The molecular pathophysiology of mood disorders: From the analysis of single molecular layers to multi-omic integration

Next-generation sequencing now enables the rapid and affordable production of reliable biological data at multiple molecular levels, collectively referred to as "omics". To maximize the potential for discovery, computational biologists have created and adapted integrative multi-omic analytical methods. When applied to diseases with traceable pathophysiology such as cancer, these new algorithms and statistical approaches have enabled the discovery of clinically relevant molecular mechanisms and biomarkers. In contrast, these methods have been much less applied to the field of molecular psychiatry, although diagnostic and prognostic biomarkers are similarly needed. In the present review, we first briefly summarize main findings from two decades of…
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A CMOS Integrator-Based Clock-Free Time-to-Digital Converter for Home-Monitoring LiDAR Sensors

This paper presents a nine-bit integrator-based time-to-digital converter (I-TDC) realized in a 180 nm CMOS technology for the applications of indoor home-monitoring light detection and ranging (LiDAR) sensors. The proposed I-TDC exploits a clock-free configuration so as to discard clock-related dynamic power consumption and some notorious issues such as skew, glitch, and synchronization. It consists of a one-dimensional (1D) flash TDC to generate coarse-control codes and an integrator with a peak detection and hold (PDH) circuit to produce fine-control codes. A thermometer-to-binary converter is added to the 1D flash TDC, yielding four-bit coarse codes so that the measured detection range can be…
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Engineered T Cells: CAR T Cell Therapy and Beyond

Purpose of review: This article reviews the current data and future directions of engineered T cell therapies in non-Hodgkin lymphomas. Recent findings: Currently, four chimeric antigen receptor (CAR) T cell products are approved: axicabtagene ciloleucel, tisagenlecleucel, lisocabtagene maraleucel, and brexucabtagene autoleucel. These products differ in construct, indication, manufacturing, clinical trial design, and toxicity profile, but all are autologous products targeting CD19. Encouraging early data is also emerging with the use of these products in additional subtypes of B cell lymphoma. Alternative engineered T cell products are also in development, including dual CD19/22 targeting CAR T cells, CD30-directed CAR T cells, allogeneic CAR…
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Delivery of superoxide dismutase by TAT and Abalone peptides for the protection of skin cells against oxidative stress

Trichoderma reesei superoxide dismutase (TrSOD) is a well characterized enzyme being stable between 30 and 90°C for 1 h with activity at pH between 2.6 and 9.0. This work aimed to clone, express, purify and evaluate the protective effect antioxidant of this enzyme on skin cells when fused to transactivator of transcription (TAT) protein transduction domain of HIV-1 and Abalone (Ab) peptides to allow cell penetration. TrSOD, TAT-TrSOD-Yfp (fused to yellow fluorescent protein) and Ab-TrSOD were expressed in E.coli and purified as soluble proteins. The cytotoxicity of the enzymes, at the concentrations of 1, 3 and 6 μmol/L, was evaluated for a…
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A CRISPR toolbox for generating intersectional genetic mouse models for functional, molecular, and anatomical circuit mapping

Background: The functional understanding of genetic interaction networks and cellular mechanisms governing health and disease requires the dissection, and multifaceted study, of discrete cell subtypes in developing and adult animal models. Recombinase-driven expression of transgenic effector alleles represents a significant and powerful approach to delineate cell populations for functional, molecular, and anatomical studies. In addition to single recombinase systems, the expression of two recombinases in distinct, but partially overlapping, populations allows for more defined target expression. Although the application of this method is becoming increasingly popular, its experimental implementation has been broadly restricted to manipulations of a limited set of common…
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development of novel therapies for pediatric cancer

development of novel therapies for pediatric cancer

DESCRIPTION (offered by applicant): Pediatric cancers are orphan malignancies that happen in sufferers who've traditionally been missed for essentially the most half by the pharmaceutical and biotechnology industries; thus, the pediatric cancers could be thought-about double orphans" - orphan ailments that happen in orphan sufferers. Although dramatic strides have been achieved over the previous 40 years within the administration of the pediatric cancers, there stay many shortcomings within the efficacies and toxicities of accessible therapies for the varied varieties of childhood malignancy. development of novel therapies for pediatric cancer The main objective of this utility is to facilitate the development of new applied…
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neurokinin-1r (sp receptor) antagonists for hiv therapy

neurokinin-1r (sp receptor) antagonists for hiv therapy

DESCRIPTION (provided by applicant): New HIV-1 therapies that utilize novel antiviral mechanisms and exert a positive immunomodulatory effect are needed. Neurokinin-1 receptor (NK-1R) antagonists target the substance P (SP) receptor and have demonstrated antiviral and immunomodulatory effects. neurokinin-1r (sp receptor) antagonists for hiv therapy The NK-1R antagonists are a new therapeutic target with the potential to interrupt a pathway critical to HIV replication. The goal of this Integrated Preclinical/Clinical Program (IPCP) is to identify an NK-1R antagonist that is: (a) active as an anti-HIV agent through interaction with chemokine/cytokine receptors (Project 1); (b) specific for NK-1R interaction with CCR-5 (Project…
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