bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Complex GNAS Imprinted Locus and Mesenchymal Stem Cells
Differentiation
Authors: Elli F. M. , Boldrin V. , Pirelli A. , Spada A. , Mantovani G. 
Published: October 2016

AbstractAll tissues and organs derive from stem cells, which are undifferentiated cells
able to differentiate into specialized cells and self-renewal. In mammals, there
are embryonic stem cells that generate germ layers, and adult stem cells, which
act as a repair system for the body and maintain the normal turnover of
regenerative organs. Mesenchymal stem cells (MSCs) are nonhematopoietic adult
multipotent cells, which reside in virtually all postnatal organs and tissues,
and, under appropriate in vitro conditions, are capable to differentiate into
osteogenic, adipogenic, chondrogenic, myogenic, and neurogenic lineages. Their
commitment and differentiation depend on several interacting signaling pathways
and transcription factors. Most GNAS-based disorders have the common feature of
episodic de novo formation of islands of extraskeletal, qualitatively normal,
bone in skin and subcutaneous fat. The tissue distribution of these lesions
suggests that pathogenesis involves abnormal differentiation of MSCs and/or more
committed precursor cells that are present in subcutaneous tissues. Data coming
from transgenic mice support the concept that GNAS is a key factor in the
regulation of lineage switching between osteoblast and adipocyte fates, and that
its role may be to prevent bone formation in tissues where bone should not form.
Despite the growing knowledge about the process of heterotopic ossification in
rare genetic disorders, the pathophysiological mechanisms by which alterations
of cAMP signaling lead to ectopic bone formation in the context of mesenchymal
tissues is not fully understood.
Nanomechanical mechanism for lipid bilayer damage induced by carbon nanotubes confined in intracellular vesicles
Authors: Zhu Wenpeng , von dem Bussche Annette , Yi Xin , Qiu Yang , Wang Zhongying , Weston Paula , Hurt Robert H. , Kane Agnes B. , Gao Huajian 
Published: October 2016

Significance
Recent experimental studies report correlations between carbon nanotube toxicity and tube length and stiffness. Very little is known, however, about the actual behavior of these fibrous nanomaterials inside living cells following uptake, and the fundamental mechanistic link between stiffness and toxicity is unclear. Here we reveal a nanomechanical mechanism by which sufficiently long and stiff carbon nanotubes damage lysosomes, a class of membrane-enclosed organelles found inside cells that are responsible for breaking down diverse biomolecules and debris. The precise material parameters needed to activate this unique mechanical toxicity pathway are identified through coupled theoretical modeling, molecular dynamics simulations, and experimental studies, leading to a predictive pathogenicity classification diagram that distinguishes toxic from biocompatible nanomaterials based on their geometry and stiffness.
Hepatitis C virus promotes virion secretion through cleavage of the Rab7 adaptor protein RILP
Authors: Wozniak Ann L. , Long Abby , Jones-Jamtgaard Kellyann N. , Weinman Steven A. 
Published: October 2016

Significance
Viruses frequently alter cellular processes to promote their own lifecycle, whereas cells adapt by initiating antiviral responses. Therefore, the outcome of viral disease depends on the balance of these factors. Hepatitis C virus (HCV) induces drastic modifications in cellular vesicle trafficking that appear to be required for the formation of viral replication complexes and the assembly/secretion of viral particles. We show that HCV promotes the production and secretion of infectious virus particles by disrupting Rab7 complexes, shifting microtubule-associated vesicles from the inwardly directed dynein motor to the outwardly directed kinesin motor complex. This shift targets them toward the cell surface. This finding that viruses cleave the Rab adaptor proteins provides insight into how viruses alter trafficking to promote virus propagation.
Human cortical–hippocampal dialogue in wake and slow-wave sleep
Authors: Mitra Anish , Snyder Abraham Z. , Hacker Carl D. , Pahwa Mrinal , Tagliazucchi Enzo , Laufs Helmut , Leuthardt Eric C. , Raichle Marcus E. 
Published: October 2016

