bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sequence variants in oxytocin pathway genes and preterm birth: a candidate gene association study
Authors: Kim Jinsil , Stirling Kara J , Cooper Margaret E , Ascoli Mario , Momany Allison M , McDonald Erin L , Ryckman Kelli K , Rhea Lindsey , Schaa Kendra L , Cosentino Viviana , Gadow Enrique , Saleme Cesar , Shi Min , Hallman Mikko , Plunkett Jevon , Teramo Kari A , Muglia Louis J , Feenstra Bjarke , Geller Frank , Boyd Heather A , Melbye Mads , Marazita Mary L , Dagle John M , Murray Jeffrey C 
Published: July 2013

Abstract

Background
Preterm birth (PTB) is a complex disorder associated with significant neonatal mortality and morbidity and long-term adverse health consequences. Multiple lines of evidence suggest that genetic factors play an important role in its etiology. This study was designed to identify genetic variation associated with PTB in oxytocin pathway genes whose role in parturition is well known.

Methods
To identify common genetic variants predisposing to PTB, we genotyped 16 single nucleotide polymorphisms (SNPs) in the oxytocin (OXT), oxytocin receptor (OXTR), and leucyl/cystinyl aminopeptidase (LNPEP) genes in 651 case infants from the U.S. and one or both of their parents. In addition, we examined the role of rare genetic variation in susceptibility to PTB by conducting direct sequence analysis of OXTR in 1394 cases and 1112 controls from the U.S., Argentina, Denmark, and Finland. This study was further extended to maternal triads (maternal grandparents-mother of a case infant, N=309). We also performed in vitro analysis of selected rare OXTR missense variants to evaluate their functional importance.

Results
Maternal genetic effect analysis of the SNP genotype data revealed four SNPs in LNPEP that show significant association with prematurity. In our case–control sequence analysis, we detected fourteen coding variants in exon 3 of OXTR, all but four of which were found in cases only. Of the fourteen variants, three were previously unreported novel rare variants. When the sequence data from the maternal triads were analyzed using the transmission disequilibrium test, two common missense SNPs (rs4686302 and rs237902) in OXTR showed suggestive association for three gestational age subgroups. In vitro functional assays showed a significant difference in ligand binding between wild-type and two mutant receptors.

Conclusions
Our study suggests an association between maternal common polymorphisms in LNPEP and susceptibility to PTB. Maternal OXTR missense SNPs rs4686302 and rs237902 may have gestational age-dependent effects on prematurity. Most of the OXTR rare variants identified do not appear to significantly contribute to the risk of PTB, but those shown to affect receptor function in our in vitro study warrant further investigation. Future studies with larger sample sizes are needed to confirm the findings of this study.
Nuclear factor kappa B modulates apoptosis in the brain endothelial cells and intravascular leukocytes of fatal cerebral malaria
Authors: Punsawad Chuchard , Maneerat Yaowapa , Chaisri Urai , Nantavisai Kwannan , Viriyavejakul Parnpen 
Published: July 2013

AbstractBackgroundCerebral malaria (CM) caused byPlasmodium falciparumis known to be associated with the sequestration of parasitized red blood cells (PRBCs) in the microvasculature and the release of soluble cytokines. In addition, the involvement of signaling molecules has gained wide interest in the pathogenesis of CM. An important signaling factor, nuclear factor kappa B (NF-κB) is known to regulate apoptosis. This work aimed to study the expression of NF-κB p65 and its correlation with apoptosis in the brain of fatal CM.MethodsThe expression of NF-κB p65 and cleaved caspase-3 in the brain of fatalP. falciparummalaria cases was investigated by immunohistochemistry. Histopathological features were analysed together with the correlations of NF-κB p65 and cleaved caspase-3 expression.ResultsNF-κB p65 activation and cleaved caspase-3 expression were significantly increased in the neurons, glial cells, vascular endothelial cells (ECs) and intravascular leukocytes of the brain in fatal CM, compared with the control brain (p< 0.001) and non-cerebral malaria (NCM) (p= 0.034). The percentage of neurons that expressed nuclear NF-κB p65 showed a positive correlation with the total score of histopathological changes (rs= 0.678;p= 0.045). Significant positive correlations were established between vascular ECs NF-κB index and ECs apoptotic index (rs= 0.717;p= 0.030) and between intravascular leukocytes NF-κB index and leukocytes apoptotic index (rs= 0.696;p= 0.037) in fatal CM.ConclusionsThis study documented that NF-κB p65 is one of the signaling factors that modulates apoptosis in the brain ECs and intravascular leukocytes of fatal CM.
Prevalence of drug resistance associated mutations in Plasmodium vivax against sulphadoxine-pyrimethamine in southern Pakistan
Authors: Raza Afsheen , Ghanchi Najia K , Khan Muhammad Shahzeb , Beg Mohammad Asim 
Published: July 2013

