Structure and decay of a proto-Y region in Tilapia, Oreochromis niloticus

Funding for Open Access provided by the UMD Libraries Open Access Publishing Fund.Sex-determination genes drive the evolution of adjacent chromosomal regions. Sexually antagonistic selection favors the accumulation of inversions that reduce recombination in regions adjacent to the sex-determination gene. Once established, the clonal inheritance of sex-linked inversions leads to the accumulation of deleterious alleles, repetitive elements and a gradual decay of sex-linked genes. This in turn creates selective pressures for the evolution of mechanisms that compensate for the unequal dosage of gene expression. Here we use whole genome sequencing to characterize the structure of a young sex chromosome and quantify sex-specific gene expression in the developing gonad. We found an 8.8 Mb block of strong differentiation between males and females that corresponds to the location of a previously mapped sex-determiner on linkage group 1 of Oreochromis niloticus. Putatively disruptive mutations are found in many of the genes within this region. We also found a significant female-bias in the expression of genes within the block of differentiation compared to those outside the block of differentiation. Eight candidate sex-determination genes were identified within this region. This study demonstrates a block of differentiation on linkage group 1, suggestive of an 8.8 Mb inversion encompassing the sex-determining locus. The enrichment of female-biased gene expression inside the proposed inversion suggests incomplete dosage compensation. This study helps establish a model for studying the early-to-intermediate stages of sex chromosome evolution.https://doi.org/10.1186/1471-2164-15-97

Wildtype epidermal growth factor receptor (Egfr) is not required for daily locomotor or masking behavior in mice

BACKGROUND: Recent studies have implicated the epidermal growth factor receptor (EGFR) within the subparaventricular zone as being a major mediator of locomotor and masking behaviors in mice. The results were based on small cohorts of mice homozygous for the hypomorphic Egfr(wa2 )allele on a mixed, genetically uncontrolled background, and on intraventricular infusion of exogenous EGFR ligands. Subsequenlty, a larger study using the same genetically mixed background failed to replicate the original findings. Since both previous approaches were susceptible to experimental artifacts related to an uncontrolled genetic background, we analyzed the locomotor behaviors in Egfr(wa2 )mutant mice on genetically defined, congenic backgrounds. METHODS: Mice carrying the Egfr(wa2 )hypomorphic allele were bred to congenicity by backcrossing greater than ten generations onto C57BL/6J and 129S1/SvImJ genetic backgrounds. Homozygous Egfr(wa2 )mutant and wildtype littermates were evaluated for defects in locomotor and masking behaviors. RESULTS: Mice homozygous for Egfr(wa2 )showed normal daily locomotor activity and masking indistinguishable from wildtype littermates at two light intensities (200–300 lux and 400–500 lux). CONCLUSION: Our results demonstrate that reduced EGFR activity alone is insufficient to perturb locomotor and masking behaviors in mice. Our results also suggest that other uncontrolled genetic or environmental parameters confounded previous experiments linking EGFR activity to daily locomotor activity and provide a cautionary tale for genetically uncontrolled studies

Recalibration of the delirium prediction model for ICU patients (PRE-DELIRIC): a multinational observational study

Purpose Recalibration and determining discriminative power, internationally, of the existing delirium prediction model (PRE-DELIRIC) for intensive care patients. Methods A prospective multicenter cohort study was performed in eight intensive care units (ICUs) in six countries. The ten predictors (age, APACHE-II, urgent and admission category, infection, coma, sedation, morphine use, urea level, metabolic acidosis) were collected within 24 h after ICU admission. The confusion assessment method for the intensive care unit (CAM-ICU) was used to identify ICU delirium. CAM-ICU screening compliance and inter-rater reliability measurements were used to secure the quality of the data. Results A total of 2,852 adult ICU patients were screened of which 1,824 (64 %) were eligible for the study. Main reasons for exclusion were length of stay <1 day (19.1 %) and sustained coma (4.1 %). CAM-ICU compliance was mean (SD) 82 ± 16 % and inter-rater reliability 0.87 ± 0.17. The median delirium incidence was 22.5 % (IQR 12.8–36.6 %). Although the incidence of all ten predictors differed significantly between centers, the area under the receiver operating characteristic (AUROC) curve of the eight participating centers remained good: 0.77 (95 % CI 0.74–0.79). The linear predictor and intercept of the prediction rule were adjusted and resulted in improved re-calibration of the PRE-DELIRIC model. Conclusions In this multinational study, we recalibrated the PRE-DELIRIC model. Despite differences in the incidence of predictors between the centers in the different countries, the performance of the PRE-DELIRIC-model remained good. Following validation of the PRE-DELIRIC model, it may facilitate implementation of strategies to prevent delirium and aid improvements in delirium management of ICU patients

