Miracle-dz/UniFAR-FTUs huggingface dataset:
Cell volume regulation in cultured cerebellar granule neurons

Cultured rat cerebellar granule neurons exposed to solutions of reduced osmolarity, responded initially by swelling followed by a regulatory volume decrease (RVD) which is completed within 15 min. Increasing external osmolarity lead to cell shrinking but no evidence of volume regulation was observed within 1 hr. Replacing Na+ by choline did not affect RVD whereas N‐methyl‐D‐glucamine accelerated the volume recovery and K+ suppressed it completely. The blockade of RVD in high extracellular K+ was only observed when chloride and nitrate but not sulfate or gluconate were the accompanying anions. Replacing intracellular Cl−, by long incubations with gluconate, markedly inhibited RVD. Removal of extracellular Ca2+ or addition of dantrolene which blocks Ca2+ released from intracellular stores had no effect on RVD. Increasing extracellular taurine prevented RVD. These results indicate that membrane permeability to K+, Cl−, and taurine is increased by hyposmolarity and suggest the involvement of these molecules in RVD in granule neurons. © 1993 Wiley‐Liss, Inc.
Le Fort III Advancement Osteotomy in the Growing Child Affected by Crouzon's and Apert's Syndromes: Presurgical and Postsurgical Growth

This is a longitudinal cephalometric study of patients with craniofacial synostosis (Crouzon's and Apert's) syndromes who underwent Le Fort III advancement during early childhood. The objectives of the study were to quantify presurgical growth, surgical results, and surgical stability as well as long-term postsurgical growth. Of the 31 patients operated on during their growth period (less than 10 years of age), 17 had sufficient records to be included in the study: at infancy, before the Le Fort III osteotomy (average age = 7.3 years, range: 4.8-10 years), and immediately after surgery. Ten of the patients were followed radiographically long term for an average of 6.1 ± 2.7 years (range: 4.5-10.8 years). The presurgical abnormal midfacial vertical growth pattern was accurately described with a progressive class III discrepancy and an increasing exophthalmos. Remarkable postoperative stability of the maxillary segment was observed. After surgery, growth of the midface was measured, together with minimal, if any, anterior growth, similar to the presurgical growth pattern and rate. No actual detrimental or beneficial effect of surgery on subsequent growth was seen. This study quantitatively confirms that the standard Le Fort III osteotomy is a stable and effective but generally not definitive procedure in childhood. This study might also serve as a control sample to compare with groups of patients undergoing distraction osteogenesis to verify the actual advantages and shortcomings of this alternative technique.
Problems in quantifying bone response to exercise in horses: a review

Abstract Detecting changes in bone during growth, training, rest from competition (spelling), and disease in horses requires imaging techniques that have a high level of accuracy and precision. Currently, most imaging techniques used in horses do not possess such characteristics and are more suitable for detecting endstage disease than subtle changes. Some are incapable of detecting changes in bone size. Non-planar techniques should be used for estimating or determining bone strength. This review outlines available imaging techniques and shows why cross-sectional procedures are required to accurately estimate bone strength. If these can be validated and improved for use in the standing horse, serial examination can be used to show the magnitude of changes in bone strength that occur during training or varying management regimens. Such knowledge can then be used to improve training and spelling regimens for equine athletes, hopefully resulting in a reduction in racing or athletic injury.
Adenosine Kinase of Trypanosoma brucei and Its Role in Susceptibility to Adenosine Antimetabolites

ABSTRACT Trypanosoma brucei cannot synthesize purines de novo and relies on purine salvage from its hosts to build nucleic acids. With adenosine being a preferred purine source of bloodstream-form trypanosomes, adenosine kinase (AK; EC 2.7.1.20) is likely to be a key player in purine salvage. Adenosine kinase is also of high pharmacological interest, since for many adenosine antimetabolites, phosphorylation is a prerequisite for activity. Here, we cloned and functionally characterized adenosine kinase from T. brucei (TbAK). TbAK is a tandem gene, expressed in both procyclic- and bloodstream-form trypanosomes, whose product localized to the cytosol of the parasites. The RNA interference-mediated silencing of TbAK suggested that the gene is nonessential under standard growth conditions. Inhibition or downregulation of TbAK rendered the trypanosomes resistant to cordycepin (3′-deoxyadenosine), demonstrating a role for TbAK in the activation of adenosine antimetabolites. The expression of TbAK in Saccharomyces cerevisiae complemented a null mutation in the adenosine kinase gene ado1. The concomitant expression of TbAK with the T. brucei adenosine transporter gene TbAT1 allowed S. cerevisiae ado1 ade2 double mutants to grow on adenosine as the sole purine source and, at the same time, sensitized them to adenosine antimetabolites. The coexpression of TbAK and TbAT1 in S. cerevisiae ado1 ade2 double mutants proved to be a convenient tool for testing nucleoside analogues for uptake and activation by T. brucei adenosine salvage enzymes.
Association of systemic risk factors with the severity of retinal hard exudates in a north Indian population with type 2 diabetes.

