Miracle-dz/UniFAR-FTUs huggingface dataset:
Variants of kappa-opioid receptor gene and mRNA in alcohol-preferring and alcohol-avoiding mice.

Results of recent studies have indicated an association between voluntary alcohol intake and activities of kappa-opioid receptor systems in animal models. We assessed the possibility that genetic differences observed in alcohol preference among mouse strains are related to possible polymorphisms of the kappa-opioid receptor gene (Oprk1). We compared DNA sequences of the coding region and the promoter/regulatory region of Oprk1 among C57BL/6ByJ (B6, alcohol-preferring), BALB/cJ (alcohol-avoiding), CXBI (alcohol-avoiding), and six B6.C and B6.I Recombinant QTL Introgression (RQI) strains, which carry approximately 3% of the donor BALB/cJ genome in the background B6 genome and showed various alcohol preferences. Although there were no sequence differences in the coding region, BALB/cJ had a single nucleotide polymorphism (SNP) in the promoter region, which was not detected in other strains. The results indicate that the difference in alcohol preference between B6 and BALB/cJ is not correlated with polymorphisms of Oprk1. However, results of further studies comparing Oprk1 mRNA expression between B6 and BALB/cJ showed that Oprk1 expression is regulated differently in these strains. Also, DBA/2J mice (alcohol-avoiding) showed expression of Oprk1 mRNA subtypes (alternatively spliced) different from B6 and BALB/cJ mice. Search of the Celera Genomics database indicated that DBA/2J had several SNP sites in the promoter/regulatory regions, which might explain the different expression of Oprk1 mRNA subtypes in this strain. The strain-dependent variation in the expression of alternatively spliced genes can be a significant source of phenotypic variation of complex traits such as alcohol preference.
Renewing membership in three community-based health insurance schemes in rural India.

Low renewal rate is a key challenge facing the sustainability of community-based health insurance (CBHI) schemes. While there is a large literature on initial enrolment into such schemes, there is limited evidence on the factors that impede renewal. This article uses longitudinal data to analyse what determines renewal, both 1 year and 2 years after the introduction of three CBHI schemes, which have been operating in rural Bihar and Uttar Pradesh since 2011. We find that initial scheme uptake is ∼23-24% and that 2 years after scheme operation, only ∼20% of the initial enrolees maintain their membership. A household's socio-economic status does not seem to play a large role in impeding renewal. In some instances, a greater understanding of the scheme boosts renewal. The link between health status and use of health care in maintaining renewal is mixed. The clearest effect is that individuals living in households that have received benefits from the scheme are substantially more likely to renew their contracts. We conclude that the low retention rates may be attributed to limited benefit packages, slow claims processing times and the gap between the amounts claimed and amounts paid out by insurance.
Endothelial MHC Class II Antigen Expression and Endarteritis Associated with Marek's Disease Virus Infection in Chickens

Experimental Marek's disease virus (MDV) infection in chickens was used to study the early pathogenesis of virus-induced atherosclerosis. Previous investigations using this model have reported the occurrence of atherosclerotic lesions after approximately 7 months postinfection. In this study, a total of 75 susceptible Cornell P-line chickens were inoculated intraperitoneally with the CU-2 strain of MDV at 3 days of age and subsequently perfused for histologic examination. At 2, 4, 8, 13, and 20 weeks postinoculation, the ascending aorta and the brachiocephalic and coronary arteries were evaluated for early changes. Expression of class II major histocompatibility complex (Ia) antigen by the vascular endothelium was demonstrated by indirect immunodetection as early as 2 weeks after virus inoculation. This change was followed by significant thickening of the intimai layer associated with mononuclear cell infiltration. All the arteries examined from the MDV-infected chickens were affected. Preliminary immunohistochemical staining showed the presence of CD3+ CD4+, and CD8+ cells among the infiltrating cells. The results suggest that an immunopathologic mechanism may be involved in the early pathogenesis of MDV-induced atherosclerosis in chickens.
The Increase in O-Linked N-Acetylglucosamine Protein Modification Stimulates Chondrogenic Differentiation Both in Vitro and in Vivo*

