Bio-informed synthesis of marine-sourced indole derivatives: suppressing gram-negative bacteria biofilm and virulence.

Biofilms cling to surfaces to form complex architectures allowing their bacterial creators to acquire multidrug resistance and claiming countless lives worldwide. Therefore, finding novel compounds that affect virulence and biofilm-forming capacity of resistant pathogenic bacteria is imperative. Recently, we identified indole-based compounds that possess anti-biofilm properties in coral-associated bacteria.

A Haloarchaeal Transcriptional Regulator That Represses the Expression of CRISPR-Associated Genes.

Clustered regularly interspaced short palindromic repeats (CRISPR)-Cas (CRISPR-associated proteins) systems provide acquired heritable protection to bacteria and archaea against selfish DNA elements, such as viruses. These systems must be tightly regulated because they can capture DNA fragments from foreign selfish elements, and also occasionally from self-chromosomes, resulting in autoimmunity. Most known species from the halophilic archaeal genus contain type I-B CRISPR-Cas systems, and the strongest hotspot for self-spacer acquisition by was a locus that contained a putative transposable element, as well as the gene , which was a very frequent target for self-targeting spacers.

The landscape of molecular chaperones across human tissues reveals a layered architecture of core and variable chaperones.

The sensitivity of the protein-folding environment to chaperone disruption can be highly tissue-specific. Yet, the organization of the chaperone system across physiological human tissues has received little attention. Through computational analyses of large-scale tissue transcriptomes, we unveil that the chaperone system is composed of core elements that are uniformly expressed across tissues, and variable elements that are differentially expressed to fit with tissue-specific requirements.

Publisher Correction: High-sensitivity and high-specificity biomechanical imaging by stimulated Brillouin scattering microscopy.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

High-sensitivity and high-specificity biomechanical imaging by stimulated Brillouin scattering microscopy.

Label-free, non-contact imaging with mechanical contrast and optical sectioning is a substantial challenge in microscopy. Spontaneous Brillouin scattering microscopy meets this challenge, but encounters a trade-off between acquisition speed and the specificity for biomechanical constituents with overlapping Brillouin bands. Stimulated Brillouin scattering microscopy overcomes this trade-off and enables the cross-sectional imaging of live Caenorhabditis elegans at the organ and subcellular levels, with both elasticity and viscosity contrasts at high specificity and with practical recording times.

Dietary restriction and gonadal signaling differentially regulate post-development quality control functions in Caenorhabditis elegans.

Protein homeostasis is remodeled early in Caenorhabditis elegans adulthood, resulting in a sharp decline in folding capacity and reduced ability to cope with chronic and acute stress. Endocrine signals from the reproductive system can ameliorate this proteostatic collapse and reshape the quality control network. Given that environmental conditions, such as food availability, impact reproductive success, we asked whether conditions of dietary restriction (DR) can also reverse the decline in quality control function at the transition to adulthood, and if so, whether gonadal signaling and dietary signaling remodel the quality control network in a similar or different manner.

Role of duplicate genes in determining the tissue-selectivity of hereditary diseases.

A longstanding puzzle in human genetics is what limits the clinical manifestation of hundreds of hereditary diseases to certain tissues, while their causal genes are expressed throughout the human body. A general conception is that tissue-selective disease phenotypes emerge when masking factors operate in unaffected tissues, but are specifically absent or insufficient in disease-manifesting tissues. Although this conception has critical impact on the understanding of disease manifestation, it was never challenged in a systematic manner across a variety of hereditary diseases and affected tissues.

No Excess Baggage: New Life Starts with a Clean Slate.

A new mechanism for clearing protein damage from maturing oocytes has been described in a recent study by Bohnert and Kenyon (2017), who demonstrated that sperm-secreted hormones activate a vascular H-ATPase pump that acidifies lysosomes and thus restores protein homeostasis.

Dietary-Induced Signals That Activate the Gonadal Longevity Pathway during Development Regulate a Proteostasis Switch in Adulthood.

