The ability to speak coherently is essential for effective communication but declines with age: older people more frequently produce tangential, off-topic speech. Little is known, however, about the ...neural systems that support coherence in speech production. Here, fMRI was used to investigate extended speech production in healthy older adults. Computational linguistic analyses were used to quantify the coherence of utterances produced in the scanner, allowing identification of the neural correlates of coherence for the first time. Highly coherent speech production was associated with increased activity in bilateral inferior prefrontal cortex (BA45), an area implicated in selection of task-relevant knowledge from semantic memory, and in bilateral rostrolateral prefrontal cortex (BA10), implicated more generally in planning of complex goal-directed behaviours. These findings demonstrate that neural activity during spontaneous speech production can be predicted from formal analysis of speech content, and that multiple prefrontal systems contribute to coherence in speech.
There are a number of long‐standing theories on how the cognitive processing of words, like ‘life’, differs from that of concrete words, like ‘knife’. This review considers current perspectives on ...this debate, focusing particularly on insights obtained from patients with language disorders and integrating these with evidence from functional neuroimaging studies. The evidence supports three distinct and mutually compatible hypotheses. (1) Concrete and words differ in their representational substrates, with concrete words depending particularly on sensory experiences and words on linguistic, emotional, and magnitude‐based information. Differential dependence on visual versus verbal experience is supported by the evidence for graded specialization in the anterior temporal lobes for concrete versus words. In addition, concrete words have richer representations, in line with better processing of these words in most aphasic patients and, in particular, patients with semantic dementia. (2) words place greater demands on executive regulation processes because they have variable meanings that change with context. This theory explains word impairments in patients with semantic‐executive deficits and is supported by neuroimaging studies showing greater response to words in inferior prefrontal cortex. (3) The relationships between concrete words are governed primarily by conceptual similarity, while those of words depend on association to a greater degree. This theory, based primarily on interference and priming effects in aphasic patients, is the most recent to emerge and the least well understood. I present analyses indicating that patterns of lexical co‐occurrence may be important in understanding these effects.
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Computational single-cell RNA-seq (scRNA-seq) methods have been successfully applied to experiments representing a single condition, technology, or species to discover and define cellular phenotypes. ...However, identifying subpopulations of cells that are present across multiple data sets remains challenging. Here, we introduce an analytical strategy for integrating scRNA-seq data sets based on common sources of variation, enabling the identification of shared populations across data sets and downstream comparative analysis. We apply this approach, implemented in our R toolkit Seurat (http://satijalab.org/seurat/), to align scRNA-seq data sets of peripheral blood mononuclear cells under resting and stimulated conditions, hematopoietic progenitors sequenced using two profiling technologies, and pancreatic cell 'atlases' generated from human and mouse islets. In each case, we learn distinct or transitional cell states jointly across data sets, while boosting statistical power through integrated analysis. Our approach facilitates general comparisons of scRNA-seq data sets, potentially deepening our understanding of how distinct cell states respond to perturbation, disease, and evolution.
Existing correlation schemes between early Paleoproterozoic successions divorce the low-latitude Makganyene glaciation in southern Africa from the Great Oxidation (GO), as recorded by the ...disappearance of mass-independent fractionation of S-isotopes (MIF-S) in sedimentary sulfide and sulfate minerals. They also suggest a younger age for the GO in southern Africa (~2.3Ga) compared with North America (~2.4Ga), which is physically implausible. A new correlation scheme is proposed in which the Makganyene glaciation is temporally linked to the GO and to the second of three Huronian glaciations in North America, the one with postglacial cap-carbonate. In the new scheme, only three glacial epochs are needed globally, all three are represented in southern Africa, and the second was a circa 2.40Ga snowball Earth coincident with the GO.
•A new correlation scheme for early Paleoproterozoic glaciations is proposed.•The second of three glacial epochs is framed by the disappearance of MIF (Δ33S).•The same glaciation was arguably a snowball Earth.•The new scheme simplifies early Paleoproterozoic Earth history.•It reconciles apparent asynchrony between MIF disappearance in North America and South Africa.
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It has been nearly 50 years since the golden age of antibiotic discovery (1945-1975) ended; yet, we still struggle to identify novel drug targets and to deliver new chemical classes of antibiotics to ...replace those rendered obsolete by drug resistance. Despite herculean efforts utilizing a wide range of antibiotic discovery platform strategies, including genomics, bioinformatics, systems biology and postgenomic approaches, success has been at best incremental. Obviously, finding new classes of antibiotics is really hard, so repeating the old strategies, while expecting different outcomes, seems to boarder on insanity. The key questions dealt with in this review include: (1) If mutation based drug resistance is the major challenge to any new antibiotic, is it possible to find drug targets and new chemical entities that can escape this outcome; (2) Is the number of novel chemical classes of antibacterials limited by the number of broad spectrum drug targets; and (3) If true, then should we focus efforts on subgroups of pathogens like Gram negative or positive bacteria only, anaerobic bacteria or other group where the range of common essential genes is likely greater?. This review also provides some examples of existing drug targets that appear to escape the specter of mutation based drug resistance, and provides examples of some intermediate spectrum strategies as well as modern molecular and genomic approaches likely to improve the odds of delivering 21st century medicines to combat multidrug resistant pathogens.
