Progesterone potentiates calcium release through IP3 receptors by an Akt-mediated mechanism in hippocampal neurons

Progesterone (P4) is a steroid hormone that plays multiple roles in the central nervous system (CNS) including promoting neuroprotection. However, the precise mechanisms involved in its neuroprotective effects are still unknown. Given that the regulation of the intracellular calcium (Ca²⁺) concentration is critical for cell survival, we determined if inositol 1, 4, 5-trisphosphate receptors (IP₃Rs) are relevant targets of P4. Using primary hippocampal neurons, we tested the hypothesis that P4 controls the gain of IP3R-mediated intracellular Ca²⁺ signaling in neurons and characterized the subcellular distribution and phosphorylation of potential signaling intermediates involved in P4s actions. Our results reveal that P4 treatment altered the intensity and distribution of IP3R immunoreactivity and induced the nuclear translocation of phosphorylated Akt. Further, P4 potentiated IP₃R-mediated intracellular Ca²⁺ responses. These results suggest a potential involvement of P4 in particular and of steroid hormone signaling pathways in general in the control of intracellular Ca²⁺ signaling and its related functions.     

Control of cell wall assembly by a histone-like protein in Mycobacteria

Bacteria coordinate assembly of the cell wall as well as synthesis of cellular components depending on the growth state. The mycobacterial cell wall is dominated by mycolic acids covalently linked to sugars, such as trehalose and arabinose, and is critical for pathogenesis of mycobacteria. Transfer of mycolic acids to sugars is necessary for cell wall biogenesis and is mediated by mycolyltransferases, which have been previously identified as three antigen 85 (Ag85) complex proteins. However, the regulation mechanism which links cell wall biogenesis and the growth state has not been elucidated. Here we found that a histone-like protein has a dual concentration-dependent regulatory effect on mycolyltransferase functions of the Ag85 complex through direct binding to both the Ag85 complex and the substrate, trehalose-6-monomycolate, in the cell wall. A histone-like protein-deficient Mycobacterium smegmatis strain has an unusual crenellated cell wall structure and exhibits impaired cessation of glycolipid biosynthesis in the growth-retarded phase. Furthermore, we found that artificial alteration of the amount of the extracellular histone-like protein and the Ag85 complex changes the growth rate of mycobacteria, perhaps due to impaired down-regulation of glycolipid biosynthesis. Our results demonstrate novel regulation of cell wall assembly which has an impact on bacterial growth.     

Involvement of ERK1/2 activation in the gene expression of senescence-associated secretory factors in human hepatic stellate cells

Molecular and Cellular Biochemistry - Senescent hepatic stellate cells (senescent HSCs) are found in patients with liver cirrhosis and have been thought to be involved in the development of...     

Between the Great War and the Great Depression: preliminary observations on the ‘missing link’ in the history of human stature in Poland

The paper traces the secular trend in stature in Poland in the interwar period. On the basis of individual measuring cards created by military authorities for Krosno and Sarny districts, the author states that the secular trend in stature that started in the mid-1860s continued between the two world wars with the velocity of at least 0.7 cm per decade, i.e. at a similar rate as in the second half of the 19th century. Although regional differences inside the Second Polish Republic were clearly visible, cohorts born during the Great War were able to make up the lost ground in their teens despite the hardships caused by the Great Depression of the 1930s.     

Asymmetric dimethylarginine and long-term adverse cardiovascular events in patients with type 2 diabetes: relation with the glycemic control

Patients with type 2 diabetes are at a high risk for acute cardiovascular events, which usually arise from the rupture of a vulnerable coronary lesion characterized by specific morphological plaque features. Thus, the identification of vulnerable plaques is of utmost clinical importance in patients with type 2 diabetes. However, there is currently no scoring system available to identify vulnerable lesions based on plaque characteristics. Thus, we aimed to characterize the diagnostic value of optical coherence tomography (OCT) - derived lesion characteristics to quantify plaque vulnerability both as individual parameters and when combined to a score in patients with type 2 diabetes. OCT was performed in the coronary culprit lesions of 112 patients with type 2 diabetes. The score, which quantifies plaque vulnerability, was defined as the predicted probability that a lesion is the cause for an acute coronary syndrome (ACS) (vs. stable angina (SAP)) based on its specific plaque morphology. Multivariable logistic regression analysis demonstrated that plaque vulnerability was independently predicted by the minimal fibrous cap thickness overlying a lesion’s lipid core (odds ratio (OR) per 10 μm 0.478, p = 0.002), the medium lipid arc (OR per 90° 13.997, p < 0.001), the presence of macrophages (OR 4.797, p = 0.015) and the lipid plaque length (OR 1.290, p = 0.098). Receiver-operating-characteristics (ROC) analyses demonstrated that these parameters combined to a score demonstrate an excellent diagnostic efficiency to identify culprit lesions of patients with ACS (vs. SAP, AUC 0.90, 95% CI 0.84-0.96). This is the first study to present a score to quantify lesion vulnerability in patients with type 2 diabetes. This score may be a valuable adjunct in decision-making and useful in guiding coronary interventions.     

