Respiratory Tree Research Articles

Chemoreceptor MCP4580 of Vibrio splendidus mediates chemotaxis toward L-glutamic acid contributing to bacterial virulence

Chemotaxis has an essential function in flagellar bacteria that allows them to sense and respond to specific environmental signals, enabling their survival and colonization. Vibrio splendidus is an important opportunistic pathogen that infects a wide range of hosts including fish, bivalve, and sea cucumber. Our study demonstrated that V. splendidus AJ01 exhibited chemotaxis toward L-glutamic acid (L-Glu), an abundant amino acid in the intestinal and respiratory tree tissues of the sea cucumber. Bacterial samples collected from two locations in soft agar swimming plates were subjected to RNA-sequencing (RNA-Seq) analysis to identify the methyl-accepting chemotaxis protein (MCP) respond to L-Glu. Among the 40 annotated chemoreceptors, MCP4580 was identified as the MCP that mediates L-Glu-response. Molecular docking and site-directed mutagenesis revealed that L-arginine at residue 81 (R81) and L-glutamine at residue 88 (Q88) in the ligand-binding domain (LBD) are crucial for L-Glu recognition. Bacterial two-hybrid assay (BTH) showed that MCP4580 forms dimers and interacts with the histidine kinase CheA via the coupling protein CheW1 and CheW2. Phosphorylation analysis showed that the binding of L-Glu to MCP4580 results in the inhibition of CheA phosphorylation mainly via CheW1. Notably, sea cucumbers stimulated with each mutant strain of chemotaxis protein exhibited reduced mortality, highlighting the importance of chemotaxis in V. splendidus virulence. The present study provides valuable insights into the molecular components and signal transduction involved in the chemotaxis of V. splendidus toward L-Glu, and highlights the importance of chemotaxis in its virulence.

The foregut in cystic fibrosis.

The aerodigestive organs share a kindred embryologic origin that allows for a more complete explanation as to how the foregut can remain a barrier to normalcy in people with cystic fibrosis (pwCF). The structures of the aerodigestive tract include the nasopharynx, the oropharynx, the hypopharynx, the esophagus, the stomach, as well as the supraglottic, glottic, and subglottic tubular airways (including the trachea). Additional gastrointestinal (GI) luminal/alimentary organs of the foregut include the duodenum. Extraluminal foregut structures include the liver, the gall bladder, the biliary tree, and the pancreas. There are a variety of neurologic controls within these complicated anatomic compartments to separate the transit of food and liquid from air. These structures share the same origin from the primitive foregut/mesenchyme. The vagus nerve is a critical structure that unites respiratory and digestive functions. This article comments on the interconnected nature of cystic fibrosis and the GI tract. As it relates to the foregut, this has been typically treated as simple "reflux" as the cause of worsened lung function in pwCF. That terms like gastroesophageal reflux (GER), gastroesophageal reflux disease (GERD), heartburn, and regurgitation are used interchangeably to reflect pathology further complicates matters; we offer a more physiologically accurate term called "GI-related aspiration" or "GRASP." Broadly, this term reflects that aspiration of foregut contents from the duodenum through the stomachto the esophagus, into the pharynx and the respiratory tree in pwCF. As a barrier to normalcy in pwCF, GRASP is fundamentally two disease processes-GERD and gastroparesis-that likely contribute most to the deterioration of lung disease in pwCF. In the modulator era, successful GRASP management will be critical, particularly in those post-lung transplantation (LTx), only through successful management of both GERD and gastroparesis. Standardization of clinical management algorithms for GRASP in CF-related GRASP is a key clinical and research gap preventing normalcy in pwCF; what exists nearly exclusively addresses surgical evaluations or offers guidance for the management of GI symptoms alone (with unclear parameters for respiratory disease considerations). We begin first by describing the result of GRASP damage to the lung in various stages of lung disease. This is followed by a discussion of the mechanisms by which the digestive tract can injure the lungs. We summarize what we anticipate future research directions will be to reduce the impact of GRASP as a barrier to normalcy in pwCF.

