Miracle-dz/UniFAR-FTUs huggingface dataset:
The chronic blockade of angiotensin I-converting enzyme eliminates the sex differences of serum cytokine levels of spontaneously hypertensive rats

Sex hormones modulate the action of both cytokines and the renin-angiotensin system. However, the effects of angiotensin I-converting enzyme (ACE) on the proinflammatory and anti-inflammatory cytokine levels in male and female spontaneously hypertensive rats (SHR) are unclear. We determined the relationship between ACE activity, cytokine levels and sex differences in SHR. Female (F) and male (M) SHR were divided into 4 experimental groups each (n = 7): sham + vehicle (SV), sham + enalapril (10 mg/kg body weight by gavage), castrated + vehicle, and castrated + enalapril. Treatment began 21 days after castration and continued for 30 days. Serum cytokine levels (ELISA) and ACE activity (fluorimetry) were measured. Male rats exhibited a higher serum ACE activity than female rats. Castration reduced serum ACE in males but did not affect it in females. Enalapril reduced serum ACE in all groups. IL-10 (FSV = 16.4 ± 1.1 pg/mL; MSV = 12.8 ± 1.2 pg/mL), TNF-α (FSV = 16.6 ± 1.2 pg/mL; MSV = 12.8 ± 1 pg/mL) and IL-6 (FSV = 10.3 ± 0.2 pg/mL; MSV = 7.2 ± 0.2 pg/mL) levels were higher in females than in males. Ovariectomy reduced all cytokine levels and orchiectomy reduced IL-6 but increased IL-10 concentrations in males. Castration eliminated the differences in all inflammatory cytokine levels (IL-6 and TNF-α) between males and females. Enalapril increased IL-10 in all groups and reduced IL-6 in SV rats. In conclusion, serum ACE inhibition by enalapril eliminated the sexual dimorphisms of cytokine levels in SV animals, which suggests that enalapril exerts systemic anti-inflammatory and anti-hypertensive effects.
Evidence That Marginal Zone B Cells Possess an Enhanced Secretory Apparatus and Exhibit Superior Secretory Activity1

Marginal zone B (MZB) cells are the first splenic B cells to initiate Ab secretion against polysaccharide-encapsulated Ags in vivo. This swift MZB cell response can be reproduced in vitro as LPS treatment induces Ab secretion in as little as 12 h. Conversely, in vitro LPS treatment of splenic follicular B (FOB) cells results in Ab secretion after 2–3 days. The basis for these distinct response kinetics is not understood. We performed ex vivo analysis of resting and LPS-stimulated murine MZB and FOB cells and found that MZB cells express higher levels of the LPS TLR complex RP105/MD-1 and respond to much lower concentrations of LPS than do FOB cells. Furthermore, increasing doses of LPS do not accelerate the kinetics by which FOB cells transition into Ab secretion. Ultrastructural analysis of resting cells demonstrated that rough endoplasmic reticulum is more abundant in MZB cells than in FOB cells. Additionally, RT-PCR and immunoblot analyses revealed that numerous endoplasmic reticulum resident chaperones and folding enzymes are expressed at greater levels in resting MZB cells than in resting FOB cells. Although both LPS-stimulated MZB and FOB cells increase expression of these factors, MZB cells exhibit a more rapid increase that correlates with accelerated kinetics of Ab secretion and higher per cell output of secreted IgM. These data indicate that MZB cells are equipped for exquisite sensitivity to bacterial components like LPS and poised for rapid, robust Ab production, making MZB cells ideally suited as frontline defenders in humoral immunity.
Whole-Genome Sequencing to Identify Mutants and Polymorphisms in Chlamydomonas reinhardtii

