Minimizing side reactions in chemoenzymatic dynamic kinetic resolution: organometallic and material strategies

Chemoenzymatic dynamic kinetic resolution (DKR) of rac-1-phenyl ethanol into R-1-phenylethanol acetate was investigated with emphasis on the minimization of side reactions. The organometallic hydrogen transfer (racemization) catalyst was varied, and this was observed to alter the rate and extent of oxidation of the alcohol to form ketone side products. The performance of highly active catalyst [(pentamethylcyclopentadienyl) IrCl2(1-benzyl,3-methyl-imidazol-2-ylidene)] was found to depend on the batch of lipase B used. The interaction between the bio- and chemo-catalysts was reduced by employing physical entrapment of the enzyme in silica using a sol-gel process. The nature of the gelation method was found to be important, with an alkaline method preferred, as an acidic method was found to initiate a further side reaction, the acid catalyzed dehydration of the secondary alcohol. The acidic gel was found to be a heterogeneous solid acid.

Defense peptides secreted by helminth pathogens: antimicrobial and/or immunomodulator molecules?

Host defense peptides (HDPs) are an evolutionarily conserved component of the innate immune response found in all living species. They possess antimicrobial activities against a broad range of organisms including bacteria, fungi, eukaryotic parasites, and viruses. HDPs also have the ability to enhance immune responses by acting as immunomodulators. We discovered a new family of HDPs derived from pathogenic helminth (worms) that cause enormous disease in animals and humans worldwide. The discovery of these peptides was based on their similar biochemical and functional characteristics to the human defense peptide LL-37. We propose that these new peptides modulate the immune response via molecular mimicry of mammalian HDPs thus providing a mechanism behind the anti-inflammatory properties of helminth infections.

WASP-52b, WASP-58b, WASP-59b, and WASP-60b: Four new transiting close-in giant planets

We present the discovery of four new transiting hot jupiters, detected mainly from SuperWASP-North and SOPHIE observations. These new planets, WASP-52b, WASP-58b, WASP-59b, and WASP-60b, have orbital periods ranging from 1.7 to 7.9 days, masses between 0.46 and 0.94 M_Jup, and radii between 0.73 and 1.49 R_Jup. Their G1 to K5 dwarf host stars have V magnitudes in the range 11.7-13.0. The depths of the transits are between 0.6 and 2.7%, depending on the target. With their large radii, WASP-52b and 58b are new cases of low-density, inflated planets, whereas WASP-59b is likely to have a large, dense core. WASP-60 shows shallow transits. In the case of WASP-52 we also detected the Rossiter-McLaughlin anomaly via time-resolved spectroscopy of a transit. We measured the sky-projected obliquity lambda = 24 (+17/-9) degrees, indicating that WASP-52b orbits in the same direction as its host star is rotating and that this prograde orbit is slightly misaligned with the stellar equator. These four new planetary systems increase our statistics on hot jupiters, and provide new targets for follow-up studies.

Variation and Change in French Morphosyntax: The Case of Collective Nouns

Collective nouns such as majorité or foule have long been of interest to linguists for their unusual semantic properties, and provide a valuable source of new data on the evolution of French grammar. This book tests the hypothesis that plural agreement with collective nouns is becoming more frequent in French. Through an analysis of data from a variety of sources, including sociolinguistic interviews, gap-fill tests and corpora, the complex linguistic and external factors which affect this type of agreement are examined, shedding new light on their interaction in this context. Broader questions concerning the methodological challenges of studying variation and change in morphosyntax, and the application of sociolinguistic generalisations to the French of France, are also addressed.

Reviews:

‘Cet ouvrage constitue un apport majeur dans le champ de la linguistique variationniste et diachronique, tant par les résultats mis au jour que par la qualité de sa démarche méthodologique.’ — Sophie Prévost, French Studies 69.4, October 2015, 578-79

‘While language variation and change have been the focal point for linguists on this side of the Atlantic, Tristram argues that studies on morphosyntactic variation in French studies are lacking due to a focus on phonology and dialectology as well as denial of variation and change in the French language. Tristram’s book is thus a welcome contribution.’ — Samira Hassa, French Review 89.3, 2016, 108

‘Anyone teaching variation in French will want to talk about the findings and reflections reported in this study. A remarkable amount of ground is covered in a small compass. This is a highly welcome addition to the Legenda list, and one must hope that further linguistics titles will be added to it before very long.’ — Nigel Armstrong, Journal of French Language Studies 26.2, 2016, 211-13

