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By force of nature, every bit of spoken language is produced at a particular speed. However, this speed is not constant-speakers regularly speed up and slow down. Variation in speech rate is influenced by a complex combination of factors, including the frequency and predictability of words, their information status, and their position within an utterance. Here, we use speech rate as an index of word-planning effort and focus on the time window during which speakers prepare the production of words from the two major lexical classes, nouns and verbs. We show that, when naturalistic speech is sampled from languages all over the world, there is a robust cross-linguistic tendency for slower speech before nouns compared with verbs, both in terms of slower articulation and more pauses. We attribute this slowdown effect to the increased amount of planning that nouns require compared with verbs. Unlike verbs, nouns can typically only be used when they represent new or unexpected information; otherwise, they have to be replaced by pronouns or be omitted. These conditions on noun use appear to outweigh potential advantages stemming from differences in internal complexity between nouns and verbs. Our findings suggest that, beneath the staggering diversity of grammatical structures and cultural settings, there are robust universals of language processing that are intimately tied to how speakers manage referential information when they communicate with one another.


Although uncomplicated urinary tract infections (UTIs) are often self-limiting, most patients will be prescribed antibiotic treatment. We assessed whether treatment with ibuprofen was non-inferior to pivmecillinam in achieving symptomatic resolution by day 4, with a non-inferiority margin of 10%.


Past life on Mars will have generated organic remains that may be preserved in present day Mars rocks. The most recent period in the history of Mars that retained widespread surface waters was the late Noachian and early Hesperian and thus possessed the potential to sustain the most evolved and widely distributed martian life. Guidance for investigating late Noachian and early Hesperian rocks is provided by studies of analogous acidic and sulfur-rich environments on Earth. Here we report organic responses for an acid stream containing acidophilic organisms whose post-mortem remains are entombed in iron sulphates and iron oxides. We find that, if life was present in the Hesperian, martian organic records will comprise microbial lipids. Lipids are a potential sizeable reservoir of fossil carbon on Mars, and can be used to distinguish between different domains of life. Concentrations of lipids, and particularly alkanoic or “fatty” acids, are highest in goethite layers that reflect high water-to-rock ratios and thus a greater potential for habitability. Goethite can dehydrate to hematite, which is widespread on Mars. Mars missions should seek to detect fatty acids or their diagenetic products in the oxides and hydroxides of iron associated with sulphur-rich environments.


Coffee’s long-term effect on cognitive function remains unclear with studies suggesting both benefits and adverse effects. We used Mendelian randomization to investigate the causal relationship between habitual coffee consumption and cognitive function in mid- to later life. This included up to 415,530 participants and 300,760 coffee drinkers from 10 meta-analysed European ancestry cohorts. In each cohort, composite cognitive scores that capture global cognition and memory were computed using available tests. A genetic score derived using CYP1A1/2 (rs2472297) and AHR (rs6968865) was chosen as a proxy for habitual coffee consumption. Null associations were observed when examining the associations of the genetic score with global and memory cognition (β = -0.0007, 95% C.I. -0.009 to 0.008, P = 0.87; β = -0.001, 95% C.I. -0.005 to 0.002, P = 0.51, respectively), with high consistency between studies (Pheterogeneity > 0.4 for both). Domain specific analyses using available cognitive measures in the UK Biobank also did not support effects by habitual coffee intake for reaction time, pairs matching, reasoning or prospective memory (P ≥ 0.05 for all). Despite the power to detect very small effects, our meta-analysis provided no evidence for causal long-term effects of habitual coffee consumption on global cognition or memory.


Although the human gut microbiome plays a prominent role in xenobiotic transformation, most of the genes and enzymes responsible for this metabolism are unknown. Recently, we linked the two-gene ‘cardiac glycoside reductase’ (cgr) operon encoded by the gut Actinobacterium Eggerthella lenta to inactivation of the cardiac medication and plant natural product digoxin. Here, we compared the genomes of 25 E. lenta strains and close relatives, revealing an expanded 8-gene cgr-associated gene cluster present in all digoxin metabolizers and absent in non-metabolizers. Using heterologous expression and in vitro biochemical characterization, we discovered that a single flavin- and [4Fe-4S] cluster-dependent reductase, Cgr2, is sufficient for digoxin inactivation. Unexpectedly, Cgr2 displayed strict specificity for digoxin and other cardenolides. Quantification of cgr2 in gut microbiomes revealed that this gene is widespread and conserved in the human population. Together, these results demonstrate that human-associated gut bacteria maintain specialized enzymes that protect against ingested plant toxins.


