Ancient DNA and deep population structure in sub-Saharan African foragers.

Multiple lines of genetic and archaeological evidence suggest that there were major demographic changes in the terminal Late Pleistocene epoch and early Holocene epoch of sub-Saharan Africa1-4. Inferences about this period are challenging to make because demographic shifts in the past 5,000 years have obscured the structures of more ancient populations3,5. Here we present genome-wide ancient DNA data for six individuals from eastern and south-central Africa spanning the past approximately 18,000 years (doubling the time depth of sub-Saharan African ancient DNA), increase the data quality for 15 previously published ancient individuals and analyse these alongside data from 13 other published ancient individuals. The ancestry of the individuals in our study area can be modelled as a geographically structured mixture of three highly divergent source populations, probably reflecting Pleistocene interactions around 80-20 thousand years ago, including deeply diverged eastern and southern African lineages, plus a previously unappreciated ubiquitous distribution of ancestry that occurs in highest proportion today in central African rainforest hunter-gatherers. Once established, this structure remained highly stable, with limited long-range gene flow. These results provide a new line of genetic evidence in support of hypotheses that have emerged from archaeological analyses but remain contested, suggesting increasing regionalization at the end of the Pleistocene epoch.

Opinion dynamics in financial markets via random networks.

We investigate financial market dynamics by introducing a heterogeneous agent-based opinion formation model. In this work, we organize individuals in a financial market according to their trading strategy, namely, whether they are noise traders or fundamentalists. The opinion of a local majority compels the market exchanging behavior of noise traders, whereas the global behavior of the market influences the decisions of fundamentalist agents. We introduce a noise parameter, q, to represent the level of anxiety and perceived uncertainty regarding market behavior, enabling the possibility of adrift financial action. We place individuals as nodes in an Erdös-Rényi random graph, where the links represent their social interactions. At any given time, individuals assume one of two possible opinion states ±1 regarding buying or selling an asset. The model exhibits fundamental qualitative and quantitative real-world market features such as the distribution of logarithmic returns with fat tails, clustered volatility, and the long-term correlation of returns. We use Student's t distributions to fit the histograms of logarithmic returns, showing a gradual shift from a leptokurtic to a mesokurtic regime depending on the fraction of fundamentalist agents. Furthermore, we compare our results with those concerning the distribution of the logarithmic returns of several real-world financial indices.

Newly identified disorder of copper metabolism caused by variants in CTR1, a high-affinity copper transporter.

The high-affinity copper transporter CTR1 is encoded by CTR1 (SLC31A1), a gene locus for which no detailed genotype-phenotype correlations have previously been reported. We describe identical twin male infants homozygous for a novel missense variant NM_001859.4:c.284 G > A (p.Arg95His) in CTR1 with a distinctive autosomal recessive syndrome of infantile seizures and neurodegeneration, consistent with profound central nervous system copper deficiency. We used clinical, biochemical and molecular methods to delineate the first recognized examples of human CTR1 deficiency. These included clinical phenotyping, brain imaging, assays for copper, cytochrome c oxidase (CCO), and mitochondrial respiration, western blotting, cell transfection experiments, confocal and electron microscopy, protein structure modeling and fetal brain and cerebral organoid CTR1 transcriptome analyses. Comparison with two other critical mediators of cellular copper homeostasis, ATP7A and ATP7B, genes associated with Menkes disease and Wilson disease, respectively, revealed that expression of CTR1 was highest. Transcriptome analyses identified excitatory neurons and radial glia as brain cell types particularly enriched for copper transporter transcripts. We also assessed the effects of Copper Histidinate in the patients' cultured cells and in the patients, under a formal clinical protocol. Treatment normalized CCO activity and enhanced mitochondrial respiration in vitro, and was associated with modest clinical improvements. In combination with present and prior studies, these infants' clinical, biochemical and molecular phenotypes establish the impact of this novel variant on copper metabolism and cellular homeostasis and illuminate a crucial role for CTR1 in human brain development. CTR1 deficiency represents a newly defined inherited disorder of brain copper metabolism.

