bluuebunny/crossref_metadata_2025_split huggingface dataset:
Population structure analyses and demographic history of the malaria vector Anopheles albimanus from the Caribbean and the Pacific regions of Colombia
Authors: Gutiérrez Lina A , Naranjo Nelson J , Cienfuegos Astrid V , Muskus Carlos E , Luckhart Shirley , Conn Jan E , Correa Margarita M 
Published: November 2009

AbstractBackgroundAnopheles albimanusis an important malaria vector in some areas throughout its distribution in the Caribbean and the Pacific regions of Colombia, covering three biogeographic zones of the neotropical region, Maracaibo, Magdalena and Chocó.MethodsThis study was conducted to estimate intra-population genetic diversity, genetic differentiation and demographic history ofAn. albimanuspopulations because knowledge of vector population structure is a useful tool to guide malaria control programmes. Analyses were based on mtDNACOIgene sequences and four microsatellite loci of individuals collected in eight populations from the Caribbean and the Pacific regions of Colombia.ResultsTwo distinctive groups were consistently detected corresponding toCOIhaplotypes from each region. A star-shaped statistical parsimony network, significant and unimodal mismatch distribution, and significant negative neutrality tests together suggest a past demographic expansion or a selective sweep inAn. albimanusfrom the Caribbean coast approximately 21,994 years ago during the late Pleistocene. Overall moderate to low genetic differentiation was observed between populations within each region. However, a significant level of differentiation among the populations closer to Buenaventura in the Pacific region was observed. The isolation by distance model best explained genetic differentiation among the Caribbean region localities: Los Achiotes, Santa Rosa de Lima and Moñitos, but it could not explain the genetic differentiation observed between Turbo (Magdalena providence), and the Pacific region localities (Nuquí, Buenaventura, Tumaco). The patterns of differentiation in the populations from the different biogeographic provinces could not be entirely attributed to isolation by distance.ConclusionThe data provide evidence for limited past gene flow between the Caribbean and the Pacific regions, as estimated by mtDNA sequences and current gene flow patterns amongAn. albimanuspopulations as measured by MS loci which may be mainly influenced by semi-permeable natural barriers in each biogeographical region that lead to the genetic differences and effective population sizes detected. The relatively high genetic differentiation in the port city of Buenaventura may be the result of specific ecological conditions, human migration and activities and/or differences in effective population sizes. This knowledge could serve to evaluate and coordinate vector control strategies in these regions of Colombia.
Gene expression profiles of mouse spermatogenesis during recovery from irradiation
Authors: Shah Fozia J , Tanaka Masami , Nielsen John E , Iwamoto Teruaki , Kobayashi Shinichi , Skakkebæk Niels E , Leffers Henrik , Almstrup Kristian 
Published: November 2009

AbstractBackgroundIrradiation or chemotherapy that suspend normal spermatogenesis is commonly used to treat various cancers. Fortunately, spermatogenesis in many cases can be restored after such treatments but knowledge is limited about the re-initiation process. Earlier studies have described the cellular changes that happen during recovery from irradiation by means of histology. We have earlier generated gene expression profiles during induction of spermatogenesis in mouse postnatal developing testes and found a correlation between profiles and the expressing cell types. The aim of the present work was to utilize the link between expression profile and cell types to follow the cellular changes that occur during post-irradiation recovery of spermatogenesis in order to describe recovery by means of gene expression.MethodsAdult mouse testes were subjected to irradiation with 1 Gy or a fractionated radiation of two times 1 Gy. Testes were sampled every third or fourth day to follow the recovery of spermatogenesis and gene expression profiles generated by means of differential display RT-PCR. In situ hybridization was in addition performed to verify cell-type specific gene expression patterns.ResultsIrradiation of mice testis created a gap in spermatogenesis, which was initiated by loss of A1 to B-spermatogonia and lasted for approximately 10 days. Irradiation with 2 times 1 Gy showed a more pronounced effect on germ cell elimination than with 1 Gy, but spermatogenesis was in both cases completely reconstituted 42 days after irradiation. Comparison of expression profiles indicated that the cellular reconstitution appeared equivalent to what is observed during induction of normal spermatogenesis.ConclusionThe data indicates that recovery of spermatogenesis can be monitored by means of gene expression, which could aid in designing radiation treatment regimes for cancer patients leading to better restoration of spermatogenesis.
Phylogeographic reconstruction of a bacterial species with high levels of lateral gene transfer
Authors: Pearson Talima , Giffard Philip , Beckstrom-Sternberg Stephen , Auerbach Raymond , Hornstra Heidie , Tuanyok Apichai , Price Erin P , Glass Mindy B , Leadem Benjamin , Beckstrom-Sternberg James S , Allan Gerard J , Foster Jeffrey T , Wagner David M , Okinaka Richard T , Sim Siew Hoon , Pearson Ofori , Wu Zaining , Chang Jean , Kaul Rajinder , Hoffmaster Alex R , Brettin Thomas S , Robison Richard A , Mayo Mark , Gee Jay E , Tan Patrick , Currie Bart J , Keim Paul 
Published: November 2009

