bluuebunny/crossref_metadata_2025_split huggingface dataset:
Surgical management of post-infarction ventricular septal defect, mitral regurgitation and ventricular aneurysm
Authors: Belete Samuel , Punjabi Karan , Afoke Jonathan , Anderson Jonathan 
Published: August 2019

ABSTRACT
A 49-year-old diabetic male was admitted to a hospital in 2018 following a 3-week history of worsening dyspnoea and pedal oedema. Early review and investigations indicated acute heart failure. Transthoracic echocardiogram (TTE) revealed mitral regurgitation (MR), aneurysmal change of the ventricles, a ventricular septal defect (VSD) and systolic dysfunction. Coronary angiogram demonstrated a significant left anterior descending and right coronary artery disease. He was diagnosed with a late presenting myocardial infarction (MI) with secondary mechanical complications. Mechanical complications of MI frequently require surgical intervention. The patient underwent a repair of VSD, mitral valve repair, excision of aneurysmal segment and coronary artery bypass grafting. Post-operative recovery was complicated by a sternal wound infection managed in conjunction with the plastic surgeons. A post-operative TTE showed a repaired ventricular septum and no residual MR. Early recognition and appropriate medical optimisation are required to achieve good patient outcomes.
The Human Right to Gender Identity: From the International Human Rights Scenario to Latin American Domestic Legislation
Authors: Arrubia Eduardo J 
Published: August 2019

Abstract
Transgender persons usually undergo significant discrimination all over the world. This is the reason why gender identity has been translated into the language of International Human Rights Law. Thus, the European Court of Human Rights has evolved along the last decades towards the recognition of this human right, and so has the Inter-American Court by releasing its recent advisory opinion on gender identity, equality and non-discrimination of same sex couples. Within this framework, some Latin American countries have passed regulations entitling trans persons to have their public records as regards their name, sex marker and image data modified. Nevertheless, these juridical norms of domestic law might not entirely comply with the standards that have been set by the Inter-American Court of Human Rights since they tend to reproduce cultural patterns of gender which lead to a pathological comprehension of transgenderism. In this analysis, Argentinian legislative experience is accounted for as a cutting-edge exemption in this matter.
Environmental effects on halo abundance and weak lensing peak statistics towards large underdense regions
Authors: Higuchi Yuichi , Inoue Kaiki Taro 
Published: August 2019

ABSTRACT
The cosmic microwave background (CMB) contains an anomalous cold spot with a surrounding hot ring, known as the Cold Spot. Inoue & Silk proposed that this feature could be explained by postulating a supervoid: if such a large underdense region exists, then the growth of matter perturbing around the spot might differ from the average value in the Universe and the differences might affect weak lensing analysis of peak statistics. To investigate environmental effects on halo number count and peak statistics, we used a publicly available ray-tracing simulation for a box size of 2250 h−1 Mpc on a side. We found that the number count for massive haloes towards the largest underdense region in the simulation decreases and the corresponding significance of the difference, based on a cosmic average, is ≥3σ. On the basis of the results of peak statistics analysis, the number of high peaks decreases with the decrement of massive haloes, but the number of low peaks increases with the lack of matter in the line of sight. The highest significance of the decrement in peak counts in large underdense regions is 5σ in the total signal-to-noise ratio. Our result implies that environmental effects on halo abundance and weak lensing peak statistic can be used to probe the presence and properties of supervoids.
Structure of the primed state of the ATPase domain of chromatin remodeling factor ISWI bound to the nucleosome
Authors: Chittori Sagar , Hong Jingjun , Bai Yawen , Subramaniam Sriram 
Published: August 2019

