Miracle-dz/UniFAR-FTUs huggingface dataset:
Phosphorylation of G Protein–Coupled Receptor Kinase 2–Interacting Protein 1 Tyrosine 392 Is Required for Phospholipase C-&ggr; Activation and Podosome Formation in Vascular Smooth Muscle Cells

Objective—Podosomes, which are actin-rich structures, contribute to cell motility, matrix remodeling, and tissue remodeling. We have shown that G protein–coupled receptor kinase 2–interacting protein 1 (GIT1) colocalizes with podosomes and is important in podosome formation in endothelial cells. Src stimulates GIT1 tyrosine phosphorylation, which is critical for phospholipase C-&ggr; (PLC&ggr;) activation. In this study, we identified specific GIT1 tyrosines required for PLC&ggr; activation and podosome formation in vascular smooth muscle cells (VSMC). Methods and Results—We used phorbol 12,13-dibutyrate (PDBU) to induce podosomes in A7r5 VSMC. GIT1 colocalized with podosomes and GIT1 knockdown using short interfering RNA significantly reduced podosome formation. PDBU stimulated GIT1 tyrosine phosphorylation. GIT1 tyrosine phosphorylation was dramatically decreased in SYF−/− cells, and it was also reduced by pretreatment with the protein kinase C (PKC) and Src inhibitors, suggesting that GIT1 phosphorylation was dependent on PKC and Src. By mutation analysis of multiple tyrosines, we found that PDBU specifically increased GIT1-Y392 phosphorylation. Overexpression of GIT1 (Y392F) but not of GIT1 (Y321F) decreased PDBU-mediated PLC&ggr; activation and podosome formation without effect on extracellular signal–regulated kinase 1/2 activation. Additionally, we provide evidence that GIT1 knockout VSMC have markedly fewer podosomes on PDBU treatment compared with wild-type VSMC. These data show that GIT1 is a key regulator of podosome formation in VSMC. Conclusion—In conclusion, our data suggest that GIT1-Y392 phosphorylation is critical for PDBU-induced podosome formation by regulating PLC&ggr; activation. We propose that specific signaling modules are assembled in a GIT1 phosphotyrosine-dependent manner as exemplified by PLC&ggr; activation versus extracellular signal–regulated kinase 1/2 activation.
Risk factors for stroke: a prospective hospital based study.

BACKGROUND The stroke is third leading cause of death in world and most patients die with an acute event in stroke. Various clinical variables have been investigated as risks factors of stroke. The study was aimed to identify these risks factors for stroke. METHODS This prospective study included 205 consecutive patients of stroke admitted in Combined Military Hospital/Sheik Khalifa Bin Zyad Hospital Muzaffarabad Azad Kashmir. The risk factors of stroke were investigated. Examination included clinical, neurological evaluation, laboratory tests, and brain CT. The follow-up at 14 days were done for all patients. Patients included were with acute first ever stroke onset of 48 hours of hospital admission. All patients completed a structured questionnaire and a physical examination and most provided blood for relevant investigations. RESULTS Two hundred and five cases stroke sub-types were (n = 156, 76%, with ischemic stroke (CI); n = 49, 24%, with intra-cerebral hemorrhagic stroke (ICH). The significant risk factors for all stroke were: Hypertension (p = 0.003), diabetes (p = < 0.001), Hypercholesterolemia (p = 0.686); atrial fibrillation (p = 0.445), cardiac diseases (p = 0.938). smoking (p = 0.926) for brain infarction and hypertension (p = 0.002), diabetes (p = < 0.001). Hypercholesterolemia (p = 0.018); atrial fibrillation (p = 0.449), cardiac diseases (p = 0.749), smoking (p = 0.829) for hemorrhagic stroke. Age significance (CI: p = 0.247 vs. ICH: p = 0.013) and age category significance were (CI: p = < 0.001 vs. ICH: p = 0.871) for subtype of stroke. High mRS (p < 0.001) low GCS score (p < 0.001) on admission were associated with worst outcome for both stroke subtype. These risk factors were all significant for CI as well as ICH. CONCLUSIONS This study signifies the association of risks factors with acute stroke. Targeted interventions that reduce these risk factors could substantially reduce the burden of stroke
WORD CO-OCCURRENCE AND THEORY OF MEANING

