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1.
Phys Rev Lett ; 132(12): 126502, 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38579201

RESUMO

LiCu_{3}O_{3} is an antiferromagnetic mixed valence cuprate where trilayers of edge-sharing Cu(II)O (3d^{9}) are sandwiched in between planes of Cu(I) (3d^{10}) ions, with Li stochastically substituting Cu(II). Angle-resolved photoemission spectroscopy (ARPES) and density functional theory reveal two insulating electronic subsystems that are segregated in spite of sharing common oxygen atoms: a Cu d_{z^{2}}/O p_{z} derived valence band (VB) dispersing on the Cu(I) plane, and a Cu 3d_{x^{2}-y^{2}}/O 2p_{x,y} derived Zhang-Rice singlet (ZRS) band dispersing on the Cu(II)O planes. First-principle analysis shows the Li substitution to stabilize the insulating ground state, but only if antiferromagnetic correlations are present. Li further induces substitutional disorder and a 2D electron glass behavior in charge transport, reflected in a large 530 meV Coulomb gap and a linear suppression of VB spectral weight at E_{F} that is observed by ARPES. Surprisingly, the disorder leaves the Cu(II)-derived ZRS largely unaffected. This indicates a local segregation of Li and Cu atoms onto the two separate corner-sharing Cu(II)O_{2} sub-lattices of the edge-sharing Cu(II)O planes, and highlights the ubiquitous resilience of the entangled two hole ZRS entity against impurity scattering.

2.
Proc Natl Acad Sci U S A ; 118(12)2021 03 23.
Artigo em Inglês | MEDLINE | ID: mdl-33731475

RESUMO

Geographic turnover in community composition is created and maintained by eco-evolutionary forces that limit the ranges of species. One such force may be antagonistic interactions among hosts and parasites, but its general importance is unknown. Understanding the processes that underpin turnover requires distinguishing the contributions of key abiotic and biotic drivers over a range of spatial and temporal scales. Here, we address these challenges using flexible, nonlinear models to identify the factors that underlie richness (alpha diversity) and turnover (beta diversity) patterns of interacting host and parasite communities in a global biodiversity hot spot. We sampled 18 communities in the Peruvian Andes, encompassing ∼1,350 bird species and ∼400 hemosporidian parasite lineages, and spanning broad ranges of elevation, climate, primary productivity, and species richness. Turnover in both parasite and host communities was most strongly predicted by variation in precipitation, but secondary predictors differed between parasites and hosts, and between contemporary and phylogenetic timescales. Host communities shaped parasite diversity patterns, but there was little evidence for reciprocal effects. The results for parasite communities contradicted the prevailing view that biotic interactions filter communities at local scales while environmental filtering and dispersal barriers shape regional communities. Rather, subtle differences in precipitation had strong, fine-scale effects on parasite turnover while host-community effects only manifested at broad scales. We used these models to map bird and parasite turnover onto the ecological gradients of the Andean landscape, illustrating beta-diversity hot spots and their mechanistic underpinnings.


Assuntos
Biodiversidade , Ecossistema , Hemípteros/parasitologia , Interações Hospedeiro-Parasita , Animais , Hemípteros/classificação , Hemípteros/genética , Dinâmica não Linear , Filogenia
3.
Am Nat ; 201(5): 741-754, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37130238

RESUMO

AbstractThe extent to which species ranges reflect intrinsic physiological tolerances is a major question in evolutionary ecology. To date, consensus has been hindered by the limited tractability of experimental approaches across most of the tree of life. Here, we apply a macrophysiological approach to understand how hematological traits related to oxygen transport shape elevational ranges in a tropical biodiversity hot spot. Along Andean elevational gradients, we measured traits that affect blood oxygen-carrying capacity-total and cellular hemoglobin concentration and hematocrit, the volume percentage of red blood cells-for 2,355 individuals of 136 bird species. We used these data to evaluate the influence of hematological traits on elevational ranges. First, we asked whether the sensitivity of hematological traits to changes in elevation is predictive of elevational range breadth. Second, we asked whether variance in hematological traits changed as a function of distance to the nearest elevational range limit. We found that birds showing greater hematological sensitivity had broader elevational ranges, consistent with the idea that a greater acclimatization capacity facilitates elevational range expansion. We further found reduced variation in hematological traits in birds sampled near their elevational range limits and at high absolute elevations, patterns consistent with intensified natural selection, reduced effective population size, or compensatory changes in other cardiorespiratory traits. Our findings suggest that constraints on hematological sensitivity and local genetic adaptation to oxygen availability promote the evolution of the narrow elevational ranges that underpin tropical montane biodiversity.


