Miracle-dz/UniFAR-FTUs huggingface dataset:
Outcome After Injection Sclerotherapy for Esophageal Variceal Bleeding in Patients with Liver cirrhosis and COPD

to find out the outcome after variceal bleeding in patients with leiver cirrhosis and COPD. This retrospective study was conducted in Gastroenterology unit HMC, peshawar and Saidu Hospital Swat from June 1998 to December 2002. The study group comprised cirrhotic and COPD patients treated with endoscopic sclerotherapy for esophageal bleeding. We conclude that occurrenece of variceal bleeding is associated with high morbidity and the frequent development of life threatening complications in patients with liver cirrhosis and COPD. Hepatitc encephalopathy, rebleeding. renal failure, and hepatocellular carcinoma are the main risk factors.
Dendritic Cells in Hepatitis B Virus Infection: Host-pathogen interaction and immune modulation

textabstractThe discovery of the Hepatitis B virus (HBV) is a typical example of the role of serendipity in scientific progress. In 1967, Dr. Blumberg investigated the link between inherited traits and susceptibility to diseases by taking blood samples from native populations all over the world. These blood samples were tested for the presence of different serum proteins using antibodies derived from blood of haemophiliac patients. Dr. Blumberg reasoned that the immune system of these patients must recognize all blood serum proteins as a result of the blood transfusions they underwent. Using this technique, he discovered a match between an antibody from a haemophiliac patient in New York and a blood serum protein from an Australian aboriginal, which he called Australian antigen. Combination of this finding with research and clinical observations led to the insight that the Australian antigen caused hepatitis or liver inflammation, which in turn led to the discovery of HBV by the virologist Dr. Dane in1970. Two years later, a blood test to identify HBV and a vaccine against the virus were invented. In 1976, Dr. Blumberg was rewarded the Nobel Prize in medicine for this discovery.
What role for genetics in the prediction of multiple sclerosis?

For most of us, the foundations of our understanding of genetics were laid by considering Mendelian diseases in which familial recurrence risks are high, and mutant alleles are both necessary and sufficient. One consequence of this deterministic teaching is that our conceptualization of genetics tends to be dominated by the notion that the genetic aspects of disease are caused by rare alleles exerting large effects. Unfortunately, the preconceptions that flow from this training are frequently erroneous and misleading in the context of common traits, where familial recurrence risks are modest, and for the most part the relevant alleles are neither rare, necessary, nor sufficient. For these common traits, the genetic architecture is far more complex, with susceptibility rather than causality resulting from the combined effects of many alleles, each exerting only a modest effect on risk. None of these alleles is sufficient to cause disease on its own, and none is essential for the development of disease. Furthermore, most are carried by large sections of the population, the vast majority of which does not develop the disease. One consequence of our innate belief in the Mendelian paradigm is that we have an inherent expectation that knowledge about the genetic basis for a disease should allow genetic testing and thereby accurate risk prediction. There is an inevitable feeling that the same should be true in complex disease, but is it? ANN NEUROL 2010;67:3–10
Rho GTPases RhoA and Rac1 Mediate Effects of Dietary Folate on Metastatic Potential of A549 Cancer Cells through the Control of Cofilin Phosphorylation*

