bluuebunny/crossref_metadata_2025 huggingface dataset:
Posterior Circulation Ischemic Stroke—Clinical Characteristics, Risk Factors, and Subtypes in a North Indian Population
Authors: Mehndiratta Manmohan , Pandey Sanjay , Nayak Rajeev , Alam Anwar
Published: March 2012

Background and Purpose: Posterior circulation stroke accounts for approximately 20% of all strokes with varied clinical presentation, which differ from strokes in anterior circulation, with reference to etiology, clinical features, and prognosis. Short penetrating and circumferential branches in the posterior circulation supply the brain stem, thalamus, cerebellum, occipital, and medial temporal lobes. Materials and Methods: We prospectively analyzed 80 participants of posterior circulation ischemic stroke from a registry of 944 participants attending a tertiary care referral university hospital. Patients were analyzed for demographics, stroke risk factors, clinical characteristics, neuroimaging, and stroke subtypes. Results: Posterior circulation ischemic stroke accounted for 80 (8.5%) of 944 of all strokes and 80 (10.45%) of 765 of ischemic stroke. Sixty-three were males with mean age 51.7 ± 14.4 years. Twenty-one participants were young (defined as age less than 45 years). Hypertension was found to be the most common risk factor (63.75%). Vertigo was the most common clinical symptom reported in 45 (56.25%) cases. Sixty-eight (85%) patients had large artery disease, 8 (10%) had documented cardioembolic source, 3 (3.75%) small artery disease, and 2 (2.5%) vasculitis. Posterior cerebral artery was most commonly involved. Topographically distal intracranial involvement was most frequent (66.25%) followed by proximal (30%) and middle intracranial territory (3.75%). Conclusions: Our study demonatrated the occurrence of posterior circulation stroke in relatively younger age group compared to the Western world. We also found higher percentage of large artery disease, while cardioembolism as a less frequent cause of posterior circulation ischemic stroke in North Indian population. Distal territory involvement was most common in our study.
Regulation of Th1/Th2 polarization by tissue inhibitor of metalloproteinase-3 via modulating dendritic cells
Authors: Shao Qianqian , Ning Hao , Lv Jiaju , Liu Yanguo , Zhao Xin , Ren Guangwen , Feng Alei , Xie Qi , Sun Jintang , Song Bingfeng , Yang Yongmei , Gao Wenjuan , Ding Kejia , Yang Meixiang , Hou Ming , Peng Jun , Qu Xun
Published: March 2012

Tissue inhibitor of metalloproteinase-3 (TIMP-3) is one of a family of proteins inhibiting matrix metalloproteinases, which has also been identified as a mediator for checking inflammation. Meanwhile, it is well known that inflammation causes the activation of the immune response. However, it is not clear whether TIMP-3 plays a role in the immune system. In the present study, we demonstrated a novel function of TIMP-3 in Th1/Th2 polarization through its influence on the antigen-presenting cells. First, TIMP-3 was found strikingly up-regulated by IL-4 during the differentiation of human dendritic cells via the p38MAPK pathway. Second, the expression of costimulatory molecule-CD86 was repressed by TIMP-3. Besides, the induction of IL-12 in matured dendritic cells was significantly inhibited in a PI3K-dependent manner. Furthermore, dendritic cells matured in the presence of TIMP-3 could stimulate allogeneic naive T helper (Th) cells to display a prominent Th2 polarization. Importantly, in an autoimmune disorder–primary immune thrombocytopenia, TIMP-3 showed a statistically positive correlation with IL-4 and platelet count, but a negative correlation with IFN-γ in patient blood samples. Collectively, these in vitro and in vivo data clearly suggested a novel role of TIMP-3 in Th1/Th2 balance in humans.
Randomized, multicenter, phase 2 study (EVOLUTION) of combinations of bortezomib, dexamethasone, cyclophosphamide, and lenalidomide in previously untreated multiple myeloma
Authors: Kumar Shaji , Flinn Ian , Richardson Paul G. , Hari Parameswaran , Callander Natalie , Noga Stephen J. , Stewart A. Keith , Turturro Francesco , Rifkin Robert , Wolf Jeffrey , Estevam Jose , Mulligan George , Shi Hongliang , Webb Iain J. , Rajkumar S. Vincent
Published: March 2012

Combinations of bortezomib (V) and dexamethasone (D) with either lenalidomide (R) or cyclophosphamide (C) have shown significant efficacy. This randomized phase 2 trial evaluated VDC, VDR, and VDCR in previously untreated multiple myeloma (MM). Patients received V 1.3 mg/m2 (days 1, 4, 8, 11) and D 40 mg (days 1, 8, 15), with either C 500 mg/m2 (days 1, 8) and R 15 mg (days 1-14; VDCR), R 25 mg (days 1-14; VDR), C 500 mg/m2 (days 1, 8; VDC) or C 500 mg/m2 (days 1, 8, 15; VDC-mod) in 3-week cycles (maximum 8 cycles), followed by maintenance with V 1.3 mg/m2 (days 1, 8, 15, 22) for four 6-week cycles (all arms) ≥ very good partial response was seen in 58%, 51%, 41%, and 53% (complete response rate of 25%, 24%, 22%, and 47%) of patients (VDCR, VDR, VCD, and VCD-mod, respectively); the corresponding 1-year progression-free survival was 86%, 83%, 93%, and 100%, respectively. Common adverse events included hematologic toxicities, peripheral neuropathy, fatigue, and gastrointestinal disturbances. All regimens were highly active and well tolerated in previously untreated MM, and, based on this trial, VDR and VCD-mod are preferred for clinical practice and further comparative testing. No substantial advantage was noted with VDCR over the 3-drug combinations. This trial is registered at www.clinicaltrials.gov (NCT00507442).
Prevalence and predictors of urinary tract infection and severe malaria among febrile children attending Makongoro health centre in Mwanza city, North-Western Tanzania
Authors: Msaki Bahati P , Mshana Stephen E , Hokororo Adolfina , Mazigo Humphrey D , Morona Domenica
Published: March 2012

