Chromatin accessibility determines cell-type specific intron retention Dynamic intron retention (IR) in vertebrate cells is of widespread biological importance. Aberrant IR is associated with numerous human diseases including cancer. Despite consistent reports demonstrating intrinsic sequence features that predispose introns to become retained, conflicting findings about cell type-specific IR regulation demand a systematic analysis in a controlled experimental setting. We integrated matched transcriptomics and epigenetics data (including DNA methylation, nucleosome occupancy, histone modifications) from primary human myeloid and lymphoid cells. Using machine learning we trained two complementary models to determine the role of epigenetic factors in the regulation of IR. We show that increased chromatin accessibility contributes substantially to the retention of introns in a cell-specific manner. We also confirm that intrinsic characteristics of introns are key for them to evade splicing. With mounting reports linking pathogenic alterations to RNA processing, our findings may have profound implications for the design of therapeutic approaches targeting aberrant splicing.
Novel feature selection method via kernel tensor decomposition for improved multi-omics data analysis BackgroundFeature selection of multi-omics data analysis remains challenging owing to the size of omics datasets, comprising approximately 102-105 features. In particular, appropriate methods to weight individual omics datasets are unclear, and the approach adopted has substantial consequences for feature selection. In this study, we extended a recently proposed kernel tensor decomposition (KTD)-based unsupervised feature extraction (FE) method to integrate multi-omics datasets obtained from common samples in a weight-free manner.

MethodKTD-based unsupervised FE was reformatted as the collection of kernelized tensors sharing common samples, which was applied to synthetic and real datasets.

ResultsThe proposed advanced KTD-based unsupervised FE method showed comparative performance to that of the previously proposed KTD method, as well as tensor decomposition-based unsupervised FE, but required reduced memory and central processing unit time. Moreover, this advanced KTD method, specifically designed for multi-omics analysis, attributes P-values to features, which is rare for existing multi-omics-oriented methods.

ConclusionsThe sample R code is available at https://github.com/tagtag/MultiR/
Cell-specific Bioorthogonal Tagging of Glycoproteins Altered glycosylation is an undisputed corollary of cancer development. Understanding these alterations is paramount but hampered by limitations underlying cellular model systems. For instance, the intricate interactions between tumour and host cannot be adequately recapitulated in monoculture of tumour-derived cell lines. More complex co-culture models usually rely on sorting procedures for proteome analyses and rarely capture the details of protein glycosylation. Here, we report a strategy termed Bio-Orthogonal Cell line-specific Tagging of Glycoproteins (BOCTAG). Cells are equipped by transfection with an artificial biosynthetic pathway that transforms bioorthogonally tagged sugars into the corresponding nucleotide-sugars. Only transfected cells incorporate bioorthogonal tags into glycoproteins in the presence of non-transfected cells. We employ BOCTAG as an imaging technique and to annotate cell-specific glycosylation sites in mass spectrometry-glycoproteomics. We demonstrate application in co-culture and mouse models, allowing for profiling of the glycoproteome as an important modulator of cellular function. The ecological consequences and evolution of retron-mediated suicide as a way to protect bacteria from being killed by phage In 1984, retrons were described as DNA sequences that code for a reverse transcriptase and a unique single-stranded DNA/RNA hybrid called multicopy single-stranded DNA (msDNA). It would not be until 2020 that a function was shown, when compelling evidence was presented that retrons can protect bacteria from infections by lytic phage via an abortive infection mechanism. When infected with the virulent mutant of the phage lambda, {lambda}VIR, and to a lesser extent other phages, a retron designated Ec48 is activated, the Escherichia coli bearing this element dies and the infecting phage is lost. With the aid of a mathematical model, we explored the a priori conditions under which retrons will protect bacterial populations from invasion by phage and when retron-bearing bacteria will evolve in populations without this element. Using E. coli with and without Ec48, and {lambda}VIR we estimated the parameters of this model and tested the hypotheses generated from our analysis of its properties. Our models and experiments suggest cells expressing retron-mediated abortive infection have no advantage over