Background: Molecular mechanisms translating effects of folate on metastasis are not clear. Results: Folate restriction inhibits methylation and membrane translocation of Rho GTPases in A549 cancer cells and provides survival advantage in mice with lung cancer. Conclusion: Folate enhances migratory ability and invasiveness of cancer cells through Rho GTPase pathways and promotes metastasis. Significance: This study highlights the interaction between nutrients and metastasis-related signaling. Folate, an important nutrient in the human diet, has been implicated in cancer, but its role in metastasis is not established. We have shown previously that the withdrawal of medium folate leads to the inhibition of migration and invasion of A549 lung carcinoma cells. Here we have demonstrated that medium folate regulates the function of Rho GTPases by enabling their carboxyl methylation and translocation to plasma membrane. Conversely, the lack of folate leads to the retention of these proteins in endoplasmic reticulum. Folate also promoted the switch from inactive (GDP-bound) to active (GTP-bound) GTPases, resulting in the activation of downstream kinases p21-activated kinase and LIM kinase and phosphorylation of the actin-depolymerizing factor cofilin. We have further demonstrated that in A549 cells two GTPases, RhoA and Rac1, but not Cdc42, are immediate sensors of folate status: the siRNA silencing of RhoA or Rac1 blocked effects of folate on cofilin phosphorylation and cellular migration and invasion. The finding that folate modulates metastatic potential of cancer cells was confirmed in an animal model of lung cancer using tail vein injection of A549 cells in SCID mice. A folate-rich diet enhanced lung colonization and distant metastasis to lymph nodes and decreased overall survival (35 versus 63 days for mice on a folate-restricted diet). High folate also promoted epithelial-mesenchymal transition in cancer cells and experimental mouse tumors. Our study provides experimental evidence for a mechanism of metastasis promotion by dietary folate and highlights the interaction between nutrients and metastasis-related signaling.
Clinical Examination of Farm Animals

Preface. Acknowledgements. Part I Introduction. 1 Principles of Clinical Examination. Part II Cattle -- Clinical Examination by Body System and Region. 2 The General Clinical Examination of Cattle. 3 Clinical Examination of the Lymphatic System. 4 Clinical Examination of the Skin. 5 Clinical Examination of the Head and Neck. 6 Clinical Examination of the Cardiovascular System. 7 Clinical Examination of the Respiratory System. 8 Clinical Examination of the Gastrointestinal System. 9 Clinical Examination of the Urinary System. 10 Clinical Examination of the Female Genital System. 11 Clinical Examination of the Male Genital System. 12 Clinical Examination of the Udder. 13 Clinical Examination of the Musculoskeletal System. 14 Clinical Examination of the Nervous System. Part III Sheep. 15 Clinical Examination of the Sheep. Part IV Pigs. 16 Clinical Examination of the Pig. Part V Goats. 17 Clinical Examination of the Goat. Bibliography. Appendix 1 Normal Physiological Values. Appendix 2 Laboratory Reference Values: Haematology. Appendix 3 Laboratory Reference Values: Biochemistry. Index.
El trabajo de fuerza en el desarrollo de la potencia en futbolistas de las divisiones menores de un equipo profesional de fútbol

Theoretically, high levels of strength correlate with improvement in manifestations of immediate muscular power, which is a decisive variable of performance in modern soccer. Purpose : to de- urpose: termine in soccer players if strength training at a high percentage (85%) of 1-RM, looking for increase in maximum strength, is more effective in improving immediate muscular power than a similar training but at 75% of 1-RM. Methodology: 60 soccer players belonging to the inferior divisions of DIM were randomly assigned to either one of two groups of 30 players each, and performed the following strength training protocols: the experimental group carried out an individual bilateral force training for knee extensors and flexors that consisted of 3 series of 5 repetitions each, at 85% of 1-RM, with 5 minutes of rest between series, twice a week during 12 weeks. The control group trained the same muscular groups, 3 series of 8 repetitions each, at 75% of 1-RM, also with 5 minutes of rest between series, twice a week during 12 weeks. At the onset, and at 6 and 12 weeks measurements were made of maximum strength (1-RM) of knee extensors and flexors and of immediate muscular power: speed in 20 m, Squat Jump and Countermovement Jump. Results : although the 60 players completed the training, data were analyzed for only 29 in the experimental group and 27 in the control one; of the remaining 4 participants, 2 left the team and 2 suffered injuries unrelated with the training. No significant differences were found between the two groups, in any of the variables, in any of the 3 measurements. Most of the variables -strength of the right knee extensors, strength of the left knee extensors, strength of the right knee flexors, strength of the left knee flexors, Squat Jump, Countermovement Jump – had statistically significant increases (p Conclusions: maximum strength training at intensities of 75 and 85% of 1-M produces significant improvement in immediate muscular power.
Computational and Biochemical Docking of the Irreversible Cocaine Analog RTI 82 Directly Demonstrates Ligand Positioning in the Dopamine Transporter Central Substrate-binding Site*

