Linking appraisal to behavioral flexibility in animals: implications for stress research

In fluctuating environments, organisms require mechanisms enabling the rapid expression of context-dependent behaviors. Here, we approach behavioral flexibility from a perspective rooted in appraisal theory, aiming to provide a better understanding on how animals adjust their internal state to environmental context. Appraisal has been defined as a multi-component and interactive process between the individual and the environment, in which the individual must evaluate the significance of a stimulus to generate an adaptive response. Within this framework, we review and reframe the existing evidence for the appraisal components in animal literature, in an attempt to reveal the common ground of appraisal mechanisms between species. Furthermore, cognitive biases may occur in the appraisal of ambiguous stimuli. These biases may be interpreted either as states open to environmental modulation or as long-lasting phenotypic traits. Finally, we discuss the implications of cognitive bias for stress research.FCT Ph.D. fellowships: (SFRH/BD/79087/2011, SFRH/BD/68528/2010), FCT strategic grant: (PEst-OE/MAR/UI0331/2011)

Mechanisms of social buffering of fear in zebrafish

The supplementary materials such the videos, are not present in the deposit due to incompatibilty of the extension of the files with the repository.Some humans thrive whereas others resign when exposed to threatening situations throughout life. Social support has been identified as an important modulator of these discrepancies in human behaviour, and other social animals also exhibit phenomena in which individuals recover better from aversive events when conspecifics are present - aka social buffering. Here we studied social buffering in zebrafish, by exposing focal fish to an aversive stimulus (alarm substance - AS) either in the absence or presence of conspecific cues. When exposed to AS in the presence of both olfactory (shoal water) and visual (sight of shoal) conspecific cues, focal fish exhibited a lower fear response than when tested alone, demonstrating social buffering in zebrafish. When separately testing each cue's effectiveness, we verified that the visual cue was more effective than the olfactory in reducing freezing in a persistent threat scenario. Finally, we verified that social buffering was independent of shoal size and coincided with a distinct pattern of co-activation of brain regions known to be involved in mammalian social buffering. Thus, this study suggests a shared evolutionary origin for social buffering in vertebrates, bringing new evidence on the behavioural, sensory and neural mechanisms underlying this phenomenon.info:eu-repo/semantics/publishedVersio

Chemical carcinogens

This chapter is part of the book “Oxford Textbook of Oncology” that gives a whole view of cancer, approaching basic concepts of oncology, etiology, epidemiology, care and characteristics of cancer in specific places. It is focused on chemical carcinogens, reviewing the origin of these compounds, their classification and mode of action, their absorption and metabolism, and the methods available to test carcinogenicity. This title includes an extensive list of main chemical compounds and a schematic representation of the absorption and metabolism of direct and indirect chemical carcinogenesis, and the process of carcinogenesis. The title was written for qualified specialist doctors in the oncology research

Anatomia e Fisiologia: evoluindo de “mãos dadas”

A Anatomia e a Fisiologia encontram-se intimamente ligadas e são unidades curriculares fundamentais em inúmeros cursos ligados às ciências da vida. Documentos ancestrais comprovam que a história da Anatomia e da Fisiologia teve início na Grécia e encontra-se associada a Hipócrates (460-370 a.C.), conhecido como o Pai da Medicina, e à sua obra “Corpus Hippocraticus”. O médico grego Claudius Galeno (129-200 d.C.) desenvolveu trabalhos nas áreas da Anatomia e da Fisiologia. Dos resultados das suas experiências em animais surge o conceito de fisiologia experimental. Galeno é considerado o “pai” da fisiologia experimental e a sua obra “Sobre o uso das partes do corpo humano” regeu a Medicina por catorze séculos, após os quais algumas das suas teorias foram contestadas. Os artistas renascentistas, como Leonardo da Vinci e Michelangelo, estudavam os corpos para obter perfeição nas formas artísticas, contribuindo para o desenvolvimento da Anatomia. Em plena época do Renascimento, surgiu pela primeira vez o significado da palavra Fisiologia de acordo com a definição de Jean Fernel (1497-1558). Este ficou conhecido pela célebre frase: “A Anatomia está para a Fisiologia como a Geografia está para a História: ambas descrevem o teatro de operações”. Jean Fernel é o marco entre a medicina medieval e a medicina da idade moderna. Vesalius (1514-1564) corrigiu erros de outros anatomistas e escreveu a obra “De humani corporis fabrica” que contribuiu para o reconhecimento da Anatomia como ciência básica. Já no século XVII, uma das maiores contribuições para a Fisiologia data de 1628, ano da publicação da obra “Exercitatio Anatomica de Motu Cordis et Sanguinis in Animalibus”, de William Harvey (1578-1657), onde pela primeira vez se descreveu a anatomia e o movimento do coração e a consequente circulação do sangue pelo corpo. O “De Motu Cordis” foi o primeiro tratado da época moderna dedicado a um tema estritamente fisiológico. Em 1876 foi fundada, em Londres, a Sociedade de Fisiologia e em 1887 nos Estados Unidos da América foi fundada a Sociedade de Fisiologia Americana. Ambas se dedicavam à investigação científica, educação e disseminação de conceitos relacionados com a fisiologia. O primeiro Congresso internacional de Anatomia decorreu em 1895, em Basileia

