bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antibiotic-Induced Perturbations of the Intestinal Microbiota Alter Host Susceptibility to Enteric Infection
Authors: Sekirov Inna , Tam Nicola M. , Jogova Maria , Robertson Marilyn L. , Li Yuling , Lupp Claudia , Finlay B. Brett 
Published: August 2008

ABSTRACT

Intestinal microbiota comprises microbial communities that reside in the gastrointestinal tract and are critical to normal host physiology. Understanding the microbiota's role in host response to invading pathogens will further advance our knowledge of host-microbe interactions.
Salmonella enterica
serovar Typhimurium was used as a model enteric pathogen to investigate the effect of intestinal microbiota perturbation on host susceptibility to infection. Antibiotics were used to perturb the intestinal microbiota. C57BL/6 mice were treated with clinically relevant doses of streptomycin and vancomycin in drinking water for 2 days, followed by oral infection with
Salmonella enterica
serovar Typhimurium. Alterations in microbiota composition and numbers were evaluated by fluorescent in situ hybridization, differential plating, and Sybr green staining. Antibiotics had a dose-dependent effect on intestinal microbiota composition. The chosen antibiotic regimen did not significantly alter the total numbers of intestinal bacteria but altered the microbiota composition. Greater preinfection perturbations in the microbiota resulted in increased mouse susceptibility to
Salmonella
serovar Typhimurium intestinal colonization, greater postinfection alterations in the microbiota, and more severe intestinal pathology. These results suggest that antibiotic treatment alters the balance of the microbial community, which predisposes the host to
Salmonella
serovar Typhimurium infection, demonstrating the importance of a healthy microbiota in host response to enteric pathogens.
Enhanced Innate Immune Responsiveness to PulmonaryCryptococcus neoformansInfection Is Associated with Resistance to Progressive Infection
Authors: Guillot Loïc , Carroll Scott F. , Homer Robert , Qureshi Salman T. 
Published: August 2008

ABSTRACTGenetically regulated mechanisms of host defense againstCryptococcus neoformansinfection are not well understood. In this study, pulmonary infection with the moderately virulentC. neoformansstrain 24067 was used to compare the host resistance phenotype of C57BL/6J with that of inbred mouse strain SJL/J. At 7 days or later after infection, C57BL/6J mice exhibited a significantly greater fungal burden in the lungs than SJL/J mice. Characterization of the pulmonary innate immune response at 3 h after cryptococcal infection revealed that resistant SJL/J mice exhibited significantly higher neutrophilia, with elevated levels of inflammatory cytokine tumor necrosis factor alpha (TNF-α) and keratinocyte-derived chemokine (KC)/CXCL1 in the airways, as well as increased whole-lung mRNA expression of chemokines KC/CXCL1, MIP-1α/CCL3, MIP-1β/CCL4, MIP-2/CXCL2, and MCP-1/CCL2 and cytokines interleukin 1β (IL-1β) and IL-1Ra. At 7 and 14 days after infection, SJL/J mice maintained significantly higher levels of TNF-α and KC/CXCL1 in the airways and exhibited a Th1 response characterized by elevated levels of lung gamma interferon (IFN-γ) and IL-12/IL-23p40, while C57BL/6J mice exhibited Th2 immunity as defined by eosinophilia and IL-4 production. Alveolar and resident peritoneal macrophages from SJL/J mice also secreted significantly greater amounts of TNF-α and KC/CXCL1 following in vitro stimulation withC. neoformans. Intracellular signaling analysis demonstrated that TNF-α and KC/CXCL1 production was regulated by NF-κB and phosphatidylinositol 3 kinase in both strains; however, SJL/J macrophages exhibited heightened and prolonged activation in response toC. neoformansinfection compared to that of C57BL/6J. Taken together, these data demonstrate that an enhanced innate immune response against pulmonaryC. neoformansinfection in SJL/J mice is associated with natural resistance to progressive infection.
Enumeration of Cytotoxic CD8 T Cells Ex Vivo during the Response toListeria monocytogenesInfection
Authors: Zaiss Dietmar M. W. , Sijts Alice J. A. M. , Mosmann Tim R. 
Published: August 2008

