Miracle-dz/UniFAR-FTUs huggingface dataset:
Evidence for Independent Genetic Influences on Fat Mass and Body Mass Index in a Pediatric Twin Sample

Objective. Insight into genetic and environmental influences on fat mass, independent of body mass index (BMI; kg/m2), is expected to enhance methods for treating pediatric obesity. However, few studies have estimated the heritability of fat mass in pediatric samples, and those conducted have relied primarily on BMI measurements. Present Study. Using bioimpedance analysis, the present study tested a series of hypotheses predicting significant genetic and environmental influences on percent body fat (PBF) above and beyond BMI. Subjects were 66 pairs of twins, including 41 monozygotic and 25 dizygotic pairs, from 3 to 17 years of age. Structural equation modeling tested hypotheses, adjusting for demographic variables. Results. Analyses indicated significant genetic influences on PBF, with genes estimated to account for 75% to 80% of the phenotypic variation. The remaining variation was attributable to nonshared environmental influences. Multivariate analyses revealed sizable genetic correlations and environmental correlations between BMI and PBF (rg = .74 andre = .67, respectively), suggesting that some genes and environmental experiences influence both phenotypes. However, analyses confirmed genetic and environmental influences on PBF above and beyond BMI. For example, 62.5% of the total genetic variation in PBF was attributable to genes that influenced PBF but not BMI. Conclusion. There seems to be a substantial genetic contribution to fat mass distinct from BMI in a sample of children and adolescents. Studies testing putative genetic or environmental determinants of pediatric obesity might be strengthened further by including research-based body composition methods. pediatric obesity, twin design, heritability, nonshared environment, bioimpedance analysis, body mass index, body composition.
Overexpression of human Raf‐1 enhances radiosensitivity in fission yeast, Schizosaccharomyces pombe

Recently we isolated Rad24, a 14‐3‐3 homologue, which is essential for DNA damage checkpoint, as a Raf‐1 interacting protein by screening a Schizosaccharomyces pombe (S. pombe) cDNA library. Raf‐1 was also found to recognize Cdc25 that is sequestered and inactivated by Rad24. In the present study, experiments were performed to determine the effect of overexpression of Raf‐1 proteins on asynchronously growing S. pombe cells. The overexpression of Rad24 induced elongated cell morphology and reduction in growth rate, resulting in cell cycle arrest while the overexpression of catalytically active Raf‐1 led to a decrease in cell size at division in S. pombe. However, the active Raf‐1 failed to rescue the growth arrest induced by Rad24 overexpression. In addition, the cells carrying catalytically active Raf‐1 were significantly more radiosensitive than those from a normal control as assessed by ultraviolet sensitivity assay, suggesting that constitutive overproduction of Raf‐1 kinase can revert DNA replication checkpoint arrest caused by UV irradiation. Taken together, these data suggest that Raf‐1 may interfere with the role of Rad24 by competing with Rad24 for binding to Cdc25 in DNA repair, bypassing the checkpoint pathway through Cdc25 activation. Copyright © 2007 John Wiley & Sons, Ltd.
Ex Vivo Responses for Interferon‐gamma and Proinflammatory Cytokine Secretion to Low‐Molecular‐Weight Antigen MTB12 of Mycobacterium tuberculosis during Human Tuberculosis

MTB12 protein, also called CFP‐2, is a major and early secreted component of Mycobacterium tuberculosis. However, its role during mycobacterial infection has been poorly characterized. In this study, we purified the native MTB12 protein and investigated the profile of MTB12‐induced cytokines [interferon (IFN)‐γ, tumour necrosis factor (TNF)‐α and interleukin (IL)‐6], in early tuberculosis (TB) patients (n = 20) and healthy controls (n = 35). The cytokine profiles were compared with those induced by the 30‐kDa antigen (Ag). In healthy controls, MTB12‐induced IFN‐γ production was markedly decreased in peripheral blood mononuclear cells compared with 30‐kDa Ag‐induced IFN‐γ. In TB patients, the mean IFN‐γ level induced by MTB12 was lower than that induced by the 30‐kDa Ag, albeit the difference was not significant. After 2 months of anti‐TB therapy, both the MTB12‐ and 30‐kDa‐induced IFN‐γ levels were significantly increased in TB patients. MTB12‐induced TNF‐α and IL‐6 levels were prominently upregulated in monocyte‐derived macrophages from TB patients, but they were not significantly different from those induced by the 30‐kDa Ag. Further, the activation of p38 mitogen‐activated protein kinase and extracellular signal‐regulated kinase was required for the induction of TNF‐α and IL‐6 by MTB12, as well as by the 30‐kDa Ag. Collectively, these data suggest that the MTB12 protein plays an essential role for proinflammatory responses through the MAPK pathway during the early stages of human TB, even though its T‐cell immunoreactivity is weaker than that of the 30‐kDa Ag.
Comparison of physical and mechanical properties of mineral trioxide aggregate and Biodentine.

