bluuebunny/crossref_metadata_2025 huggingface dataset:
Informing evidence‐based clinical practice guidelines for children with cerebral palsy at risk of osteoporosis: a systematic review
Authors: FEHLINGS DARCY , SWITZER LAUREN , AGARWAL PAYAL , WONG CHARLES , SOCHETT ETIENNE , STEVENSON RICHARD , SONNENBERG LYN , SMILE SHARON , YOUNG ELIZABETH , HUBER JOELENE , MILO‐MANSON GOLDA , KUWAIK GHASSAN ABU , GAEBLER DEBORAH
Published: November 2011

Aim  The aim of this systematic review was to inform evidence‐based clinical practice guidelines for children with cerebral palsy (CP) and low bone mineral density (BMD).

Method  A computer‐assisted literature search was focused on low BMD in children with CP, and was limited to the following interventions: weight‐bearing activities, bisphosphonate use, and vitamin D or calcium supplementation. Articles were classified according to American Academy of Neurology guidelines and recommendation classifications were given based on the evidence for the intervention increasing BMD and decreasing fragility fractures. Studies were included if they were English‐language full‐text studies, focused on children with CP, and included at least 10 participants receiving the studied interventions.

Results  Twenty‐one articles underwent full‐text review and data abstraction, including seven studies of weight‐bearing activities, five studies of vitamin D or calcium supplementation, and nine studies of bisphosphonates administration. Overall, the evidence that bisphosphonates administration increases BMD was assessed as level B (probable) while the evidence that vitamin D or calcium supplementation does so was assessed as level C (possible); there was insufficient evidence to suggest that weight‐bearing activities are an effective intervention to improve BMD. The evidence that bisphosphonates help to prevent fragility fractures was assessed as level C (possible); there was inadequate evidence to support the use of weight‐bearing activities or vitamin D or calcium supplementation to decrease fragility fractures.

Interpretation  Evidence‐based clinical practice guidelines were created outlining the suggested role of weight‐bearing activities, vitamin D and calcium supplementation, and bisphosphonate use for children with CP with low BMD at risk of fragility fractures.
Single‐event multilevel surgery for children with cerebral palsy: a systematic review
Authors: MCGINLEY JENNIFER L , DOBSON FIONA , GANESHALINGAM REKHA , SHORE BENJAMIN J , RUTZ ERICH , GRAHAM H KERR
Published: November 2011

Aim  To conduct a systematic review of single‐event multilevel surgery (SEMLS) for children with cerebral palsy, with the aim of evaluating the quality of the evidence and developing recommendations for future research.

Method  The systematic review was conducted using standard search and extraction methods in Medline, EMBASE, CINAHL, and Cochrane electronic databases. For the purposes of this review, SEMLS was defined as two or more soft‐tissue or bony surgical procedures at two or more anatomical levels during one operative procedure, requiring only one hospital admission and one period of rehabilitation. Studies were included if: (1) the primary focus was to examine the effect of SEMLS in children with cerebral palsy; (2) the results focused on multiple anatomic levels and reported findings of one or more World Health Organization International Classification of Functioning, Disability and Health (ICF) domains. Studies that focused on a single intervention or level, or on the utility of a specific outcome measure were excluded. Study quality was appraised with the Methodological Index for Non‐Randomized Studies (MINORS) and the Oxford Centre for Evidence‐Based Medicine scale. The review also examined the reporting of surgery, adverse events, and rehabilitation.

Results  Thirty‐one studies fulfilled the criteria for inclusion, over the period 1985 to October 2010. The MINORS score for these studies varied from 4 to 19, with marked variation in the quality of reporting. Study quality has improved over recent years. Valid measures of gait and function have been introduced and several of the most recent studies have addressed multiple dimensions of the ICF. A statistical synthesis of the outcome data was not conducted, although a trend towards favourable outcomes in gait was evident. Caution is advised with interpretation owing to the variable study quality. Uncontrolled studies may have resulted in an overestimation of treatment efficacy.

Interpretation  The design and reporting of studies of SEMLS are improving with the development of multidisciplinary teamwork and frameworks such as the ICF. However, the evidence base is limited by the lack of randomized clinical trials, especially when compared with other surgical interventions such as selective dorsal rhizotomy.
Osseointegration of SLActive implants in diabetic pigs
Authors: Schlegel K. A. , Prechtl C. , Möst T. , Seidl C. , Lutz R. , von Wilmowsky C.
Published: November 2011

Objectives

Diabetes mellitus is currently classified as a relative contraindication for implant treatment because of microangiopathies with the consequence of impaired bone regeneration and higher rates of implant failure. The study aim was to investigate peri‐implant bone formation in a diabetic animal model in comparison to healthy animals and to evaluate the differences between conventional (SLA®) and modified (SLActive®) titanium implant surfaces on osseointegration.

Material and methods

Each six implants were placed in the calvaria of 11 diabetic and 4 healthy domestic pigs. At 30 and 90 days after implant placement, the bone‐to‐implant contact (BIC) and bone density (BD) were appraised. Additionally, the expression of the bone‐matrix proteins collagen type I and osteocalcin was evaluated at both points in time by using immunohistochemical staining methods.

Results

Overall, BIC was reduced in the diabetic group at 30 and 90 days. After 90 days, the SLActive® implants showed significantly higher BICs compared with the SLA® implants in diabetic animals. Peri‐implant BD was higher in the SLActive® group at 30 and 90 days in healthy and diabetic animals. Collagen type I protein expression was higher using SLA® implants in diabetic pigs at 30 days. Values for osteocalcin expression were not consistent.