ABSTRACTCytotoxicity is a key effector function of CD8 T cells. However, what proportion of antigen-specific CD8 T cells in vivo exert cytotoxic activity during a functional CD8 T-cell response to infection still remains unknown. We used the Lysispot assay to directly enumerate cytotoxic CD8 T cells from the spleen ex vivo during the immune response to infection with the intracellular bacteriumListeria monocytogenes. We demonstrate that not all antigen-responsive gamma interferon (IFN-γ)-secreting T cells display cytotoxic activity. Most CD8 T cells detected at early time points of the response were cytotoxic. This percentage continuously declined during both the expansion and contraction phases to about 50% at the peak and to <10% of IFN-γ-producing cells in the memory phase. As described for clonal expansion, this elaboration of a program of differentiation after an initial stimulus was not affected by antigen or CD4 help but, like proliferation, could be influenced by later reinfection. These data indicate that cytotoxic effector function during the response to infection is regulated independently from IFN-γ secretion or expansion or contraction of the overall CD8 T-cell response.
Pleistocene pluvial lakes of the American West: a short history of research
Authors: Orme Antony R. 
Published: August 2008

AbstractScientific investigations of Pleistocene pluvial lakes in the American West occurred in five phases. The pioneer phase prior to 1870 saw former lakes identified by missionary priests, fur trappers, military expeditions and railroad surveyors. The classic phase, between 1870 and 1920, linked initially with independent surveys and, after 1879, with the United States Geological Survey and with irrigation and mining ventures, saw most lakes identified and described by such worthies as Gilbert, Russell, Gale, Waring and Thompson. A consolidation phase from 1920 to 1955 provided synthesis and new data but, in the absence of age controls, saw much speculation about temporal links between pluvial lakes, glacial stages, and climate forcing. The initial dating phase between 1955 and 1980 saw radiocarbon dating applied to late Pleistocene lakes and their Holocene relics and successors. The integrative phase since 1980, supported by enhanced field, remote sensing, laboratory and dating techniques, has seen an array of issues involving pluvial lakes linked to changes in regional ecology and global climate. In the above sequence, progress from one phase to the next reflected changes in the intellectual climate and advances in scientific methods. Today, we reflect on the episodic but cumulative increase in knowledge about late Pleistocene pluvial lakes, especially for Lake Bonneville, Lake Lahontan and the eastern California lake cascade. The record of earlier Pleistocene lakes, in some cases successors to Miocene and Pliocene lakes, is less certain because of deformation and erosion or burial. Continuing challenges involve evaluation of the Pleistocene lake record as a whole in the context of late Cenozoic tectonic and climate change, and of contemporary environmental and water-resource issues.
Piotr Alekseevich Kropotkin and his monograph
Researches on the Glacial Period
(1876)
Authors: Ivanova Tatiana K. , Markin Vyacheslav A. 
Published: August 2008

Abstract
The notable Russian scientist Piotr Alekseevich Kropotkin (1842–1921) is well known in Western countries for his writings on anarchist philosophy and various historical and political themes, but his geological and geographical work is less familiar, and his great treatise on Quaternary geology is virtually unknown in the Western world. The present paper provides a summary account of Kropotkin's Quaternary studies and his travels in the glaciated regions of Siberia and Scandinavia. He was an exponent of the ‘land-ice’ theory and traced the movements of glaciers in Scandinavia, paying particular attention to the form and structure of eskers.
The BBC and its web 2.0 partners
Authors: Sutherland Ben 
Published: August 2008

The British Broadcasting Corporation's websites, in English and in the 33 languages broadcast on the BBC World Service, are among the most powerful online providers of content -- in particular news and current affairs information -- on the internet. But as the level of individual users' internet usage and sophistication grows, BBC.co.uk is looking to advance its methods of getting this content to people beyond the provision of one simple one-size-fits-all website. Tools such as RSS feeds and desktop news alerts began the process, which, driven by a Creative Futures programme and a set of 15 "web principles", has now expanded to include the establishment of presences in, and utilisation of, Second Life, YouTube and MySpace. Meanwhile new deals allowing for content to be distributed more widely are being announced virtually on a monthly basis.
But what are the implications of such moves? Should a publicly-funded broadcaster be involved to such an extent with private interests? Is this extension of BBC News into these areas likely to attract further complaints from private media broadcasters who argue they are marginalised by the BBC"s subsidised clout? And will it leave those with limited or no ability or interest in the new interactive world underserved - or neglected altogether?
Java bytecode verification via static single assignment form
Authors: Gal Andreas , Probst Christian W. , Franz Michael 
Published: August 2008

