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Introduction: Defence Medical Services personnel regularly deploy overseas to deliver training activities as part of defence engagement (DE) to positively influence partners and others. There remains scope for medical planners to enhance our understanding of how to optimally use medical staff and assets for DE. We aimed to develop a tool to improve planning for DE activities delivering first aid training., Methods: We used nominal group technique to conduct a focus group with UK experts in planning first aid training DE activities to identify and prioritise important planning considerations within a conceptual framework based on the Defence Lines of Development. We validated and refined this framework with international experts from partner nation militaries to help strengthen the final planning tool., Results: We developed a detailed tool covering training curriculum and logistical and infrastructure requirements to deliver safe and effective DE training activities. First aid training engagement priorities include being tailored to the training audience and in harmony with the national or military healthcare services of that country. Messaging around the women, peace and security agenda should be integrated into training packages at conception to be effective., Conclusions: We propose a planning tool to aid in designing first aid training that considers the necessary components to support meaningful education and effective engagement in support of UK's strategic goals. We welcome the use of and feedback on this tool and its impact to those planning first aid training activities as part of DE operations., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Polyploidy has been suggested to negatively impact environmental stress tolerance, resulting in increased susceptibility to extreme climate events. In this study, we compared the genomic and physiological response of diploid (2n) and triploid (3n) Pacific oysters (Crassostrea gigas) to conditions present during an atmospheric heatwave that impacted the Pacific Northwestern region of the United States in the summer of 2021. Climate stressors were applied either singly (single stressor; elevated seawater temperature, 30°C) or in succession (multiple stressor; elevated seawater temperature followed by aerial emersion at 44°C), replicating conditions present within the intertidal over a tidal cycle during the event. Oyster mortality rate was elevated within stress treatments with respect to the control and was significantly higher in triploids than diploids following multiple stress exposure (36.4% vs. 14.8%). Triploids within the multiple stressor treatment exhibited signs of energetic limitation, including metabolic depression, a significant reduction in ctenidium Na + /K + ATPase activity, and the dysregulated expression of genes associated with stress response, innate immunity, glucose metabolism, and mitochondrial function. Functional enrichment analysis of ploidy-specific gene sets identified that biological processes associated with metabolism, stress tolerance, and immune function were overrepresented within triploids across stress treatments. Our results suggest that triploidy impacts the transcriptional regulation of key processes that underly the stress response of Pacific oysters, resulting in downstream shifts in physiological tolerance limits that may increase susceptibility to extreme climate events that present multiple environmental stressors. The impact of chromosome set manipulation on the climate resilience of marine organisms has important implications for domestic food security within future climate scenarios, especially as triploidy induction becomes an increasingly popular tool to elicit reproductive control across a wide range of species used within marine aquaculture., (© 2023 John Wiley & Sons Ltd.)

Objective: The aim in this study was to quantify the number, nature, and severity of injuries sustained by male and female high school students who took part in a running training program that culminated in the completion of a half or full marathon., Design: This study is a retrospective clinical audit., Methods: Injury reports from high school students (grades 9-12) who participated in a half or full marathon 30-week progressive training program comprising four training days per week (three running days and one cross-training day) were reviewed. The number of runners completing a marathon, together with the number, nature, severity of injuries, and treatment types, as reported to the program physiotherapist, were the main outcome measures., Results: Program completion was 96% ( n = 448/469). Of all participants, 186 (39.6%) were injured, with 14 withdrawing from the program due to injury. For those who completed a marathon, 172 (38%) reported 205 musculoskeletal injuries (age of injured runners: 16.3 ± 1.1 years; 88 girls (51.2%) and 84 boys (48.8%)). More than half ( n = 113, 55.1%) of the reported injuries were soft tissue injuries. Most injuries were localized to the lower leg ( n = 88, 42.9%) and were of a minor nature ( n = 181, 90%), requiring only 1-2 treatments., Conclusions: There was a low number of relatively minor injuries for high school participants taking part in a graduated and supervised marathon training program. The injury definition was conservative (i.e., any attendance to physiotherapist) and the relative severity of injuries was minor (i.e., requiring 1-2 treatment sessions). Overall, these results do not support a need to restrict high school students from taking part in marathon running, though continued emphasis on graduated program development and close supervision of young participants is recommended.

