Adjuvant therapy for children treated by enucleation at diagnosis of retinoblastoma

Introduction Advanced localized retinoblastoma can be cured by enucleation, but extraocular spread of retinoblastoma cells is associated with a high mortality. Risk-stratified adjuvant treatment with chemotherapy and radiotherapy has been shown to reduce the risk for extraocular relapse in children with histopathological risk factors. Methods Data of 184 patients with retinoblastoma and primary enucleation were collected in a prospective, multicenter, observational study between 2013 and 2020. The clinical characteristics were evaluated as risk factors and progression-free and overall survival rates were compared. Results Seventy-one percent of 184 children with retinoblastoma treated with primary enucleation were diagnosed with low risk histopathological factors (pT1/pT2a) and received no adjuvant therapy. Children with intermediate risk (pT2b,pT3; 48 children, 26.0%) and high risk for metastasis (pT4; 5 children, 2.7%) received risk-stratified adjuvant treatment. None of the children with low risk or intermediate risk (pT1-pT3) relapsed, but two of five children with high-risk retinoblastoma (pT4) developed extraocular relapses and one deceased. The 2-year progression-free survival rate and 2-year overall survival rate was 100% for children with pT1-3 retinoblastoma. However, the 2-year progression-free survival rate and 2-year overall survival rate for children with pT4 was statistically notably reduced with 2 of 5 children developing progression and 1 death among the 5 children within 2 years after diagnosis. Conclusion Primary enucleation alone and with additional risk-stratified adjuvant chemotherapy treatment provides high cure rates in patients with pT1-3 retinoblastoma, but children with pT4 retinoblastoma remain at high risk to develop extraocular retinoblastoma. International prospective clinical trials are required to evaluate reduction of intensity of adjuvant chemotherapy in some risk groups (pT2, pT3) and intensification for pT4 retinoblastoma

Large-scale mapping of mutations affecting zebrafish development

BACKGROUND: Large-scale mutagenesis screens in the zebrafish employing the mutagen ENU have isolated several hundred mutant loci that represent putative developmental control genes. In order to realize the potential of such screens, systematic genetic mapping of the mutations is necessary. Here we report on a large-scale effort to map the mutations generated in mutagenesis screening at the Max Planck Institute for Developmental Biology by genome scanning with microsatellite markers. RESULTS: We have selected a set of microsatellite markers and developed methods and scoring criteria suitable for efficient, high-throughput genome scanning. We have used these methods to successfully obtain a rough map position for 319 mutant loci from the Tübingen I mutagenesis screen and subsequent screening of the mutant collection. For 277 of these the corresponding gene is not yet identified. Mapping was successful for 80 % of the tested loci. By comparing 21 mutation and gene positions of cloned mutations we have validated the correctness of our linkage group assignments and estimated the standard error of our map positions to be approximately 6 cM. CONCLUSION: By obtaining rough map positions for over 300 zebrafish loci with developmental phenotypes, we have generated a dataset that will be useful not only for cloning of the affected genes, but also to suggest allelism of mutations with similar phenotypes that will be identified in future screens. Furthermore this work validates the usefulness of our methodology for rapid, systematic and inexpensive microsatellite mapping of zebrafish mutations

ALERT Lessons From A Biosecurity Disaster

The Managers of Australasian Herbarium Collections (MAHC) have been working with the Plant Import Operations Branch of the Australian government Department of Agriculture and Water Resources (DAWR) to align our procedures to significantly reduce the risk of herbarium specimens being destroyed when being imported into Australia. The two groups worked together productively to bring about change and to enable the resumption of the international movement of herbarium specimens after two recent international disasters. These changes include amendments to the Biosecurity Import Conditions System (BICON) which contains the Australian government's import conditions and onshore outcomes for herbarium specimens, changes to procedures at the border (airmail gateway facilities) where biosecurity documentation is assessed and parcels released, and updates to existing herbarium parcel labels, guidelines and supplier declaration templates. We will discuss lessons learned, as well as implications for researchers, collections managers or institutions who may be sending herbarium specimen material to Australia. This is a presentation on beahlf of the Managers of Australasian Herbarium Collections (MAHC), a network of herbarium Collection Managers in Australia and New Zealand

