Miracle-dz/UniFAR-FTUs huggingface dataset:
Hypertension and Exercise Training Differentially Affect Oxytocin and Oxytocin Receptor Expression in the Brain

We have previously shown that exercise training activates nucleus tractus solitarii (NTS) oxytocinergic projections, resulting in blunted exercise tachycardia. The objective of this study was to determine the effects of hypertension and training on oxytocin (OT) and OT receptor expression in the hypothalamic paraventricular nucleus (PVN) and projection areas (dorsal brain stem [DBS]). Male, normotensive, Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats were trained (55% maximal exercise capacity, 3 months) or kept sedentary, and pressure was measured weekly. DBS sections were processed for immunohistochemistry (polyclonal guinea pig anti-OT) or in situ hybridization for OT and OT receptor (35S-oligonucleotide probes). Other groups of rats had brains removed and frozen to isolate the DBS and PVN; samples were processed for OT and OT receptor cDNA reverse transcription–polymerase chain reaction amplification with &bgr;-actin as the housekeeping gene. Training was equally effective in improving running distance in both groups, with pressure reduction only in SHR (−10%, P<0.05). In trained WKY, baseline bradycardia (P<0.05) occurred simultaneously with increased NTS OT immunostaining and mRNA expression (+3.5-fold), without any change in OT receptor mRNA expression. PVN OT mRNA and DBS OT receptor mRNA expressions were significantly lower in SHR versus WKY (−39% and −56%, respectively). Training did not alter DBS OT receptor density in the SHR group but increased OT mRNA in both PVN and DBS areas (+78% and +45%, respectively). Our results show a marked hypertension-induced reduction in OT receptor mRNA expression, not altered by training. In contrast, training increased OT mRNA expression in sedentary and hypertensive rats, which may facilitate training-induced cardiac performance.
Restriction Fragment Length Polymorphism Analysis of the Fimbrillin Locus, fimA, of Porphyromonas gingivalis

With hybridization probes derived from the fimbrial locus of Porphyromonas gingivalis strain 381, fimA381 ' restriction fragment length polymorphisms (RFLPs) were examined at the fimbrillin locus in 39 human and animal strains of this species. The 39 strains were subdivided into nine RFLP groups (I-IX) after genomic digests were probed with the internal coding sequence of the fimA381 gene. Thirty-three strains showed one or more AluI fragments of moderate-to-high homology (≥77%) with the internal coding sequence of fimA381 . These strains were distributed into the first seven RFLP groups, based solely on the size of the major hybridizing AluI fragment. Five human strains (RFLP Group VIII) had only one Alu I fragment that hybridized very poorly with this probe. One animal strain did not have homology at all (RFLP Group IX). When all AluI fragments that hybridized with fimA381 were analyzed, RFLP groups I-VIII were further differentiated into 25 distinct RFLP patterns. Hybridizations were also performed with the internal coding sequence of fimA381 to probe PstI genomic digests of selected strains that appeared to have lesser homology with fimA381. These hybridizations were performed to determine the level and location of the region of poor homology within the fimA genes of these strains. The results suggested that fimbrial coding sequences are more commonly conserved between these strains in the 5'-region of the fimA locus (≥92% sequence homology). However, the five human strains of RFLP Group VIII had only one PstI fragment that hybridized very poorly with a probe derived from fimA381 coding sequence, and this sequence homology (only > 66%) was located in the central or 3'-end of the fimA gene. The 5'-region of the fimA allele in Group VIII strains did not have any detectable sequence homology. In contrast, the Group VIII strains were highly homologous with the sequences flanking the fimA381 gene. This indicates that these strains do possess a fimA allele at the same chromosomal location as fimA381 .
High-Throughput Assay for the Identification of Compounds Regulating Osteogenic Differentiation of Human Mesenchymal Stromal Cells

