231 research outputs found
Experimental bladder carcinogenesis – rodent models
Several rodent models of bladder cancer development have been established. The aim of this review article is to provide a critical
assessment of different animal models available for the study of bladder carcinogenesis, its chemoprevention and therapy. All, except
for transgenic and knockout animals, require 8–12 months experimental periods in order to generate a high yield of neoplasias.
Spontaneous bladder tumor models are extremely rare. The significance of the results from animal experiments is dependent upon the
selection of a suitable animal model. There are no rules regarding the choice of a model, it is however very useful to have knowledge
of relevant comparative medical aspects concerning this subject. We describe chemical carcinogens most commonly used to induce
bladder cancer, pellet implantation and urinary calculi, agents that promote bladder cancer, and irradiation. We also evaluated
other tools such as cell cultures, tumor implantation and transgenic models for bladder cancer, that have been developed to study
the process. The review considers how several imaging techniques can be applied to study rodent bladder carcinogenesis.Для изучения механизмов развития рака мочевого пузыря было создано несколько экспериментальных моделей на гры-
зунах. Целью обзора была сравнительная оценка различных экспериментальных моделей для изучения канцерогенеза
мочевого пузыря, профилактики и терапии. За исключением трансгенных и нокаутных животных, для получения высокого
выхода опухолей в любой экспериментальной модели требуется 8–12 мес. Модели спонтанного канцерогенеза мочевого
пузыря крайне редки. Выбор экспериментальной модели с определенными параметрами определяет значимость получен-
ных результатов. В статье описаны различные методики, используемые для индукции рака мочевого пузыря in vivo, ряд
методических подходов, таких как культура клеток, имплантация опухоли и трансгенные модели рака мочевого пузыря
и современные методы мониторинга опухолевой прогрессии
Report of the ICES\NAFO Joint Working Group on Deep-water Ecology (WGDEC), 11–15 March 2013, Floedevigen, Norway.
On 11 February 2013, the joint ICES/NAFO WGDEC, chaired by Francis Neat (UK) and attended by ten members met at the Institute for Marine Research in Floedevi-gen, Norway to consider the terms of reference (ToR) listed in Section 2. WGDEC was requested to update all records of deep-water vulnerable marine eco-systems (VMEs) in the North Atlantic. New data from a range of sources including multibeam echosounder surveys, fisheries surveys, habitat modelling and seabed imagery surveys was provided. For several areas across the North Atlantic, WGDEC makes recommendations for areas to be closed to bottom fisheries for the purposes of conservation of VMEs
Inositol is a constituent of detergent-solubilized immunoaffinity-purified rat liver 5′-nucleotidase
Unbiased yeast screens identify cellular pathways affected in Niemann-Pick disease type C
Niemann–Pick disease type C (NPC) is a rare lysosomal storage
disease caused by mutations in either the NPC1 or NPC2 genes.
Mutations in the NPC1 gene lead to the majority of clinical cases
(95%); however, the function of NPC1 remains unknown. To gain
further insights into the biology of NPC1, we took advantage of
the homology between the human NPC1 protein and its yeast
orthologue, Niemann–Pick C–related protein 1 (Ncr1). We recreated the NCR1 mutant in yeast and performed screens to identify
compensatory or redundant pathways that may be involved in
NPC pathology, as well as proteins that were mislocalized in
NCR1-deficient yeast. We also identified binding partners of the
yeast Ncr1 orthologue. These screens identified several processes
and pathways that may contribute to NPC pathogenesis. These
included alterations in mitochondrial function, cytoskeleton
organization, metal ion homeostasis, lipid trafficking, calcium
signalling, and nutrient sensing. The mitochondrial and cytoskeletal abnormalities were validated in patient cells carrying
mutations in NPC1, confirming their dysfunction in NPC disease
Safety and immunogenicity of a novel multiple antigen pneumococcal vaccine in adults: A Phase 1 randomised clinical trial
BACKGROUND:
Pneumococcal vaccines, combining multiple protein antigens, provide an alternative approach to currently marketed vaccines and may provide broader protection against pneumococcal disease. This trial evaluated the safety and immunogenicity of a novel vaccine candidate PnuBioVax in healthy young adults.
METHODS:
In a Phase 1 double-blind study, 36 subjects (18–40 years) were randomised to receive 3 doses of PnuBioVax, 28 days apart, at one of three dose levels (50, 200, 500 µg) or placebo. Safety assessments included rates of emergent adverse events (AEs), injection site and systemic reactions. Immunogenicity endpoints included antibody titre against PnuBioVax and selected pneumococcal antigens.
RESULTS:
In the placebo (n = 9) and PnuBioVax (n = 27) vaccinated subjects, there were 15 and 72, reported TEAEs, respectively. The majority of TEAEs were classified as common vaccine related AEs. There were no serious AEs. Common vaccine-related AEs occurred in 13 PnuBioVax (48%) and 2 placebo (22%) subjects and were all headaches (mild and moderate). Injection site reactions, mostly pain and tenderness (graded mild or moderate) were reported, in particular in the 200 µg and 500 µg PnuBioVax groups. There were no clinically significant changes in vital signs, ECG or blood chemistries. Subjects receiving the higher dose (200 and 500 μg) demonstrated a greater fold increase in IgG titre compared with the starting dose (50 μg) or the placebo group. The fold-increase was statistically significantly higher for 200 and 500 µg PnuBioVax vs 50 µg PnuBioVax and placebo at each timepoint post-immunisation. Most subjects receiving 200 and 500 µg PnuBioVax demonstrated a ≥2-fold increase in antibody against pneumolysin (Ply), Pneumococcal surface antigen (PsaA), PiaA (Pneumococcal iron acquisition), PspA (Pneumococcal surface protein A) and pilus proteins (RrgB and RrgA).