Lake Hillier is a hypersaline lake known for its distinctive bright pink color. The cause of this phenomenon in other hypersaline sites has been attributed to halophiles, Dunaliella, and Salinibacter, however, a systematic analysis of the microbial communities, their functional features, and the prevalence of pigment-producing-metabolisms has not been previously studied. Through metagenomic sequencing and culture-based approaches, our results evidence that Lake Hillier is composed of a diverse set of microorganisms including archaea, bacteria, algae, and viruses. Our data indicate that the microbiome in Lake Hillier is composed of multiple pigment-producer microbes, including Dunaliella, Salinibacter, Halobacillus, Psychroflexus, Halorubrum, many of which are cataloged as polyextremophiles. Additionally, we estimated the diversity of metabolic pathways in the lake and determined that many of these are related to pigment production. We reconstructed complete or partial genomes for 21 discrete bacteria (N = 14) and archaea (N = 7), only 2 of which could be taxonomically annotated to previously observed species. Our findings provide the first metagenomic study to decipher the source of the pink color of Australia's Lake Hillier. The study of this pink hypersaline environment is evidence of a microbial consortium of pigment producers, a repertoire of polyextremophiles, a core microbiome and potentially novel species., (© 2022. The Author(s).)

Pseudomonas syringae is a genetically diverse bacterial species complex responsible for numerous agronomically important crop diseases. Individual P. syringae isolates are assigned pathovar designations based on their host of isolation and the associated disease symptoms, and these pathovar designations are often assumed to reflect host specificity although this assumption has rarely been rigorously tested. Here we developed a rapid seed infection assay to measure the virulence of 121 diverse P. syringae isolates on common bean (Phaseolus vulgaris). This collection includes P. syringae phylogroup 2 (PG2) bean isolates (pathovar syringae) that cause bacterial spot disease and P. syringae phylogroup 3 (PG3) bean isolates (pathovar phaseolicola) that cause the more serious halo blight disease. We found that bean isolates in general were significantly more virulent on bean than non-bean isolates and observed no significant virulence difference between the PG2 and PG3 bean isolates. However, when we compared virulence within PGs we found that PG3 bean isolates were significantly more virulent than PG3 non-bean isolates, while there was no significant difference in virulence between PG2 bean and non-bean isolates. These results indicate that PG3 strains have a higher level of host specificity than PG2 strains. We then used gradient boosting machine learning to predict each strain's virulence on bean based on whole genome k-mers, type III secreted effector k-mers, and the presence/absence of type III effectors and phytotoxins. Our model performed best using whole genome data and was able to predict virulence with high accuracy (mean absolute error = 0.05). Finally, we functionally validated the model by predicting virulence for 16 strains and found that 15 (94%) had virulence levels within the bounds of estimated predictions. This study strengthens the hypothesis that P. syringae PG2 strains have evolved a different lifestyle than other P. syringae strains as reflected in their lower level of host specificity. It also acts as a proof-of-principle to demonstrate the power of machine learning for predicting host specific adaptation., Competing Interests: The authors have declared that no competing interests exist.

Background: A valid and reliable measure of infant neurodevelopment is needed in Suriname, South America. The Bayley Scales of Infant and Toddler Development, 3rd edition (BSID-III), was created for evaluation of United States infants and toddlers and subsequently validated for use in Dutch speaking infants of the Netherlands (BSID-III-NL). Given that Suriname was a previous Dutch colony and Dutch remains the national language of Suriname, this study sought to evaluate the psychometric properties of the BSID-III-NL in Suriname., Aims: Given that the cultural context differs between Suriname, the United States, and the Netherlands, the aims of this study were to determine if any cultural adaptations of the BSID-III-NL were needed for Surinamese infants and to evaluate its psychometric properties., Methods: Two hundred and ninety-nine infants between the ages of 10 to 26 months were assessed in three geographic regions of Suriname between May 2018 and July 2019. Minor adaptations to the BSID-III-NL imagery were made based on the input of Surinamese pediatricians and neuropsychologists who were also involved in the administration of the BSID-III-NL in Suriname. Raw scores were collected for the cognitive, communicative, and motor subscales of the BSID-III-NL. Factor structure was evaluated with exploratory factor analysis and cluster analysis, and reliability of internal consistency was assessed using Cronbach's alpha coefficient for each subscale., Results: Content validity was endorsed by pediatricians and neuropsychologists in Suriname who participated in the administration of the BSID-III-NL. Construct validity was demonstrated through agreement of items from cluster analysis where at least 81.56% of all variability was explained by clustering with correct or incorrect responses and mean raw scores in subscales increased with age group. Cronbach's alpha coefficient was above 0.77 for all subscales., Conclusions: This internationally validated developmental measure was found to be valid and reliable in assessing neurodevelopment of infants in Suriname., (Copyright © 2021 Elsevier B.V. All rights reserved.)

