Miracle-dz/UniFAR-FTUs huggingface dataset:
Cooperative propagation of local stability changes from low‐stability and high‐stability regions in a SH3 domain

Site‐directed mutagenesis has been used to produce local stability changes at two regions of the binding site surface of the α‐spectrin SH3 domain (Spc‐SH3) differing in their intrinsic stability. Mutations were made at residue 56, located at the solvent‐exposed side of the short 310 helix, and at residue 21 in the tip of the flexible RT‐loop. NMR chemical‐shift analysis and X‐ray crystallography indicated negligible changes produced by the mutations in the native structure limited to subtle rearrangements near the mutated residue and at flexible loops. Additionally, mutations do not alter importantly the SH3 binding site structure, although produce significant changes in its affinity for a proline‐rich decapeptide. The changes in global stability measured by differential scanning calorimetry are consistent the local energy changes predicted by theoretical models, with the most significant effects observed for the Ala‐Gly mutations. Propagation of the local stability changes throughout the domain structure has been studied at a per‐residue level of resolution by NMR‐detected amide hydrogen–deuterium exchange (HX). Stability propagation is remarkably efficient in this small domain, apparently due to its intrinsically low stability. Nevertheless, the HX‐core of the domain is not fully cooperative, indicating the existence of co‐operative subunits within the core, which is markedly polarized. An equilibrium ϕ‐analysis of the changes in the apparent Gibbs energies of HX per residue produced by the mutations has allowed us to characterize structurally the conformational states leading to HX. Some of these states resemble notably the folding transition state of the Spc‐SH3 domain, suggesting a great potential of this approach to explore the folding energy landscape of proteins. An energy perturbation propagates more effectively from a flexible region to the core than in the opposite direction, because the former affects a broader region of the energy landscape than the latter. This might be of importance in understanding the special thermodynamic signature of the SH3‐peptide interaction and the relevance of the dual character of SH3 binding sites. Proteins 2007. © 2007 Wiley‐Liss, Inc.
[The knowledge and attitudes of the public towards depression: an Istanbul population sample].

OBJECTIVE To assess the public's knowledge and attitudes towards depression and associated sociodemographic factors. METHOD The survey was conducted in 2000 using face-to-face interviews in the homes of 707 adults in 24 different districts of Istanbul. Logistic regression analysis was used to assess the influence of sociodemographic factors on attitudes towards depression. RESULTS The results indicate that 78.9% diagnosed the depression vignette as a mental disorder. 86.6% of the sample considered "social environmental factors" and 68.2% "weak personality" to be as the cause of depression. 43.4% of the population thought that people with depression are aggressive, and 22.8% believe that their freedom should be restricted. 51.9% percent of the subjects thought that the patient defined in the vignette should consult a physician. 94.5% percent of the respondents who thought of depression as an illness believe that depression is treatable and 54.9% of the respondents consider that the drugs used to treat depression have serious side effects. When the effect of sociodemographic factors on community attitudes was analyzed by logistic regression, age was found to have the most significant influence on community attitudes towards depression. CONCLUSION The results suggest that the public identifies depression as an illness, has a tendency to perceive depression as a social problem, believes that depression could be treated by drugs, has incorrect knowledge about drugs and treatment, and is in doubt about the acceptance of depressive patients in society.
Hybrid MMSE Precoding and Combining Designs for mmWave Multiuser Systems

Hybrid analog/digital precoding architectures are a low-complexity alternative for fully digital precoding in millimeter-wave (mmWave) MIMO wireless systems. This is motivated by the reduction in the number of radio frequency and mixed signal hardware components. Hybrid precoding involves a combination of analog and digital processing that enables both beamforming and spatial multiplexing gains in mmWave systems. This paper develops hybrid analog/digital precoding and combining designs for mmWave multiuser systems, based on the mean-squared error (MSE) criteria. In the first design with the analog combiners being determined at the users, the proposed hybrid minimum MSE (MMSE) precoder is realized by minimizing the sum-MSE of the data streams intended for the users. In the second design, both the hybrid precoder and combiners are jointly designed in an iterative manner to minimize a weighted sum-MSE cost function. By leveraging the sparse structure of mmWave channels, the MMSE precoding/combining design problems are then formulated as sparse reconstruction problems. An orthogonal matching pursuit-based algorithm is then developed to determine the MMSE precoder and combiners. Simulation results show the performance advantages of the proposed precoding/combining designs in various system settings.
Buprenorphine–Naloxone Therapy in Pain Management