cells lacking this system as a defense against phage, and we question whether the protection against phage infection is the unique selective force responsible for their evolution in bacteria. Contribution Evenness: A functional redundancy metric sensitive to trait stability in microbial communities The concept of functional redundancy has received considerable attention in both the macroecology and microbial ecology literature. As a result, multiple metrics of functional redundancy have been proposed. These vary in how they weight trait levels, species abundance, functional richness, and species richness. Here we present a new functional redundancy metric tailored for community-aggregated traits, which are traits that are quantified at the community level and can be quantitatively partitioned among species. We call this metric Contribution Evenness (CE) because it measures how evenly species contribute to a community-aggregated trait. As CE is an evenness measurement, it ranges from 0 and 1, where 0 corresponds to a single species contributing to a community-aggregated trait and 1 corresponds to all species contributing equally. Using in silico simulations of species extinctions, we demonstrate that CE reflects the stability of an ecosystem function to species extinction, a hypothesized ecological consequence of functional redundancy. As a positive control and to illustrate how CE can be used with sequence data, we analyzed the functional redundancy of eight nitrogen-transforming pathways using 2,631 metagenome-assembled genomes from 47 marine sites. CE for marine nitrogen cycle marker genes was consistent with our qualitative understanding of which nitrogen pathways are most functionally redundant in the ocean. We found that, on average, the NH4+ assimilation pathway was the most functionally redundant (0.44 {+/-} 0.08) while dissimilatory nitrate reduction was the least redundant (0.005 {+/-} 0.005). As demonstrated here, CE provides a promising framework for measuring trait stability in microbiomes. 3D Reconstructions of Mouse Skeletal Muscle Reveal a Decrease in the MICOS Complex and Altered Mitochondrial Networks Background: Skeletal muscle gradually loses mass, strength, endurance, and oxidative capacity during aging. Studies of bioenergetics and protein turnover show that mitochondria mediate this decline in function. Mitochondria cristae are essential for the production of ATP. While mitochondrial aging is associated with endoplasmic reticulum stress, fragmented mitochondria, and decreased mitochondrial capacity, the genes associated with morphological changes in mitochondria during aging still requires further elucidation Further, it is not completely understood how 3D mitochondrial networks and the specialization of mitochondria are altered during aging. Methods: We measured changes in mitochondrial morphology and mitochondrial connectivity during the aging of the mouse gastrocnemius muscle through serial block facing-scanning electron microscopy and 3D reconstruction. Nanotunnels were also measured through 3D reconstruction. CRISPR/Cas9 KO was performed to examine changes in mitochondria upon loss of the mitochondrial contact site and cristae organizing system (MICOS) complex and optic atrophy 1 (OPA-1). Metabolomics were used to find key metabolite pathways changed upon off of the MICOS complex. Results: We found changes in mitochondrial network configuration, nanotunneling, size, shape, number, contact sites, cristae organizing system (MICOS) dynamics and gene expression in skeletal muscle during aging. We also found an association of OPA-1 and the MICOS complex in the gastrocnemius with mitochondrial aging. Further, the loss of the MICOS complex was linked with decreased oxidative capacity, and altered mitochondrial metabolism. Conclusions: To our knowledge, studies of mitochondrial changes in skeletal muscle throughout aging remains limited. 3D reconstructions of nanotunnels elucidated novel patterns of mitochondrial aging in skeletal muscle. MICOS proteins decreased with age and mitochondrial morphology was similar between aged skeletal muscle and that of young mice with MICOS protein loss. In tandem, our data suggest a relationship between the MICOS complex and aging, which could be potentially linked to disease states with additional 3D reconstruction. Non-invasive imaging of gene expression and protein secretion dynamics in living mice: identification of ectopic prothrombin expression as driver of thrombosis in cancer The topology of gene expression and protein localization is a crucial characteristic of life, where the spatiotemporal dynamic of secretory proteins instruct higher order organization, including the orchestration of developmental and adaptive programs. However tools to non-invasively interrogate the fate of secretory proteins in vivo are scarce. Here we introduce a genetic tagging strategy for in