The δ subunit and NTPase HelD institute a two-pronged mechanism for RNA polymerase recycling

Cellular RNA polymerases RNAPs can become trapped on DNA or RNA, threatening genome stability and limiting free enzyme pools, but how RNAP recycling into active states is achieved remains elusive. In Bacillus subtilis, the RNAP amp; 948; subunit and NTPase HelD have been implicated in RNAP recycling. We structurally analyzed Bacillus subtilis RNAP amp; 948; HelD complexes. HelD has two long arms a Gre cleavage factor like coiled coil inserts deep into the RNAP secondary channel, dismantling the active site and displacing RNA, while a unique helical protrusion inserts into the main channel, prying the amp; 946; and amp; 946; amp; 8242; subunits apart and, aided by amp; 948;, dislodging DNA. RNAP is recycled when, after releasing trapped nucleic acids, HelD dissociates from the enzyme in an ATP dependent manner. HelD abundance during slow growth and a dimeric RNAP amp; 948; HelD 2 structure that resembles hibernating eukaryotic RNAP I suggest that HelD might also modulate active enzyme pools in response to cellular cue

The rationale and design of the antihypertensives and vascular, endothelial, and cognitive function (AVEC) trial in elderly hypertensives with early cognitive impairment: Role of the renin angiotensin system inhibition

<p>Abstract</p> <p>Background</p> <p>Prior evidence suggests that the renin angiotensin system and antihypertensives that inhibit this system play a role in cognitive, central vascular, and endothelial function. Our objective is to conduct a double-blind randomized controlled clinical trial, the antihypertensives and vascular, endothelial, and cognitive function (AVEC), to compare 1 year treatment of 3 antihypertensives (lisinopril, candesartan, or hydrochlorothiazide) in their effect on memory and executive function, cerebral blood flow, and central endothelial function of seniors with hypertension and early objective evidence of executive or memory impairments.</p> <p>Methods/Design</p> <p>The overall experimental design of the AVEC trial is a 3-arm double blind randomized controlled clinical trial. A total of 100 community eligible individuals (60 years or older) with hypertension and early cognitive impairment are being recruited from the greater Boston area and randomized to lisinopril, candesartan, or hydrochlorothiazide ("active control") for 12 months. The goal of the intervention is to achieve blood pressure control defined as SBP < 140 mm Hg and DBP < 90 mm Hg. Additional antihypertensives are added to achieve this goal if needed. Eligible participants are those with hypertension, defined as a blood pressure 140/90 mm Hg or greater, early cognitive impairment without dementia defined (10 or less out of 15 on the executive clock draw test or 1 standard deviation below the mean on the immediate memory subtest of the repeatable battery for the assessment of neuropsychological status and Mini-Mental-Status-exam >20 and without clinical diagnosis of dementia or Alzheimer's disease). Individuals who are currently receiving antihypertensives are eligible to participate if the participants and the primary care providers are willing to taper their antihypertensives. Participants undergo cognitive assessment, measurements of cerebral blood flow using Transcranial Doppler, and central endothelial function by measuring changes in cerebral blood flow in response to changes in end tidal carbon dioxide at baseline (off antihypertensives), 6, and 12 months. Our outcomes are change in cognitive function score (executive and memory), cerebral blood flow, and carbon dioxide cerebral vasoreactivity.</p> <p>Discussion</p> <p>The AVEC trial is the first study to explore impact of antihypertensives in those who are showing early evidence of cognitive difficulties that did not reach the threshold of dementia. Success of this trial will offer new therapeutic application of antihypertensives that inhibit the renin angiotensin system and new insights in the role of this system in aging.</p> <p>Trial Registration</p> <p>Clinicaltrials.gov NCT00605072</p

