Miracle-dz/UniFAR-FTUs huggingface dataset:
Complement-Fixing Antigens of Herpes Simplex Virus Types 1 and 2: Reactivity of Capsid, Envelope, and Soluble Antigens

Capsid, envelope, and nonvirion-associated soluble components of type 1 and type 2 herpes simplex virus (HSV) were obtained from infected monolayer cell cultures and used as complement fixation (CF) antigens. Capsids were prepared by treatment of cells with the nonionic detergent Nonidet-P40, envelope material by treatment of virions with ether and high pH, and soluble components were obtained from culture fluids of untreated cells. Serological studies with experimental anti-herpesvirus sera indicate that these serotypes share cross-reacting envelope, capsid, and soluble antigens with each other and with herpesvirus B but not with varicella virus. In addition, animals immunized with crude HSV preparations contain high levels of CF antibody (1:32 to 1:64) to soluble antigens, whereas sera from humans who have experienced natural infection contain low levels of antibody (≤1:8) to this antigen. Further testing with reference, capsid, and envelope antigens indicates that antibody levels to reference and capsid antigens are about the same in sera from healthy humans, whereas antibody to the envelope is decidedly lower in these sera. Herpes convalescent-phase sera contain higher levels of antibody to reference and envelope antigens than to capsid antigen.
Resolvin D2 decreases TLR4 expression to mediate resolution in human monocytes

TLRs are critical for innate immunity, but excessive activation can lead to tissue damage and disease. Specialized proresolving mediators (SPMs), including resolvin D2 (RvD2), promote the active resolution of inflammation. How SPMs regulate early LPS signaling, including activation of TLR4, is unknown. We treated human THP‐1 monocytic cells and primary human blood monocytes with RvD2 and LPS to evaluate modulation of TLRs. miRNA‐146a overexpression and inhibition were used to dissect the mechanism of RvD2‐mediated actions. We validated our studies using ELISAs for cytokines, PCR, Western blot analysis, and flow cytometry. Cells treated with 0.1% ethanol (control for RvD2) and/or PBS (control for LPS), and control microRNA mimics and inhibitors were used as controls. RvD2 reduced LPS‐induced cytokines and TLR4 expression in human monocytes by up to 75%. In THP‐1 cells, RvD2 reduced expression of TLR4, lymphocyte antigen 96 (MD‐2), and downstream signals (MyD88, TRIF, and TAK1). These effects were partially mediated through RvD2 induction of microRNA‐146a, and RvD2's actions were blocked by microRNA‐146a inhibition. These new findings reveal the ability of RvD2 to reduce TLR4 expression and attenuate LPS‐induced inflammation, providing a new area of SPM activity to investigate in this major area of therapeutic research. —Croasdell, A. , Sime, P. J., Phipps, R. P. Resolvin D2 decreases TLR4 expression tomediate resolution in humanmonocytes. FASEB J. 30, 3181–3193 (2016). www.fasebj. org
Effects of female steroid hormones on A‐type K+ currents in murine colon

Idiopathic constipation is higher in women of reproductive age than postmenopausal women or men, suggesting that female steroid hormones influence gastrointestinal motility. How female hormones affect motility is unclear. Colonic motility is regulated by ion channels in colonic myocytes. Voltage‐dependent K+ channels serve to set the excitability of colonic muscles. We investigated regulation of Kv4.3 channel expression in response to acute or chronic changes in female hormones. Patch clamp experiments and quantitative PCR were used to compare outward currents and transcript expression in colonic myocytes from male, non‐pregnant, pregnant and ovariectomized mice. Groups of ovariectomized mice received injections of oestrogen or progesterone to investigate the effects of hormone replacement. The capacitance of colonic myocytes from non‐pregnant females was larger than in males. Net outward current density in male and ovariectomized mice was higher than in non‐pregnant females and oestrogen‐treated ovariectomized mice. Current densities in late pregnancy were lower than in female controls. Progesterone had no effect on outward currents. A‐type currents were decreased in non‐pregnant females compared with ovariectomized mice, and were further decreased by pregnancy or oestrogen replacement. Kv4.3 transcripts did not differ significantly between groups; however, expression of the potassium channel interacting protein KChIP1 was elevated in ovariectomized mice compared with female controls and oestrogen‐treated ovariectomized mice. Delayed rectifier currents were not affected by oestrogen. In the mouse colon, oestrogen suppresses A‐type currents, which are important for regulating excitability. These observations suggest a possible link between female hormones and altered colonic motility associated with menses, pregnancy and menopause.
The impact of heavy metals on the activity of carbonic anhydrase from rainbow trout (Oncorhynchus mykiss) kidney

