bluuebunny/crossref_metadata_2025 huggingface dataset:
Women on Boards of Directors and Corporate Social Performance: A Meta‐Analysis
Authors: Byron Kris , Post Corinne
Published: March 2016

Research Question

Whether and how women directors influence firms' engagement in socially responsible business practices and social reputation among diverse stakeholders is unclear due to conflicting empirical evidence, the lack of a coherent theory linking these variables, and inattention to the national contexts in which these relationships occurs.

Research Findings

Results from our meta‐analysis of 87 independent samples suggest that, while generally positive, the female board representation–social performance relationship is even more positive in national contexts when boards may be more motivated to draw on the resources that women directors bring to a board (i.e., among firms operating in countries with stronger shareholder protections) and in contexts where intra‐board power distribution may be more balanced (i.e., in countries with higher gender parity).

Theoretical Implications

Future studies should more attentively examine how firms' institutional contexts enhance or mitigate the relationship between women's representation on boards and corporate social performance. Our findings also highlight the need for a comprehensive understanding of the social performance‐related knowledge, perspectives, and values that men and women bring to boards.

Practitioner/Policy Implications

Our results suggest that, to enhance any benefits of diversity for corporate social performance, efforts be directed at holding boards more accountable toward diverse stakeholders and improving the status of women in society and in the workforce.
Prospective pilots of routine data capture by paediatricians in clinics and validation of the Disabilities Complexity Scale
Authors: Horridge Karen A , Mcgarry Kenneth , Williams Jane , Whitlingum Gabriel ,   on behalf of the British Academy of Childhood Disability
Published: March 2016

Aims

To pilot prospective data collection by paediatricians at the point of care across England using a defined terminology set; demonstrate feasibility of data collection and utility of data outputs; and confirm that counting the number of needs per child is valid for quantifying complexity.

Method

Paediatricians in 16 hospital and community settings collected and anonymized data. Participants completed a survey regarding the process. Data were analysed using R version 3.1.2.

Results

Overall, 8117 needs captured from 1224 consultations were recorded. Sixteen clinicians responded positively about the process and utility of data collection. The sum of needs varied significantly (p<0.01) by level of gross motor function ascertained using the Gross Motor Function Classification System for children with cerebral palsy; epilepsy severity as defined by level of expertise required to manage it; and by severity of intellectual disability.

Interpretation

Prospective data collection at the point of clinical care proved possible without disrupting clinics, even for those with the most complex needs, and took the least time when done electronically. Counting the number of needs was easy to do, and quantified complexity in a way that informed clinical care for individuals and related directly to validated scales of functioning. Data outputs could inform more appropriate design and commissioning of quality services.
Time to generalization and prediction of survival in patients with amyotrophic lateral sclerosis: a retrospective observational study
Authors: Tortelli R. , Copetti M. , Panza F. , Fontana A. , Cortese R. , Capozzo R. , Introna A. , D'Errico E. , Zoccolella S. , Arcuti S. , Seripa D. , Simone I. L. , Logroscino G.
Published: March 2016

Background and purpose

A strong association between time to generalization (TTG), considered as the time of spreading of the clinical signs from spinal or bulbar localization to both, and survival was recently identified in patients with amyotrophic lateral sclerosis (ALS). Thus, TTG may be used as an early to intermediate end‐point in survival studies. The aim of the present study was to test TTG as a predictor of survival in ALS.

Methods

This was an observational retrospective study of ALS patients from a tertiary referral centre over a 5‐year follow‐up period.

Results

In 212 ALS patients, TTG was associated with time to death/tracheostomy [R 0.62, 95% confidence interval (CI) 0.53–0.70; P < 0.001]. In a time‐to‐event analysis, longer TTG resulted in lower risk to reach a composite outcome (death or tracheostomy) both in univariate [hazard ratio (HR) 0.98, 95% CI 0.97–0.99] and multivariate Cox analyses (HR 0.98, 95% CI 0.96–0.99). TTG predicted death/tracheostomy at 4 years (C‐statistic 0.58; 95% CI 0.53–0.63) and at 5 years (C‐statistic 0.58; 95% CI 0.53–0.62).

Conclusions

Based on the present results from a large clinical cohort, TTG may be used as a new early to intermediate end‐point to describe the ALS natural history. TTG may be potentially useful as a new primary outcome measure for clinical trials.
Geochemical fingerprinting of hydraulic fracturing fluids from Qusaiba Hot Shale and formation water from Paleozoic petroleum systems, Saudi Arabia
Authors: Birkle P.
Published: March 2016

Provenance studies of produced water are essential to trace flow dynamics and reservoir compartmentalization in petroleum systems and to quantify fluid recovery rates from unconventional fracturing. Produced water from a hydraulically fractured well in the Qusaiba Hot Shale in the Northern Exploration Area, Saudi Arabia, was daily monitored and analyzed for water chemistry, and environmental (δ2H, δ13C, δ18OH2O, δ18OSO4, δ34SSO4, δ37Cl, 87Sr/86Sr) and cosmogenic isotopes (3H, 14C, 36Cl), to differentiate from reference fluids of supply water, fracturing fluids, and formation water from adjacent Paleozoic units. Initially, recovered water is composed of fracturing fluids and subsequently replaced by a homogeneous cut of pristine formation water. Formation water is composed of dominant meteoric water (approximately 84 vol%) and minor fossil evaporated seawater. The young 14C‐apparent age between 6000 and 6700 years BP and depleted δ18O/δ2H values for the meteoric component confirm the infiltration of surface water into the Qusaiba Hot Shale interval or adjacent units during the Early Holocene Pluvial Period under cooler and wetter climatic conditions than present, which suggest the presence of a very recent, dynamic hydraulic flow system. 36Cl/Cl ratios between 102 × 10−15 and 31 × 10−15 are ambiguous and can be attributed to atmospheric recharge close to the coast, mixing of 36Cl‐enriched Quaternary meteoric recharge with 36Cl‐depleted fossil seawater, and/or hypogene production by U‐Th‐enriched host rock. Produced waters from Qusaiba Hot Shale are within the compositional range of Na‐Cl‐type formation water from Paleozoic reservoir units in northern Saudi Arabia with salinities from 30 000 to 130 000 mg l−1. As a novel technological approach for exploration wells in Northern Saudi Arabia, multi‐isotopic methods were successfully implemented to quantify flowback volumes from hydraulic fracturing, and to fingerprint pristine formation water or pore water in Paleozoic systems on their provenance, residence time, migration pathways, and secondary alteration processes.
Severe Headache or Migraine History Is Inversely Correlated With Dietary Sodium Intake: NHANES 1999–2004
Authors: Pogoda Janice M. , Gross Noah B. , Arakaki Xianghong , Fonteh Alfred N. , Cowan Robert P. , Harrington Michael G.
Published: March 2016