Pharmacological Treatment of Osteoporosis: An Update

Osteoporoza (OP) je kronična bolest kostiju koju karakterizira poremećena mikrostruktura koštane građe što vodi do smanjene koštane mase i povećanog rizika od prijeloma. Antiresorptivni lijekovi, posebice bisfosfonati, trenutno su prvi izbor u liječenju osteoporoze u većini zemalja. Međutim, oni imaju svoja ograničenja, što je potaknulo razvitak osteoanaboličkih lijekova kao što su teriparatid i romosozumab, no i oni imaju svoje štetne učinke. Ipak, neosporno je da korist lijekova za osteoporozu nadvladava potencijalne rizike. U bolesnika s visokim ili vrlo visokim rizikom od prijeloma mogu se razmotriti sekvencijalne ili kombinirane terapije s anaboličkim agensom kao početnim lijekom. S obzirom na rastuću prevalenciju osteoporoze ulažu se veliki napori kako bi se razvili lijekovi sljedeće generacije s maksimalnom učinkovitosti i što prihvatljivijim sigurnosnim profilom. U postizanju ovoga cilja potrebno je što bolje razumijevanje uloga različitih signalnih putova u patogenezi osteoporoze. Najveći napori uloženi su u razvitak lijekova koji utječu na modifikaciju Wnt signalnog puta koji mogu imati i antiresorptivno i/ili osteoanaboličko djelovanje ovisno na koju etapu, odnosno signalnu molekulu djelujemo.Osteoporosis (OP) is a chronic bone disease characterized by disturbed bone microarchitecture, which leads to reduced bone mass and increased risk of fractures. Antiresorptive drugs, especially bisphosphonates, are currently the first choice in the treatment of osteoporosis in most countries. However, their limitations prompted the development of osteoanabolic drugs such as teriparatide and romosozumab, with their own adverse effects. Still, it is undeniable that the benefits of antiosteoporosis drugs outweigh the potential risks. In patients at high or very high fracture risk, sequential or combination therapies with an anabolic agent as an initial agent may be considered. Due to the growing prevalence of osteoporosis, great efforts are being made to develop next-generation drugs with maximum effectiveness and an acceptable safety profile. Achieving this goal requires a better insight in different signaling pathways involved in the pathogenesis of osteoporosis. The greatest efforts have been made in the development of drugs that affect the modification of the Wnt signaling pathway, which can have anti-resorptive and/or osteoanabolic effects depending on the target signaling molecule

Sharing knowledge – Innovative Solutions from New Zealand Taxonomic Collections

Manaaki Whenua - Landcare Research (MWLR) is the custodian of nearly a third of New Zealand’s nationally significant natural history collections and databases. MWLR is a New Zealand Government-owned Research Institute whose purpose is to drive innovation in the management of terrestrial biodiversity and land resources. Active research programmes are associated with the collections and innovative projects to disseminate the resulting knowledge to the public have been developed. A number of these projects have focused on two-way sharing of knowledge and information with Māori, Aotearoa/New Zealand’s first people. Examples of science projects combining collections resources, community knowledge and research to produce bilingual guides, websites and teaching tools include: Ahi Pepe | Mothnet, a citizen science project that engages teachers, students and Māori with nature and science across New Zealand What is this bug?, a web-based invertebrate identification guide with bilingual translation (He Aha Tēnei Pepeke) Ngā Hekaheka o Aotearoa, a bilingual teaching resource combining scientific research with Māori ancestral knowledge and usage of fungi. Discover New Life, a project where researchers worked with students to discover and describe species new to science National New Zealand Flax Collection (HARAKEKE) , a living plant collection of weaving varieties of harakeke (NZ flax), providing plants and associated website resources on research, cultivation and traditional usage of harakeke for Māori weavers and the broader community. These projects have allowed development of ongoing relationships and knowledge sharing between MWLR natural history collections and New Zealand communities, enriching the collections and associated data for all

Containing the Spirits: Lessons learned from the Management of Australasian Herbarium Wet Collections.

Several herbaria in Australia and New Zealand have recently been required to implement changes to the way in which spirit (alcohol or wet) specimens are managed in their institutions in order to deal with various curatorial and staff health and safety challenges. We will present an overview of some of the key lessons learned from addressing issues such as mould, FAA (formalin-acetic acid and alcohol solution), inadequate housing and storage of our spirit specimens whilst also ensuring that best-practice curation standards are implemented along with appropriate work health and safety practices to protect staff. For example, the National Herbarium of New South Wales spirit collection was stored until 2017 in metal filing cabinets and open wooden shelving. Due to unstable air-conditioning resulting in high humidity and condensation, mould had formed on all of the bottles and on all wooden surfaces. The external surface of each bottle was cleaned with prior to removal from the dedicated spirit collection room, the wooden shelving was replaced with open metal shelving, and room cleaned and resealed prior to return of the collection. Monitoring of the environment and condition of the collection continues, and future actions include replacing the specimen vials, many of which have failing lids. The Western Australian Herbarium recently renovated its spirit storage area from specimens stored in boxes on fixed open shelving to individual bottles filed in metal drawers. Health and safety concerns for staff handling heavy boxes, often up ladders, combined with the inflexible and inefficient use of space on fixed shelving are now solved. Plenty of space is available for specimen expansion, and the ease of access to each specimen makes the collection simple to maintain. The next step for the collection is to protect it better by implementing climate control. FAA was used as a fixative and preservative for plant fruit, flowers and other parts pre-1992 at the Australian National Herbarium in Canberra and the Australian Tropical Herbarium in Cairns. In response to changes in the Hazardous Substance classification for Formaldehyde a program was developed that focused on worker safety during replacement of the solution in approximately 15,000 bottles by minimising exposure and managing the manual handling risks of the work, whilst also ensuring best-practice curatorial outcomes for the specimens. This is a presentation on behalf of the Managers of Australasian Herbarium Collections (MAHC), a network of herbarium Collection Managers in Australia and New Zealand

