bluuebunny/crossref_metadata_2025 huggingface dataset:
Oral Microbial Ecology and the Role of Salivary Immunoglobulin A
Authors: Marcotte Harold , Lavoie Marc C.
Published: December 2019

In the oral cavity, indigenous bacteria are often associated with two major oral diseases, caries and periodontal diseases. These diseases seem to appear following an inbalance in the oral resident microbiota, leading to the emergence of potentially pathogenic bacteria. To define the process involved in caries and periodontal diseases, it is necessary to understand the ecology of the oral cavity and to identify the factors responsible for the transition of the oral microbiota from a commensal to a pathogenic relationship with the host. The regulatory forces influencing the oral ecosystem can be divided into three major categories: host related, microbe related, and external factors. Among host factors, secretory immunoglobulin A (SIgA) constitutes the main specific immune defense mechanism in saliva and may play an important role in the homeostasis of the oral microbiota. Naturally occurring SIgA antibodies that are reactive against a variety of indigenous bacteria are detectable in saliva. These antibodies may control the oral microbiota by reducing the adherence of bacteria to the oral mucosa and teeth. It is thought that protection against bacterial etiologic agents of caries and periodontal diseases could be conferred by the induction of SIgA antibodies via the stimulation of the mucosal immune system. However, elucidation of the role of the SIgA immune system in controlling the oral indigenous microbiota is a prerequisite for the development of effective vaccines against these diseases. The role of SIgA antibodies in the acquisition and the regulation of the indigenous microbiota is still controversial. Our review discusses the importance of SIgA among the multiple factors that control the oral microbiota. It describes the oral ecosystems, the principal factors that may control the oral microbiota, a basic knowledge of the secretory immune system, the biological functions of SIgA, and, finally, experiments related to the role of SIgA in oral microbial ecology.
NontypeableHaemophilus influenzae: Pathogenesis and Prevention
Authors: Foxwell A. Ruth , Kyd Jennelle M. , Cripps Allan W.
Published: December 2019

In this paper, we describe the ability of nontypeable Haemophilus influenzae (NTHi) to coexist with the human host and the devastating results associated with disruption of the delicate state of balanced pathogenesis, resulting in both acute and chronic respiratory tract infections. It has been seen that the strains of NTHi causing disease show a marked genetic and phenotypic diversity but that changes in the lipooligosaccharide (LOS) and protein size and antigenicity in chronically infected individuals indicate that individual strains of NTHi can remain and adapt themselves to avoid expulsion from their infective niche. The lack of reliance of NTHi on a single mechanism of attachment and its ability to interact with the host with rapid responses to its environment confirmed the success of this organism as both a colonizer and a pathogen. In vitro experiments on cell and organ cultures, combined with otitis media and pulmonary models in chinchillas, rats, and mice, have allowed investigations into individual interactions between NTHi and the mammalian host. The host-organism interaction appears to be a two-way process, with NTHi using cell surface structures to directly interact with the mammalian host and using secreted proteins and LOS to change the mammalian host in order to pave the way for colonization and invasion. Many experiments have also noted that immune system evasion through antigenic variation, secretion of enzymes and epithelial cell invasion allowed NTHi to survive for longer periods despite a specific immune response being mounted to infection. Several outer membrane proteins and LOS derivatives are discussed in relation to their efficacy in preventing pulmonary infections and otitis media in animals. General host responses with respect to age, genetic makeup, and vaccine delivery routes are considered, and a mucosal vaccine strategy is suggested.
Regulation of X-Chromosome Inactivation in Development in Mice and Humans
Authors: Goto Tetsuya , Monk Marilyn
Published: December 2019

Dosage compensation for X-linked genes in mammals is accomplished by inactivating one of the two X chromosomes in females. X-chromosome inactivation (XCI) occurs during development, coupled with cell differentiation. In somatic cells, XCI is random, whereas in extraembryonic tissues, XCI is imprinted in that the paternally inherited X chromosome is preferentially inactivated. Inactivation is initiated from an X-linked locus, the X-inactivation center (Xic), and inactivity spreads along the chromosome toward both ends. XCI is established by complex mechanisms, including DNA methylation, heterochromatinization, and late replication. Once established, inactivity is stably maintained in subsequent cell generations. The function of an X-linked regulatory gene, Xist, is critically involved in XCI. The Xist gene maps to the Xic, it is transcribed only from the inactive X chromosome, and the Xist RNA associates with the inactive X chromosome in the nucleus. Investigations with Xist-containing transgenes and with deletions of the Xist gene have shown that the Xist gene is required in cis for XCI. Regulation of XCI is therefore accomplished through regulation of Xist. Transcription of the Xist gene is itself regulated by DNA methylation. Hence, the differential methylation of the Xist gene observed in sperm and eggs and its recognition by protein binding constitute the most likely mechanism regulating imprinted preferential expression of the paternal allele in preimplantation embryos and imprinted paternal XCI in extraembryonic tissues. This article reviews the mechanisms underlying XCI and recent advances elucidating the functions of the Xist gene in mice and humans.
Molecular Genetics of the GenusParacoccus: Metabolically Versatile Bacteria with Bioenergetic Flexibility
Authors: Baker Simon C. , Ferguson Stuart J. , Ludwig Bernd , Page M. Dudley , Richter Oliver-Matthias H. , van Spanning Rob J. M.
Published: December 2019