Objective

We investigated whether dietary sodium intake from respondents of a national cross‐sectional nutritional study differed by history of migraine or severe headaches.

Background

Several lines of evidence support a disruption of sodium homeostasis in migraine.

Design

Our analysis population was 8819 adults in the 1999–2004 National Health and Nutrition Examination Survey (NHANES) with reliable data on diet and headache history. We classified respondents who reported a history of migraine or severe headaches as having probable history of migraine. To reduce the diagnostic conflict from medication overuse headache, we excluded respondents who reported taking analgesic medications. Dietary sodium intake was measured using validated estimates of self‐reported total grams of daily sodium consumption and was analyzed as the residual value from the linear regression of total grams of sodium on total calories. Multivariable logistic regression that accounted for the stratified, multistage probability cluster sampling design of NHANES was used to analyze the relationship between migraine and dietary sodium.

Results

Odds of probable migraine history decreased with increasing dietary sodium intake (odds ratio = 0.93, 95% confidence interval = 0.87, 1.00, P = .0455). This relationship was maintained after adjusting for age, sex, and body mass index (BMI) with slightly reduced significance (P = .0505). In women, this inverse relationship was limited to those with lower BMI (P = .007), while in men the relationship did not differ by BMI. We likely excluded some migraineurs by omitting frequent analgesic users; however, a sensitivity analysis suggested little effect from this exclusion.

Conclusions

This study is the first evidence of an inverse relationship between migraine and dietary sodium intake. These results are consistent with altered sodium homeostasis in migraine and our hypothesis that dietary sodium may affect brain extracellular fluid sodium concentrations and neuronal excitability.
Reversible Cerebral Vasoconstriction Syndrome Without Typical Thunderclap Headache
Authors: Wolff Valérie , Ducros Anne
Published: March 2016

Reversible cerebral vasoconstriction syndrome (RCVS) is characterized by severe headache and diffuse segmental intracranial arterial constriction that resolve within three months. Stroke, which is the major complication of RCVS, can result in persistent neurological disability, and rarely causes death. Diagnosis of RCVS early in the clinical course might improve outcomes. Although recurrent thunderclap headache is the clinical hallmark of RCVS, the absence of such a pattern should not lead to discard the diagnosis. Our literature review shows that RCVS can also manifest as an unspecific headache, such as a single severe headache episode, a mild or a progressive headache. Moreover, a subset of patients with severe RCVS presents without any headache, but frequently with seizures, focal neurological deficits, confusion or coma, in the setting of stroke or posterior reversible encephalopathy syndrome. These patients may be aphasic or in comatose state, explaining their inability to give their own medical history. They may have forgotten the headache they had a few days before more dramatic symptoms, or may have a variant of the classical RCVS. By consequence, an RCVS should be suspected in patients with any unusual headache, whether thunderclap or not, and in patients with cryptogenic stroke or convexity subarachnoid hemorrhage, whether the patient also has headache or not. Diagnosis in such cases relies on the demonstration of reversible multifocal intracranial arterial stenosis and the exclusion of other causes.
Long‐Term Outcomes and Clinical Characteristics of Hypnic Headache Syndrome: 40 Patients Series From a Tertiary Referral Center
Authors: Tariq Nauman , Estemalik Emad , Vij Brinder , Kriegler Jennifer S. , Tepper Stewart J. , Stillman Mark J.
Published: March 2016

Objective

Hypnic headaches (HHs) are unique because of late life onset and characteristic periodic nocturnal awakening. We retrospectively identified 40 cases at a tertiary headache referral center over the course of 6 years and assessed response to conventional treatments.

Methods

This was a retrospective study in which patients were identified using primary and secondary ICD‐9 diagnostic codes of HHs (339.81) from October 2008 until December 2014 using the International Classification of Headache Disorders II and III‐beta criteria for diagnosis. Baseline characteristics were collected. Primary outcome was response to medications divided into 4 categories: complete response (headaches completely gone), moderate response (≥50% decrease in frequency), partial response (<50% decrease in frequency), no response.

Results

Forty (40) patients (80% females) were identified with HHs, and mean follow‐up was 929 days (range 42‐2555). Average age of headache onset was 62 years (range 44‐86). Twenty (50%) patients had previous history of migraine, 5% had bilateral cranial autonomic features, and 40% underlying sleep abnormalities. The average duration per day and frequency per month of headaches were 186 minutes (range 30‐720 minutes) and 21 days (range 5‐30), respectively. Among 15 different medications tried, the best response was seen with lithium (7/10 [70%] complete response and 2/10 [20%] moderate response). With caffeine, there was a complete response in 6/21 (28%) and moderate response in 9/21 (43%) subjects. A telephone follow‐up survey revealed that 5 patients in the bedtime caffeine group also benefited from taking a caffeinated drink at the time of awakening.

