Modeling Adeno-Associated Viral Vector 6-mediated Gene Delivery to Expanded Non-Mobilized Haemopoietic Stem Cells from Transfusion-dependent Thalassemia Patients in a Humanized Mouse.

Hematopoietic stem cells (HSC) are important targets for gene modification therapies (GMT) as they originate several serious genetic conditions including the β-haemoglobinopathies. Potentially curative GMT pose the barriers of accessibility, myeloablation-associated morbidity and prohibitive cost. GMT using non-integrating single-strand adeno-associated viral vectors (ssAAV) are a promising alternative that address these challenges directly, although the small ssAAV payload limits the capacity to package much larger gene or base editors.

Cellular mechanisms of early brain overgrowth in autistic children: elevated levels of GPX4 and resistance to ferroptosis.

Autistic individuals with disproportionate megalencephaly (ASD-DM), characterized by enlarged brains relative to body height, have higher rates of intellectual disability and face more severe cognitive challenges than autistic children with average brain sizes. The cellular and molecular mechanisms underlying this neurophenotype remain poorly understood. To investigate these mechanisms, we generated human induced pluripotent stem cells from non-autistic typically developing children and autistic children with and without disproportionate megalencephaly.

Characterizing the relationship between social determinants of health and risk of albuminuria among children with type 1 diabetes.

In a cohort of 2303 children with type 1 diabetes (T1D), we found that non-English speaking status (HR 2.82, 95% CI 1.54-5.

Evaluation of 13 Formulae for Calculated LDL-C Using Direct Homogenous Assay in a South Indian Population.

Background: LDL cholesterol (LDL-C) is regarded as a significant therapeutic target and a known risk factor for atherosclerosis. It can be calculated using the results of the other lipid tests or tested directly. Despite its shortcomings, the Friedewald formula is most frequently utilized since it is simple and practical.

Autophagy: An Emerging Target for Developing Effective Analgesics.

Inadequate treatment of acute and chronic pain causes depression, anxiety, sleep disturbances, and increased mortality. Abuse and overdose of opioids and the side effects associated with chronic use of NSAID illustrate the need for development of safer and effective pain medication. Working toward this end, an tool based on an emergent intelligence analytical platform that examines interactions between protein networks was used to identify molecular mechanisms involved in regulating the body's response to painful stimuli and drug treatments.

Genetic reduction of cilium length by targeting intraflagellar transport 88 protein impedes kidney and liver cyst formation in mouse models of autosomal polycystic kidney disease.

Polycystin-1 (PC1) and -2 (PC2), products of the PKD1 and PKD2 genes, are mutated in autosomal dominant polycystic kidney disease (ADPKD). They localize to the primary cilia; however, their ciliary function is in dispute. Loss of either the primary cilia or PC1 or PC2 causes cyst formation.

Characterisation of ACP5 missense mutations encoding tartrate-resistant acid phosphatase associated with spondyloenchondrodysplasia.

Biallelic mutations in ACP5, encoding tartrate-resistant acid phosphatase (TRACP), have recently been identified to cause the inherited immuno-osseous disorder, spondyloenchondrodysplasia (SPENCD). This study was undertaken to characterize the eight reported missense mutations in ACP5 associated with SPENCD on TRACP expression. ACP5 mutant genes were synthesized, transfected into human embryonic kidney (HEK-293) cells and stably expressing cell lines were established.

Improvement of Saccharification and Delignification Efficiency of Rut-C30 by Genetic Bioengineering.

produces various saccharification enzymes required for biomass degradation. However, the lack of an effective lignin-degrading enzyme system reduces the species' efficiency in producing fermentable sugars and increases the pre-treatment costs for biofuel production. In this study, we heterologously expressed the RMK1 versatile peroxidase gene () in the Rut-C30 strain of .

In-Vitro Subtype-Specific Modulation of HIV-1 Trans-Activator of Transcription (Tat) on RNAi Silencing Suppressor Activity and Cell Death.