Background

In malaria endemic areas, fever has been used as an entry point for presumptive treatment of malaria. At present, the decrease in malaria transmission in Africa implies an increase in febrile illnesses related to other causes among underfives. Moreover, it is estimated that more than half of the children presenting with fever to public clinics in Africa do not have a malaria infection. Thus, for a better management of all febrile illnesses among under-fives, it becomes relevant to understand the underlying aetiology of the illness. The present study was conducted to determine the relative prevalence and predictors of P. falciparum malaria, urinary tract infections and bacteremia among under-fives presenting with a febrile illness at the Makongoro Primary Health Centre, North-Western Tanzania.

Methods

From February to June 2011, a cross-sectional analytical survey was conducted among febrile children less than five years of age. Demographic and clinical data were collected using a standardized pre-tested questionnaire. Blood and urine culture was done, followed by the identification of isolates using in-house biochemical methods. Susceptibility patterns to commonly used antibiotics were investigated using the disc diffusion method. Giemsa stained thin and thick blood smears were examined for any malaria parasites stages.

Results

A total of 231 febrile under-fives were enrolled in the study. Of all the children, 20.3% (47/231, 95%CI, 15.10-25.48), 9.5% (22/231, 95%CI, 5.72-13.28) and 7.4% (17/231, 95%CI, 4.00-10.8) had urinary tract infections, P. falciparum malaria and bacteremia respectively. In general, 11.5% (10/87, 95%CI, 8.10-14.90) of the children had two infections and only one child had all three infections. Predictors of urinary tract infections (UTI) were dysuria (OR = 12.51, 95% CI, 4.28-36.57, P < 0.001) and body temperature (40-41 C) (OR = 12.54, 95% CI, 4.28-36.73, P < 0.001). Predictors of P. falciparum severe malaria were pallor (OR = 4.66 95%CI, 1.21-17.8, P = 0.025) and convulsion (OR = 102, 95% CI, 10-996, P = 0.001). Escherichia coli were the common gram negative isolates from urine (72.3%, 95% CI, 66.50-78.10) and blood (40%, 95%CI, and 33.70-46.30). Escherichia coli from urine were 100% resistant to ampicillin, 97% resistant to co-trimoxazole, 85% resistant to augmentin and 32.4% resistant to gentamicin; and they were 100%, 91.2% and 73.5% sensitive to meropenem, ciprofloxacin and ceftriaxone respectively.

Conclusion

Urinary tract infection caused by multi drug resistant Escherichia coli was the common cause of febrile illness in our setting. Improvement of malaria diagnosis and its differential diagnosis from other causes of febrile illnesses may provide effective management of febrile illnesses among children in Tanzania
Visualisation of variable binding pockets on protein surfaces by probabilistic analysis of related structure sets
Authors: Ashford Paul , Moss David S , Alex Alexander , Yeap Siew K , Povia Alice , Nobeli Irene , Williams Mark A
Published: March 2012

Background

Protein structures provide a valuable resource for rational drug design. For a protein with no known ligand, computational tools can predict surface pockets that are of suitable size and shape to accommodate a complementary small-molecule drug. However, pocket prediction against single static structures may miss features of pockets that arise from proteins' dynamic behaviour. In particular, ligand-binding conformations can be observed as transiently populated states of the apo protein, so it is possible to gain insight into ligand-bound forms by considering conformational variation in apo proteins. This variation can be explored by considering sets of related structures: computationally generated conformers, solution NMR ensembles, multiple crystal structures, homologues or homology models. It is non-trivial to compare pockets, either from different programs or across sets of structures. For a single structure, difficulties arise in defining particular pocket's boundaries. For a set of conformationally distinct structures the challenge is how to make reasonable comparisons between them given that a perfect structural alignment is not possible.

Results

We have developed a computational method, Provar, that provides a consistent representation of predicted binding pockets across sets of related protein structures. The outputs are probabilities that each atom or residue of the protein borders a predicted pocket. These probabilities can be readily visualised on a protein using existing molecular graphics software. We show how Provar simplifies comparison of the outputs of different pocket prediction algorithms, of pockets across multiple simulated conformations and between homologous structures. We demonstrate the benefits of use of multiple structures for protein-ligand and protein-protein interface analysis on a set of complexes and consider three case studies in detail: i) analysis of a kinase superfamily highlights the conserved occurrence of surface pockets at the active and regulatory sites; ii) a simulated ensemble of unliganded Bcl2 structures reveals extensions of a known ligand-binding pocket not apparent in the apo crystal structure; iii) visualisations of interleukin-2 and its homologues highlight conserved pockets at the known receptor interfaces and regions whose conformation is known to change on inhibitor binding.

