bluuebunny/crossref_metadata_2025_split huggingface dataset:
Global diversity of island floras from a macroecological perspective
Authors: Kreft Holger , Jetz Walter , Mutke Jens , Kier Gerold , Barthlott Wilhelm 
Published: December 2007

AbstractIslands harbour a significant portion of all plant species worldwide. Their biota are often characterized by narrow distributions and are particularly susceptible to biological invasions and climate change. To date, the global richness pattern of islands is only poorly documented and factors causing differences in species numbers remain controversial. Here, we present the first global analysis of 488 island and 970 mainland floras. We test the relationship between island characteristics (area, isolation, topography, climate and geology) and species richness using traditional and spatial models. Area is the strongest determinant of island species numbers (R2 = 0.66) but a weaker predictor for mainlands (R2 = 0.25). Multivariate analyses reveal that all investigated variables significantly contribute to insular species richness with area being the strongest followed by isolation, temperature and precipitation with about equally strong effects. Elevation and island geology show relatively weak yet significant effects. Together these variables account for 85% of the global variation in species richness.
The Toll‐like receptors TLR2 and TLR4 do not affect the intestinal microbiota composition in mice
Authors: Loh Gunnar , Brodziak Frances , Blaut Michael 
Published: December 2007

SummaryThe interaction between intestinal epithelial cells and microbes is partly mediated by Toll‐like receptors (TLRs). Sensing of Gram‐positive and Gram‐negative bacteria by TLR2 and TLR4, respectively, can result in immune system activation and in an exclusion of bacteria from the intestine. To test the impact of these TLRs on bacterial composition, germ‐free TLR2/TLR4 double‐knock out mice and the corresponding C57BL/10ScSn wild‐type mice where associated with fecal bacteria from one single donor mouse. In addition, C3H/HeOuJ and BALB/c mice were used in this study. Fecal bacteria were monitored over 13 weeks with denaturing‐gradient gel electrophoresis (DGGE). Colonic bacteria were enumerated by fluorescent in situ hybridization (FISH) and short‐chain fatty acids (SCFA) were measured in caecal samples. No effect of the TLRs on intestinal microbiota composition and SCFA concentrations was observed. However, the microbiota composition as reflected by DGGE band patterns differed between C3H and BALB/c mice on the one hand and C57BL/10 mice on the other hand. Corresponding differences between the mouse strains were also observed in cecal propionic, valeric and i‐valeric acid concentrations. No differences between the animals were observed in the numbers of bacteria detected by FISH. We conclude that genetic traits but not TLR2 and TLR4 have an impact on the intestinal microbiota composition.
Ecological diversification in the Bacillus cereus Group
Authors: Guinebretière Marie‐Hélène , Thompson Fabiano L. , Sorokin Alexei , Normand Philippe , Dawyndt Peter , Ehling‐Schulz Monika , Svensson Birgitta , Sanchis Vincent , Nguyen‐The Christophe , Heyndrickx Marc , De Vos Paul 
Published: December 2007

SummaryThe Bacillus cereus Group comprises organisms that are widely distributed in the environment and are of health and economic interest. We demonstrate an ‘ecotypic’ structure of populations in the B. cereus Group using (i) molecular data from Fluorescent Amplified Fragment Length Polymorphism patterns, ribosomal gene sequences, partial panC gene sequences, ‘psychrotolerant’ DNA sequence signatures and (ii) phenotypic and descriptive data from range of growth temperature, psychrotolerance and thermal niches. Seven major phylogenetic groups (I to VII) were thus identified, with ecological differences that provide evidence for a multiemergence of psychrotolerance in the B. cereus Group. A moderate thermotolerant group (VII) was basal to the mesophilic group I, from which in turn distinct thermal lineages have emerged, comprising two mesophilic groups (III, IV), an intermediate group (V) and two psychrotolerant groups (VI, II). This stepwise evolutionary transition toward psychrotolerance was particularly well illustrated by the relative abundance of the ‘psychrotolerant’rrs signature (as defined by Pruss et al.) copies accumulated in strains that varied according to the phylogenetic group. The ‘psychrotolerant’cspA signature (as defined by Francis et al.) was specific to group VI and provided a useful way to differentiate it from the psychrotolerant group II. This study illustrates how adaptation to novel environments by the modification of temperature tolerance limits has shaped historical patterns of global ecological diversification in the B. cereus Group. The implications for the taxonomy of this Group and for the human health risk are discussed.
Comparative transcriptome analysis of responses of Methanothermobacter thermautotrophicus to different environmental stimuli
Authors: Kato Souichiro , Kosaka Tomoyuki , Watanabe Kazuya 
Published: December 2007

