bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of 3 weeks’ whole body vibration training on muscle strength and functional mobility in hospitalized persons with multiple sclerosis
Authors: Claerbout Marieke , Gebara Benoit , Ilsbroukx Stefan , Verschueren Sabine , Peers Koen , Van Asch Paul , Feys Peter 
Published: November 2011

Background: Exercise therapy in persons with multiple sclerosis (MS) is effective for improving muscle strength and functional mobility. Objective: To investigate, in MS patients attending an in-patient rehabilitation program, the additional effects of a 3-week exercise program, performed on a whole body vibration platform, on muscle strength and functionality. Methods: Median Expanded Disability Status Scale (EDSS) of participating patients was 5.5. This randomized controlled trial differentiated a MS control group (n = 17) and two exercise groups performing exercises on a vibration platform (WBV-full group, n = 20) and on the platform additionally covered by a damping mat (WBV-light group, n = 18). Exercise groups performed, during 10 training sessions, six static and dynamic exercises standing on a platform vibrating at high frequency and low amplitude. Isometric muscle strength of quadriceps, hamstrings, tibialis anterior and gluteus medius was measured with a hand-held dynamometer. Functional mobility was measured with Berg Balance Scale (BBS), 3-minute walk test and Timed Get up and Go test. Results: Eight drop-outs occurred in the exercise groups (WBV-full = 4, WBV-light = 4), but were unrelated to WBV as type of intervention. Across groups, significant time effects were found for all muscle groups. For maximal quadriceps and hamstrings muscle strength, interaction effects were found with post-hoc tests indicating exercise group-significant improvements in the WBV-full group only. Significant time effects were found for all functional tests. Improvements on the BBS and 3-minute walk test were larger in training than in control groups, but no significant interactions were found. Conclusions: A 3-week exercise program on a vibration plate significantly improved muscle strength, but not functionality, in persons with MS.
Hematopoietic stem cell engineering at a crossroads
Authors: Rivière Isabelle , Dunbar Cynthia E. , Sadelain Michel 
Published: November 2011

Abstract
The genetic engineering of hematopoietic stem cells is the basis for potentially treating a large array of hereditary and acquired diseases, and stands as the paradigm for stem cell engineering in general. Recent clinical reports support the formidable promise of this approach but also highlight the limitations of the technologies used to date, which have on occasion resulted in clonal expansion, myelodysplasia, or leukemogenesis. New research directions, predicated on improved vector designs, targeted gene delivery or the therapeutic use of pluripotent stem cells, herald the advent of safer and more effective hematopoietic stem cell therapies that may transform medical practice. In this review, we place these recent advances in perspective, emphasizing the solutions emerging from a wave of new technologies and highlighting the challenges that lie ahead.
Lama1 mutations lead to vitreoretinal blood vessel formation, persistence of fetal vasculature, and epiretinal membrane formation in mice
Authors: Edwards Malia M , McLeod D Scott , Grebe Rhonda , Heng Céline , Lefebvre Olivier , Lutty Gerard A 
Published: November 2011

Abstract

Background
Valuable insights into the complex process of retinal vascular development can be gained using models with abnormal retinal vasculature. Two such models are the recently described mouse lines with mutations in Lama1, an important component of the retinal internal limiting membrane (ILM). These mutants have a persistence of the fetal vasculature of vitreous (FVV) but lack a primary retinal vascular plexus. The present study provides a detailed analysis of astrocyte and vascular development in these Lama1 mutants.

Results
Although astrocytes and blood vessels initially migrate into Lama1 mutant retinas, both traverse the peripapillary ILM into the vitreous by P3. Once in the vitreous, blood vessels anastomose with vessels of the vasa hyaloidea propria, part of the FVV, and eventually re-enter the retina where they dive to form the inner and outer retinal capillary networks. Astrocytes continue proliferating within the vitreous to form a dense mesh that resembles epiretinal membranes associated with persistent fetal vasculature and proliferative vitreoretinopathy.

