bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nociceptive DRG neurons express muscle lim protein upon axonal injury
Authors: Levin Evgeny , Andreadaki Anastasia , Gobrecht Philipp , Bosse Frank , Fischer Dietmar 
Published: March 2017

AbstractMuscle lim protein (MLP) has long been regarded as a cytosolic and nuclear muscular protein. Here, we show that MLP is also expressed in a subpopulation of adult rat dorsal root ganglia (DRG) neurons in response to axonal injury, while the protein was not detectable in naïve cells. Detailed immunohistochemical analysis of L4/L5 DRG revealed ~3% of MLP-positive neurons 2 days after complete sciatic nerve crush and maximum ~10% after 4–14 days. Similarly, in mixed cultures from cervical, thoracic, lumbar and sacral DRG ~6% of neurons were MLP-positive after 2 days and maximal 17% after 3 days. In both, histological sections and cell cultures, the protein was detected in the cytosol and axons of small diameter cells, while the nucleus remained devoid. Moreover, the vast majority could not be assigned to any of the well characterized canonical DRG subpopulations at 7 days after nerve injury. However, further analysis in cell culture revealed that the largest population of MLP expressing cells originated from non-peptidergic IB4-positive nociceptive neurons, which lose their ability to bind the lectin upon axotomy. Thus, MLP is mostly expressed in a subset of axotomized nociceptive neurons and can be used as a novel marker for this population of cells.
The cAMP-PKA pathway-mediated fat mobilization is required for cold tolerance in C. elegans
Authors: Liu Fang , Xiao Yi , Ji Xing-Lai , Zhang Ke-Qin , Zou Cheng-Gang 
Published: March 2017

AbstractLow temperature has a great impact on animal life. Homoiotherms such as mammals increase their energy expenditure to produce heat by activating the cAMP-protein kinase A (PKA)-hormone-sensitive lipase (HSL) pathway under cold stress. Although poikilothermic animals do not have the ability to regulate body temperature, whether this pathway is required for cold tolerance remains unknown. We have now achieved this using the genetically tractable model animal Caenorhabditis elegans. We demonstrate that cold stress activates PKA signaling, which in turn up-regulates the expression of a hormone-sensitive lipase hosl-1. The lipase induces fat mobilization, leading to glycerol accumulation, thereby protecting worms against cold stress. Our findings provide an example of an evolutionarily conserved mechanism for cold tolerance that has persisted in both poikilothermic and homoeothermic animals.
Performance Gains in Genome-Wide Association Studies for Longitudinal Traits via Modeling Time-varied effects
Authors: Ning Chao , Kang Huimin , Zhou Lei , Wang Dan , Wang Haifei , Wang Aiguo , Fu Jinluan , Zhang Shengli , Liu Jianfeng 
Published: March 2017

AbstractComplex traits with multiple phenotypic values changing over time are called longitudinal traits. In traditional genome-wide association studies (GWAS) for longitudinal traits, a combined/averaged estimated breeding value (EBV) or deregressed proof (DRP) instead of multiple phenotypic measurements per se for each individual was frequently treated as response variable in statistical model. This can result in power losses or even inflate false positive rates (FPRs) in the detection due to failure of exploring time-dependent relationship among measurements. Aiming at overcoming such limitation, we developed two random regression-based models for functional GWAS on longitudinal traits, which could directly use original time-dependent records as response variable and fit the time-varied Quantitative Trait Nucleotide (QTN) effect. Simulation studies showed that our methods could control the FPRs and increase statistical powers in detecting QTN in comparison with traditional methods where EBVs, DRPs or estimated residuals were considered as response variables. Besides, our proposed models also achieved reliable powers in gene detection when implementing into two real datasets, a Chinese Holstein Cattle data and the Genetic Analysis Workshop 18 data. Our study herein offers an optimal way to enhance the power of gene detection and further understand genetic control of developmental processes for complex longitudinal traits.
New crystal structure prediction of fully hydrogenated borophene by first principles calculations
Authors: Wang Zhiqiang , Lü Tie-Yu , Wang Hui-Qiong , Feng Yuan Ping , Zheng Jin-Cheng 
Published: March 2017

