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Abstract A detailed knowledge of the decay properties of the so called Hoyle state in the $$^{12}$$ 12 C nucleus ( $$E_x=7.654$$ E x = 7.654 MeV, $$0^+$$ 0 + ) is required to calculate the rate at which carbon is forged in typical red-giant stars. This paper reports on a new almost background-free measurement of the radiative decay branching ratio of the Hoyle state using advanced charged particle coincidence techniques. The exploitation, for the first time in a similar experiment, of a bidimensional map of the coincidence efficiency allows to reach an unitary value and, consequently, to strongly reduce sources of systematic uncertainties. The present results suggest a value of the radiative branching ratio of $$\Gamma _{rad}/\Gamma _{tot}=4.2(6)\cdot 10^{-4}$$ Γ rad / Γ tot = 4.2 ( 6 ) · 10 - 4 . This finding helps to resolve the tension between recent data published in the literature.

Abstract Robotic literature widely addresses deformable object manipulation, but few studies analyzed human manipulation accounting for different levels of deformability and task properties. We asked participants to grasp and insert rigid and deformable objects into holes with varying tolerances and depths, and we analyzed the grasping behavior, the reaching velocity profile, and completion times. Results indicated that the more deformable the object is, the nearer the grasping point is to the extremity to be inserted. For insertions in the long hole, the selection of the grasping point is a trade-off between task accuracy and the number of re-grasps required to complete the insertion. The compliance of the deformable object facilitates the alignment between the object and the hole. The reaching velocity profile when increasing deformability recalls the one observed when task accuracy and precision decrease. Identifying human strategy allows the implementation of human-inspired high-level reasoning algorithms for robotic manipulation.

Abstract Modelling approaches play a crucial role in supporting local public health agencies by estimating and forecasting vector abundance and seasonality. However, the reliability of these models is contingent on the availability of standardized, high-quality data. Addressing this need, our study focuses on collecting and harmonizing egg count observations of the mosquito Aedes albopictus, obtained through ovitraps in monitoring and surveillance efforts across Albania, France, Italy, and Switzerland from 2010 to 2022. We processed the raw observations to obtain a continuous time series of ovitraps observations allowing for an extensive geographical and temporal coverage of Ae. albopictus population dynamics. The resulting post-processed observations are stored in the open-access database VectAbundance.This initiative addresses the critical need for accessible, high-quality data, enhancing the reliability of modelling efforts and bolstering public health preparedness.

Abstract Is Stochastic Gradient Descent (SGD) substantially different from Metropolis Monte Carlo dynamics? This is a fundamental question at the time of understanding the most used training algorithm in the field of Machine Learning, but it received no answer until now. Here we show that in discrete optimization and inference problems, the dynamics of an SGD-like algorithm resemble very closely that of Metropolis Monte Carlo with a properly chosen temperature, which depends on the mini-batch size. This quantitative matching holds both at equilibrium and in the out-of-equilibrium regime, despite the two algorithms having fundamental differences (e.g. SGD does not satisfy detailed balance). Such equivalence allows us to use results about performances and limits of Monte Carlo algorithms to optimize the mini-batch size in the SGD-like algorithm and make it efficient at recovering the signal in hard inference problems.

Abstract The Na+-Ca2+ exchanger (NCX1) is the dominant Ca2+ extrusion mechanism in cardiac myocytes. NCX1 activity is inhibited by intracellular Na+ via a process known as Na+-dependent inactivation. A central question is whether this inactivation plays a physiological role in heart function. Using CRISPR/Cas9, we inserted the K229Q mutation in the gene (Slc8a1) encoding for NCX1. This mutation removes the Na+-dependent inactivation while preserving transport properties and other allosteric regulations. NCX1 mRNA levels, protein expression, and protein localization are unchanged in K229Q male mice. However, they exhibit reduced left ventricular ejection fraction and fractional shortening, while displaying a prolonged QT interval. K229Q ventricular myocytes show enhanced NCX1 activity, resulting in action potential prolongation, higher incidence of aberrant action potentials, a faster decline of Ca2+ transients, and depressed cell shortening. The results demonstrate that NCX1 Na+-dependent inactivation plays an essential role in heart function by affecting both cardiac excitability and contractility.

Abstract The utilization of kidneys from donors with acute kidney injury (AKI) is often limited by unpredictable post-transplantation outcomes. The aim of our study was to identify protein mediators implicated in either recovery or failure of these organs. Forty kidney biopsies from donors with (20) and without AKI (20) were selected and then subdivided according to the post-transplant outcome defined as a threshold of 45 ml/min for the eGFR at 1 year from transplantation. Tissue homogenates were analysed by western blot to assess how the levels of 17 pre-selected proteins varied across the four groups. Samples from AKI kidneys with a poor outcome showed a fourfold increase in the levels of PPARg and twofold reduction of STAT1 compared to the other groups (p

Summary: Limited information exists regarding the impact of interferons (IFNs) on the information carried by extracellular vesicles (EVs). This study aimed at investigating whether IFN-α2b, IFN-β, IFN-γ, and IFN-λ1/2 modulate the content of EVs released by primary monocyte-derived macrophages (MDM). Small-EVs (sEVs) were purified by size exclusion chromatography from supernatants of MDM treated with IFNs. To characterize the concentration and dimensions of vesicles, nanoparticle tracking analysis was used. SEVs surface markers were examined by flow cytometry. IFN treatments induced a significant down-regulation of the exosomal markers CD9, CD63, and CD81 on sEVs, and a significant modulation of some adhesion molecules, major histocompatibility complexes and pro-coagulant proteins, suggesting IFNs influence biogenesis and shape the immunological asset of sEVs. SEVs released by IFN-stimulated MDM also impact lymphocyte function, showing significant modulation of lymphocyte activation and IL-17 release. Altogether, our results show that sEVs composition and activity are affected by IFN treatment of MDM.

