Miracle-dz/UniFAR-FTUs huggingface dataset:
Isolation and characterization of a 14.5-kDa trichloroacetic-acid-soluble translational inhibitor protein from human monocytes that is upregulated upon cellular differentiation.

A trichloroacetic-acid-soluble 14.5-kDa protein (p14.5) has been isolated from human mononuclear phagocytes (MNP) by a combination of trichloroacetic acid extraction, preparative electrophoresis and hydrophobic affinity chromatography; five tryptic peptides were subjected to protein sequencing. The full-length cDNA of the protein was cloned and sequenced from a lambda gt11 human liver library. The cDNA showed a remarkable similarity to a rat protein preferentially expressed in hepatocytes and renal tubular epithelial cells. The encoded protein is 137 amino acids long and similar to members of a new hypothetical family of small proteins with presently unknown function, named YER057c/YJGF. Human recombinant p14.5 inhibits in vitro protein synthesis in a rabbit reticulocyte lysate system. Unlike other inhibitors of protein synthesis, p14.5 is not phosphorylated despite the presence of putative phosphorylation sites. The p14.5 mRNA is weakly expressed in freshly isolated monocytes but is significantly upregulated when these monocytes are subjected to differentiation. This is also reflected by a differentiation-dependent increase in the protein concentration as demonstrated by immunoblots from cytosolic fractions and fluorescence-activated flow cytometry of permeabilized cells. A differentiation-dependent mRNA and protein expression of p14.5 is further suggested by the observation of a low expression in a variety of liver and kidney tumor cells and a high expression in fully differentiated cells as assessed by immunohistochemistry and northern blots. The highest mRNA expression was found in hepatocytes and renal distal tubular epithelial cells and only weak expression was found in other human tissues as evaluated by northern blot analysis. The preferential localization of the immunoreaction product seemed to be cytoplasmatic but, in less differentiated cells, nuclear labeling was occasionally visible. Immunoblotting of subcellular fractions confirmed these data. The high degree of evolutionary conservation of p14.5, the considerable upregulation during cellular differentiation and its potential role as a translational inhibitor may reflect an involvement in basic cellular mechanisms, e.g. a differentiation-dependent regulation of protein synthesis in hepatocytes, renal tubular epithelial cells, smooth muscle cells and MNP.
Automatic selection of landmarks in T1-weighted head MRI with regression forests for image registration initialization

Medical image registration establishes a correspondence between images of biological structures and it is at the core of many applications. Commonly used deformable image registration methods are dependent on a good preregistration initialization. The initialization can be performed by localizing homologous landmarks and calculating a point-based transformation between the images. The selection of landmarks is however important. In this work, we present a learning-based method to automatically find a set of robust landmarks in 3D MR image volumes of the head to initialize non-rigid transformations. To validate our method, these selected landmarks are localized in unknown image volumes and they are used to compute a smoothing thin-plate splines transformation that registers the atlas to the volumes. The transformed atlas image is then used as the preregistration initialization of an intensity-based non-rigid registration algorithm. We show that the registration accuracy of this algorithm is statistically significantly improved when using the presented registration initialization over a standard intensity-based affine registration.
Effects of ethinyl estradiol and tamoxifen on liver DNA turnover and new synthesis and appearance of gamma glutamyl transpeptidase-positive foci in female rats.

