Solitons and production of defects in flow-aligning nematic liquid crystals under simple shear flow

The production of defects in flow-aligning nematic liquid crystals under simple shear flow is analyzed by linear stability analysis based on Leslie-Ericksen theory. It is pointed out that the equation of motion of the nematic director under simple shear flow conforms to the driven over-damped sine-Gordon equation and has a soliton solution of amplitude π. It has also been shown that the stationary state with the director uniformly oriented at a Leslie angle is only a metastable state and that the potential, which governs the motion of the director, has infinite numbers of stable stationary states. Therefore, the defects, appearing as a stable solitary solution, can be nucleated from a uniformly aligned flow-aligning type of nematic liquid crystal by shear flow. On the other hand, the bands with long axis parallel to the vorticity axis, appearing as an unstable solution, can be observed as transient patterns at low shear rate and low shear strain value. The theoretical predictions are compared with previous experimental observations.     

Protecting DNA from errors and damage: an overview of DNA repair mechanisms in plants compared to mammals

The genome integrity of all organisms is constantly threatened by replication errors and DNA damage arising from endogenous and exogenous sources. Such base pair anomalies must be accurately repaired to prevent mutagenesis and/or lethality. Thus, it is not surprising that cells have evolved multiple and partially overlapping DNA repair pathways to correct specific types of DNA errors and lesions. Great progress in unraveling these repair mechanisms at the molecular level has been made by several talented researchers, among them Tomas Lindahl, Aziz Sancar, and Paul Modrich, all three Nobel laureates in Chemistry for 2015. Much of this knowledge comes from studies performed in bacteria, yeast, and mammals and has impacted research in plant systems. Two plant features should be mentioned. Plants differ from higher eukaryotes in that they lack a reserve germline and cannot avoid environmental stresses. Therefore, plants have evolved different strategies to sustain genome fidelity through generations and continuous exposure to genotoxic stresses. These strategies include the presence of unique or multiple paralogous genes with partially overlapping DNA repair activities. Yet, in spite (or because) of these differences, plants, especially Arabidopsis thaliana, can be used as a model organism for functional studies. Some advantages of this model system are worth mentioning: short life cycle, availability of both homozygous and heterozygous lines for many genes, plant transformation techniques, tissue culture methods and reporter systems for gene expression and function studies. Here, I provide a current understanding of DNA repair genes in plants, with a special focus on A. thaliana. It is expected that this review will be a valuable resource for future functional studies in the DNA repair field, both in plants and animals.     

Possible solar origin of the 1,470-year glacial climate cycle demonstrated in a coupled model

Many palaeoclimate records from the North Atlantic region show a pattern of rapid climate oscillations, the so-called Dansgaard-Oeschger events, with a quasi-periodicity of approximately 1,470 years for the late glacial period. Various hypotheses have been suggested to explain these rapid temperature shifts, including internal oscillations in the climate system and external forcing, possibly from the Sun. But whereas pronounced solar cycles of approximately 87 and approximately 210 years are well known, a approximately 1,470-year solar cycle has not been detected. Here we show that an intermediate-complexity climate model with glacial climate conditions simulates rapid climate shifts similar to the Dansgaard-Oeschger events with a spacing of 1,470 years when forced by periodic freshwater input into the North Atlantic Ocean in cycles of approximately 87 and approximately 210 years. We attribute the robust 1,470-year response time to the superposition of the two shorter cycles, together with strongly nonlinear dynamics and the long characteristic timescale of the thermohaline circulation. For Holocene conditions, similar events do not occur. We conclude that the glacial 1,470-year climate cycles could have been triggered by solar forcing despite the absence of a 1,470-year solar cycle.     

Mutations in SIL1 cause Marinesco-Sjögren syndrome, a cerebellar ataxia with cataract and myopathy

SIL1 (also called BAP) acts as a nucleotide exchange factor for the Hsp70 chaperone BiP (also called GRP78), which is a key regulator of the main functions of the endoplasmic reticulum. We found nine distinct mutations that would disrupt the SIL1 protein in individuals with Marinesco-Sj?gren syndrome, an autosomal recessive cerebellar ataxia complicated by cataracts, developmental delay and myopathy. Identification of SIL1 mutations implicates Marinesco-Sj?gren syndrome as a disease of endoplasmic reticulum dysfunction and suggests a role for this organelle in multisystem disorders.     