Abstract

Background

Phylogeographic reconstruction of some bacterial populations is hindered by low diversity coupled with high levels of lateral gene transfer. A comparison of recombination levels and diversity at seven housekeeping genes for eleven bacterial species, most of which are commonly cited as having high levels of lateral gene transfer shows that the relative contributions of homologous recombination versus mutation for Burkholderia pseudomallei is over two times higher than for Streptococcus pneumoniae and is thus the highest value yet reported in bacteria. Despite the potential for homologous recombination to increase diversity, B. pseudomallei exhibits a relative lack of diversity at these loci. In these situations, whole genome genotyping of orthologous shared single nucleotide polymorphism loci, discovered using next generation sequencing technologies, can provide very large data sets capable of estimating core phylogenetic relationships. We compared and searched 43 whole genome sequences of B. pseudomallei and its closest relatives for single nucleotide polymorphisms in orthologous shared regions to use in phylogenetic reconstruction.

Results

Bayesian phylogenetic analyses of >14,000 single nucleotide polymorphisms yielded completely resolved trees for these 43 strains with high levels of statistical support. These results enable a better understanding of a separate analysis of population differentiation among >1,700 B. pseudomallei isolates as defined by sequence data from seven housekeeping genes. We analyzed this larger data set for population structure and allele sharing that can be attributed to lateral gene transfer. Our results suggest that despite an almost panmictic population, we can detect two distinct populations of B. pseudomallei that conform to biogeographic patterns found in many plant and animal species. That is, separation along Wallace's Line, a biogeographic boundary between Southeast Asia and Australia.

Conclusion

We describe an Australian origin for B. pseudomallei, characterized by a single introduction event into Southeast Asia during a recent glacial period, and variable levels of lateral gene transfer within populations. These patterns provide insights into mechanisms of genetic diversification in B. pseudomallei and its closest relatives, and provide a framework for integrating the traditionally separate fields of population genetics and phylogenetics for other bacterial species with high levels of lateral gene transfer.
Phosphorylation regulates human T-cell leukemia virus type 1 Rex function
Authors: Kesic Matthew , Doueiri Rami , Ward Michael , Semmes O John , Green Patrick L 
Published: November 2009

Abstract

Background
Human T-cell leukemia virus type 1 (HTLV-1) is a pathogenic complex deltaretrovirus, which is the causative agent of adult T-cell leukemia/lymphoma (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis. In addition to the structural and enzymatic viral gene products, HTLV-1 encodes the positive regulatory proteins Tax and Rex along with viral accessory proteins. Tax and Rex proteins orchestrate the timely expression of viral genes important in viral replication and cellular transformation. Rex is a nucleolar-localizing shuttling protein that acts post-transcriptionally by binding and facilitating the export of the unspliced and incompletely spliced viral mRNAs from the nucleus to the cytoplasm. HTLV-1 Rex (Rex-1) is a phosphoprotein and general protein kinase inhibition correlates with reduced function. Therefore, it has been proposed that Rex-1 function may be regulated through site-specific phosphorylation.

