Miracle-dz/UniFAR-FTUs huggingface dataset:
Heme Binding to a Conserved Cys-Pro-Val Motif Is Crucial for the Catalytic Function of Mitochondrial Heme Lyases*

Covalent attachment of heme to the apoforms of mitochondrial cytochromes c and c1 requires the activity of cytochrome c heme lyase (CCHL) and cytochrome c1 heme lyase (CC1HL), respectively. The two enzymes differ in their cytochrome specificity, but they are related in sequence, and both contain conserved Cys-Pro-Val (CPV) motifs. By using various in vitro assays we investigated whether heme can bind directly to heme lyases and whether the CPV motif may be involved in heme binding. Heme stabilized CC1HL, as a model protein, in a folded, protease-resistant conformation, stimulated the refolding of CC1HL after urea denaturation, and inhibited the import of the CC1HL precursor into mitochondria. These effects were not observed with a point mutant, CC1HLSPV, in which cysteine was replaced by serine, and with CC1HLΔCPV, in which the motif was deleted. These results show that heme lyases can bind heme directly, and they identify the CPV sequence as a structural element important for this interaction. The phenotype of a yeast mutant expressing CC1HLSPV is in good agreement with such a role of the CPV motif. The mutant cells accumulate the heme-free intermediate form of cytochrome c1 and display a severe deficiency in the holo form. We suggest that the CPV motif forms a crucial part of the substrate binding site for heme.
Comparison of fluoroscopic and imageless registration in surgical navigation of the acetabular component

Objective: This study compared the repeatability and reproducibility of acetabular component positioning using imageless and fluoroscopic-referenced navigation methods. Methods: A single cadaveric pelvis had a modular acetabular component securely fixed. Cup position was evaluated using imageless and fluoroscopic registration techniques. These were compared to measurements of a coordinate measuring machine (CMM) and a validated CT scan protocol. Results: The CMM-determined anatomical acetabular inclination measurement was 46.02° (SD = 1.07), while the CMM-determined anatomical anteversion (pubic symphysis) was 15.79° (SD = 0.41). Computed tomography revealed inclination of 42.2° (SD = 0.65); anteversion with pubic tubercle referencing of 12.1° (SD = 0.14); and anteversion with pubic symphysis referencing of 14.3° (SD = 0.89). Evaluation of repeatability (one surgeon; n = 8) with the imageless system (pubic tubercle) revealed inclination of 41.8° (SD = 0.46) and anteversion of 11.2° (SD = 0.8). For the fluoroscopic system (pubic symphysis), inclination was 42.8° (SD = 1.6) and anteversion was 17.6° (SD = 3.1). Evaluation of reproducibility (three surgeons; n = 24) with the imageless system revealed inclination of 41.8° (SD = 0.82) and anteversion of 15.2° (SD = 1.06). For the fluoroscopic system, inclination was 48.5° (SD = 0.9) and anteversion was 17.8° (SD = 2.5). Imageless referencing of cup inclination and anteversion were found to be process capable using the Six Sigma Cp and Cpk capability indices. Fluoroscopic referencing was process capable for cup inclination but not for cup anteversion (Cp − 1.1; Cpk − 1.0). An F-test revealed significantly greater variance with fluoroscopic referenced anteversion (p < 0.002). Conclusions: Imageless referencing was process capable for computer navigation of cup placement in the ex-vivo setting. Fluoroscopic referencing for pelvic landmarks is problematic as locating points from radiographic images is difficult, especially for cup anteversion.
Study of the C677T and 1298AC polymorphic genotypes of MTHFR Gene in autism spectrum disorder

