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Pestalotioid fungi were isolated in pure culture from symptomatic plants of Callistemon laevis, C. viminalis, Luma apiculata (marketed as “Myrtus luma”), Myrtus communis subsp. tarentina, and M. communis var. microphylla (M. communis ’Microphylla’), showing twig canker, dieback and defoliation. The isolates were identified to species by ITS, tef1 and tub2 sequences, which revealed the presence of six species of Neopestalotiopsis (N. camelliae-oleiferae, N. hispanica, N. iberica, N. rosae, N. rosicola, and N. zakeelii) and one species of Pestalotiopsis (P. biciliata). While most species were isolated only once or twice, the majority of isolates belonged to N. rosae (13) and N. hispanica (8). Pathogenicity was investigated by pathogenicity tests on all hosts, which confirmed the pathogenicity of all Neopestalotiopsis species on at least some of the hosts tested, while P. biciliata did not cause any disease symptoms. Neopestalotiopsis hispanica and N. rosae caused symptoms in all hosts of the present study, while the other Neopestalotiopsis species tested showed no symptoms on Luma apiculata.

Abstract Huntington’s disease (HD) is a dominant neurological disorder caused by an expanded HTT exon 1 CAG repeat that lengthens huntingtin’s polyglutamine tract. Lowering mutant huntingtin has been proposed for treating HD, but genetic modifiers implicate somatic CAG repeat expansion as the driver of onset. We find that branaplam and risdiplam, small molecule splice modulators that lower huntingtin by promoting HTT pseudoexon inclusion, also decrease expansion of an unstable HTT exon 1 CAG repeat in an engineered cell model. Targeted CRISPR-Cas9 editing shows this effect is not due to huntingtin lowering, pointing instead to pseudoexon inclusion in PMS1. Homozygous but not heterozygous inactivation of PMS1 also reduces CAG repeat expansion, supporting PMS1 as a genetic modifier of HD and a potential target for therapeutic intervention. Although splice modulation provides one strategy, genome-wide transcriptomics also emphasize consideration of cell-type specific effects and polymorphic variation at both target and off-target sites.

Abstract Background Eating disorders have one of the highest mortality rates among psychiatric illnesses. Timely intervention is crucial for effective treatment, as eating disorders tend to be chronic and difficult to manage if left untreated. Clinical practice guidelines play a vital role in improving healthcare delivery, aiming to minimize variations in care and bridge the gap between research and practice. However, research indicates an active guideline implementation approach is crucial to effective uptake. Methods Mixed methods will be used to inform and evaluate our guideline implementation approach. Semi-structured focus groups will be conducted in each of the eight provinces in Canada. Each focus group will comprise 8–10 key stakeholders, including clinicians, program administrators, and individuals with lived experience or caregivers. Qualitative data will be analyzed using conventional content analysis and the constant comparison technique and the results will be used to inform our implementation strategy. The study will then evaluate the effectiveness of our implementation approach through pre- and post-surveys, comparing changes in awareness, use, and impact of the guidelines in various stakeholder groups. Discussion Through a multifaceted implementation strategy, involving the co-creation of educational materials, tailored training, and context-specific strategies, this study intends to enhance guideline uptake and promote adherence to evidence-based practices. Our study will also contribute valuable information on the impact of our implementation strategies.

