Tubular Organs Research Articles

NKX2‐1 directly regulates Efnb2 to generate a boundary that allocates tracheal cells and defines the position of tracheoesophageal separation

Tracheoesophageal (TE) fistula is a human congenital condition characterized by an improper connection between the esophagus and trachea. These two tubular organs originate from a single foregut tube and separate from one another beginning at the site of lung bud evagination and progressing rostrally. Genetic studies in mice have identified signaling pathways that initiate dorsoventral patterning of the foregut; NKX2‐1 marks ventral, presumptive tracheal cells whereas high levels of SOX2 expression predominantly mark the dorsal, esophageal‐fated cells. Perturbation of either factor results in loss of that identity, increased expression of the opposing transcription factor, and failure of TE separation. Currently, the downstream mechanisms required to effect morphogenetic separation at the cellular and tissue level remain largely unknown. Here, we show that EPHRIN‐B2, a member of the EPH/EPHRIN signaling family, is restricted to the dorsal, esophageal‐fated cells, and that this domain of expression is required for TE separation and for maintaining the correct allocation of tracheal cells to the nascent trachea. Further, we demonstrate that NKX2‐1 directly binds at the Efnb2 locus and negatively regulates its expression, establishing an NKX2‐1/EPHRIN‐B2 TE boundary. Nkx2‐1 mosaic mutants exhibit ectopic NKX2‐1/EPHRIN‐B2 boundaries which drive ectopic tracheal separation morphogenesis in an EPHRIN‐B2 dependent manner. These results establish NKX2‐1 as a regulator of TE cell sorting and tissue separation, through modulation of EPH/EPHRIN signaling, which then serves to translate tissue identity information into morphogenetic outcomes.

Intraluminal Pressure, Multi‐Dimensional Field Imaging and Fluid Volume Recordings as a Useful Tool to Determine Peristaltic Propulsion

IntroductionPeristalsis is a collective process of intestinal muscle contractions for the passage of food through the gastrointestinal tract. Although, peristalsis has been extensively studied using spatiotemporal mapping and pressure transducers both in vivo and in vitro, the quantitative analysis of peristaltic propulsion is not fully understood. Lack of a definitive tool therefore, limited drug discovery in the field of constipation including IBSC. In this study, we used directional lighting, advanced field‐imaging techniques together with intraluminal pressure recordings to determine intestinal diameter, frequency of longitudinal muscle activity and pressure changes as well as velocity of anterograde and retrograde contractions and volume output measurements to help determine the net peristaltic activity.MethodsThe basal activity of intestinal peristalsis in terms of intraluminal pressure (ILP) changes, real‐time changes in longitudinal muscle activity and intestinal lumen diameter were measured in approximately 5 cm long segments from jejunum of mouse small intestine (male, NIH Swiss) in physiological Ringer solution. Intraluminal pressure was recorded using pressure transducers connected to the oral and aboral end of each segment mounted in Perfusion Bath for Tubular Organs, (Harvard apparatus, USA). Longitudinal muscle activity was studied using CVX400 series vision system, and LumiTrax™multi‐spectrum light (Keyence, USA) using multiple tracking points in each intestinal segment. The number, strength, and amplitude of oscillations in terms of intraluminal pressure changes and longitudinal muscle activity was analyzed using custom written programs. Luminal volume output was measured using a photo‐electric drop counter unit.ResultsThe number, amplitude, duration, and frequency of high and low amplitude changes in ILP and longitudinal muscle activity was determined using a lab‐written program. The frequency of longitudinal muscle activity correlated well with the frequency of low and high amplitude pressure changes. Frequency of both these oscillations were found to be 0.7 Hz. A reduction in the ILP was found to induce high amplitude contractions which subsided as the ILP increased. Changes in intestinal diameter with time correlated to ILP changes. A reduction in luminal diameter caused an increase in ILP and when not fully compensated caused increased fluid output. The mean velocity of the contractions over time in the regions tracked was determined to be 2.5 – 2.7mm/sec with peak anterograde contraction velocity of ‐4.06 mm/sec and retrograde contractions of 12 mm/sec. This mean velocity in presence of physiological Ringer solution was thought to determine the direction of contractions along the length of the GI tract under normal conditions.InferenceFrequency of longitudinal muscle activity and ILP oscillation showed similar frequency suggesting common pacemaker activity. The velocity of the contraction and volume output over time will help determine the overall peristaltic movement and could be used as a helpful index to gauge constipation.

