bluuebunny/crossref_metadata_2025_split huggingface dataset:
mRNA Cap Methylation Influences Pathogenesis of Vesicular Stomatitis VirusIn Vivo
Authors: Ma Yuanmei , Wei Yongwei , Zhang Xiaodong , Zhang Yu , Cai Hui , Zhu Yang , Shilo Konstantin , Oglesbee Michael , Krakowka Steven , Whelan Sean P. J. , Li Jianrong 
Published: December 2013

ABSTRACTOne role of mRNA cap guanine-N-7 (G-N-7) methylation is to facilitate the efficient translation of mRNA. The role of mRNA cap ribose 2′-O methylation is enigmatic, although recent work has implicated this as a signature to avoid detection of RNA by the innate immune system (S. Daffis, K. J. Szretter, J. Schriewer, J. Q. Li, S. Youn, J. Errett, T. Y. Lin, S. Schneller, R. Zust, H. P. Dong, V. Thiel, G. C. Sen, V. Fensterl, W. B. Klimstra, T. C. Pierson, R. M. Buller, M. Gale, P. Y. Shi, M. S. Diamond, Nature 468:452-456, 2010, doi:10.1038/nature09489). Working with vesicular stomatitis virus (VSV), we previously showed that a panel of recombinant VSVs carrying mutations at a predicted methyltransferase catalytic site (rVSV-K1651A, -D1762A, and -E1833Q) orS-adenosylmethionine (SAM) binding site (rVSV-G1670A, -G1672A, and -G4A) were defective in cap methylation and were also attenuated for growth in cell culture. Here, we analyzed the virulence of these recombinants in mice. We found that rVSV-K1651A, -D1762A, and -E1833Q, which are defective in both G-N-7 and 2′-O methylation, were highly attenuated in mice. All three viruses elicited a high level of neutralizing antibody and provided full protection against challenge with the virulent VSV. In contrast, mice inoculated with rVSV-G1670A and -G1672A, which are defective only in G-N-7 methylation, were attenuatedin vivoyet retained a low level of virulence. rVSV-G4A, which is completely defective in both G-N-7 and 2′-O methylation, also exhibited low virulence in mice despite the fact that productive viral replication was not detected in lung and brain. Taken together, our results suggest that abrogation of viral mRNA cap methylation can serve as an approach to attenuate VSV, and perhaps other nonsegmented negative-strand RNA viruses, for potential application as vaccines and viral vectors.IMPORTANCENonsegmented negative-sense (NNS) RNA viruses include a wide range of significant human, animal, and plant pathogens. For many of these viruses, there are no vaccines or antiviral drugs available. mRNA cap methylation is essential for mRNA stability and efficient translation. Our current understanding of mRNA modifications of NNS RNA viruses comes largely from studies of vesicular stomatitis virus (VSV). In this study, we showed that recombinant VSVs (rVSVs) defective in mRNA cap methylation were attenuatedin vitroandin vivo. In addition, these methyltransferase (MTase)-defective rVSVs triggered high levels of antibody responses and provided complete protection against VSV infection. Thus, this study will not only contribute to our understanding of the role of mRNA cap MTase in viral pathogenesis but also facilitate the development of new live attenuated vaccines for VSV, and perhaps other NNS RNA viruses, by inhibiting viral mRNA cap methylation.
Neighbourhood green space and the odds of having skin cancer: multilevel evidence of survey data from 267072 Australians
Authors: Astell-Burt Thomas , Feng Xiaoqi , Kolt Gregory S 
Published: December 2013

BackgroundIf green spaces encourage people to spend more time outdoors in physical, recreational and social activities, this could have unintended but important consequences for health in countries where levels of ultraviolet (UV) radiation are non-trivial. We investigated whether people who lived in neighbourhoods containing lots of green space were likely to spend more time outdoors and, subsequently, were more likely to report a case of skin cancer.MethodsMultilevel logit regression was used to fit associations between self-reported medically diagnosed skin cancer (melanoma and non-melanoma) and an objective measure of green space. These models were adjusted for measures of susceptibility (skin colour and tanning), socioeconomic variables, demographic and cultural characteristics (eg, ancestry and country of birth). Mediation analyses were conducted using self-reported measures of time spent outdoors and participation in moderate-to-vigorous physical activity (MVPA).ResultsDescriptive analyses reported a positive association between green space and skin cancer (p<0.001). Time outdoors and in MVPA was also higher among people living in greener areas. The association between green space and skin cancer was robust after adjustment. In comparison to people with 0–20% green space, for example, the adjusted odds of having skin cancer were 9% higher among those with >80% green space. Only 1.6% and less than 1% of the association was mediated by MVPA and time spent outdoors.ConclusionsNeighbourhood green space is associated with higher odds of having skin cancer in Australia. The relationship between green space and health, in its broadest terms, is likely to vary by geographical context.
The Niacin/Butyrate Receptor GPR109A Suppresses Mammary Tumorigenesis by Inhibiting Cell Survival
Authors: Elangovan Selvakumar , Pathania Rajneesh , Ramachandran Sabarish , Ananth Sudha , Padia Ravi N. , Lan Ling , Singh Nagendra , Martin Pamela M. , Hawthorn Lesleyann , Prasad Puttur D. , Ganapathy Vadivel , Thangaraju Muthusamy 
Published: December 2013

