bluuebunny/crossref_metadata_2025_split huggingface dataset:
Value Chains, Donor Interventions and Poverty Reduction: A Review of Donor Practice
Authors: Humphrey John , Navas‐Alemán Lizbeth 
Published: October 2010

SummaryValue chain interventions are increasingly popular amongst donors aiming to promote market‐oriented growth and poverty reduction. Based on the reflections of the community of practice itself and extensive desk research, this review critically examines the causal models underlying value chain interventions and asks how and to what extent their poverty alleviation impacts have been systematically investigated.Concentrating on a selection of 30 donor‐led value chain interventions, the review finds two main patterns of engagement: (a) one which funnels assistance by partnering with lead firms in the value chain –lead firm projects; and (b) one which works with chains without a lead firm –value chain linkage projects. Targeting of the poor seems more effective in value chain linkage projects and in those lead firm projects where beneficiaries are identified in both the chain's suppliers and distributors.Controversially, despite a wealth of positive anecdotal evidence, the vast majority of projects did not carry out an impact assessment of their poverty alleviation objectives and it is therefore unclear whether the value chain intervention: (a) is responsible for the improvements observed; (b) benefits the poor disproportionately; and (c) is more cost effective than other alternative approaches. Assessing the poverty alleviation effects of individual interventions in a rigorous way is costly and challenging but necessary to ensure long term effectiveness of the interventions as well as optimising the use of public funds. There is a need to carry out systematic impact assessment at the programme level to develop a strong evidence base.Finally, this review provides some guidelines for designing and managing value chain interventions, particularly regarding the identification of situations in which the value chain approach is most appropriate and those where other private sector‐oriented approaches (such as Business Development Services and Making Markets Work for the Poor) may be more suitable or complementary.
Identification of a Severe Acute Respiratory Syndrome Coronavirus-Like Virus in a Leaf-Nosed Bat in Nigeria
Authors: Quan Phenix-Lan , Firth Cadhla , Street Craig , Henriquez Jose A. , Petrosov Alexandra , Tashmukhamedova Alla , Hutchison Stephen K. , Egholm Michael , Osinubi Modupe O. V. , Niezgoda Michael , Ogunkoya Albert B. , Briese Thomas , Rupprecht Charles E. , Lipkin W. Ian 
Published: October 2010

ABSTRACT

Bats are reservoirs for emerging zoonotic viruses that can have a profound impact on human and animal health, including lyssaviruses, filoviruses, paramyxoviruses, and severe acute respiratory syndrome coronaviruses (SARS-CoVs). In the course of a project focused on pathogen discovery in contexts where human-bat contact might facilitate more efficient interspecies transmission of viruses, we surveyed gastrointestinal tissue obtained from bats collected in caves in Nigeria that are frequented by humans. Coronavirus consensus PCR and unbiased high-throughput pyrosequencing revealed the presence of coronavirus sequences related to those of SARS-CoV in a Commerson's leaf-nosed bat (
Hipposideros commersoni
). Additional genomic sequencing indicated that this virus, unlike subgroup 2b CoVs, which includes SARS-CoV, is unique, comprising three overlapping open reading frames between the M and N genes and two conserved stem-loop II motifs. Phylogenetic analyses in conjunction with these features suggest that this virus represents a new subgroup within group 2 CoVs.

IMPORTANCE
Bats (order Chiroptera, suborders Megachiroptera and Microchiroptera) are reservoirs for a wide range of viruses that cause diseases in humans and livestock, including the severe acute respiratory syndrome coronavirus (SARS-CoV), responsible for the global SARS outbreak in 2003. The diversity of viruses harbored by bats is only just beginning to be understood because of expanded wildlife surveillance and the development and application of new tools for pathogen discovery. This paper describes a new coronavirus, one with a distinctive genomic organization that may provide insights into coronavirus evolution and biology.
Multidrug-Resistant Enterococci Lack CRISPR-
cas
Authors: Palmer Kelli L. , Gilmore Michael S. 
Published: October 2010

