Catálogo de publicaciones - revistas

<jats:title>Abstract</jats:title><jats:p>There is a well-documented gap between the observed number of works produced by women and by men in science, with clear consequences for the retention and promotion of women<jats:sup>1</jats:sup>. The gap might be a result of productivity differences<jats:sup>2–5</jats:sup>, or it might be owing to women’s contributions not being acknowledged<jats:sup>6,7</jats:sup>. Here we find that at least part of this gap is the result of unacknowledged contributions: women in research teams are significantly less likely than men to be credited with authorship. The findings are consistent across three very different sources of data. Analysis of the first source—large-scale administrative data on research teams, team scientific output and attribution of credit—show that women are significantly less likely to be named on a given article or patent produced by their team relative to their male peers. The gender gap in attribution is present across most scientific fields and almost all career stages. The second source—an extensive survey of authors—similarly shows that women’s scientific contributions are systematically less likely to be recognized. The third source—qualitative responses—suggests that the reason that women are less likely to be credited is because their work is often not known, is not appreciated or is ignored. At least some of the observed gender gap in scientific output may be owing not to differences in scientific contribution, but rather to differences in attribution.</jats:p>

<jats:title>Abstract</jats:title><jats:p>Social affiliation emerges from individual-level behavioural rules that are driven by conspecific signals<jats:sup>1–5</jats:sup>. Long-distance attraction and short-distance repulsion, for example, are rules that jointly set a preferred interanimal distance in swarms<jats:sup>6–8</jats:sup>. However, little is known about their perceptual mechanisms and executive neural circuits<jats:sup>3</jats:sup>. Here we trace the neuronal response to self-like biological motion<jats:sup>9,10</jats:sup>, a visual trigger for affiliation in developing zebrafish<jats:sup>2,11</jats:sup>. Unbiased activity mapping and targeted volumetric two-photon calcium imaging revealed 21 activity hotspots distributed throughout the brain as well as clustered biological-motion-tuned neurons in a multimodal, socially activated nucleus of the dorsal thalamus. Individual dorsal thalamus neurons encode local acceleration of visual stimuli mimicking typical fish kinetics but are insensitive to global or continuous motion. Electron microscopic reconstruction of dorsal thalamus neurons revealed synaptic input from the optic tectum and projections into hypothalamic areas with conserved social function<jats:sup>12–14</jats:sup>. Ablation of the optic tectum or dorsal thalamus selectively disrupted social attraction without affecting short-distance repulsion. This tectothalamic pathway thus serves visual recognition of conspecifics, and dissociates neuronal control of attraction from repulsion during social affiliation, revealing a circuit underpinning collective behaviour.</jats:p>

<jats:title>Abstract</jats:title><jats:p>Multiple studies have established associations between human gut bacteria and host physiology, but determining the molecular mechanisms underlying these associations has been challenging<jats:sup>1–3</jats:sup>. <jats:italic>Akkermansia muciniphila</jats:italic> has been robustly associated with positive systemic effects on host metabolism, favourable outcomes to checkpoint blockade in cancer immunotherapy and homeostatic immunity<jats:sup>4–7</jats:sup>. Here we report the identification of a lipid from <jats:italic>A. muciniphila</jats:italic>’s cell membrane that recapitulates the immunomodulatory activity of <jats:italic>A. muciniphila</jats:italic> in cell-based assays<jats:sup>8</jats:sup>. The isolated immunogen, a diacyl phosphatidylethanolamine with two branched chains (a15:0-i15:0 PE), was characterized through both spectroscopic analysis and chemical synthesis. The immunogenic activity of a15:0-i15:0 PE has a highly restricted structure–activity relationship, and its immune signalling requires an unexpected toll-like receptor TLR2–TLR1 heterodimer<jats:sup>9,10</jats:sup>. Certain features of the phospholipid’s activity are worth noting: it is significantly less potent than known natural and synthetic TLR2 agonists; it preferentially induces some inflammatory cytokines but not others; and, at low doses (1% of EC<jats:sub>50</jats:sub>) it resets activation thresholds and responses for immune signalling. Identifying both the molecule and an equipotent synthetic analogue, its non-canonical TLR2–TLR1 signalling pathway, its immunomodulatory selectivity and its low-dose immunoregulatory effects provide a molecular mechanism for a model of <jats:italic>A. muciniphila’</jats:italic>s ability to set immunological tone and its varied roles in health and disease.</jats:p>

<jats:title>Abstract</jats:title><jats:p>In response to hormones and growth factors, the class I phosphoinositide-3-kinase (PI3K) signalling network functions as a major regulator of metabolism and growth, governing cellular nutrient uptake, energy generation, reducing cofactor production and macromolecule biosynthesis<jats:sup>1</jats:sup>. Many of the driver mutations in cancer with the highest recurrence, including in receptor tyrosine kinases, Ras, PTEN and PI3K, pathologically activate PI3K signalling<jats:sup>2,3</jats:sup>. However, our understanding of the core metabolic program controlled by PI3K is almost certainly incomplete. Here, using mass-spectrometry-based metabolomics and isotope tracing, we show that PI3K signalling stimulates the de novo synthesis of one of the most pivotal metabolic cofactors: coenzyme A (CoA). CoA is the major carrier of activated acyl groups in cells<jats:sup>4,5</jats:sup> and is synthesized from cysteine, ATP and the essential nutrient vitamin B5 (also known as pantothenate)<jats:sup>6,7</jats:sup>. We identify pantothenate kinase 2 (PANK2) and PANK4 as substrates of the PI3K effector kinase AKT<jats:sup>8</jats:sup>. Although PANK2 is known to catalyse the rate-determining first step of CoA synthesis, we find that the minimally characterized but highly conserved PANK4<jats:sup>9</jats:sup> is a rate-limiting suppressor of CoA synthesis through its metabolite phosphatase activity. Phosphorylation of PANK4 by AKT relieves this suppression. Ultimately, the PI3K–PANK4 axis regulates the abundance of acetyl-CoA and other acyl-CoAs, CoA-dependent processes such as lipid metabolism and proliferation. We propose that these regulatory mechanisms coordinate cellular CoA supplies with the demands of hormone/growth-factor-driven or oncogene-driven metabolism and growth.</jats:p>