Alternaria brown spot (ABS), caused by Alternaria alternata, is one of the main citrus diseases that causes heavy production losses and reductions in fruit quality worldwide. The application of chemical fungicides has a key role in the management of ABS. In this study, 48 isolates of A. alternata collected from citrus orchards since 2014 were tested in vitro for their sensitivity to pyraclostrobin and fludioxonil, the latter being temporarily registered in Italy since 2020. Pyraclostrobin sensitivity was determined using spore germination and mycelial growth assays. The effective concentration inhibiting 50% of fungal growth (EC50) was determined for each isolate. The sensitivity assays showed that the majority of A. alternata isolates tested were sensitive to pyraclostrobin. EC50 values of fludioxonil in a mycelial growth assay indicated that 100% of isolates were sensitive to this fungicide. The analysis of the cytochrome b gene showed that none of the 40 isolates with a different sensitivity profile had the G143A mutation, and the subgroup of 8 isolates analyzed by real-time PCR did not carry the G137R and F129L mutations. A subset of four more sensitive and two reduced-sensitive isolates was chosen to assess sensitivity on detached citrus leaves treated with pyraclostrobin at the maximum recommended label rate. Disease incidence and symptom severity were significantly reduced, with a small reduction reported in leaves inoculated with the reduced-sensitive isolates. Furthermore, there was no correlation between sensitivity and fitness parameters evaluated in vitro (mycelium growth and sporulation rate). These findings help the development of monitoring resistance programs and, consequently, set up effective anti-resistance strategies for managing ABS on citrus orchards.

In the present paper we propose a model describing the nonlocal behavior of an elastic body using a peridynamical approach. Indeed, peridynamics is a suitable framework for problems where discontinuities appear naturally, such as fractures, dislocations, or, in general, multiscale materials. In particular, the regional fractional Laplacian is used as the nonlocal operator. Moreover, a combination of the fractional and classical Laplacian operators is used to obtain a better description of the phenomenological response in elasticity. We consider models with linear and nonlinear perturbations. In the linear case, we prove the existence and uniqueness of the solution, while in the nonlinear case the existence of at least two nontrivial solutions of opposite sign is proved. The linear and nonlinear problems are also solved by a numerical approach which estimates the regional fractional Laplacian by means of its singular integral representation. In both cases, a numerical estimation of the solutions is obtained, using in the nonlinear case an approach involving a random variation of an initial guess of the solution. Moreover, in the linear case a parametric analysis is made in order to study the effects of the parameters involved in the model, such as the order of the fractional Laplacian and the mixture law between local and nonlocal behavior.

Successful human pregnancy needs several highly controlled steps to guarantee an oocyte’s fertilization, the embryo’s pre-implantation development, and its subsequent implantation into the uterine wall. The subsequent placenta development ensures adequate fetal nutrition and oxygenation, with the trophoblast being the first cell lineage to differentiate during this process. The placenta sustains the growth of the fetus by providing it with oxygen and nutrients and removing waste products. It is not surprising that issues with the early development of the placenta can lead to common pregnancy disorders, such as recurrent miscarriage, fetal growth restriction, pre-eclampsia, and stillbirth. Understanding the normal development of the human placenta is essential for recognizing and contextualizing any pathological aberrations that may occur. The effects of these issues may not become apparent until later in pregnancy, during the mid or advanced stages. This review discusses the process of the embryo implantation phase, the molecular mechanisms involved, and the abnormalities in those mechanisms that are thought to contribute to the development of pre-eclampsia. The review also covers the histological hallmarks of pre-eclampsia as found during the examination of placental tissue from pre-eclampsia patients.

In the contemporary world, human and natural calamities are challenging our capabilities to preserve heritage and develop innovative safeguard strategies that also address the requirement of sustainability for restoration purposes, still considering the connection between tradition and innovation. This work introduces non-invasive diagnostic practices that offer a new insight of the built environment by studying two different elements of the same architecture of San Bevignate Templar church: a thermographic mapping obtained with special post-processing procedures provided interesting information about the hidden wall pattern, while a prototypal laser scanner, called RGB-ITR, and a UAV survey supplied new insights on the precious paintings. The assessment of the masonry quality constitutes an a priori condition for a reliable estimation of its seismic vulnerability and for the planning of effective yet conservative interventions. The access keys to 'sustainability' therefore consist in the improvement of these contactless investigations, which can be performed both in passive conditions, in the case of thermography surveys, and in active ones, such as for the RGB-ITR scanner, as necessary substitutes for destructive or partial-destructive tests. The research achieved promising results for the characterisation of the architectural structure and the paintings, with the aim of a long-term monitoring of the structure and the decorative apparatus of a monumental heritage located in an area vulnerable to seismic and environmental events.

