Learning and adaptation in speech production without a vocal tract

How is the complex audiomotor skill of speaking learned? To what extent does it depend on the specific characteristics of the vocal tract? Here, we developed a touchscreen-based speech synthesizer to examine learning of speech production independent of the vocal tract. Participants were trained to reproduce heard vowel targets by reaching to locations on the screen without visual feedback and receiving endpoint vowel sound auditory feedback that depended continuously on touch location. Participants demonstrated learning as evidenced by rapid increases in accuracy and consistency in the production of trained targets. This learning generalized to productions of novel vowel targets. Subsequent to learning, sensorimotor adaptation was observed in response to changes in the location-sound mapping. These findings suggest that participants learned adaptable sensorimotor maps allowing them to produce desired vowel sounds. These results have broad implications for understanding the acquisition of speech motor control.Published versio

Shifts in Plankton, Nutrient and Light Relationships in Small Tundra Lakes Caused by Localized Permafrost Thaw

Tundra lakes located in the Mackenzie Delta uplands, NWT, Canada, are increasingly being affected by permafrost thaw in the form of shoreline retrogressive thaw slumping. This form of thaw-induced disturbance is used as a surrogate indicator of landscape-related disturbance linked to regional climate warming. We compared 22 lakes, half affected by thaw slumping and half unaffected, to determine whether water column nutrient concentrations, light availability, and plankton biomass differed between these two lake types. Total phosphorus (TP), total dissolved nitrogen (TDN), dissolved organic carbon (DOC), and chlorophyll a concentrations were higher in unaffected lakes than in slump-affected lakes. Absorbance related to water colour of both UV and photosynthetically active radiation in the water column was also higher in unaffected lakes, but bacterioplankton abundance was not different between lake types. UV light absorbance was found to be the best predictor of pelagic chlorophyll a concentrations in unaffected lakes, whereas TDN (and to a lesser extent TP) were the best predictors of pelagic chlorophyll a in slump-affected lakes. These findings indicate that slumping arising from permafrost thaw produces a shift in tundra lake nutrient, light, and phytoplankton relationships. Given the projections of continued warming, this result has significant implications for the future biogeochemical and ecological states of Arctic tundra lakes.Les lacs de toundra situés dans les hautes terres du delta du Mackenzie, dans les Territoires du Nord-Ouest, au Canada, sont de plus en plus touchés par le dégel du pergélisol en ce sens qu’il y a glissement régressif du littoral dû au dégel. Cette forme de perturbation attribuable au dégel sert d’indicateur auxiliaire en matière de perturbation du paysage liée au réchauffement climatique de la région. Nous avons comparé 22 lacs, dont la moitié était touchée par le glissement dû au dégel et l’autre moitié ne l’était pas, afin de déterminer si les concentrations en nutriments des colonnes d’eau, la disponibilité lumineuse et la biomasse du plancton différaient entre ces deux types de lacs. Les concentrations de phosphore total (PT), d’azote dissous total (ADT), de carbone organique dissous (COD) et de chlorophylle a étaient plus élevées dans les lacs non touchés quand dans les lacs où il y avait glissement du littoral. L’absorbance liée à la couleur de l’eau du rayonnement actif photosynthétique et du rayonnement actif ultraviolet dans les colonnes d’eau était également plus élevée dans les lacs non touchés, mais l’abondance du bactérioplancton ne différait pas d’un type de lac à l’autre. On a déterminé que l’absorbance de lumière ultraviolette était le meilleur prédicteur de concentrations de chlorophylle a pélagique dans les lacs non touchés, tandis que l’ADT (et le PT, dans une moindre mesure) constituaient les meilleurs prédicteurs de chlorophylle a pélagique pour ce qui est des lacs faisant l’objet d’un glissement. Ces constatations indiquent que le glissement attribuable au dégel du pergélisol altère les relations qui existent entre les nutriments, la lumière et le phytoplancton des lacs de toundra. Compte tenu des projections à l’égard d’un réchauffement continuel, ce résultat revêt d’importantes incidences sur les états biogéochimiques et écologiques des lacs de la toundra arctique

Green Inequities: Examining the Dimensions of Socioenvironmental Injustice in Marginalized Communities

