bluuebunny/crossref_metadata_2025 huggingface dataset:
Murine Mesenchymal Stem Cell Commitment to Differentiation Is Regulated by Mitochondrial Dynamics
Authors: Forni Maria Fernanda , Peloggia Julia , Trudeau Kyle , Shirihai Orian , Kowaltowski Alicia J.
Published: December 2015

Mouse skin mesenchymal stem cells (msMSCs) are dermis CD105+CD90+CD73+CD29+CD34− mesodermal precursors which, after in vitro induction, undergo chondro, adipo, and osteogenesis. Extensive metabolic reconfiguration has been found to occur during differentiation, and the bioenergetic status of a cell is known to be dependent on the quality and abundance of the mitochondrial population, which may be regulated by fusion and fission. However, little is known regarding the impact of mitochondrial dynamics on the differentiation process. We addressed this knowledge gap by isolating MSCs from Swiss female mice, inducing these cells to differentiate into osteo, chondro, and adipocytes and measuring changes in mass, morphology, dynamics, and bioenergetics. Mitochondrial biogenesis was increased in adipogenesis, as evaluated through confocal microscopy, citrate synthase activity, and mtDNA content. The early steps of adipo and osteogenesis involved mitochondrial elongation, as well as increased expression of mitochondrial fusion proteins Mfn1 and 2. Chondrogenesis involved a fragmented mitochondrial phenotype, increased expression of fission proteins Drp1, Fis1, and 2, and enhanced mitophagy. These events were accompanied by profound bioenergetic alterations during the commitment period. Moreover, knockdown of Mfn2 in adipo and osteogenesis and the overexpression of a dominant negative form of Drp1 during chondrogenesis resulted in a loss of differentiation ability. Overall, we find that mitochondrial morphology and its regulating processes of fission/fusion are modulated early on during commitment, leading to alterations in the bioenergetic profile that are important for differentiation. We thus propose a central role for mitochondrial dynamics in the maintenance/commitment of mesenchymal stem cells.
Astonishing 35S rDNA diversity in the gymnosperm species Cycas revoluta Thunb
Authors: Wang Wencai , Ma Lu , Becher Hannes , Garcia Sònia , Kovarikova Alena , Leitch Ilia J. , Leitch Andrew R. , Kovarik Ales
Published: December 2015

In all eukaryotes, the highly repeated 35S ribosomal DNA (rDNA) sequences encoding 18S-5.8S-26S ribosomal RNA (rRNA) typically show high levels of intragenomic uniformity due to homogenisation processes, leading to concerted evolution of 35S rDNA repeats. Here, we compared 35S rDNA divergence in several seed plants using next generation sequencing and a range of molecular and cytogenetic approaches. Most species showed similar 35S rDNA homogeneity indicating concerted evolution. However, Cycas revoluta exhibits an extraordinary diversity of rDNA repeats (nucleotide sequence divergence of different copies averaging 12 %), influencing both the coding and non-coding rDNA regions nearly equally. In contrast, its rRNA transcriptome was highly homogeneous suggesting that only a minority of genes (<20 %) encode functional rRNA. The most common SNPs were C > T substitutions located in symmetrical CG and CHG contexts which were also highly methylated. Both functional genes and pseudogenes appear to cluster on chromosomes. The extraordinary high levels of 35S rDNA diversity in C. revoluta, and probably other species of cycads, indicate that the frequency of repeat homogenisation has been much lower in this lineage, compared with all other land plant lineages studied. This has led to the accumulation of methylation-driven mutations and pseudogenisation. Potentially, the reduced homology between paralogs prevented their elimination by homologous recombination, resulting in long-term retention of rDNA pseudogenes in the genome.
Next Generation Sequencing in the Clinic: a Patterns of Care Study in a Retrospective Cohort of Subjects Referred to a Genetic Medicine Clinic for Suspected Lynch Syndrome
Authors: Gallego Carlos J. , Perez Matthew L. , Burt Amber , Amendola Laura M. , Shirts Brian H. , Pritchard Colin C. , Hisama Fuki M. , Bennett Robin L. , Veenstra David L. , Jarvik Gail P.
Published: December 2015

Next generation sequencing (NGS) gene panels are increasingly used in medical genetics clinics for the evaluation of common inherited cancer syndromes, but the clinical efficacy of these tests, and the factors driving clinical providers to order them are unclear. We conducted a patterns‐of‐care study to compare patients evaluated with NGS gene panels with a reference group. We abstracted demographic, socioeconomic, and clinical information in a retrospective cohort of patients referred to a large medical genetics clinic for evaluation of inherited colorectal cancer and polyposis syndromes. Patients tested with NGS gene panels were more likely to be insured compared to the reference group (85.3 % vs. 69.2 %, p = 0.0068),less likely to have prior tumor tissue testing (29.4 % vs. 54.3 %, p = 0.0004), and less likely to have an abnormal tumor tissue test result (46.7 % vs. 74.5 %, p = 0.01). No significant differences were found between groups in age, gender, race, employment status, personal history of colorectal cancer, or proportion of patients fulfilling Lynch syndrome clinical criteria. Patients with NGS testing were less likely to have a pathogenic/likely pathogenic variant detected (13.7 % vs. 31.9 %, p = 0.002). Patients referred for NGS testing to evaluate inherited colorectal cancer/polyposis risk appear to undergo tumor tissue testing less frequently than non‐NGS testing patients. Further studies are needed to assess the most effective and cost‐effective approach to genomic diagnosis in this patient population.
The Effect of Counterions of Linear Alkylbenzene Sulfonate on Skin Compatibility
Authors: Cohen Leon , Martin Mariluz , Soto Fernando , Trujillo Francisco , Sanchez Elsa
Published: December 2015

