Miracle-dz/UniFAR-FTUs huggingface dataset:
The oligomeric architecture of the archaeal exosome is important for processive and efficient RNA degradation

The exosome plays an important role in RNA degradation and processing. In archaea, three Rrp41:Rrp42 heterodimers assemble into a barrel like structure that contains a narrow RNA entrance pore and a lumen that contains three active sites. Here, we demonstrate that this quaternary structure of the exosome is important for efficient RNA degradation. We find that the entrance pore of the barrel is required for nM substrate affinity. This strong interaction is crucial for processive substrate degradation and prevents premature release of the RNA from the enzyme. Using methyl TROSY NMR techniques, we establish that the 3′ end of the substrate remains highly flexible inside the lumen. As a result, the RNA jumps between the three active sites that all equally participate in substrate degradation. The RNA jumping rate is, however, much faster than the cleavage rate, indicating that not all active site:substrate encounters result in catalysis. Enzymatic turnover therefore benefits from the confinement of the active sites and substrate in the lumen, which ensures that the RNA is at all times bound to one of the active sites. The evolution of the exosome into a hexameric complex and the optimization of its catalytic efficiency were thus likely co-occurring events.
Current advances of genetics in Inflammatory Bowel Disease

Genetic factors play an important role in the pathogenesis of inflammatory bowel diseases (IBD), including both ulcerative colitis (UC) and Crohns disease (CD). The research on genetic susceptibility of IBD has been tremendous and over 10 chromosomal regions have been identified by genome-wide scanning. The certain replicated linkage region in different studies, IBD1 (16q12), contains the CD susceptibility gene, NOD2/CARD15. Further fine mapping as well as candidate gene studies have already led to the identification of a number of other susceptibility genes including DLG5, OCT1 and 2, NOD1, HLA, and TLR4. Recent studies, particularly in CD, have highlighted a number of associations between genotype and phenotype. These, suggest that genetics also may influence the clinical manifestations of IBD including disease location, behavior, natural history and side effects of drug therapy. Genetic research in IBD has helped our understanding of the clinical heterogeneity of the disease and has started to explore the complex interactions between genetic risk factors and environmental risk factors in IBD. Although rapid advances in genomic medicine are yet to impact on routine clinical practice, it is anticipated that genetic markers in the future will be implemented in an integrated molecular diagnostic, therapeutic and prognostic approach of IBD patients.
Genetic and epigenetic changes in aberrant crypt foci and serrated polyps

Aberrant crypt foci (ACF) in colorectal mucosa are the earliest known morphological precursors to colorectal cancer and can be subclassified as dysplastic, heteroplastic (non‐dysplastic), and mixed types. Serrated adenoma (SA) is a polyp with serrated architecture and dysplasia, and can be subclassified as traditional SA or sessile SA. Sessile SA is thought to be preneoplastic and differs from most lesions in the traditional SA category because of their flat morphology and general lack of cytological dysplasia. Serrated polyps include hyperplastic polyps (HP), SA, and admixed hyperplastic‐adenomatous polyps and are considered a morphological continuum encompassing heteroplastic ACF, HP, admixed hyperplastic‐adenomatous polyps, and SA. Recent studies have uncovered other developmental pathways including a heteroplastic ACF‐HP/SA‐carcinoma sequence and a heteroplastic ACF–adenoma–carcinoma sequence. Heteroplastic ACF histopathologically resemble HP and SA. Sporadic HP are usually present in the left colon, are small, and are considered benign. However, adenocarcinoma arising in the setting of colorectal HP or SA, especially in patients with hyperplastic polyposis, has been described. The relationship between heteroplastic ACF, HP, and colorectal cancer is less certain than that of dysplastic ACF. Here, we discuss the current understanding of genetic and epigenetic alterations in the development of colorectal cancer. Our goal is to provide a conceptual framework for understanding the heteroplastic ACF–HP/SA–carcinoma sequence. (Cancer Sci 2008; 99: 1071–1076)
Ultralow‐Fouling, Functionalizable, and Hydrolyzable Zwitterionic Materials and Their Derivatives for Biological Applications