Conclusions

HH is an infrequent primary headache disorder that can present with cranial autonomic features. It can persist for years in the elderly. Lithium appeared to be the most effective treatment option, followed by caffeine at bedtime. Caffeine ingestion on awakening with an HH also demonstrated benefit. Cervicogenic headaches in the elderly and presence of active migraine are major confounders in the diagnosis of HHs.
The Typical Thunderclap Headache of Reversible Cerebral Vasoconstriction Syndrome and its Various Triggers
Authors: Ducros Anne , Wolff Valérie
Published: March 2016

During the last 10 years, reversible cerebral vasoconstriction syndrome (RCVS) has emerged as the most frequent cause of thunderclap headache (TCH) in patients without aneurysmal subarachnoid hemorrhage, and as the most frequent cause of recurrent TCHs. The typical TCHs of RCVS are multiple, recurring over a few days to weeks, excruciating, short‐lived, and brought up by exertion, sexual activities, emotion, Valsalva maneuvers, or bathing, among other triggers. All these triggers induce sympathetic activation. In a minority of cases with RCVS, TCH heralds stroke and rarely death. Early diagnosis of RCVS in patients who present with isolated headache enables proper management and might reduce the risk of eventual stroke. This review describes the characteristics, triggers, diagnosis, and management of TCH in RCVS. One aim is to underline that the TCH pattern of RCVS is so typical that it enables, according to the 2013 revision of the International Classification of Headache Disorders, the diagnosis of “probable RCVS” in patients with such a headache pattern, normal cerebral angiography, and no other cause. Another objective is to discuss the role of physical and emotional stress in RCVS and in other related conditions involving similar triggers.
Improved extraction of disulphide‐rich bioactive proteins from soya hulls: characterisation of a novel aspartic proteinase
Authors: Liu Chun , Cheng Fen‐Fen , Liu Xiao , Ma Hong‐Yu , Yang Xiao‐Quan
Published: March 2016

Soya hull, an underutilised coproduct of soya processing, was investigated as a source of disulphide‐rich bioactive proteins. A Viscozyme L‐assisted extraction method was developed to improve the yield of extracted proteins. The extracted proteins were identified by MALDI TOF–TOF MS, and the most abundant disulphide‐rich protein among identified proteins was purified and the enzymatic properties were evaluated. The results indicated that the Viscozyme L‐assisted extraction method extracted significantly (P < 0.05) more proteins (39.01%) than did the aqueous method (4.52%). The yield of the purified aspartic proteinase nepenthesin‐1‐like [Glycine max] (GmAPN1K) (the most abundant disulphide‐rich protein) is 570 mg Kg−1. The specific activity of GmAPN1K was 62.1 U mg−1 at pH 3.0 and 37 °C. The enzyme was optimally active at pH 3.0 and 55 °C. It was stable within pH range 3.0–10.0 and up to 55 °C, respectively, and was specifically inhibited by pepstatin A.
High‐Temperature Neutron Diffraction, Raman Spectroscopy, and First‐Principles Calculations of Ti3SnC2 and Ti2SnC
Authors: Bentzel Grady W. , Naguib Michael , Lane Nina J. , Vogel Sven C. , Presser Volker , Dubois Sylvain , Lu Jun , Hultman Lars , Barsoum Michel W. , Caspi El'ad N.
Published: March 2016

Herein, we report—for the first time—on the additive‐free bulk synthesis of Ti3SnC2. A detailed experimental study of the structure of the latter together with a secondary phase, Ti2SnC, is presented through the use of X‐ray diffraction (XRD), and high‐resolution transmission microscopy (HRTEM). A previous sample of Ti3SnC2, made using Fe as an additive and Ti2SnC as a secondary phase, was studied by high‐temperature neutron diffraction (HTND) and XRD. The room‐temperature crystallographic parameters of the two MAX phases in the two samples are quite similar. Based on Rietveld analysis of the HTND data, the average linear thermal expansion coefficients of Ti3SnC2 in the a and c directions were found to be 8.5 (2)·10−6 K−1 and 8.9 (1)·10−6 K−1, respectively. The respective values for the Ti2SnC phase are 10.1 (3)·10−6 K−1 and 10.8 (6)·10−6 K−1. Unlike other MAX phases, the atomic displacement parameters of the Sn atoms in Ti3SnC2 are comparable to those of the Ti and C atoms. When the predictions of the atomic displacement parameters obtained from density functional theory are compared to the experimental results, good quantitative agreement is found for the Sn atoms. In the case of the Ti and C atoms, the agreement is more qualitative. We also used first principles to calculate the elastic properties of both Ti2SnC and Ti3SnC2 and their Raman active modes. The latter are compared to experiment and the agreement was found to be good.
Crystallization Behavior and Multiferroic Properties of Bi3.15Nd0.85Ti3O12/CoFe2O4 Powders Synthesized by Sol–Gel Method
Authors: Zhang Hongjun , Ke Hua , Wang Wen , Jia Dechang , Zhou Yu
Published: March 2016

Bi3.15Nd0.85Ti3O12 (BNdT)/CoFe2O4 (CFO) composite ceramic powders with embedded structures were successfully prepared by sol–gel processing. Their crystallization behavior was characterized by XRD, DTA, FT‐IR, and HRTEM. The magnetic and ferroelectric phases of these composite ceramic powders segregate during calcination. The CFO phase forms easily at ~300°C, thereafter the BNdT matrix phase nucleates with grain growth at the CFO grain boundaries at temperatures >500°C. The CFO phase acts as a heterogeneous nucleation point for formation of the ferroelectric BNdT phase. Furthermore, the 0.5BNdT–0.5CFO composite ceramic powders go through a ferroelectric–paraelectric phase transition at 259°C, and the magnetic CFO nanoparticles (50–100 nm, under calcination at 600°C) embedded in the ferroelectric matrix, show superior magnetic behavior (Mmax = 16.50 emu/g), comparable to pure CFO nanoparticles.
High‐Performance Small‐Amount Fe2O3‐Doped (K,Na)NbO3‐Based Lead‐Free Piezoceramics with Irregular Phase Evolution
Authors: Guo Jinming , Xu Fang , Shang Xunzhong , Lu Yinmei , Li Pai , Zhou Taosheng , Zhang Zaoli , He Yunbin
Published: March 2016

