bluuebunny/crossref_metadata_2025_split huggingface dataset:
LiZIP3 is a cellular zinc transporter that mediates the tightly regulated import of zinc in Leishmania infantum parasites
Authors: Carvalho Sandra , Barreira da Silva Rosa , Shawki Ali , Castro Helena , Lamy Márcia , Eide David , Costa Vítor , Mackenzie Bryan , Tomás Ana M. 
Published: February 2015

SummaryCellular zinc homeostasis ensures that the intracellular concentration of this element is kept within limits that enable its participation in critical physiological processes without exerting toxic effects. We report here the identification and characterization of the first mediator of zinc homeostasis in Leishmania infantum, LiZIP3, a member of the ZIP family of divalent metal‐ion transporters. The zinc transporter activity of LiZIP3 was first disclosed by its capacity to rescue the growth of Saccharomyces cerevisiae strains deficient in zinc acquisition. Subsequent expression of LiZIP3 in Xenopus laevis oocytes was shown to stimulate the uptake of a broad range of metal ions, among which Zn2+ was the preferred LiZIP3 substrate (K0.5 ≈ 0.1 μM). Evidence that LiZIP3 functions as a zinc importer in L. infantum came from the observations that the protein locates to the cell membrane and that its overexpression leads to augmented zinc internalization. Importantly, expression and cell‐surface location of LiZIP3 are lost when parasites face high zinc bioavailability. LiZIP3 decline in response to zinc is regulated at the mRNA level in a process involving (a) short‐lived protein(s). Collectively, our data reveal that LiZIP3 enables L. infantum to acquire zinc in a highly regulated manner, hence contributing to zinc homeostasis.
N‐terminal lysines are essential for protein translocation via a modified ERAD system in complex plastids
Authors: Lau Julia B. , Stork Simone , Moog Daniel , Sommer Maik S. , Maier Uwe G. 
Published: February 2015

SummaryNuclear‐encoded pre‐proteins being imported into complex plastids of red algal origin have to cross up to five membranes. Thereby, transport across the second outermost or periplastidal membrane (PPM) is facilitated by SELMA (symbiont‐specific ERAD‐like machinery), an endoplasmic reticulum‐associated degradation (ERAD)‐derived machinery. Core components of SELMA are enzymes involved in ubiquitination (E1 – E3), a Cdc48 ATPase complex and Derlin proteins. These components are present in all investigated organisms with four membrane‐bound complex plastids of red algal origin, suggesting a ubiquitin‐dependent translocation process of substrates mechanistically similar to the process of retro‐translocation in ERAD. Even if, according to the current model, translocation via SELMA does not end up in the classical poly‐ubiquitination, transient mono‐/oligo‐ubiquitination of pre‐proteins might be required for the mechanism of translocation. We investigated the import mechanism of SELMA and were able to show that protein transport across the PPM depends on lysines in the N‐terminal but not in the C‐terminal part of pre‐proteins. These lysines are predicted to be targets of ubiquitination during the translocation process. As proteins lacking the N‐terminal lysines get stuck in the PPM, a ‘frozen intermediate’ of the translocation process could be envisioned and initially characterized.
Isolated mitochondrial stroke‐like episodes in an elderly patient with the MT‐ND3 gene mutation
Authors: Mukai Masako , Sugaya Keizo , Ozawa Tadashi , Goto Yu‐ichi , Yagishita Akira , Matsubara Shiro , Bokuda Kota , Miyakoshi Akinori , Nakano Imaharu 
Published: January 2015

AbstractStroke‐like episode represents a clinical hallmark of mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke‐like episodes. Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke‐like episodes are usually suspected based on clinical symptoms, such as lactic acidosis, deafness, diabetes, short stature, myopathy, and cognitive decline, often with a maternal inheritance pattern of family history. We describe an elderly woman with recurrent stroke‐like episodes, who had only a faint concomitant signs, but no family history of mitochondrial disease. Sequence analysis of the mitochondrial genome extracted from biopsied muscle showed a heteroplasmic 10158T>C mutation in the mitochondrial complex I subunit gene, MT‐ND3. This is the first adult‐onset case harboring the m.10158T>C mutation, which is known to cause lethal infant‐onset Leigh syndrome. The unique manifestations of sporadic, elderly‐onset, and isolated stroke‐like episodes suggest that it is an important differential diagnosis for ischemic stroke and extend the clinical and mutational spectrum of mitochondrial stroke‐like episodes.
Pattern of clinical presentation of congenital anomalies of the kidney and urinary tract among infants and children
Authors: Soliman Neveen A , Ali Reham I , Ghobrial Emad E , Habib Enmar I , Ziada Ali M 
Published: February 2015

