bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hepatic Progenitor Cell Proliferation and Liver Injury in α‐1‐Antitrypsin Deficiency
Authors: Brunt Elizabeth M , Blomenkamp Keith , Ahmed Muneeb , Ali Faiza , Marcus Nancy , Teckman Jeffrey 
Published: September 2010

ABSTRACTObjectives:Homozygous ZZ α‐1‐antitrypsin (a1AT) deficiency is a common genetic liver disease that causes liver injury and hepatocellular carcinoma (HCC). The a1AT mutant Z gene encodes a mutant protein that accumulates within hepatocytes leading to hepatocellular death and a hepatic regenerative response. However, the mechanisms linking hepatocellular injury to these responses are poorly understood. In this study, we examined liver injury and response in human liver and in transgenic mice for involvement of hepatic progenitor cells.Methods:Liver biopsy specimens of low‐grade, early‐stage human ZZ liver exhibiting minimal inflammation and minimal fibrosis (grade 1 and stage 1) were examined for hepatic progenitor cell (HPC) proliferation using immunoreactivity for cytokeratin‐7 (CK‐7). Transgenic mouse model liver and other selected human biopsies were also examined.Results:Increased CK‐7‐positive HPC proliferation was seen in human ZZ liver compared to normal liver, but was 5‐fold less HPC proliferation than in grade‐ and stage‐matched disease control hepatitis C–infected liver. Livers from PiZ mice, a model transgenic for the human a1AT mutant Z gene, which recapitulates the human injury, also showed HPC proliferation. Human ZZ liver and PiZ mice develop dysplasia in the liver and HCC. HCC in PiZ mice was also characterized by HPC proliferation. Progressive hepatic fibrosis with age in the PiZ mice is demonstrated for the first time in the present study.Conclusions:Chronic injury in both ZZ human and PiZ mouse liver is associated with hepatic fibrosis and a unique magnitude of HPC proliferation within the hepatic proliferative response.
There is an association between selective serotonin reuptake inhibitor use and uncomplicated peptic ulcers: a population‐based case–control study
Authors: Dall M. , Schaffalitzky de Muckadell O. B. , Lassen A. T. , Hallas J. 
Published: September 2010

Aliment Pharmacol Ther 2010; 32: 1383–1391SummaryBackground  Persons who use serotonin reuptake inhibitors (SSRIs) seem to be at increased risk of having serious upper gastrointestinal bleeding. In vitro studies have shown that SSRIs inhibit platelet aggregation. It remains unknown if SSRIs have a direct ulcerogenic effect.Aim  To investigate if there is a possible association between use of SSRIs and uncomplicated peptic ulcers.Methods  A population‐based case–control study was conducted in the county of Funen, Denmark, using local prescription database and patient register. The 4862 cases all had a first diagnosis of uncomplicated peptic ulcers from 1995 to 2009. Controls (n = 19 448), matched for age and gender, were selected by risk‐set sampling.Results  The adjusted odds ratios (OR) of uncomplicated peptic ulcers among current, recent and past users of SSRIs were 1.50 (95% CI 1.18–1.90), 1.56 (95% CI 0.98–2.49) and 1.32 (95% CI 1.08–1.61). There was no association with tricyclic antidepressants [OR 0.94 (95% CI 0.65‐1.35)]. The adjusted OR for the SSRI‐uncomplicated peptic ulcers association was 0.76 (95% CI 0.46–1.25) among users of proton pump inhibitors.Conclusions  Use of SSRI is associated with uncomplicated peptic ulcers, possibly by some effect on the healing process. We cannot exclude some effects of residual confounding or bias by frequent physician contact.
The impact of a child protection investigation: a personal reflective account
Authors: Davies Pamela 
Published: September 2010