Background Autism is currently known as “a behaviorally defined syndrome” manifested as impairment in social communication, repetitive routines and restricted interests. There is an increased risk of ASDs associated with common mutations affecting the folate/methylation cycle. Aim The aim of this study was to identify C677T and 1298AC polymorphic genotypes of MTHFR gene among a sample of Egyptian children with autism and to make a phenotype-genotype correlation for the autistic patients. Methods This case-control study was carried out from 2013 through 2015. The study included 31 children with autism and 39 children in a normal control group, the mean age of patients and control was comparable (4.5 years± 2) with males predominant in both groups. We used DSM-V-TR criteria, Stanford-Binet intelligence scale V and childhood autism rating scale (CARS) for assessments. Genotyping for MTHFR gene polymorphic loci C677T and 1298AC was performed on amplified DNA by PCR with subsequent reverse hybridization and restriction fragment length polymorphisms analysis. Data were analyzed by SPSS version 11, using Chi-Square, independent-samples t-test, and ANOVA. Results There was significant relationship between low birth weight and occurrence of autism (p<0.01), and between delayed motor and social milestones in cases of autism compared to controls (p<0.01). Heterozygosity for A1298C polymorphism was highest among patients (41.9%) followed by 35.5% mutant genotype CC and 22.6% normal AA (wild) type and Allele C was detected in patients more than in control (56.45% vs. 11.54%) (p<0.001). For C667T polymorphism, heterozygosity was also highest among patients (48.4%) followed by wild type genotypes C677 (38.7%) and 12.9% for mutant genotypes 667T. Allele T appeared more in patients than control (31.10 %vs. 5.13%) (p<0.00). Heterozygosity for CT and A–C genotypes were detected equally (46.2%) among patients with severe autism (according to CARS). Conclusion There is a significant association between severity and occurrence of autism with MTHFR gene polymorphisms C677T and A1298C. Further studies are needed on a larger scale to explore other genes polymorphisms that may be associated with autism, to correlate the genetic basis of autism.
INEQUALITY AND INFANT HEALTH: A MULTILEVEL APPROACH TO DISENTANGLING CORRELATES OF METROPOLITAN/NONMETROPOLITAN DISPARITIES IN LOW BIRTH WEIGHT INFANTS

To date, research has not adequately addressed geographic variation in birth weight due to individualand structural-level characteristics in the US. If the health care needs of infants and children in nonmetropolitan areas are to be understood, an analytic approach capturing how both individualand contextual-level inequalities operate is needed. This research utilizes multiple levels of rurality as one component of structurallevel characteristics, along with individual-level characteristics, to examine variation in birth weights. Specifically, theoretical and empirical evidence is given for associations between biological, social, and behavioral characteristics and birth weight at the individual level, and residential, socioeconomic, social capital, social environmental, and health services characteristics and birth weight at the structural-level. With variation in birth weights across groups and places in the United States, it is important to understand which children are at risk of poor health outcomes and to identify how local conditions contribute to these outcomes. The ECLS-B merged with county-level data is used to examine this problem. Results from this research indicate that most of the variation in birth weight is attributable to individual-level characteristics, such as gestation, plurality status, and maternal smoking behavior during pregnancy. However structural-level characteristics help to explain some of the variation. Various measures of rurality indicate that rural residents tend to have higher birth weights. Other structural-level measures, such as the percentage of residents in the county that are black, the number of Olsen-Type establishments in the county, and the number of health care personnel all have associations with average birth weights and the mean likelihood of low birth weight.
Improvement of CNS Defects Via Continuous Intrathecal Enzyme Replacement by Osmotic Pump in Mucopolysaccharidosis Type II Mice

Mucopolysaccharidosis type II (MPS II), also known as Hunter syndrome (OMIM 309900), is a rare, X‐linked lysosomal storage disorder caused by a deficiency of iduronate‐2‐sulfatase (IDS; EC 3.1.6.13), which is involved in the lysosomal degradation of glycosaminoglycans (GAG). Although intermittent intrathecal (IT) injection of the enzyme has been introduced as a method to overcome the blood‐brain barrier, continuous IT infusion of the enzyme would be more physiologic. This study was performed to investigate responses in the brain of MPS II mice to varying doses of continuous IT infusion of recombinant human IDS (rh‐IDS) in MPS II mice by osmotic pump in three different doses (2.4, 4.8, and 12 µg/day) of rh‐IDS for 3 weeks. The results showed that the group treated with 12 µg/day doses of rh‐IDS demonstrated decreased GAG concentrations compared to the untreated KO mice group (P = 0.003). After 3 weeks of continuous IT ERT, the brain tissues of the high‐dose IT‐treated KO mice showed a reduction of vacuolation in the cerebral cortex, thalamus and cerebellar cortex, which was not observed in the low‐ and medium‐dose KO mice groups. Moreover, the anti‐NeuN signal representing intact neuron was restored in the cortexes of the high‐dose group. In conclusion, continuous IT infusion of the deficient enzyme was effective in improving CNS defects in the MPS II mice, and could be a valuable therapeutic method for treating neurological deterioration in patients with MPS II. © 2013 Wiley Periodicals, Inc.
Human Cytomegalovirus Protein pp71 Disrupts Major Histocompatibility Complex Class I Cell Surface Expression

