Miracle-dz/UniFAR-FTUs huggingface dataset:
Experimentally induced host‐shift changes life‐history strategy in a seed beetle

Expansion of the host range in phytophagous insects depends on their ability to form an association with a novel plant through changes in host‐related traits. Phenotypic plasticity has important effects on initial survival of individuals faced with a new plant, as well as on the courses of evolutionary change during long‐term adaptation to novel conditions. Using experimental populations of the seed beetle that evolved on ancestral (common bean) or novel (chickpea) host and applying reciprocal transplant at both larval and adult stage on the alternative host plant, we studied the relationship between the initial (plastic) phases of host‐shift and the subsequent stages of evolutionary divergence in life‐history strategies between populations exposed to the host‐shift process. After 48 generations, populations became well adapted to chickpea by evolving the life‐history strategy with prolonged larval development, increased body mass, earlier reproduction, shorter lifespan and decreased plasticity of all traits compared with ancestral conditions. In chickpea‐adapted beetles, negative fitness consequences of low plasticity of pre‐adult development (revealed as severe decrease in egg‐to‐adult viability on beans) exhibited mismatch with positive effects of low plasticity (i.e. low host sensitivity) in oviposition and fecundity. In contrast, beetles adapted to the ancestral host showed high plasticity of developmental process, which enabled high larval survival on chickpea, whereas elevated plasticity in adult behaviour (i.e. high host sensitivity) resulted in delayed reproduction and decreased fecundity on chickpea. The analysis of population growth parameters revealed significant fluctuation during successive phases of the host‐shift process in A. obtectus.
Kinetic properties of mechanically activated currents in spinal sensory neurons

Dorsal root ganglion neurons in vitro express a number of types of mechanically activated currents that are thought to underlie somatic mechanosensory transduction in vivo. We have studied the inactivation properties of these currents to assess how they might influence the electrophysiological responses of dorsal root ganglion (DRG) neurons to mechanical stimulation. We show that the speed of ramp‐like mechanical stimulation determines the dynamics of mechanically activated current responses and hence the type of DRG neuron most likely to be activated. We also show that both rapidly and slowly adapting currents inactivate as a function of membrane stretch. However, the rapidly adapting current inactivation time course is mainly dependent on channel opening whilst slowly adapting current kinetics are dependent on membrane stretch. In response to repeated stimulation, slowly adapting currents inactivate less and recover more quickly than rapidly adapting currents. Therefore, vibratory stimuli tend to inactivate rapidly adapting currents whilst static stimuli tend to inactivate slowly adapting currents. Current clamp experiments show that, physiologically, the response of different types of sensory neurons is dictated primarily by the static or dynamic nature of the mechanical stimulus and the interplay between voltage‐gated and mechanically gated ion channels expressed in these neurons.
Evolution of central pattern generators and rhythmic behaviours

Comparisons of rhythmic movements and the central pattern generators (CPGs) that control them uncover principles about the evolution of behaviour and neural circuits. Over the course of evolutionary history, gradual evolution of behaviours and their neural circuitry within any lineage of animals has been a predominant occurrence. Small changes in gene regulation can lead to divergence of circuit organization and corresponding changes in behaviour. However, some behavioural divergence has resulted from large-scale rewiring of the neural network. Divergence of CPG circuits has also occurred without a corresponding change in behaviour. When analogous rhythmic behaviours have evolved independently, it has generally been with different neural mechanisms. Repeated evolution of particular rhythmic behaviours has occurred within some lineages due to parallel evolution or latent CPGs. Particular motor pattern generating mechanisms have also evolved independently in separate lineages. The evolution of CPGs and rhythmic behaviours shows that although most behaviours and neural circuits are highly conserved, the nature of the behaviour does not dictate the neural mechanism and that the presence of homologous neural components does not determine the behaviour. This suggests that although behaviour is generated by neural circuits, natural selection can act separately on these two levels of biological organization.
Increased Endothelial Nitric-Oxide Synthase Expression Reduces Hypertension and Hyperinsulinemia in Fructose-Treated Rats

