SinCMat: A single-cell-based method for predicting functional maturation transcription factors

peer reviewedA major goal of regenerative medicine is to generate tissue-specific mature and functional cells. However, current cell engineering protocols are still unable to systematically produce fully mature functional cells. While existing computational approaches aim at predicting transcription factors (TFs) for cell differentiation/reprogramming, no method currently exists that specifically considers functional cell maturation processes. To address this challenge, here, we develop SinCMat, a single-cell RNA sequencing (RNA-seq)-based computational method for predicting cell maturation TFs. Based on a model of cell maturation, SinCMat identifies pairs of identity TFs and signal-dependent TFs that co-target genes driving functional maturation. A large-scale application of SinCMat to the Mouse Cell Atlas and Tabula Sapiens accurately recapitulates known maturation TFs and predicts novel candidates. We expect SinCMat to be an important resource, complementary to preexisting computational methods, for studies aiming at producing functionally mature cells

Synthesis and Quantitative Structure–Activity Relationship of Imidazotetrazine Prodrugs with Activity Independent of O6-Methylguanine-DNA-methyltransferase, DNA Mismatch Repair and p53.

The antitumor prodrug Temozolomide is compromised by its dependence for activity on DNA mismatch repair (MMR) and the repair of the chemosensitive DNA lesion, O6-methylguanine (O6-MeG), by O6-methylguanine-DNA-methyltransferase (EC 2.1.1.63, MGMT). Tumor response is also dependent on wild-type p53. Novel 3-(2-anilinoethyl)-substituted imidazotetrazines are reported that have activity independent of MGMT, MMR and p53. This is achieved through a switch of mechanism so that bioactivity derives from imidazotetrazine-generated arylaziridinium ions that principally modify guanine-N7 sites on DNA. Mono- and bi-functional analogs are reported and a quantitative structure-activity relationship (QSAR) study identified the p-tolyl-substituted bi-functional congener as optimized for potency, MGMT-independence and MMR-independence. NCI60 data show the tumor cell response is distinct from other imidazotetrazines and DNA-guanine-N7 active agents such as nitrogen mustards and cisplatin. The new imidazotetrazine compounds are promising agents for further development and their improved in vitro activity validates the principles on which they were designed

Glioblastoma Multiforme Therapy and Mechanisms of Resistance

YesGlioblastoma multiforme (GBM) is a grade IV brain tumor characterized by a heterogeneous population of cells that are highly infiltrative, angiogenic and resistant to chemotherapy. The current standard of care, comprised of surgical resection followed by radiation and the chemotherapeutic agent temozolomide, only provides patients with a 12–14 month survival period post-diagnosis. Long-term survival for GBM patients remains uncommon as cells with intrinsic or acquired resistance to treatment repopulate the tumor. In this review we will describe the mechanisms of resistance, and how they may be overcome to improve the survival of GBM patients by implementing novel chemotherapy drugs, new drug combinations and new approaches relating to DNA damage, angiogenesis and autophagy

Utilisation de la spectrométrie de masse MALDI-TOF pour l'identification des trois espèces du complexe d'espèces C. Parapsilosis (prévalences respectives en fonction des différents sites anatomiques)

CHATENAY M.-PARIS 11-BU Pharma. (920192101) / SudocSudocFranceF

Weight loss as a treatment for obstructive sleep apnoea.

Obesity is a major health problem in well-developed societies. It is frequently associated with metabolic, cardiovascular and psychological comorbid conditions. Besides, it is known that obesity constitutes a risk factor for obstructive sleep apnoea (OSA). Weight loss has been evaluated as a treatment for OSA. We reviewed the nature of the link between obesity and OSA as well as the conservative and surgical therapeutic approaches of obesity. We consider the effectiveness of weight loss alone or combined with other modalities of treatment in OSA. We conclude that although weight loss is important and can facilitate the treatment of OSA, it can rarely cure it without being associated to classical techniques, such as nasal continuous positive airway pressure (nCPAP)

Persistent pneumomediastinum and dermatomyositis: a case report and review of the literature.

We describe a 42-year-old man with dermatomyositis and interstitial lung disease who presented with anterior neck pain and dyspnoea. Chest radiographs showed subcutaneous emphysema, pneumomediastinum and diffuse reticulonodular infiltration in both lungs. After the administration of high doses of prednisolone, an improvement of pulmonary function and respiratory symptoms was observed but the pneumomediastinum persists 12 months after diagnosis, and without any complication. We review the cases that have been reported thus far of pneumomediastinum associated with dermatomyositis and discuss the possible mechanisms involved. We conclude that pneumomediastinum is not an uncommon complication of dermatomyositis and that its aetiopathogenesis remains very unclear