Interactions of a widely used commercial anionic surfactant, linear alkylbenzene sulfonate, with zein protein, a water insoluble protein, was studied to better understand the effects of the counterion on skin irritation of anionic surfactants. The neutralizing ions used were inorganics: Li+, Na+, K+, Mg2+, and NH4+and organics: monoethanolamine, diethanolamine, and triethanolamine. According to the results obtained, the influence of counterions of anionic surfactants on zein solubilization is significant; with magnesium counterions showing lower zein solubilization. In aqueous solutions, zein solubilization by anionic surfactant is related to the effect of the counterion on the critical micelle concentration of the surfactant for the inorganic counter‐ions; for the organic counter‐ions, effects of tighter anionic binding in the micelle also contribute to zein solubilization trends.
Tensile strain-induced magnetism transition in multilayer graphene with excess electrons: Stability of the edge-quantum well
Authors: Yang Lei , Diao Dongfeng
Published: December 2015

The stability of edge-quantum well-induced strong magnetism of multilayer armchair graphene nanoribbon (AGNR) with excess electrons was investigated under applied tensile strain by density functional theory (DFT) calculations. The results indicated that: (1) The strain along the armchair edge direction led to a transition of the multilayer AGNRs from ferromagnetic state to nonmagnetic state when the strain increased to a critical value; (2) The strain induced bond length changes reduced the stability of the edge-quantum well in terms of the reduction of the electrons capturing capacity; and (3) The spin splitting of the energy bands near the Fermi level reduced with the increase of the strain, resulting in the decrease of the spin moment. This finding suggests that the magnetic properties of graphene have strong dependence on its strain states, which is crucial to the design of graphene-based magnetic devices.
Maligner: a fast ordered restriction map aligner
Authors: Mendelowitz Lee M. , Schwartz David C. , Pop Mihai
Published: December 2015

Motivation: The Optical Mapping System discovers structural variants and potentiates sequence assembly of genomes via scaffolding and comparisons that globally validate or correct sequence assemblies. Despite its utility, there are few publicly available tools for aligning optical mapping datasets.

Results: Here we present software, named ‘Maligner’, for the alignment of both single molecule restriction maps (Rmaps) and in silico restriction maps of sequence contigs to a reference. Maligner provides two modes of alignment: an efficient, sensitive dynamic programming implementation that scales to large eukaryotic genomes, and a faster indexed based implementation for finding alignments with unmatched sites in the reference but not the query. We compare our software to other publicly available tools on Rmap datasets and show that Maligner finds more correct alignments in comparable runtime. Lastly, we introduce the M-Score statistic for normalizing alignment scores across restriction maps and demonstrate its utility for selecting high quality alignments.

Availability and implementation: The Maligner software is written in C ++ and is available at https://github.com/LeeMendelowitz/maligner under the GNU General Public License.

Contact: mpop@umiacs.umd.edu
Central Nervous System Blastomycosis Without Travel to Known Endemic Area
Authors: Spallone Amy , Tobin Ellis H. , Chaturvedi Sudha , Qian Jiang
Published: December 2015

Blastomycosis is thought to be endemic to specific regions of the United States. The spectrum of disease ranges from subclinical infections to potentially fatal systemic dissemination. Single organ involvement often involves the lungs. Extrapulmonary dissemination often includes the skin, bone, and genitourinary systems. There are rare reports of isolated central nervous system blastomycosis. Herein, we report a case of isolated central nervous system infection in a patient residing in New York State without travel to known endemic regions. Diagnosis was established asBlastomyces dermatitidisby morphologic characteristics of biopsied tissue and was confirmed through real-time polymerase chain reaction assays. In addition, the culture was confirmed asB. dermatitidisby conventional and real-time polymerase chain reaction assay. The patient was treated with prolonged antifungal therapy and is clinically well. This report suggests an expansion of the endemic geography of blastomycosis and highlights the utility of molecular methods for diagnosis.
Impaired PRC2 activity promotes transcriptional instability and favors breast tumorigenesis
Authors: Wassef Michel , Rodilla Veronica , Teissandier Aurélie , Zeitouni Bruno , Gruel Nadege , Sadacca Benjamin , Irondelle Marie , Charruel Margaux , Ducos Bertrand , Michaud Audrey , Caron Matthieu , Marangoni Elisabetta , Chavrier Philippe , Le Tourneau Christophe , Kamal Maud , Pasmant Eric , Vidaud Michel , Servant Nicolas , Reyal Fabien , Meseure Dider , Vincent-Salomon Anne , Fre Silvia , Margueron Raphaël
Published: December 2015

Alterations of chromatin modifiers are frequent in cancer, but their functional consequences often remain unclear. Focusing on the Polycomb protein EZH2 that deposits the H3K27me3 (trimethylation of Lys27 of histone H3) mark, we showed that its high expression in solid tumors is a consequence, not a cause, of tumorigenesis. In mouse and human models, EZH2 is dispensable for prostate cancer development and restrains breast tumorigenesis. High EZH2 expression in tumors results from a tight coupling to proliferation to ensure H3K27me3 homeostasis. However, this process malfunctions in breast cancer. Low EZH2 expression relative to proliferation and mutations in Polycomb genes actually indicate poor prognosis and occur in metastases. We show that while altered EZH2 activity consistently modulates a subset of its target genes, it promotes a wider transcriptional instability. Importantly, transcriptional changes that are consequences of EZH2 loss are predominantly irreversible. Our study provides an unexpected understanding of EZH2's contribution to solid tumors with important therapeutic implications.
The large N-terminal region of the Brr2 RNA helicase guides productive spliceosome activation
Authors: Absmeier Eva , Wollenhaupt Jan , Mozaffari-Jovin Sina , Becke Christian , Lee Chung-Tien , Preussner Marco , Heyd Florian , Urlaub Henning , Lührmann Reinhard , Santos Karine F. , Wahl Markus C.
Published: December 2015

