A dystroglycan-laminin-integrin axis coordinates cell shape remodeling in the developing Drosophila retina.

Cell shape remodeling is a principal driver of epithelial tissue morphogenesis. While progress continues to be made in our understanding of the pathways that control the apical (top) geometry of epithelial cells, we know comparatively little about those that control cell basal (bottom) geometry. To examine this, we used the Drosophila ommatidium, which is the basic visual unit of the compound eye.

Array tomography: trails to discovery.

Tissue slicing is at the core of many approaches to studying biological structures. Among the modern volume electron microscopy (vEM) methods, array tomography (AT) is based on serial ultramicrotomy, section collection onto solid support, imaging via light and/or scanning electron microscopy, and re-assembly of the serial images into a volume for analysis. While AT largely uses standard EM equipment, it provides several advantages, including long-term preservation of the sample and compatibility with multi-scale and multi-modal imaging.

A mammalian model reveals inorganic polyphosphate channeling into the nucleolus and induction of a hyper-condensate state.

Inorganic polyphosphate (polyP) is a ubiquitous polymer that controls fundamental processes. To overcome the absence of a genetically tractable mammalian model, we developed an inducible mammalian cell line expressing Escherichia coli polyphosphate kinase 1 (EcPPK1). Inducing EcPPK1 expression prompted polyP synthesis, enabling validation of polyP analytical methods.

Phase 3 Randomized Clinical Trial of the Safety and Efficacy of Travoprost Intraocular Implant in Patients with Open-Angle Glaucoma or Ocular Hypertension.

Purpose: To evaluate the safety and intraocular pressure (IOP)-lowering efficacy of 2 models of the travoprost intraocular implant (fast-eluting [FE] and slow-eluting [SE] types) from 1 of 2 phase 3 trials (the GC-010 trial).

Design: Multicenter, randomized, double-masked, sham-controlled, noninferiority trial.

Participants: Patients with open-angle glaucoma or ocular hypertension having an unmedicated baseline mean diurnal IOP (average of 8 am, 10 am, and 4 pm time points) of ≥ 21 mmHg, and IOP of ≤ 36 mmHg at each of the 8 am, 10 am, and 4 pm timepoints at baseline.

Travoprost Intracameral Implant for Open-Angle Glaucoma or Ocular Hypertension: 12-Month Results of a Randomized, Double-Masked Trial.

Introduction: This prospective, multicenter, randomized, double-masked pivotal phase 3 trial evaluated the efficacy and safety of the travoprost intracameral SE-implant (slow-eluting implant, the intended commercial product) and FE-implant (fast-eluting implant, included primarily for masking purposes) compared to twice-daily (BID) timolol ophthalmic solution, 0.5% in patients with open-angle glaucoma (OAG) or ocular hypertension (OHT).

Methods: The trial enrolled adult patients with OAG or OHT with an unmedicated mean diurnal intraocular pressure (IOP) of ≥ 21 and unmedicated IOP ≤ 36 mmHg at each diurnal timepoint (8 A.

The vaccinia chondroitin sulfate binding protein drives host membrane curvature to facilitate fusion.

Cellular attachment of viruses determines their cell tropism and species specificity. For entry, vaccinia, the prototypic poxvirus, relies on four binding proteins and an eleven-protein entry fusion complex. The contribution of the individual virus binding proteins to virion binding orientation and membrane fusion is unclear.

Effectiveness of residential treatment services for veterans with substance use disorders: A propensity score matching evaluation.

Background: Prior reviews of substance use disorder (SUD) treatment have found mixed support for residential level of care but are limited by methodology problems and the ethical concerns of randomizing patients with severe SUD to lower levels of care.

Methods: The present study is the first to use a large archival SUD residential sample with a matched comparison group and one-year follow-up period to examine the benefits of residential treatment provided to adults clinically assessed as warranting SUD residential care. We used propensity score matching in our sample (N = 6177) of veterans with a SUD who were screened and accepted for Veterans Affairs (VA) SUD residential treatment between January 1st, 2019 and June 30th, 2019.

History and current status of contingency management programs in the Department of Veterans Affairs.

Objective: This article describes the Department of Veterans Affairs (VA) national implementation of contingency management within VA substance use disorder (SUD) treatment programs.

Methods: The rationale for implementing CM, role of VA leadership, and training and supervision procedures are detailed. The role of the Veterans Canteen Service (VCS) in sustaining the CM implementation through the donation of incentives is outlined.

A practical guide to starting SEM array tomography-An accessible volume EM technique.

The techniques collectively known as volume electron microscopy (vEM) each come with their own advantages and challenges, making them more or less suitable for any specific project. SEM array tomography (SEM-AT) is certainly no different in this respect. Requiring microtomy skills, and involving more data alignment post imaging, SEM-AT presents challenges to its users, nevertheless, as perhaps the most flexible, cost effective and potentially accessible vEM approach to regular EM facilities, it benefits those same users with multiple advantages due to its inherently non-destructive nature.

Made to measure: An introduction to quantifying microscopy data in the life sciences.

Images are at the core of most modern biological experiments and are used as a major source of quantitative information. Numerous algorithms are available to process images and make them more amenable to be measured. Yet the nature of the quantitative output that is useful for a given biological experiment is uniquely dependent upon the question being investigated.

Volume EM: a quiet revolution takes shape.

