Miracle-dz/UniFAR-FTUs huggingface dataset:
Antisense oligonucleotides directed at the bcl-xl gene product augment chemotherapy response in mesothelioma.

OBJECTIVE Malignant pleural mesothelioma (MPM) is resistant to both conventional chemotherapy and apoptosis. The bcl-2 family proteins are major determinants of apoptotic homeostasis. MPM lines and tumors routinely overexpress the anti-apoptotic protein BCL-XL. We have previously shown that antisense inhibition of BCL-XL in MPM cells leads to apoptosis. We sought to determine whether antisense oligonucleotides directed at the bcl-xl gene product would augment response to a conventional chemotherapeutic agent in human mesothelioma cell lines. METHODS The human MPM cell lines REN and I-45 were exposed to two bcl-xl antisense oligonucleotides (15999, 16009) and one sense oligonucleotide (113529) construct at varying doses, followed by IC(50) cisplatin. Cellular viability was assessed by a calorimetric assay, and apoptosis was evaluated by Hoechst staining, Annexin V staining, and sub-G(1) fluorescence-activated cell sorter analysis. Western blot analysis of BCL-2 family proteins was performed following single agent and combined treatment. Isobologram mathematical analysis was used to determine whether or not combination therapies were additive or synergistic. RESULTS Cell viability was most affected with the 15999 antisense oligonucleotides plus IC(50) cisplatin combination (70% of I-45 and 90% of REN cells killed), and apoptosis was markedly increased with this combination by all measures. Western blot demonstrated 15999 antisense oligonucleotides construct down-regulation of BCL-XL, but no further effect on expression of BCL-2 proteins with cisplatin. Isobologram analysis demonstrated 15999 + cisplatin synergistic effect. CONCLUSIONS Exposure of human MPM cells to bcl-xl antisense oligonucleotides sensitizes human mesothelioma cells to the conventional chemotherapeutic agent cisplatin. Similar approaches using a combination of molecular and conventional treatment may have clinical utility for this tumor.
The Use of Nicardipine for Electroconvulsive Therapy: A Dose-Ranging Study

A wide variety of vasoactive drugs have been used to treat the acute hypertensive response to electroconvulsive therapy (ECT). We designed this randomized, double-blind, saline-controlled, crossover study to compare three different doses of nicardipine when administered before the ECT stimulus. Twenty-five patients undergoing a series of 4 ECT treatments received bolus injections of either saline or nicardipine 20, 40, or 80 &mgr;g/kg IV in a random sequence during a standardized methohexital (1 mg/kg) and succinylcholine (1 mg/kg) anesthetic technique. The mean arterial blood pressure (MAP) and heart rate values were recorded at specific time intervals, as were the duration of seizure activity and the need for rescue labetalol. Both the 40 and 80 &mgr;g/kg doses of nicardipine reduced the percentage increase in MAP above the baseline value compared with the saline group (7% and 7% versus 30%, respectively). Nicardipine 40 and 80 &mgr;g/kg were also associated with a significant reduction in the need for labetalol (7 ± 3 mg and 5 ± 0 mg versus 22 ± 10 mg in the saline group). Compared with the 40 &mgr;g/kg dose, nicardipine 80 &mgr;g/kg was associated with a more rapid heart rate at the time the ECT stimulus was applied. The 80 &mgr;g/kg dose was also associated with a reduced MAP value on awakening compared with the baseline value (91 ± 12 mm Hg versus 102 ± 8 mm Hg). We conclude that a bolus injection of nicardipine 40 &mgr;g/kg IV immediately before the ECT stimulus was optimal for controlling the acute hemodynamic response to ECT treatments.
Shoot initiation and multiplication from a mature tree of Terminalia arjuna roxb

SummaryThis study describes a protocol for the regeneration of complete plantlets of Terminalia arjuna from nodal explants of mature trees. Shoot multiplication from nodal explants was achieved by culturing on Murashige and Skoog (MS) medium containing different concentrations of 6-benzyladenine (BA), thidiazuron or kinetin, or BA in combination with α-naphthaleneacetic acid (NAA). The best shoot multiplication response was obtained from nodal explants grown on modified MS (half-strength major salts and Fe-EDTA) medium containing 4.44 μM BA and 0.53 μM NAA. Seasonal variations significantly affected the proliferation potential of nodal explants and best proliferation was observed from explants collected during April to May. Microshoots were rooted on half-strength MS medium with 4.92 μM IBA. The rooted shoots were acclimatized successfully.
AN ORGANIC VERSUS A CONVENTIONAL FARMING SYSTEM IN KIWIFRUIT