Background: Cocaine interaction with DAT was assessed using the irreversible binding cocaine analog RTI 82. Results: Molecular modeling and peptide mapping identify adduction of RTI 82 to Phe-319 and Phe-320 of rat DAT and human DAT, respectively. Conclusion: Tropane-based pharmacophores bind to DAT in the central substrate site. Significance: Mapping the cocaine-binding site reveals new insights for medication discovery. The dopamine transporter (DAT) functions as a key regulator of dopaminergic neurotransmission via re-uptake of synaptic dopamine (DA). Cocaine binding to DAT blocks this activity and elevates extracellular DA, leading to psychomotor stimulation and addiction, but the mechanisms by which cocaine interacts with DAT and inhibits transport remain incompletely understood. Here, we addressed these questions using computational and biochemical methodologies to localize the binding and adduction sites of the photoactivatable irreversible cocaine analog 3β-(p-chlorophenyl)tropane-2β-carboxylic acid, 4′-azido-3′-iodophenylethyl ester ([125I]RTI 82). Comparative modeling and small molecule docking indicated that the tropane pharmacophore of RTI 82 was positioned in the central DA active site with an orientation that juxtaposed the aryliodoazide group for cross-linking to rat DAT Phe-319. This prediction was verified by focused methionine substitution of residues flanking this site followed by cyanogen bromide mapping of the [125I]RTI 82-labeled mutants and by the substituted cysteine accessibility method protection analyses. These findings provide positive functional evidence linking tropane pharmacophore interaction with the core substrate-binding site and support a competitive mechanism for transport inhibition. This synergistic application of computational and biochemical methodologies overcomes many uncertainties inherent in other approaches and furnishes a schematic framework for elucidating the ligand-protein interactions of other classes of DA transport inhibitors.
Real‐time computation of subdiffraction‐resolution fluorescence images

In the recent past, single‐molecule based localization or photoswitching microscopy methods such as stochastic optical reconstruction microscopy (STORM) or photoactivated localization microscopy (PALM) have been successfully implemented for subdiffraction‐resolution fluorescence imaging. However, the computational effort needed to localize numerous fluorophores is tremendous, causing long data processing times and thereby limiting the applicability of the technique. Here we present a new computational scheme for data processing consisting of noise reduction, detection of likely fluorophore positions, high‐precision fluorophore localization and subsequent visualization of found fluorophore positions in a super‐resolution image. We present and benchmark different algorithms for noise reduction and demonstrate the use of non‐maximum suppression to quickly find likely fluorophore positions in high depth and very noisy images. The algorithm is evaluated and compared in terms of speed, accuracy and robustness by means of simulated data. On real biological samples, we find that real‐time data processing is possible and that super‐resolution imaging with organic fluorophores of cellular structures with ∼20 nm optical resolution can be completed in less than 10 s.
Mitochondria Are Gate-keepers of T Cell Function by Producing the ATP That Drives Purinergic Signaling*

Background: Autocrine purinergic signaling regulates T cell function. Results: We found that mitochondria are the source of ATP that drives these signaling mechanisms. Conclusion: Mitochondria are the gate-keepers of T cell function that control purinergic signaling and T cell activation. Significance: These findings suggest that mitochondria could be therapeutic targets to modulate T cell responses. T cells play a central role in host defense. ATP release and autocrine feedback via purinergic receptors has been shown to regulate T cell function. However, the sources of the ATP that drives this process are not known. We found that stimulation of T cells triggers a spike in cellular ATP production that doubles intracellular ATP levels in <30 s and causes prolonged ATP release into the extracellular space. Cell stimulation triggered rapid mitochondrial Ca2+ uptake, increased oxidative phosphorylation, a drop in mitochondrial membrane potential (Δψm), and the accumulation of active mitochondria at the immune synapse of stimulated T cells. Inhibition of mitochondria with CCCP, KCN, or rotenone blocked intracellular ATP production, ATP release, intracellular Ca2+ signaling, induction of the early activation marker CD69, and IL-2 transcription in response to cell stimulation. These findings demonstrate that rapid activation of mitochondrial ATP production fuels the purinergic signaling mechanisms that regulate T cells and define their role in host defense.
Histone Deacetylase 3 Is Necessary for Proper Brain Development*

