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: Collective Dispersal Leads To Variance In Fitness And Maintains Offspring Size Variation Within Marine Populations; Variance in fitness is well known to influence the outcome of evolution but is rarely considered in the theory of marine reproductive strategies. In coastal environments, turbulent mesoscale eddies can collect larvae into packets, resulting in collective dispersal. Larvae in packets return to the coast or are lost offshore in groups, producing variance in fitness. Using a Markov process to calculate fixation probabilities for competing phenotypes, we examine the evolution of offspring size and spawning duration in species with benthic adults and pelagic offspring. The offspring size that provides mothers with the highest mean fitness also generates the greatest variance in fitness, but pairwise invasion plots show that bet-hedging strategies are not evolutionarily stable; maximizing expected fitness correctly predicts the unique evolutionarily stable strategy. Nonetheless, fixation can take a long time. We find that selection to increase spawning duration as a risk avoidance strategy to reduce the negative impacts of stochastic recruitment success can allow multiple offspring sizes to coexist in a population for extended periods. This has two important consequences for offspring size: (1) coexistence occurs over a broader range of sizes and is longer when spawning duration is longer because longer spawning durations reduce variation in fitness and increase the time to fixation, and (2) longer spawning durations can compensate for having a nonoptimal size and even allow less optimal sizes to reach fixation. Collective dispersal and longer spawning durations could effectively maintain offspring size variation even in the absence of good and bad years or locations. Empirical comparisons of offspring size would therefore not always reflect environment-specific differences in the optimal size., Keywords: environments, trade-off, adaptive dynamics, aggregated dispersal, bet hedging, chaotic genetic patchiness, cohesive dispersal, coral-reef fish, egg size, evolutionary ecology, kin aggregation, life-histories, reproductive success, reproductive variance, seed dispersal, turbulent dispersal, Publication Note: The publisher's version of record is available at https://doi.org/10.1086/695879

: Collective epithelial cell sheet adhesion and migration on polyelectrolyte multilayers with uniform and gradients of compliance.; Polyelectrolyte multilayers (PEMUs) are tunable thin films that could serve as coatings for biomedical implants. PEMUs built layer by layer with the polyanion poly(acrylic acid) (PAA) modified with a photosensitive 4-(2-hydroxyethoxy) benzophenone (PAABp) group and the polycation poly(allylamine hydrochloride) (PAH) are mechanically tunable by UV irradiation, which forms covalent bonds between the layers and increases PEMU stiffness. PAH-terminated PEMUs (PAH-PEMUs) that were uncrosslinked, UV-crosslinked to a uniform stiffness, or UV-crosslinked with an edge mask or through a neutral density optical gradient filter to form continuous compliance gradients were used to investigate how differences in PEMU stiffness affect the adhesion and migration of epithelial cell sheets from scales of the fish Poecilia sphenops (Black Molly) and Carassius auratus (Comet Goldfish). During the progressive collective cell migration, the edge cells (also known as 'leader' cells) in the sheets on softer uncrosslinked PEMUs and less crosslinked regions of the gradient formed more actin filaments and vinculin-containing adherens junctions and focal adhesions than formed in the sheet cells on stiffer PEMUs or glass. During sheet migration, the ratio of edge cell to internal cell (also known as 'follower' cells) motilities were greater on the softer PEMUs than on the stiffer PEMUs or glass, causing tension to develop across the sheet and periods of retraction, during which the edge cells lost adhesion to the substrate and regions of the sheet retracted toward the more adherent internal cell region. These retraction events were inhibited by the myosin II inhibitor Blebbistatin, which reduced the motility velocity ratios to those for sheets on the stiffer PEMUs. Blebbistatin also caused disassembly of actin filaments, reorganization of focal adhesions, increased cell spreading at the leading edge, as well as loss of edge cell-cell connections in epithelial cell sheets on all surfaces. Interestingly, cells throughout the interior region of the sheets on uncrosslinked PEMUs retained their actin and vinculin organization at adherens junctions after treatment with Blebbistatin. Like Blebbistatin, a Rho-kinase (ROCK) inhibitor, Y27632, promoted loss of cell-cell connections between edge cells, whereas a Rac1 inhibitor, NSC23766, primarily altered the lamellipodial protrusion in edge cells. Compliance gradient PAH-PEMUs promoted durotaxis of the cell sheets but not of individual keratocytes, demonstrating durotaxis, like plithotaxis, is an emergent property of cell sheet organization., Keywords: Collective cell migration, Durotaxis, Modulus gradient, Myosin II, Photocrosslinking, Poly(acrylic acid) (PAA), Poly(allylamine hydrochloride) (PAH), Polyelectrolyte multilayer (PEMU), Grant Number: R01 EB006158, Publication Note: This NIH-funded author manuscript originally appeared in PubMed Central at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4967014.

