bluuebunny/crossref_metadata_2025 huggingface dataset:
Native T1 value in the remote myocardium is independently associated with left ventricular dysfunction in patients with prior myocardial infarction
Authors: Nakamori Shiro , Alakbarli Javid , Bellm Steven , Motiwala Shweta R. , Addae Gifty , Manning Warren J. , Nezafat Reza
Published: February 2017

Purpose

To compare remote myocardium native T1 in patients with chronic myocardial infarction (MI) and controls without MI and to elucidate the relationship of infarct size and native T1 in the remote myocardium for the prediction of left ventricular (LV) systolic dysfunction after MI.

Materials and Methods

A total of 41 chronic MI (18 anterior MI) patients and 15 age‐matched volunteers with normal LV systolic function and no history of MI underwent cardiac magnetic resonance imaging (MRI) at 1.5T. Native T1 map was performed using a slice interleaved T1 mapping and late gadolinium enhancement (LGE) imaging. Cine MR was acquired to assess LV function and mass.

Results

The remote myocardium native T1 time was significantly elevated in patients with prior MI, compared to controls, for both anterior MI and nonanterior MI (anterior MI: 1099 ± 30, nonanterior MI: 1097 ± 39, controls: 1068 ± 25 msec, P < 0.05). Remote myocardium native T1 moderately correlated with LV volume, mass index, and ejection fraction (r = 0.38, 0.50, –0.49, respectively, all P < 0.05). LGE infarct size had a moderate correlation with reduced LV ejection fraction (r = –0.33, P < 0.05), but there was no significant association between native T1 and infarct size. Native T1 time in the remote myocardium was independently associated with reduced LV ejection fraction, after adjusting for age, gender, infarct size, and comorbidity (β = –0.34, P = 0.03).

Conclusion

In chronic MI, the severity of LV systolic dysfunction after MI is independently associated with native T1 in the remote myocardium. Diffuse myocardial fibrosis in the remote myocardium may play an important pathophysiological role of post‐MI LV dysfunction.

Level of Evidence: 1

Technical Efficacy: Stage 2

J. Magn. Reson. Imaging 2017;46:1073–1081.
Biochemical markers of cartilage metabolism are associated with walking biomechanics 6‐months following anterior cruciate ligament reconstruction
Authors: Pietrosimone Brian , Loeser Richard F. , Blackburn J. Troy , Padua Darin A. , Harkey Matthew S. , Stanley Laura E. , Luc‐Harkey Brittney A. , Ulici Veronica , Marshall Stephen W. , Jordan Joanne M. , Spang Jeffery T.
Published: February 2017

The purpose of our study was to determine the association between biomechanical outcomes of walking gait (peak vertical ground reaction force [vGRF], vGRF loading rate [vGRF‐LR], and knee adduction moment [KAM]) 6 months following anterior cruciate ligament reconstruction (ACLR) and biochemical markers of serum type‐II collagen turnover (collagen type‐II cleavage product to collagen type‐II C‐propeptide [C2C:CPII]), plasma degenerative enzymes (matrix metalloproteinase‐3 [MMP‐3]), and a pro‐inflammatory cytokine (interleukin‐6 [IL‐6]). Biochemical markers were evaluated within the first 2 weeks (6.5 ± 3.8 days) following ACL injury and again 6 months following ACLR in eighteen participants. All peak biomechanical outcomes were extracted from the first 50% of the stance phase of walking gait during a 6‐month follow‐up exam. Limb symmetry indices (LSI) were used to normalize the biomechanical outcomes in the ACLR limb to that of the contralateral limb (ACLR/contralateral). Bivariate correlations were used to assess associations between biomechanical and biochemical outcomes. Greater plasma MMP‐3 concentrations after ACL injury and at the 6‐month follow‐up exam were associated with lesser KAM LSI. Lesser KAM was associated with greater plasma IL‐6 at the 6‐month follow‐up exam. Similarly, lesser vGRF‐LR LSI was associated with greater plasma MMP‐3 concentrations at the 6‐month follow‐up exam. Lesser peak vGRF LSI was associated with higher C2C:CPII after ACL injury, yet this association was not significant after accounting for walking speed. Therefore, lesser biomechanical loading in the ACLR limb, compared to the contralateral limb, 6 months following ACLR may be related to deleterious joint tissue metabolism that could influence future cartilage breakdown. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2288–2297, 2017.
Phosphatase and tensin homolog–β‐catenin signaling modulates regulatory T cells and inflammatory responses in mouse liver ischemia/reperfusion injury
Authors: Zhu Qiang , Li Changyong , Wang Kunpeng , Yue Shi , Jiang Longfeng , Ke Michael , Busuttil Ronald W. , Kupiec‐Weglinski Jerzy W. , Zhang Feng , Lu Ling , Ke Bibo
Published: February 2017

