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Summary Evolutionary history and early association with anthropogenic environments have made Saccharomyces cerevisiae the quintessential wine yeast. This species typically dominates any spontaneous wine fermentation and, until recently, virtually all commercially available wine starters belonged to this species. The Crabtree effect, and the ability to grow under fully anaerobic conditions, contribute decisively to their dominance in this environment. But not all strains of Saccharomyces cerevisiae are equally suitable as starter cultures. In this article, we review the physiological and genetic characteristics of S. cerevisiae wine strains, as well as the biotic and abiotic factors that have shaped them through evolution. Limited genetic diversity of this group of yeasts could be a constraint to solving the new challenges of oenology. However, research in this field has for many years been providing tools to increase this diversity, from genetic engineering and classical genetic tools to the inclusion of other yeast species in the catalogues of wine yeasts. On occasion, these less conventional species may contribute to the generation of interspecific hybrids with S. cerevisiae. Thus, our knowledge about wine strains of S. cerevisiae and other wine yeasts is constantly expanding. Over the last decades, wine yeast research has been a pillar for the modernisation of oenology, and we can be confident that yeast biotechnology will keep contributing to solving any challenges, such as climate change, that we may face in the future. Saccharomyces cerevisiae typically dominates any spontaneous wine fermentation and. In this article, we review the physiological and genetic characteristics of S. cerevisiae wine strains, as well as the biotic and abiotic factors that have shaped them through evolution. Over the last decades, wine yeast research has been a pillar for the modernisation of oenology, and we can be confident that yeast biotechnology will keep contributing to solving any challengesthat we may face in the future.

The amygdala central nucleus (CeA) has been implicated in feeding regulation, but the underlying circuit mechanisms are incompletely understood. The authors show, in mice, that GABAergic serotonin receptor 2a–expressing CeA neurons are active during eating and promote positive reinforcement and food consumption, partly through long-range inhibition of the parabrachial nucleus. The complex behaviors underlying reward seeking and consumption are integral to organism survival. The hypothalamus and mesolimbic dopamine system are key mediators of these behaviors, yet regulation of appetitive and consummatory behaviors outside of these regions is poorly understood. The central nucleus of the amygdala (CeA) has been implicated in feeding and reward, but the neurons and circuit mechanisms that positively regulate these behaviors remain unclear. Here, we defined the neuronal mechanisms by which CeA neurons promote food consumption. Using in vivo activity manipulations and Ca 2+ imaging in mice, we found that GABAergic serotonin receptor 2a (Htr2a)-expressing CeA neurons modulate food consumption, promote positive reinforcement and are active in vivo during eating. We demonstrated electrophysiologically, anatomically and behaviorally that intra-CeA and long-range circuit mechanisms underlie these behaviors. Finally, we showed that CeA Htr2a neurons receive inputs from feeding-relevant brain regions. Our results illustrate how defined CeA neural circuits positively regulate food consumption.

The central amygdala (CeA) plays a crucial role in defensive and appetitive behaviours. It contains genetically defined GABAergic neuron subpopulations distributed over three anatomical subregions, capsular (CeC), lateral (CeL), and medial (CeM). The roles that these molecularly- and anatomically-defined CeA neurons play in appetitive behavior remain unclear. Using intersectional genetics in mice, we found that neurons driving food or water consumption are confined to the CeM. Separate CeM subpopulations exist for water only versus water or food consumption. In vivo calcium imaging revealed that CeM Htr2a neurons promoting feeding are responsive towards appetitive cues with little regard for their physical attributes. CeM Sst neurons involved in drinking are sensitive to the physical properties of salient stimuli. Both CeM subtypes receive inhibitory input from CeL and send projections to the parabrachial nucleus to promote appetitive behavior. These results suggest that distinct CeM microcircuits evaluate liquid and solid appetitive stimuli to drive the appropriate behavioral responses. How the numerous neuron subpopulations in the lateral (CeL) and medial (CeM) subdivisions of the central amygdala regulate appetitive behavior is poorly understood. Here, the authors report that appetitive neurons are confined to the CeM with separate subpopulations driving water only, versus water or food consumption.