Dynamic oscillation of translation and stress granule formation mark the cellular response to virus infection

Virus infection-induced global protein synthesis suppression is linked to assembly of stress granules (SGs), cytosolic aggregates of stalled translation preinitiation complexes. To study long-term stress responses, we developed an imaging approach for extended observation and analysis of SG dynamics during persistent hepatitis C virus (HCV) infection. In combination with type 1 interferon, HCV infection induces highly dynamic assembly/disassembly of cytoplasmic SGs, concomitant with phases of active and stalled translation, delayed cell division, and prolonged cell survival. Double-stranded RNA (dsRNA), independent of viral replication, is sufficient to trigger these oscillations. Translation initiation factor eIF2a phosphorylation by protein kinase R mediates SG formation and translation arrest. This is antagonized by the upregulation of GADD34, the regulatory subunit of protein phosphatase 1 dephosphorylating eIF2a. Stress response oscillation is a general mechanism to prevent long-lasting translation repression and a conserved host cell reaction to multiple RNA viruses, which HCV may exploit to establish persistence.

Subarachnoid haemorrhage (SAH):long-term cognitive outcome in patients treated with surgical clipping or endovascular coiling

Purpose: To compare long-term cognitive outcomes of patients treated with surgical clipping or endovascular coiling after subarachnoid haemorrhage (SAH). Method: Retrospective matched cohort study assessed neuropsychological functioning at least 12 months after aneurysmal SAH treatment. Fourteen patients treated by endovascular coiling and nine patients treated by surgical clipping participated. After gaining written consent, a comprehensive neuropsychological battery was completed. Standardised tests were employed to assess pre-morbid and current intellectual functioning (IQ), attention, speed of information processing, memory and executive function as well as psychosocial functioning and affect. Results: Treatment groups were not significantly different in terms of age, pre-morbid IQ, time from injury to treatment or time since injury. A significant effect of treatment on full-scale IQ score (p = 0.025), performance IQ (p = 0.045) and verbal IQ score (p = 0.029), all favouring the coiled group was observed. A medium effect size between groups difference in immediate memory (p = 0.19, partial ?(2) = 0.08) was also observed. No significant between group differences on attention, executive functioning and speed of information processing measures or mood and psychosocial functioning were noted. Both groups reported increased anxiety and memory, attention and speed of information processing deficits relative to normative data. Conclusions: Study findings indicate fewer cognitive deficits following endovascular coiling. Cognitive deficits in the clipped group may be due in part to the invasive nature of neurosurgical clipping. Further prospective research with regard to long-term cognitive and emotional outcomes is warranted. [Box: see text].

L'accord sujet-verbe en français contemporain: une étude de variation sociolinguistique

Cette communication a pour objectif de présenter et d’analyser les résultats d’une enquête portant sur l’accord sujet-verbe en français contemporain. Dans le domaine de l’accord sujet-verbe, bien que dans la plupart des cas le locuteur n’ait pas le choix de l’accord – c’est–à-dire qu’il n’y a qu’un accord possible – il existe néanmoins des contextes dans lesquels on peut trouver une variation entre l’accord singulier et le pluriel (cf. Corbett 2006 ; Grevisse 1993 ; Riegel et al 1994). Cette variation est souvent liée à une discordance entre le nombre syntaxique et le nombre sémantique. C’est le cas de certaines expressions de quantité, comme dans les exemples suivants : Singulier : « On a affaire à une minorité qui fait la loi à l’université » (Ouest France, 23-24 mai 2009, p.13) Pluriel : « Un petit millier de producteurs allemands, français et belges se sont déplacés, hier, à Bruxelles […] » (Ouest France, 26 mai 2009, p.3) Cette variation nous offre plusieurs pistes de recherche : dans une perspective linguistique, elle peut nous aider à mieux comprendre comment interagissent les différents facteurs linguistiques qui ont une influence sur l’accord, et dans une perspective sociolinguistique, elle représente un nouveau domaine à explorer pour l’étude sociolinguistique de la variation grammaticale en français, ce qui reste jusqu’à présent relativement peu étudiée. Nous traitons dans cette communication de la perspective sociolinguistique, c'est-à-dire les facteurs externes tels que l’âge, le sexe, et le niveau d’éducation du locuteur qui jouent un rôle dans l’accord sujet-verbe avec les expressions de quantité. Nous considérons en particulier la variation sexolectale : dans un premier temps, nous examinons les résultats de quelques études précédentes de la variation morphosyntaxique en français contemporain par rapport à l’influence du sexe du locuteur. Nous en concluons que les Principes élaborés par Labov (1990) pour décrire la variation sexolectale en anglais semblent être moins valables pour le cas du français de la France ; ou bien, qu’ils ne s’appliquent pas de façon simpliste. Dans un deuxième temps, nous présentons les résultats de nôtre étude, et nous voyons que pour nôtre projet aussi, les résultats pour la variation sexolectale ne s’expliquent pas facilement dans le cadre des Principes de Labov (1990).

