A murine model of variant late infantile ceroid lipofuscinosis recapitulates behavioral and pathological phenotypes of human disease.

Neuronal ceroid lipofuscinoses (NCLs; also known collectively as Batten Disease) are a family of autosomal recessive lysosomal storage disorders. Mutations in as many as 13 genes give rise to ∼10 variants of NCL, all with overlapping clinical symptomatology including visual impairment, motor and cognitive dysfunction, seizures, and premature death. Mutations in CLN6 result in both a variant late infantile onset neuronal ceroid lipofuscinosis (vLINCL) as well as an adult-onset form of the disease called Type A Kufs. CLN6 is a non-glycosylated membrane protein of unknown function localized to the endoplasmic reticulum (ER). In this study, we perform a detailed characterization of a naturally occurring Cln6 mutant (Cln6(nclf)) mouse line to validate its utility for translational research. We demonstrate that this Cln6(nclf) mutation leads to deficits in motor coordination, vision, memory, and learning. Pathologically, we demonstrate loss of neurons within specific subregions and lamina of the cortex that correlate to behavioral phenotypes. As in other NCL models, this model displays selective loss of GABAergic interneuron sub-populations in the cortex and the hippocampus with profound, early-onset glial activation. Finally, we demonstrate a novel deficit in memory and learning, including a dramatic reduction in dendritic spine density in the cerebral cortex, which suggests a reduction in synaptic strength following disruption in CLN6. Together, these findings highlight the behavioral and pathological similarities between the Cln6(nclf) mouse model and human NCL patients, validating this model as a reliable format for screening potential therapeutics

Northern Bobwhite Survival, Nest Success, and Habitat Use in Kentucky During the Breeding Season

Northern bobwhite (Colinus virginianus) populations have experienced protracted declines over much of their range. There has been an annual decrease of 2.61% since the 1960s in Kentucky, an area representative of the Mid-South where there is a lack of data on basic population parameters. Much of the decline is attributed to prevailing land-use practices and associated habitat loss. We monitored northern bobwhite on a 515-ha farm in Oldham County, Kentucky to assess survival rates, nest success rates, and habitat use in the Mid- South. The farm consisted of row crops, cool-season pastures and hay (primarily tall fescue), fallow native warm-season grass fields, and woods. We captured birds using baited funnel traps and fitted them with harness radio transmitters and monitored them daily during April–August, 2009 and 2010. We radiomarked 88 birds (40 females, 48 males) and monitored 24 nests, 9 (37.5%) of which were successful, over the 2 years. Survival rates were 25.3 and 27.9% for 2009 and 2010, respectively, based on estimates from Program MARK. Home range size (54.0, range 1⁄4 38.0–55.9 ha) did not differ by sex, age, or year (P .0.05). Quail favored food plots in both years and avoided developed areas

Fluorescent Calcium Imaging and Subsequent In Situ Hybridization for Neuronal Precursor Characterization in Xenopus laevis

Spontaneous intracellular calcium activity can be observed in a variety of cell types and is proposed to play critical roles in a variety of physiological processes. In particular, appropriate regulation of calcium activity patterns during embryogenesis is necessary for many aspects of vertebrate neural development, including proper neural tube closure, synaptogenesis, and neurotransmitter phenotype specification. While the observation that calcium activity patterns can differ in both frequency and amplitude suggests a compelling mechanism by which these fluxes might transmit encoded signals to downstream effectors and regulate gene expression, existing population-level approaches have lacked the precision necessary to further explore this possibility. Furthermore, these approaches limit studies of the role of cell-cell interactions by precluding the ability to assay the state of neuronal determination in the absence of cell-cell contact. Therefore, we have established an experimental workflow that pairs time-lapse calcium imaging of dissociated neuronal explants with a fluorescence in situ hybridization assay, allowing the unambiguous correlation of calcium activity pattern with molecular phenotype on a single-cell level. We were successfully able to use this approach to distinguish and characterize specific calcium activity patterns associated with differentiating neural cells and neural progenitor cells, respectively; beyond this, however, the experimental framework described in this article could be readily adapted to investigate correlations between any time-series activity profile and expression of a gene or genes of interest

Assessment of health in human faces is context-dependent

This work was supported by the National Environment Research Council, UK (KM), Unilever Research & Development USA and the Economic and Social Research Council (RW, DP).When making decisions between options, humans are expected to choose the option that returns the highest benefit. In practice, however, adding inferior alternatives to the choice set can alter these decisions. Here we investigated whether decisions over the facial features that people find healthy looking can also be affected by the context in which they see those faces. To do this we examined the effect of choice set on the perception of health of images of faces of light-skinned Caucasian females. We manipulated apparent facial health by changing yellowness of the skin: the healthy faces were moderately yellow and the less healthy faces were either much more yellow or much less yellow. In each experiment, two healthy faces were presented along with a third, less healthy face. When the third face was much more yellow, participants chose the more yellow of the two healthy faces more often as the most healthy. However, when the third face was the least yellow, participants chose the less yellow of the two healthy faces more often. A further experiment confirmed that this result is not due to a generalised preference for an intermediate option. These results extend our understanding of context-dependent decision-making in humans, and suggest that comparative evaluation may be a common feature across many different kinds of choices that humans have to make.PostprintPeer reviewe