AbstractAimCongenital anomalies of the kidneys and urinary tract (CAKUT) comprise various entities of structural malformations that result from defects in morphogenesis of the kidney and/or urinary tract. These anomalies are the most commonly diagnosed malformations in the prenatal period and constitute the leading cause of end‐+stage renal disease (ESRD) in children, worldwide. This prospective study was performed to report the patterns of clinical presentation and diagnosis of infants and children with such malformations.MethodsPatients with suggestive features of CAKUT, presenting to Cairo University Children Hospital over one year duration were investigated and categorized based on underlying renal structural/functional malformation and associated extra‐renal anomalies.ResultsOne hundred and seven CAKUT children were enrolled in the study. Familial clustering was identified in 14% of the cohort and syndromic CAKUT accounted for 31.8% of cases. Different anomaly entities have been identified; posterior urethral valves (PUV) being the commonest detected abnormality (36.4%). Of note, 9.3% of cohort patients had ESRD at presentation, of which 60% had PUV as their primary renal disease. Obstructive cases were noted to present significantly earlier and attain advanced CKD stages rather than non‐obstructive ones.ConclusionCAKUT is a clinically heterogeneous group of diseases with diverse clinical phenotypes. More efforts should be aimed at improving antenatal detection as well as classification with comprehensive reference to the clinical, genetic and molecular features of the diseases. The high frequency of familial and syndromic CAKUT among studied patients is seemingly a convincing reason to pursue the underlying genetic defect in future studies.
Clinical Impact of Mapping Strategies for Treatment of Ventricular Tachycardias in Patients with Structural Heart Disease
Authors: MAKIMOTO HISAKI , NAKAJIMA IKUTARO , MIYAMOTO KOJI , YAMADA YUKO , OKAMURA HIDEO , NODA TAKASHI , AIBA TAKESHI , KAMAKURA SHIRO , KUSANO KENGO , SHIMIZU WATARU , SATOMI KAZUHIRO 
Published: January 2015

BackgroundSubstrate‐based catheter ablation (CA) can be applied to more complicated cases such as hemodynamically unstable ventricular tachycardia (VT). We aimed to compare the efficacy between substrate‐based and activation/entrainment‐based ablation.MethodsWe investigated 85 consecutive patients (62 male, 53 ± 16 years) who underwent CA of VT to analyze the relationship between the ablation strategy and clinical outcome. The patients included 34 individuals with arrhythmogenic right ventricular cardiomyopathy, 16 with ischemic heart disease, 14 with dilated cardiomyopathy, 11 with sarcoidosis, and 10 with other heart diseases. The primary strategy was activation/entrainment mapping (Group‐AE, N = 35); otherwise, substrate‐based strategy was adopted (Group‐S, N = 50) because of non‐inducibility of VT or hemodynamic instability. Successful CA was defined as the non‐inducibility of any VT at the end of the procedure in those with inducible clinical VT before ablation, and substrate elimination in those without.ResultsThere were no significant differences in the left ventricular function, percentage of implantable cardioverter‐defibrillator implantations, results of CA, and number of radiofrequency applications between Group‐S and Group‐AE. During 5 years of follow‐up, there were no significant differences in sustained VT recurrences (15/50 vs. 15/35, P = 0.22), and cardiac death (2/50 vs. 3/35, P = 0.38). In patients with inducible VT before ablation, the elimination of the VT inducibility was associated with a lower recurrence rate (12/47 vs. 16/26, P = 0.003).ConclusionsThe substrate‐based strategy adopted as an alternative option when the activation/entrainment‐based strategy was unable to be performed resulted in a comparable VT recurrence rate. The extinction of VT inducibility achieved a favorable prognosis in structural heart disease patients.
Rhinovirus‐induced airway cytokines and respiratory morbidity in severely premature children
Authors: Perez Geovanny F. , Pancham Krishna , Huseni Shehlanoor , Jain Amisha , Rodriguez‐Martinez Carlos E. , Preciado Diego , Rose Mary C. , Nino Gustavo 
Published: January 2015

