The relationship of female physical attractiveness to body fatness

Funding This work was supported by NSFC grant 91431102 from the National Science Foundation of China. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Acknowledgements We are grateful to all the participants from all the countries and all the members of Molecular Energetics Group for their help on the investigation and discussion of the results.Peer reviewedPublisher PD

Severe high-molecular-weight kininogen deficiency: clinical characteristics, deficiency–causing KNG1 variants, and estimated prevalence

Background: Severe high-molecular-weight kininogen (HK) deficiency is a poorly studied autosomal recessive contact system defect caused by pathogenic, biallelic KNG1 variants. Aim: We performed the first comprehensive analysis of diagnostic, clinical, genetic, and epidemiological aspects of HK deficiency. Methods: We collected clinical information and blood samples from a newly detected HK-deficient individual and from published cases identified by a systematic literature review. Activity and antigen levels of coagulation factors were determined. Genetic analyses of KNG1 and KLKB1 were performed by Sanger sequencing. The frequency of HK deficiency was estimated considering truncating KNG1 variants from GnomAD. Results: We identified 48 cases of severe HK deficiency (41 families), of these 47 have been previously published (n = 19 from gray literature). We genotyped 3 cases and critically appraised 10 studies with genetic data. Ten HK deficiency-causing variants (one new) were identified. All of them were truncating mutations, whereas the only known HK amino acid substitution with a relevant phenotype instead causes hereditary angioedema. Conservative estimates suggest an overall prevalence of severe HK deficiency of approximately one case per 8 million population, slightly higher in Africans. Individuals with HK deficiency appeared asymptomatic and had decreased levels of prekallikrein and factor XI, which could lead to misdiagnosis. Conclusion: HK deficiency is a rare condition with only few known pathogenic variants. It has an apparently good prognosis but is prone to misdiagnosis. Our understanding of its clinical implications is still limited, and an international prekallikrein and HK deficiency registry is being established to fill this knowledge gap. Keywords: blood coagulation disorders; diagnosis; epidemiology; high-molecular-weight; kallikrein-kinin system; kininogen; partial thromboplastin tim

Identification and Characterization of the Host Protein DNAJC14 as a Broadly Active Flavivirus Replication Modulator

Viruses in the Flavivirus genus of the Flaviviridae family are arthropod-transmitted and contribute to staggering numbers of human infections and significant deaths annually across the globe. To identify cellular factors with antiviral activity against flaviviruses, we screened a cDNA library using an iterative approach. We identified a mammalian Hsp40 chaperone protein (DNAJC14) that when overexpressed was able to mediate protection from yellow fever virus (YFV)-induced cell death. Further studies revealed that DNAJC14 inhibits YFV at the step of viral RNA replication. Since replication of bovine viral diarrhea virus (BVDV), a member of the related Pestivirus genus, is also known to be modulated by DNAJC14, we tested the effect of this host factor on diverse Flaviviridae family members. Flaviviruses, including the pathogenic Asibi strain of YFV, Kunjin, and tick-borne Langat virus, as well as a Hepacivirus, hepatitis C virus (HCV), all were inhibited by overexpression of DNAJC14. Mutagenesis showed that both the J-domain and the C-terminal domain, which mediates self-interaction, are required for anti-YFV activity. We found that DNAJC14 does not block YFV nor HCV NS2-3 cleavage, and using non-inhibitory mutants demonstrate that DNAJC14 is recruited to YFV replication complexes. Immunofluorescence analysis demonstrated that endogenous DNAJC14 rearranges during infection and is found in replication complexes identified by dsRNA staining. Interestingly, silencing of endogenous DNAJC14 results in impaired YFV replication suggesting a requirement for DNAJC14 in YFV replication complex assembly. Finally, the antiviral activity of overexpressed DNAJC14 occurs in a time- and dose-dependent manner. DNAJC14 overexpression may disrupt the proper stoichiometry resulting in inhibition, which can be overcome upon restoration of the optimal ratios due to the accumulation of viral nonstructural proteins. Our findings, together with previously published work, suggest that the members of the Flaviviridae family have evolved in unique and important ways to interact with this host Hsp40 chaperone molecule

Nitration of the Pollen Allergen Bet v 1.0101 Enhances the Presentation of Bet v 1-Derived Peptides by HLA-DR on Human Dendritic Cells

Nitration of pollen derived allergens can occur by NO2 and ozone in polluted air and it has already been shown that nitrated major birch (Betula verrucosa) pollen allergen Bet v 1.0101 (Bet v 1) exhibits an increased potency to trigger an immune response. However, the mechanisms by which nitration might contribute to the induction of allergy are still unknown. In this study, we assessed the effect of chemically induced nitration of Bet v 1 on the generation of HLA-DR associated peptides. Human dendritic cells were loaded with unmodified Bet v 1 or nitrated Bet v 1, and the naturally processed HLA-DR associated peptides were subsequently identified by liquid chromatography-mass spectrometry. Nitration of Bet v 1 resulted in enhanced presentation of allergen-derived HLA-DR-associated peptides. Both the copy number of Bet v 1 derived peptides as well as the number of nested clusters was increased. Our study shows that nitration of Bet v 1 alters antigen processing and presentation via HLA-DR, by enhancing both the quality and the quantity of the Bet v 1-specific peptide repertoire. These findings indicate that air pollution can contribute to allergic diseases and might also shed light on the analogous events concerning the nitration of self-proteins