Identification of Boveria labialis parasitism in the respiratory tree of the Cultured Sea cucumber, Apostichopus japonicus

Aquaculture of the sea cucumber Apostichopus japonicus has emerged as a pivotal industry in northern China in the early 21st century. It is estimated that the cultivation area for this species spans 250,356 ha, yielding an annual production of 248,508 tons. The swift growth and intensification of sea cucumber farming practices have triggered a spectrum of diseases, resulting in significant economic detriment. This study offers an exhaustive account of a particular ciliate species, identified through smear and histopathological observations, hematoxylin-eosin staining, scanning electron microscopy, and molecular biology techniques, detailing its morphology, size, cellular architecture, and reproductive mode. The ciliate exhibits a torch-like shape, measuring 40–82 μm in length and 12–35 μm in width. It is characterized by the presence of both a macronucleus and a micronucleus. The anterior end is slender and blunt, while the posterior end is the widest part of the organism. A peristomal disc (PD) is situated at the body's terminus, with the mouth positioned centrally on the PD and a lip-like projection (6–10 μm in length) extending from one side. The organism's surface, particularly the area surrounding the oral region, is adorned with an abundance of long cilia. A single contractile vacuole is observable at the aboral end of the ciliate. It possesses 17–21 somatic kineties, complemented by 3 membranelles (M1, M2, M3) and a paroral membrane (PM) within the buccal cavity. One contractile vacuole was seen at the aboral end. There were 17–21 somatic kineties, while three membranes (M1, M2, M3) and a paroral membrane (PM) located within the buccal cavity. The first somatic kinety is notably more extended than the others, uniquely reaching a length of 10 μm around the PM. The PM, comprised of 2 somatic kineties in a “zig-zag” formation, follows a spiral path, making approximately 360-degree turns in conjunction with M1, M2, and M3, and culminates at the mouth depression. The ciliate reproduces through transverse binary fission or sexual conjugation. Based on these distinguishing features and molecular biological identification results, the ciliate is provisionally classified within the genus Boveria, as Boveria labialis. Histopathological examination has shown that these ciliates are predominantly found within the respiratory trees of their hosts, where they inflict damage to the epithelial tissues. This damage manifests as cell necrosis, structural disintegration, and the shedding of cells from the respiratory tree's epithelial lining. In severe cases, the affected respiratory tree and other viscera may be expelled. Epidemiological studies have indicated that infected individuals do not present with any overt external lesions. The findings of this research are instrumental for the management of diseases and the promotion of health within the sea cucumber aquaculture industry.

Airway basal stem cells are necessary for the maintenance of functional intraepithelial airway macrophages.

Adult stem cells play a crucial role in tissue homeostasis and repair through multiple mechanisms. In addition to being able to replace aged or damaged cells, stem cells provide signals that contribute to the maintenance and function of neighboring cells. In the lung, airway basal stem cells also produce cytokines and chemokines in response to inhaled irritants, allergens, and pathogens, which affect specific immune cell populations and shape the nature of the immune response. However, direct cell-to-cell signaling through contact between airway basal stem cells and immune cells has not been demonstrated. Recently, a unique population of intraepithelial airway macrophages (IAMs) has been identified in the murine trachea. Here, we demonstrate that IAMs require Notch signaling from airway basal stem cells for maintenance of their differentiated state and function. Furthermore, we demonstrate that Notch signaling between airway basal stem cells and IAMs is required for antigen-induced allergic inflammation only in the trachea where the basal stem cells are located whereas allergic responses in distal lung tissues are preserved consistent with a local circuit linking stem cells to proximate immune cells. Finally, we demonstrate that IAM-like cells are present in human conducting airways and that these cells display Notch activation, mirroring their murine counterparts. Since diverse lung stem cells have recently been identified and localized to specific anatomic niches along the proximodistal axis of the respiratory tree, we hypothesize that the direct functional coupling of local stem cell-mediated regeneration and immune responses permits a compartmentalized inflammatory response.