Empagliflozin for treating neutropenia and neutrophil dysfunction in 21 infants with glycogen storage disease 1b.

Empagliflozin has been successfully repurposed for treating neutropenia and neutrophil dysfunction in patients with glycogen storage disease type 1b (GSD 1b), however, data in infants are missing. We report on efficacy and safety of empagliflozin in infants with GSD 1b. This is an international retrospective case series on 21 GSD 1b infants treated with empagliflozin (total treatment time 20.6 years). Before starting empagliflozin (at a median age of 8.1 months with a median dose of 0.3 mg/kg/day) 12 patients had clinical signs and symptoms of neutrophil dysfunction. Six of these previously symptomatic patients had no further neutropenia/neutrophil dysfunction-associated findings on empagliflozin. Eight patients had no signs and symptoms of neutropenia/neutrophil dysfunction before start and during empagliflozin treatment. One previously asymptomatic individual with a horseshoe kidney developed a central line infection with pyelonephritis and urosepsis during empagliflozin treatment. Of the 10 patients who were treated with G-CSF before starting empagliflozin, this was stopped in four and decreased in another four. Eleven individuals were never treated with G-CSF. While in 17 patients glucose homeostasis remained stable on empagliflozin, four showed glucose homeostasis instability in the introductory phase. In 17 patients, no other side effects were reported, while genital (n = 2) or oral (n = 1) candidiasis and skin infection (n = 1) were reported in the remaining four. Empagliflozin had a good effect on neutropenia/neutrophil dysfunction-related signs and symptoms and a favourable safety profile in infants with GSD 1b and therefore qualifies for further exploration as first line treatment.

Newborn screening algorithm distinguishing potential symptomatic isovaleric acidemia from asymptomatic newborns.

Newborn screening (NBS) for isovaleric acidemia (IVA) reduces mortality and morbidity; however, it has also resulted in the detection of individuals with an asymptomatic or mild presentation for which early detection via newborn screening has not been proven to alter neurological outcome. We reevaluated biochemical and molecular data for newborns flagged positive for IVA in aim of developing a new screening algorithm to exclude the latter from positive screening. Among 2 794 365 newborns underwent routine newborn screening in Israel, 412 flagged positive for IVA, of which, 371 were false positives on recall sample testing and 41 positive newborns were referred to the clinic. 38/41 have biochemical and molecular confirmation in keeping with IVA. Among the 38 patients, 32% (12/38) were classified as symptomatic while, 68% (26/38) were classified as asymptomatic. 69% of the latter group harbor the known variant associated with mild potentially asymptomatic phenotype, c.932C>T; p. Ala311Val. Among asymptomatic patients, only 46% (12/26) are currently treated. Two novel variants have been detected in the IVD gene: c.487G>A; p. Ala163Thr and c.985A>G; p. Met329Val. Cut-off recalculation, of referred newborns' initial biochemical results, after classifying the referred patients to two binary groups of symptomatic and asymptomatic, resulted in an improved NBS algorithm comprising of C5 >5 µM and C5/C2>0.2 and C5/C3>4 flagging only those likely to have the classic symptomatic phenotype.

Ancient herders enriched and restructured African grasslands.

Grasslands are one of the world's most extensive terrestrial biomes and are central to the survival of herders, their livestock and diverse communities of large wild mammals1-3. In Africa, tropical soils are predominantly nutrient-limited4-6 but productive grassy patches in wooded grassland savannah ecosystems2,4 grow on fertile soils created by geologic and edaphic factors, megafauna, fire and termites4-6. Mobile pastoralists also create soil-fertility hotspots by penning their herds at night, which concentrates excrement-and thus nutrients-from grazing of the surrounding savannahs7-11. Historical anthropogenic hotspots produce high-quality forage, attract wildlife and increase spatial heterogeneity in African savannahs4,12-15. Archaeological research suggests this effect extends back at least 1,000 years16-19 but little is known about nutrient persistence at millennial scales. Here we use chemical, isotopic and sedimentary analyses to show high nutrient and 15N enrichment in on-site degraded dung deposits relative to off-site soils at five Pastoral Neolithic20 sites (radiocarbon dated to between 3,700 and 1,550 calibrated years before present (cal. BP)). This study demonstrates the longevity of nutrient hotspots and the long-term legacy of ancient herders, whose settlements enriched and diversified African savannah landscapes over three millennia.