Abstract This data descriptor presents a novel dataset collected using the quadrupedal robot ANYmal C in the Mediterranean coastal dune environment of the European Union (EU) habitats 2110 and 2120 in Sardinia, Italy. The dataset mainly consists of photos, videos, and point clouds of the coastal dunes, providing valuable information on the structure and composition of this habitat. The data was collected by a team of robotic engineers and plant scientists as result of a joint effort towards robotic habitat monitoring. The dataset is publicly available through Zenodo and can be used by researchers working in both the fields of robotics and habitat ecology and conservation. The availability of this dataset has the potential to inform future research and conservation efforts in the EU habitats 2110 and 2120, and it highlights the importance of interdisciplinary collaboration in the field of habitat monitoring. This paper serves as a comprehensive description of the dataset and the methods used to collect it, making it a valuable resource for the scientific community.

Abstract The diffuse presence of small copper ore deposits in the Alpine area, mostly exploited since Late Medieval times, led most scholars to assume that these deposits may actually be active much earlier and that many of the circulating prehistoric metal objects found in the area were produced with local copper sources. This assumption was recently validated for the Recent Bronze Age through the use of lead isotope tracers, and well supported by the archaeometallurgical evidences found in the South-Eastern Alps. However, the scarcity of available lead isotope data for pre-Bronze Age metals precluded to date the reconstruction of the metal flow through the Late Neolithic and Eneolithic (or Copper Age). Based on 49 new analyses of important archaeological objects from the Alpine region, the Po River Valley and Central Italy, mostly axes dated from the Late Neolithic to the Late Eneolithic, here we show that the diffusion of copper in Northern Italy (approximately 4500–2200 BC) includes three major periods of metal use and/or production, each related to specific ore sources. The South Alpine copper was massively used only starting from the middle of the 3rd millennium BC, in connection or slightly earlier than the Beaker event.

Abstract The study aimed to assess the metabolomic profile of the synovial fluid (SF) of dogs affected by spontaneous osteoarthritis (OA) and compare any differences based on disease progression. Sixty client-owned dogs affected by spontaneous OA underwent clinical, radiographic, and cytologic evaluations to confirm the diagnosis. The affected joints were divided into four study groups based on the Kallgreen–Lawrence classification: OA1 (mild), OA2 (moderate), OA3 (severe), and OA4 (extremely severe/deforming). The osteoarthritic joint’s SF was subjected to cytologic examination and 1H-NMR analysis. The metabolomic profiles of the study groups’ SF samples were statistically compared using one-way ANOVA. Sixty osteoarthritic joints (45 stifles, 10 shoulders and 5 elbows) were included in the study. Fourteen, 28, and 18 joints were included in the OA1, OA2, and OA3 groups, respectively (0 joints in the OA4 group). Metabolomic analysis identified 48 metabolites, five of which were significantly different between study groups: Mannose and betaine were elevated in the OA1 group compared with the OA2 group, and the 2-hydroxyisobutyrate concentration decreased with OA progression; in contrast, isoleucine was less concentrated in mild vs. moderate OA, and lactate increased in severe OA. This study identified different 1H-NMR metabolomic profiles of canine SF in patients with progressive degrees of spontaneous OA, suggesting 1H-NMR metabolomic analysis as a potential alternative method for monitoring OA progression. In addition, the results suggest the therapeutic potentials of the metabolomic pathways that involve mannose, betaine, 2-hydroxyisobutyrate, isoleucine, and lactate.

Abstract The surveying of European Union (EU) Annex I habitat “8110 - Siliceous scree of the montane to snow levels (Androsacetalia alpinae and Galeopsietalia ladani)” is generally executed by humans. However, robots could increase human monitoring capabilities. To this end, we collected information on this habitat employing the quadrupedal robot ANYmal C. These data include videos of eight different typical or early warning species. Additionally, data on four relevés are provided. These consist, for instance, of the robot state, and videos and pictures collected to evaluate the habitat conservation status. The aim of this dataset is to help researchers in a variety of fields. For instance, information on plant species collected by the robot can be utilized to develop new procedures and new metrics to assess the habitat conservation status or to train neural networks for plant classification. On the other hand, engineers can use robot state information to validate their algorithms. This database is publicly available in the provided Zenodo repository.

Abstract Effective monitoring of habitats is crucial for their preservation. As the impact of anthropic activities on natural habitats increases, accurate and up-to-date information on the state of ecosystems has become imperative. This paper presents a new dataset collected from the forests located in the Tuscan Apennines (Italy) using the ANYmal robot. The dataset provides information regarding the structure and composition of the EU priority habitat 9210*. The dataset, which is publicly available through a Zenodo repository, includes photos, videos, and point clouds of the environment. This dataset is a valuable resource for the scientific community working in the field of forest ecology and conservation and has the potential to inform future research and conservation efforts on habitat 9210*. The collaboration between robotic engineers and plant scientists provides a unique perspective on the forest ecosystem and underscores the potential for interdisciplinary work in this field. This dataset constitutes an important contribution to the ongoing effort to monitor and conserve habitats globally, particularly in light of the challenges posed by global changes.