BACKGROUND Mineral trioxide aggregate (MTA) fulfills many of the ideal properties of the root-end filling material. However, its low cohesive property often makes it difficult to handle. Biodentine, new calcium-silicate-based cement has been developed to improve some MTA drawbacks such as its difficult handling property and long-setting time. AIM The objective of this study was to compare at different times the microleakage of roots filled with Biodentine and white MTA (WMTA)-Angelus and to investigate their setting time, handling properties and compressive strength. MATERIALS AND METHODS Root canals of single-rooted teeth were instrumented, filled with either Biodentine or WMTA-Angelus (n=15 each) with two positive and two negative control roots and stored at 37°C. Sealing was assessed at 4, 24 h, 1, 2, 4, 8, and 12 weeks by a fluid filtration method. The initial setting time, handling properties, and compressive strength of the test groups were investigated by a vicat needle, questionnaire of operational hand feel, and universal instron machine, respectively. RESULTS Significant differences in microleakage were found between two groups at 4-h and 24 h (P<0.05) and no difference at 1, 2, 4, 8, and 12 weeks. No significant difference was seen in the setting time of MTA-Angelus and Biodentine, though latter was found to have better handling consistency. Compressive strength of Biodentine was significantly higher than MTA-Angelus. CONCLUSIONS The results suggest that the new calcium-silicate-based endodontic cement provides improvement in sealing ability as well as clinical manageability of dental filling materials.
The C2 Domain and Altered ATP-Binding Loop Phosphorylation at Ser359 Mediate the Redox-Dependent Increase in Protein Kinase C-δ Activity

ABSTRACT The diverse roles of protein kinase C-δ (PKCδ) in cellular growth, survival, and injury have been attributed to stimulus-specific differences in PKCδ signaling responses. PKCδ exerts membrane-delimited actions in cells activated by agonists that stimulate phosphoinositide hydrolysis. PKCδ is released from membranes as a Tyr313-phosphorylated enzyme that displays a high level of lipid-independent activity and altered substrate specificity during oxidative stress. This study identifies an interaction between PKCδ's Tyr313-phosphorylated hinge region and its phosphotyrosine-binding C2 domain that controls PKCδ's enzymology indirectly by decreasing phosphorylation in the kinase domain ATP-positioning loop at Ser359. We show that wild-type (WT) PKCδ displays a strong preference for substrates with serine as the phosphoacceptor residue at the active site when it harbors phosphomimetic or bulky substitutions at Ser359. In contrast, PKCδ-S359A displays lipid-independent activity toward substrates with either a serine or threonine as the phosphoacceptor residue. Additional studies in cardiomyocytes show that oxidative stress decreases Ser359 phosphorylation on native PKCδ and that PKCδ-S359A overexpression increases basal levels of phosphorylation on substrates with both phosphoacceptor site serine and threonine residues. Collectively, these studies identify a C2 domain-pTyr313 docking interaction that controls ATP-positioning loop phosphorylation as a novel, dynamically regulated, and physiologically relevant structural determinant of PKCδ catalytic activity.
Secretory products from infective forms of Nippostrongylus brasiliensis induce a rapid allergic airway inflammatory response