Optimal resilience of modular interacting networks.

Coupling between networks is widely prevalent in real systems and has dramatic effects on their resilience and functional properties. However, current theoretical models tend to assume homogeneous coupling where all the various subcomponents interact with one another, whereas real-world systems tend to have various different coupling patterns. We develop two frameworks to explore the resilience of such modular networks, including specific deterministic coupling patterns and coupling patterns where specific subnetworks are connected randomly. We find both analytically and numerically that the location of the percolation phase transition varies nonmonotonically with the fraction of interconnected nodes when the total number of interconnecting links remains fixed. Furthermore, there exists an optimal fraction [Formula: see text] of interconnected nodes where the system becomes optimally resilient and is able to withstand more damage. Our results suggest that, although the exact location of the optimal [Formula: see text] varies based on the coupling patterns, for all coupling patterns, there exists such an optimal point. Our findings provide a deeper understanding of network resilience and show how networks can be optimized based on their specific coupling patterns.

Underweight in the first 2 years of life and nutrition risk in later childhood: a prospective cohort study.

BACKGROUND: Children with underweight in the first 2 years have lower body mass index z-score (zBMI) and height-for-age z-score (HAZ) in later childhood. It is not known if underweight in the first 2 years is associated with nutrition risk in later childhood. OBJECTIVE: (1) Determine the relationship between underweight (zBMI < -2) in the first 2 years and nutrition risk measured by the Nutrition Screening for Toddlers and Preschoolers (NutriSTEP) score from 18 months to 5 years. (2) Explore the relationship between underweight in the first 2 years and the NutriSTEP subscores for eating behaviours and dietary intake from 18 months to 5 years. METHODS: This was a prospective study, including healthy full-term children in Canada aged 0-5 years. zBMI was calculated using measured heights and weights and the WHO growth standards. NutriSTEP score was measured using a parent-completed survey and ranged from 0 to 68. Nutrition risk was defined as a score ≥21. Linear mixed effects models were used. RESULTS: Four thousand nine hundred twenty-nine children were included in this study. At enrolment, 51.9% of participants were male. The prevalence of underweight children was 8.8%. Underweight in the first 2 years was associated with higher NutriSTEP (0.79, 95% CI: 0.29,1.29), higher eating behaviour subscore (0.24, 95% CI: 0.03, 0.46) at 3 years and higher odds of nutrition risk (OR: 1.39, 95% CI: 1.07,1.82) at 5 years. CONCLUSIONS: Children with underweight in the first 2 years had higher nutrition risk in later childhood. Further research is needed to understand the factors which influence these relationships.

Integrative geochronology calibrates the Middle and Late Stone Ages of Ethiopia's Afar Rift.

The Halibee member of the Upper Dawaitoli Formation of Ethiopia's Middle Awash study area features a wealth of Middle and Later Stone Age (MSA and LSA) paleoanthropological resources in a succession of Pleistocene sediments. We introduce these artifacts and fossils, and determine their chronostratigraphic placement via a combination of established radioisotopic methods and a recently developed dating method applied to ostrich eggshell (OES). We apply the recently developed 230Th/U burial dating of OES to bridge the temporal gap between radiocarbon (14C) and 40Ar/39Ar ages for the MSA and provide 14C ages to constrain the younger LSA archaeology and fauna to ∼24 to 21.4 ka. Paired 14C and 230Th/U burial ages of OES agree at ∼31 ka for an older LSA locality, validating the newer method, and in turn supporting its application to stratigraphically underlying MSA occurrences previously constrained only by a maximum 40Ar/39Ar age. Associated fauna, flora, and Homo sapiens fossils are thereby now fixed between 106 ± 20 ka and 96.4 ± 1.6 ka (all errors 2σ). Additional 40Ar/39 results on an underlying tuff refine its age to 158.1 ± 11.0 ka, providing a more precise minimum age for MSA lithic artifacts, fauna, and H. sapiens fossils recovered ∼9 m below it. These results demonstrate how chronological control can be obtained in tectonically active and stratigraphically complex settings to precisely calibrate crucial evidence of technological, environmental, and evolutionary changes during the African Middle and Late Pleistocene.

