bluuebunny/crossref_metadata_2025_split huggingface dataset:
VEGFA GENE variation influences hallucinations and frontotemporal morphology in psychotic disorders: a B-SNIP study
Authors: Lizano Paulo , Lutz Olivia , Ling George , Padmanabhan Jaya , Tandon Neeraj , Sweeney John , Tamminga Carol , Pearlson Godfrey , Ruaño Gualberto , Kocherla Mohan , Windemuth Andreas , Clementz Brett , Gershon Elliot , Keshavan Matcheri 
Published: October 2018

AbstractVascular endothelial growth factor A (VEGFA) dysfunction may contribute to a number of pathological processes that characterize psychotic disorders. However, the influence of VEGFA gene variants on clinical and neuroimaging phenotypes in psychotic disorders has yet to be shown. In the present study, we examined whether different VEGFA gene variants influence psychosis risk, symptom severity, cognition, and brain volume. The study group included 480 probands (Bipolar I disorder with psychosis, n = 205; Schizoaffective disorder, n = 112; Schizophrenia, n = 163) and 126 healthy controls that were recruited across six sites in the B-SNIP consortium. VEGFA variants identified for analysis (rs699947, rs833070, and rs2146323) were quantified via SNP chip array. We assessed symptoms and cognition using standardized clinical and neuropsychological batteries. The dorsolateral prefrontal cortex (DLPFC), medial temporal lobe, and hippocampal volumes were quantified using FreeSurfer. In our sample, VEGFA rs2146323 A- carriers showed reduced odds of being a proband (p = 0.037, OR = 0.65, 95% CI = 0.43–0.98) compared to noncarriers, but not for rs699947 or rs833070. In probands, rs2146323 A- carriers demonstrated fewer hallucinations (p = 0.035, Cohen’s d = 0.194), as well as significantly greater DLPFC (p < 0.05, Cohen’s d = −0.21) and parahippocampal volumes (p < 0.01, Cohen’s d = −0.27). No clinical or neuroimaging associations were identified for rs699947 or rs833070. In general, we found that the three SNPs exhibited several significant negative relationships between psychosis symptoms and brain structure. In the probands and control groups, positive relationships were identified between several cognitive and brain volume measures. The findings suggest VEGFA effects in the DLPFC and hippocampus found in animals may also extend to humans. VEGFA variations may have important implications in identifying dimensional moderators of function that could be targeted through VEGFA-mediated interventions.
Rare truncating variants in the sarcomeric protein titin associate with familial and early-onset atrial fibrillation
Authors: Ahlberg Gustav , Refsgaard Lena , Lundegaard Pia R. , Andreasen Laura , Ranthe Mattis F. , Linscheid Nora , Nielsen Jonas B. , Melbye Mads , Haunsø Stig , Sajadieh Ahmad , Camp Lu , Olesen Søren-Peter , Rasmussen Simon , Lundby Alicia , Ellinor Patrick T. , Holst Anders G. , Svendsen Jesper H. , Olesen Morten S. 
Published: October 2018

AbstractA family history of atrial fibrillation constitutes a substantial risk of developing the disease, however, the pathogenesis of this complex disease is poorly understood. We perform whole-exome sequencing on 24 families with at least three family members diagnosed with atrial fibrillation (AF) and find that titin-truncating variants (TTNtv) are significantly enriched in these patients (P = 1.76 × 10−6). This finding is replicated in an independent cohort of early-onset lone AF patients (n = 399; odds ratio = 36.8;P = 4.13 × 10−6). A CRISPR/Cas9 modified zebrafish carrying a truncating variant of titin is used to investigate TTNtv effect in atrial development. We observe compromised assembly of the sarcomere in both atria and ventricle, longer PR interval, and heterozygous adult zebrafish have a higher degree of fibrosis in the atria, indicating that TTNtv are important risk factors for AF. This aligns with the early onset of the disease and adds an important dimension to the understanding of the molecular predisposition for AF.
Coordinated targeting of cold and nicotinic receptors synergistically improves obesity and type 2 diabetes
Authors: Clemmensen Christoffer , Jall Sigrid , Kleinert Maximilian , Quarta Carmelo , Gruber Tim , Reber Josefine , Sachs Stephan , Fischer Katrin , Feuchtinger Annette , Karlas Angelos , Simonds Stephanie E. , Grandl Gerald , Loher Daniela , Sanchez-Quant Eva , Keipert Susanne , Jastroch Martin , Hofmann Susanna M. , Nascimento Emmani B. M. , Schrauwen Patrick , Ntziachristos Vasilis , Cowley Michael A. , Finan Brian , Müller Timo D. , Tschöp Matthias H. 
Published: October 2018

