bluuebunny/crossref_metadata_2025_split huggingface dataset:
Important role of indels in somatic mutations of human cancer genes
Authors: Yang Haiwang , Zhong Yan , Peng Cheng , Chen Jian-Qun , Tian Dacheng 
Published: September 2010

Abstract

Background
Cancer is clonal proliferation that arises owing to mutations in a subset of genes that confer growth advantage. More and more cancer related genes are found to have accumulated somatic mutations. However, little has been reported about mutational patterns of insertions/deletions (indels) in these genes.

Results
We analyzed indels' abundance and distribution, the relative ratio between indels and somatic base substitutions and the association between those two forms of mutations in a large number of somatic mutations in the Catalogue of Somatic Mutations in Cancer database. We found a strong correlation between indels and base substitutions in cancer-related genes and showed that they tend to concentrate at the same locus in the coding sequences within the same samples. More importantly, a much higher proportion of indels were observed in somatic mutations, as compared to meiotic ones. Furthermore, our analysis demonstrated a great diversity of indels at some loci of cancer-related genes. Particularly in the genes with abundant mutations, the proportion of 3n indels in oncogenes is 7.9 times higher than that in tumor suppressor genes.

Conclusions
There are three distinct patterns of indel distribution in somatic mutations: high proportion, great abundance and non-random distribution. Because of the great influence of indels on gene function (e.g., the effect of frameshift mutation), these patterns indicate that indels are frequently under positive selection and can often be the 'driver mutations' in oncogenesis. Such driver forces can better explain why much less frameshift mutations are in oncogenes while much more in tumor suppressor genes, because of their different function in oncogenesis. These findings contribute to our understanding of mutational patterns and the relationship between indels and cancer.
Prognostic relevance of Bmi-1 expression and autoantibodies in esophageal squamous cell carcinoma
Authors: Liu Wan-li , Guo Xian-zhi , Zhang Lan-jun , Wang Jun-ye , Zhang Ge , Guan Su , Chen Yu-min , Kong Qing-li , Xu Li-hua , Li Man-zhi , Song Li-bing , Zeng Mu-sheng 
Published: September 2010

Abstract

Background
Overexpression of Bmi-1 has been observed in a variety of cancers, and it has been suggested to be an independent prognostic marker for the patients. The objective of this study was to determine the level of Bmi-1 expression or its autoantibodies in human esophageal squamous cell carcinoma (ESCC) and to correlate it with clinicopathologic data.

Methods
We first examined Bmi-1 expression in ESCC cell lines and tumor samples by RT-PCR and Western blot analysis. We then analyzed Bmi-1 protein expression in 171 clinicopathologically characterized ESCC cases by immunohistochemistry. In addition, we detected its autoantibodies in sera of patients with ESCC by ELISA.

Results
We found that Bmi-1 expression was higher in the immortalized cells, cancer cell lines and most cancer tissue than in non-tumorous control tissue at both mRNA and protein level. In addition, Bmi-1 expression was observed in 64.3% (110 of 171) archive ESCC specimen by immunohistochemistry analysis, and the location of Bmi-1 in ESCC was in the nuclei instead of cytoplasm of tumor cells. There was a significant difference of Bmi-1 expression in patients categorized according to stage (P = 0.003) and pN classification (P = 0.047). Multivariate analysis suggested that Bmi-1 expression was an independent prognostic marker for ESCC patients. A prognostic significance of Bmi-1 was also found in the subgroup of T3~T4 and N1 tumor classification. Bmi-1 autoantibodies were detected in sera of 39.0% (62 of 159) ESCC patients. The correlations between anti-Bmi-1 antibodies and tumor stage (P = 0.040), or lymph node status (P < 0.001) were significant.

Conclusions
Our results suggest that Bmi-1 protein is a valuable marker of ESCC progression. The presence of Bmi-1 autoantibodies in sera from patients with ESCC may have clinical utility in esophageal cancer diagnosis.
Social structural factors that shape assisted injecting practices among injection drug users in Vancouver, Canada: a qualitative study
Authors: Fairbairn Nadia , Small Will , Van Borek Natasha , Wood Evan , Kerr Thomas 
Published: September 2010

Abstract

Background
Injection drug users (IDU) commonly seek manual assistance with illicit drug injections, a practice known to be associated with various health-related harms. We investigated the social structural factors that shape risks related to assisted injection and the harms that may result.

