Wheat rusts never sleep but neither do sequencers: will pathogenomics transform the way plant diseases are managed?

Field pathogenomics adds highly informative data to surveillance surveys by enabling rapid evaluation of pathogen variability, population structure and host genotype

Abattoir-based serological surveillance for transboundary and zoonotic diseases in cattle and swine in Cambodia: a pilot study in Phnom Penh province during 2019 and 2020

A pilot animal disease surveillance program was implemented at four abattoirs in Phnom Penh, Cambodia, between October 2019 and January 2020. A total of 1141 samples were collected from 477 cattle and 664 swine. Serological testing was performed using commercial antibody ELISA kits for zoonotic and high-impact animal diseases, namely brucellosis, Q fever, classical swine fever (CSF), porcine reproductive and respiratory syndrome (PRRS) and African swine fever (ASF). Only two samples tested positive for Brucella antibodies (0.2%, 95% CI 0.4–0.6, n = 1141). The seroprevalence of Q fever was 0.8% (95% CI 0.3–2.1, n = 477) in the cattle samples, while CSF, PRRS and ASF in pigs were 55.4% (95% CI 51.6–59.2, n = 655), 81.2% (95% CI 78.1–84.0, n = 655) and 2.6% (95% CI 1.6–4.1, n = 664), respectively. All 38 doubtful and 17 positive ASF antibody ELISA samples were negative when tested by real-time PCR. Univariate analyses demonstrated that the factor significantly associated with positive results of ASF was the abattoir location (p-value = 0.002). Based on logistic regression models, significant risk factors for CSF were province of origin (p-value = 1.7 × 10−6), abattoir (p-value = 3.6 × 10−11) and PRRS positivity (p-value = 0.004), and for PRRS were province of origin (p-value = 0.0004) and CSF positivity (p-value = 0.001). In conclusion, the seroprevalences of zoonotic diseases in this study were very low. The high prevalence of CSF and PRRS antibodies were most likely the result of vaccination. All ASF seropositive pigs, including those that gave equivocal results, originated from large-scale Cambodian-based commercial farms, as well as Thailand, which raises questions about possible illegal vaccination or low-pathogenicity ASF variants. The pilot abattoir serological surveillance program described here has the potential to provide a sentinel for incursions of novel and endemic pathogens, although further work is required to demonstrate its capacity to provide information on the longitudinal disease trends

The Feigned Annoyance and Frustration Test to Activate the Sympathoadrenal Medullary System

When perceived as threatening, social interactions have been shown to trigger the sympathoadrenal medullary system as well as the hypothalamic-pituitary-adrenal axis resulting in a physiologic stress response. The allostatic load placed on human health and physiology in the context of acute and chronic stress can have profound health consequences. The purpose of this study was to develop a protocol for a lab-based stress stimulus using social-evaluative threat. While several valid, stress-stimulating protocols exist, we sought to develop one that triggered a physiologic response, did not require significant lab resources, and could be completed in around 10 min. We included 53 participants (29 men and 24 women) and exposed them to a modified version of the Stroop Color-Word Interference Task during which the participants were made to feel they were performing the task poorly while the lead researcher feigned annoyance and frustration. After exposure to this Feigned Annoyance and Frustration (FAF) Test, both the men and women in this study demonstrated a statistically significant and clinically meaningful increase in subjective stress on the visual analog scale. Additionally, the men in this study demonstrated a statistically significant increase in heart rate and salivary α-amylase concentrations after exposure to the test. The women in this study did not demonstrate a statistically significant increase in the physiologic stress biomarkers. This protocol for the FAF Test shows promise to researchers with limited time and resources who are interested in experimentally activating the sympathoadrenal medullary system

Risk mapping using serologic surveillance for selected One Health and transboundary diseases in Cambodian goats