In recent years, zwitterionic materials such as poly(carboxybetaine) (pCB) and poly(sulfobetaine) (pSB) have been applied to a broad range of biomedical and engineering materials. Due to electrostatically induced hydration, surfaces coated with zwitterionic groups are highly resistant to nonspecific protein adsorption, bacterial adhesion, and biofilm formation. Among zwitterionic materials, pCB is unique due to its abundant functional groups for the convenient immobilization of biomolecules. pCB can also be prepared in a hydrolyzable form as cationic pCB esters, which can kill bacteria or condense DNA. The hydrolysis of cationic pCB esters into nonfouling zwitterionic groups will lead to the release of killed microbes or the irreversible unpackaging of DNA. Furthermore, mixed‐charge materials have been shown to be equivalent to zwitterionic materials in resisting nonspecific protein adsorption when they are uniformly mixed at the molecular scale.
Employment and Child Care Decisions of Women and the Well-Being of Their Children

This paper develops and estimates a dynamic model of employment and child care decisions of women after birth in order to evaluate the effects of mothers' decisions on children's cognitive ability. I use data from the NLSY to estimate the model. The results suggest that the effects of maternal employment and child care use on children's cognitive ability are rather sizeable. In fact, having a full-time working mother who uses child care during the first 5 years after the birth of the child is associated with a 10.4% reduction in ability test scores. Based on the estimates of the model, I assess the impact of policies related to parental leave, child care and other incentives to stay at home after birth on women's decisions and children's outcomes
Usefulness of ω-3 fatty acid supplementation in addition to mesalazine in maintaining remission in pediatric Crohn's disease: A double-blind, randomized, placebo-controlled study

AIM: To assess the value of long-chain ω-3 fatty acids (FAs) supplementation in addition to amino-salicylic-acid (5-ASA) in pediatric patients with Crohn's disease (CD). METHODS: Thirty-eight patients (20 males and 18 females, mean age 10.13 years, range 5-16 years) with CD in remission were randomized into two groups and treated for 12 mo. Group I (18 patients) received 5-ASA (50 mg/kg/d)+ω-3 FAs as triglycerides in gastro-resistant capsules, 3 g/d (eicosapentanoic acid, EPA, 400 mg/g, docosahexaenoic acid, DHA, 200 mg/g). Group II (20 patients) received 5-ASA (50 mg/kg/d)+olive oil placebo capsules. Patients were evaluated for fatty acid incorporation in red blood cell membranes by gas chromatography at baseline 6 and 12 mo after the treatment. RESULTS: The number of patients who relapsed at 1 year was significantly lower in group I than in group II (P<0.001). Patients in group I had a significant increase in the incorporation of EPA and DHA (P<0.001) and a decrease in the presence of arachidonic acids. CONCLUSION: Enteric-coated ω-3 FAs in addition to treatment with 5-ASA are effective in maintaining remission of pediatric CD.
Pathophysiology of Drug-Induced Dyskinesias

Christopher A. Lieu1,2, Vikram Shivkumar1, Timothy P. Gilmour1,2, Kala Venkiteswaran1,2, Mark J. Nolt1,3, Milind Deogaonkar4 and Thyagarajan Subramanian1,2 1Department of Neurology, The Pennsylvania State University College of Medicine and M.S. Hershey Medical Center, Hershey, Pennsylvania 2Department of Neural & Behavioral Sciences, The Pennsylvania State University College of Medicine and M.S. Hershey Medical Center, Hershey, Pennsylvania 3Functional Neurosurgical Services, Sentient, Inc., Hunt Valley, Maryland 4Center for Neurological Restoration, The Cleveland Clinic Foundation, Cleveland, Ohio USA
Exploring the performance and self-regulation of medical students through an intervention aimed at regulating the way they feel

Research has shown that how individuals feel affects their performance (Doell et al., 2006; Durand-Bush et al., 2005). Since felt experiences in the context of medicine have been shown to be of importance (Novack et al., 1997; Sotile & Sotile, 2002), and selfregulation skills have been found to help foster learning (Zimmerman, 1990), the purpose of this study was to examine the self-regulation of the felt experiences of four medical students through an intervention guided by the Resonance Performance Model (RPM) (Newburg et al., 2002), and determine how it affected self-defined standards of performance. Results of this multiple case study (Stake, 2006) showed that each student was able to identify and experience, the way they wanted to feel within their performance environment, and reach an optimal level of performance during the intervention process by attuning to and regulating the way they felt. Implications for future research on performance as a self-defined process, and the provision of opportunities for selfregulated learning in medical education are discussed. Copyright by the Faculty of Graduate and Postdoctoral Studies, University of Ottawa, Ottawa, Ontario, Canada, 2008 All Rights Reserved © Christopher R. Simon, 2008
Person Centred Dementia Care: Making Services Better