Conclusions

Lama1 and a fully intact ILM are required for normal retinal vascular development. Mutations in Lama1 allow developing retinal vessels to enter the vitreous where they anastomose with vessels of the hyaloid system which persist and expand. Together, these vessels branch into the retina to form fairly normal inner retinal vascular capillary plexi. The Lama1 mutants described in this report are potential models for studying the human conditions persistent fetal vasculature and proliferative vitreoretinopathy.
Protein composition of interband regions in polytene and cell line chromosomes of Drosophila melanogaster
Authors: Demakov Sergey A , Yu Vatolina Tatyana , Babenko Vladimir N , Semeshin Valery F , Belyaeva Elena S , Zhimulev Igor F 
Published: November 2011

AbstractBackgroundDespite many efforts, little is known about distribution and interactions of chromatin proteins which contribute to the specificity of chromomeric organization of interphase chromosomes. To address this issue, we used publicly available datasets from several recent Drosophila genome-wide mapping and annotation projects, in particular, those from modENCODE project, and compared molecular organization of 13 interband regions which were accurately mapped previously.ResultsHere we demonstrate that in interphase chromosomes ofDrosophilacell lines, the interband regions are enriched for a specific set of proteins generally characteristic of the "open" chromatin (RNA polymerase II, CHRIZ (CHRO), BEAF-32, BRE1, dMI-2, GAF, NURF301, WDS and TRX). These regions also display reduced nucleosome density, histone H1 depletion and pronounced enrichment for ORC2, a pre-replication complex component. Within the 13 interband regions analyzed, most were around 3-4 kb long, particularly those where many of said protein features were present. We estimate there are about 3500 regions with similar properties in chromosomes ofD. melanogastercell lines, which fits quite well the number of cytologically observed interbands in salivary gland polytene chromosomes.ConclusionsOur observations suggest strikingly similar organization of interband chromatin in polytene chromosomes and in chromosomes from cell lines thereby reflecting the existence of a universal principle of interphase chromosome organization.
Small interfering RNA targeting mcl-1 enhances proteasome inhibitor-induced apoptosis in various solid malignant tumors
Authors: Zhou Wei , Hu Jingzi , Tang Haimei , Wang Da , Huang Xuefeng , He Chao , Zhu Hongbo 
Published: November 2011

Abstract

Background
Targeting the ubiquitin-proteasome pathway is a promising approach for anticancer strategies. Recently, we found Bik accumulation in cancer cell lines after they were treated with bortezomib. However, recent evidence indicates that proteasome inhibitors may also induce the accumulation of anti-apoptotic Bcl-2 family members. The current study was designed to analyze the levels of several anti-apoptotic members of Bcl-2 family in different human cancer cell lines after they were treated with proteasome inhibitors.

Methods
Different human cancer cell lines were treated with proteasome inhibitors. Western blot were used to investigate the expression of Mcl-1 and activation of mitochondrial apoptotic signaling. Cell viability was investigated using SRB assay, and induction of apoptosis was measured using flow cytometry.

Results
We found elevated Mcl-1 level in human colon cancer cell lines DLD1, LOVO, SW620, and HCT116; human ovarian cancer cell line SKOV3; and human lung cancer cell line H1299, but not in human breast cancer cell line MCF7 after they were treated with bortezomib. This dramatic Mcl-1 accumulation was also observed when cells were treated with other two proteasome inhibitors, MG132 and calpain inhibitor I (ALLN). Moreover, our results showed Mcl-1 accumulation was caused by stabilization of the protein against degradation. Reducing Mcl-1 accumulation by Mcl-1 siRNA reduced Mcl-1 accumulation and enhanced proteasome inhibitor-induced cell death and apoptosis, as evidenced by the increased cleavage of caspase-9, caspase-3, and poly (ADP-ribose) polymerase.

