98 research outputs found
Optimization of dynamic soaring in a flap-gliding seabird affects its large-scale distribution at sea
Dynamic soaring harvests energy from a spatiotemporal wind gradient, allowing albatrosses to glide over vast distances. However, its use is challenging to demonstrate empirically and has yet to be confirmed in other seabirds. Here, we investigate how flap-gliding Manx shearwaters optimize their flight for dynamic soaring. We do so by deriving a new metric, the horizontal wind effectiveness, that quantifies how effectively flight harvests energy from a shear layer. We evaluate this metric empirically for fine-scale trajectories reconstructed from bird-borne video data using a simplified flight dynamics model. We find that the birdsâ undulations are phased with their horizontal turning to optimize energy harvesting. We also assess the opportunity for energy harvesting in long-range, GPS-logged foraging trajectories and find that Manx shearwaters optimize their flight to increase the opportunity for dynamic soaring during favorable wind conditions. Our results show how small-scale dynamic soaring affects large-scale Manx shearwater distribution at sea.publishedVersio
Optimization of dynamic soaring in a flap-gliding seabird affects its large-scale distribution at sea
Funding: This work was supported by the University of Oxford Christopher Welch Scholarship (to J.A.K.); ASAB Undergraduate Project Scholarship (to J.A.K.); UKRI BBSRC scholarship grant number BB/M011224/1 (to J.W. and N.G.); The Queenâs College, University of Oxford (to A.L.F.); Junior Research Fellowship at St. Johnâs College, University of Oxford (to O.P.); Merton College, University of Oxford (to T.G.); Mary Griffiths Award (to T.G.); BBSRC David Phillips Fellowship grant numbers BB/G023913/1 and BB/ G023913/2 (to C.R.); and Jesus College, University of Oxford (to G.K.T.). This project has received funding from the European Research Council (ERC) under the European Unionâs Horizon 2020 research and innovation programme (grant agreement no. 682501) (to G.K.T.)Dynamic soaring harvests energy from a spatiotemporal wind gradient, allowing albatrosses to glide over vast distances. However, its use is challenging to demonstrate empirically and has yet to be confirmed in other seabirds. Here, we investigate how flap-gliding Manx shearwaters optimize their flight for dynamic soaring. We do so by deriving a new metric, the horizontal wind effectiveness, that quantifies how effectively flight harvests energy from a shear layer. We evaluate this metric empirically for fine-scale trajectories reconstructed from bird-borne video data using a simplified flight dynamics model. We find that the birds' undulations are phased with their horizontal turning to optimize energy harvesting. We also assess the opportunity for energy harvesting in long-range, GPS-logged foraging trajectories and find that Manx shearwaters optimize their flight to increase the opportunity for dynamic soaring during favorable wind conditions. Our results show how small-scale dynamic soaring affects large-scale Manx shearwater distribution at sea.Publisher PDFPeer reviewe
CRISPR-Cas9 Knockin Mice for Genome Editing and Cancer Modeling
CRISPR-Cas9 is a versatile genome editing technology for studying the functions of genetic elements. To broadly enable the application of Cas9 in vivo, we established a Cre-dependent Cas9 knockin mouse. We demonstrated in vivo as well as ex vivo genome editing using adeno-associated virus (AAV)-, lentivirus-, or particle-mediated delivery of guide RNA in neurons, immune cells, and endothelial cells. Using these mice, we simultaneously modeled the dynamics of KRAS, p53, and LKB1, the top three significantly mutated genes in lung adenocarcinoma. Delivery of a single AAV vector in the lung generated loss-of-function mutations in p53 and Lkb1, as well as homology-directed repair-mediated Kras[superscript G12D] mutations, leading to macroscopic tumors of adenocarcinoma pathology. Together, these results suggest that Cas9 mice empower a wide range of biological and disease modeling applications.National Science Foundation (U.S.). Graduate Research Fellowship (Grant 1122374)Damon Runyon Cancer Research Foundation (Fellowship