bluuebunny/crossref_metadata_2025_split huggingface dataset:
The cholinergic basal forebrain in the ferret and its inputs to the auditory cortex
Authors: Bajo Victoria M. , Leach Nicholas D. , Cordery Patricia M. , Nodal Fernando R. , King Andrew J. 
Published: June 2014

AbstractCholinergic inputs to the auditory cortex can modulate sensory processing and regulate stimulus‐specific plasticity according to the behavioural state of the subject. In order to understand how acetylcholine achieves this, it is essential to elucidate the circuitry by which cholinergic inputs influence the cortex. In this study, we described the distribution of cholinergic neurons in the basal forebrain and their inputs to the auditory cortex of the ferret, a species used increasingly in studies of auditory learning and plasticity. Cholinergic neurons in the basal forebrain, visualized by choline acetyltransferase and p75 neurotrophin receptor immunocytochemistry, were distributed through the medial septum, diagonal band of Broca, and nucleus basalis magnocellularis. Epipial tracer deposits and injections of the immunotoxin ME20.4‐SAP (monoclonal antibody specific for the p75 neurotrophin receptor conjugated to saporin) in the auditory cortex showed that cholinergic inputs originate almost exclusively in the ipsilateral nucleus basalis. Moreover, tracer injections in the nucleus basalis revealed a pattern of labelled fibres and terminal fields that resembled acetylcholinesterase fibre staining in the auditory cortex, with the heaviest labelling in layers II/III and in the infragranular layers. Labelled fibres with small en‐passant varicosities and simple terminal swellings were observed throughout all auditory cortical regions. The widespread distribution of cholinergic inputs from the nucleus basalis to both primary and higher level areas of the auditory cortex suggests that acetylcholine is likely to be involved in modulating many aspects of auditory processing.
A NanoSIMS study on the distribution of soil organic matter, iron and manganese in a nodule from a Stagnosol
Authors: Rennert T. , Händel M. , Höschen C. , Lugmeier J. , Steffens M. , Totsche K. U. 
Published: June 2014

SummaryThe development of Stagnosols is the consequence of perched water tables, which induce periodic oxidizing and reducing conditions. These cause the spatial distribution of iron (Fe) and manganese (Mn) between the soil matrix and ferromanganese concretions or nodules. Since oxides of these metals may interact with organic matter, we studied their spatial distribution in bulk material from the Bg horizon of a Stagnosol and in a nodule separated from the horizon. We used wet‐chemical analyses and X‐ray diffractometry together with microscopic techniques and nano‐scale secondary ion mass spectrometry (NanoSIMS), the latter allowing for a submicrometre‐scale spatial resolution. X‐ray diffractometry revealed the presence of quartz, clay minerals, micas and feldspars as the dominant minerals and indicated the presence of lepidocrocite. Relative to the bulk horizon material, the nodule was strongly enriched in organic C (by a factor of 31) and pedogenic (dithionite‐extractable) Fe and Mn (by factors of 2.2 and 62). We selected two regions on a thin section of the nodule for NanoSIMS investigations after studying the element distribution by scanning‐electron microscopy (SEM): one was located in an almost closed pore, the other one along an elongated pore. The NanoSIMS measurements allowed a clearer distinction of Fe‐ and Mn‐accumulation zones than SEM‐EDS. The evaluation of the NanoSIMS measurements by unsupervised classification revealed that zones containing silicates and Mn oxides and the transitional zones between Fe and Mn oxides were particularly enriched in soil organic matter, while, with one exception, the pure Fe‐accumulation zones did not indicate the presence of soil organic matter.
Loss of cerebral white matter in primary Sjögren's syndrome: a controlled volumetric magnetic resonance imaging study
Authors: Lauvsnes M. B. , Beyer M. K. , Appenzeller S. , Greve O. J. , Harboe E. , Gøransson L. G. , Tjensvoll A. B. , Omdal R. 
Published: June 2014