Paracoccus denitrificans and its near relative Paracoccus versutus (formerly known as Thiobacilllus versutus) have been attracting increasing attention because the aerobic respiratory system of P. denitrificans has long been regarded as a model for that of the mitochondrion, with which there are many components (e.g., cytochrome aa3oxidase) in common. Members of the genus exhibit a great range of metabolic flexibility, particularly with respect to processes involving respiration. Prominent examples of flexibility are the use in denitrification of nitrate, nitrite, nitrous oxide, and nitric oxide as alternative electron acceptors to oxygen and the ability to use C1compounds (e.g., methanol and methylamine) as electron donors to the respiratory chains. The proteins required for these respiratory processes are not constitutive, and the underlying complex regulatory systems that regulate their expression are beginning to be unraveled. There has been uncertainty about whether transcription in a member of the alpha-3 Proteobacteria such as P. denitrificans involves a conventional ς70-type RNA polymerase, especially since canonical −35 and −10 DNA binding sites have not been readily identified. In this review, we argue that many genes, in particular those encoding constitutive proteins, may be under the control of a ς70RNA polymerase very closely related to that of Rhodobacter capsulatus. While the main focus is on the structure and regulation of genes coding for products involved in respiratory processes in Paracoccus, the current state of knowledge of the components of such respiratory pathways, and their biogenesis, is also reviewed.
Virus Maturation by Budding
Authors: Garoff Henrik , Hewson Roger , Opstelten Dirk-Jan E.
Published: December 2019

Enveloped viruses mature by budding at cellular membranes. It has been generally thought that this process is driven by interactions between the viral transmembrane proteins and the internal virion components (core, capsid, or nucleocapsid). This model was particularly applicable to alphaviruses, which require both spike proteins and a nucleocapsid for budding. However, genetic studies have clearly shown that the retrovirus core protein, i.e., the Gag protein, is able to form enveloped particles by itself. Also, budding of negative-strand RNA viruses (rhabdoviruses, orthomyxoviruses, and paramyxoviruses) seems to be accomplished mainly by internal components, most probably the matrix protein, since the spike proteins are not absolutely required for budding of these viruses either. In contrast, budding of coronavirus particles can occur in the absence of the nucleocapsid and appears to require two membrane proteins only. Biochemical and structural data suggest that the proteins, which play a key role in budding, drive this process by forming a three-dimensional (cage-like) protein lattice at the surface of or within the membrane. Similarly, recent electron microscopic studies revealed that the alphavirus spike proteins are also engaged in extensive lateral interactions, forming a dense protein shell at the outer surface of the viral envelope. On the basis of these data, we propose that the budding of enveloped viruses in general is governed by lateral interactions between peripheral or integral membrane proteins. This new concept also provides answers to the question of how viral and cellular membrane proteins are sorted during budding. In addition, it has implications for the mechanism by which the virion is uncoated during virus entry.
The Virulence Plasmid ofYersinia, an Antihost Genome
Authors: Cornelis Guy R. , Boland Anne , Boyd Aoife P. , Geuijen Cecile , Iriarte Maite , Neyt Cécile , Sory Marie-Paule , Stainier Isabelle
Published: December 2019

The 70-kb virulence plasmid enables Yersinia spp. (Yersinia pestis, Y. pseudotuberculosis, and Y. enterocolitica) to survive and multiply in the lymphoid tissues of their host. It encodes the Yop virulon, an integrated system allowing extracellular bacteria to disarm the cells involved in the immune response, to disrupt their communications, or even to induce their apoptosis by the injection of bacterial effector proteins. This system consists of the Yop proteins and their dedicated type III secretion apparatus, called Ysc. The Ysc apparatus is composed of some 25 proteins including a secretin. Most of the Yops fall into two groups. Some of them are the intracellular effectors (YopE, YopH, YpkA/YopO, YopP/YopJ, YopM, and YopT), while the others (YopB, YopD, and LcrV) form the translocation apparatus that is deployed at the bacterial surface to deliver the effectors into the eukaryotic cells, across their plasma membrane. Yop secretion is triggered by contact with eukaryotic cells and controlled by proteins of the virulon including YopN, TyeA, and LcrG, which are thought to form a plug complex closing the bacterial secretion channel. The proper operation of the system also requires small individual chaperones, called the Syc proteins, in the bacterial cytosol. Transcription of the genes is controlled both by temperature and by the activity of the secretion apparatus. The virulence plasmid of Y. enterocolitica and Y. pseudotuberculosis also encodes the adhesin YadA. The virulence plasmid contains some evolutionary remnants including, in Y. enterocolitica, an operon encoding resistance to arsenic compounds.
Posttranscriptional Control of Gene Expression in Yeast
Authors: McCarthy John E. G.
Published: December 2019