[(K0.43Na0.57)0.94Li0.06][(Nb0.94Sb0.06)0.95Ta0.05]O3 + x mol% Fe2O3 (KNLNST + x Fe, x = 0~0.60) lead‐free piezoelectric ceramics were prepared by conventional solid‐state reaction processing. The effects of small‐amount Fe2O3 doping on the microstructure and electrical properties of the KNLNST ceramics were systematically investigated. With increasing Fe3+ content, the orthorhombic‐tetragonal polymorphic phase transition temperature (TO‐T) of KNLNST + x Fe ceramics presented an obvious “V” type variation trend, and TO‐T was successfully shifted to near room temperature without changing TC (TC = 315°C) via doping Fe2O3 around 0.25 mol%. Electrical properties were significantly enhanced due to the coexistence of both orthorhombic and tetragonal ferroelectric phases at room temperature. The ceramics doped with 0.20 mol% Fe2O3 possessed optimal piezoelectric and dielectric properties of d33 = 306 pC/N, kp = 47.0%, = 1483 and tan δ = 0.023. It was revealed that the strong internal stress in the KNLNST + x Fe ceramics with higher Fe3+ contents (x = 0.40, 0.60) stabilized the orthorhombic phase, leading to the irregular “V” type rather than the usually observed monotonic phase transition with composition change in the ceramics.
Oxidation of ZrB2–SiC‐Graphite Composites Under Low Oxygen Partial Pressures of 500 and 1500 Pa at 1800°C
Authors: Jin Hua , Meng Songhe , Xinghong Zhang , Qingxuan Zeng , Weihua Xie
Published: March 2016

The oxidation behavior of ZrB2–SiC‐graphite composites under low oxygen partial pressures of 500 and 1500 Pa at 1800°C was investigated. The phase composition and microstructure of the oxidized scale were characterized using TEM, SEM, XRD, XPS, EDS. The analytical results indicated that a low oxygen partial pressure had a remarkable effect on the oxidation mechanism of ZrB2–SiC‐graphite composites. When oxidized at 1500 Pa, the oxidation kinetics was controlled by the rate of oxygen diffusion into the composite. When the composite was oxidized at 500 Pa, control of the oxidation kinetics changed from the rate of oxygen diffusion to the rate of the oxidation reaction. The rate of oxidation decreased with decreasing oxygen partial pressure. Higher partial pressures of oxygen resulted in less oxidation resistance by the ZrB2–SiC‐graphite composites.
Molecular evidence for biochemical diversification of phenolamide biosynthesis in rice plants
Authors: Tanabe Kimiaki , Hojo Yuko , Shinya Tomonori , Galis Ivan
Published: March 2016

Two phenolamides (PAs), p‐coumaroylputrescine and feruloylputrescine strongly accumulate in rice (Oryza sativa cv. Nipponbare) leaves subjected to attack of chewing and sucking herbivores. Here we identified and characterized in vitro three novel rice genes that mediated coumaroyl‐CoA/feruloyl‐CoA conjugation to polyamines, putrescine and agmatine. Interestingly, two genes were highly specific for their polyamine substrates, encoding putrescine N‐hydroxycinnamoyltransferase and agmatine N‐hydroxycinnamoyltransferase, while the third enzyme could use both polyamines and it was therefore annotated as putrescine/agmatine N‐hydroxycinnamoyltransferase. All genes were preferentially expressed in rice roots and developing flowers, and in addition, the putrescine/agmatine N‐hydroxycinnamoyltransferase transcripts were strongly induced by wounding in the young rice leaves. Because the wound response of this gene was only partially suppressed in the jasmonoyl‐L‐isoleucine deficient plants (Osjar1), it suggests that its upregulation (as well as inducible PAs in rice) may be largely independent of jasmonoyl‐L‐isoleucine signaling pathway. The finding of three closely related genes with a similar and/or overlapping activity in PA biosynthesis provides another striking example of rapid diversification of plant metabolism in response to environmental stresses in nature.
Lipidomic profiling analysis reveals the dynamics of phospholipid molecules in Arabidopsis thaliana seedling growth
Authors: Wang Yi‐Sheng , Yao Hong‐Yan , Xue Hong‐Wei
Published: March 2016

High‐throughput lipidomic profiling provides a sensitive approach for discovering minor lipid species. By using an advance in electrospray ionization tandem mass spectrometry, a large set of phospholipid molecular species (126 species) with high resolution were identified from Arabidopsis seedling; of them 31 species are newly identified (16 are unique in plants), including 13 species of phosphatidic acid (PA), nine phosphatidylcholine, six phosphatidylinositol and three phosphatidylserine. Further analysis of the lipidomic profile reveals dynamics of phospholipids and distinct species alterations during seedling development. PA molecules are found at the lowest levels in imbibition and follow an increasing trend during seedling growth, while phosphatidylethanolamine (PE) molecules show the opposite pattern with highest levels at imbibition and a general decreasing trend at later stages. Of PA molecular species, 34:2‐, 34:3‐, 36:4‐, 36:5‐, 38:3‐ and 38:4‐PA increase during radicle emergence, and 34:2‐ and 34:3‐PA reach highest levels during hypocotyl and cotyledon emergence from the seed coat. Conversely, molecular species of PE show higher levels in imbibition and decrease in later stages. These results suggest the crucial roles of specific molecular species and homeostasis of phospholipid molecules in seedling growth and provide insights into the mechanisms of how phospholipid molecules are involved in regulating plant development.
Neuropeptide Y (NPY) in cerebrospinal fluid from patients with Huntington's Disease: increased NPY levels and differential degradation of the NPY1–30 fragment
Authors: Wagner Leona , Björkqvist Maria , Lundh Sofia Hult , Wolf Raik , Börgel Arne , Schlenzig Dagmar , Ludwig Hans‐Henning , Rahfeld Jens‐Ulrich , Leavitt Blair , Demuth Hans‐Ulrich , Petersén Åsa , von Hörsten Stephan
Published: March 2016

