O1 haplotype diversity of the invasive colonial tunicate Didemnum vexillum in Drakes Estero and Bodega Bay

The colonial ascidian Didemnum vexillum is an invasive species with detrimental economic and ecological impacts on ecosystems where it is newly introduced. Populations of this recent marine pest are rapidly expanding along the North American coasts and provide the opportunity to assess whether population proximity and shared environmental factors influence genetic relatedness. The population in Tomales Bay, CA is the most diverse measured to date on the Northeast Pacific coast with the population composed of six different haplotypes; other locations are composed of three or four haplotypes. The diversity in Tomales Bay suggests it be an anomaly or possibly a matter associated to areas of limited diversity. D. vexillum populations in isolated areas such as Drakes Estero and Bodega Bay, CA are of close geographic range to Tomales. Drakes’ population is associated with aquaculture structures of the past and Bodega with fishing and recreational boat traffic. This study involved the genetic examination of these populations by barcoding the mitochondrial locus COI to determine haplotype distributions of Drakes Estero and Bodega Bay. From the ten Bodega and five Drakes sequences, there are at least two haplotypes represented. However, the results are preliminary; phylogenetic analysis of all sequences in comparison to the known haplotypes of D. vexillum is necessary before concluding which haplotypes are present in the populations

A proteomic approach to identify endosomal cargoes controlling cancer invasiveness

We have previously shown that Rab17 - a small GTPase associated with epithelial polarity - is specifically suppressed by ERK2 signalling to promote an invasive phenotype. However, the mechanisms through which Rab17 loss permits invasiveness, and the endosomal cargoes that are responsible for mediating this are not known. Using quantitative mass spectrometry-based proteomics, we have found that knockdown of Rab17 leads to highly selective reduction in the cellular levels of a v-SNARE (Vamp8). Moreover, proteomics and immunofluorescence indicate that Vamp-8 is associated with Rab17 at late endosomes. Reduced levels of Vamp8 promote transition between ductal carcinoma in situ (DCIS) and a more invasive phenotype. We developed an unbiased proteomic approach to elucidate the complement of receptors that redistributes between endosomes and the plasma membrane, and have pin-pointed neuropilin-2 (NRP2) as a key pro-invasive cargo of Rab17/Vamp8-regulated trafficking. Indeed, reduced Rab17 or Vamp8 levels lead to increased mobilisation of NRP2-containing late endosomes and upregulated cell surface expression of NRP2. Finally, we show that NRP2 is required for the basement membrane disruption which accompanies transition between DCIS and a more invasive phenotype

A novel scanning lens instrument for evaluating Fresnel lens performance: equipment development and initial results

A system dedicated to the optical transmittance characterization of Fresnel lenses has been developed at NREL, in collaboration with the UPM. The system quantifies the optical efficiency of the lens by generating a performance map. The shape of the focused spot may also be analyzed to understand change in the lens performance. The primary instrument components (lasers and CCD detector) have been characterized to confirm their capability for performing optical transmittance measurements. Measurements performed on SoG and PMMA lenses subject to a variety of indoor conditions (e.g., UV and damp heat) identified differences in the optical efficiency of the evaluated lenses, demonstrating the ability of the Scanning Lens Instrument (SLI) to distinguish between the aged lenses

DNM1 encephalopathy: A new disease of vesicle fission.

ObjectiveTo evaluate the phenotypic spectrum caused by mutations in dynamin 1 (DNM1), encoding the presynaptic protein DNM1, and to investigate possible genotype-phenotype correlations and predicted functional consequences based on structural modeling.MethodsWe reviewed phenotypic data of 21 patients (7 previously published) with DNM1 mutations. We compared mutation data to known functional data and undertook biomolecular modeling to assess the effect of the mutations on protein function.ResultsWe identified 19 patients with de novo mutations in DNM1 and a sibling pair who had an inherited mutation from a mosaic parent. Seven patients (33.3%) carried the recurrent p.Arg237Trp mutation. A common phenotype emerged that included severe to profound intellectual disability and muscular hypotonia in all patients and an epilepsy characterized by infantile spasms in 16 of 21 patients, frequently evolving into Lennox-Gastaut syndrome. Two patients had profound global developmental delay without seizures. In addition, we describe a single patient with normal development before the onset of a catastrophic epilepsy, consistent with febrile infection-related epilepsy syndrome at 4 years. All mutations cluster within the GTPase or middle domains, and structural modeling and existing functional data suggest a dominant-negative effect on DMN1 function.ConclusionsThe phenotypic spectrum of DNM1-related encephalopathy is relatively homogeneous, in contrast to many other genetic epilepsies. Up to one-third of patients carry the recurrent p.Arg237Trp variant, which is now one of the most common recurrent variants in epileptic encephalopathies identified to date. Given the predicted dominant-negative mechanism of this mutation, this variant presents a prime target for therapeutic intervention

Collaborative Forum 3.1: Suit Sizing for Optimal Fit

No abstract availabl

Galectin-1 Deactivates Classically Activated Microglia and Protects from Inflammation-Induced Neurodegeneration

