increase. In addition, we studied the relation between ‘physiological’ variables related to pregnancy and lactation, and the variable ‘region’ on the probability to be skin test positive.The BTB prevalences at animal and herd levels were: 21.5 % and 40.9 % in Maekel, 7.3 % and 10 % in Debub, and 0.2 % and 1.6 % in the Anseba region, respectively. Overall, in the regions included, prevalence was 11.3 %  95 % CI, 11.29 – 11.31 %) and 17.3 % , at animal and herd level, respectively. Considering positive herds only, the animal BTB prevalence was 36.8 %, 30.1 %, and 1.8 %, in Maekel, Debub and Anseba, respectively, and the overall animal prevalence within these herds was 32 %. In adult dairy cattle the probability of positive reactivity in the SICTT test was highest in pregnant animals as compared to the other categories.This study reports persistent prevalence of BTB as defined by positive SICTT in the dairy sector of Eritrea, especially in the regions of Maekel and Debub that are located in the central highlands of the country. To our understanding this is the first report that has encompassed all the major dairy farms in Eritrea and it will be instrumental in advocating future BTB control programs in the dairy sector.The online version of this article (doi:10.1186/s12917-016-0705-9) contains supplementary material, which is available to authorized users. Mycobacterium bovis (M.bovis) affecting cattle and other species. The disease in cattle appears both on intensive dairy farms and in extensive pastoral systems [M. bovis is zoonotic, and can be transmitted from animals to humans through consumption of raw milk, inhalation, and direct contact with saliva. Beside its zoonotic importance, BTB affects the livelihood of people in developing countries by compromising sustainable food supply, income and social status [Bovine tuberculosis (BTB) is a chronic, infectious and contagious disease caused by  systems –5. The s systems –9. M. bol status . In Afril status . In 2004l status .BTB is present in Eritrea , where tThus, the current study focused on the major milk producing regions , and its samples included more than 50 % of the total dairy cattle population of the country. It aimed to determine BTB prevalence and its association with various animal ‘physiological statuses’ related to pregnancy and lactation and ‘region’ in relation to positive reactivity in the SICTT throughout Eritrea’s dairy sector.Eritrea is located in the Horn of Africa and lies north of the equator between latitudes 12°22’ N and 18°02’ N, and longitudes 36°26’ E and 43°13’ E. It has an area of 124,400 square kilometres and is divided into six regions (zones) administratively, namely: Maekel, Debub, Anseba, Gash Barka, Southern and Northern Red Sea  and partially in Anseba (in the highland areas). In the pastoral system, large mobile herds are kept in the lowlands. Such husbandry system is mainly practiced in the western and eastern lowlands of the country, namely, in Gash Barka, Northern and Southern Red Sea regions, and partially in Anseba Fig. . The herIn 2011 a cross-sectional survey was conducted to assess BTB prevalence in the three major milk producing regions, Maekel, Debub, and Anseba, in Eritrea , heifer empty, heifer pregnant, lactating empty, lactating pregnant, dry pregnant) and region, was recorded for all the tested cattle (Table The SICTT was used based on the guidelines of the OIE . Two sitThe data was first entered in an Excel spreadsheet and checked for correctness by computing frequencies (pivot tables) using SPSS IBM version 20 software. Analyses of the association of the animals’ ‘physiological statuses’ on the prevalence of BTB as assessed by SICTT were performed using the statistical package R version 3.1.0 . A ‘GeneThe AIC (Akaike’s Information Criteria) selection criterion was used to select the ‘best model’. The analysis was performed in positive herds  with ≥5 animals only (Model 1 & 2) Tables  and 4. Tn = 5,667 and 927), Debub , Anseba , respectively. The region with the highest animal and herd BTB prevalence was Maekel (21.5 % and 40.9 %), followed by Debub (7.3 % and 10 %) and Anseba (0.2 % and 1.6 %). Considering only the positive herds (n = 545) in the three regions, the total number of animals tested was 5,272. These comprised 3,226 animals in Maekel, 1,647 in Debub and 399 in Anseba. The BTB animal prevalence in the positive herds was 36.8 % , 30.1 % (n = 496), and 1.8 % (n = 7) in Maekel, Debub, and Anseba, respectively. The reaction to bovine tuberculin test was strong with differences in skin thickness (PPD-B minus PPD-A) reaching 4.5 mm to 73 mm  followed by mature animals 3 - ≤ 5 years (24 %). The prevalence of SICTT