The genetic prehistory of Northern Calabria. Archeogenomic investigation of the human remains from Grotta di Pietra Sant’Angelo and Grotta della Monaca.

Given its strategic position at the center of the Mediterranean Basin, and its unique history of contacts and migrations, Calabria is an ideal region to decipher the genetic traces of at least some of the numerous demographic prehistoric events in Southern Italy. This thesis focuses on the genetic and social changes of ancient inhabitants of Calabria, covering a timeline of approximately 7000 to 3300 years ago, ranging from the Middle Neolithic to the Middle Bronze Age. We generated the first genome-wide data from Calabria, by focusing on the single inhumation of “Grotta di Pietra Sant’Angelo” (San Lorenzo Bellizzi, Cosenza) and on the vast community found buried in “Grotta della Monaca” (Sant’Agata di Esaro, Cosenza). Supported by archaeological evidence, the primary objective of this research was to employ paleogenomic evidence to decipher funerary customs, social organization, family ties, and demographic shifts in Southern Italy over a period extending beyond three millennia. The possibility of gender-related burial practices and kinship ties among the deceased was also explored. Subsequently, the biogeographical origin and ancestry of prehistoric people of Calabria was contextualized within the broad landscape of existing data on Mediterranean populations. By generating the first genomic evidence from prehistoric Calabria, unresolved questions were addressed, related to the appearance and persistence of distinct genomic components, such as the Iran-related and the Steppe-related ancestry, whose impact on ancient Southern Italian genomes remains uncharted.

The predictive role of the human gut microbiota in covid-19: implications for disease severity and post-covid syndrome

The COVID-19 pandemic, sparked by the SARS-CoV-2 virus, stirred global comparisons to historical pandemics. Initially presenting a high mortality rate, it later stabilized globally at around 0.5-3%. Patients manifest a spectrum of symptoms, necessitating efficient triaging for appropriate treatment strategies, ranging from symptomatic relief to antivirals or monoclonal antibodies. Beyond traditional approaches, emerging research suggests a potential link between COVID-19 severity and alterations in gut microbiota composition, impacting inflammatory responses. However, most studies focus on severe hospitalized cases without standardized criteria for severity. Addressing this gap, the first study in this thesis spans diverse COVID-19 severity levels, utilizing 16S rRNA amplicon sequencing on fecal samples from 315 subjects. The findings highlight significant microbiota differences correlated with severity. Machine learning classifiers, including a multi-layer convoluted neural network, demonstrated the potential of microbiota compositional data to predict patient severity, achieving an 84.2% mean balanced accuracy starting one week post-symptom onset. These preliminary results underscore the gut microbiota's potential as a biomarker in clinical decision-making for COVID-19. The second study delves into mild COVID-19 cases, exploring their implications for ‘long COVID’ or Post-Acute COVID-19 Syndrome (PACS). Employing longitudinal analysis, the study unveils dynamic shifts in microbial composition during the acute phase, akin to severe cases. Innovative techniques, including network approaches and spline-based longitudinal analysis, were deployed to assess microbiota dynamics and potential associations with PACS. The research suggests that even in mild cases, similar mechanisms to hospitalized patients are established regarding changes in intestinal microbiota during the acute phase of the infection. These findings lay the foundation for potential microbiota-targeted therapies to mitigate inflammation, potentially preventing long COVID symptoms in the broader population. In essence, these studies offer valuable insights into the intricate relationships between COVID-19 severity, gut microbiota, and the potential for innovative clinical applications.

A internação forçada do toxicodependente : uma perspectiva brasileira, sob um contraste lusitano, acerca da proporcionalidade da medida em face da dignidade da pessoa humana

A presente dissertação busca abordar a questão da restrição ao direito fundamental de liberdade da pessoa toxicodependente no Brasil, consistente, precisamente, na internação forçada para o tratamento de sua saúde e/ou para a segurança pública, sob o olhar do princípio constitucional da dignidade da pessoa humana em suas dimensões positiva, que exige uma obrigação de fazer por parte do Estado, e negativa, que cobra deste uma postura omissiva de proteção, em torno de um mesmo indivíduo; sem se olvidar do interesse público na execução da medida. Para tanto, ao longo do trabalho, a legislação brasileira atinente ao tema é posta em comparação com a sua correspondente portuguesa e, à luz, basicamente, das doutrinas desses países, são examinados direitos afetos à liberdade individual e ao direito social à saúde, sob a costura do apontado princípio estruturante das respectivas Constituições, de modo a permitir a visualização do amparo da medida restritiva no texto maior brasileiro e, ao final, uma análise crítica à ponderação de bens (direitos) realizada pelo legislador ordinário, com possíveis soluções para a sua aplicação em concreto, quando da análise da proporcionalidade da intervenção da liberdade pelo Poder Judiciário.