Background: The molecular mechanisms associated with insulin-induced chondrocyte differentiation are unknown. Results: Insulin-induced chondrocyte differentiation occurred with an early accumulation of O-linked N-acetylglucosamine-modified proteins. O-GlcNAcylation accumulation per se led to chondrocyte differentiation in vitro and in vivo. Conclusion: O-GlcNAcylation induces chondrocyte differentiation. Significance: This is the first evidence of O-GlcNAcylation regulation of chondrogenic differentiation. Insulin is an inducer of chondrocyte hypertrophy and growth plate chondrogenesis, although the specific molecular mechanisms behind these effects are mostly unknown. Our aim was to investigate whether insulin-induced chondrocyte hypertrophy occurs through a modification in the amount of O-linked N-acetylglucosamine (O-GlcNAc)-modified proteins and in the expression of the key enzymes of this pathway, O-GlcNAc transferase and O-GlcNAcase (OGA). We also studied if O-GlcNAc accumulation per se, induced by an OGA inhibitor, was able to induce pre-hypertrophic chondrocyte differentiation both in vitro and in vivo. Insulin-induced differentiation of ATDC5 pre-chondrocytes occurred alongside a gradual increase in the accumulation of O-GlcNac-modified proteins (O-GlcNAcylated proteins), as well as an increase in the expression of O-GlcNAc transferase and OGA. In the absence of insulin, O-GlcNAc accumulation induced by thiamet-G, a specific OGA inhibitor, was able to increase the gene expression of differentiation markers, as well as the activity of MMP-2 and -9. Thiamet-G also activated pERK, p-JNK, and p-p38 and the O-GlcNAcylation of Akt. Thiamet-G administration to C57/bl mice induced a significant expansion in the growth plate height and in the hypertrophic zone height. Therefore, our results show that O-GlcNAc glycosylation has chondromodulating activity.
Neuropsychological Function in Patients With Chronic Fatigue Syndrome, Multiple Sclerosis, and Depression

Patients with chronic fatigue syndrome (CFS), multiple sclerosis (MS), and major depression were compared with controls and with each other on a neuropsychological battery that included standard neuropsychological tests and a computerized set of tasks that spanned the same areas of ability. A total of 101 participants were examined, including 29 participants with CFS, 24 with MS, 23 with major depressive disorder, and 25 healthy controls. There were significant differences among the groups in 3 out of 5 cognitive domains: memory, language, and spatial ability. Assessment of psychiatric symptoms indicated that all 3 patient groups had a higher prevalence of depression than the controls. A total measure of psychiatric symptomatology also differentiated the patients from the controls. After covarying the cognitive test scores by a measure of depression, the patient groups continued to differ from controls primarily in the area of memory. The findings support the view that the cognitive deficits found in CFS cannot be attributed solely to the presence of depressive symptomatology in the patients.
Interlaboratory concordance of PD‐L1 immunohistochemistry for non‐small‐cell lung cancer

Programmed death ligand 1 (PD‐L1) immunohistochemistry has become a mandatory diagnostic test in the treatment of lung cancer. Several research initiatives have started to harmonise the five PD‐L1 immunohistochemistry assays that have been used in clinical trials. Here, we report data on interlaboratory and interassay concordance for commercial assays (‘assays’) and laboratory‐developed tests (LDTs) at 10 German testing sites.
Legionella oakridgensis: unusual new species isolated from cooling tower water

We describe a new species of Legionella represented by 10 strains isolated from industrial cooling towers. Legionella oakridgensis differed genetically from the other seven species of Legionella in DNA hybridization studies and differed serologically in direct fluorescent-antibody tests. The new species, unlike all other species except L. jordanis, did not require added L-cysteine for growth in serial transfer on charcoal-yeast extract agar. L. oakridgensis, as well as three other species tested, required L-cysteine for primary isolation from animal tissues. L. oakridgensis was the only species of Legionella that failed to produce alkaline phosphatase at pH 8.5. In all other respects, it resembled other species of Legionella, including having a high content of branched-chain cellular fatty acids and being pathogenic for guinea pigs. These bacteria have not yet been associated with human disease, but they are potential causes of legionellosis.
Investigating decoherence in a simple system.