Conclusions

Through post-processing of the output of a variety of pocket prediction software, Provar provides a flexible approach to the analysis and visualization of the persistence or variability of pockets in sets of related protein structures.
Genome wide expression profiling of two accession of G. herbaceum L. in response to drought
Authors: Ranjan Alok , Nigam Deepti , Asif Mehar H , Singh Ruchi , Ranjan Sanjay , Mantri Shrikant , Pandey Neha , Trivedi Ila , Rai Krishan Mohan , Jena Satya N , Koul Bhupendra , Tuli Rakesh , Pathre Uday V , Sawant Samir V
Published: March 2012

Background

Genome-wide gene expression profiling and detailed physiological investigation were used for understanding the molecular mechanism and physiological response of Gossypium herbaceum, which governs the adaptability of plants in drought conditions. Recently, microarray-based gene expression analysis is commonly used to decipher genes and genetic networks controlling the traits of interest. However, the results of such an analysis are often plagued due to a limited number of genes (probe sets) on microarrays. On the other hand, pyrosequencing of a transcriptome has the potential to detect rare as well as a large number of transcripts in the samples quantitatively. We used Affymetrix microarray as well as Roche's GS-FLX transcriptome sequencing for a comparative analysis of cotton transcriptome in leaf tissues under drought conditions.

Results

Fourteen accessions of Gossypium herbaceum were subjected to mannitol stress for preliminary screening; two accessions, namely Vagad and RAHS-14, were selected as being the most tolerant and most sensitive to osmotic stress, respectively. Affymetrix cotton arrays containing 24,045 probe sets and Roche's GS-FLX transcriptome sequencing of leaf tissue were used to analyze the gene expression profiling of Vagad and RAHS-14 under drought conditions. The analysis of physiological measurements and gene expression profiling showed that Vagad has the inherent ability to sense drought at a much earlier stage and to respond to it in a much more efficient manner than does RAHS-14. Gene Ontology (GO) studies showed that the phenyl propanoid pathway, pigment biosynthesis, polyketide biosynthesis, and other secondary metabolite pathways were enriched in Vagad under control and drought conditions as compared with RAHS-14. Similarly, GO analysis of transcriptome sequencing showed that the GO terms responses to various abiotic stresses were significantly higher in Vagad. Among the classes of transcription factors (TFs) uniquely expressed in both accessions, RAHS-14 showed the expression of ERF and WRKY families. The unique expression of ERFs in response to drought conditions reveals that RAHS-14 responds to drought by inducing senescence. This was further supported by transcriptome analysis which revealed that RAHS-14 responds to drought by inducing many transcripts related to senescence and cell death.

Conclusion

The comparative genome-wide gene expression profiling study of two accessions of G.herbaceum under drought stress deciphers the differential patterns of gene expression, including TFs and physiologically relevant processes. Our results indicate that drought tolerance observed in Vagad is not because of a single molecular reason but is rather due to several unique mechanisms which Vagad has developed as an adaptation strategy.
The construction of a high-density linkage map for identifying SNP markers that are tightly linked to a nuclear-recessive major gene for male sterility in Cryptomeria japonica D. Don
Authors: Moriguchi Yoshinari , Ujino-Ihara Tokuko , Uchiyama Kentaro , Futamura Norihiro , Saito Maki , Ueno Saneyoshi , Matsumoto Asako , Tani Naoki , Taira Hideaki , Shinohara Kenji , Tsumura Yoshihiko
Published: March 2012

Background

High-density linkage maps facilitate the mapping of target genes and the construction of partial linkage maps around target loci to develop markers for marker-assisted selection (MAS). MAS is quite challenging in conifers because of their large, complex, and poorly-characterized genomes. Our goal was to construct a high-density linkage map to facilitate the identification of markers that are tightly linked to a major recessive male-sterile gene (ms1) for MAS in C. japonica, a species that is important in Japanese afforestation but which causes serious social pollinosis problems.

Results

We constructed a high-density saturated genetic linkage map for C. japonica using expressed sequence-derived co-dominant single nucleotide polymorphism (SNP) markers, most of which were genotyped using the GoldenGate genotyping assay. A total of 1261 markers were assigned to 11 linkage groups with an observed map length of 1405.2 cM and a mean distance between two adjacent markers of 1.1 cM; the number of linkage groups matched the basic chromosome number in C. japonica. Using this map, we located ms1 on the 9th linkage group and constructed a partial linkage map around the ms1 locus. This enabled us to identify a marker (hrmSNP970_sf) that is closely linked to the ms1 gene, being separated from it by only 0.5 cM.

Conclusions

Using the high-density map, we located the ms1 gene on the 9th linkage group and constructed a partial linkage map around the ms1 locus. The map distance between the ms1 gene and the tightly linked marker was only 0.5 cM. The identification of markers that are tightly linked to the ms1 gene will facilitate the early selection of male-sterile trees, which should expedite C. japonica breeding programs aimed at alleviating pollinosis problems without harming productivity.
Potential serodiagnostic markers for Q fever identified in Coxiella burnetiiby immunoproteomic and protein microarray approaches
Authors: Xiong Xiaolu , Wang Xile , Wen Bohai , Graves Stephen , Stenos John
Published: March 2012

Background

Coxiella burnetii is the etiological agent of Q fever. The clinical diagnosis of Q fever is mainly based on several serological tests. These tests all need Coxiella organisms which are difficult and hazardous to culture and purify.

Results

An immunoproteomic study of C. burnetii Xinqiao strain isolated in China was conducted with the sera from experimentally infected BALB/c mice and Q fever patients. Twenty of whole proteins of Xinqiao recognized by the infection sera were identified by mass spectrometry. Nineteen of the 20 proteins were successfully expressed in Escherichia coli and used to fabricate a microarray which was probed with Q fever patient sera. As a result, GroEL, YbgF, RplL, Mip, OmpH, Com1, and Dnak were recognized as major seroreactive antigens. The major seroreactive proteins were fabricated in a small microarray and further analyzed with the sera of patients with rickettsial spotted fever, Legionella pneumonia or streptococcal pneumonia. In this analysis, these proteins showed fewer cross-reactions with the tested sera.