Human mesenchymal stromal cells are regarded as the golden standard for cell-based therapies. They present multilineage differentiation potential and trophic and immunosuppressive abilities, making them the best candidate for clinical applications. Several molecules have been described to increase bone formation and were mainly discovered by candidate approaches towards known signaling pathways controlling osteogenesis. However, their bone forming potential is still limited, making the search for novel molecules a necessity. High-throughput screening (HTS) not only allows the screening of a large number of diverse chemical compounds, but also allows the discovery of unexpected signaling pathways and molecular mechanisms for a certain application, even without the prior knowledge of the full molecular pathway. Typically HTS is performed in cell lines, however, in this manuscript we have performed a phenotypical screen on more clinically relevant human mesenchymal stromal cells, as a proof of principle that HTS can be performed in those cells and can be used to find small molecules that impact stem cell fate. From a library of pharmacologically active small molecules, we were able to identify novel compounds with increased osteogenic activity. These compounds allowed achieving levels of bone-specific alkaline phosphatase higher than any other combination previously known. By combining biochemical techniques, we were able to demonstrate that a medium to high-throughput phenotypic assay can be performed in academic research laboratories allowing the discovery of novel molecules able to enhance stem cell differentiation.
Comment on "Influence of the Southern Oscillation on tropospheric temperature" by J. D. McLean, C. R. de Freitas, and R. M. Carter

[1] McLean et al. (2009) (henceforth MFC09) claim that the El Nino–Southern Oscillation (ENSO), as represented by the Southern Oscillation Index (SOI), accounts for as much as 72% of the global tropospheric temperature anomaly and an even higher 81% of this anomaly in the tropics. They conclude that the SOI is a “dominant and consistent influence on mean global temperatures,” “and perhaps recent trends in global temperatures. ” However, their analysis is inappropriate in a number of ways and overstates the influence of ENSO on the climate system. This comment first briefly reviews what is understood about the influence of ENSO on global temperatures and then shows that the analysis of MFC09 greatly overestimates the correlation between temperature anomalies and the SOI by inflating the power in the 2–6 year time window while filtering out variability on longer and shorter time scales. The suggestion in their conclusions that ENSO may be a major contributor to recent trends in global temperature is not supported by their analysis or any physical theory presented in their paper, especially as the analysis method itself eliminates the influence of trends on the purported correlations.
Static Reference Analysis for GUI Objects in Android Software

The popularity of Android software has grown dramatically in the last few years. It is essential for researchers in programming languages and compilers to contribute new techniques in this increasingly important area. Such techniques require a foundation of program analyses for Android. The target of our work is static object reference analysis, which models the flow of object references. Existing reference analyses cannot be applied directly to Android because the software is component-based and event-driven. An Android application is driven by a graphical user interface (GUI), with GUI objects responding to user actions. These objects and the event handlers associated with them ultimately determine the possible flow of control and data. We propose the first static analysis to model GUI-related Android objects, their flow through the application, and their interactions with each other via the abstractions defined by the Android platform. A formal semantics for the relevant Android constructs is developed to provide a solid foundation for this and other analyses. Next, we propose a constraint-based reference analysis based on the semantics. The analysis employs a constraint graph to model the flow of GUI objects, the hierarchical structure of these objects, and the effects of relevant Android operations. Experimental evaluation on real-world Android applications strongly suggests that the analysis achieves high precision with low cost. The analysis enables static modeling of control/data flow that is foundational for compiler analyses, instrumentation for event/interaction profiling, static error checking, security analysis, test generation, and automated debugging. It provides a key component to be used by compile-time analysis researchers in the growing area of Android software.
Pharmacotherapy and psychotherapy for body dysmorphic disorder.