Tregs Attenuate Peripheral Oxidative Stress and Acute Phase Proteins in ALS.

Oxidative stress (OS) induces inflammation, which in turn exacerbates OS and the expression of acute phase proteins (APPs). Regulatory T lymphocyte (Treg) therapy was assessed for suppression of OS and APP responses in longitudinal serum samples from subjects with amyotrophic lateral sclerosis (ALS) enrolled in a phase I clinical trial. The first round of Treg therapy suppressed levels of oxidized low-density lipoprotein (ox-LDL). During a 6-month washout period, ox-LDL levels increased. A second round of therapy again suppressed ox-LDL levels and then rose following the cessation of treatment. Serum levels of APPs, soluble CD14, lipopolysaccharide binding protein, and C-reactive protein, were stabilized during Treg administrations, but rose during the washout period and again after therapy was discontinued. Treg therapy potentially suppresses peripheral OS and the accompanying circulating pro-inflammatory induced APPs, both of which may serve as peripheral candidates for monitoring efficacies of immunomodulating therapies. ANN NEUROL 2022;92:195-200.

Addition of galactose-1-phosphate measurement enhances newborn screening for classical galactosemia.

Galactosemia is an inborn disorder of carbohydrate metabolism of which early detection can prevent severe illness. Although the assay for galactose-1-phosphate uridyltransferase (GALT) enzyme activity has been available since the 1960s, many issues prevented it from becoming universal. In order to develop the Israeli newborn screening pilot algorithm for galactosemia, flow injection analysis tandem mass spectrometry measurement of galactose-1-phosphate in archived dried blood spots from newborns with classical galactosemia, galactosemia variants, epimerase deficiency, and normal controls, was conducted. Out of 431 330 newborns screened during the pilot study (30 months), two with classical galactosemia and four with epimerase deficiency were identified and confirmed. Five false positives and no false negatives were recorded. Following this pilot study, the Israeli final and routine newborn screening algorithm, as recommended by the Advisory Committee to the National Newborn Screening Program, now consists of galactose-1-phosphate measurement integrated into the routine tandem mass spectrometry panel as the first-tier screening test, and GALT enzyme activity as the second-tier performed to identify only newborns suspected to be at risk for classical galactosemia. The GALT enzyme activity cut-off used in the final algorithm was lowered in order to avoid false positives.

Power-law distribution of degree-degree distance: A better representation of the scale-free property of complex networks.

Whether real-world complex networks are scale free or not has long been controversial. Recently, in Broido and Clauset [A. D. Broido, A. Clauset, Nat. Commun. 10, 1017 (2019)], it was claimed that the degree distributions of real-world networks are rarely power law under statistical tests. Here, we attempt to address this issue by defining a fundamental property possessed by each link, the degree-degree distance, the distribution of which also shows signs of being power law by our empirical study. Surprisingly, although full-range statistical tests show that degree distributions are not often power law in real-world networks, we find that in more than half of the cases the degree-degree distance distributions can still be described by power laws. To explain these findings, we introduce a bidirectional preferential selection model where the link configuration is a randomly weighted, two-way selection process. The model does not always produce solid power-law distributions but predicts that the degree-degree distance distribution exhibits stronger power-law behavior than the degree distribution of a finite-size network, especially when the network is dense. We test the strength of our model and its predictive power by examining how real-world networks evolve into an overly dense stage and how the corresponding distributions change. We propose that being scale free is a property of a complex network that should be determined by its underlying mechanism (e.g., preferential attachment) rather than by apparent distribution statistics of finite size. We thus conclude that the degree-degree distance distribution better represents the scale-free property of a complex network.

Unveiling causal interactions in complex systems.