Conclusions

Our results demonstrate that these 7 Coxiella proteins gave a modest sensitivity and specificity for recognizing of Q fever patient sera, suggesting that they are potential serodiagnostic markers for Q fever.
Proteomic characterisation of endoplasmic reticulum-derived protein bodies in tobacco leaves
Authors: Joseph Minu , Ludevid M Dolors , Torrent Margarita , Rofidal Valérie , Tauzin Marc , Rossignol Michel , Peltier Jean-Benoit
Published: March 2012

Background

The N-terminal proline-rich domain (Zera) of the maize storage protein γ-zein, is able to induce the formation of endoplasmic reticulum (ER)-derived protein bodies (PBs) when fused to proteins of interest. This encapsulation enables a recombinant fused protein to escape from degradation and facilitates its recovery from plant biomass by gradient purification. The aim of the present work was to evaluate if induced PBs encapsulate additional proteins jointly with the recombinant protein. The exhaustive analysis of protein composition of PBs is expected to facilitate a better understanding of PB formation and the optimization of recombinant protein purification approaches from these organelles.

Results

We analysed the proteome of PBs induced inNicotiana benthamianaleaves by transient transformation with Zera fused to a fluorescent marker protein (DsRed). Intact PBs with their surrounding ER-membrane were isolated on iodixanol based density gradients and their integrity verified by confocal and electron microscopy. SDS-PAGE analysis of isolated PBs showed that Zera-DsRed accounted for around 85% of PB proteins in term of abundance. Differential extraction of PBs was performed for in-depth analysis of their proteome and structure. Besides Zera-DsRed, 195 additional proteins were identified including a broad range of proteins resident or trafficking through the ER and recruited within the Zera-DsRed polymer.

Conclusions

This study indicates that Zera-protein fusion is still the major protein component of the new formed organelle in tobacco leaves. The analysis also reveals the presence of an unexpected diversity of proteins in PBs derived from both the insoluble Zera-DsRed polymer formation, including ER-resident and secretory proteins, and a secretory stress response induced most likely by the recombinant protein overloading. Knowledge of PBs protein composition is likely to be useful to optimize downstream purification of recombinant proteins in molecular farming applications.
Induction of intestinal pro-inflammatory immune responses by lipoteichoic acid
Authors: Zadeh Mojgan , Khan Mohammad W , Goh Yong Jun , Selle Kurt , Owen Jennifer L , Klaenhammer Todd , Mohamadzadeh Mansour
Published: March 2012

Background

The cellular and molecular mechanisms of inflammatory bowel disease are not fully understood; however, data indicate that uncontrolled chronic inflammation induced by bacterial gene products, including lipoteichoic acid (LTA), may trigger colonic inflammation resulting in disease pathogenesis. LTA is a constituent glycolipid of Gram-positive bacteria that shares many inflammatory properties with lipopolysaccharide and plays a critical role in the pathogenesis of severe inflammatory responses via Toll-like receptor 2. Accordingly, we elucidate the role of LTA in immune stimulation and induced colitis in vivo.

Methods

To better understand the molecular mechanisms utilized by the intestinal microbiota and their gene products to induce or subvert inflammation, specifically the effect(s) of altered surface layer protein expression on the LTA-mediated pro-inflammatory response, theLactobacillus acidophilus surfacelayerprotein (Slp) genes encoding SlpB and SlpX were deleted resulting in a SlpB-and SlpX-mutant that continued to express SlpA (assigned as NCK2031).

Results

Our data show profound activation of dendritic cells by NCK2031, wild-typeL. acidophilus(NCK56), and purifiedStaphylococcus aureus-LTA. In contrary to the LTA-deficient strain NCK2025, the LTA-expressing strains NCK2031 and NCK56, as well asS. aureus-LTA, induce pro-inflammatory innate and T cell immune responses in vivo. Additionally, neither NCK2031 norS. aureus-LTA supplemented in drinking water protected mice from DSS-colitis, but instead, induced significant intestinal inflammation resulting in severe colitis and tissue destruction.

Conclusions

These findings suggest that directed alteration of two of theL. acidophilusNCFM-Slps did not ameliorate LTA-induced pro-inflammatory signals and subsequent colitis.
Video-thoracoscopic enucleation of esophageal leiomyoma
Authors: Luh Shi-Ping , Hou Sheng-Mou , Fang Chien-Chung , Chen Chi-Yi
Published: March 2012

Background

Leiomyoma is the most common benign tumor of the esophagus. Surgical enucleation is indicated in case of symptoms or an unclear diagnosis, and open thoracotomy has long been the standard approach for this procedure. However, enucleation through video assisted thoracoscopic surgery (VATS) has been developed as a preferred approach for most lesions in recent years.

Method

Herein we report our twelve patients (seven men and five women, with median age of 42 years) from 2001 to 2009, who underwent enucleation through VATS for esophageal leiomyomas, with a size from 1 to 8 cm in diameter (median: 5), and at different locations, from the thoracic outlet to near the diaphragmatic level of the thoracic esophagus. Intraoperative fiberoptic esophagoscopy was performed in two patients for localization by illumination. A right-sided approach was performed in eight cases (upper two thirds of esophagus) and the left-sided in another four cases (lower third of esophagus).

Result

The median operative time was 95 minutes (70 to 230 minutes). Four of them required small utility incisions (4-6 cm) for better exploration and manipulation. There were no major complications, such as death or empyema due to leaks from mucosal tears, and the presenting symptoms were improved during the follow-up period, from 12 to 98 months.

