Quark-hybrid matter in the cores of massive neutron stars

Using a nonlocal extension of the SU(3) Nambu-Jona-Lasinio model, which reproduces several of the key features of quantum chromodynamics, we show that mixed phases of deconfined quarks and confined hadrons (quark-hybrid matter) may exist in the cores of neutron stars as massive as around 2.1M ⊙. The radii of these objects are found to be in the canonical range of ∼12-13 km. According to our study, the transition to pure quark matter does not occur in stable neutron stars, but is shifted to neutron stars which are unstable against radial oscillations. The implications of our study for the recently discovered, massive neutron star PSR J1614-2230, whose gravitational mass is 1.97±0.04M⊙, are that this neutron star may contain an extended region of quark-hybrid matter at it center, but no pure quark matter.Facultad de Ciencias Astronómicas y Geofísica

End TB strategy: the need to reduce risk inequalities

Background Diseases occur in populations whose individuals differ in essential characteristics, such as exposure to the causative agent, susceptibility given exposure, and infectiousness upon infection in the case of infectious diseases. Discussion Concepts developed in demography more than 30 years ago assert that variability between individuals affects substantially the estimation of overall population risk from disease incidence data. Methods that ignore individual heterogeneity tend to underestimate overall risk and lead to overoptimistic expectations for control. Concerned that this phenomenon is frequently overlooked in epidemiology, here we feature its significance for interpreting global data on human tuberculosis and predicting the impact of control measures. Summary We show that population-wide interventions have the greatest impact in populations where all individuals face an equal risk. Lowering variability in risk has great potential to increase the impact of interventions. Reducing inequality, therefore, empowers health interventions, which in turn improves health, further reducing inequality, in a virtuous circle

Genomic Analyses, Gene Expression and Antigenic Profile of the Trans-Sialidase Superfamily of Trypanosoma cruzi Reveal an Undetected Level of Complexity

The protozoan parasite Trypanosoma cruzi is the etiologic agent of Chagas disease, a highly debilitating human pathology that affects millions of people in the Americas. The sequencing of this parasite's genome reveals that trans-sialidase/trans-sialidase-like (TcS), a polymorphic protein family known to be involved in several aspects of T. cruzi biology, is the largest T. cruzi gene family, encoding more than 1,400 genes. Despite the fact that four TcS groups are well characterized and only one of the groups contains active trans-sialidases, all members of the family are annotated in the T. cruzi genome database as trans-sialidase. After performing sequence clustering analysis with all TcS complete genes, we identified four additional groups, demonstrating that the TcS family is even more heterogeneous than previously thought. Interestingly, members of distinct TcS groups show distinctive patterns of chromosome localization. Members of the TcSgroupII, which harbor proteins involved in host cell attachment/invasion, are preferentially located in subtelomeric regions, whereas members of the largest and new TcSgroupV have internal chromosomal locations. Real-time RT-PCR confirms the expression of genes derived from new groups and shows that the pattern of expression is not similar within and between groups. We also performed B-cell epitope prediction on the family and constructed a TcS specific peptide array, which was screened with sera from T. cruzi-infected mice. We demonstrated that all seven groups represented in the array are antigenic. A highly reactive peptide occurs in sixty TcS proteins including members of two new groups and may contribute to the known cross-reactivity of T. cruzi epitopes during infection. Taken together, our results contribute to a better understanding of the real complexity of the TcS family and open new avenues for investigating novel roles of this family during T. cruzi infection

