Miracle-dz/UniFAR-FTUs huggingface dataset:
Immunohistochemical determination of in vivo distribution of Bax, a dominant inhibitor of Bcl-2.

The protein encoded by the bcl-2 gene is a regulator of programmed cell death and apoptosis. The cell survival-promoting activity of this protein is opposed by Bax, a homologous protein that forms heterodimers with Bcl-2 and accelerates rates of cell death. In this report, the in vivo patterns of bax gene expression were immunohistochemically assessed in the mouse, with a polyclonal antibody raised against a synthetic peptide corresponding to a unique region in the murine Bax protein. Direct comparisons were made with Bcl-2 by using anti-peptide antisera specific for the mouse Bcl-2 protein. The expression of bax was more widespread than bcl-2. For example, Bax immunoreactivity was present in the hepatocytes of the liver, the exocrine pancreas, and the renal tubule epithelial cells whereas Bcl-2 was absent from these tissues. Both the Bax and Bcl-2 proteins were present in several epithelia examined, including the small intestines, colon, breast, prostate, respiratory tract, and skin. The most intense Bax immunostaining was seen in cells located in the base of the crypts of the small intestinal mucosa, consistent with reports of high rates of spontaneous and inducible apoptosis in this region. Bcl-2 immunostaining was completely absent from these cells but was present in the absorptive epithelial cells of the small intestine. In contrast, Bax immunostaining in the colon tended to be stronger in the surface epithelial cells that had advanced up the crypts towards the lumen and that are destined for programmed cell death, whereas Bcl-2 immunoreactivity generally was stronger in the base of the colonic crypts. Similarly, bax expression in the gastric pits of the stomach occurred in a gradient such that higher levels of Bax immunostaining were found in the upper layers of gastric glands than in the lower regions. In addition, strong Bax immunostaining was detected in the androgen-dependent secretory epithelial cells of the prostate, whereas Bcl-2 was limited to the androgen-independent basal cells. Like Bcl-2, Bax was found in the thymic medulla but not the cortex, despite the propensity for immature cortical thymocytes to undergo apoptosis. Unlike Bcl-2, however, Bax immunostaining tended to be more intense in the germinal center lymphocytes of lymph nodes than in the interfollicular lymphocytes, consistent with the high rate of apoptotic cell death in the former. (ABSTRACT TRUNCATED AT 400 WORDS)
Evaluation of Two Mycotoxin Binders to Reduce Toxicity of Broiler Diets Containing Ochratoxin A and T-2 Toxin Contaminated Grain

Abstract In order to assess ochratoxin A (OA) and T-2 toxin (T-2) binding ability of two commercial sorbents, both in vitro and in vivo trials with broilers were performed. Crude OA and T-2 extracts from contaminated grain were used to assess in vitro binding ability of two sorbents (Zeotek™ [Zk] and Mycofix™ [Mx]), by quantifying free mycotoxin through an enzyme-linked immunosorbent assay (ELISA) test. For in vivo trial, a 3 × 2 × 2 factorial arrangement was used for this experiment, being the factors: adsorbents (none, Zk, and Mx), OA (0 and 567 parts per billion [ppb]) and T-2 (0 and 927 ppb). OA and T-2 contaminated wheat and corn, respectively, were added to sorghum–soybean meal diets to meet 567 ppb of OA and 927 ppb of T-2. Mycotoxins were fed alone or combined in treatments. After 21 days, blood chemistry, gross, and histological evaluations were performed. Relative weights of liver, kidney, and bursa of Fabricius were obtained. Zk had the highest OA and T-2 in vitro binding ability (100% and 8.67%, respectively). Chickens fed OA with or without sorbents had a lower body weight and feed intake reduction. However, those birds fed T-2 were partly protected by a sorbent. Birds fed both toxins showed toxic additive effects, and no protection of any adsorbent was observed. A significant reduction in plasma proteins, albumin, and globulins was a characteristic observed in all birds fed diets with OA both with or without adsorbents. Uric acid level in blood was increased in all chickens fed OA-contaminated diets. Histological findings observed in birds fed OA-contaminated diets were necrosis of kidney tubular cells, swollen and necrotic hepatocytes, bile ducts hyperplasia, and increased diameter of proventriculus glands. In birds that received T-2 alone, only the liver, with the same kind of lesions, was affected. According to these results, it can be concluded that there is not a relation between in vitro and in vivo trials. OA toxic effects could not be counteracted by any sorbent. T-2 toxicity could be partially counteracted by an adsorbent used in this research.
Polyphenol extract of ichnocarpus frutescens leaves modifies hyperglycemia in dexamethasone (dex) treated rats.

