Green-light photocleavable meso-methyl BODIPY building blocks for macromolecular chemistry

We report the design of easily accessible, photocleavable meso-methyl BODIPY monomers suitably functionalised for incorporation into macromolecules. Firstly a BODIPY-diol as a novel AA-type bifunctional monomer is reported. Secondly, from the same common BODIPY precursor, a clickable, azide functionalised AB-type hetero-bifunctional monomer was prepared. Photochemical studies of model compounds confirmed the ability of these compounds to undergo photocleavage in green light (lambda > 500 nm). Their usefulness for photoclippable macromolecular systems is then demonstrated: firstly by incorporating the diols into polyurethane hydrogels shown to undergo photocleavage and hence dissolution under visible light irradiation and secondly, the preparation of water-soluble macromolecular photocages able to photorelease small molecules. Thus the results presented herein describe a proof-of-principle for BODIPY-based photoresponsive materials, for example, for use as degradable polymers, sacrificial materials for lithography or for the delivery of caged pharmaceuticals

In the eye of a hurricane there is quiet, for just a moment, —

CHI can be a multisensory overload. Attendees endure days of workshops, presentations, evening parties, and ephemeral interactions. This paper attempts to disrupt that onslaught of activities [9]. It draws inspiration from theories and methods already in HCI—e.g. mindfulness [1], reflec- tive design [8], and slow design [4, 7]—to bring eight pages of silence to the conference. This is meant to disrupt CHI’s busy schedule and help attendees foster resilience. In pur- suit of these aims, the authors will use the time and pages offered by this paper to facilitate a group silence; quiet, for just a moment, in the midst of the hurricane that is CHI

Class-switched marginal zone B cells in spleen have relatively low numbers of somatic mutations

The vast majority of rodent splenic marginal zone (MZ)-B cells are naive IgM(+) cells. A small fraction of these MZ-B cells carry mutated V-genes, and represent IgM(+) memory MZ-B cells. Here we reveal further heterogeneity of B cells with a MZ-B cell phenotype, by providing evidence for the existence of class-switched memory MZ-B cells in the rat. In essence, we observed IGHV5 encoded Cgamma transcripts, among FACS-purified MZ-B cells, defined as HIS24(low)HIS57(bright) cells. Furthermore, we found that most IgG encoding transcripts are mutated. There is no significant difference in IGHV5 repertoire and subclass usage of these IgG encoding transcripts collected from B cells with a MZ-B cell phenotype and B cells with a follicular (FO) B cell phenotype. However, the IGHV5 genes encoding for IgG antibodies of MZ-B cells exhibited significantly fewer mutations, compared to those with a FO-B cell phenotype. In one rat we found a clonally related set of IgG encoding sequences, of which one was derived from the MZ-B cell fraction and the other from the FO-B cell fraction. We speculate that these two subpopulations of class-switched B cells are both descendants from naive FO-B cells and are generated in germinal centers. Class-switched memory cells with a MZ-B cell phenotype may provide the animal with a population of IgG memory cells that can respond rapidly to blood-borne pathogens

still a concern in patients with haematological malignancies and stem cell transplant recipients-authors' response

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Environmental Factors Affecting Large-Bodied Coral Reef Fish Assemblages in the Mariana Archipelago

Large-bodied reef fishes represent an economically and ecologically important segment of the coral reef fish assemblage. Many of these individuals supply the bulk of the reproductive output for their population and have a disproportionate effect on their environment (e.g. as apex predators or bioeroding herbivores). Large-bodied reef fishes also tend to be at greatest risk of overfishing, and their loss can result in a myriad of either cascading (direct) or indirect trophic and other effects. While many studies have investigated habitat characteristics affecting populations of small-bodied reef fishes, few have explored the relationship between large-bodied species and their environment. Here, we describe the distribution of the large-bodied reef fishes in the Mariana Archipelago with an emphasis on the environmental factors associated with their distribution. Of the factors considered in this study, a negative association with human population density showed the highest relative influence on the distribution of large-bodied reef fishes; however, depth, water temperature, and distance to deep water also were important. These findings provide new information on the ecology of large-bodied reef fishes can inform discussions concerning essential fish habitat and ecosystem-based management for these species and highlight important knowledge gaps worthy of additional research

