Overlooked? Underestimated? Effects of Substrate Curvature on Cell Behavior

In biological systems, form and function are inherently correlated. Despite this strong interdependence, the biological effect of curvature has been largely overlooked or underestimated, and consequently it has rarely been considered in the design of new cell–material interfaces. This review summarizes current understanding of the interplay between the curvature of a cell substrate and the related morphological and functional cellular response. In this context, we also discuss what is currently known about how, in the process of such a response, cells recognize curvature and accordingly reshape their membrane. Beyond this, we highlight state-of-the-art microtechnologies for engineering curved biomaterials at cell-scale, and describe aspects that impair or improve readouts of the pure effect of curvature on cells

From fiber curls to mesh waves:a platform for the fabrication of hierarchically structured nanofibers mimicking natural tissue formation

\u3cp\u3eBioinstructive scaffolds for regenerative medicine are characterized by intrinsic properties capable of directing cell response and promoting wound healing. The design of such scaffolds requires the incorporation of well-defined physical properties that mimic the native extracellular matrix (ECM). Here, inspired by epithelial tissue morphogenesis, we present a novel approach to code nanofiber materials with controlled hierarchical wavy structures resembling the configurations of native EMC fibers through using thermally shrinking materials as substrates onto which the fibers are deposited. This approach could serve as a platform for fabricating functional scaffolds mimicking various tissues such as trachea, iris, artery wall and ciliary body. Modeling affirms that the mechanical properties of the fabricated wavy fibers could be regulated through varying their wavy patterns. The nanofibrous scaffolds coded with wavy patterns show an enhanced cellular infiltration. In addition, we further investigated whether the wavy patterns could regulate transforming growth factor-beta (TGF-β) production, a key signalling pathway involved in connective tissue development. Our results demonstrated that nanofibrous scaffolds coded with wavy patterns could induce TGF-β expression without the addition of a soluble growth factor. Our new approach could open up new avenues for fabricating bioinstructive scaffolds for regenerative medicine.\u3c/p\u3

Development of an in vitro airway epithelial–endothelial cell culture model on a flexible porous poly(Trimethylene carbonate) membrane based on calu‐3 airway epithelial cells and lung microvascular endothelial cells

Due to the continuing high impact of lung diseases on society and the emergence of new respiratory viruses, such as SARS‐CoV‐2, there is a great need for in vitro lung models that more accurately recapitulate the in vivo situation than current models based on lung epithelial cell cultures on stiff membranes. Therefore, we developed an in vitro airway epithelial–endothelial cell culture model based on Calu‐3 human lung epithelial cells and human lung microvascular endothelial cells (LMVECs), cultured on opposite sides of flexible porous poly(trimethylene carbonate) (PTMC) membranes. Calu‐3 cells, cultured for two weeks at an air–liquid interface (ALI), showed good expression of the tight junction (TJ) protein Zonula Occludens 1 (ZO‐1). LMVECs cultured submerged for three weeks were CD31‐positive, but the expression was diffuse and not localized at the cell membrane. Barrier functions of the Calu‐3 cell cultures and the co‐cultures with LMVECs were good, as determined by electrical resistance measurements and fluorescein isothiocya-nate‐dextran (FITC‐dextran) permeability assays. Importantly, the Calu‐3/LMVEC co‐cultures showed better cell viability and barrier function than mono‐cultures. Moreover, there was no evidence for epithelial‐ and endothelial‐to‐mesenchymal transition (EMT and EndoMT, respec-tively) based on staining for the mesenchymal markers vimentin and α‐SMA, respectively. These results indicate the potential of this new airway epithelial–endothelial model for lung research. In addition, since the PTMC membrane is flexible, the model can be expanded by introducing cyclic stretch for enabling mechanical stimulation of the cells. Furthermore, the model can form the basis for biomimetic airway epithelial–endothelial and alveolar–endothelial models with primary lung epithelial cells.</p

Parents and Teachers' Awareness for Health Promotion: focus on nutritional status and healthy diet in the city of Indaiatuba

A infância e a adolescência são períodos extremamente relevantes na formação do ser humano, tanto no que tange ao aspecto biológico, quanto no emocional, psicológico e social. Nesta fase, os indivíduos são mais vulneráveis a algumas ameaças, dependendo do estilo de vida que adotam. Neste sentido, o presente estudo propõe apresentar um processo de sensibilização a pais e professores, na cidade de Indaiatuba, acerca da qualidade de vida de crianças e adolescentes que participam do Programa de Recreação, Incentivo e Aperfeiçoamento (PRIA) da Prefeitura de Indaiatuba, bem como aos alunos da rede de escolas municipais e estaduais, sobre os aspectos do estado nutricional e hábitos alimentares. O processo de sensibilizar famílias, mestres e educadores, visa focar para a importância da promoção da saúde infanto-juvenil, no âmbito da qualidade de vida e se dará por meio de material didático, orientações, palestras e ainda, projetar o delineamento para as próximas atividades de extensão a serem desenvolvidas para melhoria da qualidade de vida, por meio da promoção da saúde, dessa comunidadeChildhood and adolescence are periods extremely relevant in the formation of the human, both in terms of biological aspect, the emotional, psychological and social. In these periods, individuals are more vulnerable to some of the biggest threats to the lifestyle they adopt. In this sense, this study aims to present the process of sensitization of parents and teachers in community of Indaiatuba, about the quality of life children and adolescents who participate in the Recreation Program, Incentive and Improvement (PRIA) in the city, and also students of municipal and state schools on aspects of nutritional status and dietary habits. The process of sensitizing families and teachers to the importance of the promotion of children's health in the context of quality of life will be through educational material, guidelines and lectures, in addition to the project the outreach activities to be developed in next years to improve the quality of life through health promotion will be define

