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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.

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.

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.

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.

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.

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.

Abstract Lamin B1, a key component of the nuclear lamina, plays an important role in brain development. Ablation of endogenous Lamin B1 (Lmnb1) in the mouse strongly impairs embryonic brain development and corticogenesis. However, the mechanisms underlying these neurodevelopmental effects are unknown. Here, we report that Lamin B1 levels modulate the differentiation of murine neural stem cells (NSCs) into neurons and astroglial-like cells. In vitro, endogenous Lmnb1 depletion favors NSC differentiation into glial fibrillar acidic protein (GFAP)-immunoreactive cells over neurons, while overexpression of human Lamin B1 (LMNB1) increases the proportion of neurons. In Lmnb1-null embryos, neurogenesis is reduced, while in vivo Lmnb1 silencing in mouse embryonic brain by in utero electroporation of a specific Lmnb1 sh-RNA results in aberrant cortical positioning of neurons and increased expression of the astrocytic marker GFAP in the cortex of 7-day old pups. Together, these results indicate that finely tuned levels of Lamin B1 are required for NSC differentiation into neurons, proper expression of the astrocytic marker GFAP and corticogenesis.