Multi-locus transcranial magnetic stimulation system for electronically targeted brain stimulation

Background: Transcranial magnetic stimulation (TMS) allows non-invasive stimulation of the cortex. In multi-locus TMS (mTMS), the stimulating electric field (E-field) is controlled electronically without coil movement by adjusting currents in the coils of a transducer. Objective: To develop an mTMS system that allows adjusting the location and orientation of the E-field maximum within a cortical region. Methods: We designed and manufactured a planar 5-coil mTMS transducer to allow controlling the maximum of the induced E-field within a cortical region approximately 30 mm in diameter. We developed electronics with a design consisting of independently controlled H-bridge circuits to drive up to six TMS coils. To control the hardware, we programmed software that runs on a field-programmable gate array and a computer. To induce the desired E-field in the cortex, we developed an optimization method to calculate the currents needed in the coils. We characterized the mTMS system and conducted a proof-of-concept motor-mapping experiment on a healthy volunteer. In the motor mapping, we kept the transducer placement fixed while electronically shifting the E-field maximum on the precentral gyrus and measuring electromyography from the contralateral hand. Results: The transducer consists of an oval coil, two figure-of-eight coils, and two four-leaf-clover coils stacked on top of each other. The technical characterization indicated that the mTMS system performs as designed. The measured motor evoked potential amplitudes varied consistently as a function of the location of the E-field maximum. Conclusion: The developed mTMS system enables electronically targeted brain stimulation within a cortical region. (c) 2021 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).Peer reviewe

Sex-specific genetic effects in physical activity: results from a quantitative genetic analysis

Background: The objective of this study is to present a model to estimate sex-specific genetic effects on physical activity (PA) levels and sedentary behaviour (SB) using three generation families. Methods: The sample consisted of 100 families covering three generations from Portugal. PA and SB were assessed via the International Physical Activity Questionnaire short form (IPAQ-SF). Sex-specific effects were assessed by genotype-by-sex interaction (GSI) models and sex-specific heritabilities. GSI effects and heterogeneity were tested in the residual environmental variance. SPSS 17 and SOLAR v. 4.1 were used in all computations. Results: The genetic component for PA and SB domains varied from low to moderate (11 % to 46 %), when analyzing both genders combined. We found GSI effects for vigorous PA (p = 0.02) and time spent watching television (WT) (p \u3c 0.001) that showed significantly higher additive genetic variance estimates in males. The heterogeneity in the residual environmental variance was significant for moderate PA (p = 0.02), vigorous PA (p = 0.006) and total PA (p = 0.001). Sex-specific heritability estimates were significantly higher in males only for WT, with a male-to-female difference in heritability of 42.5 (95 % confidence interval: 6.4, 70.4). Conclusions: Low to moderate genetic effects on PA and SB traits were found. Results from the GSI model show that there are sex-specific effects in two phenotypes, VPA and WT with a stronger genetic influence in males

Scalar field in cosmology: Potential for isotropization and inflation

The important role of scalar field in cosmology was noticed by a number of authors. Due to the fact that the scalar field possesses zero spin, it was basically considered in isotropic cosmological models. If considered in an anisotropic model, the linear scalar field does not lead to isotropization of expansion process. One needs to introduce scalar field with nonlinear potential for the isotropization process to take place. In this paper the general form of scalar field potentials leading to the asymptotic isotropization in case of Bianchi type-I cosmological model, and inflationary regime in case of isotropic space-time is obtained. In doing so we solved both direct and inverse problem, where by direct problem we mean to find metric functions and scalar field for the given potential, whereas, the inverse problem means to find the potential and scalar field for the given metric function. The scalar field potentials leading to the inflation and isotropization were found both for harmonic and proper synchronic time.Comment: 10 page

C9ORF72 patient-derived endothelial cells drive blood-brain barrier disruption and contribute to neurotoxicity

