Miracle-dz/UniFAR-FTUs huggingface dataset:
Gastroparesis and lipid metabolism-associated dysbiosis in Wistar-Kyoto rats

This study reveals that the stress-prone Wistar-Kyoto rat strain has a baseline physiology of gastroparesis and rapid small intestine transit, together with metabolic changes consistent with lipid metabolism-associated dysbiosis, compared with nonstress-prone rats. This suggests that the Wistar-Kyoto rat strain may be an appropriate animal model for gastroparesis.
Genetic variants in miR-146a, miR-149, miR-196a2, miR-499 and their influence on relative expression in lung cancers

Abstract Background: The presence of sequence variants in miRNA genes may influence their processing, expression and binding to target mRNAs. Since single miRNA can have a large number of potential mRNA targets, even minor variations in its expression can have influences on hundreds of putative mRNAs. Methods: Here, we evaluated 101 paired samples (cancer and normal tissues) from non-small cell lung carcinoma (NSCLC) patients to study the genotype distribution of single nucleotide polymorphisms (SNPs) in miR-146a (rs2910164 C-G), miR-149 (rs2292832 C-T), miR-196a2 (rs11614913 C-T) and miR-499 (rs3746444 G-A) and their influence on the expression of respective miRNAs. Results: Relative expression of miR-146a, miR-149 and miR-499 were comparable in NSCLC and in paired control tissues. On the contrary, we clearly detected a significant increase (p<0.001) of miR-196a2 expression in NSCLC. In particular we found a significant association between miR-196a2 CC genotype and high expression, whereas TT geno-type showed a very low expression in comparison to both CT (p<0.005) and CC patients (p<0.01). We did not find any association between miR-149, miR-196a2 and miR-499 genotype and risk of NSCLC. Conversely, CG genotype of miR-146a appeared associated to an increased risk for NSCLC (p=0.042 and 1.77 OR). Conclusions: Our results seem to demonstrate that sequence variants of miR-196a2 can have an influence on its expression, while miR-146a can have a role in increasing the risk of NSCLC.
Genes essential for morphological development and antibiotic production in Streptomyces coelicolor are targets of BldD during vegetative growth

BldD is a transcriptional regulator essential for morphological development and antibiotic production in Streptomyces coelicolor. Here we identify the BldD regulon by means of chromatin immunoprecipitation‐microarray analysis (ChIP‐chip). The BldD regulon encompasses ∼167 transcriptional units, of which more than 20 are known to play important roles in development (e.g. bldA, bldC, bldH/adpA, bldM, bldN, ssgA, ssgB, ftsZ, whiB, whiG, smeA‐ssfA) and/or secondary metabolism (e.g. nsdA, cvn9, bldA, bldC, leuA). Strikingly, 42 BldD target genes (∼25% of the regulon) encode regulatory proteins, stressing the central, pleiotropic role of BldD. Almost all BldD binding sites identified by ChIP‐chip are present in the promoters of the target genes. An exception is the tRNA gene bldA, where BldD binds within the region encoding the primary transcript, immediately downstream of the position corresponding to the processed, mature 3′ end of the tRNA. Through gene overexpression, we identified a novel BldD target gene (cdgA) that influences differentiation and antibiotic production. cdgA encodes a GGDEF domain protein, implicating c‐di‐GMP in the regulation of Streptomyces development. Sequence analysis of the upstream regions of the complete regulon identified a 15 bp inverted repeat that functions as a high‐affinity binding site for BldD, as was shown by electrophoretic mobility shift assays and DNase I footprinting analysis. High‐scoring copies of the BldD binding site were found at relevant positions in the genomes of other bacteria containing a BldD homologue, suggesting the role of BldD is conserved in sporulating actinomycetes.
Effect of prolonged, submaximal exercise and carbohydrate ingestion on monocyte intracellular cytokine production in humans

