Miracle-dz/UniFAR-FTUs huggingface dataset:
Genetics of congenital hearing impairment: A clinical approach

Hearing impairment (HI) is the most frequent sensory disorder, with a genetic etiology in >50% of all cases, due to mutations in >44 identified genes. Autosomal recessive inheritance explains the majority, with GJB2 (connexin 26) mutations accounting for 15–50% of paediatric HI. Delayed presentation of HI to 11–60 months in cases of biallelic GJB2 mutations is a concern, necessitating a good audiological follow-up in addition to neonatal hearing screening. Providing a genetic diagnosis in congenital HI has implications for the prognosis, the possible risk of associated medical manifestations, and precise genetic counseling of the family, and should be integrated into the medical examinations done in order to diagnose syndromic features. Large-scale mutation detection methods, such as micro arrays, are promising for wider genetic testing, but few studies on their clinical utility have been published, so far. Limitations of interpretation of genetic test results, combined with significant ethical issues, currently do not justify to institute genetic screening for GJB2 mutations in neonates before a diagnosis of HI is established.
Molecular dynamics study of the recognition of ATP by nucleic acid aptamers

Abstract Despite their great success in recognizing small molecules in vitro, nucleic acid aptamers are rarely used in clinical settings. This is partially due to the lack of structure-based mechanistic information. In this work, atomistic molecular dynamics simulations are used to study the static and dynamic supramolecular structures relevant to the process of the wild-type (wt) nucleic acid aptamer recognition and binding of ATP. The effects brought about by mutation of key residues in the recognition site are also explored. The simulations reveal that the aptamer displays a high degree of rigidity and is structurally very little affected by the binding of ATP. Interaction energy decomposition shows that dispersion forces from π-stacking between ATP and the G6 and A23 nucleobases in the aptamer binding site plays a more important role in stabilizing the supramolecular complex, compared to hydrogen-bond interaction between ATP and G22. Moreover, metadynamics simulations show that during the association process, water molecules act as essential bridges connecting ATP with G22, which favors the dynamic stability of the complex. The calculations carried out on three mutated aptamer structures confirm the crucial role of the hydrogen bonds and π-stacking interactions for the binding affinity of the ATP nucleic acid aptamer.
Disease swamps molecular signatures of genetic‐environmental associations to abiotic factors in Tasmanian devil (Sarcophilus harrisii) populations

Landscape genomics studies focus on identifying candidate genes under selection via spatial variation in abiotic environmental variables, but rarely by biotic factors (i.e., disease). The Tasmanian devil (Sarcophilus harrisii) is found only on the environmentally heterogeneous island of Tasmania and is threatened with extinction by a transmissible cancer, devil facial tumor disease (DFTD). Devils persist in regions of long‐term infection despite epidemiological model predictions of species’ extinction, suggesting possible adaptation to DFTD. Here, we test the extent to which spatial variation and genetic diversity are associated with the abiotic environment (i.e., climatic variables, elevation, vegetation cover) and/or DFTD. We employ genetic‐environment association analyses using 6886 SNPs from 3287 individuals sampled pre‐ and post‐disease arrival across the devil's geographic range. Pre‐disease, we find significant correlations of allele frequencies with environmental variables, including 365 unique loci linked to 71 genes, suggesting local adaptation to abiotic environment. The majority of candidate loci detected pre‐DFTD are not detected post‐DFTD arrival. Several post‐DFTD candidate loci are associated with disease prevalence and were in linkage disequilibrium with genes involved in tumor suppression and immune response. Loss of apparent signal of abiotic local adaptation post‐disease suggests swamping by strong selection resulting from the rapid onset of DFTD.
Sex-based differences in pediatric supracondylar humerus fractures