Abstract

Background
In Pakistan, Plasmodium vivax and Plasmodium falciparum co-exist and usage of sulphadoxine-pyrimethamine (SP) against P. falciparum exposes P. vivax to the drug leading to generation of resistant alleles. The main aim of this study was to investigate frequency distribution of drug resistance associated mutations in pvdhfr, pvdhps genes and provide baseline molecular epidemiological data on SP-associated resistance in P. vivax from southern Pakistan.

Methods
From January 2008 to May 2009, a total of 150 samples were collected from patients tested slide-positive for P. vivax, at the Aga Khan University Hospital, Karachi, or its collection units located in Baluchistan and Sindh Province. Nested PCR using pvdhfr and pvdhps specific primers was performed for all samples.91.3% (137/150) of the samples were tested PCR positive of which 87.3% (131/137) were successfully sequenced. Sample sequencing data was analysed and compared against wild type reference sequences.

Results
In dhfr, mutations were observed at codons F57L, S58R and S117N/T. Novel non-synonymous mutations were observed at codon positions N50I, G114R and E119K while a synonymous mutation was observed at codon position 69Y. In dhps, mutations were observed at codon position A383G and A553G while novel non-synonymous mutations were observed at codon positions S373T, E380K, P384L, N389T, V392D, T393P, D459A, M601I, A651D and A661V.

Conclusion
This is the first report from southern Pakistan on SP resistance in clinical isolates of P. vivax. Results from this study confirm that diverse drug resistant alleles are circulating within this region.
Alterations in neuronal morphology and synaptophysin expression in the rat brain as a result of changes in dietary n-6: n-3 fatty acid ratios
Authors: Hajjar Toktam , Goh Yong Meng , Rajion Mohamed Ali , Vidyadaran Sharmili , Li Tan Ai , Ebrahimi Mahdi 
Published: July 2013

Abstract

Background
Polyunsaturated fatty acids (PUFA) play important roles in brain fatty acid composition and behavior through their effects on neuronal properties and gene expression. The hippocampus plays an important role in the formation of memory, especially spatial memory and navigation. This study was conducted to examine the effects of PUFA and specifically different dietary n-6: n-3 fatty acid ratios (FAR) on the number and size of hippocampal neurons and the expression of synaptophysin protein in the hippocampus of rats.

Methods
Forty 3-week old male Sprague–Dawley rats were allotted into 4 groups. The animals received experimental diets with different n-6: n-3 FAR of either 65:1, 26.5:1, 22:1 or 4.5:1 for 14 weeks.

Results
The results showed that a lowering dietary n-6: n-3 FAR supplementation can increase the number and size of neurons. Moreover, lowering the dietary n-6: n-3 FAR led to an increase in the expression of the pre-synaptic protein synaptophysin in the CA1 hippocampal subregion of the rat brain.

Conclusions
These findings support the notion that decreasing the dietary n-6: n-3 FAR will lead to an intensified hippocampal synaptophysin expression and increased neuron size and proliferation in the rat brain.
Probing the orientation of electrostatically immobilized cytochrome C by time of flight secondary ion mass spectrometry and sum frequency generation spectroscopy
Authors: Baio Joe E , Weidner Tobias , Ramey Dennis , Pruzinsky Leah , Castner David G 
Published: July 2013