vivo imaging of the secretion and expression dynamics of secretory proteins in living animals. Applying this to a prototypical liver-derived secretory protein, we demonstrate that this approach, combined with optical in-vivo imaging, uncovers extrahepatic prothrombin expression in multiple novel anatomical sites (including testes, placenta, brain, kidney, heart and lymphatic system) and in emerging tumors, resulting in significant amounts of tumor-derived prothrombin in the blood with procoagulant properties. Syngeneic cell lines from this mouse model enable unravelling regulatory mechanisms in high resolution, and in a scalable format ex vivo. Beyond discovering new functions of proteins in a targeted manner, this model allows identifying rheostats in the cross-talk between gene expression and availability of a secretory protein. It is also a valuable resource for uncovering novel (tissue-specific) therapeutic vulnerabilities. Use of lignocellulosic residue from 2G ethanol production to enhance methane production through co-digestion This is a pioneer study evaluating the methane (CH4) production potential from residues of integrated 1st (vinasse and filter cake) and 2nd (deacetylation pretreatment liquor from straw) generation (1G2G) sugarcane biorefinery, providing a fully chemical characterization of them and their relation with the anaerobic digestion (AD) process. Small-scale assays provided fundamentals for basing the co-digestion optimization by assessing the optimal co-substrates synergistic conditions. Biochemical Methane Potential (BMP) tests showed co-digestion enhanced CH4 yield of isolated substrates, reaching up to 605 NmLCH4 gVS-1. The association of vinasse and deacetylation liquor as co-substrates increased the BMP by ~38% mostly by nutritionally benefiting the methanogenic activity. The kinetic analysis confirmed that the deacetylation liquor was the co-substrate responsible for improving the CH4 production in the co-digestion systems due to the highest CH4 conversion rate. The alkaline characteristic of the liquor (pH~12) also prevented alkalizing from being added to the co-digestion, an input that normally makes the process economically unfeasible to implement on an industrial scale due to the large quantities required for buffering the reactor. The filter cake had the lowest BMP (262 NmLCH4 gVS-1) and digestibility ([&le;] 40%), further limited by the required stirring to improve the mass transfer of biochemical reactions. The present study drives towards more sustainable use of vinasse, the most voluminous waste from the sugarcane industry, and lignin-rich residues derived from pre-treatment alkaline methods, aiming at an energy-efficient utilization, by at least 16% when compared to the traditional vinasse AD. The experimental and modeling elements from this work indicated the lignin-rich liquor is the main responsible for putting the co-digestion as a disruptive technological arrangement within the 1G2G sugarcane biorefineries, reinforcing the biogas production as the hub of the bioeconomy in the agroindustrial sector. Propionate ameliorates diabetes-induced neurological dysfunction through regulating the PI3K/Akt/eNOS signaling pathway A large body of research has established diabetes-related cognitive deterioration, sometimes known as "diabetic encephalopathy." Current evidence supports that oxidative stress, neuronal apoptosis, and cerebral microcirculation weakness are associated with cognition deficits induced by diabetes. The present study explores the effect of propionate on neurological deficits, cerebral blood flow, and oxidative stress in diabetic mice. Propionate can markedly improve neurological function, which is correlated with its capabilities of stimulating nitric oxide (NO) production, increasing cerebral microcirculation, suppressing oxidative stress and reducing neuron loss in the hippocampus. In addition, the results of Western Blotting indicated that the brain-protective function of propionate in streptozocin (STZ)-induced insulin-dependent diabetes mellitus (IDDM) mice is related to phosphoinositide 3-kinase (PI3K)/serine-threonine protein kinase (Akt)/endothelial nitric oxide synthase(eNOS) signaling pathway. In a diabetic mouse model, propionate reduces cerebral microcirculation, hippocampus apoptosis, and neurological impairment. Thus, propionate, now employed as a food preservative, may also help slow diabetes-induced cognitive loss.

Graphical Abstract

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org.highwire.dtl.DTLVardef@81fa09org.highwire.dtl.DTLVardef@1469451org.highwire.dtl.DTLVardef@b37fa1org.highwire.dtl.DTLVardef@8037e7_HPS_FORMAT_FIGEXP  M_FIG C_FIG HighlightsO_LIPropionate ameliorates diabetic-induced depression-like behavior, spatial learning and memory deficits.
C_LIO_LIPropionate increases cerebral microcirculation by enhancing NO production in diabetic mice.