Synthesis of 11C-labeled retinoic acid, [11C]ATRA,via an alkenylboron precursor by Pd(0)-mediated rapid C-[11C]methylation

Retinoids are a class of chemical compounds which include both natural dietary vitamin A (retinol) metabolites and active synthetic analogs. Both experimental and clinical studies have revealed that retinoids regulate a wide variety of essential biological processes. In this study, we synthesized ¹¹C-labeled all-trans-retinoic acid (ATRA), the most potent biologically active metabolite of retinol and used in the treatment of acute promyelocytic leukemia. The synthesis of ¹¹C-labeled ATRA was accomplished by a combination of rapid Pd(0)-mediated C-[¹¹C]methylation of the corresponding pinacol borate precursor prepared by 8 steps and hydrolysis. [¹¹C]ATRA will prove useful as a PET imaging agent, particularly for elucidating the improved therapeutic activity of ATRA (natural retinoid) for acute promyelocytic leukemia by comparing with the corresponding PET probe [¹¹C]Tamibarotene (artificial retinoid).     

Detection and pathological role of intestinal protozoa in children

IntroductionIntestinal parasites are considered a growing public health problem, being protozoa the main cause of intestinal disease. The objective of our study is to compare the detection of intestinal protozoa by microscopy versus real-time PCR, as well as to determine the most prevalent protozoa in our environment in the paediatric population.MethodAn observational longitudinal study was carried out, both by microscopy and real time-PCR in stool samples from children (0‐ 15 years) received from April 2019 to March 2021.Children were classified in two groups according if they had or not had clinical parasitosis.Microscopic examination was performed in all samples using the Ritchie concentration technique with the commercial Mini PARASEP system (Movaco-Grifols®). The presence of Cryptosporidium sp. was evaluated with the modified Ziehl-Neelsen acid-fast stain. The real-time PCR was performed to all samples using the Allplex ™ gastrointestinal parasite panel 4 (Seegene®).ResultsDuring the study period, 500 samples were received, being positive 31 (6.2%) by microscopy and 256 (51.2 %) by PCR. By microscopy, Blastocystis hominis was the most frequently observed (4.8%), followed by Giardia lamblia (1.6%), Dientamoeba fragilis (0.2%) and Cryptosporidium species (0.2%). Regarding the identification by PCR, D. fragilis (35.2%) was mainly identified, followed by B. hominis (28.1%), G. lamblia (7%) and Cryptosporidium sp. (0.8%) without finding clear differences in aetiology according to age. In the case of B. hominis and D. fragilis, there were not differences in the detection of these protozoa between the control group and children with clinical parasitosis (p = 0.11).ConclusionsReal-time PCR increases the detection of intestinal protozoa, being underdiagnosed by microscopy, especially D. fragilis, in which PCR is considered the most appropriate method for its detection.     

Coproparasitological examinations and molecular determination of Eimeria species in Madura cattle reared on Madura Island,Indonesia

Madura cattle, which are native to Indonesia and mainly kept on Madura Island, East Java, are expected to contribute to improving the regional meat self-sufficiency. Eimeria spp. are the most pathogenic protozoans among gastrointestinal parasites in livestock but no molecular surveys of Eimeria spp. in Madura cattle have been conducted to date. In this study, a total of 183 fecal samples were collected from Madura cattle and 60 (32.8%) were positive for parasites of protozoans and nematodes by the sugar floatation method. Among the samples with parasites, Eimeria spp. oocysts were detected in 50 samples (27.3%) with an average OPG value of 1686.1. Eimeria spp. were successfully identified to the species level in 26 samples with Eimeria bovis being the most prevalent, followed by E. zuernii and E. aubrunensis. A total of 21 samples showed mixed infection of more than two species of Eimeria. E. bovis and E. zuernii have been recognized as having high virulency and, thus, these parasites are potential sources of severe coccidiosis and the cause of infections in other cattle. Although additional studies are warranted, these results can be helpful for improving the management and productivity of Madura cattle.