Endothelial dysfunction and decreased production of nitric oxide (NO) by endothelial NO synthase (eNOS) are implicated in the pathogenesis of hypertension and insulin resistance. Because the potential influence of increased eNOS expression/activity on these parameters is unclear, the present study examined the effects of eNOS gene therapy on insulin resistance and blood pressure alterations in a fructose-induced hypertension model in rats. As predicted, 2 weeks of fructose consumption in the drinking water resulted in elevated systolic blood pressure and insulin resistance. These and other physiologic alterations were reversed within 2 weeks after a single intravenous injection of a vector containing the human eNOS cDNA (pcDNA3.1-eNOS), whereas injection of an empty vector (pcDNA3.1) was without effect. In support of the beneficial effects of pcDNA3.1-eNOS treatment being because of enhanced eNOS expression and activity, increased eNOS protein levels were documented in aorta, liver, kidney, and heart of fructose-treated rats injected with pcDNA3.1-eNOS, and corresponding elevations in nitrite/nitrate and cGMP concentrations were observed in urine. Furthermore, pcDNA3.1-eNOS treatment prevented fructose-induced decreases in expression levels of insulin receptor substrate-1, the p110 catalytic subunit of phosphatidylinositol 3-kinase, phosphorylated Akt, and phosphorylated AMP-activated protein kinases in liver, aorta, and skeletal muscle. The results of this study cumulatively indicate that gene therapy with human eNOS decreased fructose-induced hypertension and insulin resistance in rats and suggest potential signaling pathways that mediate these effects. These data highlight the potential utility of eNOS gene therapy in the treatment of hypertension and insulin resistance.
Two‐stage methods for the analysis of pooled data

Epidemiologic studies of disease often produce inconclusive or contradictory results due to small sample sizes or regional variations in the disease incidence or the exposures. To clarify these issues, researchers occasionally pool and reanalyse original data from several large studies. In this paper we explore the use of a two‐stage random‐effects model for analysing pooled case‐control studies and undertake a thorough examination of bias in the pooled estimator under various conditions. The two‐stage model analyses each study using the model appropriate to the design with study‐specific confounders, and combines the individual study‐specific adjusted log‐odds ratios using a linear mixed‐effects model; it is computationally simple and can incorporate study‐level covariates and random effects. Simulations indicate that when the individual studies are large, two‐stage methods produce nearly unbiased exposure estimates and standard errors of the exposure estimates from a generalized linear mixed model. By contrast, joint fixed‐effects logistic regression produces attenuated exposure estimates and underestimates the standard error when heterogeneity is present. While bias in the pooled regression coefficient increases with interstudy heterogeneity for both models, it is much smaller using the two‐stage model. In pooled analyses, where covariates may not be uniformly defined and coded across studies, and occasionally not measured in all studies, a joint model is often not feasible. The two‐stage method is shown to be a simple, valid and practical method for the analysis of pooled binary data. The results are applied to a study of reproductive history and cutaneous melanoma risk in women using data from ten large case‐control studies. Copyright © 2001 John Wiley & Sons, Ltd.
Localization of alternatively spliced NMDAR1 glutamate receptor isoforms in rat striatal neurons

Alternative splicing of the mRNA encoding the N‐methyl‐D‐aspartate (NMDA) receptor subunit NR1 changes the structural, physiologic, and pharmacologic properties of the resultant NMDA receptors. We used dual label immunocytochemistry and confocal microscopy to localize the four alternatively spliced segments of the NR1 subunit (N1, C1, C2, and C2′) in rat striatal neurons. Striatofugal projection neurons and four populations of interneurons were studied. Projection neurons, which were identified by immunolabeling for calbindin and by retrograde tracing from the globus pallidus and the substantia nigra, were the only striatal neurons containing C1 segment immunoreactivity. Projection neurons were also C2 segment immunopositive, as were all other neuronal populations studied. Projection neurons were C2′ segment immunonegative. In contrast, each of the interneuron types were labeled by the antibody to the C2′ segment: nitric oxide synthase interneurons were labeled intensely, calretinin and parvalbumin neurons were labeled moderately strongly, and cholinergic neurons were also labeled but less strongly than the other types of interneurons. Parvalbumin interneurons showed distinct N1 segment immunolabeling, which was not found in other types of striatal neurons. Our results suggest that all striatal neurons studied synthesize NR1 subunit proteins, but the isoforms of the protein present in projection neurons and the several types of interneurons are distinct. This differential expression of NR1 isoforms may affect both neuronal function and selective vulnerability of neurons to injury. J. Comp. Neurol. 415:204–217, 1999. © 1999 Wiley‐Liss, Inc.
Is chlorthalidone better than hydrochlorothiazide in reducing cardiovascular events in hypertensives?

