bluuebunny/crossref_metadata_2025_split huggingface dataset:
Detection and removal of barcode swapping in single-cell RNA-seq data
Authors: Griffiths Jonathan A. , Richard Arianne C. , Bach Karsten , Lun Aaron T. L. , Marioni John C. 
Published: July 2018

AbstractBarcode swapping results in the mislabelling of sequencing reads between multiplexed samples on patterned flow-cell Illumina sequencing machines. This may compromise the validity of numerous genomic assays; however, the severity and consequences of barcode swapping remain poorly understood. We have used two statistical approaches to robustly quantify the fraction of swapped reads in two plate-based single-cell RNA-sequencing datasets. We found that approximately 2.5% of reads were mislabelled between samples on the HiSeq 4000, which is lower than previous reports. We observed no correlation between the swapped fraction of reads and the concentration of free barcode across plates. Furthermore, we have demonstrated that barcode swapping may generate complex but artefactual cell libraries in droplet-based single-cell RNA-sequencing studies. To eliminate these artefacts, we have developed an algorithm to exclude individual molecules that have swapped between samples in 10x Genomics experiments, allowing the continued use of cutting-edge sequencing machines for these assays.
A small-molecule inhibitor of SOD1-Derlin-1 interaction ameliorates pathology in an ALS mouse model
Authors: Tsuburaya Naomi , Homma Kengo , Higuchi Tsunehiko , Balia Andrii , Yamakoshi Hiroyuki , Shibata Norio , Nakamura Seiichi , Nakagawa Hidehiko , Ikeda Shin-ichi , Umezawa Naoki , Kato Nobuki , Yokoshima Satoshi , Shibuya Masatoshi , Shimonishi Manabu , Kojima Hirotatsu , Okabe Takayoshi , Nagano Tetsuo , Naguro Isao , Imamura Keiko , Inoue Haruhisa , Fujisawa Takao , Ichijo Hidenori 
Published: July 2018

AbstractAmyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disorder. Despite its severity, there are no effective treatments because of the complexity of its pathogenesis. As one of the underlying mechanisms of Cu, Zn superoxide dismutase (SOD1) gene mutation-induced ALS, SOD1 mutants (SOD1mut) commonly interact with an endoplasmic reticulum-resident membrane protein Derlin-1, triggering motoneuron death. However, the importance of SOD1-Derlin-1 interaction in in vitro human model and in vivo mouse model remains to be elucidated. Here, we identify small-molecular-weight compounds that inhibit the SOD1-Derlin-1 interaction by screening approximately 160,000 compounds. The inhibitor prevents 122 types of SOD1mut from interacting with Derlin-1, and significantly ameliorates the ALS pathology both in motoneurons derived from patient induced pluripotent stem cells and in model mice. Our data suggest that the SOD1-Derlin-1 interaction contributes to the pathogenesis of ALS and is a promising drug target for ALS treatment.
Positive and negative regulation of carbon nanotube catalysts through encapsulation within macrocycles
Authors: Blanco Matías , Nieto-Ortega Belén , de Juan Alberto , Vera-Hidalgo Mariano , López-Moreno Alejandro , Casado Santiago , González Luisa R. , Sawada Hidetaka , González-Calbet José M. , Pérez Emilio M. 
Published: July 2018

AbstractOne of the most attractive applications of carbon nanomaterials is as catalysts, due to their extreme surface-to-volume ratio. The substitution of C with heteroatoms (typically B and N as p- and n-dopants) has been explored to enhance their catalytic activity. Here we show that encapsulation within weakly doping macrocycles can be used to modify the catalytic properties of the nanotubes towards the reduction of nitroarenes, either enhancing it (n-doping) or slowing it down (p-doping). This artificial regulation strategy presents a unique combination of features found in the natural regulation of enzymes: binding of the effectors (the macrocycles) is noncovalent, yet stable thanks to the mechanical link, and their effect is remote, but not allosteric, since it does not affect the structure of the active site. By careful design of the macrocycles’ structure, we expect that this strategy will contribute to overcome the major hurdles in SWNT-based catalysts: activity, aggregation, and specificity.
The TLR-4 agonist adjuvant, GLA-SE, improves magnitude and quality of immune responses elicited by the ID93 tuberculosis vaccine: first-in-human trial
Authors: Coler Rhea N. , Day Tracey A. , Ellis Ruth , Piazza Franco M. , Beckmann Anna Marie , Vergara Julie , Rolf Tom , Lu Lenette , Alter Galit , Hokey David , Jayashankar Lakshmi , Walker Robert , Snowden Margaret Ann , Evans Tom , Ginsberg Ann , Reed Steven G. ,   The TBVPX-113 Study Team, Ashman Jill , Sagawa Zachary K. , Tait D. , Ishmukhamedov Sadritdin , Blatner Gretta , Sutton Sharon , Shepherd Barbara , Johnson Casey 
Published: July 2018