Conclusions
Our results showed that it was not only Bik but also Mcl-1 accumulation during the treatment of proteasome inhibitors, and combining proteasome inhibitors with Mcl-1 siRNA would enhance the ultimate anticancer effect suggesting this combination might be a more effective strategy for cancer therapy.
Severe inflammatory reaction induced by peritoneal trauma is the key driving mechanism of postoperative adhesion formation
Authors: Pismensky Sergei V , Kalzhanov Zhomart R , Eliseeva Marina Yu , Kosmas Ioannis P , Mynbaev Ospan A 
Published: November 2011

Abstract

Background
Many factors have been put forward as a driving mechanism of surgery-triggered adhesion formation (AF). In this study, we underline the key role of specific surgical trauma related with open surgery (OS) and laparoscopic (LS) conditions in postoperative AF and we aimed to study peritoneal tissue inflammatory reaction (TIR), remodelling specific complications of open surgery (OS) versus LS and subsequently evaluating AF induced by these conditions.

Methods
A prospective randomized study was done in 80 anaesthetised female Wistar rats divided equally into 2 groups. Specific traumatic OS conditions were induced by midline incision line (MIL) extension and tissue drying and specific LS conditions were remodelled by intraperitoneal CO2 insufflation at the 10 cm of water. TIR was evaluated at the 24th, 72nd, 120th and 168th hour by scoring scale. Statistical analysis was performed by the non-parametric t test and two-way ANOVA using Bonferroni post-tests.

Results
More pronounced residual TIR was registered after OS than after LS. There were no significant TIR interactions though highly significant differences were observed between the OS and LS groups (p < 0.0001) with regard to surgical and time factors. The TIR change differences between the OS and LS groups were pronounced with postoperative time p < 0.05 at the 24th and 72nd; p < 0.01 - 120th and p < 0.001 - 168th hrs. Adhesion free wounds were observed in 20.0 and 31.0% of cases after creation of OS and LS conditions respectively; with no significant differences between these values (p > 0.05). However larger adhesion size (41.67 ± 33.63) was observed after OS in comparison with LS (20.31 ± 16.38). The upper-lower 95% confidential limits ranged from 60.29 to 23.04 and from 29.04 to 11.59 respectively after OS and LS groups with significant differences (p = 0.03). Analogous changes were observed in adhesion severity values. Subsequently, severe TIR parameters were followed by larger sizes of severe postoperative adhesions in the OS group than those observed in the LS group.

Conclusions
MIL extension and tissue drying seem to be the key factors in the pathogenesis of adhesion formation, triggering severe inflammatory reactions of the peritoneal tissue surrounding the MIL resulting in local and systemic consequences. CO2 insufflation however, led to moderate inflammation and less adhesion formation.
Baropodometry on women suffering from chronic pelvic pain - a cross-sectional study
Authors: Kaercher Carolina W , Genro Vanessa K , Souza Carlos A , Alfonsin Mariane , Berton Greice , Cunha Filho João S 
Published: November 2011

Abstract

Background
Previous studies have associated chronic pelvic pain with a stereotyped pattern of movement and posture, lack of normal body sensations, a characteristic pain distribution. We aimed at evaluating if these postural changes are detectable in baropodometry results in patients with chronic pelvic pain.

Methods
We performed a prospective study in a university hospital. We selected 32 patients suffering from chronic pelvic pain (study group) and 30 women without this pathology (regular gynecological work out - control group). Pain scores and baropodometric analysis were performed.

Results
As expected, study group presented higher pain scores than control group. Study and control groups presented similar averages for the maximum pressures to the left and right soles as well as soles supports in the forefeet and hind feet. Women suffering from chronic pelvic pain did not present differences in baropodometric analysis when compared to healthy controls.