To determine the feasibility of growing kiwifruit organically, a kiwifruit vineyard converted to an organic farm was compared to a conventionally farmed vineyard from 1990 through 1992. January or March applications of composted chicken manure (organic system) or NH4NO3 plus CaNH 4(NO3)3 through micro sprinklers during the growing season (conventional system) were applied to give nearly equal rates of 168 kg N ha. Soil analysis showed a trend toward a higher pH and organic matter over time for the organic system. In 1992, there was a trend for the organic system to have higher NH4-N and lower NO3-N concentration in the soil. Leaf nitrogen levels from the organic system were consistently lower than those from the conventional system but were not deficient. Leaf concentrations of sodium and chloride increased over the three-year period in the organic system but not to phytotoxic levels. Leaf zinc levels were adequate and increased over time in both systems. Organically grown fruit was as firm as or firmer than conventionally grown fruit at harvest and four months after harvest. No differences were seen in percent soluble solids content. Damage from latania scale and omnivorous leaf roller was small in both systems except scale damage in the organic system in 1992. An economic analysis of the cultural practices showed that the organic system cost almost $720 per ha more then the conventional system. The grower reported fewer repack losses for organically grown fruit in 1992. We conclude that growing kiwifruit organically is feasible if an economic premium is received.
Regional cerebral blood flow in frontal lobe dementia of non-Alzheimer type.

Twenty-five out of 26 cases of autopsy-verified frontal lobe degeneration of non-Alzheimer type (FLD) were found to have focal frontal or frontotemporal blood flow reductions involving both hemispheres. The deviant case had an asymmetric frontal pathology only apparent on the right side. Focal reduction of blood flow in the frontal lobes is, however, a common and unspecific flow abnormality found in e.g. Pick's disease. Creutzfeldt-Jakob's disease, and in some cases of Alzheimer's disease. Low frontal flow has also been reported in schizophrenia and in toxic encephalopathy. Since a characteristic feature of FLD is a steady progress of the pathology, serial flow measurements extending over several years are especially informative.
Gene Regulatory Network Inference Using Prominent Swarm Intelligence Methods

Genes are the basic blue print of life in an organism containing the physiological and behavioral characteristics. A gene regulatory network (GRN) is a set of genes, or parts of genes, that interact with each other to control a specific cell function. GRN inference is the reverse engineering approach to predict the biological network from the gene expression data. Biochemical system theory based S-System is a popular model in GRN inference and the model is defined with its different parameters. The task of S-System based GRN inference is its parameter estimation which is an optimization problem. Several studies employed Particle Swarm Optimization (PSO) and other pioneer optimization techniques to estimate S-System model. In this paper several prominent swarm intelligence (SI) techniques have been studied and adapted for S-System parameter estimation. They are Group Search Optimizer, Grey Wolf Optimizer and PSO. Proficiency of optimization techniques are compared to infer GRN from SOS DNA real gene expression data and DREAM 4 Silico data.
Low-grade systemic inflammation causes endothelial dysfunction in patients with Hashimoto's thyroiditis.

OBJECTIVE The objective of this study was to assess whether low-grade systemic inflammation might contribute to the pathogenesis of endothelial dysfunction in patients with subclinical hypothyroidism (sHT) and autoimmune thyroiditis. BACKGROUND sHT patients are characterized by peripheral endothelial dysfunction and low-grade inflammation. METHODS In 53 sHT and 45 healthy subjects, we studied the forearm blood flow (strain-gauge plethysmography) response to intrabrachial acetylcholine (Ach) (0.15-15 microg/min.dl) with and without local vascular COX inhibition by intrabrachial indomethacin (50 microg/min.dl) or nitric oxide synthase blockade by N-mono methyl arginine (L-NMMA) (100 microg/min.dl) or the antioxidant vitamin C (8 mg/min.dl). The protocol was repeated 2 h after systemic nonselective COX inhibition (100 mg indomethacin) or selective COX-2 blockade (200 mg celecoxib) oral administrations. RESULTS sHT patients showed higher C-reactive protein and IL-6 values. In controls, vasodilation to Ach was blunted by L-NMMA and unchanged by vitamin C. In contrast, in sHT, the response to Ach, reduced in comparison with controls, was resistant to L-NMMA and normalized by vitamin C. In these patients, systemic but not local indomethacin normalized vasodilation to Ach and the inhibition of L-NMMA on Ach. Similar results were obtained with celecoxib. When retested after indomethacin administration, vitamin C no longer succeeded in improving vasodilation to Ach in sHT patients. Response to sodium nitroprusside was unchanged by indomethacin or celecoxib. CONCLUSIONS In sHT patients, low-grade chronic inflammation causes endothelial dysfunction and impaired nitric oxide availability by a COX-2-dependent pathway leading to increased production of oxidative stress.
Antenatal diagnosis of placenta accreta leads to reduced blood loss