Results
We conducted a phosphoryl mapping of Rex-1 over-expressed in transfected 293 T cells using a combination of affinity purification and liquid chromatography tandem mass spectrometry. We achieved 100% physical coverage of the Rex-1 polypeptide and identified five novel phosphorylation sites at Thr-22, Ser-36, Thr-37, Ser-97, and Ser-106. We also confirmed evidence of two previously identified residues, Ser-70 and Thr-174, but found no evidence of phosphorylation at Ser-177. The functional significance of these phosphorylation events was evaluated using a Rex reporter assay and site-directed mutational analysis. Our results indicate that phosphorylation at Ser-97 and Thr-174 is critical for Rex-1 function.

Conclusion
We have mapped completely the site-specific phosphorylation of Rex-1 identifying a total of seven residues; Thr-22, Ser-36, Thr-37, Ser-70, Ser-97, Ser-106, and Thr-174. Overall, this work is the first to completely map the phosphorylation sites in Rex-1 and provides important insight into the regulation of Rex-1 function.
Hypothesis of snake and insect venoms against Human Immunodeficiency Virus: a review
Authors: Meenakshisundaram Ramachandran , Sweni Shah , Thirumalaikolundusubramanian Ponniah 
Published: November 2009

Abstract

Background
Snake and insect venoms have been demonstrated to have beneficial effects in the treatment of certain diseases including drug resistant human immunodeficiency virus (HIV) infection. We evaluated and hypothesized the probable mechanisms of venoms against HIV.

Methods
Previous literatures published over a period of 30 years (1979-2009) were searched using the key words snake venom, insect venom, mechanisms and HIV. Mechanisms were identified and discussed.

Results & Conclusion
With reference to mechanisms of action, properties and components of snake venom such as sequence homology and enzymes (protease or L- amino acid oxidase) may have an effect on membrane protein and/or act against HIV at multiple levels or cells carrying HIV virus resulting in enhanced effect of anti-retroviral therapy (ART). This may cause a decrease in viral load and improvement in clinical as well as immunological status. Insect venom and human Phospholipase A2 (PLA2) have potential anti-viral activity through inhibition of virion entry into the cells. However, all these require further evaluation in order to establish its role against HIV as an independent one or as a supplement.
Evidence of recombination in Hepatitis C Virus populations infecting a hemophiliac patient
Authors: Moreno Pilar , Alvarez Macarena , López Lilia , Moratorio Gonzalo , Casane Didier , Castells Matías , Castro Silvia , Cristina Juan , Colina Rodney 
Published: November 2009

Abstract

Background/Aim
Hepatitis C virus (HCV) infection is an important cause of morbidity and mortality in patients affected by hereditary bleeding disorders. HCV, as others RNA virus, exploit all possible mechanisms of genetic variation to ensure their survival, such as recombination and mutation. In order to gain insight into the genetic variability of HCV virus strains circulating in hemophiliac patients, we have performed a phylogenetic analysis of HCV strains isolated from 10 patients with this kind of pathology.

Methods
Putative recombinant sequence was identified with the use of GARD program. Statistical support for the presence of a recombination event was done by the use of LARD program.

Results
A new intragenotypic recombinant strain (1b/1a) was detected in 1 out of the 10 hemophiliac patient studied. The recombination event was located at position 387 of the HCV genome (relative to strain AF009606, sub-type 1a) corresponding to the core gene region.

Conclusion
Although recombination may not appear to be common among natural populations of HCV it should be considered as a possible mechanism for generating genetic diversity in hemophiliacs patients.
Hepatitis A virus (HAV) packaging size limit
Authors: Konduru Krishnamurthy , Nakamura Siham M , Kaplan Gerardo G 
Published: November 2009

Abstract

Background
Hepatitis A virus (HAV), an atypical Picornaviridae that causes acute hepatitis in humans, grows poorly in cell culture and in general does not cause cytopathic effect. Foreign sequences have been inserted into different parts of the HAV genome. However, the packaging size limit of HAV has not been determined. The purpose of the present study is to investigate the maximum size of additional sequences that the HAV genome can tolerate without loosing infectivity.