Allergic asthma is responsible for widespread morbidity and mortality and its incidence has increased dramatically in industrialized countries over the past two decades. Here, we describe a new murine model of allergic asthma utilizing a novel allergen with intrinsic enzymatic activity similar to that reported for many environmental allergens. The allergen, NES, is excreted and secreted from the nematode Nippostrongylus brasiliensis, and can readily be isolated from in vitro parasite cultures. When NES is administered intranasally to presensitized mice, allergic airway disease develops, including airway hyper‐responsiveness, airway eosinophilia, IgE antibody production and Th2 cytokine production. This disease is characteristic of atopic asthma and can be induced within 11 days, thus providing a platform for the rapid analysis of allergic disease and high throughput testing of immunomodulatory factors.
Development of the Honey Bee Gut Microbiome throughout the Queen-Rearing Process

ABSTRACT The European honey bee (Apis mellifera) is used extensively to produce hive products and for crop pollination, but pervasive concerns about colony health and population decline have sparked an interest in the microbial communities that are associated with these important insects. Currently, only the microbiome of workers has been characterized, while little to nothing is known about the bacterial communities that are associated with queens, even though their health and proper function are central to colony productivity. Here, we provide a large-scale analysis of the gut microbiome of honey bee queens during their developmental trajectory and through the multiple colonies that host them as part of modern queen-rearing practices. We found that queen microbiomes underwent a dramatic shift in size and composition as they aged and encountered different worker populations and colony environments. Queen microbiomes were dominated by enteric bacteria in early life but were comprised primarily of alphaproteobacteria at maturity. Furthermore, queen gut microbiomes did not reflect those of the workers who tended them and, indeed, they lacked many of the bacteria that are considered vital to workers. While worker gut microbiotas were consistent across the unrelated colony populations sampled, the microbiotas of the related queens were highly variable. Bacterial communities in mature queen guts were similar in size to those of mature workers and were characterized by dominant and specific alphaproteobacterial strains known to be associated with worker hypopharyngeal glands. Our results suggest a model in which queen guts are colonized by bacteria from workers' glands, in contrast to routes of maternal inoculation for other animal microbiomes.
Sponsring till vilken nytta : för filantropi eller PR?

Titel: Sponsring till vilken nytta- for filantropi eller PR? Niva: C-uppsats i amnet foretagsekonomi Forfattare: Elin Jacksson och Elin Akerblom Handledare: Agneta Sundstrom Datum: 2015 - Juni Syf .
Improved detection of metastases by step sectioning and immuno-histochemical staining of axillary sentinel nodes in patients with breast carcinoma.

BACKGROUND The object of this study was to examine whether a new protocol including step-sectioning and immunohistochemistry (IHC) staining of axillary sentinel nodes (SN) would lead to detection of more metastases in patients with breast cancer. MATERIALS AND METHODS Sixty-nine tumor free sentinel lymph nodes were examined. Step frozen sectioning was performed on formalin fixed SN and stained both by hematoxylin and eosin (H and E) and cytokeratin markers using IHC. Any tumoral cell in IHC stained slides were considered as a positive result. Metastases up to 0.2 mm were considered as isolated tumor cells and 0.2 up to 2 mm as micrometastasis. RESULTS Mean age of the patients was 48.7±12.2 years. Step sectioning of the SN revealed 11 involved by metastasis which was statistically significant (p<0.001). Furthermore, 15 (21.7%) of the patients revealed positive results in IHC staining for pan-CK marker and this was also statistically significant (p=0.001). Ten patients had tumoral involvement in lymph nodes harvested from axillary dissection and 4 out of 15 lymph nodes with positive result for CK marker were isolated tumor cells. However, 4 of 10 patients with tumor positive lymph nodes in axillary dissection were negative for CK marker and in contrast 6 of the pan-CK positive SN were in patients with tumor-free axillary lymph nodes. CONCLUSIONS Both IHC and step sectioning improve the detection rate of metastases. Considering the similar power of these two methods, we recommend using either IHC staining or step sectioning for better evaluation of harvested SNs.
Chronic PMA treatment of Jurkat T lymphocytes results in decreased protein tyrosine phosphorylation and inhibition of CD3‐ but not Ti‐dependent antibody‐triggered Ca2+ signaling

