bluuebunny/crossref_metadata_2025_split huggingface dataset:
MYH9 and APOL1 are both associated with sickle cell disease nephropathy
Authors: Ashley‐Koch Allison E. , Okocha Emmanuel C. , Garrett Melanie E. , Soldano Karen , De Castro Laura M. , Jonassaint Jude C. , Orringer Eugene P. , Eckman James R. , Telen Marilyn J. 
Published: September 2011

SummaryRenal failure occurs in 5–18% of sickle cell disease (SCD) patients and is associated with early mortality. At‐risk SCD patients cannot be identified prior to the appearance of proteinuria and the pathobiology is not well understood. The myosin, heavy chain 9, non‐muscle (MYH9) and apolipoprotein L1 (APOL1) genes have been associated with risk for focal segmental glomerulosclerosis and end‐stage renal disease in African Americans. We genotyped 26 single nucleotide polymorphisms (SNPs) in MYH9 and 2 SNPs in APOL1 (representing the G1 and G2 tags) in 521 unrelated adult (18–83 years) SCD patients screened for proteinuria. Using logistic regression, SNPs were evaluated for association with proteinuria. Seven SNPs in MYH9 and one in APOL1 remained significantly associated with proteinuria after multiple testing correction (P < 0·0025). An MYH9 risk haplotype (P = 0·001) and the APOL1 G1/G2 recessive model (P < 0·0001) were strongly associated with proteinuria, even when accounting for the other. Glomerular filtration rate was negatively correlated with proteinuria (P < 0·0001), and was significantly predicted by an interaction between MYH9 and APOL1 in age‐adjusted analyses. Our data provide insight into the pathobiology of renal dysfunction in SCD, suggesting that MYH9 and APOL1 are both associated with risk.
Mitochondrial decay in ageing: ‘Qi‐invigorating’ schisandrin B as a hormetic agent for mitigating age‐related diseases
Authors: Leong Pou K , Chen Na , Ko Kam M 
Published: September 2011

Summary1. The mitochondrial free radical theory of ageing (MFRTA) proposes a primary role for mitochondrial reactive oxygen species (ROS) in the ageing process. The reductive hot spot hypothesis of mammalian ageing serves as a supplement to the MFRTA by explaining how the relatively few cells that have lost oxidative phosphorylation capacity due to mitochondrial DNA mutations can be toxic to the rest of the body and result in the development of age‐related diseases.2. Schisandrin B (SchB), which can induce both a glutathione anti‐oxidant and a heat shock response via redox‐sensitive signalling pathways, is a hormetic agent potentially useful for increasing the resistance of tissues to oxidative damage. The enhanced cellular/mitochondrial anti‐oxidant status and heat shock response afforded by SchB can preserve the structural and functional integrity of mitochondria, suggesting a potential role for SchB in ameliorating age‐related diseases.3. Future studies will focus on investigating whether SchB can produce the hormetic response in humans.
Single cysteine substitution in Bacillus thuringiensis Cry7Ba1 improves the crystal solubility and produces toxicity to Plutella xylostella larvae
Authors: Peng Donghai , Wang Fenshan , Li Nisha , Zhang Zhenyu , Song Rong , Zhu Zimin , Ruan Lifang , Sun Ming 
Published: September 2011

SummaryMany Bacillus thuringiensis isolates have no demonstrated toxicity against insects. In this study, a novel holotype crystal protein gene cry7Ba1 was isolated from a ‘non‐insecticidal’B. thuringiensis strain YBT‐978. The Cry7Ba1 protein showed high toxicity against Plutella xylostella larvae after the crystals were dissolved at pH 12.5, suggesting that the ‘non‐insecticidal’ properties of this protein were due to insolubility in the normal insect midgut pH environment. After the C‐terminal half of Cry7Ba1 was replaced by that of Cry1Ac or Cry1C proteins, the recombinant protein inclusions could be dissolved at pH 9.5, and exhibited high toxicity against P. xylostella larvae. This result proved the insolubility of Cry7Ba1 crystal was determined by the structure of its C‐terminal half. Further, six mutations were constructed by substituting cysteine residues with serine. Solubility studies showed that the crystals from mutants C697S, C834S and C854S could be dissolved at lower pH (10.5, 9.5 and 11.5 respectively). Bioassays showed that crystals from mutant C834S were toxic to P. xylostella larvae. Our discoveries suggest that a single cysteine residue located in the C‐terminal half of the protein determines the solubility and toxicity of some nontoxic crystal proteins. This study provides a strategy to isolate novel insecticidal crystal protein genes from ‘non‐insecticidal’B. thuringiensis strains.
Open radical prostatectomy in the elderly: a case for concern?
Authors: Trinh Quoc‐Dien , Schmitges Jan , Sun Maxine , Shariat Shahrokh F. , Sukumar Shyam , Tian Zhe , Bianchi Marco , Sammon Jesse , Perrotte Paul , Rogers Craig G. , Graefen Markus , Peabody James O. , Menon Mani , Karakiewicz Pierre I. 
Published: September 2011

