Further Investigation on Limb Dieback of Fig (Ficus carica) Caused by Neoscytalidium dimidiatum in California.

Fig limb dieback is a cosmopolitan disease caused by Neoscytalidium dimidiatum (Botryosphaeriaceae), characterized by branch and shoot cankers, discoloration of woody tissues, and dieback. The present study investigated the etiology of the disease in California that seems to have become prevalent among fig orchards in the last several years. During orchard surveys in Fresno, Kern, and Madera Counties over 3 years, we isolated consistently and evaluated the pathogenicity of N. dimidiatum under laboratory and field conditions. The effect of summer and winter pruning on the disease severity and the effects of different environmental and mechanical stresses, such as sunburn and wounding by mallets, were assayed. In addition, the susceptibility of six different cultivars and the effects of eradicating cankered shoots from the fig trees as a method to combat the spread of the disease were studied. Pathogenicity tests demonstrated that N. dimidiatum induces cankers on fig, mainly on wounded shoots. Results from the remaining experiments revealed that summer infection leads to more severe canker lesions than those induced by winter infection and that stressed shoots are more susceptible to infection than nonstressed shoots. 'Brown Turkey', 'Conadria', and 'Calimyrna' cultivars (all nonpersistent figs, i.e., needing pollination for fruit development) were less susceptible than the more susceptible 'Kadota', 'Sierra', and 'Black Mission' (all persistent figs, i.e., not needing pollination for fruit development). Canker removal from the orchard seems to be a good agronomic practice to avoid the spread of disease

Update of pistachio leaf spot caused by Septoria pistaciarum in light of new taxonomic advances in Italy.

Abstract Septoria leaf spot is one the most widespread disease affecting pistachio (Pistacia vera) in countries of the Mediterranean region. Traditionally, three species have been associated with pistachio, including Septoria pistaciae, Septoria pistaciarum and S. pistacina. However, recent taxonomic studies have reordered and clarified the status of Septoria and septoria-like pathogens affecting pistachio. In our study, field surveys conducted in the traditional Sicilian pistachio production area of Bronte revealed the presence of trees showing characteristic septoria-like leaf spot. Collected isolates were morphologically and molecularly characterized. Morphological characterization was based on conidia measurements and evaluation of mycelial growth on different artificial media. Tested media included CMA, MEA, OA, PDA, and SNA. Phylogenetic analysis was conducted on a multi-locus approach (ITS + tef1 + tub2) based on Maximum Parsimony and Maximum Likelihood. Results showed that our isolates clustered with S. pistaciarum. Pathogenicity test was conducted in the field using conidia suspensions in order to fulfill Koch's postulates. Presence of characteristic rounded spots and pycnidia was evaluated on the inoculated leaves 9 and 23 days after inoculation. This study represents the first update on S. pistaciarum in Italy since its first identification in 1934

Deficiency of Huntingtin Has Pleiotropic Effects in the Social Amoeba Dictyostelium discoideum

Huntingtin is a large HEAT repeat protein first identified in humans, where a polyglutamine tract expansion near the amino terminus causes a gain-of-function mechanism that leads to selective neuronal loss in Huntington's disease (HD). Genetic evidence in humans and knock-in mouse models suggests that this gain-of-function involves an increase or deregulation of some aspect of huntingtin's normal function(s), which remains poorly understood. As huntingtin shows evolutionary conservation, a powerful approach to discovering its normal biochemical role(s) is to study the effects caused by its deficiency in a model organism with a short life-cycle that comprises both cellular and multicellular developmental stages. To facilitate studies aimed at detailed knowledge of huntingtin's normal function(s), we generated a null mutant of hd, the HD ortholog in Dictyostelium discoideum. Dictyostelium cells lacking endogenous huntingtin were viable but during development did not exhibit the typical polarized morphology of Dictyostelium cells, streamed poorly to form aggregates by accretion rather than chemotaxis, showed disorganized F-actin staining, exhibited extreme sensitivity to hypoosmotic stress, and failed to form EDTA-resistant cell–cell contacts. Surprisingly, chemotactic streaming could be rescued in the presence of the bivalent cations Ca2+ or Mg2+ but not pulses of cAMP. Although hd− cells completed development, it was delayed and proceeded asynchronously, producing small fruiting bodies with round, defective spores that germinated spontaneously within a glassy sorus. When developed as chimeras with wild-type cells, hd− cells failed to populate the pre-spore region of the slug. In Dictyostelium, huntingtin deficiency is compatible with survival of the organism but renders cells sensitive to low osmolarity, which produces pleiotropic cell autonomous defects that affect cAMP signaling and as a consequence development. Thus, Dictyostelium provides a novel haploid organism model for genetic, cell biological, and biochemical studies to delineate the functions of the HD protein