The phosphatase and tensin homolog (PTEN) deleted on chromosome 10 plays an important role in regulating T cell activation during inflammatory response. Activation of β‐catenin is crucial for maintaining immune homeostasis. This study investigates the functional roles and molecular mechanisms by which PTEN–β‐catenin signaling promotes regulatory T cell (Treg) induction in a mouse model of liver ischemia/reperfusion injury (IRI). We found that mice with myeloid‐specific phosphatase and tensin homolog knockout (PTENM‐KO) exhibited reduced liver damage as evidenced by decreased levels of serum alanine aminotransferase, intrahepatic macrophage trafficking, and proinflammatory mediators compared with the PTEN‐proficient (floxed phosphatase and tensin homolog [PTENFL/FL]) controls. Disruption of myeloid PTEN‐activated b‐catenin promoted peroxisome proliferator‐activated receptor gamma (PPARγ)‐mediated Jagged‐1/Notch signaling and induced forkhead box P3 (FOXP3)1 Tregs while inhibiting T helper 17 cells. However, blocking of Notch signaling by inhibiting γ‐secretase reversed myeloid PTEN deficiency‐mediated protection in ischemia/reperfusion–triggered liver inflammation with reduced FOXP3+ and increased retinoid A receptor–related orphan receptor gamma t–mediated interleukin 17A expression in ischemic livers. Moreover, knockdown of β‐catenin or PPARγ in PTEN‐deficient macrophages inhibited Jagged‐1/Notch activation and reduced FOXP3+ Treg induction, leading to increased proinflammatory mediators in macrophage/T cell cocultures. In conclusion, our findings demonstrate that PTEN–β‐catenin signaling is a novel regulator involved in modulating Treg development and provides a potential therapeutic target in liver IRI. Liver Transplantation 23 813–825 2017 AASLD.
Adrenomedullin – new perspectives of a potent peptide hormone
Authors: Schönauer Ria , Els‐Heindl Sylvia , Beck‐Sickinger Annette G.
Published: February 2017

Adrenomedullin (ADM) is a 52‐amino acid multifunctional peptide, which belongs to the calcitonin gene‐related peptide (CGRP) superfamily of vasoactive peptide hormones. ADM exhibits a significant vasodilatory potential and plays a key role in various regulatory mechanisms, predominantly in the cardiovascular and lymphatic system. It exerts its effects by activation of the calcitonin receptor‐like receptor associated with one of the receptor activity‐modifying proteins 2 or 3. ADM was first isolated from human phaeochromocytoma in 1993. Numerous studies revealed a widespread distribution in various tissues and organs, which is reflected by its multiple physiological roles in health and disease. Because of its anti‐inflammatory, anti‐apoptotic and proliferative properties, ADM exhibits potent protective functions under diverse pathological conditions, but it is also critically involved in tumor progression. ADM has therefore raised great interest in therapeutic applications and several clinical trials already revealed promising results. However, because the receptor activation mode has not yet been fully elucidated, a rational design of potent and selective ligands is still challenging. Detailed information on the binding mode of ADM from a recently reported crystal structure as well as efforts to improve its plasma stability and bioavailability may help to overcome these limitations in the future. Copyright © 2017 European Peptide Society and John Wiley & Sons, Ltd.
Mesenchymal Stromal Cell Therapy for Chronic Lung Allograft Dysfunction: Results of a First-in-Man Study
Authors: Chambers Daniel C. , Enever Debra , Lawrence Sharon , Sturm Marian J. , Herrmann Richard , Yerkovich Stephanie , Musk Michael , Hopkins Peter M.A.
Published: February 2017

Chronic lung transplant rejection (termed chronic lung allograft dysfunction [CLAD]) is the main impediment to long-term survival after lung transplantation. Bone marrow-derived mesenchymal stromal cells (MSCs) represent an attractive cell therapy in inflammatory diseases, including organ rejection, given their relative immune privilege and immunosuppressive and tolerogenic properties. Preclinical studies in models of obliterative bronchiolitis and human trials in graft versus host disease and renal transplantation suggest potential efficacy in CLAD. The purpose of this phase 1, single-arm study was to explore the feasibility and safety of intravenous delivery of allogeneic MSCs to patients with advanced CLAD. MSCs from unrelated donors were isolated from bone marrow, expanded and cryopreserved in a GMP-compliant facility. Patients had deteriorating CLAD and were bronchiolitis obliterans (BOS) grade ≥ 2 or grade 1 with risk factors for rapid progression. MSCs (2 x 106 cells per kilogram patient weight) were infused via a peripheral vein twice weekly for 2 weeks, with 52 weeks follow-up. Ten Patients (5 male, 8 bilateral, median [interquartile range] age 40 [30–59] years, 3 BOS2, 7 BOS3) participated. MSC treatment was well tolerated with all patients receiving the full dosing schedule without any procedure-related serious adverse events. The rate of decline in forced expiratory volume in one second slowed after the MSC infusions (120 ml/month preinfusion vs. 30 ml/month postinfusion, p = .08). Two patients died at 152 and 270 days post-MSC treatment, both from progressive CLAD. In conclusion, infusion of allogeneic bone marrow-derived MSCs is feasible and safe even in patients with advanced CLAD.
Pharmacological inhibition of DNA methyltransferase 1 promotes neuronal differentiation from rodent and human nasal olfactory stem/progenitor cell cultures
Authors: Franco I. , Ortiz‐López L. , Roque‐Ramírez B. , Ramírez‐Rodríguez G.B. , Lamas M.
Published: February 2017

Nasal olfactory stem and neural progenitor cells (NOS/PCs) are considered possible tools for regenerative stem cell therapies in neurodegenerative diseases. Neurogenesis is a complex process regulated by extrinsic and intrinsic signals that include DNA‐methylation and other chromatin modifications that could be experimentally manipulated in order to increase neuronal differentiation. The aim of the present study was the characterization of primary cultures and consecutive passages (P2–P10) of NOS/PCs isolated from male Swiss‐Webster (mNOS/PCs) or healthy humans (hNOS/PCs). We evaluated and compared cellular morphology, proliferation rates and the expression pattern of pluripotency‐associated markers and DNA methylation‐associated gene expression in these cultures. Neuronal differentiation was induced by exposure to all‐trans retinoic acid and forskolin for 7 days and evaluated by morphological analysis and immunofluorescence against neuronal markers MAP2, NSE and MAP1B. In response to the inductive cues mNOS/PCs expressed NSE (75.67%) and MAP2 (35.34%); whereas the majority of the hNOS/PCs were immunopositive to MAP1B. Treatment with procainamide, a specific inhibitor of DNA methyltransferase 1 (DNMT1), increases in the number of forskolin‘/retinoic acid‐induced mature neuronal marker‐expressing mNOS/PCs cells and enhances neurite development in hNOS/PCs. Our results indicate that mice and human nasal olfactory stem/progenitors cells share pluripotency‐related gene expression suggesting that their application for stem cell therapy is worth pursuing and that DNA methylation inhibitors could be efficient tools to enhance neuronal differentiation from these cells.
DUST CAVE REVISITED: A BAYESIAN REANALYSIS OF THE RADIOCARBON RECORD
Authors: Thulman David K.
Published: February 2017