Buprenorphine–naloxone (bup/nal in 4:1 ratio; Suboxone®; Reckitt Benckiser Pharmaceuticals Incorporation, Richmond, VA) is approved by the Food and Drug Administration for outpatient office-based addiction treatment. In the past few years, bup/nal has been increasingly prescribed off-label for chronic pain management. The current data suggest that bup/nal may provide pain relief in patients with chronic pain with opioid dependence or addiction. However, the unique pharmacological profile of bup/nal confers it to be a weak analgesic that is unlikely to provide adequate pain relief for patients without opioid dependence or addiction. Possible mechanisms of pain relief by bup/nal therapy in opioid-dependent patients with chronic pain may include reversal of opioid-induced hyperalgesia and improvement in opioid tolerance and addiction. Additional studies are needed to assess the implication of bup/nal therapy in clinical anesthesia and perioperative pain management.
What explains differences between dementia patients' and their caregivers' ratings of patients' quality of life?

OBJECTIVE The authors assessed the magnitude of discrepancy between patients' and caregivers' ratings of the patients' quality of life and sought to determine whether the discrepancies are associated with patient characteristics, caregiver characteristics, or the type of relationship between the patient and caregiver. METHODS A sample of 91 patients with mild-to-moderately severe dementia and their primary family caregiver rated five domains of the patients' subjective quality of life. RESULTS Agreement between patients and caregivers was low. Caregivers rated patients' quality of life lower than patients rated their own in all five domains. Discrepancies between patients' and caregivers' ratings were not associated with the patients' cognitive performance, level of functioning, nor caregivers' reports of aggressive, attention-seeking, or sexually inappropriate behaviors, nor whether the caregiver lived with or was married to the patient. However, discrepancies were associated with level of caregiver burden and the patients' report of depressive symptoms. Patients with depression reported low quality of life, which matched caregivers' low rating of patients' quality of life. Caregivers who reported higher levels of burden rated patients' quality of life lower than did patients in all five domains of quality of life. CONCLUSIONS Discrepancies between dementia patients' and their caregivers' ratings of the patients' quality of life are associated with increased levels of caregiver burden, rather than lower levels of patients' functioning. The results of this study support the direct assessment of mild-to-moderate dementia patients about their subjective quality of life.
Systematic review and meta‐analysis of the early and late outcomes of open and endovascular repair of abdominal aortic aneurysm

Any possible long‐term benefit from endovascular (EVAR) versus open surgical repair for abdominal aortic aneurysm (AAA) remains unproven. Long‐term data from the Open Versus Endovascular Repair (OVER) trial add to the debate regarding long‐term all‐cause and aneurysm‐related mortality. The aim of this study was to investigate 30‐day and long‐term mortality, reintervention, rupture and morbidity after EVAR and open repair for AAA in a systematic review.
Gender issues and oral health in elderly Indians.

OBJECTIVES Gender disparity in health and diseases is increasingly being recognised. Therefore, it was decided to investigate gender differences in the elderly subjects (60+years) from a community-based study. The study was undertaken to evaluate the oral health status and treatment needs of urban and rural elderly and to study the impact of socio-demographic variables on them. STUDY DESIGN An urban area in South Delhi and its adjoining four villages was selected. A modified WHO-Oral Health Survey proforma and Rup-Nagpal's scale were used to record oral health and socio-demographic data respectively. In addition, diet pattern (vegetarian/non-vegetarian) and body mass index (BMI) were also recorded. Chi square test and p values were calculated for each of the studied parameters. RESULTS There were significant differences for socio-economic status, literacy level, marital and family status between elderly men and women (p<0.0001). A higher percentage of elderly women were vegetarian and overweight than elderly men (p<0.01). However, there were few differences found in the prevalence of dental caries, periodontal diseases and edentulousness between male and female elderly (p>0.01). The only difference found was in the evidence of previous dental treatment received. Elderly men had a higher percentage of filled teeth and denture wear compared to elderly women (p<0.01). CONCLUSIONS Women's oral health is significantly influenced by social, economic and psychological factors.
Preservation of surface lipids and determination of ultrastructure of Mycobacterium kansasii by freeze-substitution

