Modern humans have populated Europe for more than 45,000 years. Our knowledge of the genetic relatedness and structure of ancient hunter-gatherers is however limited, owing to the scarceness and... Show moreModern humans have populated Europe for more than 45,000 years. Our knowledge of the genetic relatedness and structure of ancient hunter-gatherers is however limited, owing to the scarceness and poor molecular preservation of human remains from that period. Here we analyse 356 ancient hunter-gatherer genomes, including new genomic data for 116 individuals from 14 countries in western and central Eurasia, spanning between 35,000 and 5,000 years ago. We identify a genetic ancestry profile in individuals associated with Upper Palaeolithic Gravettian assemblages from western Europe that is distinct from contemporaneous groups related to this archaeological culture in central and southern Europe, but resembles that of preceding individuals associated with the Aurignacian culture. This ancestry profile survived during the Last Glacial Maximum (25,000 to 19,000 years ago) in human populations from southwestern Europe associated with the Solutrean culture, and with the following Magdalenian culture that re-expanded northeastward after the Last Glacial Maximum. Conversely, we reveal a genetic turnover in southern Europe suggesting a local replacement of human groups around the time of the Last Glacial Maximum, accompanied by a north-to-south dispersal of populations associated with the Epigravettian culture. From at least 14,000 years ago, an ancestry related to this culture spread from the south across the rest of Europe, largely replacing the Magdalenian-associated gene pool. After a period of limited admixture that spanned the beginning of the Mesolithic, we find genetic interactions between western and eastern European hunter-gatherers, who were also characterized by marked differences in phenotypically relevant variants. Show less
Modern humans have populated Europe for more than 45,000 years(1,2). Our knowledge of the genetic relatedness and structure of ancient hunter-gatherers is however limited, owing to the scarceness... Show moreModern humans have populated Europe for more than 45,000 years(1,2). Our knowledge of the genetic relatedness and structure of ancient hunter-gatherers is however limited, owing to the scarceness and poor molecular preservation of human remains from that period(3). Here we analyse 356 ancient hunter-gatherer genomes, including new genomic data for 116 individuals from 14 countries in western and central Eurasia, spanning between 35,000 and 5,000 years ago. We identify a genetic ancestry profile in individuals associated with Upper Palaeolithic Gravettian assemblages from western Europe that is distinct from contemporaneous groups related to this archaeological culture in central and southern Europe(4), but resembles that of preceding individuals associated with the Aurignacian culture. This ancestry profile survived during the Last Glacial Maximum (25,000 to 19,000 years ago) in human populations from southwestern Europe associated with the Solutrean culture, and with the following Magdalenian culture that re-expanded northeastward after the Last Glacial Maximum. Conversely, we reveal a genetic turnover in southern Europe suggesting a local replacement of human groups around the time of the Last Glacial Maximum, accompanied by a north-to-south dispersal of populations associated with the Epigravettian culture. From at least 14,000 years ago, an ancestry related to this culture spread from the south across the rest of Europe, largely replacing the Magdalenian-associated gene pool. After a period of limited admixture that spanned the beginning of the Mesolithic, we find genetic interactions between western and eastern European hunter-gatherers, who were also characterized by marked differences in phenotypically relevant variants. Show less
Chinello, C.; Haan, N. de; Capitoli, G.; Trezzi, B.; Radice, A.; Pagani, L.; ... ; Magni, F. 2022
The podocyte injury, and consequent proteinuria, that characterize the pathology of idiopathic membranous nephropathy (IMN) is mediated by an autoimmune reaction against podocyte antigens. In... Show moreThe podocyte injury, and consequent proteinuria, that characterize the pathology of idiopathic membranous nephropathy (IMN) is mediated by an autoimmune reaction against podocyte antigens. In particular, the activation of pathways leading to abundant renal deposits of complement is likely to involve the binding of mannose-binding lectin (MBL) to aberrant glycans on immunoglobulins. To obtain a landscape of circulatory IgG Fc glycosylation characterizing this disease, we conducted a systematic N-glycan profiling study of IgG1, 2, and 4 by mass spectrometry. The cohort included 57 IMN patients, a pathological control group with nephrotic syndrome (PN) (n = 20), and 88 healthy control subjects. The effect of sex and age was assessed in all groups and controlled by rigorous matching. Several IgG Fc glycan traits were found to be associated with IMN. Interestingly, among them, only IgG4-related results were specific for IMN and not for PN. Hypo-galactosylation of IgG4, already shown for IMN, was observed to occur in the absence of core fucose, in line with a probable increase of pro-inflammatory IgG. In addition, elevated levels of fucosylated IgG4, along with low levels of hybrid-type glycans, were detected. Some of these IgG4 alterations are likely to be more pronounced in high PLA2R (phospholipase A2 receptor) patients. IgG Fc glycosylation patterns associated with IMN warrant further studies of their role in disease mechanisms and may eventually enrich the diagnostic spectrum regarding patient stratification. Show less
Context. According to traditional gas-phase chemical models, O$_{2}$ should be abundant in molecular clouds, but until recently, attempts to detect interstellar O$_{2}$ line emission with ground-... Show moreContext. According to traditional gas-phase chemical models, O$_{2}$ should be abundant in molecular clouds, but until recently, attempts to detect interstellar O$_{2}$ line emission with ground- and space-based observatories have failed. Aims: Following the multi-line detections of O$_{2}$ with low abundances in the Orion and {$ρ$} Oph A molecular clouds with Herschel, it is important to investigate other environments, and we here quantify the O$_{2}$ abundance near a solar-mass protostar. Methods: Observations of molecular oxygen, O$_{2}$, at 487 GHz toward a deeply embedded low-mass Class 0 protostar, NGC 1333-IRAS 4A, are presented, using the Heterodyne Instrument for the Far Infrared (HIFI) on the Herschel Space Observatory. Complementary data of the chemically related NO and CO molecules are obtained as well. The high spectral resolution data are analysed using radiative transfer models to infer column densities and abundances, and are tested directly against full gas-grain chemical models. Results: The deep HIFI spectrum fails to show O$_{2}$ at the velocity of the dense protostellar envelope, implying one of the lowest abundance upper limits of O$_{2}$/H$_{2}$ at {le}6 { imes} 10$^{-9}$ (3{$σ$}). The O$_{2}$/CO abundance ratio is less than 0.005. However, a tentative (4.5{$σ$}) detection of O$_{2}$ is seen at the velocity of the surrounding NGC 1333 molecular cloud, shifted by 1 km s$^{-1}$ relative to the protostar. For the protostellar envelope, pure gas-phase models and gas-grain chemical models require a long pre-collapse phase (~{}0.7-1 { imes} 10$^{6}$ years), during which atomic and molecular oxygen are frozen out onto dust grains and fully converted to H$_{2}$O, to avoid overproduction of O$_{2}$ in the dense envelope. The same model also reproduces the limits on the chemically related NO molecule if hydrogenation of NO on the grains to more complex molecules such as NH$_{2}$OH, found in recent laboratory experiments, is included. The tentative detection of O$_{2}$ in the surrounding cloud is consistent with a low-density PDR model with small changes in reaction rates. Conclusions: The low O$_{2}$ abundance in the collapsing envelope around a low-mass protostar suggests that the gas and ice entering protoplanetary disks is very poor in O$_{2}$. Herschel is an ESA space observatory with science instruments provided by European-led Principal Investigator consortia and with important participation from NASA.Appendices are available in electronic form at http://www.aanda.orgReduced spectra (FITS files) are only available at the CDS via anonymous ftp to http://cdsarc.u-strasbg.fr (ftp://130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/558/A58Show less