Abstract
ATP-dependent chromatin remodeling factors of SWI/SNF2 family including ISWI, SNF2, CHD1 and INO80 subfamilies share a conserved but functionally non-interchangeable ATPase domain. Here we report cryo-electron microscopy (cryo-EM) structures of the nucleosome bound to an ISWI fragment with deletion of the AutoN and HSS regions in nucleotide-free conditions and the free nucleosome at ∼ 4 Å resolution. In the bound conformation, the ATPase domain interacts with the super helical location 2 (SHL 2) of the nucleosomal DNA, with the N-terminal tail of H4 and with the α1 helix of H3. Density for other regions of ISWI is not observed, presumably due to disorder. Comparison with the structure of the free nucleosome reveals that although the histone core remains largely unchanged, remodeler binding causes perturbations in the nucleosomal DNA resulting in a bulge near the SHL2 site. Overall, the structure of the nucleotide-free ISWI-nucleosome complex is similar to the corresponding regions of the recently reported ADP bound ISWI-nucleosome structures, which are significantly different from that observed for the ADP-BeFx bound structure. Our findings are relevant to the initial step of ISWI binding to the nucleosome and provide additional insights into the nucleosome remodeling process driven by ISWI.
AT-dinucleotide rich sequences drive fragile site formation
Authors: Irony-Tur Sinai Michal , Salamon Anita , Stanleigh Noemie , Goldberg Tchelet , Weiss Aryeh , Wang Yuh-Hwa , Kerem Batsheva 
Published: August 2019

Abstract
Common fragile sites (CFSs) are genomic regions prone to breakage under replication stress conditions recurrently rearranged in cancer. Many CFSs are enriched with AT-dinucleotide rich sequences (AT-DRSs) which have the potential to form stable secondary structures upon unwinding the double helix during DNA replication. These stable structures can potentially perturb DNA replication progression, leading to genomic instability. Using site-specific targeting system, we show that targeted integration of a 3.4 kb AT-DRS derived from the human CFS FRA16C into a chromosomally stable region within the human genome is able to drive fragile site formation under conditions of replication stress. Analysis of >1300 X chromosomes integrated with the 3.4 kb AT-DRS revealed recurrent gaps and breaks at the integration site. DNA sequences derived from the integrated AT-DRS showed in vitro a significantly increased tendency to fold into branched secondary structures, supporting the predicted mechanism of instability. Our findings clearly indicate that intrinsic DNA features, such as complexed repeated sequence motifs, predispose the human genome to chromosomal instability.
Antagonistic and synergistic epigenetic modulation using orthologous CRISPR/dCas9-based modular system
Authors: Josipović Goran , Tadić Vanja , Klasić Marija , Zanki Vladimir , Bečeheli Ivona , Chung Felicia , Ghantous Akram , Keser Toma , Madunić Josip , Bošković Maria , Lauc Gordan , Herceg Zdenko , Vojta Aleksandar , Zoldoš Vlatka 
Published: August 2019

Abstract
Establishing causal relationship between epigenetic marks and gene transcription requires molecular tools, which can precisely modify specific genomic regions. Here, we present a modular and extensible CRISPR/dCas9-based toolbox for epigenetic editing and direct gene regulation. It features a system for expression of orthogonal dCas9 proteins fused to various effector domains and includes a multi-gRNA system for simultaneous targeting dCas9 orthologs to up to six loci. The C- and N-terminal dCas9 fusions with DNMT3A and TET1 catalytic domains were thoroughly characterized. We demonstrated simultaneous use of the DNMT3A-dSpCas9 and TET1-dSaCas9 fusions within the same cells and showed that imposed cytosine hyper- and hypo-methylation altered level of gene transcription if targeted CpG sites were functionally relevant. Dual epigenetic manipulation of the HNF1A and MGAT3 genes, involved in protein N-glycosylation, resulted in change of the glycan phenotype in BG1 cells. Furthermore, simultaneous targeting of the TET1-dSaCas9 and VPR-dSpCas9 fusions to the HNF1A regulatory region revealed strong and persistent synergistic effect on gene transcription, up to 30 days following cell transfection, suggesting involvement of epigenetic mechanisms in maintenance of the reactivated state. Also, modulation of dCas9 expression effectively reduced off-target effects while maintaining the desired effects on target regions.
Discrimination as an Individual Wrong
Authors: Foran Michael P 
Published: August 2019

Abstract
This article argues that anti-discrimination rights are individual rights to be free from wrongful treatment and do not directly advance group-based interests or prohibit group-based harm. In light of this, a number of recurring accounts of the wrong of discrimination, particularly the wrong of indirect discrimination, are unsustainable. Claims that indirect discrimination is concerned with harm that is done to social groups or that laws prohibiting indirect discrimination seek to reduce or eliminate advantage gaps between social groups must be rejected as inaccurate. While principles of non-discrimination and principles of affirmative action often operate harmoniously to foster respect for the moral equality of persons, they each have a general affinity with distinct ethical traditions: deontology and teleology respectively. As such, we should conclude that indirect discrimination provisions are examples of formal and not substantive equality. Where rights to non-discrimination conflict with telic equality goals, UK law protects the rights of the individual.
Biotic response to the environmental and climatic variability in a deep alpine lake (Lake Lugu) over the last 30 000 years in southwest China
Authors: Wang Qian , Hamilton Paul B , Kattel Giri , Kong Lingyang 
Published: August 2019

