bluuebunny/crossref_metadata_2025_split huggingface dataset:
Weight and fat distribution in patients taking valproate: A valproate‐discordant gender‐matched twin and sibling pair study
Authors: Petty Sandra J. , Kantor Susan , Lawrence Kate M. , Berkovic Samuel F. , Collins Marnie , Hill Keith D. , Makovey Joanna , Sambrook Philip N. , O'Brien Terence J. , Wark John D. 
Published: August 2014

SummaryObjectivesChronic treatment with valproate (VPA) is commonly associated with weight gain, which potentially has important health implications, in particular increased central fat distribution. We utilized a VPA‐discordant same‐sex, twin and matched sibling pair study design to primarily examine for differences in fat distribution between patients with epilepsy treated with VPA compared to their matched twin or sibling control. Weight, blood pressure, and leptin levels were assessed.MethodsHeight, weight, waist and hip measurements, exercise, blood pressure (BP), and serum leptin levels were measured. Body composition was measured using dual‐energy x‐ray absorptiometry (DXA). Abdominal fat was expressed as a percentage of the abdominal region (AFat%); and of whole body fat (WBF); (AFat%WBF). Mean within‐pair differences were assessed (VPA‐user and nonuser). Restricted maximum likelihood (REML) linear mixed model analysis was fitted to examine associations of anthropometrics, zygosity, gender, menopausal status, VPA dose and duration, with weight and AFat%.ResultsWe studied 19 pairs of VPA‐discordant, gender‐matched (five male, 14 female) twins and siblings. Mean (standard deviation, SD) duration of therapy for VPA users was 11.0 (7.4) years. There were no statistically significant within‐pair differences in age, height, weight, body mass index (BMI), BP, leptin level, WBF, AFat%, or AFat%WBF. For pairs in which VPA‐user was treated for >11 years there were statistically significant mean within‐pair differences in AFat%, (+7.1%, p = 0.03, n = 10 pairs), mean BP (+11.0 mm Hg, p = 0.006, n = 8 pairs); but not in AFat%WBF. VPA duration was positively associated with weight (estimate +0.98 kg/per year of VPA, p = 0.03); VPA treatment duration and dose were not significantly associated with AFat%.SignificanceThis study demonstrated a relationship between long‐term VPA use and abdominal adiposity (AFat%), which could have significant health implications. We recommend ongoing monitoring of weight, BMI, and blood pressure for patients taking VPA.
The interrelationship between anti‐Müllerian hormone, ovarian follicular populations and age in mares
Authors: Claes A. , Ball B. A. , Scoggin K. E. , Esteller‐Vico A. , Kalmar J. J. , Conley A. J. , Squires E. L. , Troedsson M. H. T. 
Published: August 2014

SummaryReasons for performing studyAnti‐Müllerian hormone (AMH) is a granulosa‐cell‐derived glycoprotein, which plays an important inhibitory role during folliculogenesis. Concentrations of AMH are highly correlated with antral follicle counts (AFCs) in other species, which in turn are related to follicular reserve. Relatively little is known about AMH and AFC in the mare.ObjectivesTo determine plasma AMH concentrations and AFCs in mares of different ages, to measure the repeatability of AMH concentrations and AFCs within and across oestrous cycles and to assess the relationship between plasma AMH concentrations and AFCs with regard to mare age and follicle size.Study designAn observational study examining the relationship between AMH, AFC and age in 45 mares.MethodsYoung (3–8 years), middle‐aged (9–18 years) and old mares (19–27 years) were examined by transrectal ultrasonography over 2 or 3 oestrous cycles. Plasma AMH concentrations and AFCs were determined, and antral follicles were classified by size into different groups.ResultsPlasma AMH concentrations varied widely between mares within similar age groups. Antral follicle counts were significantly lower in old mares than in young and middle‐aged mares, and AMH concentrations were significantly lower in old than in middle‐aged mares. A positive relationship was detected between AFC and AMH, and this relationship varied by mare age with a strong correlation in older mares (ρ = 0.86; P<0.0001), a moderate correlation in middle‐aged mares (ρ = 0.60; P = 0.01) and no correlation in young mares (ρ = 0.40, P<0.4). The AMH concentrations were significantly related to the number of antral follicles between 6 and 20 mm in diameter, and the repeatability of AFCs and AMH concentrations was high within and between oestrous cycles.ConclusionsOur findings indicate that the relationship between AMH and AFC varies across age groups, and concentrations of AMH might be a better reflection of reproductive age than calendar age.
Towards elucidating the stability, dynamics and architecture of the nucleosome remodeling and deacetylase complex by using quantitative interaction proteomics
Authors: Kloet Susan L. , Baymaz H. Irem , Makowski Matthew , Groenewold Vincent , Jansen Pascal W. T. C. , Berendsen Madeleine , Niazi Hassin , Kops Geert J. , Vermeulen Michiel 
Published: August 2014

