Enantioselektive Synthese von (1S,4R)-4-Hydroxycyclopent-2-enyl-acetat durch enzym-katalysierte Veresterung von cis-Cyclopent-2-en-1,4-diol mit Acetanhydrid. Gaschromatographische Untersuchungen zum Reaktionsmechanismus

(1S,4R)-4-Hydroxycyclopent-2-enyl-acetate (1), an attractive starting material for the synthesis of prostaglandins, was readily prepared by an enzyme-catalyzed interesterification procedure using acetic anhydride as acylation agent. As the chemical yield of the chiral monoacylation product is rather low (45%), we investigated the acylation mechanism of this reaction to optimize the product output. Kinetic measurements were carried out by means of gas chromatography on a chiral stationary phase, synthesized by methylation of β-cyclodextrin

The TATA-binding protein regulates maternal mRNA degradation and differential zygotic transcription in zebrafish

Early steps of embryo development are directed by maternal gene products and trace levels of zygotic gene activity in vertebrates. A major activation of zygotic transcription occurs together with degradation of maternal mRNAs during the midblastula transition in several vertebrate systems. How these processes are regulated in preparation for the onset of differentiation in the vertebrate embryo is mostly unknown. Here, we studied the function of TATA-binding protein (TBP) by knock down and DNA microarray analysis of gene expression in early embryo development. We show that a subset of polymerase II-transcribed genes with ontogenic stage-dependent regulation requires TBP for their zygotic activation. TBP is also required for limiting the activation of genes during development. We reveal that TBP plays an important role in the degradation of a specific subset of maternal mRNAs during late blastulation/early gastrulation, which involves targets of the miR-430 pathway. Hence, TBP acts as a specific regulator of the key processes underlying the transition from maternal to zygotic regulation of embryogenesis. These results implicate core promoter recognition as an additional level of differential gene regulation during development

Breast cancer management pathways during the COVID-19 pandemic: outcomes from the UK ‘Alert Level 4’ phase of the B-MaP-C study

Abstract: Background: The B-MaP-C study aimed to determine alterations to breast cancer (BC) management during the peak transmission period of the UK COVID-19 pandemic and the potential impact of these treatment decisions. Methods: This was a national cohort study of patients with early BC undergoing multidisciplinary team (MDT)-guided treatment recommendations during the pandemic, designated ‘standard’ or ‘COVID-altered’, in the preoperative, operative and post-operative setting. Findings: Of 3776 patients (from 64 UK units) in the study, 2246 (59%) had ‘COVID-altered’ management. ‘Bridging’ endocrine therapy was used (n = 951) where theatre capacity was reduced. There was increasing access to COVID-19 low-risk theatres during the study period (59%). In line with national guidance, immediate breast reconstruction was avoided (n = 299). Where adjuvant chemotherapy was omitted (n = 81), the median benefit was only 3% (IQR 2–9%) using ‘NHS Predict’. There was the rapid adoption of new evidence-based hypofractionated radiotherapy (n = 781, from 46 units). Only 14 patients (1%) tested positive for SARS-CoV-2 during their treatment journey. Conclusions: The majority of ‘COVID-altered’ management decisions were largely in line with pre-COVID evidence-based guidelines, implying that breast cancer survival outcomes are unlikely to be negatively impacted by the pandemic. However, in this study, the potential impact of delays to BC presentation or diagnosis remains unknown

High functional diversity stimulates diversification in experimental microbial communities

There is a growing awareness that biodiversity not only drives ecosystem services but also affects evolutionary dynamics. However, different theories predict contrasting outcomes on when do evolutionary processes occur within a context of competition. We tested whether functional diversity can explain diversification patterns. We tracked the survival and diversification of a focal bacterial species (Pseudomonas fluorescens) growing in bacterial communities of variable diversity and composition. We found that high functional diversity reduced the fitness of the focal species and, at the same time, fostered its diversification. This pattern was linked to resource competition: High diversity increased competition on a portion of the resources while leaving most underexploited. The evolved phenotypes of the focal species showed a better use of underexploited resources, albeit at a cost of lower overall growth rates. As a result, diversification alleviated the impact of competition on the fitness of the focal species. We conclude that biodiversity can stimulate evolutionary diversification, provided that sufficient alternative niches are available

