Loss and Gain of Function in SERPINB11: An Example of a Gene under Selection on Standing Variation, with Implications for Host-Pathogen Interactions

Serine protease inhibitors (SERPINs) are crucial in the regulation of diverse biological processes including inflammation and immune response. SERPINB11, located in the 18q21 gene cluster, is a polymorphic gene/pseudogene coding for a non-inhibitory SERPIN. In a genome-wide scan for recent selection, SERPINB11 was identified as a potential candidate gene for adaptive evolution in Yoruba. The present study sought a better understanding of the evolutionary history of SERPINB11, with special focus on evaluating its selective signature. Through the resequencing of coding and noncoding regions of SERPINB11 in 20 Yorubans and analyzing primate orthologous sequences, we identified a full-length SERPINB11 variant encoding a non-inhibitory SERPIN as the putative candidate of selection – probably driven to higher frequencies by an adaptive response using preexisting variation. In addition, we detected contrasting evolutionary features of SERPINB11 in primates: While primate phylogeny as a whole is under purifying selection, the human lineage shows evidence of positive selection in a few codons, all associated with the active SERPINB11. Comparative modeling studies suggest that positively selected codons reduce SERPINB11's ability to undergo the conformational changes typical of inhibitory SERPINs – suggesting that it is evolving towards a new non-inhibitory function in humans. Significant correlations between SERPINB11 variants and the environmental variables, pastoralism and pathogen richness, have led us to propose a selective advantage through host-pathogen interactions, possibly linked to an adaptive response combating the emergence of infectious diseases in recent human evolution. This work represents the first description of a resurrected gene in humans, and may well exemplify selection on standing variation triggered by drastic ecological shifts

The spectral action for Moyal planes

Extending a result of D.V. Vassilevich, we obtain the asymptotic expansion for the trace of a "spatially" regularized heat operator associated with a generalized Laplacian defined with integral Moyal products. The Moyal hyperplanes corresponding to any skewsymmetric matrix $\Theta$ being spectral triples, the spectral action introduced in noncommutative geometry by A. Chamseddine and A. Connes is computed. This result generalizes the Connes-Lott action previously computed by Gayral for symplectic $\Theta$.Comment: 20 pages, no figure, few improvment

Plasmas and Controlled Nuclear Fusion

Contains reports on three research projects.U. S. Atomic Energy Commission (Contract AT(30-1)-3980

Outliers treatment to improve the recognition of voice pathologies

In some of the processes used in data analysis, such as the recognition of pathologies and pathological subjects, the presence of anomalous instances in the dataset is an unfavorable situation that can lead to misleading results. This article presents a function that implements the identification of anomalies in dataset using the boxplot and standard deviation methods. Also was used the filling technique to treat these anomalies, in which the anomalous point value were substituted by a limit value determined by the boxplot or standard deviation methods. To improve the outliers methods some normalization processes based on the z-score, logarithmic and squared root methodologies were experimented. These outliers treatment were applied to the dataset used in the recognition of vocal pathologies (dysphonia, chronic laryngitis and vocal cords paralysis vs control), performed by a MLP and LSTM neural networks. After the experiments, both the standard deviation and the boxplot methods with z-score normalization showed very useful for pre-processing the dataset for voice pathologies recognition. The accuracy was improved between 3 and 13 points in percentage.info:eu-repo/semantics/publishedVersio

Ultrathin, flexible and MRI-compatible microelectrode array for chronic single units recording within subcortical layers

Current techniques of neuroimaging, including electrical devices, are either of low spatiotemporal resolution or invasive, impeding multiscale monitoring of brain activity at both single cell and network levels. Overcoming this issue is of great importance to assess brain's computational ability and for neurorehabilitation projects that require real-time monitoring of neurons and concomitant networks activities. Currently, that information could be extracted from functional MRI when combined with mathematical models. Novel methods enabling quantitative and long-lasting recording at both single cell and network levels will allow to correlate the MRI data with intracortical activity at single cell level, and to refine those models. Here, we report the fabrication and validation of ultra-thin, optically transparent and flexible intracortical microelectrode arrays for combining extracellular multi-unit and fMRI recordings. The sensing devices are compatible with large-scale manufacturing, and demonstrate both fMRI transparency at 4.7 T, and high electrical performance, and thus appears as a promising candidate for simultaneous multiscale neurodynamic measurements

Augmented reality-assisted ultrasound breast biopsy

Breast cancer is the most prevalent cancer in the world and the fifth-leading cause of cancer-related death. Treatment is effective in the early stages. Thus, a need to screen considerable portions of the population is crucial. When the screening procedure uncovers a suspect lesion, a biopsy is performed to assess its potential for malignancy. This procedure is usually performed using real-time Ultrasound (US) imaging. This work proposes a visualization system for US breast biopsy. It consists of an application running on AR glasses that interact with a computer application. The AR glasses track the position of QR codes mounted on an US probe and a biopsy needle. US images are shown in the user’s field of view with enhanced lesion visualization and needle trajectory. To validate the system, latency of the transmission of US images was evaluated. Usability assessment compared our proposed prototype with a traditional approach with different users. It showed that needle alignment was more precise, with 92.67 ± 2.32° in our prototype versus 89.99 ± 37.49° in a traditional system. The users also reached the lesion more accurately. Overall, the proposed solution presents promising results, and the use of AR glasses as a tracking and visualization device exhibited good performance.This work was funded by the projects “NORTE-01-0145-FEDER-000045” and “NORTE-01- 0145-FEDER-000059", supported by Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (FEDER). It was also funded by national funds, through the FCT (Fundação para a Ciência e a Tecnologia) and FCT/MCTES in the scope of the project UIDB/05549/2020, UIDP/05549/2020 and LASI-LA/P/0104/2020. The authors also acknowledge FCT, Portugal and the European Social Found, European Union, for funding support through the “Programa Operacional Capital Humano” (POCH) in the scope of the PhD grants SFRH/BD/136721/2018 (Oliveira B.) and SFRH/BD/136670 (Torres H. R.)