DRG-2117-12)Massachusetts Institute of Technology. Simons Center for the Social Brain (Postdoctoral Fellowship)European Molecular Biology Organization (Fellowship)Foundation for Polish Science (Fellowship)American Society for Engineering Education. National Defense Science and Engineering Graduate FellowshipNational Science Foundation (U.S.). Graduate Research FellowshipMassachusetts Institute of Technology (Presidential Graduate Fellowship)Human Frontier Science Program (Strasbourg, France) (Postdoctoral Fellowship)National Human Genome Research Institute (U.S.) (CEGS P50 HG006193)Howard Hughes Medical InstituteKlarman Cell ObservatoryNational Cancer Institute (U.S.) (Center of Cancer Nanotechnology Excellence Grant U54CA151884)National Institutes of Health (U.S.) (Controlled Release Grant EB000244)National Heart, Lung, and Blood Institute (Program of Excellence in Nanotechnology (PEN) Award Contract HHSN268201000045C)Massachusetts Institute of Technology (Poitras Gift 1631119)Stanley CenterSimons Foundation (6927482)Nancy Lurie Marks Family Foundation (6928117)United States. Public Health Service (National Institutes of Health (U.S.) R01-CA133404)David H. Koch Institute for Integrative Cancer Research at MIT (Marie D. and Pierre Casimir-Lambert Fund)MIT Skoltech InitiativeNational Cancer Institute (U.S.) (Koch Institute Support (Core) Grant P30-CA14051)National Institute of Mental Health (U.S.) (Directorâs Pioneer Award DP1-MH100706)National Institute of Neurological Disorders and Stroke (U.S.) (Transformative R01 Grant R01-NS 07312401)National Science Foundation (U.S.) (Waterman Award)W. M. Keck FoundationKinship Foundation. Searle Scholars ProgramKlingenstein FoundationVallee FoundationMerkin Foundatio
Increased resting hippocampal and basal ganglia perfusion in people at ultra high risk for psychosis: replication in a second cohort
Proxima Centauri b is not a transiting exoplanet
We report Spitzer Space Telescope observations during predicted transits of
the exoplanet Proxima Centauri b. As the nearest terrestrial habitable-zone
planet we will ever discover, any potential transit of Proxima b would place
strong constraints on its radius, bulk density, and atmosphere. Subsequent
transmission spectroscopy and secondary-eclipse measurements could then probe
the atmospheric chemistry, physical processes, and orbit, including a search
for biosignatures. However, our photometric results rule out planetary transits
at the 200~ppm level at 4.5, yielding a 3 upper radius limit
of 0.4~R_\rm{\oplus} (Earth radii). Previous claims of possible transits from
optical ground- and space-based photometry were likely correlated noise in the
data from Proxima Centauri's frequent flaring. Follow-up observations should
focus on planetary radio emission, phase curves, and direct imaging. Our study
indicates dramatically reduced stellar activity at near-to-mid infrared
wavelengths, compared to the optical. Proxima b is an ideal target for
space-based infrared telescopes, if their instruments can be configured to
handle Proxima's brightness.Comment: 8 pages, 3 figures, 2 tables, accepted for publication in MNRA
Integrated metastate functional connectivity networks predict change in symptom severity in clinical high risk for psychosis
The ability to identify biomarkers of psychosis risk is essential in defining effective preventive measures to potentially circumvent the transition to psychosis. Using samples of people at clinical high risk for psychosis (CHR) and Healthy controls (HC) who were administered a task fMRI paradigm, we used a framework for labelling time windows of fMRI scans as âintegratedâ FC networks to provide a granular representation of functional connectivity (FC). Periods of integration were defined using the âcartographic profileâ of time windows and kâmeans clustering, and subânetwork discovery was carried out using Network Based Statistics (NBS). There were no network differences between CHR and HC groups. Within the CHR group, using integrated FC networks, we identified a subânetwork negatively associated with longitudinal changes in the severity of psychotic symptoms. This subânetwork comprised brain areas implicated in bottomâup sensory processing and in integration with motor control, suggesting it may be related to the demands of the fMRI task. These data suggest that extracting integrated FC networks may be useful in the investigation of biomarkers of psychosis risk