The Dust Cave cultural chronology and radiocarbon sequence is one of the most important in southeastern North America. In their initial interpretation, the excavators were unable to separate the dates of the early and later strata in ways that facilitate their use for defining the associated cultural components. Here the sequence is reevaluated using Bayesian statistics, one additional date, and assessment of potential outliers. The results produce a useable sequence of non-overlapping cultural components (within the uncertainties of radiocarbon dating) that will improve our understanding the Paleoindian and Early and Middle Archaic cultural chronology in the Southeast.
The mass movement and public policy: discourses of participatory democracy in post-1994 South Africa
Authors: Brooks Heidi
Published: February 2017

Despite policy commitments and legislated mechanisms, the system of participatory democracy in post-1994 South Africa is largely considered to have failed. In order to understand how underlying ideas can help to explain weaknesses in practice, this article examines how participatory democracy is understood by the ruling African National Congress (ANC). It shows that the multiple intellectual traditions shaping the participatory model have led to a set of policy initiatives that are not without internal tension. In part, the technocratic creep associated with improving public sector performance has stymied participatory efforts by placing efficiency and delivery over democracy and empowerment. Alongside this, however, the ANC's own conception of ‘democracy’ remains interwoven with its mass movement history – linking the role of popular participation to the extension of its own hegemony. The intent of policy to deepen democracy through structures of participatory governance is thus undermined by a teleological framing of participation as an intra-movement activity.
Mexico City Spanish
Authors: Avelino Heriberto
Published: February 2017

Spanish is a Romance language spoken by approximately 405,638,110 speakers in the world (Lewis, Simons & Fenning 2013). Two major varieties are distinguished, Peninsular Spanish (Spain) and the Spanish spoken in the Americas, although it is also spoken natively in some parts of Africa, and in the United States. Spanish in the Americas comprises several dialects well differentiated by variations in the lexicon, phonology and, more importantly, in intonational patterns. In Mexico 86,211,000 (88% of the population) use Spanish as their first language, and a significant number of indigenous people have Spanish as their second language. The variety illustrated here is representative of the speech of the educated middle-class population from the metropolitan zone (three female and three male speakers in their 30s), which has as its center Mexico City, the most densely populated urban area in the country with more than 20 million people according to the Mexican National Census (INEGI 2010).
Influence of Tillage on Control of Wild Oat (Avena fatua) by the Soil-applied Herbicide Pyroxasulfone
Authors: Mangin Amy R. , Hall Linda M. , Schoenau Jeff J. , Beckie Hugh J
Published: February 2017

Wild oat control options are limited in western Canada due to resistance to most common herbicides. Control of wild oat with pyroxasulfone, a soil-applied, very-long-chain fatty-acid inhibitor, was investigated. A series of greenhouse and field experiments were conducted to isolate the effects of vertical seed position, site of herbicide interception, and tillage on wild oat control with pyroxasulfone in comparison with triallate. In greenhouse experiments, wild oat shoot length (soil surface to leaf tip) was reduced (P<0.05) in shallow-seeded wild oat compared with deep-seeded wild oat with pyroxasulfone (6.2 and 9.8 cm, respectively) and triallate (3.7 and 13.2 cm, respectively). Soil-applied pyroxasulfone remained in the top 2.5 cm of the soil with or without a simulated rainfall event. Pyroxasulfone was most effective if either the seed or the shoot 1 cm above the seed intercepted the herbicide layer. If a wild oat emerges from deeper in the soil profile, the sensitive part of the seedling may not intercept an effective rate of pyroxasulfone in the soil. In field experiments comparing deep- and shallow-seeded wild oat treated with pyroxasulfone and triallate in fields with and without tillage, there were no significant effects of tillage alone on wild oat shoot length. Deep-seeded wild oat emerged early, and while herbicides reduced shoot growth, shoots were >10 cm. Shallow-seeded wild oat had delayed emergence, possibly due to reduced soil moisture, and herbicides reduced shoot growth to <10cm. Pyroxasulfone is likely to be more effective in no-till fields where wild oat seeds are not located deep in the soil.
Increase in the radioresistance of normal skin fibroblasts but not tumor cells by mechanical injury
Authors: Chen Zelin , Wang Xin , Jin Taotao , Wang Yu , Hong Christopher S , Tan Li , Dai Tingyu , Wu Liao , Zhuang Zhengping , Shi Chunmeng
Published: February 2017