Telocytes in the esophageal wall of chickens: a tale of subepithelial telocytes

The esophagus is a tubular organ which act as a passage for food from oral cavity to stomach. Telocytes (TCs) are a unique type of interstitial cell whose existence in many organs of various species still remains unknown. In the present study, we used transmission electron microscopy (TEM) and immunohistochemistry (CD34, Vimentin, PDGFR-α) to identify subepithelial TCs in the esophageal wall of chickens. TEM micrographs confirmed the presence of TCs in the lamina propria, tunica submucosa, and tunica muscularis muscular layer of the esophageal wall. A large population of TCs were observed just beneath the epithelial layer of the esophageal wall, and the TCs demonstrated structural heterogenicity, featuring various cell body shapes of cell bodies and telopodes (Tps) with podoms, podomeres, and dichotomous branching. Furthermore, a large number of extracellular vesicles were found to be associated with TCs/Tps. Cellular extensions from TCs were observed in close proximity to blood vessels, immune cells, and mucosal glands. In the submucosa, Tps and immune cells were in very close contact. Immunohistochemical results showed that there were CD34+ cells, vimentin+ cells, and PDGFR-α+ cells in the subepithelium, lamina propria, and mucosal glands of the chicken esophageal wall, which was consistent with the TEM results. Overall, our data confirmed the existence of TCs in the chicken esophagus and suggested that TCs might contribute to epithelial regeneration and tissue homeostasis.

Extremely Aggressive Mesenteric Extragastrointestinal Stromal Tumor: A Case Report and Literature Review

Gastrointestinal stromal tumors (GISTs) are rare tumors with increasing incidence. GIST is the most common mesenchymal tumor of the gastrointestinal tract involving the elderly population with a slow progression. It originates from the interstitial cells of Cajal. GISTs that develop outside the gastrointestinal tract and have no connections with the intestinal walls or serosal surfaces of the gastrointestinal tubular organs are referred to as extraintestinal gastrointestinal stromal tumors (EGISTs). They have similar morphological and immunohistological characteristics as GISTs. Here, we describe a unique case of an extremely aggressive mesenteric GIST in a 44-year-old African American male.The patient presented to the hospital with complaints of generalized abdominal pain associated with 50-pound weight loss, decreased appetite, and constipation. He underwent computed tomography (CT) of the abdomen and pelvis which showed a large mass along the central mesentery measuring about 15 × 11 cm with adjacent metastatic nodal disease. He underwent a CT-guided biopsy of his abdominal mass with histopathology findings positive for c-kit (CD117) and discovered on GIST-1 (DOG-1) consistent with GIST. Based on TNM staging, his tumor was graded T4 with N1 given nodal involvement placing him as a stage IV. He was referred to an oncologist and was started on neoadjuvant therapy with imatinib. Mesenteric EGISTs, while rare, are known to have a worse prognosis compared to other EGISTs; hence, prompt action must be taken in aggressively treating these tumors. Factors such as mitotic index and tumor size affect the prognosis of mesenteric GISTs.

Histomorphological, histochemical and scanning electron microscopic investigation of the proventriculus (Ventriculus glandularis) of the hooded crow (Corvus cornix).