BACKGROUND Body dysmorphic disorder (BDD) is a prevalent and disabling preoccupation with a slight or imagined defect in appearance. Trials have investigated the use of serotonin reuptake inhibitors (SRIs) and cognitive behaviour therapy (CBT) for BDD. OBJECTIVES To assess the efficacy of pharmacotherapy, psychotherapy or a combination of both treatment modalities for body dysmorphic disorder. SEARCH STRATEGY We searched the Cochrane Depression, Anxiety and Neurosis Trial Register (December 2007), the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 4, 2007), MEDLINE (January 1966 to December 2007), and PsycINFO (1967 to December 2007). Ongoing and unpublished trials were located through searching the metaRegister of Controlled Trials, the CRISP and WHO ICTRP search portals (databases searched in December 2007), and through contacting key researchers and pharmaceutical companies. Additional studies were located through study reference lists. SELECTION CRITERIA Randomised controlled trials (RCTs) of patients meeting DSM or ICD diagnostic criteria for BDD, in which the trials compare pharmacotherapy, psychotherapy or multi-modal treatment groups with active or non-active control groups. Short or long-term trials were eligible. DATA COLLECTION AND ANALYSIS Two review authors independently assessed RCTs for inclusion in the review, collated trial data, and assessed trial quality. Investigators were contacted to obtain missing data. Summary effect sizes for dichotomous and continuous outcomes were calculated using a random effects model and heterogeneity was assessed. MAIN RESULTS Two pharmacotherapy and three psychotherapy trials were eligible for inclusion in the review, with data from four short-term RCTs (169 participants) available for analysis. Response data from a single placebo-controlled trial of fluoxetine suggested overall superiority of medication relative to placebo (relative risk (RR) 3.07, 95% CI 1.4 to 6.72, n = 67). Symptom severity was also significantly reduced in the RCTs of fluoxetine and clomipramine (relative to desipramine), as well as in the two CBT trials (WMD -44.96, 95% CI -54.43 to -35.49, n = 73). A low relapse rate (4/22) was demonstrated in one trial of CBT. AUTHORS' CONCLUSIONS Results from the small number of available RCTs suggest that SRIs and CBT may be useful in treating patients with BDD. The findings of these studies need to be replicated. In addition, future controlled studies in other samples, such as adolescents, and using other selective SRIs, as well as a range of psychological therapy approaches and modalities (alone and in combination), are essential in supplementing the sparse data currently available.
Cancer Management and Research Dovepress Decitabine in the Treatment of Acute Myeloid Leukemia in Elderly Patients

The majority of patients with acute myeloid leukemia (AML) are elderly and have a poor prognosis despite induction therapy. Decitabine, a DNA-hypomethylating agent that induces differentiation and apoptosis of leukemic cells, is a well-tolerated alternative to aggressive chemotherapy. It is currently FDA-approved for myelodysplastic syndrome, including patients with 20%–30% bone marrow blasts. Recent clinical attention has focused on evaluating decitabine as frontline therapy for untreated high-risk elderly AML patients. A large randomized international phase III study comparing decitabine to supportive care and cytarabine in elderly AML patients demonstrated significantly improved complete remission rates, but the survival difference did not reach significance. Due to this, decitabine did not achieve FDA approval for AML, but continues to be used off-label. Current research is focused on further defining subgroups of elderly AML patients who may derive greater benefit from decitabine therapy and combining it with other low-intensity active agents for AML.
Expression of the cannabinoid receptor CB1 in distinct neuronal subpopulations in the adult mouse forebrain

Cannabinoids can modulate motor behaviour, learning and memory, cognition and pain perception. These effects correlate with the expression of the cannabinoid receptor 1 (CB1) and with the presence of endogenous cannabinoids in the brain. In trying to obtain further insights into the mechanisms underlying the modulatory effects of cannabinoids, CB1‐positive neurons were determined in the murine forebrain at a single cell resolution. We performed a double in situ hybridization study to detect mRNA of CB1 in combination with mRNA of glutamic acid decarboxylase 65k, neuropeptide cholecystokinin (CCK), parvalbumin, calretinin and calbindin D28k, respectively. Our results revealed that CB1‐expressing cells can be divided into distinct neuronal subpopulations. There is a clear distinction between neurons containing CB1 mRNA either at high levels or low levels. The majority of high CB1‐expressing cells are GABAergic (γ‐aminobutyric acid) neurons belonging mainly to the cholecystokinin‐positive and parvalbumin‐negative type of interneurons (basket cells) and, to a lower extent, to the calbindin D28k‐positive mid‐proximal dendritic inhibitory interneurons. Only a fraction of low CB1‐expressing cells is GABAergic. In the hippocampus, amygdala and entorhinal cortex area, CB1 mRNA is present at low but significant levels in many non‐GABAergic cells that can be considered as projecting principal neurons. Thus, a complex mechanism appears to underlie the modulatory effects of cannabinoids. They might act on principal glutamatergic circuits as well as modulate local GABAergic inhibitory circuits. CB1 is very highly coexpressed with CCK. It is known that cannabinoids and CCK often have opposite effects on behaviour and physiology. Therefore, we suggest that a putative cross‐talk between cannabinoids and CCK might exist and will be relevant to better understanding of physiology and pharmacology of the cannabinoid system.
Could HLA-DR B1*11 allele be a clue for predicting extra-pulmonary sarcoidosis?