We investigated possible mechanisms associated with promotion of hepatocarcinogenesis by the synthetic estrogens mestranol (M) and ethinyl estradiol (EE). Our first objective was to determine whether chronic EE treatment was associated with hepatotoxicity accompanied by regenerative hyperplasia. Female Sprague-Dawley (SD) rats were partially hepatectomized and their liver DNA prelabeled with [3H]thymidine. Two weeks later the rats were treated with EE at three doses or M (using timed-release tablets implanted s.c.) or with 0.05% phenobarbital (PB) in the diet. The rats were killed 6 weeks later and the amount of [3H]thymidine remaining in liver DNA determined. The results showed that none of the promoters caused hepatotoxicity as detected by the loss of prelabeled DNA. EE but not M or PB caused a dramatic dose-dependent enlargement of the pituitary. Subsequent experiments were carried out to define the dose-time response of liver DNA synthesis to treatment with EE, M and PB. Female SD rats were treated with these agents and [3H]-thymidine incorporation into DNA was determined at various times thereafter. The results showed that EE at 2.5 micrograms/day and PB (0.05%) caused a rapid increase in liver DNA synthesis which peaked between 24 and 72 h and remained elevated for at least the next 7 days. Dose-response experiments with EE- and M-treated rats demonstrated that 24 h after beginning treatment, significant increases in liver DNA synthesis could be detected at an EE dose as low as 0.1 microgram/day; DNA synthesis was also significantly increased by M. The anti-estrogen tamoxifen (T), did not cause increased liver DNA synthesis. However, T at 15 micrograms/day did inhibit the induction of DNA synthesis caused by EE and M at 2.5 micrograms/day but not by PB (0.05%). The effect of T on promotion by EE of the appearance of gamma glutamyl transpeptidase (GGT)-positive foci was determined. Female SD rats were initiated with a single i.p. dose of diethylnitrosamine at 20 mg/kg given 24 h after partial hepatectomy. One week later the rats were treated with EE (5 micrograms/day), T (15 or 50 micrograms/day) or EE plus T at both doses using timed-release tablets. The rats were killed after 4 months and the incidence, number and size of the GGT foci determined. The results revealed that, as expected, EE enhanced the appearance of GGT foci. Unexpectedly, T alone at both doses also enhanced the appearance of the foci. (ABSTRACT TRUNCATED AT 400 WORDS)
Mutations in the gene encoding the alpha-subunit of rod phosphodiesterase in consanguineous Pakistani families.

PURPOSE To localize and identify the gene and mutations causing autosomal recessive retinitis pigmentosa (RP) in consanguineous Pakistani families. METHODS Families were ascertained and patients underwent complete ophthalmological examinations. Blood samples were collected and DNA was extracted. A genome-wide scan was performed using 382 polymorphic microsatellite markers on genomic DNA from affected and unaffected family members, and lod scores were calculated. RESULTS A genome-wide scan of 50 families gave a lod score of 7.4172 with D5S2015 using HOMOG1. RP in all 4 linked families mapped to a 13.85 cM (14.87 Mb) region on chromosome 5q31-33 flanked by D5S2090 and D5S422. This region harbors the PDE6A gene, which is known to cause autosomal recessive RP. Sequencing of PDE6A showed a homozygous single base pair change; c.889C->T, single base pair insertion; c.2218-2219insT, and single base pair substitution in the splice acceptor site; IVS10-2A->G in each of three families. In the fourth family linked to this region, no disease-causing mutation was identified in the PDE6A gene. CONCLUSIONS These results provide strong evidence that mutations in PDE6A result in recessive RP in three consanguineous Pakistani families. Although a fourth family was linked to markers in the 5q31-33 interval, no mutation was identified in PDE6A.
Balancing Scientific and Community Interests in Community-Based Participatory Research

Community-based participatory research is an approach to studying human populations that emphasizes extensive partnerships between researchers and community members. While there are many advantages of this approach, it also faces a number of conceptual and practical challenges, one of which is managing the conflict that sometimes arises between promoting scientific and community interests. This essay explores the potential conflict between scientific and community interests in several different stages of community-based participatory research, including research design, data interpretation, and publication, and makes some suggestions for practice and policy. To manage potential conflicts between scientific and community interests, investigators and community partners should enter into written agreements at the beginning of the study. In some cases, it may be necessary for a third party, such as a review committee from a supporting institution, the community, or a funding agency, to help investigators and community partners resolve disagreements. It may also be useful, in some situations, to publish a dissenting opinion when investigators and community partners cannot agree on how to interpret findings resulting from a study. These strategies may help address some of the challenges of implementing community-based participatory research.
Left Ventricular Mechanics in Patients with Abnormal Origin of the Left Main Coronary Artery from the Pulmonary Trunk Late after Successful Repair

