Miracle-dz/UniFAR-FTUs huggingface dataset:
Merosin (laminin‐2/4)‐driven survival signaling: Complex modulations of Bcl‐2 homologs

We have shown previously that the promotion of myofiber survival by the basement membrane component merosin (laminin‐2 [α2β1γ1]/laminin‐4 [α2β2γ1]) is dependent on the activity of the tyrosine kinase Fyn, whereas myofiber anoikis induced by merosin deficiency is dependent on the stress‐activated protein kinase p38α. To further understand such merosin‐driven survival signaling, we analyzed the expression of five Bcl‐2 homologs (Bcl‐2, Bcl‐XL, Bax, Bak, Bad) and one non‐homologous associated molecule (Bag‐1) in normal and merosin‐deficient myotubes, with or without pharmacological inhibitors for Fyn and p38. Herein, we report that (1) merosin deficiency induces anoikis and causes decreased Bcl‐2, Bcl‐XL, and Bag‐1 levels, increased Bax and Bak levels, and decreased Bad phosphorylation; (2) Bcl‐2, Bcl‐XL, Bag‐1, and Bad phosphorylation are also decreased in anoikis‐dying, Fyn‐inhibited myotubes; (3) the inhibition of p38α in Fyn‐inhibited and/or merosin‐deficient myotubes protects against anoikis and increases Bcl‐2 levels above normal, in addition to restoring Bad phosphorylation and Bag‐1 levels to normal; (4) the overexpression of merosin in deficient myotubes also rescues from anoikis and increases Bcl‐2 levels and Bad phosphorylation above normal, in addition to restoring Bcl‐XL, Bag‐1, Bax, and Bak levels to normal; and (5) Bcl‐2 overexpression is sufficient to rescue merosin‐deficient myotubes from anoikis, even though the expression/phosphorylation levels of the other homologs analyzed are not restored to normal. These results indicate that merosin‐driven myofiber survival signaling affects complex, differential modulations of individual Bcl‐2 homologs. These further suggest that Bcl‐2 can play a major role in suppressing myofiber anoikis. © 2003 Wiley‐Liss, Inc.
Laboratory correlation between vancomycin levels and serum creatinine in the nephrotoxicity of vancomycin

Abstract Reports about relationship on renal function and vancomycin exposure are conflicted and limited. Goals: To identify if high serum vancomycin levels precede changes in serum creatinine or if it is secondary to reduced glomerular filtration and to analyze associated clinical conditions. Methods: retrospective cohort study, initially of 56.555 measurements of vancomycin levels from 511 patients admitted from December 2011 to June 2012 was analyzed. Patients with uncompleted dates were excluded and the correlation analysis was performed in 127 patients that were divided into four groups based on vancomycin levels (20 mg/mL) and creatinine (1.4 mg/dL) levels. After that, 80 medical charts of these patients was reviewed for the presence of comorbidities, sepsis, acute kidney injury and use of other nephrotoxic drugs. Results: there was a significant increase in vancomycin levels, when creatinine > 1.4 mg/dL and vancomycin ≤ 20 mg/mL (Group 3) on the first measurement. It was identified there was a significant association between creatinine > 1.4 mg/mL and vancomycin > 20 mg/mL, n = 7 (Group 4) in patients aged 50–59 years. Acute kidney injury was present in patients with previous higher vancomycin levels. Conclusions: Impaired renal function occurred before vancomycin levels measurements were taken, influencing the serum levels of vancomycin in the following days. In these patients the elevation of vancomycin did not lead to a worsening in renal function. There was a positive correlation between elevated creatinine and vancomycin levels in elderly, male and septic. Patients who need more attention were those with acute kidney injury who have previous higher vancomycin levels.
Umbilical Cord Cortisol and Arterial pH Levels in Spontaneous and Induced Labors