Gestão dos recursos hídricos no processo de desenvolvimento sustentável de Cabo Verde: uma proposta

A água é vital para a sobrevivência, saúde e dignidade do ser humano e uma fonte fundamental para o seu desenvolvimento. As reservas de água potável no mundo estão sob pressão constante embora muitos ainda não tenham acesso a esse precioso líquido para atender ás necessidades básicas. A água é um recurso natural com valor económico, estratégico e social. A percepção da escassez tem levado governos, a reorganizar o ambiente institucional e definir novos direitos de propriedade por meio de um sistema de gestão participativo e descentralizado que estimule a utilização do recurso de forma racional. A investigação está direccionada à gestão e à implementação da Lei n.º 41/II/84 de 18 de Junho, que Aprova o Código de Águas que estabelece as bases gerais do regime jurídico de propriedade, protecção, conservação, desenvolvimento, administração e uso dos recursos. O enfoque da pesquisa é as Instituições Governamentais que lidam com a água e as Associações de Bacias hidrográficas que, com os seus olhares e saberes, contribuem com informações para que se construa uma Proposta de Modelo de Gestão numa perspectiva de sustentabilidade. A proposta de modelo pretende contribuir para uma gestão sustentada. A pesquisa é do tipo qualitativa e usa como metodologia o Estudo de Caso. Foi constatada a complexidade da gestão das águas em Cabo Verde, na qual existem ainda muitos entraves e desafios. A Bacia Hidrográfica é a unidade básica de gestão, onde as Associações, as Câmaras Municipais, os Serviços Autónomos de Água e Saneamento, o Instituto Nacional de Gestão dos recursos Hidricos desempenham o papel de gerí-la e preservá-la. Foram identificados como dificuldades: a posse da água não está bem clara, o que dificulta a gestão da Bacia; os conflitos sociais são frequentes quanto ao uso da água no que tange à poluição; a população rural não está devidamente contemplada na gestão dos recursos hídricos. Por fim, constatou-se que Cabo Verde possui as ferramentas para a evolução da Gestão dos Recursos Hídricos, que é o Código de Água. Water is vital for the survival, health and dignity of the human being and a basic source for development. The drinking waters reserves in the world are under constant pressure. The water can be considered a natural resource with economic, strategically and social values. The perception of the scarcity has taken governments, to reorganize the institutional environment and to define new rights of property by means of participation and decentralized system of management that stimulates the use of the resource in rational form. This investigation addressed the Administration of Water Resources in Cabo Verde and the implementation of Law n.º 41/II/84 of 18 of June, which established the National Policy of Water Resources and the National System of Management. The approach of the research is the Governmental Institutions that deal with the water and the Associations that, at a glance, contribute with information that builds the proposal of water resources management in a sustainability perspective. The proposal has as objective to provide subsidies to advance more and more the research regarding sustainability in the administration of waters. The research was qualitative and it used as methodology the Study Case. We identified as difficulties: the ownership of the water is not well clear; the social conflicts are frequent concerning how to use the water. Finally, it was evidenced that Cape Verde has the tools for the evolution of water resources management, which is the Water Code.

