The importance of immunosupression in the development of the heavy form of cytomegaloviral infection in newborn children

Objective: to study the features of disorders in T and B cell immunity and the synthesis of serum immunoglobulins of classes IgA, IgM, IgG with the aim of predicting severe cytomegalovirus infection (CMVI) in newborns.Research methods: 133 newborns with cytomegalovirus infection were examined. Lymphocytes were typed to differentiation clusters CD3, CD4, CD8, CD20 using monoclonal antibodies, IMMUNOTECH (France). The expression of membrane markers of immunocompetent cells was determined using a Beckman COULTER EpicsXLII flow laser cytofluorimeter. Depending on the severity of the condition, all children were divided into two groups: 1 — CMVI, severe form — 60 people (45,1%); 2 CMVI, moderate form — 73 people (54,9%).Results. Using the «classification trees» method, we were able to develop a differentiated approach to the prognosis of a severe form of CMVI in newborn children. Systems of inequalities were obtained, four of which classify a subgroup of newborns with severe CMVI. Conclusion: the proposed diagnostic rules can be considered screening markers for prognosis of a severe form of CMVI in newborns.

Hyperosmotic Stress Induces Unconventional Autophagy Independent of the Ulk1 Complex

ABSTRACT Autophagy is considered an adaptive mechanism against hyperosmotic stress. Although the process has been reported to be triggered by the inhibition of mTORC1, the precise downstream mechanisms remain elusive. Here, we demonstrate that hyperosmotic-stress-induced autophagy is different from conventional macroautophagy in mouse embryonic fibroblasts (MEFs) and human T24 cells. Our results indicated that cytoplasmic puncta for the isolation membrane markers WIPI2 and Atg16L increased after hyperosmotic stress. They were found to partially colocalize with puncta for a selective autophagy substrate, SQSTM1/p62, and were shown to be diminished by inhibitors of phosphatidylinositol 3-kinase (PI3K) or by knockdown of human Vps34 (hVps34), a component of PI3K. In addition, flux assays showed that SQSTM1/p62 and NcoA4 were degraded by the lysosomal pathway. Surprisingly, Ulk1, which is essential for starvation-induced macroautophagy, remained inactivated under hyperosmotic stress, which was partially caused by mTOR activity. Accordingly, the Ulk1 complex was not nucleated under hyperosmotic stress. Finally, autophagy proceeded even in MEFs deficient in RB1CC1/FIP200 or Atg13, which encode components of the Ulk1 complex. These data suggest that hyperosmotic-stress-induced autophagy represents an unconventional type of autophagy that bypasses Ulk1 signaling.

Adaptations in Mitochondrial Enzymatic Activity Occurs Independent of Genomic Dosage in Response to Aerobic Exercise Training and Deconditioning in Human Skeletal Muscle

Mitochondrial DNA (mtDNA) replication is thought to be an integral part of exercise-training-induced mitochondrial adaptations. Thus, mtDNA level is often used as an index of mitochondrial adaptations in training studies. We investigated the hypothesis that endurance exercise training-induced mitochondrial enzymatic changes are independent of genomic dosage by studying mtDNA content in skeletal muscle in response to six weeks of knee-extensor exercise training followed by four weeks of deconditioning in one leg, comparing results to the contralateral untrained leg, in 10 healthy, untrained male volunteers. Findings were compared to citrate synthase activity, mitochondrial complex activities, and content of mitochondrial membrane markers (porin and cardiolipin). One-legged knee-extensor exercise increased endurance performance by 120%, which was accompanied by increases in power output and peak oxygen uptake of 49% and 33%, respectively (p < 0.01). Citrate synthase and mitochondrial respiratory chain complex I–IV activities were increased by 51% and 46–61%, respectively, in the trained leg (p < 0.001). Despite a substantial training-induced increase in mitochondrial activity of TCA and ETC enzymes, there was no change in mtDNA and mitochondrial inner and outer membrane markers (i.e. cardiolipin and porin). Conversely, deconditioning reduced endurance capacity by 41%, muscle citrate synthase activity by 32%, and mitochondrial complex I–IV activities by 29–36% (p < 0.05), without any change in mtDNA and porin and cardiolipin content in the previously trained leg. The findings demonstrate that the adaptations in mitochondrial enzymatic activity after aerobic endurance exercise training and the opposite effects of deconditioning are independent of changes in the number of mitochondrial genomes, and likely relate to changes in the rate of transcription of mtDNA.