bluuebunny/crossref_metadata_2025_split huggingface dataset:
Selecting pseudo‐absences for species distribution models: how, where and how many?
Authors: Barbet‐Massin Morgane , Jiguet Frédéric , Albert Cécile Hélène , Thuiller Wilfried 
Published: January 2012

Summary1. Species distribution models are increasingly used to address questions in conservation biology, ecology and evolution. The most effective species distribution models require data on both species presence and the available environmental conditions (known as background or pseudo‐absence data) in the area. However, there is still no consensus on how and where to sample these pseudo‐absences and how many.2. In this study, we conducted a comprehensive comparative analysis based on simple simulated species distributions to propose guidelines on how, where and how many pseudo‐absences should be generated to build reliable species distribution models. Depending on the quantity and quality of the initial presence data (unbiased vs. climatically or spatially biased), we assessed the relative effect of the method for selecting pseudo‐absences (random vs. environmentally or spatially stratified) and their number on the predictive accuracy of seven common modelling techniques (regression, classification and machine‐learning techniques).3. When using regression techniques, the method used to select pseudo‐absences had the greatest impact on the model’s predictive accuracy. Randomly selected pseudo‐absences yielded the most reliable distribution models. Models fitted with a large number of pseudo‐absences but equally weighted to the presences (i.e. the weighted sum of presence equals the weighted sum of pseudo‐absence) produced the most accurate predicted distributions. For classification and machine‐learning techniques, the number of pseudo‐absences had the greatest impact on model accuracy, and averaging several runs with fewer pseudo‐absences than for regression techniques yielded the most predictive models.4. Overall, we recommend the use of a large number (e.g. 10 000) of pseudo‐absences with equal weighting for presences and absences when using regression techniques (e.g. generalised linear model and generalised additive model); averaging several runs (e.g. 10) with fewer pseudo‐absences (e.g. 100) with equal weighting for presences and absences with multiple adaptive regression splines and discriminant analyses; and using the same number of pseudo‐absences as available presences (averaging several runs if few pseudo‐absences) for classification techniques such as boosted regression trees, classification trees and random forest. In addition, we recommend the random selection of pseudo‐absences when using regression techniques and the random selection of geographically and environmentally stratified pseudo‐absences when using classification and machine‐learning techniques.
An objective, niche‐based approach to indicator species selection
Authors: Butler Simon J. , Freckleton Robert P. , Renwick Anna R. , Norris Ken 
Published: January 2012

Summary1. Species‐based indices are frequently employed as surrogates for wider biodiversity health and measures of environmental condition. Species selection is crucial in determining an indicator’s metric value and hence the validity of the interpretation of ecosystem condition and function it provides, yet an objective process to identify appropriate indicator species is frequently lacking.2. An effective indicator needs to (i) be representative, reflecting the status of wider biodiversity; (ii) be reactive, acting as early‐warning systems for detrimental changes in environmental conditions; (iii) respond to change in a predictable way. We present an objective, niche‐based approach for species’ selection, founded on a coarse categorisation of species’ niche space and key resource requirements, which ensures the resultant indicator has these key attributes.3. We use UK farmland birds as a case study to demonstrate this approach, identifying an optimal indicator set containing 12 species. In contrast to the 19 species included in the farmland bird index (FBI), a key UK biodiversity indicator that contributes to one of the UK Government’s headline indicators of sustainability, the niche space occupied by these species fully encompasses that occupied by the wider community of 62 species.4. We demonstrate that the response of these 12 species to land‐use change is a strong correlate to that of the wider farmland bird community. Furthermore, the temporal dynamics of the index based on their population trends closely matches the population dynamics of the wider community. However, in both analyses, the magnitude of the change in our indicator was significantly greater, allowing this indicator to act as an early‐warning system.5. Ecological indicators are embedded in environmental management, sustainable development and biodiversity conservation policy and practice where they act as metrics against which progress towards national, regional and global targets can be measured. Adopting this niche‐based approach for objective selection of indicator species will facilitate the development of sensitive and representative indices for a range of taxonomic groups, habitats and spatial scales.
Subpopulation Analysis of Heteroresistance to Fluoroquinolone in Mycobacterium tuberculosis Isolates from Beijing, China
Authors: Zhang Xiaobing , Zhao Bing , Liu Liguo , Zhu Yafang , Zhao Yanlin , Jin Qi 
Published: January 2012