Abstract Ecosystem restoration has traditionally focused on re-establishing vegetation and other foundation species at basal trophic levels, with mixed outcomes. Here, we show that threatened shorebirds could be important to restoring coastal wetland multifunctionality. We carried out surveys and manipulative field experiments in a region along the Yellow Sea affected by the invasive cordgrass Spartina alterniflora. We found that planting native plants alone failed to restore wetland multifunctionality in a field restoration experiment. Shorebird exclusion weakened wetland multifunctionality, whereas mimicking higher predation before shorebird population declines by excluding their key prey – crab grazers – enhanced wetland multifunctionality. The mechanism underlying these effects is a simple trophic cascade, whereby shorebirds control crab grazers that otherwise suppress native vegetation recovery and destabilize sediments (via bioturbation). Our findings suggest that harnessing the top-down effects of shorebirds – through habitat conservation, rewilding, or temporary simulation of consumptive or non-consumptive effects – should be explored as a nature-based solution to restoring the multifunctionality of degraded coastal wetlands.

Tidal creeks play a vital role in influencing geospatial evolution and marsh ecological communities in coastal landscapes. However, evaluating the geospatial characteristics of numerous creeks across a site and understanding their ecological relationships pose significant challenges due to the labor-intensive nature of manual delineation from imagery. Traditional methods rely on manual annotation in GIS interfaces, which is slow and tedious. This study explores the application of Attention-based Dense U-Net (ADU-Net), a deep learning image segmentation model, for automatically classifying creek pixels in high-resolution (0.5 m) orthorectified aerial imagery in coastal Georgia, USA. We observed that ADU-Net achieved an outstanding F1 score of 0.98 in identifying creek pixels, demonstrating its ability in tidal creek mapping. The study highlights the potential of deep learning models for automated tidal creek mapping, opening avenues for future investigations into the role of creeks in marshes’ response to environmental changes.

Stimuli-responsive microgels have attracted great interest in recent years as building blocks for fabricating smart surfaces with many technological applications. In particular, PNIPAM microgels are promising candidates for creating thermo-responsive scaffolds to control cell growth and detachment via temperature stimuli. In this framework, understanding the influence of the solid substrate is critical for tailoring microgel coatings to specific applications. The surface modification of the substrate is a winning strategy used to manage microgel–substrate interactions. To control the spreading of microgel particles on a solid surface, glass substrates are coated with a PEI or an APTES layer to improve surface hydrophobicity and add positive charges on the interface. A systematic investigation of PNIPAM microgels spin-coated through a double-step deposition protocol on pristine glass and on functionalised glasses was performed by combining wettability measurements and Atomic Force Microscopy. The greater flattening of microgel particles on less hydrophilic substrates can be explained as a consequence of the reduced shielding of the water–substrate interactions that favors electrostatic interactions between microgels and the substrate. This approach allows the yielding of effective control on microgel coatings that will help to unlock new possibilities for their application in biomedical devices, sensors, or responsive surfaces.

Abstract Despite the remarkable growth of the global market for robotics, robotic monitoring of habitats is still an understudied topic. This is true, among others, for the species-rich EU Annex I habitat “6210 - Semi-natural grasslands and scrubland facies on calcareous substrates”. This habitat is typically surveyed by human operators. In this work, we present a dataset concerning relevés performed through the quadrupedal robot ANYmal C. The dataset contains information from three plots, which include the robot state, videos, and images acquired to assess the habitat conservation status. Additionally, a collection of videos and pictures about two typical and one early warning species of habitat 6210 is also presented. This database is publicly available in the provided Zenodo repository and will aid researchers in several fields. Robot state information can be used by engineers to validate their algorithms, while data gathered by the robot can be used to design new methodologies and new metrics to assess the habitat conservation status or train/test classifiers (e.g. neural networks) for plant classification.

Summary: Muscular dystrophies (MDs) are incurable genetic myopathies characterized by progressive degeneration of skeletal muscles. Dystrophic mice lacking the transcription factor Nfix display morphological and functional improvements of the disease. Recently, we demonstrated that MAPK signaling pathway positively regulates Nfix in muscle development and that Cyanidin, a natural antioxidant molecule, strongly ameliorates the pathology. To explore a synergistic approach aimed at treating MDs, we administered Trametinib, a clinically approved MEK inhibitor, alone or combined with Cyanidin to adult Sgca null mice. We observed that chronic treatment with Trametinib and Cyanidin reduced Nfix in myogenic cells but, unexpectedly, caused ectopic calcifications exclusively in dystrophic muscles. The combined treatment with Cyanidin resulted in histological improvements by preventing Trametinib-induced calcifications in Diaphragm and Soleus. Collectively, this first pilot study revealed that Nfix is modulated by the MAPK pathway in MDs, and that Cyanidin partly rescued the unexpected ectopic calcifications caused by MEK inhibition.