Cell-free layer analysis in a polydimethysiloxane microchannel: A global approach

The cell-free layer (CFL) is a hemodynamic phenomenon that has an important contribution to the rheological properti es of blood flowing in microvessels. The present work aims to find the closest function describing RBCs flowing around the cell depleted layer in a polydimethysiloxane (PDMS) microchannel with a diverging and a converging bifurcation. The flow behaviour of the CFL was investigated by using a high-speed video microscopy system where special attention was devoted to its behaviour before the bifurcation and after the confluence of the microchannel. The numerical data was first obtained by using a manual tracking plugin and then analysed using the genetic algorithm approach. The results show that for the majority of the cases the function that more closely resembles the CFL boundary is the sum of trigonometric functions.The authors acknowledge the financial support provided by PTDC/SAU-ENB/116929/ 2010 and EXPL/EMS-SIS/2215/2013 from FCT (Science and Technology Foundation), COMPETE, QREN and European Union (FEDER). R.O. Rodrigues, D. Pinho and V. Faustino acknowledge respectively, the PhD scholarships SFRH/BD/97658/2013, SFRH/BD/89077/2012 and SFRH/BD/99696/2014 granted by FCT.info:eu-repo/semantics/publishedVersio

Histopathological features of organs in a rat model of mamamry carcinogenesis: a reference database

Mammary tumors’ development was induced through the intraperioneal administration of the carcinogen N-methyl-N-nitrosourea (MNU). Animals from group control were injected with the vehicle (saline solution). Animals were sacrificed at 25 weeks-old and the organs were histopathologically evaluated. A higher number of lesions was observed in the organs of animals from group MNU. The animals from group control did not present any lesion in lymph nodes. Independently of the experimental group, the internal organs presented hemodynamic alterations, degenerative and inflammatory changes. Hemodynamic changes may be consequence of euthanasia method. As expected, the higher number and the higher grade of the lesions in group MNU were due to the carcinogen administration.info:eu-repo/semantics/publishedVersio

Evaluation of renal injury caused by acute volume replacement with hydroxyethyl starch 130/0.4 or Ringer's lactate solution in pigs

This work aimed to evaluate the effects on renal tissue integrity after hydroxyethyl starch (HES) 130/0.4 and Ringer’s lactate (RL) administration in pigs under general anesthesia after acute bleeding. A total of 30 mL/kg of blood were passively removed from the femoral artery in two groups of Large White pigs, under total intravenous anesthesia with propofol and remifentanil. After bleeding, Group 1 (n =11) received RL solution (25 mL/kg) and Group 2 (n = 11) received HES 130/0.4 solution (20 mL/kg). Additionally, Group 3 (n = 6) was not submitted to bleeding or volume replacement. Pigs were euthanized and kidneys were processed for histopathological and immunohistochemical analyses. Minimal to moderate glomerular, tubular, and interstitial changes, as well as papillary necrosis, were observed in all experimental groups. Pre-apoptosis and apoptosis indicators were higher in pigs that received HES 130/0.4, indicating a higher renal insult. Both HES 130/0.4 and RL administration may cause renal injury, although renal injury may be more significant in pigs receiving HES 13/0.4. Results also suggest that total intravenous anesthesia with propofol and remifentanil may cause renal injury, and this effect can be dose related.info:eu-repo/semantics/publishedVersio

Label-free multi-step microfluidic device for mechanical characterization of blood cells: Diabetes type II