Part 1: Unpacking What We Mean by Person-Centred Care. 1. What is Person-Centred Care? 2. Valuing People. 3. Individualised Care. 4. Personal Perspectives. 5. Social Environment. 6. Care in Context. Part 2: The VIPS Framework. The VIPS Framework: Person-Centred Care for People with Dementia. References. Subject index. Author index.
Head and neck cancer in the betel quid chewing area: recent advances in molecular carcinogenesis

Head and neck cancer (HNC) is one of the 10 most frequent cancers worldwide, with an estimated over 500 000 new cases being diagnosed annually. The overall 5‐year survival rate in patients with HNC is one of the lowest among common malignant neoplasms and has not significantly changed during the last two decades. Oral cavity squamous cell carcinoma (OSCC) shares part of HNC and has been reported to be increasing in the betel quid chewing area in recent years. During 2006, OSCC has become the sixth most common type of cancer in Taiwan, and it is also the fourth most common type of cancer among men. It follows that this type of cancer wreaks a high social and personal cost. Environmental carcinogens such as betel quid chewing, tobacco smoking and alcohol drinking have been identified as major risk factors for head and neck cancer. There is growing interest in understanding the relationship between genetic susceptibility and the prevalent environmental carcinogens for HNC prevention. Within this review, we discuss the molecular and cellular aspects of HNC carcinogenesis in Taiwan, an endemic betel quid chewing area. Knowledge of molecular carcinogenesis of HNC may provide critical clues for diagnosis, prognosis, individualization of therapy and molecular therapeutics. (Cancer Sci 2008; 99: 1507–1514)
High mobility group box‐1‐inducible melanoma inhibitory activity is associated with nodal metastasis and lymphangiogenesis in oral squamous cell carcinoma

Melanoma inhibitory activity (MIA) is an 11‐kDa secretory protein isolated from malignant melanoma cells that is correlated with invasion and metastasis in various human malignancies. We examined MIA expression in 62 oral squamous cell carcinomas (OSCC) by immunohistochemistry. MIA expression was significantly associated with nodal metastasis (P = 0.00018). MIA expression was also associated with expression of high mobility group box‐1 (HMGB1) (P < 0.0001) and lymph vessel density (P < 0.0001). Expression levels of MIA, HMGB1, nuclear factor kB (NFkB) p65 and HMGB1–NFkB p65 binding were significantly higher in a metastatic human OSCC cell line (HSC3) than those in a non‐metastatic OSCC cell line (HSC4). Treatment with receptor for advanced glycation end products (RAGE) antisense or small interfering RNA and human recombinant HMGB1 (hrHMGB1) did not affect MIA expression, whereas HMGB1 antisense or siRNA treatment decreased MIA expression in HSC3 cells. Then HMGB1 enhanced MIA expression as an NFkB cofactor but not as a RAGE ligand. MIA neutralization by MIA antibodies increased extracellular signal‐related kinase 1/2 phosphorylation, but decreased p38 phosphorylation and the expression of vascular epithelial growth factor (VEGF)‐C and ‐D. Treatment with p38 inihibitor decreased VEGF‐C and ‐D expression in HSC3 cells. These results suggest that MIA expression is enhanced by the interaction of intracellular HMGB1 and NFkBp65 and MIA is closely involved in tumor progression and nodal metastasis by the increments of VEGF‐C and VEGF‐D in OSCC. (Cancer Sci 2008; 99: 1806– 1812)
Impaired removal of DNA interstrand cross‐link in Nijmegen breakage syndrome and Fanconi anemia, but not in BRCA‐defective group