Large-scale analysis of structural brain asymmetries in schizophrenia via the ENIGMA consortium

Left-right asymmetry is an important organizing feature of the healthy brain that may be altered in schizophrenia, but most studies have used relatively small samples and heterogeneous approaches, resulting in equivocal findings. We carried out the largest case-control study of structural brain asymmetries in schizophrenia, using MRI data from 5,080 affected individuals and 6,015 controls across 46 datasets in the ENIGMA consortium, using a single image analysis protocol. Asymmetry indexes were calculated for global and regional cortical thickness, surface area, and subcortical volume measures. Differences of asymmetry were calculated between affected individuals and controls per dataset, and effect sizes were meta-analyzed across datasets. Small average case-control differences were observed for thickness asymmetries of the rostral anterior cingulate and the middle temporal gyrus, both driven by thinner left-hemispheric cortices in schizophrenia. Analyses of these asymmetries with respect to the use of antipsychotic medication and other clinical variables did not show any significant associations. Assessment of age- and sex-specific effects revealed a stronger average leftward asymmetry of pallidum volume between older cases and controls. Case-control differences in a multivariate context were assessed in a subset of the data (N = 2,029), which revealed that 7% of the variance across all structural asymmetries was explained by case-control status. Subtle case-control differences of brain macro-structural asymmetry may reflect differences at the molecular, cytoarchitectonic or circuit levels that have functional relevance for the disorder. Reduced left middle temporal cortical thickness is consistent with altered left-hemisphere language network organization in schizophrenia

Sequencing illustrates the transcriptional response of Legionella pneumophila during infection and identifies seventy novel small non-coding RNAs

Second generation sequencing has prompted a number of groups to re-interrogate the transcriptomes of several bacterial and archaeal species. One of the central findings has been the identification of complex networks of small non-coding RNAs that play central roles in transcriptional regulation in all growth conditions and for the pathogen’s interaction with and survival within host cells. Legionella pneumophila is a Gram-negative facultative intracellular human pathogen with a distinct biphasic lifestyle. One of its primary environmental hosts in the free-living amoeba Acanthamoeba castellanii and its infection by L. pneumophila mimics that seen in human macrophages. Here we present analysis of strand specific sequencing of the transcriptional response of L. pneumophila during exponential and post-exponential broth growth and during the replicative and transmissive phase of infection inside A. castellanii. We extend previous microarray based studies as well as uncovering evidence of a complex regulatory architecture underpinned by numerous non-coding RNAs. Over seventy new non-coding RNAs could be identified; many of them appear to be strain specific and in configurations not previously reported. We discover a family of non-coding RNAs preferentially expressed during infection conditions and identify a second copy of 6S RNA in L. pneumophila. We show that the newly discovered putative 6S RNA as well as a number of other non-coding RNAs show evidence for antisense transcription. The nature and extent of the non-coding RNAs and their expression patterns suggests that these may well play central roles in the regulation of Legionella spp

Motivational tuning of fronto-subthalamic connectivity facilitates control of action impulses

It is critical for survival to quickly respond to environmental stimuli with the most appropriate action. This task becomes most challenging when response tendencies induced by relevant and irrelevant stimulus features are in conflict, and have to be resolved in real time. Inputs from the pre-supplementary motor area (pre-SMA) and inferior frontal gyrus (IFG) to the subthalamic nucleus (STN) are thought to support this function, but the connectivity and causality of these regions in calibrating motor control has not been delineated. In this study, we combined off-line noninvasive brain stimulation and functional magnetic resonance imaging, while young healthy human participants performed a modified version of the Simon task. We show that impairing pre-SMA function by noninvasive brain stimulation improved control over impulsive response tendencies, but only when participants were explicitly rewarded for fast and accurate responses. These effects were mediated by enhanced activation and connectivity of the IFG–STN pathway. These results provide causal evidence for a pivotal role of the IFG–STN pathway during action control. Additionally, they suggest a parallel rather than hierarchical organization of the pre-SMA–STN and IFG–STN pathways, since interruption of pre-SMA function can enhance IFG–STN connectivity and improve control over inappropriate responses.</jats:p