ABSTRACT

Clustered, regularly interspaced short palindromic repeats (CRISPR) provide bacteria and archaea with sequence-specific, acquired defense against plasmids and phage. Because mobile elements constitute up to 25% of the genome of multidrug-resistant (MDR) enterococci, it was of interest to examine the codistribution of CRISPR and acquired antibiotic resistance in enterococcal lineages. A database was built from 16
Enterococcus faecalis
draft genome sequences to identify commonalities and polymorphisms in the location and content of CRISPR loci. With this data set, we were able to detect identities between CRISPR spacers and sequences from mobile elements, including pheromone-responsive plasmids and phage, suggesting that CRISPR regulates the flux of these elements through the
E. faecalis
species. Based on conserved locations of CRISPR and CRISPR-
cas
loci and the discovery of a new CRISPR locus with associated functional genes, CRISPR3-
cas
, we screened additional
E. faecalis
strains for CRISPR content, including isolates predating the use of antibiotics. We found a highly significant inverse correlation between the presence of a CRISPR-
cas
locus and acquired antibiotic resistance in
E. faecalis
, and examination of an additional eight
E. faecium
genomes yielded similar results for that species. A mechanism for CRISPR-
cas
loss in
E. faecalis
was identified. The inverse relationship between CRISPR-
cas
and antibiotic resistance suggests that antibiotic use inadvertently selects for enterococcal strains with compromised genome defense.

IMPORTANCE
For many bacteria, including the opportunistically pathogenic enterococci, antibiotic resistance is mediated by acquisition of new DNA and is frequently encoded on mobile DNA elements such as plasmids and transposons. Certain enterococcal lineages have recently emerged that are characterized by abundant mobile DNA, including numerous viruses (phage), and plasmids and transposons encoding multiple antibiotic resistances. These lineages cause hospital infection outbreaks around the world. The striking influx of mobile DNA into these lineages is in contrast to what would be expected if a self (genome)-defense system was present. Clustered, regularly interspaced short palindromic repeat (CRISPR) defense is a recently discovered mechanism of prokaryotic self-defense that provides a type of acquired immunity. Here, we find that antibiotic resistance and possession of complete CRISPR loci are inversely related and that members of recently emerged high-risk enterococcal lineages lack complete CRISPR loci. Our results suggest that antibiotic therapy inadvertently selects for enterococci with compromised genome defense.
Combination of morphological feature analysis and immunohistochemistry is useful for screening of EML4-ALK-positive lung adenocarcinoma
Authors: Jokoji Ryu , Yamasaki Takashi , Minami Seigo , Komuta Kiyoshi , Sakamaki Yasushi , Takeuchi Kengo , Tsujimoto Masahiko 
Published: October 2010

BackgroundA subset of lung cancers harbours the fusion gene echinoderm microtubule-associated protein-like-4–anaplastic lymphoma kinase (EML4-ALK). Recently, immunohistochemistry for ALK has shown sensitivity for the detection of EML4-ALK-positive lung adenocarcinoma almost equal to that of the fluorescence in situ hybridisation (FISH) assay.AimsTo study the clinicopathological features of EML4-ALK-positive lung adenocarcinoma in a large number of surgically resected samples using immunohistochemistry, in order to establish a useful screening method for EML4-ALK-positive lung adenocarcinoma.MethodsImmunohistochemistry for ALK was used to screen for EML4-ALK-positive lung adenocarcinomas in 254 cases of surgically resected samples.ResultsEML4-ALK-positive cases were detected in 3.1% of lung adenocarcinomas (8/254). EML4-ALK-positive lung adenocarcinomas showed significant associations with intra- and/or extra-cytoplasmic mucin (p=0.0001), and cribriform pattern with excessive extracytoplasmic mucin (p<0.0001). Signet-ring cell appearance alone lacked significance (p=0.149).ConclusionEML4-ALK-positive lung adenocarcinoma has a tendency to express a characteristic morphological pattern. The combined use of morphological feature analysis and immunohistochemistry may be a useful and cost effective screening method for EML4-ALK lung adenocarcinoma.
Degree of solidarity with lifestyle and old age among citizens in the Netherlands: cross-sectional results from the longitudinal SMILE study
Authors: Bonnie Linda H A , van den Akker Marjan , van Steenkiste Ben , Vos Rein 
Published: October 2010

