Edades de corte e incidencia de enfermedades de dos sorgos forrajeros y sus rendimientos en materia seca y proteina bruta

Two forage sorghum hybrids ( ATx 623 X GL and FS25A) were grown from April 1985 to February 1987 at the Agricultural Experiment Station of the University of Puerto Rico at Lajas, Puerto Rico to determine the influence of maturity stage increases of 10 days (from the 45th to the 85th day) and how the presence and severity of foliar diseases affect the dry forage and crude protein yields. Dry matter content was higher for FS25A (16.1%) than for ATx 623 X GL (14.9%) whereas total yield for dry matter (DMY) was higher for ATx 623 X GL (3.84 t/ha) than for FS25A (3.51 t/ha). Both content and yield of dry matter increased with maturity stage in both genotypes. The sorghum hybrids did not differ significantly in crude protein content (CPC), but crude protein yield (CPY) was higher for ATx 623 X GL (421.6 kg/ha) than for FS25A (358.9 kg/ha). CPC declined with increased plant maturity. Foliar diseases appeared to limit DFY and CPY in both sorghum hybrids. Downy mildew, leaf blight, rust, grey leafspot, and zonate leafspot appeared seasonally. Leaf blight and downy mildew were the most prevalent from January to May, grey leafspot from May to September, and zonate leafspot from September to November. Rust was severe during all seasons.Se llevo a cabo un estudio con dos híbridos de sorgo forrajero (ATx 623 X GL y FS25A) de abril de 1985 a febrero de 1987 en la Subestación Experimental Agrícola de Lajas para medir la influencia sobre la producción de etapas de corte cada 10 días (desde el 45to al 85 to día) y como la incidencia de enfermedades afecta el rendimiento de forraje seco y proteína bruta. El contenido medio global de materia seca fue mayor en FS25A (16.1%) que en ATx 623 X GL (14.9). Lo contrario ocurrió con el rendimiento de forraje seco, ya que se obtuvo un rendimiento mayor con ATx 623 X GL (3.84 t./ha.) que con FS25A (3.51 t./ha.). El rendimiento de forraje seco y el contenido de materia seca aumentaron a medida que el forraje maduro. Las diferencias entre ambos híbridos en contenido medio de proteína bruta no fueron significativas. No obstante, la media ponderada para el rendimiento de proteína bruta total fue mayor para ATx 623 X GL (421.6 kg./ha.). El contenido y el rendimiento total de proteína bruta disminuyeron significativamente a medida que la etapa de corte aumentó de 45 a 85 días. Los rendimientos de forraje seco y de proteína bruta total también disminuyeron en ambos híbridos debido a la incidencia de enfermedades. Estas enfermedades fueron anublo lanoso ("downy mildew"), tizón ("leaf blight"), roya ("rust"), y mancha foliar ("zonate leafspot"). La época del año fue un factor determinante para la presencia de estas enfermedades. De enero a mayo la enfermedad más prevaleciente fue el anublo lanoso. Sin embargo, de mayo a julio predominó la mancha cercospórica y de septiembre a noviembre la mancha foliar

CXCR7 antagonism prevents axonal injury during experimental autoimmune encephalomyelitis as revealed by in vivo axial diffusivity