AbstractTuberculosis (TB) is the leading cause of infectious death worldwide. Development of improved TB vaccines that boost or replace BCG is a major global health goal. ID93 + GLA-SE is a fusion protein TB vaccine candidate combined with the Toll-like Receptor 4 agonist adjuvant, GLA-SE. We conducted a phase 1, randomized, double-blind, dose-escalation clinical trial to evaluate two dose levels of the ID93 antigen, administered intramuscularly alone or in combination with two dose levels of the GLA-SE adjuvant, in 60 BCG-naive, QuantiFERON-negative, healthy adults in the US (ClinicalTrials.gov identifier: NCT01599897). When administered as 3 injections, 28 days apart, all dose levels of ID93 alone and ID93 + GLA-SE demonstrated an acceptable safety profile. All regimens elicited vaccine-specific humoral and cellular responses. Compared with ID93 alone, vaccination with ID93 + GLA-SE elicited higher titers of ID93-specific antibodies, a preferential increase in IgG1 and IgG3 subclasses, and a multifaceted Fc-mediated effector function response. The addition of GLA-SE also enhanced the magnitude and polyfunctional cytokine profile of CD4+ T cells. The data demonstrate an acceptable safety profile and indicate that the GLA-SE adjuvant drives a functional humoral and T-helper 1 type cellular response.
Tumor size classification of the 8th edition of TNM staging system is superior to that of the 7th edition in predicting the survival outcome of pancreatic cancer patients after radical resection and adjuvant chemotherapy
Authors: Cong Lin , Liu Qiaofei , Zhang Ronghua , Cui Ming , Zhang Xiang , Gao Xiang , Guo Junchao , Dai Menghua , Zhang Taiping , Liao Quan , Zhao Yupei 
Published: July 2018

AbstractThe 8th edition of TNM staging system has been released and it incorporates many changes to the T and N classifications for pancreatic cancer. Comparative study between the 7th and 8th edition of TNM staging system from Asian population has not been reported yet. This study aimed to compare the 7th and 8th edition of staging system for pancreatic cancer by using a cohort of pancreatic cancer patients from China after R0 pancreaticoduodenectomy and adjuvant chemotherapy. The results showed according to the pT classification of 7th edition, pT3 was predominant (87.25%), however, the new edition led to a more equal distribution of pT classification. pT1, pT2 and pT3 was 27.45%, 56.86% and 15.69%, respectively. According to the new pN classification, 18.63% of the patients were pN2. The pT classification in the 8th edition was significantly superior to that in the 7th edition at stratifying patients by overall survival. The pN classification in the 8th edition failed to show an advantage over the 7th edition in stratifying patients by overall survival. Therefore, the new pT classification, but not the new pN classification, showed a significant advantage over the previous edition at predicting the overall survival of pancreatic cancer patients.
Chimpanzees overcome the tragedy of the commons with dominance
Authors: Koomen Rebecca , Herrmann Esther 
Published: July 2018

AbstractCompetition over common-pool resources (CPR) is a ubiquitous challenge for social animals. Many species face similar dilemmas, yet our understanding of the evolutionary trajectory of CPR social strategies remains unexplored. Here, we provide a first look at the social strategies of our closest living relatives, chimpanzees (Pan troglodytes), in two novel resource dilemma experiments. Dyads of chimpanzees were presented with renewable resource systems, collapsible at a quantity-dependent threshold. Dyads had to continuously resist overconsumption to maximize collective gains. In study 1, dyads of chimpanzees sustained a renewing juice source. Inequality of juice acquisition between partners predicted sustaining success, indicating that one individual dominated the task while the partner inhibited. Dyads in study 2 fed together on accumulating carrot pieces but could end the accumulation any time by grabbing an immediate selfish source of carrots. Dyads with low tolerance were more successful at collectively sustaining the resource than highly tolerant dyads. Further, the dominant individual was more likely to cause collapse in dyads with low tolerance than dyads with high tolerance. These results indicate that chimpanzees use a dominance-based monopolisation strategy moderated by social tolerance to overcome the tragedy of the commons.
HIF-1α regulates COXIV subunits, a potential mechanism of self-protective response to microwave induced mitochondrial damages in neurons
Authors: Hao Yan-Hui , Zhang Jing , Wang Hui , Wang Hao-Yu , Dong Ji , Xu Xin-Ping , Yao Bin-Wei , Wang Li-Feng , Zhou Hong-Mei , Zhao Li , Peng Rui-Yun 
Published: July 2018