Abstract Familial Hypercholesterolemia (FH) is characterized by an increase in Low-Density Lipoprotein Cholesterol (LDL-C) and by premature Cardiovascular Disease (CVD). However, it remains to be fully elucidated if FH impairs cholesterol efflux capacity (CEC), and whether CEC is related to lipoprotein subfraction distribution. This study aimed at comparing FH patients and age, sex and BMI matched controls in terms of LDL and HDL subfraction distribution as well as CEC. Forty FH patients and 80 controls, matched for age, sex and BMI, were enrolled in this case–control study. LDL and HDL subfractions were analyzed using the Quantimetrix Lipoprint System. CEC was evaluated as aq-CEC and ABCA1-CEC. FH subjects showed a significantly higher concentration of all LDL subfractions, and a shift from large to small HDL subfraction pattern relative to controls. FH subjects with previous CVD event had smaller LDL lipoproteins than controls and FH subjects without previous CVD event. Both aq-CEC and ABCA1-CEC were increased in FH patients with respect to controls. To conclude, FH subjects had a metabolic profile characterized not only by higher LDL-C but also by shift from large to small HDL subfraction phenotype. However, FH subjects showed an increase CEC than controls.

Abstract Tumour DNA sequencing is essential for precision medicine since it guides therapeutic decisions but also fosters the identification of patients who may benefit from germline testing. Notwithstanding, the tumour-to-germline testing workflow presents a few caveats. The low sensitivity for indels at loci with sequences of identical bases (homopolymers) of ion semiconductor-based sequencing techniques represents a well-known limitation, but the prevalence of indels overlooked by these techniques in high-risk populations has not been investigated. In our study, we addressed this issue at the homopolymeric regions of BRCA1/2 in a retrospectively selected cohort of 157 patients affected with high-grade ovarian cancer and negative at tumour testing by ION Torrent sequencing. Variant allele frequency (VAF) of indels at each of the 29 investigated homopolymers was systematically revised with the IGV software. Thresholds to discriminate putative germline variants were defined by scaling the VAF to a normal distribution and calculating the outliers that exceeded the mean + 3 median-adjusted deviations of a control population. Sanger sequencing of the outliers confirmed the occurrence of only one of the five putative indels in both tumour and blood from a patient with a family history of breast cancer. Our results indicated that the prevalence of homopolymeric indels overlooked by ion semiconductor techniques is seemingly low. A careful evaluation of clinical and family history data would further help minimise this technique-bound limitation, highlighting cases in which a deeper look at these regions would be recommended.

Abstract The p140Cap adaptor protein is a tumor suppressor in breast cancer associated with a favorable prognosis. Here we highlight a function of p140Cap in orchestrating local and systemic tumor-extrinsic events that eventually result in inhibition of the polymorphonuclear myeloid-derived suppressor cell function in creating an immunosuppressive tumor-promoting environment in the primary tumor, and premetastatic niches at distant sites. Integrative transcriptomic and preclinical studies unravel that p140Cap controls an epistatic axis where, through the upstream inhibition of β-Catenin, it restricts tumorigenicity and self-renewal of tumor-initiating cells limiting the release of the inflammatory cytokine G-CSF, required for polymorphonuclear myeloid-derived suppressor cells to exert their local and systemic tumor conducive function. Mechanistically, p140Cap inhibition of β-Catenin depends on its ability to localize in and stabilize the β-Catenin destruction complex, promoting enhanced β-Catenin inactivation. Clinical studies in women show that low p140Cap expression correlates with reduced presence of tumor-infiltrating lymphocytes and more aggressive tumor types in a large cohort of real-life female breast cancer patients, highlighting the potential of p140Cap as a biomarker for therapeutic intervention targeting the β-Catenin/ Tumor-initiating cells /G-CSF/ polymorphonuclear myeloid-derived suppressor cell axis to restore an efficient anti-tumor immune response.

Abstract Cardiovascular complications after lower extremity revascularization (LER) are common in diabetic patients with peripheral arterial disease (PAD) and chronic limb threatening ischemia (CLTI). The Klotho-fibroblast growth factor 23 (FGF23) axis is associated with endothelial injury and cardiovascular risk. We aimed to analyze the relationship between Klotho and FGF23 serum levels and the incidence of major adverse cardiovascular events (MACE) and major adverse limb events (MALE) after LER in diabetic patients with PAD and CLTI. Baseline levels of Klotho and FGF23, and their association with subsequent incidence of MACE and MALE were analyzed in a prospective, non-randomized study in a population of diabetic patients with PAD and CLTI requiring LER. A total of 220 patients were followed for 12 months after LER. Sixty-three MACE and 122 MALE were recorded during follow-up period. Baseline lower Klotho serum levels (295.3 ± 151.3 pg/mL vs. 446.4 ± 171.7 pg/mL, p

Epibiont communities can be used as useful ecological indicators, providing information on the ecology and health conditions of their hosts. In this study, we analyzed the cirriped community from a total of 117 dead specimens of Caretta caretta (Linnaeus, 1758) collected in the north Adriatic between the years 2020 and 2022. We recorded a total of six different species distributed in five genera of cirripeds. The two most abundant species were Chelonibia testudinaria (Linnaeus, 1758) and Platylepas hexastylos (Linnaeus, 1758), located in different areas of the body; the former mainly on the carapace, while the latter mainly on the skin. We analyzed their abundance and distribution pattern on the sea turtle’s body and used the findings to deduce the health conditions and ecological aspects of stranded specimens of C. caretta, providing new data on this threatened and vulnerable species and its epibionts. A total of 11 specimens of C. caretta were affected by DTS (Debilitative Turtle Syndrome), these specimens exhibited a significant barnacle infestation on all body parts, markedly higher than the specimens of C. caretta not affected by DTS. Studies of associated barnacles in sea turtles should be encouraged among researchers as complementary tool to infer habitat use and health status of sea turtle species.

The contribution of animal ecosystem engineers to coastal geomorphological processes is often neglected. Here, the authors combine observational, experimental and modelling work to demonstrate that ecosystem engineering by mussels is a much stronger driver of salt marsh accretion rates than expected.