The Brr2 helicase provides the key remodeling activity for spliceosome catalytic activation, during which it disrupts the U4/U6 di-snRNP (small nuclear RNA protein), and its activity has to be tightly regulated. Brr2 exhibits an unusual architecture, including an ∼500-residue N-terminal region, whose functions and molecular mechanisms are presently unknown, followed by a tandem array of structurally similar helicase units (cassettes), only the first of which is catalytically active. Here, we show by crystal structure analysis of full-length Brr2 in complex with a regulatory Jab1/MPN domain of the Prp8 protein and by cross-linking/mass spectrometry of isolated Brr2 that the Brr2 N-terminal region encompasses two folded domains and adjacent linear elements that clamp and interconnect the helicase cassettes. Stepwise N-terminal truncations led to yeast growth and splicing defects, reduced Brr2 association with U4/U6•U5 tri-snRNPs, and increased ATP-dependent disruption of the tri-snRNP, yielding U4/U6 di-snRNP and U5 snRNP. Trends in the RNA-binding, ATPase, and helicase activities of the Brr2 truncation variants are fully rationalized by the crystal structure, demonstrating that the N-terminal region autoinhibits Brr2 via substrate competition and conformational clamping. Our results reveal molecular mechanisms that prevent premature and unproductive tri-snRNP disruption and suggest novel principles of Brr2-dependent splicing regulation.
Loss of Residual Renal Function is Associated With Vascular Calcification in Hemodialysis Patients
Authors: Chen Hung‐Chih , Chou Che‐Yi , Jheng Jyun‐Shan , Chen I‐Ru , Liang Chih‐Chia , Wang Shu‐Ming , Liu Jiung‐Hsiun , Lin Shih‐Yi , Kuo Huey‐Liang , Wang I‐Kuan , Chang Chiz‐Tzung , Huang Chiu‐Ching
Published: December 2015

Vascular calcification is common in chronic hemodialysis (HD) patients and can be measured using abdominal aortic calcification (AAC). Loss of residual renal function (RRF) is associated with increased mortality in HD patients. However, the association between loss of RRF and vascular calcification is unknown. The aim of the study was to analyze the association between loss of RRF and VC in HD patients. All chronic HD (HD for more than 3 months) patients of China Medical University Hospital in 2014 were included. AAC scores were measured semi‐quantitatively based on later lumbar radiographs. Loss of RRF was defined as urine output less than 200 mL per day. The association between loss of RRF and AAC was analyzed using logistic regression. Four hundred and thirty‐eight chronic HD patients with a mean age of 63 ± 12 years were analyzed. The median (interquartile range) AAC score of all patients was 7 (2–13). The AAC score of patients with loss of RRF was 9 (3–22), significantly higher than that of patients with RRF 5 (0–17) (P = 0.004). Loss of RRF, independent of patients' age, diabetes, C‐reactive protein, calcium‐phosphorus product and vintage of dialysis was associated with higher AAC scores. Loss of RRF was associated with vascular calcification in HD patients.
The Role of Non‐Technological Innovations in Services: The Case of Food Retailing
Authors: D'Ippolito Beatrice , Timpano Francesco
Published: December 2015

A growing proportion of innovation, especially in consumer‐based industries, is linked to both aesthetic and symbolic components, yet there is still wide uncertainty as to how consumers respond to the design of products and whether their product choices are consistent across product categories. We draw attention to instances whereby less technology‐intensive initiatives can convey innovation in services industries. The focus is on the case of Eataly, a food retailer in which, it is argued, non‐technological innovations have shaped the firm's core values and triggered consumer interest towards a supermarket where, besides physical goods, experience has become the object of transaction. By emphasizing the importance for retailers of focusing not only on single products, but also on other dimensions of the firm's organization, we intend to contribute to the literature that explores changing facets of innovation in service industries.
The pathogenicity factor HrpF interacts with HrpA and HrpG to modulate type III secretion system (T3SS) function and t3ss expression in Pseudomonas syringae pv. averrhoi
Authors: Huang Yi‐Chiao , Lin Yuan‐Chuen , Wei Chia‐Fong , Deng Wen‐Ling , Huang Hsiou‐Chen
Published: December 2015

To ensure the optimal infectivity on contact with host cells, pathogenic Pseudomonas syringae has evolved a complex mechanism to control the expression and construction of the functional type III secretion system (T3SS) that serves as a dominant pathogenicity factor. In this study, we showed that the hrpF gene of P. syringae pv. averrhoi, which is located upstream of hrpG, encodes a T3SS‐dependent secreted/translocated protein. Mutation of hrpF leads to the loss of bacterial ability on elicitation of disease symptoms in the host and a hypersensitive response in non‐host plants, and the secretion or translocation of the tested T3SS substrates into the bacterial milieu or plant cells. Moreover, overexpression of hrpF in the wild‐type results in delayed HR and reduced t3ss expression. The results of protein–protein interactions demonstrate that HrpF interacts directly with HrpG and HrpA in vitro and in vivo, and protein stability assays reveal that HrpF assists HrpA stability in the bacterial cytoplasm, which is reduced by a single amino acid substitution at the 67th lysine residue of HrpF with alanine. Taken together, the data presented here suggest that HrpF has two roles in the assembly of a functional T3SS: one by acting as a negative regulator, possibly involved in the HrpSVG regulation circuit via binding to HrpG, and the other by stabilizing HrpA in the bacterial cytoplasm via HrpF–HrpA interaction prior to the secretion and formation of Hrp pilus on the bacterial surface.
Modelling Aggregation on the Large Scale and Regularity on the Small Scale in Spatial Point Pattern Datasets
Authors: Lavancier Frédéric , Møller Jesper
Published: December 2015