Significance
Reciprocal cortical–hippocampal signaling is widely believed to underlie consolidation of declarative memories. By investigating human fMRI and electrocorticography during both wake and slow-wave sleep (SWS), we find, first, that δ-band activity and infraslow activity propagate in opposite directions between the hippocampus and cortex. Second, both δ activity and infraslow activity reverse propagation directions between the hippocampus and the cortex across wake and SWS. These results highlight reciprocal communication between frequencies, and constitute direct evidence for the reversal of the human cortical–hippocampal dialogue across wake and SWS.
Sharpening vision by adapting to flicker
Authors: Arnold Derek H. , Williams Jeremy D. , Phipps Natasha E. , Goodale Melvyn A. 
Published: October 2016

Significance
Distinct anatomical visual pathways can be traced through the human central nervous system. These have been linked to specialized functions, such as encoding information about spatial forms (like the human face and text) and stimulus dynamics (flicker or movement). Our experiments are inconsistent with this strict division. They show that mechanisms responsive to flicker can alter form perception, with vision transiently sharpened by weakening the influence of flicker-sensitive mechanisms by prolonged exposure to flicker. So, next time you are trying to read fine print, you might be well advised to first view a flickering stimulus!
Immune cell screening of a nanoparticle library improves atherosclerosis therapy
Authors: Tang Jun , Baxter Samantha , Menon Arjun , Alaarg Amr , Sanchez-Gaytan Brenda L. , Fay Francois , Zhao Yiming , Ouimet Mireille , Braza Mounia S. , Longo Valerie A. , Abdel-Atti Dalya , Duivenvoorden Raphael , Calcagno Claudia , Storm Gert , Tsimikas Sotirios , Moore Kathryn J. , Swirski Filip K. , Nahrendorf Matthias , Fisher Edward A. , Pérez-Medina Carlos , Fayad Zahi A. , Reiner Thomas , Mulder Willem J. M. 
Published: October 2016

Significance
The immune system plays an essential role in the pathophysiology of major diseases such as atherosclerosis, diabetes, and cancer, which has inspired the development of numerous small molecules to modulate immune cells, intending to create immunotherapies for these diseases. Tissue- and cell-specific delivery of these small molecules is the key to transform these compounds to safe, potent immunotherapies. In this study, we present an in vivo nanoparticle screen approach that involves designing and evaluating a library of nanoparticles with distinct immune cell targeting specificity. This study carries out a systematic in vivo immune cell screening to create effective nanoparticle-based immunotherapy for modulating the pathological immune cells in atherosclerosis.
Targeted vaccination against the bevacizumab binding site on VEGF using 3D-structured peptides elicits efficient antitumor activity
Authors: Wentink Madelon Q. , Hackeng Tilman M. , Tabruyn Sebastien P. , Puijk Wouter C. , Schwamborn Klaus , Altschuh Daniele , Meloen Rob H. , Schuurman Teun , Griffioen Arjan W. , Timmerman Peter 
Published: October 2016

Significance
VEGF is the pivotal growth factor for angiogenesis, and its inhibition by passive immunotherapy results in improved survival in patients with several types of cancer. We believe that the clinical benefit could be increased by inducing a humoral immune response against VEGF through active immunization with VEGF-based peptides. In this study, we describe that correct peptide design is vital for success. We show that only 3D-structured peptides perfectly mimicking the crucial β5–turn–β6 loop of endogenous VEGF are able to induce neutralizing antibodies. We developed a vaccine with potent in vitro and in vivo VEGF-neutralizing activities, as shown in passive and active immunization tumor models. The VEGF vaccination strategy has the potential to outperform current clinical anti-VEGF treatment strategies.
Capture of micrococcin biosynthetic intermediates reveals C-terminal processing as an obligatory step for in vivo maturation
Authors: Bewley Kathryn D. , Bennallack Philip R. , Burlingame Mark A. , Robison Richard A. , Griffitts Joel S. , Miller Susan M. 
Published: October 2016