High-fat diet (HFD) increases the risk of insulin resistance and non-alcoholic steatohepatitis (NASH). Here the authors report that the heat shock proteins HSP70 and GRP78 are increased in the jejunum of rats on HFD, and their continuous infusion leads insulin resistance and NASH, while in rats on a high-fat diet infused with monoclonal antibodies against HSP70 and GRP78 these phenotypes are reversed.

Summary: The cardiac fibroblast interacts with an extracellular matrix (ECM), enabling myofibroblast maturation via a process called mechanosensing. Although in the aging male heart, ECM is stiffer than in the young mouse, myofibroblast development is impaired, as demonstrated in 2-D and 3-D experiments. In old male cardiac fibroblasts, we found a decrease in actin polymerization, α-smooth muscle actin (α-SMA), and Kindlin-2 expressions, the latter an effector of the mechanosensing. When Kindlin-2 levels were manipulated via siRNA interference, young fibroblasts developed an old-like fibroblast phenotype, whereas Kindlin-2 overexpression in old fibroblasts reversed the defective phenotype. Finally, inhibition of overactivated extracellular regulated kinases 1 and 2 (ERK1/2) in the old male fibroblasts rescued actin polymerization and α-SMA expression. Pathological ERK1/2 overactivation was also attenuated by Kindlin-2 overexpression. In contrast, old female cardiac fibroblasts retained an operant mechanosensing pathway. In conclusion, we identified defective components of the Kindlin/ERK/actin/α-SMA mechanosensing axis in aged male fibroblasts.

We present a genome assembly of Caretta caretta (the Loggerhead sea turtle; Chordata, Testudines, Cheloniidae), generated from genomic data from two unrelated females. The genome sequence is 2.13 gigabases in size. The assembly has a busco completion score of 96.1% and N50 of 130.95 Mb. The majority of the assembly is scaffolded into 28 chromosomal representations with a remaining 2% of the assembly being excluded from these.

Macrocycles have potential as therapeutics, but their libraries are currently not large enough for high-throughput screening. Here, the authors show a combinatorial approach to generate a library of almost 20’000 macrocycles by conjugating carboxylic-acid fragments to macrocyclic scaffolds, identifying nanomolar inhibitors against thrombin and binders of MDM2.

Abstract Phosphatidylinositol 4-kinases (PI4Ks) are the first enzymes that commit phosphatidylinositol into the phosphoinositide pathway. Here, we show that Arabidopsis thaliana seedlings deficient in PI4Kβ1 and β2 have several developmental defects including shorter roots and unfinished cytokinesis. The pi4kβ1β2 double mutant was insensitive to exogenous auxin concerning inhibition of root length and cell elongation; it also responded more slowly to gravistimulation. The pi4kß1ß2 root transcriptome displayed some similarities to a wild type plant response to auxin. Yet, not all the genes displayed such a constitutive auxin-like response. Besides, most assessed genes did not respond to exogenous auxin. This is consistent with data with the transcriptional reporter DR5-GUS. The content of bioactive auxin in the pi4kß1ß2 roots was similar to that in wild-type ones. Yet, an enhanced auxin-conjugating activity was detected and the auxin level reporter DII-VENUS did not respond to exogenous auxin in pi4kß1ß2 mutant. The mutant exhibited altered subcellular trafficking behavior including the trapping of PIN-FORMED 2 protein in rapidly moving vesicles. Bigger and less fragmented vacuoles were observed in pi4kß1ß2 roots when compared to the wild type. Furthermore, the actin filament web of the pi4kß1ß2 double mutant was less dense than in wild-type seedling roots, and less prone to rebuilding after treatment with latrunculin B. A mechanistic model is proposed in which an altered PI4K activity leads to actin filament disorganization, changes in vesicle trafficking, and altered auxin homeostasis and response resulting in a pleiotropic root phenotypes.

Background: Aedes albopictus, the Asian tiger mosquito, has become a prevalent pest in Italy, causing severe nuisance and posing a threat of transmission of arboviruses introduced by infected travelers. In this study, we investigated the influence of weather parameters on the seasonal population density of Aedes albopictus. Methods: A Bayesian approach was employed to identify the best meteorological predictors of species trend, using the eggs collected monthly from 2010 to 2022 by the Emilia-Romagna regional monitoring network. Results: The findings show that the winter–spring period (January to May) plays a crucial role in the size of the first generation and seasonal development of the species. Conclusions: A temperate winter and a dry and cold March, followed by a rainy and hot spring and a rainy July, seem to favor the seasonal development of Ae. albopictus.

Species interactions that can enhance habitat heterogeneity such as facilitation cascades of foundation species have been overlooked in biodiversity models. This study conducted 22 geographically distributed experiments in different ecosystems and biogeographical regions to assess the extent to which biodiversity is explained by three axes of habitat heterogeneity in facilitation cascades.