BACKGROUND The various risk factors for diabetic retinopathy and its spectrum are still poorly understood in the Indian population. AIMS To study the association of various systemic risk factors with retinal hard exudates in type 2 diabetic north Indian patients and to measure the incidence of dyslipidemia in them. SETTINGS AND DESIGN A tertiary-hospital-based cross-sectional study. MATERIALS AND METHODS An observational case-study which included 180 type 2 diabetic patients (180 eyes) of nonproliferative diabetic retinopathy (NPDR) with clinically significant macular edema (CSME). In these patients the retinal hard exudates were graded on a central 500 fundus picture using modified Airlie House classification and divided into three groups of absent or minimal hard exudates (Group 1), hard exudates present (Group 2) and prominent hard exudates (Group 3). Their association with various risk factors, namely the age of onset of diabetes and its duration, gender, insulin therapy, and various systemic parameters like hypertension, blood hemoglobin, glycosylated hemoglobin, serum (s.) creatinine levels, 24-h proteinuria and complete lipid profile including total s. cholesterol, low-density lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol (HDL), very low-density lipoprotein cholesterol (VLDL) and s. triglyceride (TG) was studied. The incidence of dyslipidemia was also calculated among these groups of patients. STATISTICAL ANALYSIS ANOVA test, linear regression analysis and Spearman's correlation test. RESULTS On univariate analysis, the retinal hard exudates were significantly associated with s. creatinine (P=0.016), systolic blood pressure (P=0.014), s. cholesterol (P < 0.001), s. LDL (P=0.008) and s. TG (P=0.013) levels. While on linear regression analysis, s. cholesterol (P < 0.001) and s. LDL cholesterol (P=0.028) were found to be independent risk factors affecting the density of retinal hard exudates. On Spearman's correlation test, the retinal hard exudates showed a significant positive correlation with systolic blood pressure (P=0.019), s. cholesterol (P < 0.001), LDL (P=0.002) and TG (P=0.014) levels. The incidence of dyslipidemia varied from as high as nearly 70% among patients of Group 3 compared to as low as 18% among Group 1 patients. CONCLUSION Serum cholesterol and LDL are independent risk factors for retinal hard exudates in type 2 diabetic north Indian patients who suffer from a remarkably high incidence of dyslipidemia.
Long-term Stability of Demethylation after Transient Exposure to 5-Aza-2′-Deoxycytidine Correlates with Sustained RNA Polymerase II Occupancy

DNA methyltransferase inhibitors are currently the standard of care for myelodysplastic syndrome and are in clinical trials for leukemias and solid tumors. However, the molecular basis underlying their activity remains poorly understood. Here, we studied the induction and long-term stability of gene reactivation at three methylated tumor suppressor loci in response to the DNA methyltransferase inhibitor 5-aza-2′-deoxycytidine (5-azaCdR) in human breast cancer cells. At the TMS1/ASC locus, treatment with 5-azaCdR resulted in partial DNA demethylation, the reengagement of RNA polymerase II (Pol II), and a shift from a repressive chromatin profile marked with H3K9me2 and H4K20me3 to an active profile enriched in H3ac and H3K4me2. Using a single-molecule approach coupling chromatin immunoprecipitation with bisulfite sequencing, we show that H3ac, H3K4me2, and Pol II selectively associated with the demethylated alleles, whereas H3K9me2 preferentially marked alleles resistant to demethylation. H4K20me3 was unaffected by DNA demethylation and associated with both unmethylated and methylated alleles. After drug removal, TMS1 underwent partial remethylation, yet a subset of alleles remained stably demethylated for over 3 months. These alleles remained selectively associated with H3K4me2, H3ac, and Pol II and correlated with a sustained low level of gene expression. TMS1 alleles reacquired H3K9me2 over time, and those alleles that became remethylated retained H3ac. In contrast, CDH1 and ESR1 were remethylated and completely silenced within ∼1 week of drug removal, and failed to maintain stably unmethylated alleles. Our data suggest that the ability to maintain Pol II occupancy is a critical factor in the long-term stability of drug-induced CpG island demethylation. Mol Cancer Res; 8(7); 1048–59. ©2010 AACR.
Intraseasonal Kelvin wave in Makassar Strait

