bluuebunny/crossref_metadata_2025 huggingface dataset:
Decreased liver triglyceride content in adult rats exposed to protein restriction during gestation and lactation: Role of hepatic triglyceride utilization
Authors: Qasem Rani J , Li Jing , Tang Hee Man , Browne Veron , Mendez‐Garcia Claudia , Yablonski Elizabeth , Pontiggia Laura , D'Mello Anil P
Published: January 2015

We have previously demonstrated that protein restriction throughout gestation and lactation reduces liver triglyceride content in adult rat offspring. However, the mechanisms mediating the decrease in liver triglyceride content are not understood. The aim of the current study was to use a new group of pregnant animals and their offspring and determine the contribution of increased triglyceride utilization via the hepatic fatty‐acid oxidation and triglyceride secretory pathways to the reduction in liver triglyceride content. Pregnant Sprague–Dawley rats received either a control or a low protein diet throughout pregnancy and lactation. Pups were weaned onto laboratory chow on day 28 and killed on day 65. Liver triglyceride content was reduced in male, but not female, low‐protein offspring, both in the fed and fasted states. The reduction was accompanied by a trend towards higher liver carnitine palmitoyltransferase‐1a activity, suggesting increased fatty‐acid transport into the mitochondrial matrix. However, medium‐chain acyl coenzyme A dehydrogenase activity within the mitochondrial matrix, expression of nuclear peroxisome proliferator activated receptor‐α, and plasma levels of β‐hydroxybutyrate were similar between low protein and control offspring, indicating a lack of change in fatty‐acid oxidation. Hepatic triglyceride secretion, assessed by blocking peripheral triglyceride utilization and measuring serum triglyceride accumulation rate, and the activity of microsomal transfer protein, were similar between low protein and control offspring. Because enhanced triglyceride utilization is not a significant contributor, the decrease in liver triglyceride content in male low‐protein offspring is likely due to alterations in liver fatty‐acid transport or triglyceride biosynthesis.
Effects of Prenatal Alcohol and Cigarette Exposure on Offspring Substance Use in Multiplex, Alcohol‐Dependent Families
Authors: O'Brien Jessica W. , Hill Shirley Y.
Published: January 2015

Background

Prenatal exposures to alcohol, cigarettes, and other drugs of abuse are associated with numerous adverse consequences for affected offspring, including increased risk for substance use and abuse. However, maternal substance use during pregnancy appears to occur more often in those with a family history of alcohol dependence. Utilizing a sample that is enriched for familial alcohol dependence and includes controls selected for virtual absence of familial alcohol dependence could provide important information on the relative contribution of familial risk and prenatal exposures to offspring substance use.

Methods

A sample of multigenerational families specifically ascertained to be at either high or low risk for developing alcohol dependence (AD) provided biological offspring for a longitudinal prospective study. High‐risk families were selected based on the presence of 2 alcohol‐dependent sisters. Low‐risk families were selected on the basis of minimal first and second‐degree relatives with AD. High‐risk (HR = 99) and Low‐risk offspring (LR = 110) were assessed annually during childhood and biennially in young adulthood regarding their alcohol, drug, and cigarette use. At the first childhood visit, mothers were interviewed concerning their prenatal use of substances.

Results

High‐risk mothers were more likely to use alcohol, cigarettes, and other drugs during pregnancy than low‐risk control mothers, and to consume these substances in greater quantities. Across the sample, prenatal exposure to alcohol was associated with increased risk for both offspring cigarette use and substance use disorders (SUD), and prenatal cigarette exposure was associated with increased risk for offspring cigarette use. Controlling for risk status by examining patterns within the HR sample, prenatal cigarette exposure remained a specific predictor of offspring cigarette use, and prenatal alcohol exposure was specifically associated with increased risk for offspring SUD.

Conclusions

Women with a family history of SUD are at increased risk for substance use during pregnancy. Both familial loading for alcohol dependence and prenatal exposure to alcohol or cigarettes are important risk factors in the development of offspring substance use. An inadequate assessment of family history may obscure important interactions between familial risk and prenatal exposures on offspring outcomes.
Perceived Medical Risks of Drinking, Alcohol Consumption, and Hepatitis C Status Among Heavily Drinking HIV Primary Care Patients
Authors: Elliott Jennifer C. , Aharonovich Efrat , O'Leary Ann , Johnston Barbara , Hasin Deborah S.
Published: January 2015

Background

Heavy drinking poses significant risks to the health and survival of individuals infected with HIV, particularly those coinfected with hepatitis C virus (HCV). However, little is known about patients’ perceptions of these risks, and whether these perceptions relate to their alcohol consumption.

Methods

A sample of 254 heavily drinking HIV primary care patients (78% male; 94.5% minority; 31.8% with HCV) reported on their perceptions of the medical risks of drinking and on their alcohol consumption prior to participation in a drinking‐reduction intervention trial.

Results

In the HIV‐infected sample as a whole, 62.9% reported that they had a medical problem made worse by drinking, and 64.3% reported restricting drinking to avoid future medical problems. Although patients coinfected with HIV/HCV reported greater efforts to restrict drinking to avoid future medical problems (adjusted odds ratio = 1.94), their reported drinking quantity and frequency did not differ from that of HIV mono‐infected patients. Awareness of medical risk was not associated with drinking level. Effort to restrict drinking to avoid medical risk was associated with lower drinking quantity, frequency, and binge frequency (ps < 0.05), but the association with binge frequency was specific to patients without HCV.

