bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rhomboid family member 2 regulates cytoskeletal stress-associated Keratin 16
Authors: Maruthappu Thiviyani , Chikh Anissa , Fell Benjamin , Delaney Paul J. , Brooke Matthew A. , Levet Clemence , Moncada-Pazos Angela , Ishida-Yamamoto Akemi , Blaydon Diana , Waseem Ahmad , Leigh Irene M. , Freeman Matthew , Kelsell David P. 
Published: January 2017

AbstractKeratin 16 (K16) is a cytoskeletal scaffolding protein highly expressed at pressure-bearing sites of the mammalian footpad. It can be induced in hyperproliferative states such as wound healing, inflammation and cancer. Here we show that the inactive rhomboid protease RHBDF2 (iRHOM2) regulates thickening of the footpad epidermis through its interaction with K16. K16 expression is absent in the thinned footpads of irhom2−/− mice compared with irhom2+/+mice, due to reduced keratinocyte proliferation. Gain-of-function mutations in iRHOM2 underlie Tylosis with oesophageal cancer (TOC), characterized by palmoplantar thickening, upregulate K16 with robust downregulation of its type II keratin binding partner, K6. By orchestrating the remodelling and turnover of K16, and uncoupling it from K6, iRHOM2 regulates the epithelial response to physical stress. These findings contribute to our understanding of the molecular mechanisms underlying hyperproliferation of the palmoplantar epidermis in both physiological and disease states, and how this ‘stress’ keratin is regulated.
A mechanosensory receptor required for food texture detection in Drosophila
Authors: Sánchez-Alcañiz Juan Antonio , Zappia Giovanna , Marion-Poll Frédéric , Benton Richard 
Published: January 2017

AbstractTextural properties provide information on the ingestibility, digestibility and state of ripeness or decay of sources of nutrition. Compared with our understanding of the chemosensory assessment of food, little is known about the mechanisms of texture detection. Here we show that Drosophila melanogaster can discriminate food texture, avoiding substrates that are either too hard or too soft. Manipulations of food substrate properties and flies' chemosensory inputs indicate that texture preferences are revealed only in the presence of an appetitive stimulus, but are not because of changes in nutrient accessibility, suggesting that animals discriminate the substrates’ mechanical characteristics. We show that texture preference requires NOMPC, a TRP-family mechanosensory channel. NOMPC localizes to the sensory dendrites of neurons housed within gustatory sensilla, and is essential for their mechanosensory-evoked responses. Our results identify a sensory pathway for texture detection and reveal the behavioural integration of chemical and physical qualities of food.
mTORC2 signalling regulates M2 macrophage differentiation in response to helminth infection and adaptive thermogenesis
Authors: Hallowell R. W. , Collins S. L. , Craig J. M. , Zhang Y. , Oh M. , Illei P. B. , Chan-Li Y. , Vigeland C. L. , Mitzner W. , Scott A. L. , Powell J. D. , Horton M. R. 
Published: January 2017

AbstractAlternatively activated macrophages (M2) have an important function in innate immune responses to parasitic helminths, and emerging evidence also indicates these cells are regulators of systemic metabolism. Here we show a critical role for mTORC2 signalling in the generation of M2 macrophages. Abrogation of mTORC2 signalling in macrophages by selective conditional deletion of the adaptor molecule Rictor inhibits the generation of M2 macrophages while leaving the generation of classically activated macrophages (M1) intact. Selective deletion of Rictor in macrophages prevents M2 differentiation and clearance of a parasitic helminth infection in mice, and also abrogates the ability of mice to regulate brown fat and maintain core body temperature. Our findings define a role for mTORC2 in macrophages in integrating signals from the immune microenvironment to promote innate type 2 immunity, and also to integrate systemic metabolic and thermogenic responses.
A Lin28 homologue reprograms differentiated cells to stem cells in the moss Physcomitrella patens
Authors: Li Chen , Sako Yusuke , Imai Akihiro , Nishiyama Tomoaki , Thompson Kari , Kubo Minoru , Hiwatashi Yuji , Kabeya Yukiko , Karlson Dale , Wu Shu-Hsing , Ishikawa Masaki , Murata Takashi , Benfey Philip N. , Sato Yoshikatsu , Tamada Yosuke , Hasebe Mitsuyasu 
Published: January 2017