Results

In vitro T7 polymerase transcripts of HAV constructs containing a 456-nt fragment coding for a blasticidin (Bsd) resistance gene, a 1,098-nt fragment coding for the same gene fused to GFP (GFP-Bsd), or a 1,032-nt fragment containing a hygromycin (Hyg) resistance gene cloned into the 2A-2B junction of the HAV genome were transfected into fetal Rhesus monkey kidney (FRhK4) cells. After antibiotic selection, cells transfected with the HAV construct containing the resistance gene for Bsd but not the GFP-Bsd or Hyg survived and formed colonies. To determine whether this size limitation was due to the position of the insertion, a 606 bp fragment coding for the Encephalomyocarditis virus (EMCV) internal ribosome entry site (IRES) sequence was cloned into the 5' nontranslated (NTR) region of HAV. The resulting HAV-IRES retained the EMCV IRES insertion for 1-2 passages. HAV constructs containing both the EMCV IRES at the 5' NTR and the Bsd-resistance gene at the 2A-2B junction could not be rescued in the presence of Bsd but, in the absence of antibiotic, the rescued viruses contained deletions in both inserted sequences.

Conclusion
HAV constructs containing insertions of approximately 500-600 nt but not 1,000 nt produced viable viruses, which indicated that the HAV particles can successfully package approximately 600 nt of additional sequences and maintain infectivity.
Activation of adenosine A2B receptors enhances ciliary beat frequency in mouse lateral ventricle ependymal cells
Authors: Genzen Jonathan R , Yang Dan , Ravid Katya , Bordey Angelique 
Published: November 2009

AbstractBackgroundEpendymal cells form a protective monolayer between the brain parenchyma and cerebrospinal fluid (CSF). They possess motile cilia important for directing the flow of CSF through the ventricular system. While ciliary beat frequency in airway epithelia has been extensively studied, fewer reports have looked at the mechanisms involved in regulating ciliary beat frequency in ependyma. Prior studies have demonstrated that ependymal cells express at least one purinergic receptor (P2X7). An understanding of the full range of purinergic receptors expressed by ependymal cells, however, is not yet complete. The objective of this study was to identify purinergic receptors which may be involved in regulating ciliary beat frequency in lateral ventricle ependymal cells.MethodsHigh-speed video analysis of ciliary movement in the presence and absence of purinergic agents was performed using differential interference contrast microscopy in slices of mouse brain (total number of animals = 67). Receptor identification by this pharmacological approach was corroborated by immunocytochemistry, calcium imaging experiments, and the use of two separate lines of knockout mice.ResultsCiliary beat frequency was enhanced by application of a commonly used P2X7agonist. Subsequent experiments, however, demonstrated that this enhancement was observed in both P2X7+/+and P2X7-/-mice and was reduced by pre-incubation with an ecto-5'-nucleotidase inhibitor. This suggested that enhancement was primarily due to a metabolic breakdown product acting on another purinergic receptor subtype. Further studies revealed that ciliary beat frequency enhancement was also induced by adenosine receptor agonists, and pharmacological studies revealed that ciliary beat frequency enhancement was primarily due to A2Breceptor activation. A2Bexpression by ependymal cells was subsequently confirmed using A2B-/-/β-galactosidase reporter gene knock-in mice.ConclusionThis study demonstrates that A2Breceptor activation enhances ciliary beat frequency in lateral ventricle ependymal cells. Ependymal cell ciliary beat frequency regulation may play an important role in cerebral fluid balance and cerebrospinal fluid dynamics.
Effective Relief of Neuropathic Pain by Adeno-Associated Virus-Mediated Expression of a Small Hairpin Rna against GTP Cyclohydrolase 1
Authors: Kim Sung Jin , Lee Won Il , Lee Yoon Sun , Kim Dong Hou , Chang Jin Woo , Kim Seong Who , Lee Heuiran 
Published: November 2009

