The enamel-dentine junction of the upper premolars of Homo naledi and other hominins: a morphometric study.

ABSTRACT.Homo naledi is a hominin species first described in 2015 based on remains from the Dinaledi Chamber in the Rising Star cave system in South Africa. There has been much debate about the taxonomy and phylogenetic relationships of H. naledi because of its unique mix of primitive and advanced features. It has a primitive body size, chest, shoulders and hips and the brain size is small both absolutely and in relation to its body size. However, it does show more advanced features in the wrist, foot and thumb. The dentition also shows mixed features, being small, as in modern humans, but retaining certain primitive features in morphology.In this study, geometric morphometric analysis was applied to the enamel-dentine junction (EDJ) of the upper premolars of H. naledi and a comparative sample of living and fossil hominins. The aims of the study were to determine whether this technique can distinguish between the upper premolars of different hominin taxa and of tooth position within taxa and, if so, to use the method to elucidate the taxonomic relationships of Homo naledi. Additionally, the study identified qualitative morphological features of the EDJ. Their frequency of expression between species and tooth position was analyzed and the differences between group mean frequencies of expression was summarised by multidimensional scaling.The principal components of shape, derived from a Procrustes analysis, were able to differentiate well between hominin taxa and between tooth position within taxa. There is a morphological trend from Paranthropus robustus at one extreme to modern Homo sapiens at the other. This is also an allometric trend, as the size of the EDJ is correlated with the first principal component of shape. At the Paranthropus extreme, the EDJ is short and broad, especially in the bucco-lingual direction. The EDJ ridge has a square or rectangular outline with expansion of the talon in a disto-lingual direction. At the other end of the trend, the EDJ is taller and narrower, with a more triangular outline due to a flatter disto-lingual portion of the EDJ ridge. Third upper premolars differ from fourth upper premolars by having taller, more distally placed buccal dentine horns.H. naledi has a unique morphology within the genus Homo. The EDJ is small but, has retained a more primitive morphology. It has a prominent distal accessory buccal dentine horn and a short main buccal dentine horn with prominent disto-lingual extension of the talon, leading to a relatively flat and broad EDJ profile. In addition, the size of the fourth upper premolar is greater than that of the third, as is seen in Australopithecus and Paranthropus and unlike other species of Homo, where the teeth are more equal in size or the third upper premolar is larger. This autapomorphy could suggest that H. naledi was adapted to a different dietary lifestyle than other members of the genus Homo.Qualitative trait analysis identified and described some features at the EDJ for the first time in the hominin study sample. Third upper premolars of the genus Homo are associated with a notch and mesial 'bulge' in the mesial EDJ ridge together with a depression or concavity in the mesial surface of the EDJ (except for H. naledi where there is a bulge but no notch); fourth upper premolars of all hominin species have a tendency to form a distinct distal accessory buccal dentine horn, except for H. neanderthalensis, where there is a distinctive distal buccal shoulder instead; A. africanus teeth are associated with prominent ridges on the buccal surface of the tooth together with extension of the buccal cingulum and lingual cingulum but P. robustus is more strongly associated with a shelf-like lingual cingulum; third upper premolars of H. neanderthalensis have a distinctive boss-shaped bulge in the buccal cingulum. P. robustus and, to a lesser extent A. africanus, show a tendency towards molarisation, with an oblique ridge, distal accessory lingual dentine horn and talon expansion. A transverse crest is almost universally present in the EDJs of all Homo species except for H. sapiens (both fossil and modern) and in H. naledi, where there is a distinctive bucco-mesial ridge in place of the transverse crest in 43% of third upper premolars. This contrasts with the outer enamel surface (OES), where transverse crests are rarely observed in Homo species

Dental morphology in homo habilis and its implications for the evolution of early homo.