AbstractPharmacological stimulation of brown adipose tissue (BAT) thermogenesis to increase energy expenditure is progressively being pursued as a viable anti-obesity strategy. Here, we report that pharmacological activation of the cold receptor transient receptor potential cation channel subfamily M member 8 (TRPM8) with agonist icilin mimics the metabolic benefits of cold exposure. In diet-induced obese (DIO) mice, treatment with icilin enhances energy expenditure, and decreases body weight, without affecting food intake. To further potentiate the thermogenic action profile of icilin and add complementary anorexigenic mechanisms, we set out to identify pharmacological partners next to icilin. To that end, we specifically targeted nicotinic acetylcholine receptor (nAChR) subtype alpha3beta4 (α3β4), which we had recognized as a potential regulator of energy homeostasis and glucose metabolism. Combinatorial targeting of TRPM8 and nAChR α3β4 by icilin and dimethylphenylpiperazinium (DMPP) orchestrates synergistic anorexic and thermogenic pathways to reverse diet-induced obesity, dyslipidemia, and glucose intolerance in DIO mice.
Decoding the intensity of sensory input by two glutamate receptors in one C. elegans interneuron
Authors: Zou Wenjuan , Fu Jiajun , Zhang Haining , Du Kang , Huang Wenming , Yu Junwei , Li Shitian , Fan Yuedan , Baylis Howard A. , Gao Shangbang , Xiao Rui , Ji Wei , Kang Lijun , Xu Tao 
Published: October 2018

AbstractHow neurons are capable of decoding stimulus intensity and translate this information into complex behavioral outputs is poorly defined. Here, we demonstrate that the C. elegans interneuron AIB regulates two types of behaviors: reversal initiation and feeding suppression in response to different concentrations of quinine. Low concentrations of quinine are decoded in AIB by a low-threshold, fast-inactivation glutamate receptor GLR-1 and translated into reversal initiation. In contrast, high concentrations of quinine are decoded by a high-threshold, slow-inactivation glutamate receptor GLR-5 in AIB. After activation, GLR-5 evokes sustained Ca2+ release from the inositol 1,4,5-trisphosphate (IP3)-sensitive Ca2+ stores and triggers neuropeptide secretion, which in turn activates the downstream neuron RIM and inhibits feeding. Our results reveal that distinct signal patterns in a single interneuron AIB can encode differential behavioral outputs depending on the stimulus intensity, thus highlighting the importance of functional mapping of information propagation at the single-neuron level during connectome construction.
Limitation of Fermi level shifts by polaron defect states in hematite photoelectrodes
Authors: Lohaus Christian , Klein Andreas , Jaegermann Wolfram 
Published: October 2018

AbstractThe optical band gap is a major selection criterion for an absorber in photocatalytic water splitting. Due to its ideal value hematite has been intensively investigated without reaching the expectation, yet. In this work, the Fermi level positions in hematite due to doping and contact formation are investigated. An upper boundary for the Fermi level position at 1.8 eV above the valence band maximum due to the formation of polarons is identified. This results in a different concept of the effective band gap for hematite which we believe is transferable to any material with competing polaron formation after optical excitation: the optical band gap of 2.2 eV deviates from an effective electronic band gap of 1.75 eV. The polaron state acts as a limit in (quasi-)Fermi level shift, restricting the potential of charge transfer reactions. Additionally, it has led to an incorrect determination of the band edge positions of hematite in electrochemical contacts.
Growth and longevity in giant barrel sponges: Redwoods of the reef or Pines in the Indo-Pacific?
Authors: McGrath Emily C. , Woods Lisa , Jompa Jamaluddin , Haris Abdul , Bell James J. 
Published: October 2018

