Explore the vast range of titles available.

Various post‐translational modifications (PTMs) fine‐tune the functions of almost all eukaryotic proteins, and co‐regulation of different types of PTMs has been shown within and between a number of proteins. Aiming at a more global view of the interplay between PTM types, we collected modifications for 13 frequent PTM types in 8 eukaryotes, compared their speed of evolution and developed a method for measuring PTM co‐evolution within proteins based on the co‐occurrence of sites across eukaryotes. As many sites are still to be discovered, this is a considerable underestimate, yet, assuming that most co‐evolving PTMs are functionally associated, we found that PTM types are vastly interconnected, forming a global network that comprise in human alone >50 000 residues in about 6000 proteins. We predict substantial PTM type interplay in secreted and membrane‐associated proteins and in the context of particular protein domains and short‐linear motifs. The global network of co‐evolving PTM types implies a complex and intertwined post‐translational regulation landscape that is likely to regulate multiple functional states of many if not all eukaryotic proteins. This study is the first large‐scale comparative analysis of multiple types of post‐translational modifications in different eukaryotic species. The resulting network of co‐evolving and functionally associated modifications reveals the global landscape of post‐translational regulation. Synopsis This study is the first large‐scale comparative analysis of multiple types of post‐translational modifications in different eukaryotic species. The resulting network of co‐evolving and functionally associated modifications reveals the global landscape of post‐translational regulation. In all, 115 149 non‐redundant post‐translational modifications (PTMs) of 13 different types were collected from 8 eukaryotes. Comparison of evolution speed reveals that carboxylation is the most conserved while SUMOylation is the fastest evolving PTM type. Co‐evolution of PTM pairs that co‐occur within proteins reveals a vastly interconnected global network of functionally associated PTM types in eukaryotes. Central to the network of functionally associated PTM types appear phosphorylation, acetylation, ubiquitination and O‐linked glycosylation that control both temporal events and processes that govern protein localization.

Linear motifs are short modules of protein sequences that play a crucial role in mediating and regulating many protein-protein interactions. The function of linear motifs strongly depends on the context, e.g. functional instances mainly occur inside flexible regions that are accessible for interaction. Sometimes linear motifs appear as isolated islands of conservation in multiple sequence alignments. However, they also occur in larger blocks of sequence conservation, suggesting an active role for the neighbouring amino acids. The evolution of regions flanking 116 functional linear motif instances was studied. The conservation of the amino acid sequence and order/disorder tendency of those regions was related to presence/absence of the instance. For the majority of the analysed instances, the pairs of sequences conserving the linear motif were also observed to maintain a similar local structural tendency and/or to have higher local sequence conservation when compared to pairs of sequences where one is missing the linear motif. Furthermore, those instances have a higher chance to co-evolve with the neighbouring residues in comparison to the distant ones. Those findings are supported by examples where the regulation of the linear motif-mediated interaction has been shown to depend on the modifications (e.g. phosphorylation) at neighbouring positions or is thought to benefit from the binding versatility of disordered regions. The results suggest that flanking regions are relevant for linear motif-mediated interactions, both at the structural and sequence level. More interestingly, they indicate that the prediction of linear motif instances can be enriched with contextual information by performing a sequence analysis similar to the one presented here. This can facilitate the understanding of the role of these predicted instances in determining the protein function inside the broader context of the cellular network where they arise.

It has become clear in outline though not yet in detail how cellular regulatory and signalling systems are constructed. The essential machines are protein complexes that effect regulatory decisions by undergoing internal changes of state. Subcomponents of these cellular complexes are assembled into molecular switches. Many of these switches employ one or more short peptide motifs as toggles that can move between one or more sites within the switch system, the simplest being on-off switches. Paradoxically, these motif modules (termed short linear motifs or SLiMs) are both hugely abundant but difficult to research. So despite the many successes in identifying short regulatory protein motifs, it is thought that only the “tip of the iceberg” has been exposed. Experimental and bioinformatic motif discovery remain challenging and error prone. The advice presented in this article is aimed at helping researchers to uncover genuine protein motifs, whilst avoiding the pitfalls that lead to reports of false discovery.

Immune checkpoint inhibition represents an important therapeutic option for advanced melanoma patients. Results from clinical studies have shown that treatment with the PD-1 inhibitors Pembrolizumab and Nivolumab provides improved response and survival rates. Moreover, combining Nivolumab with the CTLA-4 inhibitor Ipilimumab is superior to the respective monotherapies. However, use of these immunotherapies is frequently associated with, sometimes life-threatening, immune-related adverse events. Thus, more evidence-based studies are required to characterize the underlying mechanisms, towards more effective clinical management and treatment monitoring. Our study examines two sets of public adverse event data coming from FAERS and VigiBase, each with more than two thousand melanoma patients treated with Pembrolizumab. Standard disproportionality metrics are utilized to characterize the safety of Pembrolizumab and its reaction profile is compared to those of the widely used Ipilimumab and Nivolumab based on melanoma cases that report only one of them. Our results confirm known toxicological considerations for their related and distinct side-effect profiles and highlight specific immune-related adverse reactions. Our retrospective computational analysis includes more patients than examined in other studies and relies on evidence coming from public pharmacovigilance data that contain safety reports from clinical and controlled studies as well as reports of suspected adverse events coming from real-world post-marketing setting. Despite these informative insights, more prospective studies are necessary to fully characterize the efficacy of these agents.