[1] Time series observations during 2004–2006 reveal the presence of 60–90 days intraseasonal events that impact the transport and mixing environment within Makassar Strait. The observed velocity and temperature fluctuations within the pycnocline reveal the presence of Kelvin waves including vertical energy propagation, energy equipartition, and nondispersive relationship. Two current meters at 750 and 1500 m provide further evidence that the vertical structure of the downwelling Kelvin wave resembles that of the second baroclinic wave mode. The Kelvin waves derive their energy from the equatorial Indian Ocean winds, including those associated with the Madden-Julian oscillations, and propagate from Lombok Strait to Makassar Strait along the 100-m isobath. The northward propagating Kelvin waves within the pycnocline reduce the southward Makassar Strait throughflow by up to 2 Sv and induce a marked increase of vertical diffusivity.
The effect of obesity on disability vs mortality in older Americans.

BACKGROUND The association between obesity and mortality is reduced or eliminated in older subjects. In addition to mortality, disability is an important health outcome. The objectives of this study were to examine the association between body mass index (BMI), calculated as weight in kilograms divided by height in meters squared, and subsequent disability and mortality among older Americans, as well as to estimate the effect of BMI on life expectancy and disability-free life expectancy among older Americans. METHODS We studied 8359 non-Hispanic white Americans, 1931 African Americans, and 2435 Mexican Americans 65 years or older who were not disabled at baseline from 5 sites of the Established Populations for Epidemiologic Studies of the Elderly. Measures included BMI, medical conditions, activities of daily living, and demographic information. Cox proportional hazards regression analysis was used to estimate the hazard ratios (HRs) for subsequent disability and mortality during 7 years of follow-up. Total life expectancy and disability-free life expectancy were estimated using the interpolation of Markov chain approach. RESULTS The lowest HR (1.02; 95% confidence interval [CI], 0.94-1.10) for disability was at a BMI of 25 to less than 30. Subjects with BMIs of lower than 18.5 or 30 or higher at baseline were significantly more likely to experience disability during the follow-up period. In contrast, the lowest HRs for mortality were seen among subjects with BMIs of 25 to less than 30 (HR, 0.78; 95% CI, 0.72-0.85) and 30 to less than 35 (HR, 0.80; 95% CI, 0.72-0.90), with subjects with BMIs of lower than 25 or 35 or higher experiencing higher hazards for mortality. Disability-free life expectancy is greatest among subjects with a BMI of 25 to less than 30. CONCLUSION Assessments of the effect of obesity on the health of older Americans should account for mortality and incidence of disability.
How social motivation enhances economic activity and incentives in the Google Answers knowledge sharing market

What are the antecedents, inhibitors and catalysts to providing information and participating in mixed fee-based and free online contexts? We describe the behaviour of about 500 'Researchers' in the Google Answers (GA) online service and over 70,000 questions posed on this system over a 29 month period. GA is a fee-based environment. Answers provided on it are 'worth' over $20 (including tips) on average. However, labour economics of response to price and tip alone do not fully account for the online information provision market. Non-monetary incentives, such as feedback in the form of comments predict and explain some of the variance in participation. Descriptive and correlational findings presented here are based on many thousands of answers. We thus corroborate some of the hybrid theories of information provision behaviour presented to date mostly in laboratory settings. The participation of experts in GA is associated with a hybrid of material (economic) and social motivators.
Supplement of autologous ooplasm into porcine somatic cell nuclear transfer embryos does not alter embryo development