Human diseases characterized by a high sensitivity to DNA interstrand cross‐links (ICL) and predisposition to malignance include Nijmegen breakage syndrome (NBS) and Fanconi anemia (FA), which is further classified to three groups: (1) FA core‐complex group; (2) FA‐ID complex group; and (3) breast cancer (BRCA)‐defective group. The relationships between these four groups and the basic defect in ICL repair remain unclear. To study the details of ICL repair in NBS and FA, a highly sensitive PPB (psoralen–polyethylene oxide–biotin) dot blot assay was developed to provide sensitive quantitative measurements of ICL during the removal process. Studies utilizing this assay demonstrated a decreased rate of ICL removal in cells belonging to the FA core‐complex group (e.g. groups A and G) and FA‐ID complex group (group D2), while ICL removal was restored to normal levels after these cells were complemented with wt‐FANCA, wt‐FANCG and wt‐FANCD2. Conversely, FA‐D1 cells with a defective BRCA2 protein displayed normal ICL removal, although they were compromised with respect to recombination. This normal ICL removal rate in recombination‐deficient cells was confirmed by using XRCC3‐defective Chinese hamster cells, which are similarly compromised with respect to recombination and are sensitive to mitomycin C. The present study also showed that cells from patients with Nijmegen breakage syndrome were defective in ICL removal, while they were impaired in the recombination. These results indicate an obvious defect of FA and NBS in the ICL repair process, except in the BRCA‐defective group, and a separate step of recombination‐mediated repair pathway between the BRCA group and NBS. (Cancer Sci 2008; 99: 2238–2243)
DNA methyltransferase inhibitor 5‐aza‐CdR enhances the radiosensitivity of gastric cancer cells

The National Comprehensive Cancer Network guidelines recommend radiotherapy as a standard treatment for patients with a high risk of recurrence in gastric cancer. Because radiation is harmful to the surrounding organs, a radiation sensitizer might therefore be useful to decrease the side effects of patients with advanced gastric carcinoma. The aim of the current study was to clarify the effect of a DNA methyltransferase inhibitor, 5‐aza‐2′‐deoxycytidine (CdR), on radiation sensitivity in gastric cancer cells. Five gastric cancer cell lines, OCUM‐2M, OCUM‐12, KATO‐III, MKN‐45, and MKN‐74, were used. The effects of 5‐aza‐CdR with irradiation on the growth activity, cell‐cycle distribution, apoptosis, and apoptosis‐associated gene expression were examined. 5‐aza‐CdR sensitized three of five gastric cancer cell lines to radiation. A combination of irradiation and 5‐aza‐CdR significantly (P < 0.05) decreased the growth activity compared with irradiation alone in OCUM‐2M, OCUM‐12, and MKN‐45 cells, but not in KATO‐III and MKN‐74 cells. The percentage of cells in G2–M phase and the apoptotic rate with irradiation in combination with 5‐aza‐CdR were increased in OCUM‐2M, OCUM‐12, and MKN‐45 cells compared with irradiation alone, but not in KATO‐III and MKN‐74 cells. 5‐aza‐CdR increased the expression of p53, RASSF1, and death‐associated protein kinases (DAPK) genes compared with the control or irradiation alone. These findings suggest that 5‐aza‐CdR might therefore be useful as a radiation sensitizer to treat some types of gastric carcinoma. The arrest at G2–M phase and increased apoptotic rate might be partly mediated by enhanced expression of the p53, RASSF1, or DAPK gene families by 5‐aza‐CdR. (Cancer Sci 2009; 100: 181–188)
Morbidade referida e capacidade funcional de idosos

This is a descriptive cross-sectional study, which aims to describe the morbidities reported by elderly individuals and analyze their influence over the individuals’ functional capacity. The sample consisted of 47 elderly individuals aged over 60 years, who were assisted at the geriatric clinic of a public hospital in 2001, in Ribeirao Preto, Sao Paulo, Brazil. Data were collected by consulting patient records and by interviewing elders/caregivers, using a functional capacity assessment instrument. Sociodemographic characteristics revealed a feminization of aging, an average age beyond life expectancy in Brazil, there were more widows than widowers, more illiterate women than men, and most had their retirement pension as the main financial resource. In terms of functional performance, urinary incontinence and stroke (cerebrovascular accident-CVA) were the least reported morbidities, but with the highest interference on the basic activities of daily living (ADL) and instrumental activities of daily living (IADL). Women reported a greater number of morbidities and higher interference to their ADLs. Our results highlight the need to evaluate the functional capacities affected by morbidities, with a view to maintain and improve the quality of life of the elderly. Key words: Health of the Elderly. Aging. Motor activity. Morbidity.
Role of Gallium Doping in Dramatically Lowering Amorphous‐Oxide Processing Temperatures for Solution‐Derived Indium Zinc Oxide Thin‐Film Transistors