Significance
Antimicrobial thiopeptides constitute a broad family of natural compounds that are ribosomally synthesized and posttranslationally modified. This paper reports the characterization of a biosynthetic pathway for the production of the canonical thiopeptide micrococcin. These biochemical details were acquired by reconstituting the pathway in a genetically manipulable laboratory organism and then isolating and characterizing partially synthesized thiopeptide intermediates. Our findings highlight strict sequential order of biochemical conversions leading to the micrococcin product and pave the way toward using this understanding to engineer antimicrobial compounds with clinically useful properties.
Chilling-induced tomato flavor loss is associated with altered volatile synthesis and transient changes in DNA methylation
Authors: Zhang Bo , Tieman Denise M. , Jiao Chen , Xu Yimin , Chen Kunsong , Fei Zhangjun , Giovannoni James J. , Klee Harry J. 
Published: October 2016

Significance
Cold storage is widely used to extend shelf-life of agriculture products. For tomato, this handling results in reduced flavor quality. Our work provides major insights into the effects of chilling on consumer liking, the flavor metabolome and transcriptome, as well as DNA methylation status. Transcripts for some key volatile synthesis enzymes and the most important ripening-associated transcription factors are greatly reduced in response to chilling. These reductions are accompanied by major changes in the methylation status of promoter regions. Transient increases in DNA methylation occur during chilling. Our analysis provides insight into the molecular mechanisms of tomato fruit flavor loss caused by chilling.
Structural basis of recognition of farnesylated and methylated KRAS4b by PDEδ
Authors: Dharmaiah Srisathiyanarayanan , Bindu Lakshman , Tran Timothy H. , Gillette William K. , Frank Peter H. , Ghirlando Rodolfo , Nissley Dwight V. , Esposito Dominic , McCormick Frank , Stephen Andrew G. , Simanshu Dhirendra K. 
Published: October 2016

Significance
Despite the significant progress made in the last few years toward targeting phosphodiesterase-δ (PDEδ) for KRAS (Kirsten rat sarcoma isoform)-driven cancers, there is no structural information available on posttranslationally modified KRAS4b in complex with PDEδ. The KRAS4b–PDEδ structure reported here provides the structural details of the protein–protein interaction interface and the atomic details of the hypervariable region of KRAS4b. Structural comparison of the two crystal forms allowed identification of a 5-aa-long sequence motif in KRAS4b that could allow PDEδ to bind to both farnesylated and geranylgeranylated KRAS4b. Structural insights obtained from this study could be used to guide the development of improved and more specific inhibitors of the KRAS4b–PDEδ complex.
Speech function analysis to explore CLIL students’ spoken language for knowledge construction
Authors: Llinares Ana , Morton Tom 
Published: October 2016

Abstract
This chapter focuses on the register variable of tenor within systemic functional linguistics (SFL) to examine spoken interaction involving secondary CLIL history learners in two contexts: one-to-one interviews with a researcher, and role-plays with peers. Tenor refers to the role relationship between interactants, and its impact on language use. We adapt speech function analyses developed by Eggins and Slade (1997) for ordinary conversation to settings in which CLIL learners jointly construct aspects of content knowledge in one subject, history. The findings show that the negotiation and roles assigned to participants impacted on the ways the learners managed to construct history content knowledge. We argue that speech function analysis can throw light on how role relationships in spoken interaction can create or restrict affordances for the expression of content knowledge in CLIL.
LRFragLib: an effective algorithm to identify fragments for de novo protein structure prediction
Authors: Wang Tong , Yang Yuedong , Zhou Yaoqi , Gong Haipeng 
Published: October 2016

Abstract

Motivation
The quality of fragment library determines the efficiency of fragment assembly, an approach that is widely used in most de novo protein-structure prediction algorithms. Conventional fragment libraries are constructed mainly based on the identities of amino acids, sometimes facilitated by predicted information including dihedral angles and secondary structures. However, it remains challenging to identify near-native fragment structures with low sequence homology.

Results
We introduce a novel fragment-library-construction algorithm, LRFragLib, to improve the detection of near-native low-homology fragments of 7–10 residues, using a multi-stage, flexible selection protocol. Based on logistic regression scoring models, LRFragLib outperforms existing techniques by achieving a significantly higher precision and a comparable coverage on recent CASP protein sets in sampling near-native structures. The method also has a comparable computational efficiency to the fastest existing techniques with substantially reduced memory usage.

