Hepatic phosphorylation status of serine/threonine kinase 1, mammalian target of rapamycin signaling proteins, and growth rate in Holstein heifer calves in response to maternal supply of methionine.

The study investigated whether methionine supply during late pregnancy is associated with liver mammalian target of rapamycin (MTOR) pathway phosphorylation, plasma biomarkers, and growth in heifer calves born to cows fed a control diet (CON) or the control diet plus ethylcellulose rumen-protected methionine (MET; 0.09% of dry matter intake) for the last 28 d prepartum. Calves were fed and managed similarly during the first 56 d of age. Plasma was harvested at birth and 2, 7, 21, 42, and 50 d of age and was used for biomarker profiling. Liver biopsies were harvested at 4, 14, 28, and 50 d of age and used for protein expression. Body weight, hip height, hip width, wither height, body length, rectal temperature, fecal score, and respiratory score were measured weekly. Starter intake was measured daily, and average daily gain was calculated during the first 8 wk of age. During the first 7 wk of age, compared with calves in the CON group, calves in the MET group had greater body weight, hip height, wither height, and average daily gain despite similar daily starter intake. Concentration of methionine in plasma was lower at birth but increased markedly at 2 and 7 d of age in MET calves. Plasma insulin, glucose, free fatty acids, and hydroxybutyrate did not differ. A greater ratio of phosphorylated α-serine/threonine kinase (AKT):total AKT protein expression was detected in MET calves, namely due to differences at 4 d of age. The phosphorylated MTOR:total MTOR ratio also was greater in MET calves due to differences at 28 and 50 d (8 d postweaning). The decrease in phosphorylated MTOR:total MTOR between 14 and 28 d in CON calves agreed with the increase in phosphorylated eukaryotic translation initiation factor 4E binding protein 1 (EIF4EBP1):total EIF4EBP1 ratio during the same time frame. The overall expression of phosphorylated ribosomal protein S6 kinase B1 (RPS6KB1):total RPS6KB1 and phosphorylated eukaryotic translation elongation factor 2 (EEF2):total EEF2 was lower in MET calves. Regardless of methionine supply prepartum, there was an 11-fold temporal decrease from 4 to 50 d in phosphorylated AKT:total AKT. Similarly, regardless of methionine supply, there were overall decreases in phosphorylation ratios of AKT, MTOR, RPS6KB1, and eukaryotic translation initiation factor 2A (EIF2A) over time. Data provide evidence of a positive effect of methionine supply during the last month of pregnancy on rates of growth during the first 7 wk of age. Phosphorylation status of some components of the MTOR pathway in neonatal calf liver also was associated with greater maternal supply of methionine. Thus, the data suggest that molecular mechanisms in the liver might be programmed by supply of methionine during late pregnancy. The exact mechanisms coordinating the observed responses remain to be determined

A unitary correlation operator method

The short range repulsion between nucleons is treated by a unitary correlation operator which shifts the nucleons away from each other whenever their uncorrelated positions are within the replusive core. By formulating the correlation as a transformation of the relative distance between particle pairs, general analytic expressions for the correlated wave functions and correlated operators are given. The decomposition of correlated operators into irreducible n-body operators is discussed. The one- and two-body-irreducible parts are worked out explicitly and the contribution of three-body correlations is estimated to check convergence. Ground state energies of nuclei up to mass number A=48 are calculated with a spin-isospin-dependent potential and single Slater determinants as uncorrelated states. They show that the deduced energy- and mass-number-independent correlated two-body Hamiltonian reproduces all "exact" many-body calculations surprisingly well.Comment: 43 pages, several postscript figures, uses 'epsfig.cls'. Submitted to Nucl. Phys. A. More information available at http://www.gsi.de/~fm

Nanosized Chevrel phases for dendrite-free zinc–ion based energy storage: unraveling the phase transformations