The Otavi Group is a Neoproterozoic carbonate-dominated succession up to 4 km thick, which blankets the southern promontory of the Congo craton in northern Namibia. This succession was deposited ...between 770 and 580 Ma in response to north-south crustal stretching and subsequent thermal subsidence. The main shallow-water platform has a well-defined southern limit, beyond which is a distally tapered foreslope wedge of deep-water carbonate facies. The Ghaub Formation represents the younger of two Cryogenian glaciations of the platform and was deposited during the period of thermal subsidence. A deep negative δ¹³C excursion, accompanied by increased size, abundance and variety of stromatolites, occurs in the last 10 to 80 m of shallow-water carbonate on the platform beneath the Ghaub glacial erosion surface. The same phenomena are observed before the older (Sturtian) glaciation in other areas, suggesting temporal proximity of the δ¹³C excursions to glaciation. Growth of ice sheets is manifested by emergence of the platform and development of a falling-stand wedge on the foreslope, composed of upward-coarsening carbonate turbidites and debrites. Rafts of very coarse-grained, well-sorted oolite have no source on the platform. The oolite probably originated at the strandline on the foreslope and was redeposited gravitationally downslope as sea-level fell. The Ghaub Formation is a laterally continuous wedge of carbonate diamictite, limited to the distal foreslope and ca 80 m in average thickness. Tongues of massive to weakly stratified diamictite, representing proglacial rain-out and subglacial tillite, are bounded by thinner, well-bedded units consisting of hypopycnal plume fallout, ice-rafted debris, turbidites and debrites, sorted sands and gravels, and westward-directed contourites. Debris is derived from the falling-stand wedge and the top 80 m of the inner platform. The wedge rests on a laterally continuous erosion surface, presumably cut by ice, and its sedimentary makeup and stratal organization are diagnostic of an ice grounding-line wedge. The subglacial erosion surface cuts a steep-walled trough on the distal foreslope, presumably once occupied by a transverse ice-stream. In the middle of the trough stands a doubly crested moraine composed of amalgamated unstratified diamictites. Terminal deglaciation is recorded by a fining-upward, 10 m thick drape of Fe-rich carbonate debrite and turbidite, loaded with far-travelled ice-rafted debris of all sizes. If deglaciation began with the collapse of ‘sea-glacier' ice on the tropical ocean, the loss of this buttress could have triggered catastrophic ice-sheet drainage, concomitant with surface ocean ventilation. Complete deglaciation presumably was driven by ice-albedo, ice-elevation and greenhouse-gas feedbacks. The grounding-line wedge and bare upper foreslope and platform are overlain by a transgressive ‘cap dolostone', which features shallow-water sedimentary structures (sorted peloids, low-angle cross-bedding, tubestone stromatolite and giant wave ripples) from the distal foreslope to the inner platform. The structures and isotopic profiles show that it was deposited diachronously on the time scale of ice-sheet melting globally (kyr), implying very high sedimentation rates. Temperature-dependent isotope fractionation could account for the observed secular and lateral δ¹³C changes. This interpretation requires sea water pH lower than 7·3 (high pCO₂) and warming of at least 45°C in the tropics, consistent with the change in planetary albedo accompanying global deglaciation. The thickness of the highstand part of the cap-carbonate sequence on the platform implies >3 to 5 Myr of tectonic subsidence during the glacial period to create permanent accommodation. The highstand sequence prograded inward from the raised rim of the platform, inherited from karstic and glacial erosion. Sea floor cements, formerly aragonitic, are localized over palaeobathymetric highs (ice-stream moraine, platform rim and inner platform highs). Subsequent aggradation of the platform and coeval foreslope shedding were accompanied by a 0·5 km thick stratigraphic interval in which platform strata are depleted in ¹³C by up to 2·5‰, compared with coeval foreslope strata; this again suggests temperature-dependent fractionation at low pH. Above this interval, the δ¹³C gradient reverts to normal (platform strata more enriched in ¹³C than foreslope equivalents), consistent with CO₂ drawdown due to silicate weathering.