Whole-genome sequencing (WGS) provides a new platform for the identification of mutations that produce a mutant phenotype. We used Illumina sequencing to identify the mutational profile of three Chlamydomonas reinhardtii mutant strains. The three strains have more than 38,000 changes from the reference genome. NG6 is aflagellate and maps to 269 kb with only one nonsynonymous change; the V12E mutation falls in the FLA8 gene. Evidence that NG6 is a fla8 allele comes from swimming revertants that are either true or pseudorevertants. NG30 is aflagellate and maps to 458 kb that has six nonsynonomous changes. Evidence that NG30 has a causative nonsense allele in IFT80 comes from rescue of the nonswimming phenotype with a fragment bearing only this gene. This gene has been implicated in Jeune asphyxiating thoracic dystrophy. Electron microscopy of ift80-1 (NG30) shows a novel basal body phenotype. A bar or cap is observed over the distal end of the transition zone, which may be an intermediate in preparing the basal body for flagellar assembly. In the acetate-requiring mutant ac17, we failed to find a nonsynonymous change in the 676 kb mapped region, which is incompletely assembled. In these strains, 43% of the changes occur on two of the 17 chromosomes. The excess on chromosome 6 surrounds the mating-type locus, which has numerous rearrangements and suppressed recombination, and the changes extend beyond the mating-type locus. Unexpectedly, chromosome 16 shows an unexplained excess of single nucleotide polymorphisms and indels. Overall, WGS in combination with limited mapping allows fast and accurate identification of point mutations in Chlamydomonas.
Drug Transporter Genetic Variants Are Not Associated with TDF-Related Renal Dysfunction in Patients with HIV-1 Infection: A Pharmacogenetic Study

Objective To investigate whether single nucleotide polymorphisms (SNP) of drug transporter proteins for TDF is a risk factor for TDF-related renal function decrement. Methods This study investigated the association between 3 SNPs (ABCC2–24, 1249, and ABCB1 2677), which are shown to be associated with TDF-induced tubulopathy, and clinically important renal outcomes (>10ml/min/1.73m2 decrement in eGFR relative to baseline, >25% decrement in eGFR, and eGFR <60ml/min/1.73m2) in 703 HIV-1-infected Japanese patients who initiated TDF-containing antiretroviral therapy (ART). Genotyping was performed by allelic discrimination using TaqMan 5’-nuclease assays. Results 95% of the study patients were males and 66% were treatment-naïve, with median CD4 count of 249/μl, median baseline eGFR of 96ml/min/1.73m2 (IQR 84.6–109.2), and median exposure to TDF of 3.66 years (IQR 1.93–5.59). The frequencies of genotypes at -24, 1249 of ABCC2, and 2677 of ABCB1 were neither different between patients with decrement in eGFR of >10ml/min/1.73m2 and those without such decrement (ABCC2: -24, p = 0.53, 1249, p = 0.68; ABCB1: 2677, p = 0.74), nor between those without and with the other two renal outcomes (>25% decrement: ABCC2: -24, p = 0.83, 1249, p = 0.97, ABCB1: 2677, p = 0.40; eGFR <60ml/min/1.73m2: ABCC2: -24, p = 0.51, 1249, p = 0.81, ABCB1: 2677, p = 0.94). Logistic regression analysis showed that the risk genotype of the three SNPs were not associated with any of the three renal outcomes, respectively. Logistic regression model that applied either dominant, recessive, or additive model yielded the same results. Conclusions SNPs of the drug transporters for TDF are not associated with clinically important renal outcomes in patients who initiated TDF-containing ART.
Mitochondrial Subversion in Cancer

Mitochondria control essential cellular activities including generation of ATP via oxidative phosphorylation. Mitochondrial DNA (mtDNA) mutations in the regulatory D-loop region and somatic mtDNA mutations are common in primary human cancers. The biological impact of a given mutation may vary, depending on the nature of the mutation and the proportion of mutant mtDNAs carried by the cell. Identification of mtDNA mutations in precancerous lesions supports their early contribution to cell transformation and cancer progression. Introduction of mtDNA mutations in transformed cells has been associated with increased ROS production and tumor growth. Studies reveal that increased and altered mtDNA plays a role in the development of cancer but further work is required to establish the functional significance of specific mitochondrial mutations in cancer and disease progression. This review offers some insight into the extent of mtDNA mutations, their functional consequences in tumorigenesis, mitochondrial therapeutics, and future clinical application. Cancer Prev Res; 4(5); 638–54. ©2011 AACR.
Myxoid Liposarcoma with Cartilaginous Differentiation: A Case Study with Cytogenetical Analysis

