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Diet is a crucial trait of an animal’s lifestyle and ecology. The trophic level of an organism indicates its functional position within an ecosystem and holds significance for its ecology and evolution. Here, we demonstrate the use of zinc isotopes (δ66Zn) to geochemically assess the trophic level in diverse extant and extinct sharks, including the Neogene megatooth shark (Otodus megalodon) and the great white shark (Carcharodon carcharias). We reveal that dietary δ66Zn signatures are preserved in fossil shark tooth enameloid over deep geologic time and are robust recorders of each species’ trophic level. We observe significant δ66Zn differences among the Otodus and Carcharodon populations implying dietary shifts throughout the Neogene in both genera. Notably, Early Pliocene sympatric C. carcharias and O. megalodon appear to have occupied a similar mean trophic level, a finding that may hold clues to the extinction of the gigantic Neogene megatooth shark.

The Pleistocene presence of the genus Homo in continental Southeast Asia is primarily evidenced by a sparse stone tool record and rare human remains. Here we report a Middle Pleistocene hominin specimen from Laos, with the discovery of a molar from the Tam Ngu Hao 2 (Cobra Cave) limestone cave in the Annamite Mountains. The age of the fossil-bearing breccia ranges between 164–131 kyr, based on the Bayesian modelling of luminescence dating of the sedimentary matrix from which it was recovered, U-series dating of an overlying flowstone, and U-series–ESR dating of associated faunal teeth. Analyses of the internal structure of the molar in tandem with palaeoproteomic analyses of the enamel indicate that the tooth derives from a young, likely female, Homo individual. The close morphological affinities with the Xiahe specimen from China indicate that they belong to the same taxon and that Tam Ngu Hao 2 most likely represents a Denisovan. Evidence for the presence of Homo during the Middle Pleistocene is limited in continental Southeast Asia. Here, the authors report a hominin molar from Tam Ngu Hao 2 (Cobra Cave), dated to 164–131 kyr. They use morphological and paleoproteomic analysis to show that it likely belonged to a female Denisovan.

The timing of the first arrival of Homo sapiens in East Asia from Africa and the degree to which they interbred with or replaced local archaic populations is controversial. Previous discoveries from Tam Pà Ling cave (Laos) identified H. sapiens in Southeast Asia by at least 46 kyr. We report on a recently discovered frontal bone (TPL 6) and tibial fragment (TPL 7) found in the deepest layers of TPL. Bayesian modeling of luminescence dating of sediments and U-series and combined U-series-ESR dating of mammalian teeth reveals a depositional sequence spanning ~86 kyr. TPL 6 confirms the presence of H. sapiens by 70 ± 3 kyr, and TPL 7 extends this range to 77 ± 9 kyr, supporting an early dispersal of H. sapiens into Southeast Asia. Geometric morphometric analyses of TPL 6 suggest descent from a gracile immigrant population rather than evolution from or admixture with local archaic populations. Here the authors report new human fossils from Tam Pà Ling cave, Laos, consisting of a cranial and a tibial fragment, dated to 68–86 thousand years ago. This find confirms that Homo sapiens were present in Southeast Asia by this time and the shape of the fossils indicates they may have descended from non-local populations.

Stable carbon and nitrogen isotope ratios of collagen from bone and dentin have frequently been used for dietary reconstruction, but this method is limited by protein preservation. Isotopes of the trace element zinc (Zn) in bioapatite constitute a promising proxy to infer dietary information from extant and extinct vertebrates. The 66Zn/64Zn ratio (expressed as δ66Zn value) shows an enrichment of the heavy isotope in mammals along each trophic step. However, preservation of diet-related δ66Zn values in fossil teeth has not been assessed yet. Here, we analyzed enamel of fossil teeth from the Late Pleistocene (38.4–13.5 ka) mammalian assemblage of the Tam Hay Marklot (THM) cave in northeastern Laos, to reconstruct the food web and assess the preservation of original δ66Zn values. Distinct enamel δ66Zn values of the fossil taxa (δ66Zncarnivore < δ66Znomnivore < δ66Znherbivore) according to their expected feeding habits were observed, with a trophic carnivore-herbivore spacing of +0.60‰ and omnivores having intermediate values. Zn and trace element concentration profiles similar to those of modern teeth also indicate minimal impact of diagenesis on the enamel. While further work is needed to explore preservation for settings with different taphonomic conditions, the diet-related δ66Zn values in fossil enamel from THM cave suggest an excellent long-term preservation potential, even under tropical conditions that are well known to be adverse for collagen preservation. Zinc isotopes could thus provide a new tool to assess the diet of fossil hominins and associated fauna, as well as trophic relationships in past food webs.

