| 1. |
- Niemi, MEK, et al.
(author)
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- 2021
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swepub:Mat__t
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| 2. |
- Tabiri, S, et al.
(author)
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- 2021
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swepub:Mat__t
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| 3. |
- Bravo, L, et al.
(author)
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- 2021
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swepub:Mat__t
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| 4. |
- Kanai, M, et al.
(author)
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- 2023
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swepub:Mat__t
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| 5. |
- Khatri, C, et al.
(author)
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Outcomes after perioperative SARS-CoV-2 infection in patients with proximal femoral fractures: an international cohort study
- 2021
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In: BMJ open. - : BMJ. - 2044-6055. ; 11:11, s. e050830-
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Journal article (peer-reviewed)abstract
- Studies have demonstrated high rates of mortality in people with proximal femoral fracture and SARS-CoV-2, but there is limited published data on the factors that influence mortality for clinicians to make informed treatment decisions. This study aims to report the 30-day mortality associated with perioperative infection of patients undergoing surgery for proximal femoral fractures and to examine the factors that influence mortality in a multivariate analysis.SettingProspective, international, multicentre, observational cohort study.ParticipantsPatients undergoing any operation for a proximal femoral fracture from 1 February to 30 April 2020 and with perioperative SARS-CoV-2 infection (either 7 days prior or 30-day postoperative).Primary outcome30-day mortality. Multivariate modelling was performed to identify factors associated with 30-day mortality.ResultsThis study reports included 1063 patients from 174 hospitals in 19 countries. Overall 30-day mortality was 29.4% (313/1063). In an adjusted model, 30-day mortality was associated with male gender (OR 2.29, 95% CI 1.68 to 3.13, p<0.001), age >80 years (OR 1.60, 95% CI 1.1 to 2.31, p=0.013), preoperative diagnosis of dementia (OR 1.57, 95% CI 1.15 to 2.16, p=0.005), kidney disease (OR 1.73, 95% CI 1.18 to 2.55, p=0.005) and congestive heart failure (OR 1.62, 95% CI 1.06 to 2.48, p=0.025). Mortality at 30 days was lower in patients with a preoperative diagnosis of SARS-CoV-2 (OR 0.6, 95% CI 0.6 (0.42 to 0.85), p=0.004). There was no difference in mortality in patients with an increase to delay in surgery (p=0.220) or type of anaesthetic given (p=0.787).ConclusionsPatients undergoing surgery for a proximal femoral fracture with a perioperative infection of SARS-CoV-2 have a high rate of mortality. This study would support the need for providing these patients with individualised medical and anaesthetic care, including medical optimisation before theatre. Careful preoperative counselling is needed for those with a proximal femoral fracture and SARS-CoV-2, especially those in the highest risk groups.Trial registration numberNCT04323644
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| 6. |
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| 7. |
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| 8. |
- Aartsen, M. G., et al.
(author)
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Very high-energy gamma-ray follow-up program using neutrino triggers from IceCube
- 2016
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In: Journal of Instrumentation. - 1748-0221. ; 11
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Journal article (peer-reviewed)abstract
- We describe and report the status of a neutrino-triggered program in IceCube that generates real-time alerts for gamma-ray follow-up observations by atmospheric-Cherenkov telescopes (MAGIC and VERITAS). While IceCube is capable of monitoring the whole sky continuously, high-energy gamma-ray telescopes have restricted fields of view and in general are unlikely to be observing a potential neutrino-flaring source at the time such neutrinos are recorded. The use of neutrino-triggered alerts thus aims at increasing the availability of simultaneous multi-messenger data during potential neutrino flaring activity, which can increase the discovery potential and constrain the phenomenological interpretation of the high-energy emission of selected source classes (e. g. blazars). The requirements of a fast and stable online analysis of potential neutrino signals and its operation are presented, along with first results of the program operating between 14 March 2012 and 31 December 2015.
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| 9. |
- Aartsen, M. G., et al.
(author)
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Multiwavelength follow-up of a rare IceCube neutrino multiplet
- 2017
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In: Astronomy and Astrophysics. - : EDP SCIENCES S A. - 0004-6361 .- 1432-0746. ; 607
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Journal article (peer-reviewed)abstract
- On February 17, 2016, the IceCube real-time neutrino search identified, for the first time, three muon neutrino candidates arriving within 100 s of one another, consistent with coming from the same point in the sky. Such a triplet is expected once every 13.7 years as a random coincidence of background events. However, considering the lifetime of the follow-up program the probability of detecting at least one triplet from atmospheric background is 32%. Follow-up observatories were notified in order to search for an electromagnetic counterpart. Observations were obtained by Swift's X-ray telescope, by ASAS-SN, LCO and MASTER at optical wavelengths, and by VERITAS in the very-high-energy gamma-ray regime. Moreover, the Swift BAT serendipitously observed the location 100 s after the first neutrino was detected, and data from the Fermi LAT and HAWC observatory were analyzed. We present details of the neutrino triplet and the follow-up observations. No likely electromagnetic counterpart was detected, and we discuss the implications of these constraints on candidate neutrino sources such as gamma-ray bursts, core-collapse supernovae and active galactic nucleus flares. This study illustrates the potential of and challenges for future follow-up campaigns.
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| 10. |
- Abeysekara, A. U., et al.
(author)
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VERITAS and Fermi-LAT Observations of TeV Gamma-Ray Sources Discovered by HAWC in the 2HWC Catalog
- 2018
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In: Astrophysical Journal. - : Institute of Physics Publishing. - 0004-637X .- 1538-4357. ; 866:1
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Journal article (peer-reviewed)abstract
- The High Altitude Water Cherenkov (HAWC) collaboration recently published their 2HWC catalog, listing 39 very high energy (VHE; >100 GeV) gamma-ray sources based on 507 days of observation. Among these, 19 sources are not associated with previously known teraelectronvolt (TeV) gamma-ray sources. We have studied 14 of these sources without known counterparts with VERITAS and Fermi-LAT. VERITAS detected weak gamma-ray emission in the 1 TeV-30 TeV band in the region of DA 495, a pulsar wind nebula coinciding with 2HWC J1953+294, confirming the discovery of the source by HAWC. We did not find any counterpart for the selected 14 new HAWC sources from our analysis of Fermi-LAT data for energies higher than 10 GeV. During the search, we detected gigaelectronvolt (GeV) gamma-ray emission coincident with a known TeV pulsar wind nebula, SNR G54.1+0.3 (VER J1930+188), and a 2HWC source, 2HWC J1930+188. The fluxes for isolated, steady sources in the 2HWC catalog are generally in good agreement with those measured by imaging atmospheric Cherenkov telescopes. However, the VERITAS fluxes for SNR G54.1+0.3, DA 495, and TeV J2032+4130 are lower than those measured by HAWC, and several new HAWC sources are not detected by VERITAS. This is likely due to a change in spectral shape, source extension, or the influence of diffuse emission in the source region.