INTRODUCTION The leaves of Ichnocarpus frutescens are used extensively as a decoction for the treatment of diabetes mellitus by the tribals of Karnataka and Uttar Pradesh states. METHODS Anti-diabetic activity of polyphenol extract of Ichnocarpus frutescens was investigated using dexamethasone (DEX) induced hyperglycemia in Wistar rats. Experimental animals were injected subcutaneously with dexamethasone 3 mg/kg/day. After one week, hyperglycemic rats were orally treated with polyphenol extract (PPE) extracts at the dose of 300 mg/kg/day and 150 mg/kg/day for a period of 14 days. RESULTS Administration of DEX to fasted rats for 21 days resulted in insulin resistance evidenced by the significant increase in mean fasting blood glucose level (162.33 ± 4.72 mg/dl). Both 300 mg/kg and 150 mg/kg of PPE markedly reversed DEX induced mean fasting blood glucose level to 104.00 ± 3.30 mg/dl and 145.5 ± 1.99 mg/dl, respectively when compared with the positive control (p < 0.01). CONCLUSION The possible mechanism by which polyphenol extract of I. frutescens brings about its antihyperglycemic action might be through potentiation of insulin sensitivity enhanced transport of blood glucose to the peripheral tissues. However, these findings suggest that polyphenol extract of I. frutescens therapy may reduce the risk of dexamethasone induced hyperglycemia in Wistar rats. These observations suggest that I. frutescens is a potential glucose lowering agent to ameliorate glucocorticoids induced hyperglycemia.
7-difluoromethoxyl-5,4'-di-n-octylgenistein inhibits growth of gastric cancer cells through downregulating forkhead box M1.

AIM To investigate whether the 7-difluoromethoxyl-5, 4'-di-n-octylgenistein (DFOG), a novel synthetic genistein analogue, affects the growth of gastric cancer cells and its mechanisms. METHODS A series of genistein analogues were prepared by difluoromethylation and alkylation, and human gastric cancer cell lines AGS and SGC-7901 cultured in vitro were treated with various concentrations of genistein and genistein analogues. The cell viability was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The cells were incubated by DFOG at different concentrations. The growth inhibitory effects were evaluated using MTT and clonogenic assay. The distribution of the phase in cell cycle was analyzed using flow cytometric analysis with propidium iodide staining. The expression of the transcription factor forkhead box M1 (FOXM1) was analyzed by reverse transcription-polymerase chain reaction and Western blotting. The expression levels of CDK1, Cdc25B, cyclin B and p27(KIP1) protein were detected using Western blotting. RESULTS Nine of the genistein analogues had more effective antitumor activity than genistein. Among the tested analogues, DFOG possessed the strongest activity against AGS and SGC-7901 cells in vitro. DFOG significantly inhibited the cell viability and colony formation of AGS and SGC-7901 cells. Moreover, DFOG efficaciously arrested the cell cycle in G2/M phase. DFOG decreased the expression of FOXM1 and its downstream genes, such as CDK1, Cdc25B, cyclin B, and increased p27(KIP1) at protein levels. Knockdown of FOXM1 by small interfering RNA before DFOG treatment resulted in enhanced cell growth inhibition in AGS cells. Up-regulation of FOXM1 by cDNA transfection attenuated DFOG-induced cell growth inhibition in AGS cells. CONCLUSION DFOG inhibits the growth of human gastric cancer cells by down-regulating the FOXM1 expression.
Enhanced surveillance of non-O157 verotoxin-producing Escherichia coli in human stool samples from Manitoba.