The current investigation aimed to clarify the histomorphological features, scanning electron microscopy (SEM) and histochemistry of the proventriculus in the adult hooded crow (Corvus cornix). Twenty-two adult birds of both sexes were collected from El-Fayoum and Beni-Suef governorates, Egypt; ten were used for anatomical investigation, two were scanned using SEM, and ten were subjected to routine histological technique. The obtained anatomical results revealed a small-sized spindle-shaped proventriculus obliquely located in the left ventral part of the body cavity with an average body weight, length and diameter of 1.689±0.231gm, 1.54±0.383cm and 3.51±0.416cm, respectively. The histological examination revealed a typical tubular organ. The mucosa exhibited several plicae and sulci that were lined with simple columnar cells. The lamina propria was composed of collagenous connective tissue infiltrated by lymphocytes, lymphatic aggregations and tubular glands. The submucosa consisted of collagenic fibres and compound tubuloalveolar glandular lobules lined with oxynticopeptic cells and enteroendocrine cells. The oxynticopeptic cells reacted negatively with PAS and Alcian Blue stains, whereas the ductal cells reacted positively with PAS only. Enteroendocrine cells were seen singly in the lamina epithelialis mucosae and were abundant in submucosal glands. The tunica musclaris was arranged in two layers covered by serosa. The proventricular glands' openings were noticed by SEM as raised tubes with regular circular outlines surrounded by anastomosed microscopic folds. The obtained histomorphological structure of the hooded crow's proventriculus revealed some shared morphological features with most species of birds and some variations that might be attributed to their diet and feeding behaviour.

Ribbon boosts ribosomal protein gene expression to coordinate organ form and function.

Cell growth is well defined for late (postembryonic) stages of development, but evidence for early (embryonic) cell growth during postmitotic morphogenesis is limited. Here, we report early cell growth as a key characteristic of tubulogenesis in the Drosophila embryonic salivary gland (SG) and trachea. A BTB/POZ domain nuclear factor, Ribbon (Rib), mediates this early cell growth. Rib binds the transcription start site of nearly every SG-expressed ribosomal protein gene (RPG) and is required for full expression of all RPGs tested. Rib binding to RPG promoters in vitro is weak and not sequence specific, suggesting that specificity is achieved through cofactor interactions. Accordingly, we demonstrate Rib's ability to physically interact with each of the three known regulators of RPG transcription. Surprisingly, Rib-dependent early cell growth in another tubular organ, the embryonic trachea, is not mediated by direct RPG transcription. These findings support a model of early cell growth customized by transcriptional regulatory networks to coordinate organ form and function.

Histological Study of the Harderian Gland of Pati Duck (Anas platyrhynchos domesticus) of Assam during Postnatal Development

Background: The farmers are rearing duck in small scale in semi intensive system without investing more capital but it contributes a major part to uplift the socio-economic condition of the rural poor people of Assam. The Pati duck (Anas platyrhynchos domesticus) population constitutes a major indigenous non-descript economically important duck variety in the state of Assam. The Harderian gland acts as a part of the head associated lymphoid tissue (HALT) and provides local innate immunity to the upper respiratory system, to the eye and oral cavity. Since literature on histological study of Harderian gland of Pati duck is scant, hence the present study was designed to establish the basic histological details on Harderian gland at different stages of postnatal development of Pati duck of Assam. Methods: The present study was conducted on total forty five (45) numbers Pati duck of Assam at different stages of postnatal development. The experimental birds were brought to the Department of Anatomy and Histology, College of Veterinary Science, Assam Agricultural University, Khanapara, Guwahati-22 and was sacrificed according to the method of Gracy (1986). For histological study the tissue samples from the Harderian gland of all the age group were fixed in 10% neutral buffered formalin solution and processed to prepare paraffin blocks as per the procedure described by Luna (1968). The paraffin blocks were sectioned in Shandon Finesse microtome in 5 µm thickness and the sections were stained by different methods as described by Luna (1968). Result: The Harderian gland of Pati duck had a capsule, the thickness of the capsule of the Harderian gland was increased slightly along the advancement of the age. The capsular connective tissue penetrated the parenchyma of the Harderian gland in the form of septa. The collagen, reticular, elastic and nerve fibers were observed along with the capsule and as well as in the septa. The Harderian gland of the Pati duck was compound tubular gland. The columnar epithelial cells lined the tubules. There was no cortex and medulla in the gland and the tubular structure were uniformly distributed within the lobules. A central canal was present in the gland which converged to the duct of the gland. The lymphocytes, plasma cells were found in the intertubular connective tissue. The numbers or population of plasma cell and lymphocytes were accelerated by the advancement of age. The myoepithelial cells with spindle shaped nucleus were present near the basement membrane close to the secretary cells. The histology of the duct of the Harderian gland of Pati duck was like that of typical hollow tubular organs. There were few lymphatic nodules very distinctly present extended from the lamina propria to the muscle layer.