Conclusions

The results indicate the negative effect of untreated diabetes mellitus on early osseointegration of dental implants. The modified SLA® surface (SLActive®) elicited an accelerated osseointegration of dental implants, suggesting that a better prognosis for implant treatment of diabetic patients is possible.
Habitat Associations and Community Structure of Dipterocarps in Response to Environment and Soil Conditions in Brunei Darussalam, Northwest Borneo
Authors: Sukri Rahayu S. , Wahab Rodzay A. , Salim Kamariah A. , Burslem David F. R. P.
Published: November 2011

Plant habitat associations are well documented in Bornean lowland tropical forests, but few studies contrast the prevalence of associations across sites. We examined habitat associations and community composition of Dipterocarpaceae trees in two contrasting Bornean lowland mixed dipterocarp forests separated by approximately 100 km: Andulau (uniform topography, lower altitudinal range, sandy soils) and Belalong (highly dissected topography, higher altitudinal range, clay‐rich soils). Dipterocarpaceae trees ≥ 1 cm diameter at breast height (dbh) were censused in 20‐m wide belt transects established along topographic gradients at each site. Dipterocarp density, evenness, species richness, and diversity were significantly higher at Andulau than Belalong. Significant site associations (with either Andulau or Belalong) were detected for 19 (52%) of the 37 dipterocarp species tested. Dipterocarpaceae community composition at Belalong correlated with soil nutrient concentrations as well as measures of vegetation and topographic structure, but community composition at Andulau correlated with fewer habitat variables. Within each site, dipterocarp density, species richness, and diversity were consistently higher on ridges than in slopes and valleys. Significant within‐site associations to topographic habitats were less common at Andulau (10% of species tested) than at Belalong (15%). We conclude that edaphic and other environmental factors influence dipterocarp community composition at a local scale, and are more important drivers of community structure in the more variable environment at Belalong. Species richness and diversity of dipterocarps on small plots, however, were higher at Andulau, suggesting that factors other than environmental heterogeneity contribute to contrasts in dipterocarp tree species richness at small scales.
Current Status of Intravenous Thrombolysis for Acute Ischemic Stroke in Asia
Authors: Sharma Vijay K. , Ng Kay W. P. , Venketasubramanian Narayanaswamy , Saqqur Maher , Teoh Hock L. , Kaul Subash , Srivastava Padma M. V. , Sergentanis Theodoris , Suwanwela Nijasri , Nguyen Thang H. , Lawrence Wong K. S. , Chan Bernard P. L.
Published: November 2011

Background

Data regarding thrombolysis for acute ischemic stroke in Asia are scarce and only a small percentage of patients are thrombolysed. The dose of intravenous tissue plasminogen activator (IV-tPA) in Asia remains controversial. Case-controlled observation studies in Asia included only Japanese patients and suggested the clinical efficacy and safety of low-dose IV-tPA (0·6 mg/kg body weight; max 60 mg) comparable to standard dose (0·9 mg/kg body weight; max. 90 mg). Reduced treatment cost, lower symptomatic intracerebral hemorrhage risk and comparable efficacy encouraged many Asian centers to adopt low-dose or even variable-dose IV-tPA regimens. We evaluated various Asian thrombolysis studies and compared with SITS-MOST registry and NINDS trial.

Methods

We included the published studies on acute ischemic stroke thrombolysis in Asia. Unadjusted relative risks and 95% Confidence intervals were calculated for each study. Pooled estimates from random effects models were used because the tests for heterogeneity were significant.

Results

We found only 18 publications regarding acute ischemic stroke thrombolysis in Asia that included total of 9300 patients. Owing to ethnic differences, stroke severity, small number of cases in individual reports, outcome measures and tPA dose regimes, it is difficult to compare these studies. Functional outcomes were almost similar (to Japanese studies) when lower-dose IV-tPA was used in non-Japanese populations across Asia. Interestingly, with standard dose IV-tPA, considerably better functional outcomes were observed, without increasing symptomatic intracerebral hemorrhage rates.

Conclusions

Variable dose regimens of IV-tPA are used across Asia without any reliable or established evidence. Establishing a uniform IV-tPA regimen is essential since the rapid improvements in health-care facilities and public awareness are expected to increase the rates of thrombolysis in Asia.
Impact of Anticoagulation before Stroke on Stroke Severity and Long-Term Survival
Authors: Haeusler Karl Georg , Konieczny Maria , Endres Matthias , Villringer Arno , Heuschmann Peter U.
Published: November 2011

Background

Therapeutic anticoagulation by vitamin K antagonists is highly effective in reducing stroke risk in patients with atrial fibrillation. Vitamin K antagonist treatment before stroke reduces stroke severity and short-term mortality.

Aims

This study analyses vitamin K antagonists, used in patients with atrial fibrillation diagnosed before the index stroke. We also focus on the impact of preadmission anti-thrombotic medication on long-term survival.

Methods

We analyzed 2390 stroke patients consecutively admitted to the Department of Neurology, Charité Berlin, Germany between 2003 and 2004. Mean follow-up was 38 months (range 0–68). Using univariable and multivariable regression models, we identified factors for preadmission anticoagulation in patients with known atrial fibrillation and analyzed the impact of antithrombotic therapy preadmission on functional disability and long-term survival after stroke.

