Dendritic Actin Filament Nucleation Causes Traveling Waves and Patches

The polymerization of actin via branching at a cell membrane containing nucleation-promoting factors is simulated using a stochastic-growth methodology. The polymerized-actin distribution displays three types of behavior: a) traveling waves, b) moving patches, and c) random fluctuations. Increasing actin concentration causes a transition from patches to waves. The waves and patches move by a treadmilling mechanism which does not require myosin II. The effects of downregulation of key proteins on actin wave behavior are evaluated.Comment: 10 pages, 4 figure

Dental Erosion and Its Growing Importance in Clinical Practice: From Past to Present

Since the mid-1990s, the focus of studies on tooth wear has steadily shifted from the general condition towards the more specific area of dental erosion; equally, a shift has occurred from studies in adults to those in children and adolescents. During this time, understanding of the condition has increased greatly. This paper attempts to provide a critical overview of the development of this body of knowledge, from earlier perceptions to the present. It is accepted that dental erosion has a multifactorial background, in which individual and lifestyle factors have great significance. Notwithstanding methodological differences across studies, data from many countries confirm that dental erosion is common in children and young people, and that, when present, it progresses rapidly. That the condition, and its ramifications, warrants serious consideration in clinical dentistry, is clear. It is important for the oral healthcare team to be able to recognize its early signs and symptoms and to understand its pathogenesis. Preventive strategies are essential ingredients in the management of patients with dental erosion. When necessary, treatment aimed at correcting or improving its effects might best be of a minimally invasive nature. Still, there remains a need for further research to forge better understanding of the subject

Xerostomia in 75–85-year-olds: A longitudinal population study

Background: Xerostomia can pose significant problems for many elderly people. Objectives: To investigate longitudinal changes in prevalence, persistence, progression, remission and incidence of xerostomia from age 75 to 85 years. Methods: All 75-year-olds (born 1932) from two Swedish counties, Sweden were mailed a questionnaire in 2007 (N = 5195), and again in 2017 when they were aged 85 (N = 3323). The total response rates at ages 75 and 85 years were 71.9% and 60.8%, respectively. A ‘panel’, those who participated in both surveys, comprised 1701 individuals (response rate 51.2%). Results: At age 85, there was almost a doubling of self-reported ‘yes often’ xerostomia compared with age 75 (from 6.2% to 11.3%) and was almost twice as common in women than men (p < .001). When combining ‘yes often’/‘yes sometimes’, xerostomia increased from 33.4% to 49.0%, and was more so among women (p < .001). Xerostomia was commoner at night than daytime, with 23.4% reporting ‘yes often’ night-time xerostomia at 85 compared with 18.5% at 75, and was also higher in women (p < .001). Progression rates for daytime and night-time xerostomia were 34.2% and 38.1%, for persistence 67.4% and 68.6%, and for remission 24.4% and 16.5%. Average yearly incidence was higher in women than men for both daytime (3.6% vs. 3.2%) and night-time (3.9% vs. 3.7%). Regression analyses predicted protective factors for developing xerostomia reported at age 75 as good general and oral health, absence of medications/intraoral symptom/s, good chewing function and social interaction. Conclusions: Xerostomia increases markedly from age 75 to 85 years.publishedVersio

Triacylglycerol synthesis by PDAT1 in the absence of DGAT1 activity is dependent on re-acylation of LPC by LPCAT2

<p>Abstract</p> <p>Background</p> <p>The <it>Arabidopsis thaliana dgat1 </it>mutant, <it>AS11</it>, has an oil content which is decreased by 30%, and a strongly increased ratio of 18:3/20:1, compared to wild type. Despite lacking a functional DGAT1, <it>AS11 </it>still manages to make 70% of WT seed oil levels. Recently, it was demonstrated that in the absence of <it>DGAT1</it>, <it>PDAT1 </it>was essential for normal seed development, and is a dominant determinant in <it>Arabidopsis </it>TAG biosynthesis.</p> <p>Methods</p> <p>Biochemical, metabolic and gene expression studies combined with genetic crossing of selected <it>Arabidopsis </it>mutants have been carried out to demonstrate the contribution of <it>Arabidopsis </it>PDAT1 and LPCAT2 in the absence of DGAT1 activity.</p> <p>Results</p> <p>Through microarray and RT-PCR gene expression analyses of <it>AS11 </it>vs. WT mid-developing siliques, we observed consistent trends between the two methods. <it>FAD2 </it>and <it>FAD3 </it>were up-regulated and <it>FAE1 </it>down-regulated, consistent with the <it>AS11 </it>acyl phenotype. <it>PDAT1 </it>expression was up-regulated by <it>ca </it>65% while <it>PDAT2 </it>expression was up-regulated only 15%, reinforcing the dominant role of <it>PDAT1 </it>in <it>AS11 </it>TAG biosynthesis. The expression of <it>LPCAT2 </it>was up-regulated by 50-75%, while <it>LPCAT1 </it>expression was not significantly affected. <it>In vitro </it>LPCAT activity was enhanced by 75-125% in microsomal protein preparations from mid-developing <it>AS11 </it>seed <it>vs </it>WT. Co-incident homozygous knockout lines of <it>dgat1</it>/<it>lpcat2 </it>exhibited severe penalties on TAG biosynthesis, delayed plant development and seed set, even with a functional PDAT1; the double mutant <it>dgat1/lpcat1 </it>showed only marginally lower oil content than <it>AS11</it>.</p> <p>Conclusions</p> <p>Collectively, the data strongly support that in <it>AS11 </it>it is <it>LPCAT2 </it>up-regulation which is primarily responsible for assisting in PDAT1-catalyzed TAG biosynthesis, maintaining a supply of PC as co-substrate to transfer <it>sn</it>-2 moieties to the <it>sn</it>-3 position of the enlarged <it>AS11 </it>DAG pool.</p