NOX-derived ROS modulates the antibacterial immune responses in coelomocytes of Apostichopus japonicus

As an important generator of reactive oxygen species (ROS) in eukaryotic cells, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) is essential to antimicrobial host defense. AjNOX, a member of the NOX family, was identified in Apostichopus japonicus during the current investigation. It encodes a polypeptide with 571 amino acids, and it has an open reading frame of 1716 bp. The inferred amino acid sequence of AjNOX includes a transmembrane domain, a ferric reductase domain, a flavin adenine dinucleotide-binding-8 domain, and a NADPH-binding-6 domain. AjNOX shares 53.03%–42.39% sequence homology with other NOX proteins found in vertebrates and invertebrates in accordance with multiple sequence alignment. AjNOX was found in close proximity to the sea urchin SpNOX and the vertebrate NOX1–3 on the phylogenetic tree. The AjNOX gene was expressed in all of the test tissues including the body wall, muscle, intestine, respiratory tree, and coelomocytes. After being challenged with Vibrio splendidus, sea cucumber coelomocytes showed a remarkable increase in the protein and mRNA levels of AjNOX. ROS was produced less remarkably in coelomocytes as a result of AjNOX RNA interference. When the expression of AjNOX was suppressed by siRNA or inhibitor, the ability of coelomocytes to remove bacteria was drastically decreased. Reducing AjNOX-derived ROS decreased the production of inflammatory cytokines and coelomocyte apoptosis. All of these findings indicate that AjNOX may be crucial to the antibacterial immune response against the invasive pathogen V. splendidus in sea cucumbers A. japonicus.

Immune responses of sea cucumber (Apostichopus japonicus) to combined environmental stress from high temperature and oil pollution

Context High temperature and oil pollution are typical examples of environmental stress to sea cucumber (Apostichopus japonicus) in northern China. Aims Evaluate the combined effects of high temperature and oil pollution on the immune responses of sea cucumbers. Methods In this study, we investigated the immune responses in the respiratory tree of sea cucumber subjected to the optimal temperature (16°C), high temperature (26°C), Oman crude oil (OCO) water-accommodated fractions (WAF) at 16°C (WAF + 16°C) and OCO WAF at 26°C (WAF + 26°C) for 48 h. Key results All three treatments significantly up-regulated total antioxidant capacity and disturbed active oxygen species homeostasis in sea cucumbers. Moreover, all three treatments caused immune-enzyme activity disorders, manifested by a significant increase in acid–alkaline phosphatase and nitric oxide synthase activities and a noticeable decline in lysozyme activity. Conclusions Combining the integrated biomarker-response index (WAF + 26°C > 26°C > WAF + 16°C), the combined stress could result in a more adverse effect on the immune responses of sea cucumbers than do high temperature or oil pollution alone, which might further exacerbate the health challenges for sea cucumbers in response to environmental stress. Implications This study has provided an insight into the immune impacts in benthic organisms caused by high temperature and oil pollution.

Effects of hypo-osmotic stress on osmoregulation, antioxidant response, and energy metabolism in sea cucumber Holothuria moebii under desalination environment

With global climate changing, hypo-salinity events are increasing in frequency and duration because of continuous rainfall and freshwater inflow, which causes reduced cytosolic osmolarity and cellular stress responses in aquatic animals. Sea cucumbers are considered stenohaline because they lack osmoregulatory organs and are vulnerable to salinity fluctuations. In this study, we performed multiple biochemical assays, de novo transcriptomics, and widely targeted metabolomics to comprehensively explore the osmoregulatory mechanisms and physiological responses of sea cucumber Holothuria moebii to hypo-osmotic stress, which is a representative specie that is frequently exposed to hypo-saline intertidal zones. Our results found that H. moebii contracted their ambulacral feet and oral tentacles, and the coelomic fluid ion concentrations were reduced to be consistent with the environment. The microvilli of intestines and respiratory trees underwent degeneration, and the cytoplasm exhibited swelling and vacuolation. Moreover, the Na+, K+, and Cl− concentrations and Na+/K+-ATPase activity were significantly reduced under hypo-osmotic stress. The decrease in protein kinase A activity and increase in 5′-AMP level indicated a significant inhibition of the cAMP signaling pathway to regulate ion concentrations. And small intracellular organic molecules (amino acids, nucleotides and their derivatives) also play crucial roles in osmoregulation through oxidative deamination of glutamate, nucleotide catabolism, and nucleic acid synthesis. Moreover, lysosomes and peroxisomes removed oxidative damage, whereas antioxidant metabolites, such as N-acetyl amino acids and glutathione, were increased to resist oxidative stress. With prolonged hypo-osmotic stress, glycerophospholipid metabolism was enhanced to maintain membrane stability. Furthermore, acyl-CoA-binding protein activity was significantly inhibited, and only a small amount of acylcarnitine was significantly accumulated, which indicated a disruption in energy metabolism. PPAR signaling pathway and choline content were up-regulated to promote fatty acid metabolism under hypo-osmotic stress. Overall, our results provide new insights into the osmoregulatory mechanisms and physiological responses of sea cucumbers to hypo-osmotic stress.