Abstract Supracondylar humerus (SCH) fractures are reported to be approximately twice as common among boys as among girls. Little is known about sex-associated differences in fracture patterns and complications. We compared the incidence of pediatric SCH fractures, injury mechanism (high-energy or low-energy), fracture subtypes, associated neurologic injuries, and treatment types by patient sex. We reviewed 1231 pediatric SCH fractures treated at 1 center from 2008 to 2017, analyzing sex distributions overall and by year and fracture subtype. We noted patient demographic characteristics, injury mechanisms, neurologic injuries, and treatments (nonoperative or operative). Binomial 2-tailed, chi-squared, and Student's t tests were used for analysis. Multiple logistic regression was performed to assess associations between sex, age, and injury mechanism. Alpha = 0.05. We found no significant difference in the distribution of girls (52%) vs boys (48%) in our sample compared with a binomial distribution (P = .11). Annual percentages of fractures occurring in girls ranged from 46% to 63%, and sex distribution did not change significantly over time. The mean (± standard deviation) age at injury was significantly younger for girls (5.5 ± 2.5 years) than for boys (6.1 ± 2.5 years) (P < .001). High-energy injury mechanism was associated with older age (odds ratio [OR], 1.05; 95% confidence interval [CI], 1.03–1.06) but not male sex (OR, 1.04; 95% CI, 0.98–1.1). The overall incidence of neurologic injury was 9.5% but boys did not have greater odds of sustaining neurologic injury (OR, 1.03; 95% CI, 1.0–1.1). We found no sex-associated differences in the distribution of Gartland fracture subtypes (P = .13) or treatment type (P = .39). Compared with boys, girls sustain SCH fractures at a younger age. SCH fractures were distributed equally among girls and boys in our sample. Patient sex was not associated with fracture subtype, injury mechanism, neurologic injury, or operative treatment. These findings challenge the perception that SCH fracture is more common in boys than girls. Level III, retrospective study.
Evaluation of sarcoglycans, vinculin-talin-integrin system and filamin2 in α- and γ-sarcoglycanopathy: An immunohistochemical study

The sarcoglycan subcomplex (SGC) is a well-known system of interaction between extracellular matrix and sarcolemma-associated cytoskeleton in skeletal and cardiac muscle. The SGC is included in the DGC made up of sarcoplasmic subcomplex and a dystroglycan subcomplex. Recent developments in molecular genetics have demonstrated that the mutation of each single sarcoglycan gene, causes a series of recessive autosomal muscular dystrophies, dystrophin-positive, called sarcoglycanopathies or limb girdle muscular dystrophies. Our recent studies have demonstrated that costameres are a proteic machinery made up of DGC and vinculin-talin-integrin system, also revealing the colocalization of sarcoglycans and integrins in adult human skeletal muscle. These results may support the hypothesis of the existence of a bidirectional signalling between sarcoglycans and integrins in cultured L6 myocytes. The hypothesis of bidirectional signalling between sarcoglycans and integrins could be supported by the identification of a skeletal and cardiac muscle filamin2 as a gamma-sarcoglycan, delta-sarcoglycan and, hypothetically, beta1 integrin interacting protein. Our results, acquired with an immunofluorescence study on adult human skeletal muscle affected by LGMD type 2D and 2C, showed that in LGMD2D: a) alpha-sarcoglycan staining is severely reduced; b) the beta-gamma-delta-sarcoglycan subunit and all tested integrins staining are clearly detectable; c) filamin2 is normal and shows a costameric distribution. In LGMD2C: a) alpha-sarcoglycan staining is preserved; b) the beta-gamma-delta-sarcoglycan subunit staining is severely reduced; c) the alpha7B-integrin is slightly reduced and beta1D-integrin is severely reduced; d) filamin2 is severely reduced. Other tested proteins of the two systems show a normal staining pattern in both sarcoglycanopathies. Our study seems to confirm, for the first time on adult human skeletal muscle of subjects affected by LGMDs, the hypo-theses of: a) the existence, in mouse myotubes in culture, of two distinct subunits in sarcoglycans subcomplex; b) the presence of a bidirectional signalling between sarcoglycans and integrins, previously demonstrated on rat cultured L6 myocytes; c) the interaction of FLN2 with both sarcoglycans and integrins. These results may stimulate the search of yet unidentified common interactors of both fiber-extracellular matrix interaction systems.
A2AgCrBr6 (A = K, Rb, Cs) and Cs2AgCrX6(X = Cl, I) Double Perovskites: A Transition-Metal-Based Semiconducting Material Series with Remarkable Optics

