Consciousness: the last 50 years(and the next)

The mind and brain sciences began with consciousness as a central concern. But for much of the 20th century, ideological and methodological concerns relegated its empirical study to the margins. Since the 1990s, studying consciousness has regained a legitimacy and momentum befitting its status as the primary feature of our mental lives. Nowadays, consciousness science encompasses a rich interdisciplinary mixture drawing together philosophical, theoretical, computational, experimental, and clinical perspectives, with neuroscience its central discipline. Researchers have learned a great deal about the neural mechanisms underlying global states of consciousness, distinctions between conscious and unconscious perception, and self-consciousness. Further progress will depend on specifying closer explanatory mappings between (first-person subjective) phenomenological descriptions and (third-person objective) descriptions of (embodied and embedded) neuronal mechanisms. Such progress will help reframe our understanding of our place in nature and accelerate clinical approaches to a wide range of psychiatric and neurological disorders

Expression of microRNAs and target proteins in skeletal muscle of rats selectively bred for high and low running capacity

Impairments in mitochondrial function and substrate metabolism are implicated in the etiology of obesity and Type 2 diabetes. MicroRNAs (miRNAs) can degrade mRNA or repress protein translation and have been implicated in the development of such disorders. We used a contrasting rat model system of selectively bred high- (HCR) or low- (LCR) intrinsic running capacity with established differences in metabolic health to investigate the molecular mechanisms through which miRNAs regulate target proteins mediating mitochondrial function and substrate oxidation processes. Quantification of select miRNAs using the rat miFinder miRNA PCR array revealed differential expression of 15 skeletal muscles (musculus tibialis anterior) miRNAs between HCR and LCR rats (14 with higher expression in LCR; P < 0.05). Ingenuity Pathway Analysis predicted these altered miRNAs to collectively target multiple proteins implicated in mitochondrial dysfunction and energy substrate metabolism. Total protein abundance of citrate synthase (CS; miR-19 target) and voltage-dependent anion channel 1 (miR-7a target) were higher in HCR compared with LCR cohorts (~57 and ~26%, respectively; P < 0.05). A negative correlation was observed for miR-19a-3p and CS (r = 0.32, P = 0.015) protein expression. To determine whether miR-19a-3p can regulate CS in vitro, we performed luciferase reporter and transfection assays in C2C12 myotubes. MiR-19a-3p binding to the CS untranslated region did not change luciferase reporter activity; however, miR-19a-3p transfection decreased CS protein expression (∼70%; P < 0.05). The differential miRNA expression targeting proteins implicated in mitochondrial dysfunction and energy substrate metabolism may contribute to the molecular basis, mediating the divergent metabolic health profiles of LCR and HCR rat

Hybrid endoscopic thymectomy : combined transesophageal and transthoracic approach in a survival porcine model with cadaver assessment

BACKGROUND: Video-assisted thoracoscopic surgery thymectomy has been used in the treatment of Myastenia Gravis and thymomas (coexisting or not). In natural orifice transluminal endoscopic surgery, new approaches to the thorax are emerging as alternatives to the classic transthoracic endoscopic surgery. The aim of this study was to assess the feasibility and reliability of hybrid endoscopic thymectomy (HET) using a combined transthoracic and transesophageal approach. METHODS: Twelve consecutive in vivo experiments were undertaken in the porcine model (4 acute and 8 survival). The same procedure was assessed in a human cadaver afterward. For HET, an 11-mm trocar was inserted in the 2nd intercostal space in the left anterior axillary line. A 0° 10-mm thoracoscope with a 5-mm working channel was introduced. Transesophageal access was created through a submucosal tunnel using a flexible gastroscope with a single working channel introduced through the mouth. Using both flexible (gastroscope) and rigid (thoracoscope) instruments, the mediastinum was opened; the thymus was dissected, and the vessels were ligated using electrocautery alone. RESULTS: Submucosal tunnel creation and esophagotomy were performed safely without incidents in all animals. Complete thymectomy was achieved in all experiments. All animals in the survival group lived for 14 days. Thoracoscopic and postmortem examination revealed pleural adhesions on site of the surgical procedure with no signs of infection. Histological analysis of the proximal third of the esophagus revealed complete cicatrization of both mucosal defect and myotomy site. In the human cadaver, we were able to replicate all the procedure even though we were not able to identify the thymus. CONCLUSIONS: Hybrid endoscopic thymectomy is feasible and reliable. HET could be regarded as a possible alternative to classic thoracoscopic approach for patients requiring thymectomy.This project was funded by the FCT Grants project PTDC/SAU-OSM/105578/2008