Moral emotions and the envisioning of mitigating circumstances for wrongdoing

Anger may be more responsive than disgust to mitigating circumstances in judgments of wrongdoing. We tested this hypothesis in two studies where we had participants envision circumstances that could serve to mitigate an otherwise wrongful act. In Study 1, participants provided moral judgments, and ratings of anger and disgust, to a number of transgressions involving either harm or bodily purity. They were then asked to imagine and report whether there might be any circumstances that would make it all right to perform the act. Across transgression type, and controlling for covariance between anger and disgust, levels of anger were found to negatively predict the envisioning of mitigating circumstances for wrongdoing, while disgust was unrelated. Study 2 replicated and extended these findings to less serious transgressions, using a continuous measure of mitigating circumstances, and demonstrated the impact of
anger independent of deontological commitments. These findings highlight the differential relationship that anger and disgust have with the ability to envision mitigating factors.

Cathelicidin-like Helminth Defence Molecules (HDMs):Absence of Cytotoxic, Anti-microbial and Anti-protozoan Activities Imply a Specific Adaptation to Immune Modulation

Host defence peptides (HDPs) are expressed throughout the animal and plant kingdoms. They have multifunctional roles in the defence against infectious agents of mammals, possessing both bactericidal and immune-modulatory activities. We have identified a novel family of molecules secreted by helminth parasites (helminth defence molecules; HDMs) that exhibit similar structural and biochemical characteristics to the HDPs. Here, we have analyzed the functional activities of four HDMs derived from Schistosoma mansoni and Fasciola hepatica and compared them to human, mouse, bovine and sheep HDPs. Unlike the mammalian HDPs the helminth-derived HDMs show no antimicrobial activity and are non-cytotoxic to mammalian cells (macrophages and red blood cells). However, both the mammalian- and helminth-derived peptides suppress the activation of macrophages by microbial stimuli and alter the response of B cells to cytokine stimulation. Therefore, we hypothesise that HDMs represent a novel family of HDPs that evolved to regulate the immune responses of their mammalian hosts by retaining potent immune modulatory properties without causing deleterious cytotoxic effects.

CNV analysis in a large schizophrenia sample implicates deletions at 16p12.1 and SLC1A1 and duplications at 1p36.33 and CGNL1

Large and rare copy number variants (CNVs) at several loci have been shown to increase risk for schizophrenia. Aiming to discover novel susceptibility CNV loci, we analysed 6,882 cases and 11,255 controls genotyped on Illumina arrays, most of which have not been used for this purpose before. We identified genes enriched for rare exonic CNVs among cases, and then attempted to replicate the findings in an additional 14,568 cases and 15,274 controls. In a combined analysis of all samples, 12 distinct loci were enriched among cases with nominal levels of significance (P500kb), rare CNVs showed a 1.2% excess in cases after excluding known schizophrenia-associated loci, suggesting that additional susceptibility loci exist. However, even larger samples are required for their discovery.

Distinct poor prognostic subgroups of acute myeloid leukaemia, FLT3-ITD and P-glycoprotein-positive, have contrasting levels of FOXO1

Regulation of ABCB1 (P-glycoprotein/Pgp) in AML was investigated. In a historical cohort with Pgp and transcriptional regulator expression profiling data available (n=141), FOXO1 correlated with Pgp protein expression. This was confirmed in an independent cohort (n=204). Down-regulation (siRNA) or hyperactivation (nicotinamide) of FOXO1 led to corresponding changes in Pgp. Low FOXO1 expression correlated with FLT3-ITDs (p