With an interest to quest for transition metal-based halogenated double perovskites AB′B″X6 as high performance semiconducting materials for optoelectronics, this study theoretically examined the electronic structures, stability, electronic (density of states and band structures), transport (effective masses of charge carriers), and optical properties (dielectric function and absorption coefficients, etc.) of the series A2AgCrBr6 (A = K, Rb, Cs) using SCAN + rVV10. Our results showed that A2AgCrBr6 (A = Rb, Cs), but not K2AgCrBr6, has a stable perovskite structure, which was revealed using various traditionally recommended geometry-based indices. Despite this reservation, all the three systems were shown to have similar band structures, density of states, and carrier effective masses of conducting holes and electrons, as well as the nature of the real and imaginary parts of their dielectric function, absorption coefficient, refractive index, and photoconductivity spectra. The small changes observed in any specific property of the series A2AgCrBr6 were due to the changes in the lattice properties driven by alkali substitution at the A site. A comparison with the corresponding properties of Cs2AgCrX6 (X = Cl, I) suggested that halogen substitution at the X-site can not only significantly shift the position of the onset of optical absorption found of the dielectric function, absorption coefficient and refractive spectra of Cs2AgCrCl6 and Cs2AgCrI6 toward the high- and low-energy infrared regions, respectively; but that it is also responsible in modifying their stability, electronic, transport, and optical absorption preferences. The large value of the high frequency dielectric constants—together with the appreciable magnitude of absorption coefficients and refractive indices, small values of effective masses of conducting electrons and holes, and the indirect nature of the bandgap transitions, among others—suggested that cubic A2AgCrBr6 (A = Rb, Cs) and Cs2AgCrCl6 may likely be a set of optoelectronic materials for subsequent experimental characterizations.
Avaliação de níveis protéicos para a nutrição de juvenis de matrinxã (Brycon cephalus)

Matrinxa (Brycon cephalus - Gunther, 1869) a native fish species from the Amazon basin, has been causing a great deal of interest among researchers and fish culturists all over Brazil. The rising demand for the culture of this species in controlled environment is mainly due, to its ready adaptation to captivity, the acceptance of manufactured feed made with either animal or plant ingredients, along with its high commercial value. However, for a successful commercial enterprise, feed must meet protein requirements of the fish to allow high weight gain in a short period. The experiment was carried out at Embrapa Amazonia Ocidental aquaculture station. Five crude protein concentration (16, 19, 22, 25 and 28 %) in isocaloric (EB = 390 kcal/100g) diets were tested in a fully randomized experimental design with three replicas. Results obtained at the end of 210 days of study showed that diets containing 28 % crude protein promoted the highest weight gain, growth and best feed conversion among tested diets, indicating that the protein requirements for this species can be satisfactorily achieved under experimental conditions.
C-Fiber Loss as a Possible Cause of Neuropathic Pain in Schwannomatosis

Schwannomatosis is the third form of neurofibromatosis and characterized by the occurrence of multiple schwannomas. The most prominent symptom is chronic pain. We aimed to test whether pain in schwannomatosis might be caused by small-fiber neuropathy. Twenty patients with schwannomatosis underwent neurological examination and nerve conduction studies. Levels of pain perception as well as anxiety and depression were assessed by established questionnaires. Quantitative sensory testing (QST) and laser-evoked potentials (LEP) were performed on patients and controls. Whole-body magnetic resonance imaging (wbMRI) and magnetic resonance neurography (MRN) were performed to quantify tumors and fascicular nerve lesions; skin biopsies were performed to determine intra-epidermal nerve fiber density (IENFD). All patients suffered from chronic pain without further neurological deficits. The questionnaires indicated neuropathic symptoms with significant impact on quality of life. Peripheral nerve tumors were detected in all patients by wbMRI. MRN showed additional multiple fascicular nerve lesions in 16/18 patients. LEP showed significant faster latencies compared to normal controls. Finally, IENFD was significantly reduced in 13/14 patients. Our study therefore indicates the presence of small-fiber neuropathy, predominantly of unmyelinated C-fibers. Fascicular nerve lesions are characteristic disease features that are associated with faster LEP latencies and decreased IENFD. Together these methods may facilitate differential diagnosis of schwannomatosis.
Comparison of Antioxidant Activities of Isoflavones from Kudzu Root (Pueraria lobata Ohwi)