Background and purposeAlthough brain involvement is common in primary Sjögren's syndrome (pSS), results from cerebral imaging studies are inconsistent. This study aimed to perform both voxel‐wise and global brain volume analyses in a nearly population‐based pSS cohort to explore whether the patients displayed any focal or diffuse volume differences compared with healthy subjects.MethodsGlobal grey matter (GM) and white matter (WM) volumes were measured and compared in 60 patients with pSS and 60 age‐ and gender‐matched healthy subjects. Regression models were constructed with potential explanatory variables for GM and WM volumes. In the same groups, voxel‐wise morphometric analyses were performed.ResultsIn analyses of global GM and WM, the patients had lower WM volumes than healthy subjects (540 ± 63 cm3 vs. 564 ± 56 cm3, P = 0.02), but no differences in GM. Voxel‐wise analyses displayed no localized areas of GM or WM volume differences between pSS patients and healthy subjects.ConclusionIndividuals with pSS have a diffuse reduction of cerebral WM but no localized loss of WM or GM. This indicates a general deleterious effect on WM due to pSS itself.
Reducing false positive diagnoses in mild cognitive impairment: the importance of comprehensive neuropsychological assessment
Authors: Klekociuk S. Z. , Summers J. J. , Vickers J. C. , Summers M. J. 
Published: June 2014

Background and purposeLongitudinal studies of mild cognitive impairment (MCI) report that a sizeable proportion of MCI cases revert to normal levels of functioning over time. The rate of recovery from MCI indicates that existing MCI diagnostic criteria result in an unacceptably high rate of false positive diagnoses and lack adequate sensitivity and specificity.MethodsThe aim of the present study was to identify a set of neuropsychological measures able to differentiate between true positive cases of MCI from those who were unimpaired at 11 months’ follow‐up.ResultsA discriminant function analysis identified that a combination of measures of complex sustained attention, semantic memory, working memory, episodic memory and selective attention correctly classified outcome in more than 80% of cases. The rate of false positive diagnoses (5.93%) was considerably lower than is evident in previously published MCI studies.ConclusionsThe results of the present study indicate that the rate of false positive MCI diagnoses can be significantly reduced through the use of sensitive and specific neuropsychological measures of memory and non‐memory functions.
Destruction of the hepatocyte junction by intercellular invasion of Leptospira causes jaundice in a hamster model of Weil's disease
Authors: Miyahara Satoshi , Saito Mitsumasa , Kanemaru Takaaki , Villanueva Sharon Y. A. M. , Gloriani Nina G. , Yoshida Shin‐ichi 
Published: June 2014

SummaryWeil's disease, the most severe form of leptospirosis, is characterized by jaundice, haemorrhage and renal failure. The mechanisms of jaundice caused by pathogenic Leptospira remain unclear. We therefore aimed to elucidate the mechanisms by integrating histopathological changes with serum biochemical abnormalities during the development of jaundice in a hamster model of Weil's disease. In this work, we obtained three‐dimensional images of infected hamster livers using scanning electron microscope together with freeze‐cracking and cross‐cutting methods for sample preparation. The images displayed the corkscrew‐shaped bacteria, which infiltrated the Disse's space, migrated between hepatocytes, detached the intercellular junctions and disrupted the bile canaliculi. Destruction of bile canaliculi coincided with the elevation of conjugated bilirubin, aspartate transaminase and alkaline phosphatase levels in serum, whereas serum alanine transaminase and γ‐glutamyl transpeptidase levels increased slightly, but not significantly. We also found in ex vivo experiments that pathogenic, but not non‐pathogenic leptospires, tend to adhere to the perijunctional region of hepatocyte couplets isolated from hamsters and initiate invasion of the intercellular junction within 1 h after co‐incubation. Our results suggest that pathogenic leptospires invade the intercellular junctions of host hepatocytes, and this invasion contributes in the disruption of the junction. Subsequently, bile leaks from bile canaliculi and jaundice occurs immediately. Our findings revealed not only a novel pathogenicity of leptospires, but also a novel mechanism of jaundice induced by bacterial infection.
B cells as a critical node in the microbiota–host immune system network
Authors: Slack Emma , Balmer Maria L. , Macpherson Andrew J. 
Published: June 2014

SummaryMutualism with our intestinal microbiota is a prerequisite for healthy existence. This requires physical separation of the majority of the microbiota from the host (by secreted antimicrobials, mucus, and the intestinal epithelium) and active immune control of the low numbers of microbes that overcome these physical and chemical barriers, even in healthy individuals. In this review, we address how B‐cell responses to members of the intestinal microbiota form a robust network with mucus, epithelial integrity, follicular helper T cells, innate immunity, and gut‐associated lymphoid tissues to maintain host–microbiota mutualism.
Microbiota activation and regulation of innate and adaptive immunity
Authors: Alexander Katie L. , Targan Stephan R. , Elson Charles O. 
Published: June 2014

