Strong, Recent Selective Sweeps Reshape Genetic Diversity in Freshwater Bivalve \u3ci\u3eMegalonaias nervosa\u3c/i\u3e

Freshwater Unionid bivalves have recently faced ecological upheaval through pollution, barriers to dispersal, harvesting, and changes in fish–host prevalence. Currently, over 70% of species in North America are threatened, endangered or extinct. To characterize the genetic response to recent selective pressures, we collected population genetic data for one successful bivalve species, Megalonaias nervosa. We identify megabase-sized regions that are nearly monomorphic across the population, signals of strong, recent selection reshaping diversity across 73 Mb total. These signatures of selection are greater than is commonly seen in population genetic models. We observe 102 duplicate genes with high dN/dS on terminal branches among regions with sweeps, suggesting that gene duplication is a causative mechanism of recent adaptation in M. nervosa. Genes in sweeps reflect functional classes important for Unionid survival, including anticoagulation genes important for fish host parasitization, detox genes, mitochondria management, and shell formation. We identify sweeps in regions with no known functional impacts, suggesting mechanisms of adaptation that deserve greater attention in future work on species survival. In contrast, polymorphic transposable elements (TEs) appear to be detrimental and underrepresented among regions with sweeps. TE site frequency spectra are skewed toward singleton variants, and TEs among regions with sweeps are present at low frequency. Our work suggests that duplicate genes are an essential source of genetic novelty that has helped this species succeed in environments where others have struggled. These results suggest that gene duplications deserve greater attention in non-model population genomics, especially in species that have recently faced sudden environmental challenges

Strong, recent selective sweeps reshape genetic diversity in freshwater bivalve Megalonaias nervosa

Freshwater Unionid bivalves have recently faced ecological upheaval through pollution, barriers to dispersal, human harvesting, and changes in fish-host prevalence. Currently, over 70% of species are threatened, endangered or extinct. To characterize the genetic response to these recent selective pressures, we collected population genetic data for one successful bivalve species, Megalonaias nervosa. We identify megabase sized regions that are nearly monomorphic across the population, a signal of strong, recent selection reshaping genetic diversity. These signatures of selection encompass a total of 73Mb, greater response to selection than is commonly seen in population genetic models. We observe 102 duplicate genes with high dN/dS on terminal branches among regions with sweeps, suggesting that gene duplication is a causative mechanism of recent adaptation in M. nervosa. Genes in sweeps reflect functional classes known to be important for Unionid survival, including anticoagulation genes important for fish host parasitization, detox genes, mitochondria management, and shell formation. We identify selective sweeps in regions with no known functional impacts, suggesting mechanisms of adaptation that deserve greater attention in future work on species survival. In contrast, polymorphic transposable element insertions appear to be detrimental and underrepresented among regions with sweeps. TE site frequency spectra are skewed toward singleton variants, and TEs among regions with sweeps are present only at low frequency. Our work suggests that duplicate genes are an essential source of genetic novelty that has helped this successful species succeed in environments where others have struggled. These results suggest that gene duplications deserve greater attention in non-model population genomics, especially in species that have recently faced sudden environmental challenges.Comment: 6 figures, 4 supplementary tables, 31 pages tota

A Conditionally Fluorescent Peptide Reporter of Secondary Structure Modulation

Proteins containing intrinsic disorder often form secondary structure upon interaction with a binding partner. Modulating such structures presents an approach for manipulating the resultant functional outcomes. Translational repressor protein 4E‐BP1 is an example of an intrinsically disordered protein that forms an α‐helix upon binding to its protein ligand, eIF4E. Current biophysical methods for analyzing binding‐induced structural changes are low‐throughput, require large amounts of sample, or are extremely sensitive to signal interference by the ligand itself. Herein, we describe the discovery and development of a conditionally fluorescent 4E‐BP1 peptide that reports structural changes of its helix in high‐throughput format. This reporter peptide is based on conditional quenching of fluorescein by thioamides. In this case, fluorescence signal increases as the peptide becomes more ordered. Conversely, destabilization of the α‐helix results in decreased fluorescence signal. The low concentration and low volume of peptide required make this approach amenable for high‐throughput screening to discover ligands that alter peptide secondary structure.PET lights up peptide dynamics: Photoinduced electron transfer (PET) quenching of fluorescence by thioamides presents an elegant method for monitoring changes in macromolecular conformation. Here we apply this approach to monitor peptide dynamics in a 384‐well plate format. Using a fluorescein‐conjugated, 4E‐BP1‐based peptide containing an embedded thioamide, we probe its transition from disorder to a short α‐helix.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146852/1/cbic201800377.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146852/2/cbic201800377-sup-0001-misc_information.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146852/3/cbic201800377_am.pd

Motherhood, Moral Authority and the Charismatic Matriarch in the Aftermath of Lethal Violence

Images of maternal suffering are an evocative and powerful means of communication in a world where the private grief of victims has increasingly become subject to commodification and public consumption. This article looks at the influence of bereaved mothers as symbols of respect, peace and dignity in the aftermath of violence, and as a result their persuasive presence in family activism. Drawing upon two case studies, this article explores the importance of victims’ stories in public life and, in particular, the presence of the charismatic matriarch in creating communities of solidarity, raising awareness of harms that have previously gone unheard and prompting policy change. It considers the ‘canonical’ story of the mother in public life and concludes by arguing that more attention should be paid to victims’ stories and their influence on policy-making, politics and eventually in becoming public grievances