1 The present study was undertaken to examine the effect of exercise and carbohydrate (CHO) ingestion on intracellular monocyte cytokine production. Subjects performed 2 h of cycling at 70 % peak pulmonary O2 uptake (V̇O2,peak) while ingesting either an 8 % CHO beverage or a sweet placebo. Whole blood was incubated with (stimulated) or without (spontaneous) lipopolysaccharide (LPS) and surface stained for monocyte surface antigens. The cells were permeabilised, stained for intracellular cytokines and analysed using flow cytometry. 2 Exercise had no effect on the number of monocytes spontaneously producing cytokines, but the number of stimulated IL‐1α‐, TNF‐α‐ and IL‐6‐positive monocytes were elevated (P < 0·01) immediately post‐exercise and 2 h post‐exercise. These stimulated cells produced less (P < 0·05) TNF‐α immediately post‐exercise, and less (P < 0·05) TNF‐α and IL‐1α 2 h post‐exercise. There was a small, but significant increase (P < 0·05) in the plasma IL‐6 concentration immediately post‐exercise. 3 Exercise resulted in an elevation (P < 0·01) in the plasma adrenaline concentration in the placebo trial, and ingestion of CHO attenuated this increase. CHO ingestion had no effect on monocyte cytokine production, plasma IL‐6 or circulating leukocyte numbers. 4 These data suggest that circulating monocytes are not the origin of increased levels of plasma IL‐6 during exercise: prolonged cycling exercise increased the number of monocytes producing cytokines upon stimulation, but these cells produced less cytokines post‐exercise. In addition, attenuation of plasma adrenaline levels had no effect on plasma IL‐6 or monocyte cytokine production.
Vaccinia Virus A26 and A27 Proteins Form a Stable Complex Tethered to Mature Virions by Association with the A17 Transmembrane Protein

ABSTRACT During vaccinia virus replication, mature virions (MVs) are wrapped with cellular membranes, transported to the periphery, and exported as extracellular virions (EVs) that mediate spread. The A26 protein is unusual in that it is present in MVs but not EVs. This distribution led to a proposal that A26 negatively regulates wrapping. A26 also has roles in the attachment of MVs to the cell surface and incorporation of MVs into proteinaceous A-type inclusions in some orthopoxvirus species. However, A26 lacks a transmembrane domain, and nothing is known regarding how it associates with the MV, regulates incorporation of the MV into inclusions, and possibly prevents EV formation. Here, we provide evidence that A26 forms a disulfide-bonded complex with A27 that is anchored to the MV through a noncovalent interaction with the A17 transmembrane protein. In the absence of A27, A26 was unstable, and only small amounts were detected. The interaction of A26 with A27 depended on a C-terminal segment of A26 with 45% amino acid identity to A27. Deletion of A26 failed to enhance EV formation by vaccinia virus, as had been predicted. Nevertheless, the interaction of A26 and A27 may have functional significance, since each is thought to mediate binding to cells through interaction with laminin and heparan sulfate, respectively. We also found that A26 formed a noncovalent complex with A25, a truncated form of the cowpox virus A-type inclusion matrix protein. The latter association suggests a mechanism for incorporation of virions into A-type inclusions in other orthopoxvirus strains.
Hearing preservation in partial deafness treatment.

BACKGROUND Partial deafness (PD) is a condition in which hearing loss occurs in at least 1 frequency critical to speech understanding. Current options for partial deafness treatment (PDT) rely on preoperative hearing preservation, which, along with the use of different means of acoustic and electric stimulation, enable extending the indications for various assistive hearing devices. Possible solutions include acoustic methods only, the use of hearing aids or middle ear implants, electric complementation, and a combination of electric and acoustic stimulation. MATERIAL/METHODS A total of 95 patients (63 adults, 32 children) with different types of PD were treated using selected types of electrodes and the optimal "round window" approach to the inner ear, with at least 36 months of observation. RESULTS The extension of PDT indications created an opportunity for patients with different hearing impairments who obtained no benefit from a hearing aid and did not qualify for standard cochlear implant application. The authors' observations are based on the findings that preservation of preoperative hearing had been achieved in 97.1% of adult patients (8 years' observation) and in 100% of children (6 years' observation). Those results send the important message that PDT is feasible and effective. CONCLUSIONS To allow comparison of PDT results from different studies, the authors developed the Skarzynski PDT classification system, which permits the comparison of postoperative results, including the degree of hearing preservation and, more importantly, the patient's understanding of speech after treatment.
Can we win the war on obesity with pharmacotherapy?

