Tracking autophagy during proliferation and differentiation of trypanosoma brucei

Autophagy is a lysosome-dependent degradation mechanism that sequesters target cargo into autophagosomal vesicles. The Trypanosoma brucei genome contains apparent orthologues of several autophagy-related proteins including an ATG8 family. These ubiquitin-like proteins are required for autophagosome membrane formation, but our studies show that ATG8.3 is atypical. To investigate the function of other ATG proteins, RNAi compatible T. brucei were modified to function as autophagy reporter lines by expressing only either YFP-ATG8.1 or YFP-ATG8.2. In the insect procyclic lifecycle stage, independent RNAi down-regulation of ATG3 or ATG7 generated autophagy-defective mutants and confirmed a pro-survival role for autophagy in the procyclic form nutrient starvation response. Similarly, RNAi depletion of ATG5 or ATG7 in the bloodstream form disrupted autophagy, but did not impede proliferation. Further characterisation showed bloodstream form autophagy mutants retain the capacity to undergo the complex cellular remodelling that occurs during differentiation to the procyclic form and are equally susceptible to dihydroxyacetone-induced cell death as wild type parasites, not supporting a role for autophagy in this cell death mechanism. The RNAi reporter system developed, which also identified TOR1 as a negative regulator controlling YFP-ATG8.2 but not YFP-ATG8.1 autophagosome formation, will enable further targeted analysis of the mechanisms and function of autophagy in the medically relevant bloodstream form of T. brucei

Difficulties in Evaluating Lyapunov Exponents for Lie Governed Dynamics

We consider here an environment in which the fact that a semiquantum Hamiltonian obeys SU(2) symmetries poses serious difficulties if one wants to compute Lyapunov exponents.Instituto de Física La Plat

On the Persistence of Mental Health Deterioration during the COVID-19 Pandemic by Sex and Ethnicity in the UK: Evidence from Understanding Society

This is the final version. Available on open access from De Gruyter via the DOI in this recordData and code availability: The research data are distributed by the UK Data Service. Researchers who would like to use Understanding Society need to register with the UK Data Service before being allowed to apply for or download datasets. More information: https://www.understandingsociety.ac.uk/documentation/access-data. The code to replicate the analysis in this letter is publicly available from the Harvard Dataverse repository: https://doi.org/10.7910/DVN/YUOWJEWe use longitudinal data from a representative sample of the UK and compare self-reported mental health, as measured by the GHQ-12 score, at three timepoints (2017–2019, April 2020 and March 2021), for the whole sample and by sex and ethnicity. Out of the 14,382 individuals interviewed in 2017–2019 and April 2020, 10,445 were interviewed again in March 2021. The mean GHQ-12 in April 2020 is 12.37 [95% CI: 12.22, 12.52] and in March 2021 is 12.36 [95% CI: 12.21, 12.51], above that of 2017–2019: 11.13 [95% CI: 10.99, 11.26]. We do not find evidence that the level of mental health goes back to pre-pandemic levels. In terms of inequalities, while the gender gap (mean difference between women and men) in mental health deterioration among White British is closing, there is no clear evidence that the ethnic gap (mean difference between ethnic minorities and White British) among men is changing