BACKGROUND Several HLA-DR alleles have been described as a potential risk factor for sarcoidosis between distinct ethnic groups however the relationship between HLA-DR alleles and extra-pulmonary sarcoidosis (EPS) is still scarce. OBJECTIVES The aim of this prospective study is to investigate the relationship between extra-pulmonary involvement and HLA-DR genetic analysis in Turkish patients with sarcoidosis. METHODS In this study, we HLA-typed sarcoidosis patients with and without extra-pulmonary involvement, and compared with healthy control subjects. The presence of EPS was evaluated with previously defined standard criteria (ACCESS) and only patients with definite and probable involvement were accepted as positive. Sequence Specific Oligonucletide Probes method was used for typing of HLA-DRB1 alleles from DNA samples in both groups. RESULTS The frequency of HLA DRB1*15 allele was more frequent in patients with sarcoidosis than controls (% 20.4 vs % 9.6)(pcorr=0.017). According to multivariate analysis (MVA), the presence of HLA DRB1*15 was indicated as an independent risk factor for sarcoidosis (OR:2.37; 95% CI: 1.31-4.30, p=0.004). Extra-pulmonary involvement was present in 39 patients (42.9 %). When the patients with and without extra-pulmonary involvement compared, HLADRB1*11 allele was significantly higher in patients without extra-pulmonary sarcoidosis which may be concluded as a protective allele for systemic involvement (%30.8 vs. %15.4)(p<0.05). This result was also confirmed with the MVA (OR:0.35, %95 CI:0.15-0.84, p=0.018). CONCLUSIONS We demonstrated a strong positive link between the haplotype HLA DRB1*15 and sarcoidosis in a Turkish Caucasian population and a potential protective effect of HLA DRB1*11 from extra-pulmonary involvement of disease.
Human Fear Acquisition Deficits in Relation to Genetic Variants of the Corticotropin Releasing Hormone Receptor 1 and the Serotonin Transporter

The ability to identify predictors of aversive events allows organisms to appropriately respond to these events, and failure to acquire these fear contingencies can lead to maladaptive contextual anxiety. Recently, preclinical studies demonstrated that the corticotropin-releasing factor and serotonin systems are interactively involved in adaptive fear acquisition. Here, 150 healthy medication-free human subjects completed a cue and context fear conditioning procedure in a virtual reality environment. Fear potentiation of the eyeblink startle reflex (FPS) was measured to assess both uninstructed fear acquisition and instructed fear expression. All participants were genotyped for polymorphisms located within regulatory regions of the corticotropin releasing hormone receptor 1 (CRHR1 - rs878886) and the serotonin transporter (5HTTLPR). These polymorphisms have previously been linked to panic disorder and anxious symptomology and personality, respectively. G-allele carriers of CRHR1 (rs878886) showed no acquisition of fear conditioned responses (FPS) to the threat cue in the uninstructed phase, whereas fear acquisition was present in C/C homozygotes. Moreover, carrying the risk alleles of both rs878886 (G-allele) and 5HTTLPR (short allele) was associated with increased FPS to the threat context during this phase. After explicit instructions regarding the threat contingency were given, the cue FPS and context FPS normalized in all genotype groups. The present results indicate that genetic variability in the corticotropin-releasing hormone receptor 1, especially in interaction with the 5HTTLPR, is involved in the acquisition of fear in humans. This translates prior animal findings to the human realm.
Thermostable Hexameric Form of Eis (Rv2416c) Protein of M. tuberculosis Plays an Important Role for Enhanced Intracellular Survival within Macrophages