ABSTRACT Introduction: Obesity is a major health concern for several countries. The United States (U.S.) has arguably led the world in the percentage of overweight and/or obese per capita for several decades. As a result, numerous FDA-approved pharmacotherapeutic options are available for the long-term treatment of obesity. Although most of these medications have been on the U.S. market for a few years and have demonstrated efficacy for long-term weight loss in clinical trials, the impact of these medications on obesity in the U.S. has yet to be realized. Areas covered: We will review and evaluate why pharmacotherapy for obesity has not produced a meaningful reduction in the number of overweight and obese adults in the U.S. Expert commentary: Several obstacles, such as adverse drug effects, poor insurance coverage, not treating obesity as a chronic disease, and availability of other weight loss alternatives, has resulted in poor performance of pharmacotherapy for obesity in the U.S. market.
Hypothyroid symptoms and the likelihood of overt thyroid failure: a population-based case-control study.

BACKGROUND It is generally accepted that patients suffering from hypothyroidism may express few symptoms, but this has not been studied in a population-based study design. OBJECTIVES To study the array of symptoms as they are reported in newly diagnosed overt autoimmune hypothyroidism using a population-based case-control design. METHODS Patients with new overt autoimmune hypothyroidism (n=140) and their individually matched thyroid disease-free controls (n=560) recruited from the same population underwent a comprehensive program and self-reported a number of symptoms. We identified the symptoms associated with overt hypothyroidism and calculated positive (LR+) and negative (LR-) likelihood ratios as well as diagnostic odds ratios (DORs) as measures for the association between disease state and symptoms. RESULTS Among 34 symptoms investigated, 13 symptoms were statistically overrepresented in hypothyroidism. Hypothyroid patients suffered mostly from tiredness (81%), dry skin (63%), and shortness of breath (51%). Highest DORs (95% CI) were reported for tiredness (5.94 (3.70-9.60)), hair loss (4.58 (2.80-7.51)), and dry skin (4.09 (2.73-6.16)). A hypothyroidism-component-score was defined as the number of hypothyroidism-associated symptoms (range: 0-13). LR+ for participants with a hypothyroidism-component-score of 0 was 0.21 (0.09-0.39), meaning that the post-test probability was lowered to 21% of what it was before asking for symptoms. LR+ for scores of 1-2/3/4-6/7-9/10-13 were: 0.47 (0.30-0.72)/1.16 (0.70-1.87)/1.90 (1.29-2.45)/3.52 (2.30-5.36)/6.29 (2.30-17.7). CONCLUSIONS None of the individual symptoms of hypothyroidism had high LRs or DORs. Thus, neither the presence nor absence of any individual hypothyroidism symptom was reliable in the decision making of who should have their thyroid function tested. Therefore, even minor suspicion should lead to a blood test.
Thyroid hormone influences muscle mechanics in carp (Cyprinus carpio) independently from SERCA activity

ABSTRACT Thyroid hormone is a key regulator of metabolism, and in zebrafish, hypothyroidism decreases sustained and burst swimming performance. These effects are accompanied by decreases in both metabolic scope and the activity of sarco-endoplasmic reticulum ATPase (SERCA) in zebrafish. Our aim was to determine whether thyroid hormone affects skeletal muscle contractile function directly and whether these effects are mediated by influencing SERCA activity. We show that hypothyroidism reduces sustained locomotor performance but not sprint performance in carp (Cyprinus carpio). We accept our hypothesis that hypothyroidism reduces force production in isolated skeletal muscle, when compared with the thyroid hormone T2, but we reject the hypothesis that this effect is mediated by influencing SERCA activity. Blocking SERCA activity with thapsigargin reduced muscle fatigue resistance, but hypothyroidism had no effect on fatigue. Hence, thyroid hormone plays a role in determining isolated skeletal muscle mechanics, but its effects are more likely to be mediated by mechanisms other than affecting SERCA activity. Summary: Thyroid hormone plays a key role in maintaining normal levels of skeletal muscle force production in carp, but this is not mediated via SERCA.
Isokinetic maximal torque power of greek elite soccer players.

