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Abstract Vitamin B6 is a water-soluble vitamin which possesses antioxidant properties. Its catalytically active form, pyridoxal 5’-phosphate (PLP), is a crucial cofactor for DNA and amino acid metabolism. The inverse correlation between vitamin B6 and cancer risk has been observed in several studies, although dietary vitamin B6 intake sometimes failed to confirm this association. However, the molecular link between vitamin B6 and cancer remains elusive. Previous work has shown that vitamin B6 deficiency causes chromosome aberrations (CABs) in Drosophila and human cells, suggesting that genome instability may correlate the lack of this vitamin to cancer. Here we provide evidence in support of this hypothesis. Firstly, we show that PLP deficiency, induced by the PLP antagonists 4-deoxypyridoxine (4DP) or ginkgotoxin (GT), promoted tumorigenesis in eye larval discs transforming benign Ras V12 tumors into aggressive forms. In contrast, PLP supplementation reduced the development of tumors. We also show that low PLP levels, induced by 4DP or by silencing the sgll PNPO gene involved in PLP biosynthesis, worsened the tumor phenotype in another Drosophila cancer model generated by concomitantly activating RasV12 and downregulating Discs-large (Dlg) gene. Moreover, we found that Ras V12 eye discs from larvae reared on 4DP displayed CABs, reactive oxygen species (ROS) and low catalytic activity of serine hydroxymethyltransferase (SHMT), a PLP-dependent enzyme involved in thymidylate (dTMP) biosynthesis, in turn required for DNA replication and repair. Feeding Ras V12 4DP-fed larvae with PLP or ascorbic acid (AA) plus dTMP, rescued both CABs and tumors. The same effect was produced by overexpressing catalase in Ras V12 Dlg RNAi 4DP-fed larvae, thus allowing to establish a relationship between PLP deficiency, CABs, and cancer. Overall, our data provide the first in vivo demonstration that PLP deficiency can impact on cancer by increasing genome instability, which is in turn mediated by ROS and reduced dTMP levels.

Abstract The increasing availability of experimental and computational protein structures entices their use for function prediction. Here we develop an automated procedure to identify enzymes involved in metabolic reactions by assessing substrate conformations docked to a library of protein structures. By screening AlphaFold-modeled vitamin B6-dependent enzymes, we find that a metric based on catalytically favorable conformations at the enzyme active site performs best (AUROC Score=0.84) in identifying genes associated with known reactions. Applying this procedure, we identify the mammalian gene encoding hydroxytrimethyllysine aldolase (HTMLA), the second enzyme of carnitine biosynthesis. Upon experimental validation, we find that the top-ranked candidates, serine hydroxymethyl transferase (SHMT) 1 and 2, catalyze the HTMLA reaction. However, a mouse protein absent in humans (threonine aldolase; Tha1) catalyzes the reaction more efficiently. Tha1 did not rank highest based on the AlphaFold model, but its rank improved to second place using the experimental crystal structure we determined at 2.26 Å resolution. Our findings suggest that humans have lost a gene involved in carnitine biosynthesis, with HTMLA activity of SHMT partially compensating for its function.

Abstract Moiré excitons (MXs) are electron-hole pairs localised by the periodic (moiré) potential forming in two-dimensional heterostructures (HSs). MXs can be exploited, e.g., for creating nanoscale-ordered quantum emitters and achieving or probing strongly correlated electronic phases at relatively high temperatures. Here, we studied the exciton properties of WSe2/MoSe2 HSs from T = 6 K to room temperature using time-resolved and continuous-wave micro-photoluminescence also under a magnetic field. The exciton dynamics and emission lineshape evolution with temperature show clear signatures that MXs de-trap from the moiré potential and turn into free interlayer excitons (IXs) for temperatures above 100 K. The MX-to-IX transition is also apparent from the exciton magnetic moment reversing its sign when the moiré potential is not capable of localising excitons at elevated temperatures. Concomitantly, the exciton formation and decay times reduce drastically. Thus, our findings establish the conditions for a truly confined nature of the exciton states in a moiré superlattice with increasing temperature and photo-generated carrier density.

Summary: Gamma-aminobutyric acid (GABA) is the main inhibitory neurotransmitter in adults. Depolarizing GABA responses have been well characterized at neuronal-population average level during typical neurodevelopment and partially in brain disorders. However, no investigation has specifically assessed whether a mosaicism of cells with either depolarizing or hyperpolarizing/inhibitory GABAergic responses exists in animals in health/disease at diverse developmental stages, including adulthood. Here, we showed that such mosaicism is present in wild-type (WT) and down syndrome (DS) neuronal networks, as assessed at increasing scales of complexity (cultures, brain slices, behaving mice). Nevertheless, WT mice presented a much lower percentage of cells with depolarizing GABA than DS mice. Restoring the mosaicism of hyperpolarizing and depolarizing GABA-responding neurons to WT levels rescued anxiety behavior in DS mice. Moreover, we found heterogeneous GABAergic responses in developed control and trisomic human induced-pluripotent-stem-cells-derived neurons. Thus, a heterogeneous subpopulation of GABA-responding cells exists in physiological/pathological conditions in mouse and human neurons, possibly contributing to disease-associated behaviors.

