The Physiology of Mycobacterium tuberculosis in the Context of Drug Resistance: A System Biology Perspective

Tuberculosis (TB), a disease caused by Mycobacterium tuberculosis (Mtb), is the main cause of death due to an infectious disease. After more than 100 years of the discovery of Mtb, clinicians still face difficulties finding an effective treatment for the increasing number of drug-resistant cases. The difficulties in the clinical setting can be related to the slow pace at which the understanding of the physiology of this bacterium has occurred. Mtb is distinct from other microorganisms not only due to its slow growth and difficulties to study in the laboratory, but also due to its inherent physiology such as its complex cell envelope and its metabolic pathways. Understanding the physiology of drug susceptible and resistant Mtb strains is crucial for the design of an effective chemotherapy against TB. This chapter will review the mycobacterial cell envelope and major physiological pathways together with recent discoveries in Mtb drug resistance through different “omics” disciplines

Digital Transformation in Higher Education: Maturity and Challenges Post COVID-19

Digital transformation in higher education, especially after COVID-19 is inevitable. This research explores digital transformation maturity and challenges post COVID-19. The significance of the study does not only stem from the critical role of higher education in building the workforce and knowledge economy. This study triangulates the findings of multiple research instruments, including survey, interviews, case study, and direct observation. The research findings show a significant variance between the respondents’ perception of digital transformations maturity levels, and the core requirements of digital transformation maturity. The findings also show the lack of holistic vision, digital transformation competency, and data structure and processing as the leading challenges of digital transformation

Portrait of a Pathogen: The Mycobacterium tuberculosis Proteome In Vivo

Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), is a facultative intracellular pathogen that can persist within the host. The bacteria are thought to be in a state of reduced replication and metabolism as part of the chronic lung infection. Many in vitro studies have dissected the hypothesized environment within the infected lung, defining the bacterial response to pH, starvation and hypoxia. While these experiments have afforded great insight, the picture remains incomplete. The only way to study the combined effects of these environmental factors and the mycobacterial response is to study the bacterial response in vivo.We used the guinea pig model of tuberculosis to examine the bacterial proteome during the early and chronic stages of disease. Lungs were harvested thirty and ninety days after aerosol challenge with Mtb, and analyzed by liquid chromatography-mass spectrometry. To date, in vivo proteomics of the tubercle bacillus has not been described and this work has generated the first large-scale shotgun proteomic data set, comprising over 500 unique protein identifications. Cell wall and cell wall processes, and intermediary metabolism and respiration were the two major functional classes of proteins represented in the infected lung. These classes of proteins displayed the greatest heterogeneity indicating important biological processes for establishment of a productive bacterial infection and its persistence. Proteins necessary for adaptation throughout infection, such as nitrate/nitrite reduction were found at both time points. The PE-PPE protein class, while not well characterized, represented the third most abundant category and showed the most consistent expression during the infection.Cumulatively, the results of this work may provide the basis for rational drug design - identifying numerous Mtb proteins, from essential kinases to products involved in metal regulation and cell wall remodeling, all present throughout the course of infection

At the Crossroads of Sustainability: The Natural Recompositioning of Architecture

It is widely acknowledged that the mantra of sustainability has triggered a fundamental reversal in the core of design practice: If the original purpose of architecture was to protect humans from the destructive actions of nature,today it should protect nature from the damaging actions of humans. But sustainable design is far from being a coherent body of fully totalized ideas:it has a broad spectrum of disputing interpretations that oscillate between the deterministic models of energy control and technological efficiencies, and the moralistic and romantic approaches that attempt to see in nature and natural processes a fundamental way to de-escalate the global urban footprint and its associated patterns of consumption. However, mainstream green design has been evolving by progressively absorbing the narrative of deep ecology. Nature has been being integrated into architecture literally, by inserting vegetation onto buildings; digitally, by bringing environmental data into the design process (climate records, wind streams, sun rotation and air flows are computed, modelled and effectually shape architectures), and transcendentally, by claiming that sustainable architecture nurtures “the existing and evolving connections between spiritual and material consciousness.” The acknowledgement of the inexorable affiliation between architecture and the environment is, of course, not exactly new. What is distinctive today is the reification of the role of nature in architecture as an ideological stance, now totally intertwined with state-of-art data processing and the market-driven tools brought by Natural Capitalism. This paper will examine emblematic “green” buildings produced by leading architects such as Pelli Clarke Pelli, William McDonough, Stefano Boeri, Norman Foster and BIG in the light of Tim Morton’s, Slavoj Zizek and Bruno Latour’s critique of nature. It will illustrate how, despite being able to successfully forge new creative freedoms by exploring hybridizations between the domains of design and science, sustainability’s self-righteous “naturalistic” narrative is enabling a vision of the architect as an “expert manager” focused on producing projects of ecologic “beautification” while assumed to be “saving the world,” effectively depoliticizing the architectural practice. Nevertheless, these examples attest that there is a vast and fertile field of ideas to be explored and in this regard it is important to underline that we are still in the embryonic outset of the engagement of architecture with sustainability