Objective. Placenta accreta is one of the most devastating pregnancy complications. We sought to compare outcomes between women with placenta accreta when diagnosed antenatally or intrapartum, and to define predictors of the antenatal diagnosis. Design. Retrospective case–control study. Setting. University teaching hospital. Population. Twenty‐four women with placenta accreta diagnosed antenatally and 20 women discovered intrapartum. Methods. Chart review of historical and delivery‐associated variables. Rates were compared between the groups. Main Outcome Measures. Placenta accreta diagnosed antenatally or intrapartum. Results. Women with antenatal diagnosis had a lower estimated blood loss of a median of 4500ml (range 100–15000ml) compared with 7800ml (range 2500–17000ml, p=0.012) and required fewer units of packed red blood cells transfused (median 7; range 0–27 compared with 13.5; range 4–31, p=0.026). Nineteen (79%) women diagnosed antenatally had balloon catheter occlusion carried out during the cesarean section. Five (21%) had the entire placenta left in situ. There was no difference in the rate of surgical complications or duration of hospitalization. The clinical diagnosis among women with antenatal diagnosis was more often placenta percreta (p=0.013). The risk factor profile of women with antenatal diagnosis of placenta accreta included higher gravidity (p=0.014) and parity (p<0.0001), history of cesarean section (p=0.004), and placenta previa in the current pregnancy (p<0.001). Conclusions. Antenatal diagnosis of placenta accreta may reduce peripartum blood loss and the need for blood transfusion. Women with antenatal diagnosis more often have placenta previa and history of previous cesarean section, and the clinical diagnosis is more often placenta percreta.
The Associations Among Dark Personalities and Sexual Tactics Across Different Scenarios

Although malevolent individuals may be willing to use any tactic necessary to obtain sex, not all antagonistic traits will predict coercion or coaxing in all situations. A sample of 447 adult men, collected in two waves, reported their intentions to engage in coercion or coaxing of hypothetical targets. Study 1 provided three hypothetical scenarios that result in sexual rejection: (a) an expensive date, (b) a stranger, and (c) a relationship partner, and Study 2 provided the same scenarios, and three additional scenarios: (d) a rival’s partner, (e) a bet, and (f) a powerful person. A Structural Equations Model indicated that a common antagonistic factor, indicated by Social Dominance and the Dark Triad traits of psychopathy, narcissism, and Machiavellianism, predicted coaxing across all situations, whereas only psychopathy predicted coercion across all situations. In addition, narcissism accounted for additional variance in coaxing when rejected by an expensive date. These findings suggest that across the different scenarios, psychopathy is primarily associated with coercive tactics and the common malevolent core among the traits is associated with coaxing tactics.
Gender differences in the prevalence and correlates of psychotropic medication use among older adults in Israel.

BACKGROUND This study evaluates gender differences in the prevalence of psychotropic medications use among elderly Israelis and the socio-demographic, physical and mental health correlates of their use. METHOD Data were taken from a national survey that sampled the community-dwelling Jewish population aged 65-94 in Israel. Psychotropic medications were assessed from the list of all medications recorded during a faceto- face interview. The current analysis focused on three medication groups: anxiolytics, sedatives/hypnotics and antidepressants. RESULTS A significantly higher use of anxiolytics was observed among women compared to men after taking into account their worse physical and mental health. Age, not being married, sleeping problems and depressive symptoms were significant correlates among men while number of non-psychotropic medications, any life trauma and being married correlated with use of anxiolytics and sedatives/hypnotics among women. The use of antidepressants was low in men and women and was related mainly to disability in ADL. CONCLUSIONS This study points to possibly overprescribing of anxiolytics among women and low detection and treatment of depression among the elderly in general.
Development and preliminary validation of the cancer family impact scale for colorectal cancer.