Fecal microbiota is more stable during degradation and more diverse for ex situ cheetahs in Namibia compared to the USA

The relationships between gut microbiota and animal health are an important consideration increasingly influential in the management of wild and ex situ endangered species, such as the cheetah (Acinonyx jubatus). To better understand these relationships, fresh fecal samples are currently required as a non-invasive alternative for the gut microbiome. Unfortunately, fresh samples are challenging to collect in the wild. This study had two aims: 1) to determine the optimal collection time point for cheetah feces after deposit in their native environment of Namibia as a guide for wild cheetah fecal microbiome studies; and 2) to compare the fecal microbiota of two ex situ cheetah populations (Front Royal, VA, USA and Otjiwarongo, Namibia), which also consume different diets. We collected eight fresh fecal samples from cheetahs in Namibia and allowed them to decompose for four days, taking subsamples each day. The fresh Namibian samples (n = 8) were also used in objective two for comparison to fresh USA cheetah samples (n = 8). All samples were analyzed for bacterial community diversity and composition using 16S rRNA gene amplicon sequencing. First, over a five-day sampling period in Namibia, subsamples 1-3 days post-fresh showed no changes in bacterial diversity or composition compared to fresh subsamples. Second, fresh ex situ cheetah samples under Namibian conditions had increased bacterial taxa, more phylogenetically diverse bacterial communities, and compositionally distinct microbiomes from cheetahs managed in human care in the USA. However, when bacterial ASVs were weighted by relative abundance, both populations shared 69% of their total bacterial sequences indicating a conserved cheetah microbiota between the two populations. We also found few differences in predictive functions of the fecal microbiota between the populations, where only one disease-related pathway was higher in the USA samples. Overall, our findings suggest that in dry season conditions (no recorded rainfall) in Namibia, fecals may be usable for up to three days after defecation for microbial ecology studies. There are significant differences between ex situ Namibian and USA populations, and we suggest further investigation into the influence of diet, host demographics, and environment on the gut microbiota and health of cheetahs

The Effect of Pulmonary Artery Catheter Use on Costs and Long-Term Outcomes of Acute Lung Injury

Background: The pulmonary artery catheter (PAC) remains widely used in acute lung injury (ALI) despite known complications and little evidence of improved short-term mortality. Concurrent with NHLBI ARDS Clinical Trials Network Fluid and Catheters Treatment Trial (FACTT), we conducted a prospectively-defined comparison of healthcare costs and long-term outcomes for care with a PAC vs. central venous catheter (CVC). We explored if use of the PAC in ALI is justified by a beneficial cost-effectiveness profile. Methods: We obtained detailed bills for the initial hospitalization. We interviewed survivors using the Health Utilities Index Mark 2 questionnaire at 2, 6, 9 and 12 m to determine quality of life (QOL) and post-discharge resource use. Outcomes beyond 12 m were estimated from federal databases. Incremental costs and outcomes were generated using MonteCarlo simulation. Results: Of 1001 subjects enrolled in FACTT, 774 (86%) were eligible for long-term follow-up and 655 (85%) consented. Hospital costs were similar for the PAC and CVC groups ($96.8k vs.$89.2k, p = 0.38). Post-discharge to 12 m costs were higher for PAC subjects ($61.1k vs. 45.4k, p = 0.03). One-year mortality and QOL among survivors were similar in PAC and CVC groups (mortality: 35.6$14.4k and mean loss of 0.3 quality-adjusted life years (QALYs)) and a 94.2% probability of being higher than the $100k/QALY willingness-to-pay threshold. Conclusion: PAC use increased costs with no patient benefit and thus appears unjustified for routine use in ALI. Trial Registration: www.clinicaltrials.gov NCT00234767. © 2011 Clermont et al

Transcriptional recapitulation and subversion of embryonic colon development by mouse colon tumor models and human colon cancer

Colon tumors from four independent mouse models and 100 human colorectal cancers all exhibited striking recapitulation of embryonic colon gene expression from embryonic days 13.5-18.5

Transcriptional recapitulation and subversion of embryonic colon development by mouse colon tumor models and human colon cancer

