A Microphysiological System with an Anaerobic Air-Liquid Interface and Functional Mucus Layer for Coculture of Intestinal Bacteria and Primary Human Colonic Epithelium.

Coculture of intestinal bacteria with primary human intestinal epithelium provides a valuable tool for investigating host-colon bacterial interactions and for testing and screening therapeutics. However, most current intestinal model systems lack key physiological features of the in vivo colon, such as both a proper oxygen microenvironment and a mucus layer. In this work, a new in vitro colonic microphysiological system is demonstrated with a cell-derived, functional mucus that closely resembles the in vivo colonic mucosa and apical microenvironment by employing an anaerobic air-liquid interface culture. The human primary colon epithelial cells in this new in vitro system exhibit high cell viability (>98%) with ≈100 µm thick functional mucus layer on average. Successful coculture of model anaerobic gut bacterial strains Lactobacillus rhamnosus GG and Anaerobutyricum hallii without loss in human cell viability demonstrates that this new model can be an invaluable tool for future studies of the impact of commensal and pathogenic bacteria on the colon.

The dynamics of Staphylococcal infection and their treatment with antibiotics and bacteriophage in the Galleria mellonella model system.

Critical to our understanding of infections and their treatment is the role the innate immune system plays in controlling bacterial pathogens. Nevertheless, many in vivo systems are made or modified such that they do not have an innate immune response. Use of these systems denies the opportunity to examine the synergy between the immune system and antimicrobial agents. In this study we demonstrate that the larva of Galleria mellonella is an effective in vivo model for the study of the population and evolutionary biology of bacterial infections and their treatment. To do this we test three hypotheses concerning the role of the innate immune system during infection. We show: i) sufficiently high densities of bacteria are capable of saturating the innate immune system, ii) bacteriostatic drugs and bacteriophages are as effective as bactericidal antibiotics in preventing mortality and controlling bacterial densities, and iii) minority populations of bacteria resistant to a treating antibiotic will not ascend. Using a highly virulent strain of Staphylococcus aureus and a mathematical computer-simulation model, we further explore how the dynamics of the infection within the short term determine the ultimate infection outcome. We find that excess immune activation in response to high densities of bacteria leads to a strong but short-lived immune response which ultimately results in a high degree of mortality. Overall, our findings illustrate the utility of the G. mellonella model system in conjunction with established in vivo models in studying infectious disease progression and treatment.

Delphinium as a model for development and evolution of complex zygomorphic flowers.

The complex zygomorphic flowers of the early-diverging eudicot Delphinium provide an opportunity to explore intriguing evolutionary, developmental, and genetic questions. The dorsal perianth organs, consisting of a spurred sepal and the nectar-bearing spurred petal(s) in Delphinium, contribute to the dorso-ventralization and zygomorphic flower morphology. The seamless integration of the two or three dorsal petaloid spurred organs is considered a synorganization, and the resulting organ complex is referred to as a hyperorgan. The hyperorgan shows variability within the tribe due to variation in the number, size, and shape of the spurs. Research in recent decades within this tribe has enhanced our understanding of morphological evolution of flowers. More recently, functional studies using the RNAi approach of Virus-Induced Gene Silencing (VIGS) have unraveled interesting results highlighting the role of gene duplication in the functional diversification of organ identity and symmetry genes. Research in this early-diverging eudicot genus bridges the gaps in understanding the morphological innovations that are mostly studied in model grass and core eudicot clades. This first comprehensive review synthesizes eco-evo-devo research on Delphinium, developing a holistic understanding of recent advancements and establishing the genus as an exceptional model for addressing fundamental questions in developmental genetics, particularly in the evolution of complex flowers. This progress highlights Delphinium's significant potential for future studies in this field.

Mycologists and Virologists Align: Proposing Botrytis cinerea for Global Mycovirus Studies.