Abstract Autonomous vehicles offer greater passenger convenience and improved fuel efficiency. However, they are likely to increase road transport activity and life cycle greenhouse emissions, due to several rebound effects. In this study, we investigate tradeoffs between improved fuel economy and rebound effects from a life-cycle perspective. Our results show that autonomy introduces an average 21.2% decrease in operation phase emissions due to improved fuel economy while manufacturing phase emissions can surge up to 40%. Recycling efforts can offset this increase, cutting emissions by 6.65 tons of Carbon dioxide equivalent per vehicle. However, when examining the entire life cycle, autonomous electric vehicles might emit 8% more greenhouse gas emissions on average compared to nonautonomous electric vehicles. To address this, we suggest; (1) cleaner and more efficient manufacturing technologies, (2) ongoing fuel efficiency improvements in autonomous driving; (3) renewable energy adoption for charging, and (4) circular economy initiatives targeting the complete life cycle.

This study examines the impact of the spacing parameter on the efficacy of an array of hybrid modules functioning as both floating breakwaters and wave energy converters. The dual functionality is ensured by the ability of the device to autoadjust its submergence. The behavior of multiple 1:40 scaled modules was tested in the wave tank of the University of Campania “Luigi Vanvitelli”. The objective was to assess the hydraulic performance of the array by analyzing transmission, reflection, and dissipation coefficients under different wave conditions. Specifically, the transmission coefficient ranges between 0.85 and 0.51, depending on the relative wavelength and wave steepness, while the reflection and dissipation coefficients vary, respectively, between 0.70–0.20 and 0.55–0.3. In any case, the results underscore the critical importance of the spacing parameter.

Here, Prakasam and colleagues show that polyQ-expanded androgen receptor toxicity can be attenuated using artificial miRNAs targeting Lsd1 and Prmt6, two AR-co-activators overexpressed in an androgen-dependent manner specifically in skeletal muscle, thus ameliorating spinal-bulbar muscular atrophy phenotypes in flies and mice.

We experimentally demonstrate the use of an integrated optical frequency comb (OFC) for remotely generating low-phase noise millimeter-waves (mm-waves) carriers. The Indium Phosphide (InP) device is composed of phase modulators in tandem and is configurable in OFC center frequency and tone spacing. The device is applied in a centralized radio access network (C-RAN) architecture and the realized OFC is transported over 12.5 km of a conventional single-mode fiber (SMF) link aiming to remotely generate mm-waves. The impairments induced by the chromatic dispersion (CD) on the photodetected electrical carriers are evaluated, i.e., the periodic RF power fluctuations based on the electrical frequency and the SMF length. Experimental results demonstrate that, by properly managing the phase modulator bias and the phase delay supplied to the PIC, the impact of CD on the electrical carriers can be significantly reduced, leading the optical frequency comb to sum up in-phase after the photodetection process. The OFC-based and remotely generated carrier at 28 GHz is used to up-convert a 100 MHz 5G new radio (NR) signal, demonstrating suitable root mean square error vector magnitude (EVMRMS) performance. Indeed, the OFC-based 5G NR signals met the 3GPP requirements with margins up to 7.7%, which enables the 5G wireless link at 28 GHz. Therefore, the proposed system is able to remotely generate mm-waves signal while minimizing the fading impact on the electrical signals, allowing to replace high-frequency up-converters at the remote 5G radio units.

Abstract We experimentally demonstrate the use of optical frequency combs (OFCs), generated by a photonic integrated circuit (PIC), in a flexible optical distribution network based on fiber-optics and free-space optics (FSOs) links, aimed at the fifth generation of mobile network (5G) Xhauls. The Indium Phosphide (InP) monolithically integrated OFC is based on cascaded optical modulators and is broadly tunable in terms of operating wavelength and frequency spacing. Particularly, our approach relies on applying the PIC in a centralized radio access network (C-RAN) architecture, with the purpose of optically generating two low-phase noise mm-waves signals for simultaneously enabling a 12.5-km of single-mode fiber (SMF) fronthaul and a 12.5-km SMF midhaul, followed by a 10-m long FSO fronthaul link. Moreover, the demonstrator contemplates two 10-m reach 5G wireless access networks operating in the 26 GHz band, i.e. over the frequency range 2 (FR2) from the 5G NR standard. The proposed integrated OFC-based 5G system performance is in accordance to the 3rd Generation Partnership Project (3GPP) Release 15 requirements, achieving a total wireless throughput of 900 Mbit/s.