Conclusions

Over one‐third of HIV patients are unaware of the medical risks of drinking, and do not restrict use, suggesting the need for intervention in this group. Patients coinfected with HIV/HCV may report more effort to restrict drinking, but their reported drinking quantity and frequency suggest that they are actually drinking just as heavily as HIV mono‐infected patients. Awareness of medical risk was unrelated to drinking, which suggests the need for interventions consisting of more than simple education. However, reported effort to restrict drinking did predict less drinking, suggesting the importance of patient commitment and initiative in change.
Dual‐Trait Selection for Ethanol Consumption and Withdrawal: Genetic and Transcriptional Network Effects
Authors: Metten Pamela , Iancu Ovidiu D. , Spence Stephanie E. , Walter Nicole A. R. , Oberbeck Denesa , Harrington Christina A. , Colville Alexandre , McWeeney Shannon , Phillips Tamara J. , Buck Kari J. , Crabbe John C. , Belknap John K. , Hitzemann Robert J.
Published: January 2015

Background

Data from C57BL/6J (B6) × DBA/2J (D2) F2 intercrosses (B6xD2 F2), standard and recombinant inbred strains, and heterogeneous stock mice indicate that a reciprocal (or inverse) genetic relationship exists between alcohol consumption and withdrawal severity. Furthermore, some genetic studies have detected reciprocal quantitative trait loci (QTLs) for these traits. We used a novel mouse model developed by simultaneous selection for both high alcohol consumption/low withdrawal and low alcohol consumption/high withdrawal and analyzed the gene expression and genome‐wide genotypic differences.

Methods

Randomly chosen third selected generation (S3) mice (N = 24/sex/line), bred from a B6xD2 F2, were genotyped using the Mouse Universal Genotyping Array, which provided 2,760 informative markers. QTL analysis used a marker‐by‐marker strategy with the threshold for a significant log of the odds (LOD) set at 10. Gene expression in the ventral striatum was measured using the Illumina Mouse 8.2 array. Differential gene expression and the weighted gene co‐expression network analysis (WGCNA) were implemented.

Results

Significant QTLs for consumption/withdrawal were detected on chromosomes (Chr) 2, 4, 9, and 12. A suggestive QTL mapped to Chr 6. Some of the QTLs overlapped with known QTLs mapped for 1 of the traits individually. One thousand seven hundred and forty‐five transcripts were detected as being differentially expressed between the lines; there was some overlap with known withdrawal genes (e.g., Mpdz) located within QTL regions. WGCNA revealed several modules of co‐expressed genes showing significant effects in both differential expression and intramodular connectivity; a module richly annotated with kinase‐related annotations was most affected.

Conclusions

Marked effects of selection on expression and network structure were detected. QTLs overlapping with differentially expressed genes on Chr 2 (distal) and 4 suggest that these are cis‐eQTLs (Chr 2: Kif3b, Kcnq2; Chr 4: Mpdz, Snapc3). Other QTLs identified were on Chr 2 (proximal), 9, and 12. Network results point to involvement of kinase‐related mechanisms and outline the need for further efforts such as interrogation of noncoding RNAs.
Ethanol Reduces Evoked Dopamine Release and Slows Clearance in the Rat Medial Prefrontal Cortex
Authors: Shnitko Tatiana A. , Kennerly Laura C. , Spear Linda P. , Robinson Donita L.
Published: January 2015

Background

Ethanol (EtOH) intoxication affects cognitive performance, contributing to attentional deficits and poor decision making, which may occur via actions in the medial prefrontal cortex (mPFC). mPFC function is modulated by the catecholamines dopamine and norepinephrine. In this study, we examine the acute effects of EtOH on electrically evoked dopamine release and clearance in the mPFC of anesthetized rats naïve to alcohol or chronically exposed to alcohol during adolescence.

Methods

Dopamine release and clearance was evoked by electrical stimulation of the ventral tegmental area (VTA) and measured in the mPFC of anesthetized rats with fast‐scan cyclic voltammetry. In Experiments 1 and 2, effects of a high dose of EtOH (4 g/kg, intraperitoneally) on dopamine neurotransmission in the mPFC of EtOH‐naïve rats and rats given EtOH exposure during adolescence were investigated. Effects of cumulative dosing of EtOH (0.5 to 4 g/kg) on the dopamine release and clearance were investigated in Experiment 3. Experiment 4 studied effects of EtOH locally applied to the VTA on the dopamine neurotransmission in the mPFC of EtOH‐naïve rats.

Results

A high dose of EtOH decreased evoked dopamine release within 10 minutes of administration in EtOH‐naïve rats. When tested via cumulative dosing from 0.5 to 4 g/kg, both 2 and 4 g/kg EtOH inhibited evoked dopamine release in the mPFC of EtOH‐naïve rats, while 4 g/kg EtOH also slowed dopamine clearance. A similar effect on electrically evoked dopamine release in the mPFC was observed after infusion of EtOH into the VTA. Interestingly, intermittent EtOH exposure during adolescence had no effect on observed changes in mPFC dopamine release and clearance induced by acute EtOH administration.