Summary Methanothermobacter thermautotrophicus strain ΔH is a model hydrogenotrophic methanogen, for which the complete genome sequence and extensive biochemical information are available. Little is known, however, about how this organism regulates its cellular functions in response to environmental stimuli. In this study, whole‐genome oligonucleotide microarrays were constructed for M. thermautotrophicus and used to gain insights into how this organism responds to different environmental stimuli, including hydrogen depletion, shifts in pH and temperature and the occurrence of toxics (hydrogen peroxide and ammonia). Our analysis confirmed that methanogenesis genes (including mtd, mer, frh and mcr) were upregulated under hydrogen‐limited conditions, while some of them were affected by other environmental stimuli. Concerning stress responses of this organism, several unique features were revealed. First, there was no universal stress response in this organism. Second, genes for alternative redox enzymes, such as rubrerythrin, were upregulated under the oxidative stress, but those for typical antioxidant enzymes were not. Third, genes relevant to the modification of cell surface structures were differentially expressed under stress conditions. Finally, energy‐requiring CO2 assimilation systems were downregulated under stress conditions. These findings suggest that M. thermautotrophicus has complex transcriptional regulation mechanisms that facilitate it to survive in unstable ecosystems such as an anaerobic digester.
An angled insertion technique using 6‐mm needles markedly reduces the risk of intramuscular injections in children and adolescents
Authors: Hofman P. L. , Lawton S. A. , Peart J. M. , Holt J. A. , Jefferies C. A. , Robinson E. , Cutfield W. S. 
Published: December 2007

AbstractAims  The aims of this study were (i) to establish which children with Type 1 diabetes are at risk of intramuscular or intradermal insulin injections and (ii) to determine a needle length and technique that reliably administers insulin into subcutaneous fat.Methods  Seventy‐two healthy diabetic children (age 6.3–14.3 years, body mass index standard deviation score 1.0 ± 1.4) were recruited for study 1 and 37 of this cohort participated in study 2. In study 1, 200 µl air was injected into the abdomen and anterior thigh by a pinched skin‐fold technique using either a perpendicular insertion of NovoFine® 31G 6‐mm or an angled insertion of NovoFine® 30G 8‐mm needles. In study 2, subjects received injections into abdomen and anterior thigh via angled 6‐mm needles with either an unpinched or pinched technique. The site of air injection was visualized by ultrasound scan and measurements taken of subcutaneous fat thickness.Results  In study 1, intramuscular injections were detected in 32% of subjects, and in a further 22% air was visualized at the muscle fascia. In study 2, intramuscular injections occurred in 3% of subjects and a further 11% had muscle fascia air detected. No intramuscular injections occurred in subjects injecting with a 6‐mm needle and an angled pinched skin‐fold technique. Pinching abdomen and thigh skin folds increased the subcutaneous fat thickness by 192 ± 16% and 22 ± 6%, respectively. In very lean subjects, pinching thighs actually reduced subcutaneous fat thickness.Conclusions  While intramuscular injections were observed frequently using standard injection protocols, an angled 6‐mm needle technique reliably injects into the subcutaneous fat.
Delayed initiation of subcutaneous insulin therapy after failure of oral glucose‐lowering agents in patients with Type 2 diabetes: a population‐based analysis in the UK
Authors: Rubino A. , McQuay L. J. , Gough S. C. , Kvasz M. , Tennis P. 
Published: December 2007