ABSTRACT: Isoflavones and their glycosides were isolated from kudzu root, and formononetin-7-O-glucoside (ononin) was identified from the plant for the first time. Among isolated compounds, the antioxidant potency of 5 major compounds was determined using (1) 2,2-diphenyl-1-picrylhydrazyl free-radical scavenging assay, (2) thiocyanate assay in the linoleic acid model system, and (3) lipoxygenase inhibition assay. The study indicates that 5 compounds act as free-radical scavengers and inhibit both linoleic acid peroxidation and lipoxygenase activity. The 3 different assays for determining antioxidant activity revealed that activity in one test did not necessarily correlate with activity in another test. Arachidonic acid release in the intact HL-29 cancer cell, biochanin A, showed strong inhibition of about 70%, at a concentration of 50 μ. M.
Antibacterial activity of venom from funnel web spider Agelena labyrinthica (Araneae: Agelenidae)

Since the number of microorganisms that are resistant to antibiotics has been increasing steadily, the need for combating these pathogens requires new pharmaceutical agents. To produce these substances, new models have been developed in recent decades. In our study, the venom of Agelena labyrinthica (Clerck, 1757) (Araneae: Agelenidae) was tested against ten bacterial strains, specifically, testing 1/100, 1/10 and 1/1 fractions of diluted venom against these bacteria. While the 1/100 dilution was successful in only one of ten bacterial strains, the 1/10 and the 1/1 were effective on six of ten bacterial strains. The most effective results, among these three different concentrations, were observed on Bacillus subtilis. The other five strains that were also sensitive to the dilutions showed similar inhibition zones. Morphological alterations on bacterial cells and comparison with normal cells were accomplished by scanning electron microscopy (SEM). The venom-treated cells, due to their loss of cytoplasm, shrank and presented cell wall depression.
Phenotype and function of IgE-binding monocytes in equine Culicoides hypersensitivity

Human IgE-binding monocytes are identified as allergic disease mediators, but it is unknown whether IgE-binding monocytes promote or prevent an allergic response. We identified IgE-binding monocytes in equine peripheral blood as IgE+/MHCIIhigh/CD14low cells that bind IgE through an FcεRI αɣ variant. IgE-binding monocytes were analyzed monthly in Culicoides hypersensitive horses and nonallergic horses living together with natural exposure to Culicoides midges. The phenotype and frequency of IgE-binding monocytes remained consistent in all horses regardless of Culicoides exposure. All horses upregulated IgE-binding monocyte CD16 expression following initial Culicoides exposure. Serum total IgE concentration and monocyte surface IgE densities were positively correlated in all horses. We also demonstrated that IgE-binding monocytes produce IL-10, but not IL-4, IL-17A, or IFN-γ, following IgE crosslinking. In conclusion, we have characterized horse IgE-binding monocytes for the first time and further studies of these cells may provide important connections between regulation and cellular mechanisms of IgE-mediated diseases.
In vitro system for studying interactions between Citrus exocortis viroid and Gynura aurantiaca (Blume) DC. metabolism and growing conditions

Citrus exocortis viroid (CEVd) is an economically important plant pathogen, which infects a broad range of hosts. In order to investigate complex interactions among viroid, host-growing conditions, and plant secondary metabolism, we setup an in vitro system for the cultivation of CEVd-infected and viroid-free Gynura aurantiaca (Blume) DC. shoots. Both basal Murashige and Skoog (MS) medium and MS medium supplemented with cytokinines supported the growth of shoots, but viroid-free shoots performed better than infected ones. The addition of cytokinines induced an increase in the concentration of purple-reddish pigment, cyanidin tetra-glucoside (GAA), which did not depend on the presence of viroid. The differences in single strand conformation polymorphism patterns between CEVd sequence variants obtained from plants grown on medium supplemented with cytokinines and those obtained from plants grown on basal MS medium or in the greenhouse, indicated that cytokinines may influence not only the plant metabolism, but also the viroid population structure.
The Immuno-Responses of Eel (Anguilla japonica) against Edwardsiella anguillimortifera as Studied by the Immersion Method

