Antimicrobial susceptibility and characterization of Salmonella isolates from processed bison carcasses

Seventeen Salmonella enterica serovar Hadar isolates recovered from bison were found to possess a range of virulence genes and resistance to tetracycline, gentamicin, sulfamethoxazole, and streptomycin simultaneously. A 1-kb class 1 integron containing the aadA1 gene was identified in all isolates. Pulsed-field gel electrophoresis found that all isolates were closely related, indicating the possibility of cross-contamination during processing.     

A Review of Polymeric Refabrication Techniques to Modify Polymer Properties for Biomedical and Drug Delivery Applications

Polymers are extensively used in the pharmaceutical and medical field because of their unique and phenomenal properties that they display. They are capable of demonstrating drug delivery properties that are smart and novel, such properties that are not achievable by employing the conventional excipients. Appropriately, polymeric refabrication remains at the forefront of process technology development in an endeavor to produce more useful pharmaceutical and medical products because of the multitudes of smart properties that can be attained through the alteration of polymers. Small alterations to a polymer by either addition, subtraction, self-reaction, or cross reaction with other entities have the capability of generating polymers with properties that are at the level to enable the creation of novel pharmaceutical and medical products. Properties such as stimuli-responsiveness, site targeting, and chronotherapeutics are no longer figures of imaginations but have become a reality through utilizing processes of polymer refabrication. This article has sought to review the different techniques that have been employed in polymeric refabrication to produce superior products in the pharmaceutical and medical disciplines. Techniques such as grafting, blending, interpenetrating polymers networks, and synthesis of polymer complexes will be viewed from a pharmaceutical and medical perspective along with their synthetic process required to attain these products. In addition to this, each process will be evaluated according to its salient features, impeding features, and the role they play in improving current medical devices and procedures.     

Aging reduces center-surround antagonism in visual motion processing

Discriminating the direction of motion of a low-contrast pattern becomes easier with increasing stimulus area. However, increasing the size of a high-contrast pattern makes it more difficult for observers to discriminate motion. This surprising result, termed spatial suppression, is thought to be mediated by a form of center-surround suppression found throughout the visual pathway. Here, we examine the counterintuitive hypothesis that aging alters such center-surround interactions in ways that improve performance in some tasks. We found that older observers required briefer stimulus durations than did younger observers to extract information about stimulus direction in conditions using large, high-contrast patterns. We suggest that this age-related improvement in motion discrimination may be linked to reduced GABAergic functioning in the senescent brain, which reduces center-surround suppression in motion-selective neurons.     

The COP9 signalosome is vital for timely repair of DNA double-strand breaks

The DNA damage response is vigorously activated by DNA double-strand breaks (DSBs). The chief mobilizer of the DSB response is the ATM protein kinase. We discovered that the COP9 signalosome (CSN) is a crucial player in the DSB response and an ATM target. CSN is a protein complex that regulates the activity of cullin ring ubiquitin ligase (CRL) complexes by removing the ubiquitin-like protein, NEDD8, from their cullin scaffold. We find that the CSN is physically recruited to DSB sites in a neddylation-dependent manner, and is required for timely repair of DSBs, affecting the balance between the two major DSB repair pathways—nonhomologous end-joining and homologous recombination repair (HRR). The CSN is essential for the processivity of deep end-resection—the initial step in HRR. Cullin 4a (CUL4A) is recruited to DSB sites in a CSN- and neddylation-dependent manner, suggesting that CSN partners with CRL4 in this pathway. Furthermore, we found that ATM-mediated phosphorylation of CSN subunit 3 on S410 is critical for proper DSB repair, and that loss of this phosphorylation site alone is sufficient to cause a DDR deficiency phenotype in the mouse. This novel branch of the DSB response thus significantly affects genome stability.     

Estrogen receptor beta selective ligands: discovery and SAR of novel heterocyclic ligands

A series of ligands with varying heterocyclic cores and substituents that display a range of selectivity’s (up to >100x) for ER-β over ER- are reported.     