Mismatch Negativity (MMN) response studies in elderly subjects

Mismatch Negativity é potencial endógeno que reflete o processamento de diferenças ocorridas no estímulo acústico. OBJETIVO: Caracterizar as respostas do MMN em sujeitos idosos, comparar com sujeitos adultos. MATERIAL E MÉTODO: Estudo prospectivo, com 30 sujeitos, 15 do gênero masculino e 15 do gênero masculino, com idade entre 60 e 80 anos e 11 meses. Teste estatístico Mann-Whitney. Os sujeitos passaram por avaliação médica e pelos exames de Audiometria Tonal Liminar, Imitanciometria, Emissões Otoacústicas e Potenciais Auditivos de Curta e Longa Latência (MMN). RESULTADOS: A latência média foi de 161,33ms (CZA2) e 148,67ms (CZA1), gênero feminino; de 171ms (CZA2) e 159,07ms (CZA1), gênero masculino. A amplitude média foi de -2,753µV (CZA2) e -2,177µV (CZA1), gênero feminino; de -1,847µV (CZA2) e -1,953µV (CZA1), gênero masculino. Quanto aos hemisférios direito e esquerdo, variável latência, média de 166ms (CZA2) e 153,87ms (CZA1); para a variável amplitude, média de -2,316µV (CZA2) e -2,065µV (CZA1). CONCLUSÃO: Não há diferença estatística significante entre as variáveis latência e amplitude, ao se comparar os gêneros masculino e feminino, os lados direito e esquerdo nos sujeitos idosos e entre as idades cronológicas adultos e idosos.Mismatch Negativity is an endogenous potential which reflects the processing of differences incurred in the acoustic stimulus. AIM: to characterize MMN responses in elderly subjects and compare with adult subjects. MATERIALS AND METHODS: prospective study involving 30 subjects, 15 men and 15 women, aged between 60 and 80 years and 11 months. Statistical test: Mann-Whitney. The subjects went through medical evaluation, threshold tonal audiometry, immittance tests, otoacoustic emissions and short and long latency auditory potentials (MMN). RESULTS: mean latency was 161.33 ms (CZA2) and 148.67 ms (CZA1), in women; of 171 ms (CZA2) and 159.07 ms (CZA1), men. Mean amplitude was -2.753 µV (CZA2) and -2.177 µV (CZA1), women; -1.847 µV (CZA2) and -1.953 µV (CZA1), men. As to the right and left hemispheres, mean latency variable of 166 ms (CZA2) and 153.87 ms (CZA1); for the amplitude variable, mean value of -2.316 µV (CZA2) and -2.065 µV (CZA1). CONCLUSION: there is no statistically significant difference between the latency and amplitude when we compared males and females, right and left sides in the elderly and between chronologic ages between adults and elderly subjects

Novel scFv against Notch Ligand JAG1 Suitable for Development of Cell Therapies toward JAG1-Positive Tumors

Funding Information: This research was funded by the Fundação para a Ciência e Tecnologia/Ministério da Ciência, Tecnologia e Ensino Superior (FCT/MCTES, Portugal) grant PTDC/BBB-BMD/4497/2014 (to A.B.), through national funds to iNOVA4Health (UIDB/04462/2020 and UIDP/04462/2020), and the Associate Laboratory LS4FUTURE (LA/P/0087/2020). Publisher Copyright: © 2023 by the authors.The Notch signaling ligand JAG1 is overexpressed in various aggressive tumors and is associated with poor clinical prognosis. Hence, therapies targeting oncogenic JAG1 hold great potential for the treatment of certain tumors. Here, we report the identification of specific anti-JAG1 single-chain variable fragments (scFvs), one of them endowing chimeric antigen receptor (CAR) T cells with cytotoxicity against JAG1-positive cells. Anti-JAG1 scFvs were identified from human phage display libraries, reformatted into full-length monoclonal antibodies (Abs), and produced in mammalian cells. The characterization of these Abs identified two specific anti-JAG1 Abs (J1.B5 and J1.F1) with nanomolar affinities. Cloning the respective scFv sequences in our second- and third-generation CAR backbones resulted in six anti-JAG1 CAR constructs, which were screened for JAG1-mediated T-cell activation in Jurkat T cells in coculture assays with JAG1-positive cell lines. Studies in primary T cells demonstrated that one CAR harboring the J1.B5 scFv significantly induced effective T-cell activation in the presence of JAG1-positive, but not in JAG1-knockout, cancer cells, and enabled specific killing of JAG1-positive cells. Thus, this new anti-JAG1 scFv represents a promising candidate for the development of cell therapies against JAG1-positive tumors.publishersversionpublishe

Aplicação da Calorimetria Exploratória Diferencial (DSC) para Determinação da Pureza de Fármacos

O trabalho aborda um estudo comparativo entre a técnica de Cromatografia a Líquido de Alta Eficiência e a técnica de Calorimetria Exploratória Diferencial, visando avaliar a aplicação desta para a determinação direta da pureza de fármacos candidatos a materiais de referência certificados

Comparative genomic analysis of Leishmania (Viannia) peruviana and Leishmania (Viannia) braziliensis