Clinical, cognitive and neuroanatomical associations of serum NMDAR autoantibodies in people at clinical high risk for psychosis
Serum neuronal autoantibodies, such as those to the NMDA receptor (NMDAR), are detectable in a subgroup of patients with psychotic disorders. It is not known if they are present before the onset of psychosis or whether they are associated with particular clinical features or outcomes. In a case-control study, sera from 254 subjects at clinical high risk (CHR) for psychosis and 116 healthy volunteers were tested for antibodies against multiple neuronal antigens implicated in CNS autoimmune disorders, using fixed and live cell-based assays (CBAs). Within the CHR group, the relationship between NMDAR antibodies and symptoms, cognitive function and clinical outcomes over 24 month follow-up was examined. CHR subjects were not more frequently seropositive for neuronal autoantibodies than controls (8.3% vs. 5.2%; OR = 1.50; 95% CI: 0.58-3.90). The NMDAR was the most common target antigen and NMDAR IgGs were more sensitively detected with live versus fixed CBAs (p < 0.001). Preliminary phenotypic analyses revealed that within the CHR sample, the NMDAR antibody seropositive subjects had higher levels of current depression, performed worse on the Rey Auditory Verbal Learning Task (p < 0.05), and had a markedly lower IQ (p < 0.01). NMDAR IgGs were not more frequent in subjects who later became psychotic than those who did not. NMDAR antibody serostatus and titre was associated with poorer levels of functioning at follow-up (p < 0.05) and the presence of a neuronal autoantibody was associated with larger amygdala volumes (p < 0.05). Altogether, these findings demonstrate that NMDAR autoantibodies are detectable in a subgroup of CHR subjects at equal rates to controls. In the CHR group, they are associated with affective psychopathology, impairments in verbal memory, and overall cognitive function: these findings are qualitatively and individually similar to core features of autoimmune encephalitis and/or animal models of NMDAR antibody-mediated CNS disease. Overall the current work supports further evaluation of NMDAR autoantibodies as a possible prognostic biomarker and aetiological factor in a subset of people already meeting CHR criteria
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Clinical, cognitive and neuroanatomical associations of serum NMDAR autoantibodies in people at clinical high risk for psychosis
Serum neuronal autoantibodies, such as those to the NMDA receptor (NMDAR), are detectable in a subgroup of patients with psychotic disorders. It is not known if they are present before the onset of psychosis or whether they are associated with particular clinical features or outcomes. In a caseâcontrol study, sera from 254 subjects at clinical high risk (CHR) for psychosis and 116 healthy volunteers were tested for antibodies against multiple neuronal antigens implicated in CNS autoimmune disorders, using fixed and live cell-based assays (CBAs). Within the CHR group, the relationship between NMDAR antibodies and symptoms, cognitive function and clinical outcomes over 24 month follow-up was examined. CHR subjects were not more frequently seropositive for neuronal autoantibodies than controls (8.3% vs. 5.2%; OR = 1.50; 95% CI: 0.58â3.90). The NMDAR was the most common target antigen and NMDAR IgGs were more sensitively detected with live versus fixed CBAs (p < 0.001). Preliminary phenotypic analyses revealed that within the CHR sample, the NMDAR antibody seropositive subjects had higher levels of current depression, performed worse on the Rey Auditory Verbal Learning Task (p < 0.05), and had a markedly lower IQ (p < 0.01). NMDAR IgGs were not more frequent in subjects who later became psychotic than those who did not. NMDAR antibody serostatus and titre was associated with poorer levels of functioning at follow-up (p < 0.05) and the presence of a neuronal autoantibody was associated with larger amygdala volumes (p < 0.05). Altogether, these findings demonstrate that NMDAR autoantibodies are detectable in a subgroup of CHR subjects at equal rates to controls. In the CHR group, they are associated with affective psychopathology, impairments in verbal memory, and overall cognitive function: these findings are qualitatively and individually similar to core features of autoimmune encephalitis and/or animal models of NMDAR antibody-mediated CNS disease. Overall the current work supports further evaluation of NMDAR autoantibodies as a possible prognostic biomarker and aetiological factor in a subset of people already meeting CHR criteria
