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As the global population continues to grow, so does the demand for energy resources. As a consequence, using renewable energy sources as an alternative to fossil fuels has become mandatory to reduce the environmental footprint of the energy sector. Biofuels represent a renewable source of energy, but their production has raised concerns regarding their possible impacts on food security. Indeed, the current biofuel production primarily relies on food crops and arable lands. That is in conflict with the need to produce more food for an increasing world population. To overcome this incongruence, it is proposed to cultivate second-generation biofuel crops on marginal lands, since this option could bring benefits in terms of food security and sustainability. Based on the scientific literature, we addressed the following critical points: (i) whether marginal land worldwide can be considered a reasonable alternative to arable lands for biofuel production; (ii) evaluate the sustainability of biofuel production with respect to unintended negative consequences of crop cultivation such as indirect land use change, social insecurity and loss of biodiversity. It was concluded that the amount of land for growing plants can possibly sustain both food and biofuel production if marginal land are included. In this context, it becomes a priority to select biofuel crops with high productivity on marginal lands and pronounced resilience and adaptability traits. Underutilized crops such as Carthamus tinctorius , Ricinus communis , Brassica carinata , Camelina sativa etc. may fit the purpose and may represent a valuable alternative to first-generation feedstock because they require minimal agronomical input. Using underutilized crops on marginal lands can also provide important ecological services, including improving soil fertility and water regulation, increasing biodiversity and reducing soil erosion. To fully exploit this option, it will be critical to calibrate plant growth models to estimate the potential biofuel production on marginal land from second-generation feedstock and to create tools for a more rational management of this land. Graphical abstract

The present work reports the enzymatic valorisation of the protein fraction of scotta, a dairy by-product representing the exhausted liquid residue of ricotta production. Scotta was subjected to ultra-filtration with membrane cut-offs from 500 to 4 kDa and the obtained protein-enriched fractions were used for the optimization of enzyme-based digestions aimed at producing potentially bioactive peptides. Nine different commercial proteases were tested and the best digestion conditions were selected based on protein yield, fraction bioactivity and foreseen scale up processing costs. Scale up of the 3% Pancreatin or 5% Papain processes was performed up to 2 L (37°C or 60°C respectively, 1 h incubation), and the digestion efficiency increased with the reaction volume as well as antioxidant activity (up to 60 gBSA eq/L and to 1.7 gAA eq/L). Retentate 1 digested fractions also showed, for the first time in dairy-based peptides, anti-tyrosinase activity, up to 0.14 gKA eq/L. Digested proteins were sub-fractionated by means of physical membrane separations and 30-10 kDa fraction from Papain treatment showed the highest antioxidant and anti-tyrosinase activities. The peptide sequence of the most bioactive fractions was achieved.

This study aimed to determine the serum levels of free L-carnitine, acetyl-L-carnitine and 34 acyl-L-carnitine in healthy subjects and in patients with or at risk of Alzheimer's disease. Twenty-nine patients with probable Alzheimer's disease, 18 with mild cognitive impairment of the amnestic type, 24 with subjective memory complaint and 46 healthy subjects were enrolled in the study, and the levels of carnitine and acyl-carnitines were measured by tandem mass spectrometry. The concentrations of acetyl-L-carnitine progressively decreased passing from healthy subjects group (mean±SD, 5.6±1.3 μmol/L) to subjective memory complaint (4.3±0.9 μmol/L), mild cognitive impairment (4.0±0.53 μmol/L), up to Alzheimer's disease (3.5±0.6 μmol/L) group (p<0.001). The differences were significant for the comparisons: healthy subjects vs. subjective memory complaint, mild cognitive impairment or Alzheimer's disease group; and subjective memory complaint vs. Alzheimer's disease group. Other acyl-carnitines, such as malonyl-, 3-hydroxyisovaleryl-, hexenoyl-, decanoyl-, dodecanoyl-, dodecenoyl-, myristoyl-, tetradecenoyl-, hexadecenoyl-, stearoyl-, oleyl- and linoleyl-L-carnitine, showed a similar decreasing trend, passing from healthy subjects to patients at risk of or with Alzheimer's disease. These results suggest that serum acetyl-L-carnitine and other acyl-L-carnitine levels decrease along the continuum from healthy subjects to subjective memory complaint and mild cognitive impairment subjects, up to patients with Alzheimer's disease, and that the metabolism of some acyl-carnitines is finely connected among them. These findings also suggest that the serum levels of acetyl-L-carnitine and other acyl-L-carnitines could help to identify the patients before the phenotype conversion to Alzheimer's disease and the patients who would benefit from the treatment with acetyl-L-carnitine. However, further validation on a larger number of samples in a longitudinal study is needed before application to clinical practice.

Recent studies indicated sortilin-related receptor 1 (SORL1) to be a risk-gene for late-onset Alzheimer's Disease (AD), although its role in the aetiology and/or progression of this disorder is not fully understood. Here, we report the finding of a novel non-coding (nc) RNA (hereafter referred to as 51A) that maps in antisense (AS) configuration in intron 1 of SORL1 gene. 51A expression drives a splicing shift of SORL1 from the synthesis of the canonical long protein variant 1 to an alternatively spliced protein form. This process, resulting in a decreased synthesis of SORL1 variant 1, is associated with an impaired processing of APP, leading to increase of Aβ formation. Interestingly, we found that 51A is expressed in human brains, being frequently up-regulated in cerebral cortices from Alzheimer's disease patients. Altogether these findings document a novel ncRNA-dependent regulatory pathway that might have relevant implications in neurodegeneration.