Sprachentwicklung und Sprachfähigkeiten bei Kindern mit Kleinhirnläsionen

Lange Zeit wurde das Kleinhirn nur in seiner motorischen Funktion wahrgenommen. Gegenwärtig erfährt das Kleinhirn immer mehr Aufmerksamkeit, und neuere Studien belegen seine Rolle auch im Bereich höherer kognitiver Funktionen. Untersuchungen verweisen auf Defizite hinsichtlich der Sprachfähigkeiten bei Vorliegen einer kongenitalen oder erworbenen Kleinhirnläsion. Da diese Studien vorwiegend an Erwachsenen und im Rahmen allumfassender Entwicklungstests durchgeführt worden sind, zielte diese Studie darauf ab, die sprachlichen Fähigkeiten von Kindern mit Kleinhirnläsionen anhand neuropsychologischer Testverfahren spezifischer zu untersuchen. Dadurch sollte die Rolle des Kleinhirns bei linguistischen Fähigkeiten untersucht werden. Die Stichprobe dieser Querschnittsstudie umfasste zehn ProbandInnen im Alter zwischen sechs und zehn Jahren. Die PatientInnengruppe bestand aus drei Kindern mit der Diagnose Status post akute Cerebellitis, einem Kind mit Dandy-Walker Malformation und einem mit Vermishypogenesie. Die Kontrollgruppe wurde aus fünf gesunden TeilnehmerInnen gebildet. Die Gruppenauswertung zeigte einen signifikanten Unterschied in der semantisch- kategoriellen Wortflüssigkeit zwischen der PatientInnengruppe und der Kontrollgruppe. In allen weiteren linguistischen Fähigkeiten unterschieden sich die Gruppen nicht signifikant voneinander. In den individuellen Analysen wiesen die Patienten jedoch in nahezu allen Sprachaufgaben unterdurchschnittliche Ergebnisse in der expressiven und rezeptiven Sprache im Vergleich zu normativen Testwerten auf. Besonders häufig wurden Defizite in der Wortschatzleistung, der Wortfindung und der semantisch-kategoriellen Flüssigkeit beobachtet. Auch das verbale Kurz- und Langzeitgedächtnis war häufig beeinträchtigt. Die diskutierten Fallstudien lassen sich somit in die bereits bestehende Literatur einordnen und unterstreichen die Beteiligung des Kleinhirns an linguistischen Fähigkeiten.For a long time, the cerebellum was perceived only in its motor function. Nowadays, the cerebellum is receiving more and more attention, and recent studies have shown its role in higher cognitive functions, such as language skills. Studies point to deficits in language skills in the presence of a congenital or acquired cerebellar lesion. Since these studies have been conducted primarily in adults and as part of all- inclusive developmental testing, this study aimed to examine more specifically the linguistic abilities of children with cerebellar lesions using neuropsychological testing procedures. The aim was to investigate the role of the cerebellum in linguistic abilities. The sample of this cross-sectional study included ten subjects aged between six and ten years. The patient group consisted of three children with the diagnosis status-post acute cerebellitis, one child with Dandy-Walker malformation and one with vermis hypogenesis. The control group was formed by five healthy participants. The group evaluation showed a significant difference in semantic-categorical word fluency between the patient group and the control group. In all other linguistic abilities the groups did not differ significantly from each other. In the individual analyses, however, the patients showed below-average results in expressive and receptive language compared to normative test values in almost all language tasks. Deficits in vocabulary performance, word finding, and semantic-categorical fluency were observed particularly frequently. Verbal short and long-term memory was also frequently impaired. Thus, the case studies discussed in this thesis support the current assumption that the cerebellum is involved in linguistic abilities

Design of an Inkjet-Printed Rotary Bellows Actuator and Simulation of its Time-Dependent Deformation Behavior