We consider a dependent thinning of a regular point process with the aim of obtaining aggregation on the large scale and regularity on the small scale in the resulting target point process of retained points. Various parametric models for the underlying processes are suggested and the properties of the target point process are studied. Simulation and inference procedures are discussed when a realization of the target point process is observed, depending on whether the thinned points are observed or not. The paper extends previous work by Dietrich Stoyan on interrupted point processes.
Doubly Robust Inference for the Distribution Function in the Presence of Missing Survey Data
Authors: Boistard Helene , Chauvet Guillaume , Haziza David
Published: December 2015

Item non‐response in surveys occurs when some, but not all, variables are missing. Unadjusted estimators tend to exhibit some bias, called the non‐response bias, if the respondents differ from the non‐respondents with respect to the study variables. In this paper, we focus on item non‐response, which is usually treated by some form of single imputation. We examine the properties of doubly robust imputation procedures, which are those that lead to an estimator that remains consistent if either the outcome variable or the non‐response mechanism is adequately modelled. We establish the double robustness property of the imputed estimator of the finite population distribution function under random hot‐deck imputation within classes. We also discuss the links between our approach and that of Chambers and Dunstan. The results of a simulation study support our findings.
Quantile Regression for Location‐Scale Time Series Models with Conditional Heteroscedasticity
Authors: Noh Jungsik , Lee Sangyeol
Published: December 2015

This paper considers quantile regression for a wide class of time series models including autoregressive and moving average (ARMA) models with asymmetric generalized autoregressive conditional heteroscedasticity errors. The classical mean‐variance models are reinterpreted as conditional location‐scale models so that the quantile regression method can be naturally geared into the considered models. The consistency and asymptotic normality of the quantile regression estimator is established in location‐scale time series models under mild conditions. In the application of this result to ARMA‐generalized autoregressive conditional heteroscedasticity models, more primitive conditions are deduced to obtain the asymptotic properties. For illustration, a simulation study and a real data analysis are provided.
Unexpected red blood cell antibody distributions in Chinese people by a systematic literature review
Authors: Chen Chunxia , Tan Jinzhe , Wang Lixin , Han Bing , Sun Wei , Zhao Li , Huang Chunyan , Tan Bin , Qin Li
Published: December 2015

BACKGROUND

Unexpected antibodies are frequently associated with hemolytic disease of the fetus and newborn (HDFN) and hemolytic transfusion reactions (HTRs), and screening for those unexpected antibodies is critical for the safety and effectiveness of transfusion. Different populations differ in the prevalence of significant antibodies and also the low‐frequency red blood cell (RBC) antigens. In China, antibody screening has been a common practice for pretransfusion testing for more than 10 years. However, there has been no national guidelines regarding the minimum antigens on the screening cells, thus making the antibody screening tests unsatisfactory.

STUDY DESIGN AND METHODS

By a literature review, we systematically searched major databases from their inception to 2014, for publications regarding unexpected RBC antibodies, HTRs, and HDFNs in Chinese people, to explore the frequencies and clinical significance of unexpected RBC antibodies.

RESULTS

The overall prevalence of unexpected antibodies was approximately 0.2% (14,095/6,102,361). A total of 2241 patients suffered HTRs (693 patients) or HDFN (1548 patients). Among all the reported antibodies, antibodies of the Rh blood group system were the most, followed by MNS, Lewis, Kidd, Duffy, Diego, and Kell systems. Several rare but clinically significant unexpected antibodies were reported: four anti‐Lex, three anti‐Lua, one anti‐Tja, and one anti‐Hm.

CONCLUSION

All the commonly seen RBC antibodies are reported in Chinese people. However, anti‐K is very rare. Besides, anti‐Mur, anti‐Dia are clinically significant. We propose that in China, the antigens on the antibody screening cells should include those recommended by the AABB and British Committee for Standards in Haematology, as well as Dia and Mur antigens.
Kite Shield‐Shaped Wedge Recession for Treatment of Medial Patellar Luxation in Seven Small‐Breed Dogs
Authors: Katayama Masaaki , Ogaya Hikaru , Shunsuke Shimamura , Uzuka Yuji
Published: December 2015

Objective

To document the trochlear depth (TD) and clinical outcome after kite shield‐shaped wedge (K‐wedge) recession trochleoplasty in toy‐breed dogs with medial patellar luxation (MPL).

Study Design

Case series.

Animals

Seven toy‐breed dogs (<5 kg) with uni‐ or bilateral grades II–IV MPL (10 stifles).

Methods

A K‐wedge recession trochleoplasty was performed in all dogs in combination with other surgical procedures as treatment for MPL. The TD, the ratio of the proximal TD to patella thickness, and the presence of osteophytes were determined from computed tomography images taken pre‐, and 1 and 12 months postoperative. Lameness scores and MPL grade were also recorded.

Results

The TD and the ratio of proximal TD to patella thickness increased significantly immediately postoperative and remained increased at 1 and 12 months postoperative. The osteophyte score was significantly higher at 12 months postoperative than preoperative. All dogs had a reduction in MPL grade and improvement in lameness postoperative.

