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Populations genetically related to present-day Europeans first appeared in Europe at some point after 38,000-40,000 years ago, following a cold period of severe climatic disruption. These new migrants would eventually replace the pre-existing modern human ancestries in Europe, but initial interactions between these groups are unclear due to the lack of genomic evidence from the earliest periods of the migration. Here we describe the genomes of two 36,000-37,000-year-old individuals from Buran-Kaya III in Crimea as belonging to this newer migration. Both genomes share the highest similarity to Gravettian-associated individuals found several thousand years later in southwestern Europe. These genomes also revealed that the population turnover in Europe after 40,000 years ago was accompanied by admixture with pre-existing modern human populations. European ancestry before 40,000 years ago persisted not only at Buran-Kaya III but is also found in later Gravettian-associated populations of western Europe and Mesolithic Caucasus populations., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Evidence of the consumption of meat through hunting or scavenging by Early Pleistocene hominins is scarce, particularly in South Africa. Moreover, the interpretations of taphonomic evidence are subject to an important discussion commonly called the 'hunting-vs-scavenging debate.' Until today, only the Swartkrans Members 1-3 site has yielded a butchered bone assemblage large enough to permit reconstruction of carcass acquisition strategies by Early Pleistocene hominins in South Africa. This leaves an information gap between 1.4 and 1.0 Ma. Here, we provide the first evidence of meat consumption by hominins during this gap, based on the zooarchaeological study of the large mammal bone assemblage recovered from the Cooper's D site, South Africa. Based on skeletal part representation, our results show density-mediated attrition of bovid bones due to predepositional and postdepositional destruction. We argue that this attrition is the result of both abiotic (i.e., decalcification) and biotic (i.e., carnivore ravaging) processes. Bovid mortality profiles point out the involvement of ambush predators such as large felids. Bone surface modifications also indicate that the assemblage has been accumulated mostly by carnivores but with some hominin involvement as well. We observe all the stages of animal carcass processing (skinning, disarticulation, defleshing, marrow extraction) as well as the exploitation of a diversity of prey size classes at both Swartkrans Members 1-3 and Cooper's D. Thus, our study shows the importance of the Cooper's D bone assemblage for understanding Early Pleistocene hominin subsistence behaviors. Moreover, this article highlights the need for including long bone flake specimens in the analysis of large bone assemblages from South African caves to better understand the Early Pleistocene hominin bone damage record., Competing Interests: Declaration of competing interest The authors have no competing interests to declare., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Relatively high 15 N abundances in bone collagen of early anatomically modern humans in Europe have often been interpreted as a specific consumption of freshwater resources, even if mammoth is an alternative high 15 N prey. At Buran-Kaya III, access to associated fauna in a secured archaeological context and application of recently developed isotopic analyses of individuals amino acids offer the opportunity to further examine this hypothesis. The site of Buran-Kaya III is located in south Crimea and has provided a rich archaeological sequence including two Upper Palaeolithic layers, from which human fossils were retrieved and directly dated as from 37.8 to 33.1 ka cal BP. Results from bulk collagen of three human remains suggests the consumption of a high 15 N prey besides the contribution of saiga, red deer, horse and hare, whose butchered remains were present at the site. In contrast to bulk collagen, phenylalanine and glutamic acid 15 N abundances reflect not only animal but also plant protein contributions to omnivorous diet, and allow disentangling aquatic from terrestrial resource consumption. The inferred human trophic position values point to terrestrial-based diet, meaning a significant contribution of mammoth meat, in addition to a clear intake of plant protein.

The study of inter-individual variability of personality in fish is a growing field of interest but the genetic basis of this complex trait is still poorly investigated due to the difficulty in controlling fish genetic origin and life history. When available, isogenic lines that allow performing independent tests on different individuals having identical genotype constitute a very relevant experimental material to disentangle the genetic and environmental components of behavioural individuality. We took advantage of heterozygous isogenic lines to investigate the personality in rainbow trout through the analysis of their reactions to different experimental situations. To this end, seven to ten rainbow trout isogenic lines were screened for their spatial exploratory behaviour, their flight response toward a stressor and their risk taking behaviour. Results showed that some lines seemed less sensitive to new events or environmental changes and could be defined as low responsive, while others were very sensitive and defined as high responsive. The use of isogenic lines highlighted the importance of genetic factors, in combination with life history, in the expression of personality in domesticated fish.