Heritable thoracic aortic disease can result from null variants in MYLK, which encodes myosin light-chain kinase (MLCK). Data on which MYLK missense variants are pathogenic and information to guide aortic disease management are limited. Clinical data from 60 cases with MYLK pathogenic variants were analyzed (five null and two missense variants), and the effect of missense variants on kinase activity was assessed. Twenty-three individuals (39%) experienced an aortic event (defined as aneurysm repair or dissection); the majority of these events (87%) were aortic dissections. Aortic diameters were minimally enlarged at the time of dissection in many cases. Time-to-aortic-event curves showed that missense pathogenic variant (PV) carriers have earlier-onset aortic events than null PV carriers. An MYLK missense variant segregated with aortic disease over five generations but decreases MYLK kinase acitivity marginally. Functional Assays fail to identify all pathogenic variants in MYLK. These data further define the aortic phenotype associated with MYLK pathogenic variants. Given minimal aortic enlargement before dissection, an alternative approach to guide the timing of aortic repair is proposed based on the probability of a dissection at a given age.

ML modules are a powerful language mechanism for decomposing programs into reusable components. Unfortunately, they also have a reputation for being “complex” and requiring fancy type theory that is mostly opaque to non-experts. While this reputation is certainly understandable, given the many non-standard methodologies that have been developed in the process of studying modules, we aim here to demonstrate that it is undeserved. To do so, we present a novel formalization of ML modules, which defines their semantics directly by a compositional “elaboration” translation into plain System Fω (the higher-order polymorphic λ-calculus). To demonstrate the scalability of our “F-ing” semantics, we use it to define a representative, higher-order ML-style module language, encompassing all the major features of existing ML module dialects (except for recursive modules). We thereby show that ML modules are merely a particular mode of use of System Fω. To streamline the exposition, we present the semantics of our module language in stages. We begin by defining a subset of the language supporting a Standard ML-like language with second-class modules and generative functors. We then extend this sublanguage with the ability to package modules as first-class values (a very simple extension, as it turns out) and OCaml-style applicative functors (somewhat harder). Unlike previous work combining both generative and applicative functors, we do not require two distinct forms of functor or signature sealing. Instead, whether a functor is applicative or not depends only on the computational purity of its body. In fact, we argue that applicative/generative is rather incidental terminology for pure versus impure functors. This approach results in a semantics that we feel is simpler and more natural than previous accounts, and moreover prohibits breaches of abstraction safety that were possible under them.

Background and Clinical Significance: Neural tube defects (NTDs) represent a group of malformations, typically arising from a complex interplay between genetic susceptibility and environmental influences. Increasing evidence points to the contribution of rare pathogenic variants in genes involved in embryonic development in selected cases. To date, two families with NTDs carrying biallelic variants in TRIM36 and NUAK2 have been described. Specifically, germline homozygous pathogenic variants in NUAK2 were identified in three fetuses with anencephaly, thus implicating this gene as a critical regulator of neural tube closure. Case Presentation: We describe a family in which five individuals presented with sacral dimples, a subtle midline defect considered a minor malformation. Exome sequencing revealed a heterozygous missense variant, c.487G>A in NUAK2, segregating with the phenotype. Although sacral dimples are often clinically silent and do not typically cause functional impairment, their presence in multiple relatives highlights a possible shared genetic etiology. Careful phenotypic recognition of such findings can therefore provide valuable insights into underlying molecular mechanisms. Conclusions: This report extends the clinical spectrum of NUAK2-related anomalies by demonstrating a novel genotype–phenotype correlation. Our findings suggest that variants in this gene may follow a semi-dominant inheritance pattern, with heterozygous carriers manifesting milder phenotypes, such as sacral dimples, while biallelic pathogenic variants lead to severe NTDs. This observation reinforces the association between NUAK2 loss-of-function variants and NTDs and emphasizes the importance of genetic investigations in families where such dysmorphic traits recur. Ultimately, these results contribute to clarifying the molecular basis of NTDs and may inform both genetic counseling and risk stratification in affected families.

To explain the low employment rates of people with disabilities (PwDs), emerging debates have revealed an unexploited potential impact of assistive technology (AT) on human talent and the inclusion process. This article provides a systematic review to critically evaluate the current trends in the literature on AT. A systematic review was performed according to the inclusion criteria of the PRISMA-S guidelines, followed by a thematic analysis identifying the main themes by which the literature on the subject is organized. Finally, the Human Activity Assistive Technology (HAAT) model was used to deepen the contents taken into consideration in the scientific literature and to discuss the concept of workplace inclusion and its use. Forty-one studies fully met the eligibility criteria of the systematic review. The thematic analysis produced four clusters related to the impact and characteristics of AT in the workplace. Overall, the use of the HAAT model highlighted a lack of studies on the affective and socio-cultural dimensions that characterize the use of AT in the workplace. It is concluded that the deployment of AT can and should work on multiple levels to shape the workplace experiences of PwDs.

Cardiofaciocutaneous syndrome (CFCS) belongs to a group of developmental disorders due to defects in the Ras/Mitogen-Activated Protein Kinase (RAS/MAPK) signaling pathway named RASophaties. While postnatal presentation of these disorders is well known, the prenatal and neonatal characteristics are less recognized. Noonan syndrome, Costello syndrome, and CFCS diagnosis should be considered in pregnancies with a normal karyotype and in the case of ultrasound findings such as increased nuchal translucency, polyhydramnios, macrosomia and cardiac defect. Because all the RASopathies share similar clinical features, their molecular characterization is complex, time consuming and expensive. Here we report a case of CFCS prenatally diagnosed through Next Generation Prenatal Diagnosis (NGPD), a new targeted approach that allows us to concurrently investigate all the genes involved in the RASophaties.