: Commentary; Keywords: cardiac troponin, dilated cardiomyopathy, disease, epigenetic gene regulation, heart, histone methylation, induced pluripotent stem cell, inherited cardiomyopathies, muscle, mutations, myosin, nucleus, state, stem-cells, tropomyosin, troponin T, Publication Note: The publisher’s version of record is available at http://www.dx.doi.org/10.3389/fphys.2016.00418

: Commentary; Keywords: Dilated cardiomyopathy, Epigenetic gene regulation, Heart, Histone methylation, Induced pluripotent stem cell, Nucleus, Troponin T, Publication Note: This NIH-funded author manuscript originally appeared in PubMed Central at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5033966.

: Comparative Genotype-phenotype Mapping Reveals Distinct Modes of Venom Expression Evolution in the Sympatric Eastern Diamondback Rattlesnake (Crotalus adamanteus) and Eastern Coral SSnake (Micrurus fulvius); Selection is predicted to drive diversification within species and lead to local adaptation, but understanding the mechanistic details underlying this process, and thus the genetic basis of adaptive evolution, requires the mapping of genotype to phenotype. Venom is complex and involves many genes, but the specialization of the venom-gland towards toxin production allows specific transcripts to be correlated with specific toxic proteins, establishing a direct link from genotype to phenotype. To determine the extent of expression variation and identify the processes driving patterns of phenotypic diversity, we constructed genotype-phenotype maps and compared range-wide toxin-protein expression variation for two species of snake with nearly identical ranges: the eastern diamondback rattlesnake (Crotalus adamanteus) and the eastern coral snake (Micrurus fulvius). We detected significant expression variation in C. adamanteus, identified the specific loci associated with population differentiation, and found that loci expressed at all levels contributed to this divergence. Contrary to expectations, we found no expression variation in M. fulvius, suggesting that M. fulvius populations are not locally adapted. Our results not only linked expression variation at specific loci to divergence in a polygenic, complex trait, but also have extensive conservation and biomedical implications. Crotalus adamanteus is currently a candidate for Federal listing under the Endangered Species Act, and the loss of any major population would result in the irrevocable loss of a unique venom phenotype. The lack of variation in M. fulvius has significant biomedical application because our data will assist in the development of effective antivenom for this species., Keywords: Genotype-phenotype map, gene expression, adaptation, snake venom, Note: The downloadable document is the authors' original manuscript version (AKA pre-print) of the article which was eventually accepted in the journal Genetics. For the final version of record go to http://www.genetics.org/content/199/1/165 ., Citation: "Contrasting Modes and Tempos of Venom Expression Evolution in Two Snake Species" Mark J. Margres, James J. McGivern, Margaret Seavy, Kenneth P. Wray, Jack Facente, and Darin R. Rokyta. GENETICS January 2015, 199:165-176 doi:10.1534/genetics.114.172437

