Healthy male and female riders between 18 and 60 years of age, riding mountain bikes in cleats, will be recruited in Cape Town. At the first session, participants will complete an informed consent ...form, activity questionnaire and a health screening questionnaire. T-tests or Mann-Whitney U tests will be performed to assess the differences in test results before and after the fatiguing protocols, for both cognitive and physical fatigue protocols.
The proteins within the Poly-ADP Ribose Polymerase (PARP) family encompass a diverse and integral set of cellular functions. PARP1 and PARP2 have been extensively studied for their roles in DNA ...repair and as targets for cancer therapeutics. Several PARP inhibitors (PARPi) have been approved for clinical use, however, while their efficacy is promising, tumours readily develop PARPi resistance. Many other members of the PARP protein family share catalytic domain homology with PARP1/2, however, these proteins are comparatively understudied, particularly in the context of DNA damage repair and tumourigenesis. This review explores the functions of PARP4,6-16 and discusses the current knowledge of the potential roles these proteins may play in DNA damage repair and as targets for cancer therapeutics.
Gastrointestinal (GI) infections in sheep have significant implications for animal health, welfare and productivity, as well as being a source of zoonotic pathogens. Interactions between pathogens ...and epithelial cells at the mucosal surface play a key role in determining the outcome of GI infections; however, the inaccessibility of the GI tract
in vivo
significantly limits the ability to study such interactions in detail. We therefore developed ovine epithelial organoids representing physiologically important gastric and intestinal sites of infection, specifically the abomasum (analogous to the stomach in monogastrics) and ileum. We show that both abomasal and ileal organoids form self-organising three-dimensional structures with a single epithelial layer and a central lumen that are stable in culture over serial passage. We performed RNA-seq analysis on abomasal and ileal tissue from multiple animals and on organoids across multiple passages and show the transcript profile of both abomasal and ileal organoids cultured under identical conditions are reflective of the tissue from which they were derived and that the transcript profile in organoids is stable over at least five serial passages. In addition, we demonstrate that the organoids can be successfully cryopreserved and resuscitated, allowing long-term storage of organoid lines, thereby reducing the number of animals required as a source of tissue. We also report the first published observations of a helminth infecting gastric and intestinal organoids by challenge with the sheep parasitic nematode
Teladorsagia circumcincta
, demonstrating the utility of these organoids for pathogen co-culture experiments. Finally, the polarity in the abomasal and ileal organoids can be inverted to make the apical surface directly accessible to pathogens or their products, here shown by infection of apical-out organoids with the zoonotic enteric bacterial pathogen
Salmonella enterica
serovar Typhimurium. In summary, we report a simple and reliable
in vitro
culture system for generation and maintenance of small ruminant intestinal and gastric organoids. In line with 3Rs principals, use of such organoids will reduce and replace animals in host-pathogen research.
•Lung epithelial cell-derived single-cell clones display phenotypic heterogeneity.•Morphologically mesenchymal single cell-derived clones display altered EMP marker expression.•Lung epithelial ...cell-derived clones do not display genetic alterations.•Single cell-derived clones show diversity in their metabolic reflux, with increased glycolytic index in many of the clones.
Epithelial-mesenchymal plasticity (EMP) is a hallmark of cancer. By enabling cells to shift between different morphological and functional states, EMP promotes invasion, metastasis and therapy resistance. We report that near-diploid non-cancerous human epithelial lung cells spontaneously shift along the EMP spectrum without genetic changes. Strikingly, more than half of single cell-derived clones adopt a mesenchymal morphology. We independently characterise epithelial-like and mesenchymal-like clones. Mesenchymal clones lose epithelial markers, display larger cell aspect ratios and lower motility, with mostly unaltered proliferation rates. Stemness marker expression and metabolic rewiring diverge independently of phenotypes. In 3D culture, more epithelial clones become mesenchymal-like. Thus, non-cancerous epithelial cells may acquire cancer metastasis-associated features prior to genetic alterations and cancerous transformation.
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Triple-negative breast cancer (TNBC) is a sub-classification of breast carcinomas, which leads to poor survival outcomes for patients. TNBCs do not possess the hormone receptors that are frequently ...targeted as a therapeutic in other cancer subtypes and, therefore, chemotherapy remains the standard treatment for TNBC. Nuclear envelope proteins are frequently dysregulated in cancer cells, supporting their potential as novel cancer therapy targets. The Lem-domain (Lem-D) (LAP2, Emerin, MAN1 domain, and Lem-D) proteins are a family of inner nuclear membrane proteins, which share a ~45-residue Lem-D. The Lem-D proteins, including Ankle2, Lemd2, TMPO, and Emerin, have been shown to be associated with many of the hallmarks of cancer. This study aimed to define the association between the Lem-D proteins and TNBC and determine whether these proteins could be promising therapeutic targets.
GENT2, TCGA, and KM plotter were utilized to investigate the expression and prognostic implications of several Lem-D proteins: Ankle2, TMPO, Emerin, and Lemd2 in publicly available breast cancer patient data. Immunoblotting and immunofluorescent analysis of immortalized non-cancerous breast cells and a panel of TNBC cells were utilized to establish whether protein expression of the Lem-D proteins was significantly altered in TNBC. SiRNA was used to decrease individual Lem-D protein expression, and functional assays, including proliferation assays and apoptosis assays, were conducted.