Studies of the budding yeast Saccharomyces cerevisiae have greatly advanced our understanding of the posttranscriptional steps of eukaryotic gene expression. Given the wide range of experimental tools applicable to S. cerevisiae and the recent determination of its complete genomic sequence, many of the key challenges of the posttranscriptional control field can be tackled particularly effectively by using this organism. This article reviews the current knowledge of the cellular components and mechanisms related to translation and mRNA decay, with the emphasis on the molecular basis for rate control and gene regulation. Recent progress in characterizing translation factors and their protein-protein and RNA-protein interactions has been rapid. Against the background of a growing body of structural information, the review discusses the thermodynamic and kinetic principles that govern the translation process. As in prokaryotic systems, translational initiation is a key point of control. Modulation of the activities of translational initiation factors imposes global regulation in the cell, while structural features of particular 5′ untranslated regions, such as upstream open reading frames and effector binding sites, allow for gene-specific regulation. Recent data have revealed many new details of the molecular mechanisms involved while providing insight into the functional overlaps and molecular networking that are apparently a key feature of evolving cellular systems. An overall picture of the mechanisms governing mRNA decay has only very recently begun to develop. The latest work has revealed new information about the mRNA decay pathways, the components of the mRNA degradation machinery, and the way in which these might relate to the translation apparatus. Overall, major challenges still to be addressed include the task of relating principles of posttranscriptional control to cellular compartmentalization and polysome structure and the role of molecular channelling in these highly complex expression systems.
Mechanisms of Arthropod Transmission of Plant and Animal Viruses
Authors: Gray Stewart M. , Banerjee Nanditta
Published: December 2019

A majority of the plant-infecting viruses and many of the animal-infecting viruses are dependent upon arthropod vectors for transmission between hosts and/or as alternative hosts. The viruses have evolved specific associations with their vectors, and we are beginning to understand the underlying mechanisms that regulate the virus transmission process. A majority of plant viruses are carried on the cuticle lining of a vector’s mouthparts or foregut. This initially appeared to be simple mechanical contamination, but it is now known to be a biologically complex interaction between specific virus proteins and as yet unidentified vector cuticle-associated compounds. Numerous other plant viruses and the majority of animal viruses are carried within the body of the vector. These viruses have evolved specific mechanisms to enable them to be transported through multiple tissues and to evade vector defenses. In response, vector species have evolved so that not all individuals within a species are susceptible to virus infection or can serve as a competent vector. Not only are the virus components of the transmission process being identified, but also the genetic and physiological components of the vectors which determine their ability to be used successfully by the virus are being elucidated. The mechanisms of arthropod-virus associations are many and complex, but common themes are beginning to emerge which may allow the development of novel strategies to ultimately control epidemics caused by arthropod-borne viruses.
Protein Targeting to the Bacterial Cytoplasmic Membrane
Authors: Fekkes Peter , Driessen Arnold J. M.
Published: December 2019

Proteins that perform their activity within the cytoplasmic membrane or outside this cell boundary must be targeted to the translocation site prior to their insertion and/or translocation. In bacteria, several targeting routes are known; the SecB- and the signal recognition particle-dependent pathways are the best characterized. Recently, evidence for the existence of a third major route, the twin-Arg pathway, was gathered. Proteins that use either one of these three different pathways possess special features that enable their specific interaction with the components of the targeting routes. Such targeting information is often contained in an N-terminal extension, the signal sequence, but can also be found within the mature domain of the targeted protein. Once the nascent chain starts to emerge from the ribosome, competition for the protein between different targeting factors begins. After recognition and binding, the targeting factor delivers the protein to the translocation sites at the cytoplasmic membrane. Only by means of a specific interaction between the targeting component and its receptor is the cargo released for further processing and translocation. This mechanism ensures the high-fidelity targeting of premembrane and membrane proteins to the translocation site.
A Paean to
Microbiology and Molecular Biology Reviews
Authors: Schaechter Moselio
Published: December 2019

This article celebrates the accomplishments of Microbiology and Molecular Biology Reviews from its early days to the present time. The importance of this journal in the professional lives of microbiologists is emphasized, and examples of outstanding reviews are presented.
Pseudomonas syringaePhytotoxins: Mode of Action, Regulation, and Biosynthesis by Peptide and Polyketide Synthetases
Authors: Bender Carol L. , Alarcón-Chaidez Francisco , Gross Dennis C.
Published: December 2019

Coronatine, syringomycin, syringopeptin, tabtoxin, and phaseolotoxin are the most intensively studied phytotoxins of Pseudomonas syringae, and each contributes significantly to bacterial virulence in plants. Coronatine functions partly as a mimic of methyl jasmonate, a hormone synthesized by plants undergoing biological stress. Syringomycin and syringopeptin form pores in plasma membranes, a process that leads to electrolyte leakage. Tabtoxin and phaseolotoxin are strongly antimicrobial and function by inhibiting glutamine synthetase and ornithine carbamoyltransferase, respectively. Genetic analysis has revealed the mechanisms responsible for toxin biosynthesis. Coronatine biosynthesis requires the cooperation of polyketide and peptide synthetases for the assembly of the coronafacic and coronamic acid moieties, respectively. Tabtoxin is derived from the lysine biosynthetic pathway, whereas syringomycin, syringopeptin, and phaseolotoxin biosynthesis requires peptide synthetases. Activation of phytotoxin synthesis is controlled by diverse environmental factors including plant signal molecules and temperature. Genes involved in the regulation of phytotoxin synthesis have been located within the coronatine and syringomycin gene clusters; however, additional regulatory genes are required for the synthesis of these and other phytotoxins. Global regulatory genes such as gacS modulate phytotoxin production in certain pathovars, indicating the complexity of the regulatory circuits controlling phytotoxin synthesis. The coronatine and syringomycin gene clusters have been intensively characterized and show potential for constructing modified polyketides and peptides. Genetic reprogramming of peptide and polyketide synthetases has been successful, and portions of the coronatine and syringomycin gene clusters could be valuable resources in developing new antimicrobial agents.
Function and Regulation of Yeast Hexose Transporters
Authors: Özcan Sabire , Johnston Mark
Published: December 2019

