bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hearing dysfunction in heterozygous MitfMi‐wh/+ mice, a model for Waardenburg syndrome type 2 and Tietz syndrome
Authors: Ni Christina , Zhang Deming , Beyer Lisa A. , Halsey Karin E. , Fukui Hideto , Raphael Yehoash , Dolan David F. , Hornyak Thomas J. 
Published: October 2012

SummaryThe human deafness‐pigmentation syndromes, Waardenburg syndrome (WS) type 2a, and Tietz syndrome are characterized by profound deafness but only partial cutaneous pigmentary abnormalities. Both syndromes are caused by mutations in MITF. To illuminate differences between cutaneous and otic melanocytes in these syndromes, their development and survival in heterozygous Microphthalmia‐White (MitfMi‐wh/+) mice were studied and hearing function of these mice characterized. MitfMi‐wh/+ mice have a profound hearing deficit, characterized by elevated auditory brainstem response thresholds, reduced distortion product otoacoustic emissions, absent endocochlear potential, loss of outer hair cells, and stria vascularis abnormalities. MitfMi‐wh/+ embryos have fewer melanoblasts during embryonic development than their wild‐type littermates. Although cochlear melanocytes are present at birth, they disappear from the MitfMi‐wh/+ cochlea between P1 and P7. These findings may provide insight into the mechanism of melanocyte and hearing loss in human deafness‐pigmentation syndromes such as WS and Tietz syndrome and illustrate differences between otic and follicular melanocytes.
Photocycle of the LOV‐STAS Protein from the Pathogen Listeria monocytogenes.
Authors: Chan Ruby H. , Lewis James W. , Bogomolni Roberto A. 
Published: October 2012

AbstractListeria monocytogenes, a food‐borne bacterial pathogen causing significant human mortality, propagates by expressing genes in response to environmental signals, such as temperature and pH. Listeria gene (lmo0799) encodes a protein homologous to the Bacillus subtilis YtvA, which has a flavin‐light, oxygen or voltage (LOV) domain and a Sulfate Transporters Anti‐Sigma factor antagonist (STAS) output domain that regulates transcription‐initiation factor Sigma B in the bacterial stress response upon exposure to light. This could be significant for the pathogenesis of listeriosis because Sigma B has been linked to virulence of Listeria, and the Listeria Lmo0799 protein has recently been identified as a virulence factor activated by blue light. We have cloned, expressed heterologously in Escherichia coli and purified the full‐length LM‐LOV‐STAS protein. Although it exhibits photochemical activity similar to that of YtvA, LM‐LOV‐STAS lacks an almost universally conserved arginine in the flavin‐binding site, as well as another positively charged residue, a lysine in YtvA. The absence of these positive charges was found to destabilize retention of the flavin mononucleotide (FMN) chromophore in the LM‐LOV‐STAS protein, particularly at higher temperatures. The unusual sequence of the LM‐LOV‐STAS protein alters both spectral features and activation/deactivation kinetics, potentially expanding the sensory capacity of this LOV domain, e.g. to detect light plus cold.
Exploiting microRNA regulation for genetic engineering
Authors: Gentner B. , Naldini L. 
Published: October 2012

AbstractRNA interference (RNAi) has been a landmark discovery in science. A typical application is to knock down the expression of endogenous genes by delivering small interfering RNA (siRNA) into cells triggering the degradation of complementary mRNA. However, RNAi can also be exploited the other way round: making use of the huge diversity of endogenous microRNAs (miRNA), the expression of exogenously introduced genes tagged with artificial miRNA target sequences can be negatively regulated according to the activity of a given miRNA which can be tissue‐, lineage‐, activation‐ or differentiation stage specific. This has significantly expanded the regulatory potential of gene transfer vectors and will benefit both basic science and therapeutic applications. This review briefly introduces the reader to the technical basis for exploiting miRNA regulation, followed by a discussion of specific applications for miRNA‐regulated vectors/viruses in basic research, gene‐ and virotherapy.
Distinct HLA allele and haplotype distributions in four ethnic groups of China
Authors: Yao Y. , Shi L. , Tao Y. , Kulski J. K. , Lin K. , Huang X. , Xiang H. , Chu J. , Shi L. 
Published: October 2012