: Comparative analysis of glucagonergic cells, glia, and the circumferential marginal zone in the reptilian retina.; Retinal progenitors in the circumferential marginal zone (CMZ) and Müller glia-derived progenitors have been well described for the eyes of fish, amphibians, and birds. However, there is no information regarding a CMZ and the nature of retinal glia in species phylogenetically bridging amphibians and birds. The purpose of this study was to examine the retinal glia and investigate whether a CMZ is present in the eyes of reptilian species. We used immunohistochemical analyses to study retinal glia, neurons that could influence CMZ progenitors, the retinal margin, and the nonpigmented epithelium of ciliary body of garter snakes, queen snakes, anole lizards, snapping turtles, and painted turtles. We compare our observations on reptile eyes to the CMZ and glia of fish, amphibians, and birds. In all species, Sox9, Pax6, and the glucocorticoid receptor are expressed by Müller glia and cells at the retinal margin. However, proliferating cells were found only in the CMZ of turtles and not in the eyes of anoles and snakes. Similar to eyes of chickens, the retinal margin in turtles contains accumulations of GLP1/glucagonergic neurites. We find that filamentous proteins, vimentin and GFAP, are expressed by Müller glia, but have different patterns of subcellular localization in the different species of reptiles. We provide evidence that the reptile retina may contain nonastrocytic inner retinal glial cells, similar to those described in the avian retina. We conclude that the retinal glia, glucagonergic neurons, and CMZ of turtles appear to be most similar to those of fish, amphibians, and birds., Keywords: AB_1143173, AB_2110656, AB_2155784, AB_2160651, AB_2195807, AB_2239761, AB_2314539, AB_291611, AB_528427, AB_528490, AB_528504, Glia, Glucagon, Progenitor, Retina, Grant Number: R01 EY022030, R01 EY022030-03, Publication Note: This NIH-funded author manuscript originally appeared in PubMed Central at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4659723.

: Competing scaffolding proteins determine capsid size during mobilization of pathogenicity islands.; pathogenicity islands (SaPIs), such as SaPI1, exploit specific helper bacteriophages, like 80α, for their high frequency mobilization, a process termed 'molecular piracy'. SaPI1 redirects the helper's assembly pathway to form small capsids that can only accommodate the smaller SaPI1 genome, but not a complete phage genome. SaPI1 encodes two proteins, CpmA and CpmB, that are responsible for this size redirection. We have determined the structures of the 80α and SaPI1 procapsids to near-atomic resolution by cryo-electron microscopy, and show that CpmB competes with the 80α scaffolding protein (SP) for a binding site on the capsid protein (CP), and works by altering the angle between capsomers. We probed these interactions genetically and identified second-site suppressors of lethal mutations in SP. Our structures show, for the first time, the detailed interactions between SP and CP in a bacteriophage, providing unique insights into macromolecular assembly processes., Keywords: S. aureus pathogenicity island 1 (SaPI1), Staphylococcus aureus, Bacteriophage 80alpha, Biophysics, Cryo-electron microscopy, Infectious disease, Microbiology, Structural biology, Three-dimensional reconstruction, Virus structure and assembly, Grant Number: R01 AI083255, S10 OD018142, S10 RR025080, Publication Note: This NIH-funded author manuscript originally appeared in PubMed Central at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5644958.

: Comprehensive nucleosome mapping of the human genome in cancer progression; Altered chromatin structure is a hallmark of cancer, and inappropriate regulation of chromatin structure may represent the origin of transformation. Important studies have mapped human nucleosome distributions genome wide, but the role of chromatin structure in cancer progression has not been addressed. We developed a MNase-Transcription Start Site Sequence Capture method (mTSS-seq) to map the nucleosome distribution at human transcription start sites genome-wide in primary human lung and colon adenocarcinoma tissue. Here, we confirm that nucleosome redistribution is an early, widespread event in lung (LAC) and colon (CRC) adenocarcinoma. These altered nucleosome architectures are consistent between LAC and CRC patient samples indicating that they may serve as important early adenocarcinoma markers. We demonstrate that the nucleosome alterations are driven by the underlying DNA sequence and potentiate transcription factor binding. We conclude that DNA-directed nucleosome redistributions are widespread early in cancer progression. We have proposed an entirely new hierarchical model for chromatin-mediated genome regulation., Keywords: cancer, chromatin, Chromosome Section, dna, flexibility, genes, lung adenocarcinoma, MNase, nucleosome, organization, resolution, sequence, somatic mutations, susceptibility, whole genome, Publication Note: The publisher’s version of record is available at https://doi.org/10.1101/021618

: Construction and Optimization of a Large Gene Coexpression Network in Maize Using RNA-Seq Data.; With the emergence of massively parallel sequencing, genomewide expression data production has reached an unprecedented level. This abundance of data has greatly facilitated maize research, but may not be amenable to traditional analysis techniques that were optimized for other data types. Using publicly available data, a gene coexpression network (GCN) can be constructed and used for gene function prediction, candidate gene selection, and improving understanding of regulatory pathways. Several GCN studies have been done in maize (), mostly using microarray datasets. To build an optimal GCN from plant materials RNA-Seq data, parameters for expression data normalization and network inference were evaluated. A comprehensive evaluation of these two parameters and a ranked aggregation strategy on network performance, using libraries from 1266 maize samples, were conducted. Three normalization methods and 10 inference methods, including six correlation and four mutual information methods, were tested. The three normalization methods had very similar performance. For network inference, correlation methods performed better than mutual information methods at some genes. Increasing sample size also had a positive effect on GCN. Aggregating single networks together resulted in improved performance compared to single networks., Publication Note: This NIH-funded author manuscript originally appeared in PubMed Central at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5580776.