AbstractAnxiety and speculation about potential health hazards of microwaves exposure are spreading in the past decades. Hypoxia-inducible factor-1α (HIF-1α), which can be activated by reactive oxygen species (ROS), played pivotal roles in protective responses against microwave in neuron-like cells. In this study, we established 30 mW/cm2 microwave exposed animal model, which could result in revisable injuries of neuronal mitochondria, including ultrastructure and functions, such as ROS generation and cytochrome c oxidase (COX) activity. We found that the ratio of COXIV-1/COXIV-2, two isoforms of COXIV, decreased at 1 d and increased from 3 d to 14 d. Similar expression changes of HIF-1α suggested that COXIV-1 and COXIV-2 might be regulated by HIF-1α. In neuron-like cells, 30 mW/cm2 microwave down-regulated COX activity from 30 min to 6 h, and then started to recover. And, both HIF-1α transcriptional activity and COXIV-1/COXIV-2 ratio were up-regulated at 6 h and 9 h after exposure. Moreover, HIF-1α inhibition down-regulated COXIV-1 expression, promoted ROS generation, impaired mitochondrial membrane potentials (MMP), as well as abolished microwave induced ATP production. In conclusion, microwave induced mitochondrial ROS production activated HIF-1α and regulated COXIV-1 expression to restore mitochondria functions. Therefore, HIF-1α might be a potential target to impair microwave induced injuries.
Efficient targeted integration into the bovine Rosa26 locus using TALENs
Authors: Wang Ming , Sun Zhaolin , Zou Zhiyuan , Ding Fangrong , Li Ling , Wang Haiping , Zhao Chunjiang , Li Ning , Dai Yunping 
Published: July 2018

AbstractThe genetic modification of cattle has many agricultural and biomedical applications. However, random integration often results in the unstable expression of transgenes and unpredictable phenotypes. Targeting genes to the “safe locus” and stably expressing foreign genes at a high level are desirable methods for overcoming these hurdles. The Rosa26 locus has been widely used to produce genetically modified animals in some species expressing transgenes at high and consistent levels. For the first time, we identified a bovine orthologue of the mouse Rosa26 locus through a genomic sequence homology analysis. According to 5′ rapid-amplification of cDNA ends (5′RACE), 3′ rapid-amplification of cDNA ends (3′RACE), reverse transcription PCR (RT-PCR) and quantitative PCR (Q-PCR) experiments, this locus encodes a long noncoding RNA (lncRNA) comprising two exons that is expressed ubiquitously and stably in different tissues. The bovine Rosa26 (bRosa26) locus appears to be highly amenable to transcription activator-like effector nucleases (TALENs)-mediated knock-in, and ubiquitous expression of enhanced green fluorescent protein (EGFP) inserted in the bRosa26 locus was observed in various stages, including cells, embryos, fetus and cattle. Finally, we created a valuable master bRosa26-EGFP fetal fibroblast cell line in which any gene of interest can be efficiently introduced and stably expressed using recombinase-mediated cassette exchange (RMCE). The new tools described here will be useful for a variety of studies using cattle.
Competing contagion processes: Complex contagion triggered by simple contagion
Authors: Min Byungjoon , San Miguel Maxi 
Published: July 2018

AbstractEmpirical evidence reveals that contagion processes often occur with competition of simple and complex contagion, meaning that while some agents follow simple contagion, others follow complex contagion. Simple contagion refers to spreading processes induced by a single exposure to a contagious entity while complex contagion demands multiple exposures for transmission. Inspired by this observation, we propose a model of contagion dynamics with a transmission probability that initiates a process of complex contagion. With this probability nodes subject to simple contagion get adopted and trigger a process of complex contagion. We obtain a phase diagram in the parameter space of the transmission probability and the fraction of nodes subject to complex contagion. Our contagion model exhibits a rich variety of phase transitions such as continuous, discontinuous, and hybrid phase transitions, criticality, tricriticality, and double transitions. In particular, we find a double phase transition showing a continuous transition and a following discontinuous transition in the density of adopted nodes with respect to the transmission probability. We show that the double transition occurs with an intermediate phase in which nodes following simple contagion become adopted but nodes with complex contagion remain susceptible.
Femtosecond-laser-written Microstructured Waveguides in BK7 Glass
Authors: Chen George Y. , Piantedosi Fiorina , Otten Dale , Kang Yvonne Qiongyue , Zhang Wen Qi , Zhou Xiaohong , Monro Tanya M. , Lancaster David G. 
Published: July 2018