By taking advantage of the electron pathway through the heme group in cytochrome c (CytoC) electrochemists have built sensors based upon CytoC immobilized onto metal electrodes. Previous studies have shown that the electron transfer rate through the protein is a function of the position of this heme group with respect to the electrode surface. In this study a detailed examination of CytoC orientation when electrostatically immobilized onto both amine (NH3+) and carboxyl (COO-) functionalized gold is presented. Protein coverage, on both surfaces, was monitored by the change in the atomic % N, as determined by x-ray photoelectron spectroscopy. Spectral features within the in situ sum frequency generation vibrational spectra, acquired for the protein interacting with positively and negatively charged surfaces, indicates that these electrostatic interactions do induce the protein into a well ordered film. Time of flight secondary ion mass spectrometry data demonstrated a clear separation between the two samples based on the intensity differences of secondary ions stemming from amino acids located asymmetrically within CytoC (cysteine: C2H6NS+; glutamic acid: C4H6NO+ and C4H8NO2+; leucine: C5H12N+). For a more quantitative examination of orientation, we developed a ratio comparing the sum of the intensities of secondary-ions stemming from the amino acid residues at either end of the protein. The 50 % increase in this ratio, observed between the protein covered NH3+ and COO- substrates, indicates opposite orientations of the CytoC on the two different surfaces.
Effects of exercise and diet interventions on obesity-related sleep disorders in men: study protocol for a randomized controlled trial
Authors: Tan Xiao , Saarinen Antti , Mikkola Tuija M , Tenhunen Jarkko , Martinmäki Samu , Rahikainen Aki , Cheng Shumei , Eklund Niklas , Pekkala Satu , Wiklund Petri , Munukka Eveliina , Wen Xinfei , Cong Fengyu , Wang Xi , Zhang Yajun , Tarkka Ina , Sun Yining , Partinen Markku , Alen Markku , Cheng Sulin 
Published: July 2013

Abstract

Background
Sleep is essential for normal and healthy living. Lack of good quality sleep affects physical, mental and emotional functions. Currently, the treatments of obesity-related sleep disorders focus more on suppressing sleep-related symptoms pharmaceutically and are often accompanied by side effects. Thus, there is urgent need for alternative ways to combat chronic sleep disorders. This study will investigate underlying mechanisms of the effects of exercise and diet intervention on obesity-related sleep disorders, the role of gut microbiota in relation to poor quality of sleep and day-time sleepiness, as well as the levels of hormones responsible for sleep-wake cycle regulation.

Methods/design
Participants consist of 330 (target sample) Finnish men aged 30 to 65 years. Among them, we attempt to randomize 180 (target sample) with sleep disorders into exercise and diet intervention. After screening and physician examination, 101 men with sleep disorders are included and are randomly assigned into three groups: exercise (n = 33), diet (n = 35), and control (n = 33). In addition, we attempt to recruit a target number of 150 healthy men without sleep disorders as the reference group. The exercise group undergoes a six-month individualized progressive aerobic exercise program based on initial fitness level. The diet group follows a six month specific individualized diet program. The control group and reference group are asked to maintain their normal activity and diet during intervention. Measurements are taken before and after the intervention. Primary outcomes include objective sleep measurements by polysomnography and a home-based non-contact sleep monitoring system, and subjective sleep evaluation by questionnaires. Secondary outcome measures include anthropometry, body composition, fitness, sleep disorder-related lifestyle risk factors, composition of gut microbiota and adipose tissue metabolism, as well as specific hormone and neurotranmitter levels and inflammatory biomarkers from venous blood samples.

Discussion
It is expected that the improvement of sleep quality after exercise and diet intervention will be evident both in subjective and objective measures of quality of sleep. Additionally, the change of sleep quality induced by exercise and diet intervention is expected to be related to the changes in specific hormones and inflammatory biomarkers, and in the composition of gut microbiota.

Trial registration
Current Controlled Trials ISRCTN77172005
A practical strategy for responding to a case of lymphatic filariasis post-elimination in Pacific Islands
Authors: Harrington Humpress , Asugeni James , Jimuru Christopher , Gwalaa John , Ribeyro Elmer , Bradbury Richard , Joseph Hayley , Melrose Wayne , MacLaren David , Speare Rick 
Published: July 2013

Abstract

Background
Lymphatic filariasis (LF) due to Wuchereria bancrofti is being eliminated from Oceania under the Pacific Elimination of Lymphatic Filariasis Programme. LF was endemic in Solomon Islands but in the 2010-2020 Strategic Plan of the Global Programme to Eliminate LF, Solomon Islands was listed as non-endemic for LF. In countries now declared free of LF an important question is what monitoring strategy should be used to detect any residual foci of LF?
This paper describes how a new case of elephantiasis in a post-elimination setting may be used as a trigger to initiate a local survey for LF.

