Alexandre Bruni‐Cardoso

Universidade de São Paulo

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Hernandes F. Carvalho

Universidade Estadual de Campinas (UNICAMP)

Antonio Carlos Manucci

Universidade de São Paulo

Ana Paula Zen Petisco Fiore

Universidade de São Paulo

Rebeka Tomasin

New York University

Taize Machado Augusto

Faculdade de Medicina de Jundiaí

Mina J. Bissell

Lawrence Berkeley National Laboratory

Conor C. Lynch

Moffitt Cancer Center

Danilo Marchete Damas-Souza

Universidade Estadual de Campinas (UNICAMP)

Deborah Schechtman

Universidade de São Paulo

Jamie L. Inman

Lawrence Berkeley National Laboratory

Cooperative Institutions

Universidade de São Paulo

133

John Wiley & Sons (United States)

Hudson Institute

Universidade Estadual de Campinas (UNICAMP)

Universidade Cidade de São Paulo

Universidade Federal de São Paulo

Johns Hopkins University

Johns Hopkins Medicine

Universidade Estadual Paulista (Unesp)

Universidade Brasil

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Where do we aspire to publish? A position paper on scientific communication in biochemistry and molecular biology

Brazilian Journal of Medical and Biological Research (2019)

Maurı́cio S. Baptista Maria Júlia Manso Alves Guilherme M. Arantes Hugo A. Armelin Ohára Augusto

The scientific publication landscape is changing quickly, with an enormous increase in options and models. Articles can be published in a complex variety of journals that differ in their presentation format (online-only or in-print), editorial organizations that maintain them (commercial and/or society-based), editorial handling (academic or professional editors), editorial board composition (academic or professional), payment options to cover editorial costs (open access or pay-to-read), indexation, visibility, branding, and other aspects. Additionally, online submissions of non-revised versions of manuscripts prior to seeking publication in a peer-reviewed journal (a practice known as pre-printing) are a growing trend in biological sciences. In this changing landscape, researchers in biochemistry and molecular biology must re-think their priorities in terms of scientific output dissemination. The evaluation processes and institutional funding for scientific publications should also be revised accordingly. This article presents the results of discussions within the Department of Biochemistry, University of São Paulo, on this subject.

Presentation (obstetrics)

Publication

Editorial board

Scientific Communication

Scholarly Communication

Visibility

10.1590/1414-431x20198935

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Citations (2)

Peer Review #2 of "New insight into the role of MMP14 in metabolic balance (v0.2)"

Hidetoshi Mori Ramray Bhat Alexandre Bruni‐Cardoso Emily Chen Danielle Jorgens

Membrane-anchored matrix metalloproteinase 14 (MMP14) is involved broadly in organ development through both its proteolytic and signal-transducing functions.Knockout of Mmp14 (KO) in mice results in a dramatic reduction of body size and wasting followed by premature death, the mechanism of which is poorly understood.Since the mammary gland develops after birth and is thus dependent for its functional progression on systemic and local cues, we chose it as an organ model for understanding why KO mice fail to thrive.A global analysis of the mammary glands' proteome in the wild type (WT) and KO mice provided insight into an unexpected role of MMP14 in maintaining metabolism and homeostasis.We performed mass spectrometry and quantitative proteomics to determine the protein signatures of mammary glands from 7 to 11 days old WT and KO mice and found that KO rudiments had a significantly higher level of rate-limiting enzymes involved in catabolic pathways.Glycogen and lipid levels in KO rudiments were reduced, and the circulating levels of triglycerides and glucose were lower.Analysis of the ultrastructure of mammary glands imaged by electron microscopy revealed a significant increase in autophagy signatures in KO mice.Finally, Mmp14 silenced mammary epithelial cells displayed enhanced autophagy.Applied to a systemic level, these findings indicate that MMP14 is a crucial regulator of tissue homeostasis.If operative on a systemic level, these findings could explain how Mmp14 KO litter fail to thrive due to disorder inmetabolism.