ABSTRACT

The presence of heteroresistance was represented by 23% of 235 fluoroquinolone (FQ)-resistant
Mycobacterium tuberculosis
isolates in Beijing, China, from 2008 to 2010. The main mechanism of FQ heteroresistance is due to the segregation of a single
M. tuberculosis
strain in patients; the majority of isolates with multidrug-resistant tuberculosis contained a mixture of bacterial subpopulations consisting of various mutant types, suggesting that the improper use of FQ is the major cause of FQ resistance.
Inhibition of Latent Membrane Protein 1 Impairs the Growth and Tumorigenesis of Latency II Epstein-Barr Virus-Transformed T Cells
Authors: Ndour Papa Alioune , Brocqueville Guillaume , Ouk Tan-Sothéa , Goormachtigh Gautier , Morales Olivier , Mougel Alexandra , Bertout Julie , Melnyk Oleg , Fafeur Véronique , Feuillard Jean , Coll Jean , Adriaenssens Eric 
Published: January 2012

ABSTRACT

Epstein-Barr virus (EBV) is a common human herpesvirus. Infection with EBV is associated with several human malignancies in which the virus expresses a set of latent proteins, among which is latent membrane protein 1 (LMP1). LMP1 is able to transform numerous cell types and is considered the main oncogenic protein of EBV. The mechanism of action is based on mimicry of activated members of the tumor necrosis factor (TNF) receptor superfamily, through the ability of LMP1 to bind similar adapters and to activate signaling pathways. We previously generated two unique models: a monocytic cell line and a lymphocytic (NC5) cell line immortalized by EBV that expresses the type II latency program. Here we generated LMP1 dominant negative forms (DNs), based on fusion between green fluorescent protein (GFP) and
t
ransformation
e
ffector
s
ite 1 (TES1) or TES2 of LMP1. Then we generated cell lines conditionally expressing these DNs. These DNs inhibit NF-κB and Akt pathways, resulting in the impairment of survival processes and increased apoptosis in these cell lines. This proapoptotic effect is due to reduced interaction of LMP1 with specific adapters and the recruitment of these adapters to DNs, which enable the generation of an apoptotic complex involving TRADD, FADD, and caspase 8. Similar results were obtained with cell lines displaying a latency III program in which LMP1-DNs decrease cell viability. Finally, we prove that synthetic peptides display similar inhibitory effects in EBV-infected cells. DNs derived from LMP1 could be used to develop therapeutic approaches for malignant diseases associated with EBV.
Experimental Infection of Cynomolgus Macaques (Macaca fascicularis) with Human Varicella-Zoster Virus
Authors: Willer David O. , Ambagala Aruna P. N. , Pilon Richard , Chan Jacqueline K. , Fournier Jocelyn , Brooks James , Sandstrom Paul , MacDonald Kelly S. 
Published: January 2012

ABSTRACTVaricella-zoster virus (VZV) is a member of the alphaherpesvirus family and the causative agent of chickenpox and shingles. To determine the utility of cynomolgus macaques (Macaca fascicularis) as a nonhuman primate model to evaluate VZV-based simian immunodeficiency virus/human immunodeficiency virus (SIV/HIV) vaccines, we experimentally inoculated 10 animals with the parental Oka (Oka-P) strain of VZV derived from MeWo or Telo-RF cells. VZV DNA could be detected in the lungs as late as 4 days postinfection, with replicating virus detected by shell vial culture assay in one case. Infection did not result in any overt clinical symptoms but was characterized by humoral and cell-mediated immunity in a time frame and at a magnitude similar to those observed following VZV vaccination in humans. The cell line source of VZV inoculum influenced both the magnitude and polyfunctionality of cell-mediated immunity. Animals mounted a vigorous anamnestic antibody response following a second inoculation 12 weeks later. Inoculations resulted in transient increases in CD4+T-cell activation and proliferation, as well as a sustained increase in CD4+T cells coexpressing CCR5 and α4β7 integrin. In contrast to previous failed attempts to successfully utilize attenuated VZV-Oka as an SIV vaccine vector in rhesus macaques due to suboptimal infectivity and cellular immunogenicity, the ability to infect cynomolgus macaques with Oka-P VZV should provide a valuable tool for evaluating VZV-vectored SIV/HIV vaccines.
The C Terminus of the Large Tegument Protein pUL36 Contains Multiple Capsid Binding Sites That Function Differently during Assembly and Cell Entry of Herpes Simplex Virus
Authors: Schipke Julia , Pohlmann Anja , Diestel Randi , Binz Anne , Rudolph Kathrin , Nagel Claus-Henning , Bauerfeind Rudolf , Sodeik Beate 
Published: January 2012