Conclusion

VATS can be considered as an initial approach for most patients with esophageal leiomyomas, even large in size, irregular in shape, or at unfavorable location. It is a safe, minimally invasive, and effective treatment. However, conversion to open thoracotomy should be required for the sake of clinical or technical concern.
Transient expression of βC1 protein differentially regulates host genes related to stress response, chloroplast and mitochondrial functions
Authors: Andleeb Saiqa , Amin Imran , Bashir Aftab , Briddon Rob W , Mansoor Shahid
Published: March 2012

Background

Geminiviruses are emerging plant pathogens that infect a wide variety of crops including cotton, cassava, vegetables, ornamental plants and cereals. The geminivirus disease complex consists of monopartite begomoviruses that require betasatellites for the expression of disease symptoms. These complexes are widespread throughout the Old World and cause economically important diseases on several crops. A single protein encoded by betasatellites, termed βC1, is a suppressor of gene silencing, inducer of disease symptoms and is possibly involved in virus movement. Studies of the interaction of βC1 with hosts can provide useful insight into virus-host interactions and aid in the development of novel control strategies. We have used the differential display technique to isolate host genes which are differentially regulated upon transient expression of the βC1 protein of chili leaf curl betasatellite (ChLCB) in Nicotiana tabacum.

Results

Through differential display analysis, eight genes were isolated from Nicotiana tabacum, at two and four days after infitration with βC1 of ChLCB, expressed under the control of the Cauliflower mosaic virus 35S promoter. Cloning and sequence analysis of differentially amplified products suggested that these genes were involved in ATP synthesis, and acted as electron carriers for respiration and photosynthesis processes. These differentially expressed genes (DEGs) play an important role in plant growth and development, cell protection, defence processes, replication mechanisms and detoxification responses. Kegg orthology based annotation system analysis of these DEGs demonstrated that one of the genes, coding for polynucleotide nucleotidyl transferase, is involved in purine and pyrimidine metabolic pathways and is an RNA binding protein which is involved in RNA degradation.

Conclusion

βC1 differentially regulated genes are mostly involved in chloroplast and mitochondrial functions. βC1 also increases the expression of those genes which are involved in purine and pyrimidine metabolism. This information gives a new insight into the interaction of βC1 with the host and can be used to understand host-virus interactions in follow-up studies.
GCS overexpression is associated with multidrug resistance of human HCT-8 colon cancer cells
Authors: Song Min , Zang Weidong , Zhang Baohua , Cao Jing , Yang Guanrui
Published: March 2012

Purpose

Multidrug resistance is one of the main impediments to the successful treatment of colon cancer. Glucosylceramide synthase (GCS) which is related to multidrug resistance (MDR) can reduce the level of ceramide and can help cells escape from the ceramide-induced cell apoptosis. However, the underlying mechanism is still unclear.

Methods

The cell proliferation and cell toxicity were measured with Cell Counting Kit-8 (CCK-8). The mRNA levels of GCS and MDR1 were detected by semiquantitative reverse transcription-PCR amplification, the protein levels of GCS, caspase-3 and P-gp proteins were indicated by Western blotting. The apoptosis rates of cells were measured with flow cytometry.

Results

The relative mRNA levels of GCS in HCT-8, HCT-8/VCR, HCT-8/VCR- sh-mock and HCT-8/VCR-sh-GCS were 71.4 ± 1.1%, 95.1 ± 1.2%, 98.2 ± 1.5%, and 66.6 ± 2.1% respectively. The mRNA levels of MDR1 were respectively 61.3 ± 1.1%, 90.5 ± 1.4%, 97.6 ± 2.2% and 56.1 ± 1.2%. The IC50 of Cisplatin complexes were respectively 69.070 ± 0.253 μg/ml, 312.050 ± 1.46 μg/ml, 328.741 ± 5.648 μg/ml, 150.792 ± 0.967 μg/ml in HCT-8, HCT-8/VCR, HCT-8/VCR-sh-mock and HCT-8/VCR-sh-GCS. The protein levels of caspase-3 were 34.2 ± o.6%, 93.0 ± 0.7%, 109.09 ± 0.7%, 42.7 ± 1.3% respectively. The apoptosis rates of cells were 8.77 ± 0.14%, 12.75 ± 0.54%, 15.39 ± 0.41% and 8.49 ± 0.23% respectively.

Conclusion

In conclusion, our research indicated that suppression of GCS restores the sensitivity of multidrug resistance colon cancer cells to drug treatment.
Controversies in HIV cure research
Authors: Johnston Rowena , Barré‐Sinoussi Françoise
Published: March 2012

Background

Antiretroviral therapy significantly reduces HIV viral burden and prolongs life, but does not cure HIV infection. The major scientific barrier to a cure is thought to be the persistence of the virus in cellular and/or anatomical reservoirs.

Discussion

Most efforts to date, including pharmaco, immuno or gene therapy, have failed to cure patients, with the notable exception of a stem cell transplant recipient commonly known as the Berlin patient. This case has revived interest in the potential to cure HIV infection and has highlighted the need to resolve critical questions in the basic, pre‐clinical and clinical research spheres as they pertain specifically to efforts to eradicate HIV from the body of an infected person (a sterilizing cure) or at least render the need for lifelong antiretroviral therapy obsolete (functional cure). This paper describes ongoing debates in each of these research spheres as they were presented and discussed at a satellite session that took place at the 6th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention in Rome in July 2011.