SummaryInflammation-mediated neurodegeneration occurs in the acute and the chronic phases of multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). Classically activated (M1) microglia are key players mediating this process. Here, we identified Galectin-1 (Gal1), an endogenous glycan-binding protein, as a pivotal regulator of M1 microglial activation that targets the activation of p38MAPK-, CREB-, and NF-κB-dependent signaling pathways and hierarchically suppresses downstream proinflammatory mediators, such as iNOS, TNF, and CCL2. Gal1 bound to core 2 O-glycans on CD45, favoring retention of this glycoprotein on the microglial cell surface and augmenting its phosphatase activity and inhibitory function. Gal1 was highly expressed in the acute phase of EAE, and its targeted deletion resulted in pronounced inflammation-induced neurodegeneration. Adoptive transfer of Gal1-secreting astrocytes or administration of recombinant Gal1 suppressed EAE through mechanisms involving microglial deactivation. Thus, Gal1-glycan interactions are essential in tempering microglial activation, brain inflammation, and neurodegeneration, with critical therapeutic implications for MS

Retinal microvasculature and cerebral small vessel disease in the Lothian Birth Cohort 1936 and Mild Stroke Study

Abstract Research has suggested that the retinal vasculature may act as a surrogate marker for diseased cerebral vessels. Retinal vascular parameters were measured using Vessel Assessment and Measurement Platform for Images of the Retina (VAMPIRE) software in two cohorts: (i) community-dwelling older subjects of the Lothian Birth Cohort 1936 (n = 603); and (ii) patients with recent minor ischaemic stroke of the Mild Stroke Study (n = 155). Imaging markers of small vessel disease (SVD) (white matter hyperintensities [WMH] on structural MRI, visual scores and volume; perivascular spaces; lacunes and microbleeds), and vascular risk measures were assessed in both cohorts. We assessed associations between retinal and brain measurements using structural equation modelling and regression analysis. In the Lothian Birth Cohort 1936 arteriolar fractal dimension accounted for 4% of the variance in WMH load. In the Mild Stroke Study lower arteriolar fractal dimension was associated with deep WMH scores (odds ratio [OR] 0.53; 95% CI, 0.32–0.87). No other retinal measure was associated with SVD. Reduced fractal dimension, a measure of vascular complexity, is related to SVD imaging features in older people. The results provide some support for the use of the retinal vasculature in the study of brain microvascular disease

Caldera resurgence during the 2018 eruption of Sierra Negra volcano, Galápagos Islands.

Recent large basaltic eruptions began after only minor surface uplift and seismicity, and resulted in caldera subsidence. In contrast, some eruptions at Galápagos Island volcanoes are preceded by prolonged, large amplitude uplift and elevated seismicity. These systems also display long-term intra-caldera uplift, or resurgence. However, a scarcity of observations has obscured the mechanisms underpinning such behaviour. Here we combine a unique multiparametric dataset to show how the 2018 eruption of Sierra Negra contributed to caldera resurgence. Magma supply to a shallow reservoir drove 6.5 m of pre-eruptive uplift and seismicity over thirteen years, including an Mw5.4 earthquake that triggered the eruption. Although co-eruptive magma withdrawal resulted in 8.5 m of subsidence, net uplift of the inner-caldera on a trapdoor fault resulted in 1.5 m of permanent resurgence. These observations reveal the importance of intra-caldera faulting in affecting resurgence, and the mechanisms of eruption in the absence of well-developed rift systems

“I would rather be told than not know” - A qualitative study exploring parental views on identifying the future risk of childhood overweight and obesity during infancy

BACKGROUND: Risk assessment tools provide an opportunity to prevent childhood overweight and obesity through early identification and intervention to influence infant feeding practices. Engaging parents of infants is paramount for success however; the literature suggests there is uncertainty surrounding the use of such tools with concerns about stigmatisation, labelling and expressions of parental guilt. This study explores parents' views on identifying future risk of childhood overweight and obesity during infancy and communicating risk to parents. METHODS: Semi-structured qualitative interviews were conducted with 23 parents and inductive, interpretive and thematic analysis performed. RESULTS: Three main themes emerged from the data: 1) Identification of infant overweight and obesity risk. Parents were hesitant about health professionals identifying infant overweight as believed they would recognise this for themselves, in addition parents feared judgement from health professionals. Identification of future obesity risk during infancy was viewed positively however the use of a non-judgemental communication style was viewed as imperative. 2) Consequences of infant overweight. Parents expressed immediate anxieties about the impact of excess weight on infant ability to start walking. Parents were aware of the progressive nature of childhood obesity however, did not view overweight as a significant problem until the infant could walk as viewed this as a point when any excess weight would be lost due to increased energy expenditure. 3) Parental attributions of causality, responsibility, and control. Parents articulated a high level of personal responsibility for preventing and controlling overweight during infancy, which translated into self-blame. Parents attributed infant overweight to overfeeding however articulated a reluctance to modify infant feeding practices prior to weaning. CONCLUSION: This is the first study to explore the use of obesity risk tools in clinical practice, the findings suggest that identification, and communication of future overweight and obesity risk is acceptable to parents of infants. Despite this positive response, findings suggest that parents' acceptance to identification of risk and implementation of behaviour change is time specific. The apparent level of parental responsibility, fear of judgement and self-blame also highlights the importance of health professionals approach to personalised risk communication so feelings of self-blame are negated and stigmatisation avoided