Miracle-dz/UniFAR-FTUs huggingface dataset:
Methionine Sulfoxide Reductase B3-Targeted In Utero Gene Therapy Rescues Hearing Function in a Mouse Model of Congenital Sensorineural Hearing Loss.

AIMS Methionine sulfoxide reductase B3 (MsrB3), which stereospecifically repairs methionine-R-sulfoxide, is an important Msr protein that is associated with auditory function in mammals. MsrB3 deficiency leads to profound congenital hearing loss due to the degeneration of stereociliary bundles and the apoptotic death of cochlear hair cells. In this study, we investigated a fundamental treatment strategy in an MsrB3 deficiency mouse model and confirmed the biological significance of MsrB3 in the inner ear using MsrB3 knockout (MsrB3(-/-)) mice. RESULTS We delivered a recombinant adeno-associated virus encoding the MsrB3 gene directly into the otocyst at embryonic day 12.5 using a transuterine approach. We observed hearing recovery in the treated ears of MsrB3(-/-) mice at postnatal day 28, and we confirmed MsrB3 mRNA and protein expression in cochlear extracts. Additionally, we demonstrated that the morphology of the stereociliary bundles in the rescued ears of MsrB3(-/-) mice was similar to those in MsrB3(+/+) mice. INNOVATION To our knowledge, this is the first study to demonstrate functional and morphological rescue of the hair cells of the inner ear in the MsrB3 deficiency mouse model of congenital genetic sensorineural hearing loss using an in utero, virus-mediated gene therapy approach. CONCLUSION Our results provide insight into the role of MsrB3 in hearing function and bring us one step closer to hearing restoration as a fundamental therapy.
A model of behavioral treatments for self-mutilation behavior in Lesch–Nyhan syndrome

Lesch–Nyhan syndrome is a rare genetic disorder, caused by a mutation in the gene coding for the enzyme hypoxanthine-guanine phosphoribosyltransferase, which is characterized by hyperuricemia and its associated symptoms along with motor disorders and compulsive self-mutilation. We show that the temporal difference learning algorithm that has been often used to interpret dopaminergic activity in the basal ganglia offers an explanation for the self-mutilation behaviors. We propose that a dysfunctional dopamine signal inadvertently reinforces early, accidental injurious behavior that is initially caused by clumsiness owing to the motor disorders. Simulations of this model reproduce findings on the results of behavioral treatments for dealing with self-mutilation behaviors.
Real‐time PCR based analysis of metal resistance genes in metal resistant Pseudomonas aeruginosa strain J007

A uranium (U)‐resistant and ‐accumulating Pseudomonas aeruginosa strain was characterized to assess the response of toxic metals toward its growth and expression of metal resistance determinants. The bacterium showed MIC (minimum inhibitory concentration) values of 6, 3, and 2 mM for Zn, Cu, and Cd, respectively; with resistance phenotype conferred by periplasmic Cu sequestering copA and RND type heavy metal efflux czcA genes. Real‐time PCR‐based expression analysis revealed significant upregulation of both these genes upon exposure to low concentrations of metals for short duration, whereas the global stress response gene sodA encoding superoxide dismutase enzyme was upregulated only at higher metal concentrations or longer exposure time. It could also be inferred that copA and czcA are involved in providing resistance only at low metal concentrations, whereas involvement of “global stress response” phenomenon (expression of sodA) at higher metal concentration or increased exposure was evident. This study provides significant understanding of the adaptive response of bacteria surviving in metal and radionuclide contaminated environments along with the development of real‐time PCR‐based quantification method of using metal resistance genes as biomarker for monitoring relevant bacteria in such habitats.
Extracellular Thiol Isomerases and Their Role in Thrombus Formation.