Java Virtual Machines (JVMs) traditionally perform bytecode verification by way of an iterative dataflow analysis. Bytecode verification is necessary to ensure type safety because temporary variables in the JVM are not statically typed. We present an alternative verification mechanism that transforms JVM bytecode into Static Single Assignment Form (SSA) and thereby propagates definitions directly to uses. Type checking at control flow merge points can then be performed in a single pass.
Our prototype implementation of the new algorithm is faster than the standard JVM bytecode verifier. It has the additional benefit of generating SSA as a side effect, which may be immediately useful for a subsequent dynamic compilation stage.
Breastfeeding and feminism: A focus on reproductive health, rights and justice
Authors: Labbok Miriam H , Smith Paige Hall , Taylor Emily C 
Published: August 2008

Abstract
The annual Breastfeeding and Feminism Symposia aim to reposition breastfeeding as a valued part of women's (re)productive lives and rights. The symposia are designed to raise the profile of breastfeeding within the women's advocacy and feminist studies' communities, and to increase recognition among breastfeeding supporters that breastfeeding promotion could receive more socio-political support by partnering with those concerned with women's reproductive health, rights and justice, women's economic advancement, and the elimination of social, economic and health inequities. The third symposium (2007) sought to build dialogue and increase communications between and among these diverse communities. The nine articles presented in this thematic series were selected by the journal editors, and represent the core discussions at the symposium. This editorial presents the areas of synergy and strategies for action that emerged from the discussions. These strategies and this thematic issue are intended to reassert the momentum that evolved among participants, and to stimulate involvement among individuals and organizations not in attendance in promoting breastfeeding as a women's reproductive health, rights and justice concern.
Inappropriately low aldosterone concentrations in adults with AIDS-related diarrhoea in Zambia: a study of response to fluid challenge
Authors: Kaile Trevor , Zulu Isaac , Lumayi Ruth , Ashman Neil , Kelly Paul 
Published: August 2008

Abstract

Background
Chronic diarrhoea is one of the most debilitating consequences of HIV infection in sub-Saharan Africa and it carries a high mortality rate. We report unexpectedly low concentrations of circulating aldosterone in 12 patients (6 men, 6 women) in the University Teaching Hospital, Lusaka, who all had diarrhoea for over one month. Changes in serum electrolytes, blood pressure, Karnofsky score and serum aldosterone concentration were being monitored during a short study of responses to saline infusion (3 litres/24 h) over 72 hours.

Findings
At baseline, 9/12 (75%) of the patients were hyponatraemic, 10/11 (91%) were hypokalaemic, and 6/12 (50%) had undetectable aldosterone concentrations. Blood pressure and Karnofsky score rose and creatinine concentration fell in response to the infusion.

Conclusion
Circulating aldosterone concentrations were inappropriately low and complicate the profound electrolyte deficiencies resulting from chronic diarrhoea. Management of these deficiencies needs to be more aggressive than is currently practised and consideration should be given to a formal clinical trial of mineralocorticoid replacement in these severely ill patients. If the inappropriately low aldosterone reflects a general adrenal failure, it may explain a considerable proportion of the high mortality seen both before and after initiation of anti-retroviral therapy.
Detection of the transforming AKT1 mutation E17K in non-small cell lung cancer by high resolution melting
Authors: Do Hongdo , Solomon Benjamin , Mitchell Paul L , Fox Stephen B , Dobrovic Alexander 
Published: August 2008