Mycoviruses are highly genetically diverse and can significantly change their fungal host's phenotype, yet they are generally under-described in genotypic and biological studies. We propose Botrytis cinerea as a model mycovirus system in which to develop a deeper understanding of mycovirus epidemiology including diversity, impact, and the associated cellular biology of the host and virus interaction. Over 100 mycoviruses have been described in this fungal host. B. cinerea is an ideal model fungus for mycovirology as it has highly tractable characteristics-it is easy to culture, has a worldwide distribution, infects a wide range of host plants, can be transformed and gene-edited, and has an existing depth of biological resources including annotated genomes, transcriptomes, and isolates with gene knockouts. Focusing on a model system for mycoviruses will enable the research community to address deep research questions that cannot be answered in a non-systematic manner. Since B. cinerea is a major plant pathogen, new insights may have immediate utility as well as creating new knowledge that complements and extends the knowledge of mycovirus interactions in other fungi, alone or with their respective plant hosts. In this review, we set out some of the critical steps required to develop B. cinerea as a model mycovirus system and how this may be used in the future.

Pediatric Patients with Post-Burn Amputations Report Worse Long-Term Physical Function but Not Self-Appearance: A Burn Model System Study.

Some severe burn injuries may warrant amputation; however, the physical and functional adjustments resulting from post-burn amputation can have long-term consequences. This study investigates longitudinal functional and psychosocial outcomes among pediatric burn amputees. Pediatric participants enrolled in the Burn Model System national longitudinal, multicenter database between 2015-2023 with post-burn amputations were included. Participants with amputations were matched using nearest-neighbor matching to those without amputations based on burn location, age, and % total burn surface area burn size. Primary outcomes were the PROMIS Pediatric-25 Profile v2.0 Physical Function and the Children Burn Outcomes Questionnaire: appearance sub-score, both measured at 6-, 12- and 24 months post-burn. In this study, 17 participants had amputations and 17 did not (matched participants). Pairwise analyses at each timepoint found those with amputations reported significantly lower physical function scores at 24 months post-burn (54.9 ±11.6 vs. 66 ±5, p=0.013). No significant differences were found in appearance scores. This study suggests that pediatric burn amputees may potentially face greater physical impairment long-term, highlighting an important area of research that deserves further attention.

Large-eddy simulation of aerosol concentrations in a realistic urban environment: Model validation and transport mechanism.

Air pollution in urban environments exhibits large spatial and temporal variations due to high heterogeneous air flow and emissions. To address the complexity of local air pollutant dynamics, a comprehensive large-eddy simulation using the PALM model system v6.0 was conducted. The distribution of flow and vehicle emitted aerosol particles in a realistic urban environment in Malmö, Sweden, was studied and evaluated against on-site measurements made using portable instrumentation on a spring morning in 2021. The canyon transport mechanisms were investigated, and the convective and turbulent mass-transport rates compared to clarify their role in aerosol transport. The horizontal distribution of aerosols showed acceptable evaluation metrics for both mass and number. Flow and pollutant concentrations were more complex than those in idealized street canyon networks. Vertical turbulent mass-transport rate was found to dominate the mass transport process compared with the convective transport rate, contributing more than 70% of the pollutant transport process. Our findings highlight the necessity of examining various aerosol metric due their distinct dispersion behaviour. This study introduces a comprehensive high-resolution modelling framework that accounts for dynamic meteorological and aerosol background boundary conditions, real-time traffic emission, and detailed building features, offering a robust toll for local urban air quality assessment.

Assaying Lysosomal Enzyme Activity in Dictyostelium discoideum.

