Structural optimization of reversible dibromomaleimide peptide stapling

Methods to constrain peptides in a bioactive α‐helical conformation for inhibition of protein‐protein interactions represent an ongoing area of investigation in chemical biology. Recently, the first example of a reversible “stapling” methodology was described which exploits native cysteine or homocysteine residues spaced at the i and i + 4 positions in a peptide sequence together with the thiol selective reactivity of dibromomaleimides (a previous study). This manuscript reports on the optimization of the maleimide based constraint, focusing on the kinetics of macrocyclization and the extent to which helicity is promoted with different thiol containing amino acids. The study identified an optimal stapling combination of X1 = L‐Cys and X5 = L‐hCys in the context of the model peptide Ac‐X1AAAX5‐NH2, which should prove useful in implementing the dibromomaleimide stapling strategy in peptidomimetic ligand discovery programmes

Gonadal Hormones Rapidly Enhance Spatial Memory and Increase Hippocampal Spine Density in Male Rats

17β-estradiol (E(2)) rapidly, within minutes, activates behaviors and cognition by binding to membrane estrogen receptors, activating cell signaling cascades and increasing dendritic spines. In female rodents, E(2) enhances spatial memory within 2–4 hours, and spine density is increased in the CA1 area of the hippocampus within 30–60 minutes. Although chronic gonadal hormone treatments in male rats alter cognition and spines/spine synapses and acute hormone effects occur in hippocampal slices, effects of acute, in vivo hormone administration in males are unknown. Therefore, we assessed rapid effects of E(2) (20 μg/kg) and testosterone (T) (750 μg/kg) on spatial memory using the object placement task and on hippocampal spine density using Golgi impregnation. Orchidectomized rats received hormones immediately after the training trial and were tested for retention 2 hours later. Vehicle-injected orchidectomized males spent equal time exploring objects in the old and new locations, but E(2-) or T-treated subjects spent more time exploring objects at the new location, suggesting enhanced memory. Both hormones also increased spine density in CA1, but not the dentate gyrus, by 20%–40% at 30 minutes and 2 hours after injections. This report is the first, to our knowledge, to show E(2) and T enhancements of memory and spine density within such a short time frame in male rats

Attempts to identify Cassava Brown Streak Virus in western Democratic Republic of Congo

Open Access ArticleRoot necrosis similar to those of the cassava brown streak disease (CBSD) were observed on cassava in western provinces of the Democratic Republic of Congo (DR.Congo) in the early 2000’s. However molecular laboratory diagnosis were not able to detect any causative agent responsible for the attacks, hence, the disease related to these symptoms was named CBSD-like disease. In order to assess the distribution and the incidence of the CBSD-like disease, surveys were carried out in four western provinces, comprising, Kwango and Kwilu, Sud Ubangi, Kinshasa and Kongo Central. CBSD-like disease was observed in all surveyed provinces on the basis of root symptoms because foliar symptoms were different to those of the documented cases of CBSD in other parts of east Africa. CBSD-like disease incidence was high in Kongo Central and Sud Ubangi, exceeding an average of 50 %, but low in Kwango and Kwilu (32.8%) and in Kinshasa (19.1%). During the surveys, cassava leaf samples were collected for lab identification of the causal agent. PCR diagnosis was done on these samples using primers specific for the two known CBSVs. All samples tested negative with no amplification of DNA fragments of the correct size. Thus, further analysis on the causative organism is needed using Next Generation Sequencing (NGS) approaches. NGS approaches will help also to identify the causative organism in other Central Africa countries (Angola, Congo-Brazzaville and Gabon) where such cassava root necrosis have been reported or are suspected

The dimerized phase of ionic Hubbard models

We derive an effective Hamiltonian for the ionic Hubbard model at half filling, extended to include nearest-neighbor repulsion. Using a spin-particle transformation, the effective model is mapped onto simple spin-1 models in two particular cases. Using another spin-particle transformation, a slightly modified model is mapped into an SU(3) antiferromagnetic Heisenberg model whose exact ground state is known to be spontaneously dimerized. From the effective models several properties of the dimerized phase are discussed, like ferroelectricity and fractional charge excitations. Using bosonization and recent developments in the theory of macroscopic polarization, we show that the polarization is proportional to the charge of the elementary excitations

Cytokine secretion in breast cancer cells – MILLIPLEX assay data

© 2019 The Author(s) Metastatic breast cancer is the most advanced stage of breast cancer and the leading cause of breast cancer mortality. Although understanding of the cancer progression and metastasis process has improved, the bi-directional communication between the tumor cell and the tumor microenvironment is still not well understood. Breast cancer cells are highly secretory, and their secretory activity is modulated by a variety of inflammatory stimuli present in the tumor microenvironment. Here, we characterized the cytokine expression in human breast cancer cells (MDA-MB-231, MCF-7, T-47D, and BT-474) in vitro using 41 cytokine MILLIPLEX assay. Further, we compared cytokine expression in breast cancer cells to those in non-tumorigenic human breast epithelial MCF-10A cells

Charge and spin excitations of insulating lamellar copper oxides

A consistent description of low-energy charge and spin responses of the insulating Sr_2CuO_2Cl_2 lamellar system is found in the framework of a one-band Hubbard model which besides $U$ includes hoppings up to 3^{rd} nearest-neighbors. By combining mean-field calculations, exact diagonalization (ED) results, and Quantum Monte Carlo simulations (QMC), we analyze both charge and spin degrees of freedom responses as observed by optical conductivity, ARPES, Raman and inelastic neutron scattering experiments. Within this effective model, long-range hopping processes flatten the quasiparticle band around $(0,\pi)$. We calculate also the non-resonant A_{1g} and B_{1g} Raman profiles and show that the latter is composed by two main features, which are attributed to 2- and 4-magnon scattering.Comment: 6 pages, 3 figures, To be published in PRB (july

Interaction Between Hot Carrier Aging and PBTI Degradation in nMOSFETs: Characterization, Modelling and Lifetime Prediction

Modelling of the interaction between Hot Carrier Aging (HCA) and Positive Bias Temperature Instability (PBTI) has been considered as one of the main challenges in nanoscale CMOS circuit design. Previous works were mainly based on separate HCA and PBTI instead of Interacted HCA-PBTI Degradation (IHPD). The key advance of this work is to develop a methodology that enables accurate modelling of IHPD through understanding the charging/discharging and generation kinetics of different types of defects during the interaction between HCA and PBTI. It is found that degradation during alternating HCA and PBTI stress cannot be modelled by independent HCI/PBTI. Different stress sequence, i.e. HCA-PBTI-HCA and PBTI-HCA-PBTI, lead to completely different degradation kinetics. Based on the Cyclic Anti-neutralization Model (CAM), for the first time, IHPD has been accurately modelled for both short and long channel devices. Complex degradation mechanisms and kinetics can be well explained by our model. Our results show that device lifetime can be underestimated by one decade without considering interaction