The phylogenetic position of Homo habilis is central to debates over the origin and early evolution of the genus Homo. A large portion of the species hypodigm consists of dental remains, but they have only been studied at the often worn enamel surface. We investigate the morphology of the H. habilis enamel-dentine junction (EDJ), which is preserved in cases of moderate tooth wear and known to carry a strong taxonomic signal. Geometric morphometrics is used to characterise dentine crown shape and size across the entire mandibular and maxillary tooth rows, compared with a broad comparative sample (n = 712). We find that EDJ morphology in H. habilis is for the most part remarkably primitive, supporting the hypothesis that the H. habilis hypodigm has more in common with Australopithecus than later Homo. Additionally, the chronologically younger specimen OH 16 displays a suite of derived features; its inclusion in H. habilis leads to excessive levels of variation

Mutations in FGF17, IL17RD, DUSP6, SPRY4, and FLRT3 Are Identified in Individuals with Congenital Hypogonadotropic Hypogonadism

Congenital hypogonadotropic hypogonadism (CHH) and its anosmia-associated form (Kallmann syndrome [KS]) are genetically heterogeneous. Among the >15 genes implicated in these conditions, mutations in FGF8 and FGFR1 account for ∼12% of cases; notably, KAL1 and HS6ST1 are also involved in FGFR1 signaling and can be mutated in CHH. We therefore hypothesized that mutations in genes encoding a broader range of modulators of the FGFR1 pathway might contribute to the genetics of CHH as causal or modifier mutations. Thus, we aimed to (1) investigate whether CHH individuals harbor mutations in members of the so-called "FGF8 synexpression" group and (2) validate the ability of a bioinformatics algorithm on the basis of protein-protein interactome data (interactome-based affiliation scoring [IBAS]) to identify high-quality candidate genes. On the basis of sequence homology, expression, and structural and functional data, seven genes were selected and sequenced in 386 unrelated CHH individuals and 155 controls. Except for FGF18 and SPRY2, all other genes were found to be mutated in CHH individuals: FGF17 (n = 3 individuals), IL17RD (n = 8), DUSP6 (n = 5), SPRY4 (n = 14), and FLRT3 (n = 3). Independently, IBAS predicted FGF17 and IL17RD as the two top candidates in the entire proteome on the basis of a statistical test of their protein-protein interaction patterns to proteins known to be altered in CHH. Most of the FGF17 and IL17RD mutations altered protein function in vitro. IL17RD mutations were found only in KS individuals and were strongly linked to hearing loss (6/8 individuals). Mutations in genes encoding components of the FGF pathway are associated with complex modes of CHH inheritance and act primarily as contributors to an oligogenic genetic architecture underlying CHH

The Matter in Extreme Conditions instrument at the Linac Coherent Light Source

The LCLS beam provides revolutionary capabilities for studying the transient behavior of matter in extreme conditions. The particular strength of the Matter in Extreme Conditions instrument is that it combines the unique LCLS beam with high-power optical laser beams, and a suite of dedicated diagnostics tailored for this field of science. In this paper an overview of the beamline, the capabilities of the instrumentation, and selected highlights of experiments and commissioning results are presented

Risk Factors for Cervical Precancer and Cancer in HIV-Infected, HPV-Positive Rwandan Women

