bluuebunny/crossref_metadata_2025_split huggingface dataset:
Somatic sex-specific transcriptome differences in Drosophila revealed by whole transcriptome sequencing
Authors: Chang Peter L , Dunham Joseph P , Nuzhdin Sergey V , Arbeitman Michelle N 
Published: July 2011

Abstract

Background
Understanding animal development and physiology at a molecular-biological level has been advanced by the ability to determine at high resolution the repertoire of mRNA molecules by whole transcriptome resequencing. This includes the ability to detect and quantify rare abundance transcripts and isoform-specific mRNA variants produced from a gene.
The sex hierarchy consists of a pre-mRNA splicing cascade that directs the production of sex-specific transcription factors that specify nearly all sexual dimorphism. We have used deep RNA sequencing to gain insight into how the Drosophila sex hierarchy generates somatic sex differences, by examining gene and transcript isoform expression differences between the sexes in adult head tissues.

Results
Here we find 1,381 genes that differ in overall expression levels and 1,370 isoform-specific transcripts that differ between males and females. Additionally, we find 512 genes not regulated downstream of transformer that are significantly more highly expressed in males than females. These 512 genes are enriched on the × chromosome and reside adjacent to dosage compensation complex entry sites, which taken together suggests that their residence on the × chromosome might be sufficient to confer male-biased expression. There are no transcription unit structural features, from a set of features, that are robustly significantly different in the genes with significant sex differences in the ratio of isoform-specific transcripts, as compared to random isoform-specific transcripts, suggesting that there is no single molecular mechanism that generates isoform-specific transcript differences between the sexes, even though the sex hierarchy is known to include three pre-mRNA splicing factors.

Conclusions
We identify thousands of genes that show sex-specific differences in overall gene expression levels, and identify hundreds of additional genes that have differences in the abundance of isoform-specific transcripts. No transcription unit structural feature was robustly enriched in the sex-differentially expressed transcript isoforms. Additionally, we found that many genes with male-biased expression were enriched on the × chromosome and reside adjacent to dosage compensation entry sites, suggesting that differences in sex chromosome composition contributes to dimorphism in gene expression. Taken together, this study provides new insight into the molecular underpinnings of sexual differentiation.
Cocaine- and amphetamine-regulated transcript promotes the differentiation of mouse bone marrow-derived mesenchymal stem cells into neural cells
Authors: Liu Zhuo , Huang Danqing , Zhang Meijuan , Chen Zhibin , Jin Jiali , Huang Siyuan , Zhang Zhuo , Wang Zhongyuan , Chen Lei , Chen Ling , Xu Yun 
Published: July 2011

Abstract

Background
Neural tissue has limited potential to self-renew after neurological damage. Cell therapy using BM-MSCs (bone marrow mesenchymal stromal cells) seems like a promising approach for the treatment of neurological diseases. However, the neural differentiation of stem cells influenced by massive factors and interactions is not well studied at present.

Results
In this work, we isolated and identified MSCs from mouse bone marrow. Co-cultured with CART (0.4 nM) for six days, BM-MSCs were differentiated into neuron-like cells by the observation of optical microscopy. Immunofluorescence demonstrated that the differentiated BM-MSCs expressed neural specific markers including MAP-2, Nestin, NeuN and GFAP. In addition, NeuN positive cells could co-localize with TH or ChAT by double-labled immunofluorescence and Nissl bodies were found in several differentiated cells by Nissl stain. Furthermore, BDNF and NGF were increased by CART using RT-PCR.

Conclusion
This study demonstrated that CART could promote the differentiation of BM-MSCs into neural cells through increasing neurofactors, including BNDF and NGF. Combined application of CART and BM-MSCs may be a promising cell-based therapy for neurological diseases.
Primary care providers' perspective on prescribing opioids to older adults with chronic non-cancer pain: A qualitative study
Authors: Spitz Aerin , Moore Alison A , Papaleontiou Maria , Granieri Evelyn , Turner Barbara J , Reid M Carrington 
Published: July 2011

Abstract

Background
The use of opioid medications as treatment for chronic non-cancer pain remains controversial. Little information is currently available regarding healthcare providers' attitudes and beliefs about this practice among older adults. This study aimed to describe primary care providers' experiences and attitudes towards, as well as perceived barriers and facilitators to prescribing opioids as a treatment for chronic pain among older adults.