Abstract
Multiple biogeochemical variables in a sediment core from Lake Lugu in southwest China were studied to investigate the effects of regional environmental changes on the ecosystem. Subfossil Cladocera, together with diatom, pollen and geochemical records, were used to examine climate-induced changes in lake ecosystem since the Last Glacial Maximum (30 000–0 cal year BP). Consistency among these biological records indicates that the succession of zooplankton, algae and vegetation changed in response to direct and indirect climatic factors. Alterations in the nutrient supply mediated by climate-induced changes in vegetation and soil processes are likely responsible for the variability of cladocerans. During the Last Glacial Maximum, cladocerans were dominated by littoral taxa (e.g. Alona), indicating an unproductive and oligotrophic lake system. A peak distribution in the pelagic Bosmina highlights the period of increased nutrient availability at 11 500 cal year BP. The ecological changes in Cladocera at 19 000 cal year BP and diatom communities at 18 000 cal year BP reveal independent and indirect responses to nutrient and light conditions induced by solar radiation and increased monsoon intensity across the study region. The palaeoecological archives from Lake Lugu sediments highlight a complex lake ecosystem influenced by both direct and indirect changes corresponding to climate changes and shifts in regional anthropogenic pressure over the last 30 000 years.
Secretory anti-citrullinated protein antibodies in serum associate with lung involvement in early rheumatoid arthritis
Authors: Roos Ljungberg Karin , Joshua Vijay , Skogh Thomas , Eklund Anders , Sköld C. Magnus , Karimi Reza , Nyrén Sven , Svärd Anna , Catrina Anca I , Kastbom Alf 
Published: August 2019

AbstractObjectiveA ‘mucosal connection’ in RA presently attracts increasing attention. We recently described the occurrence of secretory antibodies to citrullinated protein (SC-ACPA) in sera from patients with recent-onset RA. The current study was performed to evaluate possible associations between serum levels of secretory ACPA and signs of lung involvement in patients with early, untreated RA.MethodsOne hundred and forty-two RA patients were included as part of the ‘LUng Investigation in newly diagnosed RA’ study. One hundred and six patients were examined with high-resolution CT (HRCT) and 20 patients underwent bronchoscopy, where bronchial biopsies and bronchoalveolar lavage fluid (BALF) samples were obtained. SC-ACPA in serum and BALF were detected by an enzyme-linked immunoassay. Antibody levels were related to smoking history, pulmonary function, HRCT, BALF cell counts and findings in bronchial biopsies.ResultsSC-ACPA occurred in 16% of the serum samples and in 35% of the BALF samples. SC-ACPA levels in serum correlated with SC-ACPA levels in BALF (σ = 0.50, P = 0.027) and were higher among patients with HRCT parenchymal lung abnormalities (P = 0.022) or bronchiectasis (P = 0.042). Also, ever smoking was more frequent among serum SC-ACPA-positive patients (91% vs 67%, P = 0.023), and the SC-ACPA levels correlated with the number of pack-years (σ=0.20, P = 0.020).ConclusionIn early, untreated RA, serum levels of SC-ACPA reflect lung involvement in terms of local ACPA levels, smoking and lung abnormalities on HRCT. These findings strengthen the link between mucosal ACPA responses and the lungs in RA.
Characterization of Estrogenic and Androgenic Activities for Bisphenol A-like Chemicals (BPs): In Vitro Estrogen and Androgen Receptors Transcriptional Activation, Gene Regulation, and Binding Profiles
Authors: Pelch Katherine E , Li Yin , Perera Lalith , Thayer Kristina A , Korach Kenneth S 
Published: August 2019