Background: The molecular mechanisms regulating brain development are unclear. Results: HDAC3 deletion disrupts the organization of certain neuronal cell types and the proportions of some glial cell types in the cortex and cerebellum. Conclusion: HDAC3 regulates brain development, and other HDACs cannot compensate for its function. Significance: Our study identifies a key player in the regulation of brain development. The functional role of histone deacetylase 3 (HDAC3) in the developing brain has yet to be elucidated. We show that mice lacking HDAC3 in neurons and glia of the central nervous system, Nes-Cre/HDAC3 conditional KO mice, show major abnormalities in the cytoarchitecture of the neocortex and cerebellum and die within 24 h of birth. Later-born neurons do not localize properly in the cortex. A similar mislocalization is observed with cerebellar Purkinje neurons. Although the proportion of astrocytes is higher than normal, the numbers of oligodendrocytes are reduced. In contrast, conditional knockout of HDAC3 in neurons of the forebrain and certain other brain regions, using Thy1-Cre and calcium/calmodulin dependent protein kinase II α-Cre for ablation, produces no overt abnormalities in the organization of cells within the cortex or of cerebellar Purkinje neurons at birth. However, both lines of conditional knockout mice suffer from progressive hind limb paralysis and ataxia and die around 6 weeks after birth. The mice display an increase in overall numbers of cells, higher numbers of astrocytes, and Purkinje neuron degeneration. Taken together, our results demonstrate that HDAC3 plays an essential role in regulating brain development, with effects on both neurons and glia in different brain regions.
Assessment of Congo red as a fluorescence marker for the exoskeleton of small crustaceans and the cuticle of polychaetes

In this study, the potential of the common dye Congo red as a fluorescence marker for chitin in the exoskeleton of small crustaceans and collagen in the polychaete cuticle was tested. The Congo red staining turned out to be rather efficient and yielded intensively fluorescing structures, which made a very detailed visualization by confocal laser scanning microscopy possible. The excellent results are comparable to those described for the utilization of other efficient fluorescence dyes and intense autofluorescence. The application of Congo red is easy, the fluorescence of this dye is very stable, and the excitation maximum of the structures stained with Congo red is in a range, which is covered by the lasers of most of the confocal laser scanning microscopes. These advantageous properties make the fluorescence staining by Congo red a method of choice for the detailed visualization of the external morphology of small crustaceans and polychaetes.
Biogenesis of Lysosome-related Organelles Complex-1 Subunit 1 (BLOS1) Interacts with Sorting Nexin 2 and the Endosomal Sorting Complex Required for Transport-I (ESCRT-I) Component TSG101 to Mediate the Sorting of Epidermal Growth Factor Receptor into Endosomal Compartments*

Background: EGFR lysosomal trafficking process is important for the modulation of EGF signaling. Results: Delayed EGFR degradation in BLOS1 knockdown cells is restored by the overexpressed BLOS1 fragment that interacts with both SNX2 and TSG101. Conclusion: BLOS1 mediates EGFR lysosomal trafficking. Significance: Enhancement of EGFR lysosomal degradation will be effective in the treatment of cancer or lung fibrosis. Biogenesis of lysosome-related organelles complex-1 (BLOC-1) is a component of the molecular machinery required for the biogenesis of specialized organelles and lysosomal targeting of cargoes via the endosomal to lysosomal trafficking pathway. BLOS1, one subunit of BLOC-1, is implicated in lysosomal trafficking of membrane proteins. We found that the degradation and trafficking of epidermal growth factor receptor (EGFR) were delayed in BLOS1 knockdown cells, which were rescued through BLOS1 overexpression. A key feature to the delayed EGFR degradation is the accumulation of endolysosomes in BLOS1 knockdown cells or BLOS1 knock-out mouse embryonic fibroblasts. BLOS1 interacted with SNX2 (a retromer subunit) and TSG101 (an endosomal sorting complex required for transport subunit-I) to mediate EGFR lysosomal trafficking. These results suggest that coordination of the endolysosomal trafficking proteins is important for proper targeting of EGFR to lysosomes.
3D visualization of subcellular structures of Schizosaccharomyces pombe by hard X‐ray tomography

