Mechanisms of Interference with Simian Virus 40 (SV40) DNA Replication by Trans-Dominant Mutants of SV40 Large T Antigen

Mutations at multiple sites within the simian virus 40 (SV40) early region yield large T antigens which interfere trans dominantly with the replicative activities of wild-type T antigen. A series of experiments were conducted to study possible mechanisms of interference with SV40 DNA replication caused by these mutant T antigens. First, the levels of wild-type T antigen expression in cells cotransfected with wild-type and mutant SV40 DNAs were examined; approximately equal levels of wild-type T antigen were seen, regardless of whether the cotransfected mutant was trans dominant or not. Second, double mutants that contained the mutation of inA2827, a strong trans-dominant mutation with a 12-bp linker inserted at the position encoding amino acid 520, and various mutations in other parts of the large-T-antigen coding region were constructed. The trans-dominant interference of inA2827 was not affected by second mutations within the p105Rb binding site or the amino or carboxy terminus of large T antigen. Mutation of the nuclear localization signal partially reduced the trans dominance of inA2827. The large T antigen of mutant inA2815 contains an insertion of 4 amino acids at position 168 of large T; this T antigen fails to bind SV40 DNA but is not trans dominant for DNA replication. The double mutant containing the mutations of both inA2815 and in A2827 was not trans dominant. The large T antigen of dlA2433 lacks amino acids 587 to 589, was unstable, and failed to bind p53. Combining the dlA2433 mutation with the inA2827 mutation also reversed the trans dominance completely, but the effect of the dlA2433 mutation on trans dominance can be explained by the instability of this double mutant protein. In addition, we examined several mutants with conservative point mutations in the DNA binding domain and found that most of them were not trans dominant. The implications of the results of these experiments on possible mechanisms of trans dominance are discussed

Neuroecotoxicology: effects of environmental heavy metal exposure on the brain of african giant rats

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Marine Biodegradability and Ecotoxicity of MWool((R)) Recycled Wool Fibers: A Circular-Economy-Based Material

Pollution of the marine environment by microfibers is considered a problem for ecosystem conservation. The amount of microplastic, localization of sources, and associated ecotoxicity are well known in the literature. Wastewater from washing machines is the main source of microplastic fibers in the aquatic environment, and fabrics made from recycled plastic are widely reused. The circular economy also promotes recycling of dyed natural wool materials as a basis for making new clothing, but in this case, less research has been conducted on the behaviour and effects of recycled wool microfibers in marine ecosystems. MWool((R)) (MW) and MWool((R)) carded (MWc) products made from recycled wool fibers were tested in mesocosms to investigate the biodegradation of wool fibers over a 260-day period and the effects of this process on marine ecosystems in terms of microfiber inputs and the ecotoxicological effects of by-products and chemicals released during degradation. The early degradation process was associated with the loss of artificial pigments from the dyed wool, particularly pink and red, which occurred within 30-90 days of exposure. Mean release of microparticles into contact water is significantly different from control (T0, p < 0.01) at 90 days MWc (36.6 mg/L) and 180 days MW (42.9 mg/L). The biodegradation process is accompanied by swelling of wool fibers, which is associated with a significant increase in mean wool thickness (p < 0.05, 18.8 +/-.1 mu m at T0 vs. 24.0 +/- 7.1 mu m). In both cases, the contact water was not associated with signs of ecotoxicity for the marine species tested in this study (Phaeodactylum tricornutum, Brachionus plicatilis, and Paracentrotus lividus)

Exploring the role of blockchain technology in modern high-value food supply chains: global trends and future research directions

Trust, safety, and quality are among the most important factors in the agri-food supply chains. Traceability is a powerful tool to ensure them, but implementing a transparent and effective system is a complex operation. As a result, innovative systems, like blockchain, could be introduced. Although research on its impacts in the agri-food is recent, the literature appears fragmented. The objective is to investigate the studied aspects of the blockchain adoption in agri-food, with the purpose of retrieving meaningful considerations about the current state of the art about strategic high-value supply chains, such as wine and olive oil, particularly subjected to fraudulent behaviors. A productivity measurement was applied to retrieve the evolution of the number of documents through the years, the most productive countries, the sources, the research areas, and the most significant papers in terms of number of citations received. To understand the research trends, a co-occurrence analysis was employed. Results show that most of the existing studies focus on the role of blockchain in the resolution of some critical issues as food safety and frauds. While wine is currently an emerging sector in which this approach can be implemented, olive oil still needs more attention. In both cases, blockchain could potentially help to support the profitability and sustainability of the production. The research underlines the importance of focusing on the environmental and social dimension of the blockchain phenomenon and the use of technology to improve the efficiency of agri-food chains and reduce waste and resource use