The robustness of the visual system lies in its ability to perceive degraded images. This is achieved through interacting bottom-up, recurrent, and top-down pathways that process the visual input in concordance with stored prior information. The interaction mechanism by which they integrate visual input and prior information is still enigmatic. We present a new approach using deep neural network (DNN) representation to reveal the effects of such integration on degraded visual inputs. We transformed measured human brain activity resulting from viewing blurred images to the hierarchical representation space derived from a feedforward DNN. Transformed representations were found to veer toward the original nonblurred image and away from the blurred stimulus image. This indicated deblurring or sharpening in the neural representation, and possibly in our perception. We anticipate these results will help unravel the interplay mechanism between bottom-up, recurrent, and top-down pathways, leading to more comprehensive models of vision.


Double emulsions are complex fluid systems, in which droplets of a dispersed liquid phase contain even smaller dispersed liquid droplets. Particularly, water-in-oil-in-water double emulsions provide significant advantages over simple oil-in-water emulsions for microencapsulation, such as carrier of both aqueous and oily payloads and sustained release profile. However, double emulsions are thermodynamically unstable systems consisting typically of relatively large droplets. Here we show that nanoscale water-in-oil-in-water double emulsions can be prepared by adding a silica precursor polymer, hyperbranched polyethoxysiloxane, to the oil phase without any additional surfactants. The resulting double miniemulsions are transformed to robust water@SiO2@polymer@SiO2 nanocapsules via conversion of the precursor to silica and polymerization of the oil phase. Other intriguing nanostructures like nanorattles and Janus-like nanomushrooms can also be obtained by changing preparation conditions. This simple surfactant-free double miniemulsion polymerization technique opens a promising avenue for mass production of various complex hybrid nanostructures that are amenable to numerous applications.


Eya proteins are critical developmental regulators that are highly expressed in embryogenesis but downregulated after development. Amplification and/or re-expression of Eyas occurs in many tumor types. In breast cancer, Eyas regulate tumor progression by acting as transcriptional cofactors and tyrosine phosphatases. Intriguingly, Eyas harbor a separate threonine (Thr) phosphatase activity, which was previously implicated in innate immunity. Here we describe what we believe to be a novel role for Eya3 in mediating triple-negative breast cancer-associated immune suppression. Eya3 loss decreases tumor growth in immune-competent mice and is associated with increased numbers of infiltrated CD8+ T cells, which, when depleted, reverse the effects of Eya3 knockdown. Mechanistically, Eya3 utilizes its Thr phosphatase activity to dephosphorylate Myc at pT58, resulting in a stabilized form. We show that Myc is required for Eya3-mediated increases in PD-L1, and that rescue of PD-L1 in Eya3-knockdown cells restores tumor progression. Finally, we demonstrate that Eya3 significantly correlates with PD-L1 in human breast tumors, and that tumors expressing high levels of Eya3 have a decreased CD8+ T cell signature. Our data uncover a role for Eya3 in mediating tumor-associated immune suppression, and suggest that its inhibition may enhance checkpoint therapies.


Hominin cranial remains from the Dinaledi Chamber, South Africa, represent multiple individuals of the species Homo naledi This species exhibits a small endocranial volume comparable to Australopithecus, combined with several aspects of external cranial anatomy similar to larger-brained species of Homo such as Homo habilis and Homo erectus Here, we describe the endocast anatomy of this recently discovered species. Despite the small size of the H. naledi endocasts, they share several aspects of structure in common with other species of Homo, not found in other hominins or great apes, notably in the organization of the inferior frontal and lateral orbital gyri. The presence of such structural innovations in a small-brained hominin may have relevance to behavioral evolution within the genus Homo.


Based on associated and three-dimensionally preserved cranial and postcranial remains, a new thalattosuchian crocodyliform, Magyarosuchus fitosi gen. et sp. nov. from the Lower Jurassic (Upper Toarcian) Kisgerecse Marl Formation, Gerecse Mountains, Hungary is described here. Phylogenetic analyses using three different datasets indicate that M. fitosi is the sister taxon of Pelagosaurus typus forming together the basal-most sub-clade of Metriorhynchoidea. With an estimated body length of 4.67-4.83 m M. fitosi is the largest known non-metriorhynchid metriorhynchoid. Besides expanding Early Jurassic thalattosuchian diversity, the new specimen is of great importance since, unlike most contemporaneous estuarine, lagoonal or coastal thalattosuchians, it comes from an ‘ammonitico rosso’ type pelagic deposit of the Mediterranean region of the Tethys. A distal caudal vertebra having an unusually elongate and dorsally projected neural spine implies the presence of at least a rudimentary hypocercal tail fin and a slight ventral displacement of the distal caudal vertebral column in this basal metriorhynchoid. The combination of retaining heavy dorsal and ventral armors and having a slight hypocercal tail is unique, further highlighting the mosaic manner of marine adaptations in Metriorhynchoidea.