In Cambodia, goat production and meat consumption are customary among Muslim communities. Recently, goat meat has gained popularity among Cambodians. Goat farmers use a traditional management system, including grazing, requiring minimal labour. The close proximity between humans and animals could increase the risk of zoonotic disease transmission. A serological survey was undertaken to estimate the prevalence of some priority zoonoses and high-impact animal diseases in the Cambodian goat population. A total of 540 samples were collected from goats in six provinces and analysed with commercially available enzyme-linked immunosorbent assays for Brucella species, Q fever (Coxiella burnetii), Foot and Mouth Disease virus non-structural protein (FMDV NSP) and Peste des Petits Ruminants virus (PPRV). True seroprevalences with a 95% Confidence Interval (CI), taking into account imperfect tests, risk factors and odds ratios (ORs), were calculated to better understand the disease distribution and epidemiology. Independent variables used in statistical modellings included sex, body condition score, age, vaccination history, province and commune, while dependent variables were ELISA test results. The overall true prevalence of antibodies to Brucella spp., C. burnetii, FMDV and PPRV, were 0.1% (95% CI 0.0, 1.0), 7.2% (95% CI 5.3, 9.7), 57.7% (95% CI 53.1, 62.3) and 0.0% (95% CI 0.0, 0.0), respectively. There was no identified risk factor for brucellosis and PPR. The two risk factors for C. burnetii seropositivity were sex (p-value = 0.0005) and commune (p-value <0.0001). However, only the OR of C. burnetii seropositive female goat was significant at 9.7 (95% CI 2.7, 35.5) times higher than male. The risk factors of FMD NSP seropositivity were age (p-value = 0.001) and commune (p-value <0.0001). Only the age ’more than two-year-old’ group with a significant OR of 6.2 (95% CI 2.1, 18.4) using the ’up to one-year-old’ group as the reference. In summary, Brucella spp. seroprevalence was low, while no evidence of PPRV antibodies was detected in the goat populations. C. burnetii seroprevalence in female goats was significantly higher than for males, and there were significant differences in C. burnetii seroprevalence between communes. The overall FMDV NSP seroprevalence was high, especially in older animals. Vaccination should be advocated to protect animals from FMDV and improve productivity. As the impacts of these zoonoses on human and animal health were still unknown, further investigation of these zoonotic diseases’ epidemiology is recommended

Altered Expression of Telomere-Associated Genes in Leukocytes among BRCA1 and BRCA2 Carriers

Telomere dysfunction resulting from telomere shortening and deregulation of shelterin components has been linked to the pathogenesis of age-related disorders, including cancer. Recent evidence suggests that BRCA1/2 (BRCA1 and BRCA2) tumor suppressor gene products play an important role in telomere maintenance. Although telomere shortening has been reported in BRCA1/2 carriers, the direct effects of BRCA1/2 haploinsufficiency on telomere maintenance and predisposition to cancer development are not completely understood. In this study, we assessed the telomere-associated and telomere-proximal gene expression profiles in peripheral blood leukocytes from patients with a BRCA1 or BRCA2 mutation, compared to samples from sporadic and familial breast cancer individuals. We found that 25 genes, including TINF2 gene (a negative regulator of telomere length), were significantly differentially expressed in BRCA1 carriers. Leukocyte telomere length analysis revealed that BRCA1/2 carriers had relatively shorter telomeres than healthy controls. Further, affected BRCA1/2 carriers were well differentiated from unaffected BRCA1/2 carriers by the expression of telomere-proximal genes. Our results link BRCA1/2 haploinsufficiency to changes in telomere length, telomere-associated as well as telomere-proximal gene expression. Thus, this work supports the effect of BRCA1/2 haploinsufficiency in the biology underlying telomere dysfunction in cancer development. Future studies evaluating these findings will require a large study population

Phase I, Dose-Escalation, Two-Part Trial of the PARP Inhibitor Talazoparib in Patients with Advanced Germline BRCA1/2 Mutations and Selected Sporadic Cancers

Talazoparib inhibits PARP catalytic activity, trapping PARP1 on damaged DNA and causing cell death in BRCA1/2-mutated cells. We evaluated talazoparib therapy in this two-part, phase I, first-in-human trial. Antitumor activity, MTD, pharmacokinetics, and pharmacodynamics of once-daily talazoparib were determined in an open-label, multicenter, dose-escalation study (NCT01286987). The MTD was 1.0 mg/day, with an elimination half-life of 50 hours. Treatment-related adverse events included fatigue (26/71 patients; 37%) and anemia (25/71 patients; 35%). Grade 3 to 4 adverse events included anemia (17/71 patients; 24%) and thrombocytopenia (13/71 patients; 18%). Sustained PARP inhibition was observed at doses ≥0.60 mg/day. At 1.0 mg/day, confirmed responses were observed in 7 of 14 (50%) and 5 of 12 (42%) patients with BRCA mutation–associated breast and ovarian cancers, respectively, and in patients with pancreatic and small cell lung cancer. Talazoparib demonstrated single-agent antitumor activity and was well tolerated in patients at the recommended dose of 1.0 mg/day