<p>Abstract</p> <p>Background</p> <p>Multiple Sclerosis (MS) is characterized by the pathological trafficking of leukocytes into the central nervous system (CNS). Using the murine MS model, experimental autoimmune encephalomyelitis (EAE), we previously demonstrated that antagonism of the chemokine receptor CXCR7 blocks endothelial cell sequestration of CXCL12, thereby enhancing the abluminal localization of CXCR4-expressing leukocytes. CXCR7 antagonism led to decreased parenchymal entry of leukocytes and amelioration of ongoing disease during EAE. Of note, animals that received high doses of CXCR7 antagonist recovered to baseline function, as assessed by standard clinical scoring. Because functional recovery reflects axonal integrity, we utilized diffusion tensor imaging (DTI) to evaluate axonal injury in CXCR7 antagonist- versus vehicle-treated mice after recovery from EAE.</p> <p>Methods</p> <p>C57BL6/J mice underwent adoptive transfer of MOG-reactive Th1 cells and were treated daily with either CXCR7 antagonist or vehicle for 28 days; and then evaluated by DTI to assess for axonal injury. After imaging, spinal cords underwent histological analysis of myelin and oligodendrocytes via staining with luxol fast blue (LFB), and immunofluorescence for myelin basic protein (MBP) and glutathione S-transferase-π (GST-π). Detection of non-phosphorylated neurofilament H (NH-F) was also performed to detect injured axons. Statistical analysis for EAE scores, DTI parameters and non-phosphorylated NH-F immunofluorescence were done by ANOVA followed by Bonferroni post-hoc test. For all statistical analysis a p < 0.05 was considered significant.</p> <p>Results</p> <p><it>In vivo </it>DTI maps of spinal cord ventrolateral white matter (VLWM) axial diffusivities of naïve and CXCR7 antagonist-treated mice were indistinguishable, while vehicle-treated animals exhibited decreased axial diffusivities. Quantitative differences in injured axons, as assessed via detection of non-phosphorylated NH-F, were consistent with axial diffusivity measurements. Overall, qualitative myelin content and presence of oligodendrocytes were similar in all treatment groups, as expected by their radial diffusivity values. <b/>Quantitative assessment of persistent inflammatory infiltrates revealed significant decreases within the parenchyma of CXCR7 antagonist-treated mice versus controls.</p> <p>Conclusions</p> <p>These data suggest that CXCR7 antagonism not only prevents persistent inflammation but also preserves axonal integrity. Thus, targeting CXCR7 modifies both disease severity and recovery during EAE, suggesting a role for this molecule in both phases of disease.</p

Partial change in EphA4 knockout mouse phenotype: Loss of diminished GFAP upregulation following spinal cord injury

In a previous study we found that the EphA4 receptor inhibits regeneration following spinal cord injury by blocking regrowth of axons and regulation of astrocyte reactivity. In our original studies using EphA4 null mice [Goldshmit et al., J. Neurosci., 2004] we found attenuated astrocyte reactivity following spinal cord injury. Several other studies have now supported the role of EphA4 in regulating neural regeneration but a recent study [Herrmann et al., Exp. Neurol., 2010] did not find an effect of EphA4 on astrocyte reactivity. Re-examination of astrocytic gliosis following injury in our current cohort of EphA4 null mice revealed that they no longer showed attenuation of astrocyte reactivity, however other EphA4 null mouse phenotypes, such as decreased size of the dorsal funiculus were unaltered. We hypothesised that long-term breeding on the C57Bl/6 background may influence the EphA4-mediated astrocyte phenotype and compared astrocytic gliosis at 4 days following spinal cord injury in wildtype and EphA4 null mice on the C57Bl/6 background and backcrossed C57Bl/6×129Sv(F2) mice, as well as wildtype 129Sv mice. 129Sv mice had increased GFAP expression and increased numbers of reactive GFAP astrocytes compared to C57Bl/6 mice. There was no significant effect of EphA4 deletion on GFAP expression in C57Bl/6 mice or the F2 crosses other than a moderately decreased number of EphA4 null astrocytes in C57Bl/6 mice using one of two antibodies. Therefore, there has been an apparent change in EphA4-mediated astroglial phenotype associated with long term breeding of the EphA4 colony but it does not appear to be influenced by background mouse strain

Targeting CXCR7/ACKR3 as a therapeutic strategy to promote remyelination in the adult central nervous system