The blood-brain barrier (BBB) serves as a highly intricate and dynamic interface connecting the brain and the bloodstream, playing a vital role in maintaining brain homeostasis. BBB dysfunction has been associated with multiple neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS); however, the role of the BBB in neurodegeneration is understudied. We developed an ALS patient-derived model of the BBB by using cells derived from 5 patient donors carrying C9ORF72 mutations. Brain microvascular endothelial-like cells (BMEC-like cells) derived from C9ORF72-ALS patients showed altered gene expression, compromised barrier integrity, and increased P-glycoprotein transporter activity. In addition, mitochondrial metabolic tests demonstrated that C9ORF72-ALS BMECs display a significant decrease in basal glycolysis accompanied by increased basal and ATP-linked respiration. Moreover, our study reveals that C9-ALS derived astrocytes can further affect BMECs function and affect the expression of the glucose transporter Glut-1. Finally, C9ORF72 patient-derived BMECs form leaky barriers through a cell-autonomous mechanism and have neurotoxic properties towards motor neurons

The role of the placenta in the vertical transmission of HIV-1

A transmissão vertical (TV) consiste na principal forma de infecção pelo HIV-1 em menores de 13 anos e estimativas apontam que em 25% dos casos a transmissão tenha ocorrido intraútero. Nessas circunstâncias, o vírus de alguma forma ultrapassa a membrana placentária e chega ao sangue fetal. Esta revisão tem como objetivo realizar uma breve descrição sobre os mecanismos presentes na placenta humana que são capazes de gerar susceptibilidade ou proteção à TV do HIV-1. As células placentárias produzem um enorme grupo de citocinas, quimiocinas, hormônios e receptores que podem contribuir com o desfecho da transmissão do vírus ao concepto. Além disso, a capacidade do vírus de infectar as células placentárias também pode contribuir com a sua transmissão. Entretanto, o mecanismo pelo qual o vírus é capaz de sobrepujar a membrana placentária e as consequências dessa infecção no tecido placentário não estão totalmente elucidados. Dessa forma, novas pesquisas nessa área poderão contribuir com o desenvolvimento de estratégias profiláticas eficazes para redução da TV do HIV-1Vertical transmission (VT) is the main form of infection by HIV-1 in children under 13 years and estimates show that in 25% of cases intrauterine transmission has occurred. Under these circumstances, the virus somehow overcomes the placental membrane and reaches the fetal blood. This review aims to conduct a brief description of the mechanisms present in human placenta that are capable of generating susceptibility or resistance to VT of HIV-1. Placental cells produces a huge group of cytokines, chemokines, hormones and receptors that may contribute to the outcome of virus transmission to the fetus. Moreover, the ability of the virus to infect placental cells can also contribute to its transmission. However, the mechanism by which the virus is able to overcome the placental tissue is not fully elucidated. Thus, further research in this area may contribute to the development of effective preventive strategies to reduce the VT of HIV-

Draft genome sequence of Wickerhamomyces anomalus LBCM1105, isolated from cachaça fermentation

Wickerhamomyces anomalus LBCM1105 is a yeast isolated from cachaça distillery fermentation vats, notable for exceptional glycerol consumption ability. We report its draft genome with 20.5x in-depth coverage and around 90% extension and completeness. It harbors the sequences of proteins involved in glycerol transport and metabolism.The authors gratefully acknowledge Laboratorio Nacional de Ciencia e Tecnologia do Bioetanol (CTBE) and the Centro Nacional de Pesquisa em Energia e Materiais (CNPEM) for support with the sequencing of LBCM1105. This work was supported by CAPES/Brazil (PNPD 2755/2011; PCF-PVE 021/2012), by CNPq (Brazil), processes 304815/2012 (research grant) and 305135/2015-5, and by AUXPE-PVES 1801/2012 (Process 23038.015294/2016-18) from Brazilian Government and by UFOP. C.L. is supported by the strategic program UID/BIA/04050/2013 [POCI-01-0145-FEDER-007569] funded by national funds through the FCT I.P. and by the ERDF through the COMPETE2020 - Programa Operacional de Competitividade e Internacionalizacao (POCI). DMRP is a fellow from the CNPq (Conselho Nacional de Desenvolvimento Cientifico e Tecnologico) - Brazil (310080/2018-5)