Miracle-dz/UniFAR-FTUs huggingface dataset:
Multiple Wolbachia determinants control the evolution of cytoplasmic incompatibilities in Culex pipiens mosquito populations

Wolbachia are maternally inherited endosymbionts that can invade arthropod populations through manipulation of their reproduction. In mosquitoes, Wolbachia induce embryonic death, known as cytoplasmic incompatibility (CI), whenever infected males mate with females either uninfected or infected with an incompatible strain. Although genetic determinants of CI are unknown, a functional model involving the so‐called mod and resc factors has been proposed. Natural populations of Culex pipiens mosquito display a complex CI relationship pattern associated with the highest Wolbachia (wPip) genetic polymorphism reported so far. We show here that C. pipiens populations from La Réunion, a geographically isolated island in the southwest of the Indian Ocean, are infected with genetically closely related wPip strains. Crossing experiments reveal that these Wolbachia are all mutually compatible. However, crosses with genetically more distant wPip strains indicate that Wolbachia strains from La Réunion belong to at least five distinct incompatibility groups (or crossing types). These incompatibility properties which are strictly independent from the nuclear background, formally establish that in C. pipiens, CI is controlled by several Wolbachia mod/resc factors.
Eating Behaviour and Body Satisfaction in Mediterranean Children: the Role of the Parents

Although the prevalence of fully expressed Eating Disorders is rare in young children, childhood eating disturbances are fairly common. Parents can play a facilitating role for the development of overweight and eating problems among their children. The aim of this study is to detect the possible relationships between children’s eating attitudes and behaviour and the parents’ beliefs about eating habits and body shape of their offspring. This survey was conducted in the area of Arezzo (Italy), on 900 children, aged 7-12, and on their parents/substitute caregivers. The Kids’ Eating Disorder Survey questionnaire, and the CIBUS questionnaire were administered. A fully expressed Eating Disorder was diagnosed in two kids only. KEDS total score and weight/dissatisfaction subscale score positively correlated with parents’ answers to the following CIBUS’ items (How do you consider the body shape of your son/daughter? How much does your son/daughter eats? Have you ever thought of putting your son/daughter on a diet? ). Positive correlations between the children BMI, desired BMI and the aforementioned CIBUS’ items were found. The prevalence of formal Eating Disorders in children aged 7-12 is low. Children appear to be more preoccupied with their weight than with their body shape. Parents’ beliefs about the offspring’s body shape and eating habits have a relevant impact on children’s eating attitudes and behaviour.
Groundwater flow processes and mixing in active volcanic systems: the case of Guadalajara (Mexico)

Groundwater chemistry and isotopic data from 40 production wells in the Atemajac and Toluquilla valleys, located in and around the Guadalajara metropolitan area, were determined to develop a conceptual model of groundwater flow processes and mixing. Stable water isotopes (δ 2 H, δ 18 O) were used to trace hydrological processes and tritium ( 3 H) to evaluate the relative contribution of modern water in samples. Multivariate analysis including cluster analysis and principal component analysis were used to elucidate distribution patterns of constituents and factors controlling groundwater chemistry. Based on this analysis, groundwater was classified into four groups: cold groundwater, hydrothermal groundwater, polluted groundwater and mixed groundwater. Cold groundwater is characterized by low temperature, salinity, and Cl and Na concentrations and is predominantly of Na-HCO 3 -type. It originates as recharge at "La Primavera" caldera and is found predominantly in wells in the upper Atemajac Valley. Hydrothermal groundwater is characterized by high salinity, temperature, Cl, Na and HCO 3 , and the presence of minor elements such as Li, Mn and F. It is a mixed-HCO 3 type found in wells from Toluquilla Valley and represents regional flow circulation through basaltic and andesitic rocks. Polluted groundwater is characterized by elevated nitrate and sulfate concentrations and is usually derived from urban water cycling and subordinately from agricultural return flow. Mixed groundwaters between cold and hydrothermal components are predominantly found in the lower Atemajac Valley. Twenty-seven groundwater samples contain at least a small fraction of modern water. The application of a multivariate mixing model allowed the mixing proportions of hydrothermal fluids, polluted waters and cold groundwater in sampled water to be evaluated. This study will help local water authorities to identify and dimension groundwater contamination, and act accordingly. It may be broadly applicable to other active volcanic systems on Earth.
Evidence against Functional Interaction between Aquaporin-4 Water Channels and Kir4.1 Potassium Channels in Retinal Müller Cells*