Eighteen elite Greek soccer players (age, 27.8 +/- 3.4 years; height, 176.6 +/- 5.2 cm; weight, 75.5 +/- 5.2 kg) were tested on the Cybex(R) II apparatus in order to determine 1) the maximal muscle power for the lower extremity dominant side at angular velocities of 30 degrees /sec, 90 degrees /sec, and 180 degrees /sec; 2) the total muscular output and the relative power at 30 degrees /sec; 3) the relationship between the muscle power of the agonist and antagonist musculature. The absolute maximal muscle power (Nm) at 30 degrees /sec for the different joint movements was as follows: Hip Ext = 269 +/- 39; Hip Flex = 179 +/- 29; Hip Add = 160 +/- 17; Hip Abd = 119 +/- 24; Knee Ext = 247 +/- 29; Knee Flex = 146 +/- 12; PI. Flex = 120 +/- 22; and Do. Flex = 32 +/- 6. The muscle agonist-antagonist percent relationship at 30 degrees /sec was found to be: (hip flex)/(hip ext) = 66%(hip abd)/(hip add) = 74%(knee flex)/(knee ext) = 60%(dor. fle)/(pl. fle) = 28%These findings have significant implications for preseason conditioning programs as well as for minimizing the rate of muscle injuries by restoring the correct relationship between agonist-antagonist musculature.J Orthop Sports Phys Ther 1985;6(5):293-295.
Increased sensitivity to mitochondrial permeability transition and myonuclear translocation of endonuclease G in atrophied muscle of physically active older humans

Mitochondrial dysfunction is implicated in skeletal muscle atrophy and dysfunction with aging, with strong support for an increased mitochondrial‐mediated apoptosis in sedentary rodent models. Whether this applies to aged human muscle is unknown, nor is it clear whether these changes are caused by sedentary behavior. Thus, we examined mitochondrial function [respiration, reactive oxygen species (ROS) emission, and calcium retention capacity (CRC)] in permeabilized myofibers obtained from vastus lateralis muscle biopsies of healthy physically active young (23.7±2.7 yr; mean±sd) and older (71.2±4.9 yr) men. Although mitochondrial ROS and maximal respiratory capacity were unaffected, the acceptor control ratio was reduced by 18% with aging, suggesting mild uncoupling of oxidative phosphorylation. CRC was reduced by 50% with aging, indicating sensitization of the mitochondrial permeability transition pore (mPTP) to apoptosis. Consistent with the mPTP sensitization, older muscles showed a 3‐fold greater fraction of endonuclease G (a mitochondrial proapoptotic factor)‐positive myonuclei. Aged muscles also had lower mitophagic potential, based on a 43% reduction in Parkin to the voltage‐dependent anion channel (VDAC) protein ratio. Collectively, these results show that mitochondrial‐mediated apoptotic signaling is increased in older human muscle and suggest that accumulation of dysfunctional mitochondria with exaggerated apoptotic sensitivity is due to impaired mitophagy. —Gouspillou, G. , Sgarioto, N. , Kapchinsky, S. , Purves‐Smith, F. , Norris, B. , Pion, C. H. , Barbat‐Artigas, S. , Lemieux, R, Taivassalo, T. , Morais, J. A. , Aubertin‐Leheudre, M. , Hepple, R. T. Increased sensitivity to mitochondrial permeability transition and myonuclear translocation of endonuclease G in atrophied muscle of physically active older humans. FASEB J. 28, 28–1621 (1633). www.fasebj. org
Differential Expression and Regulation of hsp70 and hsp90 by Phorbol Esters and Heat Shock (*)

Human peripheral blood monocytes (PBM) produce superoxide anions (O) by a process involving electron transfer from NADPH to O2, catalyzed by the respiratory burst enzyme NADPH oxidase. We have previously shown that phagocytosis, while activating NADPH oxidase, induced in PBM the synthesis of heat shock (HS) proteins (HSP). The present study was undertaken to establish whether this increase in HSP expression was related to O and/or to classical second messengers such as protein kinase C (PKC). Thus, the effects of the PKC activator phorbol 12-myristate 13-acetate (PMA) were compared with those of heat shock on the expression, in PBM, of the major HSP, hsp70 and hsp90, using biometabolic labeling, Western and Northern blotting, and gel mobility shift assays. PMA induced the accumulation of mRNA and an increased expression of hsp90 and, to a lesser extent, hsp/hsc70 (hsc is the cognate, constitutive form). This induction was also observed in PBM from patients with chronic granulomatous disease, a genetic defect in NADPH oxidase, and was abolished by the PKC inhibitors staurosporine and H-7. PMA did not cause activation of the HS factor, and the PMA-induced overexpression of HSP was not blocked by the transcriptional inhibitor actinomycin D. HSP-specific mRNA stability was increased after PMA exposure as compared with heat shock. These results suggest that O is not involved in the PMA-mediated induction of hsp70 and hsp90 and that, in contrast to HS, PMA increases the expression of HSP as a result of PKC-induced mRNA stabilization rather than of transcriptional activation of HS genes.
A prototype rotating slat collimator for single photon emission computed tomography

