bluuebunny/crossref_metadata_2025 huggingface dataset:
Using hyperpolarized 129Xe MRI to quantify regional gas transfer in idiopathic pulmonary fibrosis
Authors: Wang Jennifer M , Robertson Scott H , Wang Ziyi , He Mu , Virgincar Rohan S , Schrank Geoffry M , Smigla Rose Marie , O’Riordan Thomas G , Sundy John , Ebner Lukas , Rackley Craig R , McAdams Page , Driehuys Bastiaan
Published: September 2017

Background

Assessing functional impairment, therapeutic response and disease progression in patients with idiopathic pulmonary fibrosis (IPF) continues to be challenging. Hyperpolarized 129Xe MRI can address this gap through its unique capability to image gas transfer three-dimensionally from airspaces to interstitial barrier tissues to red blood cells (RBCs). This must be validated by testing the degree to which it correlates with pulmonary function tests (PFTs) and CT scores, and its spatial distribution reflects known physiology and patterns of disease.

Methods

13 healthy individuals (33.6±15.7 years) and 12 patients with IPF (66.0±6.4 years) underwent 129Xe MRI to generate three-dimensional quantitative maps depicting the 129Xe ventilation distribution, its uptake in interstitial barrier tissues and its transfer to RBCs. For each map, mean values were correlated with PFTs and CT fibrosis scores, and their patterns were tested for the ability to depict functional gravitational gradients in healthy lung and to detect the known basal and peripheral predominance of disease in IPF.

Results

129Xe MRI depicted functional impairment in patients with IPF, whose mean barrier uptake increased by 188% compared with the healthy reference population. 129Xe MRI metrics correlated poorly and insignificantly with CT fibrosis scores but strongly with PFTs. Barrier uptake and RBC transfer both correlated significantly with diffusing capacity of the lungs for carbon monoxide (r=−0.75, p<0.01 and r=0.72, p<0.01), while their ratio (RBC/barrier) correlated most strongly (r=0.94, p<0.01). RBC transfer exhibited significant anterior-posterior gravitational gradients in healthy volunteers, but not in IPF, where it was significantly impaired in the basal (p=0.02) and subpleural (p<0.01) lung.

Conclusions

Hyperpolarized129Xe MRI is a rapid and well-tolerated exam that provides region-specific quantification of interstitial barrier thickness and RBC transfer efficiency. With further development, it could become a robust tool for measuring disease progression and therapeutic response in patients with IPF, sensitively and non-invasively.
Hyphodontia (Hymenochaetales, Basidiomycota) and similar taxa from Central Asia
Authors: Gafforov Yusufjon , Riebesehl Janett , Ordynets Alexander , Langer Ewald , Yarasheva Manzura , Ghobad-Nejhad Masoomeh , Zhou Li-Wei , Wang Xue-Wei , Gugliotta Adriana de Mello
Published: September 2017

Wood-inhabiting fungi are noteworthy components of woody ecosystems that are responsible for the decomposition and turnover of wood nutrients. While the diversity and ecology of these fungi in the temperate forests has been relatively well explored, little is known on diversity of these fungi in the arid and semi-arid forest ecosystems. This is the first study on diversity, distribution, and ecology of the fungal genus Hyphodontia s.l. in the five countries of Central Asia, viz., Kazakhstan, Kyrgyzstan, Tajikistan, Turkmenistan, and Uzbekistan. Altogether, 11 species are confirmed for the region, among which the following six species are reported for the first time from Central Asia: Hyphodontia alutaria, H. pallidula, Kneiffiella alutacea, Lyomyces crustosus, L. erastii, and L. sambuci. In addition to the morphological evidence, the identity of three species is confirmed with phylogenetic analysis based on ITS nuclear ribosomal DNA region. The spectra of known hosts for many of the studied species were expanded. An annotated species list and geo-referenced distribution maps are provided as well as notes on taxonomy, ecology, and local, regional, and global distribution. An identification key to the species of Hyphodontia s.l. recorded in arid and semi-arid regions of Central Asia is also provided.
Bacteriophages: the possible solution to treat infections caused by pathogenic bacteria
Authors: El-Shibiny Ayman , El-Sahhar Salma
Published: September 2017

Since their discovery in 1915, bacteriophages have been used to treat bacterial infections in animals and humans because of their unique ability to infect their specific bacterial hosts without affecting other bacterial populations. The research carried out in this field throughout the 20th century, largely in Georgia, part of USSR and Poland, led to the establishment of phage therapy protocols. However, the discovery of penicillin and sulfonamide antibiotics in the Western World during the 1930s was a setback in the advancement of phage therapy. The misuse of antibiotics has reduced their efficacy in controlling pathogens and has led to an increase in the number of antibiotic-resistant bacteria. As an alternative to antibiotics, bacteriophages have become a topic of interest with the emergence of multidrug-resistant bacteria, which are a threat to public health. Recent studies have indicated that bacteriophages can be used indirectly to detect pathogenic bacteria or directly as biocontrol agents. Moreover, they can be used to develop new molecules for clinical applications, vaccine production, drug design, and in the nanomedicine field via phage display.
2,3,4′,5-tetrahydroxystilbene-2-O-β-d-glycoside attenuates atherosclerosis in apolipoprotein E-deficient mice: role of reverse cholesterol transport
Authors: Chen Xuemeng , Tang Kun , Peng Yi , Xu XiaoLe
Published: September 2017