: Consumption Of Benthic Cyanobacterial Mats On A Caribbean Coral Reef; Herbivory is an important process in the general structuring of coral reef benthic communities. However, evidence of its ability to control coral reef benthic cyanobacterial mats, which have recently proliferated on reefs worldwide, remains ambivalent. Here, we report that the French Angelfish (Pomacanthus paru), Striped Parrotfish (Scarus iseri), Rock Beauty (Holacanthus tricolor), Ocean Surgeonfish (Acanthurus bahianus), Blue Parrotfish (Scarus coeruleus), and Atlantic Blue Tang (Acanthurus coeruleus) consume benthic cyanobacterial mats on coral reefs in Bonaire, Netherlands. We documented the foraging patterns of P. paru and S. iseri, and found that benthic cyanobacterial mats comprised 36.7%+/- 5.8% and 15.0% +/- 1.53% (mean +/- standard error) of the total bites taken by P. paru and S. iseri respectively. This magnitude of consumption suggests that grazing by reef fishes may represent a potentially important, but previously undocumented, top-down control on benthic cyanobacterial mats on Caribbean reefs., Keywords: community, herbivory, black band disease, chemical defenses, global change, habitat use, lyngbya-majuscula, nitrogen-fixation, secondary metabolites, shallow, Publication Note: The publisher's version of record is available at https://doi.org/10.1038/s41598-019-49126-9

: Correction for Avey et al., "Discovery of a Coregulatory Interaction between Kaposi's Sarcoma-Associated Herpesvirus ORF45 and the Viral Protein Kinase ORF36".; Publication Note: This NIH-funded author manuscript originally appeared in PubMed Central at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5686716.

: Critical and direct involvement of the CD23 stalk region in IgE binding.; The low-affinity receptor for IgE, FcεRII (CD23), contributes to allergic inflammation through allergen presentation to T cells, regulation of IgE responses, and enhancement of transepithelial allergen migration. We sought to investigate the interaction between CD23, chimeric monoclonal human IgE, and the corresponding birch pollen allergen Bet v 1 at a molecular level. We expressed 4 CD23 variants. One variant comprised the full extracellular portion of CD23, including the stalk and head domain; 1 variant was identical with the first, except for an amino acid exchange in the stalk region abolishing the N-linked glycosylation site; and 2 variants represented the head domain, 1 complete and 1 truncated. The 4 CD23 variants were purified as monomeric and structurally folded proteins, as demonstrated by gel filtration and circular dichroism. By using a human IgE mAb, the corresponding allergen Bet v 1, and a panel of antibodies specific for peptides spanning the CD23 surface, both binding and inhibition assays and negative stain electron microscopy were performed. A hitherto unknown IgE-binding site was mapped on the stalk region of CD23, and the non-N-glycosylated monomeric version of CD23 was superior in IgE binding compared with glycosylated CD23. Furthermore, we demonstrated that a therapeutic anti-IgE antibody, omalizumab, which inhibits IgE binding to FcεRI, also inhibited IgE binding to CD23. Our results provide a new model for the CD23-IgE interaction. We show that the stalk region of CD23 is crucially involved in IgE binding and that the interaction can be blocked by the therapeutic anti-IgE antibody omalizumab., Keywords: B cell, CD23, IgE, Allergen, Allergy, Low-affinity IgE receptor, Grant Number: F 4605, Publication Note: This NIH-funded author manuscript originally appeared in PubMed Central at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5321597.

