bluuebunny/crossref_metadata_2025 huggingface dataset:
Deposition of homogeneous carbon‐TiO2 composites by atmospheric pressure DBD
Authors: Brunet Paul , Rincón Rocío , Margot Joëlle , Massines Françoise , Chaker Mohamed
Published: November 2016

Atmospheric pressure Dielectric Barrier Discharge (AP‐DBD) was used to deposit homogeneous carbon‐TiO2 composites. Non‐intrusive Laser Light Scattering was employed to study the transport of the nanoparticles across the plasma. The characteristics of the coating were found to depend on the gas flow and on the spray chamber used for introducing the nanoparticles (cyclonic and Scott spray chambers). According to the SEM images, higher gas flows favor the formation of more homogeneous coatings both in terms of thickness and NPs‐aggregates distribution regardless of the spray chamber. The Scott spray chamber was shown to be more efficient for the deposition of uniform coatings even at low gas flows. It also yields the highest Ti concentration that reaches up to 18%. Furthermore, the light scattered by the nanoparticles was shown to be directly related to the coating thickness, hence to the density of nanoparticles in the plasma.
The putative involvement of actin‐binding proteins and cytoskeleton proteins in pathological mechanisms of ketamine cystitis—Revealed by a prospective pilot study using proteomic approaches
Authors: Yang Hsueh‐Hui , Zhai Wei‐Jun , Kuo Hann‐Chorng
Published: November 2016

Purpose

Ketamine‐induced cystitis (KC) among chronic ketamine young abusers has increased dramatically and it has brought attention for Urologists. The underlying pathophysiological mechanism(s) of KC is still unclear. Therefore, the purpose of this study is to elucidate the possible pathophysiological mechanism(s) of KC through proteomic techniques.

Experimental design

Bladder tissues are obtained from seven patients with KC, seven patients with interstitial cystitis/bladder pain syndrome, and five control subjects who underwent video‐urodynamic study followed by augmentation enterocystoplasty to increase bladder capacity. 2DE/MS/MS‐based approach, functional classifications, and network analyses are used for proteomic and bioinformatics analyses and protein validation is carried out by Western blot analysis.

Results

Among the proteins identified, bioinformatics analyses revealed that several actin binding related proteins such as cofilin‐1, myosin light polypeptide 9, filamin A, gelsolin, lamin A are involved in the apoptosis. Besides, the contractile proteins and cytoskeleton proteins such as myosin light polypeptide 9, filamin A, and calponin are found downregulated in KC bladders.

Conclusions and clinical relevance

Increased apoptosis in KC might be mediated by actin‐binding proteins and a Ca2+‐activated protease. Rapid detrusor contraction in KC might be induced by contractile proteins and cytoskeleton proteins.
Appraisal of transplant‐related stressors, coping strategies, and psychosocial adjustment following kidney transplantation
Authors: Pisanti Renato , Lombardo Caterina , Luszczynska Aleksandra , Poli Luca , Bennardi Linda , Giordanengo Luca , Berloco Pasquale Bartolomeo , Violani Cristiano
Published: November 2016

This study examined the relations between appraisal of transplant‐related stressors, coping, and adjustment dimensions following kidney transplantation (KT). Two models were tested: (1) the main effects model proposing that stress appraisal and coping strategies are directly associated with adjustment dimensions; and (2) the moderating model of stress proposing that each coping strategy interacts with stress appraisal. Importantly, there is a lack of research examining the two models simultaneously among recipients of solid organ transplantation.

A total of 174 KT recipients completed the questionnaires. Predictors of post‐transplant adjustment included appraisal of transplant‐related stressors and coping strategies (task‐, emotion‐, and avoidance‐focused). Adjustment dimensions were psychological distress, worries about the transplant, feelings of guilt, fear of disclosure of transplant, adherence, and responsibility for the functioning of the new organ. The main and moderating effects were tested with regression analyses.

Appraisal of transplant‐related stressors and emotion‐oriented coping were related to all adjustment dimensions, except of adherence and responsibility. Task‐oriented coping was positively related to responsibility. Avoidance‐oriented coping was negatively correlated with adherence. Only 1 out of 18 hypothesized interactive terms was significant, yielding a synergistic interaction between appraisal of transplant‐related stressors and emotion‐oriented coping on the sense of guilt.

The findings have the potential to inform interventions promoting psychosocial adjustment among KT recipients.
Secreted Ectodomain of Sialic Acid-Binding Ig-Like Lectin-9 and Monocyte Chemoattractant Protein-1 Synergistically Regenerate Transected Rat Peripheral Nerves by Altering Macrophage Polarity
Authors: Kano Fumiya , Matsubara Kohki , Ueda Minoru , Hibi Hideharu , Yamamoto Akihito
Published: November 2016