Conclusion

K‐wedge recession trochleoplasty was successful in treating MPL in a series of toy‐breed dogs and offers an alternate to other trochlear recession techniques.
A single iron site confined in a graphene matrix for the catalytic oxidation of benzene at room temperature
Authors: Deng Dehui , Chen Xiaoqi , Yu Liang , Wu Xing , Liu Qingfei , Liu Yun , Yang Huaixin , Tian Huanfang , Hu Yongfeng , Du Peipei , Si Rui , Wang Junhu , Cui Xiaoju , Li Haobo , Xiao Jianping , Xu Tao , Deng Jiao , Yang Fan , Duchesne Paul N. , Zhang Peng , Zhou Jigang , Sun Litao , Li Jianqi , Pan Xiulian , Bao Xinhe
Published: December 2015

A coordinatively unsaturated single iron site confined in a graphene matrix shows an ultrahigh activity for catalytic oxidation.
Field-Evolved Mode 1 Resistance of the Fall Armyworm to Transgenic Cry1Fa-Expressing Corn Associated with Reduced Cry1Fa Toxin Binding and Midgut Alkaline Phosphatase Expression
Authors: Jakka Siva R. K. , Gong Liang , Hasler James , Banerjee Rahul , Sheets Joel J. , Narva Kenneth , Blanco Carlos A. , Jurat-Fuentes Juan L.
Published: December 2015

Insecticidal protein genes from the bacterium
Bacillus thuringiensis
(Bt) are expressed by transgenic Bt crops (Bt crops) for effective and environmentally safe pest control. The development of resistance to these insecticidal proteins is considered the most serious threat to the sustainability of Bt crops. Resistance in fall armyworm (
Spodoptera frugiperda
) populations from Puerto Rico to transgenic corn producing the Cry1Fa insecticidal protein resulted, for the first time in the United States, in practical resistance, and Bt corn was withdrawn from the local market. In this study, we used a field-collected Cry1Fa corn-resistant strain (456) of
S. frugiperda
to identify the mechanism responsible for field-evolved resistance. Binding assays detected reduced Cry1Fa, Cry1Ab, and Cry1Ac but not Cry1Ca toxin binding to midgut brush border membrane vesicles (BBMV) from the larvae of strain 456 compared to that from the larvae of a susceptible (Ben) strain. This binding phenotype is descriptive of the mode 1 type of resistance to Bt toxins. A comparison of the transcript levels for putative Cry1 toxin receptor genes identified a significant downregulation (>90%) of a membrane-bound alkaline phosphatase (ALP), which translated to reduced ALP protein levels and a 75% reduction in ALP activity in BBMV from 456 compared to that of Ben larvae. We cloned and heterologously expressed this ALP from susceptible
S. frugiperda
larvae and demonstrated that it specifically binds with Cry1Fa toxin. This study provides a thorough mechanistic description of field-evolved resistance to a transgenic Bt crop and supports an association between resistance and reduced Cry1Fa toxin binding and levels of a putative Cry1Fa toxin receptor, ALP, in the midguts of
S. frugiperda
larvae.
Comparative Evaluation of the Diagnostic Performance of the Prototype Cepheid GeneXpert Ebola Assay
Authors: Jansen van Vuren Petrus , Grobbelaar Antoinette , Storm Nadia , Conteh Ousman , Konneh Kelfala , Kamara Abdul , Sanne Ian , Paweska Janusz T.
Published: December 2015

The Ebola virus disease (EVD) outbreak in West Africa has highlighted an urgent need for point-of-care (POC) assays for the diagnosis of this devastating disease in resource-limited African countries. The diagnostic performance characteristics of a prototype Cepheid GeneXpert Ebola POC used to detect Ebola virus (EBOV) in stored serum and plasma samples collected from suspected EVD cases in Sierra Leone in 2014 and 2015 was evaluated. The GeneXpert Ebola POC is a self-contained single-cartridge automated system that targets the glycoprotein (GP) and nucleoprotein (NP) genes of EBOV and yields results within 90 min. Results from 281 patient samples were compared to the results of a TaqMan real-time reverse transcription-PCR (RT-PCR) targeting the polymerase gene and performed on two real-time PCR machines. Agreement between the three platforms was 100% at cycle threshold (

C
T

) values of ≤34.99, but discordant results were noted between

C
T

values of 35 and 45.The diagnostic sensitivity of the three platforms was 100% in 91 patient samples that were confirmed to be infectious by virus isolation. All three molecular platforms detected viral EBOV RNA in additional samples that did not contain viable EBOV. The analytical sensitivity of the GeneXpert Ebola POC for the detection of NP was higher, and comparable to that of polymerase gene detection, than that for the detection of GP when using a titrated laboratory stock of EBOV. There was no detectable cross-reactivity with other hemorrhagic fever viruses or arboviruses. The GeneXpert Ebola POC offers an easy to operate and sensitive diagnostic tool that can be used for the rapid screening of suspected EVD cases in treatment or in holding centers during EVD outbreaks.
The Evolution of Regional Species Richness: The History of the Southern African Flora
Authors: Linder H. Peter , Verboom G. Anthony
Published: December 2015

The flora of southern Africa is, for its latitude and area, very species-rich. Although the hyperdiverse Cape flora contributes almost half of this richness, three other radiations (desert, grassland, and woodland) contribute significantly to the botanical wealth of southern Africa. Each radiation occurs in a different ecological setting and has a different diversification history. Such parallel radiations can develop in suitably complex environments, given gradual change through time and no region-wide catastrophes. These four radiations cross-seeded each other, with clades spawning subclades in other radiations, thus linking all four into one complex radiation. This led to an increase in the number of diversifying clades in each radiation. Such complex radiations accumulate diversifying lineages over a long time, spawn daughter radiations on other continents, and become powerhouses of global-biodiversity generation. We suggest that several of the most species-rich regions may harbor such complex radiations.
Augmentation of CFTR maturation byS-nitrosoglutathione reductase
Authors: Zaman Khalequz , Sawczak Victoria , Zaidi Atiya , Butler Maya , Bennett Deric , Getsy Paulina , Zeinomar Maryam , Greenberg Zivi , Forbes Michael , Rehman Shagufta , Jyothikumar Vinod , DeRonde Kim , Sattar Abdus , Smith Laura , Corey Deborah , Straub Adam , Sun Fei , Palmer Lisa , Periasamy Ammasi , Randell Scott , Kelley Thomas J. , Lewis Stephen J. , Gaston Benjamin
Published: December 2015