AbstractNew crystal structures of fully hydrogenated borophene (borophane) have been predicted by first principles calculation. Comparing with the chair-like borophane (C-boropane) that has been reported in literature, we obtained four new borophane conformers with much lower total-energy. The most stable one, washboard-like borophane (W-borophane), has energy about 113.41 meV/atom lower than C-borophane. In order to explain the relative stability of different borophane conformers, the atom configuration, density of states, charge transfer, charge density distribution and defect formation energy of B-H dimer have been calculated. The results show that the charge transfer from B atoms to H atoms is crucial for the stability of borophane. In different borophane conformers, the bonding characteristics between B and H atoms are similar, but the B-B bonds in W-borophane are much stronger than that in C-borophane or other structures. In addition, we examined the dynamical stability of borophane conformers by phonon dispersions and found that the four new conformers are all dynamically stable. Finally the mechanical properties of borophane conformers along an arbitrary direction have been discussed. W-borophane possesses unique electronic structure (Dirac cone), good stability and superior mechanical properties. W-borophane has broad perspective for nano electronic device.
VLDL/LDL acts as a drug carrier and regulates the transport and metabolism of drugs in the body
Authors: Yamamoto Hideaki , Takada Tappei , Yamanashi Yoshihide , Ogura Masatsune , Masuo Yusuke , Harada-Shiba Mariko , Suzuki Hiroshi 
Published: March 2017

AbstractOnly free drugs have been believed to be carried into tissues through active or passive transport. However, considering that lipoproteins function as carriers of serum lipids such as cholesterol and triglycerides, we hypothesized that lipoproteins can associate with certain drugs and mediate their transport into tissues in lipid-associated form. Here, in vitro and in vivo studies with low density lipoprotein receptor (LDLR)-overexpressing or -knockdown cells and wild-type or LDLR-mutant mice were used to show the association of various drugs with lipoproteins and the uptake of lipoprotein-associated drugs through a lipoprotein receptor-mediated process. In clinical studies, investigation of the effect of lipoprotein apheresis on serum drug concentrations in patients with familial hypercholesterolemia demonstrated that lipoprotein-mediated drug transport occurs in humans as well as in mice. These findings represent a new concept regarding the transport and metabolism of drugs in the body and suggest that the role of lipoprotein-mediated drug transport should be considered when developing effective and safe pharmacotherapies.
Early embryonic development and spatiotemporal localization of mammalian primordial germ cell-associated proteins in the basal rodent Lagostomus maximus
Authors: Leopardo Noelia P. , Vitullo Alfredo D. 
Published: March 2017

AbstractThe gene network controlling primordial germ cell (PGC) specification in eutherian mammals has been exhaustively investigated in mice. The egg-cylinder morphology of the mouse embryo is the key event enabling inductive signals from the extra-embryonic ectoderm (ExE) to specify epiblast cells as PGCs early on. We investigated the embryonic development and the spatiotemporal localization of PGC-associated proteins in the basal Hystricognathi rodent Lagostomus maximus. L. maximus develops through a flat-disc epiblast far apart from the ExE. In the primitive streak stage, OCT4-positive cells are detected in the posterior pole of the embryo disc in the mesoderm of the proximal epiblast. In the neural plate stage, a reduced 8 to 12 OCT4-positive cell population transiently expresses FRAGILIS, STELLA and SOX17 in the posterior streak. Soon after translocation to the hindgut, pluripotent OCT4 cells start expressing VASA, and then, STELLA and FRAGILIS are turned on during migration toward the genital ridge. L. maximus shows a spatiotemporal pattern of PGC-associated markers divergent from the early PGC restriction model seen in mice. This pattern conforms to alternative models that are based on a pluripotent population in the embryonic axis, where PGCs are specified later during development.
RPI-Bind: a structure-based method for accurate identification of RNA-protein binding sites
Authors: Luo Jiesi , Liu Liang , Venkateswaran Suresh , Song Qianqian , Zhou Xiaobo 
Published: March 2017