In the realm of socioenvironmental justice, much discourse centers on equal access to green areas and on climate injustice in the United States. Marginalized communities, including Indigenous populations, are being excluded from current narratives surrounding the natural spaces that in many cases are historically tied to under-represented groups. This article aims to explore some of the many dimensions of environmental racism, green inequities, climate injustice, and access. The dimensions include but are not limited to racial gatekeeping, nature deprivation in low-income communities, green gentrification, light pollution, and access to clean water. The recommendations section serves as a guide during decisionmaking processes at the local, state, and federal level, as well as moving forward in offering impacted communities protection from environmental racism and socioenvironmental injustice to impacted communities

Social stratification without genetic differentiation at the site of Kulubnarti in Christian Period Nubia

Relatively little is known about Nubia’s genetic landscape prior to the influence of the Islamic migrations that began in the late 1st millennium CE. Here, we increase the number of ancient individuals with genome-level data from the Nile Valley from three to 69, reporting data for 66 individuals from two cemeteries at the Christian Period (~650–1000 CE) site of Kulubnarti, where multiple lines of evidence suggest social stratification. The Kulubnarti Nubians had ~43% Nilotic-related ancestry (individual variation between ~36–54%) with the remaining ancestry consistent with being introduced through Egypt and ultimately deriving from an ancestry pool like that found in the Bronze and Iron Age Levant. The Kulubnarti gene pool – shaped over a millennium – harbors disproportionately female-associated West Eurasian-related ancestry. Genetic similarity among individuals from the two cemeteries supports a hypothesis of social division without genetic distinction. Seven pairs of inter-cemetery relatives suggest fluidity between cemetery groups. Present-day Nubians are not directly descended from the Kulubnarti Nubians, attesting to additional genetic input since the Christian Period.K.A.S. was supported by a Doctoral Dissertation Research Improvement Grant from the National Science Foundation (BCS-1613577). D.R. was funded by NSF HOMINID grant BCS-1032255; NIH (NIGMS) grant GM100233; the Allen Discovery Center program, a Paul G. Allen Frontiers Group advised program of the Paul G. Allen Family Foundation; the John Templeton Foundation grant 61220; and the Howard Hughes Medical Institute

Broad Repertoire of T Cell Autoreactivity Directly from Islets of Donors with Type 1 Diabetes (T1D)

Type 1 diabetes (T1D) is an autoimmune disease characterized by the infiltration of lymphocytes into the insulin-producing β-cells in the pancreas. We have isolated live T cells sorted or grown directly from the isolated, handpicked islets of human donors with T1D. We received ~500 islet equivalent EQ of variable purity (10-90%) from 12 donors with T1D (disease duration 0.42-20 years) and from seven control donors and two donors with type 2 diabetes (T2D). A total of 321 T cell lines and clones were derived from the islets of donors with T1D (3 lines from the 9 control donors). These are 131 CD4+ lines and clones, 47 CD8+ lines and 143 lines that contain both CD4+ and CD8+ T cells. From 50 lines and clones examined to date, we have determined the autoreactivity of 19 and have seen a broad repertoire of T cell autoreactivity in the islets, including characterized targets and post-translationally modified targets. Autoreactivity of CD4+ T cell lines was to three different peptides from glutamic acid decarboxylase 65 (GAD; GAD115-127, GAD274-286, GAD555-567), proinsulin76-90, and to chromogranin A or proinsulin expressed by DR4+DQ8+ B cells transduced with lentivirus containing constructs with the open reading frames corresponding to whole autoantigens. Reactivity to modified peptides included the glucose-regulated protein 78 and islet amyloid polypeptide with arginine to citrulline modifications (GRP78292-305(Arg-Cit297) and IAPP65-84(Arg-Cit 73, 81)), deaminations (IA-2545-562(Gln-Glu 548, 551, 556), and to several insulin hybrid peptides. These autoreactive CD4+ T cell lines and clones secreted only pro-inflammatory cytokines (IFN-γ, TNFα) upon peptide stimulation. For CD8+ T cells from islets, from one donor with T1D, we saw binding of a pool of HLA-A2 pentamers loaded with insulin B10-18, IA-2797-805 and insulin specific glucose-6-phosphatase catalytic subunit related protein, IGRP265-273. These results have implications for the development of successful prevention and reversal therapeutic strategies in T1D