Influence of dietary supplementation with an amino acid mixture on inflammatory markers, immune status and serum proteome in lps-challenged weaned piglets

In order to investigate the effect of a dietary amino acid mixture supplementation in lipopolysaccharide (LPS)-challenged weaned piglets, twenty-seven 28-day-old (8.2 ± 1.0 kg) newly weaned piglets were randomly allocated to one of three experimental treatments for five weeks. Diet 1: a CTRL treatment. Diet 2: an LPS treatment, where piglets were intraperitoneally administered LPS (25 µg/kg) on day 7. Diet 3: an LPS+MIX treatment, where piglets were intraperitoneally administered LPS on day 7 and fed a diet supplemented with a mixture of 0.3% of arginine, branched-chain amino acids (leucine, valine, and isoleucine), and cystine (MIX). Blood samples were drawn on day 10 and day 35, and serum was analysed for selected chemical parameters and proteomics. The LPS and LPS+MIX groups exhibited an increase in haptoglobin concentrations on day 10. The LPS group showed an increased cortisol concentration, while this concentration was reduced in the LPS+MIX group compared to the control group. Similarly, the LPS+MIX group showed a decreased haptoglobin concentration on day 35 compared to the two other groups. Immunoglobulin concentrations were affected by treatments. Indeed, on day 10, the concentrations of IgG and IgM were decreased by the LPS challenge, as illustrated by the lower concentrations of these two immunoglobulins in the LPS group compared to the control group. In addition, the supplementation with the amino acid mixture in the LPS+MIX further decreased IgG and increased IgM concentrations compared to the LPS group. Although a proteomics approach did not reveal important alterations in the protein profile in response to treatments, LPS-challenged piglets had an increase in proteins linked to the immune response, when compared to piglets supplemented with the amino acid mixture. Overall, data indicate that LPS-challenged piglets supplemented with this amino acid mixture are more protected against the detrimental effects of LPS.This study was supported by Ajinomoto Animal Nutrition Europe, by Indukern Portugal, Lda., and by Fundação para a Ciência e a Tecnologia (FCT, Lisbon, Portugal) through projects UIDB/CVT/00276/2020 to CIISA and PEST/UID/AGR/4129/2020 to LEAF. It was also supported by national funds, through FCT Stimulus of Scientific Employment Program to author P.A.L. (DL57/2016/CP1438/CT0007) and a Ph.D. grant (SFRH/BD/143992/2019) to author D.M.R. This work had the support from the Portuguese Mass Spectrometry Net-work, integrated in the National Roadmap of Research Infrastructures of Strategic Relevance (ROTEIRO/0028/2013; LISBOA-01-0145-FEDER-022125)

Serum amyloid A proteins reduce bone mass during mycobacterial infections

IntroductionOsteopenia has been associated to several inflammatory conditions, including mycobacterial infections. How mycobacteria cause bone loss remains elusive, but direct bone infection may not be required. MethodsGenetically engineered mice and morphometric, transcriptomic, and functional analyses were used. Additionally, inflammatory mediators and bone turnover markers were measured in the serum of healthy controls, individuals with latent tuberculosis and patients with active tuberculosis. Results and discussionWe found that infection with Mycobacterium avium impacts bone turnover by decreasing bone formation and increasing bone resorption, in an IFN gamma- and TNF alpha-dependent manner. IFN gamma produced during infection enhanced macrophage TNF alpha secretion, which in turn increased the production of serum amyloid A (SAA) 3. Saa3 expression was upregulated in the bone of both M. avium- and M. tuberculosis-infected mice and SAA1 and 2 proteins (that share a high homology with murine SAA3 protein) were increased in the serum of patients with active tuberculosis. Furthermore, the increased SAA levels seen in active tuberculosis patients correlated with altered serum bone turnover markers. Additionally, human SAA proteins impaired bone matrix deposition and increased osteoclastogenesis in vitro. Overall, we report a novel crosstalk between the cytokine-SAA network operating in macrophages and bone homeostasis. These findings contribute to a better understanding of the mechanisms of bone loss during infection and open the way to pharmacological intervention. Additionally, our data and disclose SAA proteins as potential biomarkers of bone loss during infection by mycobacteria.This article is a result of the project HEALTH-UNORTE: Setting-up biobanks and regenerative medicine strategies to boost research in cardiovascular, musculoskeletal, neurological, oncological, immunological and infectious diseases (NORTE-01-0145-FEDER-000039), supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF). This work was supported by KOG-202108-00929 from the European Haematology Society, awarded to AG. Work in the MS lab was financed by FEDER - Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020 - Operacional Programme for Competitiveness and Internationalisation (POCI), Portugal 2020, and by Portuguese funds through FCT - Fundacao para a Ciencia e a Tecnologia/Ministerio da Ciencia, Tecnologia e Ensino Superior in the framework of the project POCI-01-0145-FEDER-028955 (PTDC/SAU-INF/28955/2017). AG and MS are supported by an Individual Scientific Employment contract (CEECIND/00048/2017; CEECIND/00241/2017 respectively). DS acknowledges the Portuguese Foundation for Science and Technology (FCT) for the Post-Doc fellowship (SFRH/BPD/115341/2016). RP, DS and AF have PhD grants (SFRH/BD/145217/2019; SFRH/BD/143536/2019; 2020.05949.BD, respectively) financed by FCT