The timing of radiation after mechanical injury such as in the case of surgery is considered a clinical challenge because radiation is assumed to impair wound healing. However, the physiological responses and underlying mechanisms of this healing impairment are still unclear. Here, we show that mechanical injury occurring before ionizing radiation decreases radiation-induced cell damage and increases cell repair in normal fibroblasts but not tumor cells in vitro and in vivo. At the molecular level, mechanical injury interrupts focal adhesion complexes and cell–cell cadherin interactions, transducing mechanical signals into intracellular chemical signals via activation of the phosphatidylinositol 3-kinase (PI3K), Akt, and glycogen synthase kinase 3 beta (GSK-3β) pathways. We show that subsequent nuclear translocation of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and β-catenin strengthen the stemness, antioxidant capabilities, and DNA double-strand break repair abilities of fibroblasts, ultimately contributing to increased radioresistance. Our findings demonstrate that mechanical injury to normal fibroblasts enhances radioresistance and may therefore question conventional wisdom surrounding the timing of radiation after surgery.
Development of a multilocus-based approach for sponge (phylum Porifera) identification: refinement and limitations
Authors: Yang Qi , Franco Christopher M. M. , Sorokin Shirley J. , Zhang Wei
Published: February 2017

For sponges (phylum Porifera), there is no reliable molecular protocol available for species identification. To address this gap, we developed a multilocus-based Sponge Identification Protocol (SIP) validated by a sample of 37 sponge species belonging to 10 orders from South Australia. The universal barcode COI mtDNA, 28S rRNA gene (D3–D5), and the nuclear ITS1-5.8S-ITS2 region were evaluated for their suitability and capacity for sponge identification. The highest Bit Score was applied to infer the identity. The reliability of SIP was validated by phylogenetic analysis. The 28S rRNA gene and COI mtDNA performed better than the ITS region in classifying sponges at various taxonomic levels. A major limitation is that the databases are not well populated and possess low diversity, making it difficult to conduct the molecular identification protocol. The identification is also impacted by the accuracy of the morphological classification of the sponges whose sequences have been submitted to the database. Re-examination of the morphological identification further demonstrated and improved the reliability of sponge identification by SIP. Integrated with morphological identification, the multilocus-based SIP offers an improved protocol for more reliable and effective sponge identification, by coupling the accuracy of different DNA markers.
Short stop mediates axonal compartmentalization of mucin-type core 1 glycans
Authors: Kinoshita Takaaki , Sato Chikara , Fuwa Takashi J. , Nishihara Shoko
Published: February 2017

T antigen, mucin-type core 1 O-glycan, is highly expressed in the embryonic central nervous system (CNS) and co-localizes with a Drosophila CNS marker, BP102 antigen. BP102 antigen and Derailed, an axon guidance receptor, are localized specifically in the proximal axon segment of isolated primary cultured neurons, and their mobility is restricted at the intra-axonal boundary by a diffusion barrier. However, the preferred trafficking mechanism remains unknown. In this study, the major O-glycan T antigen was found to localize within the proximal compartments of primary cultured Drosophila neurons, whereas the N-glycan HRP antigen was not. Ultrastructural analysis by atmospheric scanning electron microscopy revealed that microtubule bundles cross one another at the intra-axonal boundary, and that T antigens form circular pattern before the boundary. We then identified Short stop (Shot), a crosslinker protein between F-actin and microtubules, as a mediator for the proximal localization of T antigens; null mutation of shot cancelled preferential localization of T antigens. Moreover, F-actin binding domain of Shot was required for their proximal localization. Together, our results allow us to propose a novel trafficking pathway where Shot crosslinks F-actin and microtubules around the intra-axonal boundary, directing T antigen-carrying vesicles toward the proximal plasma membrane.
Transcriptomic investigation of wound healing and regeneration in the cnidarian Calliactis polypus
Authors: Stewart Zachary K. , Pavasovic Ana , Hock Daniella H. , Prentis Peter J.
Published: February 2017

Wound healing and regeneration in cnidarian species, a group that forms the sister phylum to Bilateria, remains poorly characterised despite the ability of many cnidarians to rapidly repair injuries, regenerate lost structures, or re-form whole organisms from small populations of somatic cells. Here we present results from a fully replicated RNA-Seq experiment to identify genes that are differentially expressed in the sea anemone Calliactis polypus following catastrophic injury. We find that a large-scale transcriptomic response is established in C. polypus, comprising an abundance of genes involved in tissue patterning, energy dynamics, immunity, cellular communication, and extracellular matrix remodelling. We also identified a substantial proportion of uncharacterised genes that were differentially expressed during regeneration, that appear to be restricted to cnidarians. Overall, our study serves to both identify the role that conserved genes play in eumetazoan wound healing and regeneration, as well as to highlight the lack of information regarding many genes involved in this process. We suggest that functional analysis of the large group of uncharacterised genes found in our study may contribute to better understanding of the regenerative capacity of cnidarians, as well as provide insight into how wound healing and regeneration has evolved in different lineages.
An Engineered Herpesvirus Activates Dendritic Cells and Induces Protective Immunity
Authors: Ma Yijie , Chen Min , Jin Huali , Prabhakar Bellur S. , Valyi-Nagy Tibor , He Bin
Published: February 2017

