bluuebunny/crossref_metadata_2025_split huggingface dataset:
Paradoxes of Intimacy: Play and the Ethics of Invisibility in North-east Brazil
Authors: SHAPIRO MATAN 
Published: June 2016

AbstractIn this article I examine ordinary ethical practices that underpin intimate relations in the Brazilian state of Maranhão. I focus ethnographically on jealousy and seduction as complementary forms of play, which simultaneously affirm and challenge such aspects of emotional relatedness as trust and love. I argue that since a measure of concealment is inherent in both these play-forms, they render invisible those actions that challenge conventional moral injunctions, such as sexual infidelity. I consequently offer an ethnographic theory of ‘invisibility’ by which opacity, uncertainty and paradox become intrinsic to the emergence of intimate relations as ethical practices in their own right.
Identification of key factors conquering developmental arrest of somatic cell cloned embryos by combining embryo biopsy and single-cell sequencing
Authors: Liu Wenqiang , Liu Xiaoyu , Wang Chenfei , Gao Yawei , Gao Rui , Kou Xiaochen , Zhao Yanhong , Li Jingyi , Wu You , Xiu Wenchao , Wang Su , Yin Jiqing , Liu Wei , Cai Tao , Wang Hong , Zhang Yong , Gao Shaorong 
Published: June 2016

AbstractDifferentiated somatic cells can be reprogrammed into totipotent embryos through somatic cell nuclear transfer. However, most cloned embryos arrest at early stages and the underlying molecular mechanism remains largely unexplored. Here, we first developed a somatic cell nuclear transfer embryo biopsy system at two- or four-cell stage, which allows us to trace the developmental fate of the biopsied embryos precisely. Then, through single-cell transcriptome sequencing of somatic cell nuclear transfer embryos with different developmental fates, we identified that inactivation of Kdm4b, a histone H3 lysine 9 trimethylation demethylase, functions as a barrier for two-cell arrest of cloned embryos. Moreover, we discovered that inactivation of another histone demethylase Kdm5b accounts for the arrest of cloned embryos at the four-cell stage through single-cell analysis. Co-injection of Kdm4b and Kdm5b can restore transcriptional profiles of somatic cell nuclear transfer embryos and greatly improve the blastocyst development (over 95%) as well as the production of cloned mice. Our study therefore provides an effective approach to identify key factors responsible for the developmental arrest of somatic cell cloned embryos.
Mitochondrial uncouplers inhibit clathrin-mediated endocytosis largely through cytoplasmic acidification
Authors: Dejonghe Wim , Kuenen Sabine , Mylle Evelien , Vasileva Mina , Keech Olivier , Viotti Corrado , Swerts Jef , Fendrych Matyáš , Ortiz-Morea Fausto Andres , Mishev Kiril , Delang Simon , Scholl Stefan , Zarza Xavier , Heilmann Mareike , Kourelis Jiorgos , Kasprowicz Jaroslaw , Nguyen Le Son Long , Drozdzecki Andrzej , Van Houtte Isabelle , Szatmári Anna-Mária , Majda Mateusz , Baisa Gary , Bednarek Sebastian York , Robert Stéphanie , Audenaert Dominique , Testerink Christa , Munnik Teun , Van Damme Daniël , Heilmann Ingo , Schumacher Karin , Winne Johan , Friml Jiří , Verstreken Patrik , Russinova Eugenia 
Published: June 2016

AbstractATP production requires the establishment of an electrochemical proton gradient across the inner mitochondrial membrane. Mitochondrial uncouplers dissipate this proton gradient and disrupt numerous cellular processes, including vesicular trafficking, mainly through energy depletion. Here we show that Endosidin9 (ES9), a novel mitochondrial uncoupler, is a potent inhibitor of clathrin-mediated endocytosis (CME) in different systems and that ES9 induces inhibition of CME not because of its effect on cellular ATP, but rather due to its protonophore activity that leads to cytoplasm acidification. We show that the known tyrosine kinase inhibitor tyrphostinA23, which is routinely used to block CME, displays similar properties, thus questioning its use as a specific inhibitor of cargo recognition by the AP-2 adaptor complex via tyrosine motif-based endocytosis signals. Furthermore, we show that cytoplasm acidification dramatically affects the dynamics and recruitment of clathrin and associated adaptors, and leads to reduction of phosphatidylinositol 4,5-biphosphate from the plasma membrane.
GPRC5A suppresses protein synthesis at the endoplasmic reticulum to prevent radiation-induced lung tumorigenesis
Authors: Wang Jian , Farris Alton B. , Xu Kaiming , Wang Ping , Zhang Xiangming , Duong Duc M. , Yi Hong , Shu Hui-Kuo , Sun Shi-Yong , Wang Ya 
Published: June 2016