The nucleosome remodeling and deacetylase (NuRD) complex is an evolutionarily conserved chromatin‐associated protein complex. Although the subunit composition of the mammalian complex is fairly well characterized, less is known about the stability and dynamics of these interactions. Furthermore, detailed information regarding protein–protein interaction surfaces within the complex is still largely lacking. Here, we show that the NuRD complex interacts with a number of substoichiometric zinc finger‐containing proteins. Some of these interactions are salt‐sensitive (ZNF512B and SALL4), whereas others (ZMYND8) are not. The stoichiometry of the core subunits is not affected by high salt concentrations, indicating that the core complex is stabilized by hydrophobic interactions. Interestingly, the RBBP4 and RBBP7 proteins are sensitive to high nonionic detergent concentrations during affinity purification. In a subunit exchange assay with stable isotope labeling by amino acids in cell culture (SILAC)‐treated nuclear extracts, RBBP4 and RBBP7 were identified as dynamic core subunits of the NuRD complex, consistent with their proposed role as histone chaperones. Finally, using cross‐linking MS, we have uncovered novel features of NuRD molecular architecture that complement our affinity purification‐MS/MS data. Altogether, these findings extend our understanding of MBD3–NuRD structure and stability.Structured digital abstract

MBD3 physically interacts with ZNF512B, HDAC1, ZMYND8, GATAD2B, SALL4, GATAD2A, ZNF592, MTA3, ZNF687, CDK2AP1, CHD3, ZNF532, HDAC2, MTA2, CHD4, MTA1, KPNA2, CHD5, RBBP4 and RBBP7 by pull down (View interaction)

CDK2AP1 physically interacts with MBD3, MTA3, HDAC2, GATAD2A, CHD4, CDK2AP1, MTA2, HDAC1, MTA1, CHD3, GATAD2B, MBD2, RBBP4 and RBBP7 by pull down (View interaction)

MBD3 physically interacts with MTA2, MTA3, RBBP4, RBBP7, HDAC2, HDAC1, CHD4, CHD3 and MTA1 by cross-linking study (View interaction)
Transcriptional and epigenetic regulation of T‐helper lineage specification
Authors: Tripathi Subhash K. , Lahesmaa Riitta 
Published: August 2014

SummaryCombined with TCR stimuli, extracellular cytokine signals initiate the differentiation of naive CD4+ T cells into specialized effector T‐helper (Th) and regulatory T (Treg) cell subsets. The lineage specification and commitment process occurs through the combinatorial action of multiple transcription factors (TFs) and epigenetic mechanisms that drive lineage‐specific gene expression programs. In this article, we review recent studies on the transcriptional and epigenetic regulation of distinct Th cell lineages. Moreover, we review current study linking immune disease‐associated single‐nucleotide polymorphisms with distal regulatory elements and their potential role in the disease etiology.
The interface between transcriptional and epigenetic control of effector and memory CD8+ T‐cell differentiation
Authors: Gray Simon M. , Kaech Susan M. , Staron Matthew M. 
Published: August 2014

SummaryImmunity to many intracellular pathogens requires the proliferation, differentiation, and function of CD8+ cytotoxic T lymphocytes (CTLs). While the majority of effector CTLs die upon clearance of the pathogen, a small proportion of them survive to become long‐lived memory CTLs. Memory CTLs can provide protective immunity against re‐exposure to the same pathogen and are the principle motivation behind T‐cell‐ based vaccine design. While a large body of cellular immunologic research has proven invaluable to define effector and memory CTLs by their different phenotypes and functions, an emerging focus in the field has been to understand how environmental cues regulate CTL differentiation on a genomic level. Genome‐wide studies to profile transcriptional and epigenetic changes during infection have revealed that dynamic changes in DNA methylation patterns and histone modifications accompany transcriptional signatures that define and regulate CTL differentiation states. In this review, we emphasize the importance of epigenetic regulation of CD8+ T‐cell differentiation and the likely role that transcription factors play in this process.
The regulatory network of B‐cell differentiation: a focused view of early B‐cell factor 1 function
Authors: Boller Sören , Grosschedl Rudolf 
Published: August 2014