Abstract Background The expression of carcino-embryonic antigen by colorectal cancer is an example of oncogenic activation of embryonic gene expression. Hypothesizing that oncogenesis-recapitulating-ontogenesis may represent a broad programmatic commitment, we compared gene expression patterns of human colorectal cancers (CRCs) and mouse colon tumor models to those of mouse colon development embryonic days 13.5-18.5. Results We report here that 39 colon tumors from four independent mouse models and 100 human CRCs encompassing all clinical stages shared a striking recapitulation of embryonic colon gene expression. Compared to normal adult colon, all mouse and human tumors over-expressed a large cluster of genes highly enriched for functional association to the control of cell cycle progression, proliferation, and migration, including those encoding MYC, AKT2, PLK1 and SPARC. Mouse tumors positive for nuclear β-catenin shifted the shared embryonic pattern to that of early development. Human and mouse tumors differed from normal embryonic colon by their loss of expression modules enriched for tumor suppressors (EDNRB, HSPE, KIT and LSP1). Human CRC adenocarcinomas lost an additional suppressor module (IGFBP4, MAP4K1, PDGFRA, STAB1 and WNT4). Many human tumor samples also gained expression of a coordinately regulated module associated with advanced malignancy (ABCC1, FOXO3A, LIF, PIK3R1, PRNP, TNC, TIMP3 and VEGF). Conclusion Cross-species, developmental, and multi-model gene expression patterning comparisons provide an integrated and versatile framework for definition of transcriptional programs associated with oncogenesis. This approach also provides a general method for identifying pattern-specific biomarkers and therapeutic targets. This delineation and categorization of developmental and non-developmental activator and suppressor gene modules can thus facilitate the formulation of sophisticated hypotheses to evaluate potential synergistic effects of targeting within- and between-modules for next-generation combinatorial therapeutics and improved mouse models

Prevention of acute kidney injury and protection of renal function in the intensive care unit

Acute renal failure on the intensive care unit is associated with significant mortality and morbidity. To determine recommendations for the prevention of acute kidney injury (AKI), focusing on the role of potential preventative maneuvers including volume expansion, diuretics, use of inotropes, vasopressors/vasodilators, hormonal interventions, nutrition, and extracorporeal techniques. A systematic search of the literature was performed for studies using these potential protective agents in adult patients at risk for acute renal failure/kidney injury between 1966 and 2009. The following clinical conditions were considered: major surgery, critical illness, sepsis, shock, and use of potentially nephrotoxic drugs and radiocontrast media. Where possible the following endpoints were extracted: creatinine clearance, glomerular filtration rate, increase in serum creatinine, urine output, and markers of tubular injury. Clinical endpoints included the need for renal replacement therapy, length of stay, and mortality. Studies are graded according to the international Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) group system Several measures are recommended, though none carries grade 1A. We recommend prompt resuscitation of the circulation with special attention to providing adequate hydration whilst avoiding high-molecular-weight hydroxy-ethyl starch (HES) preparations, maintaining adequate blood pressure using vasopressors in vasodilatory shock. We suggest using vasopressors in vasodilatory hypotension, specific vasodilators under strict hemodynamic control, sodium bicarbonate for emergency procedures administering contrast media, and periprocedural hemofiltration in severe chronic renal insufficiency undergoing coronary intervention

Heterospecific aggression differs predominately by species, rather than sex, in Lake Malawi cichlid fish

ABSTRACTBecause of their striking diversity, Lake Malawi cichlid fish have been well studied for male aggression, particularly among dominant males of closely related sister species within the framework of mate-choice and speciation. However, aggression in females has been largely ignored, and variation in aggressive behaviors between more distantly-related taxa is not well understood despite its potential impact in a complex community structure. To better understand variation in patterns of aggression between species, we presented males and females from five species of Lake Malawi cichlid with a non-predator intruder and recorded all movement and aggressive acts. Additionally, we measured excreted cortisol levels the day after the intruder assay to evaluate one physiological aspect of stress response. We identified species-specific patterns in both specific aggressive acts, and overall level of aggression. Additionally, we found that sexual dimorphism in aggressive acts varies by species and act, where the species with the most aggressive males also has aggressive females. Additionally, cortisol levels vary by taxa, and are associated with restless behavior in the intruder assay, but not levels of aggression. These findings have bearing on understanding sex differences in aggression and their impact on community structure in this important model of rapid evolution.</jats:p