The aim of this study was to evaluate the potential effects of 2,3,4′,5-tetrahydroxystilbene-2-O-β-d-glucoside (TSG) on the development of atherosclerotic plaque in ApoE−/−mice, and explore the mechanisms involved. Our data showed that after 8 weeks of treatment, TSG ameliorated serum levels of total cholesterol, triglyceride, and low density lipoprotein cholesterol, and increased serum levels of high density lipoprotein cholesterol in ApoE−/−mice. TSG suppressed hepatic steatosis, the formation of atherosclerotic lesions, and the formation of macrophage foam cells in ApoE−/−mice. Moreover, TSG improved the expressions of hepatic SR-BI, ABCG5, and CYP7A1, and up-regulated the protein expressions of aortic ABCA1 and ABCG1. An in-vitro study showed that TSG promoted macrophage cholesterol efflux and increased the protein expressions of ABCA1 and ABCG1. Our findings provide evidence for a positive role of TSG in preventing atherosclerosis by promoting reverse cholesterol transport. These effects may be achieved by stimulating cholesterol efflux through ABCA1 and ABCG1, promoting SR-BI-mediated cholesterol uptake in the liver, increasing secretion of cholesterol into bile by ABCG5, and improving cholesterol metabolism by the CYP7A1 pathway. In addition, antioxidative and anti-inflammatory effects of TSG may also contribute to its inhibitory effects on atherosclerosis. Further study is needed to investigate whether other potential mechanisms are involved in TSG-mediated atheroprotection.
Circum-Arctic lithosphere evolution
Authors: Pease V. , Coakley B.
Published: September 2017

This book is the final product of the Circum-Arctic Lithosphere Evolution (CALE) project. The project's ultimate goal is to link the onshore and offshore geology in order to develop a self-consistent set of constraints for the opening of the Amerasia Basin. The circum-Arctic is divided into seven regions, each with its own research team; the teams included geophysicists and geologists working together to integrate geological and geophysical data, from onshore to offshore. This work is summarized in the 18 papers contained in this volume.
Metrics for Community Analysis
Authors: Chakraborty Tanmoy , Dalmia Ayushi , Mukherjee Animesh , Ganguly Niloy
Published: September 2017

Detecting and analyzing dense groups or
communities
from social and information networks has attracted immense attention over the last decade due to its enormous applicability in different domains. Community detection is an
ill-defined problem
, as the nature of the communities is not known in advance. The problem has turned even more complicated due to the fact that communities emerge in the network in various forms such as disjoint, overlapping, and hierarchical. Various heuristics have been proposed to address these challenges, depending on the application in hand. All these heuristics have been materialized in the form of new
metrics
, which in most cases are used as optimization functions for detecting the community structure, or provide an indication of the goodness of detected communities during evaluation. Over the last decade, a large number of such metrics have been proposed. Thus, there arises a need for an organized and detailed survey of the metrics proposed for community detection and evaluation. Here, we present a survey of the start-of-the-art metrics used for the detection and the evaluation of community structure. We also conduct experiments on synthetic and real networks to present a comparative analysis of these metrics in measuring the goodness of the underlying community structure.
Modeling and Mining Domain Shared Knowledge for Sentiment Analysis
Authors: Zhou Guang-You , Huang Jimmy Xiangji
Published: September 2017

Sentiment classification aims to automatically predict sentiment polarity (e.g., positive or negative) of user generated sentiment data (e.g., reviews, blogs). In real applications, these user-generated sentiment data can span so many different domains that it is difficult to label the training data for all of them. Therefore, we study the problem of sentiment classification adaptation task in this article. That is, a system is trained to label reviews from one source domain but is meant to be used on the target domain. One of the biggest challenges for sentiment classification adaptation task is how to deal with the problem when two data distributions between the source domain and target domain are significantly different from one another. However, our observation is that there might exist some domain shared knowledge among certain input dimensions of different domains. In this article, we present a novel method for modeling and mining the domain shared knowledge from different sentiment review domains via a joint non-negative matrix factorization–based framework. In this proposed framework, we attempt to learn the domain shared knowledge and the domain-specific information from different sentiment review domains with several various regularization constraints. The advantage of the proposed method can promote the correspondence under the topic space between the source domain and the target domain, which can significantly reduce the data distribution gap across two domains. We conduct extensive experiments on two real-world balanced data sets from Amazon product reviews for sentence-level and document-level binary sentiment classification. Experimental results show that our proposed approach significantly outperforms several strong baselines and achieves an accuracy that is competitive with the most well-known methods for sentiment classification adaptation.
Architectural Supports to Protect OS Kernels from Code-Injection Attacks and Their Applications
Authors: Moon Hyungon , Lee Jinyong , Hwang Dongil , Jung Seonhwa , Seo Jiwon , Paek Yunheung
Published: September 2017

