Stochastic Approach to Enantiomeric Excess Amplification and Chiral Symmetry Breaking

Stochastic aspects of chemical reaction models related to the Soai reactions as well as to the homochirality in life are studied analytically and numerically by the use of the master equation and random walk model. For systems with a recycling process, a unique final probability distribution is obtained by means of detailed balance conditions. With a nonlinear autocatalysis the distribution has a double-peak structure, indicating the chiral symmetry breaking. This problem is further analyzed by examining eigenvalues and eigenfunctions of the master equation. In the case without recycling process, final probability distributions depend on the initial conditions. In the nonlinear autocatalytic case, time-evolution starting from a complete achiral state leads to a final distribution which differs from that deduced from the nonzero recycling result. This is due to the absence of the detailed balance, and a directed random walk model is shown to give the correct final profile. When the nonlinear autocatalysis is sufficiently strong and the initial state is achiral, the final probability distribution has a double-peak structure, related to the enantiomeric excess amplification. It is argued that with autocatalyses and a very small but nonzero spontaneous production, a single mother scenario could be a main mechanism to produce the homochirality.Comment: 25 pages, 6 figure

Chiral Crystal Growth under Grinding

To study the establishment of homochirality observed in the crystal growth experiment of chiral molecules from a solution under grinding, we extend the lattice gas model of crystal growth as follows. A lattice site can be occupied by a chiral molecule in R or S form, or can be empty. Molecules form homoclusters by nearest neighbor bonds. They change their chirality if they are isolated monomers in the solution. Grinding is incorporated by cutting and shafling the system randomly. It is shown that Ostwald ripening without grinding is extremely slow to select chirality, if possible. Grinding alone also cannot achieve chirality selection. For the accomplishment of homochirality, we need an enhanced chirality change on crystalline surface. With this "autocatalytic effect" and the recycling of monomers due to rinding, an exponential increase of crystal enantiomeric excess to homochiral state is realized.Comment: 10 pages, 5 figure

Vascular effects of apelin in vivo in man

ObjectivesThis study was designed to establish the direct vascular effects of apelin in vivo in man.BackgroundApelin is the endogenous ligand for the previously orphaned G-protein–coupled receptor, APJ. This novel pathway is widely expressed in the cardiovascular system and is emerging as an important mediator of cardiovascular homeostasis. In pre-clinical models, apelin causes venous and arterial vasodilation.MethodsVascular effects of apelin were assessed in 24 healthy volunteers. Dorsal hand vein diameter was measured by the Aellig technique during local intravenous infusions (0.1 to 3 nmol/min) of apelin-36, (Pyr1)apelin-13, and sodium nitroprusside (0.6 nmol/min). Forearm blood flow was measured by venous occlusion plethysmography during intrabrachial infusions of apelin-36 and (Pyr1)apelin-13 (0.1 to 30 nmol/min) and subsequently in the presence or absence of a “nitric oxide clamp” (nitric oxide synthase inhibitor, L-NG-monomethylarginine [8 μmol/min], coinfused with nitric oxide donor, sodium nitroprusside [90 to 900 ng/min]), or a single oral dose of aspirin (600 mg) or matched placebo.ResultsAlthough sodium nitroprusside caused venodilation (p < 0.0001), apelin-36 and (Pyr1)apelin-13 had no effect on dorsal hand vein diameter (p = 0.2). Both apelin isoforms caused reproducible vasodilation in forearm resistance vessels (p < 0.0001). (Pyr1)apelin-13–mediated vasodilation was attenuated by the nitric oxide clamp (p = 0.004) but unaffected by aspirin (p = 0.7).ConclusionsAlthough having no apparent effect on venous tone, apelin causes nitric oxide–dependent arterial vasodilation in vivo in man. The apelin-APJ system merits further clinical investigation to determine its role in cardiovascular homeostasis

Groups, organizations, families and movements: The sociology of social systems between interaction and society

Kühl S. Groups, organizations, families and movements: The sociology of social systems between interaction and society. Systems Research and Behavioral Science. 2020;37(3):496-515.In enhancing a proposal by Luhmann, this contribution shows that it is possible to locate different types of systems between ‘face‐to‐face‐interaction’ and ‘society’: groups, organizations, families and protest movements. The common ground of these is that they use membership to attribute persons to the system or not. However, they differ fundamentally in regard to how they understand membership. In contrast to Luhmann's differentiation between interaction, organization and society, it is not only possible to imagine different types of interlocking systems but also coequal combinations of and transitions between the different types of social systems

Elite control of HIV is associated with distinct functional and transcriptional signatures in lymphoid tissue CD8+ T cells