ABSTRACTResearchers who undertake parental perception studies agree that the views of the parents can offer valuable insights in relation to child protection work. Respondents to such studies and others who have shared their experiences of child protection investigations are usually mothers. Taken together, this body of work sheds light on some very private, emotive and often painful experiences of child protection intervention and its impact. This article lends my voice to this literature and gives further insight into the ways a mother can experience a child protection investigation. Drawing upon one incident – a swelling on a baby's head – this article draws attention to my feelings and emotions as the baby's mother. Despite a co‐operative social worker–client relationship and case closure, my analysis draws attention to issues concerning power imbalances and the concept of ‘secondary victimization’ to explain the awfulness of my experience and my convoluted emotional disquiet. The article proposes that more attention is directed to the negative feelings and emotions experienced during the investigative process through further research.
Relative down‐regulation of apoptosis and autophagy genes in colorectal cancer
Authors: Chang Ying‐Tse , Tseng Hsien‐Chun , Huang Chi‐Chou , Chen Ya‐Pei , Chiang Huei‐Ching , Chou Fen‐Pi 
Published: September 2010

Eur J Clin Invest 2010; 41 (1): 84–92AbstractBackground  Cancer is often caused by disturbance in the regulation and/or execution of programmed cell death (PCD, including apoptosis and autophagy). Our aim was to investigate these two pathways simultaneously in the same samples to understand further the pathological roles of PCDs in colorectal cancer.Materials and methods  Real time quantitative PCR (RT‐qPCR) array was used to analyse the mRNA levels of 22 apoptosis and autophagy‐related genes involved in pro‐ and anti‐action of the pathways in 15 paired (tumour and non‐cancerous part) colorectal samples using Glyceraldehyde 3‐phosphate dehydrogenase (GAPDH) as the reference gene.Results  GAPDH mRNA content was significantly higher (approximately 4·01 fold) in tumour tissue than that of paired non‐cancerous part. The absolute mRNA levels for most of the 22 genes were higher in the tumour tissue also. However, after normalization with GAPDH Ct, the expressions of all the analysed genes were decreased in the tumour tissues, except for damage‐regulated autophagy modulator (DRAM). The expression of most of the genes involved in the same pathway was closely correlated to each other in both tumour and non‐cancerous tissues, and the correlation of tumour necrosis factor receptor (TNFR) and Akt to other genes in the same pathway was increased in tumour tissues.Conclusions  The high level expression of GAPDH might reflect the metabolic state of cancer cells, and PCDs were down‐regulated in the tumour tissues when metabolic state was taken into consideration. This relative suppression of PCDs in tumour tissue is supposed to be in favour of cancer cell survival.
Ecological genetics and genomics of plant defences: evidence and approaches
Authors: Anderson Jill T. , Mitchell‐Olds Thomas 
Published: September 2010

Summary 1. Herbivores exert significant selection on plants, and plants have evolved a variety of constitutive and inducible defences to resist and tolerate herbivory. Assessing the genetic mechanisms that influence defences against herbivores will deepen our understanding of the evolution of essential phenotypic traits. 2. Ecogenomics is a powerful interdisciplinary approach that can address fundamental questions about the ecology and evolutionary biology of species, such as: which evolutionary forces maintain variation within a population? and What is the genetic architecture of adaptation? This field seeks to identify gene regions that influence ecologically important traits, assess the fitness consequences under natural conditions of alleles at key quantitative trait loci (QTLs), and test how the abiotic and biotic environment affects gene expression. 3. Here, we review ecogenomics techniques and emphasize how this framework can address long‐standing and emerging questions relating to anti‐herbivore defences in plants. For example, ecogenomics tools can be used to investigate: inducible vs. constitutive defences; tradeoffs between resistance and tolerance; adaptation to the local herbivore community; selection on alleles that confer resistance and tolerance in natural populations; and whether different genes are activated in response to specialist vs. generalist herbivores and to different types of damage. 4. Ecogenomic studies can be conducted with model species, such as Arabidopsis, or their relatives, in which case myriad molecular tools are already available. Burgeoning sequence data will also facilitate ecogenomic studies of non‐model species. Throughout this paper, we highlight approaches that are particularly suitable for ecological studies of non‐model organisms, discuss the benefits and disadvantages of specific techniques and review bioinformatic tools for analysing data. 5. We focus on established and promising techniques, such as QTL mapping with pedigreed populations, genome wide association studies, transcription profiling strategies, population genomics and transgenic methodologies. Many of these techniques are complementary and can be used jointly to investigate the genetic architecture of defence traits and selection on alleles in nature.
Abrupt spatial and numerical responses of overabundant foxes to a reduction in anthropogenic resources
Authors: Bino Gilad , Dolev Amit , Yosha Dotan , Guter Amichay , King Roni , Saltz David , Kark Salit 
Published: September 2010

