A Chemical Analog of Curcumin as an Improved Inhibitor of Amyloid Abeta Oligomerization

Amyloid-like plaques are characteristic lesions defining the neuropathology of Alzheimer's disease (AD). The size and density of these plaques are closely associated with cognitive decline. To combat this disease, the few therapies that are available rely on drugs that increase neurotransmission; however, this approach has had limited success as it has simply slowed an imminent decline and failed to target the root cause of AD. Amyloid-like deposits result from aggregation of the Aβ peptide, and thus, reducing amyloid burden by preventing Aβ aggregation represents an attractive approach to improve the therapeutic arsenal for AD. Recent studies have shown that the natural product curcumin is capable of crossing the blood-brain barrier in the CNS in sufficient quantities so as to reduce amyloid plaque burden. Based upon this bioactivity, we hypothesized that curcumin presents molecular features that make it an excellent lead compound for the development of more effective inhibitors of Aβ aggregation. To explore this hypothesis, we screened a library of curcumin analogs and identified structural features that contribute to the anti-oligomerization activity of curcumin and its analogs. First, at least one enone group in the spacer between aryl rings is necessary for measureable anti-Aβ aggregation activity. Second, an unsaturated carbon spacer between aryl rings is essential for inhibitory activity, as none of the saturated carbon spacers showed any margin of improvement over that of native curcumin. Third, methoxyl and hydroxyl substitutions in the meta- and para-positions on the aryl rings appear necessary for some measure of improved inhibitory activity. The best lead inhibitors have either their meta- and para-substituted methoxyl and hydroxyl groups reversed from that of curcumin or methoxyl or hydroxyl groups placed in both positions. The simple substitution of the para-hydroxy group on curcumin with a methoxy substitution improved inhibitor function by 6-7-fold over that measured for curcumin

Intimate partner violence against women in rural Vietnam - different socio-demographic factors are associated with different forms of violence: Need for new intervention guidelines?

Background: This population-based study investigated the different forms, magnitude and risk factors of men's violence against women in intimate relationships in a rural part of northern Vietnam and whether a difference in risk factors were at hand for the different forms of violence. Vietnam has undergone a rapid transition in the last 20 years, moving towards a more equal situation for men and women however, Confucian doctrine is still strong and little is known about men's violence against women within the Vietnamese family. Methods: This is a cross-sectional population-based study that used a questionnaire developed by the World Health Organisation for investigating women's health and violence against women in different settings. Face-to face structured interviewing was performed and 883 married women, aged 17 to 60 participated. Bi- and multivariate analyses was used for risk factor assessment. Results: The lifetime prevalence of physical violence was 30.9 percent and past year prevalence was 8.3 per cent, while the corresponding figures for physical and sexual violence combined was 32.7 and 9.2 percent. The lifetime prevalence was highest for psychological abuse ( 27.9 percent) as a single entity. In most cases the violence was of a severe nature and exercised as repeated acts over time. Woman's low educational level, husband's low education, low household income and the husband having more than one wife/partner were risk factors for lifetime and past year physical/sexual violence. The pattern of factors associated with psychological abuse alone was however different. Husband's low professional status and women's intermediate level of education appeared as risk factors. Conclusion: Men's violence against women in intimate relationships is commonly occurring in rural Vietnam. There is an obvious need of preventive and treatment activities. Our findings point at that pure psychological abuse is different from physical/sexual violence in terms of differing characteristics of the perpetrators and it might be that also different strategies are needed to reduce and prevent this violence

The Initial-Final Mass Relation among White Dwarfs in Wide Binaries

We present the initial-final mass relation derived from 10 white dwarfs in wide binaries that consist of a main sequence star and a white dwarf. The temperature and gravity of each white dwarf was measured by fitting theoretical model atmospheres to the observed spectrum using a $\chi^{2}$ fitting algorithm. The cooling time and mass was obtained using theoretical cooling tracks. The total age of each binary was estimated from the chromospheric activity of its main sequence component to an uncertainty of about 0.17 dex in log \textit{t} The difference between the total age and white dwarf cooling time is taken as the main sequence lifetime of each white dwarf. The initial mass of each white dwarf was then determined using stellar evolution tracks with a corresponding metallicity derived from spectra of their main sequence companions, thus yielding the initial-final mass relation. Most of the initial masses of the white dwarf components are between 1 - 2 M$_{\odot}$. Our results suggest a correlation between the metallicity of a white dwarf's progenitor and the amount of post-main-sequence mass loss it experiences - at least among progenitors with masses in the range of 1 - 2 M$_{\odot}$. A comparison of our observations to theoretical models suggests that low mass stars preferentially lose mass on the red giant branch.Comment: 28 pages, 8 figures, accepted for publication in Ap

The landscape of inherited and de novo copy number variants in a plasmodium falciparum genetic cross