AbstractDistinct human leukocyte antigen (HLA) allele and haplotype distributions occur in the northern and southern Han populations of China. However, different ethnic groups in China show limited regional distributions for many HLA alleles and haplotypes. Therefore, it is necessary and meaningful to study the differences in HLA allele and haplotype distribution for northern and southern ethnic groups of China. A total of 428 unrelated individuals from the Lisu, Nu, Tu and Yugur ethnic populations were genotyped for HLA‐A, ‐B, ‐C and ‐DRB1 alleles using the PCR‐Luminex typing method. The frequencies of HLA alleles and statistically inferred haplotypes were calculated. A total of 29 HLA‐A, 54 HLA‐B, 27 HLA‐C and 41 HLA‐DRB1 alleles were spread throughout these four populations with distinct allele and deduced haplotype frequencies between populations. Some alleles and deduced haplotypes exhibited significantly different distributions between northern (Tu and Yugur) and southern groups (Lisu and Nu). A phylogenetic tree and principal component analysis were used to compare the HLA polymorphism between our dataset and 19 other eastern and southeastern Asian populations. This analysis showed that Lisu and Nu belong to a cluster of southern ethnic groups, while Tu and Yugur are most closely related to other northern groups. Thus, distinct ethnic population histories were revealed by analyzing HLA allelic polymorphisms with the HLA profiles of the Lisu and Nu southern Chinese ethnic groups clearly different from the Tu and Yugur northern ethnic groups. The results will be useful for future association studies of infectious disease and contribute toward a more efficient search of organ/tissue matches for transplantation.
Economic Diplomacy and International Trade: ASEAN’s Quest to Value‐Claim
Authors: Selmier W. Travis , Oh Chang Hoon 
Published: October 2012

AbstractUtilising economic diplomacy theory, this study specifies a statistical model to reveal ASEAN members’ capacity to negotiate better international trade outcomes. Examining imports into ASEAN members from 134 nations between 1980 and 2001, we find that ASEAN’s diplomats were able to pursue more ‘value‐claiming’ in economic diplomacy than expected. While our results support the commonly accepted view in economic diplomacy that smaller nations are pressured to accept trade outcomes desired by larger nations, we also find support for a new perspective: smaller nations obtain more favourable trade outcomes, as members of a regional trade bloc, which cannot be achieved as individual nations. We find that ASEAN’s conversion to a fully fledged regional trade agreement in 1992 significantly enhanced this capacity. This study adds a different perspective to the substantial literature examining cases in trade and economic diplomacy.
Positive association between a glutathione‐S‐transferase polymorphism and lymphoma in dogs
Authors: Ginn J. , Sacco J. , Wong Y. Y. , Motsinger‐Reif A. , Chun R. , Trepanier L. A. 
Published: October 2012

AbstractGlutathione‐S‐transferase enzymes (GSTs) play an important role in the detoxification of environmental carcinogens. Defective GST genotypes are over‐represented in human cancers; in particular, low activity GSTT1 genotypes are risk factors for non‐Hodgkin lymphoma. We hypothesized that defective GSTT1 genotypes would be associated with lymphoma risk in dogs. To address this, we resequenced the exons, splice junctions, and 3′‐UTR of canine GSTT1 in dogs with lymphoma (n = 93) and age‐matched unaffected dogs (n = 86). Of 27 canine GSTT1 variants identified, the I2+28 G>A was significantly associated with lymphoma [odds ratio (OR) 6.26, 95% confidence interval (CI), 1.77–22.2], with the AA genotype found in 18.3% of affected dogs but only 3.5% of controls (P = 0.002). This intronic variant was predicted to perturb GSTT1 mRNA splicing, and may increase lymphoma risk by impairing detoxification of environmental chemicals. Confirmation of this finding in a larger population of dogs may support the inclusion of GSTT1 genotyping in epidemiologic studies of canine lymphoma risk.
Characterization of Xylan Utilization and Discovery of a New Endoxylanase in Thermoanaerobacterium saccharolyticum through Targeted Gene Deletions
Authors: Podkaminer Kara K. , Guss Adam M. , Trajano Heather L. , Hogsett David A. , Lynd Lee R. 
Published: October 2012