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On the southwest cape of the Congo craton, a subtropical carbonate bank the size of Greenland was heavily glaciated during two Cryogenian panglacial episodes spaced 10-20 Myr apart. In NW Namibia, ...the bank underwent crustal stretching with resultant Aegean Sea-type topography during the older and longer Sturtian glaciation (717-661 Ma). This is indicated by angular discordance between glacial and preglacial strata and diamictites sourced from all older units, including crystalline basement. In contrast, the bank was flat-topped and underwent broad thermal subsidence during Marinoan glaciation (646 + or - 5-635 Ma), attested by stratal parallellism and diamictites sourced from less than or equal to 100 m stratigraphic depth. However, greater than or equal to2.0kmofreliefexistedon the Marinoan continental slope, where most glacial erosion and accumulation occurred. The average rates of Marinoan erosion (2.55-6.80 m/Myr, n = 190) and accumulation (2.65-7.07 m/Myr, n = 211) are indistinguishable, implying that the location in a continental promontory did not bias erosion over accumulation. The average accumulation rates for the Sturtian and Marinoan, scaled for different averaging times, including Marinoan uncertainty, are 3.95-4.93 m/Myr (n = 183) and 2.65-7.07 m/Myr (n = 190), respectively, suggesting that a Marinoan glacioeustatic coastal escarpment substituted for rift-related Sturtian basin-and-range topography. These slow rates, comparable to long-term pre-Quaternary accumulation rates on existing abyssal plains, reconcile glacial sedimentology with the feeble hydrologic cycle of snowball Earth.
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•Meta-analysis of activation in young and older adults on semantic tasks.•Young and old activated broadly similar, left-lateralised regions.•Older people showed less activation in the typical ...left-hemisphere semantic network.•Older people showed more activation in right frontal and parietal regions.•Shift from semantic-specific to domain-general neural resources in later life.
Semantic cognition is central to understanding of language and the world and, unlike many cognitive domains, is thought to show little age-related decline. We investigated age-related differences in the neural basis of this critical cognitive domain by performing an activation likelihood estimation (ALE) meta-analysis of functional neuroimaging studies comparing young and older people. On average, young people outperformed their older counterparts during semantic tasks. Overall, both age groups activated similar left-lateralised regions. However, older adults displayed less activation than young people in some elements of the typical left-hemisphere semantic network, including inferior prefrontal, posterior temporal and inferior parietal cortex. They also showed greater activation in right frontal and parietal regions, particularly those held to be involved in domain-general controlled processing, and principally when they performed more poorly than the young. Thus, semantic processing in later life is associated with a shift from semantic-specific to domain-general neural resources, consistent with the theory of neural dedifferentiation, and a performance-related reduction in prefrontal lateralisation, which may reflect a response to increased task demands.
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Big Time Hoffman, Paul F
Annual review of earth and planetary sciences,
05/2019, Volume:
47, Issue:
1
Journal Article
Peer reviewed
Open access
The Proterozoic Eon was once regarded as the neglected middle half of Earth history. The name refers to early animals, but they did not appear until the eon (2.5-0.54 Ga) was nearly over. Eukaryotic ...cells and sexual reproduction evolved much earlier in the eon, as did chloroplasts. Molecular dioxygen, the presence of which altered the geochemical behavior of nearly every element essential to life, rose from negligible to near-modern levels, and then plummeted before rising fitfully again. Plate tectonics took on a modern form, and two supercontinents, Nuna and Rodinia, successively congregated and later dispersed. Climate regulatory failures, i.e., Snowball Earth, appear to be a uniquely Proterozoic phenomenon, having occurred twice in rapid succession near the end of the eon (from 717 to 660 Ma and from 650 to 635 Ma) and arguably once near its beginning (ca. 2.43 Ga). Dynamic sea glaciers covered Snowball Earth oceans from pole to pole, and equatorial sublimation drove slow-moving ice sheets on land. Ultimately, the gradual accumulation of CO
2
triggered rapid deglaciation and transient greenhouse aftermaths. Physically based and geologically tested, Neoproterozoic Snowball Earth appears to have molecular legacies in ancient bitumens and modern organisms. This is the story of my love affair with an eon that is now a little less neglected.
Carbonate sediments of nonglacial Cryogenian (659 to 649 Ma) and early Ediacaran (635 to 590 Ma) age exhibit large positive and negative δ13Ccarb excursions in a shallow-water marine platform in ...northern Namibia. The same excursions are recorded in fringing deep-sea fans and in carbonate platforms on other paleocontinents. However, coeval carbonates in the upper foreslope of the Namibian platform, and to a lesser extent in the outermost platform, have relatively uniform δ13Ccarb compositions compatible with dissolved inorganic carbon (DIC) in the modern ocean. We attribute the uniform values to fluid-buffered diagenesis that occurred where seawater invaded the sediment in response to geothermal porewater convection. This attribution, which is testable with paired Ca and Mg isotopes, implies that large δ13Ccarb excursions observed in Neoproterozoic platforms, while sedimentary in origin, do not reflect the composition of ancient open-ocean DIC.
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