Neutrino-nucleus cross sections for oscillation experiments

Neutrino oscillations physics is entered in the precision era. In this context accelerator-based neutrino experiments need a reduction of systematic errors to the level of a few percent. Today one of the most important sources of systematic errors are neutrino-nucleus cross sections which in the hundreds-MeV to few-GeV energy region are known with a precision not exceeding 20%. In this article we review the present experimental and theoretical knowledge of the neutrino-nucleus interaction physics. After introducing neutrino oscillation physics and accelerator-based neutrino experiments, we overview general aspects of the neutrino-nucleus cross sections, both theoretical and experimental views. Then we focus on these quantities in different reaction channels. We start with the quasielastic and quasielastic-like cross section, putting a special emphasis on multinucleon emission channel which attracted a lot of attention in the last few years. We review the main aspects of the different microscopic models for this channel by discussing analogies and differences among them.The discussion is always driven by a comparison with the experimental data. We then consider the one pion production channel where data-theory agreement remains very unsatisfactory. We describe how to interpret pion data, then we analyze in particular the puzzle related to the impossibility of theoretical models and Monte Carlo to simultaneously describe MiniBooNE and MINERvA experimental results. Inclusive cross sections are also discussed, as well as the comparison between the $\nu_\mu$ and $\nu_e$ cross sections, relevant for the CP violation experiments. The impact of the nuclear effects on the reconstruction of neutrino energy and on the determination of the neutrino oscillation parameters is reviewed. A window to the future is finally opened by discussing projects and efforts in future detectors, beams, and analysis

Physics potential of a long-baseline neutrino oscillation experiment using a J-PARC neutrino beam and Hyper-Kamiokande

39 pages, 26 figures, submitted to PTE

Uncovering genetic parameters and environmental influences on fertility, milk production, and quality in autochthonous Reggiana cattle

Reggiana is a local cattle breed from northern Italy known for its rusticity and profitability, due to the production of branded Parmigiano Reggiano cheese. To ensure the persistence of such profitability in the long term, an adequate breeding program is required. To this aim, in the present study we estimate the genetic parameters of the main productive and reproductive traits, and we evaluate the effect of genotype by environment interaction (GxE) on these traits using 2 environmental covariates: (1) productivity and (2) temperature-humidity index (THI). Milk, fat, protein, and casein yield were considered as daily production traits, whereas protein, fat, casein percentage, casein index, and somatic cell score were considered as milk quality traits. Finally, reproductive traits such as the number of inseminations, days open, calving interval, and calving-to-first-insemination interval were evaluated. Reggiana cattle produce an average of 19 kg of milk per day with 3.7% fat and 3.4% protein content and have excellent fertility parameters. Compared with other breeds, they have slightly lower heritability for production and quality for production traits (e.g., 0.12 [0.09; 0.15] for milk yield), but similar heritability for fertility traits. Milk, protein, and fat daily yields are highly correlated but negatively correlated with the percentage of protein, fat, and casein, whereas fertility traits have an unfavorable genetic correlation with daily production traits. When considering productivity, a consistent amount of variability due to GxE was observed for all daily production traits, somatic cell count, and casein index. A modest amount of GxE was observed for fertility parameters, while the percentage of solid content showed almost no GxE effect. A similar situation occurred when considering the THI, but no GxE interaction was observed for reproduction traits. In conclusion, this study provides useful information for the implementation of accurate selection plans in this local breed, accounting for environmental plasticity measured through the consistent GxE interaction observed

Potential excess spend in primary care due to NHS drug tariff variability in vitamin D preparations