Results

Atrial fibrillation was diagnosed in 534 (22.3%) of the 2390 stroke patients. In 348 (65.2%) of all atrial fibrillation patients, atrial fibrillation was already known before the index stroke. Three hundred twenty-five (93.4%) atrial fibrillation patients were amenable to anticoagulation, according to guidelines, 75 (23.1%) received vitamin K antagonists, and 20 (6.2%) had an international normalized ratio of 2–3 at the time of stroke onset. Males and younger patients were more likely to receive anticoagulation preadmission, while previous stroke had no significant impact on vitamin K antagonist prescription. Age (odds ratio 1.02 (95% confidence interval 1.00–1.04) per year), history of coronary artery disease (odds ratio 1.51 (95% confidence interval 1.01–2.26)), and therapeutic anticoagulation (odds ratio 0.28 (0.09–0.84)) were independent predictors of stroke severity. Age (hazard rates 3.11 (95% confidence interval 1.47–6.59), 4.65 (95% confidence interval 2.27–9.57), and 11.1 (95% confidence interval 4.90–25.1) for age categories 65–74, 75–84, and ≥85 years), preadmission antiplatelet therapy (hazard rate 1.85 (95% confidence interval 1.21–2.82)), and stroke severity on admission (hazard rate 1.60 (95% confidence interval 1.03–2.46) and hazard rate 3.23 (95% confidence interval 1.88–5.55) for National Institutes of Health Stroke Scale categories 6–15 and >15 points) were associated with risk of death during follow-up.

Conclusions

In patients in which atrial fibrillation was diagnosed prior to the index stroke, about 23% received anticoagulation according to guideline recommendations. Therapeutic anticoagulation at stroke onset significantly decreased the risk of moderate to severe stroke on admission but showed no significant association with long-term survival.
Detection of 2009 pandemic influenza A(H1N1) virus Infection in different age groups by using rapid influenza diagnostic tests
Authors: Gao Fengxiang , Loring Carol , Laviolette Michael , Bolton Denise , Daly Elizabeth R. , Bean Christine
Published: November 2011

Please cite this paper as: Gao et al. (2011) Detection of 2009 pandemic influenza A(H1N1) virus Infection in different age groups by using rapid influenza diagnostic tests. Influenza and Other Respiratory Viruses 6(3), e30–e34.

Background  The performance of rapid influenza diagnostic tests (RIDTs) in detecting influenza A(H1N1) 2009 has varied widely. Evaluations of RIDTs among infected individuals across all age groups have not been described in depth.

Objectives  Determine RIDT clinical sensitivity in comparison with influenza detection using real‐time RT‐PCR among patients infected with influenza A(H1N1) 2009 across all age groups.

Study design  This study analyzed respiratory specimens received by the New Hampshire Public Health Laboratories (NHPHL) from September 1, 2009, through December 31, 2009. RIDT performance was evaluated among different age groups of patients determined to be infected with influenza A (H1N1) 2009, and the association between age and RIDT sensitivity was determined.

Results  Of 1373 specimens examined, 269 tested positive for influenza A(H1N1) 2009 by real‐time RT‐PCR (rRT‐PCR) and had RIDT results available. Overall clinical sensitivity and specificity of RIDTs were 53·9 and 98·5%, respectively. By age group, clinical sensitivity was 85·7% in patients <2 years old, 60·3% in patients between 2‐ and 39 years old, and 33·3% in patients aged 40 and older. Logistic regression analysis indicated that increasing age was negatively associated with RIDT performance.

Conclusion  Rapid influenza diagnostic test sensitivity decreased significantly with increasing age. Findings from this study may impact a clinician’s interpretation of RIDT test results and ultimately have implications in clinical decision‐making.
Standard of practice on laparoscopic gastric cancer surgery in Korea and Japan: Experts’ survey
Authors: Lee HJ , Shiraishi N , Kim HH , Hiki N , Uyama I , Choi SH , Yang HK , Kitano S
Published: November 2011

Introduction

As the laparoscopic approach has become a popular gastric cancer treatment in Korea and Japan, the need for sharing current practices of surgeons who are experienced in laparoscopic gastric cancer surgery has increased.

Methods

We sent a questionnaire on laparoscopic instruments, image documentation, preoperative evaluation, surgical indication, operative methods, and postoperative management to laparoscopic experts in Korea and Japan, and 24 (14 from Korea and 10 from Japan) responded.

Results

Endoscopic ultrasound and preoperative endoscopy‐guided clipping are routinely employed, respectively, by 14 (58%) and 20 (83%) of the surgeons. Surgeons perform laparoscopy‐assisted distal gastrectomy (LADG) based on varying indications. Five surgeons (21%) performed LADG only for cases of stage T1 cancer, 15 (63%) performed LADG on patients with less than T2 lesions, and 4 (17%) performed LADG on patients with less than T3 lesions. With regard to postoperative anastomosis, 18 surgeons (75%) preferred extracorporeal anastomosis and 6 (25%) preferred intracorporeal anastomosis. The mean postoperative hospital stay was 6.5 days in Korea and 10.1 days in Japan (P < 0.001).

Conclusion

This survey can help to inform the current practice of laparoscopic gastric cancer surgery in Korea and Japan, where laparoscopic surgery is frequently performed.
Road to Ruin: Targeting Proteins for Degradation in the Endoplasmic Reticulum
Authors: Smith Melanie H. , Ploegh Hidde L. , Weissman Jonathan S.
Published: November 2011

Some nascent proteins that fold within the endoplasmic reticulum (ER) never reach their native state. Misfolded proteins are removed from the folding machinery, dislocated from the ER into the cytosol, and degraded in a series of pathways collectively referred to as ER-associated degradation (ERAD). Distinct ERAD pathways centered on different E3 ubiquitin ligases survey the range of potential substrates. We now know many of the components of the ERAD machinery and pathways used to detect substrates and target them for degradation. Much less is known about the features used to identify terminally misfolded conformations and the broader role of these pathways in regulating protein half-lives.
Climate Change, Keystone Predation, and Biodiversity Loss
Authors: Harley Christopher D. G.
Published: November 2011

