Essential role for caspase 8 in T-cell homeostasis and T-cell-mediated immunity

Defects in death receptor-mediated apoptosis have been linked to cancer and autoimmune disease in humans. The in vivo role of caspase 8, a component of this pathway, has eluded analysis in postnatal tissues because of the lack of an appropriate animal model. Targeted disruption of caspase 8 is lethal in utero. We generated mice with a targeted caspase 8 mutation that is restricted to the T-cell lineage. Despite normal thymocyte development in the absence of caspase 8, we observed a marked decrease in the number of peripheral T-cells and impaired T-cell response ex vivo to activation stimuli. caspase 8 ablation protected thymocytes and activated T-cells from CD95 ligand but not anti-CD3-induced apoptosis, or apoptosis activated by agents that are known to act through the mitochondria. caspase 8 mutant mice were unable to mount an immune response to viral infection, indicating that caspase 8 deletion in T-cells leads to immunodeficiency. These findings identify an essential, cell-stage-specific role for caspase 8 in T-cell homeostasis and T-cell-mediated immunity. This is consistent with the recent identification of caspase 8 mutations in human immunodeficiency.     

Plackett–Burman randomization method for Bacterial Ghosts preparation form E. coli JM109

Plackett–Burman randomization method is a conventional tool for variables randomization aiming at optimization. Bacterial Ghosts (BGs) preparation has been recently established using methods other than the E lysis gene. The protocol has been based mainly on using critical concentrations from chemical compounds able to convert viable cells to BGs. The Minimum Inhibition Concentration (MIC) and the Minimum Growth Concentration (MGC) were the main guide for the BGs preparation. In this study, Escherichia coli JM109 DEC has been used to produce the BGs following the original protocol. The study contained a detail protocol for BGs preparation that could be used as a guide.     

Troubles respiratoires au cours du sommeil et obésité

The relationship between sleep disorders and obesity is well documented. Several studies have examined this association. Obesity is a recognized risk factors of sleep apnea syndrome. Other publications have focused on sleep duration and obesity risk becoming a major public health problem worldwide. Several pathophysiological hypotheses have been advanced suggesting the role of intermittent hypoxia and inflammatory cytokines. The objective of this paper is to put the item from the literature data on the main sleep disorders in obese patients.     

Prognostic Impact of Serum Growth Differentiation Factor 15 Level in Acute Myeloid Leukemia Patients

Growth differentiation factor 15 (GDF15) plays an important role in cancer pathophysiology and prognosis. However, limited studies analyzed its level and prognostic value in acute myeloid leukemia (AML) patients. This study included 56 adult AML patients. Serum GDF15 level was measured at diagnosis in all patients by enzyme-linked immunosorbent assay. Remission and survival statuses were assessed at 90 days following treatment. GDF15 level was significantly higher in patients than in controls (P < 0.001). GDF15 level correlated positively with age (P < 0.001), hemoglobin level (P = 0.027), and platelet count (P = 0.024). High GDF15 above the median level was associated with inferior OS (P = 0.044) together with high platelet count (P = 0.006) and high bone marrow blast percent (P = 0.038). There was no statistically significant difference between patients with GDF15 above and below the median level regarding DFS (P = 0.881). On multivariate analysis for OS, GDF15 level was an independent risk factor (P = 0.047). In conclusion, serum GDF15 level is significantly elevated in AML patients and high GDF15 level is associated with inferior OS.     

Risk factors for hospital admission among COVID-19 patients with diabetes: A study from Saudi Arabia