Myxoid liposarcoma is a subtype of liposarcoma. This specific subtype can be identified based on its characteristic histological and cytogenetical features. The tumor has a fusion transcript of the CHOP and TLS genes, which is caused by t(12;16)(q13;p11). Most of the fusion transcripts that have been identified fall into three categories, specifically type I (exons 7-2), type II (exons 5-2), and type III (exons 8-2). A total of seven myxoid liposarcomas associated with the rare phenomenon of cartilaginous differentiation have been documented in the literature. Currently, only one of these cases has been cytogenetically analyzed, and the analysis indicated that it was a type II TLS-CHOP fusion transcript in both the typical myxoid liposarcoma and cartilaginous areas. This study presents a second report of myxoid liposarcoma with cartilaginous differentiation, and includes a cytogenetical analysis of both the myxoid and cartilaginous areas.
Defects in DNA Lesion Bypass Lead to Spontaneous Chromosomal Rearrangements and Increased Cell Death

ABSTRACT Rev3 polymerase and Mph1 DNA helicase participate in error-prone and error-free pathways, respectively, for the bypassing of template lesions during DNA replication. Here we have investigated the role of these pathways and their genetic interaction with recombination factors, other nonreplicative DNA helicases, and DNA damage checkpoint components in the maintenance of genome stability, viability, and sensitivity to the DNA-damaging agent methyl methanesulfonate (MMS). We find that cells lacking Rev3 and Mph1 exhibit a synergistic, Srs2-dependent increase in the rate of accumulating spontaneous, gross chromosomal rearrangements, suggesting that the suppression of point mutations by deletion of REV3 may lead to chromosomal rearrangements. While mph1Δ is epistatic to homologous recombination (HR) genes, both Rad51 and Rad52, but not Rad59, are required for normal growth of the rev3Δ mutant and are essential for survival of rev3Δ cells during exposure to MMS, indicating that Mph1 acts in a Rad51-dependent, Rad59-independent subpathway of HR-mediated lesion bypass. Deletion of MPH1 helicase leads to synergistic DNA damage sensitivity increases in cells with chl1Δ or rrm3Δ helicase mutations, whereas mph1Δ is hypostatic to sgs1Δ. Previously reported slow growth of mph1Δ srs2Δ cells is accompanied by G2/M arrest and fully suppressed by disruption of the Mec3-dependent DNA damage checkpoint. We propose a model for replication fork rescue mediated by translesion DNA synthesis and homologous recombination that integrates the role of Mph1 in unwinding D loops and its genetic interaction with Rev3 and Srs2-regulated pathways in the suppression of spontaneous genome rearrangements and in mutation avoidance.
The Effect of Alendronate, Risedronate, and Raloxifene on Renal Functions, Based on the Cockcroft and Gault Method, in Postmenopausal Women

Background. Oral alendronate, risedronate, and raloxifene are effective treatment options in the management of postmenopausal osteoporosis. There is little previously reported about the renal safety profiles of these three agents in osteoporosis. We aimed to assess the risk of renal toxicity associated with oral alendronate, risedronate, and raloxifene in the treatment of osteoporosis, prospectively. Methods. One hundred and twenty-seven patients with osteoporosis and osteopenia according to lumbar or femoral-neck bone mineral density t score were enrolled in the study. The patients were randomized to alendronate 70 mg once weekly (n = 47), risedronate 35 mg once weekly (n = 44), or raloxifene 60 mg per day (n = 36) for one year. Preliminary screening included medical history, physical examination, lumbar and femoral bone mineral densitometry measurement, and blood biochemical tests, including renal function tests. The biochemical markers were then assessed at the end of 12 months. Results. There was no significant difference between basal and final renal function parameters of each group. Also these parameters did not differ between the three groups after 12 months of treatment period. Conclusions. These results demonstrate that alendronate, risedronate, and raloxifene are all safe drugs for renal functions in the treatment of osteoporosis.
Pro-inflammatory cytokines in saliva of adolescents with dental caries disease.

INTRODUCTION AND OBJECTIVE Dental caries is an inflammatory disease with multifactorial etiology. The presented study was conducted to test the hypothesis that the elevation of salivary cytokines - interleukin-6 (IL-6), interleukin-8 (IL-8) and tumour necrosis factor (TNF-a) is changed in dental caries patients. IL-6, IL-8 and TNF-a are particularly relevant to inflammation, one of the very first responses of the host to a pathological insult. MATERIALS AND METHODS Whole saliva from 26 patients with dental caries, as well as 10 healthy persons, was investigated for the presence of IL-6, IL-8 and TNF-a by enzyme immunoassay - ELISA. RESULTS The results showed that an elevation of IL-6, IL-8 and TNF-a in unstimulated whole saliva in subjects with dental caries, compared with controls, increased and was statistically significant in all cases (p <0.05). The study also show a positive correlation between TNF-a and IL-8. CONCLUSIONS These data suggest links between the production of tumour necrosis factor (TNF-a), interleukin-6 (IL-6), interleukin-8 (IL-8) in saliva and dental caries disease.
CCD BV survey of 42 open clusters

