A randomized, placebo-controlled trial of long-acting dexamethasone viscous gel delivered by transforaminal injection for lumbosacral radicular pain.

ClinicalTrials.gov Identifier: NCT03372161.

Beauty is more than epidermis deep: How cell division and expansion sculpt the leaf spongy mesophyll.

As the main location of photosynthesis, leaf mesophyll cells are one of the most abundant and essential cell types on earth. Forming the bulk of the internal tissues of the leaf, their size, shape, and patterns of interconnectivity define the internal structure and surface area of the leaf, which in turn determines the efficiency of light capture and carbon fixation. Understanding how these cellular traits are controlled and translated into tissue- and organ-scale traits, and how they influence photosynthetic performance will be key to our ability to improve crop plants in the face of a changing climate.

Localized growth and remodelling drives spongy mesophyll morphogenesis.

The spongy mesophyll is a complex, porous tissue found in plant leaves that enables carbon capture and provides mechanical stability. Unlike many other biological tissues, which remain confluent throughout development, the spongy mesophyll must develop from an initially confluent tissue into a tortuous network of cells with a large proportion of intercellular airspace. How the airspace in the spongy mesophyll develops while the tissue remains mechanically stable is unknown.

Clinical and economic burden of uncontrolled severe noneosinophilic asthma.

Objectives: To quantify the clinical and economic burden of patients with severe asthma with low blood eosinophil counts (BECs) untreated with biologics.

Study Design: Retrospective cohort study in IBM MarketScan claims database.

Methods: Patients 12 years and older with severe asthma with BEC data were selected between January 1, 2013, and June 30, 2018 (date of the most recent BEC was used as the index date).

CLASP balances two competing cell division plane cues during leaf development.

Starting as small, densely packed boxes, leaf mesophyll cells expand to form an intricate mesh of interconnected cells and air spaces, the organization of which dictates the internal surface area of the leaf for light capture and gas exchange during photosynthesis. Despite their importance, little is known about the basic patterns of mesophyll cell division, and how they contribute to cell and intercellular space organization. To address this, we tracked divisions within individual cell lineages in three dimensions over time in Arabidopsis spongy mesophyll.

Repeat Epidural Injections of SP-102 (Dexamethasone Sodium Phosphate Injectable Gel) in Subjects with Lumbosacral Radiculopathy.

Purpose: SP-102 is a novel epidural steroid injection (ESI) formulation of 10 mg dexamethasone sodium phosphate in a viscous gel solution. Repeat dosing of ESIs is possible if required for pain relief, but with consideration of hypothalamic-pituitary-adrenal (HPA) axis suppression from prolonged systemic exposure. This phase I/II study investigated the effect of initial and repeat SP-102 injections on HPA suppression and analgesia.

Live imaging of microtubule organization, cell expansion, and intercellular space formation in Arabidopsis leaf spongy mesophyll cells.

Leaf spongy mesophyll cells form an interconnected network of branched cells and intercellular spaces to maximize the surface area available for light capture and photosynthetic gas exchange. To investigate the morphogenetic events leading to cell separation and branching in Arabidopsis thaliana, we used mesophyll-specific promoters to facilitate imaging of mesophyll cell shape and microtubule (MT) organization over multiple spatiotemporal scales without interference from the overlying epidermal cells. We show that cells enlarge by selective expansion of cell wall regions in contact with intercellular spaces.

Clinical and economic burden of severe asthma among US patients treated with biologic therapies.

Background: Patients with severe asthma may remain uncontrolled despite biologic therapy in addition to standard therapy, but this disease burden has not been quantified.

Objective: To estimate the clinical and economic burden in a US national sample.

Methods: Patients who have severe asthma with indicated biologic treatment (earliest use = index date) were selected from the MarketScan database between January 1, 2013, and June 30, 2018.

Wellbeing recovery inequity following the 2010/2011 Canterbury earthquake sequence: repeated cross-sectional studies.

Objective: To track population mental wellbeing following the 2010/2011 Christchurch earthquakes and after-shocks.

Methods: The Canterbury Wellbeing Survey, a cross-sectional survey of randomly selected adults aged ≥18 years resident in Christchurch, was repeated biannually from April 2013 until June 2017 and annually thereafter. The self-reported 5-item World Health Organization Well-Being Index (WHO-5) has been elicited from April 2013.