Somatic cell nuclear transfer (SCNT) is considered as the technique in which a somatic cell is introduced into an enucleated oocyte to make a cloned animal. However, it is unavoidable to lose a small amount of the ooplasm during enucleation step during SCNT procedure. The present study was aimed to uncover whether the supplement of autologous ooplasm could ameliorate the oocyte competence so as to improve low efficiency of embryo development in porcine SCNT. Autologous ooplasm-transferred (AOT) embryos were generated by the supplementation with autologous ooplasm into SCNT embryos. They were comparatively evaluated with respect to embryo developmental potential, the number of apoptotic body formation and gene expression including embryonic lineage differentiation, apoptosis, epigenetics and mitochondrial activity in comparison with parthenogenetic, in vitro-fertilized (IVF) and SCNT embryos. Although AOT embryos showed perfect fusion of autologous donor ooplasm with recipient SCNT embryos, the supplement of autologous ooplasm could not ameliorate embryo developmental potential in regard to the rate of blastocyst formation, total cell number and the number of apoptotic body. Furthermore, overall gene expression of AOT embryos was presented with no significant alterations in comparison with that of SCNT embryos. Taken together, the results of AOT demonstrated inability to make relevant values improved from the level of SCNT embryos to their IVF counterparts.
An update on transport vesicle tethering

Abstract Membrane trafficking involves the collection of cargo into nascent transport vesicles that bud off from a donor compartment, translocate along cytoskeletal tracks, and then dock and fuse with their target membranes. Docking and fusion involve initial interaction at a distance (tethering), followed by a closer interaction that leads to pairing of vesicle SNARE proteins (v-SNAREs) with target membrane SNAREs (t-SNAREs), thereby catalyzing vesicle fusion. When tethering cannot take place, transport vesicles accumulate in the cytoplasm. Tethering is generally carried out by two broad classes of molecules: extended, coiled-coil proteins such as the so-called Golgin proteins, or multi-subunit complexes such as the Exocyst, COG or Dsl complexes. This review will focus on the most recent advances in terms of our understanding of the mechanism by which tethers carry out their roles, and new structural insights into tethering complex transactions.
Has the sensitivity of soybean cultivars to ozone pollution increased with time? An analysis of published dose–response data

The rising trend in concentrations of ground‐level ozone (O3) – a common air pollutant and phytotoxin – currently being experienced in some world regions represents a threat to agricultural yield. Soybean (Glycine max (L.) Merr. ) is an O3‐sensitive crop species and is experiencing increasing global demand as a dietary protein source and constituent of livestock feed. In this study, we collate O3 exposure‐yield data for 49 soybean cultivars, from 28 experimental studies published between 1982 and 2014, to produce an updated dose–response function for soybean. Different cultivars were seen to vary considerably in their sensitivity to O3, with estimated yield loss due to O3 ranging from 13.3% for the least sensitive cultivar to 37.9% for the most sensitive, at a 7‐h mean O3 concentration (M7) of 55 ppb – a level frequently observed in regions of the USA, India and China in recent years. The year of cultivar release, country of data collection and type of O3 exposure used were all important explanatory variables in a multivariate regression model describing soybean yield response to O3. The data show that the O3 sensitivity of soybean cultivars increased by an average of 32.5% between 1960 and 2000, suggesting that selective breeding strategies targeting high yield and high stomatal conductance may have inadvertently selected for greater O3 sensitivity over time. Higher sensitivity was observed in data from India and China compared to the USA, although it is difficult to determine whether this effect is the result of differential cultivar physiology, or related to local environmental factors such as co‐occurring pollutants. Gaining further understanding of the underlying mechanisms that govern the sensitivity of soybean cultivars to O3 will be important in shaping future strategies for breeding O3‐tolerant cultivars.
Triptan Drugs, Natural Killer Cell Cytotoxicity, and Neutrophils Pro‐Matrix Metalloproteinase‐9 Secretion

Objective. — To study the effect of various triptan‐like drugs, eg, avitriptan, naratriptan, and sumatriptan, as well as the benzopyran alnitidan, on the natural killer cell (NKC) activity of peripheral blood mononuclear cell (PBMC) samples and highly purified NKC (HPNKC) preparations. We also examined the possible role of these agents as immunomodulators by studying their effect upon the in vitro secretion of pro‐matrix metalloproteinase‐9 (pMMP‐9) from whole blood and purified neutrophils samples.
Factorial Validity of the Personality Adjective Checklist in a Dutch-Speaking Sample

We examined the factorial structure of the Dutch version of the Personality Adjective Checklist (PACL–D) in a Belgian sample of 3,012 community-dwelling adults. Exploratory factor analyses revealed a 5-factor structure (Neurotic, Aggressive/Dominant, Introverted vs. Extraverted, Conscientious, and Cooperative), that showed considerable overlap with 3 of the Big Five factors (i.e., Neuroticism, Extraversion, and Conscientiousness). Moreover, the 5-factor structure closely resembled the structure found in the original American PACL and was equivalent across gender and age.
How fatty acids bind to proteins: the inside story from protein structures.