Although cervical cancer is an AIDS-defining condition, infection with human immunodeficiency virus (HIV) may only modestly increase the risk of cervical cancer. There is a paucity of information regarding factors that influence the natural history of human papillomavirus (HPV) in HIV-infected women. We examined factors associated with cervical intraepithelial neoplasia grade 3 or cancer (CIN3+) in Rwandan women infected with both HIV and HPV (HIV+/HPV+).In 2005, 710 HIV+ Rwandan women ≥25 years enrolled in an observational cohort study; 476 (67%) tested HPV+. Each woman provided sociodemographic data, CD4 count, a cervical cytology specimen and cervicovaginal lavage (CVL), which was tested for >40 HPV genotypes by MY09/MY11 PCR assay. Logistic regression models calculated odds ratios (OR) and 95% confidence intervals (CI) of associations of potential risk factors for CIN3+ among HIV+/HPV+ women.Of the 476 HIV+/HPV+ women 42 (8.8%) were diagnosed with CIN3+. Factors associated with CIN3+ included ≥7 (vs. 0-2) pregnancies, malarial infection in the previous six months (vs. never), and ≥7 (vs. 0-2) lifetime sexual partners. Compared to women infected by non-HPV16 carcinogenic HPV genotypes, HPV16 infection was positively associated and non-carcinogenic HPV infection was inversely associated with CIN3+. CD4 count was significantly associated with CIN3+ only in analyses of women with non-HPV16 carcinogenic HPV (OR = 0.62 per 100 cells/mm(3), CI = 0.40-0.97).In this HIV+/HPV+ population, lower CD4 was significantly associated with CIN3+ only in women infected with carcinogenic non-HPV16. We found a trend for higher risk of CIN3+ in HIV+ women reporting recent malarial infection; this association should be investigated in a larger group of HIV+/HPV+ women

Connecting Land–Atmosphere Interactions to Surface Heterogeneity in CHEESEHEAD19

The Chequamegon Heterogeneous Ecosystem Energy-Balance Study Enabled by a High-Density Extensive Array of Detectors 2019 (CHEESEHEAD19) is an ongoing National Science Foundation project based on an intensive field campaign that occurred from June to October 2019. The purpose of the study is to examine how the atmospheric boundary layer (ABL) responds to spatial heterogeneity in surface energy fluxes. One of the main objectives is to test whether lack of energy balance closure measured by eddy covariance (EC) towers is related to mesoscale atmospheric processes. Finally, the project evaluates data-driven methods for scaling surface energy fluxes, with the aim to improve model–data comparison and integration. To address these questions, an extensive suite of ground, tower, profiling, and airborne instrumentation was deployed over a 10 km × 10 km domain of a heterogeneous forest ecosystem in the Chequamegon–Nicolet National Forest in northern Wisconsin, United States, centered on an existing 447-m tower that anchors an AmeriFlux/NOAA supersite (US-PFa/WLEF). The project deployed one of the world’s highest-density networks of above-canopy EC measurements of surface energy fluxes. This tower EC network was coupled with spatial measurements of EC fluxes from aircraft; maps of leaf and canopy properties derived from airborne spectroscopy, ground-based measurements of plant productivity, phenology, and physiology; and atmospheric profiles of wind, water vapor, and temperature using radar, sodar, lidar, microwave radiometers, infrared interferometers, and radiosondes. These observations are being used with large-eddy simulation and scaling experiments to better understand submesoscale processes and improve formulations of subgrid-scale processes in numerical weather and climate models

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

The Atmospheric Chemistry and Climate Model Intercomparison Project (ACCMIP): Overview and description of models, simulations and climate diagnostics

The Atmospheric Chemistry and Climate Model Intercomparison Project (ACCMIP) consists of a series of time slice experiments targeting the long-term changes in atmospheric composition between 1850 and 2100, with the goal of documenting composition changes and the associated radiative forcing. In this overview paper, we introduce the ACCMIP activity, the various simulations performed (with a requested set of 14) and the associated model output. The 16 ACCMIP models have a wide range of horizontal and vertical resolutions, vertical extent, chemistry schemes and interaction with radiation and clouds. While anthropogenic and biomass burning emissions were specified for all time slices in the ACCMIP protocol, it is found that the natural emissions are responsible for a significant range across models, mostly in the case of ozone precursors. The analysis of selected present-day climate diagnostics (precipitation, temperature, specific humidity and zonal wind) reveals biases consistent with state-of-the-art climate models. The model-to-model comparison of changes in temperature, specific humidity and zonal wind between 1850 and 2000 and between 2000 and 2100 indicates mostly consistent results. However, models that are clear outliers are different enough from the other models to significantly affect their simulation of atmospheric chemistry