Trait compensation in marine gastropods: shell shape, avoidance behavior, and susceptibility to predation

Many organisms have evolved morphological and behavioral traits that reduce their susceptibility to predation. However, few studies have explicitly investigated the relationships between defensive traits and susceptibility. Here we demonstrate a negative correlation between morphological defenses and behavioral avoidance across several species of marine gastropod that is linked to vulnerability to crab predation. Snails that had relatively taller shell spires (high aspect ratio) showed greater responsiveness when exposed to predation cues than did species with disc-like shells (low aspect ratio). Our results suggest that the snail species most vulnerable to predation compensated by showing the highest levels of behavioral avoidance, and hence may be at a disadvantage in competition with less vulnerable species. This has important implications because the behavioral response of herbivorous gastropods to predation cues may play a central role in structuring rocky intertidal communities through trait-mediated indirect effects

The norovirus NS3 protein is a dynamic lipid- and microtubule-associated protein involved in viral RNA replication

Norovirus (NoV) infections are a significant health burden to society, yet the lack of reliable tissue culture systems has hampered the development of appropriate antiviral therapies. Here we show that the NoV NS3 protein, derived from murine NoV (MNV), is intimately associated with the MNV replication complex and the viral replication intermediate double-stranded RNA (dsRNA). We observed that when expressed individually, MNV NS3 and NS3 encoded by human Norwalk virus (NV) induced the formation of distinct vesicle-like structures that did not colocalize with any particular protein markers to cellular organelles but localized to cellular membranes, in particular those with a high cholesterol content. Both proteins also showed some degree of colocalization with the cytoskeleton marker β-tubulin. Although the distribution of MNV and NV NS3s were similar, NV NS3 displayed a higher level of colocalization with the Golgi apparatus and the endoplasmic reticulum (ER). However, we observed that although both proteins colocalized in membranes counterstained with filipin, an indicator of cholesterol content, MNV NS3 displayed a greater association with flotillin and stomatin, proteins known to associate with sphingolipid- and cholesterol-rich microdomains. Utilizing time-lapse epifluorescence microscopy, we observed that the membrane-derived vesicular structures induced by MNV NS3 were highly motile and dynamic in nature, and their movement was dependent on intact microtubules. These results begin to interrogate the functions of NoV proteins during virus replication and highlight the conserved properties of the NoV NS3 proteins among the seven Norovirus genogroups

Controlled variation of monomer sequence-distribution in the synthesis of aromatic poly(ether ketone)s

The effects of varying the alkali metal cation in the high-temperature nucleophilic synthesis of a semi-crystalline, aromatic poly(ether ketone) have been systematically investigated, and striking variations in the sequence-distributions and thermal characteristics of the resulting polymers were found. Polycondensation of 4,4'-dihydroxybenzophenone with 1,3-bis(4-fluorobenzoyl)benzene in diphenylsulfone as solvent, in the presence of an alkali metal carbonate M2CO3 (M= Li, Na, K, or Rb) as base, affords a range of different polymers that vary in the distribution pattern of 2-ring and 3-ring monomer units along the chain. Lithium carbonate gives an essentially alternating and highly crystalline polymer, but the degree of sequence-randomisation increases progressively as the alkali metal series is descended, with rubidium carbonate giving a fully random and non-thermally-crystallisable polymer. Randomisation during polycondensation is shown to result from reversible cleavage of the ether linkages in the polymer by fluoride ions, and an isolated sample of alternating-sequence polymer is thus converted to a fully randomised material on heating with rubidium fluoride