Methods
Twenty semi-structured qualitative interviews were conducted with IDU enrolled in the ACCESS or Vancouver Injection Drug Users Study (VIDUS) who reported requiring assistance injecting in the past six months. Audio-recorded interviews were transcribed verbatim and a thematic analysis was conducted.

Results
Barriers to self-injecting included a lack of knowledge of proper injecting technique, a loss of accessible veins, and drug withdrawal. The exchange of money or drugs for assistance with injecting was common. Harms experienced by IDU requiring assistance injecting included theft of the drug, missed injections, overdose, and risk of blood-borne disease transmission. Increased vulnerability to HIV/HCV infection within the context of intimate relationships was represented in participant narratives. IDU identified a lack of services available for those who require assistance injecting, with notable mention of restricted use of Vancouver's supervised injection facility.

Conclusions
This study documents numerous severe harms that arise from assisted injecting. Social structural factors that shape the risks related to assisted injection in the Vancouver context included intimate partner relations and social conventions requiring an exchange of goods for provision of injecting assistance. Health services for IDU who need help injecting should include targeted interventions, and supervised injection facilities should attempt to accommodate individuals who require assistance with injecting.
Can bone loss be reversed by antithyroid drug therapy in premenopausal women with Graves' disease?
Authors: Belsing Tina Z , Tofteng Charlotte , Langdahl Bente L , Charles Peder , Feldt-Rasmussen Ulla 
Published: September 2010

Abstract

Context
Hyperthyroidism can lead to reduced bone mineral density (BMD) and increased fracture risk particularly in postmenopausal women, but the mechanism behind is still unclear.

Objective
Prospective examination of the influence of thyroid hormones and/or thyroid autoantibodies on BMD in premenopause.

Design
We have examined 32 premenopausal women with untreated active Graves' disease from time of diagnosis, during 18 months of antithyroid drug therapy (ATD) and additionally 18 months after discontinuing ATD. Variables of thyroid metabolism, calcium homeostasis and body composition were measured every 3 months. BMD of lumbar spine and femoral neck were measured at baseline, 18 ± 3 and 36 ± 3 months. Data were compared to base line, a sex- and age matched control group and a group of patients with Hashimoto's thyroiditis treated with non-suppressive doses of levothyroxine.

Results
The study showed significantly (p < 0.002) lower BMD in the thyrotoxic state compared to the control group with subsequent significant improvement during 18 ± 3 months of ATD compared to baseline (p < 0.001). However, during the following 18 months after stopping ATD femoral neck BMD decreased again unrelated to age (more than 0.4% per year, p < 0,002). The wellestablished effect of thyrotoxicosis on calcium homeostasis was confirmed. The positive predictor for best BMD was TSH receptor antibodies (TRAb) while free T4 correlated negatively in the thyrotoxic female Graves' patients (p < 0.02 and p < 0.003). In healthy controls and patients with treated Graves' disease both TSH and T4 correlated negatively to the bone mass (BMC) (p < 0.003).

Conclusion
The results indicated a clinically relevant impact of thyroid function on bone modulation also in premenopausal women with Graves' disease, and further indicated the possibility for a direct action of TRAb on bones.
Migration, early axonogenesis, and Reelin-dependent layer-forming behavior of early/posterior-born Purkinje cells in the developing mouse lateral cerebellum
Authors: Miyata Takaki , Ono Yuichi , Okamoto Mayumi , Masaoka Makoto , Sakakibara Akira , Kawaguchi Ayano , Hashimoto Mitsuhiro , Ogawa Masaharu 
Published: September 2010

Abstract
Background
Cerebellar corticogenesis begins with the assembly of Purkinje cells into the Purkinje plate (PP) by embryonic day 14.5 (E14.5) in mice. Although the dependence of PP formation on the secreted protein Reelin is well known and a prevailing model suggests that Purkinje cells migrate along the 'radial glial' fibers connecting the ventricular and pial surfaces, it is not clear how Purkinje cells behave in response to Reelin to initiate the PP. Furthermore, it is not known what nascent Purkinje cells look like in vivo. When and how Purkinje cells start axonogenesis must also be elucidated.

Results
We show that Purkinje cells generated on E10.5 in the posterior periventricular region of the lateral cerebellum migrate tangentially, after only transiently migrating radially, towards the anterior, exhibiting an elongated morphology consistent with axonogenesis at E12.5. After their somata reach the outer/dorsal region by E13.5, they change 'posture' by E14.5 through remodeling of non-axon (dendrite-like) processes and a switchback-like mode of somal movement towards a superficial Reelin-rich zone, while their axon-like fibers remain relatively deep, which demarcates the somata-packed portion as a plate. In reeler cerebella, the early born posterior lateral Purkinje cells are initially normal during migration with anteriorly extended axon-like fibers until E13.5, but then fail to form the PP due to lack of the posture-change step.

