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The association of Fusarium graminearum isolate China-9 with the dsRNA mycovirus FgV-ch9 was evaluated for hypovirulence-related traits. Single conidia-originating cultures of China-9 isolate can be associated either with high, medium or low amounts of the viral dsRNAs. At high and medium dsRNA levels, China-9 isolates exhibit reduced mycelia growth rate and conidiation capacity, abnormal colony morphology, disorganized cytoplasm, as well as reduced virulence for wheat and maize plants. At low dsRNA levels the fungus shows no symptoms, however, the RNA segments can be detected by RT-PCR. Transfection of the virulent F. graminearum PH-1 isolate with purified Virus-like Particles (VLPs) of FgV-ch9 reduced its conidiation capacity, perithecia formation, and pathogenicity for wheat and maize several folds. These results further demonstrate that FgV-ch9 is associated with hypovirulence of F. graminearum.

Ten Fusarium graminearum isolates from China were screened for dsRNA mycoviruses. Five dsRNAs (2.4 to 3.5 kbp) were purified from isolate China 9, cloned, and sequenced. BLAST analysis showed that the proteins encoded by dsRNA1 possess motifs that are conserved in RNA-dependent RNA polymerases, dsRNA2 resembles the hypothetical protein encoded by dsRNA3 of Magnaporthe oryzae chrysovirus 1, dsRNA4 shares no significant similarity to any published protein, and dsRNA5 has a C2H2 zinc finger domain. Tandem mass spectrophotometry, surface protein labeling of virus-like particles, SDS-PAGE, and protein BLAST results supports the notion that three of the virus segments code for structural proteins, of which dsRNA3 possibly codes for the capsid protein. Relative quantitative RT-PCR studies of the 5 dsRNAs suggested that the segments are encapsidated separately in unequal amounts. Genomic structure and phylogenic studies support the possibility that this virus may be a candidate for the type species of a novel genus in the family Chrysoviridae.

TMVOhioV was first described 1969 by [ 1 ] because it did break resistance of tomato breeding lines containing Tm-1- and Tm-2 resistance genes. It was obtained 1987 from Wetter (Saarbrücken, Germany) and transferred into the DSMZ-Plant Virus Collection (Braunschweig, Germany). A partial sequence of TMVOhioV, the CP gene, has been reported [ 11 ] and its comparison with a TMV type isolates (TMVtype), e.g. EMBL: V01409, revealed 50 point mutations in a total of 477 nucleotides (nts) leading to the replacement of only 7 amino acids (aa). In order to investigate the mutations in the non-translated regions and the number of silent mutation in the three other open reading frames (ORF), we sequenced the complete genome of isolate TMVOhioV and compared it to those of other Tobamoviruses.

We examined the resistance phenotype of a large number of transgenic tobacco plants originating from 12 commercial (Nicotiana tabacum) cultivars expressing the sense form of the nucleoprotein (N) gene of L3, a Bulgarian isolate of tomato spotted wilt virus (TSWV). The analysis revealed that transgenic plants are completely protected against the homologous L3 isolate of TSWV irrespective of whether or not they contain detectable levels of translational product. The effectiveness of protection against the virus was investigated upon mechanical inoculation under greenhouse conditions and in field trials. Non-segregating resistant lines were selected and the inheritance of the resistance to TSWV was analysed in successive generations (R3–R6). Extensive tests under controlled conditions and two-year field trials proved that the resistance to TSWV is stable in different environments and is a stably inherited trait.

The Notch signaling pathway plays an essential role in a wide variety of biological processes including cell fate determination of vascular endothelial cells and the regulation of arterial differentiation and angiogenesis. The Notch pathway is also an essential regulator of tumor growth and survival by functioning as either an oncogene or a tumor suppressor in a context-dependent manner. Crosstalk between the Notch and other signaling pathways is also pivotal in tumor progression by promoting cancer cell growth, migration, invasion, metastasis, tumor angiogenesis, and the expansion of cancer stem cells (CSCs). In this review, we provide an overview and update of Notch signaling in endothelial cell fate determination and functioning, angiogenesis, and tumor progression, particularly in the development of CSCs and therapeutic resistance. We further summarize recent studies on how endothelial signaling crosstalk with the Notch pathway contributes to tumor angiogenesis and the development of CSCs, thereby providing insights into vascular biology within the tumor microenvironment and tumor progression.

Progressive supranuclear palsy (PSP), previously believed to be a common cause of atypical parkinsonism, is now recognised as a range of motor and behavioural syndromes that are associated with a characteristic 4-repeat tau neuropathology. New research criteria that recognise early presentations of PSP and operationalise diagnosis of the full spectrum of clinical phenotypes have been reported. The Movement Disorders Society PSP diagnostic criteria include syndromes with few or mild symptoms that are suggestive of underlying PSP pathology and could provide an opportunity for earlier therapeutic interventions in the future. These criteria also include definitions for variant PSP syndromes with different patterns of movement, language, or behavioural features than have been conclusively associated with PSP pathology. Data from new diagnostic biomarkers can be combined with the clinical features of disease to increase the specificity of the new criteria for underlying PSP pathology. Because PSP is associated with tau protein abnormalities, there is growing interest in clinical trials of new tau-directed therapies. These therapies are hypothesised to have disease-modifying effects by reducing the concentration of toxic forms of tau in the brain or by compensating for loss of tau function. Since tau pathology is also central to Alzheimer's disease and chronic traumatic encephalopathy, a successful tau therapeutic for PSP might inform treatment of other neurodegenerative diseases.

