Generation of TWO G51D SNCA missense mutation iPSC lines (CRICKi011-A, CRICKi012-A) from two individuals at risk of Parkinson's disease

Mutations or multiplications of the SNCA (Synuclein Alpha) gene cause rare autosomal dominant Parkinson's disease (PD). The SNCA G51D missense mutation is associated with a synucleinopathy that shares PD and multiple system atrophy (MSA) characteristics. We generated induced pluripotent stem cell (iPSC) lines from two individuals with SNCA G51D missense mutations at risk of PD. Dermal fibroblasts were reprogrammed to pluripotency using a non-integrating mRNA-based protocol. The resulting human iPSCs displayed normal morphology, expressed markers associated with pluripotency, and differentiated into the three germ layers. The iPSC lines could facilitate disease-modelling and therapy development studies for synucleinopathies

Teknis Penerapan Sekolah Aman Bencana (SAB) Model Pembelajaran Integrasi Kebencanaan Melalui Metode Bermain Peran Berbantuan Media Disabo Untuk Guru Sd N Pasir Panjang 01 Salem

Artikel ini akan membahas secara rinci pelaksanaan Program Kemitraan Masyarakat Tahun 2023. Program ini dirancang untuk memberikan wawasan mendalam tentang bagaimana rencana dan implementasi program tersebut dilakukan, serta dampaknya terhadap masyarakat dan pihak-pihak yang terlibat. Kegiatan ini dilatarbelakangani belum teknis penerapan sekolah aman bencana (SAB) model pembelajaran integrasi kebencanaan melalui metode bermain peran. Permasalahan pritoritas mitra yaitu guru belum mengetahui konseptual pendidikan kebencanaan di sekolah. Selain itu, guru belum mengetahui perencanaan, pelaksanaan, dan penyusunan sumber serta instrumen evaluasi. Solusi yang ditawarkan yaitu memberikan pelatihan menggunakan model pembelajaran integrasi kebencanaan melalui metode bermain peran. Metode pelaksanaan kegiatan PKM ini adalah ceramah, diskusi, workshop, peerteaching, dan penugasan. Luaran kegiatan ini yaitu peningkatan pengetahuan guru dalam menyusun rencana dan melaksanakan pembelajaran integrasi kebencanaan. Kegiatan pelatihan ini telah mencapai tujuannya. Pelatihan ini telah memberikan manfaat yang sangat besar dan tepat bagi guru-guru yang menjadi khalayak sasaran dalam kegiatan ini.Peserta sangat senang, puas dan aktif dalam mengikuti kegiatan ini. Bentuk pelatihan ini merupakan bentuk yang sangat efektif untuk memberikan wawasan baru bagi peserta.Artikel ini membahas deskripsi pelaksanaan Program Kemitraan Masyarakat Tahun 203. Kegiatan ini dilatarbelakangani belum teknis penerapan sekolah aman bencana (SAB) model pembelajaran integrasi kebencanaan melalui metode bermain peran. Permasalahan pritoritas mitra yaitu guru belum mengetahui    konseptual pendidikan kebencanaan di sekolah. Selain itu, guru belum mengetahui perencanaan, pelaksanaan, dan  penyusunan sumber serta instrumen evaluasi. Solusi yang ditawarkan yaitu memberikan pelatihan menggunakan model pembelajaran integrasi kebencanaan melalui metode bermain peran. Metode pelaksanaan kegiatan PKM ini adalah ceramah, diskusi, workshop, peerteaching, dan penugasan. Luaran kegiatan ini yaitu peningkatan pengetahuan guru dalam menyusun rencana dan melaksanakan pembelajaran integrasi kebencanaan. Kegiatan pelatihan ini telah mencapai tujuannya.Pelatihan ini telah memberikan manfaat yang sangat besar dan tepat bagi guru-guru yang menjadi khalayak sasaran dalam kegiatan ini.Peserta sangat senang, puas dan aktif dalam mengikuti kegiatan ini. Bentuk pelatihan ini merupakan bentuk yang sangat efektif untuk memberikan wawasan baru bagi peserta

The ubiquitin proteasome system in neuropathology

The ubiquitin proteasome system (UPS) orchestrates the turnover of innumerable cellular proteins. In the process of ubiquitination the small protein ubiquitin is attached to a target protein by a peptide bond. The ubiquitinated target protein is subsequently shuttled to a protease complex known as the 26S proteasome and subjected to degradative proteolysis. The UPS facilitates the turnover of proteins in several settings. It targets oxidized, mutant or misfolded proteins for general proteolytic destruction, and allows for the tightly controlled and specific destruction of proteins involved in development and differentiation, cell cycle progression, circadian rhythms, apoptosis, and other biological processes. In neuropathology, alteration of the UPS, or mutations in UPS target proteins may result in signaling abnormalities leading to the initiation or progression of tumors such as astrocytomas, hemangioblastomas, craniopharyngiomas, pituitary adenomas, and medulloblastomas. Dysregulation of the UPS may also contribute to tumor progression by perturbation of DNA replication and mitotic control mechanisms, leading to genomic instability. In neurodegenerative diseases caused by the expression of mutant proteins, the cellular accumulation of these proteins may overload the UPS, indirectly contributing to the disease process, e.g., sporadic Parkinsonism and prion diseases. In other cases, mutation of UPS components may directly cause pathological accumulation of proteins, e.g., autosomal recessive Parkinsonism and spinocerebellar ataxias. Defects or dysfunction of the UPS may also underlie cognitive disorders such as Angelman syndrome, Rett syndrome and autism, and muscle and nerve diseases, e.g., inclusion body myopathy and giant axon neuropathy. This paper describes the basic biochemical mechanisms comprising the UPS and reviews both its theoretical and proven involvement in neuropathological diseases. The potential for the UPS as a target of pharmacological therapy is also discussed

Self-organization of the human embryo in the absence of maternal tissues.