Huntington's disease (HD) is an inherited and fatal polyglutamine neurodegenerative disorder caused by an expansion of the CAG triplet repeat coding region within the HD gene. Progressive dysfunction and loss of striatal GABAergic medium spiny neurons (MSNs) may account for some of the characteristic symptoms in HD patients. Interestingly, in HD, MSNs expressing neuropeptide Y (NPY) are spared and their numbers is even up‐regulated in HD patients. Consistent with this, we report here on increased immuno‐linked NPY (IL‐NPY) levels in human cerebrospinal fluid (hCSF) from HD patients (Control n = 10; early HD n = 9; mid HD n = 11). As this antibody‐based detection of NPY may provide false positive differences as a result of the antibody‐based detections of only fragments of NPY, the initial finding was validated by investigating the proteolytic stability of NPY in hCSF using matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry (MALDI‐TOF‐MS) and selective inhibitors. A comparison between resulting NPY‐fragments and detailed epitope analysis verified significant differences in IL‐NPY1–36/3–36 and NPY1–30 levels between HD patients and control subjects with no significant differences between early vs mid HD cases. Ex vivo degradomics analysis demonstrated that NPY is initially degraded to NPY1–30 by cathepsin D in both HD patients and control subjects. Yet, NPY1–30 is then further differentially hydrolyzed by thimet oligopeptidase (TOP) in HD patients and by neprilysin (NEP) in control subjects. Furthermore, altered hCSF TOP‐inhibitor Dynorphin A1–13 (Dyn‐A1–13) and TOP‐substrate Dyn‐A1–8 levels indicate an impaired Dyn‐A‐TOP network in HD patients. Thus, we conclude that elevated IL‐NPY‐levels in conjunction with TOP‐/NEP‐activity/protein as well as Dyn‐A1–13‐peptide levels may serve as a potential biomarker in human CSF of HD.

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Huntington's disease (HD) patients' cerebrospinal fluid (CSF) exhibits higher neuropeptide Y (NPY) levels. Further degradomics studies show that CSF‐NPY is initially degraded to NPY1‐30 by Cathepsin D. The NPY1‐30 fragment is then differentially degraded in HD vs control involving Neprilysin (NEP), Thimet Oligopeptidase (TOP), and TOP‐Dynorphin‐A network. Together, these findings may help in search for HD biomarkers.
Physiological functions and pathobiology of TDP‐43 and FUS/TLS proteins
Authors: Ratti Antonia , Buratti Emanuele
Published: March 2016

The multiple roles played by RNA binding proteins in neurodegeneration have become apparent following the discovery of TAR DNA binding protein 43 kDa (TDP‐43) and fused in sarcoma/translocated in liposarcoma (FUS/TLS) involvement in amyotrophic lateral sclerosis and frontotemporal lobar dementia. In these two diseases, the majority of patients display the presence of aggregated forms of one of these proteins in their brains. The study of their functional properties currently represents a very promising target for developing the effective therapeutic options that are still lacking. This aim, however, must be preceded by an accurate evaluation of TDP‐43 and FUS/TLS biological functions, both in physiological and disease conditions. Recent findings have uncovered several aspects of RNA metabolism that can be affected by misregulation of these two proteins. Progress has also been made in starting to understand how the aggregation of these proteins occurs and spreads from cell to cell. The aim of this review will be to provide a general overview of TDP‐43 and FUS/TLS proteins and to highlight their physiological functions. At present, the emerging picture is that TDP‐43 and FUS/TLS control several aspects of an mRNA's life, but they can also participate in DNA repair processes and in non‐coding RNA metabolism. Although their regulatory activities are similar, they regulate mainly distinct RNA targets and show different pathogenetic mechanisms in amyotrophic lateral sclerosis/frontotemporal lobar dementia diseases. The identification of key events in these processes represents today the best chance of finding targetable options for therapeutic approaches that might actually make a difference at the clinical level.

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The two major RNA Binding Proteins involved in Amyotrophic Lateral Sclerosisi and Frontotemporal Dementia are TDP‐43 and FUST/TLS. Both proteins are involved in regulating all aspects of RNA and RNA life cycle within neurons, from transcription, processing, and transport/stability to the formation of cytoplasmic and nuclear stress granules. For this reason, the aberrant aggregation of these factors during disease can impair multiple RNA metabolic pathways and eventually lead to neuronal death/inactivation. The purpose of this review is to provide an up‐to‐date perspective on what we know about this issue at the molecular level.