Organ-on-a-chip platforms are utilized in global bioanalytical and toxicological studies as a way to reduce materials and increase throughput as compared to in vivo based experiments. These platforms bridge the infrastructure and regulatory gaps between in vivo animal work and human systems, with models that exemplify active biological pathways. In conjunction with the advent of increased capabilities associated with next generation sequencing and mass spectrometry based '-omic' technologies, organ-on-a-chip platforms provide an excellent opportunity to investigate the global changes at multiple biological levels, including the transcriptome, proteome and metabolome. When investigated concurrently, a complete profile of cellular and regulatory perturbations can be characterized following treatment with specific agonists. In this study, global effects were observed and analyzed following liver chip exposure to the chemical warfare agent, VX. Even though the primary mechanism of action of VX (i.e. acetylcholinesterase inhibition) is well characterized, recent in vivo studies suggest additional protein binding partners that are implicated in metabolism and cellular energetic pathways. In addition, secondary toxicity associated with peripheral organ systems, especially in human tissues, is not well defined. Our results demonstrate the potential of utilizing an organ-on-a-chip platform as a surrogate system to traditional in vivo studies. This is realized by specifically indicating significant dysregulation of several cellular processes in response to VX exposure including but not limited to amino acid synthesis, drug metabolism, and energetics pathways.

Perturbations of the cardiopharyngeal mesoderm can lead to congenital defects in individuals with 22q11.2 deletion syndrome. Here the authors use single cell RNA-sequencing to identify a multilineage primed population within the mesoderm, marked by Tbx1, which has bipotent properties to form cardiac and branchiomeric muscle cells.

The vascular endothelium contributes to metabolic regulation, however, the underlying mechanisms are not fully understood. Here the authors show that endothelial low-density lipoprotein receptor-related protein 1 regulates glucose homeostasis via osteocalcin expression.

The COVID-19 pandemic had major impacts on the seafood supply chain, also reducing fishing activity. It is worth asking if the fish stocks in the Mediterranean Sea, which in most cases have been in overfishing conditions for many years, may have benefitted from the reduction in the fishing pressure. The present work is the first attempt to make a quantitative evaluation of the fishing effort reduction due to the COVID-19 pandemic and, consequently, its impact on Mediterranean fish stocks, focusing on Adriatic Sea subareas. Eight commercially exploited target stocks (common sole, common cuttlefish, spottail mantis shrimp, European hake, red mullet, anchovy, sardine, and deepwater pink shrimp) were evaluated with a surplus production model, separately fitting the data for each stock until 2019 and until 2020. Results for the 2019 and 2020 models in terms of biomass and fishing mortality were statistically compared with a bootstrap resampling technique to assess their statistical difference. Most of the stocks showed a small but significant improvement in terms of both biomass at sea and reduction in fishing mortality, except cuttlefish and pink shrimp, which showed a reduction in biomass at sea and an increase in fishing mortality (only for common cuttlefish). After reviewing the potential co-occurrence of environmental and management-related factors, we concluded that only in the case of the common sole can an effective biomass improvement related to the pandemic restrictions be detected, because it is the target of the only fishing fleet whose activity remained far lower than expectations for the entire 2020.

Despite their recognized primary importance, marine coastal ecosystems around the globe are currently under threat, being subject to continuous local and global anthropogenic stressors. In this frame, understanding the response of coastal habitat-forming species to multiple stressors and their resilience is fundamental for the sustainable management of coastal ecosystems. In the present study, to provide some glimpses in this direction, we explored the response of the Anemonia viridis-associated microbiota to the combined anthropogenic stressors, which typically affect touristic hotspots at Mediterranean coastal sites. To this aim, two case studies have been carried out, the first in the Riccione coastal site (Italy, Center Mediterranean) and the second at Cap de Creus (Spain, North-western Mediterranean), where the A. viridis microbiota was assessed under the conditions of both high and low anthropogenic pressure. According to our findings, the A. viridis microbiota showed a relevant degree of plasticity in response to combined anthropogenic and environmental stressors, with changes that also mirrored variations in the surrounding seawater, thus indicating a close connection with the environment, from which potential symbiotic partners are selected. However, this potentially adaptive process also has a limitation, as observed in the highly anthropogenic impact site of Cap de Creus, where A. viridis-associated microbiota appeared completely unstructured, as demonstrated by an increased dispersion according to the Anna Karenina principle. This raises the question about the resilience of the A. viridis-associated microbiota under combined climate and anthropogenic threats, as well as of the anthropogenic factors driving the observed dysbiosis changes.

Abstract Human in vitro models of neural tissue with tunable microenvironment and defined spatial arrangement are needed to facilitate studies of brain development and disease. Towards this end, embedded printing inside granular gels holds great promise as it allows precise patterning of extremely soft tissue constructs. However, granular printing support formulations are restricted to only a handful of materials. Therefore, there has been a need for novel materials that take advantage of versatile biomimicry of bulk hydrogels while providing high‐fidelity support for embedded printing akin to granular gels. To address this need, Authors present a modular platform for bioengineering of neuronal networks via direct embedded 3D printing of human stem cells inside Self‐Healing Annealable Particle‐Extracellular matrix (SHAPE) composites. SHAPE composites consist of soft microgels immersed in viscous extracellular‐matrix solution to enable precise and programmable patterning of human stem cells and consequent generation mature subtype‐specific neurons that extend projections into the volume of the annealed support. The developed approach further allows multi‐ink deposition, live spatial and temporal monitoring of oxygen levels, as well as creation of vascular‐like channels. Due to its modularity and versatility, SHAPE biomanufacturing toolbox has potential to be used in applications beyond functional modeling of mechanically sensitive neural constructs.