Evaluation of the chronic toxicity of bisphenol A and bisphenol AF to sea cucumber Apostichopus japonicus after long-term single and combined exposure at environmental relevant concentration

Bisphenols are emerging endocrine disrupting pollutant, and several studies have reported that they are already ubiquitous in various environmental matrices and intend to deposit in sediment. The primary sources of bisphenols are river and sewage discharge. Sea cucumber (Apostichopus japonicus), a typical deposit feeder, is one of the most important commercial marine species in Aisa. However, the effects of the bisphenol A (BPA) and its analogues bisphenol AF (BPAF) on sea cucumber was unclear. In this study, we carried out field survey in major sea cucumber farming areas in northern China, with the aim of determining which bisphenol analogue is the major bisphenol contamination in this aquaculture area. The results showed that the presence of BPAF was detected in four sampling sites (Dalian, Tangshan, Laizhou, and Longpan). The mean level of BPAF in Laizhou sediment samples was the highest which reached to 9.007 ± 4.702 μ g/kg. Among the seawater samples, the BPAF only have been detected in the samples collected at Longpan. (0.011 ± 0.003 μ g/L). Furthermore, we conducted an experiment to evaluate the single and combined toxicity of BPA and BPAF on sea cucumbers. The concentrations were informed by the findings based on the results of field research. (0.1, 1.0, and 10 μ g/L). After exposure, the body weight gain, and specific growth rate showed no significant changes (P > 0.05). We observed the histological alterations in respiratory tree of treated sea cucumbers including the fusion and detachment of lining epithelial tissue, and increase of lumen space. However, the catalase (CAT), malondialdehyde (MDA), and glutathione (GSH) activity was not significantly changed (P > 0.05). We evaluated the effects of BPA and BPAF through calculating the integrated biomarker response index (IBR), and the results indicated that the toxicity of combined treatment was higher than single treatment. Additionally, BPAF exposure to A. japonicus was more toxic than BPA.

Infections fongiques pulmonaires (à l’exception de la pneumocystose)

AbstractThe respiratory tract is exposed daily to inhalation of a wide variety of fungal pathogens. In an immunocompetent individual with no underlying respiratory pathology, this exposure, provided it remains moderate, has no consequences, but in the case of altered integrity of the respiratory tree and/or innate or acquired immune deficiencies, the penetration of fungal agents into the respiratory tract is likely to lead to a variety of pathologies with variable clinical presentation, from localized pneumopathy to disseminated mycosis. This article reviews the main fungal agents responsible for respiratory diseases. For each pathogen, we will detail its main epidemiological characteristics, the clinical presentations and the diagnostic procedures.

How Biological Activity in Sea Cucumbers Changes as a Function of Species and Tissue.