Zinc (Zn) isotope ratios of dental enamel are a promising tracer for dietary reconstruction in archeology, but its use is still in its infancy. A recent study demonstrated a high risk of Zn contamination from nitrile, and latex gloves used during chemical sample preparation. Here we assess the potential impact of the use of such gloves during enamel sampling on the Zn isotope composition of teeth from a population of early Holocene hunter gatherers from Lapa do Santo, Lagoa Santa, Minas Gerais, Brazil. We first examined the amount of Zn and its isotopic composition released from the gloves used in this study by soaking them in weak nitric acid and water. We compared Zn isotope ratios obtained from teeth that were sampled wearing nitrile, latex or no gloves. Finally, we performed a linear mixed model (LMM) to investigate post hoc the relationship between the gloves used for sampling and the Zn isotope variability in dental enamel. We found that the gloves used in this study released a similar amount of Zn compared to previous work, but only in acidic solution. Zn isotope ratios of teeth and the LMM identified no sign of significant Zn coming from the gloves when teeth were handled for enamel sampling. We hypothesize that Zn in gloves is mostly released by contact with acids. We found that the main source of Zn isotope variability in the Lapa do Santo population was related to the developmental stage of the tooth tissues sampled. We report identical results for two individuals coming from a different archeological context. Tooth enamel formed in utero and/or during the two first years of life showed higher Zn isotope ratios than enamel formed after weaning. More work is required to systematically investigate if Zn isotopes can be used as a breastfeeding tracer.

Secure environmental contexts are crucial for hominin interpretation and comparison. The discovery of a Denisovan individual and associated fauna at Tam Ngu Hao 2 (Cobra) Cave, Laos, dating back to 164–131 ka, allows for environmental comparisons between this (sub)tropical site and the Palearctic Denisovan sites of Denisova Cave (Russia) and Baishiya Karst Cave (China). Denisovans from northern latitudes foraged in a mix of forested and open landscapes, including tundra and steppe. Using stable isotope values from the Cobra Cave assemblage, we demonstrate that, despite the presence of nearby canopy forests, the Denisovan individual from Cobra Cave primarily consumed plants and/or animals from open forests and savannah. Using faunal evidence and proxy indicators of climates, results herein highlight a local expansion of rainforest at ~ 130 ka, raising questions about how Denisovans responded to this local climate change. Comparing the diet and habitat of the archaic hominin from Cobra Cave with those of early Homo sapiens from Tam Pà Ling Cave (46–43 ka), Laos, it appears that only our species was able to exploit rainforest resources.

The capability of Pleistocene hominins to successfully adapt to different types of tropical forested environments has long been debated. In order to investigate environmental changes in Southeast Asia during a critical period for the turnover of hominin species, we analysed palaeoenvironmental proxies from five late Middle to Late Pleistocene faunas. Human teeth discoveries have been reported at Duoi U’Oi, Vietnam (70–60 ka) and Nam Lot, Laos (86–72 ka). However, the use of palaeoproteomics allowed us to discard the latter, and, to date, no human remains older than ~ 70 ka are documented in the area. Our findings indicate that tropical rainforests were highly sensitive to climatic changes over that period, with significant fluctuations of the canopy forests. Locally, large-bodied faunas were resilient to these fluctuations until the cooling period of the Marine Isotope Stage 4 (MIS 4; 74–59 ka) that transformed the overall biotope. Then, under strong selective pressures, populations with new phenotypic characteristics emerged while some other species disappeared . We argue that this climate-driven shift offered new foraging opportunities for hominins in a novel rainforest environment and was most likely a key factor in the settlement and dispersal of our species during MIS 4 in SE Asia.