: DEAD-box Protein Rok1 Orchestrates 40S and 60S Ribosome Assembly by Promoting the Release of Rrp5 from Pre-40S Ribosomes to Allow for 60S Maturation.; DEAD-box proteins are ubiquitous regulators of RNA biology. While commonly dubbed "helicases," their activities also include duplex annealing, adenosine triphosphate (ATP)-dependent RNA binding, and RNA-protein complex remodeling. Rok1, an essential DEAD-box protein, and its cofactor Rrp5 are required for ribosome assembly. Here, we use in vivo and in vitro biochemical analyses to demonstrate that ATP-bound Rok1, but not adenosine diphosphate (ADP)-bound Rok1, stabilizes Rrp5 binding to 40S ribosomes. Interconversion between these two forms by ATP hydrolysis is required for release of Rrp5 from pre-40S ribosomes in vivo, thereby allowing Rrp5 to carry out its role in 60S subunit assembly. Furthermore, our data also strongly suggest that the previously described accumulation of snR30 upon Rok1 inactivation arises because Rrp5 release is blocked and implicate a previously undescribed interaction between Rrp5 and the DEAD-box protein Has1 in mediating snR30 accumulation when Rrp5 release from pre-40S subunits is blocked., Grant Number: P41 GM103311, R01 GM086451, Publication Note: This NIH-funded author manuscript originally appeared in PubMed Central at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4900678.

: DNA replication timing alterations identify common markers between distinct progeroid diseases.; Progeroid syndromes are rare genetic disorders that phenotypically resemble natural aging. Different causal mutations have been identified, but no molecular alterations have been identified that are in common to these diseases. DNA replication timing (RT) is a robust cell type-specific epigenetic feature highly conserved in the same cell types from different individuals but altered in disease. Here, we characterized DNA RT program alterations in Hutchinson-Gilford progeria syndrome (HGPS) and Rothmund-Thomson syndrome (RTS) patients compared with natural aging and cellular senescence. Our results identified a progeroid-specific RT signature that is common to cells from three HGPS and three RTS patients and distinguishes them from healthy individuals across a wide range of ages. Among the RT abnormalities, we identified the tumor protein p63 gene () as a gene marker for progeroid syndromes. By using the redifferentiation of four patient-derived induced pluripotent stem cells as a model for the onset of progeroid syndromes, we tracked the progression of RT abnormalities during development, revealing altered RT of the gene as an early event in disease progression of both HGPS and RTS. Moreover, the RT abnormalities in progeroid patients were associated with altered isoform expression of Our findings demonstrate the value of RT studies to identify biomarkers not detected by other methods, reveal abnormal RT as an early event in progeroid disease progression, and suggest gene regulation as a potential therapeutic target., Keywords: DNA replication timing, RT signatures, TP63, Progeroid diseases, Grant Number: P01 GM085354, R01 GM083337, Publication Note: This NIH-funded author manuscript originally appeared in PubMed Central at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5754778.

: Deletion of DXZ4 on the human inactive X chromosome alters higher-order genome architecture.; During interphase, the inactive X chromosome (Xi) is largely transcriptionally silent and adopts an unusual 3D configuration known as the "Barr body." Despite the importance of X chromosome inactivation, little is known about this 3D conformation. We recently showed that in humans the Xi chromosome exhibits three structural features, two of which are not shared by other chromosomes. First, like the chromosomes of many species, Xi forms compartments. Second, Xi is partitioned into two huge intervals, called "superdomains," such that pairs of loci in the same superdomain tend to colocalize. The boundary between the superdomains lies near DXZ4, a macrosatellite repeat whose Xi allele extensively binds the protein CCCTC-binding factor. Third, Xi exhibits extremely large loops, up to 77 megabases long, called "superloops." DXZ4 lies at the anchor of several superloops. Here, we combine 3D mapping, microscopy, and genome editing to study the structure of Xi, focusing on the role of DXZ4 We show that superloops and superdomains are conserved across eutherian mammals. By analyzing ligation events involving three or more loci, we demonstrate that DXZ4 and other superloop anchors tend to colocate simultaneously. Finally, we show that deleting DXZ4 on Xi leads to the disappearance of superdomains and superloops, changes in compartmentalization patterns, and changes in the distribution of chromatin marks. Thus, DXZ4 is essential for proper Xi packaging., Keywords: CTCF, Hi‐C, X chromosome inactivation, Genome engineering, Inactive X chromosome, Grant Number: U01 HL130010, U54 HG003067, DP2 OD008540, P50 HG006193, R01 GM073120, RM1 HG006193, Publication Note: This NIH-funded author manuscript originally appeared in PubMed Central at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4978254.