Small-scale fisheries (SSFs) play essential economic, social, and cultural roles for many fleets in the Atlantic region. The basis of fisheries assessment and management is the landings reported by observers or fishers. Even though the information from the landings is essential, it can be subject to a fisher’s bias, such as the tendency to inflate catches and the refusal to fill the logs. The feasibility for managers using field surveys to validate these datasets is held up by the high costs, shortage in monitoring, and the lack of prior information. Alternatively, Benford analysis overcomes those limitations since it can be applied directly on the logbook data. This method is growing in popularity, underlining its suitability to many economic and biological fields. Hence, in this study, we inspected small-scale fisheries data by the Benford’s distribution, aiming to validate fish landing data from 27 points in Brazil’s northeastern region over 3 years. Our results suggest that 20% of landings data are considered highly imprecise (misinformation), especially from non-motorized canoes. Also, harbors in remote locations provide poorer quality data, specifically monthly catch values reported by several boats. The way we mine our data affects the sensitivity of the analysis, with monthly data being less prone to be accessed by this method than daily information. As the results match our prior knowledge on the location, we endorse the suitability of the method and reliability for assessing accuracy in fishing data. Hence, we recommend that it ought to be used as an audit tool for SSF landing data aiming to enlighten data reliance and support managers for planning management actions.

Abstract ZFP57 is required to maintain the germline-marked differential methylation at imprinting control regions (ICRs) in mouse embryonic stem cells (ESCs). Although DNA methylation has a key role in genomic imprinting, several imprinted genes are controlled by different mechanisms, and a comprehensive study of the relationship between DMR methylation and imprinted gene expression is lacking. To address the latter issue, we differentiated wild-type and Zfp57 -/- hybrid mouse ESCs into neural precursor cells (NPCs) and evaluated allelic expression of imprinted genes. In mutant NPCs, we observed a reduction of allelic bias of all the 32 genes that were imprinted in wild-type cells, demonstrating that ZFP57-dependent methylation is required for maintaining or acquiring imprinted gene expression during differentiation. Analysis of expression levels showed that imprinted genes expressed from the non-methylated chromosome were generally up-regulated, and those expressed from the methylated chromosome were down-regulated in mutant cells. However, expression levels of several imprinted genes acquiring biallelic expression were not affected, suggesting the existence of compensatory mechanisms that control their RNA level. Since neural differentiation was partially impaired in Zfp57-mutant cells, this study also indicates that imprinted genes and/or non-imprinted ZFP57-target genes are required for proper neurogenesis in cultured ESCs.

The 13th Banff Conference on Allograft Pathology was held in Vancouver, British Columbia, Canada from October 5 to 10, 2015. The cardiac session was devoted to current diagnostic issues in heart transplantation with a focus on antibody-mediated rejection (AMR) and small vessel arteriopathy. Specific topics included the strengths and limitations of the current rejection grading system, the central role of microvascular injury in AMR and approaches to semiquantitative assessment of histopathologic and immunophenotypic indicators, the role of AMR in the development of cardiac allograft vasculopathy, the important role of serologic antibody detection in the management of transplant recipients, and the potential application of new molecular approaches to the elucidation of the pathophysiology of AMR and potential for improving the current diagnostic system. Herein we summarize the key points from the presentations, the comprehensive, open and wide-ranging multidisciplinary discussion that was generated, and considerations for future endeavors.

Abstract Despite international regulation, polychlorinated biphenyls (PCBs) are routinely detected at levels threatening human and environmental health. While previous research has emphasized trophic transfer as the principle pathway for PCB accumulation, our study reveals the critical role that non-trophic interactions can play in controlling PCB bioavailability and biomagnification. In a 5-month field experiment manipulating saltmarsh macro-invertebrates, we show that suspension-feeding mussels increase concentrations of total PCBs and toxic dioxin-like coplanars by 11- and 7.5-fold in sediment and 10.5- and 9-fold in cordgrass-grazing crabs relative to no-mussel controls, but do not affect PCB bioaccumulation in algae-grazing crabs. PCB homolog composition and corroborative dietary analyses demonstrate that mussels, as ecosystem engineers, amplify sediment contamination and PCB exposure for this burrowing marsh crab through non-trophic mechanisms. We conclude that these ecosystem engineering activities and other non-trophic interactions may have cascading effects on trophic biomagnification pathways, and therefore exert strong bottom-up control on PCB biomagnification up this coastal food web.

Type 2 diabetes is associated with chronic inflammation and is characterized by insulin resistance. Here, the authors identify a crucial role for endothelial BMPER function in glucose homeostasis, and BMPER overexpression was shown to alleviate insulin resistance and hyperglycemia in diabetic mice.

Abstract We used agnostic, unsupervised machine learning to cluster a large clinical database of information on infants admitted to neonatal units in England. Our aim was to obtain insights into nutritional practice, an area of central importance in newborn care, utilising the UK National Neonatal Research Database (NNRD). We performed clustering on time-series data of daily nutritional intakes for very preterm infants born at a gestational age less than 32 weeks (n = 45,679) over a six-year period. This revealed 46 nutritional clusters heterogeneous in size, showing common interpretable clinical practices alongside rarer approaches. Nutritional clusters with similar admission profiles revealed associations between nutritional practice, geographical location and outcomes. We show how nutritional subgroups may be regarded as distinct interventions and tested for associations with measurable outcomes. We illustrate the potential for identifying relationships between nutritional practice and outcomes with two examples, discharge weight and bronchopulmonary dysplasia (BPD). We identify the well-known effect of formula milk on greater discharge weight as well as support for the plausible, but insufficiently evidenced view that human milk is protective against BPD. Our framework highlights the potential of agnostic machine learning approaches to deliver clinical practice insights and generate hypotheses using routine data.

