Dual-acting stapled peptides target both HIV-1 entry and assembly

Background: Previously, we reported the conversion of the 12-mer linear and cell-impermeable peptide CAI to a cell-penetrating peptide NYAD-1 by using an i,i + 4 hydrocarbon stapling technique and confirmed its binding to the C-terminal domain (CTD) of the HIV-1 capsid (CA) protein with an improved affinity (Kd ~ 1 μM) compared to CAI (Kd ~ 15 μM). NYAD-1 disrupts the formation of both immature- and mature-like virus particles in in vitro and cell-based assembly assays. In addition, it displays potent anti-HIV-1 activity in cell culture against a range of laboratory-adapted and primary HIV-1 isolates.<p></p> Results: In this report, we expanded the study to i,i + 7 hydrocarbon-stapled peptides to delineate their mechanism of action and antiviral activity. We identified three potent inhibitors, NYAD-36, -66 and -67, which showed strong binding to CA in NMR and isothermal titration calorimetry (ITC) studies and disrupted the formation of mature-like particles. They showed typical α-helical structures and penetrated cells; however, the cell penetration was not as efficient as observed with the i,i + 4 peptides. Unlike NYAD-1, the i,i + 7 peptides did not have any effect on virus release; however, they impaired Gag precursor processing. HIV-1 particles produced in the presence of these peptides displayed impaired infectivity. Consistent with an effect on virus entry, selection for viral resistance led to the emergence of two mutations in the gp120 subunit of the viral envelope (Env) glycoprotein, V120Q and A327P, located in the conserved region 1 (C1) and the base of the V3 loop, respectively.<p></p> Conclusion: The i,i + 7 stapled peptides derived from CAI unexpectedly target both CA and the V3 loop of gp120. This dual-targeted activity is dependent on their ability to penetrate cells as well as their net charge. This mechanistic revelation will be useful in further modifying these peptides as potent anti-HIV-1 agents.<p></p&gt

Comparative Study of the Use of Insect Meal from Spodoptera littoralis and Bactrocera zonata for Feeding Japanese Quail Chicks

A transformation of current livestock production towards a more sustainable operation is crucial to face nutritional and environmental challenges. There is an urgent demand for more sustainable high-quality feed sources to reduce environmental costs. Insects pose a potential alternative since they can be reared sustainably on food and feed residues. Know-how in mass rearing already exists for insect species used in biological pest control, such as the African cotton leafworm Spodoptera littoralis and the peach fruit fly Bactrocera zonata. The impact of a replacement of 50% of soybean meal by S. littoralis and B. zonata meal, respectively, on seven-days-old Japanese quail chicks was investigated in feeding trials. Concomitantly, the chemical compositions of the two insect meals and soybean meal were determined and compared. It was observed that the insect meals had higher protein and fat contents, lower carbohydrate contents and contained more saturated fatty acids than soybean meal. They also had higher methionine, and S. littoralis had a higher lysine content. Feeding trials resulted in improved growth, feed performance parameters, carcass characteristics, and biochemical indices for both insect meals. Consequently, both insect meals represent a promising alternative to soy in the feed of Japanese quail chicks.DFG, 414044773, Open Access Publizieren 2019 - 2020 / Technische Universität Berli

Energy Content of Colliding Plane Waves using Approximate Noether Symmetries

This paper is devoted to study the energy content of colliding plane waves using approximate Noether symmetries. For this purpose, we use approximate Lie symmetry method of Lagrangian for differential equations. We formulate the first-order perturbed Lagrangian for colliding plane electromagnetic and gravitational waves. It is shown that in both cases, there does not existComment: 18 pages, accepted for publication in Brazilian J Physic

The neglected contributions of self-efficacy to older adults’ financial capacity

An ageing population comes with its own set of challenges such as impaired financial capacity and resultant dependency on others to manage financial affairs. Dependency, in turn, as the evidence suggests, creates opportunities for financial exploitation of older adults. Related studies have primarily examined the clinical features and correlates of financial capacity or have attempted to develop its multidimensional measures. Both of which do little to resolve issues associated with impaired financial capacity. This paper aims to make a case for future researchers to assess older adults’ financial capacity from a non-clinical aspect. Drawing on the notion of self-efficacy, as encapsulated within the social cognitive theory, this paper presents evidence from a host of different domains to demonstrate the potential contributions of self-efficacy to older adults’ financial capacity. The contributions of self-efficacy in preserving older adults’ financial capacity appear to be much more profound than is currently acknowledged in the literature, thereby overlooking potentially promising and cost-effective interventions for autonomous ageing. This paper presents a novel application of self-efficacy to autonomous ageing. Within this context, potential routes to the deployment of self-efficacy-based interventions are also discussed

Nudging smokers away from lighting up: A meta-analysis of framing effect in current smokers

Should smoking cessation messages be framed in terms of gains or losses? While the risk-framing hypothesis suggests a persuasive advantage for gain-framed messages, empirical evidence so far has been mixed. In defense of the risk-framing hypothesis, researchers have suggested that the diversity of results in this literature stream can be attributed to differences in issue involvement. The present study examined these predictions by employing a meta-analysis (14 studies) comprising of a Correlated and Hierarchical Effects model with Robust Variance Estimation. There was a small persuasive advantage in favour of gain-framed messages (g = 0.104, SE = 0.049), but this contrast was not statistically significant (p = 0.070, CI95 = -0.011, 0.218). This finding is robust to the values of correlation between sampling errors of the effect sizes, influential outliers, and publication bias. Moreover, issue involvement proxied through nicotine dependence did not moderate the relative persuasiveness of gain and loss-framed messages in encouraging smoking cessation. The conclusion remains unchanged regardless of how nicotine dependence is measured and before and after controlling for study and participant characteristics. These results strongly cast doubt on the applicability of the risk-framing hypothesis that con- tinues to guide research and public-health campaigns