In seasonally breeding vertebrates, hormones coordinate changes in nervous system structure and function to facilitate reproductive readiness and success. Steroid hormones often exert their effects indirectly via regulation of neuromodulators, which in turn can coordinate the modulation of sensory input with appropriate motor output. Female plainfin midshipman fish (Porichthys notatus) undergo increased peripheral auditory sensitivity in time for the summer breeding season, improving their ability to detect mates, which is regulated by steroid hormones. Reproductive females also show differences in catecholaminergic innervation of auditory circuitry compared with winter, non-reproductive females as measured by tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholaminergic synthesis. Importantly, catecholaminergic input to the inner ear from a dopaminergic-specific forebrain nucleus is decreased in the summer and dopamine inhibits the sensitivity of the inner ear, suggesting that gonadal steroids may alter auditory sensitivity by regulating dopamine innervation. In this study, we gonadectomized non-reproductive females, implanted them with estradiol (E2) or testosterone (T), and measured TH immunoreactive (TH-ir) fibers in auditory nuclei where catecholaminergic innervation was previously shown to be seasonally plastic. We found that treatment with T, but not E2, reduced TH-ir innervation in the auditory hindbrain. T-treatment also reduced TH-ir fibers in the forebrain dopaminergic cell group that projects to the inner ear, and likely to the auditory hindbrain. Higher T plasma in the treatment group was correlated with reduced-ir TH terminals in the inner ear. These T-treatment induced changes in TH-ir fibers mimic the seasonal downregulation of dopamine in the midshipman inner ear and provide evidence that steroid hormone regulation of peripheral auditory sensitivity is mediated, in part, by dopamine., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology. All rights reserved. For permissions please email: journals.permissions@oup.com.)

Pseudomonas is a highly diverse genus that includes species that cause disease in both plants and animals. Recently, pathogenic pseudomonads from the Pseudomonas syringae and Pseudomonas fluorescens species complexes have caused significant outbreaks in several agronomically important crops in Turkey, including tomato, citrus, artichoke and melon. We characterized 169 pathogenic Pseudomonas strains associated with recent outbreaks in Turkey via multilocus sequence analysis and whole-genome sequencing, then used comparative and evolutionary genomics to characterize putative virulence mechanisms. Most of the isolates are closely related to other plant pathogens distributed among the primary phylogroups of P. syringae , although there are significant numbers of P. fluorescens isolates, which is a species better known as a rhizosphere-inhabiting plant-growth promoter. We found that all 39 citrus blast pathogens cluster in P. syringae phylogroup 2, although strains isolated from the same host do not cluster monophyletically, with lemon, mandarin orange and sweet orange isolates all being intermixed throughout the phylogroup. In contrast, 20 tomato pith pathogens are found in two independent lineages: one in the P. syringae secondary phylogroups, and the other from the P. fluorescens species complex. These divergent pith necrosis strains lack characteristic virulence factors like the canonical tripartite type III secretion system, large effector repertoires and the ability to synthesize multiple bacterial phytotoxins, suggesting they have alternative molecular mechanisms to cause disease. These findings highlight the complex nature of host specificity among plant pathogenic pseudomonads.

Meaningful engagement between biopharmaceutical companies and patient communities has increasingly become an important part of the therapeutic-development process, as such engagement improves the understanding of the multifaceted challenges and unmet needs that communities experience and provides an opportunity to inform the approach to the development of new therapies and services. Presented here are learnings from a community-advisor program designed to engage families of patients with Duchenne muscular dystrophy (DMD) in a manner that enabled caregivers to make valuable contributions to the therapeutic-development process and to the DMD community. Parents of children with DMD, representing the broader DMD community, were identified in partnership with patient-advocacy organizations and invited to participate in a community-advisor meeting with members of Wave Life Sciences. The community-advisor meeting was designed to provide participants with an opportunity to share their personal experiences with DMD, to help to inform the therapeutic-development process, and to identify potential solutions for addressing unmet needs. Three community-advisor meetings were held with a total of 30 parents, representing 36 children with DMD. Key themes that emerged from the advisors' discussion included the importance of the community's emotional and mental support, the inconsistencies in DMD care, the increased challenges and disparities faced by underserved communities, and the need for more comprehensive, holistic approaches to the treatment and management of DMD. The advisors viewed the meetings as an opportunity to share their voices with a biopharmaceutical company, coupled with the advantage of meeting other families living with similar challenges. Most of the advisors stated that this was their first advisor meeting. This community-focused approach empowered participants to voice their needs and perspectives, to brainstorm potential solutions for addressing those needs, and to initiate and foster connections in ways that had a considerable impact on one another and on therapeutic-development programs at Wave Life Sciences., Competing Interests: Disclosures This study was funded by Wave Life Sciences Ltd. J. Smith and K. Damm are employees of Wave Life Sciences. G. Hover and J. Chien are employees of Imbue Partners LLC, which was contracted by Wave Life Sciences to support the research described in this article. The authors have indicated that they have no other conflicts of interest with regard to the content of this article., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Modeling contaminant sorption data using a linear model is very common; however, the rationale for whether the y-intercept should be constrained or not remains a subject of debate. This article justifies constraining the y-intercept in the linear model to zero. By doing so, one imposes consistency on the system of linear equations, allowing for direct comparison of the sorption coefficients., (© 2020 Published by Elsevier Ltd.)