Current treatment modalities for the neurodegenerative disease multiple sclerosis (MS) use disease-modifying immunosuppressive compounds but do not promote repair. Although several potential targets that may induce myelin production have been identified, there has yet to be an approved therapy that promotes remyelination in the damaged central nervous system (CNS). Remyelination of damaged axons requires the generation of new oligodendrocytes from oligodendrocyte progenitor cells (OPCs). Although OPCs are detected in MS lesions, repair of myelin is limited, contributing to progressive clinical deterioration. In the CNS, the chemokine CXCL12 promotes remyelination via CXCR4 activation on OPCs, resulting in their differentiation into myelinating oligodendrocytes. Although the CXCL12 scavenging receptor CXCR7/ACKR3 (CXCR7) is also expressed by OPCs, its role in myelin repair in the adult CNS is unknown. We show that during cuprizone-induced demyelination, in vivo CXCR7 antagonism augmented OPC proliferation, leading to increased numbers of mature oligodendrocytes within demyelinated lesions. CXCR7-mediated effects on remyelination required CXCR4 activation, as assessed via both phospho-S339-CXCR4–specific antibodies and administration of CXCR4 antagonists. These findings identify a role for CXCR7 in OPC maturation during remyelination and are the first to use a small molecule to therapeutically enhance myelin repair in the demyelinated adult CNS

Cutaneous nociception evoked by 15-delta PGJ2 via activation of ion channel TRPA1

<p>Abstract</p> <p>Background</p> <p>A number of prostaglandins (PGs) sensitize dorsal root ganglion (DRG) neurons and contribute to inflammatory hyperalgesia by signaling through specific G protein-coupled receptors (GPCRs). One mechanism whereby PGs sensitize these neurons is through modulation of "thermoTRPs," a subset of ion channels activated by temperature belonging to the Transient Receptor Potential ion channel superfamily. Acrid, electrophilic chemicals including cinnamaldehyde (CA) and allyl isothiocyanate (AITC), derivatives of cinnamon and mustard oil respectively, activate thermoTRP member TRPA1 via direct modification of channel cysteine residues.</p> <p>Results</p> <p>Our search for endogenous chemical activators utilizing a bioactive lipid library screen identified a cyclopentane PGD₂metabolite, 15-deoxy-Δ^12,14-prostaglandin J₂(15d-PGJ₂), as a TRPA1 agonist. Similar to CA and AITC, this electrophilic molecule is known to modify cysteines of cellular target proteins. Electophysiological recordings verified that 15d-PGJ₂specifically activates TRPA1 and not TRPV1 or TRPM8 (thermoTRPs also enriched in DRG). Accordingly, we identified a population of mouse DRG neurons responsive to 15d-PGJ₂and AITC that is absent in cultures derived from TRPA1 knockout mice. The irritant molecules that activate TRPA1 evoke nociceptive responses. However, 15d-PGJ₂has not been correlated with painful sensations; rather, it is considered to mediate anti-inflammatory processes via binding to the nuclear peroxisome proliferator-activated receptor gamma (PPARγ). Our <it>in vivo </it>studies revealed that 15d-PGJ₂induced acute nociceptive responses when administered cutaneously. Moreover, mice deficient in the TRPA1 channel failed to exhibit such behaviors.</p> <p>Conclusion</p> <p>In conclusion, we show that 15d-PGJ₂induces acute nociception when administered cutaneously and does so via a TRPA1-specific mechanism.</p

Enhanced sphingosine-1-phosphate receptor 2 expression underlies female CNS autoimmunity susceptibility

Multiple sclerosis (MS) is an inflammatory disease of the CNS that is characterized by BBB dysfunction and has a much higher incidence in females. Compared with other strains of mice, EAE in the SJL mouse strain models multiple features of MS, including an enhanced sensitivity of female mice to disease; however, the molecular mechanisms that underlie the sex- and strain-dependent differences in disease susceptibility have not been described. We identified sphingosine-1-phosphate receptor 2 (S1PR2) as a sex- and strain-specific, disease-modifying molecule that regulates BBB permeability by destabilizing adherens junctions. S1PR2 expression was increased in disease-susceptible regions of the CNS of both female SJL EAE mice and female patients with MS compared with their male counterparts. Pharmacological blockade or lack of S1PR2 signaling decreased EAE disease severity as the result of enhanced endothelial barrier function. Enhanced S1PR2 signaling in an in vitro BBB model altered adherens junction formation via activation of Rho/ROCK, CDC42, and caveolin endocytosis-dependent pathways, resulting in loss of apicobasal polarity and relocation of abluminal CXCL12 to vessel lumina. Furthermore, S1PR2-dependent BBB disruption and CXCL12 relocation were observed in vivo. These results identify a link between S1PR2 signaling and BBB polarity and implicate S1PR2 in sex-specific patterns of disease during CNS autoimmunity