AbstractAims  The aim of this retrospective cohort study was to estimate the time to insulin initiation in patients with Type 2 diabetes inadequately controlled on oral glucose‐lowering agents (OGLAs).Methods  Insulin‐naïve patients failing on OGLAs were identified from The Health Improvement Network database, which collects records from general practices throughout the UK. Patients were included if they were aged ≥ 40 years, had concomitant prescriptions for ≥ 2 OGLAs, and ≥ 1 year of available records prior to the first occurrence of HbA1c ≥ 8.0% after ≥ 90 days of OGLA polytherapy at ≥ 50% of maximum recommended dosages.Results  A total of 2501 eligible patients with Type 2 diabetes who had an HbA1c above the OGLA failure threshold of ≥ 8.0% were identified (54.0% male; 30.9% aged 60–69 years). It was estimated that if all the eligible patients were followed for 5 years, 25% would initiate insulin within 1.8 years of OGLA failure (95% CI 1.6–2.0), and 50% within 4.9 years (95% CI 4.6–5.8). The presence of diabetes‐related complications had no substantial impact on the time to insulin initiation.Conclusions  This study found that 25% of patients with Type 2 diabetes had insulin initiation delayed for at least 1.8 years, and 50% of patients delayed starting insulin for almost 5 years after failure of glycaemic control with OGLA polytherapy, even in the presence of diabetes‐related complications. Interventions that reduce this delay to insulin initiation are required to help achieve and maintain recommended glycaemic targets in patients with Type 2 diabetes.
No evidence of association of the PDCD1 gene with Type 1 diabetes
Authors: Fawwaz S. , Nikamo P. , Törn C. , Landin‐Olsson M. , Lernmark Å. , Alarcón‐Riquelme M. , Kockum I. ,   the Diabetes Incidence in Sweden Study Group
Published: December 2007

AbstractAims  To test the association between the immunoreceptor PD‐1 (PDCD1) gene and Type 1 diabetes mellitus (T1DM). This gene has been reported to be associated with other autoimmune diseases such as systemic lupus erythematosus (SLE) as well as T1DM.Methods  Genotyping of single nucleotide polymorphisms (SNPs) in the PDCD1 gene was performed using polymerase chain reaction—restriction fragment length polymorphism (PCR‐RFLP), pyrosequencing and TaqMan in two separate cohorts of Swedish patients and control subjects: a family study consisting of 184 multiplex and eight simplex families and a case‐control study consisting of 586 patients and 836 control subjects. Three SNPs were genotyped: PD‐1 7146, PD‐1 7785 and PD‐1 8738.Results  We did not detect any association or linkage between SNPs in PDCD1 and T1DM. We further performed a meta‐analysis for association of PD‐1 7146, PD‐1 7785 and PD‐1 8738 to T1DM. We detected heterogeneity in association with weak evidence for overall association.Conclusions  We conclude that PDCD1 is unlikely to be a major susceptibility gene for T1DM.
Diagnostic potential of serum protein pattern in Type 2 diabetic nephropathy
Authors: Yang Y‐H. , Zhang S. , Cui J‐F. , Lu B. , Dong X‐H. , Song X‐Y. , Liu Y‐K. , Zhu X‐X. , Hu R‐M. 
Published: December 2007

AbstractAims  Microalbuminuria is the earliest clinical sign of diabetic nephropathy (DN). However, the multifactorial nature of DN supports the application of combined markers as a diagnostic tool. Thus, another screening approach, such as protein profiling, is required for accurate diagnosis. Surface enhanced laser desorption/ionization time‐of‐flight mass spectrometry (SELDI‐TOF‐MS) is a novel method for biomarker discovery. We aimed to use SELDI and bioinformatics to define and validate a DN‐specific protein pattern in serum.Methods  SELDI was used to obtain protein or polypeptide patterns from serum samples of 65 patients with DN and 65 non‐DN subjects. From signatures of protein/polypeptide mass, a decision tree model was established for diagnosing the presence of DN. We estimated the proportion of correct classifications from the model by applying it to a masked group of 22 patients with DN and 28 non‐DN subjects. The weak cationic exchange (CM10) ProteinChip arrays were performed on a ProteinChip PBS IIC reader.Results  The intensities of 22 detected peaks appeared up‐regulated, whereas 24 peaks were down‐regulated more than twofold (P < 0.01) in the DN group compared with the non‐DN groups. The algorithm identified a diagnostic DN pattern of six protein/polypeptide masses. On masked assessment, prediction models based on these protein/polypeptides achieved a sensitivity of 90.9% and specificity of 89.3%.Conclusion  These observations suggest that DN patients have a unique cluster of molecular components in serum, which are present in their SELDI profile. Identification and characterization of these molecular components will help in the understanding of the pathogenesis of DN. The serum protein signature, combined with a tree analysis pattern, may provide a novel clinical diagnostic approach for DN.
The impact of site and extent of clinically evident cardiovascular disease and atherosclerotic burden on new cardiovascular events in patients with Type 2 diabetes. The SMART study
Authors: Gorter P. M. , Visseren F. L. J. , Algra A. , Van Der Graaf Y. ,   on behalf of the SMART Study Group
Published: December 2007