Background: Congenital cytomegalovirus (cCMV) infection is frequent and potentially severe. The immunobiology of cCMV infection is poorly understood, involving cytokines that could be carried within or on the surface of extracellular vesicles (EV). We investigated intra-amniotic cytokines, mediated or not by EV, in cCMV infection. Methods: Forty infected fetuses following early maternal primary infection and forty negative controls were included. Infected fetuses were classified according to severity at birth: asymptomatic, moderately or severely symptomatic. Following the capture of EV in amniotic fluid (AF), the concentrations of 38 cytokines were quantified. The association with infection and its severity was determined using univariate and multivariate analysis. A prediction analysis based on principal component analysis was conducted. Results: cCMV infection was nominally associated with an increase in six cytokines, mainly soluble (IP-10, IL-18, ITAC, and TRAIL). EV-associated IP-10 was also increased in cases of fetal infection. Severity of fetal infection was nominally associated with an increase in twelve cytokines, including five also associated with fetal infection. A pattern of specific increase in six proteins fitted severely symptomatic infection, including IL-18soluble, TRAILsoluble, CRPsoluble, TRAILsurface, MIGinternal, and RANTESinternal. Conclusion: Fetal infection and its severity are associated with an increase in pro-inflammatory cytokines involved in Th1 immune response.

Nitrogen isotopes are widely used to study the trophic position of animals in modern food webs; however, their application in the fossil record is severely limited by degradation of organic material during fossilization. In this study, we show that the nitrogen isotope composition of organic matter preserved in mammalian tooth enamel (δ 15 N enamel ) records diet and trophic position. The δ 15 N enamel of modern African mammals shows a 3.7‰ increase between herbivores and carnivores as expected from trophic enrichment, and there is a strong positive correlation between δ 15 N enamel and δ 15 N bone-collagen values from the same individuals. Additionally, δ 15 N enamel values of Late Pleistocene fossil teeth preserve diet and trophic level information, despite complete diagenetic loss of collagen in the same specimens. We demonstrate that δ 15 N enamel represents a powerful geochemical proxy for diet that is applicable to fossils and can help delineate major dietary transitions in ancient vertebrate lineages. Enamel-bound nitrogen isotopes in modern and fossil mammal teeth preserve dietary and trophic level information. This novel geochemical archive can be used to reconstruct trophic niche in ancient ecosystems.

CREBBP truncating mutations and deletions are responsible for the well-known Rubinstein-Taybi syndrome. Recently, a new, distinct CREBBP-linked syndrome has been described: missense mutations located at the 3' end of exon 30 and the 5' portion of exon 31 induce Menke-Hennekam syndrome. Patients with this syndrome present a recognizable facial dysmorphism, intellectual disability of variable severity, microcephaly, short stature, autism, epilepsy, visual and hearing impairments, feeding problems, upper airway infections, scoliosis, and/or kyphosis. To date, all diagnoses were made postnatally. Trio-whole exome sequencing (WES) was performed in a fetus showing increased nuchal translucency persistence and aorta abnormalities at 28 weeks of gestation (WG). WES revealed a CREBBP de novo missense mutation (c.5602C>T; p.Arg1868Trp) in exon 31, previously reported as the cause of Menke-Hennekam syndrome. Termination of pregnancy was performed at 32 WG. We further reviewed the prenatal signs of Menke-Hennekam syndrome already reported. Among the 35 patients reported and diagnosed postnatally up to this day, 15 presented recognizable prenatal signs, the most frequent being intra-uterine growth retardation, brain, and cardiovascular anomalies. Menke-Hennekam is a rare syndrome with unspecific, heterogeneous, and inconstant prenatal symptoms occurring most frequently with the c.5602C>T, p.(Arg1868Trp) mutation. Therefore, the prenatal diagnosis of Menke-Hennekam syndrome is only possible by molecular investigation. Moreover, this case report and review reinforce the importance of performing prenatal WES when unspecific signs are present on imaging.