Background: Control measures adopted during the COVID-19 pandemic had a considerable impact on human daily life and lifestyles. Adherence to the recommended measures is influenced by knowledge and attitudes towards the disease. This cross-sectional study aimed to assess the level of knowledge regarding COVID-19, the related control measures, and lifestyle behaviors adopted during the pandemic in a sample of elderly Italian people. Methods: A web-based questionnaire investigating socio-demographic characteristics, knowledge of COVID-19, the related preventive measures, and lifestyle changes that occurred during the pandemic, were distributed to ≥65 years old people living in South Italy. Results: A satisfactory level of knowledge about COVID-19 and the related control measures has been found in the enrolled sample. However, a decrease in physical activity, as well as worsening sleeping and dietary habits, were found in roughly 60% of participants. Females were impacted greater by these lifestyle changes. Conclusions: Participants in this study showed a good level of knowledge regarding COVID-19 and its prevention. Nevertheless, they reported an increase in unhealthy habits that may have important health consequences in the long term and should be addressed by public health interventions targeted at older people.

Metabolic Syndrome (MS) is characterized by a low-grade inflammatory state causing an alteration of non-invasive indexes derived from blood count, namely monocyte-to-HDL ratio (MHR), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR). We analyse a population of 771 subjects (394 controls and 377 MS patients) to evaluate the best predictive index of MS. The diagnosis of MS was made according to the 2006 criteria of the International Diabetes Federation (IDF). We performed ROC curve analyses to evaluate the best predictor index of MS. MHR cut-off value was used to classify the population in two different groups and to create the outcome variable of the Recursive Partitioning and Amalgamation (RECPAM) analysis. This method is a tree-structured approach that defines \"risk profiles\" for each group of dichotomous variables. We showed that MHR index is significantly linked to body mass index (BMI), waist circumference, creatinine, C-reactive protein (CRP), Erythrocyte Sedimentation Rate (ESR). ROC curve defined an MHR cut-off value of 6.4, which was able to identify two patient groups with significant differences in waist circumference, blood pressure, creatinine, estimated glomerular filtration rate and fasting plasma glucose. RECPAM analysis demonstrated that gender, BMI categorization and hyperglycaemia were the most important risk determinants of increased MHR index that can be considered bona fide a useful and easily obtainable tool to suggest the presence of peculiar metabolic features that predict MS.

In Italy, at the end of 2020, a voluntary immunization plan against COVID-19 was introduced, involving elderly among the first target categories. The aim of this study was to assess, through an online questionnaire, the acceptance of COVID-19 vaccination in a sample of older adults from southern Italy. Of a total of 1041 respondents (41.7% males, mean age 76.6 ± 6.5), 965 (92.7%) were vaccinated or willing to be vaccinated against COVID-19, although less than half of the sample was favorable to vaccinations and agreed with mandatory immunization. Acceptance of COVID-19 vaccination was found to be positively related with higher educational level (OR = 1.875, CI95% = 1.113–3.161; p = 0.018) and having social/mass media as a main source of information (OR = 2.415 CI95% = 1.358–4.296, p = 0.003). On the contrary, an inverse relationship was found between acceptance of COVID-19 vaccination and having fulfilled the questionnaire after the introduction of green pass (OR = 0.218, CI95% = 0.129–0.369; p < 0.001). Therefore, although this evidence needs to be further confirmed, it is possible to agree with previous studies reporting that compulsory measures, such as green pass implementation, must be accompanied by effective education and information strategies of the target population.

Chryseobacterium spp. are Gram-negative, opportunistic pathogens antibiotic-resistant commonly found in the environment. The aim of this study was to investigate potential sources of Chryseobacterium infections in healthcare settings by comparing clinical and environmental isolates using phenotypic and genotypic analyses. Between June and July 2023, six cases of infection with Chryseobacterium spp. were identified in a hospital in Apulia, southern Italy. Environmental sampling (air, surfaces and water) was performed in parallel with routine clinical investigations. Isolates were subjected to antibiotic susceptibility testing and genotypic analysis using Sanger and Next-Generation Sequencing. Five cases of Chryseobacterium spp. infection were recorded in the Gastroenterology Department (Pavilion A) and one in the Vertebral Surgery Department (Pavilion B). C. indologenes was identified in blood and tracheal aspirate samples using MALDI-TOF MS. Environmental analysis carried out in the pavilions A and B isolated C. indologenes from sink tap in Pavilion B. Subsequently, genome sequencing revealed that Chryseobacterium strains misidentified as C. indologenes were more closely related to C. arthrosphaerae . Genetic analysis confirmed the cluster hypothesis involving four patients from the pavilion A, while no genetic link was found between the environmental and clinical strains. Innovative molecular methods in clinical and environmental investigations have allowed more accurate identification of the etiologic agent and possibly tracing the source of infection in the nosocomial setting. Control measures, such as patient isolation and room disinfection, have prevented the spread of infection.

Ice consumption has widely increased over the last decade. Cases of ice contamination by various microorganisms (bacteria, viruses and fungi) have been documented in the literature. In this review, we summarize the findings of selected articles on the hygienic and sanitary quality of food ice from 1 January 2013 to 31 December 2023. A total of 14 articles found via the PubMed search engine during the study period were reviewed. From the comparison between the ice produced on an industrial scale and the ice produced on a local scale in food businesses, the latter was found to be more contaminated by microorganisms. The most detected bacteria included Escherichia coli, coliforms, Pseudomonas spp., Staphylococcus aureus; three studies evaluated the presence of Vibrio cholerae and Vibrio parahaemolyticus; two studies highlighted the presence of viruses (Rotavirus and Norovirus). Finally, two studies detected the presence of fungi (molds and yeasts). Almost all authors of the studies argued that ice contamination also depends on the hygienic–sanitary quality of the ice-making machines. The results show that the information currently available in the literature on the hygienic–sanitary quality of ice is incomplete and that future national and international scientific studies need to be carried out.