Summary 1. Carnivore overabundance that results from exploitation of human derived resources can have numerous detrimental effects on local human populations and ecological communities. Experimental studies on the responses of overabundant carnivores to reductions of such resources are necessary to understand the effectiveness and impacts of resource reduction. 2. We conducted controlled experiments in two villages in which we drastically reduced the availability of anthropogenic food sources in half of each village. Spatial and numerical responses of radio‐collared red foxes Vulpes vulpes were recorded and contrasted with those of radio‐collared foxes in three similar untreated villages and pristine areas in the region. In total, we looked at survival rates of 134 foxes. 3. Prior to the resource manipulation, home range sizes (0·47 and 0·56 km2) and population densities (30 and 36 foxes km−2) in the two villages were comparable to documented low and high‐end values, respectively. 4. Fast and distinct spatial responses were observed in response to the resource manipulation, and were manifested in either increased home range size or home range shifts. In one village, foxes exposed to reduced resource availability more than doubled their home range size. 5. Survival rates of individuals in the treated areas were drastically reduced. Actual fox mortality in the two treated areas reached 100% and 64% within 12 months of the onset of resource manipulation. Estimated monthly survival in the two treated areas declined from 0·96–0·98 and 0·98–0·99 (∼0·69 and 0·78 derived annual survival) before treatment to 0·80–0·83 and 0·92–0·94 (∼<0·01 and 0·42 derived annual survival) after treatment, respectively. By contrast, average monthly survivorship in pristine areas was nearly 0·97 (∼0·69 annual survival) and in the untreated areas and other non‐treated villages was 0·95–0·99 (∼0·54–0·89 annual survival). 6.
Synthesis and applications. This study demonstrates that sound waste disposal measures are very effective in controlling populations of overabundant carnivores. Contrary to common notion, the response of foxes to reduced resources was fast, manifested more by reduced survival than by successful dispersal into adjacent pristine areas. The results offer support to the Resource Dispersion Hypothesis regarding both home range size and density (suggested by the sharp decrease in survival) as a function of the spatial and temporal dispersion of resource.
Biotic and abiotic controls on tree colonization in three early successional communities of Chiloé Island, Chile
Authors: Bustamante‐Sánchez Marcela A. , Armesto Juan J. , Halpern Charles B. 
Published: September 2010

Summary 1. Most studies of tree regeneration are limited to particular environments and may not capture variation in the biotic or abiotic factors that regulate recruitment at larger spatial scales. Critical processes such as competition and facilitation can vary spatially, along gradients in resource availability and environmental stress, and temporally, with plant development. 2. We examined patterns of natural tree recruitment and experimentally followed germination and seedling survival of five tree species (pioneer to late seral) in three early successional communities of contrasting bio‐physical environments in a rural landscape on Chiloé Island, Chile. 3. We quantified natural recruitment of juveniles and saplings and assessed relationships between tree density and local environment. We used a removal experiment to test the influence of early successional vegetation on seed germination and early survival of tree species. In each community, seeds and seedlings were placed in paired experimental plots from which vegetation was removed or left intact (control). To identify potential correlates of germination and seedling survival, we measured light transmittance and soil properties in each plot. 4. In all communities, established vegetation had either a positive or neutral effect on germination and/or survival although responses varied among life stages and species. Germination and survival were correlated with the lower levels of light in controls, consistent with negative correlations between natural tree densities and light. Vegetation cover was not dense enough to facilitate survival of late successional species, but not too dense to inhibit survival of shade‐intolerant or mid‐tolerant species. Among communities, natural densities of juveniles were greatest under conditions where experimental germination rates were highest. Seedling height growth was lowest in the community characterized by waterlogged soils, consistent with the naturally low transition rate from juveniles to saplings and a negative correlation between density of shade‐intolerant trees and soil moisture. 5.
Synthesis. Our experiments indicate strong, mostly positive controls (facilitation) on tree recruitment in early seral shrublands with differing bio‐physical environments. Benefits of shading are manifested at different stages in the life history. However, community context is critical: variation in seasonal patterns of soil moisture may explain spatial variation in the density and size structure of natural tree recruitment.
Selective REM sleep deprivation in narcolepsy
Authors: VU MANH HOANG , HURNI CHRISTOPH , MATHIS JOHANNES , ROTH CORINNE , BASSETTI CLAUDIO L. 
Published: September 2010