New genus of Ironidae (Nematoda, Enoplida) from Piip volcano (the Bering Sea).

Piipironus grandis gen. et sp. nov. is described from Piip submarine volcano, the Bering Sea. Piipironus gen. nov. shows all main characters of Thalassironinae but differs from all known ironids in the form of the amphid (spiral vs pocket-like) and the simultaneous presence of precloacal papilliform supplements and tubular postcloacal organs. Pared tubular postcloacal organs have never been described before for the family Ironidae. The combination of papilliform precloacal supplements and the pair of tubular postcloacal organs described for Piipironus grandis gen. et sp. nov. is unique among nematodes. The study of the nematofauna of the Piip submarine volcano began quite recently, and Piipironus is the second new genus of nematodes described from here from one sample of bottom sediments. This can be taken as one of the examples of the hyper-high diversity of marine nematodes.

Air sac and gill vasotocin receptor gene expression in the air-breathing catfish Heteropneustes fossilis exposed to water and air deprivation conditions.

Heteropneustes fossilis is a facultative air-breathing freshwater catfish and inhabits ponds, ditches, swamps, marshes and rivers that dry up in summers. It possesses a pair of unique tubular accessory respiratory organ (air sac), which is a modification of the gill chamber and enables it to live in water-air transition zones. In the catfish, three vasotocin (Vt) receptor gene paralogs viz., v1a1, v1a2 and v2a were identified for Vt actions. In the present study, the receptor gene transcripts were localized in the gill and air sac by in situ hybridization, and their expression levels in relation to water and air deprivation conditions were investigated by quantitative RT-PCR. The catfish were exposed to 1h and 2h in gonad inactive (resting) and gonad active (prespawning) phases. The gene paralogs showed overlapping distribution in the respiratory epithelium of primary and secondary lamellae of gills and reduced lamellae of the air sacs. In water deprivation (forced aerial mode of respiration) experiment, v2a expression showed a high fold increase in the air sac, which was unchanged or inhibited in the gill. Both v1a1 and v1a2 expression was significantly upregulated in the air sac but showed varied responses in the gill. The gill v1a1 expression was unchanged in the resting phase and modestly upregulated in the prespawning phase. The gill v1a2 expression was modestly upregulated at 1h in both phases but unchanged at 2h. In the air deprivation experiment (forced aquatic respiration), the v2a expression in the air sac was inhibited except for a mild stimulation at 1h in the prespawning phase. In the gill, the v2a expression was stimulated with a steep upregulation at 2h in the prespawning phase. Both v1a1 and v1a2 expression was significantly high in the gill but only modestly increased or unchanged in the air sac. The expression patterns point to a functional distinction; the V2 type receptor expression was higher in the air sac during forced aerial respiration, and the V1 type receptor expression was highly prominent in the gill during forced aquatic respiration. Water and air deprivation treatments caused a significant increase in plasma cortisol level, and the stimulation was higher in the water deprivation fish in the resting phase but equally prominent in the water and air deprivation groups in the prespawning phase. The results indicate that the changes in the expression patterns of Vt receptor genes may be a sequel to stress (hypoxic, metabolic and osmotic), and both Vt and cortisol may interact to counter the stress responses. This study shows that Vt has a new role in the control of air sac functions.

Vectorial Release of Human RNA Viruses from Epithelial Cells.

