Cigarette Smoking Accelerated Brain Aging and Induced Pre-Alzheimer-Like Neuropathology in Rats

Cigarette smoking has been proposed as a major risk factor for aging-related pathological changes and Alzheimer's disease (AD). To date, little is known for how smoking can predispose our brains to dementia or cognitive impairment. This study aimed to investigate the cigarette smoke-induced pathological changes in brains. Male Sprague-Dawley (SD) rats were exposed to either sham air or 4% cigarette smoke 1 hour per day for 8 weeks in a ventilated smoking chamber to mimic the situation of chronic passive smoking. We found that the levels of oxidative stress were significantly increased in the hippocampus of the smoking group. Smoking also affected the synapse through reducing the expression of pre-synaptic proteins including synaptophysin and synapsin-1, while there were no changes in the expression of postsynaptic protein PSD95. Decreased levels of acetylated-tubulin and increased levels of phosphorylated-tau at 231, 205 and 404 epitopes were also observed in the hippocampus of the smoking rats. These results suggested that axonal transport machinery might be impaired, and the stability of cytoskeleton might be affected by smoking. Moreover, smoking affected amyloid precursor protein (APP) processing by increasing the production of sAPPβ and accumulation of β–amyloid peptide in the CA3 and dentate gyrus region. In summary, our data suggested that chronic cigarette smoking could induce synaptic changes and other neuropathological alterations. These changes might serve as evidence of early phases of neurodegeneration and may explain why smoking can predispose brains to AD and dementia

The photometric observation of the quasi-simultaneous mutual eclipse and occultation between Europa and Ganymede on 22 August 2021

Mutual events (MEs) are eclipses and occultations among planetary natural satellites. Most of the time, eclipses and occultations occur separately. However, the same satellite pair will exhibit an eclipse and an occultation quasi-simultaneously under particular orbital configurations. This kind of rare event is termed as a quasi-simultaneous mutual event (QSME). During the 2021 campaign of mutual events of jovian satellites, we observed a QSME between Europa and Ganymede. The present study aims to describe and study the event in detail. We observed the QSME with a CCD camera attached to a 300-mm telescope at the Hong Kong Space Museum Sai Kung iObservatory. We obtained the combined flux of Europa and Ganymede from aperture photometry. A geometric model was developed to explain the light curve observed. Our results are compared with theoretical predictions (O-C). We found that our simple geometric model can explain the QSME fairly accurately, and the QSME light curve is a superposition of the light curves of an eclipse and an occultation. Notably, the observed flux drops are within 2.6% of the theoretical predictions. The size of the event central time O-Cs ranges from -14.4 to 43.2 s. Both O-Cs of flux drop and timing are comparable to other studies adopting more complicated models. Given the event rarity, model simplicity and accuracy, we encourage more observations and analysis on QSMEs to improve Solar System ephemerides.Comment: 23 pages, 5 appendixes, 16 figures, 7 table

Rapid detection of SMARCB1 sequence variation using high resolution melting

Background : Rhabdoid tumors are rare cancers of early childhood arising in the kidney, central nervous system and other organs. The majority are caused by somatic inactivating mutations or deletions affecting the tumor suppressor locus SMARCB1 [OMIM 601607]. Germ-line SMARCB1 inactivation has been reported in association with rhabdoid tumor, epitheloid sarcoma and familial schwannomatosis, underscoring the importance of accurate mutation screening to ascertain recurrence and transmission risks. We describe a rapid and sensitive diagnostic screening method, using high resolution melting (HRM), for detecting sequence variations in SMARCB1. Methods : Amplicons, encompassing the nine coding exons of SMARCB1, flanking splice site sequences and the 5\u27 and 3\u27 UTR, were screened by both HRM and direct DNA sequencing to establish the reliability of HRM as a primary mutation screening tool. Reaction conditions were optimized with commercially available HRM mixes. Results : The false negative rate for detecting sequence variants by HRM in our sample series was zero. Nine amplicons out of a total of 140 (6.4%) showed variant melt profiles that were subsequently shown to be false positive. Overall nine distinct pathogenic SMARCB1 mutations were identified in a total of 19 possible rhabdoid tumors. Two tumors had two distinct mutations and two harbored SMARCB1 deletion. Other mutations were nonsense or frame-shifts. The detection sensitivity of the HRM screening method was influenced by both sequence context and specific nucleotide change and varied from 1: 4 to 1:1000 (variant to wild-type DNA). A novel method involving digital HRM, followed by re-sequencing, was used to confirm mutations in tumor specimens containing associated normal tissue. Conclusions : This is the first report describing SMARCB1 mutation screening using HRM. HRM is a rapid, sensitive and inexpensive screening technology that is likely to be widely adopted in diagnostic laboratories to facilitate whole gene mutation screening

Erlotinib-induced autophagy in epidermal growth factor receptor mutated non-small cell lung cancer

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Evaluating Retinal Function in Age-Related Maculopathy with the ERG Photostress Test

PURPOSE. To evaluate the diagnostic potential of the electroretinogram (ERG) photostress test and the focal cone ERG in age-related maculopathy (ARM). METHODS. The cohort comprised 31 patients with ARM and 27 age-matched control subjects. The ERG photostress test was used to monitor cone adaptation after intense light adaptation. Focal 41- and 5-Hz cone ERGs were recorded monocularly (central 20°) to assess steady state retinal function. Univariate analysis identified electrophysiological parameters that differed between groups, and receiver operating characteristic (ROC) curves were constructed to assess their diagnostic potential. Logistic regression analysis determined the diagnostic potential of a model incorporating several independent predictors of ARM. RESULTS. The rate of recovery of the ERG photostress test was reduced (recovery was slower) in subjects with ARM. The parameter exhibited good diagnostic potential (P = 0.002, area under ROC curve = 0.74). The implicit times of the 5-Hz (a-wave, P = 0.002; b-wave, P < 0.001) and the 41-Hz (P < 0.001) focal cone ERGs were increased, and the 41-Hz focal cone ERG amplitude (P = 0.003) and focal to full-field amplitude ratio (P = 0.001) were reduced in the ARM group. Logistic regression analysis identified three independent predictors of ARM, including the rate of recovery of the ERG photostress test. CONCLUSIONS. Early ARM has a marked effect on the kinetics of cone adaptation. The clinical application of the ERG photostress test increases the sensitivity and specificity of a model for the diagnosis of ARM. Improved assessment of the functional integrity of the central retina will facilitate early diagnosis and evaluation of therapeutic interventions