Responsiveness of the Eating Disorders Quality of Life Scale (EDQLS) in a longitudinal multi-site sample

<p>Abstract</p> <p>Background</p> <p>In eating disorders (EDs), treatment outcome measurement has traditionally focused on symptom reduction rather than functioning or quality of life (QoL). The Eating Disorders Quality of Life Scale (EDQLS) was recently developed to allow for measurement of broader outcomes. We examined responsiveness of the EDQLS in a longitudinal multi-site study.</p> <p>Methods</p> <p>The EDQLS and comparator generic QoL scales were collected in person at baseline, and 3 and 6 months from 130 participants (mean age 25.6 years; range 14-60) in 12 treatment programs in four Canadian provinces. Total score differences across the time points and responsiveness were examined using both anchor- and distribution-based methods.</p> <p>Results</p> <p>98 (75%) and 85 (65%) responses were received at 3 and 6 months respectively. No statistically significant differences were found between the baseline sample and those lost to follow-up on any measured characteristic. Mean EDQLS total scores increased from 110 (SD = 24) to 124.5 (SD = 29) at 3 months and 129 (SD = 28) at 6 months, and the difference by time was tested using a general linear model (GLM) to account for repeated measurement (p < .001). Responsiveness was good overall (Cohen's d = .61 and .80), and confirmed using anchor methods across 5 levels of self-reported improvement in health status (p < .001). Effect sizes across time were moderate or large for for all age groups. Internal consistency (Chronbach's alpha=.96) held across measurement points and patterns of responsiveness held across subscales. EDQLS responsiveness exceeded that of the Quality of Life Inventory, the Short Form-12 (mental and physical subscales) and was similar to the 16-dimension quality of life scale.</p> <p>Conclusions</p> <p>The EDQLS is responsive to change in geographically diverse and clinically heterogeneous programs over a relatively short time period in adolescents and adults. It shows promise as an outcome measure for both research and clinical practice.</p

Integrated genomics and proteomics define huntingtin CAG length-dependent networks in mice.

To gain insight into how mutant huntingtin (mHtt) CAG repeat length modifies Huntington's disease (HD) pathogenesis, we profiled mRNA in over 600 brain and peripheral tissue samples from HD knock-in mice with increasing CAG repeat lengths. We found repeat length-dependent transcriptional signatures to be prominent in the striatum, less so in cortex, and minimal in the liver. Coexpression network analyses revealed 13 striatal and 5 cortical modules that correlated highly with CAG length and age, and that were preserved in HD models and sometimes in patients. Top striatal modules implicated mHtt CAG length and age in graded impairment in the expression of identity genes for striatal medium spiny neurons and in dysregulation of cyclic AMP signaling, cell death and protocadherin genes. We used proteomics to confirm 790 genes and 5 striatal modules with CAG length-dependent dysregulation at the protein level, and validated 22 striatal module genes as modifiers of mHtt toxicities in vivo