Conclusions
This data demonstrates that postural abnormalities resulting from CPP could not be demonstrated by baropodometric evaluation. Other postural measures should be addressed to evaluate pelvic pain patients.
Long noncoding intronic RNAs are differentially expressed in primary and metastatic pancreatic cancer
Authors: Tahira Ana C , Kubrusly Márcia S , Faria Michele F , Dazzani Bianca , Fonseca Rogério S , Maracaja-Coutinho Vinicius , Verjovski-Almeida Sergio , Machado Marcel CC , Reis Eduardo M 
Published: November 2011

Abstract

Background
Pancreatic ductal adenocarcinoma (PDAC) is known by its aggressiveness and lack of effective therapeutic options. Thus, improvement in current knowledge of molecular changes associated with pancreatic cancer is urgently needed to explore novel venues of diagnostics and treatment of this dismal disease. While there is mounting evidence that long noncoding RNAs (lncRNAs) transcribed from intronic and intergenic regions of the human genome may play different roles in the regulation of gene expression in normal and cancer cells, their expression pattern and biological relevance in pancreatic cancer is currently unknown. In the present work we investigated the relative abundance of a collection of lncRNAs in patients' pancreatic tissue samples aiming at identifying gene expression profiles correlated to pancreatic cancer and metastasis.

Methods
Custom 3,355-element spotted cDNA microarray interrogating protein-coding genes and putative lncRNA were used to obtain expression profiles from 38 clinical samples of tumor and non-tumor pancreatic tissues. Bioinformatics analyses were performed to characterize structure and conservation of lncRNAs expressed in pancreatic tissues, as well as to identify expression signatures correlated to tissue histology. Strand-specific reverse transcription followed by PCR and qRT-PCR were employed to determine strandedness of lncRNAs and to validate microarray results, respectively.

Results
We show that subsets of intronic/intergenic lncRNAs are expressed across tumor and non-tumor pancreatic tissue samples. Enrichment of promoter-associated chromatin marks and over-representation of conserved DNA elements and stable secondary structure predictions suggest that these transcripts are generated from independent transcriptional units and that at least a fraction is under evolutionary selection, and thus potentially functional.
Statistically significant expression signatures comprising protein-coding mRNAs and lncRNAs that correlate to PDAC or to pancreatic cancer metastasis were identified. Interestingly, loci harboring intronic lncRNAs differentially expressed in PDAC metastases were enriched in genes associated to the MAPK pathway. Orientation-specific RT-PCR documented that intronic transcripts are expressed in sense, antisense or both orientations relative to protein-coding mRNAs. Differential expression of a subset of intronic lncRNAs (PPP3CB, MAP3K14 and DAPK1 loci) in metastatic samples was confirmed by Real-Time PCR.

Conclusion
Our findings reveal sets of intronic lncRNAs expressed in pancreatic tissues whose abundance is correlated to PDAC or metastasis, thus pointing to the potential relevance of this class of transcripts in biological processes related to malignant transformation and metastasis in pancreatic cancer.
Targeting metabolism with arsenic trioxide and dichloroacetate in breast cancer cells
Authors: Sun Ramon C , Board Philip G , Blackburn Anneke C 
Published: November 2011

Abstract

Background
Cancer cells have a different metabolic profile compared to normal cells. The Warburg effect (increased aerobic glycolysis) and glutaminolysis (increased mitochondrial activity from glutamine catabolism) are well known hallmarks of cancer and are accompanied by increased lactate production, hyperpolarized mitochondrial membrane and increased production of reactive oxygen species.

Methods
In this study we target the Warburg effect with dichloroacetate (DCA) and the increased mitochondrial activity of glutaminolysis with arsenic trioxide (ATO) in breast cancer cells, measuring cell proliferation, cell death and mitochondrial characteristics.

Results
The combination of DCA and ATO was more effective at inhibiting cell proliferation and inducing cell death than either drug alone. We examined the effect of these treatments on mitochondrial membrane potential, reactive oxygen species production and ATP levels and have identified new molecular mechanisms within the mitochondria for both ATO and DCA: ATO reduces mitochondrial function through the inhibition of cytochrome C oxidase (complex IV of the electron transport chain) while DCA up-regulates ATP synthase β subunit expression. The potentiation of ATO cytotoxicity by DCA is correlated with strong suppression of the expression of c-Myc and HIF-1α, and decreased expression of the survival protein Bcl-2.