AbstractRNA and protein interactions play crucial roles in multiple biological processes, while these interactions are significantly influenced by the structures and sequences of protein and RNA molecules. In this study, we first performed an analysis of RNA-protein interacting complexes, and identified interface properties of sequences and structures, which reveal the diverse nature of the binding sites. With the observations, we built a three-step prediction model, namely RPI-Bind, for the identification of RNA-protein binding regions using the sequences and structures of both proteins and RNAs. The three steps include 1) the prediction of RNA binding regions on protein, 2) the prediction of protein binding regions on RNA, and 3) the prediction of interacting regions on both RNA and protein simultaneously, with the results from steps 1) and 2). Compared with existing methods, most of which employ only sequences, our model significantly improves the prediction accuracy at each of the three steps. Especially, our model outperforms the catRAPID by >20% at the 3rd step. All of these results indicate the importance of structures in RNA-protein interactions, and suggest that the RPI-Bind model is a powerful theoretical framework for studying RNA-protein interactions.
Fast microwave-assisted acidolysis: a new biorefinery approach for the zero-waste utilisation of lignocellulosic biomass to produce high quality lignin and fermentable saccharides
Authors: Zhou Long , Santomauro Fabio , Fan Jiajun , Macquarrie Duncan , Clark James , Chuck Christopher J. , Budarin Vitaliy 
Published: March 2017

Generally, biorefineries convert lignocellulosic biomass into a range of biofuels and further value added chemicals. However, conventional biorefinery processes focus mainly on the cellulose and hemicellulose fractions and therefore produce only low quality lignin, which is commonly burnt to provide process heat. To make full use of the biomass, more attention needs to be focused on novel separation techniques, where high quality lignin can be isolated that is suitable for further valorisation into aromatic chemicals and fuel components. In this paper, three types of lignocellulosic biomass (softwood, hardwood and herbaceous biomass) were processed by microwave-assisted acidolysis to produce high quality lignin. The lignin from the softwood was isolated largely intact in the solid residue after acidolysis. For example, a 10 min microwave-assisted acidolysis treatment produced lignin with a purity of 93% and in a yield of 82%, which is superior to other conventional separation methods reported. Furthermore, py-GC/MS analysis proved that the isolated lignin retained the original structure of native lignin in the feedstock without severe chemical modification. This is a large advantage, and the purified lignin is suitable for further chemical processing. To assess the suitability of this methodology as part of a biorefinery system, the aqueous phase, produced after acidolysis of the softwood, was characterised and assessed for its suitability for fermentation. The broth contained some mono- and di-saccharides but mainly contained organic acids, oligosaccharides and furans. While this is unsuitable forS. cerevisiaeand other common ethanol producing yeasts, two oleaginous yeasts with known inhibitor tolerances were selected:Cryptococcus curvatusandMetschnikowia pulcherrima. Both yeasts could grow on the broth, and demonstrated suitable catabolism of the oligosaccharides and inhibitors over 7 days. In addition, both yeasts were shown to be able to produce an oil with a similar composition to that of palm oil. This preliminary work demonstrates new protocols of microwave-assisted acidolysis and therefore offers an effective approach to produce high purity lignin and fermentable chemicals, which is a key step towards developing a zero-waste lignocellulosic biorefinery.
Pancreas Divisum in Children and Duodenum-Preserving Resection of the Pancreatic Head
Authors: Snajdauf Jiri , Petru Ondrej , Rygl Michal , Frybova Barbora , Bronsky Jiri , Mixa Vladimir , Keil Radan , Nahlovsky Jiri 
Published: March 2017

Introduction A retrospective study was performed to evaluate the clinical features, diagnostic methods, and treatment alternatives in children with pancreas divisum (PD).
Materials and Methods Patients who underwent treatment for PD between 1999 and 2014 at our department were evaluated for sex, age, presenting symptoms, physical examination findings, biochemical markers, diagnostic methods, treatment modalities, and results of treatment during follow-up.
Results Seven patients who underwent treatment of symptomatic PD were included in the study. The median for follow-up period was 8 years (from 26 months to 16 years). Male-to-female ratio was 4:3 and the median age at presentation was 11 years (2–14 years). Presenting symptoms were recurrent episodic epigastric pain. Pancreatitis was documented by elevated amylase or lipase levels. Endoscopic retrograde cholangiopancreatography (ERCP) was the method of diagnosis of PD in all patients. Five patients had complete PD and two had incomplete variants. Three patients improved after ERCP papillotomy. In three patients, papillotomy was unsuccessful but they have only mild episodes of pancreatitis. One patient presented at the age of 4 years with recurrent pancreatitis. She was treated surgically by duodenum-preserving resection of the pancreatic head (DPRPH) because of severe recurrent pancreatitis occurring even after ERCP papillotomy. The patient is 26 months after operation without any reported problems.
Conclusion Patients with symptomatic PD are indicated for ERCP papillotomy attempt. If there is not improvement after ERCP, then recurrent bouts of severe pancreatitis are considered as an indication for surgical procedure. DPRPH is a safe and feasible surgical alternative.
Treatment of Mandibular Angle Fractures with Single Three-Dimensional Locking Miniplates without Maxillomandibular Fixation: How Much Fixation is Required?
Authors: Rastogi Sanjay , Paul Sam , Kukreja Sumedha , Aggarwal Karun , Choudhury Rupshikha , Bhugra Amit , Niranjana Prasad Indra B. , Jawaid Moazzam 
Published: March 2017