C_LIO_LIPropionate suppresses oxidative stress and reduces neuron loss in the hippocampus.
C_LIO_LIThe brain-protective function of propionate is related to PI3K/Akt/eNOS signaling pathway.
C_LI Are microbes growing on flowers evil? Effects of old flower microbes on fruit set in a wild ginger with one-day flowers, Alpinia japonica (Zingiberaceae) Flowers are colonized and inhabited by diverse microbes. Plants rapidly replace flowers with short lifespan, and old flowers senesce. This may contribute to avoiding adverse effects of the microbes. In this study, we investigate if the flower microbial community on old flowers impedes fruit and seed production in a wild ginger with one-day flowers. We inoculated newly opened flowers with old flower microbes, and monitored the effects on fruit and seed set. We also assessed prokaryotic communities on the flowers using amplicon sequencing. We found six bacterial amplicon sequence variants (ASVs) whose proportions were increased on the inoculated flowers. These ASVs were also found on flower buds and flowers that were bagged by net or paper during anthesis, suggesting that they had been present in small numbers prior to flowering. Fruit set was negatively associated with the proportions of these ASVs, while seed set was not. The results suggest that old flowers harbor microbial communities different from those at anthesis, and that the microbes abundant on old flowers negatively affect plant reproduction. Though the short lifespan of flowers has gotten little attention, it might be an essential defense mechanism to cope with antagonistic microbes that rapidly proliferate on the flowers. Improved AlphaFold modeling with implicit experimental information Machine learning prediction algorithms such as AlphaFold1 and RoseTTAFold2 can create remarkably accurate protein models, but these models usually have some regions that are predicted with low confidence or poor accuracy3-6. We hypothesized that by implicitly including experimental information, a greater portion of a model could be predicted accurately, and that this might synergistically improve parts of the model that were not fully addressed by either machine learning or experiment alone. An iterative procedure was developed in which AlphaFold models are automatically rebuilt based on experimental density maps and the rebuilt models are used as templates in new AlphaFold predictions. We find that including experimental information improves prediction beyond the improvement obtained with simple rebuilding guided by the experimental data. This procedure for AlphaFold modeling with density has been incorporated into an automated procedure for crystallographic and electron cryo-microscopy map interpretation. Principles of mRNA targeting via the Arabidopsism6A-binding protein ECT2 Specific recognition of N6-methyladenosine (m6A) in mRNA by RNA-binding proteins containing a YT521-B homology (YTH) domain is important in eukaryotic gene regulation. The Arabidopsis YTH-domain protein ECT2 is thought to bind to mRNA at URU(m6A)Y sites, yet RR(m6A)CH is the canonical m6A consensus site in all eukaryotes and ECT2 functions require m6A binding activity. Here, we apply iCLIP (individual-nucleotide resolution cross-linking and immunoprecipitation) and HyperTRIBE (targets of RNA-binding proteins identified by editing) to define high-quality target sets of ECT2, and analyze the patterns of enriched sequence motifs around ECT2 crosslink sites. Our analyses show that ECT2 does in fact bind to RR(m6A)CH. Pyrimidine-rich motifs are enriched around, but not at m6A-sites, reflecting a preference for N6-adenosine methylation of RRACH/GGAU islands in pyrimidine-rich regions. Such motifs, particularly oligo-U and UNUNU upstream of m6A sites, are also implicated in ECT2 binding via its intrinsically disordered region (IDR). Finally, URUAY-type motifs are enriched at ECT2 crosslink sites, but their distinct properties suggest function as sites of competition between binding of ECT2 and as yet unidentified RNA-binding proteins. Our study provides coherence between genetic and molecular studies of m6A-YTH function in plants, and reveals new insight into the mode of RNA recognition by YTH-domain-containing proteins. A rat model of pregnancy in the male parabiont Male pregnancy is a unique phenomenon in syngnathidae which refers to embryo or fetus incubation by males. However, whether male mammalian animals have the potential to conceive and maintain pregnancy remains unclear. Here, we constructed a rat model of pregnancy in the male parabiont using a four-step strategy. First, a heterosexual parabiotic pair was produced by surgically joining a castrated male rat and a female rat. After 8 weeks, uterus transplantation was performed on the male parabiont. After recovery, blastocyst-stage embryos were transplanted to the grafted uterus of the male parabiont and the native uterus of the female parabiont. Caesarean section was performed at embryonic day 21.5. The success rate of the model was 3.68%, and pups were only delivered from the male parabiont under pregnant blood exposure. Our results reveal the potential for rat embryonic development in male parabionts, which may have a profound impact on reproductive biology.