Altered cellular metabolism is believed to be an important contributor to pathogenesis of the neurodegenerative disorder Huntington's disease (HD). Research has primarily focused on mitochondrial toxicity, which can cause death of the vulnerable striatal neurons, but other aspects of metabolism have also been implicated. Most previous studies have been carried out using postmortem human brain or non-human cells. Here, we studied bioenergetics in an induced pluripotent stem cell-based model of the disease. We found decreased adenosine triphosphate (ATP) levels in HD cells compared to controls across differentiation stages and protocols. Proteomics data and multiomics network analysis revealed normal or increased levels of mitochondrial messages and proteins, but lowered expression of glycolytic enzymes. Metabolic experiments showed decreased spare glycolytic capacity in HD neurons, while maximal and spare respiratory capacities driven by oxidative phosphorylation were largely unchanged. ATP levels in HD neurons could be rescued with addition of pyruvate or late glycolytic metabolites, but not earlier glycolytic metabolites, suggesting a role for glycolytic deficits as part of the metabolic disturbance in HD neurons. Pyruvate or other related metabolic supplements could have therapeutic benefit in HD.

Abstract Huntington’s disease is caused by an expanded CAG tract in HTT. The length of the CAG tract accounts for over half the variance in age at onset of disease, and is influenced by other genetic factors, mostly implicating the DNA maintenance machinery. We examined a single nucleotide variant, rs79727797, on chromosome 5 in the TCERG1 gene, previously reported to be associated with Huntington’s disease and a quasi-tandem repeat (QTR) hexamer in exon 4 of TCERG1 with a central pure repeat. We developed a method for calling perfect and imperfect repeats from exome-sequencing data, and tested association between the QTR in TCERG1 and residual age at motor onset (after correcting for the effects of CAG length in the HTT gene) in 610 individuals with Huntington’s disease via regression analysis. We found a significant association between age at onset and the sum of the repeat lengths from both alleles of the QTR (p = 2.1 × 10−9), with each added repeat hexamer reducing age at onset by one year (95% confidence interval [0.7, 1.4]). This association explained that previously observed with rs79727797. The association with age at onset in the genome-wide association study is due to a QTR hexamer in TCERG1, translated to a glutamine/alanine tract in the protein. We could not distinguish whether this was due to cis-effects of the hexamer repeat on gene expression or of the encoded glutamine/alanine tract in the protein. These results motivate further study of the mechanisms by which TCERG1 modifies onset of HD.

Chrono-nutrition studies dietary habits and their role in the onset of metabolic diseases. The aim of this study is to describe chrono-nutritional patterns based on the analysis of the eating habits of patients with severe obesity during the 24-h cycle and investigate a possible relationship between these profiles, the comorbidities, and the psychological status. From the overall evaluation of the chrono-nutritional profiles of 173 patients with severe obesity, four predominant eating patterns were obtained with a refined statistical model. A regression analysis was performed to determine the relationship between chrono-nutritional patterns, medical comorbidities, and psychological status. Profile 1 was the most frequent (46.2%) and characterised by the regular presence of the three main meals. The distribution of the chrono-nutritional profiles did not vary with BMI. Chrono-nutritional profiles affected predominantly psychological variables, with lower performances among chrono-nutritional profiles 3 (to eat during all the 24-h, with nibbling and snacking also during the night) and 4 (like the fourth but without night-eating). This finding could be useful in the assessment and treatment of patients with obesity, allowing the identification of patients with a higher probability of suffering from a psychopathological condition simply by knowing the patients’ dietary profiles.

Cerebral organoids can be used to gain insights into neuropsychiatric disorders. Here the authors carry out RNAseq characterization from organoids derived from donors with autism spectrum disorder to identify associated cell type specific driver genes.