Plasmodium falciparum population dynamics during the early phase of anti-malarial drug treatment in Tanzanian children with acute uncomplicated malaria

BACKGROUND\ud \ud This study aimed to explore Plasmodium falciparum population dynamics during the early phase of anti-malarial drug treatment with artemisinin-based combination therapy in children with clinical malaria in a high transmission area in Africa.\ud \ud METHODS\ud \ud A total of 50 children aged 1-10 years with acute uncomplicated P. falciparum malaria in Bagamoyo District, Tanzania, were enrolled. Participants were hospitalized and received supervised standard treatment with artemether-lumefantrine according to body weight in six doses over 3 days. Blood samples were collected 11 times, i.e. at time of diagnosis (-2 h) and 0, 2, 4, 8, 16, 24, 36, 48, 60 and 72 h after initiation of treatment. Parasite population dynamics were assessed using nested polymerase chain reaction (PCR)-genotyping of merozoite surface protein (msp) 1 and 2.\ud \ud RESULTS\ud \ud PCR-analyses from nine sequential blood samples collected after initiation of treatment identified 20 and 21 additional genotypes in 15/50 (30%) and 14/50 (28%) children with msp1 and msp2, respectively, non-detectable in the pre-treatment samples (-2 and 0 h combined). Some 15/20 (75%) and 14/21 (67%) of these genotypes were identified within 24 h, whereas 17/20 (85%) and 19/21 (90%) within 48 h for msp1 and msp2, respectively. The genotype profile was diverse, and varied considerably over time both within and between patients, molecular markers and their respective families.\ud \ud CONCLUSION\ud \ud PCR analyses from multiple blood samples collected during the early treatment phase revealed a complex picture of parasite sub-populations. This underlines the importance of interpreting PCR-outcomes with caution and suggests that the present use of PCR-adjustment from paired blood samples in anti-malarial drug trials may overestimate assessment of drug efficacy in high transmission areas in Africa.The study is registered at http://www.clinicaltrials.gov with identifier NCT00336375

Expansion algorithm for the density matrix

A purification algorithm for expanding the single-particle density matrix in terms of the Hamiltonian operator is proposed. The scheme works with a predefined occupation and requires less than half the number of matrix-matrix multiplications compared to existing methods at low (90%) occupancy. The expansion can be used with a fixed chemical potential in which case it is an asymmetric generalization of and a substantial improvement over grand canonical McWeeny purification. It is shown that the computational complexity, measured as number of matrix multiplications, essentially is independent of system size even for metallic materials with a vanishing band gap.Comment: 5 pages, 4 figures, to appear in Phys. Rev.

Interaction Between Solid Copper Jets and Powerful Electrical Current Pulses

The interaction between a solid copper jet and an electric current pulse is studied. Coppe

Принципы лечения очаговой гиперплазии эндометрия в постменопаузе

МЕНОПАУЗАЭНДОМЕТРИЯ ГИПЕРПЛАЗИ

Plasmodium falciparum drug resistance phenotype as assessed by patient antimalarial drug levels and Its association With pfmdr1 polymorphisms

Background. Multidrug-resistant Plasmodium falciparum is a major threat to global malaria control. Parasites develop resistance by gradually acquiring genetic polymorphisms that decrease drug susceptibility. The aim of this study was to investigate the extent to which parasites with different genetic characteristics are able to withstand individual drug blood concentrations. Methods. We analyzed 2 clinical trials that assessed the efficacy and effectiveness of artemether-lumefantrine. As a proof of concept, we used measured day 7 lumefantrine concentrations to estimate the concentrations at which reinfections multiplied. P. falciparum multidrug resistance gene 1 (pfmdr1) genotypes of these parasites were then correlated to drug susceptibility. Results. Reinfecting parasites with the pfmdr1 N86/184F/D1246 haplotype were able to withstand lumefantrine blood concentrations 15-fold higher than those with the 86Y/Y184/1246Y haplotype. Conclusions. By estimating drug concentrations, we were able to quantify the contribution of pfmdr1 single-nucleotide polymorphisms to reduced lumefantrine susceptibility. The method can be applied to all long-half-life antimalarial drugs, enables early detection of P. falciparum with reduced drug susceptibility in vivo, and represents a novel way for unveiling molecular markers of antimalarial drug resistance.Swedish Development Cooperation Agency-Department for Research Cooperation (SIDA-SAREC) [SWE 2004-3850, Bil-Tz 16/9875007059, SWE-2009-165]; World Health Organization MIM-TDR [[A60100] MAL IRM 06 03]; Goljes Foundation; Swedish medical research council [K2010-56X-21457-01-3]; Wellcome Trust of Great Britai