Rising temperature and predation result in range limits and local extinction events in an intertidal community.
A Cocoon of Freshly Accelerated Cosmic Rays Detected by Fermi in the Cygnus Superbubble
Authors: Ackermann M. , Ajello M. , Allafort A. , Baldini L. , Ballet J. , Barbiellini G. , Bastieri D. , Belfiore A. , Bellazzini R. , Berenji B. , Blandford R. D. , Bloom E. D. , Bonamente E. , Borgland A. W. , Bottacini E. , Brigida M. , Bruel P. , Buehler R. , Buson S. , Caliandro G. A. , Cameron R. A. , Caraveo P. A. , Casandjian J. M. , Cecchi C. , Chekhtman A. , Cheung C. C. , Chiang J. , Ciprini S. , Claus R. , Cohen-Tanugi J. , de Angelis A. , de Palma F. , Dermer C. D. , do Couto e Silva E. , Drell P. S. , Dumora D. , Favuzzi C. , Fegan S. J. , Focke W. B. , Fortin P. , Fukazawa Y. , Fusco P. , Gargano F. , Germani S. , Giglietto N. , Giordano F. , Giroletti M. , Glanzman T. , Godfrey G. , Grenier I. A. , Guillemot L. , Guiriec S. , Hadasch D. , Hanabata Y. , Harding A. K. , Hayashida M. , Hayashi K. , Hays E. , Jóhannesson G. , Johnson A. S. , Kamae T. , Katagiri H. , Kataoka J. , Kerr M. , Knödlseder J. , Kuss M. , Lande J. , Latronico L. , Lee S.-H. , Longo F. , Loparco F. , Lott B. , Lovellette M. N. , Lubrano P. , Martin P. , Mazziotta M. N. , McEnery J. E. , Mehault J. , Michelson P. F. , Mitthumsiri W. , Mizuno T. , Monte C. , Monzani M. E. , Morselli A. , Moskalenko I. V. , Murgia S. , Naumann-Godo M. , Nolan P. L. , Norris J. P. , Nuss E. , Ohsugi T. , Okumura A. , Orlando E. , Ormes J. F. , Ozaki M. , Paneque D. , Parent D. , Pesce-Rollins M. , Pierbattista M. , Piron F. , Pohl M. , Prokhorov D. , Rainò S. , Rando R. , Razzano M. , Reposeur T. , Ritz S. , Parkinson P. M. Saz , Sgrò C. , Siskind E. J. , Smith P. D. , Spinelli P. , Strong A. W. , Takahashi H. , Tanaka T. , Thayer J. G. , Thayer J. B. , Thompson D. J. , Tibaldo L. , Torres D. F. , Tosti G. , Tramacere A. , Troja E. , Uchiyama Y. , Vandenbroucke J. , Vasileiou V. , Vianello G. , Vitale V. , Waite A. P. , Wang P. , Winer B. L. , Wood K. S. , Yang Z. , Zimmer S. , Bontemps S.
Published: November 2011

Cosmic rays can be accelerated in the cavities carved by the stellar winds created by clusters of massive stars.
Blink
with Muscles

Thinking, Fast and Slow
by Daniel Kahneman

Farrar, Straus and Giroux, New York, 2011. 509 pp. $30. ISBN 9780374275631.
Authors: Sherman Steven J.
Published: November 2011

Writing for lay readers, Kahneman provides a comprehensive look at how humans think and reach decisions—and at the implications of his findings.
Inheriting Maternal mtDNA
Authors: Levine Beth , Elazar Zvulun
Published: November 2011

Sperm mitochondria are destroyed by autophagy at fertilization in
C. elegans
, explaining the maternal origin of mitochondria in this and perhaps other animals.
Science Adapters Wanted
Authors: Alberts Bruce
Published: November 2011

The Biological Sciences are flourishing, with an abundance of fresh, exciting discoveries that continue to spur the development of powerful new techniques and expand creative scientific investigation. And the core challenge of deeply understanding cells, tissues, and whole organisms promises endless possibilities for controlling human disease and rescuing the environment. But in this very exciting time to be a biological scientist, there is an ominous sense of a major crisis brewing. Budget realities have begun to constrain scientific progress across the board, with an especially heavy impact on the careers of young scientists. Beyond advocating for larger budgets for scientific research as a critical investment in each nation's future, how should the scientific community respond?
Blastomyces dermatitidis Antigen Detection by Quantitative Enzyme Immunoassay
Authors: Connolly Patricia , Hage Chadi A. , Bariola J. Ryan , Bensadoun Eric , Rodgers Mark , Bradsher Robert W. , Wheat L. Joseph
Published: November 2011

The second-generation MVista
Blastomyces
antigen enzyme immunoassay was not quantitative; therefore, specimens obtained previously were tested in the same assay as new specimens to assess the change in antigen levels. Furthermore, the sensitivity in serum had not been fully evaluated. The purpose of this study was to evaluate a quantitative
Blastomyces
antigen assay and detection of antigen in serum. Calibrators containing known concentrations of
Blastomyces
galactomannan were used to quantify antigen in urine and serum from patients with proven blastomycosis and from controls. Paired current and previously obtained urine specimens were tested to determine if quantification eliminated the need for concurrent testing to assess change in antigen. Pretreatment of serum with EDTA at 104°C was evaluated to determine if dissociation of immune complexes improved detection of antigenemia. Antigenuria was detected in 89.9% of patients with culture- or histopathology-proven blastomycosis. Specificity was 99.0% in patients with nonfungal infections and healthy subjects, but cross-reactions occurred in 95.6% of patients with histoplasmosis. Change in antigen level categorized as increase, no change, or decrease based on antigen units determined in the same assay agreed closely with the category of change in ng/ml determined from different assays. Pretreatment increased the sensitivity of detection of antigenemia from 35.7% to 57.1%. Quantification eliminated the need for concurrent testing of current and previously obtained specimens for assessment of changes in antigen concentration. Pretreatment increased the sensitivity for detection of antigenemia. Differentiation of histoplasmosis and blastomycosis is not possible by antigen detection.
Design and Immunogenicity of a Novel Synthetic Antigen Based on the Ligand Domain of the Plasmodium vivax Duffy Binding Protein
Authors: Ntumngia Francis B. , Adams John H.
Published: November 2011