Assuntos
Biodiversidade , Aves , Humanos , Animais , Aves/fisiologia , Fenótipo , Oxigênio , Ecologia , Altitude
4.
Cancer Immunol Immunother ; 72(11): 3475-3489, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37606856

RESUMO

BACKGROUND: Immune checkpoint inhibitors (ICI) substantially improve outcome for patients with cancer. However, the majority of patients develops immune-related adverse events (irAEs), which can be persistent and significantly reduce quality of life. Neurological irAEs occur in 1-5% of patients and can induce severe, permanent sequelae or even be fatal. In order to improve the diagnosis and treatment of neurological irAEs and to better understand their pathogenesis, we assessed whether previous neurotropic infections are associated with neurological irAEs. METHODS: Neurotropic infections that might predispose to ICI-induced neurological irAEs were analyzed in 61 melanoma patients from 3 countries, the Netherlands, Australia and Germany, including 24 patients with neurotoxicity and 37 control patients. In total, 14 viral, 6 bacterial, and 1 protozoal infections previously reported to trigger neurological pathologies were assessed using routine serology testing. The Dutch and Australian cohorts (NL) included pre-treatment plasma samples of patients treated with neoadjuvant ICI therapy (OpACIN-neo and PRADO trials; NCT02977052). In the Dutch/Australian cohort a total of 11 patients with neurological irAEs were compared to 27 control patients (patients without neurological irAEs). The German cohort (LMU) consisted of serum samples of 13 patients with neurological irAE and 10 control patients without any documented irAE under ICI therapy. RESULTS: The association of neurological irAEs with 21 possible preceding infections was assessed by measuring specific antibodies against investigated agents. The seroprevalence of all the tested viral (cytomegalovirus, Epstein-Barr-Virus, varicella-zoster virus, measles, rubella, influenza A and B, human herpes virus 6 and 7, herpes simplex virus 1 and 2, parvovirus B19, hepatitis A and E and human T-lymphotropic virus type 1 and 2), bacterial (Borrelia burgdorferi sensu lato, Campylobacter jejuni, Mycoplasma pneumoniae, Coxiella burnetti, Helicobacter pylori, Yersinia enterocolitica and Y. pseudotuberculosis) and protozoal (Toxoplasma gondii) infections was similar for patients who developed neurological irAEs as compared to control patients. Thus, the analysis provided no evidence for an association of described agents tested for seroprevalence with ICI induced neurotoxicity. CONCLUSION: Previous viral, bacterial and protozoal neurotropic infections appear not to be associated with the development of neurological irAEs in melanoma patients who underwent therapy with ICI across 3 countries. Further efforts are needed to unravel the factors underlying neurological irAEs in order to identify risk factors for these toxicities, especially with the increasing use of ICI in earlier stage disease.


Assuntos
Antineoplásicos Imunológicos , Melanoma , Humanos , Inibidores de Checkpoint Imunológico/uso terapêutico , Estudos Soroepidemiológicos , Qualidade de Vida , Antineoplásicos Imunológicos/uso terapêutico , Austrália/epidemiologia , Melanoma/tratamento farmacológico , Estudos Retrospectivos
5.
Proc Natl Acad Sci U S A ; 117(45): 28183-28190, 2020 11 10.
Artigo em Inglês | MEDLINE | ID: mdl-33109722