One-sentence summaryA rat model of pregnancy was constructed in the male parabiont using a four-step strategy.



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org.highwire.dtl.DTLVardef@1f0694eorg.highwire.dtl.DTLVardef@91997forg.highwire.dtl.DTLVardef@f47086org.highwire.dtl.DTLVardef@7a33f_HPS_FORMAT_FIGEXP  M_FIG C_FIG Partial response electromyography as a marker of action stopping Response inhibition is among the core constructs of cognitive control. It is notoriously difficult to quantify from overt behavior, since the outcome of successful inhibition is the lack of a behavioral response. Currently, the most common measure of action stopping, and by proxy response inhibition, is the model-based stop signal reaction time (SSRT) derived from the stop signal task. Recently, partial response electromyography (prEMG) has been introduced as a complementary physiological measure to capture individual stopping latencies. PrEMG refers to muscle activity initiated by the go signal that plummets after the stop signal before its accumulation to a full response. Whereas neither the SSRT nor the prEMG is an unambiguous marker for neural processes underlying response inhibition, our analysis indicates that the prEMG peak latency is better suited to investigate brain mechanisms of action stopping. This study is a methodological resource with a comprehensive overview of the psychometric properties of the prEMG in a stop signal task, and further provides practical tips for data collection and analysis. The H4K20 demethylase DPY-21 regulates thedynamics of condensin DC binding Condensin is a multi-subunit SMC complex that binds to and compacts chromosomes. Here we addressed the regulation of condensin binding dynamics using C. elegans condensin DC, which represses X chromosomes in hermaphrodites for dosage compensation. We established fluorescence recovery after photobleaching (FRAP) using the SMC4 homolog DPY-27 and showed that a well-characterized ATPase mutation abolishes its binding. Next, we performed FRAP in the background of several chromatin modifier mutants that cause varying degrees of X-chromosome derepression. The greatest effect was in a null mutant of the H4K20me2 demethylase DPY-21, where the mobile fraction of condensin DC reduced from [~]30% to 10%. In contrast, a catalytic mutant of dpy-21 did not regulate condensin DC mobility. Hi-C data in the dpy-21 null mutant showed little change compared to wild type, uncoupling Hi-C measured long-range DNA contacts from transcriptional repression of the X chromosomes. Together, our results indicate that DPY-21 has a non-catalytic role in regulating the dynamics of condensin DC binding, which is important for transcription repression. Regulatory perturbations of ribosome allocation optimize the growth proteome with a trade-off in adaptation capacity Bacteria regulate their cellular resource allocation to enable fast growth-adaptation to a variety of environmental niches. We studied the ribosomal allocation, growth and expression profiles of two sets of fast-growing mutants of Escherichia coli K-12 MG1655 in glucose minimal medium. Mutants with only 3 of the seven copies of ribosomal RNA operons grew faster than the wild-type strain in minimal media and show similar phenotype to previously studied rpoB mutants. Higher growth rates due to increased ribosome content affected resource allocation. Expression profiles of fast-growing mutants shared downregulation of hedging functions and upregulated growth functions. Mutants showed longer diauxic shifts and reduced activity of gluconeogenic promoters during glucose-acetate shifts, suggesting reduced availability of the RNA Polymerase for expressing hedging proteome. These results show that the regulation of ribosomal allocation underlies the growth/hedging phenotypes obtained from laboratory evolution experiments. We show how two different regulatory perturbations (rRNA promoters or rpoB mutations) reshape the proteome for growth with a concomitant fitness cost

HighlightsMutants with only 3 ribosomal operons grow faster than wild-type in minimal medium

 {Delta}4 rrn and rpoB mutants share phenotypic traits

Faster growth of mutants is achieved by increased ribosome content

Fast-growing mutants display reduced hedging expression and adaptation trade-offs

