A tale of two community networks program centers: Operationalizing and assessing CBPR principles and evaluating partnership outcomes

BACKGROUND: Community Networks Program (CNP) centers are required to use a community-based participatory research (CBPR) approach within their specific priority communities. Not all communities are the same and unique contextual factors and collaborators’ priorities shape each CBPR partnership. There are also established CBPR and community engagement (CE) principles shown to lead to quality CBPR in any community. However, operationalizing and assessing CBPR principles and partnership outcomes to understand the conditions and processes in CBPR that lead to achieving program and project level goals is relatively new in the science of CBPR. OBJECTIVES: We sought to describe the development of surveys on adherence to and implementation of CBPR/CE principles at two CNP centers and examine commonalities and differences in program- versus project-level CBPR evaluation. METHODS: A case study about the development and application of CBPR/CE principles for the Missouri CNP, Program for the Elimination of Cancer Disparities, and Minnesota CNP, Padres Informados/Jovenes Preparados, surveys was conducted to compare project versus program operationalization of principles. Survey participant demographics were provided by CNP. Specific domains found in CBPR/CE principles were identified and organized under an existing framework to establish a common ground. Operational definitions and the number of survey items were provided for each domain by CNP. CONCLUSION: There are distinct differences in operational definitions of CBPR/CE principles at the program and project levels of evaluation. However, commonalities support further research to develop standards for CBPR evaluation across partnerships and at the program and project levels

Screen-based identification and validation of four new ion channels as regulators of renal ciliogenesis

©2015. To investigate the contribution of ion channels to ciliogenesis, we carried out a small interfering RNA (siRNA)-based reverse genetics screen of all ion channels in the mouse genome in murine inner medullary collecting duct kidney cells. This screen revealed four candidate ion channel genes: Kcnq1, Kcnj10, Kcnf1 and Clcn4. We show that these four ion channels localize to renal tubules, specifically to the base of primary cilia. We report that human KCNQ1 Long QT syndrome disease alleles regulate renal ciliogenesis; KCNQ1-p. R518X, -p.A178T and -p.K362R could not rescue ciliogenesis after Kcnq1-siRNA-mediated depletion in contrast to wild-type KCNQ1 and benign KCNQ1-p.R518Q, suggesting that the ion channel function of KCNQ1 regulates ciliogenesis. In contrast, we demonstrate that the ion channel function ofKCNJ10 is independent of its effect on ciliogenesis. Our data suggest that these four ion channels regulate renal ciliogenesis through the periciliary diffusion barrier or the ciliary pocket, with potential implication as genetic contributors to ciliopathy pathophysiology. The new functional roles of a subset of ion channels provide new insights into the disease pathogenesis of channelopathies, which might suggest future therapeutic approaches

Adaptive Strategies in a Poly-Extreme Environment: Differentiation of Vegetative Cells in Serratia ureilytica and Resistance to Extreme Conditions

Poly-extreme terrestrial habitats are often used as analogs to extra-terrestrial environments. Understanding the adaptive strategies allowing bacteria to thrive and survive under these conditions could help in our quest for extra-terrestrial planets suitable for life and understanding how life evolved in the harsh early earth conditions. A prime example of such a survival strategy is the modification of vegetative cells into resistant resting structures. These differentiated cells are often observed in response to harsh environmental conditions. The environmental strain (strain Lr5/4) belonging to Serratia ureilytica was isolated from a geothermal spring in Lirima, Atacama Desert, Chile. The Atacama Desert is the driest habitat on Earth and furthermore, due to its high altitude, it is exposed to an increased amount of UV radiation. The geothermal spring from which the strain was isolated is oligotrophic and the temperature of 54°C exceeds mesophilic conditions (15 to 45°C). Although the vegetative cells were tolerant to various environmental insults (desiccation, extreme pH, glycerol), a modified cell type was formed in response to nutrient deprivation, UV radiation and thermal shock. Scanning (SEM) and Transmission Electron Microscopy (TEM) analyses of vegetative cells and the modified cell structures were performed. In SEM, a change toward a circular shape with reduced size was observed. These circular cells possessed what appears as extra coating layers under TEM. The resistance of the modified cells was also investigated, they were resistant to wet heat, UV radiation and desiccation, while vegetative cells did not withstand any of those conditions. A phylogenomic analysis was undertaken to investigate the presence of known genes involved in dormancy in other bacterial clades. Genes related to spore-formation in Myxococcus and Firmicutes were found in S. ureilytica Lr5/4 genome; however, these genes were not enough for a full sporulation pathway that resembles either group. Although, the molecular pathway of cell differentiation in S. ureilytica Lr5/4 is not fully defined, the identified genes may contribute to the modified phenotype in the Serratia genus. Here, we show that a modified cell structure can occur as a response to extremity in a species that was previously not known to deploy this strategy. This strategy may be widely spread in bacteria, but only expressed under poly-extreme environmental conditions