Conclusions

Taken together, these data describe EtOH‐induced reductions in the dynamics of VTA‐evoked mPFC dopamine release and clearance, with the VTA contributing to the attenuation of evoked mPFC dopamine release induced by EtOH.
Public attitude toward tiger farming and tiger conservation in Beijing, China
Authors: Liu Z. , Jiang Z. , Li C. , Fang H. , Ping X. , Luo Z. , Tang S. , Li L. , Meng Z. , Zeng Y.
Published: January 2015

There are arguments in support of and against use of tiger farming as a tool for the conservation of wild tigers Panthera tigris. Public attitude toward tiger farming can be a useful reference for tiger conservation. To fill this knowledge gap, we surveyed 677 citizens and 381 college students in Beijing to understand their knowledge of tiger conservation and attitude toward tiger farming. The results of ranking questions showed that with regard to the value of tigers, ecological, cultural and aesthetic, and scientific and educational value were ranked as the top three; legislation on wildlife protection and establishment of nature reserves were ranked as the top conservation methods; and poaching and illegal trade, human disturbance and loss of habitat were ranked as the top threatening factors. Apparently, medicinal and healthcare use as well as value as status symbols can be considered the main consumption motivations that trigger poaching and illegal trade. With regard to farming of tigers and the aspects of whether tigers should be farmed, the number of farmed tigers, how to dispose of farmed tigers and so on, we found that most of respondents considered farming of tigers to be a social undertaking and found it difficult to relate to commercial purposes. The results showed that people hold clear positions on arguments for and against the ban on tiger trade and were inclined to support the ban on trading tiger products, especially college students. We also found that the respondents were more balanced toward arguments in support of the use of farmed tigers than arguments against it.
The Feasibility of Coin Motors for Use in a Vibrotactile Display for the Blind
Authors: Stronks H. Christiaan , Parker Daniel J. , Walker Janine , Lieby Paulette , Barnes Nick
Published: January 2015

We have tested the potential of three types of vibration motors for use in a tactile vision substitution device for the blind. The motors were of the coin type, which are available off‐the‐shelf, and are characterized by their affordability, energy efficiency, and ease of implementation. The primary limitation of coin motors is the lack of control they offer over stimulus parameters. Specifically, adjusting the input voltage of a coin motor not only changes the vibration intensity, but also the vibration frequency and duration. This characteristic may result in unpredictable perceptions in psychophysical tests. By using standard psychophysical procedures, we were able to show that the tested coin motors evoked predictable magnitude perceptions across their dynamic range, following Fechner's law as if vibration intensity alone were varied. The best‐performing motor was able to generate a median number of 15 available just‐noticeable differences, meaning that it was potentially capable of conveying 16 gray levels in its dynamic range. We conclude that coin motors are potential candidates for the construction of a tactile display to substitute for lost vision.
Xin‐deficient mice display myopathy, impaired contractility, attenuated muscle repair and altered satellite cell functionality
Authors: Al‐Sajee D. , Nissar A. A. , Coleman S. K. , Rebalka I. A. , Chiang A. , Wathra R. , van der Ven P. F. M. , Orfanos Z. , Hawke T. J.
Published: January 2015

Aim

Xin is an F‐actin‐binding protein expressed during development of cardiac and skeletal muscle. We used Xin‐/‐ mice to determine the impact of Xin deficiency on different aspects of skeletal muscle health, including functionality and regeneration.

Methods

Xin‐/‐ skeletal muscles and their satellite cell (SC) population were investigated for the presence of myopathic changes by a series of histological and immunofluorescent stains on resting uninjured muscles. To further understand the effect of Xin loss on muscle health and its SCs, we studied SCs responses following cardiotoxin‐induced muscle injury. Functional data were determined using in situ muscle stimulation protocol.

Results

Compared to age‐matched wild‐type (WT), Xin‐/‐ muscles exhibited generalized myopathy and increased fatigability with a significantly decreased force recovery post‐fatiguing contractions. Muscle regeneration was attenuated in Xin‐/‐ mice. This impaired regeneration prompted an investigation into SC content and functionality. Although SC content was not different, significantly more activated SCs were present in Xin‐/‐ vs. WT muscles. Primary Xin‐/‐ myoblasts displayed significant reductions (approx. 50%) in proliferative capacity vs. WT; a finding corroborated by significantly decreased MyoD‐positive nuclei in 3 days post‐injury Xin‐/‐ muscle vs. WT. As more activated SCs did not translate to more proliferating myoblasts, we investigated whether Xin‐/‐ SCs displayed an exaggerated loss by apoptosis. More apoptotic SCs (TUNEL+/Pax7+) were present in Xin‐/‐ muscle vs. WT. Furthermore, more Xin‐/‐ myoblasts were expressing nuclear caspase‐3 compared to WT at 3 days post‐injury.

Conclusion

Xin deficiency leads to a myopathic condition characterized by increased muscle fatigability, impaired regeneration and SC dysfunction.
Quantitative Relationships Between the Cytotoxicity of Flavonoids on the Human Breast Cancer Stem‐Like Cells MCF7‐SC and Their Structural Properties
Authors: Jung Hyeryoung , Shin Soon Young , Jung Yearam , Tran Thao Anh , Lee Hye Ok , Jung Kang‐Yeoun , Koh Dongsoo , Cho Somi Kim , Lim Yoongho
Published: January 2015