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| 11. |
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| 12. |
- Acharyya, A., et al.
(author)
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Multiwavelength Observations of the Blazar PKS 0735+178 in Spatial and Temporal Coincidence with an Astrophysical Neutrino Candidate IceCube-211208A
- 2023
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In: Astrophysical Journal. - : Institute of Physics Publishing (IOPP). - 0004-637X .- 1538-4357. ; 954:1
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Journal article (peer-reviewed)abstract
- We report on multiwavelength target-of-opportunity observations of the blazar PKS 0735+178, located 2 degrees .2 away from the best -fit position of the IceCube neutrino event IceCube-211208A detected on 2021 December 8. The source was in a high -flux state in the optical, ultraviolet, X-ray, and GeV ?-ray bands around the time of the neutrino event, exhibiting daily variability in the soft X-ray flux. The X-ray data from Swift-XRT and NuSTAR characterize the transition between the low-energy and high-energy components of the broadband spectral energy distribution (SED), and the ?-ray data from Fermi-LAT, VERITAS, and H.E.S.S. require a spectral cutoff near 100 GeV. Both the X-ray and ?-ray measurements provide strong constraints on the leptonic and hadronic models. We analytically explore a synchrotron self-Compton model, an external Compton model, and a lepto-hadronic model. Models that are entirely based on internal photon fields face serious difficulties in matching the observed SED. The existence of an external photon field in the source would instead explain the observed ?-ray spectral cutoff in both the leptonic and lepto-hadronic models and allow a proton jet power that marginally agrees with the Eddington limit in the lepto-hadronic model. We show a numerical lepto-hadronic model with external target photons that reproduces the observed SED and is reasonably consistent with the neutrino event despite requiring a high jet power.
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| 13. |
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| 14. |
- Shupe, M. D., et al.
(author)
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Overview of the MOSAiC expedition : Atmosphere
- 2022
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In: Elementa. - : University of California Press. - 2325-1026. ; 10:1
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Journal article (peer-reviewed)abstract
- With the Arctic rapidly changing, the needs to observe, understand, and model the changes are essential. To support these needs, an annual cycle of observations of atmospheric properties, processes, and interactions were made while drifting with the sea ice across the central Arctic during the Multidisciplinary drifting Observatory for the Study of Arctic Climate (MOSAiC) expedition from October 2019 to September 2020. An international team designed and implemented the comprehensive program to document and characterize all aspects of the Arctic atmospheric system in unprecedented detail, using a variety of approaches, and across multiple scales. These measurements were coordinated with other observational teams to explore crosscutting and coupled interactions with the Arctic Ocean, sea ice, and ecosystem through a variety of physical and biogeochemical processes. This overview outlines the breadth and complexity of the atmospheric research program, which was organized into 4 subgroups: atmospheric state, clouds and precipitation, gases and aerosols, and energy budgets. Atmospheric variability over the annual cycle revealed important influences from a persistent large-scale winter circulation pattern, leading to some storms with pressure and winds that were outside the interquartile range of past conditions suggested by long-term reanalysis. Similarly, the MOSAiC location was warmer and wetter in summer than the reanalysis climatology, in part due to its close proximity to the sea ice edge. The comprehensiveness of the observational program for characterizing and analyzing atmospheric phenomena is demonstrated via a winter case study examining air mass transitions and a summer case study examining vertical atmospheric evolution. Overall, the MOSAiC atmospheric program successfully met its objectives and was the most comprehensive atmospheric measurement program to date conducted over the Arctic sea ice. The obtained data will support a broad range of coupled-system scientific research and provide an important foundation for advancing multiscale modeling capabilities in the Arctic.
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| 15. |
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| 16. |
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| 17. |
- De Leoz, M. L. A., et al.
(author)
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NIST Interlaboratory Study on Glycosylation Analysis of Monoclonal Antibodies: Comparison of Results from Diverse Analytical Methods
- 2020
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In: Molecular & Cellular Proteomics. - 1535-9476. ; 19:1, s. 11-30
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Journal article (peer-reviewed)abstract
- A broad-based interlaboratory study of glycosylation profiles of a reference and modified IgG antibody involving 103 reports from 76 laboratories. Glycosylation is a topic of intense current interest in the development of biopharmaceuticals because it is related to drug safety and efficacy. This work describes results of an interlaboratory study on the glycosylation of the Primary Sample (PS) of NISTmAb, a monoclonal antibody reference material. Seventy-six laboratories from industry, university, research, government, and hospital sectors in Europe, North America, Asia, and Australia submitted a total of 103 reports on glycan distributions. The principal objective of this study was to report and compare results for the full range of analytical methods presently used in the glycosylation analysis of mAbs. Therefore, participation was unrestricted, with laboratories choosing their own measurement techniques. Protein glycosylation was determined in various ways, including at the level of intact mAb, protein fragments, glycopeptides, or released glycans, using a wide variety of methods for derivatization, separation, identification, and quantification. Consequently, the diversity of results was enormous, with the number of glycan compositions identified by each laboratory ranging from 4 to 48. In total, one hundred sixteen glycan compositions were reported, of which 57 compositions could be assigned consensus abundance values. These consensus medians provide community-derived values for NISTmAb PS. Agreement with the consensus medians did not depend on the specific method or laboratory type. The study provides a view of the current state-of-the-art for biologic glycosylation measurement and suggests a clear need for harmonization of glycosylation analysis methods.
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| 18. |
- Waszak, S. M., et al.