Peripheral nerves (PNs) exhibit remarkable self-repairing reparative activity after a simple crush or cut injury. However, the neuronal transection involving a nerve gap overwhelms their repairing activity and causes persistent paralysis. Here, we show that an implantation of the serum-free conditioned medium from stem cells from human exfoliated deciduous teeth (SHED-CM) immersed in a collagen sponge into the nerve gap formed by rat facial nerves transection restored the neurological function. In contrast, SHED-CM specifically depleted of a set of anti-inflammatory M2 macrophage inducers, monocyte chemoattractant protein-1 (MCP-1) and the secreted ectodomain of sialic acid-binding Ig-like lectin-9 (sSiglec-9) lost the ability to restore neurological function in this model. Notably, the combination of MCP-1 and sSiglec-9 induced the polarization of M2 macrophages in vitro, resulting in the expression of multiple trophic factors that enhanced proliferation, migration, and differentiation of Schwann cells, blood vessel formation, and nerve fiber extension. Furthermore, the implantation of a collagen graft containing MCP-1/sSiglec-9 into the nerve gap induced anti-inflammatory M2 macrophage polarization, generated a Schwann-cell bridge instead of fibrotic scar, induced axonal regrowth, and restored nerve function. The specific elimination of M2 macrophages by Mannosylated-Clodrosome suppressed the MCP-1/sSiglec-9-mediated neurological recovery. Taken together, our data suggest that MCP-1/sSiglec-9 regenerates PNs by inducing tissue-repairing M2 macrophages and may provide therapeutic benefits for severe peripheral nerve injuries.
Evolution acceptance and epistemological beliefs of college biology students
Authors: Borgerding Lisa A. , Deniz Hasan , Anderson Elizabeth Shevock
Published: November 2016

Evolutionary theory is central to biology, and scientifically accurate evolution instruction is promoted within national and state standards documents. Previous literature has identified students’ epistemological beliefs as potential predictors of evolution acceptance. The present work seeks to explore more directly how student views of evolution are related to their epistemological beliefs. We hypothesize that evolution acceptance may be related to students’ epistemological beliefs and that this relationship may vary depending on students’ relationship to the field of biology, either as an experienced major, a new major, or a non‐major. Specifically, this manuscript investigates how college students’ evolution acceptance may be connected to Perry developmental levels for three distinct groups of students: upper‐level majors, first‐year majors, and non‐majors. A sequential explanatory mixed methods approach entailing quantitative surveys followed by individual interviews was employed. In total, 395 college‐level biology students from three classes were surveyed, and 44 students were interviewed. Descriptive quantitative trends were identified, and evolution acceptance varied predictably by both Perry level and Class. Qualitative analysis explained these quantitative findings in terms of participants’ identification with science, views of authority, views of the compatibility of evolution and religion, and appreciation for the tentative nature of science with respect to evolution. Potential implications for science educators at the college level are discussed. © 2016 Wiley Periodicals, Inc. J Res Sci Teach 54: 493–519, 2017
Surgical Treatment Results of Burn‐Related Oesophageal Strictures
Authors: Włodarczyk Janusz , Smęder Tomasz , Kużdżał Jarosław
Published: November 2016

Background

Post‐burn oesophageal stricture is a late complication, which may require surgical intervention. The aim of the study was to compare gastric and colonic conduits and to evaluate the safety, efficacy and complications of these techniques.

Methods

Retrospective analysis of all patients treated for burn‐related oesophageal strictures between 1989 and 2013. Oesophagectomy was performed via laparotomy and right thoracotomy, and/or cervical incision.

Results

Forty‐six patients, including 29 men, aged 17–67 years (mean: 41 years), had burn‐related oesophageal strictures. The post‐operative follow‐up period ranged between 3 months and 30 years. Colonic transposition was used in 23 patients. In 21 patients, the oesophageal substitute was introduced through the posterior mediastinum, and in two patients the retrosternal route was used. Gastric conduit in was used in 21 patients and jejunal interposition in one patient. One patient underwent segmental oesophageal resection with end‐to‐end anastomosis. One patient had necrosis of the colonic conduit with anastomotic leakage, two patients had oesophago‐colonic anastomosis leakage, five developed anastomotic stenosis, and two had respiratory insufficiency. Among patients with a gastric conduit, anastomotic leakage occurred in four, cervical anastomotic stenosis occurred in two, and respiratory insufficiency occurred in three, and one patient had impaired gastric emptying that required surgical re‐intervention. Operative mortality was three patients (6.5%).

Conclusions

The use of colonic and gastric conduit is an effective and safe method for restoring the continuity of the gastrointestinal tract, with an acceptable rate of post‐operative complications. Patients who undergo oesophageal resection for post‐burn stricture require post‐operative systematic endoscopic control.
High-throughput FTIR-based bioprocess analysis of recombinant cyprosin production
Authors: Sampaio Pedro N , Sales Kevin C , Rosa Filipa O , Lopes Marta B , Calado Cecília R C
Published: November 2016

To increase the knowledge of the recombinant cyprosin production process in Saccharomyces cerevisiae cultures, it is relevant to implement efficient bioprocess monitoring techniques. The present work focuses on the implementation of a mid-infrared (MIR) spectroscopy-based tool for monitoring the recombinant culture in a rapid, economic, and high-throughput (using a microplate system) mode. Multivariate data analysis on the MIR spectra of culture samples was conducted. Principal component analysis (PCA) enabled capturing the general metabolic status of the yeast cells, as replicated samples appear grouped together in the score plot and groups of culture samples according to the main growth phase can be clearly distinguished. The PCA-loading vectors also revealed spectral regions, and the corresponding chemical functional groups and biomolecules that mostly contributed for the cell biomolecular fingerprint associated with the culture growth phase. These data were corroborated by the analysis of the samples’ second derivative spectra. Partial least square (PLS) regression models built based on the MIR spectra showed high predictive ability for estimating the bioprocess critical variables: biomass (R2 = 0.99, RMSEP 2.8%); cyprosin activity (R2 = 0.98, RMSEP 3.9%); glucose (R2 = 0.93, RMSECV 7.2%); galactose (R2 = 0.97, RMSEP 4.6%); ethanol (R2 = 0.97, RMSEP 5.3%); and acetate (R2 = 0.95, RMSEP 7.0%). In conclusion, high-throughput MIR spectroscopy and multivariate data analysis were effective in identifying the main growth phases and specific cyprosin production phases along the yeast culture as well as in quantifying the critical variables of the process. This knowledge will promote future process optimization and control the recombinant cyprosin bioprocess according to Quality by Design framework.
Herpetiform keratitis and palmoplantar hyperkeratosis: warning signs for Richner‐Hanhart syndrome
Authors: Soares Diogo C. , Stroparo Mariana N. , Lian Yu C. , Takakura Cristina Y. , Wolf Sabrina , Betz Regina , Kim Chong A.
Published: November 2016