Herpes simplex viruses (HSV) are human pathogens that switch between lytic and latent infection. While attenuated HSV is explored for vaccine, the underlying event remains poorly defined. Here we report that recombinant HSV-1 with a mutation in the γ134.5 protein, a virulence factor, stimulates dendritic cell (DC) maturation which is dependent on TANK-binding kinase 1 (TBK1). When exposed to CD11+ DCs, the mutant virus that lacks the amino terminus of γ134.5 undergoes temporal replication without production of infectious virus. Mechanistically, this leads to sequential phosphorylation of interferon regulatory factor 3 (IRF3) and p65/RelA. In correlation, DCs up-regulate the expression of co-stimulatory molecules and cytokines. However, selective inhibition of TBK1 precludes phosphorylation of IRF3 and subsequent DC activation by the γ134.5 mutant. Herein, the γ134.5 mutant is immune-stimulatory and non-destructive to DCs. Remarkably, upon immunization the γ134.5 mutant induces protection against lethal challenge by the wild type virus, indicative of its vaccine potential. Furthermore, CD11+ DCs primed by the γ134.5 mutant in vivo mediate protection upon adoptive transfer. These results suggest that activation of TBK1 by engineered HSV is crucial for DC maturation, which may contribute to protective immunity.
Fewer clouds in the Mediterranean: consistency of observations and climate simulations
Authors: Sanchez-Lorenzo Arturo , Enriquez-Alonso Aaron , Calbó Josep , González Josep-Abel , Wild Martin , Folini Doris , Norris Joel R. , Vicente-Serrano Sergio M.
Published: February 2017

Clouds play a major role in the climate system, but large uncertainties remain about their decadal variations. Here we report a widespread decrease in cloud cover since the 1970 s over the Mediterranean region, in particular during the 1970 s–1980 s, especially in the central and eastern areas and during springtime. Confidence in these findings is high due to the good agreement between the interannual variations of cloud cover provided by surface observations and several satellite-derived and reanalysis products, although some discrepancies exist in their trends. Climate model simulations of the historical experiment from the Coupled Model Intercomparison Project Phase 5 (CMIP5) also exhibit a decrease in cloud cover over the Mediterranean since the 1970 s, in agreement with surface observations, although the rate of decrease is slightly lower. The observed northward expansion of the Hadley cell is discussed as a possible cause of detected trends.
Retinopathy Signs Improved Prediction and Reclassification of Cardiovascular Disease Risk in Diabetes: A prospective cohort study
Authors: Ho Henrietta , Cheung Carol Y. , Sabanayagam Charumathi , Yip Wanfen , Ikram Mohammad Kamran , Ong Peng Guan , Mitchell Paul , Chow Khuan Yew , Cheng Ching Yu , Tai E. Shyong , Wong Tien Yin
Published: February 2017

CVD risk prediction in diabetics is imperfect, as risk models are derived mainly from the general population. We investigate whether the addition of retinopathy and retinal vascular caliber improve CVD prediction beyond established risk factors in persons with diabetes. We recruited participants from the Singapore Malay Eye Study (SiMES, 2004–2006) and Singapore Prospective Study Program (SP2, 2004–2007), diagnosed with diabetes but no known history of CVD at baseline. Retinopathy and retinal vascular (arteriolar and venular) caliber measurements were added to risk prediction models derived from Cox regression model that included established CVD risk factors and serum biomarkers in SiMES, and validated this internally and externally in SP2. We found that the addition of retinal parameters improved discrimination compared to the addition of biochemical markers of estimated glomerular filtration rate (eGFR) and high-sensitivity C-reactive protein (hsCRP). This was even better when the retinal parameters and biomarkers were used in combination (C statistic 0.721 to 0.774, p = 0.013), showing improved discrimination, and overall reclassification (NRI = 17.0%, p = 0.004). External validation was consistent (C-statistics from 0.763 to 0.813, p = 0.045; NRI = 19.11%, p = 0.036). Our findings show that in persons with diabetes, retinopathy and retinal microvascular parameters add significant incremental value in reclassifying CVD risk, beyond established risk factors.
Transcriptomic analysis of common carp anterior kidney during Cyprinid herpesvirus 3 infection: Immunoglobulin repertoire and homologue functional divergence
Authors: Neave Matthew J. , Sunarto Agus , McColl Kenneth A.
Published: February 2017

Cyprinid herpesvirus 3 (CyHV-3) infects koi and common carp and causes widespread mortalities. While the virus is a significant concern for aquaculture operations in many countries, in Australia the virus may be a useful biocontrol agent for pest carp. However, carp immune responses to CyHV-3, and the molecular mechanisms underpinning resistance, are not well understood. Here we used RNA-Seq on carp during different phases of CyHV-3 infection to detect the gene expression dynamics of both host and virus simultaneously. During acute CyHV-3 infection, the carp host modified the expression of genes involved in various immune systems and detoxification pathways. Moreover, the activated pathways were skewed toward humoral immune responses, which may have been influenced by the virus itself. Many immune-related genes were duplicated in the carp genome, and often these were expressed differently across the infection phases. Of particular interest were two interleukin-10 homologues that were not expressed synchronously, suggesting neo- or sub-functionalization. The carp immunoglobulin repertoire significantly diversified during active CyHV-3 infection, which was followed by the selection of high-affinity B-cells. This is indicative of a developing adaptive immune response, and is the first attempt to use RNA-Seq to understand this process in fish during a viral infection.
Endoplasmic reticulum stress inhibition attenuates hypertensive chronic kidney disease through reduction in proteinuria
Authors: Mohammed-Ali Zahraa , Lu Chao , Marway Mandeep K. , Carlisle Rachel E. , Ask Kjetil , Lukic Dusan , Krepinsky Joan C. , Dickhout Jeffrey G.
Published: February 2017