Recipes for spin-based quantum computing

Technological growth in the electronics industry has historically been measured by the number of transistors that can be crammed onto a single microchip. Unfortunately, all good things must come to an end; spectacular growth in the number of transistors on a chip requires spectacular reduction of the transistor size. For electrons in semiconductors, the laws of quantum mechanics take over at the nanometre scale, and the conventional wisdom for progress (transistor cramming) must be abandoned. This realization has stimulated extensive research on ways to exploit the spin (in addition to the orbital) degree of freedom of the electron, giving birth to the field of spintronics. Perhaps the most ambitious goal of spintronics is to realize complete control over the quantum mechanical nature of the relevant spins. This prospect has motivated a race to design and build a spintronic device capable of complete control over its quantum mechanical state, and ultimately, performing computations: a quantum computer. In this tutorial we summarize past and very recent developments which point the way to spin-based quantum computing in the solid-state. After introducing a set of basic requirements for any quantum computer proposal, we offer a brief summary of some of the many theoretical proposals for solid-state quantum computers. We then focus on the Loss-DiVincenzo proposal for quantum computing with the spins of electrons confined to quantum dots. There are many obstacles to building such a quantum device. We address these, and survey recent theoretical, and then experimental progress in the field. To conclude the tutorial, we list some as-yet unrealized experiments, which would be crucial for the development of a quantum-dot quantum computer.Comment: 45 pages, 12 figures (low-res in preprint, high-res in journal) tutorial review for Nanotechnology; v2: references added and updated, final version to appear in journa

Clonal Haematopoiesis and Risk of Chronic Liver Disease

Chronic liver disease is a major public health burden worldwide1. Although different aetiologies and mechanisms of liver injury exist, progression of chronic liver disease follows a common pathway of liver inflammation, injury and fibrosis2. Here we examined the association between clonal haematopoiesis of indeterminate potential (CHIP) and chronic liver disease in 214,563 individuals from 4 independent cohorts with whole-exome sequencing data (Framingham Heart Study, Atherosclerosis Risk in Communities Study, UK Biobank and Mass General Brigham Biobank). CHIP was associated with an increased risk of prevalent and incident chronic liver disease (odds ratio = 2.01, 95% confidence interval (95% CI) [1.46, 2.79]; P \u3c 0.001). Individuals with CHIP were more likely to demonstrate liver inflammation and fibrosis detectable by magnetic resonance imaging compared to those without CHIP (odds ratio = 1.74, 95% CI [1.16, 2.60]; P = 0.007). to assess potential causality, Mendelian randomization analyses showed that genetic predisposition to CHIP was associated with a greater risk of chronic liver disease (odds ratio = 2.37, 95% CI [1.57, 3.6]; P \u3c 0.001). In a dietary model of non-alcoholic steatohepatitis, mice transplanted with Tet2-deficient haematopoietic cells demonstrated more severe liver inflammation and fibrosis. These effects were mediated by the NLRP3 inflammasome and increased levels of expression of downstream inflammatory cytokines in Tet2-deficient macrophages. In summary, clonal haematopoiesis is associated with an elevated risk of liver inflammation and chronic liver disease progression through an aberrant inflammatory response

LSST: from Science Drivers to Reference Design and Anticipated Data Products

(Abridged) We describe here the most ambitious survey currently planned in the optical, the Large Synoptic Survey Telescope (LSST). A vast array of science will be enabled by a single wide-deep-fast sky survey, and LSST will have unique survey capability in the faint time domain. The LSST design is driven by four main science themes: probing dark energy and dark matter, taking an inventory of the Solar System, exploring the transient optical sky, and mapping the Milky Way. LSST will be a wide-field ground-based system sited at Cerro Pach\'{o}n in northern Chile. The telescope will have an 8.4 m (6.5 m effective) primary mirror, a 9.6 deg$^2$ field of view, and a 3.2 Gigapixel camera. The standard observing sequence will consist of pairs of 15-second exposures in a given field, with two such visits in each pointing in a given night. With these repeats, the LSST system is capable of imaging about 10,000 square degrees of sky in a single filter in three nights. The typical 5$\sigma$ point-source depth in a single visit in $r$ will be $\sim 24.5$ (AB). The project is in the construction phase and will begin regular survey operations by 2022. The survey area will be contained within 30,000 deg$^2$ with $\delta<+34.5^\circ$, and will be imaged multiple times in six bands, $ugrizy$, covering the wavelength range 320--1050 nm. About 90\% of the observing time will be devoted to a deep-wide-fast survey mode which will uniformly observe a 18,000 deg$^2$ region about 800 times (summed over all six bands) during the anticipated 10 years of operations, and yield a coadded map to $r\sim27.5$. The remaining 10\% of the observing time will be allocated to projects such as a Very Deep and Fast time domain survey. The goal is to make LSST data products, including a relational database of about 32 trillion observations of 40 billion objects, available to the public and scientists around the world.Comment: 57 pages, 32 color figures, version with high-resolution figures available from https://www.lsst.org/overvie