Molecular diversity within the genus Laeonereis (Annelida, Nereididae) along the west Atlantic coast: paving the way for integrative taxonomy

The polychaete genus Laeonereis (Annelida, Nereididae) occurs over a broad geographic range and extends nearly across the entire Atlantic coast of America, from the USA to Uruguay. Despite the research efforts to clarify its diversity and systematics, mostly by morphological and ecological evidence, there is still uncertainty, mainly concerning the species Laeonereis culveri, which constitutes an old and notorious case of taxonomic ambiguity. Here, we revised the molecular diversity and distribution of Laeonereis species based on a multi-locus approach, including DNA sequence analyses of partial segments of the cytochrome c oxidase subunit I (COI), 16S rRNA, and 28S rRNA genes. We examined Laeonereis specimens collected from 26 sites along the American Atlantic coast from Massachusetts (USA) to Mar del Plata (Argentina). Although no comprehensive morphological examination was performed between different populations, the COI barcodes revealed seven highly divergent MOTUs, with a mean K2P genetic distance of 16.9% (from 6.8% to 21.9%), which was confirmed through four clustering algorithms. All MOTUs were geographically segregated, except for MOTUs 6 and 7 from southeastern Brazil, which presented partially overlapping ranges between Rio de Janeiro and Sao Paulo coast. Sequence data obtained from 16S rRNA and 28S rRNA markers supported the same MOTU delimitation and geographic segregation as those of COI, providing further evidence for the existence of seven deeply divergent lineages within the genus. The extent of genetic divergence between MOTUs observed in our study fits comfortably within the range reported for species of polychaetes, including Nereididae, thus providing a strong indication that they might constitute separate species. These results may therefore pave the way for integrative taxonomic studies, aiming to clarify the taxonomic status of the Laeonereis MOTUs herein reported.This work was supported by the FAPESP (Grants n~ 2011/50317-5, 2015/25623-6, 2017/06167-5, 2018/10313-0) and CNPq through a productivity grant to A.C.Z.A (301551/2019-7). Marcos AL Teixeira was supported by a PhD fellowship (SFRH/BD/131527/2017) from FCT. Pedro Vieira was supported by a Post-Doctoral Fellowships (BPD1/next-sea/2018, NORTE-01-0145-FEDER-000032). Filipe Costa and the University of Minho's contribution was supported by the strategic program UID/BIA/04050/2013 POCI-010145-FEDER-007569. Victor C Seixas was supported by a Post-Doctoral Fellowship sponsored by CAPES-PNPD (88882.316714/2019-01). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Electronic transport through domain walls in ferromagnetic nanowires: Co-existence of adiabatic and non-adiabatic spin dynamics

We study the effect of a domain wall on the electronic transport in ferromagnetic quantum wires. Due to the transverse confinement, conduction channels arise. In the presence of a domain wall, spin up and spin down electrons in these channels become coupled. For very short domain walls or at high longitudinal kinetic energy, this coupling is weak, leads to very few spin flips, and a perturbative treatment is possible. For very long domain wall structures, the spin follows adiabatically the local magnetization orientation, suppressing the effect of the domain wall on the total transmission, but reversing the spin of the electrons. In the intermediate regime, we numerically investigate the spin-dependent transport behavior for different shapes of the domain wall. We find that the knowledge of the precise shape of the domain wall is not crucial for determining the qualitative behavior. For parameters appropriate for experiments, electrons with low longitudinal energy are transmitted adiabatically while the electrons at high longitudinal energy are essentially unaffected by the domain wall. Taking this co-existence of different regimes into account is important for the understanding of recent experiments.Comment: 10 pages, 6 figure

Biallelic mutations in DYNC2LI1 are a rare cause of Ellis-van Creveld syndrome

Ellis van Creveld syndrome (EvC) is a chondral and ectodermal dysplasia caused by biallelic mutations in the EVC, EVC2 and WDR35 genes. A proportion of cases with clinical diagnosis of EvC, however, do not carry mutations in these genes. To identify the genetic cause of EvC in a cohort of mutation-negative patients, exome sequencing was undertaken in a family with three affected members, and mutation scanning of a panel of clinically and functionally relevant genes was performed in 24 additional subjects with features fitting/overlapping EvC. Compound heterozygosity for the c.2T>C (p.Met1?) and c.662C>T (p.Thr221Ile) variants in DYNC2LI1, which encodes a component of the intraflagellar transport-related dynein-2 complex previously found mutated in other short-rib thoracic dysplasias, was identified in the three affected members of the first family. Targeted resequencing detected compound heterozygosity for the same missense variant and a frameshift change (p.Val141*) in two siblings with EvC from a second family, while a newborn with a more severe phenotype carried two DYNC2LI1 truncating variants. Our findings indicate that DYNC2LI1 mutations are associated with a wider clinical spectrum than previously appreciated, including EvC, with the severity of the phenotype likely depending on the extent of defective DYNC2LI1 function