SummaryDuring the last decades, many studies have investigated the transcriptional and epigenetic regulation of lineage decision in the hematopoietic system. These efforts led to a model in which extrinsic signals and intrinsic cues establish a permissive chromatin context upon which a regulatory network of transcription factors and epigenetic modifiers act to guide the differentiation of hematopoietic lineages. These networks include lineage‐specific factors that further modify the epigenetic landscape and promote the generation of specific cell types. The process of B lymphopoiesis requires a set of transcription factors, including Ikaros, PU.1, E2A, and FoxO1 to ‘prime’ cis‐regulatory regions for subsequent activation by the B‐lineage‐specific transcription factors EBF1 and Pax‐5. The expression of EBF1 is initiated by the combined action of E2A and FoxO1, and it is further enhanced and maintained by several positive feedback loops that include Pax‐5 and IL‐7 signaling. EBF1 acts in concert with Ikaros, PU.1, Runx1, E2A, FoxO1, and Pax‐5 to establish the B cell‐specific transcription profile. EBF1 and Pax‐5 also collaborate to repress alternative cell fates and lock cells into the B‐lineage fate. In addition to the functions of EBF1 in establishing and maintaining B‐cell identity, EBF1 is required to coordinate differentiation with cell proliferation and survival.
Transcriptional and epigenetic networks of helper T and innate lymphoid cells
Authors: Shih Han‐Yu , Sciumè Giuseppe , Poholek Amanda C. , Vahedi Golnaz , Hirahara Kiyoshi , Villarino Alejandro V. , Bonelli Michael , Bosselut Remy , Kanno Yuka , Muljo Stefan A. , O'Shea John J. 
Published: August 2014

SummaryThe discovery of the specification of CD4+ helper T cells to discrete effector ‘lineages’ represented a watershed event in conceptualizing mechanisms of host defense and immunoregulation. However, our appreciation for the actual complexity of helper T‐cell subsets continues unabated. Just as the Sami language of Scandinavia has 1000 different words for reindeer, immunologists recognize the range of fates available for a CD4+ T cell is numerous and may be underestimated. Added to the crowded scene for helper T‐cell subsets is the continuously growing family of innate lymphoid cells (ILCs), endowed with common effector responses and the previously defined ‘master regulators’ for CD4+ helper T‐cell subsets are also shared by ILC subsets. Within the context of this extraordinary complexity are concomitant advances in the understanding of transcriptomes and epigenomes. So what do terms like ‘lineage commitment’ and helper T‐cell ‘specification’ mean in the early 21st century? How do we put all of this together in a coherent conceptual framework? It would be arrogant to assume that we have a sophisticated enough understanding to seriously answer these questions. Instead, we review the current status of the flexibility of helper T‐cell responses in relation to their genetic regulatory networks and epigenetic landscapes. Recent data have provided major surprises as to what master regulators can or cannot do, how they interact with other transcription factors and impact global genome‐wide changes, and how all these factors come together to influence helper cell function.
Vitamin E and wound healing: an evidence‐based review
Authors: Hobson Rachel 
Published: August 2014

AbstractVitamin E has been demonstrated to modulate cellular signalling, gene expression and affect wounds infected with methicillin‐resistant Staphylococcus aureus (MRSA), thus influencing wound healing. This evidence‐based review aimed to identify and evaluate current research assessing the properties of vitamin E in relation to wound healing, through its role as an antioxidant and its influence on connective tissue growth factor (CTGF), MRSA and gene transcription. Literature dated from 1996 to 2012, published in English, involving either animals or adult humans with an acute or chronic wound were included. The databases that contained relevant articles were narrowed down to four, and a total of 33 identified studies were included. The literature review revealed that there is a significant dearth of robust studies establishing the effects of vitamin E on wound healing, and further research is clearly warranted.
Higher Levels of Cystatin C Are Associated with Worse Cognitive Function in Older Adults with Chronic Kidney Disease: The Chronic Renal Insufficiency Cohort Cognitive Study
Authors: Yaffe Kristine , Kurella‐Tamura Manjula , Ackerson Lynn , Hoang Tina D. , Anderson Amanda H. , Duckworth Mark , Go Alan S. , Krousel‐Wood Marie , Kusek John W. , Lash James P. , Ojo Akinlolu , Robinson Nancy , Sehgal Ashwini R. , Sondheimer James H. , Steigerwalt Susan , Townsend Raymond R. 
Published: August 2014