RESUMO

The idea that tropical forest and savanna are alternative states is crucial to how we manage these biomes and predict their future under global change. Large-scale empirical evidence for alternative stable states is limited, however, and comes mostly from the multimodal distribution of structural aspects of vegetation. These approaches have been criticized, as structure alone cannot separate out wetter savannas from drier forests for example, and there are also technical challenges to mapping vegetation structure in unbiased ways. Here, we develop an alternative approach to delimit the climatic envelope of the two biomes in Africa using tree species lists gathered for a large number of forest and savanna sites distributed across the continent. Our analyses confirm extensive climatic overlap of forest and savanna, supporting the alternative stable states hypothesis for Africa, and this result is corroborated by paleoecological evidence. Further, we find the two biomes to have highly divergent tree species compositions and to represent alternative compositional states. This allowed us to classify tree species as forest vs. savanna specialists, with some generalist species that span both biomes. In conjunction with georeferenced herbarium records, we mapped the forest and savanna distributions across Africa and quantified their environmental limits, which are primarily related to precipitation and seasonality, with a secondary contribution of fire. These results are important for the ongoing efforts to restore African ecosystems, which depend on accurate biome maps to set appropriate targets for the restored states but also provide empirical evidence for broad-scale bistability.


Assuntos
Clima , Ecossistema , Florestas , Pradaria , África , Incêndios , Chuva , Estações do Ano , Árvores , Clima Tropical
6.
Encephale ; 48(2): 125-131, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34024498

RESUMO

OBJECTIVES: We assessed the prevalence of severe cardiovascular (CV) disease requiring hospitalization among patients with schizophrenia in France. METHOD: We included patients hospitalized with schizophrenia or psychotic disorder during 2015, in five French psychiatric hospitals. Patients with CV disease were defined as those with a correspondent ICD-10 code during a hospital stay in any general hospital, five years before or three years after the psychiatric hospitalization. CV disease included myocardial infarction (MI), stroke, heart failure (HF), coronary artery disease (CAD) or peripheral artery disease. Risk factors such as hypertension, obesity and diabetes were recorded. RESULTS: In total, 4424 patients with schizophrenia were included. Overall, 203 (4,6%) patients were diagnosed with CV disease, 93 (2.1%) with CAD, 86 (1.9%) with HF and 49 (1.1%) with stroke. The prevalence of hypertension, obesity and diabetes was 11.3%, 9.7% and 7.8%. The median (interquartile range) age of patients with MI and diabetes was 57 (49-70) and 56 (48-66) years. CONCLUSION: Patients with schizophrenia develop severe CV disease requiring hospitalization at an early age. These severe events are associated with a high prevalence of risk factors. Early screening and treatment of CV disease and risk factors is important to improve life expectancy and quality of life of these patients.


Assuntos
Doenças Cardiovasculares , Insuficiência Cardíaca , Hipertensão , Infarto do Miocárdio , Esquizofrenia , Acidente Vascular Cerebral , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/epidemiologia , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/prevenção & controle , Humanos , Hipertensão/complicações , Hipertensão/epidemiologia , Infarto do Miocárdio/complicações , Infarto do Miocárdio/epidemiologia , Obesidade/complicações , Obesidade/epidemiologia , Prevalência , Qualidade de Vida , Fatores de Risco , Esquizofrenia/complicações , Esquizofrenia/epidemiologia
7.
Phys Rev Lett ; 126(13): 132502, 2021 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-33861122

RESUMO

Isotopic distributions of fragments from fission of the neutron-deficient ^{178}Hg nuclide are reported. This experimental observable is obtained for the first time in the region around lead using an innovative approach based on inverse kinematics and the coincidence between the large acceptance magnetic spectrometer VAMOS++ and a new detection arm close to the target. The average fragment N/Z ratio and prompt neutron M_{n} multiplicity are derived and compared with current knowledge from actinide fission. A striking consistency emerges, revealing the unexpected dominant role of the proton subsystem with atomic number between the Z=28 and 50 magic numbers. The origin of nuclear charge polarization in fission and fragment deformation at scission are discussed.

8.
Phys Rev Lett ; 125(7): 077201, 2020 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-32857543

RESUMO

We achieve current-induced switching in collinear insulating antiferromagnetic CoO/Pt, with fourfold in-plane magnetic anisotropy. This is measured electrically by spin Hall magnetoresistance and confirmed by the magnetic field-induced spin-flop transition of the CoO layer. By applying current pulses and magnetic fields, we quantify the efficiency of the acting current-induced torques and estimate a current-field equivalence ratio of 4×10^{-11} T A^{-1} m^{2}. The Néel vector final state (n⊥j) is in line with a thermomagnetoelastic switching mechanism for a negative magnetoelastic constant of the CoO.