reactors was 11.3 %  at individual animal level and 17.3 % 95 % CI, 0.1727-0.1733) at herd level. The individual animal prevalence would have increased by 0.4 % had we used single intradermal tuberculin test instead of SICTT. The number of individual animals and herds tested in each of the regions were: Maekel  as well as at herd (17.3 %) level. The individual animal BTB prevalence differed between the three regions included, ranging from 21.5 % in Maekel to 7.5 % in Debub and 0.2 % in Anseba. The BTB prevalence in skin test positive herds was not uniform; it was highest (37 %) in Maekel, followed by Debub (30 %), and Anseba (2 %).The risk of having a BTB skin test positive animal was 13 times more likely in Maekel and ~9 times more likely in Debub than in Anseba  was the first place in the country where exotic breeds were introduced for dairying. It was also in this area that BTB was reported for the first time in Eritrea, in 1929, and as already indicated in the previous study  as well tigators , 28. TheM.bovis infection as compared to exotic dairy breeds [A major limitation of the present study was that the ‘breed’ of the animals tested was not sufficiently recorded by the operators during the skin testing period and thus could not be included in the analysis. However, we assume that the different breeds kept in the different regions of the country may have contributed to the relatively higher BTB prevalence observed in Maekel and Debub regions where the presence of the HF breed predominates at the farms as opposed to Anseba. Several studies have shown indigenous zebu cattle to be relatively tolerant to y breeds , 28–30. The present study indicated that pregnancy and lactation were significantly linked with the reactivity in SICTT. Lactating -pregnant cows were most at risk (OR ~ 11) to show positive reactions in the skin test compared to calves, and 2 times more compared to bulls. These results are in agreement with a similar study in Ethiopia  that repA case control study has shown that susceptibility of animals to BTB infection increases when they are fed deficient rations . CurrentOur risk factor analyses showed that ‘physiological status’ was strongly associated with SICTT positive reactivity Table , Model 2When compared to calves, bulls were at higher risk (OR ~ 5) to react to the skin test Table , Model 1The overall results of the current study resemble those of similar studies in Ethiopia , 41–43. In this study bacterial culture was not conducted due to the fact that skin test positive dairy cattle were not slaughtered after the disclosure of the results due to a lack of a compensation scheme.In order to get more insight in the importance of BTB and its epidemiology in Eritrea, as a potential basis for a control program, further investigations in dairy cattle as well as in indigenous cattle, goats and camels kept under traditional livestock production systems are underway.The current study has brought to light the persisting prevalence of BTB as well as some animal characteristics, related to pregnancy and lactation, linked with SICTT positive skin test in the dairy sector in Eritrea. The BTB risk tended to vary by region and adult lactating-pregnant animals were the most likely to be test positive.M.bovis mycobacterium bovis; PPD, purified protein derivative; PPD-A, purified protein derivative for mycobacterium avium; PPD-B, purified protein derivative for mycobacterium bovis; SICTT, single intradermal comparative tuberculin test.BTB, bovine tuberculosis; HF, Holstein Friesian; MOA, Ministry of Agriculture; NUFFIC, Netherlands University Foundation for International Cooperation; OIE, World Organization for Animal Health;


In order to assess the role of Saba Bank as a potential reservoir of diversity for the surrounding reefs, we examined the population genetic structure, abundance and health status of two prominent benthic species, the coral Montastraea cavernosa and the sponge Xestospongia muta. Sequence data were collected from 34 colonies of M. cavernosa  and 68 X. muta sponges  on Saba Bank and around Saba Island, and compared with published data across the wider Caribbean. Our data indicate that there is genetic connectivity between populations on Saba Bank and the nearby Saba Island as well as multiple locations in the wider Caribbean, ranging in distance from 100s–1000s km. The genetic diversity of Saba Bank populations of M. cavernosa (π = 0.055) and X. muta (π = 0.0010) was comparable to those in other regions in the western Atlantic. Densities and health status were determined along 11 transects of 50 m2 along the south-eastern rim of Saba Bank. The densities of M. cavernosa  were average, while the