Study Type – Therapy (case series)Level of Evidence 4What's known on the subject? and What does the study add?Adverse outcomes after radical prostatectomy are more often recorded in the elderly.In the USA, elderly patients undergoing radical prostatectomy are treated at institutions where suboptimal outcomes are recorded.OBJECTIVE
To assess the rate of adverse outcomes after open radical prostatectomy (ORP) in the elderly and to examine the effect of annual hospital caseload (AHC) and academic institutional status on adverse outcomes in these of patients.
PATIENTS AND METHODS
Within the Health Care Utilization Project Nationwide Inpatient Sample, we focused on ORPs performed between 1998 and 2007. Subsequently, we restricted to patients aged ≥75 years.
In both datasets, we examined transfusion rates, intra‐operative and postoperative complication rates, and in‐hospital mortality rates.
Stratification was performed according to AHC tertiles and academic status.
Multivariable logistic regression analyses were fitted.
RESULTS
Of 115 554 ORP patients, 2109 (1.8%) were aged ≥75 years.
In multivariable analyses performed in the entire cohort, elderly age increased homologous blood transfusion rates (P < 0.001), intra‐operative (P= 0.001) and postoperative (P < 0.001) complication rates, and the mortality rate (P= 0.007).
Most elderly were treated at low or intermediate AHC (68.5%) and non‐academic centres (56.2%).
Within the elderly cohort, intra‐operative (2.9%) and postoperative (22.2%) complications tended to be highest at low AHC institutions compared to institutions of intermediate (2.7% and 17.4%) and high AHC (1.7% and 14.5%). Similarly, intra‐operative (2.7% vs 2.1%) and postoperative complications (19.1% vs 13.9%) tended to be higher at non‐academic than academic centres.
In multivariable analyses performed in the elderly subgroup, low AHC predicted higher intra‐operative complications and higher homologous transfusions, whereas non‐academic status predicted higher postoperative complications.
CONCLUSIONS
Adverse outcomes are more often recorded in the elderly.
Most elderly are treated at institutions where suboptimal outcomes are recorded.
Osteoprotegerin gene polymorphism in diabetic Charcot neuroarthropathy
Authors: Korzon‐Burakowska A. , Jakóbkiewicz‐Banecka J. , Fiedosiuk A. , Petrova N. , Koblik T. , Gabig‐Cimińska M. , Edmonds M. , Małecki M. T. , Węgrzyn G. 
Published: September 2011

Diabet. Med. 29, 771–775 (2012)AbstractAims  Recently, an association between two polymorphisms (1181G>C and 245T>G) of the osteoprotegerin (OPG) gene and diabetic Charcot neuroarthropathy was suggested on the basis of studies of a limited number of samples derived from subjects from one geographical region (Italy). The aim of this study was to assess the presence of various osteoprotegerin gene polymorphisms in patients with diabetes and Charcot neuroarthropathy compared with subjects with diabetic neuropathy but no Charcot foot and healthy controls from another geographical region (Poland).Methods  DNA was isolated from 54 patients with Charcot neuroarthropathy, 35 subjects with diabetic neuropathy but no Charcot foot, and 95 healthy controls to evaluate OPG gene polymorphisms and their possible contribution to the development of Charcot neuroarthropathy.Results  Statistically significant differences between the group of subjects with neuropathy but no Charcot neuroarthropathy and the control group were found for 1217C>T, 950T>C and 245T>G polymorphisms, between the group of patients with Charcot neuroarthropathy and the control group for 1181G>C and 950T>C polymorphisms, and between the group of subjects with neuropathy but no Charcot neuroarthropathy and the group of patients with Charcot neuroarthropathy for 1217C>T and 245T>G polymorphisms.Conclusion  We suggest that genetic factors, particularly OPG gene polymorphisms, may play a role in the development of diabetic Charcot neuroarthropathy.
Equity and debt issuance by firms violating GAAP
Authors: Bardos Katsiaryna Salavei , Zaiats Nataliya 
Published: September 2011