Background and aimWith the increasing interest in lifestyle, health and consequences of unhealthy lifestyles for the healthcare system, a new kind of solidarity is gaining importance: lifestyle solidarity. While it might not seem fair to let other people pay for the costs arising from an unhealthy lifestyle, it does not seem fair either to punish people for their lifestyle. However, it is not clear how solidarity is assessed by people, when considering disease risks or lifestyle risks. The aim of this study was to investigate the degree of solidarity with lifestyle as well as with other factors that are related to health outcomes—for example, old age—and the relation between this degree of solidarity and various characteristics.MethodsThis cross-sectional study is part of the Dutch longitudinal SMILE study. Data on the degree of solidarity with different lifestyles and old age, and the relation between the degree of solidarity and various demographic and other variables were obtained in a questionnaire survey.ResultsSolidarity with smokers and overweight people was moderate, as was solidarity with older people. Respondents were ambivalent about athletes. Respondents who were younger, male and highly educated, and those with a healthy lifestyle, a small social network, high quality of life and an internal locus of control, showed low solidarity.ConclusionsSolidarity with an unhealthy lifestyle and old age is moderate and the degree of solidarity varies among the different subgroups.
Understanding preferences for disclosure of individual biomarker results among participants in a longitudinal birth cohort
Authors: Wilson Stephen E , Baker Erin R , Leonard Anthony C , Eckman Mark H , Lanphear Bruce P 
Published: October 2010

BackgroundTo describe the preferences for disclosure of individual biomarker results among mothers participating in a longitudinal birth cohort.MethodsWe surveyed 343 mothers that participated in the Health Outcomes and Measures of the Environment Study about their biomarker disclosure preferences. Participants were told that the study was measuring pesticide metabolites in their biological specimens, and that the health effects of these low levels of exposure are unknown. Participants were asked whether they wanted to receive their results and their child's results. In addition, they were asked about their preferred method (letter vs in person) and format (more complex vs less complex) for disclosure of results.ResultsAlmost all of the study participants wanted to receive their individual results (340/343) as well as their child's results (342/343). However, preferences for receiving results differed by education level. Mothers with less than a college degree preferred in-person disclosure of results more often than mothers with some college education or a college degree (34.3% vs 17.4% vs 7.9%, p<0.001). Similarly, mothers with less than a college education preferred a less complex disclosure format than mothers with some college education or a college degree (59.7% vs 79.1% vs 86.3%, p<0.0001).ConclusionWhile almost all study participants preferred to receive results of their individual biomarker tests, level of education was a key factor in predicting preferences for disclosure of biomarker results. To ensure effective communication of this information, disclosure of biomarker results should be tailored to the education level of the study participants.
A revised life table and survivorship curve for Albertosaurus sarcophagus based on the Dry Island mass death assemblageThis article is one of a series of papers published in this Special Issue on the theme Albertosaurus.
Authors: Erickson Gregory M. , Currie Philip J. , Inouye Brian D. , Winn Alice A. 
Published: October 2010

In 1910 a crew from the American Museum of Natural History discovered a bone bed composed primarily of the large tyrannosaurid Albertosaurus sarcophagus in what is now Dry Island Buffalo Jump Provincial Park in Alberta, Canada. Study of the remains from the site allowed the first life table and survivorship curve for a non-avian dinosaur to be created. These have served as a model for subsequent studies of dinosaurian population biology. Since 2006, the discovery and preparation of hundreds of new elements from the bone bed stand to substantially increase the minimum number of individuals (MNI) represented. This would allow testing of previous conclusions regarding the population biology of these animals and refinement of our understanding of the patterns of survivorship. Here, four formerly unrecognized individuals from the Dry Island assemblage are revealed and a revised life table presented. As in the previous analysis, a left skewed age distribution and sigmoidal survivorship pattern were found. Annual mortality rates averaged 3.47% between ages two and 13 and then increased to a mean of 19.5% prior to extinction of the cohort after 28 years of age. Mean life expectancy for individuals surviving to two years of age was 15.19 years. Mid-life increase in attrition corresponds to entrance into the breeding population. The MNI is unlikely to substantially increase, and new individuals are unlikely to affect the pattern of survivorship inferred here. Nevertheless, future excavations stand to reveal more about the anatomical and pathological variance within the Dry Island Albertosaurus population.
Deoxygenation of diarylmethanols with dilute mineral acid
Authors: Hope-Ross Kyle A. , Kadla John F. 
Published: October 2010