<p>Abstract</p> <p>Background</p> <p>Copy number is a major source of genome variation with important evolutionary implications. Consequently, it is essential to determine copy number variant (CNV) behavior, distributions and frequencies across genomes to understand their origins in both evolutionary and generational time frames. We use comparative genomic hybridization (CGH) microarray and the resolution provided by a segregating population of cloned progeny lines of the malaria parasite, <it>Plasmodium falciparum</it>, to identify and analyze the inheritance of 170 genome-wide CNVs.</p> <p>Results</p> <p>We describe CNVs in progeny clones derived from both Mendelian (i.e. inherited) and non-Mendelian mechanisms. Forty-five CNVs were present in the parent lines and segregated in the progeny population. Furthermore, extensive variation that did not conform to strict Mendelian inheritance patterns was observed. 124 CNVs were called in one or more progeny but in neither parent: we observed CNVs in more than one progeny clone that were not identified in either parent, located more frequently in the telomeric-subtelomeric regions of chromosomes and singleton <it>de novo </it>CNVs distributed evenly throughout the genome. Linkage analysis of CNVs revealed dynamic copy number fluctuations and suggested mechanisms that could have generated them. Five of 12 previously identified expression quantitative trait loci (eQTL) hotspots coincide with CNVs, demonstrating the potential for broad influence of CNV on the transcriptional program and phenotypic variation.</p> <p>Conclusions</p> <p>CNVs are a significant source of segregating and <it>de novo </it>genome variation involving hundreds of genes. Examination of progeny genome segments provides a framework to assess the extent and possible origins of CNVs. This segregating genetic system reveals the breadth, distribution and dynamics of CNVs in a surprisingly plastic parasite genome, providing a new perspective on the sources of diversity in parasite populations.</p

A pair of tess planets spanning the radius valley around the nearby mid-m dwarf ltt 3780

We present the confirmation of two new planets transiting the nearby mid-M dwarf LTT 3780 (TIC 36724087, TOI-732, $V=13.07$, $K_s=8.204$, $R_s$=0.374 R$_{\odot}$, $M_s$=0.401 M$_{\odot}$, d=22 pc). The two planet candidates are identified in a single TESS sector and are validated with reconnaissance spectroscopy, ground-based photometric follow-up, and high-resolution imaging. With measured orbital periods of $P_b=0.77$ days, $P_c=12.25$ days and sizes $r_{p,b}=1.33\pm 0.07$ R$_{\oplus}$, $r_{p,c}=2.30\pm 0.16$ R$_{\oplus}$, the two planets span the radius valley in period-radius space around low mass stars thus making the system a laboratory to test competing theories of the emergence of the radius valley in that stellar mass regime. By combining 63 precise radial-velocity measurements from HARPS and HARPS-N, we measure planet masses of $m_{p,b}=2.62^{+0.48}_{-0.46}$ M$_{\oplus}$ and $m_{p,c}=8.6^{+1.6}_{-1.3}$ M$_{\oplus}$, which indicates that LTT 3780b has a bulk composition consistent with being Earth-like, while LTT 3780c likely hosts an extended H/He envelope. We show that the recovered planetary masses are consistent with predictions from both photoevaporation and from core-powered mass loss models. The brightness and small size of LTT 3780, along with the measured planetary parameters, render LTT 3780b and c as accessible targets for atmospheric characterization of planets within the same planetary system and spanning the radius valley

The Multiplanet System TOI-421*: A Warm Neptune and a Super Puffy Mini-Neptune Transiting a G9 V Star in a Visual Binary*

We report the discovery of a warm Neptune and a hot sub-Neptune transiting TOI-421 (BD-14 1137, TIC 94986319), a bright (V = 9.9) G9 dwarf star in a visual binary system observed by the Transiting Exoplanet Survey Satellite (TESS) space mission in Sectors 5 and 6. We performed ground-based follow-up observations—comprised of Las Cumbres Observatory Global Telescope transit photometry, NIRC2 adaptive optics imaging, and FIbre-fed Echellé Spectrograph, CORALIE, High Accuracy Radial velocity Planet Searcher, High Resolution Échelle Spectrometer, and Planet Finder Spectrograph high-precision Doppler measurements—and confirmed the planetary nature of the 16 day transiting candidate announced by the TESS team. We discovered an additional radial velocity signal with a period of five days induced by the presence of a second planet in the system, which we also found to transit its host star. We found that the inner mini-Neptune, TOI-421 b, has an orbital period of Pb = 5.19672 ± 0.00049 days, a mass of Mb = 7.17 ± 0.66 M⊕, and a radius of Rb = ${2.68}_{-0.18}^{+0.19}$ R⊕, whereas the outer warm Neptune, TOI-421 c, has a period of Pc = 16.06819 ± 0.00035 days, a mass of Mc = ${16.42}_{-1.04}^{+1.06}$ M⊕, a radius of Rc = ${5.09}_{-0.15}^{+0.16}$ R⊕, and a density of ρc = ${0.685}_{-0.072}^{+0.080}$ g cm−3. With its characteristics, the outer planet (ρc = ${0.685}_{-0.072}^{+0.080}$ g cm−3) is placed in the intriguing class of the super-puffy mini-Neptunes. TOI-421 b and TOI-421 c are found to be well-suited for atmospheric characterization. Our atmospheric simulations predict significant Lyα transit absorption, due to strong hydrogen escape in both planets, as well as the presence of detectable CH4 in the atmosphere of TOI-421 c if equilibrium chemistry is assumed