Despite similar ribosomal content in rich medium the mutants present growth defects Herbivore life histories are altered by drought stress in their hosts plants Drought associated with climate change can stress plants, altering their interactions with phytophagous arthropods. Dryness not only impacts cultivated plants but also their parasites, which in some cases are favoured by drought. Herbivorous arthropods feeding on drought-stressed plants typically produce bigger offspring and develop faster. However, how much responses to abiotic factors differ among populations of a species remains poorly documented. Here, we evaluate variability among populations of a major agricultural pest, the two spotted spider mite, Tetranychus urticae, in response to drought-stress. We compare key life-history parameters of twelve populations that originate from climates ranging from wet and cool Atlantic locations to medium to dry hot Mediterranean locations. We evaluated how plant drought stress affects four life history traits: development time, fecundity, sex-ratio and emigration rate in an experiment comparing well-watered and drought-stressed bean plants. Mites feeding on drought-stressed plants developed faster and attempted to leave leaves less often, and young females were more fecund. The mites from wet temperate climates exhibited greater plasticity between the two water regimes than mites originating from dryer and hot climates. Thus, climate in the area of origin influences mite response to drought. Untargeted metabolomic analyses reveal the diversity and plasticity of the specialized metabolome in seeds of different Camelina sativa genotypes Despite the essential role of Specialized Metabolites (SMs) in the interaction of plants with the environment, studying the ability of crop seeds to produce these protective compounds has been neglected. Furthermore, seeds produce a myriad of SMs providing an interesting model to investigate their diversity and plasticity. Camelina sativa gained a lot of interest in the past few years as rustic oil seed crop. A characterization of seed SM landscapes in six camelina genotypes grown in the field and harvested during five growing seasons has been undertaken in this work. This allowed a comprehensive annotation of seed SMs combining analyses that cluster SMs based on their chemical structures and co-accumulation patterns. These data showed broad effects of the environment on the stimulation of the seed-specialized metabolome. Among well annotated compounds, flavonols were identified as the metabolic class characterised by high plasticity, revealing significant variable accumulation according to the year and/or the genotype. Lastly, a deeper characterisation of primary metabolites and lipids in two selected genotypes has been performed. We showed that, in addition to flavonols, alkaloids and glucosinolates displayed a higher phenotypic plasticity with respect to most of the primary metabolites, including some sugars and major storage compounds such as fatty acids, proteins and most lipid classes (e.g. DAG, TAG), but similar plasticity compared to free aminoacids and carboxylic acids. This work highlighted major and unexplored effects of the environment on the seed specialized metabolome demonstrating that seeds exhibit a dynamic and plastic metabolism, with an impact on seed quality.

Significance statementSeeds produce a myriad of Specialized Metabolites (SMs) with an essential role in the interaction of plants with the environment. We characterized SM landscapes, primary metabolites and lipid composition in the seeds of camelina genotypes grown in the open field in five consecutive growing seasons. Our results showed the predominant effect of the environment on the regulation of the seed - specialized metabolome, with a potential impact on seed quality of camelina that may also occur in other oilseed crops. Genetic and chemotherapeutic causes of germline hypermutation Mutation in the germline is the source of all evolutionary genetic variation and a cause of genetic disease. Previous studies have shown parental age to be the primary determinant of the number of new germline mutations seen in an individuals genome. Here we analysed the genome-wide sequences of 21,879 families with rare genetic diseases and identified 12 hypermutated individuals with between two and seven times more de novo single nucleotide variants (dnSNVs) than expected. In most of these families (8/12) the excess mutations could be attributed to the father. We determined that two of these families had genetic drivers of germline hypermutation, with the fathers carrying damaging genetic variation in known DNA repair genes, causing distinctive mutational signatures. For five families, by analysing clinical records and mutational signatures, we determined that paternal exposure to chemotherapeutic agents prior to conception was a key driver of hypermutation. Our results suggest that the germline is well protected from mutagenic effects, hypermutation is rare and relatively modest in degree and that most hypermutated individuals will not have a genetic disease. Diverse stem-chondrichthyan oral structures and evidence for an independently acquired acanthodid dentition The teeth of sharks famously form a series of transversely-organised files with conveyor-belt replacement that are borne directly on the jaw cartilages, in contrast to the dermal plate-borne dentition of bony fishes that undergoes site-specific replacement. A major obstacle in understanding how this system evolved is the poorly understood relationships of the earliest chondrichthyans and