Conclusion
This study is the first to demonstrate that targeting two key metabolic hallmarks of cancer is an effective anti-cancer strategy with therapeutic potential.
In vivo rescue of alveolar macrophages from SP-A knockout mice with exogenous SP-A nearly restores a wild type intracellular proteome; actin involvement
Authors: Phelps David S , Umstead Todd M , Quintero Omar A , Yengo Christopher M , Floros Joanna 
Published: November 2011

AbstractBackgroundMice lacking surfactant protein-A (SP-A-/-; knockout; KO) exhibit increased vulnerability to infection and injury. Although many bronchoalveolar lavage (BAL) protein differences between KO and wild-type (WT) are rapidly reversed in KO after infection, their clinical course is still compromised. We studied the impact of SP-A on the alveolar macrophage (AM) proteome under basal conditions. Male SP-A KO mice were SP-A-treated (5 micrograms/mouse) and sacrificed in 6 or 18 hr. The AM proteomes of KO, SP-A-treated KO, and WT mice were studied by 2D-DIGE coupled with MALDI-ToF/ToF and AM actin distribution was examined by phalloidon staining.ResultsWe observed: a) significant differences from KO in WT or exogenous SP-A-treated in 45 of 76 identified proteins (both increases and decreases). These included actin-related/cytoskeletal proteins (involved in motility, phagocytosis, endocytosis), proteins of intracellular signaling, cell differentiation/regulation, regulation of inflammation, protease/chaperone function, and proteins related to Nrf2-mediated oxidative stress response pathway; b) SP-A-induced changes causing the AM proteome of the KO to resemble that of WT; and c) that SP-A treatment altered cell size and F-actin distribution.ConclusionsThese differences are likely to enhance AM function. The observations show for the first time that acutein vivoSP-A treatment of KO mice, under basal or unstimulated conditions, affects the expression of multiple AM proteins, alters F-actin distribution, and can restore much of the WT phenotype. We postulate that the SP-A-mediated expression profile of the AM places it in a state of "readiness" to successfully conduct its innate immune functions and ensure lung health.
Availability of a pediatric trauma center in a disaster surge decreases triage time of the pediatric surge population: a population kinetics model
Authors: Barthel Erik R , Pierce James R , Goodhue Catherine J , Ford Henri R , Grikscheit Tracy C , Upperman Jeffrey S 
Published: November 2011

Abstract

Background
The concept of disaster surge has arisen in recent years to describe the phenomenon of severely increased demands on healthcare systems resulting from catastrophic mass casualty events (MCEs) such as natural disasters and terrorist attacks. The major challenge in dealing with a disaster surge is the efficient triage and utilization of the healthcare resources appropriate to the magnitude and character of the affected population in terms of its demographics and the types of injuries that have been sustained.

Results
In this paper a deterministic population kinetics model is used to predict the effect of the availability of a pediatric trauma center (PTC) upon the response to an arbitrary disaster surge as a function of the rates of pediatric patients' admission to adult and pediatric centers and the corresponding discharge rates of these centers. We find that adding a hypothetical pediatric trauma center to the response documented in an historical example (the Israeli Defense Forces field hospital that responded to the Haiti earthquake of 2010) would have allowed for a significant increase in the overall rate of admission of the pediatric surge cohort. This would have reduced the time to treatment in this example by approximately half. The time needed to completely treat all children affected by the disaster would have decreased by slightly more than a third, with the caveat that the PTC would have to have been approximately as fast as the adult center in discharging its patients. Lastly, if disaster death rates from other events reported in the literature are included in the model, availability of a PTC would result in a relative mortality risk reduction of 37%.

Conclusions
Our model provides a mathematical justification for aggressive inclusion of PTCs in planning for disasters by public health agencies.