Indirect evidence suggests that the Müller/glial cell water channel aquaporin-4 (AQP4) modulates K+ channel function of the closely associated Kir4.1 protein. We used patch clamp to compare Kir4.1 K+ channel function in freshly isolated Müller cells from retinas of wild-type (+/+) and AQP4 knock-out (-/-) mice. Immunocytochemistry showed a comparable Kir4.1 protein expression pattern in Müller cells from +/+ and -/- retinas, with greatest expression at their end feet. Osmotic water permeability was >4-fold reduced in -/- than in +/+ Müller cells. Resting membrane potential did not differ significantly in +/+ versus -/- Müller cells (-64 ± 1 versus -64 ± 1 mV, S.E., n = 24). Whole-cell K+ currents recorded with a micropipette inserted into the cell soma were Ba2+-sensitive and showed no significant differences in magnitude in +/+ versus -/- Müller cells (1.3 ± 0.1 versus 1.2 ± 0.1 nA at -160 mV) or in inwardly rectifying current-voltage relationships. Spatially resolved K+ currents generated by pulsed K+ injections along Müller cell bodies were also comparable in +/+ versus -/- Müller cells. Single-channel cell-attached patch clamp showed comparable unitary conductance, current-voltage data, and open probability in +/+ versus -/- Müller cells. Thus, contrary to the generally accepted view, our results provide direct evidence against functionally significant AQP4 modulation of Müller cell Kir4.1 K+ channel function.
Endothelial function in normotensive men with obstructive sleep apnea before and 6 months after CPAP treatment.

STUDY OBJECTIVES To evaluate endothelium-dependent flow-mediated dilation (FMD) and endothelium-independent nitroglycerin (NTG)-induced dilation of the brachial artery with Doppler ultrasound in patients with obstructive sleep apnea (OSA) and impact of six months of continuous positive airway pressure (CPAP) treatment. DESIGN A prospective, controlled, observational study. SETTING Single-site, clinic-based. PATIENTS Twenty-nine normotensive men with OSA (apnea-hypopnea index [AHI], mean +/- SD, 60.4 +/- 22.1-h), and 17 men without OSA (AHI 2.5 +/- 0.6-h). INTERVENTIONS Six months of CPAP therapy in OSA patients. MEASUREMENTS AND RESULTS FMD was lower in patients with OSA compared with in controls (7.19 +/- 1.78% vs 10.93 +/- 2.59%; P < 0.001) while NTG-induced vasodilation was similar in both groups (13.75 +/- 1.01% vs 14.25 +/- 1.83%; n.s.). An inverse relationship was found between FMD and AHI adjusted for age and body mass index (BMI) (beta = - 0.05, P < 0.001). Following 6 months of CPAP treatment in the OSA group, FMD was increased from 7.38 +/- 2.06% to 10.45 +/- 1.68; P = 0.001) in 20 patients compliant with the device whereas the corresponding values did not change in the non-user group (7.08 +/- 1.50% vs 7.26 +/- 1.01%). No significant changes were observed regarding the NTG-induced vasodilation after CPAP compared with the baseline values. CONCLUSIONS Our results confirm the previous reports suggesting impaired endothelium-dependent FMD in OSA, and additionally document the sustained improvement in endothelial function after 6 months of CPAP treatment in complaint patients.
Lupeol enhances radiosensitivity of human hepatocellular carcinoma cell line SMMC-7721 in vitro and in vivo

Abstract Purpose: To investigate the effect of lupeol, a pentacyclictriterpene, on the radiosensitivity of a human hepatocellular carcinoma (HCC) in vitro and in vivo xenografts. Methods: SMMC-7721 cells were exposed to γ-radiation with or without lupeol and assayed for proliferation, clonogenic survival, apoptosis and cell cycle distribution. The cells were also analyzed by Western blotting for the expression levels of the proteins involved in apoptosis. Finally radiosensitization by lupeol was assessed in HCC xenograft model. Results: Lupeol further suppressed the proliferation and colonogenic survival of the SMMC-7721 cells exposed to γ-radiation. It could also induce the accumulation of cells in G2/M phase together with γ-radiation. The data also indicated that lupeol sensitized SMMC-7721 cells exposed to γ-radiation to apoptosis and activated the apoptotic proteins including caspase-9 and PARP. Administration of lupeol with radiation in HCC xenograft model produced a significant tumor growth delay compared with radiation or lupeol alone and was well tolerated. Conclusion: Lupeol significantly enhanced the radiosensitivity of SMMC-7721 cells in vitro and in vivo. The mechanisms involved could be cell cycle arrest and induction of apoptosis. Our studies suggest that lupeol has the potential to be developed as an adjuvant for radiotherapy in HCC.
The chirality of ciliary beats