Cognitive Function in Young Persons With and Without Perinatal HIV in the AALPHI Cohort in England: Role of Non-HIV-Related Factors

BACKGROUND:  There is limited evidence about the cognitive performance of older adolescents with perinatally acquired human immunodeficiency virus (HIV) compared with HIV-negative (HIV-) adolescents. METHODS:  A total of 296 perinatally HIV-infected (PHIV+) and 97 HIV- adolescents (aged 12-21 and 13-23 years, respectively) completed 12 tests covering 6 cognitive domains. The HIV- participants had PHIV+ siblings and/or an HIV-infected mother. Domain-specific and overall (NPZ-6) z scores were calculated for PHIV+ participants, with or without Centers for Disease Control and Prevention (CDC) stage C disease, and HIV- participants. Linear regression was performed to explore predictors of NPZ-6. RESULTS:  One hundred twenty-five (42%) of the PHIV+ and 31 (32%) of the HIV- participants were male; 251 (85%) and 69 (71%), respectively, were black African; and their median ages (interquartile range) were 16 (15-18) and 16 (14-18) years, respectively. In PHIV+ participants, 247 (86%) were receiving antiretroviral therapy, and 76 (26%) had a previous CDC C diagnosis. The mean (standard deviation) NPZ-6 score was -0.81 (0.99) in PHIV+ participants with a CDC C diagnosis (PHIV+/C), -0.45 (0.80) in those without a CDC C diagnosis (PHIV+/no C), and -0.32 (0.76) in HIV- participants (P < .001). After adjustment, there was no difference in NPZ-6 scores between PHIV+/no C and HIV- participants (adjusted coefficient, -0.01; 95% confidence interval, -.22 to .20). PHIV+/C participants scored below the HIV- group (adjusted coefficient, -0.44; -.70 to -.19). Older age predicted higher NPZ-6 scores, and black African ethnicity and worse depression predicted lower NPZ-6 scores. In a sensitivity analysis including PHIV+ participants only, no HIV-related factors apart from a CDC C diagnosis were associated with NPZ-6 scores. CONCLUSIONS:  Cognitive performance was similar between PHIV+/no C and HIV- participants and indicated relatively mild impairment compared with normative data. The true impact on day-to-day functioning needs further investigation

Body composition and body fat distribution are related to cardiac autonomic control in non-alcoholic fatty liver disease patients

BACKGROUND/OBJECTIVES: Heart rate recovery (HRR), a cardiac autonomic control marker, was shown to be related to body composition (BC), yet this was not tested in non-alcoholic fatty liver disease (NAFLD) patients. The aim of this study was to determine if, and to what extent, markers of BC and body fat (BF) distribution are related to cardiac autonomic control in NAFLD patients. SUBJECTS/METHODS: BC was assessed with dual-energy X-ray absorptiometry in 28 NAFLD patients (19 men, 51±13 years, and 9 women, 47±13 years). BF depots ratios were calculated to assess BF distribution. Subjects’ HRR was recorded 1 (HRR1) and 2 min (HRR2) immediately after a maximum graded exercise test. RESULTS: BC and BF distribution were related to HRR; particularly weight, trunk BF and trunk BF-to-appendicular BF ratio showed a negative relation with HRR1 (r 1⁄4 0.613, r 1⁄4 0.597 and r 1⁄4 0.547, respectively, Po0.01) and HRR2 (r 1⁄4 0.484, r 1⁄4 0.446, Po0.05, and r 1⁄4 0.590, Po0.01, respectively). Age seems to be related to both HRR1 and HRR2 except when controlled for BF distribution. The preferred model in multiple regression should include trunk BF-to-appendicular BF ratio and BF to predict HRR1 (r2 1⁄4 0.549; Po0.05), and trunk BF-to-appendicular BF ratio alone to predict HRR2 (r2 1⁄4 0.430; Po0.001). CONCLUSIONS: BC and BF distribution were related to HRR in NAFLD patients. Trunk BF-to-appendicular BF ratio was the best independent predictor of HRR and therefore may be best related to cardiovascular increased risk, and possibly act as a mediator in age-related cardiac autonomic control variation.info:eu-repo/semantics/publishedVersio