Selecting the best candidates for resurrecting extinct-in-the-wild plants from herbaria

: Resurrecting extinct species is a fascinating and challenging idea for scientists and the general public. Whereas some theoretical progress has been made for animals, the resurrection of extinct plants (de-extinction sensu lato) is a relatively recently discussed topic. In this context, the term 'de-extinction' is used sensu lato to refer to the resurrection of 'extinct in the wild' species from seeds or tissues preserved in herbaria, as we acknowledge the current impossibility of knowing a priori whether a herbarium seed is alive and can germinate. In plants, this could be achieved by germinating or in vitro tissue-culturing old diaspores such as seeds or spores available in herbarium specimens. This paper reports the first list of plant de-extinction candidates based on the actual availability of seeds in herbarium specimens of globally extinct plants. We reviewed globally extinct seed plants using online resources and additional literature on national red lists, resulting in a list of 361 extinct taxa. We then proposed a method of prioritizing candidates for seed-plant de-extinction from diaspores found in herbarium specimens and complemented this with a phylogenetic approach to identify species that may maximize evolutionarily distinct features. Finally, combining data on seed storage behaviour and longevity, as well as specimen age in the novel 'best de-extinction candidate' score (DEXSCO), we identified 556 herbarium specimens belonging to 161 extinct species with available seeds. We expect that this list of de-extinction candidates and the novel approach to rank them will boost research efforts towards the first-ever plant de-extinction

Global Phylogeny of the Brassicaceae Provides Important Insights into Gene Discordance

The mustard family (Brassicaceae) is a scientifically and economically important family, containing the model plant Arabidopsis thaliana and numerous crop species that feed billions worldwide. Despite its relevance, most published family phylogenies are incompletely sampled, generally contain massive polytomies, and/or show incongruent topologies between datasets. Here, we present the most complete Brassicaceae genus-level family phylogenies to date (Brassicaceae Tree of Life, or BrassiToL) based on nuclear (>1,000 genes, almost all 349 genera and 53 tribes) and plastome (60 genes, 79% of the genera, all tribes) data. We found cytonuclear discordance between nuclear and plastome-derived phylogenies, which is likely a result of rampant hybridisation among closely and more distantly related species, and highlight rogue taxa. To evaluate the impact of this rampant hybridisation on the nuclear phylogeny reconstruction, we performed four different sampling routines that increasingly removed variable data and likely paralogs. Our resulting cleaned subset of 297 nuclear genes revealed high support for the tribes, while support for the main lineages remained relatively low. Calibration based on the 20 most clock-like nuclear genes suggests a late Eocene to late Oligocene ‘icehouse origin’ of the family. Finally, we propose five new or re-established tribes, including the recognition of Arabidopsideae, a monotypic tribe to accommodate Arabidopsis. With a worldwide community of thousands of researchers working on this family, our new, densely sampled family phylogeny will be an indispensable tool to further highlight Brassicaceae as an excellent model family for studies on biodiversity and plant biology

Global Brassicaceae phylogeny based on filtering of 1,000-gene dataset

The mustard family (Brassicaceae) is a scientifically and economically important family, containing the model plant Arabidopsis thaliana and numerous crop species that feed billions worldwide. Despite its relevance, most phylogenetic trees of the family are incompletely sampled and often contain poorly supported branches. Here, we present the most complete Brassicaceae genus-level family phylogenies to date (Bras-sicaceae Tree of Life or BrassiToL) based on nuclear (1,081 genes, 319 of the 349 genera; 57 of the 58 tribes) and plastome (60 genes, 265 genera; all tribes) data. We found cytonuclear discordance between the two, which is likely a result of rampant hybridization among closely and more distantly related lineages. To eval-uate the impact of such hybridization on the nuclear phylogeny reconstruction, we performed five different gene sampling routines, which increasingly removed putatively paralog genes. Our cleaned subset of 297 genes revealed high support for the tribes, whereas support for the main lineages (supertribes) was moder-ate. Calibration based on the 20 most clock-like nuclear genes suggests a late Eocene to late Oligocene origin of the family. Finally, our results strongly support a recently published new family classification, dividing the family into two subfamilies (one with five supertribes), together representing 58 tribes. This includes five recently described or re-established tribes, including Arabidopsideae, a monogeneric tribe accommodating Arabidopsis without any close relatives. With a worldwide community of thousands of researchers working on Brassicaceae and its diverse members, our new genus-level family phylogeny will be an indispensable tool for studies on biodiversity and plant biology