Lysosomes are membrane-enclosed organelles that digest intracellular material. They contain more than 50 different enzymes that can degrade a variety of macromolecules including nucleic acids, proteins, polysaccharides, and lipids. In addition to functioning within lysosomes, lysosomal enzymes are also secreted. Alterations in the levels and activities of lysosomal enzymes dysregulates lysosomes, which can lead to the intralysosomal accumulation of biological material and the development of lysosomal storage diseases (LSDs) in humans. Dictyostelium discoideum has a long history of being used to study the trafficking and functions of lysosomal enzymes. More recently, it has been used as a model system to study several LSDs. In this chapter, we outline the methods for assessing the activity of several lysosomal enzymes in D. discoideum (α-galactosidase, ß-galactosidase, α-glucosidase, ß-glucosidase, ß-N-acetylglucosaminidase, α-mannosidase, cathepsin B, cathepsin D, cathepsin F, palmitoyl protein thioesterase 1, and tripeptidyl peptidase 1).

Investigating Antiprotozoal Chemotherapies with Novel Proteomic Tools-Chances and Limitations: A Critical Review.

Identification of drug targets and biochemical investigations on mechanisms of action are major issues in modern drug development. The present article is a critical review of the classical "one drug"-"one target" paradigm. In fact, novel methods for target deconvolution and for investigation of resistant strains based on protein mass spectrometry have shown that multiple gene products and adaptation mechanisms are involved in the responses of pathogens to xenobiotics rather than one single gene or gene product. Resistance to drugs may be linked to differential expression of other proteins than those interacting with the drug in protein binding studies and result in complex cell physiological adaptation. Consequently, the unraveling of mechanisms of action needs approaches beyond proteomics. This review is focused on protozoan pathogens. The conclusions can, however, be extended to chemotherapies against other pathogens or cancer.

Pathological Defects in a Drosophila Model of Alzheimer's Disease and Beneficial Effects of the Natural Product Lisosan G.

Alzheimer's disease (AD) brains are histologically marked by the presence of intracellular and extracellular amyloid deposits, which characterize the onset of the disease pathogenesis. Increasing evidence suggests that certain nutrients exert a direct or indirect effect on amyloid ß (Aß)-peptide production and accumulation and, consequently, on AD pathogenesis. We exploited the fruit fly Drosophila melanogaster model of AD to evaluate in vivo the beneficial properties of Lisosan G, a fermented powder obtained from organic whole grains, on the intracellular Aß-42 peptide accumulation and related pathological phenotypes of AD. Our data showed that the Lisosan G-enriched diet attenuates the production of neurotoxic Aß peptides in fly brains and reduces neuronal apoptosis. Notably, Lisosan G exerted anti-oxidant effects, lowering brain levels of reactive oxygen species and enhancing mitochondrial activity. These aspects paralleled the increase in autophagy turnover and the inhibition of nucleolar stress. Our results give support to the use of the Drosophila model not only to investigate the molecular genetic bases of neurodegenerative disease but also to rapidly and reliably test the efficiency of potential therapeutic agents and diet regimens.

The kinetic study of 2-acetyl-1-pyrroline accumulation in the model system: An insight into enhancing rice flavor through the Maillard reaction.

Controlling the Maillard reaction may affect the generation of 2-acetyl-1-pyrroline, the key aroma compound in rice. In this study, the kinetics of 2-acetyl-1-pyrroline accumulation in the glucose/proline model system was comprehensively investigated and extra methylglyoxal or glyoxal was added to enhance 2-acetyl-1-pyrroline concentrations during rice cooking. Using the multi-response kinetic modeling to derive kinetic parameters, the formation of glyoxal, as the reactive intermediate, was rate-determining for the overall generation rate of 2-acetyl-1-pyrroline. Besides, although 2-acetyl-1-pyrroline generation was easier to occur with lower activation energy, much higher depletion rates of 2-acetyl-1-pyrrroline at 120 °C and 140 °C led to maximal 2-acetyl-1-pyrroline accumulation at the lower temperature of 100 °C. Furthermore, the inclusion of 0.05 µmol/kg additional methylglyoxal in cooked rice significantly enhanced 2-acetyl-1-pyrroline generation. The work suggested that the development of rice products with superior flavor quality may be achieved by the slight accumulation of intermediates prior to thermal processing.