Global and regional estimates of cancer mortality and incidence by site: II. results for the global burden of disease 2000

BACKGROUND: Mortality estimates alone are not sufficient to understand the true magnitude of cancer burden. We present the detailed estimates of mortality and incidence by site as the basis for the future estimation of cancer burden for the Global Burden of Disease 2000 study. METHODS: Age- and sex- specific mortality envelope for all malignancies by region was derived from the analysis of country life-tables and cause of death. We estimated the site-specific cancer mortality distributions from vital records and cancer survival model. The regional cancer mortality by site is estimated by disaggregating the regional cancer mortality envelope based on the mortality distribution. Estimated incidence-to-mortality rate ratios were used to back calculate the final cancer incidence estimates by site. RESULTS: In 2000, cancer accounted for over 7 million deaths (13% of total mortality) and there were more than 10 million new cancer cases world wide in 2000. More than 60% of cancer deaths and approximately half of new cases occurred in developing regions. Lung cancer was the most common cancers in the world, followed by cancers of stomach, liver, colon and rectum, and breast. There was a significant variations in the distribution of site-specific cancer mortality and incidence by region. CONCLUSIONS: Despite a regional variation, the most common cancers are potentially preventable. Cancer burden estimation by taking into account both mortality and morbidity is an essential step to set research priorities and policy formulation. Also it can used for setting priorities when combined with data on costs of interventions against cancers

Cadmium accumulation and interactions with zinc, copper, and manganese, analysed by ICP-MS in a long-term Caco-2 TC7 cell model

The influence of long-term exposure to cadmium (Cd) on essential minerals was investigated using a Caco-2 TC7 cells and a multi-analytical tool: microwave digestion and inductively coupled plasma mass spectrometry. Intracellular levels, effects on cadmium accumulation, distribution, and reference concentration ranges of the following elements were determined: Na, Mg, Ca, Cr, Fe, Mn, Co, Ni, Cu, Zn, Mo, and Cd. Results showed that Caco-2 TC7 cells incubated long-term with cadmium concentrations ranging from 0 to 10 lmol Cd/l for 5 weeks exhibited a significant increase in cadmium accumulation. Furthermore, this accumulation was more marked in cells exposed long-term to cadmium compared with controls, and that this exposure resulted in a significant accumulation of copper and zinc but not of the other elements measured. Interactions of Cd with three elements: zinc, copper, and manganese were particularly studied. Exposed to 30 lmol/l of the element, manganese showed the highest inhibition and copper the lowest on cadmium intracellular accumulation but Zn, Cu, and Mn behave differently in terms of their mutual competition with Cd. Indeed, increasing cadmium in the culture medium resulted in a gradual and significant increase in the accumulation of zinc. There was a significant decrease in manganese from 5 lmol Cd/l exposure, and no variation was observed with copper. Abbreviation: AAS – Atomic absorption spectrometry; CRM– Certified reference material; PBS – Phosphate buffered saline without calcium and magnesium; DMEM – Dubelcco’s modified Eagle’s medium

Secular evolution versus hierarchical merging: galaxy evolution along the Hubble sequence, in the field and rich environments

In the current galaxy formation scenarios, two physical phenomena are invoked to build disk galaxies: hierarchical mergers and more quiescent external gas accretion, coming from intergalactic filaments. Although both are thought to play a role, their relative importance is not known precisely. Here we consider the constraints on these scenarios brought by the observation-deduced star formation history on the one hand, and observed dynamics of galaxies on the other hand: the high frequency of bars and spirals, the high frequency of perturbations such as lopsidedness, warps, or polar rings. All these observations are not easily reproduced in simulations without important gas accretion. N-body simulations taking into account the mass exchange between stars and gas through star formation and feedback, can reproduce the data, only if galaxies double their mass in about 10 Gyr through gas accretion. Warped and polar ring systems are good tracers of this accretion, which occurs from cold gas which has not been virialised in the system's potential. The relative importance of these phenomena are compared between the field and rich clusters. The respective role of mergers and gas accretion vary considerably with environment.Comment: 18 pages, 8 figures, review paper to "Penetrating Bars through Masks of Cosmic Dust: the Hubble Tuning Fork Strikes a New Note", Pilanesberg, ed. D. Block et al., Kluwe