the profusion of morphologically and terminologically diverse bones, cartilages, splints and whorls that they possess. Here we use tomographic methods to investigate mandibular structures in several early branching  acanthodian-grade stem-chondrichthyans. We show that the dentigerous jaw bones of disparate genera of ischnacanthids are united by a common construction, being growing bones with non-shedding dentition. Mandibular splints, which support the ventro-lateral edge of the Meckels cartilage in some taxa, are formed from dermal bone and may be an acanthodid synapomorphy. We demonstrate that the teeth of Acanthodopsis are borne directly on the mandibular cartilage and that this taxon is deeply nested within an edentulous radiation, representing an unexpected independent origin of teeth. Many or even all of the range of unusual oral structures may be apomorphic, but they should nonetheless be considered when building hypotheses of tooth and jaw evolution, both in chondrichthyans and more broadly. Sarcoplasmic reticulum calcium handling in young DBA/2J vs C57BL/10 mdx models of Duchenne muscular dystrophy The DBA/2J (D2) mdx mouse has emerged as a more severe model of Duchenne muscular dystrophy when compared to the traditional C57BL/10 (C57) mdx mouse. Here, we questioned whether sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) function would differ in muscles from young D2 and C57 mdx mice. In gastrocnemius muscles, both D2- and C57 mdx mice exhibited signs of impaired Ca2+ uptake, however, this was more severe in D2 mdx mice. Maximal SERCA activity was lowered only in D2 mdx gastrocnemius muscles and not C57 mdx muscles. Furthermore, in the left ventricle and diaphragm, Ca2+ uptake was impaired in C57 mdx muscles with lowered rates of Ca2+ uptake compared with C57 WT mice, whereas in muscles from D2 mdx mice, rates of Ca2+ uptake were unattainable due to the severe impairments in their ability to transport Ca2+. Overall, our study demonstrates that SERCA function is drastically impaired in young D2 mdx mice. Visualizing cancer-originated acetate uptake through MCT1 in reactive astrocytes demarcates tumor border and extends survival in glioblastoma patients Glioblastoma multiforme (GBM) is a devastating brain tumor with dismal prognosis of only 15-month survival regardless of surgical resection. Here, we report an advanced neuroimaging technique combining 11C-acetate PET and MRI (AcePET), visualizing the boundary beyond the MRI-defined tumor. Targeted biopsy of the regions with increased 11C-acetate uptake revealed the presence of reactive astrocytes with enhanced acetate-transporter MCT1, along with cancer stem cells. Reactive astrogliosis and MCT1-dependent 11C-acetate-uptake were recapitulated in U87MG-orthotopic models. Mechanistically, glycolytic tumor cells release excessive acetate causing reactive astrogliosis, leading to the release of aberrant astrocytic GABA and H2O2, which further down-regulate the neuronal glucose uptake through GLUT3. Clincally, AcePET-guided surgery allows complete tumor resection of infiltrating cancer stem cells and extends the overall survival of patients by 5.25 months compared to conventional MRI-guided surgery. We established a new concept of the metabolic interactions between GBM cells and neighboring neurons through reactive astrocytes and developed AcePET-guided surgery to fight against GBM. Greater spear nosed bats in Panama do not use social proximity to improve foraging efficiency Group foraging animals may change their spatial relationships in response to the resource landscape. The strength of social network ties across foraging groups could then reflect the energy balance of individual group members through their effect on foraging efficiency. Greater spear-nosed bats (Phyllostomus hastatus) live in social groups where unrelated females develop group-specific social calls, defend each others offspring, and are hypothesized to coordinate social foraging to feed on balsa flowers. To test if social groups forage together, and if this increases foraging efficiency, we tracked 18 individuals from three social groups of P. hastatus on Isla Colon, Panama using high frequency GPS for 1 - 3 days each. We found that individuals commuted alone but then joined group members in small foraging patches with high densities of flowering balsas, 25 km from their roost on the mainland. Proximity-based social network measures did not predict foraging efficiency or energy expenditure, but individuals with higher social associations spent more time outside of the cave. Individuals did not coordinate movement, but close proximity among individuals increased resting bout duration and synchrony, particularly when in the same patch. These results show that stronger social proximity associations were more closely tied to resting behavior, and indicate that factors other than increased feeding efficiency may structure network relationships of group members while foraging.