Apples to Apples: Shift from Mass Ratio to Additive Molecules per Electrode Area to Optimize Li-Ion Batteries

Electrolyte additives in liquid electrolyte batteries can trigger the formation of a protective interphase (SEI) atthe electrodes that aims to suppress side reactions at the electrodes. Studies of varying amounts of additives have been done over the last years, providing a comprehensive understanding of the impact of the electrolyte formulation on the lifetime of the cells. However, these studies mostly focus on the variation of the mass fraction of additive in the electrolyte while disregarding the ratio (radd) of the additive\u27s amount of substance (nadd) to the electrode area (Aelectrode). Herein we utilize our extremely accurate automatic battery assembly system (AUTOBASS) to vary electrode area and amount of substance of the additive. The data provides strong evidence that reporting the mass ratios of electrolyte components is insufficient and the mol of additive relative to the electrodes’ area should be reported. Herein, the two most utilized additives, namely fluoroethylene carbonate (FEC) and vinylene carbonate (VC) were studied. Each additive was varied from 0.1 wt.-% - 3.0 wt.-% for VC, and 5 wt.-% - 15 wt.-% for FEC for two mass loadings of 1 mAh/cm2 and 3 mAh/cm2. To engage the community to find better descriptors, such as the proposed radd, we publish the dataset alongside this manuscript

Niobium as Alternative Material for Refractory and Active Plasmonics

The development of stable compounds for durable optics is crucial for the future of plasmonic applications. Even though niobium is mainly known as a superconducting material, it can qualify as an alternative material for high-temperature and active plasmonic applications. We utilize electron beam lithography combined with plasma etching techniques to fabricate nanoantenna arrays of niobium. Tailoring the niobium antenna geometry enables precise tuning of the plasmon resonances from the near- to the mid-infrared spectral range. Additionally, the hydrogen absorptivity as well as the high-temperature stability of the antennas have been investigated. Further advantages of niobium such as superconductivity make niobium highly attractive for a multitude of plasmonic devices ranging from active and refractory perfect absorbers/emitters to plasmon-based single photon detectors

Autonomous battery optimisation by deploying distributed experiments and simulations

Non-trivial relationships link individual materials properties to device-level performance. Device optimisation therefore calls for new automation approaches beyond the laboratory bench with tight integration of different research methods. We demonstrate a Materials Acceleration Platform (MAP) in the field of battery research based on our problem-agnostic Fast Intentional Agnostic Learning Server (FINALES) framework, which integrates simulations and physical experiments without centrally controlling them. The connected capabilities entail the formulation and characterisation of electrolytes, cell assembly and testing, early lifetime prediction, and ontology-mapped data storage provided by institutions distributed across Europe. The infrastructure is used to optimise the ionic conductivity of electrolytes and the End Of Life (EOL) of lithium-ion coin cells by varying the electrolyte formulation. We rediscover trends in ionic conductivity and investigate the effect of the electrolyte formulation on the EOL. We further demonstrate the capability of our MAP to bridge diverse research modalities, scales, and institutions enabling system-level investigations under asynchronous conditions while handling concurrent workflows on the material- and system-level, demonstrating true intention-agnosticism

Blood coagulation factor XII drives adaptive immunity during neuroinflammation via CD87-mediated modulation of dendritic cells

Aberrant immune responses represent the underlying cause of central nervous system (CNS) autoimmunity, including multiple sclerosis (MS). Recent evidence implicated the crosstalk between coagulation and immunity in CNS autoimmunity. Here we identify coagulation factor XII (FXII), the initiator of the intrinsic coagulation cascade and the kallikrein–kinin system, as a specific immune cell modulator. High levels of FXII activity are present in the plasma of MS patients during relapse. Deficiency or pharmacologic blockade of FXII renders mice less susceptible to experimental autoimmune encephalomyelitis (a model of MS) and is accompanied by reduced numbers of interleukin-17A-producing T cells. Immune activation by FXII is mediated by dendritic cells in a CD87-dependent manner and involves alterations in intracellular cyclic AMP formation. Our study demonstrates that a member of the plasmatic coagulation cascade is a key mediator of autoimmunity. FXII inhibition may provide a strategy to combat MS and other immune-related disorders