Many environmental and health problems have become a consequence of contamination of soil and water by toxic heavy metals and organic pollutants in the present age of technology. Heavy metals play vital roles in enzyme activities and other metabolic events with their bioaccumulative and nonbiodegradable properties among aquatic pollutants. Metal toxicity causes irregular metallothioneins protein synthesis, renal damage, and disruption of bone structure in humans and wildlife. In this study, we investigated in vitro effects of some metals on chemical-targeted carbonic anhydrase (CA) enzyme from rainbow trout kidney. The enzyme was purified with a specific activity of 17,285 EU × mg−1 and 31.7% yield and approximately 1800-fold using simple affinity purification method. Molecular weights of the subunit and native enzyme were estimated as 28.7 kDa and 26.9 kDa via sodium dodecyl sulfate polyacrylamide gel electrophoresis and Sephadex-G 200 column, respectively. Other kinetic properties of the enzyme were determined. Apparent Km , V max and k cat values were 0.40 mM, 0.097 µmol min−1 and 15.2 s−1 for p-nitrophenylacetate substrate, respectively. Inhibitory effects of cobalt, zinc, copper, cadmium and silver on CA activity were determined using the esterase method under in vitro conditions. IC50 and Ki values were calculated for metals. Ki values for Co2+, Zn2+, Cu2+, Cd2+ and Ag+ were 0.035, 1.2, 34.8, 103 and 257 from Lineweaver–Burk graphs, respectively. Consequently, in vitro inhibition rank order was determined as Co2+ > Zn2+ > Cu2+ > Cd2+ > Ag+. The potential inhibitor for CA was found as Co2+ from these results.
The β isotypes of tubulin in neuronal differentiation

The differences among the vertebrate β isotypes of tubulin are highly conserved in evolution, suggesting that they have functional significance. To address this, we have used differentiating neuroblastoma cells as a model system. These cells express the βI, βII, and βIII isotypes. Although there is no difference prior to differentiation, a striking difference is seen after differentiation. Both βI and βIII occur in cell bodies and neurites, while βII occurs mostly in neurites. Knocking down βI causes a large decrease in cell viability while silencing βII and βIII does not. Knocking down βII causes a large decrease in neurite outgrowth without affecting viability. Knocking down βIII has little effect on neurite outgrowth and only decreases viability if cells are treated with glutamate and glycine, a combination known to generate free radicals and reactive oxygen species. It appears, therefore, that βI is required for cell viability, βII for neurite outgrowth and βIII for protection against free radicals and reactive oxygen species. © 2010 Wiley‐Liss, Inc.
Benefits, Potential Harms, and Optimal Use of Nutritional Supplementation for Preventing Progression of Age-Related Macular Degeneration

Objective: To briefly review age-related macular degeneration (AMD), the main findings from the Age Related Eye Disease Study (AREDS) report number 8 on the use of nutritional supplements for AMD, and to focus on data suggesting that supplement use should be guided using genetic testing of AMD risk genes. Data Sources: A literature search (January 2001 through October 26, 2016) was conducted using MEDLINE and the following MeSH terms: Antioxidants/therapeutic use, Genotype, Macular Degeneration/drug therapy, Macular degeneration/genetics, Dietary Supplements, Proteins/genetics, and Zinc Compounds/therapeutic use. Bibliographies of publications identified were also reviewed. Study Selection and Data Extraction: English-language studies assessing AREDS supplement response in patients with AMD in relation to complement factor H gene (CFH) and age-related maculopathy susceptibility 2 gene (ARMS2) risk alleles were evaluated. Data Synthesis: Three of the 4 studies demonstrated a treatment interaction between ARMS2 and CFH genotypes and a differential response to supplements. The fourth study documented an interaction for the CFH genotype only. Reported response interactions included attenuated response, no response, and good response, whereas a subset showed increased progression of AMD. Conversely, one study reported no interactions between CFH and ARMS2 risk alleles and response to supplements. Conclusions: The weight of the evidence supports using genetic testing to guide selection of ocular vitamin use. This approach will avoid using supplements that could speed the progression of AMD in vulnerable patients, avoid using supplements that will have little to no effect in others, and result in appropriately using supplements in those that are likely to derive meaningful benefits.
The androgen receptor CAG repeat modifies the impact of testosterone on insulin resistance in women with polycystic ovary syndrome.