Endoplasmic reticulum (ER) stress is implicated in chronic kidney disease (CKD) development in patients and in animal models. Here we show that ER stress inhibition through 4-phenylbutyric acid (4-PBA) administration decreases blood pressure, albuminuria, and tubular casts in an angiotensin II/deoxycorticosterone acetate/salt murine model of CKD. Lower albuminuria in 4-PBA-treated mice was associated with higher levels of cubilin protein in renal tissue membrane fractions. 4-PBA decreased renal interstitial fibrosis, renal CD3+ T-cell and macrophage infiltration, mRNA expression of TGFβ1, Wnt signaling molecules, and ER stress-induced pro-inflammatory genes. CHOP deficient mice that underwent this model of CKD developed hypertension comparable to wild type mice, but had less albuminuria and tubular casts. CHOP deficiency resulted in higher nephrin levels and decreased glomerulosclerosis compared to wild type mice; this effect was accompanied by lower macrophage infiltration and fibrosis. Our findings portray ER stress inhibition as a means to alleviate hypertensive CKD by preserving glomerular barrier integrity and tubular function. These results demonstrate ER stress modulation as a novel target for preserving renal function in hypertensive CKD.
Simvastatin suppresses the DNA replication licensing factor MCM7 and inhibits the growth of tamoxifen-resistant breast cancer cells
Authors: Liang Zheyong , Li Wenjie , Liu Jie , Li Juan , He Fang , Jiang Yina , Yang Lu , Li Pingping , Wang Bo , Wang Yaochun , Ren Yu , Yang Jin , Luo Zhijun , Vaziri Cyrus , Liu Peijun
Published: February 2017

Acquired tamoxifen resistance (TamR) remains a major challenge in breast cancer endocrine therapy. The mechanism of acquiring tamoxifen resistance remains elusive, and no effective drugs are available. In this investigation, we determined that the expression of the DNA damage marker γH2AX is upregulated under minichromosome maintenance protein 7 (MCM7) knockdown in phospho Ser807/811-retinoblastoma protein (p-Rb) defect cells. In addition, the expression of p-Rb was lower in TamR cells than in parental cells, and the expression of γH2AX was significantly upregulated when MCM7 was knocked down in TamR cells. Simvastatin, an agent for hypercholesterolemia treatment, activated the MCM7/p-RB/γH2AX axis and induced DNA damage in TamR cells, especially when combined with tamoxifen. Finally, in vitro and in vivo experiments demonstrated that simvastatin combined with tamoxifen increased TamR cell apoptosis and inhibited xenograft growth. In conclusion, simvastatin may suppress TamR cell growth by inhibiting MCM7 and Rb and subsequently inducing DNA damage.
P-Selectin preserves immune tolerance in mice and is reduced in human cutaneous lupus
Authors: González-Tajuelo Rafael , Silván Javier , Pérez-Frías Alicia , de la Fuente-Fernández María , Tejedor Reyes , Espartero-Santos Marina , Vicente-Rabaneda Esther , Juarranz Ángeles , Muñoz-Calleja Cecilia , Castañeda Santos , Gamallo Carlos , Urzainqui Ana
Published: February 2017

Mice deficient in P-Selectin presented altered immunity/tolerance balance. We have observed that the absence of P-Selectin promotes splenomegaly with reduced naïve T cell population, elevated activated/effector T cell subset, increased germinal center B and Tfh populations and high production of autoreactive antibodies. Moreover, 1.5-3-month-old P-selectin KO mice showed reduced IL-10-producing leukocytes in blood and a slightly reduced Treg population in the skin. With aging and, coinciding with disease severity, there is an increase in the IL17+circulating and dermal T cell subpopulations and reduction of dermal Treg. As a consequence, P-Selectin deficient mice developed a progressive autoimmune syndrome showing skin alterations characteristic of lupus prone mice and elevated circulating autoantibodies, including anti-dsDNA. Similar to human SLE, disease pathogenesis was characterized by deposition of immune complexes in the dermoepidermal junction and renal glomeruli, and a complex pattern of autoantibodies. More important, skin biopsies of cutaneous lupus erythematosus patients did not show increased expression of P-Selectin, as described for other inflammatory diseases, and the number of vessels expressing P-Selectin was reduced.
Tubular B7-1 expression parallels proteinuria levels, but not clinical outcomes in adult minimal change disease patients
Authors: Lee Sung Woo , Baek Seon Ha , Paik Jin Ho , Kim Sejoong , Na Ki Young , Chae Dong-Wan , Chin Ho Jun
Published: February 2017

B7-1 is thought to play a pathogenic role in minimal-change disease (MCD). Recently, however, doubts have arisen regarding the role of B7-1 expression in MCD. Therefore, we aimed to identify the presence and clinical significance of B7-1 expression in MCD patients. The study participants included 28 adult MCD patients for whom kidney specimens were available. The intensity of B7-1 expression was assessed by two independent specialists. We analysed the association between the intensity of B7-1 expression and clinicopathological variables. No B7-1 expression in the glomeruli was observed in any of the 28 patients. Unexpectedly, however, 75.0% of the patients exhibited tubular B7-1 expression, with 35.7% demonstrating weak positive expressions and 39.3% demonstrating strong positive expressions. The level of proteinuria significantly increased as the intensity of tubular B7-1 expression increased. We also found trends of increasing blood urea nitrogen and serum creatinine levels with increased intensity of tubular B7-1 expression. However, we could not observe definite differences in long- and short-term clinical outcomes depending on the intensity of tubular B7-1 expression. In conclusion, B7-1 was expressed in renal tubular cells but not in glomeruli in adult MCD patients. The intensity of tubular B7-1 expression paralleled proteinuria levels, but not clinical outcomes.
Differential lactate and cholesterol synthetic activities in XY and XX Sertoli cells
Authors: Shishido Yurina , Baba Takashi , Sato Tetsuya , Shima Yuichi , Miyabayashi Kanako , Inoue Miki , Akiyama Haruhiko , Kimura Hiroshi , Kanai Yoshiakira , Ishihara Yasuhiro , Haraguchi Shogo , Miyazaki Akira , Rozman Damjana , Yamazaki Takeshi , Choi Man-Ho , Ohkawa Yasuyuki , Suyama Mikita , Morohashi Ken-ichirou
Published: February 2017