Background: Enhanced Recovery After Surgery (ERAS) focuses on optimizing each element on a treatment pathway and encouraging the patient to actively engage in his or her recovery and rehabilitation. It requires collaboration across a multidisciplinary team and has been successful in improving patient outcomes, length of stay (LOS), and costs for a wide range of surgical procedures, including musculoskeletal surgeries such as total hip and total knee replacement., Purpose: To examine the application of ERAS concepts to total shoulder replacement (TSR) surgery., Methods: Hospital Episode Statistics (HES) in England on LOS for TSR surgery were examined, and a review of literature on the use of ERAS concepts in TSR was undertaken., Results: Analysis of HES data suggested scope for improvement in reducing LOS. A review of the literature found some evidence of the use of ERAS concepts, particularly in multimodal pain management., Conclusions: Future research is now required for ERAS procedure-specific components for TSR surgery.

Steelhead Trout (Oncorhynchus mykiss) display a varied life-history, including precocious male maturation at age-1 or age-2. In wild fish, precocious male maturation represents an important component of a diverse life-history portfolio. In hatchery programs, however, it is undesirable if rearing practices increase rates of early male maturation and reduce numbers of anadromous male adults. Our study aimed to develop endocrine and molecular markers for identifying males at early stages of maturation in the spring (prior to smolt release) and evaluated the potential use of these markers for quantifying early male maturation rates at a hatchery scale. In a laboratory study, Skookumchuck winter-run Steelhead Trout were reared at a high growth rate in order to increase the occurrence of precocious male maturation. Fish were lethally sub-sampled in February, prior to the time of smolt release; in May, at the time of smolt release; and in September, when 1+ age maturing males that would spawn the following spring were clearly identifiable based solely on gonadosomatic index (GSI). In February and May samples, we measured GSI, plasma 11-ketotestosterone (11KT), mRNAs for pituitary follicle stimulating hormone (fshb) and luteinizing hormone (lhb) beta subunits, and analyzed stage of spermatogenesis by testis histology. Additionally, in May, we measured testis anti-Müllerian hormone (amh) and insulin-like growth factor 3 (igf3) mRNA. Our primary goal was to evaluate the aforementioned maturation indices for their efficacy in forecasting the proportion of fish initiating early male maturation in the spring (approximately 1 year prior to spermiation), compared to the proportion that actually matured. Combining measures of GSI, plasma 11KT, and pituitary fshb and lhb mRNA expression provided a useful, but conservative, estimate of the proportion of males initiating maturation in the spring (21%) compared to the proportion that were ultimately destined to mature (37%) the following spring. These results suggest that maturation may be less synchronous than previously appreciated and some males may have initiated maturation after our census in May., (Published by Elsevier Inc.)