10.7287/peerj.2142v0.2/reviews/2

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Citations (0)

Olfactory Dysfunction in Frontline Health Care Professionals During COVID-19 Pandemic in Brazil

Frontiers in Physiology (2021)

Mariana Ferreira Sbrana Marco Aurélio Fornazieri Alexandre Bruni‐Cardoso Vivian Iida Avelino‐Silva Deborah Schechtman

Upper respiratory viral infections can decrease the sense of smell either by inflammatory restriction of nasal airflow that carries the odorant molecules or through interference in olfactory sensory neuron function. During the coronavirus disease 2019 (COVID-19) pandemic, triggered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), worldwide reports of severe smell loss (anosmia/hyposmia) revealed a different type of olfactory dysfunction associated with respiratory virus infection. Since self-reported perception of smell is subjective and SARS-CoV-2 exposure is variable in the general population, we aimed to study a population that would be more homogeneously exposed to the virus. Here, we investigated the prevalence of olfactory loss in frontline health professionals diagnosed with COVID-19 in Brazil, one of the major epicenters of the disease. We also analyzed the rate of olfactory function recovery and the particular characteristics of olfactory deficit in this population. A widely disclosed cross-sectional online survey directed to health care workers was developed by a group of researchers to collect data concerning demographic information, general symptoms, otolaryngological symptoms, comorbidities, and COVID-19 test results. Of the 1,376 health professionals who completed the questionnaire, 795 (57.8%) were working directly with COVID-19 patients, either in intensive care units, emergency rooms, wards, outpatient clinics, or other areas. Five-hundred forty-one (39.3%) participants tested positive for SARS-CoV-2, and 509 (37%) were not tested. Prevalence of olfactory dysfunction in COVID-19-positive subjects was 83.9% (454 of 541) compared to 12.9% (42 of 326) of those who tested negative and to 14.9% (76 of 509) of those not tested. Olfactory dysfunction incidence was higher in those working in wards, emergency rooms, and intensive care units compared to professionals in outpatient clinics. In general, remission from olfactory symptoms was frequent by the time of responses. Taste disturbances were present in 74.1% of infected participants and were significantly associated with hyposmia. In conclusion, olfactory dysfunction is highly correlated with exposure to SARS-CoV-2 in health care professionals, and remission rates up to 2 weeks are high.

Anosmia

Hyposmia

Cross-sectional study

Pandemic

10.3389/fphys.2021.622987

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Citations (13)

Pten is a disconnecting node in the molecular landscape of the proliferation/quiescence decision during mammary gland acinogenesis

bioRxiv (Cold Spring Harbor Laboratory) (2023)

Rebeka Tomasin Ana Maria Rodrigues Antonio Carlos Manucci Alexandre Bruni‐Cardoso

Abstract Cell context is key for cell phenotype. Using physiologically relevant models of laminin-rich ECM (lrECM) induction of mammary epithelial cell quiescence and differentiation, we have provided a landscape of the status of key molecular players involved in the proliferation/quiescence decision. Repression of some positive regulators of the cell cycle, such as cyclins and CDKs, occurred already at the mRNA level, whereas negative regulators of the cell cycle, such as Pten and p27, were upregulated only at the protein level. Interestingly, cell cycle arrest occurred despite the active status of Fak, Src and PI3k, because their downstream proliferative signalling pathways were repressed, suggesting the existence of a disconnecting node between upstream and downstream proliferative signalling in quiescent cells. Pten fulfils this role. Inhibition of Pten increased proliferation and restored Akt/mTORC1/2 and Mapk signalling in cells exposed to lrECM. In mice, Pten levels were positively correlated to the basement membrane thickness in the developing mammary epithelia, and Pten localized to the apicolateral membrane of luminal cells both in in ducts and near the nascent lumen in terminal end bud, characteristics consistent with a role for Pten in inducing and sustaining quiescence and tissue architecture. Accordingly, in 3D acininogenesis models, Pten was required for the onset and maintenance of quiescence, cell polarity and lumen assembly. The notion that lrECM-triggered differentiation involves a signalling circuitry with many layers of regulation provides an explanation for the resilience of quiescence within a growth-suppressive microenvironment, and that perturbations in master regulators, such as Pten, could disrupt the quiescent phenotype.