SIGNIFICANCE The mammalian endoplasmic reticulum (ER) houses a large family of twenty thioredoxin-like proteins of which protein disulfide isomerase (PDI) is the archetypal member. Although the PDI family is best known for its role in oxidative protein folding of secretory proteins in the ER, these thioredoxin-like proteins fulfill ever-expanding roles, both within the secretory pathway and beyond. RECENT ADVANCES Secreted PDI family proteins have now been shown to serve a critical role in platelet thrombus formation and fibrin generation. Utilizing intravital microscopy to visualize thrombus formation in mice, we have demonstrated the presence of extracellular PDI antigen during thrombus formation following injury of the vascular wall. Inhibition of PDI abrogates thrombus formation in vivo (16, 26, 46, 55). These observations have been extended to other PDI family members, including ERp57 (39, 116, 118, 123) and ERp5 (77). The vascular thiol isomerases are those PDI family members secreted from platelets and/or endothelium (40): PDI, ERp57, ERp5, ERp72, ERp44, ERp29, and TMX3. We focus here on PDI (16, 46, 55), ERp57 (39, 116, 118, 123), and ERp5 (77), which have been implicated in thrombus formation in vivo. CRITICAL ISSUES It would appear that a system of thiol isomerase redox catalysts has been hijacked from the ER to regulate thrombus formation in the vasculature. FUTURE DIRECTIONS How this redox system is trafficked to and regulated at the cell surface, the identity of extracellular substrates, why so many thiol isomerases are required, and which thiol isomerase functions are necessary are critical unanswered questions in understanding the role of thiol isomerases in thrombus formation.
Isolation and characterization of a T4‐like phage with a relatively wide host range within Escherichia coli

Avian pathogenic Escherichia coli (APEC) causes colibacillosis in poultry, resulting in severe economic losses worldwide. Coliphages represent alternative antibacterial substitutes based on high lytic efficiency and few side‐effects. However, the complete genome sequences information of APEC phages are limited, and knowledge of undesired genes and the narrow host range restrict their applications. In this study, we isolated a virulent phage QL01, with a relatively broad lytic spectrum (41 of 78 APEC strains). Transmission electron micrography showed it belonged to the family Myoviridae with an elongated head and a contractile tail. Whole genome sequencing revealed a linear double‐stranded DNA (170,527 kb; GC content, 39.6%) with 275 possible ORFs. Comparative genome analysis revealed high homology between QL01 and other T4‐like phages. However, it also showed some unique features, for example, ORF142 and ORF143, which encode IP9 and IP8, respectively, and may counteract host resistance only exist in a few T4‐like phages such as IME08 and vB_EcoM_VR5. Furthermore, phage therapy in artificially infected ducks showed a 26.67% decrease in mortality compared with the untreated group. Our study indicates the potential antibacterial function of phage QL01 against APEC infections and highlights unique molecular features underlying the relatively broad host range.
Stress Regulates Aquaporin-8 Permeability to Impact Cell Growth and Survival.

UNLABELLED Aquaporin-8 (AQP8) allows the bidirectional transport of water and hydrogen peroxide across biological membranes. Depending on its concentration, H2O2 exerts opposite roles, amplifying growth factor signaling in physiological conditions, but causing severe cell damage when in excess. Thus, H2O2 permeability is likely to be tightly controlled in living cells. AIMS In this study, we investigated whether and how the transport of H2O2 through plasma membrane AQP8 is regulated, particularly during cell stress. RESULTS We show that diverse cellular stress conditions, including heat, hypoxia, and ER stress, reversibly inhibit the permeability of AQP8 to H2O2 and water. Preventing the accumulation of intracellular reactive oxygen species (ROS) during stress counteracts AQP8 blockade. Once inhibition is established, AQP8-dependent transport can be rescued by reducing agents. Neither H2O2 nor water transport is impaired in stressed cells expressing a mutant AQP8, in which cysteine 53 had been replaced by serine. Cells expressing this mutant are more resistant to stress-, drug-, and radiation-induced growth arrest and death. INNOVATION AND CONCLUSION The control of AQP8-mediated H2O2 transport provides a novel mechanism to regulate cell signaling and survival during stress. Antioxid. Redox Signal. 24, 1031-1044.
Cloning and characterization of the first actinomycete β‐propeller phytase from Streptomyces sp. US42

A gene encoding an extracellular phytase was cloned for the first time from an Actinomycete, Streptomyces sp. US42 and sequenced. The sequence of this gene revealed an encoded polypeptide (PHY US42) exhibiting one and six residues difference with the putative phytases of Streptomyces lividans TK24 and Streptomyces coelicolor A3(2), respectively. The molecular modeling of PHY US42 indicated that this phytase belongs to the group of β‐propeller phytases that are usually calcium‐dependent. PHY US42 was purified and characterized. Its activity was calcium‐dependent and maximal at pH 7 and 65 °C. The enzyme was perfectly stable at pH ranging from 5 to 10 and its thermostability was greatly enhanced in the presence of calcium. Indeed, PHY US42 maintained 80% of activity after 10 min of incubation at 75 °C in the presence of 5 mM CaCl2. PHY US42 was also found to exhibit high stability after incubation at 37 °C for 1 h in the presence of bovine bile and digestive proteases like of pepsin, trypsin, and chymotrypsin. Considering its biochemical properties, PHY US42 could be used as feed additive in combination with an acid phytase for monogastric animals.
Peroxisomes and Kidney Injury.