Starting from the observation that word co-occurrence analysis needs to be anchored to the theory of meaning, various issues are discussed with a view to understand what happens when the words become numbers and the software outputs (i.e. tables and charts) become texts to be interpreted. In particular, with reference to the representation of the word co-occurrences into vector-space model, linguistic and semiotic theories are presented as tools for discussing assertions as “two (or more) words that tend to occur in similar linguistic contexts (i.e. to have similar cooccurrence patterns) tend to resemble each other in meaning”. Two main references are used: to structural linguistics (particularly Z.S. Harris, L. Hjelmslev and A. Greimas) and to semiotics (particularly C.S. Peirce and U. Eco), considering meaning either within the structural relationships between expression and content forms or as result of abductive inference. Finally, looking at software outputs as multi-semiotic objects, i.e. like a sort of texts to be interpreted, the discussion addresses hermeneutic
Comparison of atypical rotaviruses from calves, piglets, lambs and man.

Some rotaviruses from calves, piglets, and lambs were detected by electron microscopic examination of faeces but not by an enzyme-linked immunosorbent assay which relies on detection of group antigen. On further examination by polyacrylamide gel electrophoresis, these viruses had 11 segments of dsRNA, as had typical rotaviruses, but arranged in atypical patterns. From humans, three rotaviruses with atypical electrophoretypes were also detected. Gnotobiotic animals were infected with atypical calf, piglet and lamb rotaviruses, and used to provide antigen and antiserum for an immunofluorescent comparison of these rotaviruses with conventional rotaviruses and other previously described atypical rotaviruses from piglets and chickens. Two atypical rotaviruses from humans failed to infect gnotobiotic piglets. The atypical rotaviruses could be tentatively categorized into two groups serologically distinct from each other and from conventional rotaviruses, and these distinctions were consistent with electrophoretypes . The atypical chicken rotavirus may form a fourth distinct group. These findings are consistent with the hypothesis that rotaviruses belong to at least four separate groups definable by serology and electrophoretype .
Blastocyst vs cleavage‐stage embryo transfer: systematic review and meta‐analysis of reproductive outcomes

Blastocyst transfer in assisted reproduction techniques could be advantageous because the timing of exposure of the embryo to the uterine environment is more analogous to a natural cycle and permits embryo self‐selection after activation of the embryonic genome on day 3. Conversely, the in-vitro environment is likely to be inferior to that in vivo, and in-vitro culture beyond embryonic genomic activation could potentially harm the embryo. Our objective was to identify, appraise and summarize the available evidence comparing the effectiveness of blastocyst vs cleavage‐stage embryo transfer.
The Influence of Synthetic Amino Acid and Casein Hydrolysate on the Endogenous Production and Urinary Excretion of Acid in Total Intravenous Alimentation

Extract: These investigations are designed to quantitate the acidogenic properties of several commonly used amino acid solutions. Infusion of amino acid solutions causes a rise in the sulfuric acid production (H+so4 to a rate of 26.8–93.1 μEq/min/1.73 m2, which is a 4− to 14-fold increase over the preinfusion rate of 6.6 μEq/min/1.73 m2. This is a reflection of the amount of sulfur-containing amino acids in the infusate; it is lower with the casein hydrolysate than with the synthetic amino acid. The increase in H+so4 is also significantly less with the 2.13% solutions than with the 4.25% solutions.The rate of organic acid production (H+oa) tends to be higher with the 4.25% casein hydrolysate (48.1 μEq/min/1.73 m2) than with both the 2.13% and the 4.25% synthetic amino acid solutions (22.4–29.3 μEq/min/1.73 m2). The latter value is not significantly different from the preinfusion rate of H+oa (20.4 μEq/min/1.73 m2). However, taken together, the results of these data are consistent with the view that the total amount of acid produced (H+so4 plus H+oa) in association with infusion of the synthetic amino acid solutions is proportionately higher than that associated with infusion of the casein hydrolysate.The absolute values for the acid excretion during amino acid infusions also show differences from the preinfusion state of 23.7 μEq/min/1.73 m2. The net acid excretion increased nearly four times during the infusion of the 4.25% synthetic, amino acid and casein hydrolysate solutions. The net acid excretion is shown to be linearly correlated with the net acid production (r = 0.974). On the other hand, only 65% of net acid production is excreted as net acid by the kidneys, and the extracellular buffering can account for only a fraction of the difference between the net acid production and excretion.These studies also provide the first conclusive evidence that the rate of endogenous acid production during glucose-water infusion is 26.9 μEq/min/1.73 m2 or 2–3 mEq/kg/24 hr.Speculation: The data presented suggest that the marked increase in endogenous acid production is related to the quantity and quality of amino acid-sulfur in the different type of infusates used in total intravenous alimentation and further suggest a significant nonextracellular buffering mechanism (possibly the skeletal system).
Characterization of Two Alternately Spliced Forms of Phospholipase D1