Objectives Vitamin D is commonly prescribed in primary care for the prevention and treatment of deficiency and for maintenance after treatment (although supplementation for maintenance and prevention can be bought over-the-counter). There is wide variation in the costs to the NHS in England of oral preparations of vitamin D, even for a single-specific dose and route.1 It is possible that the availability of multiple options for the same intended medicine, the costs of which are unlikely to be known by the prescriber, could result in an inadvertent excess spend. We aimed to estimate the annual cost-saving if only the cheapest vitamin D preparations were prescribed. Design Primary care prescribing data for 2018 were downloaded from NHS Digital (https://digital.nhs.uk).2 Monthly datasets include the number of items, quantity and cost of each drug prescribed and dispensed. Private prescriptions are not recorded. All prescription items relating to the vitamin D preparations colecalciferol and ergocalciferol, regardless of dose, route or manufacturer, were extracted. Data for each specific preparation were aggregated across all practices and all months to give the annual number of items and their cost across England. All liquid and injectable preparations were assumed to be appropriately prescribed and therefore excluded from the analysis. Combined preparations – such as calcium/vitamin D, calcium/alendronate and multivitamins – were also excluded. For each defined dose range of vitamin D, the lowest cost preparation was identified, and the potential cost-savings if only these preparations were prescribed was calculated. Setting Primary care in England. Participants All patients registered with a general practitioner in England in 2018. Main Outcome Measure The difference between actual and potential spend on vitamin D prescriptions, if only the lowest priced preparation were available. Results In 2018, over 4 million vitamin D items were prescribed in primary care, at a cost of over £21 million. If only the cheapest options were prescribed for non-liquid preparations across all dose ranges, and assuming all prescriptions were appropriate, it would have resulted in an approximate £15 million (>70%) cost-saving to the NHS. Maintenance doses of vitamin D (designated as 800 to 2000 international units per day as per NICE guidelines3) accounted for more than half of the spend (∼£12 million). It was noted that all the cheapest options available are suitable for vegetarians. Conclusion The prescribing of more expensive vitamin D preparations in primary care may have significant financial consequences, although our results relate to a single year of prescribing within NHS primary care. Since choice of preparation may intentionally be based on factors other than cost (e.g. dietary requirements, bioavailability, what was initially prescribed by a hospital), work is needed nationally to rationalise available prescribing options. If national guidance were produced, the difficulties of implementation within individual Clinical Commissioning Groups might limit economic benefit. National efficient procurement strategies are an alternative approach, but require careful consideration of legislative frameworks (such as the Public Contract Regulations 20154) with safeguards to prevent horizontal cooperation between suppliers

A multi-analytical approach for the identification of pollutant sources on black crust samples: stable isotope ratio of carbon, sulphur, and oxygen

This study is focused on the identification of pollutant sources on black crust (BC) samples from the Monumental Cemetery of Milan (Italy), through a multi-analytical approach based on the determination of stable isotope ratios of carbon, sulphur, and oxygen. Six black crust samples, mainly developed on marble sculptures over a time span of 100-150 years, were analysed. For the first time, δ13C was measured for BC samples: δ13C values of the pulverized samples (from -1.2 to +1.3 ‰) are very close to the values obtained from the carbonate matrix, whereas after the removal of the matrix through acidification, δ13C values of BC samples from Milan range from -27.2 to -22.1 ‰, with no significant variation between samples with different ratios of organic carbon to elemental carbon. In sum, the δ13C values obtained for all BC samples fall within the range of anthropogenic emissions such as vehicle traffic, coal combustion and industrial emissions. δ34S and δ18O values of sulphate from BC samples range from -6.3 to +7.0 ‰ and from +7.6 to +10.5 ‰, respectively. Coupling the analysis of the oxygen isotope ratio with that of sulphur enables a more precise identification of the origin of sulphates: the observed isotopic composition falls in the range typical for anthropogenic emission of sulphur dioxide. Overall, in this study, C, S and O isotopes were combined for the first time to assess pollutant sources on black crust samples: this multi-stable isotope approach allowed to show that the BC formation on monuments from the Monumental Cemetery of Milan mostly results from anthropogenic emissions from fossil fuels combustion by road vehicles and factories, as well as domestic heating

State of the Art and New Trends from the 2022 Gism Annual Meeting

The 2022 Italian Mesenchymal Stem Cell Group (Gruppo Italiano Staminali Mesenchimali, GISM) Annual Meeting took place on 20–21 October 2022 in Turin (Italy), with the support of the University of Turin and the City of Health and Science of Turin. The novelty of this year’s meeting was its articulation, reflecting the new structure of GISM based on six sections: (1) Bringing advanced therapies to the clinic: trends and strategies, (2) GISM Next Generation, (3) New technologies for 3D culture systems, (4) Therapeutic applications of MSC-EVs in veterinary and human medicine, (5) Advancing MSC therapies in veterinary medicine: present challenges and future perspectives, (6) MSCs: a double-edged sword: friend or foe in oncology. National and international speakers presented their scientific works with the aim of promoting an interactive discussion and training for all attendees. The atmosphere was interactive, where ideas and questions between younger researchers and senior mentors were shared in all moments of the congress