: Differential Regulation of Cyclin E by Yorkie-Scalloped Signaling in Organ Development.; Tissue integrity and homeostasis are accomplished through strict spatial and temporal regulation of cell growth and proliferation during development. Various signaling pathways have emerged as major growth regulators across metazoans; yet, how differential growth within a tissue is spatiotemporally coordinated remains largely unclear. Here, we report a role of a growth modulator Yorkie (), the homolog of Yes-associated protein (YAP), that differentially regulates its targets in wing imaginal discs; whereby Yki interacts with its transcriptional partner, Scalloped (), the homolog of the TEAD/TEF family transcription factor in mammals, to control an essential cell cycle regulator Cyclin E (CycE). Interestingly, when Yki was coexpressed with Fizzy-related (), a endocycle inducer and homolog of Cdh1 in mammals, surrounding hinge cells displayed larger nuclear size than distal pouch cells. The observed size difference is attributable to differential regulation of CycE, a target of Yki and Sd, the latter of which can directly bind to regulatory sequences, and is expressed only in the pouch region of the wing disc starting from the late second-instar larval stage. During earlier stages of larval development, when Sd expression was not detected in the wing disc, coexpression of Fzr and Yki did not cause size differences between cells along the proximal-distal axis of the disc. We show that ectopic CycE promoted cell proliferation and apoptosis, and inhibited transcriptional activity of Yki targets. These findings suggest that spatiotemporal expression of transcription factor Sd induces differential growth regulation by Yki during wing disc development, highlighting coordination between Yki and CycE to control growth and maintain homeostasis., Keywords: Yki Sd, Cell growth and proliferation, Differential regulation, Grant Number: R01 GM072562, Publication Note: This NIH-funded author manuscript originally appeared in PubMed Central at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5345706.

: Differential role of calpain-dependent protein cleavage in intermediate and long-term operant memory in Aplysia.; In addition to protein synthesis, protein degradation or protein cleavage may be necessary for intermediate (ITM) and long-term memory (LTM) to remove molecular constraints, facilitate persistent kinase activity and modulate synaptic plasticity. Calpains, a family of conserved calcium dependent cysteine proteases, modulate synaptic function through protein cleavage. We used the marine mollusk Aplysia californica to investigate the in vivo role of calpains during intermediate and long-term operant memory formation using the learning that food is inedible (LFI) paradigm. A single LFI training session, in which the animal associates a specific netted seaweed with the failure to swallow, generates short (30min), intermediate (4-6h) and long-term (24h) memory. Using the calpain inhibitors calpeptin and MDL-28170, we found that ITM requires calpain activity for induction and consolidation similar to the previously reported requirements for persistent protein kinase C activity in intermediate-term LFI memory. The induction of LTM also required calpain activity. In contrast to ITM, calpain activity was not necessary for the molecular consolidation of LTM. Surprisingly, six hours after LFI training we found that calpain activity was necessary for LTM, although this is a time at which neither persistent PKC activity nor protein synthesis is required for the maintenance of long-term LFI memory. These results demonstrate that calpains function in multiple roles in vivo during associative memory formation., Keywords: Aplysia, Associative memory, Calpain, Learning, Protein cleavage, Protein kinase M, Grant Number: R01 MH081012, R21 NS088835, Publication Note: This NIH-funded author manuscript originally appeared in PubMed Central at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6179366.