Aims. We present results of a photometric survey whose aim was to derive structural and astrophysical parameters for 42 open clusters. While our sample is definitively not representative of the total open cluster sample in the Galaxy, it does cover a wide range of cluster parameters and is uniform enough to allow for simple statistical considerations. Methods. BV wide-field CCD photometry was obtained for open clusters for which photometric, structural, and dynamical evolution parameters were determined. The limiting and core radii were determined by analyzing radial density profiles. The ages, reddenings, and distances were obtained from the solar metallicity isochrone fitting. The mass function was used to study the dynamical state of the systems, mass segregation effect and to estimate the total mass and number of cluster members. Results. This study reports on the first determination of basic parameters for 11 out of 42 observed open clusters. The angular sizes for the majority of the observed clusters appear to be several times larger than the catalogue data indicate. The core and limiting cluster radii are correlated and the latter parameter is 3.2 times larger on average. The limiting radius increases with the cluster's mass, and both the limiting and core radii decrease in the course of dynamical evolution. For dynamically not advanced clusters, the mass function slope is similar to the universal IMF slope. For more evolved systems, the effect of evaporation of low-mass members is clearly visible. The initial mass segregation is present in all the observed young clusters, whereas the dynamical mass segregation appears in clusters older than about $\log({age})$ = 8. Low-mass stars are deficient in the cores of clusters older than $\log({age})$ = 8.5 and not younger than one relaxation time.
Outline for a theory of intelligence

Intelligence is defined as that which produces successful behavior. Intelligence is assumed to result from natural selection. A model is proposed that integrates knowledge from research in both natural and artificial systems. The model consists of a hierarchical system architecture wherein: (1) control bandwidth decreases about an order of magnitude at each higher level, (2) perceptual resolution of spatial and temporal patterns contracts about an order-of-magnitude at each higher level, (3) goals expand in scope and planning horizons expand in space and time about an order-of-magnitude at each higher level, and (4) models of the world and memories of events expand their range in space and time by about an order-of-magnitude at each higher level. At each level, functional modules perform behavior generation (task decomposition planning and execution), world modeling, sensory processing, and value judgment. Sensory feedback control loops are closed at every level. >
Preemptive Analgesic and Antioxidative Effect of Curcumin for Experimental Migraine

Objective Our study aimed to investigate the analgesic and antioxidative stress effects of Curcumin (CC) in experimental migraine induced by Nitroglycerin (NTG) on rats, compared with Indomethacin (ID) and Propranolol (PP) treatments. Material and Methods Five groups of 10 rats treated i.p. were investigated: control group (healthy rats) injected with saline solution (0.9%), NTG-control group injected with NTG (1 mg/100 gbw, bw = body weight), and three groups with pretreatment applied 30 min previous to the formalin test (NTG + CC group: Curcumin (10 mg/100 gbw), NTG + PP group: Propranolol (100 μg/100 gbw), and NTG + ID group: Indomethacin (0.5 mg/100 gbw)). Formalin test was performed and number of flinches and shakes were counted. Several oxidative stress parameters were also assessed. Results The smallest values of malondialdehyde (MDA), nitric oxide (NOx), and total oxidative status (TOS) were observed on NTG + CC with significant differences as compared with the control group (p < 0.0001). The group pretreated with Curcumin proved significantly smaller number of flinches and shakes compared with both NTG + PP and NTG + ID. Conclusion Our study demonstrates a superior activity of Curcumin not only versus control, but also versus Propranolol and Indomethacin.
A comparison of leisure constraints among three outdoor recreation activities: whitewater rafting, canoeing and overnight horseback riding