Human immunodeficiency virus (HIV) is a global health concern affecting millions of individuals with a wide variety of currently circulating subtypes affecting various regions of the globe. HIV relies on multiple regulatory proteins to modify the host cell to promote replication in infected T cells, and these regulatory proteins can have subtle phenotypic differences between subtypes. One of these proteins, HIV-1 Trans-Activator of Transcription (Tat), is capable of RNA interference (RNAi) Silencing Suppressor (RSS) activity and induction of cell death in T cells.

Genetic Polymorphisms in the Open Reading Frame of the CCR5 gene From HIV-1 Seronegative and Seropositive Individuals From National Capital Regions of India.

C-C chemokine receptor type 5 (CCR5) serves as a co-receptor for Human immunodeficiency virus (HIV), enabling the virus to enter human CD4 T cells and macrophages. In the absence of CCR5, HIV strains that require CCR5 (R5 or M-tropic HIV) fail to successfully initiate infection. Various natural mutations of the CCR5 gene have been reported to interfere with the HIV-CCR5 interaction, which influences the rate of AIDS progression.

Autophagy Intertwines with Different Diseases-Recent Strategies for Therapeutic Approaches.

Autophagy is a regular and substantial "clear-out process" that occurs within the cell and that gets rid of debris that accumulates in membrane-enclosed vacuoles by using enzyme-rich lysosomes, which are filled with acids that degrade the contents of the vacuoles. This machinery is well-connected with many prevalent diseases, including cancer, HIV, and Parkinson's disease. Considering that autophagy is well-known for its significant connections with a number of well-known fatal diseases, a thorough knowledge of the current findings in the field is essential in developing therapies to control the progression rate of diseases.

Virally delivered channelrhodopsin-2 safely and effectively restores visual function in multiple mouse models of blindness.

Previous work established retinal expression of channelrhodopsin-2 (ChR2), an algal cation channel gated by light, restored physiological and behavioral visual responses in otherwise blind rd1 mice. However, a viable ChR2-based human therapy must meet several key criteria: (i) ChR2 expression must be targeted, robust, and long-term, (ii) ChR2 must provide long-term and continuous therapeutic efficacy, and (iii) both viral vector delivery and ChR2 expression must be safe. Here, we demonstrate the development of a clinically relevant therapy for late stage retinal degeneration using ChR2.

Characterization of human immunodeficiency virus Gag-specific gamma interferon-expressing cells following protective mucosal immunization with alphavirus replicon particles.

A safe, replication-defective viral vector that can induce mucosal and systemic immune responses and confer protection against many infectious pathogens, such as human immunodeficiency virus type 1 (HIV-1), may be an ideal vaccine platform. Accordingly, we have generated and tested alphavirus replicon particles encoding HIV-1 Gag from Sindbis virus (SIN-Gag) and Venezuelan equine encephalitis virus (VEE-Gag), as well as chimeras between the two (VEE/SIN-Gag). Following intramuscular (i.

Synthesis of IL-13 by human B lymphocytes: regulation and role in IgE production.

Background: Our laboratory has demonstrated previously that human tonsillar B lymphocytes express IL-13 mRNA OBJECTIVE: We sought to investigate IL-13 production by human B cells and the association between B cell-derived IL-13 and IgE secretion.

Methods: Human B lymphocytes were isolated from tonsils and purified by means of rosetting with sheep RBCs or positive or negative selection with magnetic beads. They were stimulated with anti-CD40 antibodies with or without recombinant IL-4.

Maintenance of long-term immunological memory by low avidity IgM-secreting cells in bone marrow after mucosal immunizations with cholera toxin adjuvant.

To understand the mechanisms involved in maintaining long-term immunological memory following mucosal immunizations, we determined the quality of serum hapten-specific immunoglobulins (Ig) and localized Ig-secreting cells (SC) of various isotypes in acute, persistent/resting memory and effector memory phases following oral versus intra-muscular (IM) immunizations. In the acute phase, both oral and IM immunizations induced high avidity Ig. However, in the persistent/resting memory phase, oral immunizations induced low avidity Ig while IM immunizations induced high avidity Ig.