AbstractBackgroundA recurrent somatic mutation, E17K, in the pleckstrin homology domain of theAKT1gene, has been recently described in breast, colorectal, and ovarian cancers. AKT1 is a pivotal mediator of signalling pathways involved in cell survival, proliferation and growth. The E17K mutation stimulates downstream signalling and exhibits transforming activityin vitroandin vivo.FindingsWe developed a sensitive high resolution melting (HRM) assay to detect the E17K mutation from formalin-fixed paraffin-embedded tumours. We screened 219 non-small cell lung cancer biopsies for the mutation using HRM analysis. Four samples were identified as HRM positive. Subsequent sequencing of those samples confirmed the E17K mutation in one of the cases. A rare single nucleotide polymorphism was detected in each of the remaining three samples. The E17K was found in one of the 14 squamous cell carcinomas. No mutations were found in 141 adenocarcinomas and 39 large cell carcinomas.ConclusionTheAKT1E17K mutation is very rare in lung cancer and might be associated with tumorigenesis in squamous cell carcinoma. HRM represents a rapid cost-effective and robust screening of low frequency mutations such asAKT1mutations in clinical samples.
Breast cancer susceptibility loci and mammographic density
Authors: Tamimi Rulla M , Cox David , Kraft Peter , Colditz Graham A , Hankinson Susan E , Hunter David J 
Published: August 2008

Abstract
Introduction
Recently, the Breast Cancer Association Consortium (BCAC) conducted a multi-stage genome-wide association study and identified 11 single nucleotide polymorphisms (SNPs) associated with breast cancer risk. Given the high degree of heritability of mammographic density and its strong association with breast cancer, it was hypothesised that breast cancer susceptibility loci may also be associated with breast density and provide insight into the biology of breast density and how it influences breast cancer risk.

Methods
We conducted an analysis in the Nurses' Health Study (n = 1121) to assess the relation between 11 breast cancer susceptibility loci and mammographic density. At the time of their mammogram, 217 women were premenopausal and 904 women were postmenopausal. We used generalised linear models adjusted for covariates to determine the mean percentage of breast density according to genotype.

Results
Overall, no association between the 11 breast cancer susceptibility loci and mammographic density was seen. Among the premenopausal women, three SNPs (rs12443621 [TNRc9/LOC643714], rs3817198 [lymphocyte-specific protein-1] and rs4666451) were marginally associated with mammographic density (p < 0.10). All three of these SNPs showed an association that was consistent with the direction in which these alleles influence breast cancer risk. The difference in mean percentage mammographic density comparing homozygous wildtypes to homozygous variants ranged from 6.3 to 8.0%. None of the 11 breast cancer loci were associated with postmenopausal breast density.

Conclusion
Overall, breast cancer susceptibility loci identified through a genome-wide association study do not appear to be associated with breast cancer risk.
Risks associated with magnetic resonance imaging and cervical collar in comatose, blunt trauma patients with negative comprehensive cervical spine computed tomography and no apparent spinal deficit
Authors: Dunham C Michael , Brocker Brian P , Collier B David , Gemmel David J 
Published: August 2008

Abstract
Introduction
In blunt trauma, comatose patients (Glasgow Coma Scale score 3 to 8) with a negative comprehensive cervical spine (CS) computed tomography assessment and no apparent spinal deficit, CS clearance strategies (magnetic resonance imaging [MRI] and prolonged cervical collar use) are controversial.

Methods
We conducted a literature review to delineate risks for coma, CS instability, prolonged cervical collar use, and CS MRI.

Results
Based on our search of the literature, the numbers of functional survivor patients among those who had sustained blunt trauma were as follows: 350 per 1,000 comatose unstable patients (increased intracranial pressure [ICP], hypotension, hypoxia, or early ventilator-associated pneumonia); 150 per 1,000 comatose high-risk patients (age > 45 years or Glasgow Coma Scale score 3 to 5); and 600 per 1,000 comatose stable patients (not unstable or high risk). Risk probabilities for adverse events among unstable, high-risk, and stable patients were as follows: 2.5% for CS instability; 26.2% for increased intensive care unit complications with prolonged cervical collar use; 9.3% to 14.6% for secondary brain injury with MRI transportation; and 20.6% for aspiration during MRI scanning (supine position). Additional risk probabilities for adverse events among unstable patients were as follows: 35.8% for increased ICP with cervical collar; and 72.1% for increased ICP during MRI scan (supine position).