SummaryNarcolepsy is characterized by excessive daytime sleepiness and rapid eye movement (REM) sleep abnormalities, including cataplexy. The aim of this study was to assess REM sleep pressure and homeostasis in narcolepsy. Six patients with narcolepsy and six healthy controls underwent a REM sleep deprivation protocol, including one habituation, one baseline, two deprivation nights (D1, D2) and one recovery night. Multiple sleep latency tests (MSLTs) were performed during the day after baseline and after D2. During D1 and D2 REM sleep was prevented by awakening the subjects at the first polysomnographic signs of REM sleep for 2 min. Mean sleep latency and number of sleep‐onset REM periods (SOREMs) were determined on all MSLT. More interventions were required to prevent REM sleep in narcoleptics compared with control subjects during D1 (57 ± 16 versus 24 ± 10) and D2 (87 ± 22 versus 35 ± 8, P = 0.004). Interventions increased from D1 to D2 by 46% in controls and by 53% in narcoleptics (P < 0.03). Selective REM sleep deprivation was successful in both controls (mean reduction of REM to 6% of baseline) and narcoleptics (11%). Both groups had a reduction of total sleep time during the deprivation nights (P = 0.03). Neither group had REM sleep rebound in the recovery night. Narcoleptics had, however, an increase in the number of SOREMs on MSLT (P = 0.005). There was no increase in the number of cataplexies after selective REM sleep deprivation. We conclude that: (i) REM sleep pressure is higher in narcoleptics; (ii) REM sleep homeostasis is similar in narcoleptics and controls; (iii) in narcoleptics selective REM sleep deprivation may have an effect on sleep propensity but not on cataplexy.
Isolation by distance across the Hawaiian Archipelago in the reef‐building coralPorites lobata
Authors: POLATO NICHOLAS R. , CONCEPCION GREGORY T. , TOONEN ROBERT J. , BAUMS ILIANA B. 
Published: September 2010

AbstractThere is an ongoing debate on the scale of pelagic larval dispersal in promoting connectivity among populations of shallow, benthic marine organisms. The linearly arranged Hawaiian Islands are uniquely suited to study scales of population connectivity and have been used extensively as a natural laboratory in terrestrial systems. Here, we focus on Hawaiian populations of the lobe coralPorites lobata, an ecosystem engineer of shallow reefs throughout the Pacific. Patterns of recent gene flow and population structure inP. lobatasamples (n = 318) from two regions, the Hawaiian Islands (n = 10 sites) and from their nearest neighbour Johnston Atoll, were analysed with nine microsatellite loci. Despite its massive growth form, ∼6% of the samples from both regions were the product of asexual reproduction via fragmentation. Cluster analysis and measures of genetic differentiation indicated thatP. lobatafrom the Hawaiian Islands are strongly isolated from those on Johnston Atoll (FST = 0.311;P < 0.001), with the descendants of recent migrants (n = 6) being clearly identifiable. Within the Hawaiian Islands,P. lobataconforms to a pattern of isolation by distance. Here, over 37% (P = 0.001) of the variation in genetic distance was explained by geographical distance. This pattern indicates that while the majority of ongoing gene flow in HawaiianP. lobataoccurs among geographically proximate reefs, inter‐island distances are insufficient to generate strong population structure across the archipelago.
Carbon flux rerouting during Mycobacterium tuberculosis growth arrest
Authors: Shi Lanbo , Sohaskey Charles D. , Pfeiffer Carmen , Datta Pratik , Parks Michael , McFadden Johnjoe , North Robert J. , Gennaro Maria L. 
Published: September 2010