AbstractWe examine security issuance in restated periods by firms that misreport financial statements and find that only a small per cent of such firms issues securities in the restated period. Investors are misled by mistakes made by firms issuing equity more so than other restating firms at the initial announcement of misreported earnings, but are not misled by mistakes made by debt‐issuing firms. Equity‐issuing firms that manage earnings to beat analyst expectations experience abnormally high returns in the restated period prior to security issuance. Firms that restated more reports and have higher pre‐mistake returns are more likely to issue equity. High leverage, firm size and number of restated periods are positively associated with the likelihood of debt issuance by restating firms.
Employment Protection Versus Flexicurity: On Technology Adoption in Unionised Firms*
Authors: Lommerud Kjell Erik , Straume Odd Rune 
Published: September 2011

AbstractWe analyse how different labour‐market institutions – employment protection versus ‘flexicurity’– affect technology adoption in unionised firms. We consider trade unions’ incentives to oppose or endorse labour‐saving technology and firms’ incentives to invest in such technology. Increased flexicurity – interpreted as less employment protection and a higher reservation wage for workers – unambiguously increases firms’ incentives for technology adoption. If unions have some direct influence on technology, a higher reservation wage also makes unions more willing to accept technological change. Less employment protection has the opposite effect, as this increases the downside (job losses) of labour‐saving technology.
What women want. Women’s preferences for the management of low‐grade abnormal cervical screening tests: a systematic review
Authors: Frederiksen ME , Lynge E , Rebolj M 
Published: September 2011

Please cite this paper as: Frederiksen M, Lynge E, Rebolj M. What women want. Women’s preferences for the management of low‐grade abnormal cervical screening tests: a systematic review. BJOG 2012;119:7–19.Background  If human papillomavirus (HPV) testing will replace cytology in primary cervical screening, the frequency of low‐grade abnormal screening tests will double. Several available alternatives for the follow‐up of low‐grade abnormal screening tests have similar outcomes. In this situation, women’s preferences have been proposed as a guide for management decisions.Objectives  To determine women’s preferences for the follow‐up of low‐grade cervical screening abnormalities.Search strategy  Using Medical Subject Headings (MeSH) terms, PubMed was searched for articles published up to December 2010. The reference lists of the retrieved studies were consulted.Selection criteria  Studies asking women to state a preference between active follow‐up and observation for the management of low‐grade abnormalities on screening cytology or HPV tests.Data collection and analysis  Information on study design, participants and outcomes was retrieved using a prespecified form. Studies were sorted by design.Main results  Thirteen studies were included in the review. In all five studies that surveyed women with abnormal tests before any management had started, two‐thirds preferred active follow‐up, predominantly as immediate colposcopy, to observation, predominantly as repeated Pap smears. In all but two studies testing other situations, women more often expressed a preference for active follow‐up than for observation; however, women appeared to be somewhat more willing to accept observation if reassured of the low risk of cervical cancer.Conclusions  Even for low‐grade abnormal cervical tests, women tend to prefer active management strategies. It may be a challenge to meet their expectations of optimal follow‐up when HPV testing is used in primary screening.
Effects of palmitoylation of Cys415 in helix 8 of the CB1 cannabinoid receptor on membrane localization and signalling
Authors: Oddi Sergio , Dainese Enrico , Sandiford Simone , Fezza Filomena , Lanuti Mirko , Chiurchiù Valerio , Totaro Antonio , Catanzaro Giuseppina , Barcaroli Daniela , De Laurenzi Vincenzo , Centonze Diego , Mukhopadhyay Somnath , Selent Jana , Howlett Allyn C , Maccarrone Mauro 
Published: September 2011

