Experimental Biology 2022

21 March 2022
21 March 2022

Biochemistry and Molecular Biology

Open Access

Seeded assembly in vitro does not replicate the structures of α-synuclein filaments from multiple system atrophy

Seeded assembly in vitro does not replicate the structures of α-synuclein filaments from multiple system atrophy

The assembly of certain proteins into amyloids underlies multiple neurodegenerative diseases. The spreading of these assemblies through the brain is thought to occur through a prion-like mechanism. We used filaments extracted from multiple system atrophy brains to seed recombinant α-synuclein. The resulting structures differ from those of the seeds, indicating that seeded assembly does not necessarily replicate the seed structures.

Open Access

Single-cell omics: Overview, analysis, and application in biomedical science

Single-cell omics: Overview, analysis, and application in biomedical science
Graphical abstract

In this Viewpoint, we briefly describe existing single-cell methods (genomics, transcriptomics, epigenomics, proteomics, and mulitomics), comment on available analysis tools, and give examples of method applications in the biomedical field

Free Access

Type IV secretion systems: Advances in structure, function, and activation

Type IV secretion systems: Advances in structure, function, and activation

Type IV secretion systems (T4SSs) are a functionally diverse superfamily of translocation nanomachines deployed by most species of bacteria. Collectively, T4SSs mediate the transfer of mobile genetic elements or protein toxins to other bacteria, or effector proteins or other macromolecules to eukaryotic cells to aid in infection. Recent structural and fluorescence approaches are generating exciting new insights into how T4SSs assemble in the cell envelope and recruit and translocate substrates to other cells.

Open Access

Reduced ER–mitochondria connectivity promotes neuroblastoma multidrug resistance

Mitochondria from REL neuroblastomas have attenuated apoptotic responses Mitochondrial cytochrome c release curves for neuroblastoma cell lines Bak and Bax analyses REL neuroblastomas are resistant to multimodal cancer therapeutics REL neuroblastoma cells are resistant to the cytotoxic effects of ionizing radiation despite incurring an equivalent increase in DNA damage Only reduced MAM content in neuroblastoma DX/REL pairs is correlated with attenuated mitochondrial responses to stress and chemotherapy resistance REL neuroblastomas have reduced mitochondria-associated membranes compared with patient-matched tumors from DX Chemically or genetically reducing MAMs leads to MOMP resistance Reduced Ca2+ transfer at MAMs is not required for attenuated mitochondrial responses to stress Reduced ceramides are present in REL cells with depleted MAMs Sphingomyelin concentrations in DX/REL neuroblastoma cells MAM-mediated mitochondrial resistance model Reduced ER–mitochondria connectivity promotes neuroblastoma multidrug resistance

Impaired ceramide biosynthesis at ER–mitochondria-associated membranes and lipid transfer into mitochondria decreases apoptotic signaling in relapsed tumor cells, contributing to cancer therapy resistance.

Free Access

A guide to studying protein aggregation

A guide to studying protein aggregation

The accumulation of un- or misfolded proteins can lead to the formation of amorphous or ordered aggregates. Protein aggregation is often associated with human diseases and unravelling its underlying mechanism is critical for the development of diagnostic methods or treatments. However, investigating protein aggregation is challenging due to its complex and dynamic nature. Here, we summarized some popular methods to study the various aspects and steps involved in protein aggregation.

Open Access

Lactate in contemporary biology: a phoenix risen

The concept of lactate shuttling between producer (driver) cells and tissues and consumer (recipient) Illustration of lactate shuttling during exercise (the cell-cell lactate shuttle) Illustration of lactate shuttling after consuming dietary carbohydrate: the postprandial period (the postprandial lactate shuttle) Lactate in contemporary biology: a phoenix risen

Abstract figure legend: Roles of lactate in physiology and metabolism elaborated as: cell fuelling (the preferential use of lactate over other fuel energy substrates such as glucose, fatty and keto acids in cardiac and red skeletal muscle and brain for cognition); cell signalling (the mechanisms by which lactate affects metabolism via effects on cell redox, ROS production, lactylation and covalent binding); microbiome (the role of fermentation in health and disease and the possibility of a gut-soma lactate shuttle); satiety (the role of lactate on the arcuate nucleus of the hypothalamus and gut-hypothalamic signalling); adaptation (the role of lactate in expression of glycolytic and metabolic enzymes and insulin sensitivity, the latter by TGF-β); reproduction (roles of lactate in sperm mitochondrial energetics, developing a favourable microenvironment for blastocysts and secretion of VEGF for uterine angiogenesis), and resuscitation (treatments of dehydration, acidosis, dengue, pancreatitis and hepatitis, myocardial infarction and wound healing).

Along the allostery stream: Recent advances in computational methods for allosteric drug discovery

Along the allostery stream: Recent advances in computational methods for allosteric drug discovery

This review comprehensively summarizes recent advances in computational methods for allosteric drug discovery, including the achievements along various levels of allosteric events, from the construction of allosteric databases to the identification and analysis of allosteric residues, signals, sites, and modulators.

Open Access

RNA nucleotide methylation: 2021 update

RNA nucleotide methylation: 2021 update

Identification of RNA methyltransferases is a major driving force in the field of epitranscriptomics.

Open Access

Biomarkers for respiratory diseases: Present applications and future discoveries

Biomarkers for respiratory diseases: Present applications and future discoveries

Omics-based discovery strategies facilitate the identification of next-generation candidate biomarkers in respiratory diseases. We systemically illustrate how multiple omics such as genomics, epigenomics, proteomics, metabolomics and radiomics are applied in respiratory medicine.

Open Access

FTO modifies the m6A level of MALAT and promotes bladder cancer progression

FTO modifies the m6A level of MALAT and promotes bladder cancer progression

FTO stimulates tumor growth of bladder cancer through regulating MALAT1 methylation.

MALAT1 and MAL2 interact with miR-384 for regulating tumor growth of bladder cancer.

FTO promotes bladder cancer tumor growth via MALAT1/miR-384/MAL2 axis.

Open Access

NF-κB signaling in inflammation and cancer

  • First Published: 16 December 2021
NF-κB signaling in inflammation and cancer

This year (2021) marks the 35th anniversary of the discovery of NF-κB. With so many years of in-depth research on NF-κB, people have realized that the NF-κB signaling pathway plays an important role in inflammation, immunity, cell survival and proliferation. This review summarizes the relevant knowledge of the NF-κB signaling pathway, inflammation, and cancer. The progression of the translational study and drug development targeting NF-κB for inflammatory diseases and cancer treatment and the potential obstacles will also be discussed.