As some breast cancer‐related deaths can be attributed to the metastasis of cancer stem cells, chemotherapeutic agents targeting breast cancer stem cells are of interest as a potential treatment. Flavonoids that exhibit cytotoxicity on breast cancer stem cells have rarely been observed. Thus, the objective of this study was to measure potential cytotoxic effects of 42 different flavonoids on the human breast cancer stem‐like cell line, MCF7‐SC. The relationship between flavonoid structural properties and cytotoxicity has not been reported previously; therefore, we determined quantitative structure–activity relationships using both comparative molecular field analysis and comparative molecular similarity analysis. Further biological experiments including Western blot analysis, flow cytometry, and immunofluorescence microscopy were also conducted on the most cytotoxic 8‐chloroflavanone.
Identifying designatable units for intraspecific conservation prioritization: a hierarchical approach applied to the lake whitefish species complex (Coregonusspp.)
Authors: Mee Jonathan A. , Bernatchez Louis , Reist Jim D. , Rogers Sean M. , Taylor Eric B.
Published: January 2015

The concept of the designatable unit (DU) affords a practical approach to identifying diversity below the species level for conservation prioritization. However, its suitability for defining conservation units in ecologically diverse, geographically widespread and taxonomically challenging species complexes has not been broadly evaluated. The lake whitefish species complex (Coregonusspp.) is geographically widespread in the Northern Hemisphere, and it contains a great deal of variability in ecology and evolutionary legacy within and among populations, as well as a great deal of taxonomic ambiguity. Here, we employ a set of hierarchical criteria to identifyDUs within the Canadian distribution of the lake whitefish species complex. We identified 36DUs based on (i) reproductive isolation, (ii) phylogeographic groupings, (iii) local adaptation and (iv) biogeographic regions. The identification ofDUs is required for clear discussion regarding the conservation prioritization of lake whitefish populations. We suggest conservation priorities among lake whitefishDUs based on biological consequences of extinction, risk of extinction and distinctiveness. Our results exemplify the need for extensive genetic and biogeographic analyses for any species with broad geographic distributions and the need for detailed evaluation of evolutionary history and adaptive ecological divergence when defining intraspecific conservation units.
Donor‐derived equine mesenchymal stem cells suppress proliferation of mismatched lymphocytes
Authors: Ranera B. , Antczak D. , Miller D. , Doroshenkova T. , Ryan A. , McIlwraith C. W. , Barry F.
Published: January 2015

Reasons for performing study

Recently, it has been shown that mesenchymal stem cells (MSCs) do not express the major histocompatibility complex (MHC) II antigen and are able to inhibit proliferation of MHC‐mismatched stimulated lymphocytes, enabling their use as in vivo allogeneic transplants. However, prior to clinical application of allo‐MSCs, in vitro tests are required to confirm the safety of treatment protocols.

Objectives

To evaluate the immunosuppressive capabilities of equine bone‐marrow‐derived MSCs (BM‐MSCs) on MHC‐mismatched lymphocytes.

Study design

In vitro experiment.

Methods

Phytohaemagglutinin‐stimulated peripheral blood mononuclear cells (PBMCs) from 3 Thoroughbreds (recipients) were co‐cultured with mismatched BM‐MSCs from 3 Connemara ponies (donors). Proliferation of lymphocytes was monitored by carboxyfluorescein succinimidyl ester labelling and analysed by flow cytometry. In total, 6 horses were haplotyped using microsatellites to confirm mismatching. Optimisation of the conditions to stimulate Thoroughbred lymphocytes and titration of equine anti‐CD4 and anti‐CD8 antibodies were performed. Connemara pony and Thoroughbred BM‐MSCs were isolated, expanded and characterised by tri‐lineage differentiation. Finally, BM‐MSCs from both breeds were set up in co‐culture at different ratios with stimulated Thoroughbred lymphocytes. Proliferation of CD4+ and CD8+ cells was determined by flow cytometry.

Results

A high proportion of CD4/CD8 double‐positive lymphocytes were found in freshly isolated PBMCs, although this percentage decreased after 4 days of culture. Mismatched BM‐MSCs inhibited proliferation of stimulated lymphocytes in a dose‐dependent manner, with the greatest suppression occurring at a 1:10 ratio of BM‐MSCs to PBMCs. Proliferation of CD4+ and CD8+ subpopulations decreased in 1:10 co‐culture, with statistical significance in the case of CD8+ cells, while that of the CD4/CD8 double‐positive population was similar to the phytohaemagglutinin control.

Conclusions

The results demonstrate dose‐dependent immunosuppression of stimulated lymphocytes by mismatched equine BM‐MSCs, supporting their future application in allo‐MSC clinical treatments.
Father Knows Best: Paternal Presence and Sexual Debut in African‐American Adolescents Living in Poverty
Authors: Langley Cheri
Published: January 2015

Adolescents found within single‐parent families without a residential father have reported higher levels of sexual debut and higher levels of reported pregnancy. Using data from the Mobile Youth Survey, the purpose of this study is to determine the impact of the presence of a father figure on the sexual debut of African‐American adolescents living in poverty and to determine if gender moderates the relationship between the presence of a father figure and sexual debut. Additionally, this study will examine the family processes in which the presence of a father figure can affect the sexual debut of African‐American adolescents who live within economically and socially disadvantaged communities. The results revealed that African‐American adolescents reporting a father figure had lower rates of sexual debut than those youth reporting no father figure. Gender was not found to be a significant moderator in the relationship between father figure presence and sexual debut. However, existing curfews and family rules did account for some of the effects of presence of a father figure and sexual debut. The results suggest that when adolescents have a father figure in their lives, it may reduce the possibility of early sexual debut.
How to achieve full prophylaxis in young boys with severe haemophilia A: different regimens and their effect on early bleeding and venous access
Authors: Nijdam A. , Kurnik K. , Liesner R. , Ljung R. , Nolan B. , Petrini P. , Fischer K. ,   the PedNet study group
Published: January 2015