SRY, a sex-determining gene, induces testis development in chromosomally female (XX) individuals. However, mouse XX Sertoli cells carrying Sry (XX/Sry Sertoli cells) are incapable of fully supporting germ cell development, even when the karyotype of the germ cells is XY. While it has therefore been assumed that XX/Sry Sertoli cells are not functionally equivalent to XY Sertoli cells, it has remained unclear which specific functions are affected. To elucidate the functional difference, we compared the gene expression of XY and XX/Sry Sertoli cells. Lactate and cholesterol metabolisms, essential for nursing the developing germ cells, were down-regulated in XX/Sry cells, which appears to be caused at least in part by the differential expression of histone modification enzymes SMCX/SMCY (H3K4me3 demethylase) and UTX/UTY (H3K27me3 demethylase) encoded by the sex chromosomes. We suggest that down-regulation of lactate and cholesterol metabolism that may be due to altered epigenetic modification affects the nursing functions of XX/Sry Sertoli cells.
On the coordination non-innocence of antimony in nickel(ii) complexes of the tetradentate (o-(Ph2P)C6H4)3Sb ligand
Authors: Jones J. Stuart , Wade Casey R. , Yang Mengxi , Gabbaï François P.
Published: February 2017

The coordination non-innocence of antimony toward Cl−in ClNi(o-(Ph2P)C6H4)3SbCl results from both structural and electronic effects.
Neuroprotective effect of single-wall carbon nanotubes with built-in peroxidase-like activity against β-amyloid-induced neurotoxicity
Authors: Shin Jaeha , Lee Sujin , Cha Misun
Published: February 2017

Single-wall carbon nanotubes with built-in peroxidase-like activity mediated by bacterial magnetic nanoparticles exert neuroprotective effects against β-amyloid fibrillation-induced neurotoxicity.
Syntheses, structural diversities and characterization of a series of coordination polymers with two isomeric oxadiazol-pyridine ligands
Authors: Ding Bin , Wu Jie , Wu Xiang Xia , Huo Jian Zhong , Zhu Zhao Zhou , Liu Yuan Yuan , Shi Fang Xue
Published: February 2017

In this work two positional-isomeric oxadiazol-pyridine ligands 3-(5-methyl-1,3,4-oxadiazol-2-yl)pyridine (L1) and 4-(5-methyl-1,3,4-oxadiazol-2-yl)pyridine (L2) have been designed and synthesized.
The structures and diffusion behaviors of point defects and their influences on the electronic properties of 2D stanene
Authors: Shen Limeng , Lan Mu , Zhang Xi , Xiang Gang
Published: February 2017

During the synthesis of stanene monolayers, defects are inevitably present and always affect the properties.
Heavy metals removal by EDTA-functionalized chitosan graphene oxide nanocomposites
Authors: Shahzad Asif , Miran Waheed , Rasool Kashif , Nawaz Mohsin , Jang Jiseon , Lim Seong-Rin , Lee Dae Sung
Published: February 2017

Graphene-based two-dimensional materials have been explored in a variety of applications, including the treatment of heavy-metal-rich water/wastewater.
Phosphinito palladium(ii) complexes as catalysts for the synthesis of 1,3-enynes, aromatic alkynes and ynones
Authors: Islas R. E. , Cárdenas J. , Gaviño R. , García-Ríos E. , Lomas-Romero L. , Morales-Serna J. A.
Published: February 2017

An air-stable phosphinito palladium(ii) complex has been found to be an efficient catalyst in the formation of C–C bonds.
Resonances of the anthracenyl anion probed by frequency-resolved photoelectron imaging of collision-induced dissociated anthracene carboxylic acid
Authors: Stanley Laurence H. , Anstöter Cate S. , Verlet Jan R. R.
Published: February 2017

The use of CID and photoelectron spectroscopy of organic carboxylic acid anions is discussed as a route to studying the dynamics of resonances in polyaromatic hydrocarbon (PAH) anions.
Chemical and structural investigation of zinc-oxo cluster photoresists for DUV lithography
Authors: Yeh Chun-Cheng , Liu Hung-Chuan , Heni Wajdi , Berling Dominique , Zan Hsiao-Wen , Soppera Olivier
Published: February 2017

A Zn oxo-cluster photoresist was synthesized and the impact of chemical and physicochemical parameters on photopatterning was investigated.
Comparative electronic structures of nitrogenase FeMoco and FeVco
Authors: Rees Julian A. , Bjornsson Ragnar , Kowalska Joanna K. , Lima Frederico A. , Schlesier Julia , Sippel Daniel , Weyhermüller Thomas , Einsle Oliver , Kovacs Julie A. , DeBeer Serena
Published: February 2017

High-resolution X-ray spectroscopy provides insights into the electronic structural differences between the nitrogenase FeMoco and FeVco clusters.
An enhanced Seebeck coefficient and high thermoelectric performance in p-type In and Mg co-doped Sn1−xPbxTe via the co-adjuvant effect of the resonance level and heavy hole valence band
Authors: Roychowdhury Subhajit , Shenoy U. Sandhya , Waghmare Umesh V. , Biswas Kanishka
Published: February 2017

Remarkable enhancement of the Seebeck coefficient of an Sn rich Sn1−xPbxTe system due to the synergistic effect of resonance level formation and valence band convergence.
Effort in asteroid defense under way despite funding constraints
Authors: Kramer David
Published: February 2017