Purpose of review Hydrochlorthiazide (HCTZ) is the tenth most commonly prescribed drug in recent data. Although no head-to-head trials compare HCTZ with the uncommonly prescribed chlorthalidone (CTDN) in reducing cardiovascular events (CVEs), numerous other data are available. Recent findings Head-to-head trials have shown CTDN's superiority in antihypertensive potency, particularly during the critical nighttime period (SBP difference 7.1 mmHg), due to the differences in duration of action (16–24 h for HCTZ versus 48–72 h for CTDN). In an observational cohort study, compared with HCTZ, CTDN was associated with lower left ventricular hypertrophy. In another observational cohort analysis (n = 12 866), the percentage risk reduction in CVEs from CTDN versus HCTZ was 21 [95% confidence interval (CI) 8–32], P = 0.002. In network meta-analyses of randomized trials (n = 50 946), CTDN was superior to HCTZ in reducing congestive heart failure and in reducing all CVEs: percentage risk reduction 21 (95% CI 12–28), P < 0.0001. A statistically significant reduction in CVEs by CTDN versus HCTZ persisted even when reduction in office SBP produced by the two diuretics was identical, further strengthening the case for CTDN. Summary Direct and indirect evidence demonstrates that CTDN is superior to HCTZ in reducing CVEs and is congruent with the recent changes in the guidelines for hypertension management.
Redistribution of Emergency Department Patients After Disaster-Related Closures of a Public Versus Private Hospital in New York City

Abstract Sudden hospital closures displace patients from usual sources of care and force them to access facilities that lack their prior medical records. For patients with complex needs and for nearby hospitals already strained by high volume, disaster-related hospital closures induce a public health emergency. Our objective was to analyze responses of patients from public versus private emergency departments after closure of their usual hospital after Hurricane Sandy. Using a statewide database of emergency visits, we followed patients with an established pattern of accessing 1 of 2 hospitals that closed after Hurricane Sandy: Bellevue Hospital Center and NYU Langone Medical Center. We determined how these patients redistributed for emergency care after the storm. We found that proximity strongly predicted patient redistribution to nearby open hospitals. However, for patients from the closed public hospital, this redistribution was also influenced by hospital ownership, because patients redistributed to other public hospitals at rates higher than expected by proximity alone. This differential response to hospital closures demonstrates significant differences in how public and private patients respond to changes in health care access during disasters. Public health response must consider these differences to meet the needs of all patients affected by disasters and other public health emergencies. (Disaster Med Public Health Preparedness. 2015;9:256-264).
The effects of colesevelam HCl on the single‐dose pharmacokinetics of glimepiride, extended‐release glipizide, and olmesartan medoxomil

Bile acid sequestrants can potentially bind to concomitant drugs. Single‐dose studies evaluated the effects of colesevelam on the pharmacokinetics of glimepiride, glipizide extended‐release (ER), and olmesartan medoxomil. Each study enrolled healthy subjects aged 18–45 years. The olmesartan medoxomil study used a randomized adaptive crossover design that initially compared olmesartan medoxomil alone versus simultaneously with colesevelam, then olmesartan medoxomil alone versus 4 hours before colesevelam. The other studies used a three‐period crossover design (test drug alone, test drug simultaneously with colesevelam, and test drug 4 hours before colesevelam). For the colesevelam coadministration periods, 3,750 mg once daily was dosed throughout the pharmacokinetic sampling period. After each single dose of test drug, serial blood samples were collected for determination of plasma drug concentrations and calculation of pharmacokinetic parameters. Administering colesevelam simultaneously with glimepiride or glipizide ER resulted in minor reductions (18% and 13%, respectively) in total exposure that were negated by staggering colesevelam dosing by 4 hours. Administering colesevelam simultaneously with olmesartan medoxomil resulted in a major reduction (39%) in olmesartan exposure that was reduced by staggering colesevelam dosing by 4 hours. This reduction in olmesartan exposure is not predicted to have a clinically significant impact on blood pressure control.
Germ-free and Antibiotic-treated Mice are Highly Susceptible to Epithelial Injury in DSS Colitis.

BACKGROUND AND AIMS Intestinal microbiota is required to maintain immune homeostasis and intestinal barrier function. At the same time, intraluminal bacteria are considered to be involved in inflammatory bowel disease and are required for colitis induction in animal models, with the possible exception of dextran sulphate sodium [DSS] colitis. This study was carried out to ascertain the mechanism underlying the induction of colitis by DSS in the absence of bacteria. METHODS Conventional and germ-free [GF] Naval Medical Research Institute [NMRI] mice were used, plus conventional mice treated with an antibiotic cocktail to deplete the intestinal microbiota ['pseudo-GF' or PGF mice]. The differential response to DSS was assessed. RESULTS Conventional mice developed DSS-induced colitis normally, whereas GF mice showed only minimal inflammation [no colonic thickening, lower myeloperoxidase activity, IL-6, IL-17, TNF-α, and IFN-γ secretion by splenocytes and mesenteric cell cultures, etc.]. However, these mice suffered enhanced haemorrhage, epithelial injury and mortality as a consequence of a weakened intestinal barrier, as shown by lower occludin, claudin 4, TFF3, MUC3, and IL-22. In contrast, PGF mice had a relatively normal, albeit attenuated, inflammatory response, but were less prone to haemorrhage and epithelial injury than GF mice. This was correlated with an increased expression of IL-10 and Foxp3 and preservation barrier-related markers. CONCLUSIONS We conclude that enteric bacteria are essential for the development of normal DSS-induced colitis. The absence of microbiota reduces DSS colonic inflammation dramatically but it also impairs barrier function, whereas subtotal microbiota depletion has intermediate effects at both levels.
Associations between epidermal growth factor receptor and topoisomerase II-alpha gene copy number variations, human papillomavirus positivity, and cytologic analysis in cervical cell lesions