To facilitate early prophylaxis, step‐up regimens starting prophylaxis with infusions 1× week−1were introduced. Choice of initial regimen may affect outcome. This study aims to classify initial prophylactic regimens and compare them on short‐term outcome. From the ‘European Paediatric Network for Haemophilia Management' (PedNet) registry, patients with severe haemophilia A without inhibitors, born 2000–2012, receiving prophylaxis were included. Treatment centres were classified according to the initial frequency of prophylactic infusions and the age at reaching infusions ≥3× week−1. Bleeding, and central venous access device (CVAD) use were compared at age 4 years. In 21 centres with 363 patients, three regimens were identified: (i) start prophylaxis with ≥3× week−1infusions before age three (full: 19% of centres, 18% of patients); (ii) start 1–2× week−1, increasing frequency as soon as possible (asap), reaching ≥3× week−1before age three (43% of centres, 36% of patients); (iii) start 1–2× week−1, increasing frequency according to bleeding (phenotype), reaching ≥3× week−1after age three (38% of centres, 46% of patients). Prophylaxis was started at median 1.2 years on the full and asap regimen vs 1.8 years on the phenotype regimen. Complete prevention of joint bleeds was most effective on the full regimen (32% full vs. 27% asap and 8% phenotype), though at the cost of using mostCVADs (88% full vs. 34% asap and 22% phenotype). The three prophylaxis regimens identified had different effects on early bleeding andCVADuse. This classification provides the first step towards establishing the optimum prophylactic regimen.
Attenuation of microRNA‐16 derepresses the cyclins D1, D2 and E1 to provoke cardiomyocyte hypertrophy
Authors: Huang Shuai , Zou Xiao , Zhu Jie‐Ning , Fu Yong‐Heng , Lin Qiu‐Xiong , Liang Ye‐You , Deng Chun‐Yu , Kuang Su‐Juan , Zhang Meng‐Zhen , Liao Yu‐Lin , Zheng Xi‐Long , Yu Xi‐Yong , Shan Zhi‐Xin
Published: January 2015

Cyclins/retinoblastoma protein (pRb) pathway participates in cardiomyocyte hypertrophy. MicroRNAs (miRNAs), the endogenous small non‐coding RNAs, were recognized to play significant roles in cardiac hypertrophy. But, it remains unknown whether cyclin/Rb pathway is modulated by miRNAs during cardiac hypertrophy. This study investigates the potential role of microRNA‐16 (miR‐16) in modulating cyclin/Rb pathway during cardiomyocyte hypertrophy. An animal model of hypertrophy was established in a rat with abdominal aortic constriction (AAC), and in a mouse with transverse aortic constriction (TAC) and in a mouse with subcutaneous injection of phenylephrine (PE) respectively. In addition, a cell model of hypertrophy was also achieved based on PE‐promoted neonatal rat ventricular cardiomyocyte and based on Ang‐II‐induced neonatal mouse ventricular cardiomyocyte respectively. We demonstrated that miR‐16 expression was markedly decreased in hypertrophic myocardium and hypertrophic cardiomyocytes in rats and mice. Overexpression of miR‐16 suppressed rat cardiac hypertrophy and hypertrophic phenotype of cultured cardiomyocytes, and inhibition of miR‐16 induced a hypertrophic phenotype in cardiomyocytes. Expressions of cyclins D1, D2 and E1, and the phosphorylated pRb were increased in hypertrophic myocardium and hypertrophic cardiomyocytes, but could be reversed by enforced expression of miR‐16. Cyclins D1, D2 and E1, not pRb, were further validated to be modulated post‐transcriptionally by miR‐16. In addition, the signal transducer and activator of transcription‐3 and c‐Myc were activated during myocardial hypertrophy, and inhibitions of them prevented miR‐16 attenuation. Therefore, attenuation of miR‐16 provoke cardiomyocyte hypertrophy via derepressing the cyclins D1, D2 and E1, and activating cyclin/Rb pathway, revealing that miR‐16 might be a target to manage cardiac hypertrophy.
Staff attitudes towards people with intellectual disabilities in Japan and the United States
Authors: Horner‐Johnson W. , Keys C. B. , Henry D. , Yamaki K. , Watanabe K. , Oi F. , Fujimura I. , Graham B. C. , Shimada H.
Published: January 2015

Background

Staff attitudes may affect choices available to persons with intellectual disabilities (ID). This study examined attitudes towards people with ID among staff working with people with ID in Japan and the United States.

Method

Attitudes of staff working with people with ID in Japan and the United States were compared using the Community Living Attitudes Scale, Intellectual Disabilities Form. Responses were examined via multivariate analysis of variance.

Results

In unadjusted analyses, Japanese staff exhibited a greater tendency towards Sheltering and Exclusion of people with ID and lower endorsement of Empowerment and Similarity of people with ID. After controlling for covariates, the country effect was no longer significant for Sheltering and Exclusion. Age and education were significantly associated with attitudes in the adjusted model.