Glucose, the most abundant monosaccharide in nature, is the principal carbon and energy source for nearly all cells. The first, and rate-limiting, step of glucose metabolism is its transport across the plasma membrane. In cells of many organisms glucose ensures its own efficient metabolism by serving as an environmental stimulus that regulates the quantity, types, and activity of glucose transporters, both at the transcriptional and posttranslational levels. This is most apparent in the baker’s yeast Saccharomyces cerevisiae, which has 20 genes encoding known or likely glucose transporters, each of which is known or likely to have a different affinity for glucose. The expression and function of most of these HXT genes is regulated by different levels of glucose. This review focuses on the mechanisms S. cerevisiae and a few other fungal species utilize for sensing the level of glucose and transmitting this information to the nucleus to alter HXT gene expression. One mechanism represses transcription of some HXT genes when glucose levels are high and works through the Mig1 transcriptional repressor, whose function is regulated by the Snf1-Snf4 protein kinase and Reg1-Glc7 protein phosphatase. Another pathway induces HXT expression in response to glucose and employs the Rgt1 transcriptional repressor, a ubiquitin ligase protein complex (SCF
Grr1
) that regulates Rgt1 function, and two glucose sensors in the membrane (Snf3 and Rgt2) that bind glucose and generate the intracellular signal to which Rgt1 responds. These two regulatory pathways collaborate with other, less well-understood, pathways to ensure that yeast cells express the glucose transporters best suited for the amount of glucose available.
Fungal Resistance to Plant Antibiotics as a Mechanism of Pathogenesis
Authors: Morrissey John P. , Osbourn Anne E.
Published: December 2019

Many plants produce low-molecular-weight compounds which inhibit the growth of phytopathogenic fungi in vitro. These compounds may be preformed inhibitors that are present constitutively in healthy plants (also known as phytoanticipins), or they may be synthesized in response to pathogen attack (phytoalexins). Successful pathogens must be able to circumvent or overcome these antifungal defenses, and this review focuses on the significance of fungal resistance to plant antibiotics as a mechanism of pathogenesis. There is increasing evidence that resistance of fungal pathogens to plant antibiotics can be important for pathogenicity, at least for some fungus-plant interactions. This evidence has emerged largely from studies of fungal degradative enzymes and also from experiments in which plants with altered levels of antifungal secondary metabolites were generated. Whereas the emphasis to date has been on degradative mechanisms of resistance of phytopathogenic fungi to antifungal secondary metabolites, in the future we are likely to see a rapid expansion in our knowledge of alternative mechanisms of resistance. These may include membrane efflux systems of the kind associated with multidrug resistance and innate resistance due to insensitivity of the target site. The manipulation of plant biosynthetic pathways to give altered antibiotic profiles will also be valuable in telling us more about the significance of antifungal secondary metabolites for plant defense and clearly has great potential for enhancing disease resistance for commercial purposes.
Pathology and Epizootiology of
Entomophaga maimaiga
Infections in Forest Lepidoptera
Authors: Hajek Ann E.
Published: December 2019

The insect-pathogenic fungal pathogen Entomophaga maimaiga is endemic to northeastern Asia and was first found in North America in 1989. Due to repeated epizootics and spread within populations of the major forest defoliator in northeastern North America, the gypsy moth (Lymantria dispar), this pathogen has gained much notoriety. Although this pathogen was purposely introduced to North America for biological control of L. dispar in 1910 to 1911, it is questionable whether it became established at the time of release and then remained at innocuous levels until relatively recently. Alternatively, the fungal strain present in North America today could be a more recent accidental introduction. DNA analysis demonstrates that this pathogen differs significantly from North American members of the same species complex (the Lepidoptera-specific Entomophaga aulicae species complex), and, to date, isolates of this introduced pathogen display little heterogeneity in North America. Nonsusceptible lepidopteran larvae have been identified, and either E. maimaiga is unable to penetrate the cuticle or the fungus cannot survive within the hemocoel. In the latter case, although E. maimaiga grows as protoplasts lacking cell walls in the host hemolymph, glycoproteins on plasma membranes of the protoplasts could lead to host recognition. Epizootiological studies demonstrate a clear association between fungal activity and environmental moisture but little association with host density under hypothesized conditions of high fungal density. Prediction of the occurrence of epizootics is not yet possible. E. maimaiga is easily established in new areas by releasing azygospores, but the ability to use this pathogen further for biological control will depend, in large part, on the development of mass production systems.
Rectosigmoid carcinoma presenting as full-thickness rectal prolapse
Authors: Montwedi Daniel
Published: December 2019

A 34-year-old man with recent-onset constipation presented with colonic obstruction due to a palpable rectal tumour. Colostomy relieved the obstruction and biopsy revealed carcinoma. During workup, full-thickness rectal prolapse occurred with the tumour at the apex of an intussusception. Imaging revealed a low rectal tumour and no metastases. An abdominal oncological rather than perineal resection of the rectum was planned. At laparotomy, the tumour was reduced and was seen to originate at the rectosigmoid junction. Surgery was successful and follow-up has been clear. Histology revealed an adenocarcinoma with microsatellite instability. Rectal prolapse due to tumour intussusception is very rare. In this young man, it was due to straining at stool because of constipation and tenesmus rather than pelvic floor abnormality. An associated colorectal tumour should be considered in patients with rectal prolapse. In such cases, surgical and adjuvant management may need to be modified.
Acute cerebellar ataxia due to Epstein-Barr virus under administration of an immune checkpoint inhibitor
Authors: Saikawa Hirotaka , Nagashima Hiromi , Maeda Tetsuya , Maemondo Makoto
Published: December 2019