Richner‐Hanhart syndrome (RHS, tyrosinemia type II) is a rare, autosomal recessive inborn error of tyrosine metabolism caused by tyrosine aminotransferase deficiency. It is characterized by photophobia due to keratitis, painful palmoplantar hyperkeratosis, variable mental retardation, and elevated serum tyrosine levels. Patients are often misdiagnosed with herpes simplex keratitis. We report on a a boy from Brazil who presented with bilateral keratitis secondary to RHS, which had earlier been misdiagnosed as herpes simplex keratitis.
Genetic Counseling Assistants: an Integral Piece of the Evolving Genetic Counseling Service Delivery Model
Authors: Pirzadeh‐Miller Sara , Robinson Linda S. , Read Parker , Ross Theodora S.
Published: November 2016

This study explores the potential impact of the genetic counseling assistant (GCA) position on the efficiency of the genetic counseling field, evaluates attitudes regarding expansion of the genetic counseling field to include the GCA, and presents data on GCA endeavors and GCA job tasks as reported by GCAs, certified genetic counselors (CGCs), and program directors (PDs). Data on GCA roles and attitudes toward different aspects of the GCA position were collected via surveys of CGCs who have worked with GCAs, PDs who have and have not had experience with GCAs in their programs, and GCAs. We analyzed responses from 63 individuals: 27 PDs, 22 CGCs, and 14 GCAs. GCAs’ impact on efficiency was calculated via internal analysis of genetic patient volume per genetic counselor within the University of Texas Southwestern (UTSW) patient database prior to, and since the addition of, a GCA to the practice. The response rates for PDs, CGCs, and GCAs were 27 %, 79 %, and 61 %, respectively. Every CGC stated the GCA increased their efficiency. CGCs with a GCA reported a 60 % average increase in patient volume. This figure was congruent with internal data from the UTSW cancer genetics program (58.5 % increase). Appropriate responsibilities for GCAs as reported by CGCs and PDs (>90 %) include: data entry, shipping tests, administrative tasks, research, and ordering supplies. Regarding GCAs delivering test results, there was response variation whether this should be a job duty: 42 % of CGCs agreed to GCAs delivering negative results to patients, compared to 22 % of program directors. Twenty‐two percent of PDs expressed concern about the job title “Genetic Counseling Assistant.” Ninety percent of CGCs felt that GCA was a career path to becoming a CGC, compared to 42 % of PDs. Eighty‐three percent of GCAs who decided to apply to CGC graduate programs were accepted. We conclude the addition of a GCA to a genetic counseling practice contributes to increased efficiency and is one way to expand the reach of the profession.
INCREASING THE VERACITY OF IMPLICITLY BIASED RANKINGS
Authors: Jönsson Martin L. , Sjödahl Julia
Published: November 2016

In spite of our good intentions and explicit egalitarian convictions, we habitually disfavor the underprivileged. The rapidly growing literature on implicit bias – unconscious, automatic tendencies to associate negative traits with members of particular social groups – points towards explanations of this dissonance, although rarely towards generalizable solutions. In a recent paper, Jennifer Saul (2013) draws attention to the alarming epistemological problems that implicit bias carries with it; since our judgments about each other are likely influenced by implicit bias, we have good reason to doubt their veracity. In this paper we explore a novel way to come to terms with the epistemological problem as it manifests itself in ranking situations, i.e. how we can know that the way in which we have ranked a group of people for a certain position, reflects their actual competence (or the best estimate of their competence given the evidence). On our approach, rather than attempting to make people less biased, we suggest that biased behavior can sometimes be corrected after the fact. In particular, the veracity of rankings can sometimes be improved by modifying the rankings directly. We investigate three methods that modify biased rankings, and argue that the last of these solves the epistemological problem that we are concerned with.
Topological dynamics of piecewise -affine maps
Authors: NOGUEIRA ARNALDO , PIRES BENITO , ROSALES RAFAEL A.
Published: November 2016

Let $-1<\unicode[STIX]{x1D706}<1$ and let $f:[0,1)\rightarrow \mathbb{R}$ be a piecewise $\unicode[STIX]{x1D706}$-affine contraction: that is, let there exist points $0=c_{0}<c_{1}<\cdots <c_{n-1}<c_{n}=1$ and real numbers $b_{1},\ldots ,b_{n}$ such that $f(x)=\unicode[STIX]{x1D706}x+b_{i}$ for every $x\in [c_{i-1},c_{i})$. We prove that, for Lebesgue almost every $\unicode[STIX]{x1D6FF}\in \mathbb{R}$, the map $f_{\unicode[STIX]{x1D6FF}}=f+\unicode[STIX]{x1D6FF}\,(\text{mod}\,1)$ is asymptotically periodic. More precisely, $f_{\unicode[STIX]{x1D6FF}}$ has at most $n+1$ periodic orbits and the $\unicode[STIX]{x1D714}$-limit set of every $x\in [0,1)$ is a periodic orbit.
A poroelastic fluid–structure interaction model of syringomyelia
Authors: Heil Matthias , Bertram Christopher D.
Published: November 2016