ABSTRACT

The economical production of fuels and commodity chemicals from lignocellulose requires the utilization of both the cellulose and hemicellulose fractions. Xylanase enzymes allow greater utilization of hemicellulose while also increasing cellulose hydrolysis. Recent metabolic engineering efforts have resulted in a strain of
Thermoanaerobacterium saccharolyticum
that can convert C
5
and C
6
sugars, as well as insoluble xylan, into ethanol at high yield. To better understand the process of xylan solubilization in this organism, a series of targeted deletions were constructed in the homoethanologenic
T. saccharolyticum
strain M0355 to characterize xylan hydrolysis and xylose utilization in this organism. While the deletion of β-xylosidase
xylD
slowed the growth of
T. saccharolyticum
on birchwood xylan and led to an accumulation of short-chain xylo-oligomers, no other single deletion, including the deletion of the previously characterized endoxylanase XynA, had a phenotype distinct from that of the wild type. This result indicates a multiplicity of xylanase enzymes which facilitate xylan degradation in
T. saccharolyticum
. Growth on xylan was prevented only when a previously uncharacterized endoxylanase encoded by
xynC
was also deleted in conjunction with
xynA
. Sequence analysis of
xynC
indicates that this enzyme, a low-molecular-weight endoxylanase with homology to glycoside hydrolase family 11 enzymes, is secreted yet untethered to the cell wall. Together, these observations expand our understanding of the enzymatic basis of xylan hydrolysis by
T. saccharolyticum
.
Nanocapsular Dispersion of Thymol for Enhanced Dispersibility and Increased Antimicrobial Effectiveness against Escherichia coli O157:H7 and Listeria monocytogenes in Model Food Systems
Authors: Shah Bhavini , Davidson P. Michael , Zhong Qixin 
Published: October 2012

ABSTRACT

Essential oils are marginally soluble in water, making it challenging to evenly disperse them in foods and resulting in an increased tendency to bind with food lipids and proteins, resulting in lowered antimicrobial efficacy. In the current study, free and nano-dispersed (ND) thymol were compared in terms of their antimicrobial efficacies against
Escherichia coli
O157:H7 ATCC 43889 and 43894 and
Listeria monocytogenes
strains Scott A and 101 in apple cider and 2% reduced-fat milk. Apple cider was adjusted to pHs 5.5 and 3.5, and antimicrobial tests were performed at 0.3-, 0.5-, 0.75-, and 1.0-g/liter thymol concentrations at 35, 32, 25, and 4°C. Overall, 0.5 and 1.0 g/liter thymol in nano-dispersion and along with free thymol were inhibitory and bactericidal, respectively, against bacterial strains under all treatment conditions. At pH 5.5, 0.5 g/liter ND thymol was bacteriostatic against
L. monocytogenes
and
E. coli
for up to 48 h. At pH 3.5,
L. monocytogenes
controls did not survive beyond 12 h but
E. coli
survived and was inhibited by 0.5 g/liter ND thymol after 12 and 48 h in apple cider.
E. coli
strains were significantly sensitive to 4°C and pH 3.5 (
P
< 0.05). When bacteria were tested in 2% reduced-fat milk at 35 or 32°C, ND and free thymol demonstrated inhibition at 4.5 g/liter. Thus, the current technology seems to be promising and novel, enabling thymol-containing nano-dispersions that are not only transparent but also effective against pathogens in food applications, especially in clear beverages.
A Single-Cell Genome for Thiovulum sp
Authors: Marshall Ian P. G. , Blainey Paul C. , Spormann Alfred M. , Quake Stephen R. 
Published: October 2012

ABSTRACTWe determined a significant fraction of the genome sequence of a representative ofThiovulum, the uncultivated genus of colorless sulfurEpsilonproteobacteria, by analyzing the genome sequences of four individual cells collected from phototrophic mats from Elkhorn Slough, California. These cells were isolated utilizing a microfluidic laser-tweezing system, and their genomes were amplified by multiple-displacement amplification prior to sequencing.Thiovulumis a gradient bacterium found at oxic-anoxic marine interfaces and noted for its distinctive morphology and rapid swimming motility. The genomic sequences of the four individual cells were assembled into a composite genome consisting of 221 contigs covering 2.083 Mb including 2,162 genes. This single-cell genome represents a genomic view of the physiological capabilities of isolatedThiovulumcells.Thiovulumis the second-fastest bacterium ever observed, swimming at 615 μm/s, and this genome shows that this rapid swimming motility is a result of a standard flagellar machinery that has been extensively characterized in other bacteria. This suggests that standard flagella are capable of propelling bacterial cells at speeds much faster than typically thought. Analysis of the genome suggests that naturally occurringThiovulumpopulations are more diverse than previously recognized and that studies performed in the past probably address a wide range of unrecognized genotypic and phenotypic diversities ofThiovulum. The genome presented in this article provides a basis for future isolation-independent studies ofThiovulum, where single-cell and metagenomic tools can be used to differentiate between differentThiovulumgenotypes.
Characterization of a Broad-Specificity β-Glucanase Acting on β-(1,3)-, β-(1,4)-, and β-(1,6)-Glucans That Defines a New Glycoside Hydrolase Family
Authors: Lafond Mickael , Navarro David , Haon Mireille , Couturier Marie , Berrin Jean-Guy 
Published: October 2012