Gram-negative bacterial pathogens inject type III secreted effectors (T3SEs) directly into host cells to promote pathogen fitness by manipulating host cellular processes. Despite their crucial role in promoting virulence, relatively few T3SEs have well-characterized enzymatic activities or host targets. This is in part due to functional redundancy within pathogen T3SE repertoires as well as the promiscuity of individual T3SEs that can have multiple host targets. To overcome these challenges, we generated and characterized a collection of yeast strains stably expressing 75 T3SE constructs from the plant pathogen Pseudomonas syringae This collection is devised to facilitate heterologous genetic screens in yeast, a non-host organism, to identify T3SEs that target conserved eukaryotic processes. Among 75 T3SEs tested, we identified 16 that inhibited yeast growth on rich media and eight that inhibited growth on stress-inducing media. We utilized Pathogenic Genetic Array (PGA) screens to identify potential host targets of P. syringae T3SEs. We focused on the acetyltransferase, HopZ1a, which interacts with plant tubulin and alters microtubule networks. To uncover putative HopZ1a host targets, we identified yeast genes with genetic interaction profiles most similar ( i.e. , congruent) to the PGA profile of HopZ1a and performed a functional enrichment analysis of these HopZ1a-congruent genes. We compared the congruence analyses above to previously described HopZ physical interaction datasets and identified kinesins as potential HopZ1a targets. Finally, we demonstrated that HopZ1a can target kinesins by acetylating the plant kinesins HINKEL and MKRP1, illustrating the utility of our T3SE-expressing yeast library to characterize T3SE functions., (Copyright © 2019 Lee et al.)

Although high upfront costs for the high value of gene therapy have resulted in concerns about sufficient reimbursement to allow patient access to these therapies, the significant benefits of gene therapies will not be realized unless patients have access to them. Stakeholders are discussing these issues, and the payment models being developed for the newly approved gene therapies provide an early indication of the flexibility that will be needed from treatment manufacturers, payers, and policy makers to optimize patient access. Maximizing patient access to effective gene therapies is one integral part of the overall mission of the American Society of Gene and Cell Therapy, along with maximizing the quality of therapies and minimizing their costs., (Copyright © 2018 The American Society of Gene and Cell Therapy. All rights reserved.)

While the goal of most conservation hatchery programs is to produce fish that are genetically and phenotypically indistinguishable from the wild stocks they aim to restore, there is considerable evidence that salmon and steelhead reared in hatcheries differ from wild fish in phenotypic traits related to fitness. Some evidence suggests that these phenotypic differences have a genetic basis ( e.g. , domestication selection) but another likely mechanism that remains largely unexplored is that differences between hatchery and wild populations arise as a result of environmentally-induced heritable epigenetic change. As a first step toward understanding the potential contribution of these two possible mechanisms, we describe genetic and epigenetic variation in hatchery and natural-origin adult steelhead, Oncorhynchus mykiss , from the Methow River, WA. Our main objectives were to determine if hatchery and natural-origin fish could be distinguished genetically and whether differences in epigenetic programming (DNA methylation) in somatic and germ cells could be detected between the two groups. Genetic analysis of 72 fish using 936 SNPs generated by Restriction Site Associated DNA Sequencing (RAD-Seq) did not reveal differentiation between hatchery and natural-origin fish at a population level. We performed Reduced Representation Bisulfite Sequencing (RRBS) on a subset of 10 hatchery and 10 natural-origin fish and report the first genome-wide characterization of somatic (red blood cells (RBCs)) and germ line (sperm) derived DNA methylomes in a salmonid, from which we identified considerable tissue-specific methylation. We identified 85 differentially methylated regions (DMRs) in RBCs and 108 DMRs in sperm of steelhead reared for their first year in a hatchery environment compared to those reared in the wild. This work provides support that epigenetic mechanisms may serve as a link between hatchery rearing and adult phenotype in steelhead; furthermore, DMRs identified in germ cells (sperm) highlight the potential for these changes to be passed on to future generations., (Copyright © 2018 Gavery et al.)

Calcium-triggered neurotransmission underlies most communication in the nervous system. Yet, despite the conserved and essential nature of this process, the molecular underpinnings of calcium-triggered neurotransmission have been difficult to study directly and our understanding to this date remains incomplete. Here we frame more recent efforts to understand this process with a historical perspective of the study of neurotransmitter release at the neuromuscular junction. We focus on the role of calcium channel distribution and organization relative to synaptic vesicles, as well as the nature of the calcium sensors that trigger release. Importantly, we provide a framework for understanding how the function of neurotransmitter release sites, or active zones, contributes to the function of the synapse as a whole.

