Combining ChIP-chip and Expression Profiling to Model the MoCRZ1 Mediated Circuit for Ca2+/Calcineurin Signaling in the Rice Blast Fungus

Significant progress has been made in defining the central signaling networks in many organisms, but collectively we know little about the downstream targets of these networks and the genes they regulate. To reconstruct the regulatory circuit of calcineurin signal transduction via MoCRZ1, a Magnaporthe oryzae C2H2 transcription factor activated by calcineurin dephosphorylation, we used a combined approach of chromatin immunoprecipitation - chip (ChIP-chip), coupled with microarray expression studies. One hundred forty genes were identified as being both a direct target of MoCRZ1 and having expression concurrently differentially regulated in a calcium/calcineurin/MoCRZ1 dependent manner. Highly represented were genes involved in calcium signaling, small molecule transport, ion homeostasis, cell wall synthesis/maintenance, and fungal virulence. Of particular note, genes involved in vesicle mediated secretion necessary for establishing host associations, were also found. MoCRZ1 itself was a target, suggesting a previously unreported autoregulation control point. The data also implicated a previously unreported feedback regulation mechanism of calcineurin activity. We propose that calcium/calcineurin regulated signal transduction circuits controlling development and pathogenicity manifest through multiple layers of regulation. We present results from the ChIP-chip and expression analysis along with a refined model of calcium/calcineurin signaling in this important plant pathogen

SPINE20 A global advocacy group promoting evidence-based spine care of value

PURPOSE: The Global Burden of Diseases (GBD) Studies have estimated that low back pain is one of the costliest ailments worldwide. Subsequent to GBD publications, leadership of the four largest global spine societies agreed to form SPINE20. This article introduces the concept of SPINE20, the recommendations, and the future of this global advocacy group linked to G20 annual summits. METHODS: The founders of SPINE20 advocacy group coordinated with G20 Saudi Arabia to conduct the SPINE20 summit in 2020. The summit was intended to promote evidence-based recommendations to use the most reliable information from high-level research. Eight areas of importance to mitigate spine disorders were identified through a voting process of the participating societies. Twelve recommendations were discussed and vetted. RESULTS: The areas of immediate concern were "Aging spine," "Future of spine care," "Spinal cord injuries," "Children and adolescent spine," "Spine-related disability," "Spine Educational Standards," "Patient safety," and "Burden on economy." Twelve recommendations were created and endorsed by 31/33 spine societies and 2 journals globally during a vetted process through the SPINE20.org website and during the virtual inaugural meeting November 10-11, 2020 held from the G20 platform. CONCLUSIONS: This is the first time that international spine societies have joined to support actions to mitigate the burden of spine disorders across the globe. SPINE20 seeks to change awareness and treatment of spine pain by supporting local projects that implement value-based practices with healthcare policies that are culturally sensitive based on scientific evidence

Clinical and Radiological Outcome of a new Total Cervical Disc Replacement Design

Study Design: Non-randomized prospective and single center clinical trial of the ProDisc Vivo prosthesis. Objective: Investigate the clinical and radiological results of a refined cTDR - the ProDisc Vivo - with two years of follow up (FU). The incidence of implant-related complications was recorded as a secondary outcome variable. Summary of Background Data: Previous generations of the ProDisc artificial cervical disc replacement generate high primary stability due to keel-based designs with opening of the anterior cortex during the implantation and subsequent high rates of heterotopic ossifications. Methods: Clinical outcome scores included the Neck Disability Index (NDI), Visual Analogue Scale (VAS), arm and neck pain self-assessment questionnaires. The radiological outcome included the range of motion (ROM) and the occurrence of heterotopic ossifications. The incidence of implant-related complications with new implant design was recorded as a secondary outcome variable. Results: A total of 55 patients received a single level treatment with the ProDisc Vivo cTDR between C3/4 and C6/7, with a follow up rate of 78%. The clinical outcome scores improved in all parameters significantly (p = 0.0001) (NDI: 68.3 → 17.4; VAS arm: 6.3 → 1.4; VAS neck: 4.9 → 1.6). The ROM of the index-segment didn't show a significant change (p = 0.26) (7.9° → 9.2°). Heterotopic ossifications at the index segment was found as grade 0 in 58%, grade 1 in 22%, grade 2 in 10%, grade 3 (with functional impairment of the prosthesis) in 7% and grade 4 in 3% of the cases. We observed three implant-related complications (5.5%), with two implant dislocations anteriorly and one low-grade infect. Conclusion: cTDR with ProDisc Vivo demonstrated a significant and sustained improvement of all clinical outcome parameters. A less-invasive implantation mechanism with lower primary stability of the cTDR might be a reason for a higher dislocation rate compared to the keel-based previous generation ProDisc C.ISSN:0362-2436ISSN:1528-115

Relationships between personality, emotional well-being, self-efficacy and weight management among adults with type 2 diabetes: Results from a cross-sectional survey.