SIGNIFICANCE Peroxisomes are organelles present in most eukaryotic cells. The organs with the highest density of peroxisomes are the liver and kidneys. Peroxisomes possess more than fifty enzymes and fulfill a multitude of biological tasks. They actively participate in apoptosis, innate immunity, and inflammation. In recent years, a considerable amount of evidence has been collected to support the involvement of peroxisomes in the pathogenesis of kidney injury. RECENT ADVANCES The nature of the two most important peroxisomal tasks, beta-oxidation of fatty acids and hydrogen peroxide turnover, functionally relates peroxisomes to mitochondria. Further support for their communication and cooperation is furnished by the evidence that both organelles share the components of their division machinery. Until recently, the majority of studies on the molecular mechanisms of kidney injury focused primarily on mitochondria and neglected peroxisomes. CRITICAL ISSUES The aim of this concise review is to introduce the reader to the field of peroxisome biology and to provide an overview of the evidence about the contribution of peroxisomes to the development and progression of kidney injury. The topics of renal ischemia-reperfusion injury, endotoxin-induced kidney injury, diabetic nephropathy, and tubulointerstitial fibrosis, as well as the potential therapeutic implications of peroxisome activation, are addressed in this review. FUTURE DIRECTIONS Despite recent progress, further studies are needed to elucidate the molecular mechanisms induced by dysfunctional peroxisomes and the role of the dysregulated mitochondria-peroxisome axis in the pathogenesis of renal injury. Antioxid. Redox Signal. 25, 217-231.
Metformin and anaemia: myth or reality?

Metformin is an effective antihyperglycaemic agent used extensively in treating diabetes. It has few side effects but it may inhibit vitamin B12 absorption in the distal ileum which may potentially limit its use. This study set out to determine if there is an association between metformin treatment and anaemia in a large population with diabetes mellitus. A total of 520 consecutive patients with diabetes were studied. Anaemia was defined by World Health Organization criteria of Hb <13g/dl in men, and Hb <12g/dl in women. Serum B12 was measured in the patients with significant anaemia of Hb <11g/dl. Anaemia was present in 24.6% of the study population. There was no difference in the prevalence of anaemia and the haemoglobin levels between patients on metformin and those not on metformin. In patients with significant anaemia, there was also no difference in serum vitamin B12 levels between the two groups. Metformin remains a valuable drug in the management of diabetes. Whilst the clinician must be aware of the potential association between metformin and B12 deficiency, this study in a large population with diabetes shows no significant association between metformin and anaemia, suggesting that metformin associated anaemia is rare. Copyright © 2009 John Wiley & Sons, Ltd.
Pattern of skin sensitivity to various aeroallergens in patients of bronchial asthma and/or allergic rhinitis in India