Eis protein is reported to enhance the intracellular survival of Mycobacterium tuberculosis in human macrophages. Eis protein is not only known to skew away the immunity by disturbing the protective TH1 response, but aminoglycoside acetyltransferase activity of Eis is reported to regulate autophagy, inflammation and cell death. Here we have gained insight into the structure-function properties of Eis. Eis protein is a hexameric αβ protein. Although urea and guanidinium hydrochloride (GdmCl) was found to induce one-step unfolding of Eis but size exclusion chromatography showed that GdmCl treated Eis maintained its hexameric form. SDS-PAGE assay confirmed that hexameric form of Eis is partially stable to SDS and converts into trimers and monomers. Out of these three forms, aminoglycoside acetyltransferase activity is found to be associated only with hexamers. The Tm of Eis was found to be ∼75°C. Aminoglycoside acetyltransferase Eis demonstrated remarkable heat stability retaining >80% of their activity at 70°C which falls down to ∼50% at 75°C and is completely inactive at 80°C. Further, intracellular survival assay with heated samples of M. smegmatis harboring eis gene of M. tuberculosis H37Rv demonstrated a possible role for the thermostability associated with Eis protein in the enhanced intracellular survival within macrophages. In sum, these data reveal that only hexameric form of Eis has a thermostable aminoglycoside acetyltransferase activity. This is the first report showing the thermostability associated with aminoglycoside acetyltransferase activity of Eis protein being one of the essential features for the execution of its biological role.
Expression Comparison of Oil Biosynthesis Genes in Oil Palm Mesocarp Tissue Using Custom Array

Gene expression changes that occur during mesocarp development are a major research focus in oil palm research due to the economic importance of this tissue and the relatively rapid increase in lipid content to very high levels at fruit ripeness. Here, we report the development of a transcriptome-based 105,000-probe oil palm mesocarp microarray. The expression of genes involved in fatty acid (FA) and triacylglycerol (TAG) assembly, along with the tricarboxylic acid cycle (TCA) and glycolysis pathway at 16 Weeks After Anthesis (WAA) exhibited significantly higher signals compared to those obtained from a cross-species hybridization to the Arabidopsis (p-value < 0.01), and rice (p-value < 0.01) arrays. The oil palm microarray data also showed comparable correlation of expression (r2 = 0.569, p < 0.01) throughout mesocarp development to transcriptome (RNA sequencing) data, and improved correlation over quantitative real-time PCR (qPCR) (r2 = 0.721, p < 0.01) of the same RNA samples. The results confirm the advantage of the custom microarray over commercially available arrays derived from model species. We demonstrate the utility of this custom microarray to gain a better understanding of gene expression patterns in the oil palm mesocarp that may lead to increasing future oil yield.
Dynamic Power Allocation for Downlink Interference Management in a Two-Tier OFDMA Network

We study the downlink interference problem in a two-tier orthogonal frequency-division multiple-access (OFDMA) system. Assume that macro- and femtotiers share the same spectrum and that the femtotier uses a closed-access scheme. Cross-tier and intercell interference in the two tiers is investigated. Resorting to game theory and variational inequality (VI) theory, we formulate the problem mathematically and design algorithms for the solution. With the algorithms, the femto base stations (FBSs) can dynamically allocate their power according to the feedback from the macrotier to avoid cross-tier interference and to adapt to intercell interference. The overall power allocation of the femtotier reaches an equilibrium, provided that every FBS aims to maximize its own Shannon capacity. The algorithms can be distributively implemented and can mitigate the interference quickly without unnecessary performance loss. Simulation results are provided to demonstrate the performance of our algorithms and to compare with other related algorithms.