Rummet i vårdandets värld

This study is made in the context of basic research within the field ofcaring science. The aim is to make a theoretical and ontological investigation of what the space is in the world of caring. The basic proposition is that the space, as a fundamental dimension, has an impact on how the appreciation of one's mental health and suffering is shaped, and vice versa. The overall purpose is to develop a theoretical model of space from the caring science point of view andalso to offer an ideal concept of space to caring science. Guided by a theoretical horizon (Eriksson 1993, Eriksson 1995, Eriksson 2001) and methodological approach grounded in Gadamer's philosophic and existential hermeneutics a three-stage analysis and interpretation is conducted. The hermeneutic spiral of this investigation starts through a procedure in accordance with Eriksson's model (1997) of concept definition. The goal is to clarify the etymology of the concept as well as semantic differences between synonymous concepts, i.e. to identify the different extents of the concept of `space` (`rum`) in order to bring these closer for an exploration. The second phase is to analyse and interpret a sample of narratives in order to explicate the ontological nature and meaning of the space. The material used here is literary texts. The goal is to clarify the characteristics of the very inside of the space when it is shaped in relation to the human being in encountering suffering. In the third phase an interview study is taken place. The focus of the study is directed towards the phenomenon of space as it is known by a patient in a landscape of psychiatric care, i.e. what the space is in a contextual meaning. Then, a gradual hermeneutic understanding of the space is attempted by using theories from the field of caring science as well as additional theories from other disciplines. Metaphors are used as they are vivid and expressive tools for generating meaning. Different metaphoric space formations depict here a variety of purports that, although not quite the same, share extensive elements. Six metaphorically summarized entities of meaning emerged. The comprehensive form of space is pointed out as the Mobile-Immobile Room. Furthermore, the Standby, the Asylum, the Wall and the Place. In the further dialogue with the texts the understanding has deepened ontologically. The theoretical model ofthe space sums up the vertical, horizontal and the inward extent of deepness inthe movement of mental health. Three entities of ontological meaning have emerged as three significant rooms: the Common Land emerges as the ideal concept of mutual creation in the freedom of doing, being and becoming health. On the interpersonal level it means freedom, which includes sovereignty, choice and dignity of the human being. The Ice World signifies, ultimately, the space as a kind of frozenness of despair which "wallpapers" the person's entire being in the world in the drama of suffering. The Spiritual Home is shaped when the human being has acquired the very core of his/her inner and outer placeness as a kind of "at-homeness" and rootedness. Time is a central element and the inward extent of deepness of this trialectic space. Each of the metaphors is then the human being's unique, although even paradoxical, way of conceiving reality, and mastering spiritual suffering. They condense characteristic structures and patterns of dynamic scenery, which take place within the movement of health. The space encloses a contradictory spatiality constituted through the dynamic field of meaningfulness and meaninglessness. Anyway, it is not through a purging of these contradictions but through bringing them together in a drama of suffering that the space is shaped as ontologically good and meaningful in the world of caring.

Proteção da relação de emprego sob o prisma da dignidade da pessoa humana

This work aims to show that the protection of the employment relation is one of the determining factors to respect the principle of the human dignity. The goal is initially to show the devaluation of work from antiquity to the early twentieth century, when the constitutions began to standardize protective devices. This way, the consecration of the social labor rights in the Constitution of 1988 represents the culmination of the historical achievements. This work demonstrates that such rights can not be reduced or suppressed by political conveniences, once these rights are included in the list of immutable clauses. It is displayed that to achieve the fundamental right to work is not well advised to encourage the creation of jobs that maculates the worker s dignity. The outsourced work is, therefore, a classic example of the advancement of precarious forms of contemporary labor. It is inferred that the presence of various forms of harassment results in a degradation of working environment, bringing about dire consequences on professional and personal life of the worker. Thus, decent work must be the appropriate benchmark for the creation of new jobs. It is also shown that the flexibilization of the propaganda rights by certain pressure groups has as main goal to reduce or eliminate rights, based on fallacious data depicting an increase of competitiveness and jobs. In addition, the flexibility implies a growth of the precarization of the work - a reality felt by many workers subjected to such a situation due to the unemployment phenomenon whose origin is not in the protectionism of the norms. It is necessary to expand and structure the constitutionally legitimate institutions to monitor and curb the precarized work, as well as all practices that go against the dignity of the worker. It is also shown the loss of power of the sindicates in the last few years as a consequence of the pulverization workes and the capital attacks through the productive restructure whose outsourcings and privatizations are notorious examples

Parâmetros de concretização judicial do direito fundamental à saúde no fornecimento de medicamentos