Long-term vegetation dynamics (40 yr) in the succulent Karoo, South Africa : effects of rainfall and grazing

QUESTIONS : Vegetation change in arid regions with a coefficient of rainfall exceeding 33% usually displays non-equilibrium dynamics, where abiotic factors override internal biotic controls. Irreversible changes have nonetheless also been described for arid regions. What are the contributions of internal/equilibriumvs external/non-equilibriumfactors to vegetation dynamics and can degradation due to overstocking be reversed after removal of livestock? LOCATION : Goegap Nature Reserve, Namaqualand, South Africa. METHODS : The descending point method was conducted annually from 1974 at two transects. Vegetation change was assessed in terms of vegetation cover, species composition, life-form composition, range condition, species richness and diversity. Principal coordinates analysis was used to illustrate the trajectories in floristic data, and the effects of stocking density and rainfall were examined with redundancy analysis. RESULTS : Vegetation cover, species richness and Shannon-Wiener index of diversity showed an increase and range condition improved with time. These positive changes could be related to the removal of high numbers of livestock and low wildlife numbers in the first years of survey. A gradual decline in the rate of increase in some of these parameters could be related to high grazing pressure during the later monitored years. There was a notable increase in nonsucculent chamaephytes, but the initial increase in succulent chamaephytes was not sustained. The directional change evident in perennial species composition, supports the equilibrium concept, whereby the negative changes induced by heavy grazing were partially reversed. Within the directional change, four quasi-stable states could be distinguished, which could be reconciled with the state-and-transition model. The annual component showed no directional change, but displayed event-driven, non-equilibrium dynamics by fluctuating in reaction to the timing and quantity of rainfall. CONCLUSIONS : The vegetation change displayed elements of both equilibrium and non-equilibrium dynamics, and demonstrated that the effects of heavy grazing in the Succulent Karoo were reversible. Overall, the recovery process proceeded slowly and was primarily detected in the perennial component of the vegetation. The increase in wildlife numbers in the later studied years and decline in perennial vegetation cover stress the need for active management of animal numbers to avoid vegetation degradation.University of Pretoria, the German Federal Ministry of Education and Research (BMBF) through the BIOTA South Project and the National Research Foundation (Grant no. 61277).http://onlinelibrary.wiley.com/journal/10.1111/(ISSN)1654-109X2016-04-30hb201

Multiple parallel deinonychosaurian trackways from a diverse dinosaur track assemblage of the Lower Cretaceous Dasheng Group of Shandong Province, China

Many newly-discovered dinosaur tracksites have recently been reported from the Lower Cretaceous Dasheng Group of Shandong Province. These are proving valuable as tools for characterizing the fauna in deposits almost devoid of body fossils. Here we report on a new Cretaceous site, the 14th documented in recent years, with multiple track-bearing levels, that adds ∼300 tracks to a growing database. At least two morphotypes tentatively labelled as cf. Menglongpus isp., representing a deinonychosaur, and cf. Tatarornipes isp., representing an avian theropod, add to the list of at least seven named ichnogenera attributed to avian and non-avian theropods reported from the Dasheng Group in Shandong Province. Combined with two sauropodomorph and two ornithopod ichnogenera, and unnamed turtle tracks, the genus-level ichnodiversity (∼14) is one of the highest reported for any Cretaceous unit either regionally in China or globally. The tracks identified as cf. Menglongpus isp. occur in four parallel trackways indicating a group of small didactyl bipeds of inferred deinonychosaurian affinity. Despite the lack of body fossils from the Dasheng Group in Shandong Province, a high diversity of deinonychosaur body fossils is known from the contemporary Jehol Biota from northeastern China. This similarity underscores the importance of the Shandong track assemblage as indicators of regional, tetrapod biodiversity during the Cretaceous