Throughout time, operational laws and concepts from complex systems have been employed to quantitatively model important aspects and interactions in nature and society. Nevertheless, it remains enigmatic and challenging, yet inspiring, to predict the actual interdependencies that comprise the structure of such systems, particularly when the causal interactions observed in real-world phenomena might be persistently hidden. In this article, we propose a robust methodology for detecting the latent and elusive structure of dynamic complex systems. Our treatment utilizes short-term predictions from information embedded in reconstructed state space. In this regard, using a broad class of real-world applications from ecology, neurology, and finance, we explore and are able to demonstrate our method's power and accuracy to reconstruct the fundamental structure of these complex systems, and simultaneously highlight their most fundamental operations.

Freedom of choice adds value to public goods.

Public goods, ranging from judiciary to sanitation to parkland, permeate daily life. They have been a subject of intense interdisciplinary study, with a traditional focus being on participation levels in isolated public goods games (PGGs) as opposed to a more recent focus on participation in PGGs embedded into complex social networks. We merged the two perspectives by arranging voluntary participants into one of three network configurations, upon which volunteers played a number of iterated PGGs within their network neighborhood. The purpose was to test whether the topology of social networks or a freedom to express preferences for some local public goods over others affect participation. The results show that changes in social networks are of little consequence, yet volunteers significantly increase participation when they freely express preferences. Surprisingly, the increase in participation happens from the very beginning of the game experiment, before any information about how others play can be gathered. Such information does get used later in the game as volunteers seek to correlate contributions with higher returns, thus adding significant value to public goods overall. These results are ascribable to a small number of behavioral phenotypes, and suggest that societies may be better off with bottom-up schemes for public goods provision.

Multiple metastable network states in urban traffic.

While abrupt regime shifts between different metastable states have occurred in natural systems from many areas including ecology, biology, and climate, evidence for this phenomenon in transportation systems has been rarely observed so far. This limitation might be rooted in the fact that we lack methods to identify and analyze possible multiple states that could emerge at scales of the entire traffic network. Here, using percolation approaches, we observe such a metastable regime in traffic systems. In particular, we find multiple metastable network states, corresponding to varying levels of traffic performance, which recur over different days. Based on high-resolution global positioning system (GPS) datasets of urban traffic in the megacities of Beijing and Shanghai (each with over 50,000 road segments), we find evidence supporting the existence of tipping points separating three regimes: a global functional regime and a metastable hysteresis-like regime, followed by a global collapsed regime. We can determine the intrinsic critical points where the metastable hysteresis-like regime begins and ends and show that these critical points are very similar across different days. Our findings provide a better understanding of traffic resilience patterns and could be useful for designing early warning signals for traffic resilience management and, potentially, other complex systems.

Interpretations of meaningful and ambiguous hand gestures in autistic and non-autistic adults: A norming study.

Gestures are ubiquitous in human communication, and a growing but inconsistent body of research suggests that people with autism spectrum disorder (ASD) may process co-speech gestures differently from neurotypical individuals. To facilitate research on this topic, we created a database of 162 gesture videos that have been normed for comprehensibility by both autistic and non-autistic raters. These videos portray an actor performing silent gestures that range from highly meaningful (e.g., iconic gestures) to ambiguous or meaningless. Each video was rated for meaningfulness and given a one-word descriptor by 40 autistic and 40 non-autistic adults, and analyses were conducted to assess the level of within- and across-group agreement. Across gestures, the meaningfulness ratings provided by raters with and without ASD correlated at r > 0.90, indicating a very high level of agreement. Overall, autistic raters produced a more diverse set of verbal labels for each gesture than did non-autistic raters. However, measures of within-gesture semantic similarity among the responses provided by each group did not differ, suggesting that increased variability within the ASD group may have occurred at the lexical rather than semantic level. This study is the first to compare gesture naming between autistic and non-autistic individuals, and the resulting dataset is the first gesture stimulus set for which both groups were equally represented in the norming process. This database also has broad applicability to other areas of research related to gesture processing and comprehension. The video database and accompanying norming data are available on the Open Science Framework.