A new mild and efficient method for the deoxygenation of diarylmethanols is reported. The reaction employs catalytic hydrochloric acid in ethanol at reflux for 48 h. This reaction works on a variety of diarylmethanol substrates and mitigates the need for expensive and toxic reagents such stannanes and silanes used in alternative procedures. In addition, this reaction can be used in tandem with the deprotection of acid-sensitive silyl ether protecting groups in a one-pot procedure.
Alternative Cyclin D1 Splice Forms Differentially Regulate the DNA Damage Response
Authors: Li Zhiping , Jiao Xuanmao , Wang Chenguang , Shirley L. Andrew , Elsaleh Hany , Dahl Olav , Wang Min , Soutoglou Evi , Knudsen Erik S. , Pestell Richard G. 
Published: October 2010

Abstract
The DNA damage response (DDR) activates downstream pathways including cell cycle checkpoints. The cyclin D1 gene is overexpressed or amplified in many human cancers and is required for gastrointestinal, breast, and skin tumors in murine models. A common polymorphism in the human cyclin D1 gene is alternatively spliced, resulting in cyclin D1a and D1b proteins that differ in their carboxyl terminus. Cyclin D1 overexpression enhances DNA damage–induced apoptosis. The role of cyclin D1 and the alternative splice form in regulating the DDR is not well understood. Herein cyclin D1a overexpression enhanced the DDR as characterized by induction of γH2AX phosphorylation, the assembly of DNA repair foci, specific recruitment of DNA repair factors to chromatin, and G2-M arrest. Cyclin D1 deletion in fibroblasts or small interfering RNA–mediated reduction of endogenous cyclin D1 in colon cancer cells reduced the 5-fluorouracil–mediated DDR. Mechanistic studies showed that cyclin D1a, like DNA repair factors, elicited the DDR when stably associated with chromatin. Cancer Res; 70(21); 8802–11. ©2010 AACR.
H3K9 Histone Methyltransferase G9a Promotes Lung Cancer Invasion and Metastasis by Silencing the Cell Adhesion Molecule Ep-CAM
Authors: Chen Min-Wei , Hua Kuo-Tai , Kao Hsin-Jung , Chi Chia-Chun , Wei Lin-Hung , Johansson Gunnar , Shiah Shine-Gwo , Chen Pai-Sheng , Jeng Yung-Ming , Cheng Tsu-Yao , Lai Tsung-Ching , Chang Jeng-Shou , Jan Yi-Hua , Chien Ming-Hsien , Yang Chih-Jen , Huang Ming-Shyan , Hsiao Michael , Kuo Min-Liang 
Published: October 2010

Abstract
G9a is a mammalian histone methyltransferase that contributes to the epigenetic silencing of tumor suppressor genes. Emerging evidence suggests that G9a is required to maintain the malignant phenotype, but the role of G9a function in mediating tumor metastasis has not been explored. Here, we show that G9a is expressed in aggressive lung cancer cells, and its elevated expression correlates with poor prognosis. RNAi-mediated knockdown of G9a in highly invasive lung cancer cells inhibited cell migration and invasion in vitro and metastasis in vivo. Conversely, ectopic G9a expression in weakly invasive lung cancer cells increased motility and metastasis. Mechanistic investigations suggested that repression of the cell adhesion molecule Ep-CAM mediated the effects of G9a. First, RNAi-mediated knockdown of Ep-CAM partially relieved metastasis suppression imposed by G9a suppression. Second, an inverse correlation between G9a and Ep-CAM expression existed in primary lung cancer. Third, Ep-CAM repression was associated with promoter methylation and an enrichment for dimethylated histone H3K9. G9a knockdown reduced the levels of H3K9 dimethylation and decreased the recruitment of the transcriptional cofactors HP1, DNMT1, and HDAC1 to the Ep-CAM promoter. Our findings establish a functional contribution of G9a overexpression with concomitant dysregulation of epigenetic pathways in lung cancer progression. Cancer Res; 70(20); 7830–40. ©2010 AACR.
CD4+ T-Cell Help in the Tumor Milieu Is Required for Recruitment and Cytolytic Function of CD8+ T Lymphocytes
Authors: Bos Rinke , Sherman Linda A. 
Published: October 2010