Inhibitory effects of cassiae semen extract on the formation of 2-amino-1-methyl-6-phenylimidazo [4,5-b] pyridine (PhIP) in model system.

Introduction: 2-Amino-1-methyl-6-phenylimidazole [4,5-b] pyridine (PhIP), a heterocyclic amine (HAA), is found in meat products heated at high temperatures. However, PhIP is a mutagenic and potential carcinogenic compound. Cassiae semen, a type of medicine and food homology plant, is abundant in China and has been less applied for inhibiting heterocyclic amines. Methods: To investigate the inhibitory effect of cassiae semen extract on PhIP formation within a model system and elucidate the inhibitory mechanism, an ultrasonic-assisted method with 70% ethanol was used to obtain cassiae semen extract, which was added to a model system (0.6 mmol of phenylalanine: creatinine, 1:1). PhIP was analyzed by LC-MS to determine inhibitory effect. The byproducts of the system and the mechanism of PhIP inhibition were verified by adding the extract to a model mixture of phenylacetaldehyde, phenylacetaldehyde and creatinine. Results: The results indicated that PhIP production decreased as the concentration of cassiae semen extract increased, and the highest inhibition rate was 91.9%. Byproduct (E), with a mass-charge ratio of m/z 199.9, was detected in the phenylalanine and creatinine model system but was not detected in the other systems. The cassiae semen extract may have reacted with phenylalanine to produce byproduct (E), which prevented the degradation of phenylalanine by the Strecker reaction to produce phenylacetaldehyde. Discussion: Cassiae semen extract consumed phenylalanine, which is the precursor for PhIP, thus inhibiting the formation of phenylacetaldehyde and ultimately inhibiting PhIP formation. The main objective of this study was to elucidate the mechanism by which cassiae semen inhibit PhIP formation and establish a theoretical and scientific foundation for practical control measures.

De novo assembly of transcriptomes and differential gene expression analysis using short-read data from emerging model organisms - a brief guide.

Many questions in biology benefit greatly from the use of a variety of model systems. High-throughput sequencing methods have been a triumph in the democratization of diverse model systems. They allow for the economical sequencing of an entire genome or transcriptome of interest, and with technical variations can even provide insight into genome organization and the expression and regulation of genes. The analysis and biological interpretation of such large datasets can present significant challenges that depend on the 'scientific status' of the model system. While high-quality genome and transcriptome references are readily available for well-established model systems, the establishment of such references for an emerging model system often requires extensive resources such as finances, expertise and computation capabilities. The de novo assembly of a transcriptome represents an excellent entry point for genetic and molecular studies in emerging model systems as it can efficiently assess gene content while also serving as a reference for differential gene expression studies. However, the process of de novo transcriptome assembly is non-trivial, and as a rule must be empirically optimized for every dataset. For the researcher working with an emerging model system, and with little to no experience with assembling and quantifying short-read data from the Illumina platform, these processes can be daunting. In this guide we outline the major challenges faced when establishing a reference transcriptome de novo and we provide advice on how to approach such an endeavor. We describe the major experimental and bioinformatic steps, provide some broad recommendations and cautions for the newcomer to de novo transcriptome assembly and differential gene expression analyses. Moreover, we provide an initial selection of tools that can assist in the journey from raw short-read data to assembled transcriptome and lists of differentially expressed genes.

Inhibition of interferon gamma impairs induction of experimental epidermolysis bullosa acquisita.