Conclusions
Previously unknown behaviors are revealed for a subset of Purkinje cells born early in the posteior lateral cerebellum: tangential migration; early axonogenesis; and Reelin-dependent reorientation initiating PP formation. This study provides a solid basis for further elucidation of Reelin's function and the mechanisms underlying the cerebellar corticogenesis, and will contribute to the understanding of how polarization of individual cells drives overall brain morphogenesis.
Enrichment and differential targeting of complexins 3 and 4 in ribbon-containing sensory neurons during zebrafish development
Authors: Zanazzi George , Matthews Gary 
Published: September 2010

Abstract

Background
In sensory systems with broad bandwidths, polarized receptor cells utilize highly specialized organelles in their apical and basolateral compartments to transduce and ultimately transmit signals to the rest of the nervous system. While progress has been made in elucidating the assembly of the transduction apparatus, the development of synaptic ribbon-containing terminals remains poorly understood. To begin to delineate the targeting of the exocytotic machinery specifically in ribbon-containing neurons, we have examined the expression of complexins 3 and 4 in the zebrafish visual and acousticolateral systems during the first week of development.

Results
We have identified five members of the complexin 3/4 subfamily in zebrafish that show 50 to 75% amino acid identity with mammalian complexins 3 and 4. Utilizing a polyclonal antibody that recognizes all five orthologs, we demonstrate that these proteins are enriched in ribbon-containing sensory neurons. Complexin 3/4 is rapidly targeted to presynaptic terminals in the pineal organ and retina concomitantly with RIBEYE b, a component of ribbons. In hair cells of the inner ear and lateral line, however, complexin 3/4 immunoreactivity clusters on the apical surfaces of hair cells, among their stereocilia, rather than along the basolateral plasma membrane with RIBEYE b. A complexin 4a-specific antibody selectively labels the presynaptic terminals of visual system ribbon-containing neurons.

Conclusions
These results provide evidence for the concurrent transport and/or assembly of multiple components of the active zone in developing ribbon terminals. Members of the complexin 3/4 subfamily are enriched in these terminals in the visual system and in hair bundles of the acousticolateral system, suggesting that these proteins are differentially targeted and may have multiple roles in ribbon-containing sensory neurons.
Mast cells and hypoxia drive tissue metaplasia and heterotopic ossification in idiopathic arthrofibrosis after total knee arthroplasty
Authors: Freeman Theresa A , Parvizi Javad , Dela Valle Craig J , Steinbeck Marla J 
Published: September 2010

Abstract

Background
Idiopathic arthrofibrosis occurs in 3-4% of patients who undergo total knee arthroplasty (TKA). However, little is known about the cellular or molecular changes involved in the onset or progression of this condition. To classify the histomorphologic changes and evaluate potential contributing factors, periarticular tissues from the knees of patients with arthrofibrosis were analyzed for fibroblast and mast cell proliferation, heterotopic ossification, cellular apoptosis, hypoxia and oxidative stress.

Results
The arthrofibrotic tissue was composed of dense fibroblastic regions, with limited vascularity along the outer edges. Within the fibrotic regions, elevated numbers of chymase/fibroblast growth factor (FGF)-expressing mast cells were observed. In addition, this region contained fibrocartilage and associated heterotopic ossification, which quantitatively correlated with decreased range of motion (stiffness). Fibrotic, fibrocartilage and ossified regions contained few terminal dUTP nick end labeling (TUNEL)-positive or apoptotic cells, despite positive immunostaining for lactate dehydrogenase (LDH)5, a marker of hypoxia, and nitrotyrosine, a marker for protein nitrosylation. LDH5 and nitrotyrosine were found in the same tissue areas, indicating that hypoxic areas within the tissue were associated with increased production of reactive oxygen and nitrogen species.