ABSTRACT
The largest tegument protein of herpes simplex virus type 1 (HSV1), pUL36, is a multivalent cross-linker between the viral capsids and the tegument and associated membrane proteins during assembly that upon subsequent cell entry releases the incoming capsids from the outer tegument and viral envelope. Here we show that pUL36 was recruited to cytosolic progeny capsids that later colocalized with membrane proteins of herpes simplex virus type 1 (HSV1) and the trans-Golgi network. During cell entry, pUL36 dissociated from viral membrane proteins but remained associated with cytosolic capsids until arrival at the nucleus. HSV1 UL36 mutants lacking C-terminal portions of increasing size expressed truncated pUL36 but could not form plaques. Cytosolic capsids of mutants lacking the C-terminal 735 of the 3,164 amino acid residues accumulated in the cytosol but did not recruit pUL36 or associate with membranes. In contrast, pUL36 lacking only the 167 C-terminal residues bound to cytosolic capsids and subsequently colocalized with viral and host membrane proteins. Progeny virions fused with neighboring cells, but incoming capsids did not retain pUL36, nor could they target the nucleus or initiate HSV1 gene expression. Our data suggest that residues 2430 to 2893 of HSV1 pUL36, containing one binding site for the capsid protein pUL25, are sufficient to recruit pUL36 onto cytosolic capsids during assembly for secondary envelopment, whereas the 167 residues of the very C terminus with the second pUL25 binding site are crucial to maintain pUL36 on incoming capsids during cell entry. Capsids lacking pUL36 are targeted neither to membranes for virus assembly nor to nuclear pores for genome uncoating.
Nonstructural Protein 2 of Porcine Reproductive and Respiratory Syndrome Virus Inhibits the Antiviral Function of Interferon-Stimulated Gene 15
Authors: Sun Zhi , Li Yanhua , Ransburgh Russell , Snijder Eric J. , Fang Ying 
Published: January 2012

ABSTRACTType I interferon (alpha/beta interferon [IFN-α/β]) stimulates the expression of interferon-stimulated gene 15 (ISG15), which encodes a ubiquitin-like protein, ISG15. Free ISG15 and ISG15 conjugates function in diverse cellular pathways, particularly regulation of antiviral innate immune responses. In this study, we demonstrate that ISG15 overexpression inhibits porcine reproductive and respiratory syndrome virus (PRRSV) replication in cell culture and that the antiviral activity of interferon is reduced by inhibition of ISG15 conjugation. PRRSV nonstructural protein 2 (nsp2) was previously identified as a potential antagonist of ISG15 production and conjugation. The protein contains a papain-like protease domain (PLP2) that plays a crucial role in the proteolytic cleavage of the PRRSV replicase polyproteins. PLP2 was also proposed to belong to the ovarian tumor domain-containing superfamily of deubiquitinating enzymes (DUBs), which is capable of inhibiting ISG15 production and counteracting ISG15 conjugation to cellular proteins. To determine whether this immune antagonist function could be selectively inactivated, we engineered a panel of mutants with deletions and/or mutations at the N-terminal border of the nsp2 PLP2-DUB domain. A 23-amino-acid deletion (amino acids 402 to 424 of the ORF1a-encoded protein) largely abolished the inhibitory effect of nsp2 on ISG15 production and conjugation, but no viable recombinant virus was recovered. A 19-amino-acid deletion (amino acids 402 to 420), in combination with a downstream point mutation (S465A), partially relieved the ISG15 antagonist function and yielded a viable recombinant virus. Taken together, our data demonstrate that ISG15 and ISGylation play an important role in the response to PRRSV infection and that nsp2 is a key factor in counteracting the antiviral function of ISG15.
Mucinous subtype as prognostic factor in colorectal cancer: a systematic review and meta-analysis
Authors: Verhulst J , Ferdinande L , Demetter P , Ceelen W 
Published: January 2012