AbstractAims  Patients with Type 2 diabetes and coronary heart disease (CHD) have an excess cardiovascular risk. The relationship of both other sites [cerebrovascular disease, peripheral arterial disease (PAD)] and the extent of clinically evident cardiovascular disease (CVD) with the occurrence of new cardiovascular events have not been investigated previously in patients with diabetes. We aimed to quantify this relationship and to assess the additional influence of atherosclerotic burden.Methods  From 1996 to 2005, 776 patients with Type 2 diabetes with (n = 458) and without (n = 318) clinically evident CVD were followed prospectively for cardiovascular events (cardiovascular death, non‐fatal ischaemic stroke or myocardial infarction). CVD was classified according to the site (cerebrovascular disease, CHD, PAD); the extent of atherosclerosis was expressed as the number of affected sites. Carotid intima‐media thickness and albuminuria were used as markers of atherosclerotic burden.Results  Compared with patients with diabetes without CVD, the hazard ratio (HR) for a cardiovascular event was 3.8 (95% confidence interval 1.7, 8.5), adjusted for age, gender and potential confounders, in those with cerebrovascular disease, 4.3 (1.9, 9.5) in those with CHD, and 4.6 (2.1, 10.2) in those with PAD. Findings were similar after additional adjustment for atherosclerotic burden. Adjusted HR was 3.4 (1.6, 6.9) for patients with diabetes with one affected site and 6.6 (3.0, 14.3) for those with two or more sites.Conclusions  Patients with Type 2 diabetes and cerebrovascular disease, CHD or PAD have strongly increased risks for future cardiovascular events which are comparable. This risk increases markedly with the number of different cardiovascular sites affected and is irrespective of atherosclerotic burden.
Quality of diabetes care in patients with schizophrenia and bipolar disorder: cross‐sectional study
Authors: Whyte S. , Penny C. , Phelan M. , Hippisley‐Cox J. , Majeed A. 
Published: December 2007

AbstractAims  To determine whether patients with severe mental illness receive poorer health care for diabetes than patients without.Methods  This population‐based cross‐sectional survey used electronic general practice records from 481 UK general practices contributing to the QRESEARCH database. The records of 11 043 patients with diabetes, drawn from a database population of over 9 million patients, were extracted. Unadjusted and adjusted odds ratios were calculated using unconditional logistic regression for each of 17 quality indicators for diabetes care from the new General Medical Services contract for general practitioners.Results  The presence of severe mental illness did not reduce the quality of care received; the only significant difference between groups showed that such patients were more likely to have glycated haemoglobin < 7.5%[adjusted odds ratio = 1.45 (99% confidence interval 1.20–1.76)]. Increasing age was associated with better care [adjusted odds ratios from 1.06 (1.02–1.11) to 1.61 (1.52–1.70)], but other confounding variables had no consistent effect across indicators. Overall, performance against government targets was good.Conclusions  The hypothesis of poorer diabetes care for those with severe mental illness is disproved, perhaps surprisingly, in the light of other recent UK studies showing inequalities in care for the mentally ill. The study does not reveal who is providing this good care (general practitioners, psychiatrists or diabetologists) or take account of the estimated 600 000 people in the UK with undiagnosed diabetes.
Age‐dependent accumulation of lipofuscin in perivascular and subretinal microglia in experimental mice
Authors: Xu Heping , Chen Mei , Manivannan Ayyakkannu , Lois Noemi , Forrester John V. 
Published: December 2007