10.1101/2023.03.13.532403

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Deep nuclear invaginations linked to cytoskeletal filaments: Integrated Bioimaging of epithelial cells in 3D culture - Supplemental Movies

Danielle Jorgens Jamie L. Inman Michal Wojcik Claire Robertson Hildur Pálsdóttir

10.6084/m9.figshare.c.3278171.v1

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On the road to understanding of the osteoblast adhesion: Cytoskeleton organization is rearranged by distinct signaling pathways

Journal of Cellular Biochemistry (2009)

Willian Fernando Zambuzzi Alexandre Bruni‐Cardoso José Mauro Granjeiro Maikel P. Peppelenbosch Hernandes F. Carvalho

Abstract Pre‐osteoblast adhesion attracts increasing interest in both medicine and dentistry. However, how this physiological event alters osteoblast phenotype is poorly understood. We therefore attempted to address this question by investigating key biochemical mechanism that governs pre‐osteoblast adhesion on polystyrene surface. Importantly, we found that cofilin activity was strongly modulated by PP2A (Ser/Thr phosphatase), while cell‐cycle was arrested. Accordingly, we observed that the profile of cofilin phosphorylation (at Ser03) was similar to phospho‐PP2A (at Tyr307). Also, it is plausible to suggest during pre‐osteoblast adhesion that PP2A phosphorylation at Y307 was executed by phospho‐Src (Y416). In addition, it was observed that MAPKp38, but not MAPK‐erk, played a key role on pre‐osteoblast adhesion by phosphorylating MAPKAPK‐2 and ATF‐2 (also called CRE‐BP1). Also, the up‐modulation of RhoA reported here suggests its involvement at the beginning of osteoblast attachment, while Akt remained active during all periods. Altogether, our results clearly showed that osteoblast adhesion is under an intricate network of signaling molecules, which are responsible to guide their interaction with substrate mainly via cytoskeleton rearrangement. J. Cell. Biochem. 108: 134–144, 2009. © 2009 Wiley‐Liss, Inc.

Cofilin

10.1002/jcb.22236

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Citations (50)

A molecular landscape of quiescence and proliferation highlights the role of Pten in mammary gland acinogenesis

Journal of Cell Science (2023)

Rebeka Tomasin Ana Maria Rodrigues Antonio Carlos Manucci Alexandre Bruni‐Cardoso

Cell context is key for cell state. Using physiologically relevant models of laminin-rich extracellular matrix (lrECM) induction of mammary epithelial cell quiescence and differentiation, we provide a landscape of the key molecules for the proliferation-quiescence decision, identifying multiple layers of regulation at the mRNA and protein levels. Quiescence occurred despite activity of Fak (also known as PTK2), Src and phosphoinositide 3-kinases (PI3Ks), suggesting the existence of a disconnecting node between upstream and downstream proliferative signalling. Pten, a lipid and protein phosphatase, fulfils this role, because its inhibition increased proliferation and restored signalling via the Akt, mTORC1, mTORC2 and mitogen-activated protein kinase (MAPK) pathways. Pten and laminin levels were positively correlated in developing murine mammary epithelia, and Pten localized apicolaterally in luminal cells in ducts and near the nascent lumen in terminal end buds. Consistently, in three-dimensional acinogenesis models, Pten was required for triggering and sustaining quiescence, polarity and architecture. The multilayered regulatory circuitry that we uncovered provides an explanation for the robustness of quiescence within a growth-suppressive microenvironment, which could nonetheless be disrupted by perturbations in master regulators such as Pten.