State-of-the-art Additive Manufacturing processes such as three-dimensional (3D) inkjet printing are capable of producing geometrically complex multi-material components with integrated elastomeric features. Researchers and engineers seeking to exploit these capabilities must handle the complex mechanical behavior of inkjet-printed elastomers and expect a lack of suitable design examples. We address these obstacles using a pneumatic actuator as an application case. First, an inkjet-printable actuator design with elastomeric bellows structures is presented. While soft robotics research has brought forward several examples of inkjet-printed linear and bending bellows actuators, the rotary actuator described here advances into the still unexplored field of additively manufactured pneumatic lightweight robots with articulated joints. Second, we demonstrate that the complex structural behavior of the actuator’s elastomeric bellows structure can be predicted by Finite Element (FE) simulation. To this end, a suitable hyperviscoelastic material model was calibrated and compared to recently published models in a multiaxial-state-of-stress relaxation experiment. To verify the material model, Finite Element simulations of the actuator’s deformation behavior were conducted, and the results compared to those of corresponding experiments. The simulations presented here advance the materials science of inkjet-printed elastomers by demonstrating use of a hyperviscoelastic material model for estimating the deformation behavior of a prototypic robotic component. The results obtained contribute to the long-term goal of additively manufactured and pneumatically actuated lightweight robots

β-thalassemia minor, carbohydrate malabsorption and histamine intolerance

Background: β-thalassemia minor is characterized by reduced β-haemoglobin chain synthesis and sometimes mild anaemia, although carriers of β-thalassemia minorare usually clinically asymptomatic.Nonspecific abdominal complaints may be caused by gastrointestinal carbohydrate malabsorption (lactose and fructose) and/or malabsorption of biogenic amines (histamine), or proteins (gluten). Objectives: We report on two patients with β-thalassemia minor suffering nonspecific abdominal symptoms due to a carbohydrate and histamine malabsorption. Design/methods: The diagnosis of β-thalassemia minorwas done with peripheral blood smear and cellulose acetate electrophoresis. Carbohydrate malabsorption was diagnosed with hydrogen breath tests and, histamine intolerance (HIT) with a serum diamine oxidase value <10 U/ml and more than two gastrointestinal symptoms described for HIT. Conclusion: The symptoms of gastrointestinal malabsorption in these two patients with β-thalassemia minor were treated successfully with an individually-tailored diet free of symptom causing carbohydrates and histamine

Toll-Like Receptor-Mediated Cardiac Injury during Experimental Sepsis

Sepsis is associated with global cardiac dysfunction and with high mortality rate. The development of septic cardiomyopathy is due to complex interactions of damage-associated molecular patters, cytokines, and complement activation products. The aim of this study was to define the effects of sepsis on cardiac structure, gap junction, and tight junction (TJ) proteins. Sepsis was induced by cecal ligation and puncture in male C57BL/6 mice. After a period of 24 h, the expression of cardiac structure, gap junction, and TJ proteins was determined. Murine HL-1 cells were stimulated with LPS, and mRNA expression of cardiac structure and gap junction proteins, intracellular reactive oxygen species, and troponin I release was analyzed. Furthermore, pyrogenic receptor subtype 7 (P2X7) expression and troponin I release of human cardiomyocytes (iPS) were determined after LPS exposure. In vivo, protein expression of connexin43 and α-actinin was decreased after the onset of polymicrobial sepsis, whereas in HL-1 cells, mRNA expression of connexin43, α-actinin, and desmin was increased in the presence of LPS. Expression of TJ proteins was not affected in vivo during sepsis. Although the presence of LPS and nigericin resulted in a significant troponin I release from HL-1 cells. Sepsis affected cardiac structure and gap junction proteins in mice, potentially contributing to compromised cardiac function

Increasing Expiratory Hydrogen in Lactose Intolerance Is Associated with Additional Food Intolerance/Malabsorption

Single and/or combined food intolerance/malabsorption may cause nonspecific, functional gastrointestinal (GI) complaints. In lactose-intolerant patients we evaluated the influence of additional food intolerance/malabsorption with hydrogen (H2) breath tests. In a retrospective analysis of charts from 279 lactose-intolerant patients, we found 128 patients with only lactose intolerance (LIT). Then, we identified 106 LIT patients with additional histamine intolerance (HIT). Additionally, 45 LIT and HIT patients also had fructose malabsorption (FM). A hydrogen (H2) breath test was performed to evaluate LIT and FM. A serum diamine oxidase value of &lt;10 U/mL and a response to a histamine-reduced diet was used to identify HIT. Using pairwise comparison with the Kruskal&ndash;Wallis test to associate the area under the curve (AUC) of LIT patients and, LIT with HIT, to LIT with HIT and FM it was found, that the exhaled hydrogen values were significantly higher in patients with two-fold and triple combined food intolerance/malabsorption (p &lt; 0.004 and p &lt; 0.001, respectively). Within the pool of 170 LIT patients with &gt;20 ppm increase of expiratory H2 from baseline, there were 74 LIT-only patients, 60 LIT with HIT patients, and 36 LIT patients with additional HIT and FM. With the Kruskal&ndash;Wallis test AUCs demonstrated a significant difference between all three groups (p = 0.024). In patients with LIT, the presence of additional food intolerance/malabsorption, significantly increases expiratory H2 values. We demonstrate evidence, which may suggest HIT to embody an own GI disorder as food intolerance/malabsorption