A 71-year-old male patient with adenocarcinoma of the lung and contralateral lung metastasis under administration of pembrolizumab had symptoms of cerebellar ataxia. We suspected that the symptoms were immune-related adverse events (irAE), but the patient was subsequently diagnosed as cerebellitis due to Epstein-Barr virus (EBV) infection. After steroid pulse therapy, the symptoms of cerebellar ataxia improved immediately. Immune checkpoint inhibitors (ICI) can induce neurological adverse events and cause acute cerebellar ataxia. Initially, irAEs were suspected in this case. His clinical data suggested that reactivation of the virus had occurred because the ICI affected his immune system. This is the first report of a case of acute cerebellar ataxia due to EBV under administration of an ICI.
More than 80% of total knee replacements can last for 25 years
Authors: Cook Rob , Davidson Peter , Martin Rosie
Published: December 2019

The study

Evans JT, Walker R, Evans W, Blom AW, Sayers A, Whitehouse MR

How long does a knee replacement last? A systematic review and meta-analysis of case series and national registry reports with more than 15 years of follow-up.

Published on 16 February 2019 Lancet 2019;393:655-63

This study was supported by the NIHR Biomedical Research Centre at the University Hospitals Bristol NHS Foundation Trust and the University of Bristol.

To read the full NIHR Signal, go to: https://discover.dc.nihr.ac.uk/content/signal-000776/more-than-80-of-total-knee-replacements-can-last-for-25-years
Medically assisted gender affirmation: when children and parents disagree
Authors: Dubin Samuel , Lane Megan , Morrison Shane , Radix Asa , Belkind Uri , Vercler Christian , Inwards-Breland David
Published: December 2019

Institutional guidelines for transgender children and adolescent minors fail to adequately address a critical juncture of care of this population: how to proceed if a minor and their parents have disagreements concerning their gender-affirming medical care. Through arguments based on ethical, paediatric, adolescent and transgender health research, we illustrate ethical dilemmas that may arise in treating transgender and gender diverse youth. We discuss three potential avenues for providing gender-affirming care over parental disagreement: legal carve-outs to parental consent, the mature minor doctrine and state intervention for neglect. Our discussion approaches this parent–child disagreement in a manner that prioritises the developing autonomy of transgender youth in the decision-making process surrounding medically assisted gender affirmation. We base our arguments in the literature surrounding the risks and benefits of gender-affirming therapy in transgender children and the existing legal basis for recognising minors’ decision-making authority in certain medical situations.
Endothelial nitric oxide synthase activation is required for heparin receptor effects on vascular smooth muscle cells
Authors: Li Yaqiu , Talotta-Altenburg Leanna M. , Silimperi Kayli A. , Ciabattoni Grace O. , Lowe-Krentz Linda J.
Published: December 2019

Published studies indicate that TMEM184A is a heparin receptor that interacts with and transduces stimulation from heparin in vascular cells. Previous studies have indicated that heparin increases endothelial nitric oxide synthase (eNOS) activity in bovine endothelial cells. However, the precise mechanism remains unknown. In this study, we investigated the impact of heparin treatment and TMEM184A on eNOS’s activation and the role of eNOS in heparin signaling in the cloned A7r5 rat vascular smooth muscle cell line and confirmed results in endothelial cells. We employed a combination of TMEM184A knockdown A7r5 cells along with transient eNOS knockdown and enzyme inhibitor strategies. The results indicate that heparin induces phosphorylation of eNOS. eNOS can be immunoprecipitated with TMEM184A and is internalized to the perinuclear region in a TMEM184A-dependent manner in response to heparin. We also examined how heparin treatment leads to phosphorylation of eNOS and confirmed that TMEM184A and Ca2+ were required to mediate heparin-elicited eNOS phosphorylation. Evidence supporting the involvement of transient receptor potential cation channel subfamily V member 4 with TMEM184A in this eNOS activation process is also presented.
Seven-day overfeeding enhances adipose tissue dietary fatty acid storage and decreases myocardial and skeletal muscle dietary fatty acid partitioning in healthy subjects
Authors: Noll Christophe , Montastier Émilie , Amrani Mehdi , Kunach Margaret , Frisch Frédérique , Fortin Mélanie , Bouffard Lucie , Dubreuil Stéphanie , Phoenix Serge , Cunnane Stephen C. , Guérin Brigitte , Turcotte Eric E. , Laville Martine , Carpentier André C.
Published: December 2019