Biological activity and bioactive compound content in sea cucumbers was assessed, considering Parastichopus regalis, Holothuria mammata, Holothuria forskali, and Holothuria arguinensis as species and intestine, muscle band, respiratory tree, body wall, and gonads as tissues. P. regalis had the lowest content in phenolic compounds and antioxidant activity in contrast to Holothuria species. In the respiratory tree, the highest phenolic concentration was recorded in H. arguinensis, 76.4 ± 1.2 mg GAE/100 g dw vs. 21.0-49.0 mg GAE/100 g dw in the other species. H. arguinensis had the highest DPPH and FRAP results in the gonads, 13.6 ± 0.7 mg AAE/100 g dw vs. 2.6-3.5 mg AAE/100 g dw and 27.1 ± 0.3 μmol Fe2+/g dw vs. 8.0-15.9 μmol Fe2+/g dw, respectively. Overall, P. regalis biomass presented the highest anti-inflammatory activity levels and H. arguinensis the lowest anti-inflammatory levels. The respiratory tree was the most anti-inflammatory (measured by the inhibition of cyclooxygenase-2, COX-2) tissue in H. mammata and H. forskali (also the muscle band in this case), 76.3 ± 6.3% and 59.5 ± 3.6% COX-2 inhibition in 1 mg/mL aqueous extracts, respectively. The results demonstrated a variable bioactive potential and advantage in targeting antioxidant properties in the muscle band and anti-inflammatory activity in the respiratory tree, which may constitute a starting point for a biorefinery approach envisaging multiple applications.

Morphometric analysis of airways in pre-COPD and mild COPD lungs using continuous surface representations of the bronchial lumen.

Introduction: Chronic Obstructive Pulmonary Disease (COPD) is a prevalent respiratory disease that presents a high rate of underdiagnosis during onset and early stages. Studies have shown that in mild COPD patients, remodeling of the small airways occurs concurrently with morphological changes in the proximal airways. Despite this evidence, the geometrical study of the airway tree from computed tomography (CT) lung images remains underexplored due to poor representations and limited tools to characterize the airway structure. Methods: We perform a comprehensive morphometric study of the proximal airways based on geometrical measures associated with the different airway generations. To this end, we leverage the geometric flexibility of the Snakes IsoGeometric Analysis method to accurately represent and characterize the airway luminal surface and volume informed by CT images of the respiratory tree. Based on this framework, we study the airway geometry of smoking pre-COPD and mild COPD individuals. Results: Our results show a significant difference between groups in airway volume, length, luminal eccentricity, minimum radius, and surface-area-to-volume ratio in the most distal airways. Discussion: Our findings suggest a higher degree of airway narrowing and collapse in COPD patients when compared to pre-COPD patients. We envision that our work has the potential to deliver a comprehensive tool for assessing morphological changes in airway geometry that take place in the early stages of COPD.

Effects of different visible light spectrums on phototaxis and bottom preference behavior of sea cucumber

In recent years, studies have shown that different light wavelengths have varying effects on aquaculture species. This indicates that exposure to light can significantly influence the health and development of aquatic organisms. This study investigated the effects of different visible light spectra on the behavior and physiological responses of sea cucumbers. Under blue LED and white LED illumination, the sea cucumbers exhibited shelter-seeking behavior. A phototaxis experiment found that the blue LED light elicited the strongest negative phototaxis, followed by the white LED. However, the red LED light elicited no obvious response. In the bottom zone preference experiment, blue LED and white LED illumination affected the bottom preference behaviors of some individuals compared to the control group. By measuring the mean photon flux density (MPFD) values at different illumination distances, the individuals in each group tended to stop moving when they were close to a similar MPFD value. Next, this study examined the physiological effects of red LED and blue LED illumination on sea cucumbers. Interestingly, the blue LED group exhibited higher oxygen consumption rates and thinner connective tissue in the respiratory tree during the early stage of the experiment. In contrast, no significant differences in coelomocyte phagocytosis were observed between the blue LED and red LED groups. Our findings suggested that the behaviors and physiological responses elicited by the blue or white LED light are likely caused by the number of photons in a specific time and area received by photoreceptors on the integument of sea cucumbers. Furthermore, neither long- nor short-wavelength spectra caused significant stress or damage to sea cucumbers in this study. The results obtained from this data will be beneficial for lighting usage in aquaculture environments in the future.

