Inferring past refugia and range dynamics through the integration of fossil, niche modelling and genomic data

Aim: Reconstructing species' glacial refugial history and demographic changes over time has greatly relied on comparing inferences from multiple methods while not sufficiently acknowledging their limitations. Here, we aim to integrate as fully as possible complementary methods in ecology, genomics and palaeobiology to improve the reconstruction of species biogeographical history. Location: South-western Europe. Taxon: Cabrera vole (Microtus cabrerae). Methods: We compiled and mapped the raw fossil data of the Cabrera vole for the Last Glacial Maximum (LGM) and Mid-Holocene (MH). Alongside, we projected the calibrated ecological niche model (ENM) of the species' current distribution for the LGM, the Younger Dryas and the MH. Complementarily, we used previously obtained Genotyping-by- Sequencing data to evaluate the demographic history and range expansion patterns of all four Evolutionarily Significant Units of the species, in an integrative framework. Results: ENM-inferred refugial areas and genomic modelling consistently supported northern Iberian glacial refugia for the Cabrera vole. This contrasted with the higher fossil abundance of the species in southern and eastern Iberia and southern France from the LGM to the MH. Our results suggest that populations in areas with high fossil abundance went extinct, and were later replaced by northern Iberian populations such that they did not contribute significantly to the current gene pool. Main conclusions: Our integrative approach indicates how the range of the Cabrera vole fluctuated in response to environmental change during and following the LGM. Despite methodological limitations, the ENM and genomic approaches produced generally congruent results. Instead, the fossil record may misrepresent the ancestral distribution of this species and should be considered cautiously for ancestral distribution reconstruction, considering that it also reflects the fossilization conditions. Overall, our study supports the idea that integrative approaches are essential to provide an accurate and well-supported picture of historical refugial areas and range dynamicsinfo:eu-repo/semantics/publishedVersio

Postmenopausal Osteoporosis reference genes for qPCR expression assays

Osteoporosis (OP) is a multifactorial disease influenced by genetic factors in more than half of the cases. In spite of the efforts to clarify the relationship among genetic factors and susceptibility to develop OP, many genetic associations need to be further functionally validated. Besides, some limitations as the choice of stably expressed reference genes (RG) should be overcome to ensure the quality and reproducibility of gene expression assays. To our knowledge, a validation study for RG in OP is still missing. We compared the expression levels, using polymerase chain reaction quantitative real time (qPCR) of 10 RG (G6PD, B2M, GUSB, HSP90, EF1A, RPLP0, GAPDH, ACTB, 18 S and HPRT1) to assess their suitability in OP analysis by using GeNorm, Normfinder, BestKeeper and RefFinder programs. A minimal number of two RG was recommended by GeNorm to obtain a reliable normalization. RPLP0 and B2M were identified as the most stable genes in OP studies while ACTB, 18 S and HPRT1 were inadequate for normalization in our data set. Moreover, we showed the dramatic effects of suboptimal RG choice on the quantification of a target gene, highlighting the importance in the identification of the most appropriate reference gene to specific diseases. We suggest the use of RPLP0 and B2M as the most stable reference genes while we do not recommend the use of the least stable reference genes HPRT1, 18 S and ACTB in OP expression assays using PBMC as biological source. Additionally, we emphasize the importance of individualized and careful choice in software and reference genes selection

An analysis of survival and disability milestones

Funding Information: This work was supported by Fundação para a Ciência e Tecnologia (FCT) through a Ph.D. Scholarship ( SFRH/BD/143797/2019 ) and Prémio João Lobo Antunes by Santa Casa da Misericórdia de Lisboa. Funding Information: This work was supported by Fundação para a Ciência e Tecnologia (FCT) through a Ph.D. Scholarship (SFRH/BD/143797/2019) and Prémio João Lobo Antunes by Santa Casa da Misericórdia de Lisboa. Publisher Copyright: © 2023Background: Data on the long-term survival and incidence of disability milestones after subthalamic nucleus deep brain stimulation (STN-DBS) in Parkinson's disease (PD) is limited. Objectives: To estimate mortality and assess the frequency/time-to-development of disability milestones (falls, freezing, hallucinations, dementia, and institutionalization) among PD patients post STN-DBS. Methods: A longitudinal retrospective study of patients undergoing STN-DBS. For mortality, Cox proportional hazards regression analysis was performed. For disease milestones, competing risk analyses were performed and cumulative incidence functions reported. The strength of association between baselines features and event occurrence was calculated based on adjusted hazard ratios. Results: The overall mortality for the 109 patients was 16 % (62.1 ± 21.3 months after surgery). Falls (73 %) and freezing (47 %) were both the earliest (40.4 ± 25.4 and 39.6 ± 28.4 months, respectively) and most frequent milestones. Dementia (34 %) and hallucinations (32 %) soon followed (56.2 ± 21.2 and mean 60.0 ± 20.7 months after surgery, respectively). Higher ADL scores in the OFF state and higher age at surgery were associated with falls, freezing, dementia and institutionalization. Conclusions: Long-term mortality rate is low after STN-DBS. Disease milestones occur later during the disease course, with motor milestones appearing first and at a higher frequency than cognitive ones.publishersversionpublishe