9.
Biol Lett ; 16(9): 20200428, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32898456

RESUMO

Torpor is thought to be particularly important for small endotherms occupying cold environments and with limited fat reserves to fuel metabolism, yet among birds deep torpor is both rare and variable in extent. We investigated torpor in hummingbirds at approximately 3800 m.a.s.l. in the tropical Andes by monitoring body temperature (Tb) in 26 individuals of six species held captive overnight and experiencing natural air temperature (Ta) patterns. All species used pronounced torpor, with one Metallura phoebe reaching a minimum Tb of 3.26°C, the lowest yet reported for any bird or non-hibernating mammal. The extent and duration of torpor varied among species, with overnight body mass (Mb) loss negatively correlated with both minimum Tb and bout duration. We found a significant phylogenetic signal for minimum Tb and overnight Mb loss, consistent with evolutionarily conserved thermoregulatory traits. Our findings suggest deep torpor is routine for high Andean hummingbirds, but evolved species differences affect its depth.


Assuntos
Torpor , Animais , Aves , Temperatura Corporal , Regulação da Temperatura Corporal , Humanos , Mamíferos , Filogenia
10.
Herz ; 45(3): 293-298, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-30054712

RESUMO

BACKGROUND: Chest pain is a major reason for admission to an internal emergency department, and smoking is a well-known risk factor for coronary artery disease (CAD) and acute coronary syndrome (ACS). The aim of this analysis is to illustrate the differences between smokers and nonsmokers presenting to German chest pain units (CPU) in regard to patient characteristics, CAD manifestation, treatment strategy, and prognosis. METHODS: From December 2008 to March 2014, 13,902 patients who had a complete 3­month follow-up were enrolled in the German CPU registry. The analysis comprised 5796 patients with ACS and documented smoking status. RESULTS: Of all the patients in the CPU registry, 35.2% were smokers. Compared with nonsmokers, they were 13.5 years younger (58.2 vs. 71.7 years, p < 0.001), predominantly men (77.1% vs. 65.2%, p < 0.001), and were more frequently diagnosed with single-vessel disease (32.1% vs. 25.2%) as well as ST-elevation myocardial infarction (STEMI; 23.8% vs. 15.5%, p < 0.001). Although the Global Registry of Acute Coronary Events (GRACE) Risk Score for hospital mortality was lower in the group of smokers (106.1 vs. 123.3, p < 0.001), we did not observe any differences in CPU death (0.4% vs. 0.4%, p = 0.69) and CPU major adverse cardiac event (MACE) rates (3.8% vs 2.9%, p = 0.073) between the groups. In the 3­month follow-up, we documented higher mortality rates in the nonsmoker group (1.9% vs. 2.9%, p = 0.035) in correlation with the GRACE Risk Score (80.3 vs. 105.2, p < 0.001). MACE rates were similar during the follow-up (3.1% vs. 4.1%, p = 0.065). CONCLUSION: Observations from the German CPU registry demonstrate that smoking is a strong predictor of acute CAD manifestation early in life, especially STEMI. In spite of a lower GRACE Risk Score and fewer comorbidities, smokers had a rate of hospital mortality similar to the older group of nonsmokers.


Assuntos
Síndrome Coronariana Aguda , Dor no Peito , não Fumantes , Sistema de Registros , Adulto , Dor no Peito/epidemiologia , Feminino , Alemanha/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Fumantes
11.
Clin Oral Investig ; 24(8): 2653-2662, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31713746

RESUMO

OBJECTIVES: This prospective, comparative, clinical study analyzed the postoperative bleeding risk of patients on anticoagulation therapy (AT) who were undergoing tooth extractions and osteotomies. MATERIALS AND METHODS: Patients with the following ATs were included (test groups): (1.) platelet aggregation inhibitors (PAIs), (2.) vitamin K inhibitors, (3.) low molecular weight heparin (LMWH), and (4.) direct oral anticoagulants (DOACs). Patients in the control group were not on any AT (non-AT group). Patients were subdivided into the following treatment groups: (1.) single tooth extraction, (2.) serial extraction (≥ 2 adjacent teeth), and (3.) tooth osteotomy. Pre-, intra-, and postoperative data concerning the treatment, extent of the surgery, and bleeding were recorded and statistically evaluated. RESULTS: There were 15 postoperative bleeding events in 838 patients (1.7%): four (0.7%) in the non-AT group (n = 603 patients) and 11 (4.7%) in the AT group (n = 235 patients). The surgical procedure had no statistically significant effect on postoperative bleeding frequencies. Patients taking vitamin K inhibitors had a significantly higher risk of postoperative bleeding compared with patients without AT (p < 0.00001). Four patients were hospitalized due to the severity of the bleeding (vitamin K inhibitor group). Postoperative bleeding events were all controlled with local hemostatic measures. CONCLUSIONS: The postoperative bleeding risk after tooth extractions and osteotomies in patients continuing AT is low, and bleeding can be controlled with local hemostatic measures. CLINICAL RELEVANCE: AT should be continued in patients undergoing tooth removal procedures under the provision that local hemostatic measures are applied.


