మాలిక్యులర్ మరియు జెనెటిక్ మెడిసిన్

Five cases of Even-Plus syndrome have been reported, 2 in the year 19991 and 3 in the year 20152. We recently diagnosed another female patient with Even-Plus syndrome with a postural and gait abnormality. Left patellar dislocation was identified and corrected in order to limit patient’s disability.

Rheumatoid arthritis (RA) is characterized by citrullination of peptides and proteins mediated by calciumdependent peptidyl arginine deiminase enzymes (PADs). Various mechanisms of intracellular and extracellular protein citrullination have been elucidated so far. Here, we highlight one more important possible mechanism that could lead to intracellular citrullination due to dysregulated mitochondrial Ca2+ homeostasis i.e., inability of mitochondrial uptake of Ca2+ during physiological signaling and triggering the generation of autoimmune disease. Spontaneous secretion of intracellular PAD may be the result of high cytosolic Ca2+ due to a disturbance in mitochondrial calcium homeostasis secondary to oxidative damage without any compromise to the cell membrane. Various environmental triggers like air pollutants also induce oxidative stress (OS) which may compromise the mitochondrial integrity and disturb Ca2+ homeostasis. Adoption of simple lifestyle modification like yoga and meditation optimizes reactive oxygen species (ROS) levels and maintains mitochondrial integrity by increasing COX activity, thus may curb citrullination process and its sequelae.

??????????, ?????????? ????, ??????? ????? ??????? ????? ?????? ???? ????????? ??????? ???????, ????? "??? ????? ?????, ???????? ????? ???????? ????????" ????? ???????????? ????????? ???????????????? ???????? ??? ????????. ?????? ???? ?????? ??????????? ?????? ???? ??????? ???? ??????? ????????? ?????-???? ????????? ???? ????????? ????????. ?????? ?????????????, ????? ??????????? ????????? ????????? ????? ??????????? ?????????? ??????. ?????? ?????-??????? ?????? ?????? ???? ?????? ?????????, ???? ???????? ???? ????? ?????????? ????? ?????? ???????? ????????, ????????? ????? ????????? ?????????? ????????? ????? ??????????????. ?????????? ????????? ????????? ???????? ?????????, ??? ?????? ?????? ?? ?????? ????? ?????????? ????????????????? ????? ??????? ?????????? ???????????? ????? ?????? ??????? ??????? ??????????. ???? ????????????????? ????????? ???????????????? ????? ????? ???????????? ??????? ???? ????? ??????? ???????????.

????????????? ???? ???????? ?????????? ????????? ????? ???????????? ??????????? ????? ???????? ??????? ????? ???????? ???????????? ?????????. ?????? ???? ????????? ???????????? ?????? ???????? ??????? ???????????? ???????? ????????. ????????, ?????????? ?????????? ???? ???????? ????????? ?????????? ??????, ?????????‌? ?????? ???????? ????????? ???????????? ?????? ?????????? ???????. ????? ??????? ????? ??-??????? ?????????? ????????? ????? ?????????????? ????? ????? ???????, ???? ????????????? ???? ????????? ???? ????????? ??????????? ????? ??????. ?????? 1291 ????????????? ???????? ????? ???????? ???-?????? ????????????? (IVF) ??????? ???? ???????? ????????????, ?????? ??????????, ???????? ????????, Y ?????????? ?????????????‌?? ????? ?????????? ??????????? ?????????? ????? ?????? ???? ?????????????. ?? ????????? 1291 ???? ????????? 46 ???? (3.6%) ?????????? ?????????? ?????????????. ???????? ???????? (OR 0.76, P=0.029) ????? ?????????? ?????????? ????? ???????? ????????? ???? ?????? ?????? ?????????. ?????????????, ????????????? ?????????? ????????? (OR 32.24, P <0.001) ????? ??????? ?????????????? ????????????. ????????? ?????????????? ???????? ????????, ??????????, ?????????? ?????????? (OR 4.38, P <0.001) ?????????? ??????????? ????????????. ??????? ???????????? ?????? (OR 0.21, P=0.003) ?????? ?????? ???? ???????? ?????? ?????????? ?????????? ?????????????. ?????????? ????????? ????? ??????? ?????????????? ?????????? ??????? ???????????? ????????????? ???? ????????? ????????????? (OR 4.78, P=0.003). ?????‌?????????????? ????? ??????? ???? ???????????? ?????? ?????? ????????????? ???????? ?????? ?????????? ????????? ??????????? ????? ??????? ??????? ?????????.