Correction to: MeioCapture: an efficient method for staging and isolation of meiocytes in the prophase I sub-stages of meiosis in wheat.

Following publication of the original article [1], a reader spotted an incorrect citation of the reference 14 [2] in the 'Background'. The male meiocyte isolation work described in this article [2] was carried out in rice and not in Brassica as originally stated in the 'Background' [1]. Thus, the following amendment to the Background section should be noted.

MeioCapture: an efficient method for staging and isolation of meiocytes in the prophase I sub-stages of meiosis in wheat.

Background: Molecular analysis of meiosis has been hindered by difficulties in isolating high purity subpopulations of sporogenous cells representing the succeeding stages of meiosis. Isolation of purified male meiocytes from defined meiotic stages is crucial in discovering meiosis specific genes and associated regulatory networks.

Results: We describe an optimized method termed MeioCapture for simultaneous isolation of uncontaminated male meiocytes from wheat (Triticum spp.

The Microtubule-Associated Protein CLASP Sustains Cell Proliferation through a Brassinosteroid Signaling Negative Feedback Loop.

The capacity for sustained cell division within the plant meristem is a critical determinant of organ structure and performance. This capacity is diminished in mutants lacking the microtubule-associated protein CLASP and when brassinosteroid signaling is increased. Here, we discovered that CLASP is both targeted by and promotes activity of the brassinosteroid pathway in Arabidopsis root apical meristems.

CLASP promotes stable tethering of endoplasmic microtubules to the cell cortex to maintain cytoplasmic stability in Arabidopsis meristematic cells.

Following cytokinesis in plants, Endoplasmic MTs (EMTs) assemble on the nuclear surface, forming a radial network that extends out to the cell cortex, where they attach and incorporate into the cortical microtubule (CMT) array. We found that in these post-cytokinetic cells, the MT-associated protein CLASP is enriched at sites of EMT-cortex attachment, and is required for stable EMT tethering and growth into the cell cortex. Loss of EMT-cortex anchoring in clasp-1 mutants results in destabilized EMT arrays, and is accompanied by enhanced mobility of the cytoplasm, premature vacuolation, and precocious entry into cell elongation phase.

Microtubule encounter-based catastrophe in Arabidopsis cortical microtubule arrays.

Background: The cortical microtubules (CMTs) that line the plasma membrane of interphase plant cells are extensively studied owing to their importance in forming cell walls, and their usefulness as a model system for the study of MT dynamic instability and acentrosomal MT organization. CMTs influence the orientation and structure of cellulose microfibrils in the cell wall by cooperatively forming arrays of varied patterns from parallel to netted. These CMT patterns are controlled by the combined activities of MT dynamic instability and MT-MT interactions.

Microtubules in Plant Cells: Strategies and Methods for Immunofluorescence, Transmission Electron Microscopy, and Live Cell Imaging.

Microtubules (MTs) are required throughout plant development for a wide variety of processes, and different strategies have evolved to visualize and analyze them. This chapter provides specific methods that can be used to analyze microtubule organization and dynamic properties in plant systems and summarizes the advantages and limitations for each technique. We outline basic methods for preparing samples for immunofluorescence labeling, including an enzyme-based permeabilization method, and a freeze-shattering method, which generates microfractures in the cell wall to provide antibodies access to cells in cuticle-laden aerial organs such as leaves.

Systematic review and metaanalysis of genetic association studies of urinary symptoms and prolapse in women.

Objective: Family studies and twin studies demonstrate that lower urinary tract symptoms and pelvic organ prolapse are heritable. This review aimed to identify genetic polymorphisms tested for an association with lower urinary tract symptoms or prolapse, and to assess the strength, consistency, and risk of bias among reported associations.

Study Design: PubMed and HuGE Navigator were searched up to May 1, 2014, using a combination of genetic and phenotype key words, including "nocturia," "incontinence," "overactive bladder," "prolapse," and "enuresis.

Microtubule initiation from the nuclear surface controls cortical microtubule growth polarity and orientation in Arabidopsis thaliana.