Assuntos
Hemorragia Pós-Operatória/prevenção & controle , Anticoagulantes , Heparina de Baixo Peso Molecular , Humanos , Estudos Prospectivos , Extração Dentária , Vitamina K
12.
Phys Rev Lett ; 123(9): 092503, 2019 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-31524478

RESUMO

A direct and complete measurement of isotopic fission-fragment yields of ^{239}U has been performed for the first time. The ^{239}U fissioning system was produced with an average excitation energy of 8.3 MeV in one-neutron transfer reactions between a ^{238}U beam and a ^{9}Be target at Coulomb barrier energies. The fission fragments were detected and isotopically identified using the VAMOS++ spectrometer at the GANIL facility. The measurement allows us to directly evaluate the fission models at excitation energies of fast neutrons, which are relevant for next-generation nuclear reactors. The present data, in agreement with model calculations, do not support the recently reported anomaly in the fission-fragment yields of ^{239}U, and they confirm the persistence of spherical shell effects in the Sn region at excitation energies exceeding the fission barrier by a few mega-electron volts.

13.
Proc Natl Acad Sci U S A ; 113(29): 8025-32, 2016 07 19.
Artigo em Inglês | MEDLINE | ID: mdl-27432956

RESUMO

Phylogeography, and its extensions into comparative phylogeography, have their roots in the layering of gene trees across geography, a paradigm that was greatly facilitated by the nonrecombining, fast evolution provided by animal mtDNA. As phylogeography moves into the era of next-generation sequencing, the specter of reticulation at several levels-within loci and genomes in the form of recombination and across populations and species in the form of introgression-has raised its head with a prominence even greater than glimpsed during the nuclear gene PCR era. Here we explore the theme of reticulation in comparative phylogeography, speciation analysis, and phylogenomics, and ask how the centrality of gene trees has fared in the next-generation era. To frame these issues, we first provide a snapshot of multilocus phylogeographic studies across the Carpentarian Barrier, a prominent biogeographic barrier dividing faunas spanning the monsoon tropics in northern Australia. We find that divergence across this barrier is evident in most species, but is heterogeneous in time and demographic history, often reflecting the taxonomic distinctness of lineages spanning it. We then discuss a variety of forces generating reticulate patterns in phylogeography, including introgression, contact zones, and the potential selection-driven outliers on next-generation molecular markers. We emphasize the continued need for demographic models incorporating reticulation at the level of genomes and populations, and conclude that gene trees, whether explicit or implicit, should continue to play a role in the future of phylogeography.


Assuntos
Filogenia , Animais , Austrália , Variação Genética , Filogeografia , Recombinação Genética
14.
Anaesthesist ; 68(1): 39-43, 2019 01.
Artigo em Alemão | MEDLINE | ID: mdl-30570677

RESUMO

These two case reports describe the use of transthoracic echocardiography in cardiac surgery patients during postoperative intensive care, when a pericardial hematoma developed. A focused echocardiographic examination was performed, which in both cases led to the correct diagnosis and revealed the cause for hemodynamic instability. Following additional computed tomography (CT) scans, cardiac surgery was performed on one patient, while in the other, bedside sonography was used for controlled pleural puncture and drainage of the pericardial hematoma. The case reports demonstrate that intrathoracic bleeding after cardiac surgery may develop with a latency of days to weeks, which can become hemodynamically relevant and require an intervention. Bedside point of care echocardiography opens the way for securing the diagnosis by means of CT or magnetic resonance imaging (MRI) if the circulatory state of the patient allows this prior to hematoma drainage or evacuation.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Cuidados Críticos/métodos , Ecocardiografia/métodos , Hematoma/etiologia , Complicações Pós-Operatórias , Drenagem , Tomografia Computadorizada por Raios X
15.
J Intern Med ; 284(1): 78-91, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29498764

