Local genetic context shapes the function of a gene regulatory network

Gene expression levels are influenced by multiple coexisting molecular mechanisms. Some of these interactions such as those of transcription factors and promoters have been studied extensively. However, predicting phenotypes of gene regulatory networks (GRNs) remains a major challenge. Here, we use a well-defined synthetic GRN to study in Escherichia coli how network phenotypes depend on local genetic context, i.e. the genetic neighborhood of a transcription factor and its relative position. We show that one GRN with fixed topology can display not only quantitatively but also qualitatively different phenotypes, depending solely on the local genetic context of its components. Transcriptional read-through is the main molecular mechanism that places one transcriptional unit (TU) within two separate regulons without the need for complex regulatory sequences. We propose that relative order of individual TUs, with its potential for combinatorial complexity, plays an important role in shaping phenotypes of GRNs

insights for ecological applications from the German Biodiversity Exploratories

Biodiversity, a multidimensional property of natural systems, is difficult to quantify partly because of the multitude of indices proposed for this purpose. Indices aim to describe general properties of communities that allow us to compare different regions, taxa, and trophic levels. Therefore, they are of fundamental importance for environmental monitoring and conservation, although there is no consensus about which indices are more appropriate and informative. We tested several common diversity indices in a range of simple to complex statistical analyses in order to determine whether some were better suited for certain analyses than others. We used data collected around the focal plant Plantago lanceolata on 60 temperate grassland plots embedded in an agricultural landscape to explore relationships between the common diversity indices of species richness (S), Shannon's diversity (H'), Simpson's diversity (D1), Simpson's dominance (D2), Simpson's evenness (E), and Berger–Parker dominance (BP). We calculated each of these indices for herbaceous plants, arbuscular mycorrhizal fungi, aboveground arthropods, belowground insect larvae, and P. lanceolata molecular and chemical diversity. Including these trait-based measures of diversity allowed us to test whether or not they behaved similarly to the better studied species diversity. We used path analysis to determine whether compound indices detected more relationships between diversities of different organisms and traits than more basic indices. In the path models, more paths were significant when using H', even though all models except that with E were equally reliable. This demonstrates that while common diversity indices may appear interchangeable in simple analyses, when considering complex interactions, the choice of index can profoundly alter the interpretation of results. Data mining in order to identify the index producing the most significant results should be avoided, but simultaneously considering analyses using multiple indices can provide greater insight into the interactions in a system

Quercetin pentaacetate inhibits in vitro human respiratory syncytial virus adhesion.

Made available in DSpace on 2020-12-12T01:06:20Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-01-15 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Human respiratory syncytial virus (hRSV) is one of the main etiological agents of diseases of the lower respiratory tract and is often responsible for the hospitalization of children and the elderly. To date, treatments are only palliative and there is no vaccine available. Natural products show exceptional structural diversity and they have played a vital role in drug research. Several investigations focused on applied structural modification of natural products to improved metabolic stability, solubility and biological actions them. Quercetin is a flavonoid that presents several biological activities, including anti-hRSV role. Some works criticize the pharmacological use of Quercetin because it has low solubility and low specificity. In this sense, we acetylated Quercetin structure and we used in vitro and in silico assays to compare anti-hRSV function between Quercetin (Q0) and its derivative molecule (Q1). Q1 shows lower cytotoxic effect than Q0 on HEp-2 cells. In addition, Q1 was more efficient than Q0 to protect HEp-2 cells infected with different multiplicity of infection (0.1–1 MOI). The virucidal effects of Q0 and Q1 suggest interaction between these molecules and viral particle. Dynamic molecular results suggest that Q0 and Q1 may interact with F-protein on hRSV surface in an important region to adhesion and viral infection. Q1 interaction with F-protein showed ΔG= -14.22 kcal/mol and it was more stable than Q0. Additional, MTT and plate assays confirmed that virucidal Q1 effects occurs during adhesion step of cycle hRSV replication. In conclusion, acetylation improves anti-hRSV Quercetin effects because Quercetin pentaacetate could interact with F-protein with lower binding energy and better stability to block viral adhesion. These results show alternative anti-hRSV strategy and contribute to drug discovery and development. Universidade Estadual Paulista UNESP (FCLAssis) Universidade Estadual Paulista UNESP IBILCE Centro Multiusuário de Inovação Biomolecular (CMIB) Universidade Estadual Paulista UNESP IBILCE Department of Biology University of Rome Tor Vergata, Via della Ricerca Scientifica 1 Universidade Estadual Paulista UNESP (FCLAssis) Universidade Estadual Paulista UNESP IBILCE Centro Multiusuário de Inovação Biomolecular (CMIB) Universidade Estadual Paulista UNESP IBILCE FAPESP: 2014/12298-

The state of adolescent menstrual health in low- and middle-income countries and suggestions for future action and research

In recognition of the opportunity created by the increasing attention to menstrual health at global, regional, and national levels, the World Health Organization’s Department of Sexual and Reproductive Health and Research and the UNDP-UNFPA-UNICEF-WHO-World Bank Special Programme of Research, Development and Research Training in Human Reproduction convened a global research collaborative meeting on menstrual health in adolescents in August 2018. Experts considered nine domains of menstrual health (awareness and understanding; stigma, norms, and socio-cultural practices; menstrual products; water and sanitation; disposal; empathy and support; clinical care; integration with other programmes; and financing) and answered the following five questions: (1) What is the current situation? (2) What are the factors contributing to this situation? (3) What should the status of this domain of adolescent menstrual health be in 10 years? (4) What actions are needed to achieve these goals? (5) What research is needed to achieve these goals? This commentary summarizes the consensus reached in relation to these questions during the expert consultation. In doing so, it describes the state of adolescent menstrual health in low- and middle-income countries and sets out suggestions for action and research that could contribute to meeting the holistic menstrual health needs of adolescent girls and others who menstruate worldwide

T Lymphocytes Promote the Antiviral and Inflammatory Responses of Airway Epithelial Cells

T cells modulate the antiviral and inflammatory responses of airway epithelial cells to human rhinoviruses (HRV)