Syringomyelia is a medical condition in which one or more fluid-filled cavities (syrinxes) form in the spinal cord. The syrinxes often form near locations where the spinal subarachnoid space (SSS; the fluid-filled annular region surrounding the spinal cord) is partially obstructed. Previous studies showed that nonlinear interactions between the pulsatile fluid flow in the SSS and the elastic deformation of the tissues surrounding it can generate a fluid pressure distribution that would tend to drive fluid from the SSS into the syrinx if the tissue separating the two regions was porous. This provides a potential explanation for why a partial occlusion of the SSS can induce the growth of an already existing nearby syrinx. We study this hypothesis by analysing the mass transfer between the SSS and the syrinx, using a poroelastic fluid–structure interaction model of the spinal cord that includes a representation of the partially obstructed SSS, the syrinx and the poroelastic tissues surrounding these fluid-filled cavities. Our numerical simulations show that poroelastic fluid–structure interaction can indeed cause an increase (albeit relatively small) in syrinx volume. We analyse the seepage flows and show that their structure can be captured by an analytical model which explains why the increase in syrinx volume tends to be relatively small.
THE IMPACT OF RECASTS ON THE DEVELOPMENT OF PRIMARY STRESS IN A SYNCHRONOUS COMPUTER-MEDIATED ENVIRONMENT
Authors: Parlak Özgür , Ziegler Nicole
Published: November 2016

Although previous research has demonstrated the efficacy of recasts on second language (L2) morphology and lexis (e.g., Li, 2010; Mackey & Goo, 2007), few studies have examined their effect on learners’ phonological development (although see Saito, 2015; Saito & Lyster, 2012). The current study investigates the impact of recasts on the development of lexical stress, defined as the placement of emphasis on a particular syllable within a word by making it louder and longer, in oral synchronous computer-mediated communication (SCMC) and face-to-face (FTF) interaction. Using a pretest-posttest design, intermediate learners of English were randomly assigned to one of four groups: FTF recast, SCMC recast, FTF control, or SCMC control. Pre- and posttests consisted of sentence-reading and information-exchange tasks, while the treatment was an interactive role-play task. Syllable duration, intensity, and pitch were used to analyze learners’ development of stress placement. The statistical analyses of the acoustic correlates did not yield significant differences. However, the observed patterns suggest that there is need for further investigation to understand the relationship between recasts and development of lexical stress.
Oracle-guided scheduling for controlling granularity in implicitly parallel languages
Authors: ACAR UMUT A. , CHARGUÉRAUD ARTHUR , RAINEY MIKE
Published: November 2016

A classic problem in parallel computing is determining whether to execute a thread in parallel or sequentially. If small threads are executed in parallel, the overheads due to thread creation can overwhelm the benefits of parallelism, resulting in suboptimal efficiency and performance. If large threads are executed sequentially, processors may spin idle, resulting again in sub-optimal efficiency and performance. This “granularity problem” is especially important in implicitly parallel languages, where the programmer expresses all potential for parallelism, leaving it to the system to exploit parallelism by creating threads as necessary. Although this problem has been identified as an important problem, it is not well understood—broadly applicable solutions remain elusive. In this paper, we propose techniques for automatically controlling granularity in implicitly parallel programming languages to achieve parallel efficiency and performance. To this end, we first extend a classic result, Brent's theorem (a.k.a. the work-time principle) to include thread-creation overheads. Using a cost semantics for a general-purpose language in the style of lambda calculus with parallel tuples, we then present a precise accounting of thread-creation overheads and bound their impact on efficiency and performance. To reduce such overheads, we propose an oracle-guided semantics by using estimates of the sizes of parallel threads. We show that, if the oracle provides accurate estimates in constant time, then the oracle-guided semantics reduces the thread-creation overheads for a reasonably large class of parallel computations. We describe how to approximate the oracle-guided semantics in practice by combining static and dynamic techniques. We require the programmer to provide the asymptotic complexity cost for each parallel thread and use runtime profiling to determine hardware-specific constant factors. We present an implementation of the proposed approach as an extension of the Manticore compiler for Parallel ML. Our empirical evaluation shows that our techniques can reduce thread-creation overheads, leading to good efficiency and performance.
The logic of the reverse mathematics zoo
Authors: D'AGOSTINO GIOVANNA , MARCONE ALBERTO
Published: November 2016

Building on previous work by Mummertet al.(2015, The modal logic of Reverse Mathematics.Archive for Mathematical54(3–4) 425–437), we study the logic underlying the web of implications and non-implications which constitute the so called reverse mathematics zoo. We introduce a tableaux system for this logic and natural deduction systems for important fragments of the language.
Preface to special issue: LINEARITY 2014
Authors: ALVES SANDRA , CERVESATO ILIANO
Published: November 2016

This special issue collects selected articles from the Third International Workshop on Linearity (LINEARITY 2014), which was held in Vienna, on July 13th, 2014. The workshop was a one-day satellite event of FLoC 2014, the sixth Federated Logic Conference, which was held as part of the 2014 Vienna Summer of Logic.
Gender differences in the prevalence of household food insecurity: a systematic review and meta-analysis
Authors: Jung Natália Miranda , de Bairros Fernanda Souza , Pattussi Marcos Pascoal , Pauli Sílvia , Neutzling Marilda Borges
Published: November 2016

Objective

The present review aimed to identify and synthesize literature on household food insecurity with respect to whether the respondent was male or female.