RESUMO

BACKGROUND: Acute intermittent porphyria (AIP) is an inherited disorder of haem metabolism characterized by life-threatening acute neurovisceral attacks due to the induction of hepatic δ-aminolevulinic acid synthase 1 (ALAS1) associated with hydroxymethylbilane synthase (HMBS) deficiency. So far, the treatment of choice is hemin which represses ALAS1. The main issue in the medical care of AIP patients is the occurrence of debilitating recurrent attacks. OBJECTIVE: The aim of this study was to determine whether chronic hemin administration contributes to the recurrence of acute attacks. METHODS: A follow-up study was conducted between 1974 and 2015 and included 602 French AIP patients, of whom 46 had recurrent AIP. Moreover, we studied the hepatic transcriptome, serum proteome, liver macrophage polarization and oxidative and inflammatory profiles of Hmbs-/- mice chronically treated by hemin and extended the investigations to five explanted livers from recurrent AIP patients. RESULTS: The introduction of hemin into the pharmacopeia has coincided with a 4.4-fold increase in the prevalence of chronic patients. Moreover, we showed that both in animal model and in human liver, frequent hemin infusions generate a chronic inflammatory hepatic disease which induces HO1 remotely to hemin treatment and maintains a high ALAS1 level responsible for recurrence. CONCLUSION: Altogether, this study has important impacts on AIP care underlying that hemin needs to be restricted to severe neurovisceral crisis and suggests that alternative treatment targeting the liver such as ALAS1 and HO1 inhibitors, and anti-inflammatory therapies should be considered in patients with recurrent AIP.


Assuntos
5-Aminolevulinato Sintetase/sangue , Hidroximetilbilano Sintase/fisiologia , Fígado/fisiopatologia , Porfiria Aguda Intermitente/fisiopatologia , Doença Aguda , Animais , Estudos de Coortes , Estudos Transversais , Feminino , Seguimentos , Heme Oxigenase-1/metabolismo , Hemina/administração & dosagem , Hemina/efeitos adversos , Humanos , Fígado/efeitos dos fármacos , Proteínas de Membrana/metabolismo , Camundongos Endogâmicos C57BL , Estresse Oxidativo/efeitos dos fármacos , Porfiria Aguda Intermitente/diagnóstico , Porfiria Aguda Intermitente/epidemiologia , Porfiria Aguda Intermitente/terapia , Recidiva , Fatores de Risco
16.
Int J Obes (Lond) ; 42(4): 765-774, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29211707

RESUMO

OBJECTIVE: In humans, the ontogeny of obesity throughout the life course and the genetics underlying it has been historically difficult to study. We compared, in a non-human primate model, the lifelong growth trajectories of obese and non-obese adults to assess the heritability of and map potential genomic regions implicated in growth and obesity. STUDY POPULATION: A total of 905 African green monkeys, or vervets (Chlorocebus aethiops sabaeus) (472 females, 433 males) from a pedigreed captive colony. METHODS: We measured fasted body weight (BW), crown-to-rump length (CRL), body-mass index (BMI) and waist circumference (WC) from 2000 to 2015. We used a longitudinal clustering algorithm to detect obesogenic growth, and logistic growth curves implemented in nonlinear mixed effects models to estimate three growth parameters. We used maximum likelihood variance decomposition methods to estimate the genetic contributions to obesity-related traits and growth parameters, including a test for the effects of a calorie-restricted dietary intervention. We used multipoint linkage analysis to map implicated genomic regions. RESULTS: All measurements were significantly influenced by sex, and with the exception of WC, also influenced by maternal and post-natal diet. Chronic obesity outcomes were significantly associated with a pattern of extended growth duration with slow growth rates for BW. After accounting for environmental influences, all measurements were found to have a significant genetic component to variability. Linkage analysis revealed several regions suggested to be linked to obesity-related traits that are also implicated in human obesity and metabolic disorders. CONCLUSIONS: As in humans, growth patterns in vervets have a significant impact on adult obesity and are largely under genetic control with some evidence for maternal and dietary programming. These results largely mirror findings from human research, but reflect shorter developmental periods, suggesting that the vervet offers a strong genetic model for elucidating the ontogeny of human obesity.