BACKGROUND Relatively few enhanced surveillance studies have been undertaken to investigate the extent to which verotoxin-producing non-O157 serotypes of Escherichia coli occur in stool samples received for the detection of verotoxin-producing organisms. OBJECTIVES To describe the prevalence, molecular and epidemiological characteristics, and geographical patterns associated with non-O157 verotoxin-producing E coli (VTEC) in Manitoba. RESULTS Thirty-two VTEC isolates consisting of 10 serogroups and 13 different serotypes were isolated over a 22-month period. Twenty-three isolates (71.8%) possessed verotoxin-encoding gene stx1 only, five isolates (15.6%) possessed stx2 only, two isolates (6.3%) possessed both stx1 and stx2, and two isolates (6.3%) possessed stx2c. Only three instances of indistinguishable pulsed-field gel electrophoresis patterns were identified. The age of the individuals from whom non-O157 VTEC were isolated ranged from eight months to 87 years. Mean and median ages were 30 and 22 years of age, respectively. Some areas of the province appeared to experience a higher than expected number of non-O157 E coli in comparison with the number of stools that were received from these areas. CONCLUSIONS The present study demonstrated a large number of infections associated with non-O157 VTEC in Manitoba. Most non-O157 cases appear to result from sporadic infections, and these occur typically in rural areas. Continued enhanced surveillance is necessary to understand the temporal patterns of non-O157 VTEC and the underlying epidemiological factors driving these patterns.
Promoting public understanding of population health

This chapter addresses the need to apply the information and perspectives described in this volume to improve health. The basic premise of the book is that individual behaviours are less important for producing health than are structures that underlie inequalities in a society. This concept may be thought of as a scientific revolution or new paradigm in our thinking about health, and as with most paradigm shifts, is resisted by both scientists and the general population. Putting these ideas into action will require promoting a broader public understanding and acceptance of the basic determinants of health. The subject of this chapter provides a framework with which to proceed. Citizens of the US, being less healthy than those in other rich countries, are the target group.
Investigating Incipient Speciation in Arabidopsis lyrata from Patterns of Transmission Ratio Distortion

Our understanding of the development of intrinsic reproductive isolation is still largely based on theoretical models and thorough empirical studies on a small number of species. Theory suggests that reproductive isolation develops through accumulation of epistatic genic incompatibilities, also known as Bateson–Dobzhansky–Muller (BDM) incompatibilities. We can detect these from marker transmission ratio distortion (TRD) in hybrid progenies of crosses between species or populations, where TRD is expected to result from selection against heterospecific allele combinations in hybrids. TRD may also manifest itself because of intragenomic conflicts or competition between gametes or zygotes. We studied early stage speciation in Arabidopsis lyrata by investigating patterns of TRD across the genome in F2 progenies of three reciprocal crosses between four natural populations. We found that the degree of TRD increases with genetic distance between crossed populations, but also that reciprocal progenies may differ substantially in their degree of TRD. Chromosomes AL6 and especially AL1 appear to be involved in many single- and two-locus distortions, but the location and source of TRD vary between crosses and between reciprocal progenies. We also found that the majority of single- and two-locus TRD appears to have a gametic, as opposed to zygotic, origin. Thus, while theory on BDM incompatibilities is typically illustrated with derived nuclear alleles proving incompatible in hybrid zygotes, our results suggest a prominent role for distortions emerging before zygote formation.
Effect of Empagliflozin on Tacrolimus‐Induced Pancreas Islet Dysfunction and Renal Injury

An inhibitor of sodium glucose co‐transporter type 2 (SGLT‐2) is recommended in type 2 diabetes mellitus (DM) but its use is still undetermined in tacrolimus (TAC)‐induced DM. We evaluated the effect of empagliflozin (Em) on TAC‐induced pancreatic islet dysfunction and renal injury in an experimental model of TAC‐induced DM and in vitro. TAC induced a twofold increase in SGLT‐2 expression, while Em decreased SGLT‐2 expression and further increased urinary glucose excretion compared to the TAC group. Em reduced hyperglycemia and increased plasma insulin level, pancreatic islet size, and glucose‐stimulated insulin secretion compared to the TAC group. In kidney, Em alleviated TAC‐induced renal dysfunction and decreased albumin excretion and histological injury compared with the TAC group. Increased oxidative stress and apoptotic cell death by TAC was remarkably decreased with Em in serum and pancreatic and renal tissues. In in vitro study, TAC decreased cell viability and increased reactive oxygen species (ROS) production in both insulin‐secreting beta‐cell derived (INS‐1) and human kidney‐2 (HK‐2) cell lines. Addition of Em increased cell viability and decreased ROS production in HK‐2 but not in INS‐1 cell lines. This suggests that Em is effective in controlling TAC‐induced hyperglycemia and has direct protective effect on TAC‐induced renal injury.
Macrophage‐induced cytotoxicity of N‐methyl‐D‐aspartate receptor positive neurons involves excitatory amino acids rather than reactive oxygen intermediates and cytokines