Nine hundred and eighteen patients with bronchial asthma and/or allergic rhinitis including 548 (59.69%) males and 370 (40.31%) females with a mean age of 30.10 years were studied for skin sensitivity to various aeroallergens by skin prick test. The maximum numbers of patients (261; 28.43%) were between age group of 20 to 29 years. Patients diagnosed with bronchial asthma were 191 (20.81%), allergic rhinitis were 305 (33.22%), and both bronchial asthma and allergic rhinitis were 422 (45.97%). Significant skin positive reactions (2+ and above) were found in 657 (71.57%) subjects, which included 130 (14.16%) of bronchial asthma patients, 208 (22.66%) of allergic rhinitis patients, and 319 (34.75%) of both. The younger adults aged 20-29 years were the most commonly affected group with 197 (21.46%) significant skin positive patients. Insects (43.90%) followed by various types of weed pollens (21.79%), tree pollens (15.14%), dust (14.49%), house dust mite (12.42%), fungal spores (11.98%), grass pollens (7.73%), kapok cotton (2.18%), silk (1.31%), and wool (0.76%) were the offending allergens. Among individual allergens, most common aeroallergen was moth (33%), and least common was ehretia (0.54%). Among grass pollens, Cynodon (3.05%) was most common, and least common grass pollen aeroallergen was Pennisetum (1.74%). Among weed pollens, Ageratum (5.45%) was most common, and least common was Chenopodium album (1.53%). Among tree pollens, Holoptelia (5.01%), was most common, and least common was Ehretia (0.54%). Among dust, the wheat dust (8.28%) was the most common, followed by house dust (7.08%), and least common was paper dust (1.53%). Among the fungal spores, Aspergillus fumigatus (4.25%) were the most common, and least common was Candida (1.09%). Among insects, moth (33%) followed by mosquito (31.92%) were the most common, and least common was rice weevil (12.75%). When compared with the pattern of our study, there was significantly increased in sensitization to various allergens.
Human Circulation: Regulation During Physical Stress

Dr Loring B. Rowell, of the Department of Physiology and Biophysics at the University of Washington School of Medicine, has prepared a one-volume textbook of blood circulation with emphasis on the overall regulation of the circulation in humans, especially during physical stress. The book has 13 chapters, including the introduction, and an extensive index. Chapters 1 through 6 deal with classic descriptions of the general principles of vascular control, venous control, and control of the individual vascular beds. Chapters 7 through 13 describe the overall control of circulation in humans under certain extreme conditions that require the instant adaptation of the circulatory system. The goals of the book are an overall presentation of cardiovascular regulation in humans and an emphasis on the importance of the peripheral circulation in human heart performance. Furthermore, an attempt is made to answer a number of pertinent questions regarding the effects of exercise and other
Psychometric properties of the Spanish version of the short-form Child Perceptions Questionnaire for 11-14-year-olds for assessing oral health needs of children.

OBJECTIVE To evaluate the psychometric properties of the Spanish version of the short-form of the Children Perceived Oral Health Questionnaire aimed at assessing child's oral health-related quality of life of children aged 11-14 years (CPQ11-14 ). A secondary objective was to explore its screening qualities for evaluating oral health needs and immediate referral for treatment. METHODS This cross-sectional study was conducted during August-December of 2011 in Monterrey, Mexico (n = 303 schoolchildren). The CPQ11-14 consisted of 16 items and 2 key questions. Dental caries was diagnosed by visual-tactile exam, and malocclusion by WHO index. We estimated Cronbach's alpha and Spearman's correlations and compared rank scores with the Mann-Whitney test. As we did not have a preestablished cutoff point score, we identified one with the best combination of sensitivity/specificity values using receiver operating characteristic curves. RESULTS Internal consistency was 0.85. Correlation was 0.40 (P < 0.001) between CPQ11-14 scores and self-perceived oral health rating and 0.51 (P < 0.001) between CPQ11-14 score and general well-being rating (concurrent validity). The mean score was 11.6 ± 8.6 for children in need of oral care and 8.1 ± 7.2 for those not in need of oral care (P < 0.01; discriminating validity). Sensitivity was 79.4% and specificity 48.7%; the positive and negative predictive values were 81.6% and 45.2%, respectively. CONCLUSIONS The Spanish version short-form CPQ11-14 registered acceptable psychometric properties. We were able to identify a cutoff point score with acceptable sensitivity and positive predictive value but still needs future validation before generalizing its use.
Combined genotyping strategy reveals structural differences between Aspergillus flavus lineages from different habitats impacting human health

Aspergillus flavus is a filamentous fungus which is widespread on agricultural products and also able to cause various human diseases. This species is frequently isolated from indoor air as well, furthermore, it is known as a common causal agent of keratomycosis, particularly in subtropical and tropical areas. It is also able to produce aflatoxins, one of the most carcinogenic mycotoxins which are harmful to animals and humans. In this study, 59 A. flavus isolates from four different habitats and 1 A. minisclerotigenes isolate were investigated. The isolates were identified and confirmed at the species level by the sequence analysis of a part of their calmodulin gene. Applying a combined analysis of UP‐PCR, microsatellite, and calmodulin sequence data, the four group of isolates formed separate clusters on the phylogenetic tree. Examining the distribution of mating type genes MAT1‐1 and MAT1‐2, a ratio of approximately 3:1 was determined, and no correlation was found between the carried mating type gene and the aflatoxin production capability. HPLC analysis revealed that none of the examined isolates collected from indoor air or maize in Central Europe were able to produce aflatoxins, while about half of the isolates from India produced these mycotoxins under the test conditions.
Saudi parent's attitude and practice about self-medicating their children