SummaryThe human host has coevolved with the collective of bacteria species, termed microbiota, in a complex fashion that affects both innate and adaptive immunity. Differential regulation of regulatory T‐cell and effector T‐cell responses are a direct result of specific microbial species present within the gut, and this relationship is subject to dysregulation during inflammation and disease. The microbiota varies widely between individuals and has a profound effect on how one reacts to various environmental stimuli, particularly if a person is genetically predisposed to an immune‐mediated inflammatory disorder such as inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC). Approximately, half of all CD patients have elevated antibodies to CBir1, a microbiota flagellin common to mice and humans, demonstrating flagellins as immunodominant antigens in the intestines. This review focuses on the use of flagellins as probes to study microbiota‐specific responses in the context of health and disease as well as probes of innate and adaptive responses employed by the host to deal with the overwhelming bacterial presence of the microbiota.
Dendritic cell–epithelial cell crosstalk in the gut
Authors: Rescigno Maria 
Published: June 2014

SummaryIntestinal epithelial cells are fundamental to maintain barrier integrity and to participate in food degradation and absorption, but they can also decipher signals coming from the outside world and ‘educate’ the immune system accordingly. In particular, they interact with dendritic cells (DCs) and other intraepithelial immune cells to drive tolerogenic responses under steady state, but they can also release immune mediators to recruit inflammatory cells and to elicit immunity to infectious agents. When these interactions are deregulated, immune disorders can develop. In this review, we discuss some important features of epithelial cells and DCs and their fruitful interactions.
The mucus and mucins of the goblet cells and enterocytes provide the first defense line of the gastrointestinal tract and interact with the immune system
Authors: Pelaseyed Thaher , Bergström Joakim H. , Gustafsson Jenny K. , Ermund Anna , Birchenough George M. H. , Schütte André , van der Post Sjoerd , Svensson Frida , Rodríguez‐Piñeiro Ana M. , Nyström Elisabeth E. L. , Wising Catharina , Johansson Malin E. V. , Hansson Gunnar C. 
Published: June 2014

SummaryThe gastrointestinal tract is covered by mucus that has different properties in the stomach, small intestine, and colon. The large highly glycosylated gel‐forming mucins MUC2 and MUC5AC are the major components of the mucus in the intestine and stomach, respectively. In the small intestine, mucus limits the number of bacteria that can reach the epithelium and the Peyer's patches. In the large intestine, the inner mucus layer separates the commensal bacteria from the host epithelium. The outer colonic mucus layer is the natural habitat for the commensal bacteria. The intestinal goblet cells secrete not only the MUC2 mucin but also a number of typical mucus components: CLCA1, FCGBP, AGR2, ZG16, and TFF3. The goblet cells have recently been shown to have a novel gate‐keeping role for the presentation of oral antigens to the immune system. Goblet cells deliver small intestinal luminal material to the lamina propria dendritic cells of the tolerogenic CD103+ type. In addition to the gel‐forming mucins, the transmembrane mucins MUC3, MUC12, and MUC17 form the enterocyte glycocalyx that can reach about a micrometer out from the brush border. The MUC17 mucin can shuttle from a surface to an intracellular vesicle localization, suggesting that enterocytes might control and report epithelial microbial challenge. There is communication not only from the epithelial cells to the immune system but also in the opposite direction. One example of this is IL10 that can affect and improve the properties of the inner colonic mucus layer. The mucus and epithelial cells of the gastrointestinal tract are the primary gate keepers and controllers of bacterial interactions with the host immune system, but our understanding of this relationship is still in its infancy.
Directing traffic: IL‐17 and IL‐22 coordinate pulmonary immune defense
Authors: McAleer Jeremy P. , Kolls Jay K. 
Published: June 2014