A collimator consisting of a series of highly attenuating parallel slats has been constructed and used in conjunction with a gamma-camera to approximately measure planar projections of a given radionuclide distribution. The enlarged solid angle of acceptance afforded by the slat collimator gave rise to an increased geometric efficiency of between 12 and 28 times that observed with a low-energy high-resolution (LEHR) parallel-hole collimator. When the slats rotated over the face of the detector and the camera gantry turned about the object, sufficient projections were acquired to reconstruct a three-dimensional (3-D) image using the inversion of the 3-D radon transform. The noise behavior of an algorithm for implementing this inversion was studied analytically and the resulting relationship has been verified by computer simulation. The substantially improved geometric efficiency of the slat collimator translated to improvements in reconstructed signal-to-noise ratio (SNR) by, at best, up to a factor of 2.0 with respect to standard parallel-hole collimation. The spatial resolution achieved with the slat collimator was comparable to that obtained with a LEHR collimator and no significant differences were observed in terms of scatter response. Accurate image quantification was hindered by the spatially variant response of the slat collimator.
Expression of maspin and kai1 and their clinicopathological significance in carcinogenesis and progression of gastric cancer.

OBJECTIVE To investigate the roles of maspin and kai1 expression in tumorigenesis and progression of gastric cancer. METHODS Maspin and kai1 expressions were detected in normal gastric mucosa (n = 182), gastric dysplasia (n = 69), and gastric cancer (n = 113) by immunohisto-chemistry. Their expressions were compared with clinicopathological parameters of tumors. Relationship between maspin and kai1 expression was also concerned in gastric cancer. RESULTS The positive rates of maspin expression were 79.8% (145/182), 75.4% (52/69), and 50.4% (57/113) in normal gastric mucosa, gastric dysplasia, and gastric cancer, while those of kai1 expression were 81.9% (149/182), 65.2% (49/69), and 58.4% (66/113) in corresponding tissues respectively. Gastric cancer less frequently expressed maspin than the normal gastric mucosa and gastric dysplasia (P < 0.05), while dysplasia and cancer showed less frequent expression of kai1 than normal mucosa (P < 0.05). Maspin expression showed negative association with invasive depth, metastasis, Lauren's and histological classifications (P < 0.05), but not with tumor size, Borrmann's classification, growth pattern or TNM staging (P > 0.05). Kai1 expression was negatively correlated with invasive depth, metastasis, growth pattern, Lauren's and histological classifications (P < 0.05), but not with tumor size, Borrmann's classification or TNM staging (P > 0.05). Maspin and kai1 were collaboratively expressed in gastric cancer (P < 0.05). CONCLUSIONS Down-regulated expressions of maspin and kai1 play an important role in gastric carcinogenesis. Abnormal expression of maspin and kai1 might have inhibitory effects on invasion and metastasis of gastric cancer and act as an effective and objective marker to indicate the pathobiological behaviors of gastric cancer.
The acetylation of alpha-tubulin and its relationship to the assembly and disassembly of microtubules

A tight association between Chlamydomonas alpha-tubulin acetyltransferase (TAT) and flagellar axonemes, and the cytoplasmic localization of both tubulin deacetylase (TDA) and an inhibitor of tubulin acetylation have been demonstrated by the use of calf brain tubulin as substrate for these enzymes. A major axonemal TAT of 130 kD has been solubilized by high salt treatment, purified, and characterized. Using the Chlamydomonas TAT with brain tubulin as substrate, we have studied the effects of acetylation on the assembly and disassembly of microtubules in vitro. We also determined the relative rates of acetylation of tubulin dimers and polymers. The acetylation does not significantly affect the temperature-dependent polymerization or depolymerization of tubulin in vitro. Furthermore, polymerization of tubulin is not a prerequisite for the acetylation, although the polymer is a better substrate for TAT than the dimer. The acetylation is sensitive to calcium ions which completely inhibit the acetylation of both dimers and polymers of tubulin. Acetylation of the dimer is not inhibited by colchicine; the effect of colchicine on acetylation of the polymer can be explained by its depolymerizing effect on the polymer.