To not have or to not be: Negative Verbs in Proto Tukanoan

A number of Tukanoan languages of South America are noted for their parallel semantically negative verbs ‘to not be’ and ‘to not have’. This paper reconstructs the history of both forms, showing that they developed independently as complex forms first in Proto Tukanoan (‘to not have’) and then in Proto Eastern Tukanoan (‘to not be’), and also proposes two negative particles present in these proto stages of the language family: *bã (Proto Eastern Tukanoan) and *p’e (Proto Tukanoan). These results will be discussed in the context of two negative cycles: the established Negative Existential Cycle and the recently proposed Privative Cycle

The social lives of isolates (and small language families):The case of the Northwest Amazon

The Americas are home to patches of extraordinary linguistic (genealogical) diversity. These high-diversity areas are particularly unexpected given the recent population of the Americas. In this paper, we zoom in on one such area, the Northwest Amazon, and address the question of how the diversity in this area has persisted to the present. We contrast two hypotheses that claim opposite mechanisms for the maintenance of diversity: the isolation hypothesis suggests that isolation facilitates the preservation of diversity, while the integration hypothesis proposes that conscious identity preservation in combination with contact drives diversity maintenance. We test predictions for both hypotheses across four disciplines: biogeography, cultural anthropology, population genetics and linguistics. Our results show signs of both isolation and integration, but they mainly suggest considerable diversity in how groups of speakers have interacted with their surroundings

Interpreting mismatches between linguistic and genetic patterns among speakers of Tanimuka (Eastern Tukanoan) and Yukuna (Arawakan)

Northwestern Amazonia is home to a great degree of linguistic diversity, and the human societies in that region are part of complex networks of interaction that predate the arrival of Europeans. This study investigates the population and language contact dynamics between two languages found within this region, Yukuna and Tanimuka, which belong to the Arawakan and Tukanoan language families, respectively. We use evidence from linguistics, ethnohistory, ethnography and population genetics to provide new insights into the contact dynamics between these and other human groups in NWA. Our results show that the interaction between these groups intensified in the last 500 years, to the point that it is difficult to differentiate between them genetically. However, this close interaction has led to more substantial contact-induced language changes in Tanimuka than in Yukuna, consistent with a scenario of language shift and asymmetrical power relations

Metabolomics to unveil and understand phenotypic diversity between pathogen populations

Visceral leishmaniasis is caused by a parasite called Leishmania donovani, which every year infects about half a million people and claims several thousand lives. Existing treatments are now becoming less effective due to the emergence of drug resistance. Improving our understanding of the mechanisms used by the parasite to adapt to drugs and achieve resistance is crucial for developing future treatment strategies. Unfortunately, the biological mechanism whereby Leishmania acquires drug resistance is poorly understood. Recent years have brought new technologies with the potential to increase greatly our understanding of drug resistance mechanisms. The latest mass spectrometry techniques allow the metabolome of parasites to be studied rapidly and in great detail. We have applied this approach to determine the metabolome of drug-sensitive and drug-resistant parasites isolated from patients with leishmaniasis. The data show that there are wholesale differences between the isolates and that the membrane composition has been drastically modified in drug-resistant parasites compared with drug-sensitive parasites. Our findings demonstrate that untargeted metabolomics has great potential to identify major metabolic differences between closely related parasite strains and thus should find many applications in distinguishing parasite phenotypes of clinical relevance

The social lives of isolates (and small language families): the case of the Northwest Amazon

The Americas are home to patches of extraordinary linguistic (genealogical) diversity. These high-diversity areas are particularly unexpected given the recent population of the Americas. In this paper, we zoom in on one such area, the Northwest Amazon, and address the question of how the diversity in this area has persisted to the present. We contrast two hypotheses that claim opposite mechanisms for the maintenance of diversity: the isolation hypothesis suggests that isolation facilitates the preservation of diversity, while the integration hypothesis proposes that conscious identity preservation in combination with contact drives diversity maintenance. We test predictions for both hypotheses across four disciplines: biogeography, cultural anthropology, population genetics and linguistics. Our results show signs of both isolation and integration, but they mainly suggest considerable diversity in how groups of speakers have interacted with their surroundings

Interpreting mismatches between linguistic and genetic patterns among speakers of Tanimuka (Eastern Tukanoan) and Yukuna (Arawakan)

Northwestern Amazonia is home to a great degree of linguistic diversity, and the human societies in that region are part of complex networks of interaction that predate the arrival of Europeans. This study investigates the population and language contact dynamics between two languages found within this region, Yukuna and Tanimuka, which belong to the Arawakan and Tukanoan language families, respectively. We use evidence from linguistics, ethnohistory, ethnography and population genetics to provide new insights into the contact dynamics between these and other human groups in NWA. Our results show that the interaction between these groups intensified in the last 500 years, to the point that it is difficult to differentiate between them genetically. However, this close interaction has led to more substantial contact-induced language changes in Tanimuka than in Yukuna, consistent with a scenario of language shift and asymmetrical power relations

Nippostrongylus-induced intestinal hypercontractility requires IL-4 receptor alpha-responsiveness by T cells in mice

Gut-dwelling helminthes induce potent IL-4 and IL-13 dominated type 2 T helper cell (T H 2) immune responses, with IL-13 production being essential for Nippostrongylus brasiliensis expulsion. This T H 2 response results in intestinal inflammation associated with local infiltration by T cells and macrophages. The resulting increased IL-4/IL-13 intestinal milieu drives goblet cell hyperplasia, alternative macrophage activation and smooth muscle cell hypercontraction. In this study we investigated how IL-4-promoted T cells contributed to the parasite induced effects in the intestine. This was achieved using pan T cell-specific IL-4 receptor alpha-deficient mice (iLck cre IL-4Rα −/lox ) and IL-4Rα-responsive control mice. Global IL-4Rα −/− mice showed, as expected, impaired type 2 immunity to N. brasiliensis . Infected T cell-specific IL-4Rα-deficient mice showed comparable worm expulsion, goblet cell hyperplasia and IgE responses to control mice. However, impaired IL-4-promoted T H 2 cells in T cell-specific IL-4Rα deficient mice led to strikingly reduced IL-4 production by mesenteric lymph node CD4 + T cells and reduced intestinal IL-4 and IL-13 levels, compared to control mice. This reduced IL-4/IL-13 response was associated with an impaired IL-4/IL-13-mediated smooth muscle cell hypercontractility, similar to that seen in global IL-4Rα −/− mice. These results demonstrate that IL-4-promoted T cell responses are not required for the resolution of a primary N. brasiliensis infection. However, they do contribute significantly to an important physiological manifestation of helminth infection; namely intestinal smooth muscle cell-driven hypercontractility

Understanding tumor heterogeneity as functional compartments - superorganisms revisited

Compelling evidence broadens our understanding of tumors as highly heterogeneous populations derived from one common progenitor. In this review we portray various stages of tumorigenesis, tumor progression, self-seeding and metastasis in analogy to the superorganisms of insect societies to exemplify the highly complex architecture of a neoplasm as a system of functional "castes.

Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

Background Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. Methods We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. Results Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. Conclusions Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.Peer reviewe