A mechanics-based perspective on the function of the esophagogastric junction during functional luminal imaging probe manometry

Biomechanics and Modeling in Mechanobiology - The esophagogastric junction (EGJ) is located at the distal end of the esophagus and acts as a valve allowing swallowed food to enter the stomach and...     

Signatures of host–pathogen evolutionary conflict reveal MISTR—A conserved MItochondrial STress Response network

Host–pathogen conflicts leave genetic signatures in genes that are critical for host defense functions. Using these “molecular scars” as a guide to discover gene functions, we discovered a vertebrate-specific MItochondrial STress Response (MISTR) circuit. MISTR proteins are associated with electron transport chain (ETC) factors and activated by stress signals such as interferon gamma (IFNγ) and hypoxia. Upon stress, ultraconserved microRNAs (miRNAs) down-regulate MISTR1(NDUFA4) followed by replacement with paralogs MItochondrial STress Response AntiViral (MISTRAV) and/or MItochondrial STress Response Hypoxia (MISTRH). While cells lacking MISTR1(NDUFA4) are more sensitive to chemical and viral apoptotic triggers, cells lacking MISTRAV or expressing the squirrelpox virus-encoded vMISTRAV exhibit resistance to the same insults. Rapid evolution signatures across primate genomes for MISTR1(NDUFA4) and MISTRAV indicate recent and ongoing conflicts with pathogens. MISTR homologs are also found in plants, yeasts, a fish virus, and an algal virus indicating ancient origins and suggesting diverse means of altering mitochondrial function under stress. The discovery of MISTR circuitry highlights the use of evolution-guided studies to reveal fundamental biological processes.

Host-pathogen conflicts leave genetic signatures in genes that are critical for host defense functions. This study uses these “molecular scars” as a guide to identify a vertebrate-specific mitochondrial stress response circuit that interacts with the electron transport chain and is activated by stress signals such as interferon-gamma and hypoxia.     

Species-specific effects of thermal stress on the expression of genetic variation across a diverse group of plant and animal taxa under experimental conditions

Assessing the genetic adaptive potential of populations and species is essential for better understanding evolutionary processes. However, the expression of genetic variation may depend on environmental conditions, which may speed up or slow down evolutionary responses. Thus, the same selection pressure may lead to different responses. Against this background, we here investigate the effects of thermal stress on genetic variation, mainly under controlled laboratory conditions. We estimated additive genetic variance (V_A), narrow-sense heritability (h²) and the coefficient of genetic variation (CV_A) under both benign control and stressful thermal conditions. We included six species spanning a diverse range of plant and animal taxa, and a total of 25 morphological and life-history traits. Our results show that (1) thermal stress reduced fitness components, (2) the majority of traits showed significant genetic variation and that (3) thermal stress affected the expression of genetic variation (V_A, h² or CV_A) in only one-third of the cases (25 of 75 analyses, mostly in one clonal species). Moreover, the effects were highly species-specific, with genetic variation increasing in 11 and decreasing in 14 cases under stress. Our results hence indicate that thermal stress does not generally affect the expression of genetic variation under laboratory conditions but, nevertheless, increases or decreases genetic variation in specific cases. Consequently, predicting the rate of genetic adaptation might not be generally complicated by environmental variation, but requires a careful case-by-case consideration.Subject terms: Evolutionary genetics, Climate-change ecology, Biodiversity     

Size and density mediate transitions between competition and facilitation

Species simultaneously compete with and facilitate one another. Size can mediate transitions along this competition–facilitation continuum, but the consequences for demography are unclear. We orthogonally manipulated the size of a focal species, and the size and density of a heterospecific neighbour, in the field using a model marine system. We then parameterised a size‐structured population model with our experimental data. We found that heterospecific size and density interactively altered the population dynamics of the focal species. Size determined whether heterospecifics facilitated (when small) or competed with (when large) the focal species, while density strengthened these interactions. Such size‐mediated interactions also altered the pace of the focal’s life history. We provide the first demonstration that size and density mediate competition and facilitation from a population dynamical perspective. We suspect such effects are ubiquitous, but currently underappreciated. We reiterate classic cautions against inferences about competitive hierarchies made in the absence of size‐specific data.     

Motility and ultrastructure of large granular lymphocytes on lipid bilayers reconstituted with adhesion receptors LFA-1, ICAM-1, and two isoforms of LFA-3

Large granular lymphocytes, mediators of NK activity, bind to other cells using both the LFA (lymphocyte function-associated)-1-ICAM and the CD2-LFA-3 adhesion pathways. Here we have studied the motility and ultrastructure of large granule lymphocyte (LGL) on lipid bilayers containing purified LFA-1, ICAM-1, and the transmembrane and glycophosphatidylinositol isoforms of LFA-3. LGLs moved at 8 microns/min on ICAM-1 but poorly (less than 1 microns/min) on its receptor pair LFA-1. TM-LFA-3 promoted locomotion at a rate close to ICAM-1, whereas the cells were less motile on GPI-LFA-3. The difference in the rates of locomotion on the two isoforms of LFA-3 is presumably attributable to their difference in anchoring and lateral mobility in the bilayer. In spite of the variation in motility the ultrastructure of the adhering cells was similar on all four ligands. LGLs contacted the membrane variably, i.e., cells adhering only in a few small areas or in larger areas were detected on each ligand. The relative percentage of the plasma membrane facing the lipid bilayer was greatest on ICAM-1 and least on the transmembrane isoform of LFA-3, demonstrating no correlation with motility. The ratio of adjacent plasma membrane to lipid bilayer was virtually constant for all four ligands. Activation of the LGLs with a combination of CD2 mAb T11(2) and T11(3) (T11(2/3) mAb) reduced the movement on ICAM-1 and virtually immobilized the cells on the other bilayers. In the presence of T11(2/3) mAb, the area of cell membrane attaching to bilayers containing ICAM-1 and GPI-LFA-3 was decreased and the percentage of plasma membrane facing other cells was increased. No preferential orientation of the Golgi apparatus or degranulation was detected in the absence or presence of T11(2/3) mAb, but a significantly lower percentage of LGLs on ICAM-1 contained a profile of the Golgi apparatus after exposure to T11(2/3) mAb. The results demonstrate that the motility of LGLs depends on the type of receptor in the opposing bilayer, the receptor mobility in the bilayer, and the activation of the cells. The ultrastructure of LGLs binding to any of the adhesion molecules does not have the characteristics of LGLs in cytolytic contact with target cells, suggesting that the mediation of an attack on a target requires more complex stimulus than any one of the single adhesion proteins tested here.     

Multiple Niche Compartments Orchestrate Stepwise Germline Stem Cell Progeny Differentiation

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Spruce proteome DB: a resource for conifer proteomics research

Proteomics research is hampered in many organisms due to a lack of an appropriate reference genome sequence that can be used in the interpretation of tandem mass spectrometry data for the identification of proteins. Public DNA sequence repositories have grown to considerable size and can, in most cases, serve to provide at least partial interpretation of a large-scale proteomics dataset. However, when species-specific sequences or sequences from a closely related species are available, a boutique sequence database can provide considerable increases in specificity, confidence, and completeness of protein identification. Here, we describe the development of a protein database from a large-scale expressed sequence tag and full-length complementary DNA sequencing project in the economically and ecologically important spruce (Picea) genus.