Interpreting whole genome sequencing for investigating tuberculosis transmission: a systematic review

BACKGROUND: Whole genome sequencing (WGS) is becoming an important part of epidemiological investigations of infectious diseases due to greater resolution and cost reductions compared to traditional typing approaches. Many public health and clinical teams will increasingly use WGS to investigate clusters of potential pathogen transmission, making it crucial to understand the benefits and assumptions of the analytical methods for investigating the data. We aimed to understand how different approaches affect inferences of transmission dynamics and outline limitations of the methods. METHODS: We comprehensively searched electronic databases for studies that presented methods used to interpret WGS data for investigating tuberculosis (TB) transmission. Two authors independently selected studies for inclusion and extracted data. Due to considerable methodological heterogeneity between studies, we present summary data with accompanying narrative synthesis rather than pooled analyses. RESULTS: Twenty-five studies met our inclusion criteria. Despite the range of interpretation tools, the usefulness of WGS data in understanding TB transmission often depends on the amount of genetic diversity in the setting. Where diversity is small, distinguishing re-infections from relapses may be impossible; interpretation may be aided by the use of epidemiological data, examining minor variants and deep sequencing. Conversely, when within-host diversity is large, due to genetic hitchhiking or co-infection of two dissimilar strains, it is critical to understand how it arose. Greater understanding of microevolution and mixed infection will enhance interpretation of WGS data. CONCLUSIONS: As sequencing studies have sampled more intensely and integrated multiple sources of information, the understanding of TB transmission and diversity has grown, but there is still much to be learnt about the origins of diversity that will affect inferences from these data. Public health teams and researchers should combine epidemiological, clinical and WGS data to strengthen investigations of transmission

Graduação em Arquitetura e Urbanismo da Universidade Federal de Santa Catarina,

Abstract: We offer here a set of evidence-based optimal practices for social housing, applicable in general situations. Varying examples are discussed in a Latin American context. Adaptive solutions work towards long-term sustainability and help to attach residents to their built environment. We draw upon new insights in complexity science, and in particular the work of Christopher Alexander on how to successfully evolve urban form. By applying the conceptual tools of “Pattern Languages ” and “Generative Codes”, these principles support previous solutions derived by others, which were never taken forward in a viable form. New methodologies presented here offer a promising alternative to the failures of the standard social housing typologies favored by governments around the world, which have proven to be dehumanizing and ultimately unsustainable. SECTIONS 1-4: BACKGROUND AND CRITICISM. 1. Introduction. This paper outlines promising new solutions for the future of social housing. It has been prepared as a comprehensive report by one of the authors (NAS) for Brazil, and is generally applicable to all of Latin America. One of us (AMD) is designing social housin

Habitação socialmente organizada, uma nova abordagem à estrutura urbana II: sugestões práticas para que os projetos funcionem Socially-organized housing, a new approach to urban structure II: practical suggestions for making project work

Desenvolvemos aqui nossa proposta para habitação social planejada e criada de acordo com as melhorespráticas baseadas em evidências. A partir de tradições locais e ferramentas urbanas inovadoras, o tecidourbano pode ser construído de forma a conectar-se positivamente ao usuário, ao invés de concordar comalgum traçado geométrico abstrato ideal. A falha em proceder com este modo esclarecido normalmenteleva a geometrias estéreis que não poderão nunca acomodar a vida social. Infelizmente, essa é a maneirapela qual a habitação social foi planejada por décadas, seguindo noções simplistas de ordem e eficiência.Essa abordagem não é apenas desatualizada, mas tem se mostrado como destruidora da sociedade. Temosconsiderado os múltiplos fatores que influenciam a reforma desse sistema, dando ênfase aos pontos em quemudanças drásticas se fazem necessárias (na filosofia e ideologia do urbanismo) e onde o sistema existente(nas práticas legais e construtivas) pode continuar funcionando apenas com pequenos ajustes. Felizmente,uma completa renovação de métodos construtivos urbanos podem ser implementados mantendo grandeparte da estrutura institucional existente