densities of X. muta  were generally higher with respect to other Caribbean locations. No disease or bleaching was present in any of the specimens of the coral M. cavernosa, however, we did observe partial tissue loss (77.9% of samples) as well as overgrowth (48.1%), predominantly by cyanobacteria. In contrast, the majority of observed X. muta (83.5%) showed signs of presumed bleaching. The combined results of apparent gene flow among populations on Saba Bank and surrounding reefs, the high abundance and unique genetic diversity, indicate that Saba Bank could function as an important buffer for the region. Either as a natural source of larvae to replenish genetic diversity or as a storehouse of diversity that can be utilized if needed for restoration practices.Saba Bank, a submerged atoll in the Caribbean Sea with an area of 2,200 km No disease was observed in any of the M. cavernosa colonies. Previous tissue loss (78% of colonies) and current overgrowth of a part of the colony (48.1% of colonies) was frequently observed in M. cavernosa. Cyanobacteria accounted for the vast majority of overgrowth (56.7%) followed by fleshy macro algae or turf algae (23.6%), sponges (15.8%), gorgonians (2.4%) and crustose coralline algae (1.6%). X. muta showed extensive presence of presumably cyclic bleaching [et al. [X. muta (> 20% on the transect pictures) showed partial tissue loss associated with overgrowth by algae or other sponges.Based on our survey of 11 sites, of 50 mind. m-2 . A totalleaching , which f [et al.  as ‘numeMontastraea cavernosa and the sponge Xestospongia muta appear to be connected along the whole eastern and southern rim of the Saba Bank, as well as among the populations on Saba Bank and the nearby island of Saba. Our results suggest that Saba Bank harbors viable populations that could function as a source of diversity, as the genetic diversity of the populations of M. cavernosa  and X. muta  on Saba Bank are comparable to the ranges of diversity found for these species in other Caribbean locations . FurtheM. cavernosa there appears to be unrestricted gene flow among the locations of Saba and the majority of the studied locations in the wider Caribbean. The putatively high level of genetic exchange within the studied region—despite geographical separation of over 2000 km—could be the result of specific life history traits in combination with ocean currents. Being a broadcasting species [M. cavernosa have the ability to drift with currents over distances of several hundreds of kilometers [et al. (2006) [M. cavernosa populations within the Caribbean region have also been recorded by Goodbody-Gringley et al. (2011) [et al. (2014) [et al. (2014) [For  species , the larlometers , 20. Hydlometers ) can, ho. (2006)  suggest . (2011) , Brazeau. (2014)  and Serr. (2014)  probably. (2014) , 69.X. muta, connectivity seems to be limited between the populations on Saba Bank and Belize, as well as most of the locations in the Bahamas. The migration analyses suggest that colonization of the Saba Bank was not recent, with population subdivision time for X. muta from Saba Bank versus Stirrup Cay estimated at 1.7–2.0 million years ago. Note that the absolute numbers inferred in the present study depend heavily on the assumption that the generation time is one year. Unfortunately, not much is known about generation time of sponges in natural habitats. Additionally, the inferences rely on a single locus only and may thus depend on specifics of that locus. Studying additional loci would greatly improve these analyses. The pattern of population genetic structure in X. muta appears to be most strongly related to hydrological patterns [X. muta over large distances [X. muta that they studied in Florida, Bahama’s and Belize, ranging in distance from 100–1000 km. Yet, the authors did not see evidence of isolation-by-distance, potentially indicating that X. muta larvae do have the ability to disperse over larger distances. However, due to the low number of I3-M11 haplotypes (n = 4) found in X. muta, the presence or absence of one specific haplotype can have a large impact on the Φst values. Using the same genetic marker in a congener, X. testudinaria, genetic divergence over small spatial scales of 2–100 km has been detected in Indonesia [X. testudinaria has short dispersal distances and seems to rely largely (up to 80%) on self-recruitment [X. testudinaria is a species complex with each COI haplotype possibly representing a distinct species [X. muta.For patterns  and specpatterns  and mighistances , 45. Lopistances  also foundonesia , 71. X. ruitment . It has, species , 71. It M. cavernosa colony densities on Saba Bank were found to be highly variable between sites (range 0.02–0.96 colonies m-2), but fit largely within the range of densities described by Porter et al. (1987) [-2). However, much higher densities (up to 6.32 colonies m-2) have also been found throughout in the Caribbean region [e.g. SB06 with densities of 0.02 colonies m-2). The density of X. muta on most Saba Bank sites was comparable to previous recordings in Florida where mean densities between 0.186–0.277 m-2 were found at depths ranging between 15–30 m [X. testudinaria in Indonesia. In East Kalimantan the densities ranged between 0–0.1333 in/m2 at depths between 5-10m [-2, yet X. testudinaria was most abundant at heavily disturbed reefs [. 