Developmental aspects of the tympanic membrane: Shedding light on function and disease

The ear drum, or tympanic membrane (TM), is a key component in the intricate relay that transmits air‐borne sound to our fluid‐filled inner ear. Despite early belief that the mammalian ear drum evolved as a transformation of a reptilian drum, newer fossil data suggests a parallel and independent evolution of this structure in mammals. The term “drum” belies what is in fact a complex three‐dimensional structure formed from multiple embryonic cell lineages. Intriguingly, disease affects the ear drum differently in its different parts, with the superior and posterior parts being much more frequently affected. This suggests a key role for the developmental details of TM formation in its final form and function, both in homeostasis and regeneration. Here we review recent studies in rodent models and humans that are beginning to address large knowledge gaps in TM cell dynamics from a developmental biologist's point of view. We outline the biological and clinical uncertainties that remain, with a view to guiding the indispensable contribution that developmental biology will be able to make to better understanding the TM.     

Rewiring coral: Anthropogenic nutrients shift diverse coral–symbiont nutrient and carbon interactions toward symbiotic algal dominance

Improving coral reef conservation requires heightened understanding of the mechanisms by which coral cope with changing environmental conditions to maintain optimal health. We used a long‐term (10 month) in situ experiment with two phylogenetically diverse scleractinians (Acropora palmata and Porites porites) to test how coral–symbiotic algal interactions changed under real‐world conditions that were a priori expected to be beneficial (fish‐mediated nutrients) and to be harmful, but non‐lethal, for coral (fish + anthropogenic nutrients). Analyzing nine response variables of nutrient stoichiometry and stable isotopes per coral fragment, we found that nutrients from fish positively affected coral growth, and moderate doses of anthropogenic nutrients had no additional effects. While growing, coral maintained homeostasis in their nutrient pools, showing tolerance to the different nutrient regimes. Nonetheless, structural equation models revealed more nuanced relationships, showing that anthropogenic nutrients reduced the diversity of coral–symbiotic algal interactions and caused nutrient and carbon flow to be dominated by the symbiont. Our findings show that nutrient and carbon pathways are fundamentally “rewired” under anthropogenic nutrient regimes in ways that could increase corals’ susceptibility to further stressors. We hypothesize that our experiment captured coral in a previously unrecognized transition state between mutualism and antagonism. These findings highlight a notable parallel between how anthropogenic nutrients promote symbiont dominance with the holobiont, and how they promote macroalgal dominance at the coral reef scale. Our findings suggest more realistic experimental conditions, including studies across gradients of anthropogenic nutrient enrichment as well as the incorporation of varied nutrient and energy pathways, may facilitate conservation efforts to mitigate coral loss.     

Incorporation of the Tat cell‐penetrating peptide into nanofibers improves the respective antitumor immune response

A major challenge for the development of anticancer vaccines is the induction of a safe and effective immune response, particularly mediated by CD8+ T lymphocytes, in an adjuvant‐free manner. In this respect, we present a simple strategy to improve the specific CD8+ T cell responses using KFE8 nanofibers bearing a Class I (Kb)‐restricted peptide epitope (called E. nanofibers) without the use of adjuvant. We demonstrate that incorporation of Tat, a cell‐penetrating peptide (CPP) of the HIV transactivator protein, into E. nanofibers remarkably enhanced tumor‐specific CD8+ T cell responses. E. nanofibers containing 12.5% Tat peptide (E.Tat_12.5 nanofiber) increased antigen cross‐presentation by bone marrow‐derived dendritic cells as compared with E. nanofibers, or E. nanofibers containing 25 or 50% the Tat peptide. Uptake of KFE8.Tat_12.5 nanofibers by dendritic cells (DCs) was significantly increased compared with KFE8 nanofiber lacking Tat. Peritoneal and lymph node DCs of mice immunized with E.Tat_12.5 nanofibers exhibited increased presentation of the H2kb‐epitope (reminiscent for cross‐presentation) compared with DCs obtained from E. nanofiber vaccinated mice. Tetrameric and intracellular cytokine staining revealed that vaccination with E.Tat_12.5 triggered a robust and specific CD8+ T lymphocyte response, which was more pronounced than in mice vaccinated with E. nanofibers alone. Furthermore, E.Tat_12.5 nanofibers were more potent than E. nanofiber to induce antitumor immune response and tumor‐infiltrating IFN‐γ CD8 T lymphocyte. In terms of cancer vaccine development, we propose that harnessing the nanofiber‐based vaccine platform with incorporated Tat peptide could present a simple and promising strategy to induce highly effective antitumor immune response.     