The kernel code injection is a common behavior of kernel-compromising attacks where the attackers aim to gain their goals by manipulating an OS kernel. Several security mechanisms have been proposed to mitigate such threats, but they all suffer from non-negligible performance overhead. This article introduces a hardware reference monitor, called Kargos, which can detect the kernel code injection attacks with nearly zero performance cost. Kargos monitors the behaviors of an OS kernel from outside the CPU through the standard bus interconnect and debug interface available with most major microprocessors. By watching the execution traces and memory access events in the monitored target system, Kargos uncovers attempts to execute malicious code with the kernel privilege. On top of this, we also applied the architectural supports for Kargos to the detection of ROP attacks. KS-Stack is the hardware component that builds and maintains the shadow stacks using the existing supports to detect this ROP attacks. According to our experiments, Kargos detected all the kernel code injection attacks that we tested, yet just increasing the computational loads on the target CPU by less than 1% on average. The performance overhead of the KS-Stack was also less than 1%.
Recent Advancements in DNA Damage–Transcription Crosstalk and High-Resolution Mapping of DNA Breaks
Authors: Vitelli Valerio , Galbiati Alessandro , Iannelli Fabio , Pessina Fabio , Sharma Sheetal , d'Adda di Fagagna Fabrizio
Published: September 2017

Until recently, DNA damage arising from physiological DNA metabolism was considered a detrimental by-product for cells. However, an increasing amount of evidence has shown that DNA damage could have a positive role in transcription activation. In particular, DNA damage has been detected in transcriptional elements following different stimuli. These physiological DNA breaks are thought to be instrumental for the correct expression of genomic loci through different mechanisms. In this regard, although a plethora of methods are available to precisely map transcribed regions and transcription start sites, commonly used techniques for mapping DNA breaks lack sufficient resolution and sensitivity to draw a robust correlation between DNA damage generation and transcription. Recently, however, several methods have been developed to map DNA damage at single-nucleotide resolution, thus providing a new set of tools to correlate DNA damage and transcription. Here, we review how DNA damage can positively regulate transcription initiation, the current techniques for mapping DNA breaks at high resolution, and how these techniques can benefit future studies of DNA damage and transcription.
Zinc strengthens the jejunal barrier by reversibly tightening the paracellular route
Authors: Zakrzewski Silke S. , Fromm Michael , Schulzke Jörg D. , Günzel Dorothee
Published: September 2017

During the postweaning period, piglets are prone to gastrointestinal infections. The resulting impairment of intestinal barrier function may cause diarrhea associated with growth retardation or even death of piglets. Orally applied Zn is commonly used to prevent and treat diarrhea, but its mode of action still needs to be elucidated. To analyze the molecular mechanism whereby Zn acts on porcine intestinal barrier function, ex vivo studies on piglet jejunum and accompanying in vitro studies on a porcine jejunal epithelial cell line, IPEC-J2/PS, were performed with electrophysiological tools. Feeding pharmacological Zn doses exerted no significant electrophysiologically ascertainable short- and long-term effects on jejunal barrier function ex vivo. However, in IPEC-J2/PS, basolateral Zn was cytotoxic since its application caused a release of lactate dehydrogenase and an irreversible breakdown of the epithelial barrier. In contrast, apical Zn application caused an immediate increase in paracellular resistance and a decrease in permeability to the paracellular marker fluorescein, reflecting overall barrier strengthening in vitro. Apical effects were fully reversible upon washout. This indicates that Zn supplemented to feed was completely washed out during ex vivo jejunum preparation. We conclude that there is no evidence for long-term barrier effects through prophylactic Zn supplementation and that extracellular Zn acts acutely and reversibly from the apical side via tightening the paracellular route, thus counteracting leak-flux diarrhea.

NEW & NOTEWORTHY Therapeutically administered Zn successfully treats diarrhea in veterinary and human medicine. Here we present data that Zn strengthens the porcine jejunal epithelial barrier by reversibly tightening the paracellular route for inorganic ions and small solutes. Acute or long-lasting Zn effects on transcellular transport (Cl− secretion) were not detected. We therefore conclude that Zn is useful for acutely treating leak-flux diarrhea rather than secretory diarrhea. Suitability as prophylactic feed supplement, however, is questionable.
IL-8 mediates idiopathic pulmonary fibrosis mesenchymal progenitor cell fibrogenicity
Authors: Yang Libang , Herrera Jeremy , Gilbertsen Adam , Xia Hong , Smith Karen , Benyumov Alexey , Bitterman Peter B. , Henke Craig A.
Published: September 2017

Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disease, but the mechanisms driving progression remain incompletely defined. We previously reported that the IPF lung harbors fibrogenic mesenchymal progenitor cells (MPCs), which serve as a cell of origin for IPF fibroblasts. Proliferating IPF MPCs are located at the periphery of fibroblastic foci in an active cellular front at the interface between the myofibroblast-rich focus core and adjacent normal alveolar structures. Among a large set of genes that distinguish IPF MPCs from their control counterparts, we identified IL-8 as a candidate mediator of IPF MPC fibrogenicity and driver of fibrotic progression. IPF MPCs and their progeny displayed increased steady-state levels of IL-8 and its cognate receptor CXCR1 and secreted more IL-8 than did controls. IL-8 functioned in an autocrine manner promoting IPF MPC self-renewal and the proliferation and motility of IPF MPC progeny. Secreted IL-8 also functioned in a paracrine manner stimulating macrophage migration. Analysis of IPF lung tissue demonstrated codistribution of IPF MPCs with activated macrophages in the active cellular front of the fibroblastic focus. These findings indicate that IPF MPC-derived IL-8 is capable of expanding the mesenchymal cell population and recruiting activated macrophages cells to actively evolving fibrotic lesions.
Effects of anti-inflammatory (NSAID) treatment on human tendinopathic tissue
Authors: Heinemeier Katja Maria , Øhlenschlæger Tommy F. , Mikkelsen Ulla Ramer , Sønder Freja , Schjerling Peter , Svensson Rene B. , Kjaer Michael
Published: September 2017

Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used to treat tendinopathy, but evidence for this treatment is lacking, and little is known regarding effects of NSAIDs on human tendinopathic tendon. This study investigated the effects of NSAID treatment (ibuprofen) on human tendinopathic tendon, with changes in gene expression as the primary outcome, and tendon pain, function, and blood flow as secondary outcomes. Twenty-six adults (16 men, 10 women), diagnosed with chronic Achilles tendinopathy, were randomized to 1-wk treatment with ibuprofen (600 mg ×3/day) ( n = 13) or placebo ( n = 13) (double-blinded). Ibuprofen content in blood, visual analog scale score for tendon pain at rest and activity, Victorian Institute of Sports Assessment-Achilles (VISA-A) scores for tendon function, tendon thickness (with ultrasonography), and color Doppler were measured before and 1 h after treatment. After the last posttreatment test, a full-width tendon biopsy was taken from the affected area. Real-time-RT-PCR was used to assess expression of collagen I, collagen III, transforming growth factor (TGF-β) isoforms, cyclooxygenase-2 (COX-2), angiopoietin-like 4 (ANGPTL4), and cyclic AMP-dependent transcription factor (ATF3) in tendon tissue. Expression of collagens and TGF-β isoforms showed relatively low variation and was unaffected by ibuprofen treatment. Further, no changes were seen in tendon thickness or VISA-A score. The placebo treatment reduced the color Doppler (in tendon plus surrounding tissue) compared with the ibuprofen group and also increased the perception of pain at rest. In conclusion, there was no indication that short-term ibuprofen treatment affects gene expression in human chronic tendinopathic tendon or leads to any clear changes in tendon pain or function.

NEW & NOTEWORTHY Nonsteroidal anti-inflammatory drugs are widely used in the treatment of tendinopathy, but little is known of the effects of these drugs on tendon tissue. We find that 1 wk of ibuprofen treatment has no effect on gene expression of collagen and related growth factors in adult human tendinopathic tendon in vivo (in spite of relatively low levels of variation in gene expression), suggesting that tendinopathic cells are not responsive to ibuprofen.
Glucose transport across lagomorph jejunum epithelium is modulated by AMP-activated protein kinase under hypoxia
Authors: Dengler Franziska , Rackwitz Reiko , Pfannkuche Helga , Gäbel Gotthold
Published: September 2017

The gastrointestinal epithelium possesses adaptation mechanisms to cope with huge variations in blood flow and subsequently oxygenation. Since sufficient energy supply is crucial under hypoxic conditions, glucose uptake especially must be regulated by these adaptation mechanisms. Therefore, we investigated glucose transport under hypoxic conditions. Jejunal epithelia of rabbits were incubated in Ussing chambers under short-circuit current conditions. Hypoxia was simulated by gassing with 1% O2 instead of 100% O2. The activity of sodium-coupled glucose transporter-1 (SGLT-1) was assessed by measuring the increase of short circuit current ( Isc) after the addition of 2 mM glucose to the mucosal buffer solution. We observed decreased activity of SGLT-1 after hypoxia compared with control conditions. To investigate underlying mechanisms, epithelia were exposed to agonists and antagonists of AMP-activated protein kinase (AMPK) before assessment of SGLT-1-mediated transport and the pAMPK/AMPK protein ratio. Preincubation with the antagonist restored SGLT-1 activity under hypoxic conditions to the level of control conditions, indicating an involvement of AMPK in the downregulation of SGLT-1 activity under hypoxia, which was confirmed in Western blot analysis of pAMPK/AMPK. Transepithelial flux studies using radioactively labeled glucose, ortho-methyl-glucose, fructose, and mannitol revealed no changes after hypoxic incubation. Therefore, we could exclude a decreased transepithelial glucose transport rate and increased paracellular conductance under hypoxia. In conclusion, our study hints at a decreased activity of SGLT-1 under hypoxic conditions in an AMPK-dependent manner. However, transepithelial transport of glucose is maintained. Therefore, we suggest other transport mechanisms, especially glucose transporter 1 and/or 2 to substitute SGLT-1 under hypoxia.

NEW & NOTEWORTHY To our knowledge, this is the first approach to simulate hypoxia and study its effects in the jejunal epithelium using the Ussing chamber technique. We were able show that AMPK plays a role in the downregulation of SGLT-1 and that there seems to be an upregulation of other glucose transport mechanisms in the apical membrane of lagomorph jejunum epithelium under hypoxia, securing the epithelial energy supply and thus integrity.
Effects of vehicle microdialysis solutions on cutaneous vascular responses to local heating
Authors: Smith Caroline J. , Craighead Daniel H. , Alexander Lacy M.
Published: September 2017