The Duffy binding protein is considered a leading vaccine candidate against asexual blood-stage
Plasmodium vivax
. The interaction of
P. vivax
merozoites with human reticulocytes through Duffy binding protein (DBP) and its cognate receptor is vital for parasite infection. The ligand domain of DBP (DBPII) is polymorphic, showing a diversity characteristic of selective immune pressure that tends to compromise vaccine efficacy associated with strain-specific immunity. A previous study resolved that a polymorphic region of DBPII was a dominant B-cell epitope target of human inhibitory anti-DBP antibodies, which we refer to as the DEK epitope for the amino acids in the SalI allele. We hypothesized that the polymorphic residues, which are not functionally important for erythrocyte binding but flank the receptor binding motif of DBPII, comprise variant epitopes that tend to divert the immune response away from more conserved epitopes. In this study, we designed, expressed, and evaluated the immunogenicity of a novel artificial DBPII allele, termed DEKnull, having nonpolar amino acids in the naturally occurring polymorphic charged residues of the DEK epitope. The DEKnull antigen retained erythrocyte-binding activity and elicited antibodies to shared epitopes of SalI DBPII from which it was derived. Our results confirmed that removal of the dominant variant epitope in the DEKnull vaccine lowered immunogenicity of DBPII, but inhibitory anti-DBPII antibodies were elicited against shared neutralizing epitopes on SalI. Focusing immune responses toward more conserved DBP epitopes may avoid development of a strain-specific immunity and enhance functional inhibition against broader range of DBPII variants.
SRE1
Regulates Iron-Dependent and -Independent Pathways in the Fungal Pathogen Histoplasma capsulatum
Authors: Hwang Lena H. , Seth Erica , Gilmore Sarah A. , Sil Anita
Published: November 2011

Regulation of iron acquisition genes is critical for microbial survival under both iron-limiting conditions (to acquire essential iron) and iron-replete conditions (to limit iron toxicity). In fungi, iron acquisition genes are repressed under iron-replete conditions by a conserved GATA transcriptional regulator. Here we investigate the role of this transcription factor, Sre1, in the cellular responses of the fungal pathogen
Histoplasma capsulatum
to iron. We showed that cells in which
SRE1
levels were diminished by RNA interference were unable to repress siderophore biosynthesis and utilization genes in the presence of abundant iron and thus produced siderophores even under iron-replete conditions. Mutation of a GATA-containing consensus site found in the promoters of these genes also resulted in inappropriate gene expression under iron-replete conditions. Microarray analysis comparing control and
SRE1
-depleted strains under conditions of iron limitation or abundance revealed both iron-responsive genes and Sre1-dependent genes, which comprised distinct but overlapping sets. Iron-responsive genes included those encoding putative oxidoreductases, metabolic and mitochondrial enzymes, superoxide dismutase, and nitrosative-stress-response genes; Sre1-dependent genes were of diverse functions. Genes regulated by iron levels and Sre1 included all of the siderophore biosynthesis genes, a gene involved in reductive iron acquisition, an iron-responsive transcription factor, and two catalases. Based on transcriptional profiling and phenotypic analyses, we conclude that Sre1 plays a critical role in the regulation of both traditional iron-responsive genes and iron-independent pathways such as regulation of cell morphology. These data highlight the evolving realization that the effect of Sre1 orthologs on fungal biology extends beyond the iron regulon.
Critical Role for Voltage-Dependent Anion Channel 2 in Infectious Bursal Disease Virus-Induced Apoptosis in Host Cells via Interaction with VP5
Authors: Li Zhonghua , Wang Yongqiang , Xue Yanfei , Li Xiaoqi , Cao Hong , Zheng Shijun J.
Published: November 2011

Infectious bursal disease (IBD) is an acute, highly contagious, and immunosuppressive avian disease caused by IBD virus (IBDV). Although IBDV-induced host cell apoptosis has been established, the underlying molecular mechanism is still unclear. We report here that IBDV viral protein 5 (VP5) is a major apoptosis inducer in DF-1 cells by interacting with the voltage-dependent anion channel 2 (VDAC2) in the mitochondrion. We found that in DF-1 cells, VP5-induced apoptosis can be completely abolished by 4,4′-diisothiocyanatostibene-2,2′-disulfonic acid (DIDS), an inhibitor of VDAC. Furthermore, knockdown of VDAC2 by small interfering RNA markedly inhibits IBDV-induced apoptosis associated with decreased caspase-9 and -3 activation and cytochrome
c
release, leading to increased IBDV growth in host cells. Thus, VP5-induced apoptosis during IBDV infection is mediated by interacting with VDAC2, a protein that appears to restrict viral replication via induction of cell death.
Asthma in adolescent athletes
Authors: Carlsen Kai-Håkon , Hem Erlend , Stensrud Trine
Published: November 2011

Athletes active in endurance sports are at an increased risk of acquiring asthma through their sports activities, especially so for cross-country skiers, biathlon skiers, swimmers and athletes of other endurance sports. Asthma may be present from early childhood or develop while in active sports. This article focuses on the physical activity and sports activities in children and adolescents. Exercise-induced asthma (EIA) is found in 8–10% of a normal child population of school age and in about 35% of children with current asthma.