Methods
Six focus groups were conducted with a total of 23 physicians and three nurse practitioners from two academically affiliated primary care practices and three community health centers located in New York City. Focus groups were audiotape recorded and transcribed. The data were analyzed using directed content analysis; NVivo software was used to assist in the quantification of identified themes.

Results
Most participants (96%) employed opioids as therapy for some of their older patients with chronic pain, although not as first-line therapy. Providers cited multiple barriers, including fear of causing harm, the subjectivity of pain, lack of education, problems converting between opioids, and stigma. New barriers included patient/family member reluctance to try an opioid and concerns about opioid abuse by family members/caregivers. Studies confirming treatment benefit, validated tools for assessing risk and/or dosing for comorbidities, improved conversion methods, patient education, and peer support could facilitate opioid prescribing. Participants voiced greater comfort using opioids in the setting of delivering palliative or hospice care versus care of patients with chronic pain, and expressed substantial frustration managing chronic pain.

Conclusions
Providers perceive multiple barriers to prescribing opioids to older adults with chronic pain, and use these medications cautiously. Establishing the long-term safety and efficacy of these medications, generating improved prescribing methods, and implementing provider and patient educational interventions could help to improve the management of chronic pain in later life.
Intrinsic resistance to tyrosine kinase inhibitors is associated with poor clinical outcome in metastatic renal cell carcinoma
Authors: Busch Jonas , Seidel Christoph , Weikert Steffen , Wolff Ingmar , Kempkensteffen Carsten , Weinkauf Lisa , Hinz Stefan , Magheli Ahmed , Miller Kurt , Grünwald Viktor 
Published: July 2011

Abstract

Background
Data on sequential therapy in patients with metastatic renal cell carcinoma (mRCC) and intrinsic resistance to receptor tyrosine kinase inhibitor (rTKI) treatment remains vague.

Methods
We retrospectively studied treatment characteristics and outcome of mRCC patients refractory to first rTKI therapy.

Results
Thirty-five mRCC patients (male, 18; female, 11) with primary resistance to first rTKI therapy (sunitinib, n = 28; sorafenib, n = 7) and a median treatment interval of 2.4 months (1 - 4.6) were identified. In 22 patients, progressive disease (PD) was determined by a new metastatic lesion. Of these, 16 patients received subsequent therapy with 12 patients remaining refractory and 4 patients achieving disease stabilization. In 13 patients continuous growth of existing metastatic lesions determined PD. Of these, 9 received sequential therapy with 6 achieving disease stabilization. Altogether, 25 patients were treated sequentially (rTKI: n = 15; mTOR-inhibitor: n = 10) and achieved a median PFS of 3.2 months (range, 1-16.6). Fifteen patients failed to respond to either line of therapy. Disease control was not associated with type of subsequent therapy. Median OS was 14.9 months (CI: 5.5-24.4).

Conclusion
Intrinsic resistance to rTKI is associated with a low chance of response to sequential therapy and a poor prognosis in mRCC patients.
A cyclopalladated complex interacts with mitochondrial membrane thiol-groups and induces the apoptotic intrinsic pathway in murine and cisplatin-resistant human tumor cells
Authors: Serrano Fabiana A , Matsuo Alisson L , Monteforte Priscila T , Bechara Alexandre , Smaili Soraya S , Santana Débora P , Rodrigues Tiago , Pereira Felipe V , Silva Luis S , Machado Joel , Santos Edson L , Pesquero João B , Martins Rafael M , Travassos Luiz R , Caires Antonio CF , Rodrigues Elaine G 
Published: July 2011