Design

A systematic review of prevalence studies followed by a meta-analysis was conducted between 28 August 2014 and 19 October 2014 in seven electronic databases. The search was updated in April 2016. The included studies used experience-based measures to assess household food insecurity. Dichotomous measures of food insecurity were used. Pooled odds ratios of household food insecurity prevalence in women v. men were obtained through random-effect modelling. Quality assessment, publication bias diagnostics and subgroup analysis were also performed.

Setting

Population-based studies (i.e. non-clinical populations).

Subjects

Participants aged 18 years or over.

Results

Out of the 5145 articles initially identified, forty-two studies with a total population of 233 153 were included. In general, results showed that the odds for household food insecurity was 40 % higher in studies where women were the respondent (95 % CI 1·27, 1·54; P<0·001). Besides, subgroup analysis revealed that female-headed households were 75% (95 % CI 49–96%) more likely to be food insecure than male-headed households.

Conclusions

Our results confirm the existence of gender differences in reporting household food insecurity. Furthermore, they indicate that households headed by women constitute a segment of the population that is particularly vulnerable to food insecurity.
Crime, Truth, and Justice in Modern Mexico: Notes for a National History
Authors: Piccato Pablo
Published: November 2016

With this lecture by Pablo Piccato, The Americas continues its collaboration with the New School for Social Research to publish its annual Lecture in Latin American History. The series features lectures by senior historians in the field of Latin American history across an array of topics. This is the fifth in the series.
Mars's Atmosphere Matches Earth's Turbulent Nature
Authors: Zastrow Mark
Published: November 2016

Mars is even more like Earth than we thought, according to a statistical analysis of the planet's swirling atmosphere.
Reed-Sternberg cells in Hodgkin’s lymphoma present features of cellular senescence
Authors: Gopas J , Stern E , Zurgil U , Ozer J , Ben-Ari A , Shubinsky G , Braiman A , Sinay R , Ezratty J , Dronov V , Balachandran S , Benharroch D , Livneh E
Published: November 2016

Hodgkin’s Lymphoma (HL) is one of the most prevailing malignancies in young adults. Reed–Sternberg (RS) cells in HL have distinctive large cell morphology, are characteristic of the disease and their presence is essential for diagnosis. Enlarged cells are one of the hallmarks of senescence, but whether RS cells are senescent has not been previously investigated. Here we show that RS cells have characteristics of senescent cells; RS cells in HL biopsies specifically express the senescence markers and cell cycle inhibitors p21Cip1 and p16INK4a and are negative for the proliferation marker Ki-67, suggesting that these cells have ceased to proliferate. Moreover, the RS-like cells in HL lines, stained specifically for senescence-associated β-galactosidase (SA-β-gal). Oxidative stress promoted senescence in these cells as demonstrated by their staining for p21Cip1, p16INK4a, p53 and γH2AX. Senescent cells produce copious amounts of inflammatory cytokines termed ‘senescence-associated secretory phenotype’ (SASP), primarily regulated by Nuclear Factor κB (NF-κB). Indeed, we show that NF-κB activity and NF-κB-dependent cytokines production (e.g., IL-6, TNF-α, GM-CSF) were elevated in RS-like cells. Furthermore, NF-κB inhibitors, JSH-23 and curcumin reduced IL-6 secretion from RS-like cells. Thus, defining RS cells as senescent offers new insights on the origin of the proinflammatory microenvironment in HL.
Tissue-type plasminogen activator controls neuronal death by raising surface dynamics of extrasynaptic NMDA receptors
Authors: Lesept Flavie , Chevilley Arnaud , Jezequel Julie , Ladépêche Laurent , Macrez Richard , Aimable Margaux , Lenoir Sophie , Bertrand Thomas , Rubrecht Laëtitia , Galea Pascale , Lebouvier Laurent , Petersen Karl-Uwe , Hommet Yannick , Maubert Eric , Ali Carine , Groc Laurent , Vivien Denis
Published: November 2016

N-methyl-d-aspartate receptors (NMDARs) are ion channels whose synapticversusextrasynaptic localization critically influences their functions. This distribution of NMDARs is highly dependent on their lateral diffusion at the cell membrane. Each obligatory subunit of NMDARs (GluN1 and GluN2) contains two extracellular clamshell-like domains with an agonist-binding domain and a distal N-terminal domain (NTD). To date, the roles and dynamics of the NTD of the GluN1 subunit in NMDAR allosteric signaling remain poorly understood. Using single nanoparticle tracking in mouse neurons, we demonstrate that the extracellular neuronal protease tissue-type plasminogen activator (tPA), well known to have a role in the synaptic plasticity and neuronal survival, leads to a selective increase of the surface dynamics and subsequent diffusion of extrasynaptic NMDARs. This process explains the previously reported ability of tPA to promote NMDAR-mediated calcium influx. In parallel, we developed a monoclonal antibody capable of specifically blocking the interaction of tPA with the NTD of the GluN1 subunit of NMDAR. Using this original approach, we demonstrate that the tPA binds the NTD of the GluN1 subunit at a lysine in position 178. Accordingly, when applied to mouse neurons, our selected antibody (named Glunomab) leads to a selective reduction of the tPA-mediated surface dynamics of extrasynaptic NMDARs, subsequent signaling and neurotoxicity, bothin vitroandin vivo. Altogether, we demonstrate that the tPA is a ligand of the NTD of the obligatory GluN1 subunit of NMDAR acting as a modulator of their dynamic distribution at the neuronal surface and subsequent signaling.
Epidermal-specific deletion of CD44 reveals a function in keratinocytes in response to mechanical stress
Authors: Shatirishvili M , Burk A S , Franz C M , Pace G , Kastilan T , Breuhahn K , Hinterseer E , Dierich A , Bakiri L , Wagner E F , Ponta H , Hartmann T N , Tanaka M , Orian-Rousseau V
Published: November 2016