The co‐localization of activated macrophages and damaged neurons observed in brain injury and degenerative brain diseases may hint to macrophage‐induced neuronal cytotoxicity. Recently, macrophages have been found to secrete neurotoxic molecules such as radical oxygen intermediates and glutamate, the latter interacting with N‐methyl‐D‐aspartate (NMDA) receptors. As shown in the present study, brain macrophages termed microglial cells co‐cultured with differentiated cerebellar neurons excert potent neurotoxic effects. Neurotoxicity is unlikely to be due to cytokines since tumor necrosis factor (TNF)‐α, interleukin (IL)‐1β, IL‐6 and interferon (IFN)‐α/IFN‐β/IFN‐γ had no such effects. In contrast, when treating neurons with H2O2 or oxygen radical‐generating systems cytotoxicity was induced. Furthermore, microglia were found to produce O 2− and H2O2 when triggered with phorbol 12‐myristate 13‐acetate. However, in co‐cultures of neurons and microglia, oxygen‐radical scavengers catalase and superoxide dismutase, failed to protect neurons from microglia‐induced killing. Moreover, when using undifferentiated neurons which are susceptible to H2O2 but not to NMDA receptor‐dependent killing, microglia did not destroy the neurons. Thus, the amount of reactive oxygen intermediates produced by microglia in co‐culture do not reach the critical concentrations required for neurotoxicity. As dibenzocyclohepteneimide, an antagonist to NMDA receptors neutralized neurotoxicity in microglia‐neuronal co‐cultures, excitatory amino acids released by microglia are suggested to compose the major determinant of neurotoxicity.
Isolation and characterization of expressible cDNA clones encoding the M1 and M2 subunits of mouse ribonucleotide reductase

Mammalian ribonucleotide reductase consists of two nonidentical subunits, proteins M1 and M2, which are differentially regulated during the cell cycle. We have isolated expressible cDNA clones of both subunits from an Okayama-Berg cDNA library made with mRNA from hydroxyurea-resistant, M2 protein-overproducing mouse TA3 cells. Expression of M2 protein could be demonstrated by electron paramagnetic resonance spectroscopy after transfection of COS-7 monkey cells with the plasmid. Electrophoresis and blot analyses of the parent and hydroxyurea-resistant TA3 mRNA revealed two M2 transcripts, a major one of 2.1 kilobases and a minor one of about 1.6 kilobases. Restriction endonuclease mapping of the corresponding cDNAs indicated that the two mRNAs differed only in the length of the 3' untranslated ends. By contrast, there was only one mRNA corresponding to the M1 protein, and its mobility corresponded to about 3.1 kilobases. The hydroxyurea-resistant TA3 cells contained a 50- to 100-fold excess of the M2 mRNAs over that of the parent cells and a 10-fold excess of the M1 mRNA. However, a Southern blot analysis of the corresponding genomic DNA sequences showed that the M2 gene was amplified fivefold but the M1 gene was still single copy. The complete nucleotide sequence of the 2,111-base-pair-long M2 cDNA revealed an open reading frame coding for 390 amino acids, which corresponds to a molecular weight of 45,100. The mouse M2 protein sequence was quite homologous to the equivalent protein in the clam Spisula solidissima, while the homology to the smaller subunits of Epstein-Barr virus, herpes simplex virus type 2, and Escherichia coli ribonucleotide reductases were less pronounced.
A Water Cooling System to Improve Ampacity in Underground Urban Distribution Cables

Seattle City Light (SCL) identified a thermal bottleneck that limited ampacity of 13 kV cables inside duct banks near a major substation supplying downtown Seattle. Depth of burial limited the seventy-two cables to 310 amps each instead of 510 Amps. Other cables nearby limited ampacity further. Thus the existing cables and ducts wouldn't meet near-term projected load increases. New substation construction was not feasible. Nor were customer interruptions for cable capacity improvement work. A chilled-water heat-removal system solves these problems. A prototype designed by SCL is under construction with commissioning planned for 2005. Ampacity increases by about 60% for the 13 kV cables and for 26 kV and 115 kV distribution and transmission cables near the substation. This paper describes the cooling system design, operation, environmental and safety features, and construction methods. The cooling water approach to ampacity improvement has potential application elsewhere at SCL and at other utilities
4-French–Compatible Endovascular Material Is Safe and Effective in the Treatment of Femoropopliteal Occlusive Disease: Results of the 4-EVER Trial