Abstract
GPR109A, a G-protein–coupled receptor, is activated by niacin and butyrate. Upon activation in colonocytes, GPR109A potentiates anti-inflammatory pathways, induces apoptosis, and protects against inflammation-induced colon cancer. In contrast, GPR109A activation in keratinocytes induces flushing by activation of Cox-2–dependent inflammatory signaling, and the receptor expression is upregulated in human epidermoid carcinoma. Thus, depending on the cellular context and tissue, GPR109A functions either as a tumor suppressor or a tumor promoter. However, the expression status and the functional implications of this receptor in the mammary epithelium are not known. Here, we show that GPR109A is expressed in normal mammary tissue and, irrespective of the hormone receptor status, its expression is silenced in human primary breast tumor tissues, breast cancer cell lines, and in tumor tissues of three different murine mammary tumor models. Functional expression of this receptor in human breast cancer cell lines decreases cyclic AMP production, induces apoptosis, and blocks colony formation and mammary tumor growth. Transcriptome analysis revealed that GPR109A activation inhibits genes, which are involved in cell survival and antiapoptotic signaling, in human breast cancer cells. In addition, deletion of Gpr109a in mice increased tumor incidence and triggered early onset of mammary tumorigenesis with increased lung metastasis in MMTV-Neu mouse model of spontaneous breast cancer. These findings suggest that GPR109A is a tumor suppressor in mammary gland and that pharmacologic induction of this gene in tumor tissues followed by its activation with agonists could be an effective therapeutic strategy to treat breast cancer. Cancer Res; 74(4); 1166–78. ©2013 AACR.
RNA-Binding Protein RBM24 Regulates p63 Expression via mRNA Stability
Authors: Xu Enshun , Zhang Jin , Zhang Min , Jiang Yuqian , Cho Seong-Jun , Chen Xinbin 
Published: December 2013

Abstract
p63, a p53 family member, plays pivotal roles in epidermal development, aging, and tumorigenesis. Thus, understanding how p63 expression is controlled has biological and clinical importance. RBM24 is an RNA-binding protein and shares a high sequence similarity with RBM38, a critical regulator of p63. In this study, we investigated whether RBM24 is capable of regulating p63 expression. Indeed, we found that ectopic expression of RBM24 decreased, whereas knockdown of RBM24 increased, the levels of p63 transcript and protein. To explore the underlying mechanism, we found that RBM24 was able to bind to multiple regions in the p63 3′ untranslated region and, subsequently, destabilize p63 transcript. Furthermore, we showed that the 3′ untranslated region in p63 transcript and the RNA-binding domain in RBM24 were required for RBM24 to bind p63 transcript and consequently, inhibit p63 expression. Taken together, our data provide evidence that RBM24 is a novel regulator of p63 via mRNA stability.
Implications: Our study suggests that p63 is regulated by RBM24 via mRNA stability, which gives an insight into understanding how posttranscriptional regulatory mechanisms contribute to p63 expression. Mol Cancer Res; 12(3); 359–69. ©2013 AACR.
Activation of CXCR7 Limits Atherosclerosis and Improves Hyperlipidemia by Increasing Cholesterol Uptake in Adipose Tissue
Authors: Li Xiaofeng , Zhu Mengyu , Penfold Mark E. , Koenen Rory R. , Thiemann Anna , Heyll Kathrin , Akhtar Shamima , Koyadan Seena , Wu Zhuojun , Gremse Felix , Kiessling Fabian , van Zandvoort Marc , Schall Thomas J. , Weber Christian , Schober Andreas 
Published: December 2013

Background—
The aim of this study was to determine the role of the chemokine receptor CXCR7 in atherosclerosis and vascular remodeling. CXCR7 is the alternative receptor of CXCL12, which regulates stem cell–mediated vascular repair and limits atherosclerosis via its receptor, CXCR4.