AbstractBackgroundRhinovirus (RV) has been linked to the pathogenesis of asthma. Prematurity is a risk factor for severe RV infection in early life, but is unknown if RV elicits enhanced pro‐asthmatic airway cytokine responses in premature infants. This study investigated whether young children born severely premature (<32 wks gestation) exhibit airway secretion of Th2 and Th17 cytokines during natural RV infections and whether RV‐induced Th2–Th17 responses are linked to more respiratory morbidity in premature children during the first 2 yrs of life.MethodsWe measured Th2 and Th17 nasal airway cytokines in a retrospective cohort of young children aged 0–2 yrs with PCR‐confirmed RV infection or non‐detectable virus. Protein levels of IL‐4, IL‐13, TSLP, and IL‐17 were determined with multiplex immunoassays. Demographic and clinical variables were obtained by electronic medical record (EMR) review.ResultsThe study comprised 214 children born full term (n = 108), preterm (n = 44) or severely premature (n = 62). Natural RV infection in severely premature children was associated with elevated airway secretion of Th2 (IL‐4 and IL‐13) and Th17 (IL‐17) cytokines, particularly in subjects with history of bronchopulmonary dysplasia. Severely premature children with high RV‐induced airway IL‐4 had recurrent respiratory hospitalizations (median 3.65 hosp/yr; IQR 2.8–4.8) and were more likely to have at least one pediatric intensive care unit admission during the first 2 yrs of life (OR 8.72; 95% CI 1.3–58.7; p = 0.02).ConclusionsSeverely premature children have increased airway secretion of Th2 and Th17 cytokines during RV infections, which is associated with more respiratory morbidity in the first 2 yrs of life.
Safety and effect on reported symptoms of depigmented polymerized allergen immunotherapy: a retrospective study of 2927 paediatric patients
Authors: Pfaar Oliver , Sager Angelika , Robinson Douglas S. 
Published: January 2015

AbstractBackgroundAllergen immunotherapy (AIT) is effective treatment for allergic diseases, and subcutaneous use of depigmented polymerized extracts may allow rapid up‐dosing and safe therapy. To date, there is little information on their safety and clinical effects for children and adolescents with allergic disease.MethodsWe performed a retrospective survey of patient notes of 2927 children and adolescents across 136 centres who had received subcutaneous AIT (SCIT) with depigmented polymerized extracts to pollen or mite allergens for at least 1 yr to collect documentation on safety and clinical symptoms.Results16.3% percent of patients had local reactions, of these 148 were larger than 12 cm in diameter. Systemic reactions were documented in 1.6% of children and in 0.8% of adolescents. There were no documented cases of anaphylactic shock. There were significant reductions in the frequency of patients with recorded nasal symptoms over time of treatment. Moreover, the prescribing rate of rescue medication was reduced over the course of SCIT.ConclusionThese ‘real‐life’ data from a large retrospective analysis including 2927 children and adolescents with pollen‐ and/or mite‐induced allergic rhinoconjunctivitis with/or without allergic asthma indicate that AIT with depigmented polymerized extracts is well tolerated, and they are compatible with clinical response.
Heritable site‐specific mutagenesis using TALENs in maize
Authors: Char Si Nian , Unger‐Wallace Erica , Frame Bronwyn , Briggs Sarah A. , Main Marcy , Spalding Martin H. , Vollbrecht Erik , Wang Kan , Yang Bing 
Published: February 2015

SummaryTranscription activator‐like effector nuclease (TALEN) technology has been utilized widely for targeted gene mutagenesis, especially for gene inactivation, in many organisms, including agriculturally important plants such as rice, wheat, tomato and barley. This report describes application of this technology to generate heritable genome modifications in maize. TALENs were employed to generate stable, heritable mutations at the maize glossy2 (gl2) locus. Transgenic lines containing mono‐ or di‐allelic mutations were obtained from the maize genotype Hi‐II at a frequency of about 10% (nine mutated events in 91 transgenic events). In addition, three of the novel alleles were tested for function in progeny seedlings, where they were able to confer the glossy phenotype. In a majority of the events, the integrated TALEN T‐DNA segregated independently from the new loss of function alleles, producing mutated null‐segregant progeny in T1 generation. Our results demonstrate that TALENs are an effective tool for genome mutagenesis in maize, empowering the discovery of gene function and the development of trait improvement.
A genetic strategy generating wheat with very high amylose content
Authors: Regina Ahmed , Berbezy Pierre , Kosar‐Hashemi Behjat , Li Suzhi , Cmiel Mark , Larroque Oscar , Bird Anthony R. , Swain Steve M. , Cavanagh Colin , Jobling Stephen A. , Li Zhongyi , Morell Matthew 
Published: February 2015