Assuntos
Peso Corporal/fisiologia , Chlorocebus aethiops/crescimento & desenvolvimento , Chlorocebus aethiops/fisiologia , Dieta , Obesidade/fisiopatologia , Animais , Modelos Animais de Doenças , Feminino , Masculino , Circunferência da Cintura/fisiologia
17.
Osteoarthritis Cartilage ; 25(7): 1132-1142, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28323137

RESUMO

OBJECTIVE: The role of Snorc, a novel cartilage specific transmembrane proteoglycan, was studied during skeletal development using two Snorc knockout mouse models. Hypothesizing that Snorc, like the other transmembrane proteoglycans, may be a coreceptor, we also studied its interaction with growth factors. METHODS: Skeletal development was studied in wild type (WT) and Snorc knockout mice during postnatal development by whole mount staining, X-ray imaging, histomorphometry, immunohistochemistry and qRT-PCR. Snorc promoter activity was studied by applying the LacZ reporter expressed by the targeting construct. Slot blot binding and cell proliferation assays were used to study the interaction of Snorc with several growth factors. RESULTS: Snorc expression was localized in the knee epiphyses especially to the prehypertrophic chondrocytes delineating the cartilage canals and secondary ossification center (SOC). Snorc was demonstrated to have a glycosaminoglycan independent affinity to FGF2 and it inhibited FGF2 dependent cell growth of C3H101/2 cells. In Snorc deficient mice, SOCs in knee epiphyses were smaller, and growth plate (GP) maturation was disturbed, but total bone length was not affected. Central proliferative and hypertrophic zones were enlarged with higher extracellular matrix (ECM) volume and rounded chondrocyte morphology at postnatal days P10 and P22. Increased levels of Ihh and Col10a1, and reduced Mmp13 mRNA expression were observed at P10. CONCLUSIONS: These findings suggest a role of Snorc in regulation of chondrocyte maturation and postnatal endochondral ossification. The interaction identified between recombinant Snorc core protein and FGF2 suggest functions related to FGF signaling.


Assuntos
Condrócitos/fisiologia , Proteínas de Membrana/deficiência , Osteogênese/fisiologia , Proteoglicanas/deficiência , Joelho de Quadrúpedes/fisiologia , Animais , Ossos da Extremidade Inferior/crescimento & desenvolvimento , Proliferação de Células/fisiologia , Células Cultivadas , Condrogênese/fisiologia , Epífises/crescimento & desenvolvimento , Epífises/metabolismo , Epífises/fisiologia , Feminino , Fator 2 de Crescimento de Fibroblastos/fisiologia , Genótipo , Masculino , Proteínas de Membrana/metabolismo , Camundongos Knockout , Proteoglicanas/metabolismo , Proteoglicanas/fisiologia , RNA Mensageiro/metabolismo
18.
Phys Rev Lett ; 118(16): 162501, 2017 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-28474951

RESUMO

Prompt γ-ray spectroscopy of the neutron-rich ^{96}Kr, produced in transfer- and fusion-induced fission reactions, has been performed using the combination of the Advanced Gamma Tracking Array and the VAMOS++ spectrometer. A second excited state, assigned to J^{π}=4^{+}, is observed for the first time, and a previously reported level energy of the first 2^{+} excited state is confirmed. The measured energy ratio R_{4/2}=E(4^{+})/E(2^{+})=2.12(1) indicates that this nucleus does not show a well-developed collectivity contrary to that seen in heavier N=60 isotones. This new measurement highlights an abrupt transition of the degree of collectivity as a function of the proton number at Z=36, of similar amplitude to that observed at N=60 at higher Z values. A possible reason for this abrupt transition could be related to the insufficient proton excitations in the g_{9/2}, d_{5/2}, and s_{1/2} orbitals to generate strong quadrupole correlations or to the coexistence of competing different shapes. An unexpected continuous decrease of R_{4/2} as a function of the neutron number up to N=60 is also evidenced. This measurement establishes the Kr isotopic chain as the low-Z boundary of the island of deformation for N=60 isotones. A comparison with available theoretical predictions using different beyond mean-field approaches shows that these models fail to reproduce the abrupt transitions at N=60 and Z=36.