AbstractBoth land plants and metazoa have the capacity to reprogram differentiated cells to stem cells. Here we show that the moss Physcomitrella patens Cold-Shock Domain Protein 1 (PpCSP1) regulates reprogramming of differentiated leaf cells to chloronema apical stem cells and shares conserved domains with the induced pluripotent stem cell factor Lin28 in mammals. PpCSP1 accumulates in the reprogramming cells and is maintained throughout the reprogramming process and in the resultant stem cells. Expression of PpCSP1 is negatively regulated by its 3′-untranslated region (3′-UTR). Removal of the 3′-UTR stabilizes PpCSP1 transcripts, results in accumulation of PpCSP1 protein and enhances reprogramming. A quadruple deletion mutant of PpCSP1 and three closely related PpCSP genes exhibits attenuated reprogramming indicating that the PpCSP genes function redundantly in cellular reprogramming. Taken together, these data demonstrate a positive role of PpCSP1 in reprogramming, which is similar to the function of mammalian Lin28.
A non-canonical mismatch repair pathway in prokaryotes
Authors: Castañeda-García A. , Prieto A. I. , Rodríguez-Beltrán J. , Alonso N. , Cantillon D. , Costas C. , Pérez-Lago L. , Zegeye E. D. , Herranz M. , Plociński P. , Tonjum T. , García de Viedma D. , Paget M. , Waddell S. J. , Rojas A. M. , Doherty A. J. , Blázquez J. 
Published: January 2017

AbstractMismatch repair (MMR) is a near ubiquitous pathway, essential for the maintenance of genome stability. Members of the MutS and MutL protein families perform key steps in mismatch correction. Despite the major importance of this repair pathway, MutS–MutL are absent in almost all Actinobacteria and many Archaea. However, these organisms exhibit rates and spectra of spontaneous mutations similar to MMR-bearing species, suggesting the existence of an alternative to the canonical MutS–MutL-based MMR. Here we report that Mycobacterium smegmatis NucS/EndoMS, a putative endonuclease with no structural homology to known MMR factors, is required for mutation avoidance and anti-recombination, hallmarks of the canonical MMR. Furthermore, phenotypic analysis of naturally occurring polymorphic NucS in a M. smegmatis surrogate model, suggests the existence of M. tuberculosis mutator strains. The phylogenetic analysis of NucS indicates a complex evolutionary process leading to a disperse distribution pattern in prokaryotes. Together, these findings indicate that distinct pathways for MMR have evolved at least twice in nature.
Sub-wavelength modulation of χ(2) optical nonlinearity in organic thin films
Authors: Yan Yixin , Yuan Yakun , Wang Baomin , Gopalan Venkatraman , Giebink Noel C. 
Published: January 2017

AbstractModulating the second-order nonlinear optical susceptibility (χ(2)) of materials at the nanoscale represents an ongoing technological challenge for a variety of integrated frequency conversion and nonlinear nanophotonic applications. Here we exploit the large hyperpolarizability of intermolecular charge transfer states, naturally aligned at an organic semiconductor donor–acceptor (DA) interface, as a means to control the magnitude and sign of χ(2) at the nanoscale. Focusing initially on a single pentacene-C60 DA interface, we confirm that the charge transfer transition is strongly aligned orthogonal to the heterojunction and find that it is responsible for a large interfacial nonlinearity probed via second harmonic generation that is sufficient to achieve d33>10 pm V−1, when incorporated in a non-centrosymmetric DA multilayer stack. Using grating-shadowed oblique-angle deposition to laterally structure the DA interface distribution in such multilayers subsequently enables the demonstration of a χ(2) grating with 280 nm periodicity, which is the shortest reported to date.
Rapid evolution of dispersal ability makes biological invasions faster and more variable
Authors: Ochocki Brad M. , Miller Tom E. X. 
Published: January 2017

AbstractGenetic variation in dispersal ability may result in the spatial sorting of alleles during range expansion. Recent theory suggests that spatial sorting can favour the rapid evolution of life history traits at expanding fronts, and therefore modify the ecological dynamics of range expansion. Here we test this prediction by disrupting spatial sorting in replicated invasions of the bean beetleCallosobruchus maculatusacross homogeneous experimental landscapes. We show that spatial sorting promotes rapid evolution of dispersal distance, which increases the speed and variability of replicated invasions: after 10 generations of range expansion, invasions subject to spatial sorting spread 8.9% farther and exhibit 41-fold more variable spread dynamics relative to invasions in which spatial sorting is suppressed. Correspondingly, descendants from spatially evolving invasions exhibit greater mean and variance in dispersal distance. Our results reveal an important role for rapid evolution during invasion, even in the absence of environmental filters, and argue for evolutionarily informed forecasts of invasive spread by exotic species or climate change migration by native species.
Enzyme I facilitates reverse flux from pyruvate to phosphoenolpyruvate in Escherichia coli
Authors: Long Christopher P. , Au Jennifer , Sandoval Nicholas R. , Gebreselassie Nikodimos A. , Antoniewicz Maciek R. 
Published: January 2017