Cohort profile: the 100 million Brazilian cohort

The creation of The 100 Million Brazilian Cohort was motivated by the availability of high quality but dispersed social and health databases in Brazil and the need to integrate data and evaluate the impact of policies aiming to improve the social determinants of health (e.g. social protection policies) on health outcomes, overall and in subgroups of interest in a dynamic cohort. • The baseline of The 100 Million Brazilian Cohort comprises 131 697 800 low-income individuals in 35 358 415 families from 2011 to 2018. The Cohort population is mostly composed of children and young adults, with a higher proportion of females than the general Brazilian population, who identify themselves as Brown and live in the urban area of the country. • Exposure to social protection and the follow-up of individuals are obtained through: (i) deterministic linkage using the Social Identification Number (NIS) to link the Cohort baseline to social protection programmes and to periodically renewed socioeconomic information in Cadatro U ́ nico datasets; and/or (ii) non-deterministic linkage using the CIDACS-RL non-deterministic linkage tool, to link the Cohort baseline to administrative health care datasets such as mortality (Mortality Information System, SIM), disease notification (Information System for Notifiable Diseases, SINAN), birth information (Live Birth Information System, SINASC) and nutrition status (Food and Nutrition Surveillance System, SISVAN). • So far, studies have used The 100 Million Brazilian Cohort to investigate the socioeconomic and demographic determinants of leprosy, leprosy treatment outcomes and low birthweight and to evaluate the impact of the Bolsa Familia Programme (BFP) on leprosy and child mortality. Other studies are now being conducted that are of utmost relevance to the health inequalities of Brazil and many low- and middle-income countries, and many research opportunities are being opened up with the linkage of a range of health outcomes

Effect of occlusal splint thickness on electrical masticatory muscle activity during rest and clenching

The extent of separation between the maxillary and mandibular teeth in the fabrication of interocclusal splints designed to achieve efficiency and muscle relaxation is controversial and undefined in the literature. Based on this premise, the aim of this study was to evaluate the effect of interocclusal splint thicknesses of 3 and 6 millimeters on the electrical activity of the anterior temporal and masseter muscles during rest and dental clenching. Twenty asymptomatic individuals (10 males and 10 females) were selected using the Research Diagnostic Criteria (RDC). Electromyography (EMG) was performed both with and without the 3- and 6-mm splints using the Bio EMG software package, which recorded values given in microvolts (µV). The results, which were assessed using analysis of variance (ANOVA) to a 5% significance level (p < 0.05), showed increased electrical activity of the masticatory muscles during dental clenching compared with at rest, with greater activity in the masseter muscle. The electrical activity did not differ according to the thickness of the splints or between males and females. We can conclude that both splint thicknesses are effective in treating muscle hyperactivity given their similar clinical behavior for asymptomatic individuals

Motivos de exclusão para a cirurgia de estimulação cerebral profunda na doença de Parkinson

Abstract de comunicação apresentada no Congresso SPDMov 2022 - Parkinsonismos Atípicos: Clássicos e Atípicos. Luso, 1-2 Abril 2022N/

TeV flaring activity of the AGN PKS 0625-354 in November 2018

Most $\gamma$-ray detected active galactic nuclei are blazars with one of their relativistic jets pointing towards the Earth. Only a few objects belong to the class of radio galaxies or misaligned blazars. Here, we investigate the nature of the object PKS 0625-354, its $\gamma$-ray flux and spectral variability and its broad-band spectral emission with observations from H.E.S.S., Fermi-LAT, Swift-XRT, and UVOT taken in November 2018. The H.E.S.S. light curve above 200 GeV shows an outburst in the first night of observations followed by a declining flux with a halving time scale of 5.9h. The $\gamma\gamma$-opacity constrains the upper limit of the angle between the jet and the line of sight to $\sim10^\circ$. The broad-band spectral energy distribution shows two humps and can be well fitted with a single-zone synchrotron self Compton emission model. We conclude that PKS 0625-354, as an object showing clear features of both blazars and radio galaxies, can be classified as an intermediate active galactic nuclei. Multi-wavelength studies of such intermediate objects exhibiting features of both blazars and radio galaxies are sparse but crucial for the understanding of the broad-band emission of $\gamma$-ray detected active galactic nuclei in general.Comment: 9 pages, 6 figures, accepted for publication in Astronomy & Astrophysic

A MeerKAT, e-MERLIN, H.E.S.S. and Swift search for persistent and transient emission associated with three localised FRBs

We report on a search for persistent radio emission from the one-off Fast Radio Burst (FRB) 20190714A, as well as from two repeating FRBs, 20190711A and 20171019A, using the MeerKAT radio telescope. For FRB 20171019A we also conducted simultaneous observations with the High Energy Stereoscopic System (H.E.S.S.) in very high energy gamma rays and searched for signals in the ultraviolet, optical, and X-ray bands. For this FRB, we obtain a UV flux upper limit of 1.39x10^-16 erg/cm^-2/s/Amstrong, X-ray limit of ~ 6.6x10^-14 erg/cm^-2/s and a limit on the very-high-energy gamma-ray flux (Phi) (E &gt; 120 GeV) &lt; 1.7 x 10^-12 erg/cm^-2/s. We obtain a radio upper limit of ~15 microJy/beam for persistent emission at the locations of both FRBs 20190711A and 20171019A, but detect diffuse radio emission with a peak brightness of ~53 microJy/beam associated with FRB 20190714A at z = 0.2365. This represents the first detection of the radio continuum emission potentially associated with the host (galaxy) of FRB 20190714A, and is only the third known FRB to have such an association. Given the possible association of a faint persistent source, FRB 20190714A may potentially be a repeating FRB whose age lies between that of FRB 20121102A and FRB 20180916A. A parallel search for repeat bursts from these FRBs revealed no new detections down to a fluence of 0.08 Jy ms for a 1 ms duration burst