AbstractGPRC5A functions as a lung tumour suppressor to prevent spontaneous and environmentally induced lung carcinogenesis; however, the underlying mechanism remains unclear. Here we reveal that GPRC5A at the endoplasmic reticulum (ER) membrane suppresses synthesis of the secreted or membrane-bound proteins including a number of oncogenes, the most important one being Egfr. The ER-located GPRC5A disturbs the assembly of the eIF4F-mediated translation initiation complex on the mRNA cap through directly binding to the eIF4F complex with its two middle extracellular loops. Particularly, suppression of EGFR by GPRC5A contributes significantly to preventing ionizing radiation (IR)-induced lung tumorigenesis. Thus, GPRC5A deletion enhances IR-promoted EGFR expression through an increased translation rate, thereby significantly increasing lung tumour incidence in Gprc5a−/− mice. Our findings indicate that under-expressed GPRC5A during lung tumorigenesis enhances any transcriptional stimulation through an active translational status, which can be used to control oncogene expression and potentially the resulting related disease.
An asymptomatic mutation complicating severe chemotherapy-induced peripheral neuropathy (CIPN): a case for personalised medicine and a zebrafish model of CIPN
Authors: Holloway Michael P , DeNardo Bradley D , Phornphutkul Chanika , Nguyen Kevin , Davis Colby , Jackson Cynthia , Richendrfer Holly , Creton Robbert , Altura Rachel A 
Published: June 2016

AbstractTargeted next-generation sequencing (NGS) identified a novel loss of function mutation in GARS, a gene linked to Charcot–Marie–Tooth disease (CMT), in a paediatric acute lymphoblastic leukaemia patient with severe chemotherapy-induced peripheral neuropathy (CIPN) due to vincristine. The patient was clinically asymptomatic, and lacked a family history of neuropathy. The effect of the mutation was modelled in a zebrafish knockdown system that recapitulated the symptoms of the patient both prior to and after treatment with vincristine. Confocal microscopy of pre- and post-synaptic markers revealed that the GARS knockdown results in changes to peripheral motor neurons, acetylcholine receptors and their co-localisation in neuromuscular junctions (NMJs), whereas a sensitive and reproducible stimulus–response assay demonstrated that the changes correlating with the GARS mutation in themselves fail to produce peripheral neuropathy symptoms. However, with vincristine treatment the GARS knockdown exacerbates decreased stimulus response and NMJ lesions. We propose that there is substantial benefit in the use of a targeted NGS screen of cancer patients who are to be treated with microtubule targeting agents for deleterious mutations in CMT linked genes, and for the screening in zebrafish of reagents that might inhibit CIPN.
Sex differences in neural and behavioral signatures of cooperation revealed by fNIRS hyperscanning
Authors: Baker Joseph M. , Liu Ning , Cui Xu , Vrticka Pascal , Saggar Manish , Hosseini S. M. Hadi , Reiss Allan L. 
Published: June 2016

AbstractResearchers from multiple fields have sought to understand how sex moderates human social behavior. While over 50 years of research has revealed differences in cooperation behavior of males and females, the underlying neural correlates of these sex differences have not been explained. A missing and fundamental element of this puzzle is an understanding of how the sex composition of an interacting dyad influences the brain and behavior during cooperation. Using fNIRS-based hyperscanning in 111 same- and mixed-sex dyads, we identified significant behavioral and neural sex-related differences in association with a computer-based cooperation task. Dyads containing at least one male demonstrated significantly higher behavioral performance than female/female dyads. Individual males and females showed significant activation in the right frontopolar and right inferior prefrontal cortices, although this activation was greater in females compared to males. Female/female dyad’s exhibited significant inter-brain coherence within the right temporal cortex, while significant coherence in male/male dyads occurred in the right inferior prefrontal cortex. Significant coherence was not observed in mixed-sex dyads. Finally, for same-sex dyads only, task-related inter-brain coherence was positively correlated with cooperation task performance. Our results highlight multiple important and previously undetected influences of sex on concurrent neural and behavioral signatures of cooperation.
DNA studies are necessary for accurate patient diagnosis in compound heterozygosity for Hb Adana (HBA2:c.179>A) with deletional or nondeletional α-thalassaemia
Authors: Tan Jin Ai Mary Anne , Kho Siew Leng , Ngim Chin Fang , Chua Kek Heng , Goh Ai Sim , Yeoh Seoh Leng , George Elizabeth 
Published: June 2016