AbstractThere is a deficiency of low-loss microstructured waveguides that can be fabricated with a single laser-pass to minimize stress build-up, which can enable enhanced functionality and higher compactness for integrated optical devices. We demonstrate, for the first time, a series of multi-ring claddings each with a pair of cores in BK7 glass. Each waveguide was fabricated using only a single laser-pass at 1 MHz pulse repetition rate, 5 mm/s translation speed, 250 fs pulse width, over a set of pulse energies. We obtained the lowest-reported propagation loss of 0.062 dB/cm, measured at 1155 nm wavelength from the waveguide written with 340 nJ pulse energy. The maximum observed numerical aperture is 0.020, measured at 1155 nm wavelength from the waveguide written with 620 nJ pulse energy. Such waveguides could be incorporated in integrated Raman laser platforms for biomedical applications.
Non-dissociative structural transitions of the Watson-Crick and reverse Watson-Crick А·Т DNA base pairs into the Hoogsteen and reverse Hoogsteen forms
Authors: Brovarets’ Ol’ha O. , Tsiupa Kostiantyn S. , Hovorun Dmytro M. 
Published: July 2018

AbstractIn this study it was theoretically shown that discovered by us recently (Brovarets’et al.,Frontiers in Chemistry, 2018, 6:8; doi: 10.3389/fchem.2018.00008) high-energetical, significantly non-planar (symmetry C1), short-lived wobbled conformers of the classical Watson-Crick А·Т(WC), reverse Watson-Crick А·Т(rWC), Hoogsteen А·Т(Н) and reverse Hoogsteen А·Т(rН) DNA base pairs are the intermediates of their pairwise А∙Т(WC)/А∙Т(rWC) ↔ А∙Т(H)/А∙Т(rH) conformational transformations. These transitions do not require for their realization the energy-consumable anisotropic rotation of the amino group of A around the exocyclic C6-N6 bond. They are controlled by the non-planar transition states with quasi-orthogonal geometry (symmetry C1) joined by the single intermolecular (Т)N3H···N6(А) H-bond (~4 kcal∙mol−1). The Gibbs free energies of activation for these non-dissociative, dipole-active conformational transitions consist 7.33 and 7.81 kcal∙mol−1, accordingly. Quantum-mechanical (QM) calculations in combination with Bader’s quantum theory of “Atoms in Molecules” (QTAIM) have been performed at the MP2/aug-cc-pVDZ//B3LYP/6-311++G(d,p) level of QM theory in the continuum with ε = 4 under normal conditions.
Stochastic sequestration dynamics: a minimal model with extrinsic noise for bimodal distributions and competitors correlation
Authors: Del Giudice Marco , Bosia Carla , Grigolon Silvia , Bo Stefano 
Published: July 2018

AbstractMany biological processes are known to be based on molecular sequestration. This kind of dynamics involves two types of molecular species, namely targets and sequestrants, that bind to form a complex. In the simple framework of mass-action law, key features of these systems appear to be threshold-like profiles of the amounts of free molecules as a function of the parameters determining their possible maximum abundance. However, biochemical processes are probabilistic and take place in stochastically fluctuating environments. How these different sources of noise affect the final outcome of the network is not completely characterised yet. In this paper we specifically investigate the effects induced by a source of extrinsic noise onto a minimal stochastic model of molecular sequestration. We analytically show how bimodal distributions of the targets can appear and characterise them as a result of noise filtering mediated by the threshold response. We then address the correlations between target species induced by the sequestrant and discuss how extrinsic noise can turn the negative correlation caused by competition into a positive one. Finally, we consider the more complex scenario of competitive inhibition for enzymatic kinetics and discuss the relevance of our findings with respect to applications.
Structural insights into ubiquitin phosphorylation by PINK1
Authors: Okatsu Kei , Sato Yusuke , Yamano Koji , Matsuda Noriyuki , Negishi Lumi , Takahashi Akiko , Yamagata Atsushi , Goto-Ito Sakurako , Mishima Masaki , Ito Yutaka , Oka Toshihiko , Tanaka Keiji , Fukai Shuya 
Published: July 2018