Highly rearranged gene orders and rapid evolutionary rates in the mitochondrial genomes of Apodida (Echinodermata: Holothuroidea)

Mitochondrial genome (mitogenome) is a frequently-used tool for phylogenetic and evolutionary studies among metazoans, however, it was still poorly represented in some invertebrate groups, including holothurians. Apodida is one of the most ancient orders of Holothuroidea, with unique characteristics in lacking tube feet and the respiratory tree. Here, we sequenced six mitogenomes from the holothurian order Apodida (Synaptidae and Chiridotidae) and compared them with other available holothurian mitogenomes. The apodan mitogenomes present positive GC skews and negative AT skews, a pattern diametrically opposite to that found in the mitogenomes of other holothurians. The amino acid genetic distances of the 13 protein-coding genes (PCGs) were the highest between Apodida and other holothurians. The mitochondrial gene orders within Apodida were extensively rearranged at the species level, and also were unique from the arrangement patterns of other holothurians. Phylogenetic relationships based on two different criteria: (i) nucleotides sequences with all codon positions (PCG123) and (ii) Neutral Transitions Excluded model (NTE) confirmed the monophyly and basal position of the order Apodida with a long branch. The NTE phylogeny generated a low variation of branch length, but it did not ameliorate the long branch length of Apodida. The divergence time estimation suggested that the Apodida originated in the Middle Carboniferous, implying that they survived the extinction event that occurred in the boundary of the Permian and Triassic. The NTE dataset revealed younger age than that generated by PCG123 dataset. Apodida is accompanied by a faster evolutionary rate than other holothurians (0.0069 vs 0.0043 subs/s/my). The absence of tube feet and the respiratory tree may play an important role in the dramatic evolutionary changes of apodan mitogenomes.

Isolation of Extracellular Vesicles of Holothuria (Sea Cucumber Eupentacta fraudatrix).

Extracellular vesicles (EVs), carriers of molecular signals, are considered a critical link in maintaining homeostasis in mammals. Currently, there is growing interest in studying the role of EVs, including exosomes (subpopulation of EVs), in animals of other evolutionary levels, including marine invertebrates. We have studied the possibility of obtaining appropriate preparations of EVs from whole-body extract of holothuria Eupentacta fraudatrix using a standard combination of centrifugation and ultracentrifugation. However, the preparations were heavily polluted, which did not allow us to conclude that they contained vesicles. Subsequent purification by FLX gel filtration significantly reduced the pollution but did not increase vesicle concentration to a necessary level. To detect EVs presence in the body of holothurians, we used transmission electron microscopy of ultrathin sections. Late endosomes, producing the exosomes, were found in the cells of the coelom epithelium covering the gonad, digestive tube and respiratory tree, as well as in the parenchyma cells of these organs. The study of purified homogenates of these organs revealed vesicles (30-100 nm) morphologically corresponding to exosomes. Thus, we can say for sure that holothurian cells produce EVs including exosomes, which can be isolated from homogenates of visceral organs.

Abundance of microbial community genes encoding terminal proteins of the aerobic and denitrification respiratory chains as indicators of ecohydrologic gradients in a coastal temperate rainforest

The persistence of soil organic carbon (SOC) is closely linked to the capacity of the soil microbial community to catalyze oxidative degradation of organic matter. This study uses a landscape-scale metagenomics approach to examine the relative abundances of genes encoding different terminal electron acceptors used for aerobic respiration and denitrification between soil microbial communities across an ecohydrologic gradient. The perhumid zone of the North Pacific coastal temperate rainforest serves as a template to test the associations between these differing respiratory pathways, soil conditions, and tree species biomass. We used the occurrence of reads in soil metagenomes as a proxy for the relative abundance of genes across the ecohydrologic gradient and identified distinct microbial fingerprints differentiating the driest (upland forest) and wettest (palustrine scrub-shrub and palustrine emergent wetland) ecosystem types. There was little gene-based differentiation between the ecosystem types at the wettest end of the ecohydrologic gradient - scrub-shrub wetland and emergent wetlands – while forested wetlands, which occur as gradient sites between upland forests and emergent wetlands on the landscape, were characterized by substantial metagenomic variability and, consequently, overlapped in their soil metagenome with the other ecosystem classes. Hydrology, as measured by groundwater depth was a predictor of O2 and N-oxide reductase abundances. High affinity O2 reductase genes were associated with wetter topographic positions, which has not been shown at the ecosystem scale, or in soils in-situ previously. N-oxide reductase genes were more associated with plant communities found at wetland sites but were not related to soil inorganic nitrogen, suggesting that nitrate supply may be limiting to denitrifiers ubiquitously across this gradient. Two plant species, Tsuga heterophylla (TSHE) and Pinus contorta spp. contorta (PICO), were more strongly correlated with O2-reductase and N-oxide reductase genes than site hydrology, respectively. This research represents a step toward fingerprinting the ecosystem microbiome using genes coding for specific terminal electron acceptors that control the fate of SOC and their ecohydrologic controls.