The free cortisol concentration in umbilical cord plasma and the pH of umbilical artery blood were determined in 108 full-term fetuses delivered vaginally. Eighty-six of the labors were spontaneous and 22 were induced with oxytocin. The cortisol values correlated significantly with the pH values (r= −.608, P<.001). The cortisol values averaged 0.73 ±0.48 (µ mole/liter in the spontaneous labor group and 0.65 ± 0.42 µmole/liter in the induced labor group. No statistically significant differences (P>.05) in the cortisol and pH values emerged between the groups. The results indicate that the human fetus reacts readily to intrauterine hypoxia and acidosis with endogenic cortisol secretion in both spontaneous and induced labors.
Interleukin‐33 exacerbates acute colitis via interleukin‐4 in mice

Interleukin‐33 (IL‐33) and its receptor ST2 are over‐expressed in clinical colitis tissue. However, the significance of these observations is at present unknown. Significantly, we demonstrate here that IL33 and ST2 are the primary early genes induced in the inflamed colon of BALB/c mice following dextran sulphate sodium (DSS)‐induced experimental ulcerative colitis. Accordingly diarrhoea and DSS‐induced colon inflammation were impaired in ST2−/− BALB/c mice and exacerbated in wild‐type mice by treatment with exogenous recombinant IL‐33, associated respectively with reduced and enhanced expression of chemokines (CXCL9 and CXCL10), and inflammatory (IL‐4, IL‐13, IL‐1, IL‐6, IL‐17) and angiogenic (vascular endothelial growth factor) cytokines in vivo. The exacerbation effect of treatment with recombinant IL‐33 on DSS‐induced acute colitis was abolished in IL‐4−/− BALB/c mice. Hence, IL‐33 signalling via ST2, by inducing an IL‐4‐dependent immune response, may be a major pathogenic factor in the exacerbation of ulcerative colitis.
Fundamental movement skill performance of preschool children in relation to family context

Abstract Evidence suggests the development of fundamental movement skill (FMS) is a key factor in promoting long-term physical activity. Low levels of activity among preschool children and the relationship between physical activity and the development of fundamental movement skills underline the need to determine the factors associated with children's development of such skills. As parents play an important role in the socialization process, the aim of this study was to examine correlates of family and neighbourhood characteristics as well as parental behaviour and beliefs on FMS performance in 4- to 6-year-old preschool children. Relationships between preschool children's FMS performance and family contextual variables were examined within a sample of 846 preschool children. Results identified positive associations of FMS performance with parental education, father's physical activity, transport to school by bicycle, and the high value placed by parents high on sport-specific aspects of children's physical activity. Variables negatively associated with preschool children's FMS performance included father–child interaction in TV-viewing and reading books, the high importance placed by parents on winning and performance in children's physical activity. Furthermore, the ambiguity of associations between FMS performance and parental beliefs underlined its complexity.
Associated autoimmune diseases following complete remission of myasthenia gravis

We read with interest the article by Christensen et al. concerning associated autoimmune diseases in myasthenia gravis (1) and agree with the most of their conclusions. We also encountered two myasthenia gravis (MG) patients with associated autoimmune diseases (AAD), who had optic neuritis and Evans syndrome (idiopathic thrombocytopenic purpura and autoimmune hemolytic anemia), respectively. We show such unique patients, and we would like to pose several questions. Patient 1, a 45-year-old woman was diagnosed as M G (Osserman classification, group IIB) in 1977. The received thymectomy in July 1986. Pathological examination demonstrated thymic hyperplasia. Following thymectomy, prednisolone therapy was performed for one year. Afterward, she recovered completely from M G in 1987. On July 30, 1993, she noticed blurred vision in the left eye and was admitted to our department. Neurological examination revealed a loss of vision (Vs = 0.04) and enlarged central scotoma. The remaining neurological findings were normal, including external ophthalmoplegia and muscle fatiguability. Serum anti-AchR antibodies were 4.0 nmol/l (normal < 0.6). CSF analysis showed mild elevation of protein (48 mg/dl). Visual evoked potential disclosed severe prolongation of P,,, latency in the left eye. Other evoked potentials and brain MRI were normal. Therefore, we diagnosed as left retrobulbar optic neuritis after remission of MG. Methylprednisolone pulse (1 .O g, 3 days) and oral prednisolone (80 mg/day) treatments attenuated the loss of vision in the left eye (Vs = 0.7). Patient 2, a 44-year-old man was diagnosed as M G (Osserman classification, group IIB) in 1985. Thymectomy and steroid therapy were performed in 1990, He had complete remission of M G (no medications) for the recent 4 years. Suddenly, he developed gingival bleeding, anemia, and jaundice in February 1995. Physical examination showed severe anemia, jaundice, petechial hemorrhages in the mouth, and hepato-splenomegaly. Neurological examination was normal. Hematological analysis showed normocytic normochromic anemia (RBC, 170 x 104/pl), thrommyasthenia gravis
Induction of apoptosis in cancer: new therapeutic opportunities

