Perturbations of Gauss-Bonnet Black Strings in Codimension-2 Braneworlds

We derive the Lichnerowicz equation in the presence of the Gauss-Bonnet term. Using the modified Lichnerowicz equation we study the metric perturbations of Gauss-Bonnet black strings in Codimension-2 Braneworlds.Comment: 26 pages, no figures, clarifying comments and one reference added, to be published in JHE

Serological response to a single dose of a SARS-CoV-2 mRNA vaccine

The delays in the production and delivery of COVID-19 vaccines and the growing number of fatal infections across the globe raised the question whether it would be more advantageous to vaccinate a larger group of individuals with one dose instead of a smaller one with two doses. Through a group of vaccinated healthcare workers, we describe the qualitative and quantitative serological response to a single dose of the BNT162b2 vaccine. We found that, before the second dose inoculation, 95.3 % (182/191) already had anti-SARS-CoV-2 IgG and, half of them, antibodies concentrations against RBD (the key target of neutralizing antibodies) that reached maximum values for the used evaluation immunoassay. In order to improve the execution of vaccination programs, further studies are needed to assess whether there are individuals for whom a single dose of mRNA vaccine or a delay in the inoculation of the second dose, produce a sufficient immune response. Additionally, follow-up studies will help in understanding post-vaccination immunity, how long it lasts and how it relates to infection and reinfection.This work was supported by FCT Special Support Research4Covid (Project 186)

Evaluation of SARS-CoV-2 interferon gamma release assay in BNT162b2 vaccinated healthcare workers

To predict protective immunity to SARS-CoV-2, cellular immunity seems to be more sensitive than humoral immunity. Through an Interferon-Gamma (IFN-γ) Release Assay (IGRA), we show that, despite a marked decrease in total antibodies, 94.3% of 123 healthcare workers have a positive cellular response 6 months after inoculation with the 2nd dose of BNT162b2 vaccine. Despite the qualitative relationship found, we did not observe a quantitative correlation between IFN-γ and IgG levels against SARS-CoV-2. Using stimulated whole blood from a subset of participants, we confirmed the specific T-cell response to SARS-CoV-2 by dosing elevated levels of the IL-6, IL-10 and TNF-α. Through a 20-month follow-up, we found that none of the infected participants had severe COVID-19 and that the first positive cases were only 12 months after the 2nd dose inoculation. Future studies are needed to understand if IGRA-SARS-CoV-2 can be a powerful diagnostic tool to predict future COVID-19 severe disease, guiding vaccination policies. © 2024 Ramos et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.This research was funded by Fundação para a Ciência e Tecnologia (FCT) (http://www.fct.pt) Special Support Research4Covid, grant number 186. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Loss of DNMT1o Disrupts Imprinted X Chromosome Inactivation and Accentuates Placental Defects in Females

The maintenance of key germline derived DNA methylation patterns during preimplantation development depends on stores of DNA cytosine methyltransferase-1o (DNMT1o) provided by the oocyte. Dnmt1omat-/- mouse embryos born to Dnmt1Δ1o/Δ1o female mice lack DNMT1o protein and have disrupted genomic imprinting and associated phenotypic abnormalities. Here, we describe additional female-specific morphological abnormalities and DNA hypomethylation defects outside imprinted loci, restricted to extraembryonic tissue. Compared to male offspring, the placentae of female offspring of Dnmt1Δ1o/Δ1o mothers displayed a higher incidence of genic and intergenic hypomethylation and more frequent and extreme placental dysmorphology. The majority of the affected loci were concentrated on the X chromosome and associated with aberrant biallelic expression, indicating that imprinted X-inactivation was perturbed. Hypomethylation of a key regulatory region of Xite within the X-inactivation center was present in female blastocysts shortly after the absence of methylation maintenance by DNMT1o at the 8-cell stage. The female preponderance of placental DNA hypomethylation associated with maternal DNMT1o deficiency provides evidence of additional roles beyond the maintenance of genomic imprints for DNA methylation events in the preimplantation embryo, including a role in imprinted X chromosome inactivation. © 2013 McGraw et al

Aging Skin: Nourishing from Out-In. Lessons from Wound Healing

Skin lesion therapy, peculiarly in the elderly, cannot be isolated from understanding that the skin is an important organ consisting of different tissues. Furthermore, dermis health is fundamental for epidermis integrity, and so adequate nourishment is mandatory in maintaining skin integrity. The dermis nourishes the epidermis, and a healthy epidermis protects the dermis from the environment, so nourishing the dermis through the epidermal barrier is a technical problem yet to be resolved. This is also a consequence of the laws and regulations restricting cosmetics, which cannot have properties that pass the epidermal layer. There is higher investment in cosmetics than in the pharmaceutical industry dealing with skin therapies, because the costs of drug registration are enormous and the field is unprofitable. Still, wound healing may be seen as an opportunity to “feed” the dermis directly. It could also verify whether providing substrates could promote efficient healing and test optimal skin integrity maintenance, if not skin rejuvenation, in an ever aging population

The Importance of Design in the Development of a Portable and Modular Iot-Based Detection Device for Clinical Applications

The integration of human factors engineering methods within the medical device design and development process has been highlighted by international standards organizations. Such methods are contributing to the development of safer medical devices, more suitable to users' needs. Errors during device operation might hamper effective patient diagnosis and treatment, or eventually lead to injury or death. Thus, the designing process of a medical device is indeed crucial to user experience and safety operation. This paper presents a human-centred design analysis of a novel IoT-based screening prototype (iLoF) based on Artificial Intelligence algorithms built-in in a patented-photonics system developed by a deep tech startup. The influence of the design process during the development of the prototype was addressed, based on a human-centred design methodology and considering the device's application environment. iLoF's prototype on-field applicability was evaluated considering a single case-study carried out at one of the main hospitals in Portugal through interviews to ten healthcare professionals with high experience in laboratorial testing. A benchmark assessment and a comparison matrix along with the market products are also presented to fully understand the technology state and to find new solutions that can influence iLoF's product development. © Published under licence by IOP Publishing Ltd