In Brazil, social rights have always been considered secondary legal categories, whose implementation could wait for the pending of political decisions. At the end of the Second World War, International Law emphasizes the protection of human beings, raising his dignity as a legal pillar of the legal orders and one of the main foundations of Constitutions. At the post-positivism Constitutionalism, the realization of social rights receives special attention with the assumption of supremacy and normativity of the Constitutions, while the judiciary participates in the realization of democracy, not only as applicator of laws, but also as the guardian of constitutionality of the acts and administrative omissions, creatively contributing to the constitutional achievement, filling gaps and normative state omissions. In this aspect, the supply of medicines, whose costs can not be supported by the individual, keep a close connection with the right to life, health and dignity of the human being, as the subject of numerous lawsuits directed against the Public Administration. Such phenomenon has caused intense debate regarding judicial activism and legitimacy of these decisions, particularly on the need to define what are the limits and possibilities considering the principle of separation of powers and the principle of reserve of the possible; bieng this the problematic developed in this research. Thus, this research aims to verify the legitimacy of judicial decisions that determines to the Public Administration the compulsory providing of medicine to those who can not afford the cost of their treatment, as well as, contribute to the dogmatic constructions of parameters to be observed by judicial interference. Regarding the methodology, this research has an investigative and descriptive caracter and an theoretical approach based on bibliographical data collection (judicial and doutrine decisions) that received qualitative treatment and dialectical approach. As a result, it is known that the judicial decision that determines the supply of medicines to those individuals who can not afford them with their own resources is legitimate and complies with the democratic principle, not violating the principle of separation of powers and the reserve of the possible, since the judicial decison is not stripped with an uniform and reasonable criteria, failing to contain high burden of subjectivism and witch signifies a possible exacerbation of functions by the judiciary, suffering, in this case, of requirement of legal certainty. It is concluded that the Court decision that determines the government the providing of medicine to those who can not afford the cost of treatment should be based on parameters such as: the protection of human dignity and the minimum existencial principle, the inafastable jurisdiction principle; compliance critique of the possible reserve principle; subsidiarity of judicial intervention; proportionality (quantitative and qualitative) in the content of the decision; the questioning about the reasons for non-delivery of the drug through administrative via; and, finally, the attention not to turn the judiciary into a mere production factor of the pharmaceutical industry, contributing to the cartelization of the right to health

Reactivation of protein aggregates by mortalin and Tid1-the human mitochondrial Hsp70 chaperone system.

The mitochondrial 70-kDa heat shock protein (mtHsp70), also known in humans as mortalin, is a central component of the mitochondrial protein import motor and plays a key role in the folding of matrix-localized mitochondrial proteins. MtHsp70 is assisted by a member of the 40-kDa heat shock protein co-chaperone family named Tid1 and a nucleotide exchange factor. Whereas, yeast mtHsp70 has been extensively studied in the context of protein import in the mitochondria, and the bacterial 70-kDa heat shock protein was recently shown to act as an ATP-fuelled unfolding enzyme capable of detoxifying stably misfolded polypeptides into harmless natively refolded proteins, little is known about the molecular functions of the human mortalin in protein homeostasis. Here, we developed novel and efficient purification protocols for mortalin and the two spliced versions of Tid1, Tid1-S, and Tid1-L and showed that mortalin can mediate the in vitro ATP-dependent reactivation of stable-preformed heat-denatured model aggregates, with the assistance of Mge1 and either Tid1-L or Tid1-S co-chaperones or yeast Mdj1. Thus, in addition of being a central component of the protein import machinery, human mortalin together with Tid1, may serve as a protein disaggregating machine which, for lack of Hsp100/ClpB disaggregating co-chaperones, may carry alone the scavenging of toxic protein aggregates in stressed, diseased, or aging human mitochondria.

Dynamics and diversity of the 'Atopobium cluster' in the human faecal microbiota, and phenotypic characterization of 'Atopobium cluster' isolates

This study monitored the dynamics and diversity of the human faecal 'Atopobium cluster' over a 3-month period using a polyphasic approach. Fresh faecal samples were collected fortnightly from 13 healthy donors (6 males and 7 females) aged between 26 and 61 years. Fluorescence in situ hybridization was used to enumerate total (EUB338mix) and 'Atopobium cluster' (ATO291) bacteria, with counts ranging between 1.12 × 1011 and 9.95 × 1011, and 1.03 × 109 and 1.16 × 1011 cells (g dry weight faeces)-1, respectively. The 'Atopobium cluster' population represented 0.2-22 % of the total bacteria, with proportions donor-dependent. Denaturing gradient gel electrophoresis (DGGE) using 'Atopobium cluster'-specific primers demonstrated faecal populations of these bacteria were relatively stable, with bands identified as Collinsella aerofaciens, Collinsella intestinalis/Collinsella stercoris, Collinsella tanakaei, Coriobacteriaceae sp. PEAV3-3, Eggerthella lenta, Gordonibacter pamelaeae, Olsenella profusa, Olsenella uli and Paraeggerthella hongkongensis in the DGGE profiles of individuals. Colony PCR was used to identify 'Atopobium cluster' bacteria isolated from faeces (n = 224 isolates). 16S rRNA gene sequence analysis of isolates demonstrated Collinsella aerofaciens represented the predominant (88 % of isolates) member of the 'Atopobium cluster' found in human faeces, being found in nine individuals. Eggerthella lenta was identified in three individuals (3.6 % of isolates). Isolates of Collinsella tanakaei, an 'Enorma' sp. and representatives of novel species belonging to the 'Atopobium cluster' were also identified in the study. Phenotypic characterization of the isolates demonstrated their highly saccharolytic nature and heterogeneous phenotypic profiles, and 97 % of the isolates displayed lipase activity.