The nanoscale form of the Chevrel phase, Mo$_6$S$_8$, is demonstrated to be a highly efficient zinc-free anode in aqueous zinc ion hybrid supercapacitors (ZIHSCs). The unique morphological characteristics of the material when its dimensions approach the nanoscale result in fast zinc intercalation kinetics that surpass the ion transport rate reported for some of the most promising materials, such as TiS$_2$ and TiSe$_2$. In situ Raman spectroscopy, post-mortem X-ray diffraction, Hard X-ray photoelectron spectroscopy, and density functional theory (DFT) calculations were combined to understand the overall mechanism of the zinc ion (de)intercalation process. The previously unknown formation of the sulfur-deficient Zn$_{2,9}$Mo$_{15}$S$_{19}$ (Zn$_{1,6}$Mo$_6$S$_{7,6}$) phase is identified, leading to a re-evaluation of the mechanism of the (de)intercalation process. A full cell comprised of an activated carbon (YEC-8A) positive electrode delivers a cell capacity of 38 mA h g$^{-1}$ and an energy density of 43.8 W h kg$^{-1}$ at a specific current density of 0.2 A g$^{-1}$. The excellent cycling stability of the device is demonstrated for up to 8000 cycles at 3 A g$^{-1}$ with a coulombic efficiency close to 100%. Post-mortem microscopic studies reveal the absence of dendrite formation at the nanosized Mo$_6$S$_8$ anode, in stark contrast to the state-of-the-art zinc electrode

Molecular basis for passive immunotherapy of Alzheimer's disease

Amyloid aggregates of the amyloid-{beta} (A{beta}) peptide are implicated in the pathology of Alzheimer's disease. Anti-A{beta} monoclonal antibodies (mAbs) have been shown to reduce amyloid plaques in vitro and in animal studies. Consequently, passive immunization is being considered for treating Alzheimer's, and anti-A{beta} mAbs are now in phase II trials. We report the isolation of two mAbs (PFA1 and PFA2) that recognize A{beta} monomers, protofibrils, and fibrils and the structures of their antigen binding fragments (Fabs) in complex with the A{beta}(1–8) peptide DAEFRHDS. The immunodominant EFRHD sequence forms salt bridges, hydrogen bonds, and hydrophobic contacts, including interactions with a striking WWDDD motif of the antigen binding fragments. We also show that a similar sequence (AKFRHD) derived from the human protein GRIP1 is able to cross-react with both PFA1 and PFA2 and, when cocrystallized with PFA1, binds in an identical conformation to A{beta}(1–8). Because such cross-reactivity has implications for potential side effects of immunotherapy, our structures provide a template for designing derivative mAbs that target A{beta} with improved specificity and higher affinity

Translationally invariant treatment of pair correlations in nuclei: I. Spin and isospin dependent correlations

We study the extension of our translationally invariant treatment of few-body nuclear systems to heavier nuclei. At the same time we also introduce state-dependent correlation operators. Our techniques are tailored to those nuclei that can be dealt with in LS coupling, which includes all nuclei up to the shell closure at A=40. We study mainly p-shell nuclei in this paper. A detailed comparison with other microscopic many-body approaches is made, using a variety of schematic nuclear interactions. It is shown that our methodology produces very good energies, and presumably also wave functions, for medium mass nuclei

Summary of the ISEV workshop on extracellular vesicles as disease biomarkers, held in Birmingham, UK, during December 2017

This report summarises the presentations and activities of the ISEV Workshop on extracellular vesicle biomarkers held in Birmingham, UK during December 2017. Among the key messages was broad agreement about the importance of biospecimen science. Much greater attention needs to be paid towards the provenance of collected samples. The workshop also highlighted clear gaps in our knowledge about pre-analytical factors that alter extracellular vesicles (EVs). The future utility of certified standards for credentialing of instruments and software, to analyse EV and for tracking the influence of isolation steps on the structure and content of EVs were also discussed. Several example studies were presented, demonstrating the potential utility for EVs in disease diagnosis, prognosis, longitudinal serial testing and stratification of patients. The conclusion of the workshop was that more effort focused on pre-analytical issues and benchmarking of isolation methods is needed to strengthen collaborations and advance more effective biomarkers