Methods
The index case, a 44 year old male, presented to Atoifi Adventist Hospital, Malaita, Solomon Islands in April 2011 with elephantiasis of the lower leg. Persistent swelling had commenced 16 months previously. He was negative for antigen by TropBio Og4C3 ELISA and for microfilaria. A week later a survey of 197 people aged from 1 year to 68 years was conducted at Alasi, the index case’s village, by a research team from Atoifi Adventist Hospital and Atoifi College of Nursing. This represented 66.3% of the village population. Blood was collected between 22:00 and 03:00 by finger-prick and made into thick smears to detect microfilaria and collected onto filter paper for W. bancrofti antigen tests. A second group of 110 specimens was similarly collected from residents of the Hospital campus and inpatients. W. bancrofti antigen was tested for using the Trop-Bio Og4C3 test.

Results
One sample (1/307) from an 18 year old male from Alsai was positive for W. bancrofti antigen. No samples were positive for microfilaria. Although antigen-positivity indicated a live worm, the case was regarded as having been acquired some years previously.

Conclusions
We propose that when LF has been eliminated from a country, a case of elephantiasis should be a trigger to conduct a survey of the case’s community using a decision pathway. W. bancrofti antigen should be tested for with screening for microfilariae in antigen positive cases. The field survey was designed and conducted by local researchers, highlighting the value of local research capacity in remote areas.
Differential expression of PTEN gene correlates with phenotypic heterogeneity in three cases of patients showing clinical manifestations of PTEN hamartoma tumour syndrome
Authors: Paparo Lorella , Rossi Giovanni Battista , Delrio Paolo , Rega Daniela , Duraturo Francesca , Liccardo Raffaella , Debellis Mario , Izzo Paola , De Rosa Marina 
Published: July 2013

Abstract
Cowden syndrome (CS), Bannayan-Riley-Ruvalcaba syndrome (BRRS) and proteus syndrome are disorders known as PTEN hamartoma tumour syndrome (PHTS), that can show remarkable clinical overlap and are all caused by germline PTEN mutations.
We here present two families, one affected by CS and the other affected by BRRS, both carriers of specific pathogenetic missense mutation in exon 5 of PTEN gene, within the catalitic domain. Both PHTS families exhibited extremely variable phenotypes, showing inter- and intra- familial variability. One of the two characterised mutations, the c.320A- > T; p.107Asp- > Val, identified in the CS family, was not previously described in the literature. Furthermore, the BRRS family, carrier of the c.406 T- > C; p.136Cys- > Arg mutation, shows a substantial alteration of PTEN protein expression that well correlates with intra-familial phenotypic variability.
Finally, we describe an apparently sporadic case of an 80-year-old man, with a very low level of PTEN mRNA and protein expression, both in healthy and tumour colon mucosa, associated with a very atypical phenotype. He developed a metastatic colorectal carcinoma, macrocephaly and pheochromocytoma.
According to literature data, our observations confirm that PTEN mutations of catalytic domain can cause different syndromes. We suggest that PTEN expression could represent one of the mechanisms involved in the remarkable heterogeneity of the clinical PHTS manifestations within affected families. Furthermore, constitutive strong decrease of PTEN expression in colon normal mucosa could be associated with late onset of colorectal cancer.
Increasing protein production by directed vector backbone evolution
Authors: Jakob Felix , Lehmann Christian , Martinez Ronny , Schwaneberg Ulrich 
Published: July 2013