ABSTRACT The human cytomegalovirus tegument protein pp71 is the product of the UL82 gene. Roles for pp71 in stimulating gene transcription, increasing infectivity of viral DNA, and the degradation of retinoblastoma family proteins have been described. Here we report a novel function for pp71 in limiting accumulation of cell surface major histocompatibility complex (MHC) class I complexes. MHC molecules were analyzed in glioblastoma cells exposed to a replication-defective adenovirus expressing UL82 (Adpp71) or after transient transfection of the UL82 gene. Accumulation of cell surface MHC class I levels diminished in a specific and dose-dependent manner after exposure to Adpp71 but not after exposure to an adenovirus expressing β-galactosidase (Adβgal). UL82 expression did not interfere with accumulation of either MHC class I heavy-chain transcript or protein, nor did UL82 expression correlate with markers of apoptosis. Rather, UL82 expression correlated with an increased proportion of MHC class I molecules exhibiting sensitivity to endoglycosidase H treatment. Finally, we show that, in cells infected with recombinant virus strain missing all of the unique short region MHC class I evasion genes, disruption of UL82 expression by short, interfering RNAs led to increased accumulation of cell surface MHC class I complexes. These findings support a novel role for HCMV pp71 in disruption of the MHC class I antigen presentation pathway.
Effect of inotropic interventions on contraction and Ca2+ transients in the human heart.

The present study investigated the influences of inotropic intervention on the intracellular Ca2+ transient (intracellular Ca2+ concentration ([Ca2+]i)) and contractile twitch. Isometric twitch and [Ca2+]i (fura 2 ratio method) were measured simultaneously (1 Hz, 37 degrees C) after stimulation with Ca2+ (0.9-3.2 mM), the cardiac glycoside ouabain (Oua; 0.1 microM), the beta1- and beta2-adrenoceptor-agonist isoprenaline (Iso; 1-10 nM), and the Ca2+ sensitizer EMD-57033 (30 microM) by using isolated human nonfailing right auricular trabeculae (n = 19). Inotropic interventions increased force of contraction and peak rate of tension rise (+T) significantly. Only Iso stimulated peak rate of tension decay (-T) higher than +T (P < 0.05), thereby reducing time of contraction (Ttwitch). EMD-57033 increased +T more effectively than -T and prolonged Ttwitch (P < 0.05). Ca2+, Oua, and Iso, but not EMD-57033, increased systolic Ca2+. Diastolic Ca2+ increased after stimulation with Oua or Ca2+, but not in the presence of EMD-57033. Iso shortened the Ca2+ transient and did not influence diastolic Ca2+. In conclusion, positive inotropic agents differently affect force and [Ca2+]i depending on their mode of action. Inotropic interventions influence diastolic Ca2+ and thus may be less advantageous in a situation with altered intracellular Ca2+ homeostasis (e.g., heart failure due to dilated cardiomyopathy).
ASSOCIATION BETWEEN CHANGES IN MACULAR VASCULATURE IN OPTICAL COHERENCE TOMOGRAPHY- AND FLUORESCEIN- ANGIOGRAPHY AND DISTRIBUTION OF MACULAR PIGMENT IN TYPE 2 IDIOPATHIC MACULAR TELANGIECTASIA