Lay SummarySocial foraging can increase foraging efficiency on hard-to-find food sources. Miniaturized high-frequency GPS allowed us to test this on groups of greater spear-nosed bats. We estimated food intake rates, energy expenditure, and the strength of bat social relationships. In contrast to our expectations, we did not find a relationship between bat social relationships and energy expenditure or foraging efficiency. However, bats took longer resting breaks when group members were close. Why these bats commute 25 km individually across the ocean to then forage near each other thus requires further investigation. Affordable Caenorhabditis elegans tracking system for classroom use For decades the nematode C. elegans has served as an outstanding research organism owing to its unsurpassed experimental amenability. This advantage has also made this tiny worm an attractive vehicle for science instruction across higher learning institutions. However, the prohibitive cost associated with the automated behavioral assessment of these animals remains an obstacle preventing their full adoption in undergraduate and high school settings. To improve this situation, we developed an inexpensive worm tracking system for use by high school interns and undergraduate students. Over the past two years this tracker has been successfully used by undergraduate students in our introductory Cell and Molecular lab (BSC220) at Illinois State University. Here we describe and demonstrate the use of our inexpensive worm tracking system. Heterologous vaccination regimens with self-amplifying RNA and Adenoviral COVID vaccines induce robust immune responses in mice Several vaccines have demonstrated efficacy against SARS-CoV-2 mediated disease, yet there is limited data on the immune response induced by heterologous vaccination regimens using alternate vaccine modalities. Here, we present a detailed description of the immune response, in mice, following vaccination with a self-amplifying RNA (saRNA) vaccine and an adenoviral vectored vaccine (ChAdOx1 nCoV-19/AZD1222) against SARS-CoV-2. We demonstrate that antibody responses are higher in two dose heterologous vaccination regimens than single dose regimens. Neutralising titres after heterologous prime-boost were at least comparable or higher than the titres measured after homologous prime boost vaccination with viral vectors. Importantly, the cellular immune response after a heterologous regimen is dominated by cytotoxic T cells and Th1+ CD4 T cells which is superior to the response induced in homologous vaccination regimens in mice. These results underpin the need for clinical trials to investigate the immunogenicity of heterologous regimens with alternate vaccine technologies. Inhibition of microbial deconjugation of micellar bile acids protects against intestinal permeability and liver injury Altered host-microbe interactions and increased intestinal permeability have been implicated in the pathogenesis of a range of diseases. However, the mechanisms by which gut microbes affect epithelial barrier integrity remain unclear. Few host-produced metabolites that protect against epithelial damage have been identified, and whether microbial metabolism of host factors alters intestinal barrier function is unknown. Here, we investigate the effects of bacterial metabolism of host-produced bile acid (BA) metabolites on epithelial barrier integrity. We observe that rats fed a choline-deficient, high-fat diet (CDAHFD) exhibit reduced abundance of host-produced conjugated BAs in the intestine at early timepoints coinciding with increased permeability. We show that in vitro, conjugated BAs protect gut epithelial monolayers from damage caused by bacterially produced unconjugated BAs through micelle formation. We then demonstrate that inhibition of BA deconjugation using a small molecule inhibitor of gut bacterial bile salt hydrolase (BSH) enzymes prevents development of pathologic intestinal permeability and hepatic inflammation in CDAHFD-fed rats. Finally, we show that the predominant conjugated BAs in humans protect against epithelial barrier disruption in vitro. Our study identifies a protective role for conjugated BAs in intestinal epithelial barrier function and suggests that rational manipulation of microbial BA metabolism could be leveraged to regulate gut barrier integrity.