The increasing interest to establish significant correlations between blood cell mechanical measurements and blood diseases, has led to the promotion of microfluidic devices as attractive clinical tools for potential use in diagnosis. A multi-step microfluidic device able to separate red and white blood cells (RBCs and WBCs) from plasma and simultaneously measure blood cells deformability (5 and 20% of hematocrit) is presented in this paper. The device employs passive separation based on the cross-flow filtration principle, introduced at each daughter channel. At the outlets, hyperbolic geometries allow single-cell deformability analysis. The device was tested with blood from five healthy and fifteen diabetic type II voluntary donors. The results have shown that WBCs have lower deformability than RBCs, and no significant differences were observed in WBCs from healthy and pathological blood samples. In contrast, RBCs have shown significant differences, with pathological cells exhibiting lower deformability. Shear rheology has shown that blood from patients with type II diabetes has higher viscosity than blood from healthy donors. This microfluidic device has demonstrated the ability to reduce cell concentration at the outlets down to 1%, an ideal cell concentration for assessing the blood cells deformability, under healthy and pathological conditions. The results provide new insights and quantitative information about the hemodynamics of in vitro type II diabetes mellitus RBCs. Thus, such device can be a promising complement in clinical diagnosis and biological research as part of an integrated blood-on-a-chip system.This work was supported by Projects NORTE-01-0145-FEDER- 028178, NORTE-01-0145-FEDER-029394, NORTE-01-0145-FEDER- 030171 funded by COMPETE2020, NORTE2020, PORTUGAL2020, and FEDER. This work was also supported by Fundação para a Ciência e a Tecnologia (FCT) under the strategic grants UIDB/04077/2020 and UIDB/00532/2020. D. Pinho and V. Faustino acknowledge the Ph.D. scholarships SFRH/BD/89077/2012 and SFRH/BD/99696/2014, respectively, both provided by FCT. Susana Catarino thanks FCT for her contract funding provided through 2020.00215.CEECIND. F. T. Pinho is thankful to FCT for financial support through projects LA/P/0045/2020 of the Associate Laboratory in Chemical Engineering (ALiCE) and projects UIDB/00532/2020 and UIDP/00532/2020 of Centro de Estudos de Fenómenos de Transporte.info:eu-repo/semantics/publishedVersio

Synthesis of bioconjugate sesterterpenoids with phospholipids and polyunsaturated fatty acids

A series of sesterterpenoid bioconjugates with phospholipids and polyunsaturated fatty acids (PUFAs) have been synthesized for biological activity testing as antiproliferative agents in several cancer cell lines. Different substitution analogues of the original lipidic ether edelfosine (1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine) are obtained varying the sesterterpenoid in position 1 or 2 of the glycerol or a phosphocholine or PUFA unit in position 3. Simple bioconjugates of sesterterpenoids and eicosapentaenoic acid (EPA) have been obtained too. All synthetic derivatives were tested against the human tumour cell lines HeLa (cervix) and MCF-7 (breast). Some compounds showed good IC50 (0.3 and 0.2 μM) values against these cell lines.This work was supported by grants from the Spanish Ministry of Economy and Competitiveness (SAF2011-30518 and SAF2014-59716-R). Junta de Castilla y León BIO/SA59/15.Peer reviewe

Label-free multi-step microfluidic device for mechanical characterization of blood cells: diabetes type II

The increasing interest to establish significant correlations between blood cell mechanical measurements and blood diseases, has led to the promotion of microfluidic devices as attractive clinical tools for potential use in diagnosis. A multi-step microfluidic device able to separate red and white blood cells (RBCs and WBCs) from plasma and simultaneously measure blood cells deformability (5 and 20% of hematocrit) is presented in this paper. The device employs passive separation based on the cross-flow filtration principle, introduced at each daughter channel. At the outlets, hyperbolic geometries allow single-cell deformability analysis. The device was tested with blood from five healthy and fifteen diabetic type II voluntary donors. The results have shown that WBCs have lower deformability than RBCs, and no significant differences were observed in WBCs from healthy and pathological blood samples. In contrast, RBCs have shown significant differences, with pathological cells exhibiting lower deformability. Shear rheology has shown that blood from patients with type II diabetes has higher viscosity than blood from healthy donors. This microfluidic device has demonstrated the ability to reduce cell concentration at the outlets down to 1%, an ideal cell concentration for assessing the blood cells deformability, under healthy and pathological conditions. The results provide new insights and quantitative information about the hemodynamics of in vitro type II diabetes mellitus RBCs. Thus, such device can be a promising complement in clinical diagnosis and biological research as part of an integrated blood-on-a-chip system.This work was supported by Projects NORTE-01-0145-FEDER-028178, NORTE-01-0145-FEDER-029394, NORTE-01-0145-FEDER-030171 funded by COMPETE2020, NORTE2020, PORTUGAL2020, and FEDER. This work was also supported by Fundacao para a Ciencia e a Tecnologia (FCT) under the strategic grants UIDB/04077/2020 and UIDB/00532/2020. D. Pinho and V. Faustino acknowledge the Ph.D. scholarships SFRH/BD/89077/2012 and SFRH/BD/99696/2014, respectively, both provided by FCT. Susana Catarino thanks FCT for her contract funding provided through 2020.00215.CEECIND. F. T. Pinho is thankful to FCT for financial support through projects LA/P/0045/2020 of the Associate Laboratory in Chemical Engineering (ALiCE) and pro-jects UIDB/00532/2020 and UIDP/00532/2020 of Centro de Estudos de Fenomenos de Transporte