EIA is caused by the markedly increased ventilation during exercise, with increased heat and water loss through respiration, leading to bronchial constriction. The risk of developing asthma in the young athlete is related to the repeated daily training activity with increased epithelial damage of the airways, delayed repair due to the daily repetition of the training and increased airway mucosal inflammation. The increased environmental exposure through the sports activity to environmental agents, such as cold, dry air in skiers and chlorine compounds in swimmers, increases symptoms and signs of asthma and bronchial hyper-responsiveness, either worsening an existing asthma or leading to a novel disease in a previously healthy athlete.

Several specific aspects of daily training life, environmental exposure, diagnostic procedures and aspects of treatment related to the regulations of medication use in sports need particular attention when addressing the adolescent athlete with respiratory symptoms.
ON 1D REVERSIBLE CELLULAR AUTOMATA WITH REFLECTIVE BOUNDARY OVER THE PRIME FIELD OF ORDER p
Authors: AKIN HASAN , SAH FERHAT , SIAP IRFAN
Published: November 2011

In this paper, we study one dimensional finite linear cellular automata with reflective boundary condition by using matrix algebra built on the field ℤp. We present an algorithm for determining the reversibility of this family of cellular automata. We also answer the reversibility question for some special subfamilies. Finally, we present some examples of this family of cellular automata under the reflective boundary condition.
ANALYSIS OF THE $B \to K^*_2(1430), a_2(1320), f_2(1270)$ FORM-FACTORS WITH LIGHT-CONE QCD SUM RULES
Authors: WANG ZHI-GANG
Published: November 2011

In this paper, we study the [Formula: see text] form-factors with the light-cone QCD sum rules, where the B-meson light-cone distribution amplitudes are used. In calculations, we observe that the line-shapes of the B-meson light-cone distribution amplitude ϕ+(ω) have significant impacts on the values of the form-factors, and expect to obtain severe constraints on the parameters of the B-meson light-cone distribution amplitudes from the experimental data in the future.
l-Mimosine blocks cell proliferation via upregulation of B-cell translocation gene 2 and N-myc downstream regulated gene 1 in prostate carcinoma cells
Authors: Chung Li-Chuan , Tsui Ke-Hung , Feng Tsui-Hsia , Lee Shiow-Ling , Chang Phei-Lang , Juang Horng-Heng
Published: November 2011

l-Mimosine, an iron chelator and a prolyl 4-hydroxylase inhibitor, blocks many cancer cells at the late G1 phase. B-cell translocation gene 2 ( Btg2) regulates the G1/S transition phases of the cell cycle. N- myc downstream regulated gene 1 ( Ndrg1) is a differentiation-inducing gene upregulated by hypoxia. We evaluated the molecular mechanisms of l-mimosine on cell cycle modulation in PC-3 and LNCaP prostate carcinoma cells. The effect of l-mimosine on cell proliferation of prostate carcinoma cells was determined by the [3H]thymidine incorporation and flow cytometry assays. l-Mimosine arrested the cell cycle at the G1 phase in PC-3 cells and at the S phase in LNCaP cells, thus attenuating cell proliferation. Immunoblot assays indicated that hypoxia and l-mimosine stabilized hypoxia-inducible factor-1α (HIF-1α) and induced Btg2 and Ndrg1 protein expression, but downregulated protein levels of cyclin A in both PC-3 and LNCaP cells. l-Mimosine treatment decreased cyclin D1 protein in PC-3 cells, but not in LNCaP cells. Dimethyloxalylglycine, a pan-prolyl hydroxylase inhibitor, also induced Btg2 and Ndrg1 protein expression in LNCaP cells. The transient gene expression assay revealed that l-mimosine treatment or cotransfection with HIF-1α expression vector enhanced the promoter activities of Btg2 and Ndrg1 genes. Knockdown of HIF-1α attenuated the increasing protein levels of both Btg2 and Ndrg1 by hypoxia or l-mimosine in LNCaP cells. Our results indicated that hypoxia and l-mimosine modulated Btg2 and Ndrg1 at the transcriptional level, which is dependent on HIF-1α. l-Mimosine enhanced expression of Btg2 and Ndrg1, which attenuated cell proliferation of the PC-3 and LNCaP prostate carcinoma cells.
Presence of the Ca2+-activated chloride channel anoctamin 1 in the urethra and its role in excitatory neurotransmission
Authors: Sancho Maria , García-Pascual Angeles , Triguero Domingo
Published: November 2011

We investigated the cellular distribution of the calcium-activated chloride channel (CaCC), anoctamin 1, in the urethra of mice, rats, and sheep by both immunofluorescence and PCR. We studied its role in urethral contractility by examining the effects of chloride-free medium and of several CaCC inhibitors on noradrenergic and cholinergic excitatory responses, and on nitrergic relaxations in urethral preparations. In all species analyzed, CaCC played a key role in urethral contractions, influencing smooth muscle cells activated by increases in intracellular calcium, probably due to calcium influx but with a minor contribution by IP3-mediated calcium release. The participation of CaCC in relaxant responses was negligible. Strong anoctamin 1 immunoreactivity was detected in the smooth muscle cells and urothelia of sheep, rat, and mouse urethra, but not in the interstitial cells of Cajal (ICC) in any of these species. RT-PCR confirmed the expression of anoctamin 1 mRNA in the rat urethra. This anoctamin 1 in urethral smooth muscle probably mediates the activity of chloride in contractile responses in different species, However, the lack of anoctamin 1 in ICCs challenges its proposed role in regulating urethral contractility in a manner similar to that observed in the gut.
Adenosine A3receptor stimulation reduces muscle injury following physical trauma and is associated with alterations in the MMP/TIMP response
Authors: Urso Maria L. , Wang Ruibo , Zambraski Edward J. , Liang Bruce T.
Published: November 2011