Cannabis Use is Associated With Reduced 30-Day All-cause Readmission Among Hospitalized Patients With Irritable Bowel Syndrome: A Nationwide Analysis.

BACKGROUND: Cannabinoid receptors are potential therapeutic targets in a variety of gastrointestinal tract disorders. The authors hypothesize that the use of cannabis use is associated with better control of symptoms associated with irritable bowel syndrome (IBS). This study aimed to examine the utilization of inpatient services by patients with IBS who did and did not report the use of cannabis. METHODS: This is a retrospective cohort study that utilized the 2016 Nationwide Readmissions Database. Inclusion criteria included a principal diagnosis of IBS. The primary outcome was 30-day hospital readmission rates for IBS-specific causes. Secondary outcomes included the 30-day hospital readmission rates for all causes, resource utilization, and the 5 most common principal diagnoses and independent risk factors associated with readmission. RESULTS: Of the 7163 patients with IBS identified in the National Readmission Database, 357 reported the use of cannabis. The 30-day IBS-specific readmission rates were 1.5% in patients who reported cannabis use and 1.1% in those who did not report cannabis use (P=0.53). Among the cannabis users, none of the variables evaluated served as a significant predictor of IBS-specific readmission; median income was a predictor for readmission among those who did not report cannabis use (odds ratio, 2.77; 95% confidence interval, 1.15-6.67; P=0.02). The 30-day readmission rates for all causes were 8.1% and 12.7% for patients who did and did not report cannabis use, respectively. After adjusting for confounders, the odds of 30-day readmission for all causes were lower among patients who reported cannabis use compared with those who did not (adjusted odds ratio, 0.53; 95% confidence interval, 0.28-0.99; P=0.04). The 5 most frequent diagnoses at readmission among patients who did not report cannabis use were enterocolitis because of Clostridioides difficile, IBS without diarrhea, sepsis, noninfective gastroenteritis and colitis, and acute kidney failure. By contrast, the 5 most frequent readmission diagnoses for cannabis users were cyclical vomiting, IBS with diarrhea, endometriosis, right upper quadrant abdominal pain, and nausea with vomiting. A discharge disposition of "against medical advice" was identified as an independent risk factor for 30-day hospital readmission for all causes among patients who reported cannabis use. By contrast, higher comorbidity scores and discharges with home health care were independent predictors of 30-day hospital readmission for all causes among patients who did not report cannabis use. Private insurance was an independent factor associated with lower rates of readmission for all causes among those who did not report cannabis use. CONCLUSION: Our review of the National Readmission Database revealed no statistically significant differences in 30-day readmission rates for IBS-specific causes when comparing patients who reported cannabis use with those who did not. However, the authors found that cannabis use was associated with reduced 30-day hospital readmission rates for all causes.

Effect of maternal vitamin D supplementation on nasal pneumococcal acquisition, carriage dynamics and carriage density in infants in Dhaka, Bangladesh.

BACKGROUND: Invasive pneumococcal disease is a major cause of infant morbidity and death worldwide. Vitamin D promotes anti-pneumococcal immune responses in vitro, but whether improvements in infant vitamin D status modify risks of nasal pneumococcal acquisition in early life is not known. METHODS: This is a secondary analysis of data collected in a trial cohort in Dhaka, Bangladesh. Acute respiratory infection (ARI) surveillance was conducted from 0 to 6 months of age among 1060 infants of women randomized to one of four pre/post-partum vitamin D dose combinations or placebo. Nasal swab samples were collected based on standardized ARI criteria, and pneumococcal DNA quantified by qPCR. Hazards ratios of pneumococcal acquisition and carriage dynamics were estimated using interval-censored survival and multi-state modelling. RESULTS: Pneumococcal carriage was detected at least once in 90% of infants by 6 months of age; overall, 69% of swabs were positive (2616/3792). There were no differences between any vitamin D group and placebo in the hazards of pneumococcal acquisition, carriage dynamics, or carriage density (p > 0.05 for all comparisons). CONCLUSION: Despite in vitro data suggesting that vitamin D promoted immune responses against pneumococcus, improvements in postnatal vitamin D status did not reduce the rate, alter age of onset, or change dynamics of nasal pneumococcal colonization in early infancy. Trial registration Registered in ClinicalTrials.gov with the registration number of NCT02388516 and first posted on March 17, 2015.