The resolution of these debates may have important implications for the search for a cure, the most efficient ways to identify and test promising interventions, and ultimately the availability of such a cure to diverse groups of HIV patients around the world.
MAnorm: a robust model for quantitative comparison of ChIP-Seq data sets
Authors: Shao Zhen , Zhang Yijing , Yuan Guo-Cheng , Orkin Stuart H , Waxman David J
Published: March 2012

ChIP-Seq is widely used to characterize genome-wide binding patterns of transcription factors and other chromatin-associated proteins. Although comparison of ChIP-Seq data sets is critical for understanding cell type-dependent and cell state-specific binding, and thus the study of cell-specific gene regulation, few quantitative approaches have been developed. Here, we present a simple and effective method, MAnorm, for quantitative comparison of ChIP-Seq data sets describing transcription factor binding sites and epigenetic modifications. The quantitative binding differences inferred by MAnorm showed strong correlation with both the changes in expression of target genes and the binding of cell type-specific regulators.
Liver hyperplasia after tamoxifen induction of Myc in a transgenic medaka model
Authors: Menescal Luciana A. , Schmidt Cornelia , Liedtke Daniel , Schartl Manfred
Published: March 2012

Myc is a global transcriptional regulator and one of the most frequently overexpressed oncogenes in human tumors. It is well established that activation of Myc leads to enhanced cell proliferation but can also lead to increased apoptosis. The use of animal models expressing deregulated levels of C-myc has helped elucidate its function in normal cells and also give insights on how Myc initiates and maintains tumorigenesis. Analyses of the medaka (Oryzias latipes) genome uncovered the unexpected presence of two C-myc gene copies in this teleost species. Comparison of these C-myc versions to other vertebrate species, revealed that one gene, c-myc17, differs by the loss of some conserved regulatory protein motifs present in all other known c-myc genes. To investigate how such differences might affect the basic biological functions of Myc, we generated a tamoxifen inducible in vivo model utilizing a natural, fish-specific myc gene. Using this model we show that when activated, C-myc17 leads to increased proliferation and to apoptosis in a dose dependent manner, similar to human Myc. We have also shown that long-term C-myc17 activation triggers liver hyperplasia in adult fish, allowing this newly established transgenic medaka model to be used to study the transition from hyperplasia to liver cancer and to identify of Myc-induced tumorgenesis modifiers.
Translation of the cell adhesion molecule ALCAM in axonal growth cones – regulation and functional importance
Authors: Thelen Karsten , Maier Bettina , Faber Marc , Albrecht Christian , Fischer Paulina , Pollerberg G. Elisabeth
Published: March 2012

ALCAM is a cell adhesion molecule that is present on extending axons and has been shown to be crucial for elongation and navigation of retinal ganglion cell (RGC) axons. In the present study, we show that ALCAM mRNA is present in axonal growth cones of RGCs in vivo and in vitro, and that translation of ALCAM occurs in RGC growth cones separated from their soma. This growth cone translation is regulated by the 3′-untranslated region (3′-UTR) of ALCAM and depends on the activity of the kinases ERK and TOR (target of rapamycin). We also investigated the impact of the growth cone translation of ALCAM on axonal functions. Growth cone translation of ALCAM is crucial for the enhanced elongation of axons extending in contact with ALCAM protein. The local translation of ALCAM in the growth cone is able to rapidly counterbalance experimentally induced ALCAM internalization, thereby contributing to the maintenance of constant ALCAM levels in the plasma membrane. Assays where RGC axons have the choice to grow on laminin or both ALCAM and laminin – as is the case in the developing retina – reveal that the axonal preference for ALCAM-containing lanes depends on translation of ALCAM in growth cones. Taken together, these results show for the first time that translation of a cell adhesion molecule in growth cones, as well as the impact of this local translation on the behavior of axon and growth cone.
Effect of foam sclerotherapy on healing and long-term recurrence in chronic venous leg ulcers
Authors: Kulkarni S R , Slim F J A , Emerson L G , Davies C , Bulbulia R A , Whyman M R , Poskitt K R
Published: March 2012

Introduction

The ESCHAR trial showed that superficial venous surgery and compression in chronic venous ulceration achieved a 24-week healing rate of 65% and 12-month recurrence rate of 12%. Foam sclerotherapy treatment is an alternative to surgery. The aim of this study is to assess the effect of foam sclerotherapy on ulcer healing and recurrence in chronic venous leg ulcers.

Methods

Chronic venous leg ulcers (CEAP [clinical, aetiological, anatomical and pathological elements] 5 and CEAP 6) with superficial venous reflux were treated between March 2006 and June 2011 with ultrasound-guided foam sclerotherapy and compression. Venous duplex was performed on all legs before and after treatment. Twenty-four-week ulcer healing and one- and four-year ulcer recurrence rates were calculated using Kaplan–Meier survival analysis.

Results

Two hundred legs (186 patients) with chronic venous ulcers (CEAP 5: n = 163 and CEAP 6: n = 37) were treated with foam sclerotherapy. Complete occlusion was achieved in 185/200 (92.5%) limbs, short segment occlusion in 14/200 (7%) limbs and one leg segment failed to occlude. One patient suffered an asymptomatic non-occlusive deep vein thrombosis (DVT) diagnosed on duplex scan at one week and one presented with an occlusive DVT three weeks following a normal scan at one week. One patient developed an asymptomatic occlusive DVT at two weeks following a non-occlusive DVT diagnosed on initial one-week scan. Eighteen patients were lost to follow-up (3 moved away and 15 died of unrelated causes). The 24-week healing rate was 71.1% and one- and four-year recurrence rates were 4.7% and 28.1%, respectively.