SummaryRespiratory infections and diseases are among the leading causes of death worldwide, and effective treatments probably require manipulating the inflammatory response to pathogenic microbes or allergens. Here, we review mechanisms controlling the production and functions of interleukin‐17 (IL‐17) and IL‐22, cytokines that direct several aspects of lung immunity. Innate lymphocytes (γδ T cells, natural killer cells, innate lymphoid cells) are the major source of IL‐17 and IL‐22 during acute infections, while CD4+ T‐helper 17 (Th17) cells contribute to vaccine‐induced immunity. The characterization of dendritic cell (DC) subsets has revealed their central roles in T‐cell activation. CD11b+ DCs stimulated with bacteria or fungi secrete IL‐1β and IL‐23, potent inducers of IL‐17 and IL‐22. On the other hand, recognition of viruses by plasmacytoid DCs inhibits IL‐1β and IL‐23 release, increasing susceptibility to bacterial superinfections. IL‐17 and IL‐22 primarily act on the lung epithelium, inducing antimicrobial proteins and neutrophil chemoattractants. Recent studies found that stimulation of macrophages and DCs with IL‐17 also contributes to antibacterial immunity, while IL‐22 promotes epithelial proliferation and repair following injury. Chronic diseases such as asthma and chronic obstructive pulmonary disease have been associated with IL‐17 and IL‐22 responses directed against innocuous antigens. Future studies will evaluate the therapeutic efficacy of targeting the IL‐17/IL‐22 pathway in pulmonary inflammation.
Anatomical localization of commensal bacteria in immune cell homeostasis and disease
Authors: Fung Thomas C. , Artis David , Sonnenberg Gregory F. 
Published: June 2014

SummaryThe mammalian gastrointestinal (GI) tract is colonized by trillions of beneficial commensal bacteria that are essential for promoting normal intestinal physiology. While the majority of commensal bacteria are found in the intestinal lumen, many species have also adapted to colonize different anatomical locations in the intestine, including the surface of intestinal epithelial cells (IECs) and the interior of gut‐associated lymphoid tissues. These distinct tissue localization patterns permit unique interactions with the mammalian immune system and collectively influence intestinal immune cell homeostasis. Conversely, dysregulated localization of commensal bacteria can lead to inappropriate activation of the immune system and is associated with numerous chronic infectious, inflammatory, and metabolic diseases. Therefore, regulatory mechanisms that control proper anatomical containment of commensal bacteria are essential to maintain tissue homeostasis and limit pathology. In this review, we propose that commensal bacteria associated with the mammalian GI tract can be anatomically defined as (i) luminal, (ii) epithelial‐associated, or (iii) lymphoid tissue‐resident, and we discuss the role and regulation of these microbial populations in health and disease.
Intestinal IgA production and its role in host‐microbe interaction
Authors: Gutzeit Cindy , Magri Giuliana , Cerutti Andrea 
Published: June 2014

SummaryComplex and diverse communities of bacteria establish mutualistic and symbiotic relationships with the gut after birth. The intestinal immune system responds to bacterial colonization by acquiring a state of hypo‐responsiveness against commensals and active readiness against pathogens. The resulting homeostatic balance involves a continuous dialog between the microbiota and lymphocytes with the intermediation of epithelial and dendritic cells. This dialog causes massive production of immunoglobulin A (IgA), a non‐inflammatory antibody specialized in mucosal protection. Here, we discuss recent advances on the regulation of intestinal IgA responses and their role in host‐microbe interaction.
Maturation of the enteric mucosal innate immune system during the postnatal period
Authors: Fulde Marcus , Hornef Mathias W. 
Published: June 2014

SummaryThe innate immune system instructs the host on microbial exposure and infection. This information is critical to mount a protective innate and adaptive host response to microbial challenge, but is also involved in homeostatic and adaptive processes that adjust the organism to meet environmental requirements. This is of particular importance for the neonatal host during the transition from the protected fetal life to the intense and dynamic postnatal interaction with commensal and pathogenic microorganisms. Here, we discuss both adaptive and developmental mechanisms of the mucosal innate immune system that prevent inappropriate stimulation and facilitate establishment of a stable homeostatic host–microbial interaction after birth.
IL‐15: a central regulator of celiac disease immunopathology
Authors: Abadie Valérie , Jabri Bana 
Published: June 2014