The immersion method for the immunization of eel (Anguilla japonica) with the pathogen, Edwardsiella anguillimortifera, was studied and the results are summarized as follows:(1) Using the immersion method the immune response of eels can be induced effectively. (2) The effect of the treatment of hyperosmotic solution on the immunization of eels against E. anguillimortifera was evaluated. Following hyperosmotic treatment in 5.32% NaCl bath for 3 min, the eels were then immunized by soaking in the bacterial suspension for 3 min with heatkilled or formalin-killed Edwardsiella. The maximum titers in 5.32% NaCl pretreated eels were 1024 and 256 respectively, at fifth week after immunization. However, the maximum titers in the other two groups without osmotic shock were 256 and 128 respectively, at fourth week and seventh week after immunization. (3) The cumulative mortality of the eels against E. anguillimortifera challenge was higher in both groups with hyperosmotic pretreatment even though both had higher antibody titers. (4) The opsonic index of serum of immunized eels was 5.29. (5) In comparison with the control eels, the phagocytosis of the peritoneal leukocytes of the immunized eels increased significantly and specifically.
Patterns of coral–dinoflagellate associations in Acropora: significance of local availability and physiology of Symbiodinium strains and host–symbiont selectivity

Like other reef-building corals, members of the genus Acropora form obligate endosymbioses with dinoflagellates (zooxanthellae) belonging to the genus Symbiodinium. Both Symbiodinium and its hosts are diverse assemblages, and the relationships between host and algal genotypes are unclear. In this study, we determined phylogenetic relationships between Symbiodinium isolates from a wide range of Acropora species and plotted the algal genotypes onto a molecular phylogeny of 28 Acropora species, using the same samples for the host and symbiont genotyping. In addition, we performed a preliminary survey of zooxanthella distribution in Acropora species from the central Great Barrier Reef. Three of the four known major zooxanthellae clades were represented in the 168 samples examined, and within the major clade C, three distinct subclades were identified. No evidence was found for coevolution, but several clear patterns of specificity were identified. Moreover, composition of the zooxanthella pool varied among locales and in one host species we found light–related patterns of zooxanthella distribution
Comparison of Intraoral and Extraoral Digital Scanners: Evaluation of Surface Topography and Precision

The aim of this study was to evaluate the surface topography and the precision measurements of different intraoral and extraoral digital scanners. A reference model of a maxillary arch with four implant analogs was prepared and scanned by three intraoral and two extraoral scanners. The reference model was scanned fifteen times with each digital scanning system, investigating the surface topography and precision measurements for the same-arch and cross-arch measurements. The data was exported to 3D inspection and mesh-processing software (GOM Inspect, Braunschweig, Germany). Statistical analysis was performed using a one-way Analysis of Variance (ANOVA) with the Tukey method for pairwise comparisons. The effect of parameters on generating the surface topography was analyzed by Univariate Linear Regression Analysis. Of the scanner systems evaluated, iTero (IT) exhibited the most number of triangulation points, followed by Trios 3 Shape (TR) and Straumann Cares (SC). There were no significant differences observed in the surface topography when comparing flat and contoured surfaces, the anterior and posterior position, and interproximal areas. For the precision measurement in the same quadrant, no statistical difference was noted between intra- and extraoral scanners. However, the extraoral scanners showed substantially higher precision measurements for the cross-arch measurement. Surface topography did not correlate to precision. Rather, precision correlated with the scanning mechanism. For a quadrant scanning, both intraoral and extraoral scanners are recommended, but extraoral scanners are recommended for a full-arch scanning.