(author)
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Spectrum and prevalence of genetic predisposition in medulloblastoma: a retrospective genetic study and prospective validation in a clinical trial cohort
- 2018
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In: Lancet Oncology. - : Elsevier BV. - 1470-2045. ; 19:6, s. 785-798
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Journal article (peer-reviewed)abstract
- Background Medulloblastoma is associated with rare hereditary cancer predisposition syndromes; however, consensus medulloblastoma predisposition genes have not been defined and screening guidelines for genetic counselling and testing for paediatric patients are not available. We aimed to assess and define these genes to provide evidence for future screening guidelines. Methods In this international, multicentre study, we analysed patients with medulloblastoma from retrospective cohorts (International Cancer Genome Consortium [ICGC] PedBrain, Medulloblastoma Advanced Genomics International Consortium [MAGIC], and the CEFALO series) and from prospective cohorts from four clinical studies (SJMB03, SJMB12, SJYC07, and I-HIT-MED). Whole-genome sequences and exome sequences from blood and tumour samples were analysed for rare damaging germline mutations in cancer predisposition genes. DNA methylation profiling was done to determine consensus molecular subgroups: WNT (MBWNT), SHH (MBSHH), group 3 (MBGroup3), and group 4 (MBGroup4). Medulloblastoma predisposition genes were predicted on the basis of rare variant burden tests against controls without a cancer diagnosis from the Exome Aggregation Consortium (ExAC). Previously defined somatic mutational signatures were used to further classify medulloblastoma genomes into two groups, a clock-like group (signatures 1 and 5) and a homologous recombination repair deficiency-like group (signatures 3 and 8), and chromothripsis was investigated using previously established criteria. Progression-free survival and overall survival were modelled for patients with a genetic predisposition to medulloblastoma. Findings We included a total of 1022 patients with medulloblastoma from the retrospective cohorts (n=673) and the four prospective studies (n=349), from whom blood samples (n=1022) and tumour samples (n=800) were analysed for germline mutations in 110 cancer predisposition genes. In our rare variant burden analysis, we compared these against 53 105 sequenced controls from ExAC and identified APC, BRCA2, PALB2, PTCH1, SUFU, and TP53 as consensus medulloblastoma predisposition genes according to our rare variant burden analysis and estimated that germline mutations accounted for 6% of medulloblastoma diagnoses in the retrospective cohort. The prevalence of genetic predispositions differed between molecular subgroups in the retrospective cohort and was highest for patients in the MBSHH subgroup (20% in the retrospective cohort). These estimates were replicated in the prospective clinical cohort (germline mutations accounted for 5% of medulloblastoma diagnoses, with the highest prevalence [14%] in the MBSHH subgroup). Patients with germline APC mutations developed MBWNT and accounted for most (five [71%] of seven) cases of MBWNT that had no somatic CTNNB1 exon 3 mutations. Patients with germline mutations in SUFU and PTCH1 mostly developed infant MBSHH. Germline TP53 mutations presented only in childhood patients in the MBSHH subgroup and explained more than half (eight [57%] of 14) of all chromothripsis events in this subgroup. Germline mutations in PALB2 and BRCA2 were observed across the MBSHH, MBGroup3, and MBGroup4 molecular subgroups and were associated with mutational signatures typical of homologous recombination repair deficiency. In patients with a genetic predisposition to medulloblastoma, 5-year progression-free survival was 52% (95% CI 4069) and 5-year overall survival was 65% (95% CI 5281); these survival estimates differed significantly across patients with germline mutations in different medulloblastoma predisposition genes. Interpretation Genetic counselling and testing should be used as a standard-of-care procedure in patients with MBWNT and MBSHH because these patients have the highest prevalence of damaging germline mutations in known cancer predisposition genes. We propose criteria for routine genetic screening for patients with medulloblastoma based on clinical and molecular tumour characteristics. Copyright (c) 2018 The Author(s). Published by Elsevier Ltd.
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| 19. |
- Wortman, J. R., et al.
(author)
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The 2008 update of the Aspergillus nidulans genome annotation: A community effort
- 2009
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In: Fungal Genetics and Biology. - : Elsevier BV. - 1096-0937 .- 1087-1845. ; 46, s. S2-S13
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Journal article (peer-reviewed)abstract
- The identification and annotation of protein-coding genes is one of the primary goals of whole-genome sequencing projects, and the accuracy of predicting the primary protein products of gene expression is vital to the interpretation of the available data and the design of downstream functional applications. Nevertheless, the comprehensive annotation of eukaryotic genomes remains a considerable challenge. Many genomes submitted to public databases, including those of major model organisms, contain significant numbers of wrong and incomplete gene predictions. We present a community-based reannotation of the Aspergillus nidulans genome with the primary goal of increasing the number and quality of protein functional assignments through the careful review of experts in the field of fungal biology. (C) 2009 Elsevier Inc. All rights reserved.
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| 20. |
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| 21. |
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| 22. |
- Abeysekara, A. U., et al.
(author)
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A Luminous and Isolated Gamma-Ray Flare from the Blazar B2 1215+30
- 2017
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In: Astrophysical Journal. - : Institute of Physics Publishing (IOPP). - 0004-637X .- 1538-4357. ; 836:2
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Journal article (peer-reviewed)abstract
- B2 1215+30 is a BL-Lac-type blazar that was first detected at TeV energies by the MAGIC atmospheric Cherenkov telescopes and subsequently confirmed by the Very Energetic Radiation Imaging Telescope Array System (VERITAS) observatory with data collected between 2009 and 2012. In 2014 February 08, VERITAS detected a large-amplitude flare from B2. 1215+30 during routine monitoring observations of the blazar 1ES. 1218+304, located in the same field of view. The TeV flux reached 2.4 times the Crab Nebula flux with a variability timescale of <3.6 hr. Multiwavelength observations with Fermi-LAT, Swift, and the Tuorla Observatory revealed a correlated high GeV flux state and no significant optical counterpart to the flare, with a spectral energy distribution where the gamma-ray luminosity exceeds the synchrotron luminosity. When interpreted in the framework of a onezone leptonic model, the observed emission implies a high degree of beaming, with Doppler factor delta > 10, and an electron population with spectral index p < 2.3.
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| 23. |
- Gerkin, RC, et al.
(author)
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The best COVID-19 predictor is recent smell loss: a cross-sectional study
- 2020
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In: medRxiv : the preprint server for health sciences. - : Cold Spring Harbor Laboratory.
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Journal article (other academic/artistic)abstract
- BackgroundCOVID-19 has heterogeneous manifestations, though one of the most common symptoms is a sudden loss of smell (anosmia or hyposmia). We investigated whether olfactory loss is a reliable predictor of COVID-19.MethodsThis preregistered, cross-sectional study used a crowdsourced questionnaire in 23 languages to assess symptoms in individuals self-reporting recent respiratory illness. We quantified changes in chemosensory abilities during the course of the respiratory illness using 0-100 visual analog scales (VAS) for participants reporting a positive (C19+; n=4148) or negative (C19-; n=546) COVID-19 laboratory test outcome. Logistic regression models identified singular and cumulative predictors of COVID-19 status and post-COVID-19 olfactory recovery.ResultsBoth C19+ and C19-groups exhibited smell loss, but it was significantly larger in C19+ participants (mean±SD, C19+: -82.5±27.2 points; C19-: -59.8±37.7). Smell loss during illness was the best predictor of COVID-19 in both single and cumulative feature models (ROC AUC=0.72), with additional features providing negligible model improvement. VAS ratings of smell loss were more predictive than binary chemosensory yes/no-questions or other cardinal symptoms, such as fever or cough. Olfactory recovery within 40 days was reported for ∼50% of participants and was best predicted by time since illness onset.ConclusionsAs smell loss is the best predictor of COVID-19, we developed the ODoR-19 tool, a 0-10 scale to screen for recent olfactory loss. Numeric ratings ≤2 indicate high odds of symptomatic COVID-19 (4<OR<10), which can be deployed when viral lab tests are impractical or unavailable.
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| 24. |
- Grigoroglou, C., et al.