Epithelial cells are apico-basolateral polarized cells that line all tubular organs and are often targets for infectious agents. This review focuses on the release of human RNA virus particles from both sides of polarized human cells grown on transwells. Most viruses that infect the mucosa leave their host cells mainly via the apical side while basolateral release is linked to virus propagation within the host. Viruses do this by hijacking the cellular factors involved in polarization and trafficking. Thus, understanding epithelial polarization is essential for a clear understanding of virus pathophysiology.

Automated anatomical labeling of a topologically variant abdominal arterial system via probabilistic hypergraph matching.

Automated anatomical vessel labeling of the abdominal arterial system is a crucial topic in medical image processing. One reason for this is the importance of the abdominal arterial system in the human body, and another is that such labeling is necessary for the related disease diagnoses, treatments and epidemiological population analyses. We define a hypergraph representation of the abdominal arterial system as a family tree model with a probabilistic hypergraph matching framework for automated vessel labeling. Then we treat the labelling problem as the convex optimization problem and solve it with the maximum a posteriori(MAP) combined the likelihood obtained by geometric labelling with the family tree topology-based knowledge. Geometrically, we utilize XGBoost ensemble learning with an intrinsic geometric feature importance analysis for branch-level labeling. In topology, the defined family tree model of the abdominal arterial system is transferred as a Markov chain model using a constrained traversal order method and further the Markov chain model is optimized by a hidden Markov model (HMM). The probability distribution of the target branches for each candidate anatomical name is predicted and effectively embedded in the HMM model. This approach is evaluated with the leave-one-out method on 37 clinical patients' abdominal arteries, and the average accuracy is 91.94%. The obtained results are better than those of the state-of-art method with an F1 score of 93.00% and a recall of 93.00%, as the proposed method simultaneously handles the anatomical structural variability and discriminates between the symmetric branches. It is demonstrated to be suitable for labelling branches of the abdominal arterial system and can also be extended to similar tubular organ networks, such as arterial or airway networks.

Intestinal Stem Cell-on-Chip to Study Human Host-Microbiota Interaction.

The gut is a tubular organ responsible for nutrient absorption and harbors our intestinal microbiome. This organ is composed of a multitude of specialized cell types arranged in complex barrier-forming crypts and villi covered by a mucosal layer controlling nutrient passage and protecting from invading pathogens. The development and self-renewal of the intestinal epithelium are guided by niche signals controlling the differentiation of specific cell types along the crypt-villus axis in the epithelium. The emergence of microphysiological systems, or organ-on-chips, has paved the way to study the intestinal epithelium within a dynamic and controlled environment. In this review, we describe the use of organ-on-chip technology to control and guide these differentiation processes in vitro. We further discuss current applications and forthcoming strategies to investigate the mechanical processes of intestinal stem cell differentiation, tissue formation, and the interaction of the intestine with the microbiota in the context of gastrointestinal diseases.

Ciliary Hedgehog signaling patterns the digestive system to generate mechanical forces driving elongation

How tubular organs elongate is poorly understood. We found that attenuated ciliary Hedgehog signaling in the gut wall impaired patterning of the circumferential smooth muscle and inhibited proliferation and elongation of developing intestine and esophagus. Similarly, ablation of gut-wall smooth muscle cells reduced lengthening. Disruption of ciliary Hedgehog signaling or removal of smooth muscle reduced residual stress within the gut wall and decreased activity of the mechanotransductive effector YAP. Removing YAP in the mesenchyme also reduced proliferation and elongation, but without affecting smooth muscle formation, suggesting that YAP interprets the smooth muscle-generated force to promote longitudinal growth. Additionally, we developed an intestinal culture system that recapitulates the requirements for cilia and mechanical forces in elongation. Pharmacologically activating YAP in this system restored elongation of cilia-deficient intestines. Thus, our results reveal that ciliary Hedgehog signaling patterns the circumferential smooth muscle to generate radial mechanical forces that activate YAP and elongate the gut.