Conclusions
Taken together, we suggest that hypoxia-associated oxidative stress initiates mast cell proliferation and FGF secretion, spurring fibroblast proliferation and tissue fibrosis. Fibroblasts within this hypoxic environment undergo metaplastic transformation to fibrocartilage, followed by heterotopic ossification, resulting in increased joint stiffness. Thus, hypoxia and associated oxidative stress are potential therapeutic targets for fibrosis and metaplastic progression of idiopathic arthrofibrosis after TKA.
Expression of transcription factors snail, slug, and twist in human bladder carcinoma
Authors: Yu Qinchao , Zhang Kejun , Wang Xinsheng , Liu Xiangping , Zhang Zemi 
Published: September 2010

AbstractBackgroundSlug, Snail, and Twist are transcription factors that regulate the expression of tumor suppressors such as E-cadherin. In this study, we aimed to examine the expression of these transcription factors in human bladder carcinoma.MethodsWe first investigated expression of Slug, Snail, Twist and E-cadherin in five bladder Carcinoma cell lines by reverse transcription-polymerase chain reaction and western blotting. Furthermore, we investigated Slug, Snail, and Twist and E-cadherin expression by immunohistochemistry with bladder carcinoma (tumor, n = 120; background, n = 42).ResultsExpression of Slug mRNA and protein was detected in all cell lines, Twist was clearly expressed in two out of five bladder carcinoma cell lines, Snail was not expressed, and E-cadherin was detected in 3 cell lines. 44.2% (53/120) of human bladder Carcinoma tissues and 38%(16/42) background tissue showed an expression of Twist; 62.5%(75/120) of human bladder Carcinoma tissues and 40%(17/42) background tissue showed an expression of Slug, 15.8% (19/120) of human bladder Carcinoma tissues and 76%(32/42) background tissue showed an expression of Snail, and 25.8% (31/120) cases were negative for E-cadherin expression in carcinoma tissues. Expression of Slug and Twist shows increased levels in tumors, whereas Snail seems reduced. Statistically significant correlations were found between Twist, Slug, and E-cadherin expression. Immunohistochemistry analysis showed that Twist was elevated with increasing tumor stage (P= 0.001), the grade (P< 0.001), the progression (P= 0.035). Slug was elevated and Snail was reduced with increasing nodal involvement (tumor-node-metastasis status) (P= 0.004,P= 0.01). E-cadherin was reduced in expression corresponding with tumor grade (P< 0.01). Positive Twist, Slug and E-cadherin expression clearly predicted poorer PFS (P= 0.042,P= 0.014,P= 0.001). In the multivariate analysis, only Snail and E-cadherin expression were independent prognostic factors for OS (P = 0.002,P< 0.001).ConclusionsThese data demonstrate that Twist, Snail and Slug have inappropriate expression in bladder carcinoma and that this may play a part in the progression of human bladder carcinoma.
Effectiveness of dry needling and injections of myofascial trigger points associated with plantar heel pain: a systematic review
Authors: Cotchett Matthew P , Landorf Karl B , Munteanu Shannon E 
Published: September 2010

AbstractBackgroundPlantar heel pain (plantar fasciitis) is one of the most common musculoskeletal pathologies of the foot. Plantar heel pain can be managed with dry needling and/or injection of myofascial trigger points (MTrPs) however the evidence for its effectiveness is uncertain. Therefore, we aimed to systematically review the current evidence for the effectiveness of dry needling and/or injections of MTrPs associated with plantar heel pain.MethodsWe searched specific electronic databases (MEDLINE, EMBASE, AMED, CINAHL, SPORTDiscus and AMI) in April 2010 to identify randomised and non‐randomised trials. We included trials where participants diagnosed with plantar heel pain were treated with dry needling and/or injections (local anaesthetics, steroids, Botulinum toxin A and saline) alone or in combination with acupuncture. Outcome measures that focussed on pain and function were extracted from the data. Trials were assessed for quality using the Quality Index tool.ResultsThree quasi‐experimental trials matched the inclusion criteria: two trials found a reduction in pain for the use of trigger point dry needling when combined with acupuncture and the third found a reduction in pain using 1% lidocaine injections when combined with physical therapy. However, the methodological quality of the three trials was poor, with Quality Index scores ranging form 7 to 12 out of a possible score of 27. A meta‐analysis was not conducted because substantial heterogeneity was present between trials.ConclusionsThere is limited evidence for the effectiveness of dry needling and/or injections of MTrPs associated with plantar heel pain. However, the poor quality and heterogeneous nature of the included studies precludes definitive conclusions being made. Importantly, this review highlights the need for future trials to use rigorous randomised controlled methodology with measures such as blinding to reduce bias. We also recommend that such trials adhere to the Standards for Reporting Interventions in Controlled Trials of Acupuncture (STRICTA) to ensure transparency.
Endogenous PGE2 promotes the induction of human Th17 responses by fungal β-glucan
Authors: Gagliardi Maria Cristina , Teloni Raffaela , Mariotti Sabrina , Bromuro Carla , Chiani Paola , Romagnoli Giulia , Giannoni Federico , Torosantucci Antonella , Nisini Roberto 
Published: September 2010

