Parents exposed to warming produce offspring lower in weight and condition

The parental environment can alter offspring phenotypes via the transfer of non‐genetic information. Parental effects may be viewed as an extension of (within‐generation) phenotypic plasticity. Smaller size, poorer physical condition, and skewed sex ratios are common responses of organisms to global warming, yet whether parental effects alleviate, exacerbate, or have no impact on these responses has not been widely tested. Further, the relative non‐genetic influence of mothers and fathers and ontogenetic timing of parental exposure to warming on offspring phenotypes is poorly understood. Here, we tested how maternal, paternal, and biparental exposure of a coral reef fish (Acanthochromis polyacanthus) to elevated temperature (+1.5°C) at different ontogenetic stages (development vs reproduction) influences offspring length, weight, condition, and sex. Fish were reared across two generations in present‐day and projected ocean warming in a full factorial design. As expected, offspring of parents exposed to present‐day control temperature that were reared in warmer water were shorter than their siblings reared in control temperature; however, within‐generation plasticity allowed maintenance of weight, resulting in a higher body condition. Parental exposure to warming, irrespective of ontogenetic timing and sex, resulted in decreased weight and condition in all offspring rearing temperatures. By contrast, offspring sex ratios were not strongly influenced by their rearing temperature or that of their parents. Together, our results reveal that phenotypic plasticity may help coral reef fishes maintain performance in a warm ocean within a generation, but could exacerbate the negative effects of warming between generations, regardless of when mothers and fathers are exposed to warming. Alternatively, the multigenerational impact on offspring weight and condition may be a necessary cost to adapt metabolism to increasing temperatures. This research highlights the importance of examining phenotypic plasticity within and between generations across a range of traits to accurately predict how organisms will respond to climate change.     

Synthesis of β-Peptide Standards for Use in Model Prebiotic Reactions

A one-pot method was developed for the preparation of a series of β-alanine standards of moderate size (2 to ≥12 residues) for studies concerning the prebiotic origins of peptides. The one-pot synthesis involved two sequential reactions: (1) dry-down self-condensation of β-alanine methyl ester, yielding β-alanine peptide methyl ester oligomers, and (2) subsequent hydrolysis of β-alanine peptide methyl ester oligomers, producing a series of β-alanine peptide standards. These standards were then spiked into a model prebiotic product mixture to confirm by HPLC the formation of β-alanine peptides under plausible reaction conditions. The simplicity of this approach suggests it can be used to prepare a variety of β-peptide standards for investigating differences between α- and β-peptides in the context of prebiotic chemistry.     

Genetic background influences survival of infections with Salmonella enterica serovar Typhimurium in the Collaborative Cross

Salmonella infections typically cause self-limiting gastroenteritis, but in some individuals these bacteria can spread systemically and cause disseminated disease. Salmonella Typhimurium (STm), which causes severe systemic disease in most inbred mice, has been used as a model for disseminated disease. To screen for new infection phenotypes across a range of host genetics, we orally infected 32 Collaborative Cross (CC) mouse strains with STm and monitored their disease progression for seven days by telemetry. Our data revealed a broad range of phenotypes across CC strains in many parameters including survival, bacterial colonization, tissue damage, complete blood counts (CBC), and serum cytokines. Eighteen CC strains survived to day 7, while fourteen susceptible strains succumbed to infection before day 7. Several CC strains had sex differences in survival and colonization. Surviving strains had lower pre-infection baseline temperatures and were less active during their daily active period. Core body temperature disruptions were detected earlier after STm infection than activity disruptions, making temperature a better detector of illness. All CC strains had STm in spleen and liver, but susceptible strains were more highly colonized. Tissue damage was weakly negatively correlated to survival. We identified loci associated with survival on Chromosomes (Chr) 1, 2, 4, 7. Polymorphisms in Ncf2 and Slc11a1, known to reduce survival in mice after STm infections, are located in the Chr 1 interval, and the Chr 7 association overlaps with a previously identified QTL peak called Ses2. We identified two new genetic regions on Chr 2 and 4 associated with susceptibility to STm infection. Our data reveal the diversity of responses to STm infection across a range of host genetics and identified new candidate regions for survival of STm infection.     

Actin exposure upon tissue injury is a targetable wound site-specific protein marker

BackgroundIdentification of wound-specific markers would represent an important step toward damaged tissue detection and targeted delivery of biologically important materials to injured sites. Such delivery could minimize the amount of therapeutic materials that must be administered and limit potential collateral damage on nearby normal tissues. Yet, biological markers that are specific for injured tissue sites remain elusive.MethodsIn this study, we have developed an immunohistological approach for identification of protein epitopes specifically exposed in wounded tissue sites.ResultsUsing ex-vivo tissue samples in combination with fluorescently-labeled antibodies we show that actin, an intracellular cytoskeletal protein, is specifically exposed upon injury. The targetability of actin in injured sites has been demonstrated in vivo through the specific delivery of anti-actin conjugated particles to the wounded tissue in a lethal rat model of grade IV liver injury.ConclusionsThese results illustrate that identification of injury-specific protein markers and their targetability for specific delivery is feasible.General significanceIdentification of wound-specific targets has important medical applications as it could enable specific delivery of various products, such as expression vectors, therapeutic drugs, hemostatic materials, tissue healing, or scar prevention agents, to internal sites of penetrating or surgical wounds regardless of origin, geometry or location.     

Prenatal data impacts common bottlenose dolphin (Tursiops truncatus) growth parameters estimated by length‐at‐age curves

Compilation of marine mammal demographic data is central to management efforts. However, marine mammal length‐at‐age growth curves demonstrate limitations. Physiological growth parameters of terrestrial mammals are typically estimated using curvilinear models fit to size‐at‐age data along a time series from conception to senescence. The difficulty of collecting and aging prenatal cetaceans is addressed here, and growth parameters of common bottlenose dolphins (Tursiops truncatus) along coastal Texas were estimated using length‐at‐age information from a broader scope of age classes, including late‐term fetuses. A Gompertz growth curve fit to pre‐ and postnatal data underestimated size parameters, but demonstrated similar growth rate constants (k) to an exclusively postnatal model. However, when growth parameters were broken out, the absolute growth rate (G) and rate of growth decay (g) decreased (0.44 from 0.27 and 0.55 from 0.39, respectively), which underscores the importance of reporting k in its expanded form (G/g). Although the Gompertz fits most age classes well, it cannot explain growth in all age classes. We argue that a novel sigmoidal model would be more useful for inference.     

The design and discovery of novel amide CCR5 antagonists

The synthesis of a range of novel amine-containing structures and their primary potency as inhibitors of HIV-1 fusion via blocking of the CCR5 receptor is described. The development of the medicinal chemistry strategy and SAR’s which led to the identification of the piperidine amide compounds 33 and 36 as excellent leads for further evaluation is described, along with key physicochemical data which highlighted their lead potential.