Statistical analyses of freeway traffic flows

This paper concerns the exploration of statistical models for the analysis of observational freeway flow data, and the development of empirical models to capture and predict short‐term changes in traffic flow characteristics on sequences of links in a partially detectorized freeway network. A first set of analyses explores regression models for minute‐by‐minute traffic flows, taking into account time of day, day of the week, and recent upstream detector‐based flows. Day‐ and link‐specific random effects are used in a hierarchical statistical modelling framework. A second set of analyses captures day‐specific idiosyncrasies in traffic patterns by including parameters that may vary throughout the day. Model fit and short‐term predictions of flows are thus improved significantly. A third set of analyses includes recent downstream flows as additional predictors. These further improvements, though marginal in most cases, can be quite radically useful in cases of very marked breakdown of freeway flows on some links. These three modelling stages are described and developed in analyses of observational flow data from a set of links on Interstate Highway 5 (I‐5) near Seattle. Copyright © 2002 John Wiley & Sons, Ltd.     

Antiandrogenic potency of drugs,evaluated by urinary enzyme excretion technique

Zusammenfassung Bei Ratten konnte nach der Verabreichung von Nitrotrifluoromethylisobutyranilid, einer neuen antiandrogen wirksamen Substanz, ein signifikanter Abfall der sauren Phosphatase-Aktivität im Harn festgestellt werden. Andere Harnenzymaktivitäten (alkalische Phosphatase, «Leucinaminopeptidase») blieben unbeeinflusst. Die Aktivität der sauren Phosphatase im Serum zeigte nach zweiwöchiger Verabreichung des Antiandrogens keine signifikante Veränderung. Die Bestimmung der sauren Phosphatase-Aktivität im Harn eignet sich demnach zum einfachen «Screening» antiandrogener Wirkungen.     

Immunocytochemical demonstration of contractile cells in the human ovarian follicle

Actin- and myosin-like immunoreactivity is found in cells located in the theca externa of the follicle wall of the human ovary, and corresponding to previously observed myoid cells. The immunocytochemical observation provides direct structural evidence that non-vascular contractile cells are also present in the follicle wall in humans. As expected, perifollicular blood vessels showed a positive immunoreaction for actin and myosin in their smooth muscle walls.     

Defective tryptophan catabolism underlies inflammation in mouse chronic granulomatous disease

Half a century ago, chronic granulomatous disease (CGD) was first described as a disease fatally affecting the ability of children to survive infections. Various milestone discoveries have since been made, from an insufficient ability of patients' leucocytes to kill microbes to the underlying genetic abnormalities. In this inherited disorder, phagocytes lack NADPH oxidase activity and do not generate reactive oxygen species, most notably superoxide anion, causing recurrent bacterial and fungal infections. Patients with CGD also suffer from chronic inflammatory conditions, most prominently granuloma formation in hollow viscera. The precise mechanisms of the increased microbial pathogenicity have been unclear, and more so the reasons for the exaggerated inflammatory response. Here we show that a superoxide-dependent step in tryptophan metabolism along the kynurenine pathway is blocked in CGD mice with lethal pulmonary aspergillosis, leading to unrestrained Vgamma1(+) gammadelta T-cell reactivity, dominant production of interleukin (IL)-17, defective regulatory T-cell activity and acute inflammatory lung injury. Although beneficial effects are induced by IL-17 neutralization or gammadelta T-cell contraction, complete cure and reversal of the hyperinflammatory phenotype are achieved by replacement therapy with a natural kynurenine distal to the blockade in the pathway. Effective therapy, which includes co-administration of recombinant interferon-gamma (IFN-gamma), restores production of downstream immunoactive metabolites and enables the emergence of regulatory Vgamma4(+) gammadelta and Foxp3(+) alphabeta T cells. Therefore, paradoxically, the lack of reactive oxygen species contributes to the hyperinflammatory phenotype associated with NADPH oxidase deficiencies, through a dysfunctional kynurenine pathway of tryptophan catabolism. Yet, this condition can be reverted by reactivating the pathway downstream of the superoxide-dependent step.     

A novel retinoblastoma therapy from genomic and epigenetic analyses

Retinoblastoma is an aggressive childhood cancer of the developing retina that is initiated by the biallelic loss of RB1. Tumours progress very quickly following RB1 inactivation but the underlying mechanism is not known. Here we show that the retinoblastoma genome is stable, but that multiple cancer pathways can be epigenetically deregulated. To identify the mutations that cooperate with RB1 loss, we performed whole-genome sequencing of retinoblastomas. The overall mutational rate was very low; RB1 was the only known cancer gene mutated. We then evaluated the role of RB1 in genome stability and considered non-genetic mechanisms of cancer pathway deregulation. For example, the proto-oncogene SYK is upregulated in retinoblastoma and is required for tumour cell survival. Targeting SYK with a small-molecule inhibitor induced retinoblastoma tumour cell death in vitro and in vivo. Thus, retinoblastomas may develop quickly as a result of the epigenetic deregulation of key cancer pathways as a direct or indirect result of RB1 loss.