S-nitrosoglutathione (GSNO) reductase regulates novel endogenous S-nitrosothiol signaling pathways, and mice deficient in GSNO reductase are protected from airways hyperreactivity. S-nitrosothiols are present in the airway, and patients with cystic fibrosis (CF) tend to have low S-nitrosothiol levels that may be attributed to upregulation of GSNO reductase activity. The present study demonstrates that 1) GSNO reductase activity is increased in the cystic fibrosis bronchial epithelial (CFBE41o−) cells expressing mutant F508del-cystic fibrosis transmembrane regulator (CFTR) compared with the wild-type CFBE41o−cells, 2) GSNO reductase expression level is increased in the primary human bronchial epithelial cells expressing mutant F508del-CFTR compared with the wild-type cells, 3) GSNO reductase colocalizes with cochaperone Hsp70/Hsp90 organizing protein (Hop; Stip1) in human airway epithelial cells, 4) GSNO reductase knockdown with siRNA increases the expression and maturation of CFTR and decreases Stip1 expression in human airway epithelial cells, 5) increased levels of GSNO reductase cause a decrease in maturation of CFTR, and 6) a GSNO reductase inhibitor effectively reverses the effects of GSNO reductase on CFTR maturation. These studies provide a novel approach to define the subcellular location of the interactions between Stip1 and GSNO reductase and the role of S-nitrosothiols in these interactions.
Developmental acceleration of bradykinin-dependent relaxation by prenatal chronic hypoxia impedes normal development after birth
Authors: Blum-Johnston Carla , Thorpe Richard B. , Wee Chelsea , Romero Monica , Brunelle Alexander , Blood Quintin , Wilson Rachael , Blood Arlin B. , Francis Michael , Taylor Mark S. , Longo Lawrence D. , Pearce William J. , Wilson Sean M.
Published: December 2015

Bradykinin-induced activation of the pulmonary endothelium triggers nitric oxide production and other signals that cause vasorelaxation, including stimulation of large-conductance Ca2+-activated K+(BKCa) channels in myocytes that hyperpolarize the plasma membrane and decrease intracellular Ca2+. Intrauterine chronic hypoxia (CH) may reduce vasorelaxation in the fetal-to-newborn transition and contribute to pulmonary hypertension of the newborn. Thus we examined the effects of maturation and CH on the role of BKCachannels during bradykinin-induced vasorelaxation by examining endothelial Ca2+signals, wire myography, and Western immunoblots on pulmonary arteries isolated from near-term fetal (∼140 days gestation) and newborn, 10- to 20-day-old, sheep that lived in normoxia at 700 m or in CH at high altitude (3,801 m) for >100 days. CH enhanced bradykinin-induced relaxation of fetal vessels but decreased relaxation in newborns. Endothelial Ca2+responses decreased with maturation but increased with CH. Bradykinin-dependent relaxation was sensitive to 100 μM nitro-l-arginine methyl ester or 10 μM 1 H-[1,2,4]oxadiazolo[4,3- a]quinoxalin-1-one, supporting roles for endothelial nitric oxide synthase and soluble guanylate cyclase activation. Indomethacin blocked relaxation in CH vessels, suggesting upregulation of PLA2pathways. BKCachannel inhibition with 1 mM tetraethylammonium reduced bradykinin-induced vasorelaxation in the normoxic newborn and fetal CH vessels. Maturation reduced whole cell BKCachannel α1-subunit expression but increased β1-subunit expression. These results suggest that CH amplifies the contribution of BKCachannels to bradykinin-induced vasorelaxation in fetal sheep but stunts further development of this vasodilatory pathway in newborns. This involves complex changes in multiple components of the bradykinin-signaling axes.
Megace Mystery: A Case of Central Adrenal Insufficiency
Authors: Mehta Kunal , Weiss Irene , Goldberg Michael D.
Published: December 2015

Megestrol acetate (MA) is a synthetic progestin with both antineoplastic and orexigenic properties. In addition to its effects on the progesterone receptor, MA also binds the glucocorticoid receptor. Some patients receiving MA therapy have been reported to develop clinical features of glucocorticoid excess, while others have experienced the clinical syndrome of cortisol deficiency—either following withdrawal of MA therapy or during active treatment. We describe a patient who presented with clinical and biochemical features of central adrenal insufficiency. Pituitary function was otherwise essentially normal, and the etiology of the isolated ACTH suppression was initially unclear. The use of an exogenous glucocorticoid was suspected but was initially denied by the patient; ultimately, the culprit medication was uncovered when a synthetic steroid screen revealed the presence of MA. The patient’s symptoms improved after she was switched to hydrocortisone. Clinicians should be aware of the potential effects of MA on the hypothalamic-pituitary-adrenal (HPA) axis.
Mitochondrial Dysfunction and Autophagy in Hepatic Ischemia/Reperfusion Injury
Authors: Go Kristina L. , Lee Sooyeon , Zendejas Ivan , Behrns Kevin E. , Kim Jae-Sung
Published: December 2015