Availability and Implementation
The source code is available for download at http://166.111.152.91/Downloads.html

Supplementary information
Supplementary data are available at Bioinformatics online.
A massive dense gas cloud close to the nucleus of the Seyfert galaxy NGC 1068
Authors: Furuya Ray S. , Taniguchi Yoshiaki 
Published: October 2016

Abstract
Using the ALMA archival data of both 12CO (6–5) line and 689-GHz continuum emission towards the archetypical Seyfert galaxy, NGC 1068, we identified a distinct continuum peak separated by 15 pc from the nuclear radio component S1 in projection. The continuum flux gives a gas mass of ∼2 × 105 M⊙ and bolometric luminosity of ∼108 L⊙, leading to a star formation rate of ∼0.1 M⊙ yr−1. Subsequent analysis on the line data suggest that the gas cloud has a size of ∼10 pc, yielding to a mean H2 number density of ∼105 cm−3. We therefore refer to the gas as a “massive dense gas cloud”: the gas density is high enough to form a “protostar cluster” with a stellar mass of ∼104 M⊙. We found that the gas stands at a unique position between galactic and extraglactic clouds in the diagrams of start formation rate (SFR) vs. gas mass proposed by Lada et al. (2012, ApJ, 745, 190) and surface density of gas vs. SFR density by Krumholz and McKee (2005, ApJ, 630, 250). All the gaseous and star-formation properties may be understood in terms of the turbulence-regulated star formation scenario. Since there are two stellar populations with ages of 300 Myr and 30 Myr in the 100 pc scale circumnulear region, we discuss that NGC 1068 has experienced at least three episodic star-formation events with the likelihood that the inner star-forming region is the younger. Together with several lines of evidence that the dynamics of the nuclear region is decoupled from that of the entire galactic disk, we discuss that the gas inflow towards the nuclear region of NGC 1068 may be driven by a past minor merger.
Fabrication of Waterproof, Breathable Composite Liquid Dressing and Its Application in Diabetic Skin Ulcer Repair
Authors: Xia Dong-Lin , Chen Yan-Pei , Wang Yu-Fei , Li Xiao-Dong , Bao Ning , He Hong , Gu Hai-Ying 
Published: October 2016

ABSTRACT

OBJECTIVES:
Diabetic patients are at increased risk of severe skin infections. Covering the wound as early as possible can prevent infection and shorten the course of treatment. In this study, the authors fabricated a waterproof and breathable composite liquid dressing (CLD) that formed a barrier to bacteria and shortened healing time of diabetic rat skin ulcers.

METHODS:
The CLD was prepared in a formulation that, on evaporation of the liquid carrier, acts as a waterproof, breathable coating on injured skin. The coating was analyzed for water resistance, moisture vapor transmission rate (MVTR), bacterial barrier properties, sustained-release function, and biosafety. A chemically induced rat model of diabetic foot ulcers was used to examine the wound healing effect of CLD and CLD that contained Dermlin (Yensen Biotech Co, Jiangyin, Jiangsu, China). The wound healing rate, histologic changes, and epidermal growth factor expression were also evaluated.

RESULTS:
The CLD functioned as an effective barrier against infection, was waterproof, had a suitable MVTR, and had effective biosafety. The synergistic effects of CLD and Dermlin had a rapid wound closure rate. Histologic analysis and measurement of epidermal growth factor expression through an in vivo test revealed that the possible mechanism of the CLD effects included the reduction of inflammation and promotion of cell proliferation.

CONCLUSIONS:
Early treatment with the CLD can prevent infection. In combination with Dermlin, the CLD may promote better wound closure in diabetic skin ulcers. The authors’ study suggests a novel strategy for ulcer healing.
Pressure Ulcers in the Intensive Care Unit: An Analysis of Skin Barrier Risk Factors
Authors: He Minjuan , Tang Amao , Ge Xuedi , Zheng Jie 
Published: October 2016

ABSTRACT

OBJECTIVE:
The aim of this study was to determine whether skin barrier factors were associated with the common complication of pressure ulcers (PrUs) in intensive care unit (ICU) patients. It is unclear whether skin barrier factors influence the development of PrUs.