Many eukaryotic cells possess cilia which are motile, whip-like appendages that can oscillate and thereby induce motion and fluid flows. These organelles contain a highly conserved structure called the axoneme, whose characteristic architecture is based on a cylindrical arrangement of nine doublets of microtubules. Complex bending waves emerge from the interplay of active internal forces generated by dynein motor proteins within the structure. These bending waves are typically chiral and often exhibit a sense of rotation. In order to study how the shape of the beat emerges from the axonemal structure, we present a three-dimensional description of ciliary dynamics based on the self-organization of dynein motors and microtubules. Taking into account both bending and twisting of the cilium, we determine self-organized beating patterns and find that modes with both a clockwise and anticlockwise sense of rotation exist. Because of the axonemal chirality, only one of these modes is selected dynamically for given parameter values and properties of dynein motors. This physical mechanism, which underlies the selection of a beating pattern with specific sense of rotation, triggers the breaking of the left–right symmetry of developing embryos which is induced by asymmetric fluid flows that are generated by rotating cilia.
Eye Movement Monitoring Reveals Differential Influences of Emotion on Memory

Research shows that memory for emotional aspects of an event may be enhanced at the cost of impaired memory for surrounding peripheral details. However, this has only been assessed directly via verbal reports which reveal the outcome of a long stream of processing but cannot shed light on how/when emotion may affect the retrieval process. In the present experiment, eye movement monitoring (EMM) was used as an indirect measure of memory as it can reveal aspects of online memory processing. For example, do emotions modulate the nature of memory representations or the speed with which such memories can be accessed? Participants viewed central negative and neutral scenes surrounded by three neutral objects and after a brief delay, memory was assessed indirectly via EMM and then directly via verbal reports. Consistent with the previous literature, emotion enhanced central and impaired peripheral memory as indexed by eye movement scanning and verbal reports. This suggests that eye movement scanning may contribute and/or is related to conscious access of memory. However, the central/peripheral tradeoff effect was not observed in an early measure of eye movement behavior, i.e., participants were faster to orient to a critical region of change in the periphery irrespective of whether it was previously studied in a negative or neutral context. These findings demonstrate emotion's differential influences on different aspects of retrieval. In particular, emotion appears to affect the detail within, and/or the evaluation of, stored memory representations, but it may not affect the initial access to those representations.
Pharmacokinetics of dipeptidylpeptidase‐4 inhibitors

Type 2 diabetes (T2DM) is a complex disease combining defects in insulin secretion and insulin action. New compounds have been developed for improving glucose‐induced insulin secretion and glucose control, without inducing hypoglycaemia or weight gain. Dipeptidylpeptidase‐4 (DPP‐4) inhibitors are new oral glucose‐lowering agents, so‐called incretin enhancers, which may be used as monotherapy or in combination with other antidiabetic compounds. Sitagliptin, vildaglipin and saxagliptin are already on the market in many countries, either as single agents or in fixed‐dose combined formulations with metformin. Other DPP‐4 inhibitors, such as alogliptin and linagliptin, are currently in late phase of development. The present paper summarizes and compares the main pharmacokinetics (PK) properties, that is, absorption, distribution, metabolism and elimination, of these five DPP‐4 inhibitors. Available data were obtained in clinical trials performed in healthy young male subjects, patients with T2DM, and patients with either renal insufficiency or hepatic impairment. PK characteristics were generally similar in young healthy subjects and in middle‐aged overweight patients with diabetes. All together gliptins have a good oral bioavailability which is not significantly influenced by food intake. PK/pharmacodynamics characteristics, that is, sufficiently prolonged half‐life and sustained DPP‐4 enzyme inactivation, generally allow one single oral administration per day for the management of T2DM; the only exception is vildagliptin for which a twice‐daily administration is recommended because of a shorter half‐life. DPP‐4 inhibitors are in general not substrates for cytochrome P450 (except saxagliptin that is metabolized via CYP 3A4/A5) and do not act as inducers or inhibitors of this system. Several metabolites have been documented but most of them are inactive; however, the main metabolite of saxagliptin also exerts a significant DPP‐4 inhibition and is half as potent as the parent compound. Renal excretion is the most important elimination pathway, except for linagliptin whose metabolism in the liver appears to be predominant. PK properties of gliptins, combined with their good safety profile, explain why no dose adjustment is necessary in elderly patients or in patients with mild to moderate hepatic impairment. As far as patients with renal impairment are concerned, significant increases in drug exposure for sitagliptin and saxagliptin have been reported so that appropriate reductions in daily dosages are recommended according to estimated glomerular filtration rate. The PK characteristics of DPP‐4 inhibitors suggest that these compounds are not exposed to a high risk of drug–drug interactions. However, the daily dose of saxagliptin should be reduced when coadministered with potent CYP 3A4 inhibitors. In conclusion, besides their pharmacodynamic properties leading to effective glucose‐lowering effect without inducing hypoglycaemia or weight gain, DPP‐4 inhibitors show favourable PK properties, which contribute to a good efficacy/safety ratio for the management of T2DM in clinical practice.
Redox‐active metals in commercial preparations of lipopolysaccharide: implications for studies of cellular responses to bacterial products