AIM The aim of our study was to develop a measure of how a family history of colorectal cancer (CRC) affects families from the viewpoint of unaffected family members. METHOD Using data from 1,285 participants (637 families) in the Johns Hopkins Colon Cancer Genetic Testing study, we developed and validated The Cancer Family Impact Scale (CFIS), an instrument for use in studies investigating relationships among family factors and CRC prevention behaviors when family history is a risk factor. RESULTS Through exploratory factor analysis (EFA) using a 50% random sample of participants, we identified 5 latent constructs among 18 items: (1) NEGATIVE: negative effects of cancer on the family; (2) POSITIVE: positive effects of cancer on the family; (3) COMMUNICATE: how families communicate about cancer; (4) FLOW: how information about cancer is conveyed in families; and (5) NORM: how individuals react to family norms about cancer. Confirmatory factor analysis (CFA) on the same sample showed the CFIS to have a reasonably good fit (chi(2) = 389.97, degree of freedom (df ) = 122, root mean square error of approximation = 0.06 [0.05-0.07], comparative fit index = 0.90, Tucker-Lewis index = 0.88, goodness of fit index = 0.94), and findings were cross-validated on the remaining 50% of the participants. The reliability of the scale was alpha = 0.65. CONCLUSIONS The CFIS could be used to clarify the role that family factors play in the association between CRC family history and CRC prevention behaviors, and also aid in the development and evaluation of family-based cancer prevention interventions.
The Role of Bone Marrow Stem Cells in Liver Regeneration

Hepatic oval cells involved in some forms of liver regeneration express many markers also found on hematopoietic stem cells (HSCs). In addition, multiple independent reports have demonstrated that bone marrow cells can give rise to several hepatic epithelial cell types, including oval cells, hepatocytes, and duct epithelium. These observations have resulted in the hypothesis that bone marrow resident stem cells, specifically HSCs, are an important source for liver epithelial cell replacement, particularly during chronic injury. The function of such stem cells in hepatic injury responses is the topic of this article. Taken together, the published data on the role of bone marrow stem cells in liver damage suggest that they do not play a significant physiological role in the replacement of epithelial cells in any known form of hepatic injury. Fully functional bone marrow-derived hepatocytes exist but are extremely rare and are generated by cell fusion, not stem cell differentiation. Nonetheless, bone marrow-derived cells may play important indirect roles in liver regeneration. First, they may serve as a source for the replacement of endothelial cells. Second, hematopoietic cells, including lymphocytes, neutrophils, macrophages, and platelets, may provide crucial factors required for efficient healing of damaged liver.
Transcriptional Profiles of Mart-1(27-35) Epitope Specific TCReng Human CD8+ and CD4+ T Cells upon Epitope Encounter as Elucidated by RNASeq

Adoptive cell therapy (ACT) with in vitro expanded populations of T cells engineered to express tumor epitope specific T cell receptors (TCR) is now undergoing clinical trials for various malignancies. In this context, ACT with the melanoma epitope, Mart-1(27-35), specific TCR engineered T cells has shown encouraging results in metastatic melanoma. A number of biological processes regulating T cell functions have, however, turned out to be impediments in this form of cancer therapy. As such, efforts are underway to gain a fuller understanding of the biology (functionality and constraints) of TCR-engineered (TCReng) T cells so as to extract more robust therapeutic effects from ACT. Traditional T cell-based assays are, however, somewhat inadequate for the purpose. Using Next Generation RNASeq (NGS) and qRT-PCR assays, we examined the transcriptome of melanoma epitope, Mart-1(27-35), specific TCReng human T cells. We found that the transcriptional profiles of the Mart-1(27-35), specific TCReng T cell (both CD8+ and CD4+) is remarkably similar when exposed to the cognate peptide. The genes responsible for T-cell activation, apoptosis, cellular proliferation, cytolytic response, and T-cell differentiation showed similar patterns of expression. Further, our analysis also revealed a number of alternate splice variants and novel isoforms related to immune response previously not associated with T cell activation, as well as expression of a number of recently discovered long non-coding RNAs (lncRNA).
Enzyme Efficiency but Not Thermostability Drives Cefotaxime Resistance Evolution in TEM-1 β-Lactamase