BackgroundMucinous adenocarcinoma (MAC) of the colorectum has been known and studied for many years. The prognostic significance of this histological subtype remains controversial. The authors reviewed the prognostic significance of mucinous differentiation in colorectal cancer.Materials and methodsA systematic web-based search was performed using Web of Knowledge and Medline. Articles published in English, German or French which used the WHO definition of MAC and described cohort studies, case–control studies or cross-sectional studies comparing survival in patients with MAC and adenocarcinoma (AC) not otherwise specified were included. Data on first author, year of publication, country, number of patients included, prevalence of MAC, % stage IV disease, % disease located in the proximal colon, mean age at presentation, % male patients and 5-year overall survival were extracted from individual studies. A fixed-effects meta-analysis model was used for analysis. The primary outcome was survival, expressed as the HR. Differences between categorical outcome parameters were quantified using the RR and corresponding 95% CI.Results44 studies and 222 256 patients were included. The RR for proximal disease versus distal disease was 1.55 (95% CI 1.53 to 1.58). Mucinous differentiation was less frequent in male subjects (RR 0.93 (95% CI 0.91 to 0.94)). Interestingly, the prevalence of stage IV disease was similar in MAC and AC (RR 0.99 (95% CI 0.96 to 1.02)). Thirty-five articles were included in the survival analysis. A worse survival in MAC versus AC was demonstrated (HR 1.05 (95% CI 1.02 to 1.08)). Conversely, three out of four studies reported a better survival in MAC with microsatellite instability (MSI). Due to heterogeneity a meta-analysis on the effect of MSI was not possible.ConclusionMAC more often originates from the right colon and is less frequent in male subjects. The authors did not identify a difference in the proportion of stage IV patients at presentation. Mucinous differentiation results in a 2–8% increased hazard of death, which persists after correction for stage. More research is needed to define the interaction between mucinous differentiation, MSI and outcome.
Upregulation of miR-196a andHOTAIRDrive Malignant Character in Gastrointestinal Stromal Tumors
Authors: Niinuma Takeshi , Suzuki Hiromu , Nojima Masanori , Nosho Katsuhiko , Yamamoto Hiroyuki , Takamaru Hiroyuki , Yamamoto Eiichiro , Maruyama Reo , Nobuoka Takayuki , Miyazaki Yasuaki , Nishida Toshirou , Bamba Takeo , Kanda Tatsuo , Ajioka Yoichi , Taguchi Takahiro , Okahara Satoshi , Takahashi Hiroaki , Nishida Yasunori , Hosokawa Masao , Hasegawa Tadashi , Tokino Takashi , Hirata Koichi , Imai Kohzoh , Toyota Minoru , Shinomura Yasuhisa 
Published: January 2012

AbstractLarge intergenic noncoding RNAs (lincRNA) have been less studied than miRNAs in cancer, although both offer considerable theranostic potential. In this study, we identified frequent upregulation of miR-196a and lincRNA HOTAIR in high-risk gastrointestinal stromal tumors (GIST). Overexpression of miR-196a was associated with high-risk grade, metastasis and poor survival among GIST specimens. miR-196a genes are located within the HOX gene clusters and microarray expression analysis revealed that the HOXC and HOTAIR gene were also coordinately upregulated in GISTs which overexpress miR-196a. In like manner, overexpression of HOTAIR was also strongly associated with high-risk grade and metastasis among GIST specimens. RNA interference–mediated knockdown of HOTAIR altered the expression of reported HOTAIR target genes and suppressed GIST cell invasiveness. These findings reveal concurrent overexpression of HOX genes with noncoding RNAs in human cancer in this setting, revealing miR-196a and HOTAIR as potentially useful biomarkers and therapeutic targets in malignant GISTs. Cancer Res; 72(5); 1126–36. ©2012 AACR.
Microsatellite Instability and DNA Mismatch Repair Protein Deficiency in Lynch Syndrome Colorectal Polyps
Authors: Yurgelun Matthew B. , Goel Ajay , Hornick Jason L. , Sen Ananda , Turgeon Danielle Kim , Ruffin Mack T. , Marcon Norman E. , Baron John A. , Bresalier Robert S. , Syngal Sapna , Brenner Dean E. , Boland C. Richard , Stoffel Elena M. 
Published: January 2012