SummaryInterleukin‐15 (IL‐15) exerts many biological functions essential for the maintenance and function of multiple cell types. Although its expression is tightly regulated, IL‐15 upregulation has been reported in many organ‐specific autoimmune disorders. In celiac disease, an intestinal inflammatory disorder driven by gluten exposure, the upregulation of IL‐15 expression in the intestinal mucosa has become a hallmark of the disease. Interestingly, because it is overexpressed both in the gut epithelium and in the lamina propria, IL‐15 acts on distinct cell types and impacts distinct immune components and pathways to disrupt intestinal immune homeostasis. In this article, we review our current knowledge of the multifaceted roles of IL‐15 with regard to the main immunological processes involved in the pathogenesis of celiac disease.
Intestinal dendritic cells in the regulation of mucosal immunity
Authors: Bekiaris Vasileios , Persson Emma K. , Agace William W. 
Published: June 2014

SummaryThe intestine presents a huge surface area to the outside environment, a property that is of critical importance for its key functions in nutrient digestion, absorption, and waste disposal. As such, the intestine is constantly exposed to dietary and microbial‐derived foreign antigens, to which immune cells within the mucosa must suitably respond to maintain intestinal integrity, while also providing the ability to mount effective immune responses to potential pathogens. Dendritic cells (DCs) are sentinel immune cells that play a central role in the initiation and differentiation of adaptive immune responses. In the intestinal mucosa, DCs are located diffusely throughout the intestinal lamina propria, within gut‐associated lymphoid tissues, including Peyer's patches and smaller lymphoid aggregates, as well as in intestinal‐draining lymph nodes, including mesenteric lymph nodes. The recognition that dietary nutrients and microbial communities in the intestine influence both mucosal and systemic immune cell development and function as well as immune‐mediated disease has led to an explosion of literature in mucosal immunology in recent years and a growing interest in the functionality of intestinal DCs. In the current review, we discuss recent findings from our group and others that have provided important insights regarding murine and human intestinal lamina propria DCs and highlighted marked developmental and functional heterogeneity within this compartment. A thorough understanding of the role these subsets play in the regulation of intestinal immune homeostasis and inflammation will help to define novel strategies for the treatment of intestinal pathologies and contribute to improved rational design of mucosal vaccines.
The role of type I interferons in intestinal infection, homeostasis, and inflammation
Authors: Cho Hyeseon , Kelsall Brian L. 
Published: June 2014

SummaryType I interferons are a widely expressed family of effector cytokines that promote innate antiviral and antibacterial immunity. Paradoxically, they can also suppress immune responses by driving production of anti‐inflammatory cytokines, and dysregulation of these cytokines can contribute to host‐mediated immunopathology and disease progression. Recent studies describe their anti‐inflammatory role in intestinal inflammation and the locus containing IFNAR, a heterodimeric receptor for the type I interferons has been identified as a susceptibility region for human inflammatory bowel disease. This review focuses on the role of type I IFNs in the intestine in health and disease and their emerging role as immune modulators. Clear understanding of type I IFN‐mediated immune responses may provide avenues for fine‐tuning existing IFN treatment for infection and intestinal inflammation.
Sequence diversity and molecular evolutionary rates between buffalo and cattle
Authors: Moaeen‐ud‐Din M. , Bilal G. 
Published: June 2014

SummaryIdentification of genes of importance regarding production traits in buffalo is impaired by a paucity of genomic resources. Choice to fill this gap is to exploit data available for cow. The cross‐species application of comparative genomics tools is potential gear to investigate the buffalo genome. However, this is dependent on nucleotide sequences similarity. In this study, gene diversity between buffalo and cattle was determined using 86 gene orthologues. There was approximately 3% difference in all genes in terms of nucleotide diversity and 0.267 ± 0.134 in amino acids, indicating the possibility for successfully using cross‐species strategies for genomic studies. There were significantly higher non‐synonymous substitutions both in cattle and buffalo; however, there was similar difference in terms of dN– dS (4.414 versus 4.745) in buffalo and cattle, respectively. Higher rate of non‐synonymous substitutions at similar level in buffalo and cattle indicated a similar positive selection pressure. Results for relative rate test were assessed with the chi‐squared test. There was no significance difference on unique mutations between cattle and buffalo lineages at synonymous sites. However, there was a significance difference on unique mutations for non‐synonymous sites, indicating ongoing mutagenic process that generates substitutional mutation at approximately the same rate at silent sites. Moreover, despite of common ancestry, our results indicate a different divergent time among genes of cattle and buffalo. This is the first demonstration that variable rates of molecular evolution may be present within the family Bovidae.