[*] Prof. T. J. Marks, Dr. A. Facchetti, Dr. S. Jeong, Y. -G. Ha Department of Chemistry and the Materials Research Center Northwestern University 2145 Sheridan Road, Evanston, IL 60208 (USA) E-mail: t-marks@northwestern.edu; a-facchetti@northwestern.edu Prof. J. Moon Department of Materials Science and Engineering Yonsei University 134 Shinchon-dong, Seodaemun-gu, Seoul 120-749 (Korea) [+] Present address: Korea Research Institute of Chemical Technology, 19 Sinseongno, Yuseong, Daejeon 305-600 (Korea)
An outbreak of Haemorrhagic Septicaemia in bovines and its management.

An outbreak of Haemorrhagic Septicaemia was reported in Simara Village of Aurangabad, Bihar, India with mortality of twenty cattle and buffaloes in mid February, 2010. Thereafter, Haemorrhagic Septicaemia affected animals were successfully controlled by using enrofloxacin along with meloxicam and corticosteroid. The preventation and control measures suggested were animal movement control, proper disposal of carcasses by deep burial with strong lime powder treatment and lime powder was also sprinkled in the animals shed.
ASSESSMENT OF KNOWLEDGE AMONG HEALTH CARE PROVIDERS REGARDING INTRAMUSCULAR INJECTION ADMINISTRATION

Objectives: The aim was to assess the existing knowledge of intramuscular (IM) injection administration technique among health care providers in teaching hospital. Methods: A cross-sectional study was conducted among medical interns, final year nursing students, and MBBS Phase-II students (health care providers) of Mandya Institute of Medical Sciences, Mandya. A total of 257 health care providers participated in this study and were asked to narrate the steps of IM injection technique. The correctness of technique was graded using a standard checklist of 10 steps. Knowledge was assessed by number of steps answered correctly by them. Results: Out of 257 participants, all the steps of IM injection technique were correctly answered by 18.8% of nursing students, and 17% of medical interns. Knowledge of site selection and sterilization of site for IM injection was good among all the groups (97.7%). Steps involving angle of insertion of needle into the muscle, checking whether needle is correctly inserted into muscle, proper disposal of syringe and sanitization of hand after the procedure was answered correctly by 89.1%, 72.3%, 42.8% and 45.5% of participants respectively. Conclusion: Nursing students and medical interns had better knowledge regarding technique of IM injection when compared to MBBS Phase-II students. However, the knowledge concerning the disposal of syringe and sanitization in the hand was better among nursing students than the other two groups. Even though, medical interns and nursing students have responded well, still there is a scope for further improvement in the procedure. Keywords: Health care providers, Intramuscular injection, Knowledge.
Activated hepatic stellate cells promote tumorigenicity of hepatocellular carcinoma

Liver cirrhosis is the main risk factor for the development of hepatocellular carcinoma (HCC). Activated hepatic stellate cells (HSC) are the effector cells of hepatic fibrosis and also infiltrate the HCC stroma where they might play a critical role in HCC progression. Here we aimed to analyze the effects of activated HSC on the proliferation and growth of HCC cell lines in vitro and in vivo. Conditioned media (CM) collected from HSC significantly induced proliferation and migration of HCC cells cultured in monolayers. In a 3‐dimensional spheroid coculture system, HSC promoted HCC growth and diminished the extent of central necrosis. In accordance, in vivo simultaneous implantation of HSC and HCC cells into nude mice promoted tumor growth and invasiveness, and inhibited necrosis formation. As potential mechanism of the tumorigenic effects of HSC we identified activation of NFkappaB and extracellular‐regulated kinase (ERK) in HCC cells, two signaling cascades that play a crucial role in HCC progression. In summary, our data indicate that stromal HSC promotes HCC progression and suggest the HSC–HCC interaction as an interesting tumor differentiation‐independent target for therapy of this highly aggressive cancer. (Cancer Sci 2009; 100: 646–653)