ABSTRACTHere we report the cloning of thePa_3_10940gene from the coprophilic fungusPodospora anserina, which encodes a C-terminal family 1 carbohydrate binding module (CBM1) linked to a domain of unknown function. The function of the gene was investigated by expression of the full-length protein and a truncated derivative without the CBM1 domain in the yeastPichia pastoris. Using a library of polysaccharides of different origins, we demonstrated that the full-length enzyme displays activity toward a broad range of β-glucan polysaccharides, including laminarin, curdlan, pachyman, lichenan, pustulan, and cellulosic derivatives. Analysis of the products released from polysaccharides revealed that this β-glucanase is an exo-acting enzyme on β-(1,3)- and β-(1,6)-linked glucan substrates and an endo-acting enzyme on β-(1,4)-linked glucan substrates. Hydrolysis of short β-(1,3), β-(1,4), and β-(1,3)/β-(1,4) gluco-oligosaccharides confirmed this striking feature and revealed that the enzyme performs in an exo-type mode on the nonreducing end of gluco-oligosaccharides. Excision of the CBM1 domain resulted in an inactive enzyme on all substrates tested. To our knowledge, this is the first report of an enzyme that displays bifunctional exo-β-(1,3)/(1,6) and endo-β-(1,4) activities toward beta-glucans and therefore cannot readily be assigned to existing Enzyme Commission groups. The amino acid sequence has high sequence identity to hypothetical proteins within the fungal taxa and thus defines a new family of glycoside hydrolases, the GH131 family.
Crystal Structure of the Klebsiella pneumoniae NFeoB/FeoC Complex and Roles of FeoC in Regulation of Fe
2+
Transport by the Bacterial Feo System
Authors: Hung Kuo-Wei , Tsai Jia-Yin , Juan Tzu-Hsuan , Hsu Yen-Lan , Hsiao Chwan-Deng , Huang Tai-Huang 
Published: October 2012

ABSTRACT

Feo is a transport system commonly used by bacteria to acquire environmental Fe
2+
. It consists of three proteins: FeoA, FeoB, and FeoC. FeoB is a large protein with a cytosolic N-terminal domain (NFeoB) that contains a regulatory G protein domain and a helical S domain. The C-terminal region of FeoB is a transmembrane domain that likely acts as the Fe
2+
permease. NFeoB has been shown to form a trimer pore that may function as an Fe
2+
gate. FeoC is a small winged-helix protein that possesses four conserved cysteine residues with a consensus sequence that likely provides binding sites for the [Fe-S] cluster. Therefore, FeoC is presumed to be an [Fe-S] cluster-dependent regulator that directly controls transcription of the
feo
operon. Despite the apparent significance of the Feo system, however, the function of FeoC has not been experimentally demonstrated. Here, we show that
Klebsiella pneumoniae
FeoC (
Kp
FeoC) forms a tight complex with the intracellular N-terminal domain of FeoB (
Kp
NFeoB). The crystal structure of the complex reveals that
Kp
FeoC binds to
Kp
NFeoB between the switch II region of the G protein domain and the effector S domain and that the long
Kp
FeoC W1 loop lies above the
Kp
NFeoB nucleotide-binding site. These interactions suggest that
Kp
FeoC modulates the guanine nucleotide-mediated signal transduction process. Moreover, we showed that binding of
Kp
FeoC disrupts pore formation by interfering with
Kp
NFeoB trimerization. These results provide strong evidence suggesting that
Kp
FeoC plays a crucial role in regulating Fe
2+
transport in
Klebsiella pneumonia
in addition to the presumed gene regulator role.
Phage Shock Protein C (PspC) of Yersinia enterocolitica Is a Polytopic Membrane Protein with Implications for Regulation of the Psp Stress Response
Authors: Flores-Kim Josué , Darwin Andrew J. 
Published: October 2012