BACKGROUND AND PURPOSE The CB1 cannabinoid receptor is regulated by its association with membrane microdomains such as lipid rafts. Here, we investigated the role of palmitoylation of the CB1 receptor by analysing the functional consequences of site‐specific mutation of Cys415, the likely site of palmitoylation at the end of helix 8, in terms of membrane association, raft targeting and signalling.EXPERIMENTAL APPROACH The palmitoylation state of CB1 receptors in rat forebrain was assessed by depalmitoylation/repalmitoylation experiments. Cys415 was replaced with alanine by site‐directed mutagenesis. Green fluorescence protein chimeras of both wild‐type and mutant receptors were transiently expressed and functionally characterized in SH‐SY5Y cells and HEK‐293 cells by means of confocal microscopy, cytofluorimetry and competitive binding assays. Confocal fluorescence recovery after photobleaching was used to assess receptor membrane dynamics, whereas signalling activity was assessed by [35S]GTPγS, cAMP and co‐immunoprecipitation assays.KEY RESULTS Endogenous CB1 receptors in rat brain were palmitoylated. Mutation of Cys415 prevented the palmitoylation of the receptor in transfected cells and reduced its recruitment to plasma membrane and lipid rafts; it also increased protein diffusional mobility. The same mutation markedly reduced the functional coupling of CB1 receptors with G‐proteins and adenylyl cyclase, whereas depalmitoylation abolished receptor association with a specific subset of G‐proteins.CONCLUSIONS AND IMPLICATIONS CB1 receptors were post‐translationally modified by palmitoylation. Mutation of Cys415 provides a receptor that is functionally impaired in terms of membrane targeting and signalling.LINKED ARTICLES This article is part of a themed section on Cannabinoids in Biology and Medicine. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2012.165.issue‐8. To view Part I of Cannabinoids in Biology and Medicine visit http://dx.doi.org/10.1111/bph.2011.163.issue‐7
Human obesity and endothelium‐dependent responsiveness
Authors: Campia Umberto , Tesauro Manfredi , Cardillo Carmine 
Published: September 2011

Obesity is an ongoing worldwide epidemic. Besides being a medical condition in itself, obesity dramatically increases the risk of development of metabolic and cardiovascular disease. This risk appears to stem from multiple abnormalities in adipose tissue function leading to a chronic inflammatory state and to dysregulation of the endocrine and paracrine actions of adipocyte‐derived factors. These, in turn, disrupt vascular homeostasis by causing an imbalance between the NO pathway and the endothelin 1 system, with impaired insulin‐stimulated endothelium‐dependent vasodilation. Importantly, emerging evidence suggests that the vascular dysfunction of obesity is not just limited to the endothelium, but also involves the other layers of the vessel wall. In particular, obesity‐related changes in medial smooth muscle cells seem to disrupt the physiological facilitatory action of insulin on the responsiveness to vasodilator stimuli, whereas the adventitia and perivascular fat appear to be a source of pro‐inflammatory and vasoactive factors that may contribute to endothelial and smooth muscle cell dysfunction, and to the pathogenesis of vascular disease. While obesity‐induced vascular dysfunction appears to be reversible, at least in part, with weight control strategies, these have not proved sufficient to prevent the metabolic and cardiovascular complication of obesity on a large scale. While a number of currently available drugs have shown potentially beneficial vascular effects in patients with obesity and the metabolic syndrome, elucidation of the pathophysiological mechanisms underlying vascular damage in obese patients is necessary to identify additional pharmacologic targets to prevent the cardiovascular complications of obesity, and their human and economic costs.LINKED ARTICLES This article is part of a themed section on Fat and Vascular Responsiveness. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2012.165.issue‐3
Risk of bias of animal studies on regenerative procedures for periodontal and peri‐implant bone defects – a systematic review
Authors: Faggion Clovis Mariano , Giannakopoulos Nikolaos Nikitas , Listl Stefan 
Published: September 2011

AbstractObjectives(1) To assess the risk of bias of studies in which animal models were used for investigating regenerative therapies for periodontal and peri‐implant defects. (2) To investigate changes in risk of bias by comparing samples drawn from two different publication periods.Material & MethodsWe searched the PubMed and LILACS electronic databases, independently and in duplicate, for randomized and controlled trials published from 1998 to 2000 and from 2008 to 2010. Hand searching included search of 10 dental journals, in the issues published between August 2008 and August 2010. Studies on non‐human primates and canines were included. We assessed independently and in triplicate the risk of bias with reference to a six‐item checklist based on the Cochrane Collaboration's tool for assessing the risk of bias and information about formal sample size calculation.ResultsOne hundred and seven studies were included in the review. Checklist items were poorly reported in the studies selected, and therefore for most of the studies, the risk of bias was unclear.ConclusionAs a result of the unclear risk of bias of animal studies in periodontal and peri‐implant treatments, it is difficult to determine the accuracy of treatment effect estimates. There is a need for standardization of reporting procedures on animal experiments.
Mechanisms of protection induced by attenuated simian immunodeficiency virus. IV. Protection against challenge with virus grown in autologous simian cells
Authors: Almond N. , Corcoran T. , Hull R. , Walker B. , Rose J. , Sangster R. , Silvera K. , Silvera R , Cranage M. , Rud E. , Stott E.J. 
Published: September 2011