Effectiveness of naturally occurring Aphis gossypii on tomato plants as a bio-indicator for heavy metals in Riyadh and Hafar Al-Batin,Saudi Arabia

Although certain pollutants can be biologically degraded by microorganisms, rendering their impact short-term, others can not be impaired, such that their effect persists. The present study evaluates the effectiveness of using a field-collected aphid, Aphis gossypii, as a bio-indicator for heavy metals in tomato farms in Riyadh and Hafar Al-Batin, Saudi Arabia. Heavy metals were selected (Cd, Cu, Zn, and Pb) and measured for comparative screening in field-collected plants, soil, and aphids using inductively coupled plasma-mass spectrometry (ICP-MS). Field-collected aphids from both studied regions were identified as Aphis gossypii. In Riyadh, there was no significant difference observed for Cd, Cu, and Zn for all experimental samples, while, Pb was showed differences among samples especially tomato leaves None of the studied samples in Hafar Al-Batin were showed statistically significant differences in Cd, in reverse to significant differences in the other heavy metals. Comparing concentrations of selected heavy metals between the two studied regions was showed that neither region showed a significant difference in heavy metals except for Cu. This study demonstrates that tomato leaf samples showed the highest concentrations of most studied heavy metals, followed by soil, then aphids. Aphids were utilized as a bio-indicator of heavy metals in the studied regions.     

The deleterious effect of stress‐induced depression on rat liver: Protective role of resveratrol and dimethyl fumarate via inhibiting the MAPK/ERK/JNK pathway

This study aimed to uncover the protective potentiality of resveratrol and dimethyl fumarate (DMF) in the liver of a chronic unpredictable mild stress (CUMS)‐induced depression animal model. Resveratrol and DMF significantly alleviated CUMS‐induced behavioral abnormalities in stressed rats through improving sucrose preference in sucrose preference test and decreasing immobility time in a forced swimming test. They also mitigated serum corticosterone levels and elevated serum serotonin levels, which were formerly disturbed in CUMS rats. The hepatoprotective effect is evidenced by improvement in hepatic histopathological examinations, as well as normalized serum alanine aminotransferase and aspartate aminotransferase activities. Molecular signaling of resveratrol and DMF was estimated by diminishing hepatic expression of phosphorylated p38 mitogen‐activated protein kinase (MAPK), extracellular signal‐regulated kinase1/2 (ERK1/2), and c‐Jun N‐terminal kinase (JNK). Consequently, they improved the hepatic antioxidant and anti‐inflammatory activities as elaborated by the normalization of total antioxidant capacity, glutathione, malondialdehyde, nuclear factor‐κB, tumor necrosis factor‐α, and myeloperoxidase levels. In addition, they inhibited hepatocyte apoptosis as evidenced by the increased expression of B‐cell lymphoma 2, the decreased expression of Bax, as well as the suppressed activity of caspase‐3. In conclusion, resveratrol and DMF purveyed a significant anti‐depressant effect, which may be mediated, at least in part, via inhibiting the MAPK/ERK/JNK pathway in the CUMS rat model.     

Nutrient sequestration potential of water primrose Ludwigia stolinefera (Guill. & Perr.) P.H. Raven: A strategy for restoring wetland eutrophication

The current work investigates the capacity of the water primrose (Ludwigia stolinefera) to sequester inorganic and organic nutrients in its biomass to restore eutrophic wetlands, besides its nutritive quality as fodder for animals. The nutrient elements and nutritive value of the water primrose were assessed seasonally in polluted and unpolluted watercourses. The water primrose plants’ highest biomass was attained during summer; then, it was significantly reduced till it reached its lowest value during winter. In the polluted canal, the plant root and shoot accumulated higher contents of all nutrient elements (except Na and Mg) rather than in the unpolluted Nile. They accumulated most investigated nutrients in the growing season during summer. The shoots accumulated higher contents of N, P, Ca, and Mg than the root, which accumulated higher concentrations of Na and K. Therefore, summer season is the ideal time to harvest water primrose for removing the maximum nutrients for restoring eutrophic watercourses. The aboveground tissues had the highest values of ether extract (EE) during spring and the highest crude fibers (CF) and total proteins (TP) during summer. In contrast, the belowground tissues had the lowest EE, CF, and TP during winter. In spring, autumn, and winter seasons, the protein content in the grazeable parts (shoots) of the water primrose was within the range, while in summer, it was higher than the minimum requirement for the maintenance of animals. There was a decrease in crude fibers and total proteins, while an increase in soluble carbohydrates content in the below- and above-ground tissues of water primrose under pollution stress. The total protein, lipids, and crude fibers of the aboveground parts of water primrose support this plant as a rough forage.