Resolution of Fetal Hydrops-not a Favorable Outcome in Congenital Pulmonary Malformation Type 1

Background: Congenital pulmonary airway malformations (CPAMs) comprise a spectrum of anatomical anomalies of the lungs and respiratory tree. The natural history of prenatally diagnosed CPAM varies from in utero resolution to progression to hydrops and intrauterine death. The majority of fetuses (90%) have a good outcome. However, in a minority (10%), the mass may grow so large that it is associated with complications and becomes life-threatening to the fetus. Clinical Description: Prenatal diagnosis of giant left CPAM type 1 was made at 24 weeks of gestation in a 29-year-old primigravida woman. The lesion consisted of multiple large cysts with a CPAM volume ratio of 4.7. Since the diagnosis, the mass was associated with nonimmune fetal hydrops and polyhydramnios which got worse throughout the following 4 weeks of gestation. Doppler studies remained normal until term. Management: The family received prenatal counseling. Parents refused termination of pregnancy and any other invasive or pharmacological therapy in light of the bad prognosis. The pregnancy was strictly monitored using standard fetal lung parameters. By 31 weeks' gestation, hydrops spontaneously improved to resolution but without any change in the size of the cysts. A baby girl was delivered at term, with birth asphyxia, who, despite all efforts by a multidisciplinary team, could not be revived. Autopsy and histopathological findings were compatible with type 1 CPAM. Conclusion: Hydrops is a well-known complication in fetuses with congenital cystic adenomatoid malformation. The present case reminds the possibility of its spontaneous resolution during pregnancy, even though the cyst size remains unaltered. The eventual neonatal survival depends not on the presence of hydrops but on the cyst volume and underlying lung hypoplasia.

Assessment of single and combined effects of bisphenol-A and its analogue bisphenol-S on biochemical and histopathological responses of sea cucumber Holothuria poli

Bisphenols (BPs) are among emerging pollutants that have been frequently detected in different compartments of marine ecosystems and elicited great concern due to their potential toxicity to marine organisms. This work aimed to investigate the toxicity of bisphenol A (BPA) and bisphenol S (BPS) on oxidative stress markers, neurotoxicity and histopathological alterations in sea cucumbers (Holothuria poli). The results showed that exposure to 200 μg/L of BPA and BPS produced oxidative stress, neurotoxicity in the digestive tract and respiratory tree, and several types of histopathological lesions in tissues of the respiratory tree of the sea cucumber, posing a health hazard to this aquatic organism. In addition, BPA has greater effects than BPS on the generation of oxidative stress marked by the inductions of catalase (CAT), glutathione S-transferase (GST) and malondialdehyde (MDA) levels and neurotoxicity shown by the decrease in acetylcholinesterase activity (AChE). The respiratory tree of sea cucumbers might be an appropriate tissue for assessing CAT, MDA and AChE activity levels, which are reliable biomarkers that may be useful in marine biomonitoring studies. Evaluation of histopathological lesions of the respiratory tree suggests that BPA and BPS and their mixture cause various tissue alterations that may be associated with oxidative stress damage and neurotoxicity. In conclusion, this study showed that oxidative stress (CAT and MDA) and neurotoxicity (AChE) markers, as well as respiratory tree lesions, are sensitive biomarkers for the assessment of BPA and BPS toxicity in sea cucumbers.

Glucocorticoids are differentially synthesized along the murine and human respiratory tree.