Abstract: Attenuated simian immunodeficiency virus (SIV) induces potent protection against infection with wild‐type virus, but the mechanism of this immunity remains obscure. Allogeneic antibodies, which arise within animals as a result of SIV infection, might protect against challenge with exogenous SIV grown in allogeneic cells. To test this hypothesis, eight macaques were infected with attenuated SIV and subsequently challenged with wild‐type SIV grown in autologous cells or heterologous cells.The results clearly demonstrated that animals infected with attenuated SIV are protected against wild‐type SIV grown in autologous or heterologous cells. Thus, the hypothesis that live attenuated SIV protects by the induction of allogeneic antibodies is not tenable.
Teratogenic IgG From Sera of Women With Spontaneous Abortions Seem to Induce Anomalies and Yolk Sac Damage in Rat Embryos. A Possible Method to Detect Abortions of Immunologic Origin
Authors: Abir Ronit , Ornoy Asher 
Published: September 2011

PROBLEM: Spontaneous abortions due to immunological rejection of the embryo may be avoided by immunotherapy with paternal allogeneic leukocytes but there is no appropriate method to detect and differentiate this group of aborters from other groups.METHODS: In previous studies we have demonstrated that in about two‐thirds of sera from women with spontaneous abortions the IgG antibodies are responsible (alone or in combination with other factors) for the embryotoxic effects of these sera on cultured rat embryos. We presently cultured 10.5‐day‐old rat embryos on highly teratogenic serum (“high risk” serum that induced anomalies in more than 50% of the embryos) from women with spontaneous abortions, where the IgG fraction was exchanged with IgG from control sera and vice‐versa. We studied by Transmission Electron Microscopy (TEM) the extent of yolk sac damage in comparison to the rate of embryonic anomalies.RESULTS: In cases where IgG antibodies were teratogenic, embryos cultured in control sera with IgG from “high risk” sera exhibited ultrastructural yolk sac damage as well as embryonic anomalies, and the yolk sacs cultured in “high risk” sera with control IgG were normal. In cases in which the IgG exchange did not change the rate of anomalies, as IgG was not teratogenic, yolk sacs from embryos cultured in “high risk” sera remained damaged, while yolk sacs from embryos cultured in control sera after IgG exchange stayed normal. Although no significant difference in total IgG levels was found between the groups, a higher IgG1 level in sera from women with teratogenic IgG was observed in comparison to control women's sera. The obstetrical history of the women with two or more abortions who took part in our study showed that there were more cases of unknown etiology of the abortion in the women from the “high risk” group.CONCLUSIONS: The serum and the IgG fraction from women with habitual abortions can be tested in whole embryo culture to evaluate the embryonic and yolk sac damage. On this basis it may be possible to detect the women in whom the habitual abortions result from immunological rejection.
Effect of Pregnancy on Thymic T Cell Development
Authors: Ruhsinghani Asha G. , Bhatia Sudershan K. , Tygrett Lorraine T. , Waldschmidt Thomas J. 
Published: September 2011

PROBLEM: The thymus gland decreases in size during pregnancy. The significance of this alteration is not known.METHOD: In this report, we examined thymic function by evaluating the development of T lymphocytes in the thymus of pregnant Balb/c mice at 15 and 20 days gestation using multi‐color flow cytometry. Comparative analysis was made with non‐pregnant mice, postpartum lactating mice, and postpartum non‐lactating mice.RESULTS: Progressive reduction of thymic size and cellularity during pregnancy was observed. All of the CD4 and CD8 defined subsets were reduced, with a disproportionate loss of CD4+, CD8+ double positive cells. Examination of the CD4‐, CD8‐ double negative compartment revealed a predominance of TCR α,β+ double negative cells, and a striking loss of precursor cells. The CD3‐, CD4‐, CD8‐ triple negative thymic subset was composed almost entirely of the earliest population (CD44+, CD25‐), with the remaining maturational stages (CD44+, CD25+; CD44‐, CD25+; and CD44‐, CD25‐) depleted. At 2 weeks postpartum, the subset ratios normalized, and the total cell count showed recovery.CONCLUSION: T cell development is blocked at the precursor level during the mouse pregnancy. These effects are transient, and gradual recovery is observed in the postpartum period.