Microdialysis is a minimally invasive technique often paired with laser Doppler flowmetry to examine cutaneous microvascular function, yet presents with several challenges, including incompatibility with perfusion of highly lipophilic compounds. The present study addresses this methodological concern, with an emphasis on the independent effects of commonly used vehicle dialysis solutions to improve solubility of pharmacological agents with otherwise low aqueous solubility. Four microdialysis fibers were placed in the ventral forearm of eight subjects (4 men, 4 women; 25 ± 1 yr) with sites randomized to serve as 1) control (lactated Ringer’s), 2) Sodium carbonate-bicarbonate buffer administered at physiological pH [SCB-HCl; pH 7.4, achieved via addition of hydrochloric acid (HCl)], 3) 0.02% ethanol, and 4) 2% dimethyl sulfoxide (DMSO). After baseline (34°C), vehicle solutions were administered throughout a standardized local heating protocol to 42°C. Laser Doppler flowmetry provided an index of blood flow. Cutaneous vascular conductance was calculated and normalized to maximum (%CVCmax, sodium nitroprusside and 43°C local heat). The SCB-HCl solution increased baseline %CVCmax (control: 9.7 ± 0.8; SCB-HCl: 21.5 ± 3.5%CVCmax; P = 0.03), but no effects were observed during heating or maximal vasodilation. There were no differences with perfusion of ethanol or DMSO at any stage of the protocol ( P > 0.05). These data demonstrate the potential confounding effects of some vehicle dialysis solutions on cutaneous vascular function. Notably, this study provides evidence that 2% DMSO and 0.02% ethanol are acceptable vehicles with no confounding local vascular effects to a standardized local heating protocol at the concentrations presented.

NEW & NOTEWORTHY This study examined the independent effects of common vehicle solutions on cutaneous vascular responses. A basic buffer (SCB-HCl) caused baseline vasodilation; 2% DMSO and 0.02% ethanol had no effects. This highlights the need for considering potential confounding effects of solubilizing solutions when combined with low aqueous soluble pharmacological agents. Importantly, DMSO and ethanol do not appear to influence cutaneous vascular function during baseline or local heating at the concentrations studied, allowing their use without confounding effects.
Genome-Wide Testing of Exonic Variants and Breast Cancer Risk in the California Teachers Study
Authors: Lacson John Charles A. , Ma Huiyan , Lee Eunjung , Neuhausen Susan L. , Anton-Culver Hoda , Reynolds Peggy , Nelson David O. , Ziogas Argyrios , Van Den Berg David , Deapen Dennis M. , Bernstein Leslie , Schumacher Fredrick R.
Published: September 2017

Background: Few studies have focused on the relationship of exonic variation with breast cancer and subtypes defined by tumor markers: estrogen receptor (ER), progesterone receptor (PR), and HER2.

Methods: We genotyped 1,764 breast cancer patients and 1,400 controls from the California Teachers Study cohort using the Infinium HumanExome Beadchip. Individual variant and gene-based analyses were conducted for overall breast cancer and by individual tumor marker subtype.

Results: No exonic variants or gene-based analyses were statistically significantly associated with breast cancer overall or by ER-, PR-, or HER2-defined subtype.

Conclusions: We did not detect any novel statistically significant exonic variants with overall breast cancer risk or by subtype.

Impact: Exonic variants in the exome chip may not be associated with overall breast cancer or subtype susceptibility. Cancer Epidemiol Biomarkers Prev; 26(9); 1462–5. ©2017 AACR.
Reflections on the Structural-Functional Evolution of the Hippocampus: What Is the Big Deal about a Dentate Gyrus
Authors: Bingman Verner P. , Muzio Rubén N.
Published: September 2017

The vertebrate hippocampal formation has been central in discussions of comparative cognition, nurturing an interest in understanding the evolution of variation in hippocampal organization among vertebrate taxa and the functional consequences of that variation. Assuming some similarity between the medial pallium of extant amphibians and the hippocampus of stem tetrapods, we propose the hypothesis that the hippocampus of modern amniotes began with a medial pallium characterized by a relatively undifferentiated cytoarchitecture, more direct thalamic and olfactory sensory inputs, and a broad role in associative learning and memory processes that nonetheless included the map-like representation of space. From this modest beginning evolved the cognitively more specialized hippocampal formation of birds and the hippocampus of mammals with its confounding dentate gyrus. Much has been made of trying to identify a dentate homologue in birds, but there are compelling reasons to believe no such structural homologue/functional equivalent exists. The uniqueness of the mammalian dentate then raises the question of what might be the functional consequences of a hippocampus with a dentate compared to one without. One might be tempted to speculate that the presence of a dentate gyrus facilitates so-called pattern separation, but birds with their suspected dentate-less hippocampus display excellent hippocampal-dependent pattern separation relying on space. Perhaps one consequence of a dentate is a hippocampus better designed to process a broader array of stimuli beyond space to more robustly support episodic memory. What is clear is that any meaningful reconstruction of hippocampal evolution and the eventual identification of any subdivisional homologies will require more data on the neurobiological and functional properties of the nonmammalian hippocampus, particularly those of amphibians and reptiles.
Comparative Contemplations on the Hippocampus
Authors: Witter Menno P. , Kleven Heidi , Kobro Flatmoen Asgeir
Published: September 2017

The hippocampus in mammals is a morphologically well-defined structure, and so are its main subdivisions. To define the homologous structure in other vertebrate clades, using these morphological criteria has been difficult, if not impossible, since the typical mammalian morphology is absent. Although there seems to be consensus that the most medial part of the pallium represents the hippocampus in all vertebrates, there is no consensus on whether all mammalian hippocampal subdivisions are present in the derivatives of the medial pallium in all vertebrate groups. The aim of this paper is to explore the potential relevance of connections to define the hippocampus across vertebrates, with a focus on mammals, reptiles, and birds.
Contribution of Genoarchitecture to Understanding Hippocampal Evolution and Development
Authors: Medina Loreta , Abellán Antonio , Desfilis Ester
Published: September 2017