With some exceptions, wine fermentation has increasingly relied on the use of Saccharomyces cerevisiae starters since the last decades of the past century. However, there is growing interest on the understanding of spontaneous wine fermentation, as well as on the use of complementary non- Saccharomyces wine starters. This in turn raises the question of the importance of interspecific interactions in winemaking and the underlying mechanisms. An important question about these interspecies recognition mechanisms is whether or not it is mediated by physical contact between yeast cells. To address this topic, different laboratories have developed diverse devices to cultivate at least two yeast species in the same growth medium without cell-to-cell contact between them. In this work, we compared four of the most popular systems and found that one of them (twin-bottles exchange through a flat membrane) showed very limited metabolite exchange. Among the other systems (Transwell, dialysis tube, or active exchange through hollow fiber cross-flow filtration devices), each one showed specific characteristics that made them more or less suitable, depending on the objectives of each experiment. The option showing the best versatility and efficiency was the use of active exchange. Our results highlight the importance of carefully characterizing the compartmentalization system when drawing conclusions about the impact of cell-to-cell contact in fermentation experiments.

Classical human astroviruses (HAstV) are a global cause of viral gastroenteritis, particularly in children and immunocompromised individuals. Despite their clinical significance, the biology of HAstV remains poorly understood. In particular, the identification of cellular receptors and coreceptors has been elusive. Recent studies have identified the human neonatal Fc receptor (FcRn) as a functional receptor and dipeptidyl peptidase IV (DPP4) as an entry factor for HAstV. However, the precise roles of FcRn and DPP4 during HAstV infection are unknown. To learn about their function, we used FcRn-knockout (KO), DPP4-KO, and FcRn/DPP4 double-KO Caco-2 cells generated via CRISPR/Cas9. Our results showed that DPP4 serves as the receptor for classical HAstV. In contrast, infectious virus assays and confocal fluorescence microscopy revealed that FcRn acts as a coreceptor, facilitating viral internalization and the release of the RNA genome. The half-time for HAstV-1 genome uncoating was delayed threefold in FcRn-KO Caco-2 cells compared to WT cells. Additionally, the characterization of HAstV-8 variants with reduced FcRn binding capacity allowed the identification of two amino acids in the viral capsid spike protein, D471 and N512, critical for the spike-FcRn interaction. These amino acid residues are part of the epitope footprint of neutralizing monoclonal antibodies (Nt-MAbs) to HAstV previously mapped by X-ray crystallography. Further experiments using virus infectivity and attachment assays, along with Nt-MAbs targeting HAstV-1, suggest that the binding sites for FcRn and DPP4 are spatially proximal on the viral spike, defining a functional domain for cell infection. Notably, the infectivity of the divergent HAstV-VA1 was independent of these two proteins, highlighting the receptor variability across HAstV clades. These findings provide new insights into the mechanism of HAstV infection, offering relevant implications for the development of antiviral therapies and vaccines targeting this significant human pathogen.

According to their results, only a small proportion of the amino acids from synthetic must is directly incorporated into proteins by S. cerevisiae. Interestingly, their detailed analysis is providing mechanistic explanations to phenomena like the maximal level of higher alcohol production found at intermediary nitrogen doses (Rollero et al., , this isssue), which take into account the contribution of amino acid catabolism and central carbon metabolism to the α‐ketoacids pool, and their dependence on nitrogen source availability. [...]patterns of isotope enrichment confirm some higher alcohols (isobutanol and isoamyl alcohol), esters (isoamyl acetate and isobutyl acetate) and organic acids (isovalerate and isobutyrate), structurally related to valine and leucine, all derive from the same α‐ketoacids. [...]recently, our understanding of yeast regulation of the metabolism of nitrogen sources, and the production of volatile compounds were either based on relatively simple synthetic media, or confounded by contradictory results from complex or natural media.

In this work, we present power and quality measurements of four transmissions using different emission technologies in an indoor environment, specifically a corridor, at the frequency of 868 MHz under two non-line-of-sight (NLOS) conditions. A narrowband (NB) continuous wave (CW) signal has been transmitted, and its received power has been measured with a spectrum analyzer, LoRa and Zigbee signals have also been transmitted, and their Received Signal Strength Indicator (RSSI) and bit error rate (BER) have been measured using the transceivers themselves; finally, a 20 MHz bandwidth 5G QPSK signal has also been transmitted and their quality parameters, such as SS-RSRP, SS-RSRQ and SS-RINR, have been measured using a SA. Thereafter, two fitting models, the Close-in (CI) model and the Floating-Intercept (FI) model, were used to analyze the path loss. The results show that slopes below 2 for the NLOS-1 zone and above 3 for the NLOS-2 zone have been found. Moreover, the CI and FI model behave very similarly in the NLOS-1 zone, while in the NLOS-2 zone, the CI model has poor accuracy in contrast to the FI model, which achieves the best accuracy in both NLOS situations. From these models, the power predicted with the FI model has been correlated with the measured BER value, and power margins have been established for which LoRa and Zigbee would each reach a BER greater than 5%; likewise, −18 dB has been established for the SS-RSRQ of 5G transmission.