Conclusion

Foam sclerotherapy is effective in abolition of superficial venous reflux and may contribute to similar ulcer healing and long-term recurrence rates to superficial venous surgery. Foam sclerotherapy is an attractive alternative to surgery in this group of patients.
Intra-arterial injection, a rare but serious complication of sclerotherapy
Authors: Hafner F , Froehlich H , Gary T , Brodmann M
Published: March 2012

Intra-arterial injections represent the most feared complication of sclerotherapy for varicose veins. We present a case of an inadvertent intra-arterial injection of polidocanol at the left medial calf in a 59-year-old woman with subsequent arterial occlusions of the posterior tibial artery and foot arteries. Despite several therapeutic interventions, lower-limb amputation could not be prevented. We conducted a PubMed search for articles reporting arterial complications related to sclerotherapy, in order to evaluate aetiology, clinical presentation, therapeutic management and outcome of sclerotherapy-associated intra-arterial injections during the past 50 years. Intra-arterial injection of a sclerosing solution was reported in 63 cases, mostly after injection near the ankle region or the distal medial calf. Clinical presentation was frequently characterized by immediate pain during injection and distal ischaemia with subsequent tissue loss. Despite several treatment approaches, amputation could not be prevented in 31 cases (52.5%). The pathophysiology of arterial complications related to intra-arterial injection and advisable therapeutic interventions are discussed. Inadvertent intra-arterial injection represents a limb-threatening complication of sclerotherapy. Target-oriented and prompt therapy seems inevitable in order to reduce the risk of permanent tissue loss and amputation.
Cholinesterase Inhibitor Adjunctive Therapy for Cognitive Impairment and Depressive Symptoms in Older Adults with Depression
Authors: McDermott Cara L , Gray Shelly L
Published: March 2012

Objective:

To review the primary literature regarding the use of cholinesterase inhibitors (ChEIs) as adjunctive therapy for cognitive enhancement and improvement of depressive symptoms for older adults with depression.

Data Sources:

A literature search of MEDLINE (1950-September 2011) was conducted, using the search term depression in combination with cholinesterase inhibitor, donepezil, galantamine, or rivastigmine. A search of reference citations was conducted to identify additional references.

Study Selection and Data Extraction:

English-language clinical trials were evaluated. Studies that included subjects with Alzheimer's disease, dementia, Parkinson disease, bipolar disorder, or schizophrenia were excluded. Four clinical studies met our criteria,

Data Synthesis:

We identified 4 randomized, double-blind, placebo-controlled trials that ranged in sample size from 20 to 130. Galantamine 16 mg daily was evaluated in 2 trials lasting 8 and 24 weeks. Neither study found a statistically significant difference in measures of cognition or Hamilton Rating Scale for Depression scores. Donepezil augmentation was evaluated in a 1-year and a 2-year trial. Donepezil was found to improve global cognition at 1 year, but the benefit did not persist at year 2. Subjects with mild cognitive impairment at baseline who received donepezil experienced higher depression recurrence than did those who took placebo (p = 0.03); this effect was not observed in cognitively intact subjects (p = 0.39).

Conclusions:

There is no clear benefit for ChEI therapy as an adjunct to antidepressant therapy for depressed older adults.
Zellulare Neuronale Netzwerke zur schnellen bildbasierten Regelung von Materialbearbeitungsprozessen
Authors: Strohm Peter , Blug Andreas , Carl Daniel , Höfler Heinrich
Published: March 2012

Kameras, welche auf Zellularen Neuronalen Netzwerken basieren, können neue Anwendungsgebiete für die industrielle Bildverarbeitung erschließen, weil diese Technologie die Integration von Rechenelementen in die elektronische Beschaltung der Pixel von CMOS-Kameras ermöglicht. Insbesondere Regel- und Steuerungssysteme profitieren von der hohen Rechenleistung und den kurzen Latenzzeiten dieser neuartigen Kameratechnologie. Dieser Artikel verdeutlicht das anhand dreier Anwendungen aus den Bereichen Laserschweißen, Laserablation und Drahtziehen, welche mit konventionellen Bildverarbeitungssystemen nicht möglich sind.
Präzise IR-basierte Temperaturmessung — eine Fallstudie für die automatische Gesundheitsüberwachung von Milchkühen
Authors: Wirthgen Tom , Zipser Stephan , Geidel Steffi , Franze Ulrike
Published: March 2012

In der modernen Tierhaltung besteht zunehmend Bedarf nach neuen automatisierten Lösungen zur Gesundheitsüberwachung. Die Infrarotthermographie (IRT) könnte dies leisten, hohe Messunsicherheiten und großer manueller Aufwand verhindern dies jedoch derzeit. Über die Kombination aus strahlungsbasierter Korrektur zur deutlichen Reduzierung der Messunsicherheit, modellbasierter Korrektur der Umgebungseinflüsse sowie einer automatischen Segmentierung als Basis für die Berechnung diagnostisch relevanter Temperaturmerkmale konnte die IRT erfolgreich für veterinäre Massenuntersuchungen zur Anwendung gebracht werden.
Malaysia in 2011
Authors: O'Shannassy Michael
Published: March 2012

Ethno-religious controversies, noisy demands for political change, and growing concerns over the slow pace of crucial economic reforms all served to highlight Malaysia's constantly shifting sociopolitical terrain in 2011. With the prospect of an early general election, it remains to be seen whether the ruling coalition can regain the middle ground.
The Philippines in 2011
Authors: De Castro Renato Cruz
Published: March 2012

Early this year, a majority of Filipinos indicated in a national survey that they are not sure if Benigno Aquino, III, will succeed or fail in his presidency. This uncertainty stems from his unconventional style of governance and the gravity of the domestic and international problems he faces. Moreover, his style of governance is generally perceived by the Filipinos as reactive and lacklusterâ€”a fact attributed to his first year in office, a difficult period of learning and adjustment.
Papua New Guinea in 2011
Authors: Anere Ray
Published: March 2012