A modifier of Huntington's disease onset at the MLH1 locus

Huntington’s disease (HD) is a dominantly inherited neurodegenerative disease caused by an expanded CAG repeat in HTT. Many clinical characteristics of HD such as age at motor onset are determined largely by the size of HTT CAG repeat. However, emerging evidence strongly supports a role for other genetic factors in modifying the disease pathogenesis driven by mutant huntingtin. A recent genome-wide association analysis to discover genetic modifiers of HD onset age provided initial evidence for modifier loci on chromosomes 8 and 15 and suggestive evidence for a locus on chromosome 3. Here, genotyping of candidate single nucleotide polymorphisms in a cohort of 3,314 additional HD subjects yields independent confirmation of the former two loci and moves the third to genome-wide significance at MLH1, a locus whose mouse orthologue modifies CAG length-dependent phenotypes in a Htt-knock-in mouse model of HD. Both quantitative and dichotomous association analyses implicate a functional variant on 32% of chromosomes with the beneficial modifier effect that delays HD motor onset by 0.7 years/allele. Genomic DNA capture and sequencing of a modifier haplotype localize the functional variation to a 78 kb region spanning the 3’end of MLH1 and the 5’end of the neighboring LRRFIP2, and marked by an isoleucinevaline missense variant in MLH1. Analysis of expression Quantitative Trait Loci (eQTLs) provides modest support for altered regulation of MLH1 and LRRFIP2, raising the possibility that the modifier affects regulation of both genes. Finally, polygenic modification score and heritability analyses suggest the existence of additional genetic modifiers, supporting expanded, comprehensive genetic analysis of larger HD datasets

Predictors of survival and toxicity in patients on adjuvant therapy with 5-fluorouracil for colorectal cancer

The present study aimed at investigating whether the simultaneous evaluation of pharmacokinetic, pharmacogenetic and demographic factors could improve prediction on toxicity and survival in colorectal cancer patients treated with adjuvant 5-fluorouracil (5FU)/leucovorin therapy. One hundred and thirty consecutive, B2 and C Duke's stage colorectal cancer patients were prospectively enrolled. 5FU pharmacokinetics was evaluated at the first cycle. Thymidylate synthase (TYMS) 5′UTR and 3′UTR polymorphisms and methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms were assessed in peripheral leukocytes. Univariate and multivariate analyses were applied to evaluate which variables could predict chemotherapy-induced toxicity, disease-free survival (DFS) and overall survival (OS). Multivariate analysis showed that: (a) low 5FU clearance was an independent predictive factor for severe toxicity (OR=7.32; P<0.0001); (b) high-5FU clearance predicted poorer DFS (HR=1.96; P=0.041) and OS (HR=3.37; P=0.011); (c) advanced age was associated with shorter DFS (HR=3.34; P=0.0008) and OS (HR=2.66; P=0.024); (d) the C/C genotype of the MTHFR C677T polymorphism was protective against grade 3–4 toxicity (P=0.040); (e) none of the TYMS polymorphisms could explain 5FU toxicity or clinical outcome

Huntingtin facilitates polycomb repressive complex 2

Huntington's disease (HD) is caused by expansion of the polymorphic polyglutamine segment in the huntingtin protein. Full-length huntingtin is thought to be a predominant HEAT repeat α-solenoid, implying a role as a facilitator of macromolecular complexes. Here we have investigated huntingtin's domain structure and potential intersection with epigenetic silencer polycomb repressive complex 2 (PRC2), suggested by shared embryonic deficiency phenotypes. Analysis of a set of full-length recombinant huntingtins, with different polyglutamine regions, demonstrated dramatic conformational flexibility, with an accessible hinge separating two large α-helical domains. Moreover, embryos lacking huntingtin exhibited impaired PRC2 regulation of Hox gene expression, trophoblast giant cell differentiation, paternal X chromosome inactivation and histone H3K27 tri-methylation, while full-length endogenous nuclear huntingtin in wild-type embryoid bodies (EBs) was associated with PRC2 subunits and was detected with trimethylated histone H3K27 at Hoxb9. Supporting a direct stimulatory role, full-length recombinant huntingtin significantly increased the histone H3K27 tri-methylase activity of reconstituted PRC2 in vitro, and structure–function analysis demonstrated that the polyglutamine region augmented full-length huntingtin PRC2 stimulation, both in HdhQ111 EBs and in vitro, with reconstituted PRC2. Knowledge of full-length huntingtin's α-helical organization and role as a facilitator of the multi-subunit PRC2 complex provides a novel starting point for studying PRC2 regulation, implicates this chromatin repressive complex in a neurodegenerative disorder and sets the stage for further study of huntingtin's molecular function and the impact of its modulatory polyglutamine region