CONCLUSIONS:
All dose levels were considered safe and well tolerated. There was a statistically significant increase in anti-PnuBioVax IgG titres at the 200 and 500 µg dose levels compared to 50 µg and placebo. Trial registration number: NCT02572635https://www.clinicaltrials.gov
pUL21 is a viral phosphatase adaptor that promotes herpes simplex virus replication and spread.
The herpes simplex virus (HSV)-1 protein pUL21 is essential for efficient virus replication and dissemination. While pUL21 has been shown to promote multiple steps of virus assembly and spread, the molecular basis of its function remained unclear. Here we identify that pUL21 is a virus-encoded adaptor of protein phosphatase 1 (PP1). pUL21 directs the dephosphorylation of cellular and virus proteins, including components of the viral nuclear egress complex, and we define a conserved non-canonical linear motif in pUL21 that is essential for PP1 recruitment. In vitro evolution experiments reveal that pUL21 antagonises the activity of the virus-encoded kinase pUS3, with growth and spread of pUL21 PP1-binding mutant viruses being restored in adapted strains where pUS3 activity is disrupted. This study shows that virus-directed phosphatase activity is essential for efficient herpesvirus assembly and spread, highlighting the fine balance between kinase and phosphatase activity required for optimal virus replication.Wellcome Trust Senior Research Fellowship (219447/Z/19/Z),
Wellcome Trust Senior Research Fellowship (106207/Z/14/Z), Biotechnology and Biological Sciences Research Council Research Grant (BB/M021424/1),
Sir Henry Dale Fellowship, jointly funded by the Wellcome Trust and the Royal Society (098406/Z/12/B)
Tribomechanical Properties of PVA/Nomex® Composite Hydrogels for Articular Cartilage Repair
Due to the increasing prevalence of articular cartilage diseases and limitations faced by current therapeutic methodologies, there is an unmet need for new materials to replace damaged cartilage. In this work, poly(vinyl alcohol) (PVA) hydrogels were reinforced with different amounts of Nomex® (known for its high mechanical toughness, flexibility, and resilience) and sterilized by gamma irradiation. Samples were studied concerning morphology, chemical structure, thermal behavior, water content, wettability, mechanical properties, and rheological and tribological behavior. Overall, it was found that the incorporation of aramid nanostructures improved the hydrogel’s mechanical performance, likely due to the reinforcement’s intrinsic strength and hydrogen bonding to PVA chains. Additionally, the sterilization of the materials also led to superior mechanical properties, possibly related to the increased crosslinking density through the hydrogen bonding caused by the irradiation. The water content, wettability, and tribological performance of PVA hydrogels were not compromised by either the reinforcement or the sterilization process. The best-performing composite, containing 1.5% wt. of Nomex®, did not induce cytotoxicity in human chondrocytes. Plugs of this hydrogel were inserted in porcine femoral heads and tested in an anatomical hip simulator. No significant changes were observed in the hydrogel or cartilage, demonstrating the material’s potential to be used in cartilage replacement
sFDvent: A global trait database for deep‐sea hydrothermal‐vent fauna
Motivation: Traits are increasingly being used to quantify global biodiversity patterns,
with trait databases growing in size and number, across diverse taxa. Despite grow‐
ing interest in a trait‐based approach to the biodiversity of the deep sea, where the
impacts of human activities (including seabed mining) accelerate, there is no single re‐
pository for species traits for deep‐sea chemosynthesis‐based ecosystems, including
hydrothermal vents. Using an international, collaborative approach, we have compiled
the first global‐scale trait database for deep‐sea hydrothermal‐vent fauna – sFD‐
vent (sDiv‐funded trait database for the Functional Diversity of vents). We formed a
funded working group to select traits appropriate to: (a) capture the performance of
vent species and their influence on ecosystem processes, and (b) compare trait‐based
diversity in different ecosystems. Forty contributors, representing expertise across
most known hydrothermal‐vent systems and taxa, scored species traits using online
collaborative tools and shared workspaces. Here, we characterise the sFDvent da‐
tabase, describe our approach, and evaluate its scope. Finally, we compare the sFD‐
vent database to similar databases from shallow‐marine and terrestrial ecosystems to
highlight how the sFDvent database can inform cross‐ecosystem comparisons. We
also make the sFDvent database publicly available online by assigning a persistent,
unique DOI.
Main types of variable contained: Six hundred and forty‐six vent species names,
associated location information (33 regions), and scores for 13 traits (in categories:
community structure, generalist/specialist, geographic distribution, habitat use, life
history, mobility, species associations, symbiont, and trophic structure). Contributor
IDs, certainty scores, and references are also provided.
Spatial location and grain: Global coverage (grain size: ocean basin), spanning eight
ocean basins, including vents on 12 mid‐ocean ridges and 6 back‐arc spreading
centres.
Time period and grain: sFDvent includes information on deep‐sea vent species, and
associated taxonomic updates, since they were first discovered in 1977. Time is not
recorded. The database will be updated every 5 years.
Major taxa and level of measurement: Deep‐sea hydrothermal‐vent fauna with spe‐
cies‐level identification present or in progress.
Software format: .csv and MS Excel (.xlsx).This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited
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