Background Recent studies show that transcriptional activation of GTP cyclohydrolase I (GCH1) in dorsal root ganglia (DRG) is significantly involved in the development and persistency of pain symptoms. We thus hypothesize that neuropathic pain may be attenuated by down-regulation of GCH1 expression, and propose a gene silencing system for this purpose. Results To interrupt GCH1 synthesis, we designed a bidirectional recombinant adeno-associated virus encoding both a small hairpin RNA against GCH1 and a GFP reporter gene (rAAV-shGCH1). After rAAV-shGCH1 was introduced into the sciatic nerve prior to or following pain-inducing surgery, therapeutic efficacy and the underlying mechanisms were subsequently validated in animal models. The GFP expression data indicates that rAAV effectively delivered transgenes to DRG. Subsequently reduced GCH1 expression was evident from immunohistochemistry and western-blotting analysis. Along with the down-regulation of GCH1, the von Frey test correspondingly indicated a sharp decline in pain symptoms upon both pre- and post-treatment with rAAV-shGCH1. Interestingly, GCH1 down-regulation additionally led to decreased microglial activation in the dorsal horn, implying an association between pain attenuation and reduced inflammation. Conclusion Therefore, the data suggests that GCH1 levels can be reduced by introducing rAAV-shGCH1, leading to pain relief. Based on the results, we propose that GCH1 modulation may be developed as a clinically applicable gene therapy strategy to treat neuropathic pain.
Conditional Gene Deletion Reveals Functional Redundancy of GABABReceptors in Peripheral NociceptorsIn Vivo
Authors: Gangadharan Vijayan , Agarwal Nitin , Brugger Stefan , Tegeder Imgard , Bettler Bernhard , Kuner Rohini , Kurejova Martina 
Published: November 2009

Backgroundγ-aminobutyric acid (GABA) is an important inhibitory neurotransmitter which mainly mediates its effects on neurons via ionotropic (GABAA) and metabotropic (GABAB) receptors. GABABreceptors are widely expressed in the central and the peripheral nervous system. Although there is evidence for a key function of GABABreceptors in the modulation of pain, the relative contribution of peripherally- versus centrally-expressed GABABreceptors is unclear.ResultsIn order to elucidate the functional relevance of GABABreceptors expressed in peripheral nociceptive neurons in pain modulation we generated and analyzed conditional mouse mutants lacking functional GABAB(1)subunit specifically in nociceptors, preserving expression in the spinal cord and brain (SNS-GABAB(1)−/−mice). Lack of the GABAB(1)subunit precludes the assembly of functional GABABreceptor. We analyzed SNS-GABAB(1)−/−mice and their control littermates in several models of acute and neuropathic pain. Electrophysiological studies on peripheral afferents revealed higher firing frequencies in SNS-GABAB(1)−/−mice compared to corresponding control littermates. However no differences were seen in basal nociceptive sensitivity between these groups. The development of neuropathic and chronic inflammatory pain was similar across the two genotypes. The duration of nocifensive responses evoked by intraplantar formalin injection was prolonged in the SNS-GABAB(1)−/−animals as compared to their control littermates. Pharmacological experiments revealed that systemic baclofen-induced inhibition of formalin-induced nociceptive behaviors was not dependent upon GABAB(1)expression in nociceptors.ConclusionThis study addressed contribution of GABABreceptors expressed on primary afferent nociceptive fibers to the modulation of pain. We observed that neither the development of acute and chronic pain nor the analgesic effects of a systematically-delivered GABABagonist was significantly changed upon a specific deletion of GABABreceptors from peripheral nociceptive neurons in vivo. This lets us conclude that GABABreceptors in the peripheral nervous system play a less important role than those in the central nervous system in the regulation of pain.