SummaryA hallmark of the Mycobacterium tuberculosis life cycle is the pathogen's ability to switch between replicative and non‐replicative states in response to host immunity. Transcriptional profiling by qPCR of ∼ 50 M. tuberculosis genes involved in central and lipid metabolism revealed a re‐routing of carbon flow associated with bacterial growth arrest during mouse lung infection. Carbon rerouting was marked by a switch from metabolic pathways generating energy and biosynthetic precursors in growing bacilli to pathways for storage compound synthesis during growth arrest. Results of flux balance analysis using an in silico metabolic network were consistent with the transcript abundance data obtained in vivo. Similar transcriptional changes were seen in vitro when M. tuberculosis cultures were treated with bacteriostatic stressors under different nutritional conditions. Thus, altered expression of key metabolic genes reflects growth rate changes rather than changes in substrate availability. A model describing carbon flux rerouting was formulated that (i) provides a coherent interpretation of the adaptation of M. tuberculosis metabolism to immunity‐induced stress and (ii) identifies features common to mycobacterial dormancy and stress responses of other organisms.
Calcium ion‐mediated assembly and function of glycosylated flagellar sheath of marine magnetotactic bacterium
Authors: Lefèvre Christopher T. , Santini Claire‐Lise , Bernadac Alain , Zhang Wei‐Jia , Li Ying , Wu Long‐Fei 
Published: September 2010

SummaryFlagella of some pathogens or marine microbes are sheathed by an apparent extension of the outer cell membrane. Although flagellar sheath has been reported for almost 60 years, little is known about its function and the mechanism of its assembly. Recently, we have observed a novel type of sheath that encloses a flagellar bundle, instead of a single flagellum, in a marine magnetotactic bacterium MO‐1. Here, we reported isolation and characterization of the sheath which can be described as a six‐start, right‐handed helical tubular structure with a diameter of about 100 nm, and a pitch of helix of about 260 nm. By proteomic, microscopic and immunolabelling analyses, we showed that the sheath of MO‐1 consists of glycoprotein with an apparent molecular mass > 350 kDa. This protein, named sheath‐associated protein (Sap), shows homology with bacterial adhesins and eukaryotic calcium‐dependent adherent proteins (cadherin). Most importantly, we showed that calcium ions mediate the assembly of the tubular‐shaped sheath and disintegration of the sheath was deleterious for smooth swimming of MO‐1 cells. The disintegrated sheath was efficiently reconstituted in vitro by adding calcium ions. Altogether, these results demonstrate a novel bacterial Ca2+‐dependent surface architecture, which is essential for bacterial swimming.
The dawning of a ‘Golden era’ in lantibiotic bioengineering
Authors: Field Des , Hill Colin , Cotter Paul D. , Ross R. Paul 
Published: September 2010

SummaryThere are many examples of highly modified antimicrobial peptides in nature, many of which are non‐ribosomally synthesized. However, the bacterial lantibiotics are produced as gene‐encoded pre‐peptides that are subsequently modified by dedicated enzyme systems to form extraordinarily potent inhibitors. Consequently, they are much more amenable to bioengineering which could lead to the generation of a new arsenal of potent antimicrobials. However, although bioengineering of these compounds has been underway for at least two decades, significant progress has only been reported in recent years. This review charts these recent developments which suggest that we are entering a ‘Golden era’ of lantibiotic bioengineering.