Luminal Ca2+ depletion during the unfolded protein response in Xenopus oocytes: Cause and consequence

The endoplasmic reticulum (ER) is a Ca2+ storing organelle that plays a critical role in the synthesis, folding and post-translational modifications of many proteins. The ER enters into a condition of stress when the load of newly synthesized proteins exceeds its folding and processing capacity. This activates a signal transduction pathway called the unfolded protein response (UPR) that attempts to restore homeostasis. The precise role of ER Ca2+ in the initiation of the UPR has not been defined. Specifically, it has not been established whether ER Ca2+ dysregulation is a cause or consequence of ER stress. Here, we report that partial depletion of ER Ca2+ stores induces a significant induction of the UPR, and leads to the retention of a normally secreted protein Carboxypeptidase Y. Moreover, inhibition of protein glycosylation by tunicamycin rapidly induced an ER Ca2+ leak into the cytosol. However, blockade of the translocon with emetine inhibited the tunicamycin-induced Ca2+ release. Furthermore, emetine treatment blocked elF2α phosphorylation and reduced expression of the chaperone BiP. These findings suggest that Ca2+ may be both a cause and a consequence of ER protein misfolding. Thus, it appears that ER Ca2+ leak is a significant co-factor for the initiation of the UPR.Fil: Paredes, R. Madelaine. University of Texas; Estados UnidosFil: Bollo, Mariana Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaFil: Holstein, Deborah. University of Texas; Estados UnidosFil: Lechleiter, James D.. University of Texas; Estados Unido

Neuromyelitis optica spectrum disorders associated with systemic sclerosis: a case report and literature review

Neuromyelitis optica (NMO) is an autoimmune demyelinating disease of the central nervous system (CNS) afecting predominantly the spinal cord, brainstem, and optic nerves [1]. NMOSD may be associated with a variety of immunemediated disorders, such as systemic lupus erythematosus, Sjögren syndrome, and other organ-specifc autoimmune diseases [2], though accurate information about their prevalence is not available [3]. Systemic sclerosis (SSc) is characterized by vascular alterations, activation of the immune system, and tissue fbrosis [4]. Only a few cases of coexisting systemic sclerosis (SSc) and NMOSD are described [1, 5–9]. We report a case of an NMOSD AQP4-IgG antibodypositive patient associated with SSc and a review of the available evidence of the relationship between these autoimmune disease

Las estadísticas demográfico sanitarias del peronismo: indicios y evidencias sobre su producción y sus aplicaciones político-burocráticas (1944-1955)

Las discusiones sobre el desempeño de las políticas públicas del peronismo clásico han tenido una renovación de preguntas, gracias a una serie de autores que precisaron las intenciones y los alcances de los discursos políticos. Existió entonces una sociodicea cohesionadora de la nueva elite en el poder, alrededor de políticas ultraexpansivas, cuya cara más visible fueron las iniciativas del Consejo Nacional de Posguerra (1944-1946), que continuaron con los dos planes quinquenales (1947-1951 y 1953-1957), dirigidos de forma sucesiva por la Secretaría Técnica (1946-1949), el Ministerio de Asuntos Técnicos (1949-1954) y la Secretaría de Asuntos Técnicos (1954-1955)…Fil: Salvatore, Ricardo D.. Universidad Torcuato Di Tella; ArgentinaFil: González Bollo, Hernán Gustavo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Instituto de Geografía, Historia y Ciencias Sociales. Universidad Nacional del Centro de la Provincia de Buenos Aires. Instituto de Geografía, Historia y Ciencias Sociales; ArgentinaXIV Jornadas Interescuelas-Departamentos de HistoriaMendozaArgentinaUniversidad Nacional de Cuyo. Facultad de Filosofía y Letras. Departamento de Histori

A New Kind of Quinonic-Antibiotic Useful Against Multidrug-Resistant S. aureus and E. faecium Infections

Indexación: Scopus.A rapid emergence of resistant bacteria is occurring worldwide, endangering the efficacy of antibiotics and reducing the therapeutic arsenal available for treatment of infectious diseases. In the present study, we developed a new class of compounds with antibacterial activity obtained by a simple, two step synthesis and screened the products for in vitro antibacterial activity against ATCC® strains using the broth microdilution method. The compounds exhibited minimum inhibitory concentrations (MIC) of 1⁻32 μg/mL against Gram-positive ATCC® strains. The structure⁻activity relationship indicated that the thiophenol ring is essential for antibacterial activity and the substituents on the thiophenol ring module, for antibacterial activity. The most promising compounds detected by screening were tested against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecium (VREF) clinical isolates. We found remarkable activity against VREF for compounds 7 and 16, were the MIC50/90 were 2/4 µg/mL and 4/4 µg/mL, respectively, while for vancomycin the MIC50/90 was 256/512 µg/mL. Neither compound affected cell viability in any of the mammalian cell lines at any of the concentrations tested. These in vitro data show that compounds 7 and 16 have an interesting potential to be developed as new antibacterial drugs against infections caused by VREF.https://www.mdpi.com/1420-3049/23/7/177

Comparative clinico-pathological observations in young Zebu (Bos indicus) cattle experimentally infected with Trypanosoma vivax isolates from tsetse infested and non-tsetse infested areas of Northwest Ethiopia

BACKGROUND: The Northwest region of Ethiopia is affected by both tsetse and non-tsetse transmitted trypanosomosis with a huge impact on livestock productivity. The objective of this experimental study was to determine clinical and pathological findings in young Zebu cattle experimentally infected with Trypanosoma vivax isolates from tsetse infested and non-tsetse infested areas of Northwest Ethiopia. A total of 18 cattle (Bos indicus) aged between 6 and 12 months, purchased from a trypanosome-free and confirmed to be trypanosome negative divided into three groups of six animals were used. Animals in the first two groups (Group TT: tsetse infested isolate infected and Group NT: non-tsetse infested isolate infected) received 2 mL of infected blood from donor animals at 10(6) trypanosomes/mL, and the remaining group was non-infected control (NIC). Each group was observed for a period of eight consecutive weeks, daily for clinical signs and once per week for parasitaemia. Postmortem examinations were done on euthanized animals, and tissue samples were taken for histopathological analysis. RESULTS: The prepatent period of the disease was earlier in the NT group 6 days post infection (dpi) than TT group 12 dpi. The infection was characterized by reduced feed intake, intermittent pyrexia and parasitaemia, enlarged lymph nodes, lacrimation, reduced feed intake and emaciation. Less frequently diarrhea, oedema and nervous signs were observed in both groups of infected animals. At necropsy, infected animals showed enlarged spleen, enlarged lymph nodes, pneumonic and emphysematous lung, enlarged liver, and haemorrhages on the brain and intestine. Histopathological analysis revealed lymphoid hyperplasia of the spleen, necrosis of the liver, encephalitis and hyperplasia of lymph nodes. CONCLUSION: Trpanosoma vivax isolates from both tsetse infested and non-tsetse areas showed a variety of virulence factors leading to the development of acute clinical signs, gross and histopathological lesions. However, the parasitaemia and clinical signs appeared earlier in the NT compared to TT infected groups

Seroconversion and indolent course of COVID-19 in patients with multiple sclerosis treated with fingolimod and teriflunomide

Non applicale in quanto si tratta di di una Letter to the Edito