Neuroinflammation is highest in areas of disease progression in semantic dementia.

Despite epidemiological and genetic data linking semantic dementia to inflammation, the topography of neuroinflammation in semantic dementia, also known as the semantic variant of primary progressive aphasia, remains unclear. The pathology starts at the tip of the left temporal lobe where, in addition to cortical atrophy, a strong signal appears with the tau PET tracer 18F-flortaucipir, even though the disease is not typically associated with tau but with TDP-43 protein aggregates. Here, we characterized the topography of inflammation in semantic variant primary progressive aphasia using high-resolution PET and the tracer 11C-PBR28 as a marker of microglial activation. We also tested the hypothesis that inflammation, by providing non-specific binding targets, could explain the 18F-flortaucipir signal in semantic variant primary progressive aphasia. Eight amyloid-PET-negative patients with semantic variant primary progressive aphasia underwent 11C-PBR28 and 18F-flortaucipir PET. Healthy controls underwent 11C-PBR28 PET (n = 12) or 18F-flortaucipir PET (n = 12). Inflammation in PET with 11C-PBR28 was analysed using Logan graphical analysis with a metabolite-corrected arterial input function. 18F-flortaucipir standardized uptake value ratios were calculated using the cerebellum as the reference region. Since monoamine oxidase B receptors are expressed by astrocytes in affected tissue, selegiline was administered to one patient with semantic variant primary progressive aphasia before repeating 18F-flortaucipir scanning to test whether monoamine oxidase B inhibition blocked flortaucipir binding, which it did not. While 11C-PBR28 uptake was mostly cortical, 18F-flortaucipir uptake was greatest in the white matter. The uptake of both tracers was increased in the left temporal lobe and in the right temporal pole, as well as in regions adjoining the left temporal pole such as insula and orbitofrontal cortex. However, peak uptake of 18F-flortaucipir localized to the left temporal pole, the epicentre of pathology, while the peak of inflammation 11C-PBR28 uptake localized to a more posterior, mid-temporal region and left insula and orbitofrontal cortex, in the periphery of the damage core. Neuroinflammation, greatest in the areas of progression of the pathological process in semantic variant primary progressive aphasia, should be further studied as a possible therapeutic target to slow disease progression.

New geological and palaeontological age constraint for the gorilla-human lineage split.

The palaeobiological record of 12 million to 7 million years ago (Ma) is crucial to the elucidation of African ape and human origins, but few fossil assemblages of this period have been reported from sub-Saharan Africa. Since the 1970s, the Chorora Formation, Ethiopia, has been widely considered to contain ~10.5 million year (Myr) old mammalian fossils. More recently, Chororapithecus abyssinicus, a probable primitive member of the gorilla clade, was discovered from the formation. Here we report new field observations and geochemical, magnetostratigraphic and radioisotopic results that securely place the Chorora Formation sediments to between ~9 and ~7 Ma. The C. abyssinicus fossils are ~8.0 Myr old, forming a revised age constraint of the human-gorilla split. Other Chorora fossils range in age from ~8.5 to 7 Ma and comprise the first sub-Saharan mammalian assemblage that spans this period. These fossils suggest indigenous African evolution of multiple mammalian lineages/groups between 10 and 7 Ma, including a possible ancestral-descendent relationship between the ~9.8 Myr old Nakalipithecus nakayamai and C. abyssinicus. The new chronology and fossils suggest that faunal provinciality between eastern Africa and Eurasia had intensified by ~9 Ma, with decreased faunal interchange thereafter. The Chorora evidence supports the hypothesis of in situ African evolution of the Gorilla-Pan-human clade, and is concordant with the deeper divergence estimates of humans and great apes based on lower mutation rates of ~0.5 × 10(-9) per site per year (refs 13 - 15).