The genomes of two key bumblebee species with primitive eusocial organization

Background: The shift from solitary to social behavior is one of the major evolutionary transitions. Primitively eusocial bumblebees are uniquely placed to illuminate the evolution of highly eusocial insect societies. Bumblebees are also invaluable natural and agricultural pollinators, and there is widespread concern over recent population declines in some species. High-quality genomic data will inform key aspects of bumblebee biology, including susceptibility to implicated population viability threats. Results: We report the high quality draft genome sequences of Bombus terrestris and Bombus impatiens, two ecologically dominant bumblebees and widely utilized study species. Comparing these new genomes to those of the highly eusocial honeybee Apis mellifera and other Hymenoptera, we identify deeply conserved similarities, as well as novelties key to the biology of these organisms. Some honeybee genome features thought to underpin advanced eusociality are also present in bumblebees, indicating an earlier evolution in the bee lineage. Xenobiotic detoxification and immune genes are similarly depauperate in bumblebees and honeybees, and multiple categories of genes linked to social organization, including development and behavior, show high conservation. Key differences identified include a bias in bumblebee chemoreception towards gustation from olfaction, and striking differences in microRNAs, potentially responsible for gene regulation underlying social and other traits. Conclusions: These two bumblebee genomes provide a foundation for post-genomic research on these key pollinators and insect societies. Overall, gene repertoires suggest that the route to advanced eusociality in bees was mediated by many small changes in many genes and processes, and not by notable expansion or depauperation

Sequence Homology at the Breakpoint and Clinical Phenotype of Mitochondrial DNA Deletion Syndromes

Mitochondrial DNA (mtDNA) deletions are a common cause of mitochondrial disorders. Large mtDNA deletions can lead to a broad spectrum of clinical features with different age of onset, ranging from mild mitochondrial myopathies (MM), progressive external ophthalmoplegia (PEO), and Kearns-Sayre syndrome (KSS), to severe Pearson syndrome. The aim of this study is to investigate the molecular signatures surrounding the deletion breakpoints and their association with the clinical phenotype and age at onset. MtDNA deletions in 67 patients were characterized using array comparative genomic hybridization (aCGH) followed by PCR-sequencing of the deletion junctions. Sequence homology including both perfect and imperfect short repeats flanking the deletion regions were analyzed and correlated with clinical features and patients' age group. In all age groups, there was a significant increase in sequence homology flanking the deletion compared to mtDNA background. The youngest patient group (<6 years old) showed a diffused pattern of deletion distribution in size and locations, with a significantly lower sequence homology flanking the deletion, and the highest percentage of deletion mutant heteroplasmy. The older age groups showed rather discrete pattern of deletions with 44% of all patients over 6 years old carrying the most common 5 kb mtDNA deletion, which was found mostly in muscle specimens (22/41). Only 15% (3/20) of the young patients (<6 years old) carry the 5 kb common deletion, which is usually present in blood rather than muscle. This group of patients predominantly (16 out of 17) exhibit multisystem disorder and/or Pearson syndrome, while older patients had predominantly neuromuscular manifestations including KSS, PEO, and MM. In conclusion, sequence homology at the deletion flanking regions is a consistent feature of mtDNA deletions. Decreased levels of sequence homology and increased levels of deletion mutant heteroplasmy appear to correlate with earlier onset and more severe disease with multisystem involvement

How and why community hospital clinicians document a positive screen for intimate partner violence: a cross-sectional study