Abstract
Recombinant protein production in prokaryotic and eukaryotic organisms was a key enabling technology for the rapid development of industrial and molecular biotechnology. However, despite all progress the improvement of protein production is an ongoing challenge and of high importance for cost-effective enzyme production. With the epMEGAWHOP mutagenesis protocol for vector backbone optimization we report a novel directed evolution based approach to increase protein production levels by randomly introducing mutations in the vector backbone. In the current study we validate the epMEGAWHOP mutagenesis protocol for three different expression systems. The latter demonstrated the general applicability of the epMEGAWHOP method. Cellulase and lipase production was doubled in one round of directed evolution by random mutagenesis of pET28a(+) and pET22b(+) vector backbones. Protease production using the vector pHY300PLK was increased ~4-times with an average of ~1.25 mutations per kb vector backbone. The epMEGAWHOP does not require any rational understanding of the expression machinery and can generally be applied to enzymes, expression vectors and related hosts. epMEGAWHOP is therefore from our point of view a robust, rapid and straight forward alternative for increasing protein production in general and for biotechnological applications.
A comparative survey of genetic diversity among a set of Caricaceae accessions using microsatellite markers
Authors: Sengupta Samik , Das Basabdatta , Prasad Manoj , Acharyya Pinaki , Ghose Tapas Kumar 
Published: July 2013

AbstractA preliminary survey of genetic diversity among 34 commercially popularCarica papayacultivars from India and abroad, 6 accessions ofVasconcelleaspecies and 1 accession ofJacaratia spinosa, was done using 20 simple sequence repeat (SSR) markers. The SSR profiles were used to find out total number of alleles, null and rare alleles, Polymorphism Information Content (PIC) values and to calculate similarity matrix using Jaccard’s coefficient. The subsequent dendrogram was made by unweighted pair-group method of arithmetic average (UPGMA) and neighbor-joining method. Based on these parameters a comparison was made between the Indian papaya cultivars and the rest of the accessions. All the markers showed polymorphism and a total of 140 alleles were identified. The average number of alleles was 7 alleles/locus. Categorically theVasconcelleaandJacaratiaspecies had 54 alleles, the 7 non-IndianCarica papayaaccessions had 70 and the 27 Indian accessions had 102 alleles. The average PIC value was 0.735 per marker. A total of 37 rare alleles were identified.Jacaratia spinosahad 17 rare alleles. Nineteen null alleles were detected among theCarica papayaaccessions. ACarica papayaaccession from South Africa, Hortus Gold had 5 null alleles. The genetic similarity among the accessions ranged from 7% to 67%. In the dendrogram, theVasconcellea and Jacaratia spinosaaccessions separated as a distinct cluster from the rest of theCarica papayaaccessions. The study indicated that the accessions of IndianCarica papayacultivars included in this survey are genetically more diverse than the non-IndianCarica papayacultivars.
Gene expression changes with age in skin, adipose tissue, blood and brain
Authors: Glass Daniel , Viñuela Ana , Davies Matthew N , Ramasamy Adaikalavan , Parts Leopold , Knowles David , Brown Andrew A , Hedman Åsa K , Small Kerrin S , Buil Alfonso , Grundberg Elin , Nica Alexandra C , Di Meglio Paola , Nestle Frank O , Ryten Mina ,   the UK Brain Expression consortium,   the MuTHER consortium, Durbin Richard , McCarthy Mark I , Deloukas Panagiotis , Dermitzakis Emmanouil T , Weale Michael E , Bataille Veronique , Spector Tim D 
Published: July 2013

Abstract
Background
Previous studies have demonstrated that gene expression levels change with age. These changes are hypothesized to influence the aging rate of an individual. We analyzed gene expression changes with age in abdominal skin, subcutaneous adipose tissue and lymphoblastoid cell lines in 856 female twins in the age range of 39-85 years. Additionally, we investigated genotypic variants involved in genotype-by-age interactions to understand how the genomic regulation of gene expression alters with age.

Results
Using a linear mixed model, differential expression with age was identified in 1,672 genes in skin and 188 genes in adipose tissue. Only two genes expressed in lymphoblastoid cell lines showed significant changes with age. Genes significantly regulated by age were compared with expression profiles in 10 brain regions from 100 postmortem brains aged 16 to 83 years. We identified only one age-related gene common to the three tissues. There were 12 genes that showed differential expression with age in both skin and brain tissue and three common to adipose and brain tissues.

Conclusions
Skin showed the most age-related gene expression changes of all the tissues investigated, with many of the genes being previously implicated in fatty acid metabolism, mitochondrial activity, cancer and splicing. A significant proportion of age-related changes in gene expression appear to be tissue-specific with only a few genes sharing an age effect in expression across tissues. More research is needed to improve our understanding of the genetic influences on aging and the relationship with age-related diseases.