AbstractDescribing life history dynamics of functionally important species is critical for successful management. Barrel sponges (Xestospongia spp.) fill ecologically important roles on coral reefs due to their large size and water column interactions. Studies of Caribbean X. muta suggest they may be up to 1000 s of years old. However, nothing is known of barrel sponge growth rates outside the Caribbean. We assessed Indo-Pacific barrel sponge demography with a focus on specific growth rate (SGR), density, and mean volume across four sites of varying habitat quality. Four growth models were compared using Akaike’s Information Criterion using a multi-model inference approach. Age was extrapolated and validated based on sponge size on a shipwreck of known age. Sponges from different sites showed differences in density, volume gained, and mean volume, but not growth rates. Interestingly, SGRs were slightly slower than that of X. muta, yet growth models supported rapid growth; published estimates of comparably sized X. muta were over twice as old as Indo-Pacific sponges (53–55 as compared to 23 years of age, respectively), although extrapolation errors are likely to increase with sponge size. This suggests that barrel sponge growth rates in the Indo-Pacific might be more comparable to Pines rather than Redwoods.
Age-related waning of immune responses to BCG in healthy children supports the need for a booster dose of BCG in TB endemic countries
Authors: Whittaker Elizabeth , Nicol Mark P. , Zar Heather J. , Tena-Coki Nontobeko G. , Kampmann Beate 
Published: October 2018

AbstractIn the absence of a more effective vaccine against TB and in the interest of developing one, it is essential to understand immune responses associated with BCG protection. We comprehensively characterized T cell populations in BCG-vaccinated children over time. Blood from 78 healthy, BCG-vaccinated children representing four age groups (<1 yr, ≥1 yr <2 yr, ≥2 yr <5 yr, ≥5 yr), was stimulated in vitro for 24 hours and 6 days with live BCG to induce effector and central memory responses. Antigen-specific CD4, CD8, γδ and regulatory T cell populations were phenotyped and intracellular and secreted cytokines measured by flow cytometry and multiplex ELISA respectively. Our results demonstrated that populations of naïve T cells predominated in infants, compared to older children. However, BCG-specific effector CD4 T cell responses were equivalent and antigen-specific CD4 T cell proliferative capacity was increased in infants compared to older children. Increases in innate immune responses including γδ T cell responses and secreted pro-inflammatory cytokines were noted with increasing age. In conclusion, we identified that the capacity to expand and differentiate effector T cells in response to BCG stimulation wanes with increasing age, which may indicate waning central memory immunity. Booster vaccination could be considered to maintain the antigen-specific central memory pool and possibly enhance the duration of protection.
Anisotropic Dirac Fermions in BaMnBi2 and BaZnBi2
Authors: Ryu Hyejin , Park Se Young , Li Lijun , Ren Weijun , Neaton Jeffrey B. , Petrovic Cedomir , Hwang Choongyu , Mo Sung-Kwan 
Published: October 2018

AbstractWe investigate the electronic structure of BaMnBi2 and BaZnBi2 using angle-resolved photoemission spectroscopy and first-principles calculations. Although they share similar structural properties, we show that their electronic structure exhibit dramatic differences. A strong anisotropic Dirac dispersion is revealed in BaMnBi2 with a decreased asymmetry factor compared with other members of AMnBi2 (A = alkali earth or rare earth elements) family. In addition to the Dirac cones, multiple bands crossing the Fermi energy give rise to a complex Fermi surface topology for BaZnBi2. We further show that the strength of hybridization between Bi-p and Mn-d/Zn-s states is the main driver of the differences in electronic structure for these two related compounds.
Transposon mutagenesis screen in mice identifies TM9SF2 as a novel colorectal cancer oncogene
Authors: Clark Christopher R. , Maile Makayla , Blaney Patrick , Hellweg Stefano R. , Strauss Anna , Durose Wilaiwan , Priya Sambhawa , Habicht Juri , Burns Michael B. , Blekhman Ran , Abrahante Juan E. , Starr Timothy K. 
Published: October 2018

AbstractNew therapeutic targets for advanced colorectal cancer (CRC) are critically needed. Our laboratory recently performed an insertional mutagenesis screen in mice to identify novel CRC driver genes and, thus, potential drug targets. Here, we define Transmembrane 9 Superfamily 2 (TM9SF2) as a novel CRC oncogene. TM9SF2 is an understudied protein, belonging to a well conserved protein family characterized by their nine putative transmembrane domains. Based on our transposon screen we found that TM9SF2 is a candidate progression driver in digestive tract tumors. Analysis of The Cancer Genome Atlas (TCGA) data revealed that approximately 35% of CRC patients have elevated levels of TM9SF2 mRNA, data we validated using an independent set of CRC samples. RNAi silencing of TM9SF2 reduced CRC cell growth in an anchorage-independent manner, a hallmark of cancer. Furthermore, CRISPR/Cas9 knockout of TM9SF2 substantially diminished CRC tumor fitness in vitro and in vivo. Transcriptome analysis of TM9SF2 knockout cells revealed a potential role for TM9SF2 in cell cycle progression, oxidative phosphorylation, and ceramide signaling. Lastly, we report that increased TM9SF2 expression correlates with disease stage and low TM9SF2 expression correlate with a more favorable relapse-free survival. Taken together, this study provides evidence that TM9SF2 is a novel CRC oncogene.
The relationship between plasma ferritin levels and body mass index among adolescents
Authors: Shattnawi Khulood K. , Alomari Mahmoud A. , Al-Sheyab Nihaya , Bani Salameh Ayman 
Published: October 2018