BACKGROUND: This two-part study examines primary care clinicians' chart documentation and attitudes when confronted by a positive waiting room screen for intimate partner violence (IPV). METHODS: Patients at community hospital-affiliated health centers completed a screening questionnaire in waiting rooms that primary care providers (PCPs) were subsequently given at the time of the visit. We first reviewed the medical records of patients who screened positive for IPV, evaluating the presence and quality of documentation. Next we administered a survey to PCPs that measured their knowledge, attitudes and practice regarding IPV. RESULTS: Seventy-two percent of charts contained some documentation of IPV, however only 10% contained both a referral and safety plan. PCPs were more likely to refer patients (p < .05) who screened positively for mood or anxiety disorders, disclosed that they feared for their safety or were economically disadvantaged. Those that feared for their safety or endorsed mood or anxiety disorders were more likely to have notation of a safety plan in their records. When surveyed, 81.6% of clinicians strongly agreed that it is their role to inquire about IPV, but only 68% expressed confidence in their ability to manage it. In contrast, 93% expressed confidence in managing depression. Sixty-seven percent identified time constraints as a barrier to care. Predictors of PCP confidence in treating patients who have experienced IPV (p < .05) included hours of recent training and clinical experience with IPV. CONCLUSION: Mandatory waiting room screening for IPV does not result in high levels of referral or safety planning by PCPs. Despite the implementation of a screening process, clinicians lack confidence and time to address IPV in their patient populations suggesting that alternative methods of training and supporting PCPs need to be developed

The Medical Action Ontology: A tool for annotating and analyzing treatments and clinical management of human disease.

BACKGROUND: Navigating the clinical literature to determine the optimal clinical management for rare diseases presents significant challenges. We introduce the Medical Action Ontology (MAxO), an ontology specifically designed to organize medical procedures, therapies, and interventions. METHODS: MAxO incorporates logical structures that link MAxO terms to numerous other ontologies within the OBO Foundry. Term development involves a blend of manual and semi-automated processes. Additionally, we have generated annotations detailing diagnostic modalities for specific phenotypic abnormalities defined by the Human Phenotype Ontology (HPO). We introduce a web application, POET, that facilitates MAxO annotations for specific medical actions for diseases using the Mondo Disease Ontology. FINDINGS: MAxO encompasses 1,757 terms spanning a wide range of biomedical domains, from human anatomy and investigations to the chemical and protein entities involved in biological processes. These terms annotate phenotypic features associated with specific disease (using HPO and Mondo). Presently, there are over 16,000 MAxO diagnostic annotations that target HPO terms. Through POET, we have created 413 MAxO annotations specifying treatments for 189 rare diseases. CONCLUSIONS: MAxO offers a computational representation of treatments and other actions taken for the clinical management of patients. Its development is closely coupled to Mondo and HPO, broadening the scope of our computational modeling of diseases and phenotypic features. We invite the community to contribute disease annotations using POET (https://poet.jax.org/). MAxO is available under the open-source CC-BY 4.0 license (https://github.com/monarch-initiative/MAxO). FUNDING: NHGRI 1U24HG011449-01A1 and NHGRI 5RM1HG010860-04

Fussy Feeders: Phyllosoma Larvae of the Western Rocklobster (Panulirus cygnus) Demonstrate Prey Preference

The Western Rocklobster (Panulirus cygnus) is the most valuable single species fishery in Australia and the largest single country spiny lobster fishery in the world. In recent years a well-known relationship between oceanographic conditions and lobster recruitment has become uncoupled, with significantly lower recruitment than expected, generating interest in the factors influencing survival and development of the planktonic larval stages. The nutritional requirements and wild prey of the planktotrophic larval stage (phyllosoma) of P. cygnus were previously unknown, hampering both management and aquaculture efforts for this species. Ship-board feeding trials of wild-caught mid-late stage P. cygnus phyllosoma in the eastern Indian Ocean, off the coast of Western Australia, were conducted in July 2010 and August-September 2011. In a series of experiments, phyllosoma were fed single and mixed species diets of relatively abundant potential prey items (chaetognaths, salps, and krill). Chaetognaths were consumed in 2–8 times higher numbers than the other prey, and the rate of consumption of chaetognaths increased with increasing concentration of prey. The highly variable lipid content of the phyllosoma, and the fatty acid profiles of the phyllosoma and chaetognaths, indicated they were from an oligotrophic oceanic food chain where food resources for macrozooplankton were likely to be constrained. Phyllosoma fed chaetognaths over 6 days showed significant changes in some fatty acids and tended to accumulate lipid, indicating an improvement in overall nutritional condition. The discovery of a preferred prey for P. cygnus will provide a basis for future oceanographic, management and aquaculture research for this economically and ecologically valuable species