Objective: Our aim was to evaluate left ventricular (LV) mechanics by using speckle tracking echocardiography (STE) in asymptomatic patients with abnormal origin of the left main coronary artery from the pulmonary trunk (ALCAPA), late after successful repair, in the presence of LV ejection fraction (EF) >50%. Methods: We studied 30 ALCAPA patients (median age 4 years, range 1-25 years, NYHA class I, LVEF >50%) and 16 healthy age- and sex-matched controls (median age 5 years, range 1-25 years). All underwent standard echocardiographic evaluation and STE. Results: LV dimensions and LVEF (63.6 ± 8.2% vs. 64.1 ± 5.1%, p = 0.826) were not different between patients and controls. Diastolic parameters were significantly abnormal in our patients versus controls (E/e' average: 11.9 ± 5.8 vs. 6.6 ± 3.0, p = 0.0014). Global LV longitudinal strain was significantly lower in ALCAPA patients versus controls (-17.6 ± 3.5% vs. -23.4 ± 3.1%, p < 0.0001). LV torsion (9.1 ± 4.9° vs. 11.9 ± 3.3°, p = 0.046) was significantly impaired in ALCAPA patients. Conclusions: After successful repair in asymptomatic ALCAPA patients, despite an LVEF >50%, diastolic function, LV longitudinal deformation and LV torsion remain impaired. We suggest including a detailed study of the diastolic function and cardiac mechanics in the clinical follow-up of these patients to identify the subgroup of patients at higher risk.
PmrA(Con) Confers pmrHFIJKL-Dependent EGTA and Polymyxin Resistance on msbB Salmonella by Decorating Lipid A with Phosphoethanolamine

ABSTRACT Mutations in pmrA were recombined into Salmonella strain ATCC 14028 msbB to determine if pmrA-regulated modifications of lipopolysaccharide could suppress msbB growth defects. A mutation that functions to constitutively activate pmrA [pmrA(Con)] suppresses msbB growth defects on EGTA-containing media. Lipid A structural analysis showed that Salmonella msbB pmrA(Con) strains, compared to Salmonella msbB strains, have increased amounts of palmitate and phosphoethanolamine but no aminoarabinose addition, suggesting that aminoarabinose is not incorporated into msbB lipid A. Surprisingly, loss-of-function mutations in the aminoarabinose biosynthetic genes restored EGTA and polymyxin sensitivity to Salmonella msbB pmrA(Con) strains. These blocks in aminoarabinose biosynthesis also prevented lipid A phosphoethanolamine incorporation and reduced the levels of palmitate addition, indicating previously unknown roles for the aminoarabinose biosynthetic enzymes. Lipid A structural analysis of the EGTA- and polymyxin-resistant triple mutant msbB pmrA(Con) pagP::Tn10, which contains phosphoethanolamine but no palmitoylated lipid A, suggests that phosphoethanolamine addition is sufficient to confer EGTA and polymyxin resistance on Salmonella msbB strains. Additionally, palmitoylated lipid A was observed only in wild-type Salmonella grown in the presence of salt in rich media. Thus, we correlate EGTA resistance and polymyxin resistance with phosphoethanolamine-decorated lipid A and demonstrate that the aminoarabinose biosynthetic proteins play an essential role in lipid A phosphoethanolamine addition and affect lipid A palmitate addition in Salmonella msbB strains.
Long-Term Anoxia Tolerance (Multi-Level Regulation of Gene Expression in the Amphibious Plant Acorus calamus L.)

Acorus calamus is a monocotyledonous wetland plant that can withstand extremely long periods of anoxia. We have investigated the expression of genes coding for pyruvate decarboxylase (Pdc), alcohol dehydrogenase (Adh), and fructose-1,6-bisphosphate aldolase (Ald) during periods of anoxia ranging from 2 h to 2 months. Upon anoxic incubation, Pdc mRNA levels peak at 6 h, followed by Adh and Ald, which peak at 12 and 72 h, respectively. Subsequently, the mRNA levels of all three genes decline within days to low levels. In contrast, alcohol dehydrogenase (ADH) protein levels increase steadily for at least a week and then remain constant. Native gel electrophoresis demonstrates the presence of two sets of ADH isozymes, one present constitutively, the other enhanced during anoxia. Translation initiation factor 4A protein levels, used as a control, remain constant during 2 months of anoxia. The results suggest that A. calamus has developed a complex anaerobic response consisting of differential regulation of transcription, translation, and posttranslational processes.
Effectiveness of Sutureless Percutaneous Placement of Cuffed Tunneled Hemodialysis Catheters Applying Statlock Attachment Devices