Rationale: The extent of the genetic relatedness among Pseudomonas aeruginosa isolates and its impact on clinical outcomes in the cystic fibrosis (CF) population is poorly understood., Objectives: The objectives of this study were to determine the prevalence of clonal P. aeruginosa infection in Canada and to associate P. aeruginosa genotypes with clinical outcomes., Methods: This was an observational study of adult and pediatric patients with CF across Canada. Isolates were typed using multilocus sequence typing. A clone was defined as sharing at least six of seven alleles. Genotyping results were associated with clinical outcomes, including forced expiratory volume in 1 second, body mass index, rate of pulmonary exacerbation, and death/transplant., Results: A total of 1,537 P. aeruginosa isolates were genotyped to 403 unique sequence types (STs) in 402 individuals with CF. Although 39% of STs were shared, most were shared only among a small number of subjects, and the majority (79%) of the genetic diversity in P. aeruginosa isolates was observed between patients. There were no significant differences in clinical outcomes according to genotype. However, patients with a dynamic, changing ST infection pattern had both a steeper decline in forced expiratory volume in 1 second (-2.9% predicted change/yr, 95% confidence interval [CI] = -3.8 to -1.9 compared with 0.4, 95% CI = -0.3 to 1.0; P < 0.001) and body mass index (-1.0 percentile change/yr, 95% CI = -1.6 to -0.3 compared with -0.1, 95% CI = -0.7 to 0.5; P = 0.047) than those with a stable infection with the same ST., Conclusions: There was no widespread sharing of dominant clones in our CF population, and the majority of the genetic diversity in P. aeruginosa was observed between patients. Changing genotypes over time within an individual was associated with worse clinical outcomes.

Objective: We describe a detailed solution for maintaining high-capacity, data-intensive network flows (eg, 10, 40, 100 Gbps+) in a scientific, medical context while still adhering to security and privacy laws and regulations., Materials and Methods: High-end networking, packet-filter firewalls, network intrusion-detection systems., Results: We describe a "Medical Science DMZ" concept as an option for secure, high-volume transport of large, sensitive datasets between research institutions over national research networks, and give 3 detailed descriptions of implemented Medical Science DMZs., Discussion: The exponentially increasing amounts of "omics" data, high-quality imaging, and other rapidly growing clinical datasets have resulted in the rise of biomedical research "Big Data." The storage, analysis, and network resources required to process these data and integrate them into patient diagnoses and treatments have grown to scales that strain the capabilities of academic health centers. Some data are not generated locally and cannot be sustained locally, and shared data repositories such as those provided by the National Library of Medicine, the National Cancer Institute, and international partners such as the European Bioinformatics Institute are rapidly growing. The ability to store and compute using these data must therefore be addressed by a combination of local, national, and industry resources that exchange large datasets. Maintaining data-intensive flows that comply with the Health Insurance Portability and Accountability Act (HIPAA) and other regulations presents a new challenge for biomedical research. We describe a strategy that marries performance and security by borrowing from and redefining the concept of a Science DMZ, a framework that is used in physical sciences and engineering research to manage high-capacity data flows., Conclusion: By implementing a Medical Science DMZ architecture, biomedical researchers can leverage the scale provided by high-performance computer and cloud storage facilities and national high-speed research networks while preserving privacy and meeting regulatory requirements., (© The Author 2017. Published by Oxford University Press on behalf of the American Medical Informatics Association.)

Sablefish (Anoplopoma fimbria) is a marine groundfish that supports valuable fisheries in the North Pacific Ocean and holds promise for marine aquaculture. Limited information is available, however, about its reproductive biology. This study aimed to characterize the complete reproductive cycle, including seasonal changes in gonadal development (macroscopic and histological), plasma sex steroid levels (17β-estradiol -E2-, and 11-ketotestosterone -11KT-), gonadosomatic and hepatosomatic indices (GSI, and HSI), and condition factor (K) of female and male sablefish captured off the Washington coast. Adult fish (209 females, 159 males) were caught by longline monthly from August 2012 to August 2013. Early signs of recruitment of ovarian follicles into secondary growth, indicated by oocytes containing small yolk granules and cortical alveoli, were first observed in March. Oogenesis progressed during spring and summer, and fully vitellogenic follicles were first observed in July. Vitellogenic growth was correlated with increases in plasma E2, GSI, HSI and K. Periovulatory females, indicated by fully-grown oocytes with migrating germinal vesicles and hydrated oocytes, were found from November to February. At this stage, plasma E2 and GSI reached maximal levels. In males, proliferating cysts containing spermatocytes were first observed in April. Testicular development proceeded during spring and summer, a period during which all types of male germ cells were found. The first clusters of spermatozoa appeared in July, concomitant with a 5.2-fold increase in GSI. Spermiating males were observed from November to April; at this time, spermatids were absent or greatly reduced, and testis lobules were filled with spermatozoa. The highest levels of plasma 11KT were found in males at this stage. Postspawning ovaries and testes, and basal steroids levels were found in fish captured from February to April. These results suggest that sablefish in coastal Washington initiate their reproductive cycle in March/April and spawn primarily in January/February.