(author)
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Effectiveness of collaborative care in reducing suicidal ideation: An individual participant data meta-analysis
- 2021
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In: General Hospital Psychiatry. - : Elsevier BV. - 0163-8343. ; 71, s. 27-35
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Journal article (peer-reviewed)abstract
- To assess whether CC is more effective at reducing suicidal ideation in people with depression compared with usual care, and whether study and patient factors moderate treatment effects. Method: We searched Medline, Embase, PubMed, PsycINFO, CINAHL, CENTRAL from inception to March 2020 for Randomised Controlled Trials (RCTs) that compared the effectiveness of CC with usual care in depressed adults, and reported changes in suicidal ideation at 4 to 6 months post-randomisation. Mixed-effects models accounted for clustering of participants within trials and heterogeneity across trials. This study is registered with PROSPERO, CRD42020201747. Results: We extracted data from 28 RCTs (11,165 patients) of 83 eligible studies. We observed a small significant clinical improvement of CC on suicidal ideation, compared with usual care (SMD, 0.11 [95%CI, 0.15 to 0.08]; I-2, 0.47% [95%CI 0.04% to 4.90%]). CC interventions with a recognised psychological treatment were associated with small reductions in suicidal ideation (SMD, 0.15 [95%CI -0.19 to 0.11]). CC was more effective for reducing suicidal ideation among patients aged over 65 years (SMD, 0.18 [95%CI -0.25 to 0.11]). Conclusion: Primary care based CC with an embedded psychological intervention is the most effective CC framework for reducing suicidal ideation and older patients may benefit the most.
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| 25. |
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| 26. |
- Archer, E., et al.
(author)
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Biodiversity and ecosystem services on the African continent - What is changing, and what are our options?
- 2021
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In: Environmental Development. - : Elsevier BV. - 2211-4645 .- 2211-4653. ; 37
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Journal article (peer-reviewed)abstract
- Throughout the world, biodiversity and nature's contributions to people are under threat, with clear changes evident. Biodiversity and ecosystem services have particular value in Africa- yet they are negatively impacted by a range of drivers, including land use and climate change. In this communication, we show evidence of changing biodiversity and ecosystem services in Africa, as well as the current most significant drivers of change. We then consider five plausible futures for the African continent, each underlain by differing assumptions. In three out of the five futures under consideration, negative impacts on biodiversity and ecosystem services are likely to persist. Those two plausible futures prioritizing environment and sustainability, however, are shown as the most likely paths to achieving long term development objectives without compromising the continent's biodiversity and ecosystem services. Such a finding shows clearly that achievement of such objectives cannot be separated from full recognition of the value of such services.
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| 27. |
- Kaput, J, et al.
(author)
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The case for strategic international alliances to harness nutritional genomics for public and personal health
- 2005
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In: The British journal of nutrition. - : Cambridge University Press (CUP). - 0007-1145 .- 1475-2662. ; 94:5, s. 623-632
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Journal article (peer-reviewed)abstract
- Nutrigenomics is the study of how constituents of the diet interact with genes, and their products, to alter phenotype and, conversely, how genes and their products metabolise these constituents into nutrients, antinutrients, and bioactive compounds. Results from molecular and genetic epidemiological studies indicate that dietary unbalance can alter gene–nutrient interactions in ways that increase the risk of developing chronic disease. The interplay of human genetic variation and environmental factors will make identifying causative genes and nutrients a formidable, but not intractable, challenge. We provide specific recommendations for how to best meet this challenge and discuss the need for new methodologies and the use of comprehensive analyses of nutrient–genotype interactions involving large and diverse populations. The objective of the present paper is to stimulate discourse and collaboration among nutrigenomic researchers and stakeholders, a process that will lead to an increase in global health and wellness by reducing health disparities in developed and developing countries.
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| 28. |
- Ming, D.W., et al.
(author)
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Volatile and organic compositions of sedimentary rocks in Yellowknife Bay, Gale Crater, Mars
- 2014
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In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 343:6169
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Journal article (peer-reviewed)abstract
- H2O, CO2, SO2, O2, H2, H2S, HCl, chlorinated hydrocarbons, NO, and other trace gases were evolved during pyrolysis of two mudstone samples acquired by the Curiosity rover at Yellowknife Bay within Gale crater, Mars. H2O/OH-bearing phases included 2:1 phyllosilicate(s), bassanite, akaganeite, and amorphous materials. Thermal decomposition of carbonates and combustion of organic materials are candidate sources for the CO2. Concurrent evolution of O2 and chlorinated hydrocarbons suggests the presence of oxychlorine phase(s). Sulfides are likely sources for sulfur-bearing species. Higher abundances of chlorinated hydrocarbons in the mudstone compared with Rocknest windblown materials previously analyzed by Curiosity suggest that indigenous martian or meteoritic organic carbon sources may be preserved in the mudstone; however, the carbon source for the chlorinated hydrocarbons is not definitively of martian origin.
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| 29. |
- Morin, Phillip A., et al.
(author)
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Geographic and temporal dynamics of a global radiation and diversification in the killer whale
- 2015
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In: Molecular Ecology. - : Wiley. - 0962-1083 .- 1365-294X. ; 24:15, s. 3964-3979
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Journal article (peer-reviewed)abstract
- Global climate change during the Late Pleistocene periodically encroached and then released habitat during the glacial cycles, causing range expansions and contractions in some species. These dynamics have played a major role in geographic radiations, diversification and speciation. We investigate these dynamics in the most widely distributed of marine mammals, the killer whale (Orcinus orca), using a global data set of over 450 samples. This marine top predator inhabits coastal and pelagic ecosystems ranging from the ice edge to the tropics, often exhibiting ecological, behavioural and morphological variation suggestive of local adaptation accompanied by reproductive isolation. Results suggest a rapid global radiation occurred over the last 350000years. Based on habitat models, we estimated there was only a 15% global contraction of core suitable habitat during the last glacial maximum, and the resources appeared to sustain a constant global effective female population size throughout the Late Pleistocene. Reconstruction of the ancestral phylogeography highlighted the high mobility of this species, identifying 22 strongly supported long-range dispersal events including interoceanic and interhemispheric movement. Despite this propensity for geographic dispersal, the increased sampling of this study uncovered very few potential examples of ancestral dispersal among ecotypes. Concordance of nuclear and mitochondrial data further confirms genetic cohesiveness, with little or no current gene flow among sympatric ecotypes. Taken as a whole, our data suggest that the glacial cycles influenced local populations in different ways, with no clear global pattern, but with secondary contact among lineages following long-range dispersal as a potential mechanism driving ecological diversification.
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| 30. |
- Pfohl, J., et al.