Caretaker Brca1: keeping the genome in the straight and narrow

Inheritance of germline BRCA1 mutations is associated with a high risk of breast and ovarian cancers. A multitude of cellular functions has been ascribed to BRCA1, including transcription activation and various aspects of DNA repair. So far, indirect evidence has indicated a role for BRCA1 in the repair of double-strand breaks. Recently, an elegant gene targeting design was used to provide definitive evidence that BRCA1 promotes homologous recombination and limits nonhomologous mutagenic repair processes. This reaffirms the role of BRCA1 as caretaker in preserving genomic integrity

The Long-Lived Disks in the Eta Chamaeleontis Cluster

We present IRS spectra and revised MIPS photometry for the 18 members of the Eta Chamaeleontis cluster. Aged 8 Myr, the Eta Cha cluster is one of the few nearby regions within the 5-10 Myr age range, during which the disk fraction decreases dramatically and giant planet formation must come to an end. For the 15 low-mass members, we measure a disk fraction ~50%, high for their 8 Myr age, and 4 of the 8 disks lack near-IR excesses, consistent with the empirical definition of "transition'' disks. Most of the disks are comparable to geometrically flat disks. The comparison with regions of different ages suggests that at least some of the "transition" disks may represent the normal type of disk around low-mass stars. Therefore, their flattened structure and inner holes may be related to other factors (initial masses of the disk and the star, environment, binarity), rather than to pure time evolution. We analyze the silicate dust in the disk atmosphere, finding moderate crystalline fractions (~10-30%) and typical grain sizes ~1-3 micron, without any characteristic trend in the composition. These results are common to other regions of different ages, suggesting that the initial grain processing occurs very early in the disk lifetime (<1 Myr). Large grain sizes in the disk atmosphere cannot be used as a proxy for age, but are likely related to higher disk turbulence. The dust mineralogy varies between the 8-12micron and the 20-30 micron features, suggesting high temperature dust processing and little radial mixing. Finally, the analysis of IR and optical data on the B9 star Eta Cha reveals that it is probably surrounded by a young debris disk with a large inner hole, instead of being a classical Be star.Comment: 35 pages, 6 tables, 8 figures; Accepted by Ap

Towards evidence-based conservation of subterranean ecosystems

Subterranean ecosystems are among the most widespread environments on Earth, yet we still have poor knowledge of their biodiversity. To raise awareness of subterranean ecosystems, the essential services they provide, and their unique conservation challenges, 2021 and 2022 were designated International Years of Caves and Karst. As these ecosystems have traditionally been overlooked in global conservation agendas and multilateral agreements, a quantitative assessment of solution-based approaches to safeguard subterranean biota and associated habitats is timely. This assessment allows researchers and practitioners to understand the progress made and research needs in subterranean ecology and management. We conducted a systematic review of peer-reviewed and grey literature focused on subterranean ecosystems globally (terrestrial, freshwater, and saltwater systems), to quantify the available evidence-base for the effectiveness of conservation interventions. We selected 708 publications from the years 1964 to 2021 that discussed, recommended, or implemented 1,954 conservation interventions in subterranean ecosystems. We noted a steep increase in the number of studies from the 2000s while, surprisingly, the proportion of studies quantifying the impact of conservation interventions has steadily and significantly decreased in recent years. The effectiveness of 31% of conservation interventions has been tested statistically. We further highlight that 64% of the reported research occurred in the Palearctic and Nearctic biogeographic regions. Assessments of the effectiveness of conservation interventions were heavily biased towards indirect measures (monitoring and risk assessment), a limited sample of organisms (mostly arthropods and bats), and more accessible systems (terrestrial caves). Our results indicate that most conservation science in the field of subterranean biology does not apply a rigorous quantitative approach, resulting in sparse evidence for the effectiveness of interventions. This raises the important question of how to make conservation efforts more feasible to implement, cost-effective, and long-lasting. Although there is no single remedy, we propose a suite of potential solutions to focus our efforts better towards increasing statistical testing and stress the importance of standardising study reporting to facilitate meta-analytical exercises. We also provide a database summarising the available literature, which will help to build quantitative knowledge about interventions likely to yield the greatest impacts depending upon the subterranean species and habitats of interest. We view this as a starting point to shift away from the widespread tendency of recommending conservation interventions based on anecdotal and expert-based information rather than scientific evidence, without quantitatively testing their effectiveness.Peer reviewe