Solié, Contestabile et al. show that the superior colliculus to ventral tegmental area (VTA) pathway encodes orienting behavior toward conspecifics, and modulates VTA dopamine neurons projecting onto dorsolateral striatum perturbing social interaction.

This article reports on the dataset gathered following the census of 83 present-day Infralittoral Prograding Wedges (IPWs), surveyed on the inner continental shelf of the Central-Eastern Tyrrhenian Sea. The purpose of the census was to explore their bathymetric range and assess the observational laws governing this variability. The ensued dataset (Campania Region IPW Dataset, CRID) includes geographic, topographic and morpho-bathymetric indices, descriptive of each IPW and more, the exposure of each IPW to wave forcing (Geographical fetch, Effective fetch and extreme significant wave height, HS). In this work, histograms contribute to describe all the variables and highlight the dominant features of each IPW. Location maps univocally links the geographic position of each IPW to the appropriate attribute record in the dataset. Further, thematic maps illustrate eight wave fields obtained by offshore-to-nearshore transformation by as many sea states scenarios with 200-year return period. Such wave fields are used as sources for significant wave height representing wave conditions over each IPW.This dataset could be implemented with new measures at a broader scale, by following analogue procedures for measurements, to enlarge the observational scale on IPWs and improve the numerical models which might eventually derive by the analysis of this dataset.

Environmental problems are among the most pressing issues in the modern world, including the shortage of clean drinking water partially caused by contamination from various industries and the excessive emission of CO2 primarily from the massive use of fossil fuels. Consequently, it is crucial to develop inexpensive, effective, and environmentally friendly methods for wastewater treatment and CO2 reduction, turning them into useful feedstocks. This study explores a unique method that addresses both challenges by utilizing ZnO, which is recognized as one of the most active semiconductors for photocatalysis, as well as a cost-effective electrocatalyst for the CO2 reduction reaction (CO2RR). Specifically, we investigate the influence of the morphology of various ZnO nanostructures synthesized via different low-cost routes on their photocatalytic properties for degrading the rhodamine-B dye (RhB) and on their electrocatalytic performance for the CO2RR. Our results show that the ZnO lamella morphology achieves the best performance compared to the nanorod and nanoparticle structures. This outcome is likely attributed to the lamella’s higher aspect ratio, which plays a critical role in determining the structural, optical, and electrical properties of ZnO.

Abstract The future envisaged global-scale quantum-communication network will comprise various nodes interconnected via optical fibers or free-space channels, depending on the link distance. The free-space segment of such a network should guarantee certain key requirements, such as daytime operation and the compatibility with the complementary telecom-based fiber infrastructure. In addition, space-to-ground links will require the capability of designing light and compact quantum devices to be placed in orbit. For these reasons, investigating available solutions matching all the above requirements is still necessary. Here we present a full prototype for daylight quantum key distribution at 1550 nm exploiting an integrated silicon-photonics chip as state encoder. We tested our prototype in the urban area of Padua (Italy) over a 145 m-long free-space link, obtaining a quantum bit error rate around 0.5% and an averaged secret key rate of 30 kbps during a whole sunny day (from 11:00 to 20:00). The developed chip represents a cost-effective solution for portable free-space transmitters and a promising resource to design quantum optical payloads for future satellite missions.

Driven by the development of the oil and gas sector, Qatar has made remarkable economic achievements over the past few decades. However, Qatar’s high dependence on fossil fuels has resulted in a rapid increase in its CO2 emissions. As such, the country may be facing a trade-off between achieving continued economic growth and carbon emissions reductions. This study empirically analyzes the relationship between economic growth and carbon emissions in Qatar, using annual data of income and CO2 emissions from 1970 to 2018. The analysis was conducted by employing the Environmental Kuznets Curve (EKC) framework and the Decoupling Index (DI) approach. The EKC was evaluated using the Fully Modified Ordinary Least Squares cointegration method. Additionally, a robustness check was conducted by Canonical Cointegrating Regression (CCR) cointegration method to confirm the results attained by FMOLS. The findings support the evidence of an N-shaped relationship and suggest that the country is currently undergoing expanding relative decoupling. Although findings show that Qatar’s per capita emissions have been declining over the last few years, additional measures such as energy conservation, energy efficiency and renewable energy are required to allow cost-effective carbon emission reductions.