This article is part of the Frontotemporal Dementia special issue.
Muscle biopsies from human muscle diseases with myopathic pathology reveal common alterations in mitochondrial function
Authors: Sunitha Balaraju , Gayathri Narayanappa , Kumar Manish , Keshava Prasad Thottethodi Subrahmanya , Nalini Atchayaram , Padmanabhan Balasundaram , Srinivas Bharath Muchukunte Mukunda
Published: March 2016

Muscle diseases are clinically and genetically heterogeneous and manifest as dystrophic, inflammatory and myopathic pathologies, among others. Our previous study on the cardiotoxin mouse model of myodegeneration and inflammation linked muscle pathology with mitochondrial damage and oxidative stress. In this study, we investigated whether human muscle diseases display mitochondrial changes. Muscle biopsies from muscle disease patients, represented by dysferlinopathy (dysfy) (dystrophic pathology; n = 43), polymyositis (PM) (inflammatory pathology; n = 24), and distal myopathy with rimmed vacuoles (DMRV) (distal myopathy; n = 31) were analyzed. Mitochondrial damage (ragged blue and COX‐deficient fibers) was revealed in dysfy, PM, and DMRV cases by enzyme histochemistry (SDH and COX‐SDH), electron microscopy (vacuolation and altered cristae) and biochemical assays (significantly increased ADP/ATP ratio). Proteomic analysis of muscle mitochondria from all three muscle diseases by isobaric tag for relative and absolute quantitation labeling and liquid chromatography‐tandem mass spectrometry (LC‐MS/MS) analysis demonstrated down‐regulation of electron transport chain (ETC) complex subunits, assembly factors and Krebs cycle enzymes. Interestingly, 80 of the under‐expressed proteins were common among the three pathologies. Assay of ETC and Krebs cycle enzyme activities validated the MS data. Mitochondrial proteins from muscle pathologies also displayed higher tryptophan (Trp) oxidation and the same was corroborated in the cardiotoxin model. Molecular modeling predicted Trp oxidation to alter the local structure of mitochondrial proteins. Our data highlight mitochondrial alterations in muscle pathologies, represented by morphological changes, altered mitochondrial proteome and protein oxidation, thereby establishing the role of mitochondrial damage in human muscle diseases.

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We investigated whether human muscle diseases display mitochondrial changes. Muscle biopsies from dysferlinopathy (Dysfy), polymyositis (PM), and distal myopathy with rimmed vacuoles (DMRV) displayed morphological and biochemical evidences of mitochondrial dysfunction. Proteomic analysis revealed down‐regulation of electron transport chain (ETC) subunits, assembly factors, and tricarboxylic acid (TCA) cycle enzymes, with 80 proteins common among the three pathologies. Mitochondrial proteins from muscle pathologies also displayed higher Trp oxidation that could alter the local structure.

Cover image for this issue: doi: 10.1111/jnc.13324.
“Like My Grandparent, But Not”: A Qualitative Investigation of Skip‐Generation Stepgrandchild–Stepgrandparent Relationships
Authors: Chapman Ashton , Coleman Marilyn , Ganong Lawrence
Published: March 2016

Families have become increasingly diverse and complex, which has made defining family membership more ambiguous. Issues surrounding family identity, belonging, and shared kinship are relevant in many types of complex families, but they are critically important for stepfamilies. In this study the authors examined stepgrandchild–stepgrandparent relationships; specifically, they explored how 27 stepgrandchildren (M age = 20.8) thought and felt about their relationships with 35 skip‐generation stepgrandparents (i.e., stepgrandparents who did not help raise stepgrandchildren's parents but who have been in the lives of stepgrandchildren from birth or early childhood). Most stepgrandchild–stepgrandparent relationships (n = 24/35) were described as emotionally close and supportive. Stepgrandchildren who perceived stepgrandparents as fulfilling traditional grandparent roles and whose parents modeled and facilitated warm, close relationships with stepgrandparents were most likely to perceive these intergenerational steprelationships as important. The findings have implications for kinship identification in diverse and complex families.
Clove bud (Syzygium aromaticum) improved blood and hepatic antioxidant indices in laying hens receiving low n‐6 to n‐3 ratios
Authors: Rahman Alizadeh M. , Mahdavi A. H. , Rahmani H. R. , Jahanian E.
Published: March 2016

This study was carried out to investigate the effects of different levels of clove bud (Syzygium aromaticum) powder and vitamin E on serum lipid profile, enzyme activities and antioxidant indices, as well as hepatic biochemical and histological alterations in laying hens receiving different n‐6 to n‐3 ratios. A total of 160 laying hens, 43 weeks of age, were allotted to 8 experimental diets with 5 cages of 4 birds each. Dietary treatments consisted of two ratios of n‐6 to n‐3 (16.71 and 2.35), three levels of clove bud (0.0, 2.0 and 4.0 g/kg) and a high vitamin E level (200 mg/kg, as a positive control in each level of n‐6 to n‐3 ratio) in a 2 × 4 factorial arrangement during 70 days of the experiment. Results showed that a decline in the n‐6 to n‐3 ratio led to a reduction in serum cholesterol concentration (p < 0.05) and an increase in serum HDL content (p < 0.05). Additionally, decreasing n‐6 to n‐3 ratio and increasing clove bud level caused a remarkable decline in serum aspartate aminotransferase (p < 0.05 and p < 0.001) and alanine aminotransferase (p < 0.05 and p < 0.05) enzyme activities. Furthermore, total antioxidant capacity (p < 0.05 and p < 0.001) as well as serum vitamin E concentration (p < 0.05 and p < 0.001) was decreased and enhanced by low n‐6 to n‐3 ratio diets (LRD) and clove bud powder respectively. Decreasing the n‐6 to n‐3 ratio lowered hepatic lipid (p < 0.05) and glycogen contents (p < 0.01) as well as tissue integrity (p < 0.05), and raised liver MDA concentration (p < 0.001), markedly. Nevertheless, increments in clove bud content led to a reduction (p < 0.01) in liver relative weight (p < 0.05) and hepatic fat vacuole numbers. In general, the best synergistic responses on modulating of blood lipids and serum enzyme activities were observed when the highest level of clove bud was supplemented in the diets with low n‐6 to n‐3 ratio. Likewise, antioxidant indices were improved by administration of dietary clove bud powder although feeding fish oil was observed to elevate the susceptibility of blood and hepatocytes to lipid peroxidation.
Dry matter and digesta particle size gradients along the goat digestive tract on grass and browse diets
Authors: Clauss M. , Fritz J. , Tschuor A. , Braun U. , Hummel J. , Codron D.
Published: March 2016