AbstractHaemoglobin (Hb) Adana (HBA2:c.179>A) interacts with deletional and nondeletional α-thalassaemia mutations to produce HbH disorders with varying clinical manifestations from asymptomatic to severe anaemia with significant hepatosplenomegaly. Hb Adana carriers are generally asymptomatic and haemoglobin subtyping is unable to detect this highly unstable α-haemoglobin variant. This study identified 13 patients with compound heterozygosity for Hb Adana with either the 3.7 kb gene deletion (-α3.7), Hb Constant Spring (HbCS) (HBA2:c.427T>C) or Hb Paksé (HBA2:429A>T). Multiplex Amplification Refractory Mutation System was used for the detection of five deletional and six nondeletional α-thalassaemia mutations. Duplex-PCR was used to confirm Hb Paksé and HbCS. Results showed 84.6% of the Hb Adana patients were Malays. Using DNA studies, compound heterozygosity for Hb Adana and HbCS (αcodon 59α/αCSα) was confirmed in 11 patients. A novel point in this investigation was that DNA studies confirmed Hb Paksé for the first time in a Malaysian patient (αcodon 59α/αPakséα) after nine years of being misdiagnosis with Hb Adana and HbCS (αcodon 59α/αCSα). Thus, the reliance on haematology studies and Hb subtyping to detect Hb variants is inadequate in countries where thalassaemia is prevalent and caused by a wide spectrum of mutations.
Common UCP2 variants contribute to serum urate concentrations and the risk of hyperuricemia
Authors: Yang Luyu , Dong Zheng , zhou Jingru , Ma Yanyun , Pu Weilin , Zhao Dongbao , He Hongjun , Ji Hengdong , Yang Yajun , Wang Xiaofeng , Xu Xia , Pang Yafei , Zou Hejian , Jin Li , Yang Chengde , Wang Jiucun 
Published: June 2016

AbstractElevated serum urate, which is regulated at multiple levels including genetic variants, is a risk factor for gout and other metabolic diseases. This study aimed to investigate the association between UCP2 variants and serum urate as well as hyperuricemia in a Chinese population. In total, 4332 individuals were genotyped for two common UCP2 variants, −866G/A and Ala55Val. These loci were not associated either serum urate level or with a risk of hyperuricemia in the total group of subjects. However, in females, −866G/A and Ala55Val were associated with a lower serum urate (P = 0.006 and 0.014, seperately) and played a protective role against hyperuricemia (OR = 0.80, P = 0.018; OR = 0.79, P = 0.016). These associations were not observed in the males. After further stratification, the two loci were associated with serum urate in overweight, but not underweight females. The haplotype A-T (−866G/A-Ala55Val) was a protective factor for hyperuricemia in the female subgroup (OR = 0.80, P = 0.017). This present study identified a novel gene, UCP2, that influences the serum urate concentration and the risk of hyperuricemia and the degree of association varies with gender and BMI levels.
The use of the terrestrial snails of the genera Megalobulimus and Thaumastus as representatives of the atmospheric carbon reservoir
Authors: Macario Kita D. , Alves Eduardo Q. , Carvalho Carla , Oliveira Fabiana M. , Ramsey Christopher Bronk , Chivall David , Souza Rosa , Simone Luiz Ricardo L. , Cavallari Daniel C. 
Published: June 2016

AbstractIn Brazilian archaeological shellmounds, many species of land snails are found abundantly distributed throughout the occupational layers, forming a contextualized set of samples within the sites and offering a potential alternative to the use of charcoal for radiocarbon dating analyses. In order to confirm the effectiveness of this alternative, one needs to prove that the mollusk shells reflect the atmospheric carbon isotopic concentration in the same way charcoal does. In this study, 18 terrestrial mollusk shells with known collection dates from 1948 to 2004 AD, around the nuclear bombs period, were radiocarbon dated. The obtained dates fit the SH1-2 bomb curve within less than 15 years range, showing that certain species from theThaumastusandMegalobulimusgenera are reliable representatives of the atmospheric carbon isotopic ratio and can, therefore, be used to date archaeological sites in South America.
Significance of duon mutations in cancer genomes
Authors: Yadav Vinod Kumar , Smith Kyle S. , Flinders Colin , Mumenthaler Shannon M. , De Subhajyoti 
Published: June 2016