Looking for Nano- and Microplastics in Meiofauna Using Advanced Methodologies

: Meiofauna (body size within 30–1000 µm) are the community of microscopic invertebrates that live at the bottom of marine and freshwater ecosystems and play a key role in the food webs of these environments. Several studies have addressed the adverse effects of anthropic stressors on meiofauna; however, data on the presence and impact of plastic debris in wild meiofaunal organisms are scant. Since the amount of microplastic waste in sediments may surge rapidly, ascertaining the ingestion of these xenobiotics by the abundant micrometazoan community is necessary to understand their potential accumulation in aquatic food webs and their hazard to the health of the ecosystem. The absence of documentation in this regard may be due to the difficulty in detecting the small size of the plastic fragments meiofauna may potentially ingest. To overcome this difficulty, we developed an integrated approach based on different microscopic/spectroscopic techniques suitable for detecting plastic particles of sizes down to 200 nm.Meiofauna (body size within 30–1000 m) are the community of microscopic invertebrates that live at the bottom of marine and freshwater ecosystems and play a key role in the food webs of these environments. Several studies have addressed the adverse effects of anthropic stressors on meiofauna; however, data on the presence and impact of plastic debris in wild meiofaunal organisms are scant. Since the amount of microplastic waste in sediments may surge rapidly, ascertaining the ingestion of these xenobiotics by the abundant micrometazoan community is necessary to understand their potential accumulation in aquatic food webs and their hazard to the health of the ecosystem. The absence of documentation in this regard may be due to the difficulty in detecting the small size of the plastic fragments meiofauna may potentially ingest. To overcome this difficulty, we developed an integrated approach based on different microscopic/spectroscopic techniques suitable for detecting plastic particles of sizes down to 200 nm

Progression of motor subtypes in Huntington’s disease. a 6-year follow-up study

The objective of this study is to investigate the progression of predominantly choreatic and hypokinetic-rigid signs in Huntington's disease (HD) and their relationship with cognitive and general functioning over time. The motor signs in HD can be divided into predominantly choreatic and hypokinetic-rigid subtypes. It has been reported in cross-sectional studies that predominantly choreatic HD patients perform better on functional and cognitive assessments compared to predominantly hypokinetic-rigid HD patients. The course of these motor subtypes and their clinical profiles has not been investigated longitudinally. A total of 4135 subjects who participated in the European HD Network REGISTRY study were included and classified at baseline as either predominantly choreatic (n = 891), hypokinetic-rigid (n = 916), or mixed-motor (n = 2328), based on a previously used method. The maximum follow-up period was 6 years. The mixed-motor group was not included in the analyses. Linear mixed models were constructed to investigate changes in motor subtypes over time and their relationship with cognitive and functional decline. Over the 6-year follow-up period, the predominantly choreatic group showed a significant decrease in chorea, while hypokinetic-rigid symptoms slightly increased in the hypokinetic-rigid group. On the Total Functional Capacity, Stroop test, and Verbal fluency task the rate of change over time was significantly faster in the predominantly choreatic group, while on all other clinical assessments the decline was comparable for both groups. Our results suggest that choreatic symptoms decrease over time, whereas hypokinetic-rigid symptoms slightly increase in a large cohort of HD patients. Moreover, different motor subtypes can be related to different clinical profiles

Ameliorative effect of mimo2 (a novel compound from Moringa oleifera leaves) against vanadium-induced neurotoxicity

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Thalamic inputs to dorsomedial striatum are involved in inhibitory control: evidence from the five-choice serial reaction time task in rats

Rationale Corticostriatal circuits are widely implicated in the top-down control of attention including inhibitory control and behavioural flexibility. However, recent neurophysiological evidence also suggests a role for thalamic inputs to striatum in behaviours related to salient, reward-paired cues. Objectives Here, we used designer receptors exclusively activated by designer drugs (DREADDs) to investigate the role of parafascicular (Pf) thalamic inputs to the dorsomedial striatum (DMS) using the five-choice serial reaction time task (5CSRTT) in rats. Methods The 5CSRTT requires sustained attention in order to detect spatially and temporally distributed visual cues and provides measures of inhibitory control related to impulsivity (premature responses) and compulsivity (perseverative responses). Rats underwent bilateral Pf injections of the DREADD vector, AAV2-CaMKIIa-HA-hM4D(Gi)-IRES-mCitrine. The DREADD agonist, clozapine N-oxide (CNO; 1 μl bilateral; 3 μM) or vehicle, was injected into DMS 1 h before behavioural testing. Task parameters were manipulated to increase attention load or reduce stimulus predictability respectively. Results We found that inhibition of the Pf-DMS projection significantly increased perseverative responses when stimulus predictability was reduced but had no effect on premature responses or response accuracy, even under increased attentional load. Control experiments showed no effects on locomotor activity in an open field. Conclusions These results complement previous lesion work in which the DMS and orbitofrontal cortex were similarly implicated in perseverative responses and suggest a specific role for thalamostriatal inputs in inhibitory control

The ameliorative effects of a phenolic derivative of Moringa oleifera leave against vanadium-induced neurotoxicity in mice

Vanadium, a transition series metal released during some industrial activities, induces oxidative stress and lipid peroxidation. Ameliorative effect of a pure compound from the methanolic extract of Moringa oleifera leaves, code-named MIMO2, in 14-day old mice administered with vanadium (as sodium metavanadate 3 mg/kg) for 2 weeks was assessed. Results from body weight monitoring, muscular strength, and open field showed slight reduction in body weight and locomotion deficit in vanadium-exposed mice, ameliorated with MIMO2 co-administration. Degeneration of the Purkinje cell layer and neuronal death in the hippocampal CA1 region were observed in vanadium-exposed mice and both appeared significantly reduced with MIMO2 co-administration. Demyelination involving the midline of the corpus callosum, somatosensory and retrosplenial cortices was also reduced with MIMO2. Microglia activation and astrogliosis observed through immunohistochemistry were also alleviated. Immunohistochemistry for myelin, axons and oligodendrocyte lineage cells were also carried out and showed that in vanadium-treated mice brains, oligodendrocyte progenitor cells increased NG2 immunolabelling with hypertrophy and bushy, ramified appearance of their processes. MIMO2 displayed ameliorative and antioxidative effects in vanadium-induced neurotoxicity in experimental murine species. This is likely the first time MIMO2 is being used in vivo in an animal model