Epidermolysis bullosa acquisita (EBA) is a muco-cutaneous autoimmune disease characterized and caused by autoantibodies targeting type VII collagen (COL7). The treatment of EBA is notoriously difficult, with a median time to remission of 9 months. In preclinical EBA models, we previously discovered that depletion of regulatory T cells (Treg) enhances autoantibody-induced, neutrophil-mediated inflammation and blistering. Increased EBA severity in Treg-depleted mice was accompanied by an increased cutaneous expression of interferon gamma (IFN-γ). The functional relevance of IFN-γ in EBA pathogenesis had been unknown. Given that emapalumab, an anti-IFN-γ antibody, is approved for primary hemophagocytic lymphohistiocytosis patients, we sought to assess the therapeutic potential of IFN-γ inhibition in EBA. Specifically, we evaluated if IFN-γ inhibition has modulatory effects on skin inflammation in a pre-clinical EBA model, based on the transfer of COL7 antibodies into mice. Compared to isotype control antibody, anti-IFN-γ treatment significantly reduced clinical disease manifestation in experimental EBA. Clinical improvement was associated with a reduced dermal infiltrate, especially Ly6G+ neutrophils. On the molecular level, we noted few changes. Apart from reduced CXCL1 serum concentrations, which has been demonstrated to promote skin inflammation in EBA, the expression of cytokines was unaltered in the serum and skin following IFN-γ blockade. This validates IFN-γ as a potential therapeutic target in EBA, and possibly other diseases with a similar pathogenesis, such as bullous pemphigoid and mucous membrane pemphigoid.

A Robust In Vitro Culture Model and Generation of Memory Monocytes.

Innate monocytes can be trained or reprogrammed to adopt distinct memory states, such as low-grade inflammation and immune exhaustion, bearing fundamental relevance to the pathogenesis of both acute diseases such as sepsis as well as chronic diseases such as atherosclerosis. Therefore, it is critically important to develop a regimen for generating memory monocytes in vitro in order to better define key monocyte memory states with diverse potentials for proliferation, differentiation, and activation, as well as underlying mechanisms. Here, we describe an efficient in vitro system to propagate a large number of highly purified murine memory monocytes through sustaining bone marrow-derived monocytes with macrophage colony-stimulating factor (M-CSF, 10 ng/mL)-containing medium, together with other polarization agents such as lipopolysaccharide (LPS) for a 5-day period. This method can yield high-purity monocytes, capable of exhibiting dynamic memory behaviors upon training with various polarizing agents.

Suillus: an emerging model for the study of ectomycorrhizal ecology and evolution.

Research on mycorrhizal symbiosis has been slowed by a lack of established study systems. To address this challenge, we have been developing Suillus, a widespread ecologically and economically relevant fungal genus primarily associated with the plant family Pinaceae, into a model system for studying ectomycorrhizal (ECM) associations. Over the last decade, we have compiled extensive genomic resources, culture libraries, a phenotype database, and protocols for manipulating Suillus fungi with and without their tree partners. Our efforts have already resulted in a large number of publicly available genomes, transcriptomes, and respective annotations, as well as advances in our understanding of mycorrhizal partner specificity and host communication, fungal and plant nutrition, environmental adaptation, soil nutrient cycling, interspecific competition, and biological invasions. Here, we highlight the most significant recent findings enabled by Suillus, present a suite of protocols for working with the genus, and discuss how Suillus is emerging as an important model to elucidate the ecology and evolution of ECM interactions.

Do astigmatid teeth matter: a tribological review of cheliceral chelae in co-occuring mites from UK beehives.