The mechanisms by which lipopolyaccharide (LPS) activates cells have been the subject of intense investigation for many years. Whereas much information on this process has been collected for mammalian species, little is known about the signalling path‐ways operative in other animals. One general mode of cellular activation that has been recently pro‐posed for pathways independent of the primary mammalian LPS receptor, CD14, involves reactive oxygen species (ROS) as intermediates in LPS‐induced signalling pathways. Therefore, we used 2′,7′‐dichlorodihydrofluorescein, a fluorogenic probe of redox activity, to examine LPS‐induced oxidative responses of a macrophage‐like cell line from the rainbow trout, RTS11. Lipopolysaccharide dose‐dependently increased oxidation of this probe by RTS11 cells, and a variety of other cell lines. This process was inhibited by catalase, superoxide dismutase and NG‐methylarginine citrate, an inhibitor of nitric oxide synthases, suggesting the involvement of a diverse assortment of cellular ROS. More careful dissection of this phenomenon led us to conclude that the increase in oxidation was, in fact, due almost entirely to metals, particularly copper, in some LPS preparations, which is something to consider when experimenting with LPS.
Melt-electrowriting of 3D anatomically relevant scaffolds to recreate a pancreatic acinar unit in vitro

Melt-electrowriting (MEW) belongs to the group of advanced additive manufacturing techniques and consists of computer-aided design (CAD)-assisted polymer extrusion combined with a high-voltage supply to achieve deposition of polymeric fibers with diameters in the micrometric range (1 to 20 μm) similar to the size of natural extracellular matrix fibers. In this work, we exploit MEW to design and fabricate a three-dimensional (3D) model that resembles the morphology of the exocrine pancreatic functional unit without the need of supports, mandrels, or sacrificial materials. Optimized process parameters resulted in a MEW scaffold having regular fibers (19 ± 5 μm size) and an acinar cavity showing high shape fidelity. Then, human foreskin fibroblasts (HFF1) and human pancreatic ductal epithelial cells (HPDE), wild-type HPDE, and HPDE overexpressing KRAS oncogene were allowed to colonize the entire 3D structure and the acinar cavity. Thus, a physiologically relevant 3D model was created in vitro after 24 days using a co-culture protocol (14 days of HFF1 alone plus 10 days of HPDE and HFF1 co-culture). The effect of cell crosstalk within the MEW scaffolds was also assessed by monitoring HFF1 secretion of interleukin (IL)-6, a pro-inflammatory cytokine responsible for the inflammatory cascade occurring in pancreatic cancer. High levels of IL-6 were detected only when fibroblasts were co-cultured with the HPDE overexpressing KRAS. These findings confirmed that the MEW 3D in vitro model is able to recreate the characteristic hallmark of the pathological condition where cancer oncogenes mediate fibroblast activities.
Antifungal Activity and Pharmacokinetics of Posaconazole (SCH 56592) in Treatment and Prevention of Experimental Invasive Pulmonary Aspergillosis: Correlation with Galactomannan Antigenemia