???????????? ???????? ???????????? ????? ????????? ???? ??-???????? ????????????? ????? ????????? ?????????? ???? ?????????? ??????. ? ????????? ???????????????? ??????????? ???? ??????? ????? ??????????? ??????? ???? ??????? ???????? ????? ????????? ?????? ???????????????. ????-???? ????? DNA ???????? ???? ??-???????? ????????????? ?????????????? ????? ?????? ??????? ??????? ???????? ?????????????‌?? ????????????. ? ????????? 971 ??????? ???????, ?? ???? ????? DNA 18?? 15 (83.33%)?? ????? ???? ?????????‌??, 5?? 4 (80.00%) ???????? 18?? ????? 1?? 0 (0.00%) ?????????? ?????????????? 13. ????-?? ??????? ????????? ????? ??????????‌??? ????????? ????????????? ???????, ???? ?????? ????????? ????????????? ??-?????????? ???????????‌?? ???? ??????????? ?????????????, ????? ????????????? ??????? ?????????? ?????????? ???? ?????? ??????????‌?? ?????????? ?????????. ?? ??????????? ??????????‌?? ????????‌??????? ????? ????? ???????????????, ?????? ?????????? ?????????? ?????? ????? ????????????. ???????????? ????????? ?????? ????? ?????????? ?????????? ????????????????, ????? ?????????? ???? ????-????????? ????????? ?????????‌?? ???????? ????????. ?????????? ????? ????????‌???????? ???? ??? ???????????? ?????????? ???????????????? ??????? ???????? ???? ????????? ?????????? ?????????. ????????? ????????? ????????????? ????????? ??????, ????? ?????????? ??????????????? ???????? ?????????????‌?? ????? ????-????????? ????????????? ?????? ????? ??????.

Betaine demonstrations antioxidative activity, enhances organic osmolytic activity and is an important cofactor in methylation. However, the main mechanisms betaine-induced autophagy in human dermal skin cells are not yet completely understood. Therefore, we hypothesized that betaine induces of autophagy. Thus, the autophagic effects exerted by betaine through activation of LKB1-AMPK signaling in human dermal fibroblasts (HDFs) and human epidermal keratinocytes (HEKs) were assessed. Betaine enhanced LKB1 and AMPK phosphorylation in HEKs, and LKB1, AMPK induced autophagy through mTOR downregulation. Beatine-induced autophagy was inhibited in cells transiently transfected with AMPK siRNA. Increased autophagosome activity was confirmed by LC3B-II formation and by increased perinuclear LC3B-II puncta in betaine-treated HEKs. according to our in vitro findings, and in vivo studies in HR-1 hairless mice demonstrated that betaine treatment significantly reduced the activity of the senescence-associated marker β-galactosidase (SA-β-gal) and increased p-LKB1 and p-AMPK levels compared with UVB-irradiated skin tissues. Collectively, our findings suggest that betaine-dependent autophagy diminishes mouse skin senescence and betaine may reduce HEK senescence through an LKB1-AMPK-dependent mechanism.

In this commentary, we discussed the new exciting progress in CRISPR based screening technology field and highlight recent developments in the area of CRISPR-based functional genomics. High-throughput functional genomics using CRISPR-Cas9 revolutionized our ability to decipher cellular function in health and disease. Despite its limitations, the simplicity and effectiveness of CRISPR/Cas9 based screening, makes an enormous impact on genomic screening and thus scientific discovery.

???????: ????? ???? ????? ???????????? ????????????‌?? ??????? ???????? ???????? ?????????? ?????????? ?????????? ???? QF-PCR, ????????????? ????? CMA ????? ????????? ?????????? ?? ????????? ??????????? ? ??????? ????? ???????. ????????: ???? ????? ??????? ???????????? ???? ???????????? ???????‌??? 139 ?????? ????? ????????? ???????? ??????. ???????: 28 ???? ??????? ?????????? ?????????? ??????????????? (????? ??????? 20.1%). ?????? ??????????? ???? ?????? (?????? 17.2%) QF-PCR ?????? ?????????? ?????????????. ? ????????? ???????????? ??????? 4 ?????????? ?????????? (2.9% ??????) CMA ?????/???? ????????????? ?????? ????????????? ????? 28 (1.4%) ????? ????? ?????????? ????????? ??????? CMA ?????? ??????????????? ???? QF-PCR ????? ????????? ?????????????? ?????? ??????????????. ???????: ????????? ??????????‌?? QF-PCR ??????????? ?????-???? ???????? ??????. ?? ????????? CMA ???????? ????? ?????? ????? ????????? ?????? ??????????????? ?????? ??????? ??????? ?????? ????????? ?????.