I present the results of some simple calculations designed to study the loss of quantum coherence. The relevant physical issues are briefly reviewed, and then a very simple toy'' model is analyzed. Exact solutions are found using numerical techniques. The type of decoherence exhibited by the model can be changed by varying a coupling strength. I study the system from two points of view. One, the Schmidt paths approach, is closely related to the conventional approach of studying decoherence by checking the form of the density matrix. The consistent histories approach is also used, and the relationship between the two approaches is explored.
Correlation between preoperative computed tomography and operative findings in functional endoscopic sinus surgery

This study investigated the correlation between diagnostic parameters and surgical findings in patients undergoing functional endoscopic sinus surgery (FESS) for chronic sinusitis. The parameters that were reviewed included the radiologist's report on the computed tomographic (CT) scan, the surgeon's reading of the CT scan, the operative findings, and the histopathology report.
Does Interscalene Catheter Placement with Stimulating Catheters Improve Postoperative Pain or Functional Outcome After Shoulder Surgery? A Prospective, Randomized and Double-Blinded Trial

BACKGROUND: In this prospective, randomized, double-blind trial we investigated the use of stimulating catheters in patients during and after shoulder surgery; functional improvement being the primary outcome measurement. METHODS: After eliciting an adequate muscular twitch at ≤0.5 mA nerve stimulation output, the perineural catheter was advanced either blindly (conventional catheter = CC group, n = 20) or guided by stimulation via the catheter (stimulating catheter = SC group, n = 20). A bolus of 40 mL prilocaine 1% and 10 mL ropivacaine 0.75% was injected, followed by a patient-controlled infusion of ropivacaine 0.2% (8 mL/h infusion rate, bolus 2 mL, lockout time 20 min). RESULTS: Onset of motor block was faster in the SC group, whereas sensory block did not differ between groups. Median pain scores on two postoperative days were equal. Improvement of the objective shoulder function score (Constant Murley Score) 6 wk postoperatively was enhanced to a clinically relevant extent in the SC group compared to the CC group (P < 0.01). CONCLUSIONS: We conclude that the use of a stimulating catheter results in a faster onset of motor block, unaltered postoperative pain, and a significantly improved functional outcome 6 wk after shoulder surgery.
Farnesyl Pyrophosphate Synthase Is an Essential Enzyme in Trypanosoma brucei

We report the cloning and sequencing of a gene encoding the farnesyl pyrophosphate synthase (FPPS) ofTrypanosoma brucei. The protein (TbFPPS) is an attractive target for drug development because the growth of T. bruceihas been shown to be inhibited by analogs of its substrates, the nitrogen containing bisphosphonates currently in use in bone resorption therapy. The protein predicted from the nucleotide sequence of the gene has 367 amino acids and a molecular mass of 42 kDa. Several sequence motifs found in other FPPSs are present in TbFPPS, including an 11-mer peptide insertion present also in the Trypanosoma cruziFPPS. Heterologous expression of TbFPPS inEscherichia coli produced a functional enzyme that was inhibited by several nitrogen-containing bisphosphonates, such as pamidronate and risedronate. Risedronate was active in vivoagainst T. brucei infection in mice (giving a 60% survival rate), but pamidronate was not effective. The essential nature ofTbFPPS was studied using RNA interference (RNAi) to inhibit the expression of the gene. Expression of TbFPPSdouble-stranded RNA in procyclic trypomastigotes caused specific degradation of mRNA. After 4 days of RNAi, the parasite growth rate declined and the cells subsequently died. Similar results were obtained with bloodstream form trypomastigotes, except that the RNAi system in this case was leaky and mRNA levels and parasites recovered with time. Molecular modeling and structure-activity investigations of enzyme and in vitro growth inhibition data resulted in similar pharmacophores, further validating TbFPPS as the target for bisphosphonates. These results establish that FPPS is essential for parasite viability and validate this enzyme as a target for drug development.
Hand carriage of aerobic Gram-negative rods by health care personnel

