Pathogenic Germline Variants in 10,389 Adult Cancers

We conducted the largest investigation of predisposition variants in cancer to date, discovering 853 pathogenic or likely pathogenic variants in 8% of 10,389 cases from 33 cancer types. Twenty-one genes showed single or cross-cancer associations, including novel associations of SDHA in melanoma and PALB2 in stomach adenocarcinoma. The 659 predisposition variants and 18 additional large deletions in tumor suppressors, including ATM, BRCA1, and NF1, showed low gene expression and frequent (43%) loss of heterozygosity or biallelic two-hit events. We also discovered 33 such variants in oncogenes, including missenses in MET, RET, and PTPN11 associated with high gene expression. We nominated 47 additional predisposition variants from prioritized VUSs supported by multiple evidences involving case-control frequency, loss of heterozygosity, expression effect, and co-localization with mutations and modified residues. Our integrative approach links rare predisposition variants to functional consequences, informing future guidelines of variant classification and germline genetic testing in cancer. A pan-cancer analysis identifies hundreds of predisposing germline variants

Blocking caspase activity prevents transsynaptic neuronal apoptosis and the loss of inhibition in lamina II of the dorsal horn after peripheral nerve injury.

We show that transsynaptic apoptosis is induced in the superficial dorsal horn (laminas I-III) of the spinal cord by three distinct partial peripheral nerve lesions: spared nerve injury, chronic constriction, and spinal nerve ligation. Ongoing activity in primary afferents of the injured nerve and glutamatergic transmission cause a caspase-dependent degeneration of dorsal horn neurons that is slow in onset and persists for several weeks. Four weeks after spared nerve injury, the cumulative loss of dorsal horn neurons, determined by stereological analysis, is >20%. GABAergic inhibitory interneurons are among the neurons lost, and a marked decrease in inhibitory postsynaptic currents of lamina II neurons coincides with the induction of apoptosis. Blocking apoptosis with the caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp(OMe)-fluoromethylketone (zVAD) prevents the loss of GABAergic interneurons and the reduction of inhibitory currents. Partial peripheral nerve injury results in pain-like behavioral changes characterized by hypersensitivity to tactile or cold stimuli. Treatment with zVAD, which has no intrinsic analgesic properties, attenuates this neuropathic pain-like syndrome. Preventing nerve injury-induced apoptosis of dorsal horn neurons by blocking caspase activity maintains inhibitory transmission in lamina II and reduces pain hypersensitivity

Behaviour of captive Ostrich chicks from 10 days to 5 months of age

The behaviour of ostrich chicks bred in captivity was studied by using groups with 30 birds in five age groups: from 10 to 40 days of age; from 41 to 60 days of age; from 61 to 90 days of age; from 91 to 120 days of age and from 121 to 150 days of age. Six birds at each age were ringed around one of their feet and observed for four consecutive days for eight hours daily in three periods (in the morning, at noon and in the afternoon), following the "one-zero" method for sampling. The order for observation of behaviour of the six selected birds was performed randomly at every thirty minutes, totalling 16 periods or 80 minutes/bird/day. Fourteen types of behaviour were observed. There were differences among ages for behaviour like standing, walking, running, ingesting stones, ingesting feces, picking and attacking. Non-parametric-tests were used to analyse the behaviour according to age of the bird and to the periods of the day. There was a statistical difference between in the morning and at noon periods on behaviours standing, walking, eating ration and in litophagia, which were observed more frequently at the first hours of the day. When periods of the morning and afternoon were compared, the birds' age had a significant effect on behaviour sand bathing. When the periods noon/afternoon were compared, the behaviours which presented significant differences were walking, running, drinking water, eating ration, litophagia, coprophagia, dancing, sand bathing, whose occurrence was the highest during dusk. It was observed that the behaviour of young ostriches diverge according to the age and to day period

Unforeseen consequences of conservation management practices: case study on herding rhino as an anti‐poaching measure

The current biodiversity crisis calls for effective conservation measures. However, some measures may have unforeseen negative consequences on individual species. Herding, a management practice currently used in some wildlife species to protect animals from poachers, can cause habituation to humans, which unintentionally might increase their risk of being poached at a later time. Herding could also negatively impact animal welfare and physiology when perceived as a stressor, with potential negative consequences at the individual and population level. In this study, we tested the following hypotheses: 1) herding elicits habituation to humans in white rhino, and 2) this practice affects the behavior and physiological state of rhino, but they can habituate to it. To that aim, we investigated the effects of herding on the response of rhino to initially unfamiliar people, expression of aggressive and discomfort behaviors, and fecal glucocorticoid metabolite (fGCM) concentrations (a commonly used indicator of physiological stress) in two cohorts of six and 10 semi‐wild orphan white rhino. Rhino did not interrupt their activity to an approaching person on foot (99%) or in a vehicle (94%), indicating habituation to humans. Aggressive and discomfort behaviors were displayed more often while being herded, and their frequency increased significantly with increasing herding pressure. Finally, overall mean fGCM concentrations were 16.1% higher under herding compared to non‐herding conditions, but individual fGCM levels varied up to 17‐fold under each scenario, suggesting that herding might not elicit a physiological stress response in these animals. While rhino security is paramount in the current poaching crisis, management practices must ensure that they do not impact negatively at the individual and population level.University of Pretoria, Epi‐Use and National Research Foundation South Africa.https://zslpublications.onlinelibrary.wiley.com/journal/146917952021-10-07hj2021Centre for Wildlife ManagementMammal Research InstituteParaclinical SciencesProduction Animal Studie