?????????: 1997?? ???? ????????????? ?? ???? ????????? ???????, ???? ?????????????? ?????????? 13 ?????? ????????? 10?? ????????? ???? ??? ????? ??????????? (???? ???????????) ?????????? ??????? (???? ???????????) ???????????? ??????? ????? ?????? ????? ????????????. ???? ????????? ????????? ????? ???????? ????, ??? ????? '?????‌????????? ????‌????'?? ??????????? ??????, ??? ???? ????? ???????? ????? ???????????‌?? ??????????? ??????? ????????? ????????? ??????. ???????-????? ?????? ??? ???????? ?? ???? ?????? ?????????????, ??? ???? ?????? ?????????‌?? ????????? ?????‌????????? ????????? ?????????????? ???????????????? ????? ???????? ??????? ????????? ???????? ??? ??????????? ?????????????. ???? ????? ????????????? ??????: ???????????? ???????? ????? ?????????? ???????? ?????? ??????????, ???????? ????? ???????? ??????-??????? ????? ????? ??????‌?????? ???????????????? ???? ??????????? ?????????. mRNA ???? ????????????‌???? ???????? ????????, ??? ?????? ???????? ??????????????? ??????? ??????????????? ???????? (PDE y = ((A / (x + B)5 ) / (eC/ ( x + B) – 1))?? ????????????. ????? ??????????? ????? ????????? ?????????????? ???????? A, B ????? C ?????????‌? ???? ????? ???????? PDE?? mRNA ?????? ??????? ???????‌?? ?????????? ???? ??????? ?????????? ?????? ????????????????? ?? ???? ????????? ?????? ????? ??????? ??????-????????????? ????? ?????-????????????? ????‌????‌?? mRNA ???? ????? PDE-?????? ?????????? ?????????????. ????‌????, ????? ?????‌????????????? ?????‌????????? ????‌?? ?? ??????????? ???????? ?????????? ????? ???????, ???? ????????? 3 ???? ??????? ?????? ????? ???? ?????? ?????? ????? ???????, ???, ?????? ????????? ????????: ????????????, ?? ?????? ???? mRNA ??????? ?????-??????? ????????? ???????????????. ????? ????? ????, ??????? ??????????????? ???????? (PDE) ???????? ??????????? ???????? ???????? ????????????, "??????-????????????? ?????‌????????? ????‌????" ????? "?????-????????????? ?????‌????????? ????‌????"?? ????????? ???????? ????????? ????? ??? ??????? ?????????????. ????????? ??? ??????? ????? ??????? ??????????? ???????????.

????????? ????????? ???????? (APP) ??????????????? ????? ????‌?????????????? ??????????? ???????????? α, β ????? γ ??????? ?????? ??????????????. ??????????????? ???????????‌??, Aβ40 ????? Aβ42 ????????‌?? ??????? ??????? ????????? ?????? ?????????, ??? ????? ??????????????? ?????? ????? ???????, ???????? ?????????? ??????. ????? ??????????? ????????? (ASD) ???? ?????? ????????? ???? ????????? ?????? ?????????, ????? ASD ????? ?????? ????? APP ????? ????????? ????? ?????? ???????? ????? ?????????????. mGluR5 ??????????‌??? ??????? ?????????? ???????? APP ????? Aβ ????????? ????? ???? ?????‌?? ASD ????????? ???????????. ASD ???? ????? ???????????? ????? ?????????? ???????????????????? ASD ????????? ????? ??????????????? ????????????????? ??????????? ??????????? ??????????? ???????????.

???? ???????? ????? ??????????‌?? ?????? ?????????? ??????? ??????????. ????? ?????????? ????? ????? ???????????? ???????? ????? ?????????? ??????????? ????? ????? ??????????, ??????? ?????????? ????? ????????? ???????? ????? ????? ????????? ????? ????? ?????????? ??????????? ?????????????. ? ???????????? ???????????? ????? '????? ?????????? ?????????', ??????????-?????????? ????? ?????????? ??????????? ??????? ????????‌?? ????? ????????? ????? ????? ???? ?????????‌? ????? ?????? ??????? ????? ????????? ????????? ????????????? ?????? ?????? ????? ???????. ????? ?????????? ???????? ????? ???? ???????? ??????? ??????????? '????????? ??' ??????? ??????? ?????? ????? ??????????? ????? ??????? ???? ????????????? ???? '??????????? ?????' ????? ????????-?????? ??????? ????? ????? ?????????? ??????? ??????? ???? '???????? ?????'?? ????????????. ????? ?????????? ????????, ???????? ????? ????? ????-??????? ????????‌?? ????? ??? ??????????? ??????? ?????????, ???????????? ???????????? ?????????? ????????? ????????? ????? ??????????? ????? ?????????? ????? ??????? ?????????? ????? ?????????? ????????? ????????????? ????? ?????????? ????? ???????????? ??????????????? ????? ?????????? ?????. ? ?????????? ??????????-????????? ????????????? ????? ????? ???? ????? ????? ??????? ???? ??????????? ????????? ????????? ????? ???????????? ??????????-???????? ??????????? ??????????.

?????????? ????????? ????????? (GDM) ????? ???????? ??????? ???????????????, ??? ?????????? ????? ???? ????????????. GDM ????? ????? ????????? ???????? ???????? ?????? ????? ???????. GDM ????? ????????? 1-14% ???? ??????? ????? ??????? ????? ????? ????? ?????????? ??????????? ?????????? ??????? ???????. ? ????? ?????? ????????, ????????????, ?????????????, ??? ???????? ????? ??????? ???? GDM ????? ????? ????? ??????? ????????????.