Histone-acetylation: a link between Alzheimer's disease and post-traumatic stress disorder?

The orchestration of gene-expression programs is essential for cellular homeostasis. Epigenetic processes provide to the cell a key mechanism that allows the regulation of gene-expression networks in response to environmental stimuli. Recently epigenetic mechanisms such as histone-modifications have been implicated with cognitive function and altered epigenome plasticity has been linked to the pathogenesis of neurodegenerative and neuropsychiatric diseases. Thus, key regulators of epigenetic gene-expression have emerged as novel drug targets for brain diseases. Numerous recent review articles discuss in detail the current findings of epigenetic processes in brain diseases. The aim of this article is not to give yet another comprehensive overview of the field but to specifically address the question why the same epigenetic therapies that target histone-acetylation may be suitable to treat seemingly different diseases such as Alzheimer's disease and post-traumatic stress disorder

Campylobacter jejuni infection of conventionally colonized mice lacking nucleotide-oligomerization-domain-2

Background The nucleotide-binding oligomerisaton protein 2 (NOD2) constitutes a pivotal sensor of bacterial muramyl dipeptide and assures expression of distinct antimicrobial peptides and mediators produced by enterocytes and immune cells directed against pathogens including Campylobacter jejuni. We here elucidated the role of NOD2 during murine C. jejuni infection in more detail. Results Conventionally colonized NOD2 deficient (NOD2−/−) mice and corresponding wildtype (WT) counterparts were perorally infected with C. jejuni strain 81–176 on three consecutive days. The pathogen colonized both WT and NOD2−/− mice only sporadically until day 14 post infection (p.i.). However, the slightly higher prevalence of C. jejuni in NOD2−/− mice was accompanied by higher intestinal Escherichia coli loads known to facilitate C. jejuni colonization. Neither overt macroscopic (clinical) nor microscopic sequelae (such as colonic epithelial apoptosis) could be observed upon murine C. jejuni infection of either genotype. Innate immune responses were less distinctly induced in C. jejuni infected NOD2−/− versus WT mice as indicated by lower colonic numbers of neutrophils in the former. Conversely, adaptive immune cell counts including T lymphocytes were higher in large intestines of NOD2−/− as compared to WT mice that were paralleled by increased colonic IL-6 secretion and higher TNF and IL-18 mRNA expression levels in large intestines of the former. Only in NOD2−/− mice, however, colonic IL-22 mRNA expression was down-regulated at day 14 p.i. Whereas viable commensal intestinal bacteria could exclusively be detected in mesenteric lymph nodes and livers of NOD2−/− mice, bacterial translocation rates to kidneys and spleen were NOD2 independent. Notably, large intestinal mRNA expression levels of mucin-2, constituting a pivotal factor involved in epithelial barrier integrity, were comparable in naive and C. jejuni infected mice of either genotype. Conclusion NOD2 is involved in the well-balanced regulation of innate and adaptive pro- inflammatory immune responses of conventional mice upon C. jejuni infection

Canine vaccination in Germany: A survey of owner attitudes and compliance

Background: Vaccination is the most important preventive measure for protection against infectious diseases in humans and companion animals. Nevertheless, scepticism about the safety and importance of vaccines is increasing in human and in veterinary medicine. Although owner attitudes towards vaccination have been investigated in cats, there are no similar studies in dogs. The goals of this study were therefore to investigate the vaccination status of dogs in Germany, to determine owner compliance with vaccination and to identify factors that play a role in owners' decisions to have their dogs vaccinated. Methods Data were collected from August 2018 to February 2019 using an online survey targeting dog owners in Germany. A total of 3,881 questionnaires were evaluated, and factors associated with the vaccination status of dogs were determined by a linear logistic regression model using Akaike information criterion. Cohen's kappa statistic was used to evaluate agreement between questionnaire and 340 vaccination passports submitted voluntarily by owners. Results: A total of 46.8% (n = 1,818/3,881) of dogs were vaccinated with core vaccines according to current guidelines with the lowest vaccination rate for leptospirosis (50.1%;n = 1,941/3,874). Dog's age (16 weeks to 15 months) (odds ratio (OR): 3.08;95% CI: 2.05-4.68), type (working dog) (OR: 2.06;95% CI: 1.22-3.53) and travelling abroad within previous 36 months (OR: 1.82;95% CI: 1.12-2.96) had the strongest 'positive' association with the vaccination status. Recommendation from a veterinarian not to vaccinate against leptospirosis had the strongest 'negative' association (OR: 0.08;95% CI: 0.04-0.18). Conclusion The study revealed a need for improvement in vaccination compliance because of inadequate vaccination coverage, especially for leptospirosis, in dogs. Factors influencing owner compliance were numerous. Vaccination recommendations made by the veterinarian had a strong association with the vaccination status and should be used to increase canine vaccination rates

Hashtags em curadorias transmídia para festivais de cinema e a experiência do MixBrasil

A partir das mudanças de comportamento de espectadores de filmes e festivais de cinema relacionados à pandemia, informações sobre conteúdos dos eventos passaram a ser fornecidos quase exclusivamente de forma digital. O uso de hashtags tem como objetivo facilitar a navegação e aumentar engajamento de espectadores de festivais de cinema em plataformas digitais. Para curadores de festivais oferece o desafio de pensar em novos eixos para programação incluindo diferentes mídias além do que tradicionalmente é chamado cinema, como séries e espetáculos teatrais que passaram a ser concebidos para exibição digital. O Festival MixBrasil iniciou processo de introdução de hashtags na informação de toda programação com objetivo de fazer através delas a convergência de diferentes linguagens e formatos

Interleukin-18 Mediates Immune Responses to Campylobacter jejuni Infection in Gnotobiotic Mice