Conclusion
Blunt trauma coma functional survivor (independent living) rates are alarming. When a comprehensive CS computed tomography evaluation is negative and there is no apparent spinal deficit, CS instability is unlikely (2.5%). Secondary brain injury from the cervical collar or MRI is more probable than CS instability and jeopardizes cerebral recovery. Brain injury severity, probability of CS instability, cervical collar risk, and MRI risk assessments are essential when deciding whether CS MRI is appropriate and for determining the timing of cervical collar removal.
Downregulation of protein disulfide isomerase in sepsis and its role in tumor necrosis factor-alpha release
Authors: Zhou Mian , Jacob Asha , Ho Natalie , Miksa Michael , Wu Rongqian , Maitra Subir R , Wang Ping 
Published: August 2008

Abstract
Introduction
Protein disulfide isomerase (PDI) is an important factor for the protein modification step in the post-translational event. PDI plays an essential role in cell survival under various stress conditions. It has been reported that PDI can serve as a negative regulator of nuclear factor-kappa-B (NF-κB) and that it can inhibit lipopolysaccharide (LPS)-induced proinflammatory cytokine production in macrophages. Thus, PDI may be an intracellular anti-inflammatory molecule. Although we have previously shown that Kupffer cell-derived proinflammatory cytokines cause liver injury in sepsis, the effect of sepsis on PDI expression as well as the effect of PDI inhibition on cytokine production have not been investigated. We therefore hypothesized that sepsis downregulates PDI expression and that the inhibition of PDI promotes proinflammatory cytokine production.

Method
Adult male rats were subjected to sepsis by cecal ligation and puncture (CLP) or endotoxemia (continuous infusion of 1 μg/kg body weight LPS by an osmotic pump) for 20 hours. Hepatic tissues were collected and PDI gene expression was determined. In additional experiments, cells from a macrophage-like cell line, RAW 264.7, were treated with 100 ng/mL LPS for 4 hours and protein expressions were measured. RAW 264.7 cells were also treated with bacitracin, a specific PDI inhibitor, for 24 hours, and tumor necrosis factor-alpha (TNF-α) gene and protein expression as well as its release in the cell supernatant were determined. To further confirm the beneficial effect of PDI in sepsis, RAW 264.7 cells were transfected with PDI short interfering RNA (siRNA) and PDI gene expression and TNF-α release were measured by quantitative polymerase chain reaction and enzyme-linked immunosorbent assay, respectively.

Results
PDI gene expression was significantly decreased by 28% and 69% at 20 hours after CLP or LPS infusion, respectively. LPS also decreased PDI protein expression by 33% in RAW 264.7 cells. Incubation of RAW 264.7 cells with bacitracin significantly increased TNF-α gene expression and TNF-α release as well as its cellular levels in a dose-dependent manner. Transfection of RAW 264.7 cells with PDI siRNA produced an average 36.8% inhibition of the PDI gene expression. This downregulation was correlated with a 3.19-fold increase in TNF-α release into the cell supernatant.

Conclusion
Taken together, these results suggest that downregulation of PDI by sepsis significantly increases proinflammatory cytokine production. Thus, prevention of PDI downregulation in sepsis may be a novel approach to attenuate hyperinflammation and to reduce tissue injury under such conditions.
Novel genes dramatically alter regulatory network topology in amphioxus
Authors: Zhang Qing , Zmasek Christian M , Dishaw Larry J , Mueller M Gail , Ye Yuzhen , Litman Gary W , Godzik Adam 
Published: August 2008

Abstract
Background
Regulation in protein networks often utilizes specialized domains that 'join' (or 'connect') the network through specific protein-protein interactions. The innate immune system, which provides a first and, in many species, the only line of defense against microbial and viral pathogens, is regulated in this way. Amphioxus (Branchiostoma floridae), whose genome was recently sequenced, occupies a unique position in the evolution of innate immunity, having diverged within the chordate lineage prior to the emergence of the adaptive immune system in vertebrates.

Results
The repertoire of several families of innate immunity proteins is expanded in amphioxus compared to both vertebrates and protostome invertebrates. Part of this expansion consists of genes encoding proteins with unusual domain architectures, which often contain both upstream receptor and downstream activator domains, suggesting a potential role for direct connections (shortcuts) that bypass usual signal transduction pathways.

Conclusion
Domain rearrangements can potentially alter the topology of protein-protein interaction (and regulatory) networks. The extent of such arrangements in the innate immune network of amphioxus suggests that domain shuffling, which is an important mechanism in the evolution of multidomain proteins, has also shaped the development of immune systems.