ABSTRACT The antifungal efficacy, safety, and pharmacokinetics of posaconazole (SCH 56592) (POC) were investigated in treatment and prophylaxis of primary pulmonary aspergillosis due to Aspergillus fumigatus in persistently neutropenic rabbits. Antifungal therapy consisted of POC at 2, 6, and 20 mg/kg of body weight per os; itraconazole (ITC) at 2, 6, and 20 mg/kg per os; or amphotericin B (AMB) at 1 mg/kg intravenously. Rabbits treated with POC showed a significant improvement in survival and significant reductions in pulmonary infarct scores, total lung weights, numbers of pulmonary CFU per gram, numbers of computerized-tomography-monitored pulmonary lesions, and levels of galactomannan antigenemia. AMB and POC had comparable therapeutic efficacies by all parameters. By comparison, animals treated with ITC had no significant changes in outcome variables in comparison to those of untreated controls (UC). Rabbits receiving prophylactic POC at all dosages showed a significant reduction in infarct scores, total lung weights, and organism clearance from lung tissue in comparison to results for UC (P < 0.01). There was dosage-dependent microbiological clearance of A. fumigatus from lung tissue in response to POC. Serum creatinine levels were greater (P < 0.01) in AMB-treated animals than in UC and POC- or ITC-treated rabbits. There was no elevation of serum hepatic transaminase levels in POC- or ITC-treated rabbits. The pharmacokinetics of POC and ITC in plasma demonstrated dose dependency after multiple dosing. The 2-, 6-, and 20-mg/kg dosages of POC maintained plasma drug levels above the MICs for the entire 24-h dosing interval. In summary, POC at ≥6 mg/kg/day per os generated sustained concentrations in plasma of ≥1 μg/ml that were as effective in the treatment and prevention of invasive pulmonary aspergillosis as AMB at 1 mg/kg/day and more effective than cyclodextrin ITC at ≥6 mg/kg/day per os in persistently neutropenic rabbits.
Comprehensive discharge planning and home follow-up of hospitalized elders: a randomized clinical trial.

CONTEXT Comprehensive discharge planning by advanced practice nurses has demonstrated short-term reductions in readmissions of elderly patients, but the benefits of more intensive follow-up of hospitalized elders at risk for poor outcomes after discharge has not been studied. OBJECTIVE To examine the effectiveness of an advanced practice nurse-centered discharge planning and home follow-up intervention for elders at risk for hospital readmissions. DESIGN Randomized clinical trial with follow-up at 2, 6, 12, and 24 weeks after index hospital discharge. SETTING Two urban, academically affiliated hospitals in Philadelphia, Pa. PARTICIPANTS Eligible patients were 65 years or older, hospitalized between August 1992 and March 1996, and had 1 of several medical and surgical reasons for admission. INTERVENTION Intervention group patients received a comprehensive discharge planning and home follow-up protocol designed specifically for elders at risk for poor outcomes after discharge and implemented by advanced practice nurses. MAIN OUTCOME MEASURES Readmissions, time to first readmission, acute care visits after discharge, costs, functional status, depression, and patient satisfaction. RESULTS A total of 363 patients (186 in the control group and 177 in the intervention group) were enrolled in the study; 70% of intervention and 74% of control subjects completed the trial. Mean age of sample was 75 years; 50% were men and 45% were black. By week 24 after the index hospital discharge, control group patients were more likely than intervention group patients to be readmitted at least once (37.1 % vs 20.3 %; P<.001). Fewer intervention group patients had multiple readmissions (6.2% vs 14.5%; P = .01) and the intervention group had fewer hospital days per patient (1.53 vs 4.09 days; P<.001). Time to first readmission was increased in the intervention group (P<.001). At 24 weeks after discharge, total Medicare reimbursements for health services were about $1.2 million in the control group vs about $0.6 million in the intervention group (P<.001). There were no significant group differences in post-discharge acute care visits, functional status, depression, or patient satisfaction. CONCLUSIONS An advanced practice nurse-centered discharge planning and home care intervention for at-risk hospitalized elders reduced readmissions, lengthened the time between discharge and readmission, and decreased the costs of providing health care. Thus, the intervention demonstrated great potential in promoting positive outcomes for hospitalized elders at high risk for rehospitalization while reducing costs.