We previously reported the cloning of a cDNA encoding human phosphatidylcholine-specific phospholipase D1 (PLD1), an ADP-ribosylation factor (ARF)-activated phosphatidylcholine-specific phospholipase D (Hammond, S. M., Tsung, S., Autschuller, Y., Rudge, S. A., Rose, K., Engebrecht, J., Morris, A. J., and Frohman, M. A. (1995) J. Biol. Chem. 270, 29640-29643). We have now identified an evolutionarily conserved shorter splice variant of PLD1 lacking 38 amino acids (residues 585-624) that arises from regulated splicing of an alternate exon. Both forms of PLD1 (PLD1a and 1b) have been expressed in Sf9 cells using baculovirus vectors and purified to homogeneity by detergent extraction and immunoaffinity chromatography. PLD1a and 1b have very similar properties. PLD1a and 1b activity is Mg2+dependent but insensitive to changes in free Ca2+ concentration. Phosphatidylinositol 4,5-bisphosphate and phosphatidylinositol 3,4,5-trisphosphate activate PLD1a and 1b but a range of other acidic phospholipids are ineffective. PLD1a and 1b are highly responsive to activation by GTP-γS-liganded ADP-ribosylation factor-1 (ARF-1) and can also be activated to a lesser extent by three purified RHO family monomeric GTP-binding proteins, RHO A, RAC-1, and CDC42. Activation of PLD1a and 1b by the RHO family monomeric GTP-binding proteins is GTP-dependent and synergistic with ARF-1. Purified protein kinase C-α activates PLD1a and 1b in a manner that is stimulated by phorbol esters and does not require ATP. Activation of PLD1a and 1b by protein kinase C-α is synergistic with ARF and with the RHO family monomeric GTP-binding proteins, suggesting that these three classes of regulators interact with different sites on the enzyme.
A New Microstructural Parameter for the Characterization of Porous Ceramics Derived from a Combination of Stochastic and Mechanical Modeling

Fiber-reinforced ceramics with a porous matrix possess good thermal insulation properties combined with high mechanical strength and damage tolerance. Therefore, they are being considered as good candidate materials for refractory applications in burners of stationary gas turbines or in other high temperature applications. To correlate the properties of porous materials with their microstructure, typically porosity is being considered as the dominant parameter. In this work, we suggest the average coordination number, i.e. the average number of connections that each grain of the porous material has to its neighboring grains, as additional and possibly even more fundamental microstructural parameter to describe material properties. To investigate this new parameter, a combination of stochastic and mechanical modeling is applied to study microstructural influences on the elastic properties of porous ceramics. This is accomplished by generating representative volume elements (RVE) with tailored microstructural features by a parametric stochastic microstructure model. These RVE are designed such that they mimic the microstructure of sintered porous ceramics by an assembly of overlapping spherical grains. In the next step, the elastic properties of the RVEs are characterized by finite element analysis, which yields the effective Young’s modulus of each RVE by virtue of a homogenization process. With this method it is possible to treat porosity and average coordination number of sintered grains as independent parameters. The results reveal that the average coordination number exhibits a very strong correlation with the Young’s modulus of the material. Moreover, it is seen that RVEs with the same average coordination number, but largely different porosities only differ very slightly in their elastic properties such that the correlation is almost unique. This finding is substantiated and discussed in terms of the load distribution in microstructures with different porosities and average coordination numbers.
Detecting faults in information poor systems using neurofuzzy models

Considers the problem of detecting faults in information poor systems where an accurate mathematical model is difficult to produce, the data available for training a black-box model are incomplete, and measurements are sparse and of poor quality. The problem of detecting faults in the cooling coil of an air-conditioning system is used as an illustrative example. Results are presented which demonstrate the advantages of using a neurofuzzy model-based detection scheme with a variable threshold. The performance is compared to that of an ideal model-based fault detector and that of detectors with fixed thresholds. The sensitivity of the diagnosis to the type and magnitude of the fault is also examined. Experimental data collected from a full-scale air-conditioning system are used to design and test a fault detector.
Effect of Mechanical Stimulation on the Differentiation of Cord Stem Cells