(author)
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Highly deformed rotational structures in 136Pm
- 2000
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In: Physical Review C - Nuclear Physics. - 0556-2813. ; 62:3, s. 313041-313045
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Journal article (peer-reviewed)abstract
- Four highly deformed structures in the odd-odd nucleus 13661Pm75 were observed via the 105Pd(35Cl,2p2n) reaction at 180 and 173 MeV using the GAMMASPHERE γ-ray spectrometer and the Microball charged-particle detector array. Quadrupole moment measurements were performed on all of the bands. In contrast to lighter odd-Ζ Pm and Pr nuclei, bands based on the g9/2[404]9/2 proton orbital were not observed. Instead, the four observed sequences are assigned as a coupling of an i13/2 neutron with the low-Ω h11/2 and mixed d5/2g7/2 orbitals. Comparisons with neighboring highly deformed structures are discussed and cranked Nilsson-Strutinsky calculations for 136Pm are presented.
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| 31. |
- Archer, M, et al.
(author)
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Role of α- and β-adrenergic signaling in phenotypic targeting: significance in benign and malignant urologic disease
- 2021
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In: Cell communication and signaling : CCS. - : Springer Science and Business Media LLC. - 1478-811X. ; 19:1, s. 78-
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Journal article (peer-reviewed)abstract
- The urinary tract is highly innervated by autonomic nerves which are essential in urinary tract development, the production of growth factors, and the control of homeostasis. These neural signals may become dysregulated in several genitourinary (GU) disease states, both benign and malignant. Accordingly, the autonomic nervous system is a therapeutic target for several genitourinary pathologies including cancer, voiding dysfunction, and obstructing nephrolithiasis. Adrenergic receptors (adrenoceptors) are G-Protein coupled-receptors that are distributed throughout the body. The major function of α1-adrenoceptors is signaling smooth muscle contractions through GPCR and intracellular calcium influx. Pharmacologic intervention of α-and β-adrenoceptors is routinely and successfully implemented in the treatment of benign urologic illnesses, through the use of α-adrenoceptor antagonists. Furthermore, cell-based evidence recently established the antitumor effect of α1-adrenoceptor antagonists in prostate, bladder and renal tumors by reducing neovascularity and impairing growth within the tumor microenvironment via regulation of the phenotypic epithelial-mesenchymal transition (EMT). There has been a significant focus on repurposing the routinely used, Food and Drug Administration-approved α1-adrenoceptor antagonists to inhibit GU tumor growth and angiogenesis in patients with advanced prostate, bladder, and renal cancer. In this review we discuss the current evidence on (a) the signaling events of the autonomic nervous system mediated by its cognate α- and β-adrenoceptors in regulating the phenotypic landscape (EMT) of genitourinary organs; and (b) the therapeutic significance of targeting this signaling pathway in benign and malignant urologic disease.
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| 32. |
- Blum, K., et al.
(author)
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Neuroquantum Theories of Psychiatric Genetics: Can Physical Forces Induce Epigenetic Influence on Future Genomes?
- 2015
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In: Neuroquantology. - 1303-5150. ; 13:1, s. 90-103
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Journal article (peer-reviewed)abstract
- This paper serves to encourage quantum physicists to engage in psychiatric based research on the brain and its functions (i.e., consciousness, memory, attention). By using physics theorems such as Einstein's theory of relativity and the string theory, both physicists and geneticists alike may be able to elucidate potential links between components of the universe and their effects on the human brain. We have outlined some interesting posits including the cosmos' role in evolutionary biology, alpha bonding in biological molecules, and environmentally induced epigenetic effects on genetics. We also explore how physical forces can influence human memory, behavioral traits, and rates of addiction. Impulsiveness is used to exemplify how environmental changes can contribute to epigenetics and its hereditary alterations. We propose the idea of the presence of a "mental universe," where brain functionality like consciousness is a continuum of physically altered pathways. The realization that the universe and all of its precepts remains a mystery is reflected in the lack of a standardized "unified" physics theorem and mathematical equation that can explain universal dimensions (physical and mental), and as such, so is the complex nature of the functionality of the human brain. We provide herein a suggestion to remedy possible confusion, whereby we attempt to show the relationship of brain as a complex quantum-like organ and the impact of epigenetics on behavioral expression.
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| 33. |
- Onofri, E, et al.
(author)
-
Dysgraphia in Relation to Cognitive Performance in Patients with Alzheimer’s Disease
- 2013
-
In: Journal of Intellectual Disability - Diagnosis and Treatment. - : Lifescience Global. - 2292-2598. ; 1:2, s. 113-124
-
Journal article (peer-reviewed)abstract
- Dysgraphia has been observed in patients presenting mild to moderate levels of Alzheimer’s disease (AD) in several studies. In the present study, 30 AD patients and 30 matched healthy controls, originating from the Lazio region, Rome, Italy, were examined on tests of letter-writing ability and cognitive performance over a series of 10 test days that extended over 19 days (Test days: 1, 3, 5, 7, 9 11, 13, 15, 17, and 19). Consistent deficits by the AD patients over the initial cognition test (PQ1), 2nd cognition test (PQ2) and the difference between them (D∆), expressing deterioration, and writing-time compared the group of healthy control subjects were obtained. Furthermore, the performances of the AD patients on the PQ1, D∆ and writing-time, but not the PQ2, tests deteriorated from the 1st five days of testing (Days 1-9) to the 2nd five days (11-19). Both AD patients’ and healthy controls’ MMSE scores were markedly and significantly correlated with performance of PQ1, writing-time and PQ2. The extent of dysgraphia and progressive deficits in the AD patients implicate multiple brain regions in the loss of functional integrity.
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| 34. |
- Palmroth, M., et al.
(author)
-
Magnetosheath jet properties and evolution as determined by a global hybrid-Vlasov simulation
- 2018
-
In: Annales Geophysicae. - : Copernicus GmbH. - 0992-7689 .- 1432-0576. ; 36:5, s. 1171-1182
-
Journal article (peer-reviewed)abstract
- We use a global hybrid-Vlasov simulation for the magnetosphere, Vlasiator, to investigate magnetosheath high-speed jets. Unlike many other hybrid-kinetic simulations, Vlasiator includes an unscaled geomagnetic dipole, indicating that the simulation spatial and temporal dimensions can be given in SI units without scaling. Thus, for the first time, this allows investigating the magnetosheath jet properties and comparing them directly with the observed jets within the Earth's magnetosheath. In the run shown in this paper, the interplanetary magnetic field (IMF) cone angle is 30°, and a foreshock develops upstream of the quasi-parallel magnetosheath. We visually detect a structure with high dynamic pressure propagating from the bow shock through the magnetosheath. The structure is confirmed as a jet using three different criteria, which have been adopted in previous observational studies. We compare these criteria against the simulation results. We find that the magnetosheath jet is an elongated structure extending earthward from the bow shock by ∼ 2.6 RE, while its size perpendicular to the direction of propagation is ∼ 0.5R/E. We also investigate the jet evolution and find that the jet originates due to the interaction of the bow shock with a high-dynamic-pressure structure that reproduces observational features associated with a short, large-amplitude magnetic structure (SLAMS). The simulation shows that magnetosheath jets can develop also under steady IMF, as inferred by observational studies. To our knowledge, this paper therefore shows the first global kinetic simulation of a magnetosheath jet, which is in accordance with three observational jet criteria and is caused by a SLAMS advecting towards the bow shock.