Background Human Campylobacter jejuni infections are progressively rising worldwide. Information about the molecular mechanisms underlying campylobacteriosis, however, are limited. In the present study we investigated whether cytokines such as IL-23, IL-22 and IL-18, which share pivotal functions in host immunity, were involved in mediating intestinal and systemic immunopathological responses upon C. jejuni infection. Methodology/Principal Findings To assure stable infection, gnotobiotic (i.e. secondary abiotic) IL- 23p19-/-, IL-22-/- and IL-18-/- mice were generated by broad-spectrum antibiotic treatment. Following peroral C. jejuni strain 81–176 infection, mice of all genotypes harbored comparably high pathogenic loads in their intestines. As compared to wildtype controls, however, IL-18-/- mice displayed less distinct C. jejuni induced sequelae as indicated by less pronounced large intestinal shrinkage and lower numbers of apoptotic cells in the colonic epithelial layer at day 8 postinfection (p.i.). Furthermore, lower colonic numbers of adaptive immune cells including regulatory T cells and B lymphocytes were accompanied by less distinct secretion of pro-inflammatory cytokines such as TNF and IFN-γ and lower IL-17A mRNA expression levels in colonic ex vivo biopsies of infected IL-18-/- as compared to wildtype mice. Upon C. jejuni infection, colonic IL-23p19 expression was up-regulated in IL-18-/- mice only, whereas IL-22 mRNA levels were lower in uninfected and infected IL-23p19-/- as well as infected IL-18-/- as compared to respective wildtype control mice. Remarkably, not only intestinal, but also systemic infection-induced immune responses were less pronounced in IL-18-/- mice as indicated by lower TNF, IFN-γ and IL-6 serum levels as compared to wildtype mice. Conclusion/Significance We here show for the first time that IL-18 is essentially involved in mediating C. jejuni infection in the gnotobiotic mouse model. Future studies need to further unravel the underlying regulatory mechanisms orchestrating pathogen-host interaction

Immune responses upon Campylobacter jejuni infection of secondary abiotic mice lacking nucleotide-oligomerization-domain-2

Background Campylobacter jejuni infections are of rising importance worldwide. Given that innate immune receptors including nucleotide-oligomerization- domain-2 (Nod2) are essentially involved in combating enteropathogenic infections, we here surveyed the impact of Nod2 in murine campylobacteriosis. Methods and results In order to overcome physiological colonization resistance preventing from C. jejuni infection, we generated secondary abiotic Nod2−/− and wildtype (WT) mice by broad-spectrum antibiotic treatment. Mice were then perorally infected with C. jejuni strain 81-176 on 2 consecutive days and could be stably colonized by the pathogen at high loads. Notably, Nod2 deficiency did not affect gastrointestinal colonization properties of C. jejuni. Despite high intestinal pathogenic burdens mice were virtually uncompromised and exhibited fecal blood in single cases only. At day 7 postinfection (p.i.) similar increases in numbers of colonic epithelial apoptotic cells could be observed in mice of either genotype, whereas C. jejuni infected Nod2−/− mice displayed more distinct regenerative properties in the colon than WT controls. C. jejuni infection was accompanied by increases in distinct immune cell populations such as T lymphocytes and regulatory T cells in mice of either genotype. Increases in T lymphocytes, however, were less pronounced in large intestines of Nod2−/− mice at day 7 p.i. when compared to WT mice, whereas colonic numbers of B lymphocytes were elevated in WT controls only upon C. jejuni infection. At day 7 p.i., colonic pro-inflammatory mediators including nitric oxide, TNF, IFN-γ and IL-22 increased more distinctly in Nod2−/− as compared to WT mice, whereas C. jejuni induced IL-23p19 and IL-18 levels were lower in the large intestines of the former. Converse to the colon, however, ileal concentrations of nitric oxide, TNF, IFN-γ, IL-6 and IL-10 were lower in Nod2−/− as compared to WT mice at day 7 p.i. Even though MUC2 was down-regulated in C. jejuni infected Nod2−/− mice, this did not result in increased pathogenic translocation from the intestinal tract to extra-intestinal compartments. Conclusion In secondary abiotic mice, Nod2 signaling is involved in the orchestrated host immune responses upon C. jejuni infection, but does not control pathogen loads in the gastrointestinal tract

O processo e organização do trabalho na agroindústria canavieira

Este estudo se propõe a refletir sobre a organização do processo de trabalho em um setor de "ponta" da agricultura paulista: a agroindústria canavieira, setor este onde se processam transformações de cunho tecnológico que interferem estruturalmente nos padrões vigentes de relações de trabalho. Na perspectiva adotada, estes três temas: organização do trabalho, relações de trabalho e tecnologia se encontram imbicados em um eixo principal, o qual norteia as transformações processadas no setor

Anomalous impact and strain responses in helical carbon nanotube foams

We describe the quasistatic and dynamic response of helical carbon nanotube (HCNT) foams in compression. Similarly to other CNT foams, HCNT foams exhibit preconditioning effects in response to cyclic loading; however, their fundamental deformation mechanisms are unique. In quasistatic compression, HCNT foams exhibit strain localization and collective structural buckling, nucleating at different weak sections throughout their thickness. In dynamic compression, they undergo progressive crushing, governed by the intrinsic density gradient along the thickness of the sample. HCNT micro-bundles often undergo brittle fracture that originates from nanoscale defects. Regardless of this microstructural damage, bulk HCNT foams exhibit super-compressibility and recover more than 90% of large compressive strains (up to 80%). When subjected to striker impacts, HCNT foams mitigate impact stresses more effectively compared to other CNT foams comprised of non-helical CNTs ([similar]50% improvement). The unique mechanical properties we revealed demonstrate that the HCNT foams are ideally suited for applications in packaging, impact protection, and vibration mitigation