CD44, a large family of transmembrane glycoproteins, plays decisive roles in physiological and pathological conditions. CD44 isoforms are involved in several signaling pathways essential for life such as growth factor-induced signaling by EGF, HGF or VEGF. CD44 is also the main hyaluronan (HA) receptor and as such is involved in HA-dependent processes. To allow a genetic dissection of CD44 functions in homeostasis and disease, we generated a Cd44 floxed allele allowing tissue- and time-specific inactivation of all CD44 isoforms in vivo. As a proof of principle, we inactivated Cd44 in the skin epidermis using the K14Cre allele. Although the skin of such Cd44Δker mutants appeared morphologically normal, epidermal stiffness was reduced, wound healing delayed and TPA induced epidermal thickening decreased. These phenotypes might be caused by cell autonomous defects in differentiation and HA production as well as impaired adhesion and migration on HA by Cd44Δker keratinocytes. These findings support the usefulness of the conditional Cd44 allele in unraveling essential physiological and pathological functions of CD44 isoforms.
Knockout of Ccr2 alleviates photoreceptor cell death in rodent retina exposed to chronic blue light
Authors: Hu Zizhong , Zhang Yi , Wang Junling , Mao Pingan , Lv Xuehua , Yuan Songtao , Huang Zhengru , Ding Yuzhi , Xie Ping , Liu Qinghuai
Published: November 2016

Age-related macular degeneration (AMD), the leading cause of visual loss after the age of 60 years, is a degenerative retinal disease involving a variety of environmental and hereditary factors. Although it has been implicated that immune system is involved in the disease progression, the exact role that microglia has is still unclear. Here we demonstrated that knockout of Ccr2 gene could alleviate photoreceptor cell death in mice retinas exposed to chronic blue light. In Ccr2−/− mice, a damaged microglia recruitment was shown in retina and this could protect the visual function in electroretinogram and alleviate the photoreceptor apoptosis, which thus helped attenuate the blue light-induced retinopathy. We further found an increased co-location of NLRP3, Iba-1, and IL-1β in fluorescence and a concomitant increased protein expression of NLRP3, caspase-1, and IL-1β in western blotting in chronic blue light-induced retinopathy. Moreover, the activation of microglia and their cellular NLRP3 inflammasomes occurred as an earlier step before the structural and functional damage of the mice retinas, which collectively supported that microglial NLRP3 inflammasome might be the key to the chronic blue light-induced retinopathy.
Skin-derived stem cells as a source of primordial germ cell- and oocyte-like cells
Authors: Ge Wei , Cheng Shun-Feng , Dyce Paul W , De Felici Massimo , Shen Wei
Published: November 2016

The skin is a unique organ that contains a variety of stem cells for the maintenance of skin homeostasis and the repair of skin tissues following injury and disease. Skin-derived stem cells (SDSCs) constitute a heterogeneous population of stem cells generated in vitro from dermis, which can be cultured as spherical aggregates of cells in suspension culture. Under certain in vitro or in vivo conditions, SDSCs show multipotency and can generate a variety of neural, mesodermal, and endodermal cell types such as neurons, glia, fibroblasts, adipocytes, muscle cells, chondroblasts, osteoblats, and islet β-cell-like cells. SDSCs are likely derived from multipotent stem cells located in the hair follicles that are, in turn, derived from embryonic migratory neural crest or mesoderm cells. During the past decade, a wave of reports have shown that germ cells can be generated from various types of stem cells. It has been shown that SDSCs are able to produce primordial germ cell-like cells in vitro, and even oocyte-like cells (OLCs). Whether these germ cell-like cells (GCLCs) can give rise to viable progeny remains, however, unknown. In this review, we will discuss the origin and characteristics of SDSCs from which the GCLC are derived, the possible mechanisms of this differentiation process, and finally the prospective biomedical applications of the SDSC-derived GCLCs.
Decreased expression of microRNA-17 and microRNA-20b promotes breast cancer resistance to taxol therapy by upregulation of NCOA3
Authors: Ao Xiang , Nie Peipei , Wu Baoyan , Xu Wei , Zhang Tao , Wang Songmao , Chang Haocai , Zou Zhengzhi
Published: November 2016

Chemoresistance is a major obstacle to effective breast cancer chemotherapy. However, the underlying molecular mechanisms remain unclear. In this study, nuclear receptor coactivator 3 (NCOA3) was found to be significantly increased in taxol-resistant breast cancer tissues and cells. Moreover, overexpression of NCOA3 enhanced breast cancer cell resistance to taxol, whereas depletion of NCOA3 decreased taxol resistance. Subsequently, we investigated whether NCOA3 expression was regulated by miRNAs in breast cancer. By bioinformatics prediction in combination with the data of previous report, miR-17 and miR-20b were selected as the potential miRNAs targeting NCOA3. By real-time PCR analysis, we found that miR-17 and miR-20b were significantly reduced in taxol-resistant breast cancer tissues and cells. In addition, we provided some experimental evidences that miR-17 and miR-20b attenuated breast cancer resistance to taxolin vitroandin vivomodels. Furthermore, by luciferase reporter assays, we further validated that both miR-17 and miR-20b directly binded the 3′-untranslated region ofNCOA3mRNA and inhibited its expression in breast cancer cells. Finally, both miR-17 and miR-20b levels were found to be significantly negatively correlated withNCOA3mRNA levels in breast cancer tissues. Together, our results indicated that loss of miR-17 and miR-20b enhanced breast cancer resistance to taxol by upregulating NCOA3 levels. Our study suggested miR-17, miR-20b and NCOA3 may serve as some predictive biomarkers and potential therapeutic targets in taxol-resistant breast cancer treatment.
ERK/Drp1-dependent mitochondrial fission is involved in the MSC-induced drug resistance of T-cell acute lymphoblastic leukemia cells
Authors: Cai Jianye , Wang Jiancheng , Huang Yinong , Wu Haoxiang , Xia Ting , Xiao Jiaqi , Chen Xiaoyong , Li Hongyu , Qiu Yuan , Wang Yingnan , Wang Tao , Xia Huimin , Zhang Qi , Xiang Andy Peng
Published: November 2016