Autonomous cell proliferation is one of the hallmarks of cancer cells, driven by activated growth-promoting oncogenes. However, deregulated activation of these oncogenes also triggers apoptosis via multiple pathways. Among them, the ARF-p53 pathway appears to play a major role in mediating oncogene-induced apoptosis. Consequently, suppression of apoptosis by inactivation of p53 and other tumor suppressors is central to tumor development. These findings have broad implications in understanding cancer genetics and therapy. They help define the roles for oncogenes and tumor suppressor genes in tumorigenesis. Furthermore, the notion that cancer cells often carry specific defects in apoptotic pathways but are inherently sensitive to apoptosis as a result of deregulated proliferation, offers numerous opportunities for manipulating apoptosis in directions of clinical application.
Atopy and bronchial reactivity in Australian and Melanesian populations

In order to compare the prevalence of atopy and bronchial hyperreactivity among Papua New Guinian (P.N.G.) and Australian populations, skin prick tests and methacholine bronchial challenge tests were performed. A civilian and an army population from each country were examined and those with past or present asthma, recent respiratory tract infection and chronic lung disease were excluded. No statistical difference in the prevalence of atopy was found between the four populations. In the P.N. G. population 40 and 49%, and in the Australian population 27 and 39%, were found to be atopic, without symptoms of past or present allergic disease. The house dust mites were the commonest allergens in all populations. In response to methacholine (0·3 mg), only 6% of subjects had falls in 1 sec forced expiratory volume (FEV1) of more than 12% (upper limit of normal range) and only two were in the asthmatic range. There was no correlation between the degree of bronchial hyper‐reactivity and atopic status; however, the degree of bronchial hyperreactivity was slightly greater in the New Guinea civilian than in the Australian civilian population. In the absence of asthma, atopic status does not appear to cause increased bronchial reactivity, suggesting that some factor other than atopy must be present for the development of bronchial hyperreactivity characteristic of asthma.
Cytoplasmic Carbonic Anhydrase II of Rat Coagulating Gland Is Secreted via the Apocrine Export Mode

Two different pathways for protein secretion are described for epithelial cells of rat coagulating gland and dorsal prostate: the classical merocrine and the alternative apocrine release mode. Apocrine-secreted proteins are synthesized on cytoplasmic polyribosomes and are subsequently exported in protrusions on the apical cell surface (aposomes). In this article we report the identification and purification to homogeneity of a 29-kD protein from the secretion of rat coagulating gland. N-terminal amino acid sequence analyses revealed 100% identity to rat brain carbonic anhydrase II (CAH II). In addition, the 29-kD protein showed CAH enzyme activity. On Western blot analysis, a polyclonal anti-CAH II antibody raised in rabbit reacted specifically with the rat and human but not bovine CAH II isoforms. Immunohistochemical studies on rat coagulating gland showed strong labeling for CAH II protein in aposomes. Immunoelectron microscopy confined CAH II protein to the cytoplasm and aposomes, whereas no staining was visible in the compartments of the classical merocrine route, the endoplasmic reticulum and Golgi apparatus. The resident cytoplasmic protein lactate dehydrogenase, however, was not found in the secretion. Taken together, the morphological and biochemical data clearly indicate that cytoplasmic CAH II from rat coagulating gland is specifically selected and then secreted via the apocrine pathway.
The organization of intrinsic brain activity differs between genders: A resting‐state fMRI study in a large cohort of young healthy subjects