Ischemia/reperfusion (I/R) injury remains a major complication of liver resection, transplantation, and hemorrhagic shock. Although the mechanisms that contribute to hepatic I/R are complex and diverse involving the interaction of cell injury in hepatocytes, immune cells, and endothelium, mitochondrial dysfunction is a cardinal event culminating in hepatic reperfusion injury. Mitochondrial autophagy, so-called mitophagy, is a key cellular process that regulates mitochondrial homeostasis and eliminates damaged mitochondria in a timely manner. Growing evidence accumulates that I/R injury is attributed to defective mitophagy. This review aims to summarize the current understanding of autophagy and its role in hepatic I/R injury and highlight the various therapeutic approaches that have been studied to ameliorate injury.
Effluent Tenascin-C Levels Reflect Peritoneal Deterioration in Peritoneal Dialysis: MAJOR IN PD Study
Authors: Hirahara Ichiro , Kusano Eiji , Imai Toshimi , Morishita Yoshiyuki , Inoue Makoto , Akimoto Tetsu , Saito Osamu , Muto Shigeaki , Nagata Daisuke
Published: December 2015

Peritoneal deterioration causing structural changes and functional decline is a major complication of peritoneal dialysis (PD). The aim of this study was to explore effluent biomarkers reflecting peritoneal deterioration. In an animal study, rats were intraperitoneally administered with PD fluids adding 20 mM methylglyoxal (MGO) or 20 mM formaldehyde (FA) every day for 21 days. In the MGO-treated rats, tenascin-C (TN-C) levels in the peritoneal effluents were remarkably high and a cluster of TN-C-positive mesothelial cells with epithelial-to-mesenchymal transition- (EMT-) like change excessively proliferated at the peritoneal surface, but not in the FA-treated rats. Effluent matrix metalloproteinase-2 (MMP-2) levels increased in both the MGO- and FA-treated rats. In a clinical study at 18 centers between 2006 and 2013, effluent TN-C and MMP-2 levels were quantified in 182 PD patients with end-stage renal disease. Peritoneal function was estimated using the peritoneal equilibration test (PET). From the PET results, the D/P Cr ratio was correlated with effluent levels of TN-C (ρ= 0.57,p<0.001) and MMP-2 (ρ= 0.73,p<0.001). We suggest that TN-C in the effluents may be a diagnostic marker for peritoneal deterioration with EMT-like change in mesothelial cells in PD.
In Vitro Biological Evaluation of Electrospun Polycaprolactone/Gelatine Nanofibrous Scaffold for Tissue Engineering
Authors: Lim Mim Mim , Sun Tao , Sultana Naznin
Published: December 2015

The fabrication of biocompatible and biodegradable scaffolds which mimic the native extracellular matrix of tissues to promote cell adhesion and growth is emphasized recently. Many polymers have been utilized in scaffold fabrication, but there is still a need to fabricate hydrophilic nanosized fibrous scaffolds with an appropriate degradation rate for skin tissue engineering applications. In this study, nanofibrous scaffolds of a biodegradable synthetic polymer, polycaprolactone (PCL), and blends of PCL with a natural polymer, gelatine (Ge), in three different compositions: 85 : 15, 70 : 30, and 50 : 50 were fabricated via an electrospinning technique. The nanofibrous scaffold prepared from 14% w/v PCL/Ge (70 : 30) exhibited more balanced properties of homogeneous nanofibres with an average fibre diameter of 155.60 ± 41.13 nm, 83% porosity, and surface roughness of 176.27 ± 2.53 nm. In vitro cell culture study using human skin fibroblasts (HSF) demonstrated improved cell attachment with a flattened morphology on the PCL/Ge (70 : 30) nanofibrous scaffold and accelerated proliferation on day 3 compared to the PCL nanofibrous scaffold. These results show that the PCL/Ge (70 : 30) nanofibrous scaffold was more favourable and has the potential to be a promising scaffold for skin tissue engineering applications.
Bilateral Multifocal Choroidal Osteoma with Choroidal Neovascularization
Authors: MirNaghi Mousavi , Nasser Shoeibi , SeyedehMaryam Hosseini , Ali Saadat Targhi
Published: December 2015

Choroidal osteoma has been reported to be unilateral in approximately 80% of cases diagnosed with this condition. Herein we report the clinical characteristics and multimodal imaging findings in a rare case of bilateral multifocal choroidal osteoma. A 32-year-old female presented with decreased visual acuity (VA) in the right eye (20/100), though she had normal VA (20/20) in the left eye. Ophthalmoscopy and multimodal imaging investigation revealed bilateral multifocal choroidal osteoma complicated by choroidal neovascularization (CNV) in the right eye. Following three injections of intravitreal bevacizumab (IVB) for CNV in the right eye, VA improved to 20/40.
Differential Transform Method with Complex Transforms to Some Nonlinear Fractional Problems in Mathematical Physics
Authors: Mohyud-Din Syed Tauseef , Awan Farah Jabeen , Ahmad Jamshad , Hassan Saleh M.
Published: December 2015

This paper witnesses the coupling of an analytical series expansion method which is called reduced differential transform with fractional complex transform. The proposed technique is applied on three mathematical models, namely, fractional Kaup-Kupershmidt equation, generalized fractional Drinfeld-Sokolov equations, and system of coupled fractional Sine-Gordon equations subject to the appropriate initial conditions which arise frequently in mathematical physics. The derivatives are defined in Jumarie’s sense. The accuracy, efficiency, and convergence of the proposed technique are demonstrated through the numerical examples. It is observed that the presented coupling is an alternative approach to overcome the demerit of complex calculation of fractional differential equations. The proposed technique is independent of complexities arising in the calculation of Lagrange multipliers, Adomian’s polynomials, linearization, discretization, perturbation, and unrealistic assumptions and hence gives the solution in the form of convergent power series with elegantly computed components. All the examples show that the proposed combination is a powerful mathematical tool to solve other nonlinear equations also.
Activation of the Mammalian Target of Rapamycin in the Rostral Ventromedial Medulla Contributes to the Maintenance of Nerve Injury-Induced Neuropathic Pain in Rat
Authors: Wang Jian , Feng Da-Yun , Li Zhi-Hua , Feng Ban , Zhang Han , Zhang Ting , Chen Tao , Li Yun-Qing
Published: December 2015