AbstractMutations of PTEN-induced putative kinase 1 (PINK1) and the E3 ubiquitin (Ub) ligase parkin can cause familial parkinsonism. These two proteins are essential for ubiquitylation of damaged mitochondria and subsequent degradation. PINK1 phosphorylates Ser65 of Ub and the Ub-like (UBL) domain of parkin to allosterically relieve the autoinhibition of parkin. To understand the structural mechanism of the Ub/UBL-specific phosphorylation by PINK1, we determined the crystal structure of Tribolium castaneum PINK1 kinase domain (TcPINK1) in complex with a nonhydrolyzable ATP analogue at 2.5 Å resolution. TcPINK1 consists of the N- and C-terminal lobes with the PINK1-specific extension. The ATP analogue is bound in the cleft between the N- and C-terminal lobes. The adenine ring of the ATP analogue is bound to a hydrophobic pocket, whereas the triphosphate group of the ATP analogue and two coordinated Mg ions interact with the catalytic hydrophilic residues. Comparison with protein kinases A and C (PKA and PKC, respectively) unveils a putative Ub/UBL-binding groove, which is wider than the peptide-binding groove of PKA or PKC to accommodate the globular head of Ub or UBL. Further crosslinking analyses suggested a PINK1-interacting surface of Ub. Structure-guided mutational analyses support the findings from the present structural analysis of PINK1.
Enhanced physicochemical stability and efficacy of angiotensin I-converting enzyme (ACE) - inhibitory biopeptides by chitosan nanoparticles optimized using Box-Behnken design
Authors: Auwal Shehu Muhammad , Zarei Mohammad , Tan Chin Ping , Basri Mahiran , Saari Nazamid 
Published: July 2018

AbstractBromelain-generated biopeptides from stone fish protein exhibit strong inhibitory effect against ACE and can potentially serve as designer food (DF) with blood pressure lowering effect. Contextually, the DF refer to the biopeptides specifically produced to act as ACE-inhibitors other than their primary role in nutrition and can be used in the management of hypertension. However, the biopeptides are unstable under gastrointestinal tract (GIT) digestion and need to be stabilized for effective oral administration. In the present study, the stone fish biopeptides (SBs) were stabilized by their encapsulation in sodium tripolyphosphate (TPP) cross-linked chitosan nanoparticles produced by ionotropic gelation method. The nanoparticles formulation was then optimized via Box-Behnken experimental design to achieve smaller particle size (162.70 nm) and high encapsulation efficiency (75.36%) under the optimum condition of SBs:Chitosan mass ratio (0.35), homogenization speed (8000 rpm) and homogenization time (30 min). The SBs-loaded nanoparticles were characterized for morphology by transmission electron microscopy (TEM), physicochemical stability and efficacy. The nanoparticles were then lyophilized and analyzed using Fourier transform infra-red spectroscopy (FTIR) and X-ray diffraction (XRD). The results obtained indicated a sustained in vitro release and enhanced physicochemical stability of the SBs-loaded nanoparticles with smaller particle size and high encapsulation efficiency following long period of storage. Moreover, the efficacy study revealed improved inhibitory effect of the encapsulated SBs against ACE following simulated GIT digestion.
AU040320 deficiency leads to disruption of acrosome biogenesis and infertility in homozygous mutant mice
Authors: Guidi Luiz G. , Holloway Zoe G. , Arnoult Christophe , Ray Pierre F. , Monaco Anthony P. , Molnár Zoltán , Velayos-Baeza Antonio 
Published: July 2018

AbstractStudy of knockout (KO) mice has helped understand the link between many genes/proteins and human diseases. Identification of infertile KO mice provides valuable tools to characterize the molecular mechanisms underlying gamete formation. The KIAA0319L gene has been described to have a putative association with dyslexia; surprisingly, we observed that homozygous KO males for AU040320, KIAA0319L ortholog, are infertile and present a globozoospermia-like phenotype. Mutant spermatozoa are mostly immotile and display a malformed roundish head with no acrosome. In round spermatids, proacrosomal vesicles accumulate close to the acroplaxome but fail to coalesce into a single acrosomal vesicle. In wild-type mice AU040320 localises to the trans-Golgi-Network of germ cells but cannot be detected in mature acrosomes. Our results suggest AU040320 may be necessary for the normal formation of proacrosomal vesicles or the recruitment of cargo proteins required for downstream events leading to acrosomal fusion. Mutations in KIAA0319L could lead to human infertility; we screened for KIAA0319L mutations in a selected cohort of globozoospermia patients in which no genetic abnormalities have been previously identified, but detected no pathogenic changes in this particular cohort.