In this study, we evaluated the effect of mechanical stimulation on the differentiation of umbilical cord-derived mesenchymal stem cells (UC-MSCs) in osteogenic medium using a Flexcell system that imposed cyclic uniaxial mechanical stimulation at a strain of 0%, 5%, or 10% (5 s of stretch and 15 s of relaxation) for 10 days. The expression of MSC surface antigens (CD73, CD90, and CD105) was significantly decreased as strain increased. Mechanical stimulation inhibited the growth of UC-MSCs and slightly raised lactate dehydrogenase production. Mechanically stimulated groups produced more elastin and sulfated glycosaminoglycan than unstimulated groups and these increases were in proportion to the degree of strain. Reverse transcription-polymerase chain reaction analysis revealed that mechanical stimulation induced a significant increase in the mRNA expression of osteoblast differentiation markers. The mRNA levels of osteopontin, osteonectin, and type I collagen in the 5% and 10% strained groups were significantly higher than those in the 0% strained group. From the Western blot analysis, UC-MSCs produced bone sialoprotein and vimentin in a mechanical strain-dependent manner. Thus, cyclic mechanical loading was able to enhance the differentiation of human UC-MSCs into osteoblast-like cells as determined by osteogenic gene and protein expression. Furthermore, this finding has important implications for the use of the combination of mechanical and osteogenic differentiation media for UC-MSCs in tissue engineering and regenerative medicine.
Flavanol-Enriched Cocoa Powder Alters the Intestinal Microbiota, Tissue and Fluid Metabolite Profiles, and Intestinal Gene Expression in Pigs.

BACKGROUND Consumption of cocoa-derived polyphenols has been associated with several health benefits; however, their effects on the intestinal microbiome and related features of host intestinal health are not adequately understood. OBJECTIVE The objective of this study was to determine the effects of eating flavanol-enriched cocoa powder on the composition of the gut microbiota, tissue metabolite profiles, and intestinal immune status. METHODS Male pigs (5 mo old, 28 kg mean body weight) were supplemented with 0, 2.5, 10, or 20 g flavanol-enriched cocoa powder/d for 27 d. Metabolites in serum, urine, the proximal colon contents, liver, and adipose tissue; bacterial abundance in the intestinal contents and feces; and intestinal tissue gene expression of inflammatory markers and Toll-like receptors (TLRs) were then determined. RESULTS O-methyl-epicatechin-glucuronide conjugates dose-dependently increased (P< 0.01) in the urine (35- to 204-fold), serum (6- to 186-fold), and adipose tissue (34- to 1144-fold) of pigs fed cocoa powder. The concentration of 3-hydroxyphenylpropionic acid isomers in urine decreased as the dose of cocoa powder fed to pigs increased (75-85%,P< 0.05). Compared with the unsupplemented pigs, the abundance ofLactobacillusspecies was greater in the feces (7-fold,P= 0.005) and that ofBifidobacteriumspecies was greater in the proximal colon contents (9-fold,P= 0.01) in pigs fed only 20 or 10 g cocoa powder/d, respectively. Moreover, consumption of cocoa powder reducedTLR9gene expression in ileal Peyer's patches (67-80%,P< 0.05) and mesenteric lymph nodes (43-71%,P< 0.05) of pigs fed 2.5-20 g cocoa powder/d compared with pigs not supplemented with cocoa powder. CONCLUSION This study demonstrates that consumption of cocoa powder by pigs can contribute to gut health by enhancing the abundance ofLactobacillusandBifidobacteriumspecies and modulating markers of localized intestinal immunity.
Effects of a ginger extract on knee pain in patients with osteoarthritis.