Conclusions

While attitudes in Japan appeared less supportive of community inclusion of people with ID, some of the differences between countries were attributable to other staff characteristics such as age and education. Findings provide new information about how attitudes of staff in each country compare with each other.
Chromosome inversions, adaptive cassettes and the evolution of species' ranges
Authors: Kirkpatrick Mark , Barrett Brian
Published: January 2015

A chromosome inversion can spread when it captures locally adapted alleles or when it is introduced into a species by hybridization with adapted alleles that were previously absent. We present a model that shows how both processes can cause a species range to expand. Introgression of an inversion that carries novel, locally adapted alleles is a particularly powerful mechanism for range expansion. The model supports the earlier proposal that introgression of an inversion triggered a large range expansion of a malaria mosquito. These results suggest a role for inversions as cassettes of genes that can accelerate adaptation by crossing species boundaries, rather than protecting genomes from introgression.
LACK, a RACK1 ortholog, facilitates cytochrome c oxidase subunit expression to promote Leishmania major fitness
Authors: Cardenas Daviel , Carter Pamela M. , Nation Catherine S. , Pizarro Juan C. , Guidry Jessie , Aiyar Ashok , Kelly Ben L.
Published: January 2015

Leishmania are kinetoplastid parasites that cause the sandfly‐transmitted disease leishmaniasis. To maintain fitness throughout their infectious life cycle, Leishmania must undergo rapid metabolic adaptations to the dramatically distinct environments encountered during transition between sandfly and vertebrate hosts. We performed proteomic and immunoblot analyses of attenuated L. major strains deficient for LACK, the Leishmania ortholog of the mammalian receptor for activated c kinase (RACK1), that is important for parasite thermotolerance and virulence. This approach identified cytochrome c oxidase (LmCOX) subunit IV as a LACK‐dependent fitness protein. Consistent with decreased levels of LmCOX subunit IV at mammalian temperature, and in amastigotes, LmCOX activity and mitochondrial function were also impaired in LACK‐deficient L. major under these conditions. Importantly, overexpression of LmCOX subunit IV in LACK‐deficient L. major restored thermotolerance and macrophage infectivity. Interestingly, overexpression of LmCOX subunit IV enhanced LmCOX subunit VI expression at mammalian temperature. Collectively, our data suggest LACK promotes Leishmania adaptation to the mammalian host environment by sustaining LmCOX subunit IV expression and hence energy metabolism in response to stress stimuli such as heat. These findings extend the repertoire of RACK1 protein utility to include a role in mitochondrial function.
Novel export control of a Legionella Dot/Icm substrate is mediated by dual, independent signal sequences
Authors: Jeong Kwang Cheol , Sutherland Molly C. , Vogel Joseph P.
Published: January 2015

The Legionella pneumophila Dot/Icm T4SS injects ∼ 300 protein effector proteins into host cells. Dot/Icm substrates have been proposed to contain a carboxy‐terminal signal sequence that is necessary and sufficient for export, although both traits have been demonstrated for only a small fraction of these proteins. In this study, we discovered that export of the substrate SidJ is mediated by dual signal sequences that include a conventional C‐terminal domain and a novel internal motif. The C‐terminal signal sequence facilitates secretion of SidJ into host cells at early points of infection, whereas the internal signal sequence mediates secretion at later time points. Interestingly, only the internal signal sequence is necessary for complementation of the intracellular growth defect of a ΔsidJ mutant. Although this is the first report of a Dot/Icm substrate being secreted by an internal signal sequence, many other substrates may be exported in a similar manner. In addition, efficient translocation of SidJ is dependent on the chaperone‐like type IV adaptors IcmS/IcmW. Five IcmS/IcmW binding domains that are distinct from both signal sequences were elucidated and, interestingly, only secretion mediated by the internal signal sequence requires IcmS/IcmW. Thus, Legionella employs multiple sophisticated molecular mechanisms to regulate the export of SidJ.
Integration of chemotaxis, transport and catabolism in Pseudomonas putida and identification of the aromatic acid chemoreceptor PcaY
Authors: Luu Rita A. , Kootstra Joshua D. , Nesteryuk Vasyl , Brunton Ceanne N. , Parales Juanito V. , Ditty Jayna L. , Parales Rebecca E.
Published: January 2015

Aromatic and hydroaromatic compounds that are metabolized through the β‐ketoadipate catabolic pathway serve as chemoattractants for Pseudomonas putida F1. A screen of P. putida F1 mutants, each lacking one of the genes encoding the 18 putative methyl‐accepting chemotaxis proteins (MCPs), revealed that pcaY encodes the MCP required for metabolism–independent chemotaxis to vanillate, vanillin, 4‐hydroxybenzoate, benzoate, protocatechuate, quinate, shikimate, as well as 10 substituted benzoates that do not serve as growth substrates for P. putida F1. Chemotaxis was induced during growth on aromatic compounds, and an analysis of a pcaY‐lacZ fusion revealed that pcaY is expressed in the presence of β‐ketoadipate, a common intermediate in the pathway. pcaY expression also required the transcriptional activator PcaR, indicating that pcaY is a member of the pca regulon, which includes three unlinked gene clusters that encode five enzymes required for the conversion of 4‐hydroxybenzoate to tricarboxylic acid cycle intermediates as well as the major facilitator superfamily transport protein PcaK. The 4‐hydroxybenzoate permease PcaK was shown to modulate the chemotactic response by facilitating the uptake of 4‐hydroxybenzoate, which leads to the accumulation of β‐ketoadipate, thereby increasing pcaY expression. The results show that chemotaxis, transport and metabolism of aromatic compounds are intimately linked in P. putida.
Identification of the novel KIR2DL2*013 allele from a southern Chinese Han individual
Authors: Zhen J.‐X. , Wang D.‐M. , Deng Z.‐H.
Published: January 2015

