Antibiotics Overuse and Bacterial Resistance

Antibiotic usage has become very widespread, as they are used to treat so many infectious diseases today. Antimicrobial agents exert their actions via different mechanisms including blockage of cell wall synthesis, interference of protein and/or nucleic acid synthesis, interruption of cell membrane structure, and inhibition of a metabolic pathway. The treatment of bacterial infections with antimicrobial agents has become more difficult due to the capability of bacteria to develop resistance to antibiotics. Erroneous diagnosing, misconceptions, and improper physician-patient dynamics have led to overuse of antibiotics and the emergence of drug-resistant bacteria. Bacterial colonies have been shown to confer advantageous genetic information with ease, which is cause for concern. This, in turn, leads to a heightened urgency to create new forms of treatment that are effective against a greater proportion of a given bacterial colony. Effective ways of decreasing resistance include better diagnostic techniques, proper education and assessments, optimization of antibiotics usage, drug synergism, vaccine implementation, global efforts to combat resistance, and development of new antimicrobial agents

Tau-Mediated Nuclear Depletion and Cytoplasmic Accumulation of SFPQ in Alzheimer's and Pick's Disease

Tau dysfunction characterizes neurodegenerative diseases such as Alzheimer's disease (AD) and frontotemporal lobar degeneration (FTLD). Here, we performed an unbiased SAGE (serial analysis of gene expression) of differentially expressed mRNAs in the amygdala of transgenic pR5 mice that express human tau carrying the P301L mutation previously identified in familial cases of FTLD. SAGE identified 29 deregulated transcripts including Sfpq that encodes a nuclear factor implicated in the splicing and regulation of gene expression. To assess the relevance for human disease we analyzed brains from AD, Pick's disease (PiD, a form of FTLD), and control cases. Strikingly, in AD and PiD, both dementias with a tau pathology, affected brain areas showed a virtually complete nuclear depletion of SFPQ in both neurons and astrocytes, along with cytoplasmic accumulation. Accordingly, neurons harboring either AD tangles or Pick bodies were also depleted of SFPQ. Immunoblot analysis of human entorhinal cortex samples revealed reduced SFPQ levels with advanced Braak stages suggesting that the SFPQ pathology may progress together with the tau pathology in AD. To determine a causal role for tau, we stably expressed both wild-type and P301L human tau in human SH-SY5Y neuroblastoma cells, an established cell culture model of tau pathology. The cells were differentiated by two independent methods, mitomycin C-mediated cell cycle arrest or neuronal differentiation with retinoic acid. Confocal microscopy revealed that SFPQ was confined to nuclei in non-transfected wild-type cells, whereas in wild-type and P301L tau over-expressing cells, irrespective of the differentiation method, it formed aggregates in the cytoplasm, suggesting that pathogenic tau drives SFPQ pathology in post-mitotic cells. Our findings add SFPQ to a growing list of transcription factors with an altered nucleo-cytoplasmic distribution under neurodegenerative conditions