Background: Cervical cancer is the second most common gynecologic cancer worldwide. Human papillomavirus (HPV) infection is a leading etiological factor in cervical carcinoma.The aim of this study was to compare HPV positivity, EGFR and TOP2A gene copy number variations and cervical cytologic findings. Materials and Methods: The study group comprised 100 female volunteers between 21-64 years old. Cytologic analysis was performed using the liquid-based cytology technique. HPV DNA testing was performed in all cases. Copy number variations that belong to EGFR and TOP2A genes evaluated by using FISH analysis. Results: Cytologic analysis of the cervical samples revealed abnormal findings in 13 of the 100 study subjects. ASCUS , LSIL, HSIL were determined in 8, 2 and 3 cases respectively as the result of cytologic analysis on all cases. Forty-one (41%) of the 100 women were HPV-positive. Chi-square analysis confirmed that HPV-positive women showed significantly more abnormal cytology (P = 0.035). EGFR deletion, TOP2A deletion and both EGFR and TOP2A deletion were determined in 1, 8 and 1 cases respectively. We found no statistical difference in abnormal cytologic findings between subjects with these gene deletions and subjects with normal gene copy numbers (P > 0.05 for both). No cases of amplification were determined for either gene. Conclusion: As a result, HPV positivity and the determination of changes that may occur in the gene copy number in patients with abnormal cytology can be an important tool on account of prognosis. Research with more patients may be suggested.
Characterization of virus-specific RNA synthesized in bovine cells infected with bovine viral diarrhea virus

Infection of bovine kidney cells with bovine viral diarrhea virus resulted in the synthesis of a single species of virus-specific RNA. Electrophoresis of this RNA on agarose-urea and agarose-formaldehyde gels indicated that it had a molecular weight of 2.9 X 10(6), corresponding to 8,200 bases (8.2 kilobases). This 8.2-kilobase RNA was resistant to RNase A treatment at 1 microgram/ml but was digested at higher concentrations of RNase (10 micrograms/ml). Sedimentation on neutral sucrose gradients indicated that the majority of this RNA (98%) sedimented at 21S, with a small amount sedimenting at 33S. Sedimentation on formaldehyde-containing sucrose gradients resulted in the conversion of all of the RNA to the faster-sedimenting form. At no time after infection were we able to detect virus-specific RNA species of lower molecular weight than the 8.2-kilobase RNA. The implications of these findings with respect to the means of replication of various togaviruses are discussed.
Effects of Sitagliptin and Metformin Treatment on Incretin Hormone and Insulin Secretory Responses to Oral and “Isoglycemic” Intravenous Glucose

Dipeptidyl peptidase-4 (DPP-4) inhibitors prevent degradation of incretin hormones (glucagon-like peptide 1 [GLP-1] and glucose-dependent insulinotropic polypeptide [GIP]), whereas metformin may increase GLP-1 levels. We examined, in a four-period crossover trial, the influence of metformin (2,000 mg/day), sitagliptin (100 mg/day), or their combination, on GLP-1 responses and on the incretin effect in 20 patients with type 2 diabetes, comparing an oral glucose challenge (75 g, day 5) and an “isoglycemic” intravenous glucose infusion (day 6). Fasting total GLP-1 was significantly increased by metformin and not changed by sitagliptin. After oral glucose, metformin increased and sitagliptin significantly decreased (by 53%) total GLP-1. Fasting and postload intact GLP-1 increased with sitagliptin but not with metformin. After oral glucose, only sitagliptin, but not metformin, significantly augmented insulin secretion, in monotherapy and as an add-on to metformin. The incretin effect was not changed numerically with any of the treatments. In conclusion, sitagliptin increased intact GLP-1 and GIP through DPP-4 inhibition but reduced total GLP-1 and GIP (feedback inhibition) without affecting the numerical contribution of the incretin effect. Insulin secretion with sitagliptin treatment was similarly stimulated with oral and “isoglycemic” intravenous glucose. This points to an important contribution of small changes in incretin concentrations within the basal range or to additional insulinotropic agents besides GLP mediating the antidiabetic effects of DPP-4 inhibition.