Gene expression in Leishmania is regulated predominantly by gene dosage

ABSTRACT Leishmania tropica, a unicellular eukaryotic parasite present in North and East Africa, the Middle East, and the Indian subcontinent, has been linked to large outbreaks of cutaneous leishmaniasis in displaced populations in Iraq, Jordan, and Syria. Here, we report the genome sequence of this pathogen and 7,863 identified protein-coding genes, and we show that the majority of clinical isolates possess high levels of allelic diversity, genetic admixture, heterozygosity, and extensive aneuploidy. By utilizing paired genome-wide high-throughput DNA sequencing (DNA-seq) with RNA-seq, we found that gene dosage, at the level of individual genes or chromosomal “somy” (a general term covering disomy, trisomy, tetrasomy, etc.), accounted for greater than 85% of total gene expression variation in genes with a 2-fold or greater change in expression. High gene copy number variation (CNV) among membrane-bound transporters, a class of proteins previously implicated in drug resistance, was found for the most highly differentially expressed genes. Our results suggest that gene dosage is an adaptive trait that confers phenotypic plasticity among natural Leishmania populations by rapid down- or upregulation of transporter proteins to limit the effects of environmental stresses, such as drug selection. IMPORTANCE Leishmania is a genus of unicellular eukaryotic parasites that is responsible for a spectrum of human diseases that range from cutaneous leishmaniasis (CL) and mucocutaneous leishmaniasis (MCL) to life-threatening visceral leishmaniasis (VL). Developmental and strain-specific gene expression is largely thought to be due to mRNA message stability or posttranscriptional regulatory networks for this species, whose genome is organized into polycistronic gene clusters in the absence of promoter-mediated regulation of transcription initiation of nuclear genes. Genetic hybridization has been demonstrated to yield dramatic structural genomic variation, but whether such changes in gene dosage impact gene expression has not been formally investigated. Here we show that the predominant mechanism determining transcript abundance differences (>85%) in Leishmania tropica is that of gene dosage at the level of individual genes or chromosomal somy

Transnational Governance as Contested Institution-Building: China, Merchants, and Contract Rules in the Cotton Trade

We are in an era of uncertainty over whose rules will govern global economic integration. With the growing market share of Chinese firms and the power of the Chinese state it is unclear if Western firms will continue to dominate transnational governance. Exploring these dynamics through a study of contract rules in the global cotton trade, this article conceptualizes commodity chain governance as a contested process of institution-building. To this end, the global commodity chain/global value chain (GCC/GVC) framework must be revised to better account for the broader institutional context of commodity chain governance, institutional variation across space, and strategic action in the construction of legitimate governance arrangements. I provide a more dynamic model of GCC governance that stresses how strategic action, existing institutions, and dominant discourses intersect as firms and states compete for institutional power within a commodity chain. This advances our understandings of how commodity chain governance emerges and changes over time

Oxidation behavior and microstructural evolution of Ti-6Al-4V and Ti-6Al-4V-1B sheet

A direct comparison between the oxidation behavior of Ti-6Al-4V and Ti-6Al-4V + 1B has been conducted to elucidate whether the addition of boron to Ti-6Al-4V impacts the oxidation behavior. Industrially prepared sheet of Ti-6Al-4V and Ti-6Al-4V + 1B were oxidized at temperatures between 650 and 950 °C for holding times of 25 and 50 h. Weight-gain measurements and characterization of surface and near-surface microstructures showed that the addition of 1 wt% B increased the material’s oxidation resistance. Additionally, the ingress of oxygen tends to decrease the solubility of other alloying species in α-Ti and leads to the formation of a distinctive and atypical microstructure with a distinct morphology

A survey of current and past Pediatric Infectious Diseases fellows regarding training

<p>Abstract</p> <p>Background</p> <p>The objectives of this study were to characterize the satisfaction of Pediatric Infectious Diseases fellows with their training and to understand how opinions about training have changed over time.</p> <p>Methods</p> <p>Anonymous survey studies were conducted with questions designed to include areas related to the 6 ACGME core competencies. Surveys for current fellows were distributed by fellowship directors, while surveys for graduates were mailed to all individuals with Pediatric Infectious Diseases certification.</p> <p>Results</p> <p>Response rates for current fellows and graduates were 50% and 52%, respectively. Most fellows (98%) and graduates (92%) perceived their overall training favorably. Training in most clinical care areas was rated favorably, however both groups perceived relative deficiencies in several areas. Current fellows rated their training in other competency areas (e.g., systems-based practice, research, and ethics) more favorably when compared to past graduates. Recent graduates perceived their training more favorably in many of these areas compared to past graduates.</p> <p>Conclusions</p> <p>Pediatric Infectious Diseases fellowship training is well regarded by the majority of current and past trainees. Views of current fellows reflect improved satisfaction with training in a variety of competency areas. Persistent deficiencies in clinical training likely reflect active barriers to education. Additional study is warranted to validate perceived deficiencies and to establish consensus on the importance of these areas to infectious diseases training.</p