1987)  for soutn region , 17. The 15–30 m , 51, but87  for sen 5-10m . In Sulaed reefs .M. cavernosa colonies confirms previous accounts [M. cavernosa colonies do appear to be under stress, as exemplified by old tissue loss in the majority of the colonies and partial overgrowth of cyanobacteria, sponges or macro algae. The observed tissue loss might be the consequence of past mass bleaching events that affected reefs worldwide, including Saba Bank [M. cavernosa are known to be susceptible to bleaching, in some cases affecting up to 80% of the colonies [http://www.aoml.noaa.gov/phod/cyclone/data/ca.html). To our knowledge, however, there are no reports of substantial bleaching having occurred in the Caribbean region in 2013.The absence of any disease in accounts , 8, 9 onaba Bank . No distaba Bank , 76. As colonies , 28. TheX. muta (> 80%) on Saba Bank showed signs of bleaching in the form of circular shaped white spots. In fact, all observed larger individuals (diameter > 50 cm) had these bleached spots  [X. muta on the bank [X. muta is known to be seasonal with a peak during the fall [In contrast, the vast majority of ed spots . In addi 15–30 m . Our obs. (2006)  in the Fthe fall , the obsX. muta on Saba Bank indicate a healthy population, yet a significant portion of the sponges is affected by partial bleaching and although long term effects of this phenomenon are unknown, there is a risk of a reduction in population size. X. muta plays a crucial role in the coral reef ecosystem providing habitat complexity [e.g. crustaceans and brittle stars) [e.g. [X. muta populations would likely cause a significant change in ecosystem functioning.At present, the densities and genetic diversity of mplexity , 78 and mplexity , 79, 80 e stars) , 81, 82.e stars) , 42, thes) [e.g. , 83–87. This is the first study to examine the potential of Saba Bank as a buffer in the region, either as a natural source of larvae to replenish genetic diversity in the region or as a storehouse of diversity that can be utilized if needed for restoration practices. Although our results are not conclusive on the direction of gene flow, they do underline the potential of Saba Bank to serve an essential ecological role within the region. There are no large land masses nearby and consequently the reefs have suffered less from pollution, coastal development and run-off. Saba Bank reefs, however, are not immune to global environmental threats such as the rise in sea surface temperature or acidification, and are subjected to local threats including fishing of natural herbivores  and explorations for natural resources as well . Due to S1 Fig2) overlaps with 1 m of the transect line (length between the two black dots. Only M. cavernosa (blue arrow) and X. muta (green arrow) within the red square were counted.Red square (1 m(EPS)Click here for additional data file.S2 FigTwo pairwise comparisons were made: Saba Bank versus SSPC , and Saba Bank versus Stirrup Cay (Bahamas). Migration rates are given here forward in time.; line colors represent four independent simulation runs; A = simulated ancestral population.(EPS)Click here for additional data file.S1 Tableincluding novel sequences and those obtained from GenBank.(DOCX)Click here for additional data file.S2 Table(DOCX)Click here for additional data file.S3 TableM. cavernosa were sampled.Significant values (p < 0.05) provided in bold. At site SB06 no (DOCX)Click here for additional data file.S4 Table(DOCX)Click here for additional data file.S5 Tablex = millions of individuals in population x; A = simulated ancestral population, T = population subdivision time (millions of years ago), 2Nm1,2 = number of migrants population 1 (Saba Bank) receives from population 2 (SSPC or Stirrup Cay) per year. SSPC refers to data of the pooled Bahamas sites: Stirrup Cay and Plana Cay.Maximum posterior probability estimates in demographic units for four isolation-with-migration simulation runs. For details of simulations see text. N(DOCX)Click here for additional data file.