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| 35. |
- Smith, Bradley P., et al.
(author)
-
Taxonomic status of the Australian dingo : the case for Canis dingo Meyer, 1793
- 2019
-
In: Zootaxa. - : MAGNOLIA PRESS. - 1175-5326 .- 1175-5334. ; 4564:1, s. 173-197
-
Journal article (peer-reviewed)abstract
- The taxonomic status and systematic nomenclature of the Australian dingo remain contentious, resulting in decades of inconsistent applications in the scientific literature and in policy. Prompted by a recent publication calling for dingoes to be considered taxonomically as domestic dogs (Jackson et al. 2017, Zootaxa 4317, 201-224), we review the issues of the taxonomy applied to canids, and summarise the main differences between dingoes and other canids. We conclude that (1) the Australian dingo is a geographically isolated (allopatric) species from all other Canis, and is genetically, phenotypically, ecologically, and behaviourally distinct; and (2) the dingo appears largely devoid of many of the signs of domestication, including surviving largely as a wild animal in Australia for millennia. The case of defining dingo taxonomy provides a quintessential example of the disagreements between species concepts (e.g., biological, phylogenetic, ecological, morphological). Applying the biological species concept sensu stricto to the dingo as suggested by Jackson et al. (2017) and consistently across the Canidae would lead to an aggregation of all Canis populations, implying for example that dogs and wolves are the same species. Such an aggregation would have substantial implications for taxonomic clarity, biological research, and wildlife conservation. Any changes to the current nomen of the dingo (currently Canis dingo Meyer, 1793), must therefore offer a strong, evidence-based argument in favour of it being recognised as a subspecies of Canis lupus Linnaeus, 1758, or as Canis familiaris Linnaeus, 1758, and a successful application to the International Commission for Zoological Nomenclature - neither of which can be adequately supported. Although there are many species concepts, the sum of the evidence presented in this paper affirms the classification of the dingo as a distinct taxon, namely Canis dingo.
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| 36. |
- Smith, Madison M., et al.
(author)
-
Thin and transient meltwater layers and false bottoms in the Arctic sea ice pack—Recent insights on these historically overlooked features
- 2023
-
In: Elementa: Science of the Anthropocene. - 2325-1026. ; 11:1
-
Research review (peer-reviewed)abstract
- The rapid melt of snow and sea ice during the Arctic summer provides a significant source of low-salinity meltwater to the surface ocean on the local scale. The accumulation of this meltwater on, under, and around sea ice floes can result in relatively thin meltwater layers in the upper ocean. Due to the small-scale nature of these upper-ocean features, typically on the order of 1 m thick or less, they are rarely detected by standard methods, but are nevertheless pervasive and critically important in Arctic summer. Observations during the Multidisciplinary drifting Observatory for the Study of Arctic Climate (MOSAiC) expedition in summer 2020 focused on the evolution of such layers and made significant advancements in understanding their role in the coupled Arctic system. Here we provide a review of thin meltwater layers in the Arctic, with emphasis on the new findings from MOSAiC. Both prior and recent observational datasets indicate an intermittent yet longlasting (weeks to months) meltwater layer in the upper ocean on the order of 0.1 m to 1.0 m in thickness, with a large spatial range. The presence of meltwater layers impacts the physical system by reducing bottom ice melt and allowing new ice formation via false bottom growth. Collectively, the meltwater layer and false bottoms reduce atmosphere-ocean exchanges of momentum, energy, and material.The impacts on the coupled Arctic system are far-reaching, including acting as a barrier for nutrient and gas exchange and impacting ecosystem diversity and productivity.
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| 37. |
- Archer, A, et al.
(author)
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Fasting-induced FGF21 is repressed by LXR activation via recruitment of an HDAC3 corepressor complex in mice
- 2012
-
In: Molecular endocrinology (Baltimore, Md.). - : The Endocrine Society. - 1944-9917 .- 0888-8809. ; 26:12, s. 1980-1990
-
Journal article (peer-reviewed)abstract
- The liver plays a pivotal role in the physiological adaptation to fasting and a better understanding of the metabolic adaptive responses may give hints on new therapeutic strategies to control the metabolic diseases. The liver X receptors (LXRs) are well-established regulators of lipid and glucose metabolism. More recently fibroblast growth factor 21 (FGF21) has emerged as an important regulator of energy homeostasis. We hypothesized that the LXR transcription factors could influence Fgf21 expression, which is induced in response to fasting. Wild-type, LXRα−/−, and LXRβ−/− mice were treated for 3 d with vehicle or the LXR agonist GW3965 and fasted for 12 h prior to the killing of the animals. Interestingly, serum FGF21 levels were induced after fasting, but this increase was blunted when the mice were treated with GW3965 independently of genotypes. Compared with wild-type mice, GW3965-treated LXRα−/− and LXRβ−/− mice showed improved insulin sensitivity and enhanced ketogenic response at fasting. Of note is that during fasting, GW3965 treatment tended to reduce liver triglycerides as opposed to the effect of the agonist in the fed state. The LXR-dependent repression of Fgf21 seems to be mainly mediated by the recruitment of LXRβ onto the Fgf21 promoter upon GW3965 treatment. This repression by LXRβ occurs through the recruitment and stabilization of the repressor complex composed of retinoid-related orphan receptor-α/Rev-Erbα/histone deacetylase 3 onto the Fgf21 promoter. Our data clearly demonstrate that there is a cross talk between the LXR and FGF21 signaling pathways in the adaptive response to fasting.
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| 38. |
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| 39. |
- Benavent, N., et al.
(author)
-
Substantial contribution of iodine to Arctic ozone destruction
- 2022
-
In: Nature Geoscience. - : Springer Science and Business Media LLC. - 1752-0894 .- 1752-0908. ; 15, s. 770-773
-
Journal article (peer-reviewed)abstract
- Unlike bromine, the effect of iodine chemistry on the Arctic surface ozone budget is poorly constrained. We present ship-based measurements of halogen oxides in the high Arctic boundary layer from the sunlit period of March to October 2020 and show that iodine enhances springtime tropospheric ozone depletion. We find that chemical reactions between iodine and ozone are the second highest contributor to ozone loss over the study period, after ozone photolysis-initiated loss and ahead of bromine.
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| 40. |
- Dumoulin, Mireille, et al.