The mammalian target of rapamycin (mTOR), a serine-threonine protein kinase, integrates extracellular signals, thereby modulating several physiological and pathological processes, including pain. Previous studies have suggested that rapamycin (an mTOR inhibitor) can attenuate nociceptive behaviors in many pain models, most likely at the spinal cord level. However, the mechanisms of mTOR at the supraspinal level, particularly at the level of the rostral ventromedial medulla (RVM), remain unclear. Thus, the aim of this study was to elucidate the role of mTOR in the RVM, a key relay region for the descending pain control pathway, under neuropathic pain conditions. Phosphorylated mTOR was mainly expressed in serotonergic spinally projecting neurons and was significantly increased in the RVM after spared nerve injury- (SNI-) induced neuropathic pain. Moreover, in SNI rat brain slices, rapamycin infusion both decreased the amplitude instead of the frequency of spontaneous excitatory postsynaptic currents and reduced the numbers of action potentials in serotonergic neurons. Finally, intra-RVM microinjection of rapamycin effectively alleviated established mechanical allodynia but failed to affect the development of neuropathic pain. In conclusion, our data provide strong evidence for the role of mTOR in the RVM in nerve injury-induced neuropathic pain, indicating a novel mechanism of mTOR inhibitor-induced analgesia.
Robust Satellite Scheduling Approach for Dynamic Emergency Tasks
Authors: Zhai Xuejun , Niu Xiaonan , Tang Hong , Wu Lixin , Shen Yonglin
Published: December 2015

Earth observation satellites play a significant role in rapid responses to emergent events on the Earth’s surface, for example, earthquakes. In this paper, we propose a robust satellite scheduling model to address a sequence of emergency tasks, in which both the profit and robustness of the schedule are simultaneously maximized in each stage. Both the multiobjective genetic algorithm NSGA2 and rule-based heuristic algorithm are employed to obtain solutions of the model. NSGA2 is used to obtain a flexible and highly robust initial schedule. When every set of emergency tasks arrives, a combined algorithm called HA-NSGA2 is used to adjust the initial schedule. The heuristic algorithm (HA) is designed to insert these tasks dynamically to the waiting queue of the initial schedule. Then the multiobjective genetic algorithm NSGA2 is employed to find the optimal solution that has maximum revenue and robustness. Meanwhile, to improve the revenue and resource utilization, we adopt a compact task merging strategy considering the duration of task execution in the heuristic algorithm. Several experiments are used to evaluate the performance of HA-NSGA2. All simulation experiments show that the performance of HA-NSGA2 is significantly improved.
Reconstruction of a Robin Coefficient by a Predictor-Corrector Method
Authors: Ma Yun-Jie
Published: December 2015

The present paper is devoted to solving a nonlinear inverse problem of identifying a Robin coefficient from boundary temperature measurement. A numerical algorithm on the basis of the predictor-corrector method is designed to restore the approximate solution and the performance of the method is verified by simulating several examples. The convergence with respect to the amount of noise in the data is also investigated.
Cloud Particles Differential Evolution Algorithm: A Novel Optimization Method for Global Numerical Optimization
Authors: Li Wei , Wang Lei , Yao Quanzhu , Jiang Qiaoyong , Yu Lei , Wang Bin , Hei Xinhong
Published: December 2015

We propose a new optimization algorithm inspired by the formation and change of the cloud in nature, referred to as Cloud Particles Differential Evolution (CPDE) algorithm. The cloud is assumed to have three states in the proposed algorithm. Gaseous state represents the global exploration. Liquid state represents the intermediate process from the global exploration to the local exploitation. Solid state represents the local exploitation. The best solution found so far acts as a nucleus. In gaseous state, the nucleus leads the population to explore by condensation operation. In liquid state, cloud particles carry out macrolocal exploitation by liquefaction operation. A new mutation strategy called cloud differential mutation is introduced in order to solve a problem that the misleading effect of a nucleus may cause the premature convergence. In solid state, cloud particles carry out microlocal exploitation by solidification operation. The effectiveness of the algorithm is validated upon different benchmark problems. The results have been compared with eight well-known optimization algorithms. The statistical analysis on performance evaluation of the different algorithms on 10 benchmark functions and CEC2013 problems indicates that CPDE attains good performance.
Dynamic Fracture Toughness of TaC/CNTs/SiC CMCs Prepared by Spark Plasma Sintering
Authors: Xie Qiaoyun , Wosu Sylvanus N.
Published: December 2015

This study focuses on the fracture toughness of TaC and carbon nanotubes (CNTs) reinforced SiC ceramic matrix composites (CMCs), prepared by spark plasma sintering (SPS) technique. A high densification of 98.4% was achieved under the sintering parameter of 133°C/min, 1800°C, and 90 MPa pressure. Vickers indentation was employed to measure the indentation toughness on the polished surface of ceramic samples, SEM was applied to directly observe the crack propagation after indentation, and split Hopkinson pressure bar (SHPB) was developed to determine the dynamic fracture toughness within the ceramic samples subjected to an impact in a three-point bending configuration.