Objectives:To elucidate the risk factors for hospital admission among COVID-19 patients with type 2 diabetes mellitus (T2DM).Methods:This retrospective study was conducted at the Prince Sultan Military Medical City, Riyadh, Saudi Arabia between May 2020 and July 2020. Out of 7,260 COVID-19 patients, 920 were identified as T2DM. After the exclusion process, 806 patients with T2DM were included in this analysis. Patients’ data were extracted from electronic medical records. A logistic regression model was performed to estimate the risk factors of hospital admission.Results:Of the total of 806 COVID-19 patients with T2DM, 48% were admitted in the hospital, 52% were placed under home isolation. Older age between 70-79 years (OR [odd ratio] 2.56; p=0.017), ≥80 years (OR 6.48; p=0.001) were significantly more likely to be hospitalized compared to <40 years. Similarly, patients with higher HbA1c level of ≥9% compared to <7%; (OR 1.58; p=0.047); patients with comorbidities such as, hypertension (OR 1.43; p=0.048), cardiovascular disease (OR 1.56; p=0.033), cerebrovascular disease (OR 2.38; p=0.016), chronic pulmonary disease (OR 1.51; p=0.018), malignancy (OR 2.45; p=0.025), chronic kidney disease (CKD) IIIa, IIIb, IV (OR 2.37; p=0.008), CKD V (OR 5.07; p=0.007) were significantly more likely to be hospitalized. Likewise, insulin-treated (OR 1.46; p=0.03) were more likely to require hospital admission compared to non-insulin treated patients.Conclusion:Among COVID-19 patients with diabetes, higher age, high HbA1c level, and presence of other comorbidities were found to be significant risk factors for the hospital admission.     

Migration of sea urchin primordial germ cells

COVER PHOTOGRAPH: EMT and migration of sea urchin PGCs. Live‐cell confocal micrographs of 34 and 43 hour old purple sea urchin, Strongylocentrotus purpuratus, gastrulae. The germline marker, Sp‐Vasa, is yellow and the apical marker, Sp‐ABCG2a, is cyan. From Campanale et al., Developmental Dynamics 243:917–927.     

Calpain inhibition stabilizes the platelet proteome and reactivity in diabetes

Platelets from patients with diabetes are hyperreactive and demonstrate increased adhesiveness, aggregation, degranulation, and thrombus formation, processes that contribute to the accelerated development of vascular disease. Part of the problem seems to be dysregulated platelet Ca(2+) signaling and the activation of calpains, which are Ca(2+)-activated proteases that result in the limited proteolysis of substrate proteins and subsequent alterations in signaling. In the present study, we report that the activation of μ- and m-calpain in patients with type 2 diabetes has profound effects on the platelet proteome and have identified septin-5 and the integrin-linked kinase (ILK) as novel calpain substrates. The calpain-dependent cleavage of septin-5 disturbed its association with syntaxin-4 and promoted the secretion of α-granule contents, including TGF-β and CCL5. Calpain was also released by platelets and cleaved CCL5 to generate a variant with enhanced activity. Calpain activation also disrupted the ILK-PINCH-Parvin complex and altered platelet adhesion and spreading. In diabetic mice, calpain inhibition reversed the effects of diabetes on platelet protein cleavage, decreased circulating CCL5 levels, reduced platelet-leukocyte aggregate formation, and improved platelet function. The results of the present study indicate that diabetes-induced platelet dysfunction is mediated largely by calpain activation and suggest that calpain inhibition may be an effective way of preserving platelet function and eventually decelerating atherothrombosis development.     

Influence of Age and Tooth Loss on Masticatory Muscles Characteristics: A Population Based MR Imaging Study

Background

Aging is associated with a decline in masticatory muscles mass and performance. The present study aims to examine the differences in the cross-sectional areas of the masseter, medial and lateral pterygoid muscles in relation to age and the present dental status in a population-based magnetic resonance imaging study.

Methods

This cross sectional study involved 747 subjects aged between 30–89 years (344 male, 403 female) who underwent both a whole body MRI and a full oral examination. The cross-sectional areas of the masseter, medial and lateral pterygoid muscles were measured from MRI images using the software Osirix. Dental and prosthetic status data from the oral examination were classified according to Eichner index. The method of generalized least squares, also called growth curve model, was used to examine the associations between the cross-sectional areas, age and tooth status.

Results

The cross-sectional area of the lateral pterygoid muscle decreased substantially with age in women but did not depend on age in men. The medial pterygoid muscle depended on age but an effect modification by gender was uncertain. Masseter muscle was weakly associated with age but strongly associated with the number of teeth in both genders.

Conclusions

Our findings suggest that age has a heterogeneous effect on masticatory muscles. This indicates that age related changes to the masticatory muscles are muscle specific and are not consistent between the different muscles.