The aim of this simple nonrandomized and observational study was to evaluate the efficacy of single three-dimensional (3D) plate for the treatment of mandibular angle fractures without maxillomandibular fixation.A total of 30 patients with noncomminuted fractures of mandibular angle requiring open reduction and internal fixation were included in the study. All the patients were treated by open reduction and internal fixation using single 3D titanium locking miniplate placed with the help of transbuccal trocar or Synthes 90-degree hand piece and screw driver. 3D locking titanium miniplates used in our study was four-holed, box-shaped plate, and screws with 2 mm diameter and 8 mm length. The following clinical parameters were assessed for each patient at each follow-up visit: pain (visual analog scale: 0–5), swelling (visual analog scale: 0–5), mouth opening, infection, paresthesia, hardware failure (plate fracture), occlusal discrepancies, and mobility between fracture fragments.A significant decrease in pain level was seen during the follow-up visits. No statistically significant changes were seen in swelling, but mouth opening increased in the subsequent visits. Also better results were seen in terms of fracture stability and occlusion in the postoperative period. Two cases of infection and two cases of hardware failure were noted in sixth postoperative week.3D plating system is an easy to use alternative to conventional miniplates to treat mandibular angle fractures that uses lesser foreign material, thus reducing the operative time and overall cost of the treatment. Better fracture stability and occlusion was also achieved using the 3D plating system.
Genotyp-Phänotyp-Korrelation bei Patienten mit CRB1-Mutationen
Authors: Papadopoulou Laiou C. , Preising M. , Bolz H. , Lorenz B. 
Published: March 2017

Zusammenfassung
Hintergrund Mutationen im CRB1-Gen wurden bei frühkindlicher schwerer Netzhautdegeneration (EOSRD, early-onset severe retinal dystrophy) und Stäbchen-Zapfen-Degeneration des Kindesalters identifiziert. Diese Studie beschreibt das phänotypische Spektrum bei krankheitsverursachenden CRB1-Mutationen in den ersten beiden Lebensdekaden.
Material und Methoden Acht Patienten im Alter von 3 Monaten bis 20 Jahren wurden einer ophthalmologischen Untersuchung mit Prüfung des bestkorrigierten Visus (BCVA), Farbsehprüfung, Funduskopie, optischer Kohärenztomografie (SD-OCT) und Fundusautofluoreszenz (FAF) unterzogen. Die SD-OCTs wurden mit der DIOCTA-Auswertesoftware sowie manuell einer Schichtanalyse unterzogen. In Abhängigkeit von der Kooperationsfähigkeit der Patienten wurden eine Ganzfeldelektroretinografie (ffERG, ISCEV-Standard) sowie eine Goldmann-Perimetrie durchgeführt.
Ergebnisse Fünf der Patienten trugen Mutationen, die zu einem Verlust des Genproduktes führten (Spleißmutationen, Nonsense-Mutationen, Leserasterverschiebungen) und zeigten bereits in den ersten Lebensmonaten ein massiv reduziertes Sehvermögen (BCVAmax: 0,04). Der 6. Patient trug eine homozygote Missense-Mutation und zeigte im Alter von 6 Jahren einen BCVAmax von 0,05. Zwei weitere Patienten mit einer hypomorphen Missense-Mutation auf mindestens einem Allel zeigten einen besseren Visuserhalt mit BCVA bis zu 0,5 im Alter von 20 Jahren. Das ffERG lag bei allen Patienten unter der Norm und war bei der Mehrheit nicht mehr ableitbar. Das Gesichtsfeld war stark eingeschränkt. Die Photorezeptorschichten waren im SD-OCT, soweit überhaupt abgrenzbar, deutlich reduziert. Die Schichtdicke der inneren Körnerschicht nahm mit zunehmender Degeneration zu. Die Analyse der A-Scans zwischen Nervenfaserschicht (RNFL) und Bruch-Membran zeigte eine besser erhaltene Netzhautschichtung bei den Patienten mit Missense-Mutationen.
Schlussfolgerung Patienten mit CRB1-Mutationen zeigen in erster Linie einen schweren Phänotyp mit stark reduziertem Sehvermögen von Geburt an. Missense-Mutationen mit einer möglichen Restfunktion des Genprodukts sind mit leichteren Phänotypen assoziiert. Eine schwere und progrediente Gesichtsfeldeinschränkung war allgemein in der 1. Lebensdekade vorhanden. Die reduzierte Abgrenzbarkeit der retinalen Schichtung im SD-OCT deutet auf einen Verlust der strukturellen Integrität aller Netzhautschichten hin.
Trk receptor signaling and sensory neuron fate are perturbed in human neuropathy caused by
Gars
mutations
Authors: Sleigh James N. , Dawes John M. , West Steven J. , Wei Na , Spaulding Emily L. , Gómez-Martín Adriana , Zhang Qian , Burgess Robert W. , Cader M. Zameel , Talbot Kevin , Yang Xiang-Lei , Bennett David L. , Schiavo Giampietro 
Published: March 2017