The bone marrow microenvironment facilitates the proliferation and survival of leukemia cells, contributing to disease relapse. Bone marrow-derived mesenchymal stem cells (MSCs) are well known to promote cancer chemoresistance via soluble factors and cell adhesion. However, little is known about the effects of MSCs on the mitochondrial dynamics of T-cell acute lymphoblastic leukemia (T-ALL) cells, or how this may influence the chemoresistance of these cells. Here, we tested both indirect (Transwell) and direct coculture strategies, and found that MSCs protected T-ALL cells from chemotherapeutic cell death and cytotoxicity under both culture conditions. In addition, cell viability was higher in the direct contact system compared with the Transwell system. We further showed that exposure of T-ALL cells to MSCs decreased mitochondrial reactive oxygen species (ROS) levels and promoted a pro-glycolytic shift that was characterized by increased glucose uptake and lactate production with concomitant reductions in adenosine triphosphate production and mitochondrial membrane potential. In T-ALL cells cocultured with MSCs, the mitochondrial morphology of T-ALL cells were altered from elongation to fragmentation because of the extracellular signal-regulated kinase activation-mediated phosphorylation of the pro-fission factor, dynamin-related protein 1 (Drp1), at residue S616. Consistent with this, the expression of S616-phosphorylated Drp1 recapitulated the mitochondrial dynamics, mitochondrial ROS levels, metabolic switching and chemoresistance seen in T-ALL cells cocultured with MSCs. These findings suggest that the ability of MSCs to trigger Drp1 activation-induced changes in mitochondrial dynamics is crucial to their ability to protect cells against chemotherapeutic agents.
High-energy electron emission from metallic nano-tips driven by intense single-cycle terahertz pulses
Authors: Li Sha , Jones R. R.
Published: November 2016

Electrons ejected from atoms and subsequently driven to high energies in strong laser fields enable techniques from attosecond pulse generation to imaging with rescattered electrons. Analogous processes govern strong-field electron emission from nanostructures, where long wavelength radiation and large local field enhancements hold the promise for producing electrons with substantially higher energies, allowing for higher resolution time-resolved imaging. Here we report on the use of single-cycle terahertz pulses to drive electron emission from unbiased nano-tips. Energies exceeding 5 keV are observed, substantially greater than previously attained at higher drive frequencies. Despite large differences in the magnitude of the respective local fields, we find that the maximum electron energies are only weakly dependent on the tip radius, for 10 nm<R<1,000 nm. Due to the single-cycle nature of the field, the high-energy electron emission is predicted to be confined to a single burst, potentially enabling a variety of applications.
Structure-conserving spontaneous transformations between nanoparticles
Authors: Krishnadas K. R. , Baksi Ananya , Ghosh Atanu , Natarajan Ganapati , Pradeep Thalappil
Published: November 2016

Ambient, structure- and topology-preserving chemical reactions between two archetypal nanoparticles, Ag25(SR)18 and Au25(SR)18, are presented. Despite their geometric robustness and electronic stability, reactions between them in solution produce alloys, AgmAun(SR)18 (m+n=25), keeping their M25(SR)18 composition, structure and topology intact. We demonstrate that a mixture of Ag25(SR)18 and Au25(SR)18 can be transformed to any arbitrary alloy composition, AgmAun(SR)18 (n=1–24), merely by controlling the reactant compositions. We capture one of the earliest events of the process, namely the formation of the dianionic adduct, (Ag25Au25(SR)36)2−, by electrospray ionization mass spectrometry. Molecular docking simulations and density functional theory (DFT) calculations also suggest that metal atom exchanges occur through the formation of an adduct between the two clusters. DFT calculations further confirm that metal atom exchanges are thermodynamically feasible. Such isomorphous transformations between nanoparticles imply that microscopic pieces of matter can be transformed completely to chemically different entities, preserving their structures, at least in the nanometric regime.
Spin exchange broadening of magnetic resonance lines in a high-sensitivity rotating K-Rb-21Ne co-magnetometer
Authors: Chen Yao , Quan Wei , Zou Sheng , Lu Yan , Duan Lihong , Li Yang , Zhang Hong , Ding Ming , Fang Jiancheng
Published: November 2016