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Intracranial and subcortical volumes in adolescents with earlyâonset psychosis: A multisite megaâanalysis from the ENIGMA consortium
Earlyâonset psychosis disorders are serious mental disorders arising before the age of 18âyears. Here, we investigate the largest neuroimaging dataset, to date, of patients with earlyâonset psychosis and healthy controls for differences in intracranial and subcortical brain volumes. The sample included 263 patients with earlyâonset psychosis (mean age: 16.4â±â1.4âyears, mean illness duration: 1.5â±â1.4âyears, 39.2% female) and 359 healthy controls (mean age: 15.9â±â1.7âyears, 45.4% female) with magnetic resonance imaging data, pooled from 11 clinical cohorts. Patients were diagnosed with earlyâonset schizophrenia (n = 183), affective psychosis (n = 39), or other psychotic disorders (n = 41). We used linear mixedâeffects models to investigate differences in intracranial and subcortical volumes across the patient sample, diagnostic subgroup and antipsychotic medication, relative to controls. We observed significantly lower intracranial (Cohen's d = â0.39) and hippocampal (d = â0.25) volumes, and higher caudate (d = 0.25) and pallidum (d = 0.24) volumes in patients relative to controls. Intracranial volume was lower in both earlyâonset schizophrenia (d = â0.34) and affective psychosis (d = â0.42), and earlyâonset schizophrenia showed lower hippocampal (d = â0.24) and higher pallidum (d = 0.29) volumes. Patients who were currently treated with antipsychotic medication (n = 193) had significantly lower intracranial volume (d = â0.42). The findings demonstrate a similar pattern of brain alterations in earlyâonset psychosis as previously reported in adult psychosis, but with notably low intracranial volume. The low intracranial volume suggests disrupted neurodevelopment in adolescent earlyâonset psychosis
A genome-wide association study of resistance to HIV infection in highly exposed uninfected individuals with hemophilia A
Human genetic variation contributes to differences in susceptibility to HIV-1 infection. To search for novel host resistance factors, we performed a genome-wide association study (GWAS) in hemophilia patients highly exposed to potentially contaminated factor VIII infusions. Individuals with hemophilia A and a documented history of factor VIII infusions before the introduction of viral inactivation procedures (1979-1984) were recruited from 36 hemophilia treatment centers (HTCs), and their genome-wide genetic variants were compared with those from matched HIV-infected individuals. Homozygous carriers of known CCR5 resistance mutations were excluded. Single nucleotide polymorphisms (SNPs) and inferred copy number variants (CNVs) were tested using logistic regression. In addition, we performed a pathway enrichment analysis, a heritability analysis, and a search for epistatic interactions with CCR5 Î32 heterozygosity. A total of 560 HIV-uninfected cases were recruited: 36 (6.4%) were homozygous for CCR5 Î32 or m303. After quality control and SNP imputation, we tested 1 081 435 SNPs and 3686 CNVs for association with HIV-1 serostatus in 431 cases and 765 HIV-infected controls. No SNP or CNV reached genome-wide significance. The additional analyses did not reveal any strong genetic effect. Highly exposed, yet uninfected hemophiliacs form an ideal study group to investigate host resistance factors. Using a genome-wide approach, we did not detect any significant associations between SNPs and HIV-1 susceptibility, indicating that common genetic variants of major effect are unlikely to explain the observed resistance phenotype in this populatio
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