Increased myocardial partitioning of dietary fatty acids (DFA) and decreased left ventricular (LV) function is associated with insulin resistance in prediabetes. We hypothesized that enhanced myocardial DFA partitioning and reduced LV function might be induced concomitantly with reduced insulin sensitivity upon a 7-day hypercaloric (+50% in caloric intake), high-saturated fat (~11%energy), and simple carbohydrates (~54%energy) diet (HIGHCAL) versus an isocaloric diet (ISOCAL) with a moderate amount of saturated fat (~8%energy) and carbohydrates (~50%energy). Thirteen healthy subjects (7 men/6 women) underwent HIGHCAL versus ISOCAL in a randomized crossover design, with organ-specific DFA partitioning and LV function measured using the oral 14( R,S)-[18F]fluoro-6-thia-heptadecanoic acid and [11C]acetate positron emission tomography methods at the end of both interventions. HIGHCAL induced a decrease in insulin sensitivity indexes with no significant change in body composition. HIGHCAL led to increased subcutaneous abdominal (+4.2 ± 1.6%, P < 0.04) and thigh (+2.4 ± 1.2%, P < 0.08) adipose tissue storage and reduced cardiac (−0.31 ± 0.11 mean standard uptake value [(SUV), P < 0.03] and skeletal muscle (−0.17 ± 0.08 SUV, P < 0.05) DFA partitioning without change in LV function. We conclude that early increase in adipose tissue DFA storage protects the heart and skeletal muscles from potential deleterious effects of DFA.
Decreased amplitude and reliability of odor-evoked responses in two mouse models of autism
Authors: Geramita Matthew A. , Wen Jing A. , Rannals Matthew D. , Urban Nathan N.
Published: December 2019

Sensory processing deficits are increasingly recognized as core symptoms of autism spectrum disorders (ASDs). However the molecular and circuit mechanisms that lead to sensory deficits are unknown. We show that two molecularly disparate mouse models of autism display similar deficits in sensory-evoked responses in the mouse olfactory system. We find that both Cntnap2- and Shank3-deficient mice of both sexes exhibit reduced response amplitude and trial-to-trial reliability during repeated odor presentation. Mechanistically, we show that both mouse models have weaker and fewer synapses between olfactory sensory nerve (OSN) terminals and olfactory bulb tufted cells and weaker synapses between OSN terminals and inhibitory periglomerular cells. Consequently, deficits in sensory processing provide an excellent candidate phenotype for analysis in ASDs.

NEW & NOTEWORTHY The genetics of autism spectrum disorder (ASD) are complex. How the many risk genes generate the similar sets of symptoms that define the disorder is unknown. In particular, little is understood about the functional consequences of these genetic alterations. Sensory processing deficits are important aspects of the ASD diagnosis and may be due to unreliable neural circuits. We show that two mouse models of autism, Cntnap2- and Shank3-deficient mice, display reduced odor-evoked response amplitudes and reliability. These data suggest that altered sensory-evoked responses may constitute a circuit phenotype in ASDs.
Oxytocin increases inhibitory synaptic transmission and blocks development of long-term potentiation in the lateral amygdala
Authors: Crane J. W. , Holmes N. M. , Fam J. , Westbrook R. F. , Delaney A. J.
Published: December 2019

Oxytocin (OT) is a neuroactive peptide that influences the processing of fearful stimuli in the amygdala. In the central nucleus of the amygdala, the activation of OT receptors alters neural activity and ultimately suppresses the behavioral response to a fear conditioned stimulus. Receptors for OT are also found in the lateral amygdala (LA), and infusion of OT into the basolateral amygdala complex affects the formation and consolidation of fear memories. Yet, how OT receptor activation alters neurons and neural networks in the LA is unknown. In this study we used whole cell electrophysiological recordings to determine how OT-receptor activation changes synaptic transmission and synaptic plasticity in the LA of Sprague-Dawley rats. Our results demonstrate that OT-receptor activation results in a 200% increase in spontaneous inhibitory transmission in the LA that leads to the activation of presynaptic GABAB receptors. The activation of these receptors inhibits excitatory transmission in the LA, blocking long-term potentiation of cortical inputs onto LA neurons. Hence, this study provides the first demonstration that OT influences synaptic transmission and plasticity in the LA, revealing a mechanism that could explain how OT regulates the formation and consolidation of conditioned fear memories in the amygdala.

NEW & NOTEWORTHY This study investigates modulation of synaptic transmission by oxytocin (OT) in the lateral amygdala (LA). We demonstrate that OT induces transient increases in spontaneous GABAergic transmission by activating interneurons in the basolateral amygdala. The resultant increase in GABA release in the LA activates presynaptic GABAB receptors on both inhibitory and excitatory inputs onto LA neurons, reducing release probability at these synapses. We subsequently demonstrate that OT modulates synaptic plasticity at cortical inputs to the LA.
Studies on the Mechanism of Glutamate Metabolism in NTG-Induced Migraine Rats Treated with DCXF
Authors: Ni Ni , Wang Qingqing , Lin Xiao , Hong Yanlong , Feng Yi , Shen Lan
Published: December 2019

Objective. To explore the mechanism of the antimigraine effect by active components extracted from the Dachuanxiong prescription (DCXF), nitroglycerin- (NTG-) induced migraine rats were used to detect the change of glutamate metabolism and the overall metabolic profile at different time points in the serum and Trigeminocervical complex(TCC) samples.Method. The biological samples that were obtained at 30 minutes, 60 minutes, and 90 minutes after model establishment or drug administration were tested by GC-TOF-MS. Then, real-time PCR and western blot were applied to detect changes in the expression of some substances involved in glutamate metabolism.Result. DCXF could improve the metabolic profile of serum and TCC in migraine rats and showed the time trend of treatment, mainly involved by amino acid metabolism (glutamate, aspartic acid, and alanine metabolism). In addition, DCXF could increase the expressions of GS at 60 min and 90 min and EAAT1 at 90 min. The results of GS protein were similar to that of mRNA.Conclusion. The antimigraine effect of DCXF could be achieved by improving the metabolic profile and increasing the expressions of GS and EAAT1 to promote the glutamate cycle of TCC and serum samples in NTG-induced migraine rats to a certain extent.
Sensor-Based Weightlifting Workout Assisting System Design and Its Practical Implementation
Authors: Luzar Marcel , Czajkowski Andrzej , Kasperowicz Rafał , Rot Maciej , Semegen Mateusz , Korbicz Józef
Published: December 2019