A brief exposure of skin to a low-power, non-tissue damaging laser light has been demonstrated to augment immune responses to intradermal vaccination. Both preclinical and clinical studies show that this approach is simple, effective, safe and well tolerated compared to standard chemical or biological adjuvants. Until now, these laser exposures have been performed using a diode-pumped solid-state laser (DPSSL) devices, which are expensive and require labor-intensive maintenance and special training. Development of an inexpensive, easy-to-use and small device would form an important step in translating this technology toward clinical application. Here we report that we have established a handheld, near-infrared (NIR) laser device using semiconductor diodes emitting either 1061, 1258, or 1301nm light that costs less than $4000, and that this device replicates the adjuvant effect of a DPSSL system in a mouse model of influenza vaccination. Our results also indicate that a broader range of NIR laser wavelengths possess the ability to enhance vaccine immune responses, allowing engineering options for the device design. This small, low-cost device establishes the feasibility of using a laser adjuvant approach for mass-vaccination programs in a clinical setting, opens the door for broader testing of this technology with a variety of vaccines and forms the foundation for development of devices ready for use in the clinic., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Objective: We describe use cases and an institutional reference architecture for maintaining high-capacity, data-intensive network flows (e.g., 10, 40, 100 Gbps+) in a scientific, medical context while still adhering to security and privacy laws and regulations., Materials and Methods: High-end networking, packet filter firewalls, network intrusion detection systems., Results: We describe a "Medical Science DMZ" concept as an option for secure, high-volume transport of large, sensitive data sets between research institutions over national research networks., Discussion: The exponentially increasing amounts of "omics" data, the rapid increase of high-quality imaging, and other rapidly growing clinical data sets have resulted in the rise of biomedical research "big data." The storage, analysis, and network resources required to process these data and integrate them into patient diagnoses and treatments have grown to scales that strain the capabilities of academic health centers. Some data are not generated locally and cannot be sustained locally, and shared data repositories such as those provided by the National Library of Medicine, the National Cancer Institute, and international partners such as the European Bioinformatics Institute are rapidly growing. The ability to store and compute using these data must therefore be addressed by a combination of local, national, and industry resources that exchange large data sets. Maintaining data-intensive flows that comply with HIPAA and other regulations presents a new challenge for biomedical research. Recognizing this, we describe a strategy that marries performance and security by borrowing from and redefining the concept of a "Science DMZ"-a framework that is used in physical sciences and engineering research to manage high-capacity data flows., Conclusion: By implementing a Medical Science DMZ architecture, biomedical researchers can leverage the scale provided by high-performance computer and cloud storage facilities and national high-speed research networks while preserving privacy and meeting regulatory requirements., (© The Author 2016. Published by Oxford University Press on behalf of the American Medical Informatics Association.)

Physiological information is rarely used in descriptions of maturity for managed, wild fish species; however, the use of physiological data holds great promise to provide important detail on the complexities of oocyte development and maturity. Investigating southern flounder ( Paralichthys lethostigma )-an overfished commercial and recreational fishery resource-we examined pre-spawn physiological changes in females to provide further detail of the maturation process. Given that adults of this species complete maturation and spawn in unknown offshore locations, information on pre-spawn physiological changes is particularly informative for both size- and age-based patterns of maturity. We evaluated seasonal and ontogenetic changes in hormone concentrations in blood plasma that are commonly associated with sexual maturation, in addition to quantifying and classifying lipid stored in liver tissue. We found a strong positive relationship between body weight and lipid content during all months, as well as evidence for mobilization of lipids among larger females in September and October, presumably for gonadal development. Throughout the sampling period, the lipid content of smaller individuals was dominated by structural lipids (as opposed to storage lipids). In contrast, larger individuals possessed greater amounts of storage lipids. This suggests that larger, putatively maturing individuals were accumulating storage lipids for later production of vitellogenin. Females sampled for blood sex steroids and ovarian histology showed different testosterone and estradiol concentrations between putatively maturing and immature fish, and temporal variation with peaks in October and November. Overall, emerging patterns of liver lipid content and composition and blood steroid concentrations describe a multi-month maturation process that is often managed one dimensionally over short time periods. Insights from this work will improve our understanding of the life history of southern flounder, with the potential for better understanding of the dynamics of offshore spawning migration and informing subsequent species management.