19.
Insect Mol Biol ; 25(5): 541-9, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27126627

RESUMO

Peptides and proteins have been largely neglected in the analysis of insect tarsal adhesives. After extraction of the protein fraction of the tarsal secretion of the desert locust, Schistocerca gregaria, and Madagascar hissing cockroach, Gromphadorhina portentosa, we combined Fourier transform infrared spectroscopy (FTIR), sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) and matrix-assisted laser desorption/ionization mass spectrometry (MALDI-TOF MS) analyses for protein mass detection. In both these insects, SDS-PAGE analysis revealed several protein bands ranging from 8-190 kDa in both the tarsal secretion and the tibia control sample. Two (S. gregaria) and one (G. portentosa) protein bands exclusively occurred in the tarsal secretion and can be considered to belong to peptides and proteins specific to this secretion. MALDI-TOF analyses revealed 83 different proteins/peptides of 1-7 kDa in S. gregaria, and 48 of 1-11 kDa in G. portentosa. 59 (S. gregaria) and 27 (G. portentosa) proteins exclusively occurred in the tarsal secretion. In G. portentosa, a characteristic series of signal peaks occurred in the range of c. 10-12 kDa, each peak being approximately 160 Da apart. Such a pattern is indicative of proteins modified by glycosylation. Our approach demonstrates that extensive sampling involving considerable time and manpower to sample the adhesive fluid directly from the tarsi opens up a perspective for extracting peptides and proteins in sufficient quantities. This makes them accessible to the field of proteomics and thus to elucidate their possible function in the adhesive process.


Assuntos
Baratas/química , Gafanhotos/química , Proteínas de Insetos/análise , Animais , Eletroforese em Gel de Poliacrilamida , Peptídeos/análise , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Espectroscopia de Infravermelho com Transformada de Fourier
20.
Clin Oral Implants Res ; 27(10): 1274-1282, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26592859

RESUMO

OBJECTIVES: This prospective clinical comparative study aimed to analyze the postoperative bleeding risk of patients continuing their anticoagulation therapy (AT) and undergoing implant surgery and bone grafting procedures. MATERIALS AND METHODS: The treatments ranged from the insertion of single or multiple dental implants over implant exposures to sinus floor augmentation and vertical and/or lateral bone grafting with autologous bone grafts. The patients of the test groups (AT groups) were treated with platelet aggregation inhibitors (PAIs), Vitamin-K inhibitors, Vitamin-K inhibitor withdrawal bridged with heparin (LMWH), or new/direct oral anticoagulants (NOACs/DOACs). Patients of the control group were non-anticoagulated (non-AT group). Surgical procedures were performed in the same manner in all groups. Pre, intra, and postoperative data concerning the treatment, extent of the surgery and bleedings was recorded and statistically evaluated. RESULTS: There were seven postoperative bleedings in 564 patients (1.2%), four in the AT groups (3.4%), and three in the non-AT group (0.6%). No thromboembolic complication occurred in the whole observation period. The invasiveness of the surgical procedure had no statistically significant effect on bleeding frequencies. Patients taking Vitamin-K inhibitors had a significantly higher risk of a postoperative bleeding compared to patients without any AT (P = 0.038). Two patients were hospitalized due to the severity of the bleeding as a precautionary measure (one in the non-AT and one in the PAI group). All bleedings were easily controllable with local hemostatic measures. There was no postoperative bleeding recorded for patients taking DOACs. CONCLUSIONS: Anticoagulation therapy should be continued in patients undergoing implant surgery and bone grafting procedures avoiding thromboembolic complications. Surgeons should always apply the most minimally invasive approach to reduce postoperative risks and be able to apply local hemostatic measures in terms of a bleeding complication.


Assuntos
Anticoagulantes/efeitos adversos , Transplante Ósseo/efeitos adversos , Implantação Dentária/efeitos adversos , Inibidores da Agregação Plaquetária/efeitos adversos , Hemorragia Pós-Operatória/induzido quimicamente , Adulto , Anticoagulantes/uso terapêutico , Humanos , Inibidores da Agregação Plaquetária/uso terapêutico , Estudos Prospectivos , Vitamina K/antagonistas & inibidores
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