A US interagency program is refining methods of deflecting asteroids as it works toward finding tens of thousands of undetected near-Earth objects.
How did a scientific Siberia turn into AstroBoulder?
Authors: Bassi Joseph P.
Published: February 2017

Boulder, Colorado, grew to become an important science center in part because nearby mountains provided an excellent spot for solar observation. But local scientists’ connections to the Northeast establishment and some clever PR didn’t hurt.
Dynamics of a human spiral wave
Authors: Welsh Andrea J. , Greco Edwin F. , Fenton Flavio H.
Published: February 2017

With a few simple instructions, participants at the Atlanta Science Festival mimicked a phenomenon that can have fatal consequences in biological systems.
Formation mechanisms of superoxide radical and hydrogen peroxide in chloroplasts, and factors determining the signalling by hydrogen peroxide
Authors: Ivanov Boris N. , Borisova-Mubarakshina Maria M. , Kozuleva Marina A.
Published: February 2017

Reduction of O2 molecule to superoxide radical, O2•−, in the photosynthetic electron transport chain is the first step of hydrogen peroxide, H2O2, production in chloroplasts in the light. The mechanisms of O2 reduction by ferredoxin, by the components of the plastoquinone pool, and by the electron transfer cofactors in PSI are analysed. The data indicating that O2•− and H2O2 can be produced both outside and within thylakoid membrane are presented. The H2O2 production in the chloroplast stroma is described as a result of either dismutation of O2•− or its reduction by stromal reductants. Formation of H2O2 within thylakoid membrane in the reaction of O2•− with plastohydroquinone is examined. The significance of both ways of H2O2 formation for specificity of the signal being sent by photosynthetic electron transport chain to cell adaptation systems is discussed.
Biochemical Genetics of Fundulus heteroclitus (L.): V. Inheritance of 10 Biochemical Loci
Authors: Brown D. C. , Ropson I. J. , Powers D. A.
Published: February 2017

Starch gel electrophoresis has shown that natural populations of Fundulus heteroclitus have electrophoretic variants for at least 21 loci. We provide inheritance data for 10 polymorphic systems: esterases (Est-B, EST-C, and Est-D); aspartate amlnotransferases (Aat-A, and Aat-B); mannosephosphate isomerase (Mpl-A); acid phosphatase (Ap-A); phosphoglucomutase (Pgm-B); hexose-6-phosphate dehydrogenase (H6pdh-A); and fumarase (Fum-A). Variants for nine of these loci segregate as autosomally inherited codominant alleles. The other system, EST-C, does not reflect such inheritance. We have identified two possible linkage groups: H6pdh-A may be loosely linked to Pgm-B, and Fum-A appears to be linked to Pgm-A. Tissue specificity and intracellular localization for all these loci are also presented.
Cerebellar volume in autism: Meta-analysis and analysis of the ABIDE cohort
Authors: Traut Nicolas , Beggiato Anita , Bourgeron Thomas , Delorme Richard , Rondi-Reig Laure , Paradis Anne-Lise , Toro Roberto
Published: February 2017

Cerebellar volume abnormalities have been often suggested as a possible endophenotype for autism spectrum disorder (ASD). We aimed at objectifying this possible alteration by performing a systematic meta-analysis of the literature, and an analysis of the Autism Brain Imaging Data Exchange (ABIDE) cohort. Our meta-analysis sought to determine a combined effect size of ASD diagnosis on different measures of the cerebellar anatomy, as well as the effect of possible factors of variability across studies. We then analysed the cerebellar volume of 328 patients and 353 controls from the ABIDE project. The meta-analysis of the literature suggested a weak but significant association between ASD diagnosis and increased cerebellar volume (p=0.049, uncorrected), but the analysis of ABIDE did not show any relationship. The studies in the literature were generally underpowered, however, the number of statistically significant findings was larger than expected. Although we could not provide a conclusive explanation for this excess of significant findings, our analyses would suggest publication bias as a possible reason. Finally, age, sex and IQ were important sources of cerebellar volume variability, however, independent of autism diagnosis.
Compaction of Duplex Nucleic Acids upon Native Electrospray Mass Spectrometry
Authors: Porrini Massimiliano , Rosu Frédéric , Rabin Clémence , Darré Leonardo , Gómez Hansel , Orozco Modesto , Gabelica Valérie
Published: February 2017

Native mass spectrometry coupled to ion mobility spectrometry is a promising tool for structural biology. Intact complexes can be transferred to the mass spectrometer and, if native conformations survive, collision cross sections give precious information on the structure of each species in solution. Based on several successful reports for proteins and their complexes, the conformation survival becomes more and more taken for granted. Here we report on the fate of nucleic acids conformation in the gas phase. Disturbingly, we found that DNA and RNA duplexes, at the electrospray charge states naturally obtained from native solution conditions (≥ 100 mM aqueous NH4OAc), are significantly more compact in the gas phase compared to the canonical solution structures. The compaction is observed for short (12-bp) and long (36-bp) duplexes, and for DNA and RNA alike. Molecular modeling (density functional calculations on small helices, semi-empirical calculations on up to 12-bp, and molecular dynamics on up to 36-bp duplexes) demonstrates that the compaction is due to phosphate group self-solvation prevailing over Coulomb-driven expansion. Molecular dynamics simulations starting from solution structures do not reproduce the experimental compaction. To be experimentally relevant, molecular dynamics sampling should reflect the progressive structural rearrangements occurring during desolvation. For nucleic acid duplexes, the compaction observed for low charge states results from novel phosphate-phosphate hydrogen bonds formed across both grooves at the very late stages of electrospray.