The current power struggle has taken on historical proportions, interrupting the four-year-old Somare government in Papua New Guinea one year short of its full five-year term. In August 2011, Speaker of Parliament Jeffrey Nape declared the Office of Prime Minister vacant, resulting in Parliament electing Peter O'Neill as the new prime minister. Late in the year, the Supreme Court ruled otherwise.
The United States and Asia in 2011
Authors: Paal Douglas
Published: March 2012

The Obama administration moved to stabilize 2010's deteriorating relations with China and exploit the opportunity to deepen ties with China's nervous neighbors. Diplomatic, economic, and security initiatives were melded to “rebalance” American resources and attention to Asia in the 21st century. Early 2011 euphoria about China's rise and gloom about America's decline began to reverse themselves by end 2011. Obama made a key policy statement about the Asia-Pacific region in his address to Australia's Parliament.
Haplotype Analysis and Linkage Disequilibrium at Five Loci inEragrostis tef
Authors: Smith Shavannor M , Yuan Yinan , Doust Andrew N , Bennetzen Jeffrey L
Published: March 2012

Eragrostis tef (Zucc.), a member of the Chloridoideae subfamily of grasses, is one of the most important food crops in Ethiopia. Lodging is the most important production problem in tef. The rht1 and sd1 dwarfing genes have been useful for improving lodging resistance in wheat and rice, respectively, in what has been known as the “Green Revolution.” All homologs of rht1 and sd1 were cloned and sequenced from 31 tef accessions collected from across Ethiopia. The allotetraploid tef genome was found to carry two rht1 homologs. From sequence variation between these two putative homologs, an approximate ancestral divergence date of 6.4 million years ago was calculated for the two genomes within tef. Three sd1 homologs were identified in tef, with unknown orthologous/paralogous relationships. The genetic diversity in the 31 studied accessions was organized into a relatively small number of haplotypes (2−4) for four of these genes, whereas one rht1 homeologue exhibited 10 haplotypes. A low level of nucleotide diversity was observed at all loci. Linkage disequilibrium analysis demonstrated strong linkage disequilibrium, extending the length of the five genes investigated (2−4 kb), with no significant decline. There was no significant correlation between haplotypes of any of these genes and their recorded site of origin.
Genetic Screen for Regulators of Lymph Gland Homeostasis and Hemocyte Maturation inDrosophila
Authors: Tan Kai Li , Goh Siow Chong , Minakhina Svetlana
Published: March 2012

Blood cell development in the Drosophila lymph gland is controlled by multiple factors, most of them conserved from flies to mammals. The Drosophila homolog of vertebrate PDCD2, Zfrp8, is required in Drosophila hematopoietic stem cell development. Zfrp8 mutant larvae show a disruption of homeostasis in the lymph gland and vast lymph gland overgrowth. The loss of one copy of Zfrp8 also causes a lymph gland enlargement. This dominant phenotype can be modified by heterozygous mutations in cell-cycle genes and several genes functioning in blood development. To identify additional genes that function in hematopoiesis, we screened a collection of second and third chromosome deficiencies for modifiers of Zfrp8 heterozygous phenotype. Using deficiency mapping, available single gene mutations, and RNAi lines, we identified several novel factors required for lymph gland development and hemocyte differentiation. Distinct lymph gland phenotypes of nine of these genes are reported here for the first time. Importantly, the orthologs of four of them have a role in mammalian blood development and leukemogenesis. Our work has shown that the number of genes regulating normal blood cell development in Drosophila is much larger than expected, and that the complex molecular mechanisms regulating hemocyte differentiation are comparable to those in vertebrates.
Homology-Dependent Silencing by an Exogenous Sequence in theDrosophilaGermline
Authors: Pöyhönen Maria , de Vanssay Augustin , Delmarre Valérie , Hermant Catherine , Todeschini Anne Laure , Teysset Laure , Ronsseray Stéphane
Published: March 2012

The study of P transposable element repression in Drosophila melanogaster led to the discovery of the trans-silencing effect (TSE), a homology-dependent repression mechanism by which a P-transgene inserted in subtelomeric heterochromatin (Telomeric Associated Sequences) represses in trans, in the female germline, a homologous P-lacZ transgene inserted in euchromatin. TSE shows variegation in ovaries and displays a maternal effect as well as epigenetic transmission through meiosis. In addition, TSE is highly sensitive to mutations affecting heterochromatin components (including HP1) and the Piwi-interacting RNA silencing pathway (piRNA), a homology-dependent silencing mechanism that functions in the germline. TSE appears thus to involve the piRNA-based silencing proposed to play a major role in P repression. Under this hypothesis, TSE may also be established when homology between the telomeric and target loci involves sequences other than P elements, including sequences exogenous to the D. melanogaster genome. We have tested whether TSE can be induced via lacZ sequence homology. We generated a piggyBac-otu-lacZ transgene in which lacZ is under the control of the germline ovarian tumor promoter, resulting in strong expression in nurse cells and the oocyte. We show that all piggyBac-otu-lacZ transgene insertions are strongly repressed by maternally inherited telomeric P-lacZ transgenes. This repression shows variegation between egg chambers when it is incomplete and presents a maternal effect, two of the signatures of TSE. Finally, this repression is sensitive to mutations affecting aubergine, a key player of the piRNA pathway. These data show that TSE can occur when silencer and target loci share solely a sequence exogenous to the D. melanogaster genome. This functionally supports the hypothesis that TSE represents a general repression mechanism which can be co-opted by new transposable elements to regulate their activity after a transfer to the D. melanogaster genome.