We organized this special issue on “Dopaminergic Foundations of Personality and Individual Differences” with the goal of illuminating the diversity of roles that dopamine plays in personality and individual differences. To introduce this topic, we provide a brief sketch of the current understanding of the functions of the dopamine system. In doing so, we place the diverse contributions to this research topic in the context of this rich, evolving literature.For several years, theory and research in Personality Neuroscience has linked dopamine function with various aspects of personality and individual differences. This literature builds on research in basic neuroscience concerning the role of dopamine in behavior and experience, with the aim of understanding the ways in which this neurotransmitter system influences The dopamine system can be divided into several anatomically defined branches or pathways. The nigrostriatal pathway (projecting from the substantia nigra to the striatum) is involved in motor control, and has long been of interest in the context of Parkinson's Disease and its therapeutic management via dopamine replacement  and negative symptoms , and mesolimbic dopamine to positive symptoms   is implicated in higher cognitive functions such as working memory and decision-making —and that these effects are diametrically opposed for extraverted and introverted individuals. These findings are potentially explained in terms of extraversion-related individual differences in pre- and post-synaptic responsivity to the dopamine antagonist.Our first two articles demonstrate that the effects of dopaminergic pharmacological agents are entirely dependent on extraverted personality: Cooper and colleagues replicate their recent finding that extraversion is associated with a neural index of the dopaminergic teacher signal specified in models of reinforcement learning, and show that this generalizes to a conceptually related trait concerning reward anticipation. Knyazev shows that, in more extraverted individuals, there is a relation between self-referential thoughts and alpha power in the posterior hub of the Default Mode Network—a resting state network that has been implicated in self-centered cognition, and which appears to have a basis in dopaminergic neurotransmission.Our next two articles relate extraversion to EEG-derived indices of reward system activity: Pickering and Pesola identify a number of specific parameters within biologically-plausible models of reward learning that potentially represent the neural substrates of traits such as extraversion . Skatova and colleagues model extraversion-related differences on a reinforcement learning task in terms of two distinct forms of learning that are difficult to dissociate in typical studies of this kind. After discarding participants who were not engaged with the learning task, they found that extraversion is related to error-driven learning processes, distinct from other learning processes.A further two articles focussing on extraversion and reward-processing employ computational models of reward learning: Treadway and colleagues focus on chronic perceptions of stress, which they find is associated with reduced processing of reward and punishment in the medial prefrontal cortex. Schultheiss and Schiepe-Tiska focus on the implicit motive “need for power” , which they theorize may have a basis in dopamine-driven learning processes centered on the striatum. Richter and colleagues report that the degree to which both monetary rewards and punishments modulate reaction time and BOLD measures of interference processing  covaries with the DRD2/ANKK1 TaqIA polymorphism of the dopamine D2 receptor gene. Relatedly, findings by Kawasaki and Yamaguchi suggest that the degree to which visual working memory capacity increases for preferred versus non-preferred colors may constitute another useful indicator of reward sensitivity that may be linked to brain dopamine in future work.Reward-related processes have also been implicated in several individual differences constructs beyond extraversion: Jiang and colleagues conclude from their qualitative review of the literature that a specific dopaminergic gene variant, the D4 receptor gene exon III (DRD4) polymorphism, influences prosocial behavior depending on environmental influences. Reuter and colleagues underscore this conclusion by showing that the extent to which individuals behave fairly in the ultimatum game depends on genetic variants of not only the DRD4 but also the D2 receptor gene (DRD2/ANKK1 TaqIA).The rewarding impact of prosocial actions and outcomes  during procedural learning. Their observed associations with BOLD response in several dopamine-relevant regions, including the striatum, are consistent with dopamine's role in both procedural learning and psychosis-proneness.The role that dopamine appears to play in symptoms of schizophrenia has clear implications for individual differences reflecting psychosis-proneness and schizotypy. In the first of two papers on this topic, Chermahini and Hommel report a replication of their prior work showing a curvilinear association between spontaneous eye-blink rate  and creativity (divergent thinking), with optimal performance at average eye-blink rates .As noted in our