The novel KIR2DL2*013 allele differs from the closest allele KIR2DL2*00302 by two non‐synonymous mutations.
AEF1/MPR25 is implicated in RNA editing of plastid atpF and mitochondrial nad5, and also promotes atpF splicing in Arabidopsis and rice
Authors: Yap Aaron , Kindgren Peter , Colas des Francs‐Small Catherine , Kazama Tomohiko , Tanz Sandra K. , Toriyama Kinya , Small Ian
Published: January 2015

RNA editing is an essential mechanism that modifies target cytidines to uridine in both mitochondrial and plastid mRNA. Target sites are recognized by pentatricopeptide repeat (PPR) proteins. Using bioinformatics predictions based on the code describing sequence recognition by PPR proteins, we have identified an Arabidopsis editing factor required for editing of atpF in plastids. A loss‐of‐function mutation in ATPF EDITING FACTOR 1 (AEF1, AT3G22150) results in severe variegation, presumably due to decreased plastid ATP synthase levels. Loss of editing at the atpF site is coupled with a large decrease in splicing of the atpF transcript, even though the editing site is within an exon and 53 nucleotides distant from the splice site. The rice orthologue of AEF1, MPR25, has been reported to be required for editing of a site in mitochondrial nad5 transcripts, and we confirm that editing of the same site is affected in the Arabidopsis aef1 mutant. We also show that splicing of chloroplast atpF transcripts is affected in the rice mpr25 mutant. AEF1 is thus highly unusual for an RNA editing specificity factor in that it has functions in both organelles.
How Compressibility Influences the Mechanical Bidomain Model
Authors: Sharma Kharananda , Roth Bradley John
Published: January 2015

Compressibility influences the mechanical bidomain model describing the elastic properties of the tissue. In this model, the displacements of the intracellular and extracellular spaces are analyzed individually, and differences in these displacements give rise to membrane forces. In our present analysis, two length constants are associated with the membrane spring constant; one contains the shear moduli and the other contains the bulk moduli. The analytical solutions in our examples indicate that the monodomain part does not contribute to the membrane forces. Accounting for compressibility has its largest impact on the intracellular and extracellular pressures. The bidomain contribution to the pressure obeys the Helmholtz equation rather than LaplaceвЂ™s equation. This model helps us to estimate the membrane forces that cause tissue remodeling and mechanotransduction.
Random Vibration and Accelerated Life Testing
Authors: Pointer Jon S.
Published: January 2015

Increasingly random vibration testing is being utilized to validate products that are exposed to high levels of vibration across a wide frequency range when in use. Basic methods utilize the inverse power law and step test to failure to correlate test time at amplified vibration levels to predicted life at in-use conditions. However, many areas of this practice are debated including the selection of a proper exponent for life calculations, selection of test time and test levels, and correlation between dissimilar test and in-use vibration profiles. This paper explores the current literature on the topic and recommends a step by step method for utilizing random vibration testing to validate products that are subjected to a high degree of in-use vibration variability.
Stiffness Optimization and Comparison of Tensile Trusses With Constant Envelope and Cable Material
Authors: Hennessey Michael P. , Kumar Sameer , Geletu Temam M.
Published: January 2015

We evaluate and compare the stiffness properties of 6 different configurations of tensile trusses. More specifically, given a constant structural envelope and amount of homogeneous isotropic linear elastic cable material, the stiffness properties of the configurations are analyzed with constant cross-sectional area cables. The configurations include: (1) a Stewart platform, (2) Stewart platform with full spine, 3 cable tie-offs, and slip joint, (3) 6-loop dual-reeved system with partial spine, (4) 4-node/4-loop dual-reeved system, (5) double Stewart platform, and (6) 3D extension of a 2D 2 cable system. In each case, we use analytical results for the evaluation of the stiffness matrix, with some new stiffness matrix results being presented. Of the 6 competing configurations considered, no one configuration was uniformly better than all others, but both the double Stewart platform and the Stewart platform with full spine, 3 cable tie-offs, and slip joint performed quite well, of course given free, massless, rigid body material.
Numerical Investigations of the Air Flow Patterns and Temperature Distribution in a Museum Showroom, King Tutankhamun’s Gallery, Egyptian Museum
Authors: Zaki Ahmed H. , Khalil Essam E. , Bialy Esmail M. , Abdelmaksoud Waleed A.
Published: January 2015

The use of numerical simulation methods for the Cultural Heritage is of increasing importance for the analysis, conservation, restoration and appreciation of works of art. This is particularly important when their preservation and planned maintenance is the primary aim [1, 2]. King Tutankhamen’s gallery at the Egyptian museum is chosen for our study. The conservation of such artworks requires precise control of the indoor microclimatic conditions. Thus, a suitable HVAC system with reliable control is often necessary for a museum, to maintain acceptable indoor thermal-hygrometric parameters and air velocity and also to minimize the deviations of these parameters from the design values. An investigation of airflow characteristics inside King Tutankhamen’s gallery at the Egyptian museum is studied. The effect of visitors within the gallery space is discussed. Lighting is mainly neglected and its effect is shown in a limited procedure. The variability of inlet air velocities and the grills location in the gallery is studied to achieve a better understanding of the closest solution for air distribution within the gallery.
Rational Solutions and Rogue Waves in Nonlinear Schrödinger Equation With Varying Coefficients
Authors: Song Ni , Zhang Wei , Zhou Sha. , Wang Qian
Published: January 2015