Purpose: We investigate the association between morphologic findings in optical coherence tomography angiography (OCTA) as a new method offering the visualization of deeper layers of retinal vasculature and fluorescein angiography (FA) and macular pigment imaging and in Type 2 macular telangiectasia. Methods: Fourty-two eyes of 21 patients with macular telangiectasia (38–68 years, 14 female) were examined by FA and OCTA and 24 eyes additionally with dual-wavelength autofluorescence. Early and late FA, macular pigment density images, and (after segmentation of retinal vasculature into superficial and deep capillary network and outer) OCTA images were graded into standardized categories. Agreement between the methods was evaluated statistically. Results: In OCTA, a reduction of density of superficial capillaries, dilated vessels in the deep capillary network, anastomoses toward the superficial capillary network, and “new” vessels in the outer retina layers can be detected. The described anatomical features, especially in the deep capillary plexus and outer retina corresponded well with changes in FA. Classes of macular pigment distribution correlated most with classes of changes in OCTA superficial capillary plexus. Conclusion: Progressive changes in macular telangiectasia apparent in FA and macular pigment imaging are most obvious in the deep capillary network and outer retina in OCTA. Optical coherence tomography angiography offers a noninvasive technology to analyze vascular changes in the retina and choroid of patients with macular telangiectasia.
A negative birth experience: prevalence and risk factors in a national sample.

BACKGROUND A woman's dissatisfaction with the experience of labor and birth may affect her emotional well-being and willingness to have another baby. The aim of this study was to investigate the prevalence and risk factors of a negative birth experience in a national sample. METHODS A longitudinal cohort study of 2541 women recruited from all antenatal clinics in Sweden during 3 weeks spread over 1 year was conducted. Data were collected by three questionnaires, which measured women's global experience of labor and birth 1 year after the birth, and obtained information on possible risk factors during pregnancy and 2 months after the birth. RESULTS Seven percent of the women had a negative birth experience. The following risk factors were found: (1) factors related to unexpected medical problems, such as emergency operative delivery, induction, augmentation of labor, and infant transfer to neonatal care; (2) factors related to the woman's social life, such as unwanted pregnancy and lack of support from partner; (3) factors related to the woman's feelings during labor, such as pain and lack of control; and (4) factors that may be easier to influence by the caregivers, such as insufficient time allocated to the woman's own questions at antenatal checkups, lack of support during labor, and administration of obstetric analgesia. CONCLUSIONS Many risk factors were related to unexpected medical problems and participants' social background. Of the established methods to improve women's birth experience, childbirth education and obstetric analgesia seemed to be less effective, whereas support in labor and listening to the woman's own issues may be underestimated.
[HIV prevalence among populations at risk, using sentinel surveillance data from 1995 to 2009 in China].

OBJECTIVE To effectively monitor the time trend of HIV prevalence and epidemic among injecting drug users (IDUs), female sex workers (FSWs), sexually transmitted disease (STD) clinic attendants, men who have sex with men (MSM) and pregnant women etc., to provide information for evaluation on strategies regarding comprehensive HIV prevention and effectiveness of intervention, in China. METHODS Cross-sectional studies had been repeatedly conducted on sentinel surveillance program with uniformed questionnaire and collection of venous blood specimen among IDUs, FSWs, STD clinic attendants, MSM and pregnant women, from 1995 to 2009. RESULTS HIV prevalence (median) among IDUs had been increasing rapidly since 1996, reaching the plateau (19.2%) in 1999-2000, then gradually decreasing in 2001-2003, and leveling off since 2004 in those relatively hard-hit epidemic provinces. HIV prevalence among drug users had increased a bit since 2001, achieving high level (2.9%) in 2004 before leveling off, showing a slight downward trend in the past two years among the medially-hit epidemic provinces, while it maintained at a low level in those low epidemic provinces. HIV prevalence (median) among FSWs had been slightly increasing, reaching a high level (1.5%) in 1999, then decreased and maintained at a low level in relatively hard-hit provinces. HIV prevalence among FSWs maintained at a low level in medially-hit and low epidemic provinces. HIV prevalence (median) among STD clinic attendants had been maintained at a lower level, lower than 0.7%. HIV prevalence among MSM had been consistently greater than 1%, and was increasing year by year, becoming one of the most important drivers of the HIV/AIDS epidemic over the past years. HIV prevalence (median) among pregnant women had slightly been increasing since 1997, then leveling off over the past years in those relatively hard-hit provinces (0.3%). HIV prevalence among pregnant women had maintained at a low level in the medial and low epidemic provinces. CONCLUSION Data from sentinel surveillance programs showed a leveling-off situation on HIV prevalence rates among IDUs, FSWs, sexually transmitted infections clinic patients and pregnant women. However, HIV prevalence among MSM had increased significantly since 2005, indicating the high speed of transmission among this population. Epidemic among IDUs had still been concentrated in those relatively hard-hit epidemic provinces. As for FSWs and STD patients, the overall epidemic remained at low level, but the areas of epidemic kept expanding.
Molecular cloning and characterization of two genes encoding sigma factors that direct transcription from a Bacillus thuringiensis crystal protein gene promoter