The Lem-D proteins were generally overexpressed in TNBC patient samples at the mRNA level and showed variable expression at the protein level in TNBC cell lysates. Similarly, protein levels were generally negatively correlated with patient survival outcomes. siRNA-mediated depletion of the individual Lem-D proteins in TNBC cells induced aberrant nuclear morphology, decreased proliferation, and induced cell death. However, minimal effects on nuclear morphology or cell viability were observed following Lem-D depletion in non-cancerous MCF10A cells.
There is evidence to suggest that Ankle2, TMPO, Emerin, and Lemd2 expressions are correlated with breast cancer patient outcomes, but larger patient sample numbers are required to confirm this. siRNA-mediated depletion of these proteins was shown to specifically impair TNBC cell growth, suggesting that the Lem-D proteins may be a specific anti-cancer target.
The pathogenicity of some Phytophthora species recently described from Western Australia, together with P. cinnamomi as a control, was tested against seven Western Australian native plant species in ...the glasshouse. Host species were Banksia grandis, B. littoralis, B. occidentalis, Casuarina obesa, Corymbia calophylla, Eucalyptus marginata and Lambertia inermis. Twenty‐two Phytophthora species were grown on a vermiculite, millet seed and V8 substrate and used as soil inoculum when the plant hosts were approximately 3 months old. Pathogenicity was assessed after 6 weeks and plants were scored for death, root damage, and percentage reduction of shoot growth compared with control plants. The pathogenicity of P. cinnamomi was confirmed. Phytophthora niederhauserii was shown to be similar to P. cinnamomi in pathogenicity and of concern ecologically. Other species that killed one or more hosts were P. boodjera, P. constricta, P. elongata, P. moyootj and P. rosacearum, while P. condilina, P. gibbosa, P. gregata, P. litoralis and P. ‘personii’ caused significant reduction to shoot and/or root growth, but did not kill plants. Host species susceptible to the highest number of Phytophthora species were B. grandis, B. littoralis, B. occidentalis and E. marginata. No Phytophthora species tested killed C. calophylla.
The increasing resistance to anthelmintics has necessitated the exploration of alternative control strategies of gastrointestinal nematode (GIN) infections. A sustainable option is genetic selection ...based on differences in susceptibility to GIN infection between and within breeds of sheep. Here, three-month-old Canaria Hair breed (GIN-resistant) and Canaria Sheep breed (GIN-susceptible) showed no significant between-breed differences after trickle infection with
, whereas considerable individual variability was found in both breeds. Next, data from lambs of both breeds were used to explore the relationships between parasitological variables and
-specific IgA levels, local immune cell populations, and abomasal lymph node gene expression to understand the possible mechanisms underlying resistance. Mucosal IgA levels as well as numbers of globular leukocytes and MHC-II
cells were associated with protection. Analysis of lymph node gene expression revealed the associations between lower parasite numbers and cumulative fecal egg counts and several immune pathways, such as leukocyte cell adhesion, activation and differentiation of T cells, in particular CD4
and IL-4 production. The data obtained here may inform on the relationship between phenotypic resistance variability and protective responses at the humoral, cellular, and transcriptomic levels, thus contributing to identifying immune responses in young lambs that could be used as markers for selection.
The presence of components of the RNA interference (RNAi) pathway in Psoroptes ovis, an ectoparasitic mite responsible for psoroptic mange, was investigated through interrogation of the P. ovis ...genome. Homologues of transcripts representing critical elements for achieving effective RNAi in the mite, Tetranychus urticae and the model organisms Caenorhabditis elegans and Drosophila melanogaster were identified and, following the development of a non-invasive immersion method of double stranded RNA delivery, gene silencing by RNAi was successfully demonstrated in P. ovis. Significant reductions in transcript levels were achieved for three target genes which encode the Group 2 allergen (Pso o 2), mu-class glutathione S-transferase (PoGST-mu1) and beta-tubulin (Poβtub). This is the first demonstration of RNAi in P. ovis and provides a mechanism for mining transcriptomic and genomic datasets for novel control targets against this economically important ectoparasite.
•All reviewed countries stipulate a unique set of phytosanitary measures.•Only phytosanitary certificates and import inspection are required by all countries.•Little is known about quality of ...implementation and impact of individual measures.
The trade in plants for planting (P4P) is one of the major pathways for the introduction of pests. The strong increase in world trade in the past decades appears to have led to an increase in introductions of species transported by this pathway, and highlights the need for effective phytosanitary legislation and measures. The phytosanitary regulations in most countries are based on the International Plant Protection Convention and the World Trade Organisation's Agreement on Sanitary and Phytosanitary Measures, but there are large differences in countries’ approaches to managing the risk of introducing invasive alien species through international plant trade. We reviewed elements of the phytosanitary legislations of ten countries on all continents and aimed to find regulations that prevent biological invasions. We found large differences in countries’ phytosanitary regulations. New Zealand and Australia have the strictest phytosanitary regulations, while Europe maintains a general authorization for P4P imports. The remaining countries have regulations between these extremes. The evidence is sparse regarding the quality of implementation and effectiveness, and impact of individual phytosanitary measures. We recommend that National Plant Protection Organisations collect detailed information on P4P imports and the effectiveness of phytosanitary measures. Such information could provide a basis to improve a country's phytosanitary regulatory framework or could be used in risk assessments.