A leading intellectual challenge in evolutionary genetics is to identify the specific phenotypes that drive adaptation. Enzymes offer a particularly promising opportunity to pursue this question, because many enzymes’ contributions to organismal fitness depend on a comparatively small number of experimentally accessible properties. Moreover, on first principles the demands of enzyme thermostability stand in opposition to the demands of catalytic activity. This observation, coupled with the fact that enzymes are only marginally thermostable, motivates the widely held hypothesis that mutations conferring functional improvement require compensatory mutations to restore thermostability. Here, we explicitly test this hypothesis for the first time, using four missense mutations in TEM-1 β-lactamase that jointly increase cefotaxime Minimum Inhibitory Concentration (MIC) ∼1500-fold. First, we report enzymatic efficiency (kcat/KM) and thermostability (Tm, and thence ΔG of folding) for all combinations of these mutations. Next, we fit a quantitative model that predicts MIC as a function of kcat/KM and ΔG. While kcat/KM explains ∼54% of the variance in cefotaxime MIC (∼92% after log transformation), ΔG does not improve explanatory power of the model. We also find that cefotaxime MIC rises more slowly in kcat/KM than predicted. Several explanations for these discrepancies are suggested. Finally, we demonstrate substantial sign epistasis in MIC and kcat/KM, and antagonistic pleiotropy between phenotypes, in spite of near numerical additivity in the system. Thus constraints on selectively accessible trajectories, as well as limitations in our ability to explain such constraints in terms of underlying mechanisms are observed in a comparatively “well-behaved” system.
Genetic Contributions to the Midsagittal Area of the Corpus Callosum

The degree to which genes and environment determine variations in brain structure and function is fundamentally important to understanding normal and disease-related patterns of neural organization and activity. We studied genetic contributions to the midsagittal area of the corpus callosum (CC) in pedigreed baboons (68 males, 112 females) to replicate findings of high genetic contribution to that area of the CC reported in humans, and to determine if the heritability of the CC midsagittal area in adults was modulated by fetal development rate. Measurements of callosal area were obtained from high-resolution MRI scans. Heritability was estimated from pedigree-based maximum likelihood estimation of genetic and non-genetic variance components as implemented in Sequential Oligogenic Linkage Analysis Routines (SOLAR). Our analyses revealed significant heritability for the total area of the CC and all of its subdivisions, with h2 = . 46 for the total CC, and h2 = . 54, . 37, . 62, . 56, and . 29 for genu, anterior midbody, medial midbody, posterior midbody and splenium, respectively. Genetic correlation analysis demonstrated that the individual subdivisions shared between 41% and 98% of genetic variability. Combined with previous research reporting high heritability of other brain structures in baboons, these results reveal a consistent pattern of high heritability for brain morphometric measures in baboons.
An approach to proteomic analysis of human tumors

A strategy for proteomic analysis of microdissected cells derived from human tumor specimens is described and demonstrated by using esophageal cancer as an example. Normal squamous epithelium and corresponding tumor cells from two patients were procured by laser‐capture microdissection and studied by two‐dimensional polyacrylamide gel electrophoresis (2D‐PAGE). Fifty thousand cells resolved approximately 675 distinct proteins (or isoforms) with molecular weights ranging between 10 and 200 kDa and isoelectric points of pH 3–10. Comparison of the microdissected protein profiles showed a high degree of similarity between the matched normal‐tumor samples (98% identical). However, 17 proteins showed tumor‐specific alterations, including 10 that were uniquely present in the tumors and seven that were observed only in the normal epithelium. Two of the altered proteins were characterized by mass spectrometry and immunoblot analysis and were identified as cytokeratin 1 and annexin I. Acquisition of 2D‐PAGE protein profiles, visualization of disregulated proteins, and subsequent determination of the identity of selected proteins through high‐sensitivity MS‐MS microsequencing are possible from microdissected cell populations. These separation and analytical techniques are uniquely capable of detecting tumor‐specific alterations. Continued refinement of techniques and methodologies to determine the abundance and status of proteins in vivo holds great promise for future study of normal cells and associated neoplasms. Mol. Carcinog. 27:158–165, 2000. Published by Wiley‐Liss Inc.