Objectives: To investigate, using resting state (RS) functional MRI (fMRI), gender‐related differences of functional connectivity (FC) and functional network connectivity (FNC) of the human brain. Experimental design: One‐hundred and four young healthy subjects (48/56 men/women), aged between 20 and 29 years, underwent a 10‐min RS fMRI acquisition. Independent component analysis (ICA) and statistical parametric mapping were used to assess gender‐related differences in RSNs, with and without correction for regional gray matter (GM) volume. The relationships among all RSNs was also assessed using a FNC method. Principal observations: For all networks, significant between‐group differences of RS activity were found. Between‐group comparisons of RSNs changed when adjusting for GM volume, as follows: (1) there was only marginal effect on the analysis of sensory (i.e., sensorimotor, visual, and auditory) networks; and (2) there was a significantly increased difference when cognitive networks (apart from one related to attention) were considered. Compared with women, men experienced increased FC in parietal and occipital regions in most RSNs, whereas women experienced a higher RS FC in frontal and temporal regions, and in the cerebellum. When compared to women, increased FNC was found in men between several cognitive and sensory networks, whereas women showed an increased FNC only between attention and right working‐memory networks. Conclusions: The organization of intrinsic FC and FNC differ between genders. The detected differences could contribute to the understanding of the known between‐gender variation in task‐related recruitments, and the patterns of abnormalities detected in neurologic and psychiatric diseases with a gender prevalence. Hum Brain Mapp, 2013. © 2012 Wiley Periodicals, Inc.
INTESTINAL EPITHELIAL LESIONS ASSOCIATED WITH SIGNET RING CELL CARCINOMA OF THE COLON AND SMALL INTESTINE

Aims: The purpose of this study was to investigate the epithelial lesions associated with signet ring cell carcinoma (SRCC) of the colon and small intestine and the possible mechanism of tumour development. Methods: Twenty‐seven cases of adenocarcinoma with a signet ring cell (SRC) component of the colon and small intestine were divided into three groups depending on the association of the SRCC with: (1) epithelium without definite epithelial dysplasia, (2) adenoma, and (3) common type of adenocarcinoma (CTCA) with SRCC component occupying more than 50%, 30%, or less than 30% of the tumour. Results: Most carcinomas were of T3 or T4 type, using the TNM standard staging system. The SRCC component was histopathologically similar in all groups. In group 1 (four cases, linitis plastica type), the overlying epithelium was normal or showed indefinite epithelial dysplasia and occasionally contained intra‐epithelial SRCs. In groups 2 and 3 (two and 21 cases, respectively), seven cases contained multiple foci of intra‐epithelial SRCs in areas separated from the invasive carcinoma. Transitional areas between SRCC and adenoma or CTCA were also identified. Immunostaining for p53 showed a varied extent of positive reactivity in 23 SRCC. The degree and the extent of reactivity appeared to increase with the stage of the carcinoma. Most intraepithelial SRCs were immunoreactive for p53. Linitis plastica SRCC was associated with extensive p53 reactivity of the 'atypical' and the adjacent 'normal' epithelium. Conclusions: SRCC may arise from either CTCA, adenoma, 'atypical' epithelium or a combination of these epithelia. SRCC accounts for the bulk of carcinoma in each of these categories. In linitis plastica SRCC, positive reactivity for p53 is extensive in the adjacent 'normal' colonic epithelium and extends as far as 3 cm from the microscopically identified SRCC margin
Suicide attempts and ideation among adults in Addis Ababa, Ethiopia

Attempted suicide is one of the major risk factors for completed suicide, is associated with psychiatric disorders, and is also a potentially fatal event. We describe here a study of suicide attempts and ideation in a representative sample of 10203 adults in Addis Ababa. The study was conducted between January and March 1994. The prevalence of current suicidal ideation was 2.7%). Lifetime prevalence of suicidal attempt was 0.9%. Most of the attempts (66%)) occurred when subjects were under 25 years of age. Hanging was the preferred method for men and poisonings for women. There were no significant associations between suicide attempt and sex, ethnicity or religion. Current suicidal ideation was more common in men than women, odds ratio (95% confidence interval), OR (95% CI): 0.67 (0.48, 0.93). There was a statistically significant trend of decreasing risk of ideation with increasing age and educational attainment. There was a 68% decrease in the risk of ideation in the 60 years of age and above group compared to the 15–24 year group: OR (95% CI): 0.32 (0.16, 0.62). Marital status, ethnicity, and religion were not associated with suicidal ideation.
Hepatocyte Growth Factor–c-MET Signaling Mediates the Development of Nonsensory Structures of the Mammalian Cochlea and Hearing