ObjectivesTo determine the association between cognition and levels of cystatin C in persons with chronic kidney disease (CKD).DesignProspective observational study.SettingChronic Renal Insufficiency Cohort Cognitive Study.ParticipantsIndividuals with a baseline cognitive assessment completed at the same visit as serum cystatin C measurement (N = 821; mean age 64.9, 50.6% male, 48.6% white).MeasurementsLevels of serum cystatin C were categorized into tertiles; cognitive function was assessed using six neuropsychological tests. Scores on these tests were compared across tertiles of cystatin C using linear regression and logistic regression to examine the association between cystatin C level and cognitive performance (1 standard deviation difference from the mean).ResultsAfter multivariable adjustment for age, race, education, and medical comorbidities in linear models, higher levels of cystatin C were associated with worse cognition on the modified Mini‐Mental State Examination, Buschke Delayed Recall, Trail‐Making Test Part (Trails) A and Part B, and Boston Naming (P < .05 for all). This association remained statistically significant for Buschke Delayed Recall (P = .01) and Trails A (P = .03) after additional adjustment for estimated glomerular filtration rate (eGFR). The highest tertile of cystatin C was associated with greater likelihood of poor performance on Trails A (odds ratio (OR) = 2.17, 95% confidence interval (CI) = 1.16–4.06), Trails B (OR = 1.89, 95% CI = 1.09–3.27), and Boston Naming (OR = 1.85, 95% CI = 1.07–3.19) than the lowest tertile after multivariate adjustment in logistic models.ConclusionIn individuals with CKD, higher serum cystatin C levels were associated with worse cognition and greater likelihood of poor cognitive performance on attention, executive function, and naming. Cystatin C is a marker of cognitive impairment and may be associated with cognition independent of eGFR.
Hydrogen sulfide is essential for Schwann cell responses to peripheral nerve injury
Authors: Park Byung Sun , Kim Hyun‐Wook , Rhyu Im Joo , Park Chan , Yeo Seung Geun , Huh Youngbuhm , Jeong Na Young , Jung Junyang 
Published: August 2014

AbstractHydrogen sulfide (H2S) functions as a physiological gas transmitter in both normal and pathophysiological cellular events. H2S is produced from substances by three enzymes: cystathionine β‐synthase (CBS), cystathionine γ‐lyase (CSE), and 3‐mercaptopyruvate sulfurtransferase (MST). In human tissues, these enzymes are involved in tissue‐specific biochemical pathways for H2S production. For example, CBS and cysteine aminotransferase/MST are present in the brain, but CSE is not. Thus, we examined the expression of H2S production‐related enzymes in peripheral nerves. Here, we found that CSE and MST/cysteine aminotransferase, but not CBS, were present in normal peripheral nerves. In addition, injured sciatic nerves in vivo up‐regulated CSE in Schwann cells during Wallerian degeneration (WD); however, CSE was not up‐regulated in peripheral axons. Using an ex vivo sciatic nerve explant culture, we found that the inhibition of H2S production broadly prevented the process of nerve degeneration, including myelin fragmentation, axonal degradation, Schwann cell dedifferentiation, and Schwann cell proliferation in vitro and in vivo. Thus, these results indicate that H2S signaling is essential for Schwann cell responses to peripheral nerve injury.
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Hydrogen sulfide (H2S) functions as a physiological gas transmitter in both normal and pathophysiological cellular events. H2S is produced from cystathionine β‐synthase (CBS), cystathionine γ‐lyase (CSE), and 3‐mercaptopyruvate sulfur transferase (MST). Here, we found that CSE and MST/CAT were present in normal peripheral nerves. Injured static nerves in vivo up‐regulated CSE in Schwann cells during Wallerian degeneration, but CSE was not up‐regulated in peripheral axons.
Comparison of Results from Cupping and Descriptive Sensory Analysis of Colombian Brewed Coffee
Authors: Di Donfrancesco B. , Gutierrez Guzman N. , Chambers E. 
Published: August 2014