Purpose: To report the 1-year results of a prospective multicenter trial to evaluate the safety and efficacy of treating symptomatic femoropopliteal occlusive disease using 4-F–compatible materials and no closure device. Methods: The non-randomized 4-EVER trial ( 4 -F e ndo v ascular tr e atment app r oach to infrainguinal disease) was conducted at 5 European hospitals ( ClinicalTrials.gov identifier NCT01413139). The protocol mandated the use of only 4-F sheaths, self-expanding nitinol stents (Astron Pulsar or Pulsar-18 stent), and balloons from a single manufacturer. Between June 2010 and June 2011, 120 symptomatic patients (82 men; mean age 71±9.7 years, range 47–90), primarily claudicants, treated for 120 femoropopliteal lesions (>90% TASC A/B) were enrolled. The mean lesion length was 71.0±45.9 mm. Follow-up evaluations were scheduled on day 1 and at 1, 6, 12, and 24 months. A duplex ultrasound was performed on all follow-up visits to determine vessel patency (primary outcome measure at 1 year), and biplanar radiography was performed at 12 and 24 months to assess stent fracture. Results: Stents were successfully implanted in all patients: an Astron Pulsar stent in 70 (58.3%) lesions and a Pulsar-18 stent in 46 (38.3%); 4 (3.3%) patients had both stents implanted for flow-limiting dissection after predilation. No closure devices were used; the mean manual compression time was 8.1 minutes (2–15). Four (3.3%) patients developed significant hematoma at the puncture site, but none required surgical repair. The overall 12-month primary patency rate was 81.4%: 85.2% for the Astron Pulsar and 73.4% for the Pulsar-18 (p=0.236). Freedom from target lesion revascularization at 12 months for the entire cohort was 89.3%. Conclusion: Compared to published historical data for superficial femoral artery type A/B lesion stenting using 6-F devices, the 4-F devices applied in this trial showed similar patency at 12 months, fewer access site complications, and shorter manual compression times, supporting the supposition that 4-F endovascular treatment is safe and effective.
N-Acetylcysteine’s Role in Sepsis and Potential Benefit in Patients With Microcirculatory Derangements

Objective: To review the data surrounding the utility of N-acetylcysteine (NAC) in sepsis and identify areas needed for additional research. Data Sources: A review of articles describing the mechanisms of action and clinical use of NAC in sepsis. Summary of Review: Despite many advances in critical care medicine, still as many as 50% of patients with septic shock die. Treatments thus far have focused on resuscitation and restoration of macrocirculatory targets in the early phases of sepsis, with less focus on microcirculatory dysfunction. N-acetylcysteine, due to its anti-inflammatory and antioxidative properties, has been readily investigated in sepsis and has yielded largely incongruous and disappointing results. In addition to its known anti-inflammatory and antioxidative roles, one underappreciated property of NAC is its ability to vasodilate the microcirculation and improve locoregional blood flow. Some investigators have sought to capitalize on this mechanism with promising results, as evidenced by microcirculatory vasodilation, improvements in regional blood flow and oxygen delivery, and reductions in lactic acidosis, organ failure, and mortality. Conclusion: In addition to its antioxidant and anti-inflammatory properties, N-acetylcysteine possesses vasodilatory properties that could benefit the microcirculation in sepsis. It is imperative that we investigate these properties to uncover NAC’s full potential for benefit in sepsis.
A Highly Reliable Lateral MEMS Switch Utilizing Undoped Polysilicon as Isolation Material

The lateral actuated switch requires an isolation structure to provide mechanical coupling and electrical isolation between the actuator and the contacts. This isolation structure usually imposes extra difficulty on the fabrication process. In previous reports, we demonstrated a thermal actuated lateral switch, where the nitride isolation structure was a weak point, leading to reliability problems. In this paper, we developed a modified switch utilizing undoped polysilicon as the isolation material. The undoped-polysilicon isolation structure requires only one extra step of sheltered implantation, and it provides robust mechanical connection. A 20-mum-long undoped-polysilicon isolation structure has a current leakage of less than 2 nA under a 15-V operation voltage. The proposed switch works under a 12-V driving voltage with 60-mW input power. The time response is measured to be 130 mus, and a maximum operation frequency of 4.5 kHz is reached. An ON-state insertion loss of -0.41 dB at 20 GHz and an OFF-state isolation of -20 dB at 20 GHz have been achieved on the normal low-resistivity silicon substrate. The undoped-polysilicon isolation method can be used in other surface-micromachined lateral switches as well.