OBJECTIVE Hyperandrogenism is a central feature of the polycystic ovary syndrome (PCOS) and might worsen insulin resistance (IR) often seen in PCOS. Androgens act through the androgen receptor (AR). A polymorphic CAG repeat sequence within the AR gene was reported to modulate its transactivation activity. Therefore, we investigated a putative interaction between testosterone and the CAG repeat length polymorphism with respect to IR. DESIGN In 63 PCOS women with normal glucose tolerance free testosterone, the biallelic CAG repeat length and a multiplicative interaction term were investigated by multiple linear regression analysis for an association with IR as indicated by the homeostasis model assessment of IR (HOMA-IR). RESULTS Free testosterone was correlated with HOMA-IR. The impact of testosterone on HOMA-IR was modified by the AR CAG length as indicated by an interaction term. This interaction remained significant after adjustment for smoking, age and body mass index. While there was a positive association of free testosterone with HOMA-IR, the interaction term was inversely associated. The model, which explained 42.5% of the variation of HOMA-IR predicted that in carriers of short CAG lengths, an increase in testosterone increased IR. This effect attenuated with rising biallelic CAG length until it turns into the opposite at a CAG length longer than 23. The results were confirmed by using CIGMA as another measure of IR. CONCLUSIONS The association between testosterone and IR is modified by the CAG repeat polymorphism within the AR. Therefore, the evaluation of testosterone effects on IR seems to require consideration of the AR CAG repeat polymorphism in PCOS women.
The success rate and complications of awake caudal epidural bupivacaine alone or in combination with intravenous midazolam and ketamine in pre-term infants

Background: The aim of the present study is to compare the success rate and complications of caudal epidural bupivacaine alone or in combination with intravenous (IV) midazolam and ketamine in awake infants undergoing lower abdominal surgery. Materials and Methods: In this double-blind, clinical trial study, 90 infants (aged below 3 months and weight below 5 kg) with American Society of Anaesthesiologists I-II, were divided into three groups of each 30: Group 1 received bupivacaine 0.25%, 1 mL/kg for caudal epidural block; Groups 2 and 3 received caudal block with same dose bupivacaine along with IV pre-treatment with midazolam 0.1 mg/kg or IV midazolam 0.1 mg/kg and ketamine 0.3 mg/kg, respectively. Results: The success rates in Groups 2 and 3 were 93.3% and 93.1%, respectively, compared with a caudal block with bupivacaine alone 80%; P = 0.015). There was no significant difference among the three groups in terms of mean systolic and diastolic blood pressures and mean heart rate at intervals of 0, 20, 40 and 60 min (P < 0.05). There were no significant differences in the pain scores >3 on the Neonatal Infant Pain Scale at three intervals (30, 60 and 120 min) after surgery among the three groups. The complications such as apnoea or desaturation were not found in any of the studied groups. Conclusions: Adding IV ketamine and/or midazolam to bupivacaine caudal epidural block in the conscious infants can positively affect block success rate.
Leukemic Phase of B-Cell Lymphomas Mimicking Chronic Lymphocytic Leukemia and Variants at Presentation