SummaryResistant starch (RS), a type of dietary fibre, plays an important role in human health; however, the content of RS in most modern processed starchy foods is low. Cereal starch, when structurally manipulated through a modified starch biosynthetic pathway to greatly increase the amylose content, could be an important food source of RS. Transgenic studies have previously revealed the requirement of simultaneous down‐regulation of two starch branching enzyme (SBE) II isoforms both located on the long arm of chromosome 2, namely SBEIIa and SBEIIb, to elevate the amylose content in wheat from ~25% to ~75%. The current study revealed close proximity of genes encoding SBEIIa and SBEIIb isoforms in wheat with a genetic distance of 0.5 cM on chromosome 2B. A series of deletion and single nucleotide polymorphism (SNP) loss of function alleles in SBEIIa, SBEIIb or both was isolated from two different wheat populations. A breeding strategy to combine deletions and SNPs generated wheat genotypes with altered expression levels of SBEIIa and SBEIIb, elevating the amylose content to an unprecedented ~85%, with a marked concomitant increase in RS content. Biochemical assays were used to confirm the complete absence in the grain of expression of SBEIIa from all three genomes in combination with the absence of SBEIIb from one of the genomes.
Adding Expert Contributions to the Spatiotemporal Modelling of Avalanche Activity Under Different Climatic Influences
Authors: Lavigne A. , Eckert N. , Bel L. , Parent E. 
Published: February 2015

SummaryWe address the question of introducing expert knowledge in a hierarchical Bayesian spatiotemporal model. Specifically, we combine avalanche count data and an expert prior judgement about avalanche climatology to cluster French Alpine townships into two coherent groups. A spatial regression defines the a priori probability of belonging to each group and an innovative method is proposed to elicit its parameters by working with an expert on replicates of simulated maps. As a benefit of the extra data knowledge, we show the existence of robust north–south clusters of decreasing–increasing avalanche activity resulting from the interaction of local climate change patterns with altitude distribution. Spatial dependence of avalanche activity has also been inferred and is characterized by an anisotropy, with longer dependence along the north-west–south-east axis.
Crystal structures and inhibitor binding properties of plant class V chitinases: the cycad enzyme exhibits unique structural and functional features
Authors: Umemoto Naoyuki , Kanda Yuka , Ohnuma Takayuki , Osawa Takuo , Numata Tomoyuki , Sakuda Shohei , Taira Toki , Fukamizo Tamo 
Published: February 2015

SummaryA class V (glycoside hydrolase family 18) chitinase from the cycad Cycas revoluta (CrChiA) is a plant chitinase that has been reported to possess efficient transglycosylation (TG) activity. We solved the crystal structure of CrChiA, and compared it with those of class V chitinases from Nicotiana tabacum (NtChiV) and Arabidopsis thaliana (AtChiC), which do not efficiently catalyze the TG reaction. All three chitinases had a similar (α/β)8 barrel fold with an (α + β) insertion domain. In the acceptor binding site (+1, +2 and +3) of CrChiA, the Trp168 side chain was found to stack face‐to‐face with the +3 sugar. However, this interaction was not found in the identical regions of NtChiV and AtChiC. In the DxDxE motif, which is essential for catalysis, the carboxyl group of the middle Asp (Asp117) was always oriented toward the catalytic acid Glu119 in CrChiA, whereas the corresponding Asp in NtChiV and AtChiC was oriented toward the first Asp. These structural features of CrChiA appear to be responsible for the efficient TG activity. When binding of the inhibitor allosamidin was evaluated using isothermal titration calorimetry, the changes in binding free energy of the three chitinases were found to be similar to each other, i.e. between −9.5 and −9.8 kcal mol−1. However, solvation and conformational entropy changes in CrChiA were markedly different from those in NtChiV and AtChiC, but similar to those of chitinase A from Serratia marcescens (SmChiA), which also exhibits significant TG activity. These results provide insight into the molecular mechanism underlying the TG reaction and the molecular evolution from bacterial chitinases to plant class V chitinases.
Incidence of gammopathies in long‐term plasmapheresis donors at Canadian Blood Services
Authors: Palmer Douglas S. , Scalia Vito , O'Toole Joan , Welch Christine , Yi Qilong , Goldman Mindy 
Published: February 2015