Abstract
Colorectal cancers associated with Lynch syndrome are characterized by deficient DNA mismatch repair (MMR) function. Our aim was to evaluate the prevalence of microsatellite instability (MSI) and loss of MMR protein expression in Lynch syndrome–associated polyps. Sixty-two colorectal polyps—37 adenomatous polyps, 23 hyperplastic polyps, and 2 sessile serrated polyps (SSP)—from 34 subjects with germline MMR gene mutations were tested for MSI using a single pentaplex PCR for five mononucleotide repeat microsatellite markers, and also for expression of MLH1, MSH2, MSH6, and PMS2 proteins by immunohistochemistry. High-level MSI (MSI-H) was seen in 15 of 37 (41%) adenomatous polyps, one of 23 (4%) hyperplastic polyps, and one of two (50%) SSPs. Loss of MMR protein expression was seen in 18 of 36 (50%) adenomatous polyps, zero of 21 hyperplastic polyps, and zero of two SSPs. Adenomatous polyps 8 mm or larger in size were significantly more likely to show MSI-H [OR, 9.98; 95% confidence interval (CI), 1.52–65.65; P = 0.02] and deficient MMR protein expression (OR, 3.17; 95% CI, 1.20–8.37; P = 0.02) compared with those less than 8 mm in size. All (six of six) adenomatous polyps 10 mm or larger in size showed both MSI-H and loss of MMR protein expression by immunohistochemistry. Our finding that the prevalence of MMR deficiency increases with the size of adenomatous polyps suggests that loss of MMR function is a late event in Lynch syndrome–associated colorectal neoplasia. Although testing large adenomatous polyps may be of value in the diagnostic evaluation of patients with suspected Lynch syndrome, the absence of an MMR-deficient phenotype in an adenoma cannot be considered as a strong evidence against Lynch syndrome, as it is with colorectal carcinomas. Cancer Prev Res; 5(4); 574–82. ©2012 AACR.
Angiogenic Factors and the Risk of Adverse Outcomes in Women With Suspected Preeclampsia
Authors: Rana Sarosh , Powe Camille E. , Salahuddin Saira , Verlohren Stefan , Perschel Frank H. , Levine Richard J. , Lim Kee-Hak , Wenger Julia B. , Thadhani Ravi , Karumanchi S. Ananth 
Published: January 2012

Background—
An imbalance in circulating angiogenic factors plays a central role in the pathogenesis of preeclampsia.

Methods and Results—

We prospectively studied 616 women who were evaluated for suspected preeclampsia. We measured plasma levels of antiangiogenic soluble fms-like tyrosine kinase 1 (sFlt1) and proangiogenic placental growth factor (PlGF) at presentation and examined for an association between the sFlt1/PlGF ratio and subsequent adverse maternal and perinatal outcomes within 2 weeks. The median sFlt1/PlGF ratio at presentation was elevated in participants who experienced any adverse outcome compared with those who did not (47.0 [25th–75th percentile, 15.5–112.2] versus 10.8 [25th–75th percentile, 4.1–28.6];
P
<0.0001). Among those presenting at <34 weeks (n=167), the results were more striking (226.6 [25th–75th percentile, 50.4–547.3] versus 4.5 [25th–75th percentile, 2.0–13.5];
P
<0.0001), and the risk was markedly elevated when the highest sFlt1/PlGF ratio tertile was compared with the lowest (odds ratio, 47.8; 95% confidence interval, 14.6–156.6). Among participants presenting at <34 weeks, the addition of sFlt1/PlGF ratio to hypertension and proteinuria significantly improved the prediction for subsequent adverse outcomes (area under the curve, 0.93 for hypertension, proteinuria, and sFlt1/PlGF versus 0.84 for hypertension and proteinuria alone;
P
=0.001). Delivery occurred within 2 weeks of presentation in 86.0% of women with an sFlt1/PlGF ratio ≥85 compared with 15.8% of women with an sFlt1/PlGF ratio <85 (hazard ratio, 15.2; 95% confidence interval, 8.0–28.7).

Conclusions—
In women with suspected preeclampsia presenting at <34 weeks, circulating sFlt1/PlGF ratio predicts adverse outcomes occurring within 2 weeks. The accuracy of this test is substantially better than that of current approaches and may be useful in risk stratification and management. Additional studies are warranted to validate these findings.