The cell wall architecture of a slowly growing mycobacterium, Mycobacterium kansasii, was examined by freeze-substitution following growth in vitro. Freeze-substituted bacteria were marked by the presence of an electron-translucent space (or electron-transparent zone [ETZ] described by previous workers [T. Yamamoto, M. Nishiura, N. Harada, and T. Imaeda, Int. J. Lepr. 26:111-114, 1958]) surrounding the majority of cells. At least two morphotypes of mycobacteria were revealed by freeze-substitution. In the first, a relatively thin (11 +/- 2.3 to 3.5 +/- 3.1 nm), uniform ETZ surrounded intact cells which contained cytoplasm filled with well-stained ribosomes and a DNA nucleoid distributed throughout the cell. The second morphotype consisted of a small proportion of organisms that were distorted in shape and were surrounded by a much thicker (59 +/- 2.6 to 198 +/- 2.5 nm) ETZ in areas of the cell which appeared to have retracted from the space it had originally occupied, leaving depressions in the ETZ. The lipid nature of the ETZ was demonstrated because cells were devoid of an ETZ when organisms were freeze-substituted in the absence of osmium tetroxide in the substitution medium or treated with neutral lipid solvents (acetone or ethanol) before freeze-substitution. Moreover, thin-layer chromatography of acetone or ethanol extracts obtained from solvent-treated cells identified a lipid component which corresponded to the M. kansasii-specific phenolic glycolipid. In contrast, negligible amounts of glycolipids were detected in extracts obtained from control HEPES (N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid) buffer-treated cells, and these cells retained an ETZ. These results demonstrate that species-specific phenolic glycolipids are essential components in the architecture of the M. kansasii ETZ. Furthermore, we show that freeze-substitution is a reliable technique for the retention and precise preservation of lipid-containing polymers in the mycobacterial cell wall.
Deciphering the structural code for proteins: helical propensities in domain classes and statistical multiresidue information in alpha-helices.

We made several statistical analyses in a large sample of nearly 4,000 helices (from 546 redundancy-controlled PDB protein subunits), which give new insights into the helical properties of globular proteins. In a first experiment, the amino acid composition of the whole sample was compared with the composition of two helical sample subgroups (the "mainly-alpha" and the "(alpha/beta)8 barrel" domain classes); we reached the conclusion that composition-based helical propensities for secondary structure prediction do not depend on the structural class. Running a five-residue window through the whole sample, the positional composition revealed that positive and negative residues are located throughout the helices and tend to neutralize the macrodipole effect. On this basis, we analyzed charged triplets using a running five-residue window. The conclusion was that only mixed charged residues [positive (+) and negative (-)] located at positions 1-2-5 and 1-4-5 are clearly favored. In these locations the most abundant are (- -.+) and (-.+ +), and this shows the existence of side chain microdipoles, which neutralize the large macrodipole of the helix. We made a systematic statistical analysis of charged, dipolar, and hydrophobic + aromatic residues, which enabled us to work out rules that should be useful for modeling and design purposes. Finally, we analyzed the relative abundance of all the different amphipathic double-arcs that are present in helices formed by octapeptides (8) and nonapeptides (18). All of the double-arcs that make up Schiffer and Edmundson's classical helical wheel are found in abundance in the sample.
Streptococcus pyogenes Arginine and Citrulline Catabolism Promotes Infection and Modulates Innate Immunity

ABSTRACT A bacterium's ability to acquire nutrients from its host during infection is an essential component of pathogenesis. For the Gram-positive pathogen Streptococcus pyogenes, catabolism of the amino acid arginine via the arginine deiminase (ADI) pathway supplements energy production and provides protection against acid stress in vitro. Its expression is enhanced in murine models of infection, suggesting an important role in vivo. To gain insight into the function of the ADI pathway in pathogenesis, the virulence of mutants defective in each of its enzymes was examined. Mutants unable to use arginine (ΔArcA) or citrulline (ΔArcB) were attenuated for carriage in a murine model of asymptomatic mucosal colonization. However, in a murine model of inflammatory infection of cutaneous tissue, the ΔArcA mutant was attenuated but the ΔArcB mutant was hyperattenuated, revealing an unexpected tissue-specific role for citrulline metabolism in pathogenesis. When mice defective for the arginine-dependent production of nitric oxide (iNOS−/−) were infected with the ΔArcA mutant, cutaneous virulence was rescued, demonstrating that the ability of S. pyogenes to utilize arginine was dispensable in the absence of nitric oxide-mediated innate immunity. This work demonstrates the importance of arginine and citrulline catabolism and suggests a novel mechanism of virulence by which S. pyogenes uses its metabolism to modulate innate immunity through depletion of an essential host nutrient.
Feelings of rewards among family caregivers during ongoing palliative care