AbstractCirculatory Ferritin concentration varies with age, sex, and body composition. Studies that determine the relationship of different body weight measurements with plasma ferritin concentration in adolescents are lacking. A descriptive cross-sectional design was utilized. Data collection involved self-reporting demographics, blood samples, and body composition measures for a sample of 814 healthy Jordanian adolescents. Ferritin deficiency was observed in 55.8% of the study population. Simple linear regression showed that BMI, gender, location, and smoking status 2.5%, 3.9%, 0.4%, and 0.4%, respectively, associated positively with plasma ferritin level (p < 0.05). After controlling for gender, location, and smoking status, additional hierarchal multiple linear regression showed that BMI explained 2.2% of plasma ferritin (p < 0.000). However, the obesity-stratified hierarchal multiple linear regression, showed that BMI explained 2.1% of plasma ferritin in the overweight and obese (HI) adolescents (p = 0.02), but not in the under and normal weight (LO) adolescents (p = 0.91). After controlling for gender, location, and smoking status, the ANCOVA showed that plasma ferritin level was greater (p < 0.000) in the HI (19.00 ± 13.6) versus the LO (15.20 ± 10.4) obesity group. Our results indicated that normal ferritin level among obese people does not necessarily indicate normal iron storage.
The consequences of porcine IVM medium supplementation with follicular fluid become reflected in embryo quality, yield and gene expression patterns
Authors: Pawlak Piotr , Warzych Ewelina , Cieslak Adam , Malyszka Natalia , Maciejewska Eliza , Madeja Zofia Eliza , Lechniak Dorota 
Published: October 2018

AbstractOocyte and embryo developmental competence are shaped by multiple extrinsic and intrinsic factors. One of the most extensive research areas in the last decade is the regulation of lipid metabolism in oocytes and embryos of different species. We hypothesized that differences in developmental competence of oocytes and embryos between prepubertal and cyclic gilts may arise due to distinct fatty acid profiles in follicular fluid. We found that supplementation of oocyte maturation media with follicular fluid from prepubertal pigs affected quality and development of embryos from prepubertal pigs while embryos of cyclic pigs were not affected. PLIN2, SCD and ACACA transcripts involved in lipid metabolism were upregulated in embryos originating from oocytes of prepubertal pigs matured with autologous follicular fluid. The surface occupied by lipid droplets tend to increase in oocytes matured with follicular fluid from prepubertal pigs regardless oocyte origin. The change into follicular fluid of cyclic pigs increased the efficiency of embryo culture and improved quality, while gene expression was similar to embryos obtained from cyclic gilts. We assume that the follicular fluids of prepubertal and cyclic pigs influenced the quality of oocytes and embryos obtained from prepubertal pigs which are more susceptible to suboptimal in vitro culture conditions.
Choosing appropriate prosthetic ankle work to reduce the metabolic cost of individuals with transtibial amputation
Authors: Ingraham Kimberly A. , Choi Hwan , Gardinier Emily S. , Remy C. David , Gates Deanna H. 
Published: October 2018