The type VII secretion system of <i>Staphylococcus aureus</i> secretes a nuclease toxin that targets competitor bacteria

The type VII protein secretion system (T7SS) plays a critical role in the virulence of human pathogens including Mycobacterium tuberculosis and Staphylococcus aureus. Here we report that the S. aureus T7SS secretes a large nuclease toxin, EsaD. The toxic activity of EsaD is neutralised during its biosynthesis through complex formation with an antitoxin, EsaG, which binds to its C-terminal nuclease domain. The secretion of EsaD is dependent upon a further accessory protein, EsaE, that does not interact with the nuclease domain, but instead binds to the EsaD N-terminal region. EsaE has a dual cytoplasmic/membrane localization and membrane-bound EsaE interacts with the T7SS secretion ATPase, EssC, implicating EsaE in targeting the EsaDG complex to the secretion apparatus. EsaD and EsaE are co-secreted whereas EsaG is found only in the cytoplasm and may be stripped off during the secretion process. Strain variants of S. aureus that lack esaD encode at least two copies of EsaG-like proteins most likely to protect themselves from the toxic activity of EsaD secreted by esaD(+) strains. In support of this, a strain overproducing EsaD elicits significant growth inhibition against a sensitive strain. We conclude that T7SSs may play unexpected and key roles in bacterial competitiveness

The Enigmatic Esx Proteins:Looking Beyond Mycobacteria

Bacteria export proteins across membranes using a range of transport machineries. Type VII secretion systems (T7SSs), originally described in mycobacteria, are now known to be widespread across diverse bacterial phyla. Recent studies have characterized secretion components and mechanisms of type VII secretion in pathogenic and environmental bacteria. A variety of functions have been attributed to T7SS substrates, including interactions with eukaryotes and with other bacteria. Here, we evaluate the growing body of knowledge on T7SSs, with focus on the nonmycobacterial systems, reviewing their phylogenetic distribution, structure and function in diverse settings

Metabolic and immune effects of immunotherapy with proinsulin peptide in human new-onset type 1 diabetes*

Immunotherapy using short immunogenic peptides of disease-related autoantigens restores immune tolerance in preclinical disease models. We studied safety and mechanistic effects of injecting human leukocyte antigen–DR4(DRB1*0401)–restricted immunodominant proinsulin peptide intradermally every 2 or 4 weeks for 6 months in newly diagnosed type 1 diabetes patients. Treatment was well tolerated with no systemic or local hypersensitivity. Placebo subjects showed a significant decline in stimulated C-peptide (measuring insulin reserve) at 3, 6, 9, and 12 months versus baseline, whereas no significant change was seen in the 4-weekly peptide group at these time points or the 2-weekly group at 3, 6, and 9 months. The placebo group’s daily insulin use increased by 50% over 12 months but remained unchanged in the intervention groups. C-peptide retention in treated subjects was associated with proinsulin-stimulated interleukin-10 production, increased FoxP3 expression by regulatory T cells, low baseline levels of activated β cell–specific CD8 T cells, and favorable β cell stress markers (proinsulin/C-peptide ratio). Thus, proinsulin peptide immunotherapy is safe, does not accelerate decline in β cell function, and is associated with antigen-specific and nonspecific immune modulation

Study of the B−→Λc+Λˉc−K−B^{-} \to \Lambda_{c}^{+} \bar{\Lambda}_{c}^{-} K^{-} decay

The decay $B^{-} \to \Lambda_{c}^{+} \bar{\Lambda}_{c}^{-} K^{-}$ is studied in proton-proton collisions at a center-of-mass energy of $\sqrt{s}=13$ TeV using data corresponding to an integrated luminosity of 5 $\mathrm{fb}^{-1}$ collected by the LHCb experiment. In the $\Lambda_{c}^+ K^{-}$ system, the $\Xi_{c}(2930)^{0}$ state observed at the BaBar and Belle experiments is resolved into two narrower states, $\Xi_{c}(2923)^{0}$ and $\Xi_{c}(2939)^{0}$, whose masses and widths are measured to be $$m(\Xi_{c}(2923)^{0}) = 2924.5 \pm 0.4 \pm 1.1 \,\mathrm{MeV}, \\ m(\Xi_{c}(2939)^{0}) = 2938.5 \pm 0.9 \pm 2.3 \,\mathrm{MeV}, \\ \Gamma(\Xi_{c}(2923)^{0}) = \phantom{000}4.8 \pm 0.9 \pm 1.5 \,\mathrm{MeV},\\ \Gamma(\Xi_{c}(2939)^{0}) = \phantom{00}11.0 \pm 1.9 \pm 7.5 \,\mathrm{MeV},$$ where the first uncertainties are statistical and the second systematic. The results are consistent with a previous LHCb measurement using a prompt $\Lambda_{c}^{+} K^{-}$ sample. Evidence of a new $\Xi_{c}(2880)^{0}$ state is found with a local significance of $3.8\,\sigma$, whose mass and width are measured to be $2881.8 \pm 3.1 \pm 8.5\,\mathrm{MeV}$ and $12.4 \pm 5.3 \pm 5.8 \,\mathrm{MeV}$, respectively. In addition, evidence of a new decay mode $\Xi_{c}(2790)^{0} \to \Lambda_{c}^{+} K^{-}$ is found with a significance of $3.7\,\sigma$. The relative branching fraction of $B^{-} \to \Lambda_{c}^{+} \bar{\Lambda}_{c}^{-} K^{-}$ with respect to the $B^{-} \to D^{+} D^{-} K^{-}$ decay is measured to be $2.36 \pm 0.11 \pm 0.22 \pm 0.25$, where the first uncertainty is statistical, the second systematic and the third originates from the branching fractions of charm hadron decays.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-028.html (LHCb public pages