Volume Electron Microscopy is a group of techniques that reveal the 3D ultrastructure of cells and tissues through volumes greater than 1 cubic micron. A burgeoning grass roots community effort is fast building the profile, and revealing the impact, of vEM technology in the life sciences and clinical research.

Rethink reporting of evaluation results in AI.

Aggregate metrics and lack of access to results limit understanding.

Measurement-based care in Veterans Health Administration mental health residential treatment.

In 2016, the Veterans Health Administration (VHA) launched the Measurement-Based Care (MBC) in Mental Health Initiative to support the use of patient-reported outcome measures (PROMs) across mental health services to increase veteran engagement and promote collaborative treatment planning. The present study reported on the administrations of PROMs across all residential stays within the VHA's Mental Health Residential Rehabilitation Treatment Programs between October 1, 2018, and September 30, 2019 ( = 29,111). We subsequently explored a subsample of veterans attending substance use residential treatment during the same period who completed the Brief Addiction Monitor-Revised (BAM-R; Cacciola et al.

Perivascular cells induce microglial phagocytic states and synaptic engulfment via SPP1 in mouse models of Alzheimer's disease.

Alzheimer's disease (AD) is characterized by synaptic loss, which can result from dysfunctional microglial phagocytosis and complement activation. However, what signals drive aberrant microglia-mediated engulfment of synapses in AD is unclear. Here we report that secreted phosphoprotein 1 (SPP1/osteopontin) is upregulated predominantly by perivascular macrophages and, to a lesser extent, by perivascular fibroblasts.

Characterization of the structure and control of the blood-nerve barrier identifies avenues for therapeutic delivery.

The blood barriers of the nervous system protect neural environments but can hinder therapeutic accessibility. The blood-brain barrier (BBB) is well characterized, consisting of endothelial cells with specialized tight junctions and low levels of transcytosis, properties conferred by contacting pericytes and astrocytes. In contrast, the blood-nerve barrier (BNB) of the peripheral nervous system is poorly defined.

The ultrastructural organization of endoplasmic reticulum-plasma membrane contacts is conserved in epithelial cells.

Contacts between the endoplasmic reticulum and the plasma membrane (ER-PM contacts) have important roles in membrane lipid and calcium dynamics, yet their organization in polarized epithelial cells has not been thoroughly described. Here we examine ER-PM contacts in hepatocytes in mouse liver using electron microscopy, providing the first comprehensive ultrastructural study of ER-PM contacts in a mammalian epithelial tissue. Our quantitative analyses reveal strikingly distinct ER-PM contact architectures spatially linked to apical, lateral, and basal PM domains.

Poxviruses package viral redox proteins in lateral bodies and modulate the host oxidative response.

All poxviruses contain a set of proteinaceous structures termed lateral bodies (LB) that deliver viral effector proteins into the host cytosol during virus entry. To date, the spatial proteotype of LBs remains unknown. Using the prototypic poxvirus, vaccinia virus (VACV), we employed a quantitative comparative mass spectrometry strategy to determine the poxvirus LB proteome.

Three-dimensional Characterization of Interorganelle Contact Sites in Hepatocytes using Serial Section Electron Microscopy.

Transmission electron microscopy has been long considered to be the gold standard for the visualization of cellular ultrastructure. However, analysis is often limited to two dimensions, hampering the ability to fully describe the three-dimensional (3D) ultrastructure and functional relationship between organelles. Volume electron microscopy (vEM) describes a collection of techniques that enable the interrogation of cellular ultrastructure in 3D at mesoscale, microscale, and nanoscale resolutions.

Structure modeling hints at a granular organization of the Golgi ribbon.

Background: In vertebrate cells, the Golgi functional subunits, mini-stacks, are linked into a tri-dimensional network. How this "ribbon" architecture relates to Golgi functions remains unclear. Are all connections between mini-stacks equal? Is the local structure of the ribbon of functional importance? These are difficult questions to address, without a quantifiable readout of the output of ribbon-embedded mini-stacks.

The Management of Substance Use Disorders: Synopsis of the 2021 U.S. Department of Veterans Affairs and U.S. Department of Defense Clinical Practice Guideline.

Description: In August 2021, leadership within the U.S. Department of Veterans Affairs (VA) and U.

USP17 is required for peripheral trafficking of lysosomes.

Expression of the deubiquitinase USP17 is induced by multiple stimuli, including cytokines (IL-4/6), chemokines (IL-8, SDF1), and growth factors (EGF), and several studies indicate it is required for cell proliferation and migration. However, the mechanisms via which USP17 impacts upon these cellular functions are unclear. Here, we demonstrate that USP17 depletion prevents peripheral lysosome positioning, as well as trafficking of lysosomes to the cell periphery in response to EGF stimulation.

Making cataract surgery possible in patients with ankylosing spondylitis: A new positioning technique.

Importance: Patients with Ankylosing Spondylitis frequently have fixed kyphosis of their spine together with pain. This makes achieving acceptable head position for ocular surgery difficult. The proposal of new methods that result in successful intraocular surgery will reduce morbidity and sight loss in this group of patients.

Integrating palliative care and heart failure: a protocol for a realist synthesis (PalliatHeartSynthesis).

Introduction: Heart failure affects over 26 million people worldwide with prevalence expected to grow due to an ageing global population. Palliative care can address the holistic needs of patients with heart failure, and integrated palliative care in heart failure management has been indicated to improve outcomes for patients. Despite known benefits for integrated palliative care in heart failure management, implementation is poor across the majority of global health services.