Abstract
Bisphenol A (BPA) is a high production volume chemical widely used in plastics, food packaging, and many other products. It is well known that endocrine-disrupting chemicals might be harmful to human health due to interference with normal hormone actions. Recent studies report widespread usage and exposure to many BPA-like chemicals (BPs) that are structurally or functionally similar to BPA. However, the biological actions and toxicity of those BPs are still relatively unknown. To address this data gap, we used in vitro cell models to evaluate the ability of 22 BPs to induce or inhibit estrogenic and androgenic activity. BPA, Bisphenol AF (BPAF), bisphenol Z (BPZ), bisphenol C (BPC), tetramethyl bisphenol A (TMBPA), bisphenol S (BPS), bisphenol E (BPE), 4,4-bisphenol F (4,4-BPF), bisphenol AP (BPAP), bisphenol B (BPB), tetrachlorobisphenol A (TCBPA), and benzylparaben (PHBB) induced estrogen receptor (ER)α and/or ERβ-mediated activity. With the exception of BPS, TCBPA, and PHBB, these same BPs were also androgen receptor (AR) antagonists. Only 3 BPs were found to be ER antagonists. Bisphenol P (BPP) selectively inhibited ERβ-mediated activity and 4-(4-phenylmethoxyphenyl)sulfonylphenol (BPS-MPE) and 2,4-bisphenol S (2,4-BPS) selectively inhibited ERα-mediated activity. None of the BPs induced AR-mediated activity. In addition, we identify that the BPs can bind to ER or AR with varying degrees by a molecular modeling analysis. Taken together, these findings help us to understand the molecular mechanism of BPs and further consideration of their usage in consumer products.
Reversibility of Neuroimaging Markers Influenced by Lifetime Occupational Manganese Exposure
Authors: Edmondson David A , Ma Ruoyun E , Yeh Chien-Lin , Ward Eric , Snyder Sandy , Azizi Elham , Zauber S Elizabeth , Wells Ellen M , Dydak Ulrike 
Published: August 2019

Abstract
Manganese (Mn) is a neurotoxicant that many workers are exposed to daily. There is limited knowledge about how changes in exposure levels impact measures in magnetic resonance imaging (MRI). We hypothesized that changes in Mn exposure would be reflected by changes in the MRI relaxation rate R1 and thalamic γ-aminobutyric acid (GABAThal). As part of a prospective cohort study, 17 welders were recruited and imaged on 2 separate occasions approximately 2 years apart. MRI relaxometry was used to assess changes of Mn accumulation in the brain. Additionally, GABA was measured using magnetic resonance spectroscopy in the thalamic and striatal regions of the brain. Air Mn exposure ([Mn]Air) and cumulative exposure indexes of Mn (Mn-CEI) for the past 3 months (Mn-CEI3M), past year (Mn-CEI12M), and lifetime (Mn-CEILife) were calculated using personal air sampling and a comprehensive work history, whereas toenails were collected for analysis of internal Mn body burden. Finally, welders’ motor function was examined using the Unified Parkinson’s Disease Rating Scale (UPDRS). Median exposure decreased for all exposure measures between the first and second scan. ΔGABAThal was significantly correlated with ΔMn-CEI3M (ρ = 0.66, adjusted p = .02), ΔMn-CEI12M (ρ = 0.70, adjusted p = .006), and Δ[Mn]Air (ρ = 0.77, adjusted p = .002). ΔGABAThal significantly decreased linearly with ΔMn-CEI3M (quantile regression, β = 15.22, p = .02) as well as Δ[Mn]Air (β = 1.27, p = .04). Finally, Mn-CEILife interacted with Δ[Mn]Air in the substantia nigra where higher Mn-CEILife lessened the ΔR1 per Δ[Mn]Air (F-test, p = .005). Although R1 and GABA changed with Mn exposure, UPDRS was unaffected. In conclusion, our study shows that effects from changes in Mn exposure are reflected in thalamic GABA levels and brain Mn levels, as measured by R1, in most brain regions.
Allometric growth in meiofaunal invertebrates: do all kinorhynchs show homogeneous trends?
Authors: Cepeda Diego , Álamo David , Sánchez Nuria , Pardos Fernando 
Published: August 2019