Objective: The objective of this study was to test the parental self-medication attitude and practice toward their children in Saudi Arabia. Materials and Methods: A cross-sectional study was conducted. Non-probability convenient random sampling method was used to select the participants. A total of 750 parents from different cities in the Saudi Arabia were involved in the study. Results: The obtained response rate was 80%. The majority of participants were used to treat their children by western medicines. Most of respondents self-medicated their children in the month previous to the study period. The most common reported self-treated symptom was fever, although the most frequently used medicines were paracetamol and antibiotics. The attitude to treat fever was higher in males than in females (P = 0.021). The initial response for most participants in case of self treatment failure was to consult physicians in public hospitals; education level of participants showed significant difference (P = 0.041). The main reasons for self-medication were long waiting time in the clinics and high consultation fees. Occupation showed a significant differences (P = 0.008). Conclusion: The current study revealed the fact that parental self-medication among public in Saudi Arabia is a routine practice. The researchers suggested introduction of parental educational interventions throughout the Saudi Arabia to ensure that children will receive best pharmaceutical care.
The Let's Go Program for Community Participation: A Feasibility Study

ABSTRACT Community participation positively influences health and wellness. As individuals age, chronic disease and changes in physical and cognitive capacities may influence community participation in older adults resulting in social isolation, depression, and decreased health. Aims: The aim of this study was to evaluate the feasibility of implementing Let's Go, a four-week multimodal community mobility program designed to prevent decline in community participation in older adults (≥60 years old) living in an urban area who self-identified as having difficulty with community mobility. Methods: Using a pre–post measure design, participants’ (N = 7) knowledge, confidence, and participation in community mobility were evaluated. Results: All participants increased their knowledge of alternative transportation options and their confidence in community mobility. The majority of participants maintained or increased their autonomy outdoors and social participation (85.71%) and increased the frequency of community trips (85.71%). Conclusions: A multimodal community mobility program can increase community participation in older adults who report community mobility deficits. Additional studies are needed to support these findings.
Correlação entre a suplementação de proteína e carboidrato e variáveis antropométricas e de força em indivíduos submetidos a um programa de treinamento com pesos

La gran mayoria de los individuos que se adhieren a los programas regulares de ejercicios con pesos tienen gran preocupacion estetica que se resume al aumento de la fuerza y masa muscular con empleo del entrenamiento asociado a la suplementacion. El objetivo de este trabajo era verificar la ingestion de una dieta hiperproteica (4g.kg-1.d-1), unido al entrenamiento que provoca un aumento mas grande de la masa muscular y fuerza cuando se lo compara al modelo normoproteico dietetico. METODOLOGIA: Dieciseis voluntarios divididos en dos grupos segun el suplementacion: con proteina (HP), recibiendo 4g.kg-1.d-1, y con hidratos de carbono (NP), en la cantidad calorica de suplementacion proteica (225g.d1). Los dos grupos se sometieron al entrenamiento con pesos para los musculos biceps y triceps, 3 veces por semana durante 8 semanas. La fuerza, la masa muscular, el area de seccion transverso muscular, se analizaron asi como el cortisol y la insulina. RESULTADOS: El grupo HP presento el consumo de la proteina mas grande y el grupo NP, de hidratos de carbono. Los grupos tambien presentaron diferencia en los valores del cortisol. El grupo NP presento la correlacion positiva entre el aumento mas grande en la ingestion de hidratos de carbono (%) y el area de aumento M, y tambien entre la fuerza para el ejercicio del triceps (TFR2) y el aumento de la masa muscular y la ingestion mas grande de hidratos de carbono. CONCLUSION: Este estudio hace pensar en que la correlacion entre la ingestion de hidratos de carbono y el aumento del area muscular y de la fuerza para el ejercicio triceps por el grupo NP esta relacionada con la situacion metabolica favorable para la sintesis proteica.