AbstractCD4 help for CD8+ T lymphocytes prevents tolerance and promotes the survival of effector and memory CD8+ T cells. Here, we describe additional helper functions that require CD4+ T cells within the tumor environment. CD8+ T-cell recruitment, proliferation, and effector function within the tumor were greatly enhanced by tumor-specific CD4+ T cells. Recruitment of CD8+ T cells was accelerated by IFN-γ–dependent production of chemokines. Production of interleukin-2 by tumor resident CD4+ T cells enhanced CD8+ T-cell proliferation and upregulated expression of granzyme B. These results highlight a novel role for tumor-specific CD4+ T cells in promoting CD8+ T-cell recruitment and cytolytic function, two previously unappreciated aspects of tumor-specific CD4 help. Cancer Res; 70(21); 8368–77. ©2010 AACR.
Tuberous Sclerosis Complex 1: An Epithelial Tumor Suppressor Essential to Prevent Spontaneous Prostate Cancer in Aged Mice
Authors: Kladney Raleigh D. , Cardiff Robert D. , Kwiatkowski David J. , Chiang Gary G. , Weber Jason D. , Arbeit Jeffrey M. , Lu Zhi Hong 
Published: October 2010

Abstract
The phosphoinositide 3-kinase (PI3K) pathway regulates mammalian cell growth, survival, and motility and plays a major pathogenetic role in human prostate cancer (PCa). However, the oncogenic contributions downstream of the PI3K pathway made by mammalian target of rapamycin complex 1 (mTORC1)–mediated cell growth signal transduction in PCa have yet to be elucidated in detail. Here, we engineered constitutive mTORC1 activation in prostate epithelium by a conditional genetic deletion of tuberous sclerosis complex 1 (Tsc1), a potent negative regulator of mTORC1 signaling. Epithelial inactivation was not immediately tumorigenic, but Tsc1-deficient mice developed prostatic intraepithelial neoplasia (mPIN) in lateral and anterior prostates by 6 months of age, with increasing disease penetrance over time. Lateral prostate lesions in 16- to 22-month-old mutant mice progressed to two types of more advanced lesions, adenomatous gland forming lesion (Type 1) and atypical glands embedded in massively expanded reactive stroma (Type 2). Both Type 1 and Type 2 lesions contained multiple foci of microinvasive carcinoma. Epithelial neoplastic and atypical stromal lesions persisted despite 4 weeks of RAD001 chemotherapy. Rapalogue resistance was not due to AKT or extracellular signal-regulated kinase 1/2 activation. Expression of the homeobox gene Nkx3.1 was lost in Tsc1-deficient mPIN, and it cooperated with TSC1 loss in mPIN initiation in doubly mutant Tsc1:Nkx3.1 prostatic epithelial knockout mice. Thus, TSC1 inactivation distal to PI3K and AKT activation is sufficient to activate a molecular signaling cascade producing prostatic neoplasia and focal carcinogenesis. Cancer Res; 70(21); 8937–47. ©2010 AACR.
Peptide Vaccination after T-Cell Transfer Causes Massive Clonal Expansion, Tumor Eradication, and Manageable Cytokine Storm
Authors: Ly Long V. , Sluijter Marjolein , Versluis Mieke , Luyten Gre P.M. , van der Burg Sjoerd H. , Melief Cornelis J.M. , Jager Martine J. , van Hall Thorbald 
Published: October 2010

Abstract
Adoptive T-cell transfer (ACT) is successfully applied as a cancer treatment that is based on the activation and effector functions of tumor-specific T cells. Here, we present results from a mouse model in which ACT is combined with a long peptide–based vaccine comprising gp100 T-cell epitopes. Transferred CD8+ T cells expanded up to 1,000-fold after peptide vaccination, leading to a 3-fold increase in white blood cell count and a very high frequency in the generation of antigen-specific memory T cells, the generation of which tended to correlate with effective antitumor responses. An enormous pool of effector T cells spread widely to different tissues, including the skin and the immune-privileged eye, where they mediate tumor eradication. Importantly, these striking T-cell dynamics occurred in immunocompetent mice without prior hematologic conditioning. Continued activation of the specific T-cell pool by vaccination led to strong T-cell–mediated cytokine storm and lethality due to multi-organ failure. However, this immunopathology could be prevented by controlling the rapid biodistribution of the peptide or by using a weakly agonistic peptide. Together, these results identify a peptide vaccination strategy that can potently accentuate effective ACT in non-lymphodepleted hosts. Cancer Res; 70(21); 8339–46. ©2010 AACR.