brief introduction, the role of dopamine in cognitive function also appears to extend to creative problem solving. DeYoung proposes that the over-arching function of the dopamine system is to promote exploration, which he divides into cognitive exploration  and behavioral exploration . His model provides an elegant framework for integrating the various contributions to this special issue, as well as the broader literature concerning the dopaminergic foundations of personality and individual differences.How can we make coherent sense of the variety of individual differences phenomena in which dopamine appears to be involved? In the final article in our special issue, The sixteen articles in this special issue are a testament to the significant advances that have been made in personality neuroscience and related fields in recent years. Some of these articles have yielded novel findings, while others have served the important task of replicating and consolidating existing research. Overall, they should leave most readers convinced that dopamine function does play a role in personality and other individual differences. Equally, they demonstrate that there is no simple one-to-one correspondence between the neurotransmitter dopamine and any single personality trait. This has often been noted (e.g., Zuckerman, The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


During spermatogenesis, the blood-testis barrier (BTB) segregates the adluminal  and basal compartments in the seminiferous epithelium, thereby creating a privileged adluminal environment that allows post-meiotic spermatid development to proceed without interference of the host immune system. A key feature of the BTB is its continuous remodeling within the Sertoli cells, the major somatic component of the seminiferous epithelium. This remodeling is necessary to allow the transport of germ cells towards the seminiferous tubule interior, while maintaining intact barrier properties. Here we demonstrate that the actin nucleation promoting factor Neuronal Wiskott-Aldrich Syndrome Protein (N-WASP) provides an essential function necessary for BTB restructuring, and for maintaining spermatogenesis. Our data suggests that the N-WASP-Arp2/3 actin polymerization machinery generates branched-actin arrays at an advanced stage of BTB remodeling. These arrays are proposed to mediate the restructuring process through endocytic recycling of BTB components. Disruption of N-WASP in Sertoli cells results in major structural abnormalities to the BTB, including mis-localization of critical junctional and cytoskeletal elements, and leads to disruption of barrier function. These impairments result in a complete arrest of spermatogenesis, underscoring the critical involvement of the somatic compartment of the seminiferous tubules in germ cell maturation. Mammalian spermatogenesis takes place within a sheltered environment, whereby somatic Sertoli cells protect and guide germ cells as they mature and differentiate. A key structure generated by the protective Sertoli cell epithelium is the blood-testis barrier (BTB), a composite of junctional and cytoskeletal elements, which prevents exposure of post-meiotic spermatids to the immune system. The BTB is a highly dynamic structure, which needs to be dismantled and rapidly rebuilt, in order to allow passage of maturing preleptotene spermatocytes, without compromising their isolation. Here we show that N-WASP, a conserved facilitator of formation of branched actin microfilament arrays, provides a function that is essential for maintenance of an intact BTB. Genetic disruption of N-WASP in mouse Sertoli cells leads to loss of BTB impermeability, resulting in a complete arrest of spermatogenesis at early and post-meiotic stages. Based on the localization patterns of key elements, we propose that branched-actin filaments participate in recycling of BTB materials to ensure the dynamic and efficient maintenance of this structure, one of a series of blood-tissue barriers that preserve privileged organ environments. Production of sperm in mammals takes place within the seminiferous tubules of the testis. A prominent aspect of this process is a complex series of interactions between the maturing germ cells and the somatic Sertoli cell epithelium, which performs a variety of guidance and protective roles critical for spermatogenic differentiation The BTB is composed of a unique combination of junctional and cytoskeletal structures, making it one of the tightest blood-tissue barriers in the mammalian body A key feature of spermatogenesis is the vectorial journey of maturing spermatocytes, which differentiate from type B spermatogonia residing at the base of the seminiferous epithelium, where the spermatogonial stem-cells are located. With the essential aid of the encompassing Sertoli epithelium, the immotile, inter-connected and differentiating spermatocytes are transported between the Sertoli cells towards the tubule interior. The spermatocytes encounter the BTB as they reach the preleptotene phase of meiosis, at which time they undergo a remarkable “seamless” passage through the barrier We have recently proposed a model for the molecular mechanism underlying spermatogenic transport through the BTB Neuronal Wiskott-Aldrich Syndrome Protein , the ubiquitous and broadly expressed member of the WAS protein family Desert Hedgehog (Dhh)-Cre SC-cKO males were strongly reduced to ∼5% of age-matched controls , and more mature (step 13–16) elongating/elongated spermatids were completely absent , a feature that we ascribe to the overall smaller size of the Sertoli cell population (described below).Tissue specific disruption of N-WASP in Sertoli cells see also  was achicontrols Fig. 1A,SC-cKO mice, beyond early meiotic phases. To verify this assertion, and rule out the possibility that the observed phenotypes reflect secondary consequences of spermatogenic arrest, we compared the morphologies of seminiferous tubules from younger (21- and 35-day-old) control and mutant mice, closer to the onset of sexual maturity . This was now supported by assessing the size of the Sertoli cell population in sectioned tubules using GATA-1, a nuclear Sertoli cell marker SC-cKO mice was considerably disrupted, as F-actin was no longer confined to the basal ES at the BTB, but was instead diffusely localized throughout the basal compartment  from basal to adluminal tubule compartments n = 5 mice), FITC-inulin failed to penetrate the BTB, which lies close to the basement membrane, and no fluorescence was found inside the adluminal compartment (SC-cKO mouse testes (n = 5 mice), and could be detected as far as the tubule lumen  SC-cKO seminiferous epithelium. We examined this issue directly by assessing the localization patterns of representative apical ES components. Nectin-3, a spermatid-specific adhesion molecule that mediates Sertoli cell-spermatid attachment at the apical ES SC-cKO Sertoli cells, and no longer restricted to the adluminal compartment  576  407 serves as a molecular switch regulating BTB adhesion capacities, via changes in actin polymerization kinetics SC-cKO mice. Expression levels of the p-FAK-Tyr614 form were significantly lower, while the key phosphorylated form p-FAK-Tyr438 was practically undetectable via either immunoblot or immunofluorescence microscopy  and gap junction (connexin-43) components of the BTB are either significantly mis-localized or absent altogether. Importantly, major structural abnormalities are apparent in organization of the basal ES, the unique, hallmark component of the BTB. In particular, the tightly packed arrangement of basal ES microfilaments is disrupted, and this key cytoskeletal structure becomes dispersed in the Sertoli cell cytoplasm. Similar dispersal is observed for N-cadherin, an adherens junction component that normally displays tight association with the basal ES. Impairment of the adhesive properties of the BTB are further implied by the marked reduction in levels of phospho-FAK proteins, key regulators of ES-based adhesion. Taken together, these data present a substantial list of defects in BTB structure and functional properties, demonstrating that disruption of N-WASP in Sertoli cells results in significant deterioration of BTB barrier capabilities.SC-cKO tubules is in marked contrast to elements of the branched-actin nucleation system, which retain their proper spatiotemporal localization patterns. Both Arp3, a subunit of the Arp2/3 complex, and drebrin E, a factor that mediates Arp3 localization in Sertoli cells, preserve their tight basal localization during stage VIII of the seminiferous epithelial cycle in the mutant tubules. These observations are significant for several reasons. First, they argue that abnormal localization patterns do not result from a general disruption of cytoplasmic organization in N-WASPSC-cKO tubules, but are likely to arise from specific defects caused by the absence of actin nucleation. This assertion is also supported by the morphological similarities between N-WASPSC-cKO tubules at different ages, implying that mutant phenotypes are a primary consequence of disrupting N-WASP function, and not a result of tissue degeneration over time. Second, our observations identify a particular juncture during which lack of N-WASP function becomes apparent. A timeline consistent with the various observations suggests proper localization of the Arp2/3 complex (mediated in part by drebrin E) to the basal aspect of Sertoli cells, at the stage when BTB restructuring is required. Under normal circumstances, N-WASP then acts to stimulate Arp2/3 and promote nucleation of branched actin arrays necessary for BTB restructuring. The actual involvement of the N-WASP-Arp2/3 machinery is likely to take place after restructuring is underway, and when many of the BTB components are transiently displaced, to allow the dynamic events of the process to unfold. Arrest of restructuring in the N-WASPSC-cKO mutant tubules occurs therefore at a critical phase, when the BTB has been dismantled, but is now incapable of forming a new intact barrier, such as at the rear end of the preleptotene spermatocytes under transport at the immunological barrier.The generally disorganized spatial distribution of junctional and cytoskeletal BTB components in N-WASPSC-cKO seminiferous tubules, we propose the following model for branched actin mediation of BTB restructuring  why spermatocytes fail to mature properly following BTB failure. The latter issue may be a reflection of additional impairments to Sertoli cell function, as these