SUMMARY A quantitative culture technique (hand washed in a glove containing broth for 30 s) was used to determine the frequency of hand carriage of aerobic Gram-negative rods by various groups of health care workers and 104 control subjects. Overall, 31 % of health care workers carried aerobic Gram-negative rods on their hands compared to 59% of control subjects (P < 0.001). Enterobacter agglomerans accounted for 40% of the isolates, and other Enterobacter spp. 7%. Other organisms included Acinetobacter calcoaceticus 21 %, Serratia spp. 11%, Klebsiella spp. 10%, Moraxella spp. 3%, Pseudomonas spp. 3%, Proteus spp. 1.5%, Escherichia coli 1%; Morganella morganii, Citrobacter freundii, Aeromonas sp. and an isolate that was not speciated accounted for 0.5% each. We conclude that endemic hand carriage of aerobic Gram-negative rods by health care personnel is common, but significantly less than that of control subjects. Enterobacter agglomerans is found so frequently on the hands of control subjects that it must be considered part of the normal hand flora.
Sensitization of CD4+ T Cells to Coagulation Factor VIII: Response in Congenital and Acquired Hemophilia Patients and in Healthy Subjects

Summary Antibodies (Ab) that inhibit factor VIII (fVIII) may develop in patients with hemophilia A and rarely in individuals without congenital fVIII deficiency (acquired hemophilia). Synthesis of fVIII inhibitors requires CD4+ T cells. We investigated the proliferative response of blood CD4+ cells from 11 patients with congenital or acquired hemophilia and 12 healthy subjects, to recombinant human fVIII, and to pools of overlapping synthetic peptides spanning the sequences of individual fVIII domains. All patients had CD4+ cells that responded to fVIII. The intensity of the responses fluctuated over time: several patients had brief periods when they did not respond to fVIII. All healthy subjects had transient CD4+ responses to fVIII, that were significantly lower than those of hemophilia patients. Also, healthy subjects responded to fVIII less frequently and for shorter periods than hemophilia patients. All patients and healthy subjects recognized several fVIII domains: the A3 domain was recognized most strongly and frequently. The transient sensitization of CD4+ cells to fVIII in healthy subjects suggests that inadequate tolerization of CD4+ cells to fVIII, due to lack of endogenous fVIII, is an important factor in the development of clinically significant anti-fVIII antibodies in hemophilia A.
Histone H3 Threonine 11 Phosphorylation Is Catalyzed Directly by the Meiosis-Specific Kinase Mek1 and Provides a Molecular Readout of Mek1 Activity in Vivo

Saccharomyces cerevisiae Mek1 is a CHK2/Rad53-family kinase that regulates meiotic recombination and progression upon its activation in response to DNA double-strand breaks (DSBs). The full catalog of direct Mek1 phosphorylation targets remains unknown. Here, we show that phosphorylation of histone H3 on threonine 11 (H3 T11ph) is induced by meiotic DSBs in S. cerevisiae and Schizosaccharomyces pombe. Molecular genetic experiments in S. cerevisiae confirmed that Mek1 is required for H3 T11ph and revealed that phosphorylation is rapidly reversed when Mek1 kinase is no longer active. Reconstituting histone phosphorylation in vitro with recombinant proteins demonstrated that Mek1 directly catalyzes H3 T11 phosphorylation. Mutating H3 T11 to nonphosphorylatable residues conferred no detectable defects in otherwise unperturbed meiosis, although the mutations modestly reduced spore viability in certain strains where Rad51 is used for strand exchange in place of Dmc1. H3 T11ph is therefore mostly dispensable for Mek1 function. However, H3 T11ph provides an excellent marker of ongoing Mek1 kinase activity in vivo. Anti-H3 T11ph chromatin immunoprecipitation followed by deep sequencing demonstrated that H3 T11ph was highly enriched at presumed sites of attachment of chromatin to chromosome axes, gave a more modest signal along chromatin loops, and was present at still lower levels immediately adjacent to DSB hotspots. These localization patterns closely tracked the distribution of Red1 and Hop1, axis proteins required for Mek1 activation. These findings provide insight into the spatial disposition of Mek1 kinase activity and the higher order organization of recombining meiotic chromosomes.
Cost efficiency and its determinants in the hotel industry