The hippocampal formation is a highly conserved structure of the medial pallium that works in association with the entorhinal cortex, playing a key role in memory formation and spatial navigation. Although it has been described in several vertebrates, the presence of comparable subdivisions across species remained unclear. This panorama has started to change in recent years thanks to the identification of some of the genes that regulate the development of the hippocampal formation in the mouse and help to delineate its subdivisions based on molecular features. Some of these genes have been used to try to identify subdivisions in chicken and lizards comparable to those of the mammalian hippocampal formation and the entorhinal cortex. Here, we review some of these data, which suggest the existence of fields comparable to the dentate gyrus, CA3, CA1, subiculum, as well as medial and lateral parts of the entorhinal cortex in all amniotes. We also analyze available data suggesting the existence of serial connections between these fields, speculate on the possible existence of auto-associative loops in CA3, and discuss general principles governing the formation of the connections.
The Avian Hippocampal Formation and the Stress Response
Authors: Smulders Tom V.
Published: September 2017

Though widely studied for its function in memory and navigation, the hippocampal formation (HF) in mammals also plays an important role in regulating the stress response. If this is an ancestral feature of the hippocampus, then it is likely that the avian HF plays a similar role. Indeed, the avian HF strongly expresses both mineralocorticoid and glucocorticoid receptors, and has indirect projections to the paraventricular nucleus of the hypothalamus, which controls the hypothalamic-pituitary-adrenal (HPA) axis. Hippocampal lesions increase HPA activity, while electrical stimulation suppresses it. In addition, adult hippocampal neurogenesis in birds is reduced in response to different acute and chronic stressors, as it is in mammals. Because the mammalian hippocampus is functionally specialized along its septotemporal axis, with the temporal pole playing a more important role in the stress response, the hypothesis is put forward that a similar functional specialization exists in birds along the rostrocaudal hippocampal axis. Some, though not all, of the evidence supports a rostrocaudal functional gradient. The evidence for whether this is equivalent to the mammalian septotemporal organization is currently ambiguous at best and needs to be more extensively investigated.
Increased Mobilization of CD45+CD34+VLA-4+ Cells in Acute Viral Myocarditis Induced by Coxsackievirus B3
Authors: Gao Xingcui , Wei Bin , Deng Yan , Huang Yan Lan , Wu Weifeng
Published: September 2017

Objectives: Bone marrow-derived cells (BMCs) have recently been identified to play a vital role in repairing damaged myocardium; however, it is not known whether or not mobilization of BMCs is involved in the pathogenesis of acute viral myocarditis (VMC). Thus, we analyzed the expression of CD45+CD34+VLA-4+ cells and vascular cell adhesion protein-1 (VCAM-1) in a murine model of acute VMC. Methods: Male BALB/c mice were intraperitoneally infected with coxsackievirus B3 to establish acute VMC. The frequency of CD45+CD34+VLA-4+ cells in the heart, peripheral blood, and bone marrow was examined by flow cytometry 3, 7, 14, and 28 days after injection. Cardiac VCAM-1 and pathology scores were determined by immunohistochemistry, and myocardial VCAM-1, IL-1β, and TNF-α were analyzed by RT-PCR and Western blot. Results: In mice with acute VMC, the CD45+CD34+VLA-4+ cell population in the heart was significantly increased by day 7 and then decreased; in contrast, the CD45+CD34+VLA-4+ cell population decreased in the bone marrow and peripheral blood by day 3 and then increased. High expression of VCAM-1 was detected in the heart in parallel with CD45+CD34+VLA-4+ cell expression. Conclusions: In mice with acute VMC, VCAM-1-induced CD45+CD34+VLA-4+ cell mobilization into the injured heart is involved in the repair of injured myocardium.
On the Value of Reptilian Brains to Map the Evolution of the Hippocampal Formation
Authors: Reiter Sam , Liaw Hua-Peng , Yamawaki Tracy M. , Naumann Robert K. , Laurent Gilles
Published: September 2017

Our ability to navigate through the world depends on the function of the hippocampus. This old cortical structure plays a critical role in spatial navigation in mammals and in a variety of processes, including declarative and episodic memory and social behavior. Intense research has revealed much about hippocampal anatomy, physiology, and computation; yet, even intensely studied phenomena such as the shaping of place cell activity or the function of hippocampal firing patterns during sleep remain incompletely understood. Interestingly, while the hippocampus may be a ‘higher order' area linked to a complex cortical hierarchy in mammals, it is an old cortical structure in evolutionary terms. The reptilian cortex, structurally much simpler than the mammalian cortex and hippocampus, therefore presents a good alternative model for exploring hippocampal function. Here, we trace common patterns in the evolution of the hippocampus of reptiles and mammals and ask which parts can be profitably compared to understand functional principles. In addition, we describe a selection of the highly diverse repertoire of reptilian behaviors to illustrate the value of a comparative approach towards understanding hippocampal function.
Endoscopic Mucosectomy in a Child Presenting with Gastric Heterotopia of the Rectum
Authors: Soares Joana , Ferreira Carla , Marques Margarida , Corujeira Susana , Tavares Marta , Lopes Joanne , Carneiro Fátima , Amil Dias Jorge , Trindade Eunice
Published: September 2017