Summary In winemaking, the use of alternative yeast starters is becoming increasingly popular. They contribute to the diversity and complexity of wine sensory features and are typically used in combination with Saccharomyces cerevisiae, to ensure complete fermentation. This practice has drawn the interest on interactions between different oenological yeasts, which are also relevant in spontaneous and conventional fermentations, or in the vineyard. Although several interactions have been described and some mechanisms have been suggested, the possible involvement of extracellular vesicles (EVs) has not yet been considered. This work describes the production of EVs by six wine yeast species (S. cerevisiae, Torulaspora delbrueckii, Lachancea thermotolerans, Hanseniaspora uvarum, Candida sake and Metschnikowia pulcherrima) in synthetic grape must. Proteomic analysis of EV‐enriched fractions from S. cerevisiae and T. delbrueckii showed enrichment in glycolytic enzymes and cell‐wall‐related proteins. The most abundant protein found in S. cerevisiae, T. delbrueckii and L. thermotolerans EV‐enriched fractions was the enzyme exo‐1,3‐β‐glucanase. However, this protein was not involved in the here‐observed negative impact of T. delbrueckii extracellular fractions on the growth of other yeast species. These findings suggest that EVs may play a role in fungal interactions during wine fermentation and other aspects of wine yeast biology. This work describes the production of EVs by six wine yeast species in synthetic grape must. EVs from S. cerevisiae, and T. delbrueckii carried glycolytic enzymes and cell‐wall related proteins. The most abundant protein found in T. delbrueckii, was exo‐1,3‐β‐glucanase, but it was not involved in its negative impact on other yeast species.

Glioblastoma (GBM), characterized by fast growth and invasion into adjacent tissue, is the most aggressive cancer of brain origin. Current protocols, which include cytotoxic chemotherapeutic agents, effectively treat localized disease; however, these aggressive therapies present side effects due to the high doses administered. Therefore, more efficient ways of drug delivery have been studied to reduce the therapeutic exposure of the patients. We have isolated and fully characterized small extracellular vesicles (EVs) from seven patient-derived GBM cell lines. After loading them with two different drugs, Temozolomide (TMZ) and EPZ015666, we observed a reduction in the total amount of drugs needed to trigger an effect on tumor cells. Moreover, we observed that GBM-derived small EVs, although with lower target specificity, can induce an effect on pancreatic cancer cell death. These results suggest that GBM-derived small EVs represent a promising drug delivery tool for further preclinical studies and potentially for the clinical development of GBM treatments.

Non‐Saccharomyces yeast species are increasingly used in winemaking in combination with Saccharomyces cerevisiae to modulate sensory attributes or as processing aids. Consequently, there is academic and practical interest in understanding how different yeast species interact with each other in grape must. Although interactions will depend on the metabolic capabilities of the strains involved, there are other possible interaction mechanisms between wine yeasts. In this work we used extracellular vesicle (EV)‐enriched fractions from different non‐Saccharomyces species to challenge S. cerevisiae inoculated in synthetic grape must. The results show that the previously described response to EVs of Metschnikowia pulcherrima was not an isolated phenomenon, but that S. cerevisiae responds in a general way to EVs of other yeast species. Meta‐analysis of the results points to protein biosynthesis and carbon catabolite repression as general targets; both being stimulated by the interaction, beyond the acclimatisation to the synthetic juice experienced by the control cells. The intensity of the response showed differences between the four species; while the transcriptional response to M. pulcherrima EVs clearly diverges from that to EVs of the other yeast species, which show greater similarity to each other. Extracellular fractions enriched in vesicles of either Metschnikowia pulcherrima, Hanseniaspora uvarum, Torulaspora delbrueckii and Candida sake elicit a transcriptomic response in Saccharomyces cerevisiae shortly after inoculation in synthetic grape must. Both protein biosynthesis and carbon catabolite repression appear stimulated by EVs, while the use of alternative carbon sources is downregulated.