AbstractThe bacterial phosphoenolpyruvate-carbohydrate phosphotransferase system (PTS) consists of cascading phosphotransferases that couple the simultaneous import and phosphorylation of a variety of sugars to the glycolytic conversion of phosphoenolpyruvate (PEP) to pyruvate. As the primary route of glucose uptake in E. coli, the PTS plays a key role in regulating central carbon metabolism and carbon catabolite repression, and is a frequent target of metabolic engineering interventions. Here we show that Enzyme I, the terminal phosphotransferase responsible for the conversion of PEP to pyruvate, is responsible for a significant in vivo flux in the reverse direction (pyruvate to PEP) during both gluconeogenic and glycolytic growth. We use 13C alanine tracers to quantify this back-flux in single and double knockouts of genes relating to PEP synthetase and PTS components. Our findings are relevant to metabolic engineering design and add to our understanding of gene-reaction connectivity in E. coli.
αV-class integrins exert dual roles on α5β1 integrins to strengthen adhesion to fibronectin
Authors: Bharadwaj Mitasha , Strohmeyer Nico , Colo Georgina P. , Helenius Jonne , Beerenwinkel Niko , Schiller Herbert B. , Fässler Reinhard , Müller Daniel J. 
Published: January 2017

AbstractUpon binding to the extracellular matrix protein, fibronectin, αV-class and α5β1 integrins trigger the recruitment of large protein assemblies and strengthen cell adhesion. Both integrin classes have been functionally specified, however their specific roles in immediate phases of cell attachment remain uncharacterized. Here, we quantify the adhesion of αV-class and/or α5β1 integrins expressing fibroblasts initiating attachment to fibronectin (≤120 s) by single-cell force spectroscopy. Our data reveals that αV-class integrins outcompete α5β1 integrins. Once engaged, αV-class integrins signal to α5β1 integrins to establish additional adhesion sites to fibronectin, away from those formed by αV-class integrins. This crosstalk, which strengthens cell adhesion, induces α5β1 integrin clustering by RhoA/ROCK/myosin-II and Arp2/3-mediated signalling, whereas overall cell adhesion depends on formins. The dual role of both fibronectin-binding integrin classes commencing with an initial competition followed by a cooperative crosstalk appears to be a basic cellular mechanism in assembling focal adhesions to the extracellular matrix.
Spatial and temporal boundaries of NMDA receptor hypofunction leading to schizophrenia
Authors: Nakazawa Kazu , Jeevakumar Vivek , Nakao Kazuhito 
Published: January 2017

AbstractThe N-methyl-d-aspartate receptor hypofunction is one of the most prevalent models of schizophrenia. For example, healthy subjects treated with uncompetitive N-methyl-d-aspartate receptor antagonists elicit positive, negative, and cognitive-like symptoms of schizophrenia. Patients with anti-N-methyl-d-aspartate receptor encephalitis, which is likely caused by autoantibody-mediated down-regulation of cell surface N-methyl-d-aspartate receptors, often experience psychiatric symptoms similar to schizophrenia initially. However, where and when N-methyl-d-aspartate receptor hypofunction occurs in the brain of schizophrenic patients is poorly understood. Here we review the findings from N-methyl-d-aspartate receptor antagonist and autoantibody models, postmortem studies on N-methyl-d-aspartate receptor subunits, as well as the global and cell-type-specific knockout mouse models of subunit GluN1. We compare various conditional GluN1 knockout mouse strains, focusing on the onset of N-methyl-d-aspartate receptor deletion and on the cortical cell-types. Based on these results, we hypothesize that N-methyl-d-aspartate receptor hypofunction initially occurs in cortical GABAergic neurons during early postnatal development. The resulting GABA neuron maturation deficit may cause reduction of intrinsic excitability and GABA release, leading to disinhibition of pyramidal neurons. The cortical disinhibition in turn could elicit glutamate spillover and subsequent homeostatic down regulation of N-methyl-d-aspartate receptor function in pyramidal neurons in prodromal stage. These two temporally-distinct N-methyl-d-aspartate receptor hypofunctions may be complimentary, as neither alone may not be able to fully explain the entire schizophrenia pathophysiology. Potential underlying mechanisms for N-methyl-d-aspartate receptor hypofunction in cortical GABA neurons are also discussed, based on studies of naturally-occurring N-methyl-d-aspartate receptor antagonists, neuregulin/ErbB4 signaling pathway, and theoretical analysis of excitatory/inhibitory balance.
Automated analysis of connected speech reveals early biomarkers of Parkinson’s disease in patients with rapid eye movement sleep behaviour disorder
Authors: Hlavnička Jan , Čmejla Roman , Tykalová Tereza , Šonka Karel , Růžička Evžen , Rusz Jan 
Published: January 2017