Modeling the Past: The Paleoethnological Evidence

This chapter considers the earliest Paleolithic, Oldowan (Mode 1), and Acheulean (Mode 2) cultures of the Old Continent and the traces left by the earliest hominids since their departure from Africa. According to the most recent archaeological data, they seem to have followed two main dispersal routes across the Arabian Peninsula toward the Levant, to the north, and the Indian subcontinent, to the east. According to recent discoveries at Dmanisi in the Caucasus, the first Paleolithic settlement of Europe is dated to some 1.75 Myr ago, which indicates that the first “out of Africa” took place at least slightly before this date. The data available for Western Europe show that the first Paleolithic sites can be attributed to the period slightly before 1.0 Myr ago. The first well-defined “structural remains” so far discovered in Europe are those of Isernia La Pineta in Southern Italy, where a semicircular artificial platform made of stone boulders and animal bones has been excavated. The first hand-thrown hunting weapons come from the site of Scho¨ningen in north Germany, where the first occurrence of wooden spears, more than 2 m long, has been recorded from a site attributed to some 0.37 Myr ago. Slightly later began the regular control of fire. Although most of the archaeological finds of these ages consist of chipped stone artifacts, indications of art seem to be already present in the Acheulean of Africa and the Indian subcontinent

Supervised walking groups to increase physical activity in elderly women with and without hypertension: effect on pulse wave velocity.

To date, only a few studies have evaluated the effect of physical activity on PWVcf in the elderly. In the current study, 21 community-dwelling women, with a mean age of 68.19\ub15.72 years and a mean BMI of 28.63\ub14.69\u2009kg\u2009m(-2), participated in moderate physical activity sessions for 1\u2009h per day and 2 days each week under the supervision of a qualified physical education instructor for a total of 24 weeks. At the beginning of the study, at 3 months and at 6 months, the study participants' body weight, waist circumference, sagittal abdominal diameter (SAD) and body composition by dual energy X-ray absorptiometry (DEXA) were recorded along with the participants' Physical Activity Scale for the Elderly questionnaire. Total low-density-lipoprotein and high-density lipoprotein cholesterol; triglycerides (TGs) and HbA1c; blood pressure (BP); and arterial stiffness, as determined by carotid-femoral and carotid-radial pulse wave velocity (PWVcf, PWVcr), were also assessed. During the follow-up period, the waist and SAD significantly decreased, whereas fat-free mass, BMI and weight did not decrease. A significant decline in TGs was observed. A significant decline in PWVcf, even after adjusting for mean arterial pressure, heart rate triglycerides and waist diameter changes, was observed. In a sub-analysis that examined the effect of physical activity separately in the hypertensive and normotensive subjects, we observed a significant decline in PWVcf in the hypertensive subjects and a nonsignificant tendency in the normotensive subjects. The data showed an association between light aerobic physical activity in the elderly and decreased PWVcf, even after adjusting for changes in systolic BP (SBP), TGs and central adiposity. These results suggest a beneficial effect of moderate physical activity on subclinical vascular damage, particularly in hypertensive subjects

Smart environment effectiveness analysis of a pursuit and evasion scenario.

[[abstract]]The internet of things (IoT) has become a trend in interactive environments for providing information to decision-makers. Anti-submarine warfare (ASW) is a typical pursuit and evasion (PE) game that is a very complicated process. The ASW helicopter is assigned to execute the final phase of hunting the submarine with a torpedo attack. In most cases, a single helicopter is assigned to detect the submarine by dipping sonar, and then drops a torpedo. Once the dipping sonar goes off, uncertainty takes over, with the possible result of losing track of the submarine. To prevent this problem, using the IoT concept to create a wireless sensor network (WSN) in the area of interest for keeping ears on the evading submarine is a potential solution. The objective of this paper is to gain insights into this PE scenario so as to quantify the interaction result in order to demonstrate the effectiveness of the helicopter in terms of hunting the submarine. Monte Carlo simulation has been developed as the analytical tool, and ANOVA was used to verify the significance of the output measure of effectiveness (MOE) before analysis. The results show that a slow, unalerted submarine has a very low chance of survival. An alerted submarine has very high chance of survival, but when the proposed sonobuoy WSN is in place, this situation benefitting the submarine will be reversed. The WSN has been proved to be effective in a single helicopter carrying out its ASW task.[[notice]]補正完