Six cases of non-Hodgkin B-cell lymphoma that mimicked either chronic lymphocytic leukemia (CLL) or a CLL variant at presentation are reported. The patients ranged from 54 to 89 years and included three females and three males. All six patients had prominent peripheral blood lymphocytosis at presentation; the initial morphologic impression was CLL in three cases, CLL/prolymphocytic leukemia (PLL) in two cases, and PLL in one. Five patients had bone marrow biopsies; each showed a lymphoid infiltrate in a focally random, interstitial, and/or diffuse pattern. Flow cytometric immunophenotyping showed CD20-positive B cells with surface immunoglobulin (Ig) light chain restriction in all six patients. The five cases resembling CLL or CLL/PLL had at least a subset of CD5-positive B cells, whereas CD5 was absent in the one case that resembled PLL. CD23 was positive in three of the four cases studied that resembled CLL or CLL/PLL; CD79b was positive in three, FMC7 was positive in two, and surface Ig and CD20 were brightly positive in three. A t(11;14) (q13;q32) was found in four cases that resembled CLL or CLL/PLL; they were subsequently diagnosed as mantle cell lymphoma. The remaining two cases mimicking CLL or PLL were diagnosed as lymphomas of follicle center origin with leukemic phase based on the presence of t(14;18) (q32;q21). Thus although the morphology of these six cases resembled CLL or variants, and immunophenotyping by flow cytometry showed overlapping features, genetic studies enabled distinction of these leukemic non-Hodgkin lymphoma from chronic lymphocytic leukemia or variants.
IL 6 Mediates Immune and Colorectal Cancer Cell Cross-talk via miR-21 and miR-29 b

Tumors are surrounded and infiltrated by a variety of stromal cell types, including fibroblasts, immune cells, and vascular endothelial cells, which interact with malignant cells to generate the tumormicroenvironment (TME). This complex environment is thought to be regulated by the tumor in order to promote its survival and progression and thus constitutes a potential target for cancer therapy. However, intercellular communication within the microenvironment is not yet well understood. The current study investigates the mechanism by which cancer and immune cells communicate using an in vitro coculture model. It is demonstrated that IL6, a proinflammatory cytokine, secreted by immune cells promotes colorectal cancer cell invasiveness. In addition, in the presence of IL6, the cancer cells were able to secrete circulating miRNAs miR-21 and miR-29b to further induce immune cell IL6 production. Activated immune cells were also found to release miR-21 into the TME. Taken together, these mechanistic findings provide a better understanding of intercellular communication between immune and cancer cells in the TME and offer insight into some of the key players that mediate this cross-talk. Implications: This study demonstrates that cocultured cancer and immune cells communicate via IL6 and circulating miRNAs to sustain chronic inflammation and promote prometastatic cancer cell behavior. In addition, critical players are identified that mediate intercellular communication in the TME and suggest possible therapeutic approaches that target the microenvironment. Mol Cancer Res; 13(11); 1502–8. 2015 AACR.
PREVALENCE OF HAEMONCHUS CONTORTUS IN MARKHOR OF CHITRAL GOL NATIONAL PARK

This study was conducted to investigate infection of Haemonchus contortus in the markhor population of Chitral Gol National Park (CGNP). For this purpose 25 faecal samples were collected randomly from different spots at enough distance from each other to prevent repetition. These samples were then microscopically analyzed for the presence of H. contortus. Out of these 25 samples, 10 (40%) were positive for the parasite. Diagnosis was made through larval identification most of which were in L2 stagemolting into L3. Our study shows H. contortus presence in markhor population of CGNP. To investigate the health status of markhor, damage being caused by the parasite and role of local livestock in transmitting the parasite to markhors of the park, however, needs further comprehensive surveys.
Heme Oxygenase-1 Is Not Decreased in Preeclamptic Placenta and Does Not Negatively Regulate Placental Soluble fms-Like Tyrosine Kinase-1 or Soluble Endoglin Secretion