SummaryFundus autofluorescence (AF) imaging by confocal scanning laser ophthalmoscopy has been widely used by ophthalmologists in the diagnosis/monitoring of various retinal disorders. It is believed that fundus AF is derived from lipofuscin in retinal pigment epithelial (RPE) cells; however, direct clinicopathological correlation has not been possible in humans. We examined fundus AF by confocal scanning laser ophthalmoscopy and confocal microscopy in normal C57BL/6 mice of different ages. Increasingly strong AF signals were observed with age in the neuroretina and subretinal/RPE layer by confocal scanning laser ophthalmoscopy. Unlike fundus AF detected in normal human subjects, mouse fundus AF appeared as discrete foci distributed throughout the retina. Most of the AF signals in the neuroretina were distributed around retinal vessels. Confocal microscopy of retinal and choroid/RPE flat mounts demonstrated that most of the AF signals were derived from Iba‐1+ perivascular and subretinal microglia. An age‐dependent accumulation of Iba‐1+ microglia at the subretinal space was observed. Lipofuscin granules were detected in large numbers in subretinal microglia by electron microscopy. The number of AF+ microglia and the amount of AF granules/cell increased with age. AF granules/lipofuscin were also observed in RPE cells in mice older than 12 months, but the number of AF+ RPE cells was very low (1.48 mm−2 and 5.02 mm−2 for 12 and 24 months, respectively) compared to the number of AF+ microglial cells (20.63 mm−2 and 76.36 mm−2 for 6 and 24 months, respectively). The fluorescence emission fingerprints of AF granules in subretinal microglia were the same as those in RPE cells. Our observation suggests that perivascular and subretinal microglia are the main cells producing lipofuscin in normal aged mouse retina and are responsible for in vivo fundus AF. Microglia may play an important role in retinal aging and age‐related retinal diseases.
Diagnostic and prognostic significance of gene expression profiling in lymphomas
Authors: LEICH ELLEN , HARTMANN ELENA MARIA , CHRISTOF BUREK  , OTT GERMAN , ROSENWALD ANDREAS 
Published: December 2007

Gene expression profiling is a powerful tool to uncover complex molecular networks in cancer and, specifically, in malignant lymphomas. Within diffuse large B‐cell lymphomas (DLBCL), two major molecular subtypes, the activated B‐cell‐like (ABC) and the germinal center B‐cell‐like (GCB) DLBCL, can be defined. Compared to GCB DLBCL, ABC DLBCL shows a vast difference in gene expression and constitutively expresses NFκB and its target genes. In retrospective analyses, the molecular phenotype of ABC DLBCL is associated with inferior survival. Gene expression profiling furthermore allows the molecular separation of Burkitt lymphoma (BL) from DLBCL and reveals a Burkitt‐specific signature which is also expressed by a subset of tumors that are currently classified as DLBCL. Whether patients with a DLBCL displaying a Burkitt‐specific gene expression signature may benefit from alternative therapeutic approaches will have to be determined in future prospective clinical trials.In follicular lymphoma (FL), two outcome‐related signatures, termed Immune response 1 (IR1) and Immune response 2 (IR2), have been identified by gene expression profiling, indicating a significant role of the microenvironment in tumor development and progression. IR1, composed of genes mostly expressed by T‐cells, was found to be associated with a more favorable clinical course, and IR2, enriched for genes expressed by macrophages and follicular dendritic cells, was found to be associated with an inferior clinical course. In mantle cell lymphoma (MCL), a gene expression‐based proliferation signature of 20 different genes was identified that is able to predict survival of MCL patients in a linear fashion. Future efforts will have to be directed towards the translation of relevant molecular diagnostic and prognostic markers derived from the wealth of gene expression data into clinical tests and towards the development of novel, targeted therapies.
The C3-V4 Region Is a Major Target of Autologous Neutralizing Antibodies in Human Immunodeficiency Virus Type 1 Subtype C Infection
Authors: Moore Penny L. , Gray Elin S. , Choge Isaac A. , Ranchobe Nthabeleng , Mlisana Koleka , Abdool Karim Salim S. , Williamson Carolyn , Morris Lynn 
Published: December 2007

ABSTRACT
The early autologous neutralizing antibody response in human immunodeficiency virus type 1 (HIV-1) subtype C infections is often characterized by high titers, but the response is type specific with little to no cross-neutralizing activity. The specificities of these early neutralizing antibodies are not known; however, the type specificity suggests that they may target the variable regions of the envelope. Here, we show that cross-reactive anti-V3 antibodies developed within 3 to 12 weeks in six individuals but did not mediate autologous neutralization. Using a series of chimeric viruses, we found that antibodies directed at the V1V2, V4, and V5 regions contributed to autologous neutralization in some individuals, with V1V2 playing a more substantial role. However, these antibodies did not account for the total neutralizing capacity of these sera against the early autologous virus. Antibodies directed against the C3-V4 region were involved in autologous neutralization in all four sera studied. In two sera, transfer of the C3-V4 region rendered the chimera as sensitive to antibody neutralization as the parental virus. Although the C3 region, which contains the highly variable α2-helix was not a direct target in most cases, it contributed to the formation of neutralization epitopes as substitution of this region resulted in neutralization resistance. These data suggest that the C3 and V4 regions combine to form important structural motifs and that epitopes in this region are major targets of the early autologous neutralizing response in HIV-1 subtype C infection.