Purpose A prospective, randomized-controlled trail was conducted to evaluate the effectiveness of securing tunneled hemodialysis (HD) catheters with sutureless StatLock attachment devices (Bard Access Systems) compared to traditional suture fixation. Methods At a university teaching hospital 11 patients with chronic renal failure received cuffed tunneled HD catheters. In the study group (n=36) the HD catheters were secured with a sutureless StatLock attachment device, whereas the control group HD catheters were fixated with sutures only. The intended intermediate use of the tunneled HD catheters was 42 ± 7 days until the arteriovenous fistula was sufficient. All catheters were placed by an interventional radiologist using ultrasound for the puncture of the internal jugular vein. We evaluated the success and complication rate of tunneled catheter implantation. Results The primary success rate for implantation of HD catheters was 100%. There was an overall complication rate of 8.3% in the study group (one hematoma in the subcutaneous catheter tract and two central venous thromboses). In the control group the overall complication rate was 13.9% (two hematomas, one central venous thrombosis and two catheter displacements). The two catheter displacements required a HD catheter exchange. In addition, four local irritations at the HD catheter entry site were seen only in the control group and were rated as minor complications. Conclusions The sutureless placement technique is safe and effective with a low complication rate, and is superior to the traditional suture fixation of tunneled catheters.
CbrA Is a Flavin Adenine Dinucleotide Protein That Modifies the Escherichia coli Outer Membrane and Confers Specific Resistance to Colicin M

ABSTRACT Colicin M (Cma) is a protein toxin produced by Escherichia coli that kills sensitive E. coli cells by inhibiting murein biosynthesis in the periplasm. Recombinant plasmids carrying cbrA (formerly yidS) strongly increased resistance of cells to Cma, whereas deletion of cbrA increased Cma sensitivity. Transcription of cbrA is positively controlled by the two-component CreBC system. A ΔcreB mutant was highly Cma sensitive because little CbrA was synthesized. Treatment of CbrA-overproducing cells by osmotic shock failed to render cells Cma sensitive because the cells were resistant to osmotic shock. In a natural environment with a growth-limiting nutrient supply, cells producing CbrA defend themselves against colicin M synthesized by competing cells. Isolated CbrA is a protein with noncovalently bound flavin adenine dinucleotide. Sequence comparison and structure prediction assign the closest relative of CbrA with a known crystal structure as digeranylgeranyl-glycerophospholipid reductase of Thermoplasma acidophilum. CbrA is found in Escherichia coli, Citrobacter, and Salmonella bongori but not in other enterobacteria. The next homologs with the highest identity (over 50%) are found in the anaerobic Clostridium botulinum group 1 and a few other Firmicutes.
Attachment representations and response to video-feedback intervention for professional caregivers

Interventions to improve caregiving may have different effects for persons with autonomous or nonautonomous attachment representations. The current study used the Adult Attachment Interview to investigate attachment representations of professional caregivers who participated in an intervention to improve interaction with children and adults with serious intellectual and visual disabilities. Caregivers (N = 51) completed a video-feedback interaction program. Twice during a baseline period and three times during the intervention period, each caregiver was videotaped during a standard situation with their client. Of the caregivers, 28 were classified as autonomous, 12 as dismissing, and 11 as preoccupied. Unresolved loss or trauma (n = 7) was not included in the analyses. Generally, interaction quality improved from baseline to intervention period as indicated by confirmation of signals, responsiveness to signals, and affective mutuality. Caregivers with dismissing classifications continued to show less confirmation of clients' signals. Caregivers with dismissing or preoccupied classifications improved their responsiveness to the level of caregivers with autonomous classifications. Attachment representations may modify in some ways the impact of interventions to improve caregiving.
Rapamycin Reduces CCR5 Density Levels on CD4 T Cells, and This Effect Results in Potentiation of Enfuvirtide (T-20) against R5 Strains of Human Immunodeficiency Virus Type 1 In Vitro