We have previously demonstrated that in response to traumatic injury in skeletal muscle, there is a dysregulation of the matrix metalloproteases (MMPs) and their inhibitors (TIMPs), a response hypothesized to interfere with proper skeletal muscle regeneration. Moreover, we have shown that pharmacological activation of the adenosine A3receptor by Cl-IBMECA in skeletal muscle can protect against ischemia-reperfusion and eccentric exercise injury. However, the mechanism by which Cl-IBMECA protects muscle tissue is poorly defined. This study evaluated the effects of Cl-IBMECA on MMP/TIMP expression in skeletal muscle and tested the hypothesis that adenosine A3receptor-stimulated protection of skeletal muscle following traumatic injury is associated with a blunting of MMPs involved in inflammatory processes and collagen degradation, and an increase in MMPs associated with extracellular matrix remodeling. Sixty C57BL/6J male mice were injected with Cl-IBMECA ( n = 30) or a vehicle ( n = 30), and Evans blue dye. Injury was induced by applying a cold steel probe (−79°C) to the tibialis anterior (TA) muscle for 10 s. TA muscles from uninjured and injured legs were collected 3, 10, and 24 h postinjury for analysis of muscle injury and MMP/TIMP mRNA and protein levels. Twenty-four hours postinjury, 56.8% of the fibers were damaged in vehicle-treated mice vs. 35.4% in Cl-IBMECA-treated mice ( P = 0.02). Cl-IBMECA treatment reduced membrane type 1 (MT1)-MMP, MMP-3, MMP-9, and TIMP-1 mRNA expression 2- to 20-fold compared with vehicle-treated mice ( P < 0.05). Cl-IBMECA decreased protein levels of latent/shed MT1-MMP 23–2,000%, respectively, 3–10 h postinjury. In Cl-IBMECA-treated mice, latent MMP-2 was decreased 20% 3 h postinjury, active MMP-3 was decreased 64% 3 h postinjury, and latent/active MMP-9 was decreased 417,631% 3 h postinjury and 20% 10 h postinjury. Protein levels of active MMP-2 and latent MMP-3 were increased 25% and 74% 3 h postinjury, respectively. The present study elucidates a new protective role of adenosine A3receptor stimulation in posttraumatic skeletal muscle injury.
Bacillus anthracis lethal toxin alters regulation of visceral sympathetic nerve discharge
Authors: Garcia A. A. , Fels R. J. , Mosher L. J. , Kenney M. J.
Published: November 2011

Bacillus anthracis infection is a pathophysiological condition that is complicated by progressive decreases in mean arterial pressure (MAP). Lethal toxin (LeTx) is central to the pathogenesis of B. anthracis infection, and the sympathetic nervous system plays a critical role in physiological regulation of acute stressors. However, the effect of LeTx on sympathetic nerve discharge (SND), a critical link between central sympathetic neural circuits and MAP regulation, remains unknown. We determined visceral (renal, splenic, and adrenal) SND responses to continuous infusion of LeTx [lethal factor (100 μg/kg) + protective antigen (200 μg/kg) infused at 0.5 ml/h for ≤6 h] and vehicle (infused at 0.5 ml/h) in anesthetized, baroreceptor-intact and baroreceptor (sinoaortic)-denervated (SAD) Sprague-Dawley rats. LeTx infusions produced an initial state of cardiovascular and sympathetic nervous system activation in intact and SAD rats. Subsequent to peak LeTx-induced increases in arterial blood pressure, intact rats demonstrated a marked hypotension that was accompanied by significant reductions in SND (renal and splenic) and heart rate (HR) from peak levels. After peak LeTx-induced pressor and sympathoexcitatory responses in SAD rats, MAP, SND (renal, splenic, and adrenal), and HR were progressively and significantly reduced, supporting the hypothesis that LeTx alters the central regulation of sympathetic nerve outflow. These findings demonstrate that the regulation of visceral SND is altered in a complex manner during continuous anthrax LeTx infusions and suggest that sympathetic nervous system dysregulation may contribute to the marked hypotension accompanying B. anthracis infection.
Mechanical properties of human patellar tendon at the hierarchical levels of tendon and fibril
Authors: Svensson René B. , Hansen Philip , Hassenkam Tue , Haraldsson Bjarki T. , Aagaard Per , Kovanen Vuokko , Krogsgaard Michael , Kjaer Michael , Magnusson S. Peter
Published: November 2011

Tendons are strong hierarchical structures, but how tensile forces are transmitted between different levels remains incompletely understood. Collagen fibrils are thought to be primary determinants of whole tendon properties, and therefore we hypothesized that the whole human patellar tendon and its distinct collagen fibrils would display similar mechanical properties. Human patellar tendons ( n = 5) were mechanically tested in vivo by ultrasonography. Biopsies were obtained from each tendon, and individual collagen fibrils were dissected and tested mechanically by atomic force microscopy. The Young's modulus was 2.0 ± 0.5 GPa, and the toe region reached 3.3 ± 1.9% strain in whole patellar tendons. Based on dry cross-sectional area, the Young's modulus of isolated collagen fibrils was 2.8 ± 0.3 GPa, and the toe region reached 0.86 ± 0.08% strain. The measured fibril modulus was insufficient to account for the modulus of the tendon in vivo when fibril content in the tendon was accounted for. Thus, our original hypothesis was not supported, although the in vitro fibril modulus corresponded well with reported in vitro tendon values. This correspondence together with the fibril modulus not being greater than that of tendon supports that fibrillar rather than interfibrillar properties govern the subfailure tendon response, making the fibrillar level a meaningful target of intervention. The lower modulus found in vitro suggests a possible adverse effect of removing the tissue from its natural environment. In addition to the primary work comparing the two hierarchical levels, we also verified the existence of viscoelastic behavior in isolated human collagen fibrils.
Activity-dependent regulation of synaptic strength by PSD-95 in CA1 neurons
Authors: Zhang Peng , Lisman John E.
Published: November 2011

