Atrazine-induced apoptosis of splenocytes in BALB/C mice

<p>Abstract</p> <p>Background</p> <p>Atrazine (2-chloro-4-ethytlamino-6-isopropylamine-1,3,5-triazine; ATR), is the most commonly applied broad-spectrum herbicide in the world. Unintentional overspray of ATR poses an immune function health hazard. The biomolecular mechanisms responsible for ATR-induced immunotoxicity, however, are little understood. This study presents on our investigation into the apoptosis of splenocytes in mice exposed to ATR as we explore possible immunotoxic mechanisms.</p> <p>Methods</p> <p>Oral doses of ATR were administered to BALB/C mice for 21 days. The histopathology, lymphocyte apoptosis and the expression of apoptosis-related proteins from the Fas/Fas ligand (FasL) apoptotic pathway were examined from spleen samples.</p> <p>Results</p> <p>Mice administered ATR exhibited a significant decrease in spleen and thymus weight. Electron microscope histology of ultrathin sections of spleen revealed degenerative micromorphology indicative of apoptosis of splenocytes. Flow cytometry revealed that the percentage of apoptotic lymphocytes increased in a dose-dependent manner after ATR treatment. Western blots identified increased expression of Fas, FasL and active caspase-3 proteins in the treatment groups.</p> <p>Conclusions</p> <p>ATR is capable of inducing splenocytic apoptosis mediated by the Fas/FasL pathway in mice, which could be the potential mechanism underlying the immunotoxicity of ATR.</p

Congenital myasthenic syndromes in two kinships with end-plate acetylcholine receptor and utrophin deficiency

We studied two families with five affected members suffering from ptosis and slowly progressive limb-girdle muscle weakness. All patients had abnormal decremental response on low-frequency nerve stimulation, but there were no repetitive responses to single stimuli. The patients improved on anti-acetylcholinesterase drugs. Intercostal muscle was obtained for special studies from one patient of each family. In vitro microelectrode studies were done in Patient 1. Miniature end-plate potentials were of low amplitude, and the quantal content of the evoked end-plate potentials was normal. Light microscopy revealed a marked type 1 fiber predominance. Acetylcholinesterase reactivity was dispersed over increased length of individual fibers in Patient 2. On morphometry of the end-plate ultrastructure, the number of secondary synaptic clefts per neuromuscular junction and the expansion of the postsynaptic area were markedly reduced. In Patient 1, but not in Patient 2, the envelopment of the nerve terminal by Schwann cell was increased. Acetylcholine-receptor (AChR) density was reduced as judged by the reduced immunoreactivity to antibodies against different receptor subunits. Immunohistochemical analysis of proteins known to be involved in orchestrating the end-plate structure showed deficiency of the AChR-associated protein utrophin. These patients appear to have a defect in the development or maintenance of the postsynaptic clefts; whether this defect results from or causes a reduced expression of utrophin or AChR is unclear

Reciprocal Regulation of Anaerobic and Aerobic Cell Wall Mannoprotein Gene Expression in Saccharomyces cerevisiae

The DAN/TIR genes encode nine cell wall mannoproteins in Saccharomyces cerevisiae which are expressed during anaerobiosis (DAN1, DAN2, DAN3, DAN4, TIR1, TIR2, TIR3, TIR4, and TIP1). Most are expressed within an hour of an anaerobic shift, but DAN2 and DAN3 are expressed after about 3 h. At the same time, CWP1 and CWP2, the genes encoding the major mannoproteins, are down-regulated, suggesting that there is a programmed remodeling of the cell wall in which Cwp1 and Cwp2 are replaced by nine anaerobic counterparts. TIP1, TIR1, TIR2, and TIR4 are also induced during cold shock. Correspondingly, CWP1 is down-regulated during cold shock. As reported elsewhere, Mox4 is a heme-inhibited activator, and Mot3 is a heme-induced repressor of the DAN/TIR genes (but not of TIP1). We show that CWP2 (but not CWP1) is controlled by the same factors, but in reverse fashion—primarily by Mot3 (which can function as either an activator or repressor) but also by Mox4, accounting for the reciprocal regulation of the two groups of genes. Disruptions of TIR1, TIR3, or TIR4 prevent anaerobic growth, indicating that each protein is essential for anaerobic adaptation. The Dan/Tir and Cwp proteins are homologous, with the greatest similarities shown within three subgroups: the Dan proteins, the Tip and Tir proteins, and, more distantly, the Cwp proteins. The clustering of homology corresponds to differences in expression: the Tip and Tir proteins are expressed during hypoxia and cold shock, the Dan proteins are more stringently repressed by oxygen and insensitive to cold shock, and the Cwp proteins are oppositely regulated by oxygen and temperature

Mutations in the pericentrin (PCNT) gene cause primordial dwarfism.

Contains fulltext : 70830.pdf (publisher's version ) (Closed access)Fundamental processes influencing human growth can be revealed by studying extreme short stature. Using genetic linkage analysis, we find that biallelic loss-of-function mutations in the centrosomal pericentrin (PCNT) gene on chromosome 21q22.3 cause microcephalic osteodysplastic primordial dwarfism type II (MOPD II) in 25 patients. Adults with this rare inherited condition have an average height of 100 centimeters and a brain size comparable to that of a 3-month-old baby, but are of near-normal intelligence. Absence of PCNT results in disorganized mitotic spindles and missegregation of chromosomes. Mutations in related genes are known to cause primary microcephaly (MCPH1, CDK5RAP2, ASPM, and CENPJ)