The dentition of the chelal moveable digit in cohabiting astigmatids from UK beehives (i.e., Carpoglyphus lactis (Linnaeus), Glycyphagus domesticus (DeGeer), and Tyrophagus putrescentiae (Schrank)) is characterised for the first time using quantitative tribological measures within a 2D mechanical model. The trophic function of astigmatid chelae are reviewed in terms of macroscopic tools used by humans including hooking devices, pliers, shears, rasps and saws. Comparisons to oribatid claws and isopod dactyli are made. The overall pattern of the moveable digit form of T. putrescentiae is not just a uniformly shrunken/swollen version between the other two taxa at either the macro- or micro-scale. Mastication surface macro-roughness values are in the range of international Roughness Grade Numbers N5-N6. The moveable digit of C. lactis has low rugosity values compared to the glycyphagid and acarid (which are topographically more similar and match that roughness typical of some coral reef surfaces). C. lactis has the most plesiomorphic moveable digit form. The mastication surface of all three species as a chewing tool is distinctly ornamented despite the moveable digit of C. lactis looking like a bar-like beam. The latter has more opportunities to be a multifunctional tool behaviourally than the other two species. Little evidence of any differences in the 'spikiness' of any 'toothiness' is found. Some differences with laboratory cultured specimens are found in C. lactis and possibly T. putrescentiae suggesting where selection on the digit may be able to occur. The chelal surface of T. putrescentiae has been deformed morphologically during evolution the most, that of C. lactis the least. Repeated localised surface differentiation is a feature of the moveable digit in G. domesticus compared to the likely more concerted changes over certain nearby locations in T. putrescentiae. An impactful chelal teeth design is present in G. domesticus but this is more equivocal in T. putrescentiae. Pockets within the mastication surface of the glycyphagid (and to some extent for the acarid) may produce foodstuff crunch forces of the scale of the chelal tips of oribatids. The moveable digit dentition of G. domesticus is adapted to shred foodstuff (like a ripsaw) more than that of the grazing/shearing dentition of T. putrescentiae. The collecting 'picker' design of C. lactis posterior teeth matches the size of Bettsia alvei hyphae which attacks hive-stored pollen. Detritus accumulated in chelal digit gullets through a sawing action matches the smallest observed ingested material. The dentition of C. lactis should produce less friction when moving through food material than G. domesticus. C. lactis is the most hypocarnivorous and may 'skim' through fluids when feeding. Astigmatid teeth do matter. The three commensal species can avoid direct competition. Future work is proposed in detail.

Potential application of carduma (Cetengraulis mysticetus) and plumuda (Opisthonema spp.) fish paste for the development of a leberkäse (liver loaf) fish product: Physicochemical and functional properties.

This study investigated the potential use of fish paste from two pelagic species (Cetengraulis mysticetus or carduma in Colombia and Opisthonema sp. or plumuda in Colombia), either separately or combined, as a substitute for external fat sources in a Leberkäse product. Three stages were analyzed, evaluating biometric proportions, body performance, and meat batters containing different concentrations of fish pastes. Physicochemical and instrumental characterization analyses were performed to determine the effect of the type of fish paste and the level of its inclusion in the final product. Results showed that plumuda fish paste had higher protein and ash content than carduma fish paste, and the inclusion of carduma fish paste in meat batters led to a greater loss of liquid and lower emulsion and gel stability values. The study also established selection criteria for the two pelagic fish species that could be useful for the fishing industry. Overall, the study demonstrated that Leberkäse can be produced using these pelagic species with a relatively simple processing technology.

Relationship between Flavonoid Chemical Structures and Their Antioxidant Capacity in Preventing Polycyclic Aromatic Hydrocarbons Formation in Heated Meat Model System.

The relationship between the chemical structures of six flavonoids and their abilities to inhibit the formation of polycyclic aromatic hydrocarbons (PAHs) in a heated meat model system was investigated. The PAH8 forming in samples was analyzed by using QuEChERS coupled GC-MS. Inhibitory effects of PAHs were myricetin (72.1%) > morin (55.7%) > quercetin (57.3%) > kaempferol (49.9%) > rutin (32.7%) > taxifolin (30.2%). The antioxidant activities of these flavonoids, assessed through (1, 1-diphenyl-2-picrylhydrazyl) free radical scavenging activity assay (DPPH), [2,2'-azinobis (3-ethylbenzothiazoline-6-sulphonic acid)] free radical scavenging activity assay (ABTS) and ferric ion reducing antioxidant power assay (FRAP) assays, exhibited a significant negative correlation with PAH reduction. Notably, myricetin that contained three hydroxyl groups on the B-ring, along with a 2,3-double bond in conjugation with a 4-keto moiety on the C-ring, demonstrated strong antioxidant properties and free radical scavenging abilities, which significantly contributed to their ability to inhibit PAH formation. However, rutin and taxifolin, substituted at the C-3 position of the C-ring, decreased the PAH inhibitory activity. The ABTS assay proved the most effective in demonstrating the correlation between flavonoid antioxidant properties and their capacity to inhibit PAH formation in heated meat model systems. Thus, the inhibition of PAHs can be achieved by dietary flavonoids according to their chemical structures.