: Differential serotonergic modulation across the main and accessory olfactory bulbs.; There are serotonergic projections to both the main (MOB) and the accessory olfactory bulb (AOB). Current-clamp experiments demonstrate that serotonergic afferents are largely excitatory for mitral cells (MCs) in the MOB where 5-HT receptors mediate a direct excitatory action. Serotonergic afferents are predominately inhibitory for MCs in the AOB. There are two types of inhibition: indirect inhibition mediated through the 5-HT receptors on GABAergic interneurons and direct inhibition via the 5-HT receptors on MCs. Differential 5-HT neuromodulation of MCs across the MOB and AOB could contribute to select behaviours such as olfactory learning or aggression. Mitral cells (MCs) contained in the main (MOB) and accessory (AOB) olfactory bulb have distinct intrinsic membrane properties but the extent of neuromodulation across the two systems has not been widely explored. Herein, we investigated a widely distributed CNS modulator, serotonin (5-HT), for its ability to modulate the biophysical properties of MCs across the MOB and AOB, using an in vitro, brain slice approach in postnatal 15-30 day mice. In the MOB, 5-HT elicited three types of responses in 93% of 180 cells tested. Cells were either directly excited (70%), inhibited (10%) or showed a mixed response (13%)- first inhibition followed by excitation. In the AOB, 82% of 148 cells were inhibited with 18% of cells showing no response. Albeit located in parallel partitions of the olfactory system, 5-HT largely elicited MC excitation in the MOB while it evoked two different kinetic rates of MC inhibition in the AOB. Using a combination of pharmacological agents, we found that the MC excitatory responses in the MOB were mediated by 5-HT receptors through a direct activation. In comparison, 5-HT-evoked inhibitory responses in the AOB arose due to a polysynaptic, slow-onset inhibition attributed to 5-HT receptor activation exciting GABAergic interneurons. The second type of inhibition had a rapid onset as a result of direct inhibition mediated by the 5-HT class of receptors. The distinct serotonergic modulation of MCs between the MOB and AOB could provide a molecular basis for differential chemosensory behaviours driven by the brainstem raphe nuclei into these parallel systems., Keywords: 5-HT, Mitral cell, Olfaction, Olfactory bulb, Serotonin, Grant Number: R01 DC013080, Publication Note: This NIH-funded author manuscript originally appeared in PubMed Central at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5451723.

: Dinosaur incubation periods directly determined from growth-line counts in embryonic teeth show reptilian-grade development.; Birds stand out from other egg-laying amniotes by producing relatively small numbers of large eggs with very short incubation periods (average 11-85 d). This aspect promotes high survivorship by limiting exposure to predation and environmental perturbation, allows for larger more fit young, and facilitates rapid attainment of adult size. Birds are living dinosaurs; their rapid development has been considered to reflect the primitive dinosaurian condition. Here, nonavian dinosaurian incubation periods in both small and large ornithischian taxa are empirically determined through growth-line counts in embryonic teeth. Our results show unexpectedly slow incubation (2.8 and 5.8 mo) like those of outgroup reptiles. Developmental and physiological constraints would have rendered tooth formation and incubation inherently slow in other dinosaur lineages and basal birds. The capacity to determine incubation periods in extinct egg-laying amniotes has implications for dinosaurian embryology, life history strategies, and survivorship across the Cretaceous-Paleogene mass extinction event., Keywords: Dinosauria, Neornithes, Embryology, Extinction, Teeth, Publication Note: This NIH-funded author manuscript originally appeared in PubMed Central at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5255600.

: Direct and indirect effects of the El Niño Southern Oscillation on development and survival of young of a tropical passerine; The El Niño Southern Oscillation (ENSO) is a global phenomenon that influences climate variation and, in turn, the ecological processes affecting the abundance and distribution of populations across taxa. For example, the ENSO can profoundly influence the development and survival of pelagic species, but the extent to which the ENSO affects offspring of terrestrial species is less well known. We used piecewise structural equation modeling to investigate the direct and indirect relationship between the ENSO and offspring development and survival in a terrestrial tropical passerine, the lance-tailed manakin (Chiroxiphia lanceolata). The Oceanic Niño Index (ONI), a measure of the ENSO, was negatively related to individual growth rate, maximum number of lesion developed by nestlings, and hatching day-of-year; which in turn mediated indirect effects on fledging success and recruitment. Further the ONI was a better predictor of nestling development compared to local temperature and rainfall. Our study establishes a link between the ENSO and the development and survival of young of a terrestrial species and underscores the need to better understand how offspring cope with global climate variation., Lance-tailed manakin, Chiroxiphia lanceolata, Oceanic Niño Index, climate, El Niño, La Niña, Growth rate, Piecewise structural equation model, Data relevant to this project were collected with support from National Science Foundation (NSF) Grants 0843334 and 1453408 (CAREER) awarded to E.H.D., the Florida State University, and the Max Planck Institute for Ornithology

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