This study employs a stochastic frontier model to estimate cost efficiency and its determinants in the hotel industry in Spain between 2008 and 2012. Measuring cost efficiency provides useful information on the performance of hotels to management, shareholders and, in general, to all stakeholders. Cost control is an issue managers are particularly concerned about, as it gives a competitive advantage that allows hotels to perform better. The results indicate that the inefficiency in average costs for the sample considered is 32.44% and is time invariant. The results also show that labour productivity, the accumulation of knowledge and location are factors that largely determine the differences in efficiency between hotels. These findings have important implications for public policymakers and hotel management, specifically, policies aimed at improving the skills of hotels’ human resources should be encouraged. Likewise, both location and the accumulation of knowledge are strategic resources that hotel management must include in their competitive strategies to increase efficiency.
A Spodoptera exigua Cadherin Serves as a Putative Receptor for Bacillus thuringiensis Cry1Ca Toxin and Shows Differential Enhancement of Cry1Ca and Cry1Ac Toxicity

ABSTRACT Crystal toxin Cry1Ca from Bacillus thuringiensis has an insecticidal spectrum encompassing lepidopteran insects that are tolerant to current commercially used B. thuringiensis crops (Bt crops) expressing Cry1A toxins and may be useful as a potential bioinsecticide. The mode of action of Cry1A is fairly well understood. However, whether Cry1Ca interacts with the same receptor proteins as Cry1A remains unproven. In the present paper, we first cloned a cadherin-like gene, SeCad1b, from Spodoptera exigua (relatively susceptible to Cry1Ca). SeCad1b was highly expressed in the larval gut but scarcely detected in fat body, Malpighian tubules, and remaining carcass. Second, we bacterially expressed truncated cadherin rSeCad1bp and its interspecific homologue rHaBtRp from Helicoverpa armigera (more sensitive to Cry1Ac) containing the putative toxin-binding regions. Competitive binding assays showed that both Cry1Ca and Cry1Ac could bind to rSeCad1bp and rHaBtRp, and they did not compete with each other. Third, Cry1Ca ingestion killed larvae and decreased the weight of surviving larvae. Dietary introduction of SeCad1b double-stranded RNA (dsRNA) reduced approximately 80% of the target mRNA and partially alleviated the negative effect of Cry1Ca on larval survival and growth. Lastly, rSeCad1bp and rHaBtRp differentially enhanced the negative effects of Cry1Ca and Cry1Ac on the larval mortalities and growth of S. exigua and H. armigera. Thus, we provide the first lines of evidence to suggest that SeCad1b from S. exigua is a functional receptor of Cry1Ca.
Oximetry and indications for tracheotomy for amyotrophic lateral sclerosis.

STUDY OBJECTIVE To explore the use of oximetry as a guide for using respiratory aids and tracheotomy in the treatment of patients with amyotrophic lateral sclerosis (ALS). SETTING A retrospective review of all ALS patients presenting to a neuromuscular disease clinic since 1996. METHODS Patients who were symptomatic for nocturnal hypoventilation were prescribed noninvasive ventilation (NIV). Patients with assisted cough peak flows of < 300 L/min were prescribed oximeters and access to mechanically assisted coughing (MAC) to prevent or reverse decreases in baseline pulse oximetric saturation (Spo(2)) levels of < 95%. The number of decreases in baseline Spo(2) that could be normalized by any combination of NIV and MAC and the duration of normalization were recorded. When the baseline was not or could not be normalized, the time to acute respiratory failure and tracheotomy or death were recorded. RESULTS Twenty-five patients became dependent on NIV, including 13 patients who received NIV continuously for a mean (+/- SD) period of 19.7 +/- 16.9 months, without desaturation (group 1). For another 76 patients, the daytime baseline Spo(2) level decreased to < 95% 78 times. For 41 patients, the baseline level was corrected by NIV/MAC (group 2) for a mean duration of 11.1 +/- 8.7 months before desaturation reoccurred for 27 patients. Of the latter patients, 11 underwent tracheotomy, 14 died in < 2 months, and 2 had their condition again corrected by the addition of MAC therapy. For 35 patients, the desaturation was not or could not be normalized (group 3). Thirty-three of these 35 patients required tracheotomy or died within 2 months. The only significant difference between groups 1 and 2 and group 3 was significantly poorer glottic function in the patients in group 3. CONCLUSION Tracheotomy or death is highly likely within 2 months of a decrease in baseline Spo(2) that cannot be corrected by NIV or MAC. The long-term use of NIV and MAC, and the avoidance of tracheotomy is dependent on glottic function rather than on inspiratory or expiratory muscle failure.