Two sigma factors, sigma 35 and sigma 28, direct transcription from the Bt I and Bt II promoters of the cryIA(a) gene of Bacillus thuringiensis; this gene encodes a lepidopteran-specific crystal protoxin. These sigma factors were biochemically characterized in previous work (K. L. Brown and H. R. Whiteley, Proc. Natl. Acad. Sci. USA 85:4166-4170, 1988; K. L. Brown and H. R. Whiteley, J. Bacteriol. 172:6682-6688, 1990). In this paper, we describe the cloning of the genes encoding these two sigma factors, as well as their nucleotide and deduced amino acid sequences. The deduced amino acid sequences of the sigma 35 and sigma 28 genes show 88 and 85% identity, respectively, to the sporulation-specific sigma E and sigma K polypeptides of Bacillus subtilis. Transformation of the sigma 35 and sigma 28 genes into B. subtilis shows that the respective B. thuringiensis sigma factor genes can complement spoIIG55 (sigma E) and spoIIIC94 (sigma K) defects. Further, B. thuringiensis core polymerase reconstituted with either the sigma 35 or sigma 28 polypeptide directs transcription from B. subtilis promoters recognized by B. subtilis RNA polymerase containing sigma E and sigma K, respectively. Thus, sigma 35 and sigma 28 of B. thuringiensis appear to be functionally equivalent to sigma E and sigma K of B. subtilis. However, unlike the situation for sigma K in B. subtilis, the homologous sigma 28 gene in B. thuringiensis does not result from a late-sporulation-phase chromosomal rearrangement of two separate, partial genes.
Heterogeneous preferences for recreation-oriented management in commercial forests: the role of citizens’ socioeconomic characteristics and recreational profiles

The management of forests for multiple benefits, such as recreational services alongside timber production, can greatly benefit from the knowledge of public preferences for management-related forest attributes. This paper investigates citizens’ recreational use and preferences for recreation-oriented management in the case of state-owned commercial forests in Finland using data from a choice experiment study. We focus on attributes related to the typical management practices applied to enhance recreation: scenic buffer zones along waters, game bird habitats, and the quality of scenery along hiking trails. Recreational use and its frequency were found to be related to citizens’ background and specific outdoor activities. The scenic buffer zones were the most important attribute to the citizens. While the recreation-enhancing practices were generally valued, respondent segments with distinct preferences were found. Preference heterogeneity was related to citizens’ socioeconomic characteristics and recreational profiles.
Crystal structure of FadR, a fatty acid‐responsive transcription factor with a novel acyl coenzyme A‐binding fold

FadR is a dimeric acyl coenzyme A (acyl CoA)‐binding protein and transcription factor that regulates the expression of genes encoding fatty acid biosynthetic and degrading enzymes in Escherichia coli. Here, the 2.0 Å crystal structure of full‐length FadR is described, determined using multi‐wavelength anomalous dispersion. The structure reveals a dimer and a two‐domain fold, with DNA‐binding and acyl‐CoA‐binding sites located in an N‐terminal and C‐terminal domain, respectively. The N‐terminal domain contains a winged helix–turn–helix prokaryotic DNA‐binding fold. Comparison with known structures and analysis of mutagenesis data delineated the site of interaction with DNA. The C‐terminal domain has a novel fold, consisting of a seven‐helical bundle with a crossover topology. Careful analysis of the structure, together with mutational and biophysical data, revealed a putative hydrophobic acyl‐CoA‐binding site, buried in the core of the seven‐helical bundle. This structure aids in understanding FadR function at a molecular level, provides the first structural scaffold for the large GntR family of transcription factors, which are keys in the control of metabolism in bacterial pathogens, and could thus be a possible target for novel chemotherapeutic agents.