AbstractAllometry determines relevant modifications in metazoan morphology and biology and is affected by many different factors, such as ontogenetic constraints and natural selection. A linear mixed model approach and reduced major axis regression were used to explore evolutionary interspecific allometric trends between the total trunk length and the lengths of the segments and spines in the phylum Kinorhyncha at three taxonomic levels: the whole phylum, the class and the family. Statistically significant results were found in all the trunk segments, meaning that these body units grow proportionally correlated with the body, contrary to the results obtained for the spines. Developmental and morphophysiological constraints could lead to negative allometry in the first and last segments, because these body regions in kinorhynchs are essential to the implementation of some of the main biological functions, such as feeding and locomotion. The differential arrangement of cuticular appendages between the taxonomic groups considered seems to cause different evolutionary trends, because positive allometry may appear if a segment requires more space to accommodate a large number of organs and appendages, and vice versa. The presence of sexual dimorphism could also define positive allometry of a segment, owing to the need to harbour the sexually dimorphic appendages and their associated structures.
Citrullination of pyruvate kinase by PADI1 and PADI3 regulates glycolysis and cancer cell proliferation
Authors: Coassolo Sebastien , Davidson Guillaume , Negroni Luc , Gambi Giovanni , Daujat Sylvain , Romier Christophe , Davidson Irwin 
Published: August 2019

AbstractCHD3 and CHD4 are mutually exclusive ATPase subunits of the Nucleosome Remodelling and Deacetylation (NuRD) complex that regulates gene expression. CHD4 is essential for growth of multiple patient derived melanoma xenografts and for breast cancer. Here we show that CHD4 regulates expression of PADI1 (Protein Arginine Deiminase 1) and PADI3 in multiple cancer cell types modulating citrullination of three arginines of the allosterically-regulated glycolytic enzyme pyruvate kinase M2 (PKM2). Citrullination reprograms cross-talk between PKM2 ligands lowering its sensitivity to the inhibitors Tryptophan, Alanine and Phenylalanine and promoting activation by Serine. Citrullination thus bypasses normal physiological regulation by low Serine levels to promote excessive glycolysis defining a novel pathway regulating proliferation of melanoma and other cancer cells. We provide unique insight as to how conversion of arginines to citrulline impacts key interactions within PKM2 that act in concert to reprogram its activity as an additional mechanism regulating this important enzyme.
Sex differences in seizure at presentation in glioma population
Authors: Ranjbar Sara , Anderies Barrett J , Singleton Kyle W , Johnston Sandra K , Rickertsen Cassandra R , Sharma Akanshka , Porter Alyx B , Mrugala Maciej M , Hu Leland S , Mitchell J Ross , Rubin Joshua B , Swanson Kristin R 
Published: August 2019

AbstractSeizures are common presenting symptoms of primary brain tumors. Mechanisms of epileptogenesis are still unknown and are believed to be multifactorial. Previous studies have indicated correlation of seizure with tumor location. Recent investigations of our group have shown image-based parameters have sex-specific implications for patient outcome. In this retrospective study, we examined the association of tumor location with the probability and risk of seizure in male and female glioma patients.
Multimerization of Zika Virus-NS5 causes a ciliopathy and forces premature neurogenesis
Authors: Saade Murielle , Ferrero Diego S , Blanco-Ameijeiras José , Gonzalez-Gobartt Elena , Ruiz-Arroyo Victor M , Martínez-Sáez Elena , Cajal Santiago Ramón y , Verdaguer Nuria , Martí Elisa 
Published: August 2019

AbstractZika virus (ZikV) is a flavivirus that infects neural tissues, causing congenital microcephaly. ZikV has evolved multiple mechanisms to restrict proliferation and enhance cell death, although the underlying cellular events involved remain unclear. Here we show that the ZikV-NS5 protein interacts with host proteins at the base of the primary cilia in neural progenitor cells, causing an atypical non-genetic ciliopathy and premature neuron delamination. Furthermore, in human microcephalic fetal brain tissue, ZikV-NS5 persists at the base of the motile cilia in ependymal cells, which also exhibit a severe ciliopathy. While the enzymatic activity of ZikV-NS5 appears to be dispensable, the Y25, K28 and K29 residues in the protein, that are involved in NS5-oligomerization, are essential for the localization and interaction with components of the cilium base, promoting ciliopathy and premature neurogenesis. These findings lay the foundation to develop therapies that target ZikV-NS5-multimerization, preventing the developmental malformations associated with congenital Zika syndrome