Ureteral injury during laparoscopic rectal resection and concurrent laparoscopic repair by uretero-ureterostomy

Iatrogenic ureteral injury is an uncommon but severe complication of laparoscopic colorectal surgery. If it is detected intraoperatively, conversion to open surgery is usually inevitable. Here, we described a complete ureteral transection during laparoscopic low anterior resection, which was simultaneously repaired by laparoscopic uretero-ureterostomy. The most important points during the anastomosis of two tiny tubular tissues are dissecting the tubular organs without trauma, obtaining meticulous hemostasis without causing any necrosis, and achieving accurate approximation of tissues with the sutures. To the best of our knowledge, this is the first report that focused on laparoscopic repair of ureteral injury during laparoscopic colorectal surgery. As there are still few data on laparoscopic repair of ureteral lesions, no firm conclusions can be drawn. But, in appropriate cases, if intracorporeal suture expertise is available, laparoscopic repair can be done during colorectal surgery.

Correct regionalization of a tissue primordium is essential for coordinated morphogenesis.

During organ development, tubular organs often form from flat epithelial primordia. In the placodes of the forming tubes of the salivary glands in the Drosophila embryo, we previously identified spatially defined cell behaviors of cell wedging, tilting, and cell intercalation that are key to the initial stages of tube formation. Here, we address what the requirements are that ensure the continuous formation of a narrow symmetrical tube from an initially asymmetrical primordium whilst overall tissue geometry is constantly changing. We are using live-imaging and quantitative methods to compare wild-type placodes and mutants that either show disrupted cell behaviors or an initial symmetrical placode organization, with both resulting in severe impairment of the invagination. We find that early transcriptional patterning of key morphogenetic transcription factors drives the selective activation of downstream morphogenetic modules, such as GPCR signaling that activates apical-medial actomyosin activity to drive cell wedging at the future asymmetrically placed invagination point. Over time, transcription of key factors expands across the rest of the placode and cells switch their behavior from predominantly intercalating to predominantly apically constricting as their position approaches the invagination pit. Misplacement or enlargement of the initial invagination pit leads to early problems in cell behaviors that eventually result in a defective organ shape. Our work illustrates that the dynamic patterning of the expression of transcription factors and downstream morphogenetic effectors ensures positionally fixed areas of cell behavior with regards to the invagination point. This patterning in combination with the asymmetric geometrical setup ensures functional organ formation.

Development of Radiofrequency Ablation Generator and Balloon-Based Catheter for Microendoluminal Thin-Layer Ablation Therapy Using the Rat Duodenum as a Model of Low-Impedance Tissue.

Radiofrequency ablation (RFA) is a routinely used, safe, and effective method for the tissue destruction. Often, in case of its application in malignant conditions, the extent of tissue destruction is insufficient due to the size of the target lesion, as well as due to the risk of heat-induced damage to the surrounding organs. Nevertheless, there are conditions requiring superficial precise-depth ablation with preservation of deeper layers. These are represented, for example, by mucosal resurfacing in case of Barrett's esophagus or treatment of recurrent mucosal bleeding in case of chronic radiation proctitis. Recently, new indications for intraluminal RFA use emerged, especially in the pancreatobiliary tract. In the case of intraductal use of RFA (e.g., biliary and pancreatic tract), there are currently available rigid and needle tip catheters. An expandable balloon-based RFA catheter suitable for use in such small-diameter tubular organs could be of benefit due to possible increase of contact between the probe and the target tissue; however, to prevent excessive tissue damage, a compatible generator suitable for low-impedance catheter/tissue is essential. This project aimed to develop a radiofrequency ablation generator and bipolar balloon-based catheter optimized for the application in the conditions of low-impedance tissue and (micro)endoluminal environment. Subsequent evaluation of biological effect in vivo was performed using duodenal mucosa in Wistar rat representing conditions of endoluminal radiofrequency ablation of low-impedance tissue. Experiments confirming the safety and feasibility of RFA with our prototype devices were conducted.