Cell-non-autonomous signals dictate the functional state of cellular quality control systems, remodeling the ability of cells to cope with stress and maintain protein homeostasis (proteostasis). One highly regulated cell-non-autonomous switch controls proteostatic capacity in adulthood. Signals from the reproductive system down-regulate cyto-protective pathways, unless countered by signals reporting on germline proliferation disruption.

Uncoupling the Trade-Off between Somatic Proteostasis and Reproduction in Models of Polyglutamine Diseases.

somatic protein homeostasis (proteostasis) is actively remodeled at the onset of reproduction. This proteostatic collapse is regulated cell-nonautonomously by signals from the reproductive system that transmit the commitment to reproduction to somatic cells. Here, we asked whether the link between the reproductive system and somatic proteostasis could be uncoupled by activating downstream effectors in the gonadal longevity cascade.

An Asymmetrically Balanced Organization of Kinases versus Phosphatases across Eukaryotes Determines Their Distinct Impacts.

Protein phosphorylation underlies cellular response pathways across eukaryotes and is governed by the opposing actions of phosphorylating kinases and de-phosphorylating phosphatases. While kinases and phosphatases have been extensively studied, their organization and the mechanisms by which they balance each other are not well understood. To address these questions we performed quantitative analyses of large-scale 'omics' datasets from yeast, fly, plant, mouse and human.

A Differentiation Transcription Factor Establishes Muscle-Specific Proteostasis in Caenorhabditis elegans.

Safeguarding the proteome is central to the health of the cell. In multi-cellular organisms, the composition of the proteome, and by extension, protein-folding requirements, varies between cells. In agreement, chaperone network composition differs between tissues.

Chaperone families and interactions in metazoa.

Quality control is an essential aspect of cellular function, with protein folding quality control being carried out by molecular chaperones, a diverse group of highly conserved proteins that specifically identify misfolded conformations. Molecular chaperones are thus required to support proteins affected by expressed polymorphisms, mutations, intrinsic errors in gene expression, chronic insult or the acute effects of the environment, all of which contribute to a flux of metastable proteins. In this article, we review the four main chaperone families in metazoans, namely Hsp60 (where Hsp is heat-shock protein), Hsp70, Hsp90 and sHsps (small heat-shock proteins), as well as their co-chaperones.

Remodeling of Proteostasis Upon Transition to Adulthood is Linked to Reproduction Onset.

Protein folding and clearance networks sense and respond to misfolded and aggregation-prone proteins by activating cytoprotective cell stress responses that safeguard the proteome against damage, maintain the health of the cell, and enhance lifespan. Surprisingly, cellular proteostasis undergoes a sudden and widespread failure early in Caenorhabditis elegans adulthood, with marked consequences on proteostasis functions later in life. These changes in the regulation of quality control systems, such as chaperones, the ubiquitin proteasome system and cellular stress responses, are controlled cell-nonautonomously by the proliferation of germline stem cells.

Using Caenorhabditis elegans as a model system to study protein homeostasis in a multicellular organism.

The folding and assembly of proteins is essential for protein function, the long-term health of the cell, and longevity of the organism. Historically, the function and regulation of protein folding was studied in vitro, in isolated tissue culture cells and in unicellular organisms. Recent studies have uncovered links between protein homeostasis (proteostasis), metabolism, development, aging, and temperature-sensing.

Germline stem cell arrest inhibits the collapse of somatic proteostasis early in Caenorhabditis elegans adulthood.

All cells rely on highly conserved protein folding and clearance pathways to detect and resolve protein damage and to maintain protein homeostasis (proteostasis). Because age is associated with an imbalance in proteostasis, there is a need to understand how protein folding is regulated in a multicellular organism that undergoes aging. We have observed that the ability of Caenorhabditis elegans to maintain proteostasis declines sharply following the onset of oocyte biomass production, suggesting that a restricted protein folding capacity may be linked to the onset of reproduction.