10.1242/jcs.261178

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Citations (5)

Issue Information

The Prostate (2017)

Venkata Tissue Jayashree Yellepeddi Rajan Radhakrishnan Hengjun Xiao Jun Wang

Rest of World), €6139 (Europe), £4854 (UK).Prices are exclusive of tax.Asia-Pacifi c GST, Canadian GST/HST and European VAT will be applied at the appropriate rates.For more information on current tax rates, please go to www.wileyonlinelibrary.com/tax-vat.The price includes online access to the current and all online backfi les to January 1st 2014, where available.For other pricing options, including access information and terms and conditions, please visit www.wileyonlinelibrary.

10.1002/pros.23409

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Mitochondrial Morphology Regulates Organellar Ca²⁺Uptake and Changes Cellular Ca²⁺Homeostasis

bioRxiv (Cold Spring Harbor Laboratory) (2019)

Alicia J. Kowaltowski Sergio L. Menezes‐Filho Essam A. Assali Isabela G. Gonçalves Phablo Abreu

Abstract Changes in mitochondrial size and shape have been implicated in several physiological processes, but their role in mitochondrial Ca 2+ uptake regulation and overall cellular Ca 2+ homeostasis is largely unknown. Here we show that modulating mitochondrial dynamics towards increased fusion through expression of a dominant negative form of the fission protein DRP1 (DRP1‐DN) markedly increased both mitochondrial Ca 2+ retention capacity and Ca 2+ uptake rates in permeabilized C2C12 cells. Similar results were seen using the pharmacological fusion‐promoting M1 molecule. Conversely, promoting a fission phenotype through the knockdown of the fusion protein mitofusin 2 (MFN2) strongly reduced mitochondrial Ca 2+ uptake speed and capacity in these cells. These changes were not dependent on modifications in inner membrane potentials or the mitochondrial permeability transition. Implications of mitochondrial morphology modulation on cellular calcium homeostasis were measured in intact cells; mitochondrial fission promoted lower basal cellular calcium levels and lower endoplasmic reticulum (ER) calcium stores, as measured by depletion with thapsigargin. Indeed, mitochondrial fission was associated with ER stress. Additionally, the calcium‐replenishing process of store‐operated calcium entry (SOCE) was impaired in MFN2 knockdown cells, while DRP1‐DN‐promoted fusion resulted in faster cytosolic Ca 2+ increase rates. Overall, our results show a novel role for mitochondrial morphology in the regulation of mitochondrial Ca 2+ uptake, which impacts on cellular Ca 2+ homeostasis.

MFN2

Mitochondrial apoptosis-induced channel

Thapsigargin

Homeostasis

DNAJA3

Calcium Signaling

Uniporter

10.1101/624981

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Citations (2)

Deep nuclear invaginations linked to cytoskeletal filaments: Integrated bioimaging of epithelial cells in 3D culture

Journal of Cell Science (2016)

Danielle Jorgens Jamie L. Inman Michal Wojcik Claire Robertson Hildur Pálsdóttir

The importance of context in regulation of gene expression is now an accepted principle; yet the mechanism by which the microenvironment communicates with the nucleus and chromatin in healthy tissues is poorly understood. A functional role for nuclear and cytoskeletal architecture is suggested by the phenotypic differences observed between epithelial and mesenchymal cells. Capitalizing on recent advances in cryogenic techniques, volume electron microscopy, and super-resolution light microscopy, we studied human mammary epithelial cells in 3D cultures forming growth-arrested acini. Intriguingly, we found deep nuclear invaginations and tunnels traversing the nucleus, encasing cytoskeletal actin and/or intermediate filaments, which connect to the outer nuclear envelope. The cytoskeleton is connected also to both other cells via desmosome adhesion complexes and to the cell's ECM via hemidesmosomes. This finding supports a physical/mechanical link from the desmosomes and hemidesmosomes to the nucleus, which previously was hypothesized but now is visualized for the first time. These unique structures including the nuclear invaginations and the cytoskeletal connectivity to the cell nucleus is consistent with a dynamic reciprocity between the nucleus and the outside of epithelial cells and tissues.

Hemidesmosome

Nuclear lamina

10.1242/jcs.190967

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Citations (79)