Publications by authors named "B F Brian"

Purpose: Rational self-medication (SM) practice among healthcare students is essential to promote the safe, effective, and economical use of medicines for self-diagnosed conditions. The study aimed to assess pharmacy students' knowledge, attitude, and practice about responsible self-medication.

Methodology: A cross-sectional online survey was conducted among Ugandan pharmacy students for one month from March 1 to March 31, 2024.

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Article Synopsis
  • Adeno-associated viral (AAV) vectors are effective for in vivo gene therapy but are challenged by the immune system, particularly CD8 T-cell responses against transgene products.* -
  • The study found that blocking multiple innate immune pathways is necessary to reduce immune responses; however, simply blocking these pathways might not completely prevent immune activation, especially at higher vector doses.* -
  • A strategy incorporating CpG depletion and TLR9 inhibitory sequences, along with muscle-specific promoters, showed promise in sustaining transgene expression with minimal immune activation, highlighting the complexity of immune responses in gene therapy.*
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Here, we report that the LynB splice variant of the Src-family kinase Lyn exerts a dominant immunosuppressive function in vivo, whereas the LynA isoform is uniquely required to restrain autoimmunity in female mice. We used CRISPR-Cas9 gene editing to constrain splicing and expression, generating single-isoform LynA knockout (LynA) or LynB mice. Autoimmune disease in total Lyn mice is characterized by production of antinuclear antibodies, glomerulonephritis, impaired B cell development, and overabundance of activated B cells and proinflammatory myeloid cells.

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The kinase Csk is the primary negative regulator of the Src-family kinases (SFKs, e.g., Lck, Fyn, Lyn, Hck, Fgr, Blk, Yes), phosphorylating a tyrosine on the SFK C-terminal tail that mediates autoinhibition.

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Myeloid cells (macrophages, monocytes, dendritic cells, and granulocytes) survey the body for signs of infection and damage and regulate tissue homeostasis, organogenesis, and immunity. They express receptors that initiate the inflammatory response, send signals that alter the vascular and cytokine milieu, and oversee the recruitment, differentiation, and activation of other myeloid and adaptive immune cells. Their activation must therefore be tightly regulated, optimized for maximal innate-immune protection with a minimum of collateral tissue damage or disorganization.

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