AbstractFunctional mutations in coding regions not only affect the structure and function of the protein products, but may also modulate their expression in some cases. This class of mutations, recently dubbed “duon mutations” due to their dual roles, can potentially have major impacts on downstream pathways. However their significance in diseases such as cancer remain unclear. In a survey covering 4606 samples from 19 cancer types and integrating allelic expression, overall mRNA expression, regulatory motif perturbation and chromatin signatures in one composite index called REDACT score, we identified potential duon mutations. Several such mutations are detected in known cancer genes in multiple cancer types. For instance a potential duon mutation in TP53 is associated with increased expression of the mutant allelic gene copy, thereby possibly amplifying the functional effects on the downstream pathways. Another potential duon mutation in SF3B1 is associated with abnormal splicing and changes in angiogenesis and matrix degradation related pathways. Our findings emphasize the need to interrogate the mutations in coding regions beyond their obvious effects on protein structures.
Chemical chaperones reduce ER stress and adipose tissue inflammation in high fat diet-induced mouse model of obesity
Authors: Chen Yaqin , Wu Zhihong , Zhao Shuiping , Xiang Rong 
Published: June 2016

AbstractObesity, which is characteristic by chronic inflammation, is defined as abnormal or excessive fat accumulation in adipose tissues. Endoplasmic reticulum (ER) stress is increased in adipose tissue of obese state and is known to be strongly associated with chronic inflammation. The aim of this study was to investigate the effect of ER stress on adipokine secretion in obese mice and explore the potential mechanisms. In this study, we found high-fat diet induced-obesity contributed to strengthened ER stress and triggered chronic inflammation in adipose tissue. Chemical chaperones, 4-PBA and TUDCA, modified metabolic disorders and decreased the levels of inflammatory cytokines in obese mice fed a high-fat diet. The alleviation of ER stress is in accordance with the decrease of free cholesterol in adipose tissue. Furthermore chemical chaperones suppress NF-κB activity in adipose tissue of obese mice in vivo. In vitro studies showed IKK/NF-κB may be involved in the signal transduction of adipokine secretion dysfunction induced by ER stress. The present study revealed the possibility that inhibition of ER stress may be a novel drug target for metabolic abnormalities associated with obesity. Further studies are now needed to characterize the initial incentive of sustained ER stress in obese.
Structural and biochemical characterization of the cell fate determining nucleotidyltransferase fold protein MAB21L1
Authors: de Oliveira Mann Carina C. , Kiefersauer Reiner , Witte Gregor , Hopfner Karl-Peter 
Published: June 2016

AbstractThe exceptionally conserved metazoan MAB21 proteins are implicated in cell fate decisions and share considerable sequence homology with the cyclic GMP-AMP synthase. cGAS is the major innate immune sensor for cytosolic DNA and produces the second messenger 2′-5′, 3′-5′ cyclic GMP-AMP. Little is known about the structure and biochemical function of other proteins of the cGAS-MAB21 subfamily, such as MAB21L1, MAB21L2 and MAB21L3. We have determined the crystal structure of human full-length MAB21L1. Our analysis reveals high structural conservation between MAB21L1 and cGAS but also uncovers important differences. Although monomeric in solution, MAB21L1 forms a highly symmetric double-pentameric oligomer in the crystal, raising the possibility that oligomerization could be a feature of MAB21L1. In the crystal, MAB21L1 is in an inactive conformation requiring a conformational change - similar to cGAS - to develop any nucleotidyltransferase activity. Co-crystallization with NTP identified a putative ligand binding site of MAB21 proteins that corresponds to the DNA binding site of cGAS. Finally, we offer a structure-based explanation for the effects of MAB21L2 mutations in patients with eye malformations. The underlying residues participate in fold-stabilizing interaction networks and mutations destabilize the protein. In summary, we provide a first structural framework for MAB21 proteins.
Antithrombin controls tumor migration, invasion and angiogenesis by inhibition of enteropeptidase
Authors: Luengo-Gil Ginés , Calvo María Inmaculada , Martín-Villar Ester , Águila Sonia , Bohdan Nataliya , Antón Ana I. , Espín Salvador , Ayala de la Peña Francisco , Vicente Vicente , Corral Javier , Quintanilla Miguel , Martínez-Martínez Irene 
Published: June 2016