The stria vascularis is a nonsensory structure that is essential for auditory hair cell function by maintaining potassium concentration of the scala media. During mouse embryonic development, a subpopulation of neural crest cell-derived melanocytes migrates and incorporates into a subregion of the cochlear epithelium, forming the intermediate cell layer of the stria vascularis. The relation of this developmental process to stria vascularis function is currently unknown. In characterizing the molecular differentiation of developing peripheral auditory structures, we discovered that hepatocyte growth factor (Hgf) is expressed in the future stria vascularis of the cochlear epithelium. Its receptor tyrosine kinase, c-Met, is expressed in the cochlear epithelium and melanocyte-derived intermediate cells in the stria vascularis. Genetic dissection of HGF signaling via c-MET reveals that the incorporation of the melanocytes into the future stria vascularis of the cochlear duct requires c-MET signaling. In addition, inactivation of either the ligand or receptor developmentally resulted in a profound hearing loss at young adult stages. These results suggest a novel connection between HGF signaling and deafness via melanocyte deficiencies. SIGNIFICANCE STATEMENT We found the roles of hepatocyte growth factor (HGF) signaling in stria vascularis development for the first time and that lack of HGF signaling in the inner ear leads to profound hearing loss in the mouse. Our findings reveal a novel mechanism that may underlie human deafness DFNB39 and DFNB97. Our findings reveal an additional example of context-dependent c-MET signaling diversity, required here for proper cellular invasion developmentally that is essential for specific aspects of auditory-related organogenesis.
A comparison between different fouling-release elastomer coatings containing surface-active polymers

Surface-active polymers derived from styrene monomers containing siloxane (S), fluoroalkyl (F) and/or ethoxylated (E) side chains were blended with an elastomer matrix, either poly(dimethyl siloxane) (PDMS) or poly(styrene-b-(ethylene-co-butylene)-b-styrene) (SEBS), and spray-coated on top of PDMS or SEBS preformed films. By contact angle and X-ray photoelectron spectroscopy measurements, it was found that the surface-active polymer preferentially populated the outermost layers of the coating, despite its low content in the blend. However, the self-segregation process and the response to the external environment strongly depended on both the chemistry of the polymer and the type of matrix used for the blend. Additionally, mechanical testing showed that the elastic modulus of SEBS-based coatings was one order of magnitude higher than that of the corresponding PDMS-based coatings. The coatings were subjected to laboratory bioassays with the marine alga Ulva linza. PDMS-based coatings had superior fouling-release properties compared to the SEBS-based coatings.
Postnatal Development of Type II Collagen and Aggrecan mRNA Expression in a Rabbit Craniomandibular Joint

The aim of this study was to investigate the postnatal growth changes in the condyle and disc of the rabbit craniomandibular joint (CMJ). Forty‐eight rabbits from newborn to an age of 120 days were divided into eight groups, and chondrocytic differentiation and function were evaluated within the CMJ by in situ hybridization of type II collagen and aggrecan mRNA. The morphology of the posterior band and the bilaminar zone were similar in the newborn group and were composed primarily of mesenchymal cells and capillaries. After weaning, mastication loading induced the differentiation of mesenchymal cells, which was accompanied by structural differentiation between the posterior band and the bilaminar zone. Aggrecan first appeared in the posterior band of the disc at 30 days postnatally, when the rabbits began to masticate solid food. Type II collagen emerged in the disc at the age of 45 days. Both genes coexpressed in the deeper half of the proliferative layer, the whole hypertrophic layer, and the mineralized layer of the condylar cartilage and staining intensity increased with age. The coexpression of aggrecan and Type II collagen indicates the maturation of chondrocyte differentiation in the disc and condyle, which contributes to the biomechanical characteristics of the CMJ that resist functional stimulation. Anat Rec 293:1574–1580, 2010. © 2010 Wiley‐Liss, Inc.