AbstractBackgroundSystemic therapy for cancer metastatic lesions is difficult and generally renders a poor clinical response. Structural analogs of cisplatin, the most widely used synthetic metal complexes, show toxic side-effects and tumor cell resistance. Recently, palladium complexes with increased stability are being investigated to circumvent these limitations, and a biphosphinic cyclopalladated complex {Pd2[S(-)C2, N-dmpa]2(μ-dppe)Cl2} named C7a efficiently controls the subcutaneous development of B16F10-Nex2 murine melanoma in syngeneic mice. Presently, we investigated the melanoma cell killing mechanism induced by C7a, and extended preclinical studies.MethodsB16F10-Nex2 cells were treatedin vitrowith C7a in the presence/absence of DTT, and several parameters related to apoptosis induction were evaluated. Preclinical studies were performed, and mice were endovenously inoculated with B16F10-Nex2 cells, intraperitoneally treated with C7a, and lung metastatic nodules were counted. The cytotoxic effects and the respiratory metabolism were also determined in human tumor cell lines treatedin vitrowith C7a.ResultsCyclopalladated complex interacts with thiol groups on the mitochondrial membrane proteins, causes dissipation of the mitochondrial membrane potential, and induces Bax translocation from the cytosol to mitochondria, colocalizing with a mitochondrial tracker. C7a also induced an increase in cytosolic calcium concentration, mainly from intracellular compartments, and a significant decrease in the ATP levels. Activation of effector caspases, chromatin condensation and DNA degradation, suggested that C7a activates the apoptotic intrinsic pathway in murine melanoma cells. In the preclinical studies, the C7a complex protected against murine metastatic melanoma and induced death in several human tumor cell lineagesin vitro, including cisplatin-resistant ones. The mitochondria-dependent cell death was also induced by C7a in human tumor cells.ConclusionsThe cyclopalladated C7a complex is an effective chemotherapeutic anticancer compound against primary and metastatic murine and human tumors, including cisplatin-resistant cells, inducing apoptotic cell death via the intrinsic pathway.
Peptide binding prediction for the human class II MHC allele HLA-DP2: a molecular docking approach
Authors: Patronov Atanas , Dimitrov Ivan , Flower Darren R , Doytchinova Irini 
Published: July 2011

AbstractBackgroundMHC class II proteins bind oligopeptide fragments derived from proteolysis of pathogen antigens, presenting them at the cell surface for recognition by CD4+ T cells. Human MHC class II alleles are grouped into three loci: HLA-DP, HLA-DQ and HLA-DR. In contrast to HLA-DR and HLA-DQ, HLA-DP proteins have not been studied extensively, as they have been viewed as less important in immune responses than DRs and DQs. However, it is now known that HLA-DP alleles are associated with many autoimmune diseases. Quite recently, the X-ray structure of the HLA-DP2 molecule (DPA*0103, DPB1*0201) in complex with a self-peptide derived from the HLA-DR α-chain has been determined. In the present study, we applied a validated molecular docking protocol to a library of 247 modelled peptide-DP2 complexes, seeking to assess the contribution made by each of the 20 naturally occurred amino acids at each of the nine binding core peptide positions and the four flanking residues (two on both sides).ResultsThe free binding energies (FBEs) derived from the docking experiments were normalized on a position-dependent (npp) and on an overall basis (nap), and two docking score-based quantitative matrices (DS-QMs) were derived: QMnpp and QMnap. They reveal the amino acid preferences at each of the 13 positions considered in the study. Apart from the leading role of anchor positions p1 and p6, the binding to HLA-DP2 depends on the preferences at p2. No effect of the flanking residues was found on the peptide binding predictions to DP2, although all four of them show strong preferences for particular amino acids. The predictive ability of the DS-QMs was tested using a set of 457 known binders to HLA-DP2, originating from 24 proteins. The sensitivities of the predictions at five different thresholds (5%, 10%, 15%, 20% and 25%) were calculated and compared to the predictions made by the NetMHCII and IEDB servers. Analysis of the DS-QMs indicated an improvement in performance. Additionally, DS-QMs identified the binding cores of several known DP2 binders.ConclusionsThe molecular docking protocol, as applied to a combinatorial library of peptides, models the peptide-HLA-DP2 protein interaction effectively, generating reliable predictions in a quantitative assessment. The method is structure-based and does not require extensive experimental sequence-based data. Thus, it is universal and can be applied to model any peptide - protein interaction.
Effect of silibinin on endothelial dysfunction and ADMA levels in obese diabetic mice
Authors: Li Volti Giovanni , Salomone Salvatore , Sorrenti Valeria , Mangiameli Andrea , Urso Vincenzo , Siarkos Ilias , Galvano Fabio , Salamone Federico 
Published: July 2011

