The genetic impact associated to the Neolithic spread in Europe has been widely debated over the last 20 years. Within this context, ancient DNA studies have provided a more reliable picture by directly analyzing the protagonist populations at different regions in Europe. However, the lack of available data from the original Near Eastern farmers has limited the achieved conclusions, preventing the formulation of continental models of Neolithic expansion. Here we address this issue by presenting mitochondrial DNA data of the original Near-Eastern Neolithic communities with the aim of providing the adequate background for the interpretation of Neolithic genetic data from European samples. Sixty-three skeletons from the Pre Pottery Neolithic B (PPNB) sites of Tell Halula, Tell Ramad and Dja'de El Mughara dating between 8,700–6,600 cal. B.C. were analyzed, and 15 validated mitochondrial DNA profiles were recovered. In order to estimate the demographic contribution of the first farmers to both Central European and Western Mediterranean Neolithic cultures, haplotype and haplogroup diversities in the PPNB sample were compared using phylogeographic and population genetic analyses to available ancient DNA data from human remains belonging to the Linearbandkeramik-Alföldi Vonaldiszes Kerámia and Cardial/Epicardial cultures. We also searched for possible signatures of the original Neolithic expansion over the modern Near Eastern and South European genetic pools, and tried to infer possible routes of expansion by comparing the obtained results to a database of 60 modern populations from both regions. Comparisons performed among the 3 ancient datasets allowed us to identify K and N-derived mitochondrial DNA haplogroups as potential markers of the Neolithic expansion, whose genetic signature would have reached both the Iberian coasts and the Central European plain. Moreover, the observed genetic affinities between the PPNB samples and the modern populations of Cyprus and Crete seem to suggest that the Neolithic was first introduced into Europe through pioneer seafaring colonization. Since the original human expansions out of Africa 200,000 years ago, different prehistoric and historic migration events have taken place in Europe. Considering that the movement of the people implies a consequent movement of their genes, it is possible to estimate the impact of these migrations through the genetic analysis of human populations. Agricultural and husbandry practices originated 10,000 years ago in a region of the Near East known as the Fertile Crescent. According to the archaeological record this phenomenon, known as “Neolithic”, rapidly expanded from these territories into Europe. However, whether this diffusion was accompanied or not by human migrations is greatly debated. In the present work, mitochondrial DNA –a type of maternally inherited DNA located in the cell cytoplasm- from the first Near Eastern Neolithic populations was recovered and compared to available data from other Neolithic populations in Europe and also to modern populations from South Eastern Europe and the Near East. The obtained results show that substantial human migrations were involved in the Neolithic spread and suggest that the first Neolithic farmers entered Europe following a maritime route through Cyprus and the Aegean Islands.

Acute exposure to acrylamide (ACR), a type-2 alkene, may lead to a ataxia, skeletal muscles weakness and numbness of the extremities in human and laboratory animals. In the present manuscript, ACR acute neurotoxicity has been characterized in adult zebrafish, a vertebrate model increasingly used in human neuropharmacology and toxicology research. At behavioral level, ACR-treated animals exhibited “depression-like” phenotype comorbid with anxiety behavior. At transcriptional level, ACR induced down-regulation of regeneration-associated genes and up-regulation of oligodendrocytes and reactive astrocytes markers, altering also the expression of genes involved in the presynaptic vesicle cycling. ACR induced also significant changes in zebrafish brain proteome and formed adducts with selected cysteine residues of specific proteins, some of them essential for the presynaptic function. Finally, the metabolomics analysis shows a depletion in the monoamine neurotransmitters, consistent with the comorbid depression and anxiety disorder, in the brain of the exposed fish.

Ancient DNA from bones and teeth of 60 individuals from four extinct human populations from Tierra del Fuego-Patagonia (Selknam, Yamana, Kaweskar and Aonikenk) has been extracted and the mitochondrial DNA (mtDNA) amplified by using the polymerase chain reaction. High-resolution analysis of endonuclease restriction site variation in the mtDNA and sequencing of its hypervariable non-coding control region, revealed complete absence of two of the four primary mito-chondrial haplotype groups present in contemporary Amerinds, namely A and B. In contrast, haplogroups C and D were found in all but one sample with frequencies of ∼38% and 60%. These results, together with the decreasing incidence of group A in more southerly latitudes in the American continent and the absence of cluster B above 55° North in America and Asia, argue that the first settlers entering America 21 000–14 000 years ago already lacked both mtDNA lineages.

Terrorist use of organophosphorus-based nerve agents and toxic industrial chemicals against civilian populations constitutes a real threat, as demonstrated by the terrorist attacks in Japan in the 1990 s or, even more recently, in the Syrian civil war. Thus, development of more effective countermeasures against acute organophosphorus poisoning is urgently needed. Here, we have generated and validated zebrafish models for mild, moderate and severe acute organophosphorus poisoning by exposing zebrafish larvae to different concentrations of the prototypic organophosphorus compound chlorpyrifos-oxon. Our results show that zebrafish models mimic most of the pathophysiological mechanisms behind this toxidrome in humans, including acetylcholinesterase inhibition, N-methyl-D-aspartate receptor activation and calcium dysregulation as well as inflammatory and immune responses. The suitability of the zebrafish larvae to in vivo high-throughput screenings of small molecule libraries makes these models a valuable tool for identifying new drugs for multifunctional drug therapy against acute organophosphorus poisoning.