AbstractPowered ankle prostheses have been designed to reduce the energetic burden that individuals with transtibial amputation experience during ambulation. There is an open question regarding how much power the prosthesis should provide, and whether approximating biological ankle kinetics is optimal to reduce the metabolic cost of users. We tested 10 individuals with transtibial amputation walking on a treadmill wearing the BiOM powered ankle prosthesis programmed with 6 different power settings (0–100%), including a prosthetist-chosen setting, chosen to approximate biological ankle kinetics. We measured subjects’ metabolic cost of transport (COT) and the BiOM’s net ankle work during each condition. Across participants, power settings greater than 50% resulted in lower COT than 0% or 25%. The relationship between power setting, COT, and net ankle work varied considerably between subjects, possibly due to individual adaptation and exploitation of the BiOM’s reflexive controller. For all subjects, the best tested power setting was higher than the prosthetist-chosen setting, resulting in a statistically significant and meaningful difference in COT between the best tested and prosthetist-chosen power settings. The results of this study demonstrate that individuals with transtibial amputation may benefit from prescribed prosthetic ankle push-off work that exceeds biological norms.
Association between circulating tumor necrosis factor-related biomarkers and estimated glomerular filtration rate in type 2 diabetes
Authors: Kamei Nozomu , Yamashita Mami , Nishizaki Yuji , Yanagisawa Naotake , Nojiri Shuko , Tanaka Kanako , Yamashita Yoshinori , Shibata Terumi , Murakoshi Maki , Suzuki Yusuke , Gohda Tomohito 
Published: October 2018

AbstractChronic inflammation plays a crucial role in the development/progression of diabetic kidney disease. The involvement of tumor necrosis factor (TNF)-related biomarkers [TNFα, progranulin (PGRN), TNF receptors (TNFR1 and TNFR2)] and uric acid (UA) in renal function decline was investigated in patients with type 2 diabetes (T2D). Serum TNF-related biomarkers and UA levels were measured in 594 Japanese patients with T2D and an eGFR ≥30 mL/min/1.73 m2. Four TNF-related biomarkers and UA were negatively associated with estimated glomerular filtration rate (eGFR). In a logistic multivariate model, each TNF-related biomarker and UA was associated with lower eGFR (eGFR <60mL /min/1.73 m2) after adjustment for relevant covariates (basic model). Furthermore, UA and TNF-related biomarkers other than PGRN added a significant benefit for the risk factors of lower eGFR when measured together with a basic model (UA, ΔAUC, 0.049, p < 0.001; TNFα, ΔAUC, 0.022, p = 0.007; TNFR1, ΔAUC, 0.064, p < 0.001; TNFR2, ΔAUC, 0.052, p < 0.001) in receiver operating characteristic curve analysis. TNFR ligands were associated with lower eGFR, but the associations were not as strong as those with TNFRs or UA in patients with T2D and an eGFR ≥30 mL/min/1.73 m2.
The Cancer/Testes (CT) Antigen HORMAD1 promotes Homologous Recombinational DNA Repair and Radioresistance in Lung adenocarcinoma cells
Authors: Gao Yanzhe , Kardos Jordan , Yang Yang , Tamir Tigist Y. , Mutter-Rottmayer Elizabeth , Weissman Bernard , Major Michael B. , Kim William Y. , Vaziri Cyrus 
Published: October 2018

AbstractThe Cancer/Testes (CT) Antigen HORMAD1 is germ cell-restricted and plays developmental roles in generation and processing of meiotic DNA Double Strand Breaks (DSB). Many tumors aberrantly overexpress HORMAD1 yet the potential impact of this CT antigen on cancer biology is unclear. We tested a potential role of HORMAD1 in genome maintenance in lung adenocarcinoma cells. We show that HORMAD1 re-distributes to nuclear foci and co-localizes with the DSB marker γH2AX in response to ionizing radiation (IR) and chemotherapeutic agents. The HORMA domain and C-term disordered oligomerization motif are necessary for localization of HORMAD1 to IR-induced foci (IRIF). HORMAD1-depleted cells are sensitive to IR and camptothecin. In reporter assays, Homologous Recombination (HR)-mediated repair of targeted ISce1-induced DSBs is attenuated in HORMAD1-depleted cells. In Non-Homologous End Joining (NHEJ) reporter assays, HORMAD1-depletion does not affect repair of ISce1-induced DSB. Early DSB signaling events (including ATM phosphorylation and formation of γH2AX, 53BP1 and NBS1 foci) are intact in HORMAD1-depleted cells. However, generation of RPA-ssDNA foci and redistribution of RAD51 to DSB are compromised in HORMAD1-depleted cells, suggesting that HORMAD1 promotes DSB resection. HORMAD1-mediated HR is a neomorphic activity that is independent of its meiotic partners (including HORMAD2 and CCDC36. Bioinformatic analysis of TCGA data show that similar to known HR pathway genes HORMAD1 is overexpressed in lung adenocarcinomas. Overexpression of HR genes is associated with specific mutational profiles (including copy number variation). Taken together, we identify HORMAD1-dependent DSB repair as a new mechanism of radioresistance and a probable determinant of mutability in lung adenocarcinoma.