Abstract
C. albicans β-glucan induces PGE2 production by human DC and promotes Th17 cell expansion.
The interaction of PAMPs with cells of the innate immune system shapes the adaptive host response. Here, we report that β-glucan, a major fungal PAMP purified from Candida albicans, stimulates human DCs to secrete a pro-Th17 cytokine pattern. Notably, β-glucan induces PGE2 production, which has been shown to play a pivotal role in Th17 cell expansion. Inhibition of PGE2 synthesis or blockade of PGE2 receptors EP2 and EP4 drastically reduces IL-23 production by β-glucan-activated DCs, suggesting that endogenous PGE2 amplifies IL-23 synthesis in response to the C. albicans PAMP. Moreover β-glucan promotes the expansion of Th17 cells, which is strongly decreased by EP2 and EP4 receptor blockade on DCs. Our results highlight a novel role for PGE2 in the regulation of innate and adaptive immune response triggered by recognition of a prominent, highly conserved fungal PAMP such as β-glucan.
Arsenic modulates APOBEC3G-mediated restriction to HIV-1 infection in myeloid dendritic cells
Authors: Stalder Romaine , Blanchet Fabien , Mangeat Bastien , Piguet Vincent 
Published: September 2010

Abstract
An APOBEC3G-dependent restriction operates in blood-derived myeloid dendritic cells, which can be relieved by arsenic trioxide.
DC are major targets of HIV-1 during the early events of infection. Yet, HIV-1 infects these cells only inefficiently in vitro as compared with CD4+T lymphocytes. Accordingly, we have previously identified a strong post-entry block to HIV-1 replication in MDDC as a result of the cellular restriction factor A3G. Furthermore, we have demonstrated that As2O3, a drug used to treat acute promyelocytic leukemia, can fully eliminate the potent post-entry restriction of HIV-1 infection in MDDC and in blood-derived MyDC by mechanisms that were unclear. We are now exploring the interplay between As2O3 and A3G-mediated restriction in primary DC subsets. Here, we report that As2O3 counteracts A3G-mediated restriction in MyDC but not in MDDC. RNAi of A3G in MyDC indicated that the As2O3-mediated increase of HIV-1 infection was largely dependent on the presence of the cellular restriction factor. This study reveals an unexpected interplay between As2O3 and A3G-mediated restriction to HIV-1 infection in primary human MyDC.
T-bet-independent effects of IL-12 family cytokines on regulation of Th17 responses to experimental T. cruzi infection
Authors: Cobb Dustin , Hambright Derek , Smeltz Ronald B 
Published: September 2010

Abstract
IFN-γ is not required for T-bet-dependent inhibition of Th17 responses to T. cruzi infection, but can synergize with IL-12 to reduce T. cruzi-specific IL-17 production.
Tbx21 (i.e., T-bet) is an IFN-γ-inducible transcription factor that promotes Th1 differentiation. Previously, we reported that Tbx21−/− mice develop a robust Th17 response to the parasite Trypanosoma cruzi, including CD4+ T cell subsets producing IL-17 and IFN-γ. Because of the known inhibitory effects of IFN-γ on Th17 cells, the purpose of this study was to determine the contribution of IFN-γ to regulation of Th17 differentiation during the course of T. cruzi infection. We observed that infection of IFN-γ−/− or Stat-1−/− mice generated increased numbers of IL-17-producing cells. In sharp contrast to infected Stat-1−/− or Tbx21−/− mice, however, IFN-γ−/− mice developed a lower overall Th17 response, suggesting that IFN-γ was not required for T-bet-dependent activity, including T-bet-dependent expression of CXCR3. To determine if IFN-γ could influence Th17 responses indirectly by acting on APCs, we neutralized IFN-γ in cultures containing APC and T. cruzi antigens. Although anti-IFN-γ increased IL-17 production modestly, anti-IFN-γ and anti-IL-12 led to a significant enhancement of T. cruzi-specific IL-17 (P&lt;0.01). In contrast to the inhibitory effects of IL-12, IL-23 was able to stimulate Tbx21−/− T cells and cause a striking increase in T. cruzi-specific IL-17. These data show that the IL-12 family of cytokines can influence Th17 responses in a T-bet-independent manner and that the effects of IFN-γ are not necessarily related to its ability to induce T-bet expression in T cells.