Carrageenans from Red Seaweeds As Promoters of Growth and Elicitors of Defense Response in Plants

Plants incessantly encounter abiotic and biotic stresses that limit their growth and productivity. However, conversely, plant growth can also be induced by treatments with various abiotic and biotic elicitors. Carrageenans are sulfated linear polysaccharides that represent major cellular constituents of seaweeds belonging to red algae (Rhodophyta). Recent research has unraveled the biological activity of carrageenans and of their oligomeric forms, the oligo carrageenans (OCs), as promoters of plant growth and as elicitors of defense responses against pests and diseases. In this review, we discuss the molecular mechanisms by which carrageenans and OCs mediate plant growth and plant defense responses. Carrageenans and OCs improve plant growth by regulating various metabolic processes such as photosynthesis and ancillary pathways, cell division, purine and pyrimidine synthetic pathways as well as metabolic pathways involved in nitrogen and sulfur assimilation. Carrageenans and OCs also induce plant defense responses against viroids, viruses, bacteria, fungi and insects by modulating the activity of different defense pathways, including salicylate, jasmonate and ethylene signaling pathways. Further studies will likely substantiate the beneficial effects of carrageenans and of OCs on plant growth and plant defense responses and open new avenues for their use in agriculture and horticultural industry

All-oral metronomic DEVEC schedule in elderly patients with peripheral T cell lymphoma

Purpose: Peripheral T cell lymphomas (PTCLs) have an overall poor prognosis. Indeed, registry data in elderly patients show that the median progression-free survival (mPFS) following first- and second-line therapies are only 6.7 and 3.1 months, respectively. The aim of the study is to show the activity of metronomic chemotherapy, a regular administration of low chemotherapeutic drug doses allowing a favourable toxicity profile, on elderly PTCL patients. Methods: We report a series of 17 PTCL patients, treated with the all-oral metronomic schedule DEVEC (prednisolone–etoposide–vinorelbine–cyclophosphamide) in four Italian centres. Patients 5/17 (29.4%) were treatment-naïve (naïve) and 12/17 (70.6%) were relapsed-refractory (RR), respectively. The median age was 83 years (range 71–87) and 71.5 years (range 56–85) for naïve and RR, respectively. In vitro activity of metronomic vinorelbine (VNR), etoposide (ETO) and their concomitant combination on HH, a PTCL cell line, was also assessed. Results: Histology: PTCL-not-otherwise-specified = 12; angioimmunoblastic = 2; NK/T nasal type = 1; adult-type leukaemia lymphoma = 1, transformed Mycosis Fungoides = 1. The overall response rate was 80 and 58% in naïve and RR, respectively; whereas the PFS was 20 in naïve (95% CI 0–43) and 11 months (95% CI 4.2–17.8) in RR. The occurrence of relevant adverse events was 23.5%, which was managed with ETO dose reduction. In vitro experiments showed that both metronomic VNR and ETO caused a significant inhibitory activity on HH cells and a strong synergism when administered concomitantly. Conclusion: All-oral DEVEC showed an encouraging activity and acceptable toxicity. This schedule deserves further studies in elderly PTCL also for assessing combinations with targeted drugs

Synaptogyrin-2 influences replication of Porcine circovirus 2

Porcine circovirus 2 (PCV2) is a circular single-stranded DNA virus responsible for a group of diseases collectively known as PCV2 Associated Diseases (PCVAD). Variation in the incidence and severity of PCVAD exists between pigs suggesting a host genetic component involved in pathogenesis. A large-scale genome-wide association study of experimentally infected pigs (n = 974), provided evidence of a host genetic role in PCV2 viremia, immune response and growth during challenge. Host genotype explained 64% of the phenotypic variation for overall viral load, with two major Quantitative Trait Loci (QTL) identified on chromosome 7 (SSC7) near the swine leukocyte antigen complex class II locus and on the proximal end of chromosome 12 (SSC12). The SNP having the strongest association, ALGA0110477 (SSC12), explained 9.3% of the genetic and 6.2% of the phenotypic variance for viral load. Dissection of the SSC12 QTL based on gene annotation, genomic and RNA-sequencing, suggested that a missense mutation in the SYNGR2 (SYNGR2 p.Arg63Cys) gene is potentially responsible for the variation in viremia. This polymorphism, located within a protein domain conserved across mammals, results in an amino acid variant SYNGR2 p.63Cys only observed in swine. PCV2 titer in PK15 cells decreased when the expression of SYNGR2 was silenced by specific-siRNA, indicating a role of SYNGR2 in viral replication. Additionally, a PK15 edited clone generated by CRISPR-Cas9, carrying a partial deletion of the second exon that harbors a key domain and the SYNGR2 p.Arg63Cys, was associated with a lower viral titer compared to wildtype PK15 cells (\u3e24 hpi) and supernatant (\u3e48hpi)(P \u3c 0.05). Identification of a non-conservative substitution in this key domain of SYNGR2 suggests that the SYNGR2 p.Arg63Cys variant may underlie the observed genetic effect on viral load