The nuclear envelope in plant cells has long been known to be a microtubule organizing center (MTOC), but its influence on microtubule organization in the cell cortex has been unclear. Here we show that nuclear MTOC activity favors the formation of longitudinal cortical microtubule (CMT) arrays. We used green fluorescent protein (GFP)-tagged gamma tubulin-complex protein 2 (GCP2) to identify nuclear MTOC activity and GFP-tagged End-Binding Protein 1b (EB1b) to track microtubule growth directions.

Systematic review and meta-analysis of candidate gene association studies of lower urinary tract symptoms in men.

Context: Although family studies have shown that male lower urinary tract symptoms (LUTS) are highly heritable, no systematic review exists of genetic polymorphisms tested for association with LUTS.

Objective: To systematically review and meta-analyze studies assessing candidate polymorphisms/genes tested for an association with LUTS, and to assess the strength, consistency, and potential for bias among pooled associations.

Evidence Acquisition: A systematic search of the PubMed and HuGE databases as well as abstracts of major urologic meetings was performed through to January 2013.

Cell geometry guides the dynamic targeting of apoplastic GPI-linked lipid transfer protein to cell wall elements and cell borders in Arabidopsis thaliana.

During cellular morphogenesis, changes in cell shape and cell junction topology are fundamental to normal tissue and organ development. Here we show that apoplastic Glycophosphatidylinositol (GPI)-anchored Lipid Transfer Protein (LTPG) is excluded from cell junctions and flat wall regions, and passively accumulates around their borders in the epidermal cells of Arabidopsis thaliana. Beginning with intense accumulation beneath highly curved cell junction borders, this enrichment is gradually lost as cells become more bulbous during their differentiation.

CLASP interacts with sorting nexin 1 to link microtubules and auxin transport via PIN2 recycling in Arabidopsis thaliana.

Polarized movement of auxin generates concentration gradients within plant tissues to control cell division patterns and growth direction by modulating microtubule organization. In this study, we identify a reverse mechanism, wherein microtubules influence polar auxin transport. We show that the microtubule-associated protein CLASP interacts with the retromer component sorting nexin 1 (SNX1) to mediate an association between endosomes and microtubules.

Increased incidence of Escherichia coli bacteremia post-Christchurch earthquake 2011: possible associations.

Introduction: Earthquakes are natural events that contribute to the transmission of infectious diseases. The aim of this research was to determine whether the observed increase in Escherichia coli (E. coli) bloodstream infections (BSI) during the period March-June 2011 was associated with the February 2011 Christchurch earthquake.

A PLETHORA-auxin transcription module controls cell division plane rotation through MAP65 and CLASP.

Despite their pivotal role in plant development, control mechanisms for oriented cell divisions have remained elusive. Here, we describe how a precisely regulated cell division orientation switch in an Arabidopsis stem cell is controlled by upstream patterning factors. We show that the stem cell regulatory PLETHORA transcription factors induce division plane reorientation by local activation of auxin signaling, culminating in enhanced expression of the microtubule-associated MAP65 proteins.

Cell edges accumulate gamma tubulin complex components and nucleate microtubules following cytokinesis in Arabidopsis thaliana.

Microtubules emanate from distinct organizing centers in fungal and animal cells. In plant cells, by contrast, microtubules initiate from dispersed sites in the cell cortex, where they then self-organize into parallel arrays. Previous ultrastructural evidence suggested that cell edges participate in microtubule nucleation but so far there has been no direct evidence for this.

Nanoscale and geometric influences on the microtubule cytoskeleton in plants: thinking inside and outside the box.

The dynamic microtubule (MT) cytoskeleton found in the cell cortex of plants drives cell expansion via cell wall modifications. In the last decade, live cell imaging studies employing green fluorescent protein have helped unravel the mechanisms behind how cells arrange cortical MTs into complex arrays and shape cell expansion. In this review, we explore the reverse scenario: how cell geometry and organelles influence and constrain the organization and behavior of cortical MTs.

A CLASP-modulated cell edge barrier mechanism drives cell-wide cortical microtubule organization in Arabidopsis.

It is well known that the parallel order of microtubules in the plant cell cortex defines the direction of cell expansion, yet it remains unclear how microtubule orientation is controlled, especially on a cell-wide basis. Here we show through 4D imaging and computational modelling that plant cell polyhedral geometry provides spatial input that determines array orientation and heterogeneity. Microtubules depolymerize when encountering sharp cell edges head-on, whereas those oriented parallel to those sharp edges remain.