CaMKII and PSD-95 are the two most abundant postsynaptic proteins in the postsynaptic density (PSD). Overexpression of either can dramatically increase synaptic strength and saturate long-term potentiation (LTP). To do so, CaMKII must be activated, but the same is not true for PSD-95; expressing wild-type PSD-95 is sufficient. This raises the question of whether PSD-95's effects are simply an equilibrium process [increasing the number of AMPA receptor (AMPAR) slots] or whether activity is somehow involved. To examine this question, we blocked activity in cultured hippocampal slices with TTX and found that the effects of PSD-95 overexpression were greatly reduced. We next studied the type of receptors involved. The effects of PSD-95 were prevented by antagonists of group I metabotropic glutamate receptors (mGluRs) but not by antagonists of ionotropic glutamate receptors. The inhibition of PSD-95-induced strengthening was not simply a result of inhibition of PSD-95 synthesis. To understand the mechanisms involved, we tested the role of CaMKII. Overexpression of a CaMKII inhibitor, CN19, greatly reduced the effect of PSD-95. We conclude that PSD-95 cannot itself increase synaptic strength simply by increasing the number of AMPAR slots; rather, PSD-95's effects on synaptic strength require an activity-dependent process involving mGluR and CaMKII.
Impact of neural noise on a sensory-motor pathway signaling impending collision
Authors: Jones Peter W. , Gabbiani Fabrizio
Published: November 2011

Noise is a major concern in circuits processing electrical signals, including neural circuits. There are many factors that influence how noise propagates through neural circuits, and there are few systems in which noise levels have been studied throughout a processing pathway. We recorded intracellularly from multiple stages of a sensory-motor pathway in the locust that detects approaching objects. We found that responses are more variable and that signal-to-noise ratios (SNRs) are lower further from the sensory periphery. SNRs remain low even with the use of stimuli for which the pathway is most selective and for which the neuron representing its final sensory level must integrate many synaptic inputs. Modeling of this neuron shows that variability in the strength of individual synaptic inputs within a large population has little effect on the variability of the spiking output. In contrast, jitter in the timing of individual inputs and spontaneous variability is important for shaping the responses to preferred stimuli. These results suggest that neural noise is inherent to the processing of visual stimuli signaling impending collision and contributes to shaping neural responses along this sensory-motor pathway.
Tonic GABAA receptor conductance in medial subnucleus of the tractus solitarius neurons is inhibited by activation of μ-opioid receptors
Authors: Herman Melissa A. , Gillis Richard A. , Vicini Stefano , Dretchen Kenneth L. , Sahibzada Niaz
Published: November 2011

Our laboratory previously reported that gastric activity is controlled by a robust GABAA receptor-mediated inhibition in the medial nucleus of the tractus solitarius (mNTS) ( Herman et al. 2009 ), and that μ-opioid receptor activation inhibits gastric tone by suppression of this GABA signaling ( Herman et al. 2010 ). These data raised two questions: 1) whether any of this inhibition was due to tonic GABAA receptor-mediated conductance in the mNTS; and 2) whether μ-opioid receptor activation suppressed both tonic and phasic GABA signaling. In whole cell recordings from rat mNTS neurons, application of three GABAA receptor antagonists (gabazine, bicuculline, and picrotoxin) produced a persistent reduction in holding current and decrease in population variance or root mean square (RMS) noise, suggesting a blockade of tonic GABA signaling. Application of gabazine at a lower concentration abolished phasic currents, but had no effect on tonic currents or RMS noise. Application of the δ-subunit preferring agonist gaboxadol (THIP) produced a dose-dependent persistent increase in holding current and RMS noise. Pretreatment with tetrodotoxin prevented the action of gabazine, but had no effect on the THIP-induced current. Membrane excitability was unaffected by the selective blockade of phasic inhibition, but was increased by blockade of both phasic and tonic currents. In contrast, activation of tonic currents decreased membrane excitability. Application of the μ-opioid receptor agonist DAMGO produced a persistent reduction in holding current that was not observed following pretreatment with a GABAA receptor antagonist and was not evident in mice lacking the δ-subunit. These data suggest that mNTS neurons possess a robust tonic inhibition that is mediated by GABAA receptors containing the δ-subunit, that determines membrane excitability, and that is partially regulated by μ-opioid receptors.
Immune Microenvironment in Colorectal Cancer: A New Hallmark to Change Old Paradigms
Authors: de la Cruz-Merino Luis , Henao Carrasco Fernando , Vicente Baz David , Nogales Fernández Esteban , Reina Zoilo Juan José , Codes Manuel de Villena Manuel , Pulido Enrique Grande
Published: November 2011

Impact of immune microenvironment in prognosis of solid tumors has been extensively studied in the last few years. Specifically in colorectal carcinoma, increased knowledge of the immune events around these tumors and their relation with clinical outcomes have led to consider immune microenvironment as one of the most important prognostic factors in this disease. In this review we will summarize and update the current knowledge with respect to this intriguing and complex new hallmark of cancer, paying special attention to infiltration by T-infiltrating lymphocytes and their subtypes in colorectal cancer, as well as its eventual clinical translation in terms of long-term prognosis. Finally, we suggest some possible investigational approaches based on combinatorial strategies to trigger and boost immune reaction against tumor cells.