OBJECTIVE To evaluate the efficacy and safety of a standardized and highly concentrated extract of 2 ginger species, Zingiber officinale and Alpinia galanga (EV.EXT 77), in patients with osteoarthritis (OA) of the knee. METHODS Two hundred sixty-one patients with OA of the knee and moderate-to-severe pain were enrolled in a randomized, double-blind, placebo-controlled, multicenter, parallel-group, 6-week study. After washout, patients received ginger extract or placebo twice daily, with acetaminophen allowed as rescue medication. The primary efficacy variable was the proportion of responders experiencing a reduction in "knee pain on standing," using an intent-to-treat analysis. A responder was defined by a reduction in pain of > or = 15 mm on a visual analog scale. RESULTS In the 247 evaluable patients, the percentage of responders experiencing a reduction in knee pain on standing was superior in the ginger extract group compared with the control group (63% versus 50%; P = 0.048). Analysis of the secondary efficacy variables revealed a consistently greater response in the ginger extract group compared with the control group, when analyzing mean values: reduction in knee pain on standing (24.5 mm versus 16.4 mm; P = 0.005), reduction in knee pain after walking 50 feet (15.1 mm versus 8.7 mm; P = 0.016), and reduction in the Western Ontario and McMaster Universities osteoarthritis composite index (12.9 mm versus 9.0 mm; P = 0.087). Change in global status and reduction in intake of rescue medication were numerically greater in the ginger extract group. Change in quality of life was equal in the 2 groups. Patients receiving ginger extract experienced more gastrointestinal (GI) adverse events than did the placebo group (59 patients versus 21 patients). GI adverse events were mostly mild. CONCLUSION A highly purified and standardized ginger extract had a statistically significant effect on reducing symptoms of OA of the knee. This effect was moderate. There was a good safety profile, with mostly mild GI adverse events in the ginger extract group.
Lubiprostone Prevents Nonsteroidal Anti-Inflammatory Drug–Induced Small Intestinal Damage by Suppressing the Expression of Inflammatory Mediators via EP4 Receptors

Lubiprostone, a bicyclic fatty acid derived from prostaglandin E1, has been used to treat chronic constipation and irritable bowel syndrome, and its mechanism of action has been attributed to the stimulation of intestinal fluid secretion via the activation of the chloride channel protein 2/cystic fibrosis transmembrane regulator (ClC-2/CFTR) chloride channels. We examined the effects of lubiprostone on indomethacin-induced enteropathy and investigated the functional mechanisms involved, including its relationship with the EP4 receptor subtype. Male Sprague-Dawley rats were administered indomethacin (10 mg/kg p.o.) and killed 24 hours later to examine the hemorrhagic lesions that developed in the small intestine. Lubiprostone (0.01–1 mg/kg) was administered orally twice 30 minutes before and 9 h after the indomethacin treatment. Indomethacin markedly damaged the small intestine, accompanied by intestinal hypermotility, a decrease in mucus and fluid secretion, and an increase in enterobacterial invasion as well as the up-regulation of inducible nitric-oxide synthase (iNOS) and tumor necrosis factor α (TNFα) mRNAs. Lubiprostone significantly reduced the severity of these lesions, with the concomitant suppression of the functional changes. The effects of lubiprostone on the intestinal lesions and functional alterations were significantly abrogated by the coadministration of AE3-208 [4-(4-cyano-2-(2-(4-fluoronaphthalen-1-yl)propionylamino)phenyl)butyric acid], a selective EP4 antagonist, but not by CFTR(inh)-172, a CFTR inhibitor. These results suggest that lubiprostone may prevent indomethacin-induced enteropathy via an EP4 receptor-dependent mechanism. This effect may be functionally associated with the inhibition of intestinal hypermotility and increase in mucus/fluid secretion, resulting in the suppression of bacterial invasion and iNOS/TNFα expression, which are major pathogenic events in enteropathy. The direct activation of CFTR/ClC-2 chloride channels is not likely to have contributed to the protective effects of lubiprostone.
Combined medical treatment using dutasteride and tamsulosin for lower urinary tract symptoms suggestive of benign prostatic hyperplasia

Importance of the field: Benign prostatic hyperplasia (BPH) is the fourth most commonly diagnosed medical condition in the elderly. Selective α-blockers (tamsulosin) and dual 5α-reductase inhibitors (dutasteride) have an important role in the medical treatment of symptomatic BPH. Safety and efficacy of combination therapy with dutasteride and tamsulosin as well as long-term benefit on prevention of disease progression have been widely studied in recent trials. Areas covered in this review: The present article summarizes the pharmacologic properties of both dutasteride and tamsulosin. Clinical efficacy of combination therapy in different trials has also been reported. Major randomized trials on this concept published between 2000 and 2010 have been covered in this article. What the reader will gain: Long-term efficacy and safety of combination therapy and its beneficial effect on quality of life and risk reduction of need for BPH-related surgeries have been discussed. Take home message: Combination therapy with dutasteride and tamsulosin is a highly efficacious medical treatment in patients with moderate-to-severe lower urinary tract symptoms due to benign prostatic enlargement, which could be safely tolerated and administrated for ≥ 4 years.