Structural anatomy of telomere OB proteins

Telomere DNA-binding proteins protect the ends of chromosomes in eukaryotes. A subset of these proteins are constructed with one or more OB folds and bind with G+T-rich single-stranded DNA found at the extreme termini. The resulting DNA-OB protein complex interacts with other telomere components to coordinate critical telomere functions of DNA protection and DNA synthesis. While the first crystal and NMR structures readily explained protection of telomere ends, the picture of how single-stranded DNA becomes available to serve as primer and template for synthesis of new telomere DNA is only recently coming into focus. New structures of telomere OB fold proteins alongside insights from genetic and biochemical experiments have made significant contributions towards understanding how protein-binding OB proteins collaborate with DNA-binding OB proteins to recruit telomerase and DNA polymerase for telomere homeostasis. This review surveys telomere OB protein structures alongside highly comparable structures derived from replication protein A (RPA) components, with the goal of providing a molecular context for understanding telomere OB protein evolution and mechanism of action in protection and synthesis of telomere DNA.     

Andromonoecy and fruit set in three genera of the Proteaceae

It has been suggested by some authors that the low fruit to flower ratio in some Proteaceae is due to andromonoecy, while others, looking particularly at Banksia , have not been able to find evidence for male flowers in the inflorescences. Stirlingia latifolia, Xylomelum occidentals and X. angustifolium are clearly andromonoecous, while no evidence for this condition could be found in Brabejum stellatifoliutn. Production of fertile fruit is related to andromonoecy in Xylomelum and S. latifolia but not in Brabejum. It is unlikely that all-encompassing solutions will be found to what initially seem to be widespread traits in the family, especially in regard to pollination biology, as the genera in the family occupy widely different environments and have very diverse ecological ranges.     

A Cross-linking Mass Spectrometry Approach Defines Protein Interactions in Yeast Mitochondria

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Highlights

• •XL-MS reveals new PPIs in yeast mitochondria under glycerol and glucose condition.
• •Significant but limited results from quantitative XL-MS experiments.
• •Ndi1 participates in a CIII₂CIV₂ respiratory supercomplex.
• •Min8 promotes assembly of Cox12 into an intermediate complex IV.

     

Multiomic Metabolic Enrichment Network Analysis Reveals Metabolite–Protein Physical Interaction Subnetworks Altered in Cancer

Metabolism is recognized as an important driver of cancer progression and other complex diseases, but global metabolite profiling remains a challenge. Protein expression profiling is often a poor proxy since existing pathway enrichment models provide an incomplete mapping between the proteome and metabolism. To overcome these gaps, we introduce multiomic metabolic enrichment network analysis (MOMENTA), an integrative multiomic data analysis framework for more accurately deducing metabolic pathway changes from proteomics data alone in a gene set analysis context by leveraging protein interaction networks to extend annotated metabolic models. We apply MOMENTA to proteomic data from diverse cancer cell lines and human tumors to demonstrate its utility at revealing variation in metabolic pathway activity across cancer types, which we verify using independent metabolomics measurements. The novel metabolic networks we uncover in breast cancer and other tumors are linked to clinical outcomes, underscoring the pathophysiological relevance of the findings.     

Mitochondrial Oxidative Phosphorylation Complex Regulates NLRP3 Inflammasome Activation and Predicts Patient Survival in Nasopharyngeal Carcinoma

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Highlights

• •Flow cytometry analysis is used to isolate ASC speck⁽⁺⁾ NPC cells.
• •Proteome analysis of ASC speck⁽⁺⁾ NPC cells reveals enriched mitochondrial OxPhos proteins.
• •OxPhos proteins mediate NLRP3 inflammasome activation through mtROS.
• •OxPhos proteins, NDUFB8 and ATP5B are correlated with NPC local recurrence.

     

DNA Sequences from Formalin-Fixed Nematodes: Integrating Molecular and Morphological Approaches to Taxonomy

To effectively integrate DNA sequence analysis and classical nematode taxonomy, we must be able to obtain DNA sequences from formalin-fixed specimens. Microdissected sections of nematodes were removed from specimens fixed in formalin, using standard protocols and without destroying morphological features. The fixed sections provided sufficient template for multiple polymerase chain reaction-based DNA sequence analyses.     

Ionotropic Receptors as a Driving Force behind Human Synapse Establishment

The origin of nervous systems is a main theme in biology and its mechanisms are largely underlied by synaptic neurotransmission. One problem to explain synapse establishment is that synaptic orthologs are present in multiple aneural organisms. We questioned how the interactions among these elements evolved and to what extent it relates to our understanding of the nervous systems complexity. We identified the human neurotransmission gene network based on genes present in GABAergic, glutamatergic, serotonergic, dopaminergic, and cholinergic systems. The network comprises 321 human genes, 83 of which act exclusively in the nervous system. We reconstructed the evolutionary scenario of synapse emergence by looking for synaptic orthologs in 476 eukaryotes. The Human–Cnidaria common ancestor displayed a massive emergence of neuroexclusive genes, mainly ionotropic receptors, which might have been crucial to the evolution of synapses. Very few synaptic genes had their origin after the Human–Cnidaria common ancestor. We also identified a higher abundance of synaptic proteins in vertebrates, which suggests an increase in the synaptic network complexity of those organisms.     

Emerging infectious diseases and animal social systems

Emerging infectious diseases threaten a wide diversity of animals, and important questions remain concerning disease emergence in socially structured populations. We developed a spatially explicit simulation model to investigate whether—and under what conditions—disease-related mortality can impact rates of pathogen spread in populations of polygynous groups. Specifically, we investigated whether pathogen-mediated dispersal (PMD) can occur when females disperse after the resident male dies from disease, thus carrying infections to new groups. We also examined the effects of incubation period and virulence, host mortality and rates of background dispersal, and we used the model to investigate the spread of the virus responsible for Ebola hemorrhagic fever, which currently is devastating African ape populations. Output was analyzed using regression trees, which enable exploration of hierarchical and non-linear relationships. Analyses revealed that the incidence of disease in single-male (polygynous) groups was significantly greater for those groups containing an average of more than six females, while the total number of infected hosts in the population was most sensitive to the number of females per group. Thus, as expected, PMD occurs in polygynous groups and its effects increase as harem size (the number of females) increases. Simulation output further indicated that population-level effects of Ebola are likely to differ among multi-male–multi-female chimpanzees and polygynous gorillas, with larger overall numbers of chimpanzees infected, but more gorilla groups becoming infected due to increased dispersal when the resident male dies. Collectively, our results highlight the importance of social system on the spread of disease in wild mammals.