Comparison of percutaneous vs oral infection of hamsters with the hookworm Ancylostoma ceylanicum: Parasite development,pathology and primary immune response

BackgroundHundreds of millions of people in poor countries continue to suffer from disease caused by bloodfeeding hookworms. While mice and rats are not reliably permissive hosts for any human hookworm species, adult Golden Syrian hamsters are fully permissive for the human and animal pathogen Ancylostoma ceylanicum. Similar to humans, hamsters may be infected with A. ceylanicum third-stage larvae orally or percutaneously. Oral infection typically leads to consistent worm yields in hamsters but may not accurately reflect the clinical and immunological manifestations of human infection resulting from skin penetration.Methodology/Principal findingsIn this study we compared host responses following percutaneous infection to those utilizing an established oral infection protocol. Infected hamsters exhibited a dose-dependent pathology, with 1000 percutaneous larvae (L3) causing anemia and adult worm recovery comparable to that of 50 orally administered L3. A delayed arrival and maturity of worms in the intestine was observed, as was variation in measured cellular immune responses. A long-term study found that the decline in blood hemoglobin was more gradual and did not reach levels as low, with the nadir of disease coming later in percutaneously infected hamsters. Both groups exhibited moderate growth delay, an effect that was more persistent in the percutaneously infected group. Fecal egg output also peaked later and at lower levels in the percutaneously infected animals. In contrast to orally infected hamsters, antibody titers to larval antigens continued to increase throughout the course of the experiment in the percutaneous group.Conclusions/SignificanceThese results demonstrate that the route of infection with A. ceylanicum impacts disease pathogenesis, as well as humoral and cellular immune responses in an experimental setting. These data further validate the utility of the Golden Syrian hamster as a model of both oral and percutaneous infection with human hookworms.     

Optimizing return‐on‐effort for coral nursery and outplanting practices to aid restoration of the Great Barrier Reef

Coral nursery and outplanting practices have grown in popularity worldwide for targeted restoration of degraded “high value” reef sites, and recovery of threatened taxa. Success of these practices is commonly gauged from coral propagule growth and survival, which fundamentally determines the return‐on‐effort (RRE) critical to the cost‐effectiveness and viability of restoration programs. In many cases, RRE has been optimized from past successes and failures, which therefore presents a major challenge for locations such as the Great Barrier Reef (GBR) where no local history of restoration exists to guide best practice. In establishing the first multi‐taxa coral nursery on the GBR (Opal Reef, February 2018), we constructed a novel scoring criterion from concurrent measurements of growth and survivorship to guide our relative RRE, including nursery propagule numbers (stock density). We initially retrieved RRE scores from a database of global restoration efforts to date (n = 246; 52 studies) to evaluate whether and how success commonly varied among coral taxa. We then retrieved RRE scores for Opal Reef using initial growth and survivorship data for six key coral taxa, to demonstrate that RRE scores were high for all taxa predominantly via high survivorship over winter. Repeated RRE scoring in summer is therefore needed to capture the full dynamic range of success where seasonal factors regulating growth versus survivorship differ. We discuss how RRE scoring can be easily adopted across restoration practices globally to standardize and benchmark success, but also as a tool to aid decision‐making in optimizing future propagation (and outplanting) efforts.     

Cofeeding intra‐ and interspecific transmission of an emerging insect‐borne rickettsial pathogen

Cat fleas (Ctenocephalides felis) are known as the primary vector and reservoir of Rickettsia felis, the causative agent of flea‐borne spotted fever; however, field surveys regularly report molecular detection of this infectious agent from other blood‐feeding arthropods. The presence of R. felis in additional arthropods may be the result of chance consumption of an infectious bloodmeal, but isolation of viable rickettsiae circulating in the blood of suspected vertebrate reservoirs has not been demonstrated. Successful transmission of pathogens between actively blood‐feeding arthropods in the absence of a disseminated vertebrate infection has been verified, referred to as cofeeding transmission. Therefore, the principal route from systemically infected vertebrates to uninfected arthropods may not be applicable to the R. felis transmission cycle. Here, we show both intra‐ and interspecific transmission of R. felis between cofeeding arthropods on a vertebrate host. Analyses revealed that infected cat fleas transmitted R. felis to naïve cat fleas and rat fleas (Xenopsylla cheopis) via fleabite on a nonrickettsemic vertebrate host. Also, cat fleas infected by cofeeding were infectious to newly emerged uninfected cat fleas in an artificial system. Furthermore, we utilized a stochastic model to demonstrate that cofeeding is sufficient to explain the enzootic spread of R. felis amongst populations of the biological vector. Our results implicate cat fleas in the spread of R. felis amongst different vectors, and the demonstration of cofeeding transmission of R. felis through a vertebrate host represents a novel transmission paradigm for insect‐borne Rickettsia and furthers our understanding of this emerging rickettsiosis.