We have treated Jurkat T lymphocytes with a concentration (160 nM) of phorbol myristyl acetate (PMA) that down‐regulates conventional and novel protein kinase C (PKC) isozymes and we have investigated the effects on Ca2+ signaling and protein tyrosine phosphorylation using mAb (C305) directed against the β‐subunit of the Ti heterodimer or the ɛ/δ‐component of the CD3 complex (mAb Leu 4 or OKT 3). The levels of expression of PKC α, βI, βII, and δ were reduced by 90% or more in PMA‐treated cells, whereas the expression of PKCθ decreased by ∼30%. In contrast, the chronic treatment with PMA increased the expression of PKCɛ and PKCζ. There was a lack of Ca2+ response and myo‐inositol trisphosphate (IP3) production in PMA‐treated cells when they were exposed to mAb Leu 4 but the cells responded to mAb C305. The treatment with PMA did not affect the surface expression of Ti or CD3. The overall levels of tyrosine‐phosphorylated proteins were markedly reduced in PMA‐treated cells. We investigated whether these observations were related to defects in signal transduction related to protein tyrosine kinase (PTK) of the src and syk families. The electrophoretic mobilities of p59fyn or ZAP‐70 were not changed in PMA‐treated cells but p56Ick migrated as a large band of Mr 60–62 kDa. The decreased mobility of p56Ick was related to a state of hyperphosphorylation. The activity of modified p56Ick was not up‐regulated in activated Jurkat cells. Our data suggest that clonotypic Ti can trigger Ca2+ mobilization independently of conventional PKC isoforms. Our observations further suggest that conventional PKC isoforms are involved early in the cascade of events associated with Jurkat T lymphocyte activation.
Attenuation of vasodilatation with skeletal muscle fatigue in hamster retractor

1 We tested the hypothesis that muscle fatigue would attenuate vasodilatory responsiveness throughout the resistance network. The retractor muscle of anaesthetized hamsters was contracted (once per 2 s for 1 min) at duty cycles of 2.5, 10 and 20 % before and after fatiguing contractions that diminished peak tension and muscle glycogen by >50 %. Arterioles and feed arteries (FA) dilated maximally during fatiguing contractions. Resting vasomotor tone consistently recovered following contractions. 2 Peak blood flow was proportional to integrated tension (tension × time, expressed in mN mm−2 s); both increased with duty cycle and decreased with fatigue. Total integrated vasodilatory responses (diameter × time, expressed in μm s) increased with duty cycle and decreased with fatigue. Vasodilatation during contractions plateaued at ≥50 % of peak integrated tension. Post‐contraction vasodilatation increased with integrated tension and both were attenuated with fatigue. 3 As integrated tension increased, distal arterioles dilated first and to the greatest extent relative to proximal arterioles and FA. Fatigue had little effect on dilatation of distal arterioles whereas dilatation of proximal arterioles and FA was suppressed. Latency of onset for vasodilatation decreased as duty cycle increased and was unaffected by fatigue. 4 Vasodilatation and blood flow increase in proportion to integrated tension, with an ascending locus of vasomotor control and prolongation of post‐contraction vasodilatation. With muscle fatigue, the locus of flow control resides in distal arterioles; both ascending and post‐contraction vasodilatations are attenuated despite normal vasomotor tone.
Occurrence of aflatoxin M1 in Korean dairy products determined by ELISA and HPLC

The occurrence of aflatoxin M1 (AFM1)in pasteurized milk and dairy products was investigated by using direct competitive enzyme-linked immunosorbent assay (ELISA) and high-performance liquid chromatography (HPLC). The recoveries of AFM1 from the samples spiked at levels between 5 and 500 pg/ml were 88.0–106.5% for pasteurized milk and 84.0–94.0% for yoghurt by ELISA. By HPLC, the recoveries were 103–120% for pasteurized milk and 87.0–93.0% for yoghurt. The limits of detection were found to be 2 pg/ml by ELISA and 10 pg/ml by HPLC. Among a total of 180 samples collected in Seoul, Korea, the incidence of AFM1 in pasteurized milk, infant formula, powdered milk and yoghurt was 76, 85, 75, and 83%, respectively, with a mean concentration of 18, 46, 200, and 29 pg/g, respectively, when determined by ELISA. These results obtained by ELISA were closely related to those by HPLC for AFM1 (r2 = 0.9783).
Recognition and treatment recommendations for generalized anxiety disorder and major depressive episode: a cross-sectional study among general practitioners in norway.