BACKGROUNDTo investigate the long‐term consequences of repeated plasmapheresis on donor health, their donation histories and demographic data were reviewed to determine the frequency of development of monoclonal (Mc) gammopathies or other gamma globulin abnormalities (OGGAs).STUDY DESIGN AND METHODSSamples from apheresis plasma donors collected at Canadian Blood Services were tested initially and every 4 months for total protein (TP) followed by serum protein electrophoresis (SPE). Out‐of‐range samples or those showing abnormal band patterns were forwarded to a hospital laboratory for additional investigation.RESULTSOf 52,972 donors who donated 471,446 apheresis plasmas over 9 years, 89,490 samples were sent for TP and SPE testing. Of 3005 samples forwarded for further investigation, abnormal immunofixation electrophoresis (IFE) results were found in 209 (0.4%) donors, 85 from first‐time (FT) and 124 from repeat (RPT) plasma donors during participation in the program. There were 167 donors with Mc gammopathies (73 FT, 94 RPT) and 42 with OGGAs (12 FT, 30 RPT). FT or RPT donors with Mc gammopathies or OGGAs were significantly older than those with normal SPEs. RPT donors with Mc gammopathies or OGGAs also had a longer donation period than donors with normal SPEs.CONCLUSIONSThe incidence of Mc gammopathies (2.41 per 1000 donors) did not significantly increase from 2004 to 2012. Older donors had a higher incidence of Mc gammopathies and longer donation periods than their healthy counterparts. Overall, gammopathy rates were below those reported over the same age range in the general population.
Predictors of hemoglobin in Danish blood donors: results from the Danish Blood Donor Study
Authors: Kotzé Sebastian R. , Pedersen Ole B. , Petersen Mikkel S. , Sørensen Erik , Thørner Lise W. , Sørensen Cecilie J. , Rigas Andreas S. , Hjalgrim Henrik , Rostgaard Klaus , Ullum Henrik , Erikstrup Christian 
Published: February 2015

BACKGROUNDIt is well known that blood donors are at increased risk of iron deficiency and subsequent development of iron deficiency anemia. We aimed to investigate the effect of factors influencing hemoglobin (Hb) levels.STUDY DESIGN AND METHODSInitiated in 2010, the Danish Blood Donor Study is a population‐based study and biobank. We performed multivariable linear regression analysis to assess the effects of donation activity, physiologic and lifestyle factors, and diet on Hb levels among 15,197 donors. We also performed multivariable logistic regression to evaluate the effects of these factors on the risk of having low Hb (defined as Hb below the 10th percentile among men and women, respectively) and of a decrease in Hb greater than 0.5 mmol/L (0.8 g/dL) between successive donations. All analyses were performed stratified for sex and smoking status. We also tested a previously used model for the prediction of Hb.RESULTSThe strongest predictors of Hb and risk of low Hb were low ferritin (<15 ng/mL) and current use of iron supplementation (yes/no). No dietary factors were found to be consistently significant in multivariable models predicting Hb levels, risk of having low Hb, or risk of a decrease in Hb greater than 0.5 mmol/L. We found similar effects to previous studies of factors in the predictive model, with little additional effect of including smoking status and ferritin.CONCLUSIONSAs ferritin was the strongest predictor of Hb, this study supports the implementation of regular ferritin measurement as a method of risk assessment among blood donors.
Osteosarcoma tissues and cell lines from patients with differing serum alkaline phosphatase concentrations display minimal differences in gene expression patterns
Authors: Rodrigues L. C. de Sá , Holmes K. E. , Thompson V. , Piskun C. M. , Lana S. E. , Newton M. A. , Stein T. J. 
Published: February 2015

AbstractSerum alkaline phosphatase (ALP) concentration is a prognostic factor for osteosarcoma in multiple studies, although its biological significance remains incompletely understood. To determine whether gene expression patterns differed in osteosarcoma from patients with differing serumALPconcentrations, microarray analysis was performed on 18 primary osteosarcoma samples and six osteosarcoma cell lines from dogs with normal and increased serumALPconcentration. No differences in gene expression patterns were noted between tumours or cell lines with differing serumALPconcentration using a gene‐specific two‐samplet‐test. Using a more sensitive empirical Bayes procedure, defective in cullin neddylation 1 domain containing 1 (DCUN1D1) was increased in both the tissue and cell lines of the normalALPgroup. Using quantitative PCR (qPCR), differences inDCUN1D1expression between the two groups failed to reach significance. The homogeneity of gene expression patterns of osteosarcoma associated differing serumALPconcentrations are consistent with previous studies suggesting serumALPconcentration is not associated with intrinsic differences of osteosarcoma cells.