The paper is devoted to the problem of counting repetitions and automatic weight stack detection in a weightlifting machine used for weight training. Some weightlifting machines include a weight stack that can be adjusted by a user. For example, the user can choose to increase or reduce the weight load using the weight stack, thus changing the difficulty level of a particular exercise. Users may want to perform a desired number of repetitions of an exercise or to perform an exercise with a desired range of motion when using such weightlifting machines. From a medical point of view, it is often required that an exact number of repetitions of a given load are performed in order to aid in a prompt recovery. This paper describes a complete design of the system and the algorithm that allows one to collect data from such a machine. Data can then be used for various purposes: in overviews and statistical analysis of a number of workouts. The approach presented in this paper is part of an application for European patent number 18461537.5-1126.
Chemokine and Cytokine Cascade Caused by Skewing of the Th1-Th2 Balance Is Associated with High Intracranial Pressure in HIV-Associated Cryptococcal Meningitis
Authors: Xu Lijun , Guo Yongzheng , Zhao Yizhou , Xu Yufan , Peng Xiuming , Yang Zongxing , Tao Ran , Huang Ying , Xu Yan , Chen Yaokai , Zhu Biao
Published: December 2019

Purpose. Serum cytokines/chemokines play important roles in cryptococcal meningitis, but it is unclear whether cytokines/chemokines in cerebrospinal fluid (CSF) contribute to high intracranial pressure (HICP) in HIV-associated cryptococcal meningitis (HCM). Methods. CSF cytokines/chemokines were assayed in 17 HIV-uninfected patients, 26 HIV-infected patients without CNS infection, and 39 HCM patients at admission. Principal component analysis and correlation and logistic regression analyses were used to assess the relationships between these parameters. Results. The CSF Th1, Th2, and macrophage cytokines showed an obvious increase in HCM patients as compared to the HIV-uninfected patients and HIV-infected patients without CNS infection. CSF IL-6, GM-CSF, and IL-8 were positively correlated with CSF fungal burden. Serum CD4 count, CSF Th1 cytokines (TNF-α, TNF-β, IL-12, IL-1β, and INF-α2), and Th2 cytokines (IL-5 and IL-6) were closely related to cryptococcal meningitis. Furthermore, both Th1 cytokines (TNF-α, TNF-β, INF-γ, and IL-12) and Th2 cytokines (IL-4 and IL-10) contribute to HICP. Conclusion. Overall, the present findings indicated that both pro- and anti-inflammatory cytokines of Th1, Th2, and macrophage origin contributed to the development of HCM. Specifically, the chemokine and cytokine cascade caused by skewing of the Th1-Th2 balance and reduced CD4 count were found to be important contributors to HICP. Summary. Our research suggested that chemokine and cytokine cascade caused by skewing of the Th1-Th2 balance in HIV-infected patients played more important role than Cryptococcus numbers and size in CSF on the development of high intracranial pressure in HIV-associated cryptococcal meningitis, providing a new understanding of mechanisms of HCM.
Primary Myiasis in Surgical Wound of Mandible Symphisis Fracture
Authors: Lauand Gustavo A. , Lima Felipe G. G. P. , da Silva Ricardo P. , Santiago Larissa Rodrigues , Dantas Jonas B. , Silva Cláudia J. , Furtado Lair M.
Published: December 2019

A 42 year old patient was referred to the Department of Oral and Maxillofacial Surgery of the Federal University of Uberlândia, for treatment of mandibular fractures (condyles and symphysis), a victim of a run over. The symphysis was surgically approached, using as surgical access the pre-existing laceration in the submental region. Five days after discharge, the patient returned with dehiscence of the wound and physical examination showed infestation by larvae in the symphysis. Mechanical removal and debridement were performed under local anesthesia, where plate exposure was noted. The patient underwent oral ivermectin therapy, intravenous antibiotic therapy and a thorough debridement was performed under general anesthesia due to the invasion of deep spaces in the supra-hyoid region. After 2 weeks, it presented with purulent drainage at the site. The miniplates were replaced by a 2.4 mm reconstruction plate and antibiotic therapy was maintained. Due to the social risk, the patient remained hospitalized for 45 days, when he was discharged with outpatient return, but did not attend the returns.
Interlayer Working Conditions Classification and Treatment Measures of Airport Asphalt Pavement Overlay
Authors: Ye Hongyu , Wang Xuancang , Fang Naren , Su Ziyuan , Sun Xiaowen
Published: December 2019