SARS-CoV-2 seroprevalence in healthcare workers: The experience of a Portuguese COVID-19 front-line hospital during the 1st pandemic wave

Background: Healthcare workers (HCW) are at increased risk of SARS-CoV-2 infection. Here, we describe the SARS-CoV-2 seroprevalence in HCW who work daily at a COVID-19 front-line hospital in Portugal. Methods: To this end, the seroprevalence of 1027 HCW, assessed after the peak of the first pandemic wave, was determined using the following immunoassays: Euroimmun Anti-SARS-CoV-2 ELISA IgG (Euroimmun, Luebeck, Germany), Abbott SARS-CoV-2 IgG (Abbott Laboratories, Chicago), and Elecsys Anti-SARS-CoV–2 Total (Roche Diagnostics, Basel, Switzerland). Results: We found a 2.7% seroprevalence, very close to the one determined in the community (2.9%) for the same period. Conclusions: This low SARS-CoV–2 seroprevalence highlights the effectiveness of infection prevention and control measures implemented very early in the pandemic, namely the use of appropriate personal protective equipment.This research was supported by a grant from FCT Research4-COVID–19 (Project n° 186_596855206 – CertCOV)

Female Behaviour Drives Expression and Evolution of Gustatory Receptors in Butterflies

Secondary plant compounds are strong deterrents of insect oviposition and feeding, but may also be attractants for specialist herbivores. These insect-plant interactions are mediated by insect gustatory receptors (Grs) and olfactory receptors (Ors). An analysis of the reference genome of the butterfly Heliconius melpomene, which feeds on passion-flower vines (Passiflora spp.), together with whole-genome sequencing within the species and across the Heliconius phylogeny has permitted an unprecedented opportunity to study the patterns of gene duplication and copy-number variation (CNV) among these key sensory genes. We report in silico gene predictions of 73 Gr genes in the H. melpomene reference genome, including putative CO2, sugar, sugar alcohol, fructose, and bitter receptors. The majority of these Grs are the result of gene duplications since Heliconius shared a common ancestor with the monarch butterfly or the silkmoth. Among Grs but not Ors, CNVs are more common within species in those gene lineages that have also duplicated over this evolutionary time-scale, suggesting ongoing rapid gene family evolution. Deep sequencing (∼1 billion reads) of transcriptomes from proboscis and labial palps, antennae, and legs of adult H. melpomene males and females indicates that 67 of the predicted 73 Gr genes and 67 of the 70 predicted Or genes are expressed in these three tissues. Intriguingly, we find that one-third of all Grs show female-biased gene expression (n = 26) and nearly all of these (n = 21) are Heliconius-specific Grs. In fact, a significant excess of Grs that are expressed in female legs but not male legs are the result of recent gene duplication. This difference in Gr gene expression diversity between the sexes is accompanied by a striking sexual dimorphism in the abundance of gustatory sensilla on the forelegs of H. melpomene, suggesting that female oviposition behaviour drives the evolution of new gustatory receptors in butterfly genomes

Amyloid precursor protein drives down-regulation of mitochondrial oxidative phosphorylation independent of amyloid beta

Amyloid precursor protein (APP) and its extracellular domain, soluble APP alpha (sAPPα) play important physiological and neuroprotective roles. However, rare forms of familial Alzheimer’s disease are associated with mutations in APP that increase toxic amyloidogenic cleavage of APP and produce amyloid beta (Aβ) at the expense of sAPPα and other non-amyloidogenic fragments. Although mitochondrial dysfunction has become an established hallmark of neurotoxicity, the link between Aβ and mitochondrial function is unclear. In this study we investigated the effects of increased levels of neuronal APP or Aβ on mitochondrial metabolism and gene expression, in human SH-SY5Y neuroblastoma cells. Increased non-amyloidogenic processing of APP, but not Aβ, profoundly decreased respiration and enhanced glycolysis, while mitochondrial DNA (mtDNA) transcripts were decreased, without detrimental effects to cell growth. These effects cannot be ascribed to Aβ toxicity, since higher levels of endogenous Aβ in our models do not cause oxidative phosphorylation (OXPHOS) perturbations. Similarly, chemical inhibition of β-secretase decreased mitochondrial respiration, suggesting that non-amyloidogenic processing of APP may be responsible for mitochondrial changes. Our results have two important implications, the need for caution in the interpretation of mitochondrial perturbations in models where APP is overexpressed, and a potential role of sAPPα or other non-amyloid APP fragments as acute modulators of mitochondrial metabolism

Optimal perceived timing: integrating sensory information with dynamically updated expectations

The environment has a temporal structure, and knowing when a stimulus will appear translates into increased perceptual performance. Here we investigated how the human brain exploits temporal regularity in stimulus sequences for perception. We find that the timing of stimuli that occasionally deviate from a regularly paced sequence is perceptually distorted. Stimuli presented earlier than expected are perceptually delayed, whereas stimuli presented on time and later than expected are perceptually accelerated. This result suggests that the brain regularizes slightly deviant stimuli with an asymmetry that leads to the perceptual acceleration of expected stimuli. We present a Bayesian model for the combination of dynamically-updated expectations, in the form of a priori probability of encountering future stimuli, with incoming sensory information. The asymmetries in the results are accounted for by the asymmetries in the distributions involved in the computational process