Physical properties of the digesta vary along the ruminant digestive tract. They also vary within the forestomach, leading to varying degrees of rumen contents stratification in ‘moose‐type’ (browsing) and ‘cattle‐type’ (intermediate and grazing) ruminants. We investigated the dry matter concentration (DM) and the mean digesta particle size (MPS) within the forestomach and along the digestive tract in 10 goats fed grass hay or dried browse after a standardized 12‐h fast, euthanasia and freezing in the natural position. In all animals, irrespective of diet, DM showed a peak in the omasum and an increase from caecum via colon towards the faeces and a decrease in MPS between the reticulum and the omasum. Both patterns are typical for ruminants in general. In the forestomach, there was little systematic difference between more cranial and more caudal locations (‘horizontal stratification’), with the possible exception of large particle segregation in the dorsal rumen blindsac on the grass diet. In contrast, the typical (vertical) contents stratification was evident for DM (with drier contents dorsally) and, to a lower degree, for MPS (with larger particles dorsally). Although evident in both groups, this stratification was more pronounced on the grass diet. The results support the interpretation that differences in rumen contents stratification between ruminants are mainly an effect of species‐specific physiology, but can be enhanced due to the diet consumed.
Organic aggregates formed by benthopleustophyte brown algaAcinetospora crinita(Acinetosporaceae, Ectocarpales)
Authors: Giani Michele , Sartoni Gianfranco , Nuccio Caterina , Berto Daniela , Ferrari Carla Rita , Najdek Mirjana , Sist Paola , Urbani Ranieri
Published: March 2016

This work presents the elemental, polysaccharide, and fatty acid compositions of benthic aggregates formed by the filamentous brown algaAcinetospora crinita, which are widely spread on the rocky bottoms of the Mediterranean Sea. The aggregates can be characterized as mineralized centers in which regeneration of nutrients and recycling of dissolved organic matter actively occur and favor the development of an abundant phytoplankton community. Analyses of the stable isotopes of C and N display their marine origin and could provide evidence of the processes that occur inside/outside of the aggregates. The monosaccharide compositions of Adriatic and Tyrrhenian mucilages produced by brown algaA. crinitawere quite similar. In particular, the Adriatic sample compositions resembled the average composition of the Tyrrhenian high molecular weight exopolymers, and the observed differences could be ascribed to different degradation stages. The fatty acid patterns found for the aggregates were similar to those observed in the isolatedA. crinitaalgae with variable contributions from embedded diatom species. The bacterial contribution to the fatty acid pool was quite low, most likely due to the known poor conditions for their heterotrophic growth.
Decreased expression of E‐cadherin by Porphyromonas gingivalis‐lipopolysaccharide attenuates epithelial barrier function
Authors: Abe‐Yutori M. , Chikazawa T. , Shibasaki K. , Murakami S.
Published: March 2016

Background and Objective

The gingival epithelium is a first line of defense against bacterial challenge. E‐cadherin (E‐cad) plays an important role in cell–cell adhesion as a barrier in the epithelium. Recently, a decrease in the expression of E‐cad has been observed in inflamed gingival tissue. The aims of this study were to clarify the changes in E‐cad expression and barrier function in human gingival epithelial cells stimulated with Porphyromonas gingivalis‐lipopolysaccharide (P. gingivalis‐LPS) and to evaluate the influence of these changes on the inflammatory reaction. Furthermore, to clarify the mechanism of the E‐cad changes induced by P. gingivalis‐LPS, we focused on reactive oxygen species (ROS) that are reported to induce a decrease in E‐cad expression.

Material and Methods: Human gingival epithelial cells were incubated in Humedia‐KG2 in the presence or absence of P. gingivalis‐LPS and antioxidants to analyze ROS involvement in P. gingivalis‐LPS‐induced E‐cad changes. E‐cad protein expression was analyzed by immunofluorescence staining. To investigate barrier function and inflammatory changes, we performed transport and cytokine assays using gingival epithelial cells and macrophages co‐culture model in transwell plates. Medium containing 10 μg/mL P. gingivalis‐LPS (transport substance) was added to the upper compartment, which harvested gingival epithelial cells, and medium without P. gingivalis‐LPS was added to the lower compartment, which harvested macrophages. In the transport assay, P. gingivalis‐LPS penetration was analyzed using the Limulus amebocyte lysate test. In the cytokine assay, we examined the change in tumor necrosis factor‐α (TNF‐α) production from the macrophages in the lower compartment using enzyme‐linked immunosorbent assay.

Results

Expression of E‐cad in human gingival epithelial cells was decreased by P. gingivalis‐LPS, and the decrease in E‐cad accelerated the penetration of P. gingivalis‐LPS through the monolayer. In addition, the concentration of TNF‐α was higher under the E‐cad reduced monolayer. Antioxidants, particularly vitamin E and l‐ascorbic acid 2‐phosphate magnesium salt, inhibited the decrease in E‐cad expression, penetration of P. gingivalis‐LPS and increase in TNF‐α.