Abstract Objectives: Palliative family caregivers appear to experience the rewards of caregiving concurrent with burdens and negative feelings. Relatively few studies have attended to the positive and rewarding aspects in palliative family caregiving. In addition, most studies on rewards are retrospective and examine the experiences of bereaved family caregivers. The present study aimed at describing feelings of reward among family caregivers during ongoing palliative care. A further aim was to compare the experience of rewards in relation to sex and age. Methods: The sample consisted of 125 family caregivers and took place in three specialist palliative care units and one hematology unit. Participants answered a questionnaire including demographic background questions and the Rewards of Caregiving Scale (RCS). Descriptive statistics were employed to describe characteristics of the participants and the level of rewards. A Mann–Whitney U test was used to compare differences between groups of different sex and age. Results: Palliative family caregivers reported general high levels of reward. The greatest source of rewards involved feelings of being helpful to patients. This was closely followed by giving something to patients that brought them happiness and being there for them. The smallest sources of rewards were related to personal growth, self-satisfaction, and personal meaning. There was also an association between rewards and age but not between men and women. Significance of results: Family caregivers experienced the rewards of caregiving during ongoing palliative care despite their unique and stressful situation. Feelings of reward seem to be about handling a situation in a satisfying way, feeling competent and confident to take care of the patient and thereby feeling proud. Support could preferably be designed to improve a family caregiver's ability to care and to facilitate the positive aspects and rewards of caregiving and focus on strengths and resources.
Phospholipid Transfer Protein Interacts with and Stabilizes ATP-binding Cassette Transporter A1 and Enhances Cholesterol Efflux from Cells*

Phospholipid lipid transfer protein (PLTP) is ubiquitously expressed in animal tissues and plays multiple roles in lipoprotein metabolism, but the function of peripheral PLTP is still poorly understood. Here we show that one of its possible functions is to transport cholesterol and phospholipids from cells to lipoprotein particles by a process involving PLTP interactions with cellular ATP-binding cassette transporter A1 (ABCA1). When ABCA1 was induced in murine macrophages or ABCA1-transfected baby hamster kidney cells, PLTP gained the ability to promote cholesterol and phospholipid efflux from cells. Although PLTP alone had lipid efflux activity, its maximum activity was observed in the presence of high density lipoprotein particles. Pulsechase studies showed that the interaction of PLTP with ABCA1-expressing cells played a role in promoting lipid efflux. Overexpression of ABCA1 dramatically increased binding of both PLTP and apoA-I to common sites on the cell surface. Both PLTP and apoA-I were covalently cross-linked to ABCA1, each protein blocked cross-linking of the other, and both PLTP and apoA-I stabilized ABCA1 protein. These results are consistent with PLTP and apoA-I binding to ABCA1 at the same or closely related sites. Thus, PLTP mimics apolipoproteins in removing cellular lipids by the ABCA1 pathway, except that PLTP acts more as an intermediary in the transfer of cellular lipids to lipoprotein particles.
Sex-Based Differences in the Clinical Presentation of Patients With Symptomatic Hip Labral Tears

Background: An increasing body of literature describes the clinical presentation and demographics of patients with hip labral tears. The differences in pelvic structure and joint laxity between sexes have been described; however, no study has evaluated differences in the clinical presentation of patients with symptomatic labral tears between sexes. Purpose: To describe the differences between sexes in demographics, clinical history, physical examination, and intraoperative findings in patients with symptomatic labral tears. Study Design: Cohort study; Level of evidence, 3. Methods: Data were prospectively collected between February 2008 and February 2013 on 1401 patients who had symptomatic labral tears and underwent arthroscopic surgery. Hips with previous pathologic disorders were excluded. Data on demographics and clinical history were gathered, and a physical examination was performed. Preoperative pain was estimated on the visual analog scale (VAS), and 4 hip-specific patient-reported outcomes (PROs) were administered to evaluate functional status. Intraoperative findings were recorded. Results: A total of 654 patients met our inclusion/exclusion criteria, with 320 males and 334 females. The median age for males was 38.3 years (range, 15.0-69.6 years) and for females 40.4 years (range, 13.1-66.8 years). Male patients had a higher incidence of acute injury than females (39.6% vs 27.6%, respectively; P < .05) and a higher incidence of workers’ compensation status (14.1% vs 4.5%, respectively; P < .05). Females had increased range of motion compared with males, which was statistically significant for all range of motion measurements (P < .05). The anterior impingement test was positive in 94.4% of females and 92.9% of males, the flexion/abduction/external rotation test was positive in 59.5% of females and 61.5% of males, and the lateral impingement test was positive in 55.0% of females and 59.2% of males, but there was no statistically significant difference between sexes in any of the tests. Pain with palpation over the greater trochanter was positive in 22.0% of males and 36.9% of females (P < .0001). Females had lower PROs; however, VAS scores were similar. Conclusion: Male and female patients differ in their hip structure, biomechanics, and operative findings of symptomatic labral tears. However, they do not differ substantially in clinical presentation, except that males are more likely to report an acute injury and females are more likely to be evaluated with increased range of motion.