AbstractFor generations, the evaluation of speech abnormalities in neurodegenerative disorders such as Parkinson’s disease (PD) has been limited to perceptual tests or user-controlled laboratory analysis based upon rather small samples of human vocalizations. Our study introduces a fully automated method that yields significant features related to respiratory deficits, dysphonia, imprecise articulation and dysrhythmia from acoustic microphone data of natural connected speech for predicting early and distinctive patterns of neurodegeneration. We compared speech recordings of 50 subjects with rapid eye movement sleep behaviour disorder (RBD), 30 newly diagnosed, untreated PD patients and 50 healthy controls, and showed that subliminal parkinsonian speech deficits can be reliably captured even in RBD patients, which are at high risk of developing PD or other synucleinopathies. Thus, automated vocal analysis should soon be able to contribute to screening and diagnostic procedures for prodromal parkinsonian neurodegeneration in natural environments.
Using effect size benchmarks to assess when alien impacts are actually alien
Authors: Smith Helen M. , Dickman Chris R. , Banks Peter B. 
Published: January 2017

AbstractAlien predators have on average twice the impact on native prey populations than do native predators, and are a severe threat to wildlife globally. Manipulation experiments can be used to quantify the impact of an alien predator on its prey population/s, but unless the results are compared to benchmarks, it is unclear whether this impact is indeed greater than that of a native predator. Here we use the Australian garden skink Lampropholis delicata and alien black rat Rattus rattus to test if black rats are an additive source of predation for the skink, and to judge whether the effect size of rat-impact on the skink represents that of an alien or native predator. We used replicated experiments to exclude black rats at local and landscape scales to test how rats affect skink activity and trapping frequency. Both manipulations had positive effects on skinks, however, the population-level effect size was lower than that described for alien predators but similar to that expected for native predators. We suggest that Australian skinks may respond appropriately to predatory alien rats because they coevolved with endemic Rattus species. This adds novel insights into the varying levels of impact that alien predators have on native prey.
Functional characterization of NES and GES responsible for the biosynthesis of (E)-nerolidol and (E,E)-geranyllinalool in Tripterygium wilfordii
Authors: Su Ping , Hu Tianyuan , Liu Yujia , Tong Yuru , Guan Hongyu , Zhang Yifeng , Zhou Jiawei , Huang Luqi , Gao Wei 
Published: January 2017

AbstractTriptolide and celastrol, two principal bioactive compounds in Tripterygium wilfordii, are produced from geranylgeranyl diphosphate (GGPP) and farnesyl diphosphate ((E,E)-FPP) through terpenoid biosynthesis pathway. However, little is known about T. wilfordii terpene synthases which could competitively utilize GGPP and (E,E)-FPP as substrates, producing C15 and C20 tertiary alcohols. Here we firstly cloned the genes encoding nerolidol synthase (NES) and geranyllinalool synthases (GES1, GES2), which are responsible for the biosynthesis of (E)-nerolidol and (E,E)-geranyllinalool. In vitro characterization of recombinant TwNES and TwGES1 revealed both were functional enzymes that could catalyze the conversion of (E,E)-FPP and GGPP to (E)-nerolidol and (E,E)-geranyllinalool, which were consistent with the results of yeast fermentation. Biochemical characterization revealed TwNES and TwGES1 had strong dependency for Mg2+, Km and Kcat/Km values of TwNES for (E,E)-FPP were 12.700 μM and 0.029 s−1/μM, and TwGES1 for GGPP were 2.039 μM and 0.019 s−1/μM. Real-time PCR analysis showed the expression levels of NES and GES1 increased by several fold in the suspension cells treated with alamethicin, indicating TwNES and TwGES1 are likely to utilize GGPP and (E,E)-FPP to generate tertiary alcohols as precursor of plant volatiles, which play important roles in the ecological interactions between T. wilfordii and other organisms.
A UK wide cohort study describing management and outcomes for infants with surgical Necrotising Enterocolitis
Authors: Allin Benjamin , Long Anna-May , Gupta Amit , Knight Marian , Lakhoo Kokila ,   British Association of Paediatric Surgeons Congenital Anomalies Surveillance System Necrotising Enterocolitis Collaboration, Kazmierski Marcin , Kenny Simon , Lopes Joana , Cusick Eleri , Parsons Gilian , McCabe Amanda , Upadhyaya Manasvi , Walker Gregor , De Coppi Paulo , Besarovic Sania , Thakkar Hemanshoo , Tullie Lucinda , Sutcliffe Jonathan , Eradi Bala , Ross Andrew , Maphango Nomsa , Motiwale Sandeep , Salloum Adnan , Pardy Caroline , Waly Ramy , Charlesworth Paul , Craigie Ross , Lall Anupam , Lindley Richard , Johal Navroop , Njere Ike , Mortell Alan , Nandi Bip , Jones Abigail , Fouad Dina , tan Yew-Wei , Kufeji Dorothy , Stanwell Joanna , Lakshminarayanan Bhanu , Burge David , Wetherill Charlotte , Niyogi Anindya , Parsons Chris , Doyle Miriam , Turner Alex , Yardley Ian , Shrestha Ram , Mullassery Dhanya , Paramalingham Saravankumar , Ragazzi Simone 
Published: January 2017