Abstract CSF shunting with adjustable valve is the treatment of idiopathic normal pressure hydrocephalus. The opening pressure valve setting is left to the neurosurgeon’s experience. Aqueductal CSF stroke volume by phase-contrast magnetic resonance measures the CSF passing through the Sylvian aqueduct and it changes with intracranial hydrodynamics. We sought to identify a window of stroke volume differences associated with the best clinical outcome and lowest rate of complications. The records of 69 patients were reviewed. At every clinical check, stroke volume, opening pressure valve, clinical outcome, and CSF overdrainage were analyzed. The correlation between stroke volume differences and negative outcome was also analyzed. The median follow-up was 2.3 years (range 0.3–10.4 years). The odds of negative outcome between two consecutive checks significantly increased by 16% (95%CI 4–28%, p = 0.006). Taking the lowest risk group as reference, the odds ratio of negative outcome was 1.16 (95%CI 0.51–2.63, p = 0.726) for SV differences less than − 37.6 µL, while it was 1.96 (95%CI 0.97–3.98, p = 0.062) for stroke volume changes above + 23.1 µL. Maintaining stroke volume values within a definite range might help maximize clinical benefit and avoid the risk of CSF overdrainage.

Three-dimensional modeling and non-invasive diagnosis are fundamental prerequisites for planning reliable assessments of the seismic vulnerability, renovation and conservation of heritage buildings. In the case of multi-layered, huge and complex ancient constructions, various problems can be encountered in the early design phases of interventions, among which there is often a lack of an adequate building documentation. Such issues include drawings that are without a metric scale, not detailed, not updated or not reflecting the real situation. In addition, the fragility of these constructions requires an accurate census of every sign of deterioration in order to prepare an ad hoc intervention for the site. As an example, in this paper, the results of a survey regarding the Patriarchal Basilica of Santa Maria Assunta (Aquileia, Italy) are reported. The basilica has a rich history of about two thousand years. in which each era has marked the actual architectural layout with its own culture and art. The result is an intricate association of complementary and/or interdependent elements that make the building very complex. Given the need to obtain accurate documentation, a realistic representation and a simulation of the criticalities of the structure, which previously did not exist or were not sufficiently accurate, a multi-methodological and multi-scale diagnosis was performed. In detail, the ground-penetrating radar (GPR) technique was applied to verify the presence of structures still buried under some internal surfaces, and a topographic survey, terrestrial laser scanning (TLS), and structure for motion (SfM) aerial and terrestrial photogrammetry were integrated for the detailed survey of the entire internal and external macro-structure. The resulting outcome provided the comprehensive information needed for preparing projects for the preservation, management and restoration of the basilica and the buildings connected to it.

Abstract Facioscapulohumeral muscular dystrophy (FSHD) is a myopathy with prevalence of 1 in 20,000. Almost all patients affected by FSHD carry deletions of an integral number of tandem 3.3 kilobase repeats, termed D4Z4, located on chromosome 4q35. Assessment of size of D4Z4 alleles is commonly used for FSHD diagnosis. However, the extended molecular testing has expanded the spectrum of clinical phenotypes. In particular, D4Z4 alleles with 9–10 repeat have been found in healthy individuals, in subjects with FSHD or affected by other myopathies. These findings weakened the strict relationship between observed phenotypes and their underlying genotypes, complicating the interpretation of molecular findings for diagnosis and genetic counseling. In light of the wide clinical variability detected in carriers of D4Z4 alleles with 9–10 repeats, we applied a standardized methodology, the Comprehensive Clinical Evaluation Form (CCEF), to describe and characterize the phenotype of 244 individuals carrying D4Z4 alleles with 9–10 repeats (134 index cases and 110 relatives). The study shows that 54.5% of index cases display a classical FSHD phenotype with typical facial and scapular muscle weakness, whereas 20.1% present incomplete phenotype with facial weakness or scapular girdle weakness, 6.7% display minor signs such as winged scapula or hyperCKemia, without functional motor impairment, and 18.7% of index cases show more complex phenotypes with atypical clinical features. Family studies revealed that 70.9% of relatives carrying 9–10 D4Z4 reduced alleles has no motor impairment, whereas a few relatives (10.0%) display a classical FSHD phenotype. Importantly all relatives of index cases with no FSHD phenotype were healthy carriers. These data establish the low penetrance of D4Z4 alleles with 9–10 repeats. We recommend the use of CCEF for the standardized clinical assessment integrated by family studies and further molecular investigation for appropriate diagnosis and genetic counseling. Especially in presence of atypical phenotypes and/or sporadic cases with all healthy relatives is not possible to perform conclusive diagnosis of FSHD, but all these cases need further studies for a proper diagnosis, to search novel causative genetic defects or investigate environmental factors or co-morbidities that may trigger the pathogenic process. These evidences are also fundamental for the stratification of patients eligible for clinical trials. Our work reinforces the value of large genotype–phenotype studies to define criteria for clinical practice and genetic counseling in rare diseases.

Cryopreservation is standard protocol prior to using NK cells in immunotherapy. Here the authors show that cryopreservation substantially reduces the clinical utility of these cells owing to a defect in their motility, an effect that might account for failure to treat some cancers with NK cell immunotherapy.

Coastal restoration tends to be failure-prone and expensive. Temmink and colleagues improve seagrass and cordgrass transplant survival in field experiments using biodegradable structures which temporarily mimic self-facilitation occurring in mature vegetation stands, and combine onsite and laboratory measurements on sediment stability and stem movement to test the biophysical mechanisms.