HSD3B1 genotype identifies glucocorticoid responsiveness in severe asthma

Asthma resistance to glucocorticoid treatment is a major health problem with unclear etiology. Glucocorticoids inhibit adrenal androgen production. However, androgens have potential benefits in asthma. HSD3B1 encodes for 3β-hydroxysteroid dehydrogenase-1 (3β-HSD1), which catalyzes peripheral conversion from adrenal dehydroepiandrosterone (DHEA) to potent androgens and has a germline missense-encoding polymorphism. The adrenal restrictive HSD3B1(1245A) allele limits conversion, whereas the adrenal permissive HSD3B1(1245C) allele increases DHEA metabolism to potent androgens. In the Severe Asthma Research Program (SARP) III cohort, we determined the association between DHEA-sulfate and percentage predicted forced expiratory volume in 1 s (FEV1PP). HSD3B1(1245) genotypes were assessed, and association between adrenal restrictive and adrenal permissive alleles and FEV1PP in patients with (GC) and without (noGC) daily oral glucocorticoid treatment was determined (n = 318). Validation was performed in a second cohort (SARP I&II; n = 184). DHEA-sulfate is associated with FEV1PP and is suppressed with GC treatment. GC patients homozygous for the adrenal restrictive genotype have lower FEV1PP compared with noGC patients (54.3% vs. 75.1%; P < 0.001). In patients with the homozygous adrenal permissive genotype, there was no FEV1PP difference in GC vs. noGC patients (73.4% vs. 78.9%; P = 0.39). Results were independently confirmed: FEV1PP for homozygous adrenal restrictive genotype in GC vs. noGC is 49.8 vs. 63.4 (P < 0.001), and for homozygous adrenal permissive genotype, it is 66.7 vs. 67.7 (P = 0.92). The adrenal restrictive HSD3B1(1245) genotype is associated with GC resistance. This effect appears to be driven by GC suppression of 3β-HSD1 substrate. Our results suggest opportunities for prediction of GC resistance and pharmacologic intervention

Cerebellar Ataxia With Anti-DNER Antibodies: Outcomes and Immunologic Features

BACKGROUND AND OBJECTIVES: There is no report on the long-term outcomes of ataxia with antibodies against Delta and Notch-like epidermal growth factor-related (DNER). We aimed to describe the clinical-immunologic features and long-term outcomes of patients with anti-DNER antibodies. METHODS: Patients tested positive for anti-DNER antibodies between 2000 and 2020 were identified retrospectively. In those with available samples, immunoglobulin G (IgG) subclass analysis, longitudinal cerebellum volumetry, human leukocyte antigen isotyping, and CSF proteomic analysis were performed. Rodent brain membrane fractionation and organotypic cerebellar slices were used to study DNER cell-surface expression and human IgG binding to the Purkinje cell surface. RESULTS: Twenty-eight patients were included (median age, 52 years, range 19-81): 23 of 28 (82.1%) were male and 23 of 28 (82.1%) had a hematologic malignancy. Most patients (27/28, 96.4%) had cerebellar ataxia; 16 of 28 (57.1%) had noncerebellar symptoms (cognitive impairment, neuropathy, and/or seizures), and 27 of 28 (96.4%) became moderately to severely disabled. Half of the patients (50%) improved, and 32.1% (9/28) had no or slight disability at the last visit (median, 26 months; range, 3-238). Good outcome significantly associated with younger age, milder clinical presentations, and less decrease of cerebellar gray matter volumes at follow-up. No human leukocyte antigen association was identified. Inflammation-related proteins were overexpressed in the patients' CSF. In the rodent brain, DNER was enriched in plasma membrane fractions. Patients' anti-DNER antibodies were predominantly IgG1/3 and bound live Purkinje cells in vitro. DISCUSSION: DNER ataxia is a treatable condition in which nearly a third of patients have a favorable outcome. DNER antibodies bind to the surface of Purkinje cells and are therefore potentially pathogenic, supporting the use of B-cell-targeting treatments