Remodelling of the human embryo at implantation is indispensable for successful pregnancy. Yet it has remained mysterious because of the experimental hurdles that beset the study of this developmental phase. Here, we establish an in vitro system to culture human embryos through implantation stages in the absence of maternal tissues and reveal the key events of early human morphogenesis. These include segregation of the pluripotent embryonic and extra-embryonic lineages, and morphogenetic rearrangements leading to generation of a bilaminar disc, formation of a pro-amniotic cavity within the embryonic lineage, appearance of the prospective yolk sac, and trophoblast differentiation. Using human embryos and human pluripotent stem cells, we show that the reorganization of the embryonic lineage is mediated by cellular polarization leading to cavity formation. Together, our results indicate that the critical remodelling events at this stage of human development are embryo-autonomous, highlighting the remarkable and unanticipated self-organizing properties of human embryos.This work was supported by the Wellcome Trust grant to M.Z- G. Work in Dr. K.K.N lab was supported by The Francis Crick Institute, which receives its core funding from Cancer Research UK, the Medical Research Council and the Wellcome Trust. Dr. M.N.S. was initially supported by a Ramon Areces Spanish Foundation Fellowship, and subsequently by an EMBO Postdoctoral Fellowship. Dr. S.V was supported by a Post Doc Pool Grant from the Finnish Cultural Foundation. Dr. GR was supported by a Newton Fellowship.This is the author accepted manuscript. It is currently under an indefinite embargo pending publication by Nature Publishing Group

Clinical and spectrophotometric evaluation after chlorhexidine use in periodontal flap surgery: A prospective randomized clinical trial.

Abstract PURPOSE: To evaluate by a clinical spectrophotometric analysis the staining side effect of a 0.2% chlorhexidine (CHX) mouthrinse containing an anti-discoloration system (ADS) compared with a 0.12% and a 0.2% CHX mouthrinse, after periodontal surgery. The efficacy of the products and the patient's opinion and acceptance were also assessed. METHODS: The study was carried out on 60 subjects scheduled for periodontal flap surgery at the Unit of Periodontology and Dental Hygiene (University of Trieste, Italy). After surgery, the subjects were randomly prescribed to rinse for 1 week with 10 ml of a 0.12% CHX (Group 1), 0.2% CHX (Group 2) or 0.2% ADS CHX (Group 3). Before surgery (TO), 7 days (T1) and 14 days (T2) after surgery, following variables were recorded: gingival parameters at the surgically treated sites (Full-Mouth Plaque Score, Full-Mouth Bleeding Score and Modified Gingival Index), tooth pigmentation measured as AE, patient perception and acceptance of the mouthrinses. RESULTS: 53 subjects completed the study. The difference among treatments related to gingival variables was not statistically significant. No statistical differences were found for dental pigmentation among the mouthrinses over time nor for discomfort at each follow-up examination. A slightly less acceptance rate was observed for 0.2% CHX. The following conclusions were drawn: (1) 0.2% CHX with ADS did not cause less brown pigmentation than the 0.2% CHX or than the 0.12% CHX; (2) 0.2% ADS CHX was as effective as CHX without ADS in reducing gingival signs of inflammation in the post-surgical early healing phase; (3) 0.2% CHX showed the lowest score in terms of taste acceptance compared with 0.12% and ADS CHX

Model of arterial tree and peripheral control for the study of physiological and assisted circulation

Peripheral vasomotion, interstitial liquid exchange, and cardiovascular system behaviour are investigated by means of a lumped parameter model of the systemic and peripheral circulation, from the aortic valve to the venules. This modelling work aims at combining arterial tree hemodynamics description, active peripheral flow regulation, and fluid exchange. The arterial compartment is constructed with 63 RCL segments and 30 peripheral districts including myogenic control on arterioles, metabolic control on venules, and Starling filtration through capillary membrane. The arterial behaviour is characterised as to the long term stability of pressure/flow waves in the different segments. Peripheral districts show auto-regulatory capabilities against pressure changes over a wide range and also self-sustained oscillations mimicking vasomotor activity. A preliminary study was carried out as to the model response to changes induced by cardiopulmonary bypass (CPB). Among the induced alterations, the system responds mainly to haemodilution, which increased peripheral fluid loss and oedema beyond the compensatory capabilities of local regulation mechanisms. This resulted in an overall increase total arterial resistance. Local transport deficits were assessed for each district according to the different metabolic demand. This study shows the requirement of a suitable description of both arteries and peripheral mechanisms in order to describe cardiovascular response non-physiological conditions, as well as assisted circulation or other pathological conditions