The use of polychlorinated biphenyls (PCBs) has been banned for several decades. PCBs have a long biological half-life and high liposolubility which leads to their bioaccumulation and biomagnification through food chains over a wide range of trophic levels. Exposure can lead to changes in animal physiology and behavior and has been demonstrated in both experimental and field analyses. There are also potential risks to high trophic level predators, including humans. A maternal transfer has been demonstrated in fish as PCBs bind to lipids in eggs. In this study, behavioral traits (exploration and free swimming, with or without challenges) of contaminated zebrafish (Danio rerio) adults and their offspring (both as five-day-old larvae and as two-month-old fish reared under standard conditions) were measured using video-tracking. Long-term dietary exposure to a mixture of non-coplanar PCBs was used to mimic known environmental contamination levels and congener composition. Eight-week-old fish were exposed for eight months at 26-28 °C. Those exposed to an intermediate dose (equivalent to that found in the Loire Estuary, ∑(CB)=515 ng g⁻¹ dry weight in food) displayed behavioral disruption in exploration capacities. Fish exposed to the highest dose (equivalent to that found in the Seine Estuary, ∑(CB)=2302 ng g⁻¹ dry weight in food) displayed an increased swimming activity at the end of the night. In offspring, larval activity was increased and two-month-old fish occupied the bottom section of the tank less often. These findings call for more long-term experiments using the zebrafish model; the mechanisms underlying behavioral disruptions need to be understood due to their implications for both human health and their ecological relevance in terms of individual fitness and survival., (© 2013 Elsevier Inc. All rights reserved.)

Wild-type (WT) zebrafish are commonly used in behavioral tests, but the term WT is not a precise description, and corresponds to many different strains (e.g., AB, TU, WIK, and others). Previous studies compared the physiological, behavioral, or metabolic characteristics of different zebrafish strains (indigenous WT populations versus laboratory WT strains). AB and TU are widely used, but at least one study has demonstrated behavioral differences between them. To choose the most appropriate strain for our experiments, we systematically screened behavioral responses of AB and TU fish in several assays. We analyzed the locomotion activity and responses to a light/dark challenge in adults and larvae, and exploratory behavior and color conditioning in adults. Differences were observed for all tests, the strains displaying particular behavior depending on the tests. As larvae, TU displayed a wider activity range than AB larvae at the onset of locomotor behavior; as adults, TU were more reactive to sudden light transitions and recovered the swimming activity faster in T-maze or homebase release in novel tank tests, whereas AB fish had more contrasted circadian rhythms and performed better in color learning. Strain-specific behavior should be considered when designing experiments using behavior.

Although individual electronic tagging using passive integrated acoustic (PIT) tags is established, it is mainly for fish >60 mm in length and is unsuitable for fish of <30 mm, like zebrafish. We used radio frequency identification (RFID) microtags (1 mm in diameter and 6 mm in length, with a mass of ~10 mg) to individually identify juvenile zebrafish (length 16-42 mm, mass 138-776 mg) for the first time, and studied the effects of intracoelomic implantation on fish survival and microtag loss, growth, spawning and exploratory behaviour. After 5.5 months, both high survival (82%) and low microtag loss (11%) were achieved. The smallest surviving fish weighed 178 mg, and success in microtag reading was 73% for the size class 350-450 mg (26 mm). Greater success was achieved when fish were larger at the time of tagging but no negative effects on growth were observed for any size class and some tagged fish spawned. No significant differences in behavioural responses could be detected between tagged fish and untagged controls after 2 months. Overall, the results suggest that the tagging method is highly suitable for fish as small as zebrafish juveniles. We think this method will provide significant advances for researchers of the ever-growing fish model community and more generally for all small-fish users. Tagging is essential when one needs to identify fish (e.g. particular genotypes with no external cue), to run longitudinal monitoring of individual biological traits (e.g. growth) or to repeat assays with the same individual at discrete points in time (e.g. behaviour studies). Such a method will find applications in physiology, genetics, behaviour and (eco)toxicology fields.