Social interaction during adolescence strongly influences brain function and behavior, and the recent pandemic has emphasized the devastating effect of social distancing on mental health. While accumulating evidence has shown the importance of the reward system in encoding specific aspects of social interaction, the consequences of social isolation on the reward system and the development of social skills later in adulthood are still largely unknown. Here, we found that 1 week of social isolation during adolescence in male mice increased social interaction at the expense of social habituation and social novelty preference. Behavioral changes were accompanied by the acute hyperexcitability of putative dopamine (pDA) neurons in the ventral tegmental area and long-lasting expression of GluA2-lacking AMPARs at excitatory inputs onto pDA neurons that project to the prefrontal cortex. Social isolation-dependent behavioral deficits and changes in neural activity and synaptic plasticity were reversed by chemogenetic inhibition of oxytocin neurons in the paraventricular nucleus of the hypothalamus. These results demonstrate that social isolation in male mice has acute and long-lasting effects on social interaction and suggest that homeostatic adaptations mediate these effects within the reward circuit.

Author guidelines for journals could help to promote transparency, openness, and reproducibility

Abstract In eukaryotes, pyridoxal kinase (PDXK) acts in vitamin B6 salvage pathway to produce pyridoxal 5′-phosphate (PLP), the active form of the vitamin, which is implicated in numerous crucial metabolic reactions. In Drosophila, mutations in the dPdxk gene cause chromosome aberrations (CABs) and increase glucose content in larval hemolymph. Both phenotypes are rescued by the expression of the wild type human PDXK counterpart. Here we expressed, in dPdxk 1 mutant flies, four PDXK human variants: three (D87H, V128I and H246Q) listed in databases, and one (A243G) found in a genetic screening in patients with diabetes. Differently from human wild type PDXK, none of the variants was able to completely rescue CABs and glucose content elicited by dPdxk 1 mutation. Biochemical analysis of D87H, V128I, H246Q and A243G proteins revealed reduced catalytic activity and/or reduced affinity for PLP precursors which justify this behavior. Although these variants are rare in population and carried in heterozygous condition, our findings suggest that in certain metabolic contexts and diseases in which PLP levels are reduced, the presence of these PDXK variants could threaten genome integrity and increase cancer risk.

The paper concentrates on Hellenistic jewelry, which dates from the fourth to first century BCE, and strives to answer the question: how do the different decorative functions of Hellenistic jewelry represent the various roles and social obligations of its elite Greek female wearers? Four thematic parallels exist between jewelry and women, including beauty, sexuality, fertility, and wealth. To examine these connections, this paper studies classical literary sources that focus on female sexuality and the social expectations of women. Examples include segments taken from the Homeric Hymn to Aphrodite, the poetry of Sappho and Ibycus, an epithalamium, and Plutarch’s Life of Demetrius. The content of these sources are extracted and compared to the decorative functions of four Hellenistic jewelry pieces, which include an embellished necklace, pair of Eros earrings, diadem, and jewelry set. Based upon the research, physical attributes of Hellenistic jewelry reflect the responsibilities of elite Greek women to groom their appearance, be sexually desirable, produce legitimate heirs, and demonstrate wealth and prestige. By analyzing these similarities, one becomes aware of the extreme commoditization of ancient Greek women.

A perturbed uptake of micronutrients, such as minerals and vitamins, impacts on different human diseases, including cancer and neurological disorders. Several data converge towards a crucial role played by many micronutrients in genome integrity maintenance and in the establishment of a correct DNA methylation pattern. Failure in the proper accomplishment of these processes accelerates senescence and increases the risk of developing cancer, by promoting the formation of chromosome aberrations and deregulating the expression of oncogenes. Here, the main recent evidence regarding the impact of some B vitamins on DNA damage and cancer is summarized, providing an integrated and updated analysis, mainly centred on vitamin B6. In many cases, it is difficult to finely predict the optimal vitamin rate that is able to protect against DNA damage, as this can be influenced by a given individual's genotype. For this purpose, a precious resort is represented by model organisms which allow limitations imposed by more complex systems to be overcome. In this review, we show that Drosophila can be a useful model to deeply understand mechanisms underlying the relationship between vitamin B6 and genome integrity.

As the human life expectancy increases, age-linked diseases have become more and more frequent. The worldwide increment of dementia cases demands medical solutions, but the current available drugs do not meet all the expectations. Recently the attention of the scientific community was attracted by natural compounds, used in ancient medicine, known for their beneficial effects and high tolerability. This review is focused on Ginger (Zingiber officinale) and explore its properties against Alzheimer’s Disease and Vascular Dementia, two of the most common and devastating forms of dementia. This work resumes the beneficial effects of Ginger compounds, tested in computational in vitro and in vivo models of Alzheimer’s Disease and Vascular Dementia, along with some human tests. All these evidences suggest a potential role of the compounds of ginger not only in the treatment of the disease, but also in its prevention.