Methods and Results—

Wire-induced injury of the carotid artery was performed in mice with a ubiquitous, conditional deletion of CXCR7 and in mice treated with the synthetic CXCR7 ligand CCX771. The effect of CCX771 treatment on atherosclerosis was studied in apolipoprotein E–deficient (
Apoe

−/−

) mice fed a high-fat diet for 12 weeks. Lipoprotein fractions were quantified in the plasma of
Apoe

−/−

mice by fast protein liquid chromatography. Uptake of DiI-labeled very low-density lipoprotein to adipose tissue was determined by 2-photon microscopy. We show that genetic deficiency of
Cxcr7
increased neointima formation and lesional macrophage accumulation in hyperlipidemic mice after vascular injury. This was related to increased serum cholesterol levels and subsequent hyperlipidemia-induced monocytosis. Conversely, administration of the CXCR7 ligand CCX771 to
Apoe

−/−

mice inhibited lesion formation and ameliorated hyperlipidemia after vascular injury and during atherosclerosis. Treatment with CCX771 reduced circulating very low-density lipoprotein levels but not low-density lipoprotein or high-density lipoprotein levels and increased uptake of very low-density lipoprotein into
Cxcr7
-expressing white adipose tissue. This effect of CCX771 was associated with an enhanced lipase activity and reduced expression of Angptl4 in adipose tissue.

Conclusions—
CXCR7 regulates blood cholesterol by promoting its uptake in adipose tissue. This unexpected cholesterol-lowering effect of CXCR7 is beneficial for atherosclerotic vascular diseases, presumably via amelioration of hyperlipidemia-induced monocytosis, and can be augmented with a synthetic CXCR7 ligand.
Impact of High-Fidelity Simulation and Pharmacist-Specific Didactic Lectures in Addition to ACLS Provider Certification on	Pharmacy Resident ACLS Performance
Authors: Bartel Billie J. 
Published: December 2013

Purpose: This pilot study explored the use of multidisciplinary high-fidelity simulation and additional pharmacist-focused training methods in training postgraduate year 1 (PGY1) pharmacy residents to provide Advanced Cardiovascular Life Support (ACLS) care. Pharmacy resident confidence and comfort level were assessed after completing these training requirements. Methods: The ACLS training requirements for pharmacy residents were revised to include didactic instruction on ACLS pharmacology and rhythm recognition and participation in multidisciplinary high-fidelity simulation ACLS experiences in addition to ACLS provider certification. Surveys were administered to participating residents to assess the impact of this additional education on resident confidence and comfort level in cardiopulmonary arrest situations. Results: The new ACLS didactic and simulation training requirements resulted in increased resident confidence and comfort level in all assessed functions. Residents felt more confident in all areas except providing recommendations for dosing and administration of medications and rhythm recognition after completing the simulation scenarios than with ACLS certification training and the didactic components alone. All residents felt the addition of lectures and simulation experiences better prepared them to function as a pharmacist in the ACLS team. Conclusion: Additional ACLS training requirements for pharmacy residents increased overall awareness of pharmacist roles and responsibilities and greatly improved resident confidence and comfort level in performing most essential pharmacist functions during ACLS situations.
The Affordable Care Act on Loyalty Programs for Federal Beneficiaries
Authors: Piacentino Justin J. , Williams Karl G. 
Published: December 2013

Objective: To discuss changes in the law that allow community pharmacy loyalty programs to include and offer incentives to Medicare and Medicaid beneficiaries. Summary: The retailer rewards exception of the Patient Protection and Affordable Care Act of 2010 and its change to the definition of remuneration in the civil monetary penalties of the Anti-Kickback Statute now allow incentives to be earned on federal benefit tied prescription out-of-pocket costs. The criteria required to design a compliant loyalty program are discussed. Conclusion: Community pharmacies can now include Medicare and Medicaid beneficiaries in compliant customer loyalty programs, where allowed by state law. There is a need for research directly on the influence of loyalty programs and nominal incentives on adherence.
Description of a Medical Writing Rotation for a Postgraduate Pharmacy Residency Program
Authors: Brown Jamie N. , Tiemann Kelsey A. , Ostroff Jared L. 
Published: December 2013