Activation of the unfolded protein response in human acute myeloid leukemia

There is accumulating evidence for the involvement of the unfolded protein response (UPR) in the pathogenesis of many tumor types in humans. This is particularly the case in rapidly growing solid tumors in which the demand for oxygen and nutrients can exceed the supply until new tumor-initiated blood vessels are formed. In contrast, the role of the UPR during leukemogenesis remains largely unknown. Acute myeloid leukemia (AML) is a genetically heterogeneous clonal disorder characterized by the accumulation of somatic mutations in hematopoietic progenitor cells that alter the physiological regulation of self-renewal, survival, proliferation, or differentiation. The CCAAT/enhancer-binding protein alpha (CEBPA) gene is a key myeloid transcription factor and a frequent target for disruption in AML. In particular, translation of CEBPA mRNA can be specifically blocked by binding of the chaperone calreticulin (CALR), a well-established effector of the UPR, to a stem loop structure within the 5' region of the CEBPA mRNA. The relevance of this mechanism was first elucidated in certain AML subtypes carrying the gene rearrangements t(3;21) or inv(16). In our recent work, we could demonstrate the induction of key effectors of the UPR in leukemic cells of AML patients comprising all subtypes (according to the French-American-British (FAB) classification for human AML). The formation of the spliced variant of the X-box binding protein (XBP1s) was detectable in 17.4% (17 of 105) of AML patients. Consistent with an activated UPR, this group had significantly increased expression of the UPR target genes CALR, the 78 kDa glucose-regulated protein (GRP78), and the CCAAT/enhancer-binding protein homologous protein (CHOP). Consistently, in vitro studies confirmed that calreticulin expression was upregulated via activation of the ATF6 pathway in myeloid leukemic cells. As a consequence, CEBPA protein expression was inhibited in vitro as well as in leukemic cells from patients with activated UPR. We therefore propose a model of the UPR being involved in leukemogenesis through induction of calreticulin along the ATF6 pathway, thereby ultimately suppressing CEBPA translation and contributing to the block in myeloid differentiation and cell-cycle deregulation which represent key features of the leukemic phenotype. From a more clinical point of view, the presence of activated UPR in AML patient samples was found to be associated with a favorable disease course.

The human side of social technology for climate change mitigation and human development: the case of "efficient stoves" in Brazil

Carbon management has gradually gained attention within the overall environmental management and corporate social responsibility agendas. The clean development mechanism, from Kyoto Protocol, was envisioned as connecting carbon market and sustainable development objectives in developing countries. Previous research has shown that this potential is rarely being achieved. The paper explores how the incorporation of the human side into carbon management reinforces its contribution to generate human development in local communities and to improve the company's image. A case study of a Brazilian company is presented, with the results of the application of an analytical model that incorporates the human side and human development. The selected project is an "efficient stoves" programme. "Efficient stoves" are recognised in Brazil as social technologies. Results suggest that the fact that social technologies value the human side of the technology plays a key role when it comes to analysing the co-benefits of the project implementation.

Human SULT1A genes: Cloning and activity assays of the SULT1A promoters

The three human SULT1A sulfotransferase enzymes are closely related in amino acid sequence (>90%), yet differ in their substrate preference and tissue distribution. SULT1A1 has a broad tissue distribution and metabolizes a range of xenobiotics as well as endogenous substrates such as estrogens and iodothyronines. While the localization of SULT1A2 is poorly understood, it has been shown to metabolize a number of aromatic amines. SULT1A3 is the major catecholamine sulfonating form, which is consistent with it being expressed principally in the gastrointestinal tract. SULT1A proteins are encoded by three separate genes, located in close proximity to each other on chromosome 16. The presence of differential 5′-untranslated regions identified upon cloning of the SULT1A cDNAs suggested the utilization of differential transcriptional start sites and/or differential splicing. This chapter describes the methods utilized by our laboratory to clone and assay the activity of the promoters flanking these different untranslated regions found on SULT1A genes. These techniques will assist investigators in further elucidating the differential mechanisms that control regulation of the human SULT1A genes. They will also help reveal how different cellular environments and polymorphisms affect the activity of SULT1A gene promoters.