There is a continuing need to hasten and improve protein-ligand docking to facilitate the next generation of drug discovery. As the drug-like chemical space reaches into the billions of molecules, increasingly powerful computer systems are required to probe, as well as tackle, the software engineering challenges needed to adapt existing docking programs to use next-generation massively parallel processing systems. We demonstrate docking setup using the wrapper code approach to optimize the DOCK program for large-scale computation as well as docking analysis using variance and promiscuity as examples. Wrappers provide faster docking speeds when compared with the naive multi-threading system MPI-DOCK, making future endeavors in large-scale docking more feasible; in addition, eliminating highly variant or promiscuous compounds will make databases more useful., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Plants reside within an environment rich in potential pathogens. Survival in the presence of such threats requires both effective perception of, and appropriate responses to, pathogenic attack. While plants lack an adaptive immune system, they have a highly developed and responsive innate immune system able to detect and inhibit the growth of the vast majority of potential pathogens. Many of the critical interactions that characterize the relationship between plants and pathogens are played out in the intercellular apoplastic space. The initial perception of pathogen invasion is often achieved through specific plant receptor-like kinases that recognize conserved molecular patterns presented by the pathogen or respond to the molecular debris caused by cellular damage. The perception of either microbial or damage signals by these receptors initiates a response that includes the production of peptides and small molecules to enhance cellular integrity and inhibit pathogen growth. In this review, we discuss the roles of apoplastic peptides and small molecules in modulating plant-pathogen interactions.

Bacterial phytopathogens utilize a myriad of virulence factors to modulate their plant hosts in order to promote successful pathogenesis. One potent virulence strategy is to inject these virulence proteins into plant cells via the type III secretion system. Characterizing the host targets and the molecular mechanisms of type III secreted proteins, known as effectors, has illuminated our understanding of eukaryotic cell biology. As a result, these effectors can serve as molecular probes to aid in our understanding of plant cellular processes, such as immune signalling, vesicle trafficking, cytoskeleton stability and transcriptional regulation. Furthermore, given that effectors directly and specifically interact with their targets within plant cells, these virulence proteins have enormous biotechnological potential for manipulating eukaryotic systems., (© 2013 The Authors. Published by Society for Applied Microbiology and Blackwell Publishing Ltd. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.)

Background: Throughout oogenesis, cell-cell communication via gap junctions (GJs) between oocytes and surrounding follicle cells (theca and granulosa cells), and/or amongst follicle cells is required for successful follicular development. To gain a fundamental understanding of ovarian GJs in teleosts, gene transcripts encoding GJ proteins, connexins (cx), were identified in the coho salmon, Oncorhynchus kisutch, ovary. The spatiotemporal expression of four ovarian cx transcripts was assessed, as well as their potential regulation by follicle-stimulating hormone (FSH), luteinizing hormone (LH) and insulin-like growth factor 1 (IGF1)., Methods: Salmonid ovarian transcriptomes were mined for cx genes. Four gene transcripts designated cx30.9, cx34.3, cx43.2, and cx44.9 were identified. Changes in gene expression across major stages of oogenesis were determined with real-time, quantitative RT-PCR (qPCR) and cx transcripts were localized to specific ovary cell-types by in situ hybridization. Further, salmon ovarian follicles were cultured with various concentrations of FSH, LH and IGF1 and effects of each hormone on cx gene expression were determined by qPCR., Results: Transcripts for cx30.9 and cx44.9 were highly expressed at the perinucleolus (PN)-stage and decreased thereafter. In contrast, transcripts for cx34.3 and cx43.2 were low at the PN-stage and increased during later stages of oogenesis, peaking at the mid vitellogenic (VIT)-stage and maturing (MAT)-stage, respectively. In situ hybridization revealed that transcripts for cx34.3 were only detected in granulosa cells, but other cx transcripts were detected in both oocytes and follicle cells. Transcripts for cx30.9 and cx44.9 were down-regulated by FSH and IGF1 at the lipid droplet (LD)-stage, whereas transcripts for cx34.3 were up-regulated by FSH and IGF1 at the LD-stage, and LH and IGF1 at the late VIT-stage. Transcripts for cx43.2 were down-regulated by IGF1 at the late VIT-stage and showed no response to gonadotropins., Conclusion: Our findings demonstrate the presence and hormonal regulation of four different cx transcripts in the salmon ovary. Differences in the spatiotemporal expression profile and hormonal regulation of these cx transcripts likely relate to their different roles during ovarian follicle differentiation and development.