The interactions of fatty acids with proteins have been probed with a great variety of techniques and strategies. Many approaches have substituted covalently labeled fatty acids or structurally related molecules. Information from such studies ultimately requires validation by studies with natural fatty acids. However, even the best conventional approaches with natural fatty acids generally have revealed only limited aspects of fatty acid-protein interactions. In contrast, recent crystallographic and NMR studies of several proteins with bound fatty acids provide complete three-dimensional structures with molecular details of these interactions. This presentation reviews three examples of proteins that are indirectly or directly involved in cell signaling: a protein in the plasma compartment (human serum albumin); a protein family in the cytosolic compartment of mammalian cells (fatty-acid-binding proteins), and a nuclear protein (peroxisome proliferator-activated receptor): it also discusses the structures of these proteins and their binding pocket(s), compares their specific modes of interactions with fatty acids, and discusses established and potential roles of fatty acid-protein interactions in cell signaling.
Detection of HSV-1 variants highly resistant to the helicase-primase inhibitor BAY 57-1293 at high frequency in 2 of 10 recent clinical isolates of HSV-1.

OBJECTIVES BAY 57-1293 is a helicase-primase inhibitor (HPI) from a new class of antivirals that are highly efficacious in herpes simplex virus (HSV)-1 animal infection models. Resistant mutants with point mutations in the helicase (UL5) were reported to be present in laboratory isolates at a low frequency of approximately 10(-6). In contrast, we have shown elsewhere that some laboratory isolates contain resistant variants at higher frequency (10(-4)). Therefore, we screened 10 recent clinical isolates of HSV-1 for BAY 57-1293-resistant virions. METHODS Clinical isolates were screened by a plaque reduction assay in Vero cells to determine the frequency of occurrence of BAY 57-1293-resistant variants. The helicase gene for the resistant variants was sequenced. RESULTS One isolate contained highly resistant variants at 10(-4) and another at 10(-5). Both variants contained a previously reported BAY 57-1293 resistance mutation (K356N) in UL5 and were >5000-fold resistant. CONCLUSIONS Occurrence of HPI-resistant viruses at high frequency in a clinical isolate is intriguing. Two alternative hypotheses are proposed to explain this phenomenon. It is also surprising that two unrelated clinical isolates contain an identical HPI resistance mutation. These results have important implications for HPI drug-resistance monitoring during subsequent clinical trials.
Disappearing Myelodysplastic Syndrome-Associated Hemolytic Anemia in Leukemic Transformation

Background: Here we report 2 rare cases of acute myeloid leukemia (AML) complicated with hemolytic anemia limited to the myelodysplastic syndrome (MDS) stage, and disappearing in leukemic transformation. Methods/Results: A 66-year-old man with MDS-RAEB-2 was admitted to hospital for severe anemia with increased reticulocyte counts. Hemolytic anemia was suspected, and it was ameliorated by methylprednisolone pulse therapy. Although anemia grew worse when steroids were tapered off, later improvement coincided with an increase in myeloblasts in the peripheral blood, i.e. with leukemic transformation. In another case, a 68-year-old man was admitted to hospital when laboratory findings showed a white blood cell count of 24,800/µl with increased myeloblasts (62.5%), leading to the diagnosis of AML with multilineage dysplasia. Following a decrease in blasts due to anti-cancer drugs, supporting the MDS-RAEB-2 status, severe anemia with increased reticulocytes and positive direct antiglobulin test was diagnosed, suggesting the existence of autoimmune hemolytic anemia, which was then ameliorated by steroid therapy. Conclusions: The simultaneous loss of autoimmunity and leukemic cell expansion observed in our cases may possibly suggest a common underlying mechanism.