A novel human tyrosine hydroxylase (HTH) messenger RNA subgroup generated by alternative splicing and characterized by the absence of the third exon was recently identified. The corresponding putative protein lacks 74 amino acids including Ser31 and Ser40, two major phosphorylation sites implicated in the regulation of HTH activity. These mRNA species are detected in adrenal medulla and are overexpressed in patients suffering from progressive supranuclear palsy, a neurodegenerative disease mostly affecting catecholaminergic neurons of the basal ganglia. In the present work, an HTH protein isoform lacking exon 3 was identified in human adrenal medulla. For this purpose, an antibody was raised against the HTH exon 3. The effect of the removal of exon 3 on the enzymatic activity of HTH was studied in vitro by comparing a purified recombinant fusion protein without exon 3 (glutathione S-transferase (GST)-HTHDelta3) to the equivalent protein containing exon 3 (GST-HTH3). In initial velocity conditions, GST-HTHDelta3 has 30% of the maximal velocity of GST-HTH3. Moreover, the skipping of exon 3 results in the absence of activation of GST-HTH by heparin and increases by 10-fold the retroinhibition constant for dopamine, demonstrating the involvement of exon 3 in the regulation of HTH enzymatic activity. The identification of a variably expressed HTH isoform that lacks an exon implicated in activity regulation supports the view that HTH alternative splicing contributes to the functional diversity within the catecholaminergic system and may be implicated in some neurological diseases.

Alternative splicing of human tyrosine hydroxylase (TH) pre-mRNA produces four mRNAs leading to four different TH isoforms and is thought to have important regulatory functions. We show that the diversity of TH mRNAs is greater than previously described in the autonomous nervous system: New splice junctions corresponding to the skipping of exon 3 were identified by amplification of cDNA synthesized from pheochromocytoma RNA. In all cases the reading frame was maintained. These species were assayed by RNase protection experiments; their abundance (4-6%) was comparable to that of the previously identified human TH-3 and -4 species in normal adrenal medulla. However, higher levels (11-34%) of these species were found in adrenal medullas of patients suffering from progressive supranuclear palsy. Whether such changes are specific to the disease or the consequences of the stress associated with this severe neurodegeneration remains to be established.

Tyrosine hydroxylase (TH) catalyzes the first and rate-limiting step in the biosynthesis of catecholamines. Among the various mechanisms implicated in the regulation of TH activity, alternative splicing of TH primary transcript has been described as a characteristic of higher primates and Drosophila. We investigated whether there is such a regulatory mechanism in the rat. Reverse transcriptase-PCR experiments were performed with RNA from PC12 cells. A new TH mRNA species was evidenced, resulting from the use of an alternative donor site in exon 2. RNase protection assays and in situ hybridization experiments detected this mRNA species in the adrenal medulla but not in the main catecholaminergic nuclei of the CNS. The corresponding putative protein lacks 33 amino acids in the N-terminal regulatory domain. A recombinant protein was produced in E. coli. Its in vitro specific activity was similar to that of the previously identified TH protein.

Pharmacological and clinical findings suggest that the dopamine transporter (DAT) gene may be involved in the genetic predisposition to schizophrenia. Linkage of a Taq I VNTR polymorphism in the DAT gene to schizophrenia was studied in multiplex schizophrenic families from Rouen, France (n = 10) and the Island of La Réunion (n = 21). Neither the lod score method nor nonparametric methods (the affected pedigree member method of Weeks and Lange [1988] and the sibling method of Green and Woodrow [1977]) provided any evidence for linkage. An association study, carried out within a group of 91 unrelated schizophrenic patients from Rouen and 91 matched control subjects, examined a 40 base-pair repeat polymorphism located in the 3' nontranslated end of the DAT mRNA. There was no significant difference in allelic or genotypic frequencies between the two groups. These results exclude any substantial involvement of the DAT gene in the pathogenesis of schizophrenia in the population studied.

A new structural polymorphism (Ser311/Cys311) in the dopamine D2 receptor (DRD2) gene has recently been reported to be associated with schizophrenia, particularly in patients with a positive family history of schizophrenia (Arinimi et al., 1994). However these findings remain controversial (Asherson et al., 1994; Nanko et al., 1994; Nöthen et al., 1994; Shaikh et al., 1994). Thus we investigated the role of the Cys311 mutation in schizophrenia using both association and family studies. First, we screened for the Cys311 mutation in 113 unrelated Caucasian schizophrenics (mean age 42 +/- 0.6; 34 females and 79 males) including 25 familial cases, and 184 unrelated controls (mean age 49 +/- 0.5, 74 females and 110 males) free of any psychiatric disorders. Diagnoses were ascertained according to DSM-III criteria (Campion et al., 1994). All patients and controls were native to the area of Rouen.