PATIENT POPULATION:
The sample was composed of 102 ICU patients (54 men, 48 women). The patients ranged in age from 23 to 88 years, with a mean age of 55.7 (SD, 19.1) years.

METHODS:
Demographic variables and the score for the Acute Physiology and Chronic Health Evaluation IV were recorded on admission. The Braden Scale assessment and measurements of the skin barrier factors were performed daily. Standard care for the prevention of PrUs was strictly administered, and PrUs that developed were evaluated according to the recommendations of the US National Pressure Ulcer Advisory Panel 2007 (Note: The authors used the 2007 recommendations at the time of their study.). Data were analyzed using descriptive statistics and logistic regression.

RESULTS:
The mean score for the Braden Scale was 11.2, and the incidence of PrUs was 31.4%. Lower moisture content of the stratum corneum and higher skin surface pH at the lower sacrum and hip were risk factors for PrUs, whereas scapular and heel skin barrier factors were not.

CONCLUSION:
Nursing strategies aimed at preventing PrUs should place added emphasis on the lower sacral and hip regions.
Systemic vasculitis and the lung
Authors: Talarico Rosaria , Barsotti Simone , Elefante Elena , Baldini Chiara , Tani Chiara , Mosca Marta 
Published: October 2016

Purpose of review
The purpose of this review is to provide a critical analysis of the recent literature on this topic, with particular focus on the most relevant studies published over the last year.

Recent findings
Many studies are published every year on the diagnosis, pathogenesis and treatment of pulmonary involvement in antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV). The main subjects covered by this article are the pathogenesis, diagnosis and clinical aspects of lung involvement in ANCA-associated vasculitis and non-ANCA-associated vasculitis.

Summary
Lung involvement is a common feature in systemic vasculitis. The lungs are one of the most frequently involved organs in systemic vasculitis. In order to provide an update on the recent advances in the pathogenesis, clinical features and novel treatments of lung involvement in systemic vasculitis, a systematic MedLine search has been performed.
Most of the data analyzed have confirmed that lung involvement seems to develop more frequently in patients with myeloperoxidase-ANCA-positive AAV, mainly in those with a diagnosis of microscopic polyangiitis (MPA), compared with patients with proteinase 3 ANCA-positive AAV. Moreover, among non-ANCA-associated vasculitis lung involvement may represent a worrying complication of the disease, mainly when associated with vascular involvement.
Buttress Plating Versus Anterior-to-Posterior Lag Screws for Fixation of the Posterior Malleolus: A Biomechanical Study
Authors: Bennett Chase , Behn Anthony , Daoud Adam , Nork Sean , Sangeorzan Bruce , Dikos Gregory , Bishop Julius 
Published: October 2016

Objectives:
The preferred method of fixation for posterior malleolus fractures remains controversial, and practices vary widely among surgeons. The purpose of this study was to compare anterior-to-posterior (AP) lag screws with posterior buttress plating for fixation of posterior malleolus fractures in a human cadaveric model.

Methods:
Posterior malleolus fractures involving 30% of the distal tibial articular surface were created in 7 pairs of fresh frozen cadaveric ankles. One specimen in each pair was randomly assigned to fixation with either 2 AP lag screws or a one-third tubular buttress plate without supplemental lag screws. Each specimen was then subjected to cyclic loading from 0% to 50% of body weight for 5000 cycles followed by loading to failure. Outcome measures included permanent axial displacement during each test cycle (axial displacement at no load), peak axial displacement during each test cycle (axial displacement at 50% body weight), load at 1-mm axial displacement, ultimate load, and axial displacement at ultimate load.

Results:
The buttress plate group showed significantly less peak axial displacement at all time points during cyclic loading. Permanent axial displacement was significantly less in the buttress plate group beginning at cycle 200. There were no significant differences between the 2 groups during load-to-failure testing.

Conclusion:
Posterior malleolus fractures treated with posterior buttress plating showed significantly less displacement during cyclical loading compared with fractures fixed with AP lag screws. Surgeons should consider these findings when selecting a fixation strategy for these common fractures. Further research is warranted to investigate the clinical implications of these biomechanical findings.