ABSTRACT The CCR5 chemokine receptor plays a pivotal role in human immunodeficiency virus type 1 (HIV-1) infection. Several studies have suggested that CCR5 density levels in individuals are rate limiting for infection. In addition, CCR5 density levels influence the antiviral activity of the HIV-1 fusion inhibitor enfuvirtide (T-20) against R5 strains. In the present study we demonstrate that rapamycin (RAPA), a drug approved for the treatment of renal transplantation rejection, reduces CCR5 density levels on CD4 T cells and inhibits R5 HIV-1 replication. In addition, RAPA increased the antiviral activity of T-20 against R5 strains of the virus in a cell-cell fusion assay and as shown by quantification of early products of viral reverse transcription. Median-effect analysis of drug interaction between RAPA and T-20 in infectivity assays using donor peripheral blood mononuclear cells demonstrated that the RAPA-T-20 combination is synergistic against R5 strains of HIV-1 and this synergy translates into T-20 dose reductions of up to ∼33-fold. Importantly, RAPA effects on replication levels and T-20 susceptibility of R5 strains of HIV-1 were observed at drug concentrations that did not inhibit cell proliferation. These results suggest that low concentrations of RAPA may potentiate the antiviral activity of T-20 against R5 strains of HIV-1, which are generally present throughout the course of infection and are less sensitive to T-20 inhibition than are X4 strains.
Cardiac autonomic nervous dysfunction detected by both heart rate variability and heart rate turbulence in prediabetic patients with isolated impaired fasting glucose

Objective: Cardiac autonomic nervous dysfunction (CAND), a severe complication of diabetes, has also been shown to affect prediabetic patients. The role of isolated impaired fasting plasma glucose (IFG), a subtype of prediabetes, is not clear in the pathogenesis of CAND. The aim of this study was to examine the relationship between isolated IFG and cardiac autonomic function using heart rate variability (HRV) and heart rate turbulence (HRT) indices derived from 24-h Holter–electrocardiogram recordings. Methods: This observational, prospective, cross-sectional study examined 400 consecutive subjects divided into three groups according to oral glucose tolerance test results: the control group [Group I, fasting plasma glucose (FPG) <100 mg/dL and normal glucose tolerance, n=193], the isolated IFG group (Group II, FPG ≥100 and <126 mg/dL, n=134), and the isolated impaired glucose tolerance (IGT), both IFG and IGT, or newly diagnosed diabetes’ group (Group III, n=73). Patients with non-sinus rhythm, known diabetes mellitus, coronary artery disease, heart failure, severe valvular disease, or receiving medical therapy that may affect HRV and HRT indices were excluded. Time domain HRV parameters, turbulence onset (TO), turbulence slope (TS), and HRT category were examined. Chi-square, one-way analysis of variance, Kruskal–Wallis H, and Mann–Whitney U tests were used to compare variables where appropriate. The correlation between Holter data and FPG levels was analyzed using the Spearman’s test. Multiple linear regression analysis was performed to identify independent predictors of the HRV and HRT parameters. Results: Median (interquartile range 25–75) FPG levels in Groups I, II, and III were 89 (83/93) mg/dL, 109 (104/116) mg/dL, and 174 (150.5/197) mg/dL, respectively. There were significant differences in HRV and HRT parameters between and among all groups. While HRV parameters and TS decreased from Group I to Group III, TO and HRT category gradually increased. Additionally, FPG level was significantly correlated with SDNN, r=–0.220; SDNN index, r=–0.192; SDANN, r=–0.207; RMSSD, r=–0.228; pNN50, r=–0.226; TO, r=0.354; and TS, r=–0.331 (all p<0.001). Conclusion: CAND, as detected by both HRV and HRT, appear to be present in the isolated IFG subtype of prediabetes.