ABSTRACT

Phage shock proteins B (PspB) and C (PspC) are integral cytoplasmic membrane proteins involved in inducing the
Yersinia enterocolitica
Psp stress response. A fundamental aspect of these proteins that has not been studied in depth is their membrane topologies. Various
in silico
analyses universally predict that PspB is a bitopic membrane protein with the C terminus inside. However, similar analyses yield conflicting predictions for PspC: a bitopic membrane protein with the C terminus inside, a bitopic membrane protein with the C terminus outside, or a polytopic protein with both termini inside. Previous studies of
Escherichia coli
PspB-LacZ and PspC-PhoA fusion proteins supported bitopic topologies, with the PspB C terminus inside and the PspC C terminus outside. Here we have used a series of independent approaches to determine the membrane topologies of PspB and PspC in
Y. enterocolitica
. Our data support the predicted arrangement of PspB, with its C terminus in the cytoplasm. In contrast, data from multiple independent approaches revealed that both termini of PspC are located in the cytoplasm. Additional experiments suggested that the C terminus of PspC might be the recognition site for the FtsH protease and an interaction interface with PspA, both of which would be compatible with its newly proposed cytoplasmic location. This unexpected arrangement of PspC allows a new model for events underlying activation of the Psp response, which is an excellent fit with observations from various previous studies.
Factors that prolong the ‘postmortem interval until finding’ (PMI-f) among community-dwelling elderly individuals in Japan: analysis of registration data
Authors: Ito Tomoko , Tamiya Nanako , Takahashi Hideto , Yamazaki Kentaro , Yamamoto Hideki , Sakano Shoji , Kashiwagi Masayo , Miyaishi Satoru 
Published: October 2012

ObjectivesTo clarify the factors affecting ‘postmortem interval until finding’ (PMI-f) among elderly unexpected death cases.DesignCross-sectional study.SettingAll area of Yamagata prefecture in Japan.ParticipantsEntering subjects were 5675 elderly cases with age of ≥65 years selected from all 9002 cases of unexpected death from 2002 to 2007 in Yamagata prefecture between 2002 and 2007. Our final study subjects consisted of 3387 cases sampled with several criteria to assess the factors to prolong PMI-f.Primary outcome measuresThe outcome was the postmortem interval until finding (PMI-f) as the time from death until finding the body which we defined in this study.Results‘Living alone’ showed the highest adjusted HR (3.73, 95% CI 3.37 to 4.13), also ‘unnatural death’ (1.50, 1.28 to 1.75), ‘found at own home’ (1.37, 1.22 to 1.55) and ‘younger subjects’ (0.99, 0.98 to 0.99). In the model including interactions with the household situation, we found ‘male subjects living alone’ and ‘female subjects living with family’ tended to be found later.ConclusionsPMI-f is an effective outcome for quantitative analyses of risk of bodies left. To prevent the elderly dead bodies left for long time, it is necessary to keep regular home-based contact with elderly individuals living alone.
Lack of association between genetic variability and multiple pain-related outcomes in a large cohort of patients with advanced cancer: the European Pharmacogenetic Opioid Study (EPOS)
Authors: Fladvad Torill , Fayers Peter , Skorpen Frank , Kaasa Stein , Klepstad Pål 
Published: October 2012

ObjectiveThis study examined whether the choice of pain-related outcome to represent opioid efficacy influenced findings in a genetic association study. Data from the European Pharmacogenetic Opioid Study, which used opioid dose as the outcome, were analysed in respect of six alternative outcomes: average pain intensity, pain right now, worst pain intensity, pain at its least, pain relief and pain interference.DesignCancer pain patients using an opioid for moderate or severe pain were included. The pain outcomes were obtained using the Brief Pain Inventory. Genetic variation was analysed for 112 single nucleotide polymorphisms (SNPs) in 25 candidate genes relevant for opioid efficacy. The patients were randomly divided into a development and a validation sample and linear regression was used to compare the equality of means in the six outcomes. The influence of non-genetic factors was controlled for, the regression analyses were stratified by country, and the results were corrected for multiple testing.Results2201 cancer pain patients were included. Their mean age was 62.4 years and mean average pain was 3.5. None of the examined SNPs exceeded p values corrected for multiple testing for any of the outcomes.ConclusionsNone of the outcomes were associated with variation in the selected SNPs, as previously shown for opioid dose. Thus, we observed that findings related to associations between genetic variability and opioid efficacy were consistent for several alternative outcomes.