Synaptogyrin-2 influences replication of Porcine circovirus 2

Porcine circovirus 2 (PCV2) is a circular single-stranded DNA virus responsible for a group of diseases collectively known as PCV2 Associated Diseases (PCVAD). Variation in the incidence and severity of PCVAD exists between pigs suggesting a host genetic component involved in pathogenesis. A large-scale genome-wide association study of experimentally infected pigs (n = 974), provided evidence of a host genetic role in PCV2 viremia, immune response and growth during challenge. Host genotype explained 64% of the phenotypic variation for overall viral load, with two major Quantitative Trait Loci (QTL) identified on chromosome 7 (SSC7) near the swine leukocyte antigen complex class II locus and on the proximal end of chromosome 12 (SSC12). The SNP having the strongest association, ALGA0110477 (SSC12), explained 9.3% of the genetic and 6.2% of the phenotypic variance for viral load. Dissection of the SSC12 QTL based on gene annotation, genomic and RNA-sequencing, suggested that a missense mutation in the SYNGR2 (SYNGR2 p.Arg63Cys) gene is potentially responsible for the variation in viremia. This polymorphism, located within a protein domain conserved across mammals, results in an amino acid variant SYNGR2 p.63Cys only observed in swine. PCV2 titer in PK15 cells decreased when the expression of SYNGR2 was silenced by specific-siRNA, indicating a role of SYNGR2 in viral replication. Additionally, a PK15 edited clone generated by CRISPR-Cas9, carrying a partial deletion of the second exon that harbors a key domain and the SYNGR2 p.Arg63Cys, was associated with a lower viral titer compared to wildtype PK15 cells (\u3e24 hpi) and supernatant (\u3e48hpi)(P \u3c 0.05). Identification of a non-conservative substitution in this key domain of SYNGR2 suggests that the SYNGR2 p.Arg63Cys variant may underlie the observed genetic effect on viral load

The implications of baseline bone‐health assessment at initiation of androgen‐deprivation therapy for prostate cancer

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142891/1/bju14075.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/142891/2/bju14075_am.pd

Anti-glomerular basement membrane disease superimposed on membranous nephropathy: a case report and review of the literature

<p>Abstract</p> <p>Introduction</p> <p>Anti-glomerular basement membrane disease is a rare autoimmune disorder characterized by pulmonary hemorrhage, crescentic glomerulonephritis and the presence of circulating anti-glomerular basement membrane antibodies. The simultaneous occurrence of both anti-glomerular basement membrane disease and membranous nephropathy is rare.</p> <p>Case presentation</p> <p>A 59-year-old Hispanic man presented with acute onset of nausea and vomiting and was found to have renal insufficiency. Work-up included a kidney biopsy, which revealed anti-glomerular basement membrane disease with underlying membranous nephropathy. He was treated with emergent hemodialysis, intravenous corticosteroids, plasmapheresis, and cyclophosphamide without improvement in his renal function.</p> <p>Conclusion</p> <p>Simultaneous anti-glomerular basement membrane disease and membranous nephropathy is very rare. There have been 16 previous case reports in the English language literature that have been associated with a high mortality and morbidity, and a very high rate of renal failure resulting in hemodialysis. Co-existence of membranous nephropathy and anti-glomerular basement membrane disease may be immune-mediated, although the exact mechanism is not clear.</p

Development and Experimental Validation of a 20K Atlantic Cod (Gadus morhua) Oligonucleotide Microarray Based on a Collection of over 150,000 ESTs

The collapse of Atlantic cod (Gadus morhua) wild populations strongly impacted the Atlantic cod fishery and led to the development of cod aquaculture. In order to improve aquaculture and broodstock quality, we need to gain knowledge of genes and pathways involved in Atlantic cod responses to pathogens and other stressors. The Atlantic Cod Genomics and Broodstock Development Project has generated over 150,000 expressed sequence tags from 42 cDNA libraries representing various tissues, developmental stages, and stimuli. We used this resource to develop an Atlantic cod oligonucleotide microarray containing 20,000 unique probes. Selection of sequences from the full range of cDNA libraries enables application of the microarray for a broad spectrum of Atlantic cod functional genomics studies. We included sequences that were highly abundant in suppression subtractive hybridization (SSH) libraries, which were enriched for transcripts responsive to pathogens or other stressors. These sequences represent genes that potentially play an important role in stress and/or immune responses, making the microarray particularly useful for studies of Atlantic cod gene expression responses to immune stimuli and other stressors. To demonstrate its value, we used the microarray to analyze the Atlantic cod spleen response to stimulation with formalin-killed, atypical Aeromonas salmonicida, resulting in a gene expression profile that indicates a strong innate immune response. These results were further validated by quantitative PCR analysis and comparison to results from previous analysis of an SSH library. This study shows that the Atlantic cod 20K oligonucleotide microarray is a valuable new tool for Atlantic cod functional genomics research

Glycoprotein L sets the neutralization profile of murid herpesvirus 4

Antibodies readily neutralize acute, epidemic viruses, but are less effective against more indolent pathogens such as herpesviruses. Murid herpesvirus 4 (MuHV-4) provides an accessible model for tracking the fate of antibody-exposed gammaherpesvirus virions. Glycoprotein L (gL) plays a central role in MuHV-4 entry: it allows gH to bind heparan sulfate and regulates fusion-associated conformation changes in gH and gB. However, gL is non-essential: heparan sulfate binding can also occur via gp70, and the gB–gH complex alone seems to be sufficient for membrane fusion. Here, we investigated how gL affects the susceptibility of MuHV-4 to neutralization. Immune sera neutralized gL− virions more readily than gL+ virions, chiefly because heparan sulfate binding now depended on gp70 and was therefore easier to block. However, there were also post-binding effects. First, the downstream, gL-independent conformation of gH became a neutralization target; gL normally prevents this by holding gH in an antigenically distinct heterodimer until after endocytosis. Second, gL− virions were more vulnerable to gB-directed neutralization. This covered multiple epitopes and thus seemed to reflect a general opening up of the gH–gB entry complex, which gL again normally restricts to late endosomes. gL therefore limits MuHV-4 neutralization by providing redundancy in cell binding and by keeping key elements of the virion fusion machinery hidden until after endocytosis