Angular analysis of B0→K∗(892)0ℓ+ℓ−B^0 \to K^\ast(892)^0 \ell^+ \ell^-

We present a measurement of angular observables, $P_4'$, $P_5'$, $P_6'$, $P_8'$, in the decay $B^0 \to K^\ast(892)^0 \ell^+ \ell^-$, where $\ell^+\ell^-$ is either $e^+e^-$ or $\mu^+\mu^-$. The analysis is performed on a data sample corresponding to an integrated luminosity of $711~\mathrm{fb}^{-1}$ containing $772\times 10^{6}$ $B\bar B$ pairs, collected at the $\Upsilon(4S)$ resonance with the Belle detector at the asymmetric-energy $e^+e^-$ collider KEKB. Four angular observables, $P_{4,5,6,8}'$ are extracted in five bins of the invariant mass squared of the lepton system, $q^2$. We compare our results for $P_{4,5,6,8}'$ with Standard Model predictions including the $q^2$ region in which the LHCb collaboration reported the so-called $P_5'$ anomaly.Comment: Conference paper for LHC Ski 2016. SM prediction for $P_{6}'$ corrected and reference for arXiv:1207.2753 adde

Determination of load capacity of a nongasketed flange joint under combined internal pressure, axial and bending loading for safe strength and sealing

Performance of a bolted flange joint is characterized mainly due to its ‘strength’ and ‘sealing capability’. A number of analytical and experimental studies have been conducted to study these characteristics only under internal pressure loading. A very limited work is found in literature under combined internal pressure and bending loading. Due to the ignorance of external loads i.e. bending and axial in addition to the internal pressure loading, an optimized performance of the bolted flange joint can not be achieved. The present design codes do not address the effects of combined loading on the structural integrity and sealing ability. To investigate joint strength and sealing capability under combined loading, an extensive comparative experimental and numerical study of a non-gasketed flange joint with two different taper angles on the flange surface and with different load combinations is carried out and overall joint performance and behavior is discussed. Actual joint load capacity is determined under both the design and proof test pressures with maximum additional external loading (axial and bending) that can be applied for safe joint performance

Measurement of the CKM Matrix Element ∣Vcb∣|V_{cb}| from B0→D∗−ℓ+νℓB^{0} \to D^{*-} \ell^+ \nu_\ell at Belle

We present a new measurement of the CKM matrix element $|V_{cb}|$ from $B^{0} \to D^{*-} \ell^+ \nu_\ell$ decays, reconstructed with the full Belle data set of $711 \, \rm fb^{-1}$ integrated luminosity. Two form factor parameterizations, originally conceived by the Caprini-Lellouch-Neubert (CLN) and the Boyd, Grinstein and Lebed (BGL) groups, are used to extract the product $\mathcal{F}(1)\eta_{\rm EW}|V_{cb}|$ and the decay form factors, where $\mathcal{F}(1)$ is the normalization factor and $\eta_{\rm EW}$ is a small electroweak correction. In the CLN parameterization we find $\mathcal{F}(1)\eta_{\rm EW}|V_{cb}| = (35.06 \pm 0.15 \pm 0.56) \times 10^{-3}$, $\rho^{2}=1.106 \pm 0.031 \pm 0.007$, $R_{1}(1)=1.229 \pm 0.028 \pm 0.009$, $R_{2}(1)=0.852 \pm 0.021 \pm 0.006$. For the BGL parameterization we obtain $\mathcal{F}(1)\eta_{\rm EW}|V_{cb}|= (34.93 \pm 0.23 \pm 0.59)\times 10^{-3}$, which is consistent with the World Average when correcting for $\mathcal{F}(1)\eta_{\rm EW}$. The branching fraction of $B^{0} \to D^{*-} \ell^+ \nu_\ell$ is measured to be $\mathcal{B}(B^{0}\rightarrow D^{*-}\ell^{+}\nu_{\ell}) = (4.90 \pm 0.02 \pm 0.16)\%$. We also present a new test of lepton flavor universality violation in semileptonic $B$ decays, $\frac{{\cal B }(B^0 \to D^{*-} e^+ \nu)}{{\cal B }(B^0 \to D^{*-} \mu^+ \nu)} = 1.01 \pm 0.01 \pm 0.03~$. The errors correspond to the statistical and systematic uncertainties respectively. This is the most precise measurement of $\mathcal{F}(1)\eta_{\rm EW}|V_{cb}|$ and form factors to date and the first experimental study of the BGL form factor parameterization in an experimental measurement

Measurement of branching fraction and direct CPCP asymmetry in charmless B+→K+K−π+B^+ \to K^+K^- \pi^+ decays at Belle

We report a study of the charmless hadronic decay of the charged $B$ meson to the three-body final state $K^+ K^- \pi^+$. The results are based on a data sample that contains $772\times10^6$ $B \bar{B}$ pairs collected at the $\Upsilon(4S)$ resonance with the Belle detector at the KEKB asymmetric-energy $e^+ e^-$ collider. The measured inclusive branching fraction and the direct $CP$ asymmetry are $(5.38\pm0.40\pm0.35)\times 10^{-6}$ and $-0.170\pm0.073\pm0.017$, respectively, where the first uncertainties are statistical and the second are systematic. The $K^{+}K^{-}$ invariant mass distribution of the signal candidates shows an excess in the region below $1.5$ GeV/$c^2$, which is consistent with the previous studies from BaBar and LHCb. In addition, strong evidence of a large direct $CP$ asymmetry is found in the $K^{+}K^{-}$ low-invariant-mass region.Comment: 7 pages, 3 figure