The bonding strength between the overlays of an airport asphalt pavement directly affects its service life. In this study, a finite element model of asphalt overlay on airport pavement of Juba Airport in South Sudan was established, and the elastic modulus of overlay, thickness of overlay, running state of aircraft, variation trend of interlayer shear stress under the action of load and temperature were obtained. The AHP-entropy method was used to calculate the combined weight of each influencing factor. The climate in hot and humid areas was further zoned, and a comprehensive classification of airport asphalt pavement overlay between hot and humid tropics was obtained. Four interlayer treatment measures (asphalt precoating, two oils and one aggregate, geotextile, and geogrid) and three interlayer materials (SBS-modified asphalt, ordinary hot asphalt, and SBS-modified emulsified asphalt) were designed and tested. Through shear test, wheel-load fatigue test, and pressurized seepage test, the variation trends of interlayer shear, crack resistance, and waterproofing under different combination schemes were obtained. Finally, the matching relationship between different working conditions and interlayer treatment measures was established. The results show that the actual working conditions of an airport asphalt pavement can be divided into three levels. Combined with the performance ranking of different materials and interlayer treatment measures, the recommended interlayer treatment measures for comprehensive classifications I, II, and III are two oils and one material + SBS-modified asphalt, asphalt precoating, or geogrid + SBS-modified emulsified asphalt or ordinary hot asphalt, and geotextile + ordinary hot asphalt, respectively. The working conditions in Juba Airport in South Sudan can be classified as comprehensive classification II, the recommended treatment measures for geogrid + ordinary hot asphalt.
Iconografia musical na obra de Henri Rousseau
Authors: Lima Andrei Fernando Ferreira
Published: December 2019

Número significativo de artistas, teóricos da música e historiadores da arte exploraram a diversidade e complexidade dos nexos entre pintura e música ao longo dos séculos. No domínio das artes visuais, as referências à música são abundantes, ganhando expressão tanto pelos temas iconográficos quanto pela reflexão sobre os fundamentos da linguagem musical (ritmo, harmonia, cromatismo). A partir das analogias e interferências entre as duas formas de expressão, propomos uma leitura crítica desse fenômeno na obra de Henri Rousseau, artista francês que desenvolveu uma iconografia particular inspirada no assunto, através da qual explora as possibilidades de representação pictórica da música, tendo em vista efeitos de sentido integrados às suas narrativas visuais.
O humanismo oriental de Adeodato Barreto e o contexto político internacional dos anos 30
Authors: Vecchi Lucas Henrique Lima , Braga Duarte Nuno Drumond
Published: December 2019

Civilização hindu, do ensaísta goês Adeodato Barreto no ano de 1935, além de ser uma apresentação ao público português da civilização milenar indiana, foca a “Nova Índia”, renascida para a luta anticolonial de Gandhi e de Tagore. Possui referências a um vasto panorama internacional dos anos 30, passando pelos fascismos, pelo colonialismo europeu e, implicitamente, pelo salazarismo português. O objetivo deste texto é mostrar como o seu discurso de defesa da Índia se relaciona com uma crítica ao fascismo, ao totalitarismo e ao colonialismo. Para esse efeito exploraremos também a concepção de humanismo oriental enquanto forma de indianismo goês.
Doubly Robust Estimation of Causal Effect
Authors: Li Xiaochun , Shen Changyu
Published: December 2019

Propensity score–based methods or multiple regressions of the outcome are often used for confounding adjustment in analysis of observational studies. In either approach, a model is needed: A model describing the relationship between the treatment assignment and covariates in the propensity score–based method or a model for the outcome and covariates in the multiple regressions. The 2 models are usually unknown to the investigators and must be estimated. The correct model specification, therefore, is essential for the validity of the final causal estimate. We describe in this article a doubly robust estimator which combines both models propitiously to offer analysts 2 chances for obtaining a valid causal estimate and demonstrate its use through a data set from the Lindner Center Study.
ATAERKİL SÖYLEMİN MEDYADAKİ İZDÜŞÜMÜ: RİNSO REKLAM FİLMİ ÜZERİNE BİR İNCELEME
Authors: HEKİMOĞLU Gülsüm
Published: December 2019

Toplumsal sınıf ayrımcılığından ve ırk ayrımcılığından daha örtülü ve daha
ısrarlı şekilde devam eden toplumsal cinsiyet ayrımcılığı, insan ilişkilerinin
‘doğal’ ve ‘değiştirilemez’ bir parçası gibi sunulmaktadır. Bu sunumun en
etkili yollarından biri kitle iletişim araçlarıdır. Cinsiyete yönelik
stereotiplere ve toplumsal cinsiyetin yüklediği rollere en çok rastlanılan
medya görüngülerinden biri de reklamlardır. Bu nedenle reklamların toplumsal
cinsiyet üzerine etkisiyle ilgili pek çok araştırma yapılmıştır. Bu çalışmada
ise Rinso gibi küresel markalı bir temizlik ürününün Türkiye’deki reklam filmi
tartışılmıştır. İncelenen reklam filmi van Dijk’in ideolojik söylem analizi
yöntemiyle çözümlenmiştir. Bu tarz ideolojik anlatımlar kitle iletişim kodları
üzerinden kurumsallaşmaktadır. İncelenen reklam filminde, toplumsal cinsiyete
bağlı rollerin temizlik ürünlerinin imajlarıyla ilişkilendirilerek verildiği görülmüştür.
Yemek yapan, çocuk bakan, tüketen, kıskanan halleriyle temsil edilen ve
karikatürize edilen kadın imajı, ataerkil bakış açısının desteklediği sanrısal
algıyı beslemiştir.