Gastric mucosal heterotopia has been described in all levels of the gastrointestinal tract. Its occurrence in the rectum is uncommon. We report the case of a 4-year-old boy referred to Pediatric Gastroenterology for intermittent rectal bleeding for the past 2 years. Total ileocolonoscopy revealed a flat, well-circumscribed lesion of 4 cm, with elevated margins, localized at 10 cm from the anal verge. Histologic examination showed typical gastric mucosa of the oxyntic type. Treatment with proton pump inhibitors was started without resolution of the symptoms and, therefore, an endoscopic mucosal resection was performed. Heterotopic gastric mucosa represents a rare cause of rectal bleeding in children and endoscopic evaluation is fundamental for diagnosis. Although not usually performed in pediatric ages, endoscopic mucosectomy allows complete resolution of the problem avoiding surgery.
Smoking Trajectories during the Perinatal Period and Their Risk Factors: The Nationally Representative French ELFE (Etude Longitudinale Française Depuis l'Enfance) Birth Cohort Study
Authors: El-Khoury Fabienne , Sutter-Dallay Anne-Laure , Van Der Waerden Judith , Surkan Pamela , Martins Silvia , Keyes Katherine , de Lauzon-Guillain Blandine , Charles Marie-Aline , Melchior Maria
Published: September 2017

Background: In France, rates of perinatal smoking are among the highest worldwide; however, perinatal smoking trajectories and associated factors have still not been adequately researched. Methods: Among women participating in the French nationally representative etude longitudinale française depuis l'enfance birth cohort (n = 15,540), perinatal smoking trajectories were estimated using group-based modelling. Associated characteristics were studied using multinomial logistic regression. Results: Four trajectories were identified: non-smokers (59%), quitters (20%), persistent moderate (12%) and persistent heavy (9%) smokers. Older age, being native French, low socioeconomic position, persistent psychological difficulties and alcohol use in pregnancy, lack of social support, partner's smoking, mistimed pregnancy, and child formula feeding at birth were associated with persistent heavy smoking. Most of these factors were also associated, but to a lesser extent, with persistent moderate smoking, except for age and migrant status, which had opposite effects. Women who successfully lost weight prior to pregnancy had higher levels of quitting smoking. Conclusion: Women's long-term smoking trajectories vary in terms of initial tobacco consumption level but also in relation to socio-demographic, psychological, behavioral and partner characteristics. Health professionals in contact with pregnant smokers should address perceived risks and benefits of smoking, including partner's smoking and weight-gain concerns.
Autoimmune Myelofibrosis: Clinical Features, Course, and Outcome
Authors: Piatek Caroline I. , Vergara-Lluri Maria E. , Pullarkat Vinod , Siddiqi Imran N. , O'Connell Casey , Brynes Russell K. , Feinstein Donald I.
Published: September 2017

Background: Autoimmune myelofibrosis (AIMF) is an underrecognized cause of nonmalignant bone marrow fibrosis which occurs in the presence or absence of a defined systemic autoimmune disease. Patients with AIMF present with cytopenias and autoantibodies, and have a distinctive nonclonal myelofibrosis on bone marrow examination. AIMF is distinguished from primary myelofibrosis by the absence of splenomegaly, eosinophilia, or basophilia, and the absence of abnormal myeloid, erythroid, or megakaryocytic morphology. Objectives: The objective of the study was to describe the clinical presentation and outcomes of patients with AIMF. Methods: We conducted a single-institution, retrospective chart review of patients diagnosed with AIMF to investigate clinical presentations, therapies, and outcomes. Results: Twelve patients with AIMF were identified with a mean follow-up of 5.8 years. All patients had detectable autoantibodies and the majority had concomitant autoimmune disorders. Four patients experienced a complete response of cytopenias and 3 patients experienced a partial response (PR) of cytopenias with immunosuppressive therapy. One patient achieved a PR following splenectomy. No patients were diagnosed with myeloproliferative neoplasms during the follow-up period. Conclusions: AIMF contributes to cytopenias in the subset of patients with various autoimmune disorders. The majority of patients with AIMF experience an improvement in cytopenias with immunosuppressive therapy.
Observational Monitoring of Patients with Aplastic Anemia and Low/Intermediate-1 Risk of Myelodysplastic Syndromes Complicated with Iron Overload
Authors: Du Yali , Long Zhangbiao , Chen Miao , Han Bing , Hou Bo , Feng Feng
Published: September 2017

Background: This study focuses on the iron overload (IOL) of patients with transfused aplastic anemia (AA) or a low/intermediate-1 risk of myelodysplastic syndrome (MDS). Methods: Ninety-two AA or MDS patients with IOL were prospectively recruited. Clinical data were collected every 6 months, and organ magnetic resonance imaging T2* values were collected annually. Patients with IOL were chelated. Results: Serum ferritin was correlated with liver T2* and pancreatic T2* in the AA and MDS groups. Transfusion amounts were correlated with serum ferritin values, liver T2*, and pancreatic T2* in the AA group. At the 6-month and 1-year evaluations, patients with sufficient chelation experienced significant decreases in serum ferritin, and those with decreased serum ferritin experienced an obvious increase in hemoglobin. At their 1-year-follow-up, patients with adequate chelation showed significant increases in hepatic T2*, cardiac T2*, and left ventricular ejection fraction (LVEF). Patients with decreased serum ferritin (including those without chelation) experienced an increase in hemoglobin, hepatic T2*, cardiac T2*, and LVEF. Conclusion: The transfusion amount was more reliable at predicting IOL in patients with AA than in those with MDS. Adequate iron chelation can decrease serum ferritin levels and may improve hepatic T2*, cardiac T2*, and LVEF levels. A decrease in serum ferritin, even in the absence of chelation, may also benefit patients.
Alpha-Synuclein to the Rescue: Immune Cell Recruitment by Alpha-Synuclein during Gastrointestinal Infection
Authors: Labrie Viviane , Brundin Patrik
Published: September 2017