Synthetic glucocorticoids (GC) are effective in the treatment of inflammatory diseases of the lung. However, long-term use leads to severe side effects. Endogenous GC can be synthesized locally, either de novo from cholesterol in a 11β-hydroxylase (Cyp11b1)-dependent manner, or by reactivation from 11-dehydrocorticosterone/cortisone by 11β-hydroxysteroid dehydrogenase 1 (Hsd11b1). We aimed to define the molecular pathways of endogenous GC synthesis along the respiratory tree to provide a basis for understanding how local GC synthesis contributes to tissue homeostasis. Expression of steroidogenic enzymes in murine lung epithelium was analyzed by macroscopic and laser capture microdissection, followed by RT-qPCR. Flow cytometry analysis was performed to identify the cellular source of steroidogenic enzymes. Additionally, the induction of steroidogenic enzyme expression in the lung was analyzed after lipopolysaccharide (LPS) injection. mRNA and protein expression of steroidogenic enzymes was confirmed in human lung tissue by RT-qPCR and immunohistochemistry. Furthermore, GC synthesis was examined in ex vivo cultures of fresh tissue from mice and human lobectomy patients. We observed that the murine and human lung tissue differentially expresses synthesis pathway-determining enzymes along the respiratory tree. We detected Hsd11b1 expression in bronchial, alveolar, club and basal epithelial cells, whereas Cyp11b1 expression was detectable only in tracheal epithelial cells of mice. Accordingly, de novo synthesis of bioactive GC occurred in the large conducting airways, whereas reactivation occurred everywhere along the respiratory tree. Strikingly, Cyp11b1 but not Hsd11b1 expression was enhanced in the trachea upon LPS injection in mice. We report here the differential synthesis of bioactive GC along the murine and human respiratory tree. Thus, extra-adrenal de novo GC synthesis and reactivation may differentially contribute to the regulation of immunological and inflammatory processes in the lung.

The Holothuria leucospilota genome elucidates sacrificial organ expulsion and bioadhesive trap enriched with amyloid-patterned proteins

Some tropical sea cucumbers of the family Holothuriidae can efficiently repel or even fatally ensnare predators by sacrificially ejecting a bioadhesive matrix termed the Cuvierian organ (CO), so named by the French zoologist Georges Cuvier who first described it in 1831. Still, the precise mechanisms for how adhesiveness genetically arose in CO and how sea cucumbers perceive and transduce danger signals for CO expulsion during defense have remained unclear. Here, we report the first high-quality, chromosome-level genome assembly of Holothuria leucospilota, an ecologically significant sea cucumber with prototypical CO. The H. leucospilota genome reveals characteristic long-repeat signatures in CO-specific outer-layer proteins, analogous to fibrous proteins of disparate species origins, including spider spidroin and silkworm fibroin. Intriguingly, several CO-specific proteins occur with amyloid-like patterns featuring extensive intramolecular cross-β structures readily stainable by amyloid indicator dyes. Distinct proteins within the CO connective tissue and outer surface cooperate to give the expelled matrix its apparent tenacity and adhesiveness, respectively. Genomic evidence offers further hints that H. leucospilota directly transduces predator-induced mechanical pressure onto the CO surface through mediation by transient receptor potential channels, which culminates in acetylcholine-triggered CO expulsion in part or in entirety. Evolutionarily, innovative events in two distinct regions of the H. leucospilota genome have apparently spurred CO's differentiation from the respiratory tree to a lethal defensive organ against predators.

Analysis of Microplastic in Holothuria leucospilota (Echinodermata-Holothuroidea) and Sediments from Karachi coast, (Northern Arabian Sea)

Microplastics are found in all aquatic environments, and they can have several negative impacts on marine life. In this study, the distribution of microplastics in the sediment and in the organs (gut, respiratory tree, and tentacles) of sea cucumber (Holothuria leucospilota) collected from Mubarak Village and Cape Monze on the Karachi coast of Pakistan were investigated. The microplastic amount in different organs of H. leucospilota was found as 15.3-40.45 pieces/individual in the gut, 15.45-23.9 pieces/individual in the respiratory tree, 8.9-9.55 pieces/individual in tentacles. The microplastic amount of sediment samples was 57.40-129.35 pieces/kg. Fibers were the dominant microplastic type, up to 99% of all samples. The results of the present study show that the region is contaminated with microplastics both in biota and in sediments.