Burning Cold: Involvement of TRPA1 in Noxious Cold Sensation

Soon after its discovery ten years ago, the ion channel TRPA1 was proposed as a sensor of noxious cold. Evidence for its activation by painfully cold temperatures (below ~15° C) has been mixed, however. Some groups found that cold elicits a nonselective conductance in cells expressing TRPA1; others found no activation, or argued that activation is an indirect effect of elevated $Ca^{ 2+}$ . Sensory cells from the trigeminal and dorsal root ganglia that are activated by cold were sometimes correlated with those cells expressing TRPA1; other times not. Mice lacking TRPA1 showed behavioral defi cits for some assays of painful cold sensation, but not others. New evidence tends to support direct activation of TRPA1 by cold, and the slow and relatively weak activation of TRPA1 by cold helps reconcile some confl icting studies

The glutathione biosynthetic pathway of Plasmodium is essential for mosquito transmission

1Infection of red blood cells (RBC) subjects the malaria parasite to oxidative stress. Therefore, efficient antioxidant and redox systems are required to prevent damage by reactive oxygen species. Plasmodium spp. have thioredoxin and glutathione (GSH) systems that are thought to play a major role as antioxidants during blood stage infection. In this report, we analyzed a critical component of the GSH biosynthesis pathway using reverse genetics. Plasmodium berghei parasites lacking expression of gamma-glutamylcysteine synthetase (γ-GCS), the rate limiting enzyme in de novo synthesis of GSH, were generated through targeted gene disruption thus demonstrating, quite unexpectedly, that γ-GCS is not essential for blood stage development. Despite a significant reduction in GSH levels, blood stage forms of pbggcs− parasites showed only a defect in growth as compared to wild type. In contrast, a dramatic effect on development of the parasites in the mosquito was observed. Infection of mosquitoes with pbggcs− parasites resulted in reduced numbers of stunted oocysts that did not produce sporozoites. These results have important implications for the design of drugs aiming at interfering with the GSH redox-system in blood stages and demonstrate that de novo synthesis of GSH is pivotal for development of Plasmodium in the mosquito

EphA4 Blockers Promote Axonal Regeneration and Functional Recovery Following Spinal Cord Injury in Mice

Upregulation and activation of developmental axon guidance molecules, such as semaphorins and members of the Eph receptor tyrosine kinase family and their ligands, the ephrins, play a role in the inhibition of axonal regeneration following injury to the central nervous system. Previously we have demonstrated in a knockout model that axonal regeneration following spinal cord injury is promoted in the absence of the axon guidance protein EphA4. Antagonism of EphA4 was therefore proposed as a potential therapy to promote recovery from spinal cord injury. To further assess this potential, two soluble recombinant blockers of EphA4, unclustered ephrin-A5-Fc and EphA4-Fc, were examined for their ability to promote axonal regeneration and to improve functional outcome following spinal cord hemisection in wildtype mice. A 2-week administration of either of these blockers following spinal cord injury was sufficient to promote substantial axonal regeneration and functional recovery by 5 weeks following injury. Both inhibitors produced a moderate reduction in astrocytic gliosis, indicating that much of the effect of the blockers may be due to promotion of axon growth. These studies provide definitive evidence that soluble inhibitors of EphA4 function offer considerable therapeutic potential for the treatment of spinal cord injury and may have broader potential for the treatment of other central nervous system injuries