(author)
-
A camelid antibody fragment inhibits the formation of amyloid fibrils by human lysozyme.
- 2003
-
In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 424:6950, s. 783-8
-
Journal article (peer-reviewed)abstract
- Amyloid diseases are characterized by an aberrant assembly of a specific protein or protein fragment into fibrils and plaques that are deposited in various organs and tissues, often with serious pathological consequences. Non-neuropathic systemic amyloidosis is associated with single point mutations in the gene coding for human lysozyme. Here we report that a single-domain fragment of a camelid antibody raised against wild-type human lysozyme inhibits the in vitro aggregation of its amyloidogenic variant, D67H. Our structural studies reveal that the epitope includes neither the site of mutation nor most residues in the region of the protein structure that is destabilized by the mutation. Instead, the binding of the antibody fragment achieves its effect by restoring the structural cooperativity characteristic of the wild-type protein. This appears to occur at least in part through the transmission of long-range conformational effects to the interface between the two structural domains of the protein. Thus, reducing the ability of an amyloidogenic protein to form partly unfolded species can be an effective method of preventing its aggregation, suggesting approaches to the rational design of therapeutic agents directed against protein deposition diseases.
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| 41. |
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| 42. |
- Freissinet, C., et al.
(author)
-
Organic molecules in the Sheepbed Mudstone, Gale Crater, Mars
- 2015
-
In: Journal of Geophysical Research - Planets. - 2169-9097 .- 2169-9100. ; 120:3, s. 495-514
-
Journal article (peer-reviewed)abstract
- The Sample Analysis at Mars (SAM) instrument [Mahaffy et al., 2012] onboard the Mars Science Laboratory (MSL) Curiosity rover is designed to conduct inorganic and organic chemical analyses of the atmosphere and the surface regolith and rocks to help evaluate the past and present habitability potential of Mars at Gale Crater [Grotzinger et al., 2012]. Central to this task is the development of an inventory of any organic molecules present to elucidate processes associated with their origin, diagenesis, concentration and long-term preservation. This will guide the future search for biosignatures [Summons et al., 2011]. Here we report the definitive identification of chlorobenzene (150–300 parts per billion by weight (ppbw)) and C2 to C4 dichloroalkanes (up to 70 ppbw) with the SAM gas chromatograph mass spectrometer (GCMS), and detection of chlorobenzene in the direct evolved gas analysis (EGA) mode, in multiple portions of the fines from the Cumberland drill hole in the Sheepbed mudstone at Yellowknife Bay. When combined with GCMS and EGA data from multiple scooped and drilled samples, blank runs and supporting laboratory analog studies, the elevated levels of chlorobenzene and the dichloroalkanes cannot be solely explained by instrument background sources known to be present in SAM. We conclude that these chlorinated hydrocarbons are the reaction products of martian chlorine and organic carbon derived from martian sources (e.g. igneous, hydrothermal, atmospheric, or biological) or exogenous sources such as meteorites, comets or interplanetary dust particles.
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| 43. |
- Hietala, H., et al.
(author)
-
In Situ Observations of a Magnetosheath High-Speed Jet Triggering Magnetopause Reconnection
- 2018
-
In: Geophysical Research Letters. - : American Geophysical Union (AGU). - 0094-8276 .- 1944-8007. ; 45:4, s. 1732-1740
-
Journal article (peer-reviewed)abstract
- Magnetosheath high-speed jets-localized dynamic pressure enhancements typically of similar to 1 Earth radius in size-impact the dayside magnetopause several times per hour. Here we present the first in situ measurements suggesting that such an impact triggered magnetopause reconnection. We use observations from the five Time History of Events and Macroscale Interactions during Substorms spacecraft in a string-of-pearls configuration on 7 August 2007. The spacecraft recorded magnetopause in-and-out motion during an impact of a magnetosheath jet (V-N similar to -300km/s along the magnetopause normal direction). There was no evidence for reconnection for the preimpact crossing, yet three probes observed reconnection after the impact. We infer that the jet impact compressed the originally thick (60-70 d(i)), high magnetic shear (140-160 degrees magnetopause until it was thin enough for reconnection to occur. Magnetosheath high-speed jets could therefore act as a driver for bursty dayside reconnection.
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| 44. |
- Korach-Andre, M, et al.
(author)
-
Liver X receptors regulate de novo lipogenesis in a tissue-specific manner in C57BL/6 female mice
- 2011
-
In: American journal of physiology. Endocrinology and metabolism. - : American Physiological Society. - 1522-1555 .- 0193-1849. ; 301:1, s. E210-E222
-
Journal article (peer-reviewed)abstract
- The liver X receptors (LXRs) play a key role in cholesterol and bile acid metabolism but are also important regulators of glucose metabolism. Recently, LXRs have been proposed as a glucose sensor affecting LXR-dependent gene expression. We challenged wild-type (WT) and LXRαβ−/−mice with a normal diet (ND) or a high-carbohydrate diet (HCD). Magnetic resonance imaging showed different fat distribution between WT and LXRαβ−/−mice. Surprisingly, gonadal (GL) adipocyte volume decreased on HCD compared with ND in WT mice, whereas it slightly increased in LXRαβ−/−mice. Interestingly, insulin-stimulated lipogenesis of isolated GL fat cells was reduced on HCD compared with ND in LXRαβ−/−mice, whereas no changes were observed in WT mice. Net de novo lipogenesis (DNL) calculated from V̇o2and V̇co2was significantly higher in LXRαβ−/−than in WT mice on HCD. Histology of HCD-fed livers showed hepatic steatosis in WT mice but not in LXRαβ−/−mice. Glucose tolerance was not different between groups, but insulin sensitivity was decreased by the HCD in WT but not in LXRαβ−/−mice. Finally, gene expression analysis of adipose tissue showed induced expression of genes involved in DNL in LXRαβ−/−mice compared with WT animals as opposed to the liver, where expression of DNL genes was repressed in LXRαβ−/−mice. We thus conclude that absence of LXRs stimulates DNL in adipose tissue, but suppresses DNL in the liver, demonstrating opposite roles of LXR in DNL regulation in these two tissues. These results show tissue-specific regulation of LXR activity, a crucial finding for drug development.
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| 45. |
- Leshin, L.A., et al.
(author)
-
Volatile, Isotope, and Organic Analysis of Martian Fines with the Mars Curiosity Rover
- 2013
-
In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 341:6153
-
Journal article (peer-reviewed)abstract
- Samples from the Rocknest aeolian deposit were heated to ~835°C under helium flow and evolved gases analyzed by Curiosity’s Sample Analysis at Mars instrument suite. H2O, SO2, CO2, and O2 were the major gases released. Water abundance (1.5 to 3 weight percent) and release temperature suggest that H2O is bound within an amorphous component of the sample. Decomposition of fine-grained Fe or Mg carbonate is the likely source of much of the evolved CO2. Evolved O2 is coincident with the release of Cl, suggesting that oxygen is produced from thermal decomposition of an oxychloride compound. Elevated δD values are consistent with recent atmospheric exchange. Carbon isotopes indicate multiple carbon sources in the fines. Several simple organic compounds were detected, but they are not definitively martian in origin.