cells guide and nurture sperm differentiation throughout the process. One aspect to consider in this context is the involvement of branched actin arrays in the formation of the apical ES, which displays many structural similarities to the ES portion of the BTB, and acts to anchor mature spermatids to the apical end of the Sertoli-cell epithelium just prior to their release into the tubule lumen. The relatively early arrest of spermatogenesis in N-WASPIn conclusion, we describe here an essential requirement for the molecular machinery promoting polymerization of branched actin arrays in the events that mediate dynamic formation of the BTB, and hence, in the proper progress of mammalian spermatogenesis, particularly spermiogenesis. Our findings suggest that this process employs a complex interplay between junctional remodeling, vesicular trafficking and dynamic organization of the actin cytoskeleton, to ensure differentiation while maintaining the integrity of a key blood-tissue barrier.N-WASP was specifically deleted in Sertoli cells of the mouse testis as previously described Dhh-Cre bearing mice N-WASP−Dhh-Cre/+; N-WASP−/+ progeny. These F1 mice were then crossed to mice homozygous for the conditional KO allele N-WASPfloxDhh-Cre; N-WASPflox/N-WASP− males  were identified among the progeny. Mice at age 21- and 35-day postpartum (dpp), as well as at 8-, 9-, and 11-week (wk) of age were used. Age-matched wild type (WT) N-WASPflox/N-WASP− mice served as the corresponding control mice. Data shown herein are representative findings from single experiments, but each experiment was repeated with at least n = 3–5 mutant mice and the corresponding number of WT controls, and yielded similar results.The use of animals for the studies reported herein was approved by The Rockefeller University Institutional Animal Care and Use Committee with Protocol Number 12-506. Dhh-Cre; N-WASPflox/N-WASP− males  versus aged-matched N-WASPflox/N-WASP− WT (control) mice, as earlier described s (Asingle), Apr (Apaired) and short chain of Aal  spermatogonia including SSC Morphometric analysis was performed to score Utf1- or GATA-1-positive cells in the seminiferous epithelium of mice from in vivo in mice, a functional assay was performed, as earlier described n = 5 control (WT) mice vs. n = 5 N-WASPSC-cKO mice) were under anesthesia with ketamine HCl (∼100 mg/kg b.w.) together with an analgesic xylazine (∼10 mg/kg b.w.), administered intramuscularly (i.m.). A small incision, about 0.5-cm, was made in the skin over the jugular vein to expose the blood vessel, and ∼1 mg FITC-inulin dissolved in ∼75 µl PBS  was administered into the jugular vein via a 28-gauge needle. About 45 min thereafter, mice were euthanized by CO2 asphyxiation by slow (20–30% per minute) displacement of chamber air with compressed CO2 for ∼12 min. Testes were removed, snap-frozen in liquid nitrogen, and embedded in Tissue-Tek O.C.T.  compound (Sakura). Frozen sections (10 µm) were obtained in a cryostat at −21°C. Fluorescence images were obtained using an Olympus BX61 Fluorescence Microscope. Mice from both control (WT) and conditional KO groups were processed in the same experimental session for comparison to avoid inter-experimental variations. To yield semi-quantitative information regarding the BTB integrity, distance (D) traveled by the fluorescence tag (DFITC-inulin) from the basement membrane in a seminiferous tubule versus radius of the tubule (DRadius) in N-WASPSC-cKO testes was compared to WT control mice. For oblique sections of tubules, DRadius was obtained by averaging the shortest and the longest distance from the basement membrane. About 30 tubules were randomly scored from each mouse testis and a total of 5 mice from each group was scored and compared.To assess if the disruption of N-WASP in Sertoli cells would impede BTB integrity DC™ Protein Assay kit (Bio-Rad), using BSA as a standard. About 30–50 µg of protein lysate from each sample was used for immunoblotting. Immunoblots were visualized by enhanced chemiluminescence (ECL), using a kit prepared as described http://mesonpi.cat.cbpf.br/e2002/cursos/NotasAula/ScnImage.pdf). Data were normalized against β-actin, which served as a protein loading control.Immunoblotting was performed using lysates from 3–4 mouse testes, as earlier described 2PO4 and 0.15 M NaCl, pH 7.4 at 22°C) for 10 min. Sections were permeabilized in 0.1% Triton X-100 (v/v) in PBS prior to blocking in 10% normal goat serum (v/v) for 30 min. After overnight incubation with a primary antibody  were added to the sections in succession, and a color reaction was obtained using 3-amino-9-ethylcarbazole  as the chromogenic substrate.Immunohistochemistry (IHC) was performed using paraffin-embedded mouse testes as described Bouin's solution-fixed 4-µm-thick paraffin sections were used for H&E staining as described t-test was used to compare changes in protein levels between N-WASPSC-cKO and age-matched control mice, in which the relative protein level was arbitrarily set at 1. For immunofluorescence analysis, each time point represented at least n = 3 mice. For immunoblotting data, each bar is the mean±SD of 4 mice including control group. P<0.05 was interpreted as statistically significant.GB-STAT  was used for statistical analysis. Student's