Human otic progenitor cell models of congenital hearing loss reveal potential pathophysiologic mechanisms of Zika virus and cytomegalovirus infections.

Congenital hearing loss is a common chronic condition affecting children in both developed and developing nations. Viruses correlated with congenital hearing loss include human cytomegalovirus (HCMV) and Zika virus (ZIKV), which causes congenital Zika syndrome. The mechanisms by which HCMV and ZIKV infections cause hearing loss are poorly understood. It is challenging to study human inner ear cells because they are encased in bone and also scarce as autopsy samples. Recent advances in culturing human stem cell-derived otic progenitor cells (OPCs) have allowed us herein to describe successful in vitro infection of OPCs with HCMV and ZIKV, and also to propose potential mechanisms by which each viral infection could affect hearing. We find that ZIKV infection rapidly and significantly induces the expression of type I interferon and interferon-stimulated genes, while OPC viability declines, at least in part, from apoptosis. In contrast, HCMV infection did not appear to upregulate interferons or cause a reduction in cell viability, and instead disrupted expression of key genes and pathways associated with inner ear development and function, including Cochlin, nerve growth factor receptor, SRY-box transcription factor 11, and transforming growth factor-beta signaling. These findings suggest that ZIKV and HCMV infections cause congenital hearing loss through distinct pathways, that is, by inducing progenitor cell death in the case of ZIKV infection, and by disruption of critical developmental pathways in the case of HCMV infection. IMPORTANCE: Congenital virus infections inflict substantial morbidity and devastating disease in neonates worldwide, and hearing loss is a common outcome. It has been difficult to study viral infections of the human hearing apparatus because it is embedded in the temporal bone of the skull. Recent technological advances permit the differentiation of otic progenitor cells (OPCs) from human-induced pluripotent stem cells. This paper is important for demonstrating that inner ear virus infections can be modeled in vitro using OPCs. We infected OPCs with two viruses associated with congenital hearing loss: human cytomegalovirus (HCMV), a DNA virus, or Zika virus (ZIKV), an RNA virus. An important result is that the gene expression and cytokine production profiles of HCMV/ZIKV-infected OPCs are markedly dissimilar, suggesting that mechanisms of hearing loss are also distinct. The specific molecular regulatory pathways identified in this work could suggest important targets for therapeutics.

Ultrafast sound production mechanism in one of the smallest vertebrates.

Motion is the basis of nearly all animal behavior. Evolution has led to some extraordinary specializations of propulsion mechanisms among invertebrates, including the mandibles of the dracula ant and the claw of the pistol shrimp. In contrast, vertebrate skeletal movement is considered to be limited by the speed of muscle, saturating around 250 Hz. Here, we describe the unique propulsion mechanism by which Danionella cerebrum, a miniature cyprinid fish of only 12 mm length, produces high amplitude sounds exceeding 140 dB (re. 1 µPa, at a distance of one body length). Using a combination of high-speed video, micro-computed tomography (micro-CT), RNA profiling, and finite difference simulations, we found that D. cerebrum employ a unique sound production mechanism that involves a drumming cartilage, a specialized rib, and a dedicated muscle adapted for low fatigue. This apparatus accelerates the drumming cartilage at over 2,000 g, shooting it at the swim bladder to generate a rapid, loud pulse. These pulses are chained together to make calls with either bilaterally alternating or unilateral muscle contractions. D. cerebrum use this remarkable mechanism for acoustic communication with conspecifics.