AbstractAntithrombin is a key inhibitor of the coagulation cascade, but it may also function as an anti-inflammatory, anti-angiogenic, anti-viral and anti-apoptotic protein. Here, we report a novel function of antithrombin as a modulator of tumor cell migration and invasion. Antithrombin inhibited enteropeptidase on the membrane surface of HT-29, A549 and U-87 MG cells. The inhibitory process required the activation of antithrombin by heparin, and the reactive center loop and the heparin binding domain were essential. Surprisingly, antithrombin non-covalently inhibited enteropeptidase, revealing a novel mechanism of inhibition for this serpin. Moreover, as a consequence of this inhibition, antithrombin was cleaved, resulting in a molecule with anti-angiogenic properties that reduced vessel-like formation of endothelial cells. The addition of antithrombin and heparin to U-87 MG and A549 cells reduced motility in wound healing assays, inhibited the invasion in transwell assays and the degradation of a gelatin matrix mediated by invadopodia. These processes were controlled by enteropeptidase, as demonstrated by RNA interference experiments. Carcinoma cell xenografts in nude mice showed in vivo co-localization of enteropeptidase and antithrombin. Finally, treatment with heparin reduced experimental metastasis induced by HT29 cells in vivo. In conclusion, the inhibition of enteropeptidase by antithrombin may have a double anti-tumor effect through inhibiting a protease involved in metastasis and generating an anti-angiogenic molecule.
Hot carrier multiplication on graphene/TiO2 Schottky nanodiodes
Authors: Lee Young Keun , Choi Hongkyw , Lee Hyunsoo , Lee Changhwan , Choi Jin Sik , Choi Choon-Gi , Hwang Euyheon , Park Jeong Young 
Published: June 2016

AbstractCarrier multiplication (i.e. generation of multiple electron–hole pairs from a single high-energy electron, CM) in graphene has been extensively studied both theoretically and experimentally, but direct application of hot carrier multiplication in graphene has not been reported. Here, taking advantage of efficient CM in graphene, we fabricated graphene/TiO2 Schottky nanodiodes and found CM-driven enhancement of quantum efficiency. The unusual photocurrent behavior was observed and directly compared with Fowler’s law for photoemission on metals. The Fowler’s law exponent for the graphene-based nanodiode is almost twice that of a thin gold film based diode; the graphene-based nanodiode also has a weak dependence on light intensity—both are significant evidence for CM in graphene. Furthermore, doping in graphene significantly modifies the quantum efficiency by changing the Schottky barrier. The CM phenomenon observed on the graphene/TiO2 nanodiodes can lead to intriguing applications of viable graphene-based light harvesting.
Posttraumatic Stress Disorder after Vaginal Delivery at Primiparous Women
Authors: Milosavljevic Maja , Lecic Tosevski Dusica , Soldatovic Ivan , Vukovic Olivera , Miljevic Cedo , Peljto Amir , Kostic Milutin , Olff Miranda 
Published: June 2016

AbstractAlthough severe gynaecological pathology during delivery and negative outcome have been shown to be related with posttraumatic stress disorder (PTSD) little is known about traumatic experiences following regular delivery, at the expected time and with a healthy child. The objective of our study was to determine the prevalence of PTSD during postpartum period after vaginal delivery and its risk factors. The sample included 126 primiparous women. Monthly, for the next three months, the women were assessed for PTSD using the gold standard interview for PTSD, Clinician-Administered PTSD Scale (CAPS). Risk factors were assessed including sociodemographic variables, personal medical history and clinical variables. After the first month, 2.4% women had acute full PTSD and another 9.5% had clinically significant level of PTSD symptoms. Following the second and the third month, partial PTSD was found in 5.9% and 1.3% of the women, respectively, and none of participants had full PTSD. Obstetrical interventions were the only significant risk factor for the development of PTSD. Symptoms of postpartum PTSD are not rare after a traumatic delivery, and associated with specific obstetrical risk factors. Awareness of these risk factors may stimulate interventions to prevent this important and neglected postpartum disorder.