Cellular structures of the fission yeast, Schizosaccharomyces pombe, were examined by using hard X‐ray tomography. Since cells are nearly transparent to hard X‐rays, Zernike phase contrast and heavy metal staining were introduced to improve image contrast. Through using such methods, images taken at 8 keV displayed sufficient contrast for observing cellular structures. The cell wall, the intracellular organelles and the entire structural organization of the whole cells were visualized in three‐dimensional at a resolution better than 100 nm. Comparison between phase contrast and absorption contrast was also made, indicating the obvious advantage of phase contrast for cellular imaging at this energy. Our results demonstrate that hard X‐ray tomography with Zernike phase contrast is suitable for cellular imaging. Its unique abilities make it have potential to become a useful tool for revealing structural information from cells, especially thick eukaryotic cells.
Neuropathy in idiopathic Parkinson disease: An Iatrogenic problem?

We read with interest the article by Toth et al reporting a high occurrence (55%) of neuropathy in idiopathic Parkinson disease (IPD). They found a strong association, without demonstrating a causative effect, between L-dopa exposure, methylmalonic acid level, and neuropathy severity. Previously we reported, in 18 IPD patients, epidermal nerve fiber (ENF), Meissner corpuscle (MC), and sensory loss more evident on the more affected side, without correlation with age, disease duration, and apparently drug treatment (4 patients were untreated). MC loss correlated instead with disease severity. These findings suggest that the neuropathic involvement occurs early in IPD, representing 1 of the neuropathological aspects of a multisystem neurodegenerative disease. However, inspired by Toth’s work, we calculated the cumulative L-dopa intake for each of our IPD patients and studied 3 more untreated subjects. We found that L-dopa exposure did not correlate with ENF density in thigh (p 1⁄4 0.36), leg (p 1⁄4 0.25), and fingertip (p 1⁄4 0.37), whereas it correlated (p < 0.05) with MC density (Fig A), in agreement with the association between L-dopa intake and nerve conduction velocity (NCV) found by Toth. In fact, both MC count and NCV explore, in different ways, large fibers. However, in our patients, L-dopa intake correlated also (p < 0.02) with disease severity (see Fig B), which in turn correlated (p < 0.05) with MC loss (see Fig C). The same correlations between L-dopa exposure, IPD severity, and neuropathy were reported by Toth, leaving unclear the role of therapy and disease severity in the development of large fiber neuropathy in IPD. Examining our data from treated and untreated patients separately, we observed a loss of ENF in both groups (see Fig G, I vs E), whereas a loss of MCs was present only in the treated patients (see Fig , H vs D). In untreated patients, MCs showed, however, evident morphological anomalies (see Fig F vs D). ENF loss in IPD appears, then, unrelated to drug treatment. Conversely, we could not determine the exact role of L-dopa treatment and disease severity in the degeneration of large fiber endings. Finally, Toth’s electrophysiological findings show a discrepancy with ours (abnormality 1⁄4 55% vs 0%) that resolves considering the different Unified Parkinson Disease Rating Scale scores (42.1627.9 vs 26.6610.2) and L-dopa exposure (1.7261.14 kg vs 1.0361.39 kg) of the 2 populations. Our patients are more similar to the subgroup without neuropathy studied by Toth, which, however, could have shown morphological abnormalities using skin biopsy. Therefore, a larger study including both electrophysiological and morphological methods should be performed to evaluate the neurotoxicity of L-dopa and the possible protective effect of cobalamin supplementation.