Abstract

Background
Cardiovascular diseases (CVD) in diabetic patients have endothelial dysfunction as a key pathogenetic event. Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase (NOS), plays a pivotal role in endothelial dysfunction. Different natural polyphenols have been shown to preserve endothelial function and prevent CVD. In this study, we assessed the effect of silibinin, a widely used flavonolignan from milk thistle, on ADMA levels and endothelial dysfunction in db/db mice.

Methods
Eight-week-old db/db mice were administrated a 20 mg/Kg i.p. daily dose of silibinin (n = 6) or vehicle (n = 6) for four weeks. Heterozygous lean db/m mice served as control. Plasma, aorta and liver ADMA levels were determined by ELISA. Vascular reactivity to phenilephrine (PE), acetylcholine (ACh), sodium nitroprusside (SNP) and ADMA was assessed in isolated aortic segments, in wire myograph.

Results
Plasma and aorta ADMA levels were higher in db/db than in control lean mice. Silibinin administration markedly decreased plasma ADMA; consistently, aorta ADMA was reduced in silibinin-treated animals. Plasma and aorta ADMA levels exhibited a positive correlation, whereas liver ADMA was inversely correlated with both plasma and aorta ADMA concentrations. Endothelium-(NO)-dependent vasodilatation to ACh was impaired in db/db mice and was restored in the silibinin group, in accordance with the observed reduction of plasma and vascular levels of ADMA. Endothelium-independent vasodilatation to SNP was not modified by silibinin administration; contractile tone induced in isolated aorta from db/db mice by challenging with exogenous ADMA was not affected by the treatment.

Conclusions
Silibinin markedly improves endothelial dysfunction in db/db mice by reducing circulating and vascular ADMA levels. Clinical studies are warranted to assess the efficacy of silibinin for cardiovascular protection.
Climate forcing and desert malaria: the effect of irrigation
Authors: Baeza Andres , Bouma Menno J , Dobson Andy P , Dhiman Ramesh , Srivastava Harish C , Pascual Mercedes 
Published: July 2011

Abstract

Background
Rainfall variability and associated remote sensing indices for vegetation are central to the development of early warning systems for epidemic malaria in arid regions. The considerable change in land-use practices resulting from increasing irrigation in recent decades raises important questions on concomitant change in malaria dynamics and its coupling to climate forcing. Here, the consequences of irrigation level for malaria epidemics are addressed with extensive time series data for confirmed Plasmodium falciparum monthly cases, spanning over two decades for five districts in north-west India. The work specifically focuses on the response of malaria epidemics to rainfall forcing and how this response is affected by increasing irrigation.

Methods and Findings
Remote sensing data for the Normalized Difference Vegetation Index (NDVI) are used as an integrated measure of rainfall to examine correlation maps within the districts and at regional scales. The analyses specifically address whether irrigation has decreased the coupling between malaria incidence and climate variability, and whether this reflects (1) a breakdown of NDVI as a useful indicator of risk, (2) a weakening of rainfall forcing and a concomitant decrease in epidemic risk, or (3) an increase in the control of malaria transmission. The predictive power of NDVI is compared against that of rainfall, using simple linear models and wavelet analysis to study the association of NDVI and malaria variability in the time and in the frequency domain respectively.

Conclusions
The results show that irrigation dampens the influence of climate forcing on the magnitude and frequency of malaria epidemics and, therefore, reduces their predictability. At low irrigation levels, this decoupling reflects a breakdown of local but not regional NDVI as an indicator of rainfall forcing. At higher levels of irrigation, the weakened role of climate variability may be compounded by increased levels of control; nevertheless this leads to no significant decrease in the actual risk of disease. This implies that irrigation can lead to more endemic conditions for malaria, creating the potential for unexpectedly large epidemics in response to excess rainfall if these climatic events coincide with a relaxation of control over time. The implications of our findings for control policies of epidemic malaria in arid regions are discussed.
Plasmodium falciparum glutamate dehydrogenase a is dispensable and not a drug target during erythrocytic development
Authors: Storm Janet , Perner Jan , Aparicio Isabela , Patzewitz Eva-Maria , Olszewski Kellen , Llinas Manuel , Engel Paul C , Müller Sylke 
Published: July 2011