OBJECTIVE Undertreatment by general practitioners (GPs) of patients who have generalized anxiety disorder (GAD) and major depressive episodes (MDEs) is well known. Overtreatment by GPs of patients without these disorders has received little attention. The aim of this study was to estimate GPs' recommended overtreatment (recommendation of treatment to patients who, on the basis of diagnostic self-ratings, had neither GAD nor MDE) and undertreatment (not recommending treatment to patients who, on the basis of self-ratings, had GAD or MDE) and to describe patient variables associated with overtreatment. METHOD In a cross-sectional design (during 3 consecutive days in September 2001), 136 Norwegian GPs evaluated 1332 patients. Diagnostic reference standards were patients' ratings of validated DSM-IV criteria-based questionnaires. GPs identified somatic diseases and mental disorders according to all accumulated information. For their diagnoses of MDE and GAD, the Clinical Global Impressions-Severity of Illness scale was used as a supplement, and GPs suggested treatment for these disorders. RESULTS The GPs recommended overtreatment in 11% (132/1245) of cases. The rates of under-treatment were 64% (18/28) and 49% (23/47) for GAD and MDE, respectively. For comorbid GAD and MDE the rate of undertreatment was 17% (2/12). Mental reason for patient's current visit and poor self-rated subjective health were strongly associated with overtreatment. CONCLUSION Our preliminary study indicates that overtreatment by GPs of patients who, according to self-rating, do not have GAD or MDE could represent a problem. Criteria-based diagnostic descriptions might be of limited relevance for the practice of GPs, and the issue of overtreatment should be investigated further in studies with improved design.
Flagellin stimulation of intestinal epithelial cells triggers CCL20-mediated migration of dendritic cells

Enteropathogenic bacteria elicit mucosal innate and adaptive immune responses. We investigated whether gut epithelial cells played a role in triggering an adaptive immune response by recruiting dendritic cells (DCs). Immature DCs are selectively attracted by the CCL20 chemokine. The expression of the CCL20 gene in human intestinal epithelial cell lines was up-regulated by pathogenic bacteria, including Salmonella species, but not by indigenous bacteria of the intestinal flora. The Salmonella machinery for epithelial cell invasion was not required for CCL20 gene activation. Flagellin but not the lipopolysaccharide was found to be the Salmonella factor responsible for stimulation of epithelial CCL20 production. CCL20 in turn triggered a specific migration of immature DCs. Our data show that crosstalk between bacterial flagellin and epithelial cells is essential for the recruitment of DCs, a mechanism that could be instrumental to initiate adaptive immune responses in the gut.
Functional Outcome 3 Months after Stroke Predicts Long-Term Survival

Background: When reporting stroke survival and prognostic factors with a possible effect on outcome, the starting point for the observation of a clinical cohort usually is the onset of stroke or the acute admission of a patient. Thus, acute and early mortality inflict prognosis on long-term outcome. In order to give a more robust analysis of long-term survival after the acute period we chose to start our observation with 3-month survivors. Methods: We used data from Riks-Stroke, the Swedish quality register for stroke care, together with survival information from the Swedish population register to explore the influence of disability level 3 months after stroke on long-term survival. The main analysis included 15,959 stroke patients, registered during 2001–2002, who had been independent in primary activities of daily living before stroke, had suffered an ischaemic or a haemorrhagic stroke and reported no previous stroke. Results: Impaired functional outcome after stroke was an independent predictor of poor survival. Patients with modified Rankin scale (mRS) grades 3, 4 and 5 had hazard ratios of 1.7, 2.5 and 3.8, respectively, as compared with patients with lower mRS grades. In addition to high mRS, male sex, high age, diabetes, smoking, hypertension therapy at stroke onset, atrial fibrillation and depressed mood were also recognized as significant predictors of poor survival using a multiple Cox regression model. Conclusion: The influence of disability on survival is stronger than that of several other well-known prognostic factors. This finding indicates that any intervention in the acute phase that may improve functional status at 3 months will also have favourable secondary effects on survival in the long term.