AbstractThe Royal College of Surgeons have proposed using outcomes from necrotising enterocolitis (NEC) surgery for revalidation of neonatal surgeons. The aim of this study was therefore to calculate the number of infants in the UK/Ireland with surgical NEC and describe outcomes that could be used for national benchmarking and counselling of parents. A prospective nationwide cohort study of every infant requiring surgical intervention for NEC in the UK was conducted between 01/03/13 and 28/02/14. Primary outcome was mortality at 28-days. Secondary outcomes included discharge, post-operative complication, and TPN requirement. 236 infants were included, 43(18%) of whom died, and eight(3%) of whom were discharged prior to 28-days post decision to intervene surgically. Sixty infants who underwent laparotomy (27%) experienced a complication, and 67(35%) of those who were alive at 28 days were parenteral nutrition free. Following multi-variable modelling, presence of a non-cardiac congenital anomaly (aOR 5.17, 95% CI 1.9–14.1), abdominal wall erythema or discolouration at presentation (aOR 2.51, 95% CI 1.23–5.1), diagnosis of single intestinal perforation at laparotomy (aOR 3.1 95% CI 1.05–9.3), and necessity to perform a clip and drop procedure (aOR 30, 95% CI 3.9–237) were associated with increased 28-day mortality. These results can be used for national benchmarking and counselling of parents.
Sodium-myoinositol cotransporter-1, SMIT1, mediates the production of reactive oxygen species induced by hyperglycemia in the heart
Authors: Van Steenbergen Anne , Balteau Magali , Ginion Audrey , Ferté Laura , Battault Sylvain , Ravenstein Christophe de Meester de , Balligand Jean-Luc , Daskalopoulos Evangelos-Panagiotis , Gilon Patrick , Despa Florin , Despa Sanda , Vanoverschelde Jean-Louis , Horman Sandrine , Koepsell Hermann , Berry Gerard , Hue Louis , Bertrand Luc , Beauloye Christophe 
Published: January 2017

AbstractHyperglycemia (HG) stimulates the production of reactive oxygen species in the heart through activation of NADPH oxidase 2 (NOX2). This production is independent of glucose metabolism but requires sodium/glucose cotransporters (SGLT). Seven SGLT isoforms (SGLT1 to 6 and sodium-myoinositol cotransporter-1, SMIT1) are known, although their expression and function in the heart remain elusive. We investigated these 7 isoforms and found that only SGLT1 and SMIT1 were expressed in mouse, rat and human hearts. In cardiomyocytes, galactose (transported through SGLT1) did not activate NOX2. Accordingly, SGLT1 deficiency did not prevent HG-induced NOX2 activation, ruling it out in the cellular response to HG. In contrast, myo-inositol (transported through SMIT1) reproduced the toxic effects of HG. SMIT1 overexpression exacerbated glucotoxicity and sensitized cardiomyocytes to HG, whereas its deletion prevented HG-induced NOX2 activation. In conclusion, our results show that heart SMIT1 senses HG and triggers NOX2 activation. This could participate in the redox signaling in hyperglycemic heart and contribute to the pathophysiology of diabetic cardiomyopathy.