The objective of this study was to examine the associations between personality, general and diabetes-specific well-being and self-efficacy, and weight management indicators, among adults with type 2 diabetes. In addition, to examine whether personality provides incremental explanation of variance in weight management indicators. Australian adults with type 2 diabetes (N = 270; 56% women; age: 61±12 years) were recruited via the national diabetes registry. An online survey included measures of: personality (HEXACO-PI-R), weight management indicators (physical activity, healthy diet, body mass index [BMI]), general well-being (WHO-5), general self-efficacy (GSE), diabetes distress (DDS) and diabetes self-efficacy (DMSES). Analyses included bivariate correlations and linear regression, adjusted for demographic, clinical, and psychological variables. All six personality domains showed significant correlation with at least one weight management indicator: physical activity with extraversion (r = .28), conscientiousness (r = .18) and openness (r = .19); healthy diet with honesty-humility (r = .19), extraversion (r = .24), and agreeableness (r = .14); and BMI with emotionality (r = .20) and extraversion (r = -.20). The strongest associations with general and diabetes-specific well-being and self-efficacy were apparent for extraversion, emotionality and conscientiousness (range: r = -.47-.66). Beyond covariates, personality domains explained additional variance for physical activity (Adjusted R2 = .31, R2 difference = .03, p = .03; openness: β = .16, p = .02, emotionality: β = .15, p = .04) and healthy diet (Adjusted R2 = .19, R2 difference = .03, p = .02; honesty-humility: β = .20, p = .002, extraversion: β = .19, p = .04) but not BMI. This study shows that personality is associated with weight management indicators and psychological factors among adults with type 2 diabetes. Further research is needed, including objective measurement of weight management indictors, to examine how personality influences the experience of type 2 diabetes

A retrospective analysis of bone mineral status in patients requiring spinal surgery

Abstract Background Impaired bone quality is associated with poor outcome of spinal surgery. The aim of the study was to assess the bone mineral status of patients scheduled to undergo spinal surgery and to report frequencies of bone mineral disorders. Methods We retrospectively analyzed the bone mineral status of 144 patients requiring spinal surgery including bone mineral density by dual-energy X-ray absorptiometry (DXA) as well as laboratory data with serum levels of 25-hydroxyvitamin D (25-OH-D), parathyroid hormone, calcium, bone specific alkaline phosphate, osteocalcin, and gastrin. High-resolution peripheral quantitative computed tomography (HR-pQCT) was additionally performed in a subgroup of 67 patients with T-Score below − 1.5 or history of vertebral fracture. Results Among 144 patients, 126 patients (87.5%) were older than 60 years. Mean age was 70.1 years. 42 patients (29.1%) had suffered from a vertebral compression fracture. 12 previously undiagnosed vertebral deformities were detected in 12 patients by vertebral fracture assessment (VFA). Osteoporosis was present in 39 patients (27.1%) and osteopenia in 63 patients (43.8%). Only 16 patients (11.1%) had received anti-osteoporotic therapy, while 54 patients (37.5%) had an indication for specific anti-osteoporotic therapy but had not received it yet. The majority of patients had inadequate vitamin D status (73.6%) and 34.7% of patients showed secondary hyperparathyroidism as a sign for a significant disturbed calcium homeostasis. In a subgroup of 67 patients, severe vertebral deformities were associated with stronger deficits in bone microarchitecture at the distal radius compared to the distal tibia. Conclusions This study shows that bone metabolism disorders are highly prevalent in elderly patients scheduled for spinal surgery. Vertebral deformities are associated with a predominant deterioration of bone microstructure at the distal radius. As impaired bone quality can compromise surgical outcome, we strongly recommend an evaluation of bone mineral status prior to operation and anti-osteoporotic therapy if necessary

The Response Regulator RRG-1 Functions Upstream of a Mitogen-activated Protein Kinase Pathway Impacting Asexual Development, Female Fertility, Osmotic Stress, and Fungicide Resistance in Neurospora crassa

Two-component systems, consisting of proteins with histidine kinase and/or response regulator domains, regulate environmental responses in bacteria, Archaea, fungi, slime molds, and plants. Here, we characterize RRG-1, a response regulator protein from the filamentous fungus Neurospora crassa. The cell lysis phenotype of Δrrg-1 mutants is reminiscent of osmotic-sensitive (os) mutants, including nik-1/os-1 (a histidine kinase) and strains defective in components of a mitogen-activated protein kinase (MAPK) pathway: os-4 (MAPK kinase kinase), os-5 (MAPK kinase), and os-2 (MAPK). Similar to os mutants, Δrrg-1 strains are sensitive to hyperosmotic conditions, and they are resistant to the fungicides fludioxonil and iprodione. Like os-5, os-4, and os-2 mutants, but in contrast to nik-1/os-1 strains, Δrrg-1 mutants do not produce female reproductive structures (protoperithecia) when nitrogen starved. OS-2-phosphate levels are elevated in wild-type cells exposed to NaCl or fludioxonil, but they are nearly undetectable in Δrrg-1 strains. OS-2-phosphate levels are also low in Δrrg-1, os-2, and os-4 mutants under nitrogen starvation. Analysis of the rrg-1D921N allele, mutated in the predicted phosphorylation site, provides support for phosphorylation-dependent and -independent functions for RRG-1. The data indicate that RRG-1 controls vegetative cell integrity, hyperosmotic sensitivity, fungicide resistance, and protoperithecial development through regulation of the OS-4/OS-5/OS-2 MAPK pathway