Estimate of the Spontaneous Mutation Rate in Chlamydomonas reinhardtii

The nature of spontaneous mutations, including their rate, distribution across the genome, and fitness consequences, is of central importance to biology. However, the low rate of mutation has made it difficult to study spontaneous mutagenesis, and few studies have directly addressed these questions. Here, we present a direct estimate of the mutation rate and a description of the properties of new spontaneous mutations in the unicellular green alga Chlamydomonas reinhardtii. We conducted a mutation accumulation experiment for ∼350 generations followed by whole-genome resequencing of two replicate lines. Our analysis identified a total of 14 mutations, including 5 short indels and 9 single base mutations, and no evidence of larger structural mutations. From this, we estimate a total mutation rate of 3.23 × 10(−10)/site/generation (95% C.I. 1.82 × 10(−10) to 5.23 × 10(−10)) and a single base mutation rate of 2.08 × 10(−10)/site/generation (95% C.I., 1.09 × 10(−10) to 3.74 × 10(−10)). We observed no mutations from A/T → G/C, suggesting a strong mutational bias toward A/T, although paradoxically, the GC content of the C. reinhardtii genome is very high. Our estimate is only the second direct estimate of the mutation rate from plants and among the lowest spontaneous base-substitution rates known in eukaryotes

Selection on non-social traits limits the invasion of social cheats

While the conditions that favour the maintenance of cooperation have been extensively investigated, the significance of non-social selection pressures on social behaviours has received little attention. In the absence of non-social selection pressures, patches of cooperators are vulnerable to invasion by cheats. However, we show both theoretically, and experimentally with the bacterium Pseudomonas fluorescens, that cheats may be unable to invade patches of cooperators under strong non-social selection (both a novel abiotic environment and to a lesser extent, the presence of a virulent parasite). This is because beneficial mutations are most likely to arise in the numerically dominant cooperator population. Given the ubiquity of novel selection pressures on microbes, these results may help to explain why cooperation is the norm in natural populations of microbes

Crystal Structure of (E)-2-[(2- bromo-3-pyridyl)methylidene]-6-methoxy-3,4-dihydronaphthalen-1-one and 3-[(E)-(6- methoxy-3,4-dihydronaphth-2-oylidene)methyl]-1H-pyridin-2-one

The title compounds C17H14BrNO2, (I), and C17H15NO3, (II), were obtained from the reaction of 6-meth­oxy-3,4-di­hydro-2H-naphthalen-1-one and 2-bromo­nicotinaldehyde in ethanol. Compound (I) was the expected product and compound (II) was the oxidation product from air exposure. In the crystal structure of compound (I), there are no short contacts or hydrogen bonds. The structure does display [pi]-[pi] inter­actions between adjacent benzene rings and adjacent pyridyl rings. Compound (II) contains two independent mol­ecules, A and B, in the asymmetric unit; both are non-planar, the dihedral angles between the meth­oxy­benzene and 1H-pyridin-2-one mean planes being 35.07 (9)° in A and 35.28 (9)°in B. In each mol­ecule, the 1H-pyridin-2-one unit participates in inter­molecular N-H...O hydrogen bonding to another mol­ecule of the same type (A to A or B to B). The structure also displays [pi]-[pi] inter­actions between the pyridyl and the benzene rings of non-equivalent mol­ecules (viz., A to B and B to A)

Development, printability and post-curing studies of formulations of materials resistant to microbial attachment for use in inkjet based 3D printing

Purpose: This paper aims to print 3D structures from polymers that resist bacterial attachment by reactive jetting of acrylate monomers. Design/methodology/approach: The first step towards printing was ink development. Inks were characterised to carry out an estimation of their potential printability using the Z parameter to predict stable jetting conditions. Printability conditions were optimised for each ink using a Dimatix DMP-2800, which enabled 3D structures to be fabricated. Findings: UV photo-initiated polymers, which resist bacterial attachment, were found to be printable using piezo-based inkjet printers. The waveform required for each ink depends on the value of the Z parameter. Once the waveform and the printability parameters were optimised, 3D objects were fabricated. Research limitations/implications: This methodology has been confirmed as an effective method to 3D print materials that have been demonstrated to be bacteria resistant. However, ink curing depends on modification of some parameters (such as photoinitiator concentration or UV exposure time) which would result in an improvement of the curing process post jetting. Social implications: The combination of inkjet based 3D printing with new materials resistant to bacterial attachment means the possibility of building customised medical devices with a high level of complexity and bespoke features can be fully realised. The scope and variability of the devices produced will exceed what can be achieved using standard fabrication methodologies and can be applied to reduce the incidence of device associated infections and to address increased morbidity, mortality and health care costs associated with nosocomial infections. Originality/value: In this paper, the novel use of materials that resist bacterial attachment has been described to build 3D structures using material jetting. Its value lies on the potential impact this methodology could produce in the biomedical device and research fields