Purpose: To provide a description of a pharmacy residency rotation dedicated to medical writing developed at a tertiary care academic medical center. Summary: Contribution to the medical literature is an important component of professional pharmacy practice, and there are many benefits seen by practitioners actively involved in scholarly activities. Residency programs have an opportunity to expand beyond the standard roles of postgraduate pharmacist training but rarely is there formal instruction on medical writing skills or are scholarship opportunities provided to residents. In order to address this deficiency, a residency program may consider the implementation of a formal Medical Writing rotation. This rotation is designed to introduce the resident to medical writing through active discussion on medical writing foundational topics, engage the resident in a collaborative review of a manuscript submitted to a peer-reviewed professional journal, and support the resident in the design and composition of manuscript of publishable quality. Conclusion: A structured Medical Writing rotation during a pharmacy resident’s training can help develop the skills necessary to promote scholarly activities and foster resident interest in future pursuit of professional medical writing.
Intraosseous and Extraosseous Blood Supply to the Medial Cuneiform
Authors: Kraus Jonathan C. , McKeon Kathleen E. , Johnson Jeffrey E. , McCormick Jeremy J. , Klein Sandra E. 
Published: December 2013

Background: Osteotomies of the medial cuneiform are commonly used to correct forefoot deformity. Bone healing occurs despite periosteal stripping of the dorsal and medial surfaces of this widely articulated bone followed by osteotomy in the midsection of the bone. The objective of this study was to characterize the blood supply of the medial cuneiform. Methods: Thirty matched pairs of adult cadaver legs, 60 legs total, were amputated below the knee, and arterial casts were created with India ink and latex. Soft tissues were debrided, allowing visualization of the extraosseous blood vessels. In 53 specimens the vascular supply to the medial cuneiform was photographed and recorded. Forty-nine specimens were then cleared using a modified Spälteholz technique. The intraosseous vascularity of the medial cuneiform was successfully characterized and reviewed in 48 of these specimens. Results: The extraosseous blood supply was similar to previous reports with a middle pedicle branch originating from the dorsalis pedis artery. The medial plantar and superficial medial plantar artery supplied the plantar aspect of the bone. Intraosseous analysis showed a dense capillary network throughout the cuneiform, with typically one central medial major and several minor nutrient arteries noted. Areas of hypovascularity were infrequent and when noted occurred at inconsistent locations. Conclusion: These findings support the clinical suspicion that the medial cuneiform is well vascularized from multiple sources. The plantar blood supply is likely sufficient to allow bone healing after dorsal periosteal exposure and possible injury to the middle pedicle branch of the distal medial tarsal artery. Clinical Relevance: A medial cuneiform opening wedge osteotomy can be used to correct forefoot deformity. This study investigates the blood supply to that bone to better characterize the healing potential of the medial cuneiform.
Vascular Risk Factors and Mild Cognitive Impairment in the Elderly Population in Southwest China
Authors: Zou Yan , Zhu Qinlan , Deng Yongtao , Duan Jingxi , Pan Ling , Tu Qi , Dai Rong , Zhang Xuemei , Chu Leung-Wing , Lü Yang 
Published: December 2013

Objectives: Increasing evidence has demonstrated that vascular risk factors (VRFs) contribute to cognitive impairment in the elderly population. Prevention and administration of VRFs can be a vital strategy for delaying cognitive impairment. This study aimed to determine the impact of VRFs on cognitive function of the aged people from Chongqing, Southwest China. Methods: A total of 597 participants (≥60 years) from hospital and community population were enrolled in the cross-sectional study. Participants were screened for hypertension, coronary heart disease (CHD), and cerebrovascular disease (CVD). Blood pressure (BP) and blood lipid were also measured. Cognitive function was assessed with Mini-Mental State Examination and Clinical Dementia Rating. Logistic regression analysis was used to look for VRFs impacting mild cognitive impairment (MCI). Then we investigated the relationship between different types of vascular diseases and MCI. Results: A total of 457 participants showed normal cognitive function and 140 participants showed MCI. After adjusting for age, gender, and education, logistic regression analysis demonstrated that hypertension, CHD, systolic BP, total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) were independently associated with MCI; however, CVD, diastolic BP, triglyceride, and high-density lipoprotein cholesterol were not associated with MCI. Moreover, vascular diseases significantly contributed to MCI compared with no vascular disease; however, no significant difference in incident MCI was found among different combinations of vascular diseases. Conclusions: Hypertension, CHD, TC, and LDL-C are independent risk factors for MCI. Moreover, patients with vascular diseases have a higher risk of MCI; however, the amount of vascular diseases does not increase the risk of MCI.
Intrinsic Predictive Factors of Noncontact Lateral Ankle Sprain in Collegiate Athletes
Authors: Kobayashi Takumi , Yoshida Masahiro , Yoshida Makoto , Gamada Kazuyoshi 
Published: December 2013