AbstractSensory profiles of 13 coffee samples from the Huila Region, Colombia were evaluated using two different sensory panels: a highly trained descriptive sensory panel and a group of Q‐certified coffee cuppers. The trained panel consisted of six descriptive panelists who developed a lexicon to evaluate and then test the coffee samples. Four “cuppers” scored the same samples based on the Specialty Coffee Association of America “cupping protocol.” In addition, cuppers generated tasting notes to characterize the different coffee samples. Data indicated little overlap between the two methods and a low relationship between the two different sets of terms. Moreover, tasting notes by cuppers indicate lack of agreement on the terms used to describe samples, with only four terms used by more than two assessors to describe a single coffee product out of a total of 59 terms used by the cuppers. The results indicate that the cupping method and sensory descriptive methods provide different information that cannot be used as an alternative to each other when describing coffee products. Instead, the results suggest that the two types of data may be used synergistically to evaluate the quality and the sensory properties to better characterize coffee samples.Practical ApplicationsThis research shows that “expert” coffee cupper data and trained sensory panel data cannot be used interchangeably. Thus, for research purposes sensory panel information is necessary for tracking changes in sensory properties.
The solid-state continuum: a perspective on the interrelationships between different solid-state forms in drug substance and drug product
Authors: Elder David P , Patterson James E , Holm René 
Published: August 2014

Abstract

Objective
The objective of the review is to provide an overview of the nomenclature used in the solid-state continuum and relate these to the development of drug substances and drug products.

Key findings
The importance of a rational approach to solid-state form selection, including integrated decision making (ensuring equal weight is given to the needs of the drug substance and the drug product), is vital for the effective development of a drug candidate. For example, how do secondary processing considerations influence the selection of drug substance solid-state form and resulting formulation, and how can drug substance solid-state form be used to optimise secondary processing? Further, the potential use of ‘crystal’ engineering to optimise stability, purity and optical resolutions, and the linked regulatory requirements, will be discussed.

Summary
The nomenclature used in the solid-state continuum, which contains a large number of different crystalline and non-crystalline forms, for example, amorphous systems, was reviewed. Further, the significant role of the drug substance within the solid oral dose form from a physicochemical perspective was covered.
Records of the Moon‐forming impact and the 470 Ma disruption of the L chondrite parent body in the asteroid belt from U‐Pb apatite ages of Novato (L6)
Authors: Yin Qing‐Zhu , Zhou Qin , Li Qiu‐Li , Li Xian‐Hua , Liu Yu , Tang Guo‐Qiang , Krot Alexander N. , Jenniskens Peter 
Published: August 2014

AbstractNovato, a newly observed fall in the San Francisco Bay area, is a shocked and brecciated L6 ordinary chondrite containing dark and light lithologies. We have investigated the U‐Pb isotope systematics of coarse Cl‐apatite grains of metamorphic origin in Novato with a large geometry ion microprobe. The U‐Pb systematics of Novato apatite reveals an upper intercept age of 4472 ± 31 Ma and lower intercept age of 473 ± 38 Ma. The upper intercept age is within error identical to the U‐Pb apatite age of 4452 ± 21 Ma measured in the Chelyabinsk LL5 chondrite. This age is interpreted to reflect a massive collisional resetting event due to a large impact associated with the peak arrival time at the primordial asteroid belt of ejecta debris from the Moon‐forming giant impact on Earth. The lower intercept age is consistent with the most precisely dated Ar‐Ar ages of 470 ± 6 Ma of shocked L chondrites, and the fossil meteorites and extraterrestrial chromite relicts found in Ordovician limestones with an age of 467.3 ± 1.6 Ma in Sweden and China. The lower intercept age reflects a major disturbance related to the catastrophic disruption of the L chondrite parent body most likely associated with the Gefion asteroid family, which produced an initially intense meteorite bombardment of the Earth in Ordovician period and reset and degassed at least approximately 35% of the L chondrite falls today. We predict that the 470 Ma impact event is likely to be found on the Moon and Mars, if not Mercury.
Ambulatory measurement of the ECG T‐wave amplitude
Authors: van Lien René , Neijts Melanie , Willemsen Gonneke , de Geus Eco J. C. 
Published: August 2014

AbstractAmbulatory recording of the preejection period (PEP) can be used to measure changes in cardiac sympathetic nervous system (SNS) activity under naturalistic conditions. Here, we test the ECG T‐wave amplitude (TWA) as an alternative measure, using 24‐h ambulatory monitoring of PEP and TWA in a sample of 564 healthy adults. The TWA showed a decrease in response to mental stress and a monotonic decrease from nighttime sleep to daytime sitting and more physically active behaviors. Within‐participant changes in TWA were correlated with changes in the PEP across the standardized stressors (r = .42) and the unstandardized naturalistic conditions (mean r = .35). Partialling out changes in heart rate and vagal effects attenuated these correlations, but they remained significant. Ambulatory TWA cannot replace PEP, but simultaneous recording of TWA and PEP provides a more comprehensive picture of changes in cardiac SNS activity in real‐life settings.