Elevated placental release of the antiangiogenic factors, soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin (sENG), is central to the pathophysiology of preeclampsia. It is widely accepted that heme oxygenase-1 (HO-1) is decreased in preeclamptic placenta and negatively regulates sFlt-1 and sENG production. We set out to verify these contentions. There was no difference in HO-1 mRNA or protein levels in preterm preeclamptic placentas (n=17) compared with gestationally matched controls (n=27). In silico analysis of microarray studies did not identify decreased placental HO-1 expression in preeclamptic placenta. Silencing HO-1 in primary trophoblasts did not affect sFlt-1 protein secretion after 24 or 48 hours. Silencing nuclear factor (erythroid-derived 2)-like 2 (transcription factor that upregulates HO-1) in trophoblasts also did not affect sFlt-1 secretion. Administering tin protoporphyrin IX dichloride (HO-1 inhibitor) or cobalt protoporphyrin (HO-1 inducer) into placental explants did not affect sFlt-1 or sENG secretion. Silencing HO-1 in 2 types of primary endothelial cells (human umbilical vein endothelial and uterine microvascular endothelial cells) significantly increased sFlt-1 secretion but not sENG secretion. However, HO-1 silencing selectively increased mRNA expression of sFlt-1 i13 (generically expressed sFlt-1 variant) but not of sFlt-1 e15a (sFlt-1 variant mainly expressed in placenta). Furthermore, adding tin protoporphyrin IX dichloride decreased sFlt-1, whereas adding HO-1 inducers (cobalt protoporphyrin, dimethyl fumarate, and rosiglitazone) either had no effect or increased sFlt-1 or sENG secretion (these trends are opposite to what is expected). We conclude that HO-1 expression is not decreased in preeclamptic placenta and HO-1 does not negatively regulate placental sFlt-1 and sENG secretion in placental or endothelial cells.
Spirituality and Complex Partial Epileptic-Like Signs

Using a sample of 262 undergraduate volunteers, correlational and regressional analyses were completed to examine the relation of self-reported complex partial epileptic-like signs to a five-dimensional model of spirituality assessed by the Expressions of Spirituality Inventory. Analyses show that spirituality is significantly predictive of Complex Partial Epileptic-like Signs. Scores from subscales Paranormal Beliefs, Experiential/Phenomenological Dimension, and Existential Well-being uniquely accounted for significant portions of Complex Partial Epileptic-like Signs variance. ESI Cognitive Orientation Toward Spirituality significantly correlated with Complex Partial Epileptic-like Signs but it was not a significant predictor in regression analyses. ESI Religiousness was unrelated to Complex Partial Epileptic-like Signs in all analyses. This pattern of relations remained largely the same when participants' age, sex, and reported religious involvement were controlled. The paper includes a discussion of the meaning of the findings and suggestions for research.
Targeting Hepatitis B Virus-Infected Cells with a T-Cell Receptor-Like Antibody

ABSTRACT Virus-specific CD8 T cells are activated when their T-cell receptors (TCRs) recognize the specific viral peptide/major histocompatibility complex (MHC) class I (pMHC) complexes present on the surface of infected cells. Antibodies able to recognize the specific pMHC can mimic TCR specificity and both represent a valuable biological tool to visualize pMHC complexes on infected cells and serve as a delivery system for highly targeted therapies. To evaluate these possibilities, we created a monoclonal antibody able to specifically recognize a hepatitis B virus (HBV) envelope epitope (Env at positions 183 to 91 [Env183-91]) presented by the HLA-A201 molecule, and we tested its ability to recognize HBV-infected hepatocytes and to deliver a cargo to a specific target. We demonstrate that this antibody detects and visualizes the processed product of HBV proteins produced in naturally HBV-infected cells, is not inhibited by soluble HBV proteins present in patient sera, and mediates the intracellular delivery of a fluorescent molecule to target cells. Additionally, compared to CD8 T cells specific for the same HBV epitope, the TCR-like antibody has both a superior sensitivity and a specificity focused on distinct amino acids within the epitope. These data demonstrate that a T-cell receptor-like antibody can be used to determine the quantitative relationship between HBV replication and specific antigen presentation to CD8 T cells and serves as a novel therapeutic delivery platform for personalized health care for HBV-infected patients.
Crude Oil and Agricultural Futures: An Analysis of Correlation Dynamics

Correlations between oil and agricultural commodities have varied over previous decades, impacted by renewable fuels policy and turbulent economic conditions. We estimate smooth transition conditional correlation models for 12 agricultural commodities and WTI crude oil. While a structural change in correlations occurred concurrently with the introduction of biofuel policy, oil and food price levels are also key influences. High correlation between biofuel feedstocks and oil is more likely to occur when food and oil price levels are high. Correlation with oil returns is strong for biofuel feedstocks, unlike with other agricultural futures, suggesting limited contagion from energy to food markets.