The similarity transformation and direct ansatz are applied to obtain rogue wave solutions of nonlinear Schrödinger equation with varying coefficients. These obtained solutions can be used to describe the possible formation mechanisms for optical rogue wave phenomenon in optical fibres. Moreover their dynamical behaviors are exhibited for chosen different functions. This will further excite the possibility of relative researchers and potential applications of rogue waves in other related fields.
Toward a Market-Based Lean Startup Product Design Method for the Developing World
Authors: Pease Jordan F. , Dean Jered H. , Van Bossuyt Douglas L.
Published: January 2015

The question of how to effectively design products for consumers in the developing world has been widely debated. Several methodologies have been developed to address this issue focusing on human centered and community centered methods, but few methods are rooted in market-centered approaches. Recent advances in market-centered design from lean startup methodologies hold promise for the development of new methods that allow effective product design for consumers in the developing world. This paper contributes a method from which consumer level products can be designed to effectively supply the under-served markets of the developing world with innovative and sustainable solutions. Utilizing an iterative method based on three fundamental hypotheses, the Lean Design for Developing World Method (LDW) seeks to provide products that are economically viable, have strong market growth potential, and have a net positive impact on the customers and their communities.
Methodology for Optimization of Friction Draft Gear Design
Authors: Wu Qing , Cole Colin , Spiryagin Maksym
Published: January 2015

Evidence gathered from industry indicates that railway coupling system failures have become a limitation for further developments of heavy haul trains. Friction draft gears have implications for both longitudinal train dynamics and rolling stock fatigue; therefore, optimization of friction draft gears could be a possible solution to conquer the limitation. In this paper, a methodology for optimization of friction draft gear design based on an advanced friction draft gear model is proposed. The methodology proposes using simulation techniques such as longitudinal train dynamics simulation and a Genetic Algorithm to develop improved parameters.
Talking to TAD: Animating an Everyday Object for Use in Augmented Workspaces
Authors: DeVito Matthew P. , Ramani Karthik
Published: January 2015

Workspaces augmented by multitouch and gesture-sensing systems are quickly becoming a reality, but studies appear to limit themselves to interacting with displays. With the continued progress of the ubiquitous computing movement, everyday objects are coming to life and will soon enter these augmented spaces. Little has been studied regarding gestural control of everyday objects capable of movement in three-dimensional space. In the present study, we augment an office lamp for gestural interaction and use it toward finding more natural gestures for augmented workspace interaction with physical objects. We begin by surveying the current literature on user-defined gesture sets and digital augmentation of lamps to determine features desirable in the design of an actuated desk lamp. A prototypical Tabletop Assistive Droid (TAD) is then used in a study conducted to determine and analyze a feasible user-defined gesture set.
Fault Tolerant Gaits for a Six-Legged Robot With One Locked or Uncontrollable Failure
Authors: Du Hui , Gao Feng , Pan Yang
Published: January 2015

Multi-legged robots need fault tolerant gaits if one or more legs are broken down and cannot have maintenance when in long-distance operations or hash environments. There are two common faults of robot actuations: locked and uncontrollable failure. In this paper, a novel parallel-parallel six-legged robot as our prototype has good fault tolerant capability to continue walking with a locked or uncontrollable leg. The leg sequence and the formula of the leg/body stride length are driven based on gait study and robot kinematics. Then, a continuous fault tolerant gait is proposed which enables the robot maintain high speed and stability.
Harmonic Balance for Large-Amplitude Vibrations in Snap-Through Structures
Authors: Panigrahi Smruti R. , Feeny Brian F. , Diaz Alejandro R.
Published: January 2015

A simple nonlinear Duffing oscillator has been studied for its snap-through behavior at large-amplitude vibrations. Using the harmonic balance method we have developed an algorithm to find particular amplitude and frequency relations in two-term and three-term approximations when the solution lies outside of the separatrix on the phase space, i.e. when the oscillator exhibits snap-through behavior.
Design of an Endoscopic Micro Optical Part for Fabrication With Micro Two Shot Injection Moulding
Authors: Said Luke , Farrugia Philip , Rochman Arif , Vella Pierre
Published: January 2015

Micro two shot injection moulding (μtwo shot IM) is a manufacturing process capable of simultaneously replicating two polymeric parts and assembling them; removing the requirement for costly micro assembly. Endoscopes are used in medical environments to observe areas that are otherwise unobservable. μTwo shot IM has the potential to simultaneously replicate and assemble polymer lenses for endoscope imaging and assembling them to their required housing. In view of this, this paper contributes a case study part for application of μtwo shot injection moulding in the fabrication of an endoscopic micro optical component. This paper covers several aspects involved in the design of such a part. This novel design concept consists of an optical component and a housing component moulded sequentially on top of each other using μtwo shot IM. The lens component consisted of three lenses with a common base moulded as the first shot. The second shot moulded on onto the optical component was the housing component incorporating an external thread for interchangeability. From a material selection exercise it was concluded that cyclic olefin copolymer (COC) shall be used as the optical material and polyoxymethylene (POM) shall be used as the housing material. One major concern in the design of such a part is the deformation of the optical material by the housing material due to softening via heat transfer. Simulations of such a scenario were carried out and it was indicated that the functionality of the optical material shall not be compromised.