Abstract

Background

Plasmodium falciparum contains three genes encoding potential glutamate dehydrogenases. The protein encoded by gdha has previously been biochemically and structurally characterized. It was suggested that it is important for the supply of reducing equivalents during intra-erythrocytic development of Plasmodium and, therefore, a suitable drug target.

Methods
The gene encoding the NADP(H)-dependent GDHa has been disrupted by reverse genetics in P. falciparum and the effect on the antioxidant and metabolic capacities of the resulting mutant parasites was investigated.

Results
No growth defect under low and elevated oxygen tension, no up- or down-regulation of a number of antioxidant and NADP(H)-generating proteins or mRNAs and no increased levels of GSH were detected in the D10Δgdha
parasite lines. Further, the fate of the carbon skeleton of [13C] labelled glutamine was assessed by metabolomic studies, revealing no differences in the labelling of α-ketoglutarate and other TCA pathway intermediates between wild type and mutant parasites.

Conclusions
First, the data support the conclusion that D10Δgdha
parasites are not experiencing enhanced oxidative stress and that GDHa function may not be the provision of NADP(H) for reductive reactions. Second, the results imply that the cytosolic, NADP(H)-dependent GDHa protein is not involved in the oxidative deamination of glutamate but that the protein may play a role in ammonia assimilation as has been described for other NADP(H)-dependent GDH from plants and fungi. The lack of an obvious phenotype in the absence of GDHa may point to a regulatory role of the protein providing glutamate (as nitrogen storage molecule) in situations where the parasites experience a limiting supply of carbon sources and, therefore, under in vitro conditions the enzyme is unlikely to be of significant importance. The data imply that the protein is not a suitable target for future drug development against intra-erythrocytic parasite development.
Vaginal treatment of endometrial cancer: role in the elderly
Authors: Moscarini Massimo , Ricciardi Enzo , Quarto Alessandro , Maniglio Paolo , Caserta Donatella 
Published: July 2011

Abstract

Background
To compare abdominal hysterectomy, the most currently used for treating cancer of the endometrium, to the vaginal hysterectomy in term of survival, morbidity and failure rates.

Methods
We retrospectively analyzed 68 cases divided into two sub-groups. A study group of 31 cases received vaginal surgery; a control group of 37 cases was treated with a laparotomy. Mean operative time, median hospital stay, intra- and post-operative complications, DFS and OS time as well as occurrence of local or distant recurrences have been evaluated and reported. Cases included patients with a higher rate of medical morbidities (p = 0.01) than controls.

Results
Mean age was 76.2 and 70.4 years in the vaginal (V) group and abdominal (A) group respectively. Mean operative time was longer for the group A. Group V patients had a lower mean post-operative hospital stay (p < 0.05). Differences in the two groups regarding intra- and post-operative complications, occurrence of local or distant recurrences and DFS time were not statistically significant. Disease specific survival time at 5 years scored 97% for group V, and 97% for group A.

Conclusions
Results show how vaginal approach had a similar outcome in selected patients. Vaginal surgery could therefore be the proper choice in patients with early stages and lower surgical risk, in addition to elderly patients exposed to a higher surgical risk.
Primary Leiomyoma of the pleura
Authors: Qiu Xiaoming , Zhu Daxin , Wei Sen , Chen Gang , Chen Jun , Zhou Qinghua 
Published: July 2011

Abstract
Primary leiomyoma of the pleura is extremely rare. A 45-year-old man presented with a complaint of right chest pain. Chest computed tomography demonstrated a solid, round pleural mass in the right anterior chest wall. The mass was completely resected, and histopathological examination revealed a localized primary pleural leiomyoma. The patient was followed and has been disease-free for over 15 months. This is the first report of primary leiomyoma of the pleura in China. A review of the literature on primary leiomyoma of the pleura is presented.