Prodigious polyphyly in Pleuroceridae (Gastropoda: Cerithioidea)

Phylogenomic studies with hundreds or thousands of loci are rare for most invertebrate groups, including freshwater gastropods. This can prevent understanding of phylogeny, which hinders many areas of research. Pleuroceridae is a family of freshwater snails that is highly imperiled and plays an essential role in the ecology of many freshwater systems of the eastern United States. However, the evolutionary history of the family is not understood, and the systematics of the family has not been revised in a modern framework. Pleurocerids display a variety of egg-deposition behaviors and shell shapes, making the family an ideal system for studying evolution of invertebrate life history and morphology. However, past mitochondrial-based phylogenetic analyses have failed to produce meaningful phylogenetic hypotheses, preventing conclusions about pleurocerid systematics and evolution. Here, we generated a novel anchored hybrid enrichment probe set with phylogenetic utility for Pleuroceridae. We sampled pleurocerids from across their range to test the probe set and generated a backbone phylogeny. Our analyses uncovered striking levels of polyphyly among currently accepted genera. Numerous species were also polyphyletic, indicative of unrecognized diversity. Phylogenetic patterns also revealed considerable convergence of shell morphologies. In contrast, anatomical and life history features appeared to be much less homoplastic. Despite generic paraphyly, high support for most major clades and phylogenetic cohesiveness of non-shell characters indicate utility of the AHE probe set for studying pleurocerid evolution

Strength in diversity: enhancing learning in vocationally-orientated, master's level courses

Postgraduate education in geography, especially at the Master’s level, is undergoing significant changes in the developed world. There is an expansion of vocationally-oriented degree programmes, increasing recruitment of international students, integration of work place skills, and the engagement of non-traditional postgraduate students as departments respond to policies for a more ‘inclusive’ higher education. This paper sets the context by outlining some programmatic changes in selected countries (Australia, the UK, and the USA). We briefly reflect on how postgraduate ‘bars’ or ‘levels’ are defined and explore in detail what ‘diversity’ or ‘heterogeneity’ means in these new postgraduate settings. The paper then explores some examples of practice drawn from our own experiences, whilst recognising that relevance will vary in other contexts. Finally we consider how diversity can be harnessed as a strength that has potential to enhance taught elements of contemporary postgraduate education in and beyond the discipline

Comparative Analyses of Transcriptional Profiles in Mouse Organs Using a Pneumonic Plague Model after Infection with Wild-Type Yersinia pestis CO92 and Its Braun Lipoprotein Mutant

We employed Murine GeneChips to delineate the global transcriptional profiles of the livers, lungs, and spleens in a mouse pneumonic plague infection model with wild-type (WT) Y. pestis CO92 and its Braun lipoprotein (Δlpp) mutant with reduced virulence. These organs showed differential transcriptional responses to infection with WT Y. pestis, but the overall host functional processes affected were similar across all three tissues. Gene expression alterations were found in inflammation, cytokine signaling, and apoptotic cell death-associated genes. Comparison of WT and Δlpp mutant-infected mice indicated significant overlap in lipopolysaccharide- (LPS-) associated gene expression, but the absence of Lpp perturbed host cell signaling at critical regulatory junctions resulting in altered immune response and possibly host cell apoptosis. We generated a putative signaling pathway including major inflammatory components that could account for the synergistic action of LPS and Lpp and provided the mechanistic basis of attenuation caused by deletion of the lpp gene from Y. pestis in a mouse model of pneumonic plague

Carbamazepine alone and in combination with doxycycline attenuates isoproterenol-induced cardiac hypertrophy

β-adrenergic signaling is involved in the development of cardiac hypertrophy (CH), justifying the use of β-blockers as a therapy to minimize and postpone the consequences of this disease. Evidence suggests that adenylate cyclase, a downstream effector of the β-adrenergic pathway, might be a therapeutic target. We examined the effects of the anti-epileptic drug carbamazepine (CBZ), an inhibitor of adenylate cyclase. In a murine cardiac hypertrophy model, carbamazepine significantly attenuates isoproteronol (ISO)-induced cardiac hypertrophy. Carbamazepine also has an effect in transverse aortic banding induced cardiac hypertrophy (TAB) (P=0.07). When carbamazepine was given in combination with the antibiotic doxycycline (DOX), which inhibits matrix metalloproteinases (MMPs), therapeutic outcome measured by heart weight-to-body weight and heart weight-to-tibia length ratios was improved compared to either drug alone. Additionally, the combination therapy resulted in an increase in the survival rate over a 56-day period compared to that of untreated mice with cardiac hypertrophy or either drug used alone. Moreover, in support of a role for carbamaze -pine as a β-adrenergic antagonist via cAMP inhibition, a lower heart rate and a lower level of the activated phosphorylated form of the cAMP Response Element-Binding (CREB) were observed in heart extracts from mice treated with carbamazepine. Gene expression analysis identified 19 genes whose expression is significantly altered in treated animals and might be responsible for the added benefit provided by the combination therapy. These results suggest that carbamazepine acts as a β-adrenergic antagonist. Carbamazepine and doxycycline are approved by the US Food and Drug Administration (FDA) as drugs that might complement medications for cardiac hypertrophy or serve as an alternative therapy to traditional β-blockers. Furthermore, these agents reproducibly impact the expression of genes that may serve as additional therapeutic targets in the management of cardiac hypertrophy