Atomic co-magnetometers can be utilized for high-precision angular velocity sensing or fundamental physics tests. The sensitivity of a co-magnetometer determines the angle random walk of an angular velocity sensor and the detection limit for a fundamental physics test. A high-sensitivity K-Rb-21Ne co-magnetometer, which is utilized for angular velocity sensing, is presented in this paper. A new type of spin relaxation of Rb atom spins, which can broaden the zero-field magnetic resonance lines of the co-magnetometer, is discovered. Further studies show that the spin relaxation of Rb atoms is caused by a high Rb electron magnetization field. With this discovery, the total relaxation rate of Rb atoms is optimized to improve the sensitivity of the co-magnetometer. Moreover, its sensitivity is optimized by suppressing various noises. Especially, to suppress laser-related noises, the co-magnetometer is designed such that the sensitive axis of the co-magnetometer can be fixed to the direction in which the projection input of the earth’s rotation is 0. This is called a rotating co-magnetometer. A magnetic field sensitivity of 1.0 fT/Hz−1/2@5 Hz, which is equal to an angular velocity sensitivity of 2.1 × 10−8 rad s−1 Hz−1/2@5 Hz, is demonstrated using a spherical vapour cell with a diameter of 14 mm.
Meta-analysis of gene expression studies in endometrial cancer identifies gene expression profiles associated with aggressive disease and patient outcome
Authors: O’Mara Tracy A. , Zhao Min , Spurdle Amanda B.
Published: November 2016

Although endometrioid endometrial cancer (EEC; comprising ~80% of all endometrial cancers diagnosed) is typically associated with favourable patient outcome, a significant portion (~20%) of women with this subtype will relapse. We hypothesised that gene expression predictors of the more aggressive non-endometrioid endometrial cancers (NEEC) could be used to predict EEC patients with poor prognosis. To explore this hypothesis, we performed meta-analysis of 12 gene expression microarray studies followed by validation using RNA-Seq data from The Cancer Genome Atlas (TCGA) and identified 1,253 genes differentially expressed between EEC and NEEC. Analysis found 121 genes were associated with poor outcome among EEC patients. Forward selection likelihood-based modelling identified a 9-gene signature associated with EEC outcome in our discovery RNA-Seq dataset which remained significant after adjustment for clinical covariates, but was not significant in a smaller RNA-Seq dataset. Our study demonstrates the value of employing meta-analysis to improve the power of gene expression microarray data, and highlight genes and molecular pathways of importance for endometrial cancer therapy.
Novel Agonist Bioisosteres and Common Structure-Activity Relationships for The Orphan G Protein-Coupled Receptor GPR139
Authors: Shehata Mohamed A. , Nøhr Anne C. , Lissa Delphine , Bisig Christoph , Isberg Vignir , Andersen Kirsten B. , Harpsøe Kasper , Björkling Fredrik , Bräuner-Osborne Hans , Gloriam David E.
Published: November 2016

GPR139 is an orphan class A G protein-coupled receptor found mainly in the central nervous system. It has its highest expression levels in the hypothalamus and striatum, regions regulating metabolism and locomotion, respectively, and has therefore been suggested as a potential target for obesity and Parkinson’s disease. The two aromatic amino acids L-Trp and L-Phe have been proposed as putative endogenous agonists, and three structurally related benzohydrazide, glycine benzamide, and benzotriazine surrogate agonist series have been published. Herein, we assayed 158 new analogues selected from a pharmacophore model, and identified 12 new GPR139 agonists, containing previously untested bioisosteres. Furthermore, we present the first combined structure-activity relationships, and a refined pharmacophore model to serve as a rationale for future ligand identification and optimization.
Suilysin-induced Platelet-Neutrophil Complexes Formation is Triggered by Pore Formation-dependent Calcium Influx
Authors: Zhang Shengwei , Zheng Yuling , Chen Shaolong , Huang Shujing , Liu Keke , Lv Qingyu , Jiang Yongqiang , Yuan Yuan
Published: November 2016

Platelet activation and platelet–neutrophil interactions have been found to be involved in inflammation, organ failure and soft-tissue necrosis in bacterial infections. Streptococcus suis, an emerging human pathogen, can cause streptococcal toxic-shock syndrome (STSS) similarly to Streptococcus pyogenes. Currently, S. suis–platelet interactions are poorly understood. Here, we found that suilysin (SLY), the S. suis cholesterol-dependent cytolysin (CDC), was the sole stimulus of S. suis that induced platelet-neutrophil complexes (PNC) formation. Furthermore, P-selectin released in α-granules mediated PNC formation. This process was triggered by the SLY-induced pore forming-dependent Ca2+ influx. Moreover, we demonstrated that the Ca2+ influx triggered an MLCK-dependent pathway playing critical roles in P-selectin activation and PNC formation, however, PLC-β-IP3/DAG-MLCK and Rho-ROCK-MLCK signalling were not involved. Additionally, the “outside-in” signalling had a smaller effect on the SLY-induced P-selectin release and PNC formation. Interestingly, other CDCs including pneumolysin and streptolysin O have also been found to induce PNC formation in a pore forming-dependent Ca2+ influx manner. It is possible that the bacterial CDC-mediated PNC formation is a similar response mechanism used by a wide range of bacteria. These findings may provide useful insight for discovering potential therapeutic targets for S. suis-associated STSS.
Effect of nematic ordering on electronic structure of FeSe
Authors: Fedorov A. , Yaresko A. , Kim T. K. , Kushnirenko Y. , Haubold E. , Wolf T. , Hoesch M. , Grüneis A. , Büchner B. , Borisenko S. V.
Published: November 2016

Electronically driven nematic order is often considered as an essential ingredient of high-temperature superconductivity. Its elusive nature in iron-based superconductors resulted in a controversy not only as regards its origin but also as to the degree of its influence on the electronic structure even in the simplest representative material FeSe. Here we utilized angle-resolved photoemission spectroscopy and density functional theory calculations to study the influence of the nematic order on the electronic structure of FeSe and determine its exact energy and momentum scales. Our results strongly suggest that the nematicity in FeSe is electronically driven, we resolve the recent controversy and provide the necessary quantitative experimental basis for a successful theory of superconductivity in iron-based materials which takes into account both, spin-orbit interaction and electronic nematicity.