Intraneuronal accumulation of misfolded alpha-synuclein in the central and peripheral nervous systems is strongly linked to Parkinson disease (PD) and other related synucleinopathies. In rare inherited forms of PD, point mutations or gene multiplications mediate the formation of alpha-synuclein protein aggregates. However, in most PD cases it is presumed that the combined effects of ageing and environmental factors drive the formation of alpha-synuclein aggregates. Despite advances regarding alpha-synuclein pathobiology, the normal functions of this protein and factors that regulate its expression are not well understood. We discuss a recent study reporting that viral infection induces alpha-synuclein expression in neurons of the gastrointestinal tract. Alpha-synuclein levels increased during norovirus infection in the duodenum of children. In an in vitro paradigm, monomeric and oligomeric alpha-synuclein acted as chemoattractants for neutrophils and monocytes, and promoted the maturation of dendritic cells. This suggests that alpha-synuclein facilitates immune responses to infection. We explore the possibility that intestinal infections, and associated inflammation, place individuals at increased risk of PD by increasing alpha-synuclein levels and promoting the formation of alpha-synuclein aggregates that propagate in a prion-like fashion via the vagal nerve to the brainstem.
Detection of atrial fibrillation in patients with embolic stroke of undetermined source by prolonged monitoring with implantable loop recorders
Authors: Israel Carsten , Kitsiou Alkisti , Kalyani Malik , Deelawar Sameera , Ejangue Lucy Ekosso , Rogalewski Andreas , Hagemeister Christoph , Minnerup Jens , Schäbitz Wolf-Rüdiger
Published: September 2017

Recently, the clinical entity embolic stroke of undetermined source (ESUS) has been defined for patients with ischemic strokes, where neither a cardioembolic nor a non-cardiac source can be detected. These patients may suffer from asymptomatic atrial fibrillation (AF), terminating spontaneously and thus eluding detection. Implantable loop recorders (ILR) with automatic AF detection algorithms can detect short-lasting, subclinical AF. The aim of this study was to prospectively assess and predict AF detection in patients with ESUS using ILR with daily remote interrogation. Patients with acute ESUS received an ILR, were seen every 6 months and additionally interrogated their ILR daily using remote monitoring. The incidence of AF detection was assessed and parameters which might predict AF detection (clinical and from magnetic resonance tomography) were analysed. ILR implantation was performed in 123 patients on average 20 days after stroke. During a mean follow-up of 12.7±5.5 months, AF was documented and manually confirmed in 29 of 123 patients (23.6%). First AF detection occurred on average after 3.6±3.4 months of monitoring. Patients with AF were on average older, had a higher CHA2DS2-VASc score and more often cerebral microangiopathy. In conclusion, AF can be documented in approximately 25% of patients with the diagnosis of ESUS after careful work-up within a year of monitoring by an ILR and daily remote interrogation. This had important therapeutic consequences (initiation of anticoagulation for secondary stroke prevention) in these patients.
Registro Geral de Imóveis, propriedade e Estado Nacional no Segundo Reinado
Authors: Rodrigues Pedro Parga
Published: September 2017

O objetivo é relacionar os debates legislativos e jurídicos para promulgação da Lei Hipotecária número 1.237 de 1864 à construção do Estado Nacional no Segundo Reinado e à institucionalização da ordem jurídica liberal. Serão consideradas as disputas relacionadas à criação do registro das alienações de imóveis e de hipotecas.
Another approximation to the Spanish series Cuéntame cómo pasó: the special episodes
Authors: Pousa Laura García
Published: September 2017

The television series Cuéntame cómo pasó (2001-) employs both fiction and a documentar approach to create a telling portrait of the final years of the Franco dictatorship in Spain and the transition of the country to Democracy through a protagonist family named Los Alcántara (The Alcántara). From the more than 250 broadcasted episodes the object of analysis in this article is the episodes that are considered as special, those which investigate the cultural meaning of the era through the universe created in the series. This focus enables us to understand how the dramatic force of Cuéntame como pasó permits the creation of diverse and individual episodes, thanks to the continuous self-referential dramatic games at play.
Em torno da crítica literária em jornal: sobre Lima Barreto e José Veríssimo
Authors: Domingues Rachel Bertol
Published: September 2017

The article aims to analyze the relationship of the literary critic José Veríssimo (1857-1916) with the writer Lima Barreto (1881-1922). It takes press as a starting point. Both the critic and the writer worked at the newspaper, which inspires Lima’s debut novel. But beyond their confluence of ideas, the relationship is analyzed by the prism of the communication circuit in which they are inserted. Criticism is taken as an instance related to journalism. Primary sources contribute to the composition of snapshots of the communication circuit that allows to analyze Sevcenko’s proposal that Veríssimo was a “tutelary master” of Lima. This proposition is confirmed in some aspects, especially with regard to social criticism.