New and Interesting Fungi. 1 Crous, P W; Schumacher, R K; Wingfield, M J ...
Fungal Systematics and Evolution,
06/2018, Letnik:
1, Številka:
1
Journal Article
Recenzirano
Odprti dostop
This study introduces two new families, one new genus, 22 new species, 10 new combinations, four epitypes, and 16 interesting new host and / or geographical records. Cylindriaceae (based on ...Cylindrium elongatum) is introduced as new family, with three new combinations.
Xyladictyochaetaceae (based on Xyladictyochaeta lusitanica) is introduced to accommodate Xyladictyochaeta. Pseudoanungitea gen. nov. (based on P. syzygii) is described on stems of Vaccinium myrtillus (Germany). New species include: Exophiala eucalypticola
on Eucalyptus obliqua leaf litter, Phyllosticta hakeicola on leaves of Hakea sp., Setophaeosphaeria citricola on leaves of Citrus australasica, and Sirastachys cyperacearum on leaves of Cyperaceae (Australia); Polyscytalum chilense
on leaves of Eucalyptus urophylla (Chile); Pseudoanungitea vaccinii on Vaccinium myrtillus (Germany); Teichospora quercus on branch tissue of Quercus sp. (France); Fusiconidium lycopodiellae on stems of Lycopodiella inundata, Monochaetia
junipericola on twig of Juniperus communis, Myrmecridium sorbicola on branch tissues of Sorbus aucuparia, Parathyridaria philadelphi on twigs of Philadelphus coronarius, and Wettsteinina philadelphi on twigs of Philadelphus coronarius (Germany);
Zygosporium pseudogibbum on leaves of Eucalyptus pellita (Malaysia); Pseudoanungitea variabilis on dead wood (Spain); Alfaria acaciae on leaves of Acacia propinqua, Dictyochaeta mimusopis on leaves of Mimusops caffra, and Pseudocercospora breonadiae
on leaves of Breonadia microcephala (South Africa); Colletotrichum kniphofiae on leaves of Kniphofia uvaria, Subplenodomus iridicola on Iris sp., and Trochila viburnicola on twig cankers on Viburnum sp.(UK); Polyscytalum neofecundissimum
on Quercus robur leaf litter, and Roussoella euonymi on fallen branches of Euonymus europaeus (Ukraine). New combinations include: Cylindrium algarvense on leaves of Eucalyptus sp. (Portugal), Cylindrium purgamentum on leaf litter (USA),
Cylindrium syzygii on leaves of Syzygium sp. (Australia), Microdochium musae on leaves of Musa sp. (Malaysia), Polyscytalum eucalyptigenum on Eucalyptus grandis × pellita (Malaysia), P. eucalyptorum on leaves of Eucalyptus
(Australia), P. grevilleae on leaves of Grevillea (Australia), P. nullicananum on leaves of Eucalyptus (Australia), Pseudoanungitea syzygii on Syzygium cordatum leaf litter (South Africa), and Setophaeosphaeria sidae on leaves of
Sida sp. (Brazil). New records include: Sphaerellopsis paraphysata on leaves of Phragmites sp., Vermiculariopsiella dichapetali on leaves of Melaleuca sp. and Eucalyptus regnans, and Xyladictyochaeta lusitanica on leaf litter of Eucalyptus
sp. (Australia); Camarosporidiella mackenziei on twigs of Caragana sp. (Finland); Cyclothyriella rubronotata on twigs of Ailanthus altissima, Rhinocladiella quercus on Sorbus aucuparia branches (Germany); Cytospora viticola on stems of
Vitis vinifera (Hungary); Echinocatena arthrinioides on leaves of Acacia crassicarpa (Malaysia); Varicosporellopsis aquatilis from garden soil (Netherlands); Pestalotiopsis hollandica on needles of Cupressus sempervirens (Spain), Pseudocamarosporium
africanum on twigs of Erica sp. (South Africa), Pseudocamarosporium brabeji on branch of Platanus sp. (Switzerland); Neocucurbitaria cava on leaves of Quercus ilex (UK); Chaetosphaeria myriocarpa on decaying wood of Carpinus betulus, Haplograhium
delicatum on decaying Carpinus betulus wood (Ukraine). Epitypes are designated for: Elsinoë mimosae on leaves of Mimosa diplotricha (Brazil), Neohendersonia kickxii on Fagus sylvatica twig bark (Italy), Caliciopsis maxima on fronds of
Niphidium crassifolium (Brazil), Dictyochaeta septata on leaves of Eucalyptus grandis × urophylla (Chile), and Microdochium musae on leaves of Musa sp. (Malaysia).
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