Conclusion

These results suggest that the decrease in E‐cad caused by P. gingivalis‐LPS leads to destruction of the epithelial barrier function in human gingival epithelial cells, and finally accelerates the inflammatory reaction under the barrier. Antioxidants, particularly vitamin E and l‐ascorbic acid 2‐phosphate magnesium salt, may restore the impaired function by scavenging ROS, which are related to the decrease in E‐cad expression by P. gingivalis‐LPS.
High levels of heavy metal accumulation in dental calculus of smokers: a pilot inductively coupled plasma mass spectrometry study
Authors: Yaprak E. , Yolcubal İ. , Sinanoğlu A. , Doğrul‐Demiray A. , Guzeldemir‐Akcakanat E. , Marakoğlu İ.
Published: March 2016

Background and Objective

Various trace elements, including toxic heavy metals, may exist in dental calculus. However, the effect of environmental factors on heavy metal composition of dental calculus is unknown. Smoking is a major environmental source for chronic toxic heavy metal exposition. The aim of this study is to compare toxic heavy metal accumulation levels in supragingival dental calculus of smokers and non‐smokers.

Material and Methods

A total of 29 supragingival dental calculus samples were obtained from non‐smoker (n = 14) and smoker (n = 15) individuals. Subjects with a probability of occupational exposure were excluded from the study. Samples were analyzed by inductively coupled plasma mass spectrometry in terms of 26 metals and metalloids, including toxic heavy metals.

Results

Toxic heavy metals, arsenic (p < 0.05), cadmium (p < 0.05), lead (p < 0.01), manganese (p < 0.01) and vanadium (p < 0.01) levels were significantly higher in smokers than non‐smokers. The levels of other examined elements were similar in both groups (p > 0.05).

Conclusion

Within the limitations of this study, it can be concluded that the elementary composition of dental calculus may be affected by environmental factors such as tobacco smoke. Therefore, dental calculus may be utilized as a non‐invasive diagnostic biological material for monitoring chronic oral heavy metal exposition. However, further studies are required to evaluate its diagnostic potential.
Hypoxia‐inducible factor‐1α inhibits interleukin‐6 and ‐8 production in gingival epithelial cells during hypoxia
Authors: Takedachi M. , Iyama M. , Sawada K. , Mori K. , Yamamoto S. , Morimoto C. , Yanagita M. , Murakami S.
Published: March 2016

Background and Objective

Hypoxia has been widely studied in inflammatory diseases as it can modulate the inflammatory response, mainly via the hypoxia‐inducible factor (HIF). However, little is known about the effects of hypoxia and the role of HIF in the inflammatory responses to periodontitis.

In this study, we focused on the gingival epithelium that is exposed to relatively low levels of oxygen. We investigated whether hypoxic conditions have an impact on inflammatory responses in human gingival epithelial cells (HGECs).

Material and Methods

Pimonidazole HCl, which accumulates in hypoxic cells, was administered intraperitoneally to C57BL/6 mice with or without Porphyromonas gingivalis infection. Immunohistochemistry was then performed to detect the hypoxic cells in periodontal tissue. Immortalized HGECs were cultured under hypoxic conditions with or without interleukin (IL)‐1β, and the expression levels of IL‐6 and IL‐8 were measured by real‐time reverse transcription–polymerase chain reaction and enzyme‐linked immunosorbent assay. HIF‐1α expression was detected by western blotting. The DNA‐binding activity of HIF‐1α was determined by a DNA‐binding enzyme‐linked immunosorbent assay. The involvement of HIF‐1α in the hypoxic response was examined by transfection with HIF‐1α siRNA.

Results

Immunohistochemistry revealed pimonidazole HCl accumulation in the gingival epithelium of both normal and P. gingivalis‐infected mice, with a slightly stronger signal in the P. gingivalis‐infected mice than in the normal mice. The IL‐1β‐induced IL‐6 and IL‐8 production by HGECs was suppressed under hypoxic conditions. HIF‐1α accumulated during hypoxia, and this accumulation was further enhanced by IL‐1β treatment. The hypoxia‐dependent suppression of IL‐6 and IL‐8 expression was reversed by treating the cells with HIF‐1α siRNA.

Conclusion

Our results suggest that the gingival epithelium is exposed to low oxygen tension in periodontal tissue and that this hypoxic condition modulates the local inflammatory response of gingival epithelial cells in an HIF‐1α‐dependent manner.
Eosinophilic Enteritis in Horses with Motor Neuron Disease
Authors: Díez de Castro E. , Zafra R. , Acevedo L.M. , Pérez J. , Acosta I. , Rivero J.L.L. , Aguilera‐Tejero E.
Published: March 2016

Background

Equine motor neuron disease (EMND) is a neuromuscular disorder that affects adult horses. AlthoughEMNDhas been linked to vitamin E deficiency, its etiopathogenesis is poorly understood.

Objectives

To describe clinical features, laboratory results, and postmortem findings in a series of young horses with motor neuron disease (MND).

Animals

A herd of 15 young Andalusian horses with weakness, weight loss, muscle atrophy, and muscle fasciculations related to restricted intake of green forage.

Methods

A case series is presented in which horses were subjected to a clinical examination and plasma vitamin E measurement. Five severely affected horses were euthanized for detailed postmortem examination. Muscle specimens were taken from theM. sacrocaudalis dorsalis medialisand theM. gluteus mediusfor histopathologic and morphometric evaluation.

Results

MNDwas diagnosed in 5 horses based on clinical signs, low serum levels of vitamin E (0.11 ± 0.05 mg/dL; normal range,: 0.3–1.5 mg/dL), changes in muscle histopathology (neurogenic atrophy), and spinal cord lesions (neuronal chromatolysis in ventral horns). An unexpected postmortem finding was the presence of intestinal inflammation (catarrhal enteritis, edema, and eosinophilic infiltrate) associated with the presence of giant ciliated protozoa in all of the horses.

Conclusions

Although a mechanistic link could not be established, it is hypothesized that intestinal inflammation may have been involved in the decreased absorption of vitamin E, thus favoring the development ofMND.