Background: Lateral ankle sprain (LAS) is one of the most common injuries in sports. Despite extensive research, intrinsic factors that predict initial and recurrent noncontact LAS remain undefined. Purpose: To identify the predictive factors of initial and recurrent noncontact LAS, focusing on ankle flexibility and/or alignment in collegiate athletes. Study Design: Case-control study; Level of evidence, 3. Methods: A total of 191 athletes were assessed during the preseason for factors predictive of noncontact LAS. The baseline measurements included weightbearing dorsiflexion range of motion (ROM), leg-heel angle, foot internal rotation angle in plantar flexion, classification according to the mortise test, and navicular–medial malleolus (NMM) distance. Occurrence of noncontact LAS and participation in practice and games were prospectively recorded for 11 months. Results: Of the 191 athletes assessed, 169 (145 males, 24 females) completed the study; 125 athletes had a history of ankle sprain. During the observational period, 16 athletes suffered noncontact LAS (0.58 per 1000 athlete-exposures) consisting of 4 initial sprains and 12 recurrences. The hazard ratio estimated by a Cox regression analysis showed that athletes with an NMM distance ≥4.65 cm were 4.14 times more likely to suffer an initial noncontact LAS than were athletes with a shorter NMM distance (95% confidence interval, 1.12-14.30) and that athletes with a weightbearing dorsiflexion ROM >49.5° were 1.12 times as likely to suffer a recurrent noncontact LAS compared with athletes with a lower ROM (95% confidence interval, 1.05-1.20). Conclusion: NMM distance predicts initial noncontact LAS, and weightbearing dorsiflexion ROM predicts recurrent noncontact LAS.
Gadd45a regulates hematopoietic stem cell stress responses in mice
Authors: Chen Yulin , Ma Xiaoming , Zhang Meimei , Wang Xiaomin , Wang Changxin , Wang Hu , Guo Peng , Yuan Weiping , Rudolph Karl Lenhard , Zhan Qimin , Ju Zhenyu 
Published: December 2013

Key Points
Loss of Gadd45a enhances HSC reconstitution on hematopoietic stress. Gadd45a regulates DNA damage responses in HSCs.
Reconstruction of the lipid metabolism for the microalga Monoraphidium neglectum from its genome sequence reveals characteristics suitable for biofuel production
Authors: Bogen Christian , Al-Dilaimi Arwa , Albersmeier Andreas , Wichmann Julian , Grundmann Michael , Rupp Oliver , Lauersen Kyle J , Blifernez-Klassen Olga , Kalinowski Jörn , Goesmann Alexander , Mussgnug Jan H , Kruse Olaf 
Published: December 2013

Abstract

Background
Microalgae are gaining importance as sustainable production hosts in the fields of biotechnology and bioenergy. A robust biomass accumulating strain of the genus Monoraphidium (SAG 48.87) was investigated in this work as a potential feedstock for biofuel production. The genome was sequenced, annotated, and key enzymes for triacylglycerol formation were elucidated.

Results

Monoraphidium neglectum was identified as an oleaginous species with favourable growth characteristics as well as a high potential for crude oil production, based on neutral lipid contents of approximately 21% (dry weight) under nitrogen starvation, composed of predominantly C18:1 and C16:0 fatty acids. Further characterization revealed growth in a relatively wide pH range and salt concentrations of up to 1.0% NaCl, in which the cells exhibited larger structures. This first full genome sequencing of a member of the Selenastraceae revealed a diploid, approximately 68 Mbp genome with a G + C content of 64.7%. The circular chloroplast genome was assembled to a 135,362 bp single contig, containing 67 protein-coding genes. The assembly of the mitochondrial genome resulted in two contigs with an approximate total size of 94 kb, the largest known mitochondrial genome within algae. 16,761 protein-coding genes were assigned to the nuclear genome. Comparison of gene sets with respect to functional categories revealed a higher gene number assigned to the category “carbohydrate metabolic process” and in “fatty acid biosynthetic process” in M. neglectum when compared to Chlamydomonas reinhardtii and Nannochloropsis gaditana, indicating a higher metabolic diversity for applications in carbohydrate conversions of biotechnological relevance.

Conclusions
The genome of M. neglectum, as well as the metabolic reconstruction of crucial lipid pathways, provides new insights into the diversity of the lipid metabolism in microalgae. The results of this work provide a platform to encourage the development of this strain for biotechnological applications and production concepts.