BACKGROUND: The Leishmania (Viannia) braziliensis complex is responsible for most cases of New World tegumentary leishmaniasis. This complex includes two closely related species but with different geographic distribution and disease phenotypes, L. (V.) peruviana and L. (V.) braziliensis. However, the genetic basis of these differences is not well understood and the status of L. (V.) peruviana as distinct species has been questioned by some. Here we sequenced the genomes of two L. (V.) peruviana isolates (LEM1537 and PAB-4377) using Illumina high throughput sequencing and performed comparative analyses against the L. (V.) braziliensis M2904 reference genome. Comparisons were focused on the detection of Single Nucleotide Polymorphisms (SNPs), insertions and deletions (INDELs), aneuploidy and gene copy number variations. RESULTS: We found 94,070 variants shared by both L. (V.) peruviana isolates (144,079 in PAB-4377 and 136,946 in LEM1537) against the L. (V.) braziliensis M2904 reference genome while only 26,853 variants separated both L. (V.) peruviana genomes. Analysis in coding sequences detected 26,750 SNPs and 1,513 indels shared by both L. (V.) peruviana isolates against L. (V.) braziliensis M2904 and revealed two L. (V.) braziliensis pseudogenes that are likely to have coding potential in L. (V.) peruviana. Chromosomal read density and allele frequency profiling showed a heterogeneous pattern of aneuploidy with an overall disomic tendency in both L. (V.) peruviana isolates, in contrast with a trisomic pattern in the L. (V.) braziliensis M2904 reference. Read depth analysis allowed us to detect more than 368 gene expansions and 14 expanded gene arrays in L. (V.) peruviana, and the likely absence of expanded amastin gene arrays. CONCLUSIONS: The greater numbers of interspecific SNP/indel differences between L. (V.) peruviana and L. (V.) braziliensis and the presence of different gene and chromosome copy number variations support the classification of both organisms as closely related but distinct species. The extensive nucleotide polymorphisms and differences in gene and chromosome copy numbers in L. (V.) peruviana suggests the possibility that these may contribute to some of the unique features of its biology, including a lower pathology and lack of mucosal development. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-015-1928-z) contains supplementary material, which is available to authorized users

A crise social desenhada pelas crianças: imaginação e conhecimento social

A crise social e económica que tem atingido o mundo desde 2008, com efeitos especialmente sentidos nos países do Sul da Europa, causou impactos fortes e visíveis na infância, como o aumento das taxas efetivas e de risco de pobreza e a vulnerabilidade e a exposição a fatores de risco social e de perda consistente de direitos. A análise dessas incidências tem vindo a ser trabalhada num conjunto de relatórios nacionais e internacionais, de ONG’s e estudos académicos. No entanto, poucos estudos têm dedicado atenção ao modo como a interpretação das representações das crianças sobre a crise é feita e sobre as expressões específicas que estas assumem na sua vida quotidiana. As crianças são capazes de observar os modos como a crise impacta o seu próprio grupo geracional, bem como os adultos que mais lhe são próximos. Da mesma forma, promovem interpretações económicas sobre os fenómenos, sejam elas mais “ingénuas” ou mais complexas. Este artigo incide sobre as representações das crianças sobre a crise social e económica em Portugal. São especialmente analisadas narrativas gráficas produzidas por crianças oriundas de classes trabalhadoras, com idades compreendidas entre os 6 e os 10 anos de idade. Por meio dessas narrativas, as crianças constroem formas visuais a partir da sua imaginação sobre a sua condição. Assim, a imaginação das crianças é um modo de acesso ao conhecimento na sociedade onde se inserem e aos seus modos próprios de compreensão de realidades complexas.The social and economic crisis that has hit the world since 2008, with effects strongly felt in the countries of Southern Europe, has had fierce and visible impacts in childhood with the increase of the effective rates, the risk of poverty and vulnerability, and the exposure to factors of social risk and consistent loss of rights. The analysis of these incidents has been worked on in a series of national and international reports from NGOs and academic studies. However, few studies have devoted attention to the way in which the interpretation of the representations of children about the crisis is made and the specific expressions that they assume in their daily lives. Children are able to observe the ways in which the crisis affects their own generational group as well as the adults closest to them. In the same way, they promote economic interpretations of phenomena, whether “naïve” or more complex. This article focuses on the representations of children about the social and economic crisis in Portugal. Graphical narratives produced by children from working classes, aged between 6 and 10 years old, are given focus. From these narratives, children construct visual forms from their imagination about their social condition. Thus, the child’s imagination is a way of accessing knowledge in the society they belong to and their own way of understanding complex realities.CIEC - Centro de Investigação em Estudos da Criança, IE, UMinho (UI 317 da FCT), Portugalinfo:eu-repo/semantics/publishedVersio

End TB strategy: the need to reduce risk inequalities.

BACKGROUND: Diseases occur in populations whose individuals differ in essential characteristics, such as exposure to the causative agent, susceptibility given exposure, and infectiousness upon infection in the case of infectious diseases. DISCUSSION: Concepts developed in demography more than 30 years ago assert that variability between individuals affects substantially the estimation of overall population risk from disease incidence data. Methods that ignore individual heterogeneity tend to underestimate overall risk and lead to overoptimistic expectations for control. Concerned that this phenomenon is frequently overlooked in epidemiology, here we feature its significance for interpreting global data on human tuberculosis and predicting the impact of control measures. We show that population-wide interventions have the greatest impact in populations where all individuals face an equal risk. Lowering variability in risk has great potential to increase the impact of interventions. Reducing inequality, therefore, empowers health interventions, which in turn improves health, further reducing inequality, in a virtuous circle