The functional properties of circulating CD8+ T cells have been associated with immune control of HIV. However, viral replication occurs predominantly in secondary lymphoid tissues, such as lymph nodes (LNs). We used an integrated single-cell approach to characterize effective HIV-specific CD8+ T cell responses in the LNs of elite controllers (ECs), defined as individuals who suppress viral replication in the absence of antiretroviral therapy (ART). Higher frequencies of total memory and follicle-homing HIV-specific CD8+ T cells were detected in the LNs of ECs compared with the LNs of chronic progressors (CPs) who were not receiving ART. Moreover, HIV-specific CD8+ T cells potently suppressed viral replication without demonstrable cytolytic activity in the LNs of ECs, which harbored substantially lower amounts of CD4+ T cell–associated HIV DNA and RNA compared with the LNs of CPs. Single-cell RNA sequencing analyses further revealed a distinct transcriptional signature among HIV-specific CD8+ T cells from the LNs of ECs, typified by the down-regulation of inhibitory receptors and cytolytic molecules and the up-regulation of multiple cytokines, predicted secreted factors, and components of the protein translation machinery. Collectively, these results provide a mechanistic framework to expedite the identification of novel antiviral factors, highlighting a potential role for the localized deployment of noncytolytic functions as a determinant of immune efficacy against HIV

Isomorphic diffuse glioma is a morphologically and molecularly distinct tumour entity with recurrent gene fusions of MYBL1 or MYB and a benign disease course

The “isomorphic subtype of diffuse astrocytoma” was identified histologically in 2004 as a supratentorial, highly differentiated glioma with low cellularity, low proliferation and focal diffuse brain infiltration. Patients typically had seizures since childhood and all were operated on as adults. To define the position of these lesions among brain tumours, we histologically, molecularly and clinically analysed 26 histologically prototypical isomorphic diffuse gliomas. Immunohistochemically, they were GFAP-positive, MAP2-, OLIG2- and CD34-negative, nuclear ATRX-expression was retained and proliferation was low. All 24 cases sequenced were IDH-wildtype. In cluster analyses of DNA methylation data, isomorphic diffuse gliomas formed a group clearly distinct from other glial/glio-neuronal brain tumours and normal hemispheric tissue, most closely related to paediatric MYB/MYBL1-altered diffuse astrocytomas and angiocentric gliomas. Half of the isomorphic diffuse gliomas had copy number alterations of MYBL1 or MYB (13/25, 52%). Gene fusions of MYBL1 or MYB with various gene partners were identified in 11/22 (50%) and were associated with an increased RNA-expression of the respective MYB-family gene. Integrating copy number alterations and available RNA sequencing data, 20/26 (77%) of isomorphic diffuse gliomas demonstrated MYBL1 (54%) or MYB (23%) alterations. Clinically, 89% of patients were seizure-free after surgery and all had a good outcome. In summary, we here define a distinct benign tumour class belonging to the family of MYB/MYBL1-altered gliomas. Isomorphic diffuse glioma occurs both in children and adults, has a concise morphology, frequent MYBL1 and MYB alterations and a specific DNA methylation profile. As an exclusively histological diagnosis may be very challenging and as paediatric MYB/MYBL1-altered diffuse astrocytomas may have the same gene fusions, we consider DNA methylation profiling very helpful for their identification

Fluctuation Induced Homochirality

We propose a new mechanism for the achievment of homochirality in life without any autocatalytic production process. Our model consists of a spontaneous production together with a recycling cross inhibition in a closed system. It is shown that although the rate equations for this system predict no chiral symmetry breaking, the stochastic master equation predicts complete homochirality. This is because the fluctuation induced by the discreteness of population numbers of participating molecules plays essential roles. This fluctuation conspires with the recyling cross inhibition to realize the homochirality.Comment: 13 pages, 6 figure

Late Byzantine Mineral Soda High Alumina Glasses from Asia Minor: A New Primary Glass Production Group

The chemical characterisation of archaeological glass allows the discrimination between different glass groups and the identification of raw materials and technological traditions of their production. Several lines of evidence point towards the large-scale production of first millennium CE glass in a limited number of glass making factories from a mixture of Egyptian mineral soda and a locally available silica source. Fundamental changes in the manufacturing processes occurred from the eight/ninth century CE onwards, when Egyptian mineral soda was gradually replaced by soda-rich plant ash in Egypt as well as the Islamic Middle East. In order to elucidate the supply and consumption of glass during this transitional period, 31 glass samples from the assemblage found at Pergamon (Turkey) that date to the fourth to fourteenth centuries CE were analysed by electron microprobe analysis (EPMA) and by laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS). The statistical evaluation of the data revealed that the Byzantine glasses from Pergamon represent at least three different glass production technologies, one of which had not previously been recognised in the glass making traditions of the Mediterranean. While the chemical characteristics of the late antique and early medieval fragments confirm the current model of glass production and distribution at the time, the elemental make-up of the majority of the eighth- to fourteenth-century glasses from Pergamon indicate the existence of a late Byzantine glass type that is characterised by high alumina levels. Judging from the trace element patterns and elevated boron and lithium concentrations, these glasses were produced with a mineral soda different to the Egyptian natron from the Wadi Natrun, suggesting a possible regional Byzantine primary glass production in Asia Minor