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| 46. |
- Pavlova, E. V., et al.
(author)
-
B cell lymphoma and myeloma in murine Gaucher's disease
- 2013
-
In: Journal of Pathology. - : Wiley. - 0022-3417. ; 231:1, s. 88-97
-
Journal article (peer-reviewed)abstract
- Multiple myeloma and B cell lymphoma are leading causes of death in Gaucher's disease but the nature of the stimulus driving the often noted clonal expansion of immunoglobulin-secreting B cells and cognate lymphoid malignancy is unknown. We investigated the long-term development of B cell malignancies in an authentic model of non-neuronopathic Gaucher's disease in mice: selective deficiency of -glucocerebrosidase in haematopoietic cells [Gba(tm1Karl/tm1Karl)Tg(Mx1-cre)1Cgn/0, with excision of exons 9-11 of the murine GBA1 gene, is induced by poly[I:C]. Mice with Gaucher's disease showed visceral storage of -glucosylceramide and greatly elevated plasma -glucosylsphingosine [median 57.9 (range 19.8-159) nm;n = 39] compared with control mice from the same strain [median 0.56 (range 0.04-1.38) nm;n = 29] (p < 0.0001). Sporadic fatal B cell lymphomas developed in 11 of 21 GD mice (6-24 months) but only two of eight control animals developed tumours by age 24 months. Unexpectedly, most mice with overt lymphoma had absent or few Gaucher cells but local inflammatory macrophages were present. Eleven of 39 of Gaucher mice developed monoclonal gammopathy, but in the control group only one animal of 25 had clonal immunoglobulin abnormalities. Seven of 10 of the B cell lymphomas were found to secrete a monoclonal paraprotein and the lymphomas stained intensely for pan-B cell markers; reactive T lymphocytes were also present in tumour tissue. In the Gaucher mouse strain, it was notable that, as in patients with this disease, CD138(+) plasma cells frequently surrounded splenic macrophages engorged with glycosphingolipid. Our strain of mice, with inducible deficiency of -glucocerebrosidase in haematopoietic cells and a high frequency of sporadic lethal B cell malignancies, faithfully recapitulates human Gaucher's disease: it serves as a tractable model to investigate the putative role of bioactive sphingolipids in the control of B cell proliferation and the pathogenesis of myelomatosisthe most prevalent human cancer associated with this disorder. Copyright (c) 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
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| 47. |
- Pavlova, Elena V., et al.
(author)
-
Inhibition of UDP-glucosylceramide synthase in mice prevents Gaucher disease-associated B-cell malignancy
- 2015
-
In: Journal of Pathology. - : Wiley. - 0022-3417. ; 235:1, s. 113-124
-
Journal article (peer-reviewed)abstract
- Clonal B-cell proliferation is a frequent manifestation of Gaucher disease-a sphingolipidosis associated with a high risk of multiple myeloma and non-Hodgkin lymphoma. Gaucher disease is caused by genetic deficiency of acid -glucosidase, the natural substrates of which (-d-glucosylceramide and -d-glucosylsphingosine) accumulate, principally in macrophages. Mice with inducible deficiency of -glucosidase [Gba(tm1Karl/tm1Karl)Tg(MX1-cre)1Cgn/0] serve as an authentic model of human Gaucher disease; we have recently reported clonal B-cell proliferation accompanied by monoclonal serum paraproteins and cognate tumours in these animals. To explore the relationship between B-cell malignancy and the biochemical defect, we treated Gaucher mice with eliglustat tartrate (GENZ 112638), a potent and selective inhibitor of the first committed step in glycosphingolipid biosynthesis. Twenty-two Gaucher mice received 300mg/kg of GENZ 112638 daily for 3-10 months from 6 weeks of age. Plasma concentrations of -d-glucosylceramide and the unacylated glycosphingolipid, -d-glucosylsphingosine, declined. After administration of GENZ 112638 to Gaucher mice for 3-10 months, serum paraproteins were not detected and there was a striking reduction in the malignant lymphoproliferation: neither lymphomas nor plasmacytomas were found in animals that had received the investigational agent. In contrast, 14 out of 60 Gaucher mice without GENZ 112638 treatment developed these tumours; monoclonal paraproteins were detected in plasma from 18 of the 44 age-matched mice with Gaucher disease that had not received GENZ 112638. Long-term inhibition of glycosphingolipid biosynthesis suppresses the development of spontaneous B-cell lymphoma and myeloma in Gaucher mice. Copyright (c) 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
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| 48. |
- Raghavan, Maanasa, et al.
(author)
-
Genomic evidence for the Pleistocene and recent population history of Native Americans
- 2015
-
In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 349:6250
-
Journal article (peer-reviewed)abstract
- Howand when the Americas were populated remains contentious. Using ancient and modern genome-wide data, we found that the ancestors of all present-day Native Americans, including Athabascans and Amerindians, entered the Americas as a single migration wave from Siberia no earlier than 23 thousand years ago (ka) and after no more than an 8000-year isolation period in Beringia. After their arrival to the Americas, ancestral Native Americans diversified into two basal genetic branches around 13 ka, one that is now dispersed across North and South America and the other restricted to North America. Subsequent gene flow resulted in some Native Americans sharing ancestry with present-day East Asians (including Siberians) and, more distantly, Australo-Melanesians. Putative "Paleoamerican" relict populations, including the historical Mexican Pericues and South American Fuego-Patagonians, are not directly related to modern Australo-Melanesians as suggested by the Paleoamerican Model.
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| 49. |
- Ricci, S., et al.
(author)
-
Altered Cytokine and BDNF Levels in Autism Spectrum Disorder
- 2013
-
In: Neurotoxicity research. - : Springer. - 1029-8428 .- 1476-3524. ; 24:4, s. 491-501
-
Journal article (peer-reviewed)abstract
- The contribution of neuroimmune functioning and brain-derived neurotrophic factor (BDNF) to functional dysregulation in autism spectrum disorder was assessed in 29 patients under treatment in two specialized centers of Basilicata (Chiaromonte and Matera), Southern Italy, through analysis of serum levels of cytokines and BDNF. Elevated levels of the pro-inflammatory cytokine, including interleukin-1, interleukin-6, interleukin-12, interleukin-23, tumor necrosis factor-alpha and BDNF were observed, regardless of age and gender. Comparisons were made with age-and gender-related healthy controls. The present findings reinforce current notions regarding immunoexcitotoxic mechanisms contributing to the pathophysiology of autistic disorder.
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| 50. |
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