The purpose of this study was to compare leisure constraints across three outdoor recreation activities, whitewater rafting, canoeing, and overnight horseback riding, in the context of the three-dimensional leisure constraints model proposed by Crawford and Godbey (1987). The sample consisted of 650 outdoor enthusiasts from 14 U.S. states who showed an interest in outdoor recreation but did not participate in any of these activities in the last two years. A confirmatory factor analysis partially supported the three-dimensional model across the three activities. The model, however, failed to incorporate some of the constraint items. Comparison of leisure constraints showed that the importance of constraints varied across the three activities. Overall, rafting had the most intrapersonal constraints, horseback riding had the most structural constraints, and canoeing had the least constraints overall. Item-wise comparisons revealed different results than the factor-wise comparison. The implications of these findings for further research and providers are discussed.
Making the Environmental Justice Grade: The Relative Burden of Air Pollution Exposure in the United States

This paper assesses whether the Clean Air Act and its Amendments have been equally successful in ensuring the right to healthful air quality in both advantaged and disadvantaged communities in the United States. Using a method to rank air quality established by the American Lung Association in its 2009 State of the Air report along with EPA air quality data, we assess the environmental justice dimensions of air pollution exposure and access to air quality information in the United States. We focus on the race, age, and poverty demographics of communities with differing levels of ozone and particulate matter exposure, as well as communities with and without air quality information. Focusing on PM2.5 and ozone, we find that within areas covered by the monitoring networks, non-Hispanic blacks are consistently overrepresented in communities with the poorest air quality. The results for older and younger age as well as poverty vary by the pollution metric under consideration. Rural areas are typically outside the bounds of air quality monitoring networks leaving large segments of the population without information about their ambient air quality. These results suggest that substantial areas of the United States lack monitoring data, and among areas where monitoring data are available, low income and minority communities tend to experience higher ambient pollution levels.
Mono-spectral (greyscale) imaging for Nanoscale physical character analysis of Silica from lake deposition: An experimental study

Digital microphotography and image analysis is considered as an important tool in sedimentology and mineralogy for the assessment of physical characteristics at micro and nano level. The authors attempted to analyse the physical characteristic like surface condition of a silica grain of a lake deposition layer from mono-spectral imaging at nanometre scale. For that purpose a silica grain was picked up from microphotography of a thin section of sediment layer and 1μm X 1μm base image in greyscale was prepared for operation with sophisticated software. Reflectance capacity of the particle has been considered to measure the topographic condition. Contour plot from the base image was prepared along with a topographic image prepared on the basis of blackbody law. A complete topography map of silica grain was prepared on the basis of two previous plots. A 3D image and four profiles were also consulted for understanding the geometry of the surface of silica. Roughness analysis was also done from the mono-spectral image.
AAV‐mediated delivery of BDNF augments neurogenesis in the normal and quinolinic acid‐lesioned adult rat brain

Brain‐derived neurotrophic factor (BDNF) plays a major role in regulating the survival and fate of progenitor cells in the adult brain. In order to extend previous observations in the normal adult brain and advance our knowledge regarding the effect of BDNF on neurogenesis in the injured brain, this study directly compared the effect of BDNF on basal and injury‐induced neurogenesis in relation to progenitor cell distribution and levels of neuronal differentiation and survival. BDNF was overexpressed in the subventricular zone (SVZ) via recombinant adeno‐associated virus (AAV1/2) delivery, and newly generated cells were identified using bromodeoxyuridine (BrdU) labelling. Selective striatal cell loss was induced in a subgroup of rats by unilateral striatal injection of quinolinic acid (QA) 21 days after AAV1/2 injection. In the normal brain, BDNF overexpression significantly increased BrdU‐positive cell numbers in the rostral migratory stream, indicating enhanced progenitor cell migration. Following QA lesioning, we observed a reduction in BrdU immunoreactivity in the SVZ. Overexpression of BDNF restored BrdU‐positive cell numbers in the QA‐lesioned SVZ to that observed in the normal brain. Most significantly, BDNF enhanced the recruitment of progenitor cells to the QA‐lesioned striatum and promoted neuronal differentiation in both the normal and QA‐lesioned striatum. Our findings indicate that BDNF augments the recruitment, neuronal differentiation and survival of progenitor cells in both neurogenic and non‐neurogenic regions of the normal or QA‐lesioned brain. Enhanced expression of BDNF may therefore be a viable strategy for augmenting neurogenesis from endogenous progenitor cells.
Smart polymer-clay composite nanomaterials

We present the first phase behaviour study of South Australian NAu.1 Nontronite clays (1) exfoliated in water and their orientation response in varying magnetic fields. We also describe a novel route for the grafting of water-soluble thermo-responsive polymers onto the edges of the nanoclay platelets.