Background Excessive fatigue and insomnia are common among shift workers and can lead to negative effects such as reduced work performance, processing errors, accidents at work, absenteeism, reduced quality of life, and symptoms of depression. Moreover, work in rotating shifts can be a risk factor for different somatic and psychiatric diseases and may contribute to poor health, especially in elder adults and women. This review aims to show non-pharmacological preventive measures against fatigue and insomnia in shift workers. Method Computerized literature searches in MedLine and in the Cochrane Library were performed with the following key words: shift work disorder, fatigue, insomnia, shift work, measures, treatment, therapy, strategies and coping. The search was limited to non-pharmacological studies that were conducted on human subjects and published as English-language articles in peer-reviewed journals since 1970. Additional studies were identified through the reference sections of relevant articles. Eighteen articles on fatigue in shift workers, including six original research articles with a total sample size of 3504 probands consisting of industrial workers, office employees, aircraft maintenance engineers, and non-shift workers working in simulated shifts, were analyzed, as well as seven articles on insomnia, including an original research article with a sample size of 26 media workers. Also, 4 reviews on shift work disorder were analyzed. Main The occurrence of fatigue and insomnia in shift workers associated with a working period is described as shift work disorder. Estimations on the prevalence of shift work disorder in shift workers vary between 5 % and about 20 %; about one in three shift workers is affected by insomnia and up to 90 % of shift workers report regular fatigue and sleepiness at the workplace. We concluded that there is a necessity for treatments to improve the sleep quality of the shift working population. The most common non-pharmacological recommendations to improve sleep quality and to reduce insomnia and fatigue were scheduling, bright light exposure, napping, psychoeducation for sleep hygiene, and cognitive-behavioral measures. Conclusion Some important preventive coping strategies for fatigue associated with shift work such as napping and exposure to bright light have already been investigated and are generally approved. A few studies also provide good evidence for the efficacy of cognitive-behavioral techniques in the treatment of chronic primary and comorbid insomnia. These coping strategies summarized in this paper should be considered in the workplace health promotion programs of each work environment to improve working conditions for shift workers and to save money.

Summary The workshop entitled 'Interventions to Slow Aging in Humans: Are We Ready?' was held in Erice, Italy, on October 8-13, 2013, to bring together leading experts in the biology and genetics of aging and obtain a consensus related to the discovery and development of safe interventions to slow aging and increase healthy lifespan in humans. There was consensus that there is sufficient evidence that aging interventions will delay and prevent disease onset for many chronic conditions of adult and old age. Essential pathways have been identified, and behavioral, dietary, and pharmacologic approaches have emerged. Although many gene targets and drugs were discussed and there was not complete consensus about all interventions, the participants selected a subset of the most promising strategies that could be tested in humans for their effects on healthspan. These were: (i) dietary interventions mimicking chronic dietary restriction (periodic fasting mimicking diets, protein restriction, etc.); (ii) drugs that inhibit the growth hormone/IGF-I axis; (iii) drugs that inhibit the mTOR-S6K pathway; or (iv) drugs that activate AMPK or specific sirtuins. These choices were based in part on consistent evidence for the pro-longevity effects and ability of these interventions to prevent or delay multiple age-related diseases and improve healthspan in simple model organisms and rodents and their potential to be safe and effective in extending human healthspan. The authors of this manuscript were speakers and discussants invited to the workshop. The following summary highlights the major points addressed and the conclusions of the meeting.

In preclinical studies, davunetide promoted microtubule stability and reduced tau phosphorylation. Because progressive supranuclear palsy (PSP) is linked to tau pathology, davunetide could be a treatment for PSP. We assessed the safety and efficacy of davunetide in patients with PSP. In a double-blind, parallel group, phase 2/3 trial, participants were randomly assigned with permuted blocks in a 1:1 ratio to davunetide (30 mg twice daily, intranasally) or placebo for 52 weeks at 48 centres in Australia, Canada, France, Germany, the UK, and the USA. Participants met the modified Neuroprotection and Natural History in Parkinson Plus Syndrome study criteria for PSP. Primary endpoints were the change from baseline in PSP Rating Scale (PSPRS) and Schwab and England Activities of Daily Living (SEADL) scale at up to 52 weeks. All participants and study personnel were masked to treatment assignment. Analysis was by intention to treat. The trial is registered with Clinicaltrials.gov, number NCT01110720. 313 participants were randomly assigned to davunetide (n=157) or to placebo (n=156), and 241 (77%) completed the study (118 and 156 in the davunetide and placebo groups, respectively). There were no differences in the davunetide and placebo groups in the baseline PSPRS and SEADL. The davunetide and placebo groups did not differ in the change from baseline in PSPRS (median 11·8 [95% CI 10·5 to 13·0] vs 11·8 [10·5 to 13·0], respectively, p=0·41) or SEADL (−0·20 [−0·20 to −0·17] vs −0·20 [−0·22 to −0·17], respectively, p=0·92). 54 serious adverse events were reported in each of the treatment groups, including 11 deaths in the davunetide group and ten in the placebo group. The frequency of nasal adverse events was greater in the davunetide group than in the placebo group (epistaxis 18 [12%] of 156 vs 13 [8%] of 156, rhinorrhoea 15 [10%] vs eight [5%], and nasal discomfort 15 [10%] vs one [<1%]). Davunetide is not an effective treatment for PSP. Clinical trials of disease-modifying treatment are feasible in patients with PSP and should be pursued with other promising tau-directed treatments. Allon Therapeutics.