Significance
The mechanisms triggering motor and sensory nerve dysfunction in the genetically diverse Charcot–Marie–Tooth disease (CMT) remain unresolved, as does the reason for the lack of sensory pathology observed in distal hereditary motor neuropathies, which can be associated with CMT genes. To unravel the pathways leading to afferent deterioration, we have studied the sensory nervous system of CMT type 2D (CMT2D) mice. Our work demonstrates that the specific cellular identity of sensory nerves is perturbed in mutant mice prenatally, and that this is likely caused by aberrant interaction of mutant CMT2D protein with Trk receptors impacting their prodifferentiation/development signaling. CMT therefore manifests through malfunctioning of the complex interplay between developmental, maturation, and survival programs, which has important implications for therapeutic timing.
ErbB2 regulates autophagic flux to modulate the proteostasis of APP-CTFs in Alzheimer’s disease
Authors: Wang Bo-Jeng , Her Guor Mour , Hu Ming-Kuan , Chen Yun-Wen , Tung Ying-Tsen , Wu Pei-Yi , Hsu Wen-Ming , Lee Hsinyu , Jin Lee-Way , Hwang Sheng-Ping L. , Chen Rita P.-Y. , Huang Chang-Jen , Liao Yung-Feng 
Published: March 2017

Significance
We demonstrate that ErbB2 can regulate autophagic flux through its direct interaction with Beclin-1, which effectively blocks autophagy initiation. Although the expression of ErbB2 becomes dormant during adulthood, it becomes reactivated during the pathogenesis of Alzheimer’s disease (AD), blocking the autophagy-mediated clearance of amyloid precursor protein (APP) C-terminal fragments (CTFs) [99-residue CTF (C99)]. Consequently, the accumulated APP-C99 can be further processed by γ-secretase, resulting in augmented production of amyloid-β and the APP intracellular domain. The chemical inhibition of ErbB2 by CL-387,785 effectively rescues the cognitive impairment of APP/presenilin-1 (PS1) transgenic AD mice. The present study thus defines a molecular basis by which the aberrant expression of ErbB2 could instigate the pathogenesis of AD. These findings provide the proof-of-principle evidence for rational design of ErbB2-targeted therapeutics for AD.
Pore translocation of knotted DNA rings
Authors: Suma Antonio , Micheletti Cristian 
Published: March 2017

Significance
Pore translocation, the driven passage of molecules through narrow channels, has become an important tool for probing DNA properties. In a recent breakthrough experiment, this technique was used to detect knots that form spontaneously in DNA filaments and can hence impact their in vivo functionality. Here, by using an accurate model, we simulate the translocation of knotted DNA, expose its unexpectedly rich phenomenology, and clarify the implications for experiments. We show that knot translocation occurs in two possible modes, depending on the knot initial position and size. These properties also account for the typically late occurrence of the knot passage event. Finally, the passage duration is found to depend more on the translocation velocity of the knot than its size.