Developmental expression patterns of toolkit genes in male accessory gland of Drosophila parallels those of mammalian prostate.

ABSTRACTConservation of genetic toolkits in disparate phyla may help reveal commonalities in organ designs transcending their extreme anatomical disparities. A male accessory sexual organ in mammals, the prostate, for instance, is anatomically disparate from its analogous, phylogenetically distant counterpart – the male accessory gland (MAG) – in insects like Drosophila. It has not been ascertained if the anatomically disparate Drosophila MAG shares developmental parallels with those of the mammalian prostate. Here we show that the development of Drosophila mesoderm-derived MAG entails recruitment of similar genetic toolkits of tubular organs like that seen in endoderm-derived mammalian prostate. For instance, like mammalian prostate, Drosophila MAG morphogenesis is marked by recruitment of fibroblast growth factor receptor (FGFR) – a signalling pathway often seen recruited for tubulogenesis – starting early during its adepithelial genesis. A specialisation of the individual domains of the developing MAG tube, on the other hand, is marked by the expression of a posterior Hox gene transcription factor, Abd-B, while Hh-Dpp signalling marks its growth. Drosophila MAG, therefore, reveals the developmental design of a unitary bud-derived tube that appears to have been co-opted for the development of male accessory sexual organs across distant phylogeny and embryonic lineages.This article has an associated First Person interview with the first author of the paper.

Soft robotic constrictor for in vitro modeling of dynamic tissue compression

Here we present a microengineered soft-robotic in vitro platform developed by integrating a pneumatically regulated novel elastomeric actuator with primary culture of human cells. This system is capable of generating dynamic bending motion akin to the constriction of tubular organs that can exert controlled compressive forces on cultured living cells. Using this platform, we demonstrate cyclic compression of primary human endothelial cells, fibroblasts, and smooth muscle cells to show physiological changes in their morphology due to applied forces. Moreover, we present mechanically actuatable organotypic models to examine the effects of compressive forces on three-dimensional multicellular constructs designed to emulate complex tissues such as solid tumors and vascular networks. Our work provides a preliminary demonstration of how soft-robotics technology can be leveraged for in vitro modeling of complex physiological tissue microenvironment, and may enable the development of new research tools for mechanobiology and related areas.

Growth-profile configuration for specific deformations of tubular organs: A study of growth-induced thinning and dilation of the human cervix.

Growth is a significant factor that results in deformations of tubular organs, and particular deformations associated with growth enable tubular organs to perform certain physiological functions. Configuring growth profiles that achieve particular deformation patterns is critical for analyzing potential pathological conditions and for developing corresponding clinical treatments for tubular organ dysfunctions. However, deformation-targeted growth is rarely studied. In this article, the human cervix during pregnancy is studied as an example to show how cervical thinning and dilation are generated by growth. An advanced hyperelasticity theory called morphoelasticity is employed to model the deformations, and a growth tensor is used to represent growth in three principle directions. The computational results demonstrate that both negative radial growth and positive circumferential growth facilitate thinning and dilation. Modeling such mixed growth represents an advancement beyond commonly used uniform growth inside tissues to study tubular deformations. The results reveal that complex growth may occur inside tissues to achieve certain tubular deformations. Integration of further biochemical and cellular activities that initiate and mediate such complex growth remains to be explored.

Colloidal structure and proton conductivity of the gel within the electrosensory organs of cartilaginous fishes

SummaryCartilaginous fishes possess gel-filled tubular sensory organs called Ampullae of Lorenzini (AoL) that are used to detect electric fields. Although recent studies have identified various components of AoL gel, it has remained unclear how the molecules are structurally arranged and how their structure influences the function of the organs. Here we describe the structure of AoL gel by microscopy and small-angle X-ray scattering and infer that the material is colloidal in nature. To assess the relative function of the gel's protein constituents, we compared the microscopic structure, X-ray scattering, and proton conductivity properties of the gel before and after enzymatic digestion with a protease. We discovered that while proteins were largely responsible for conferring the viscous nature of the gel, their removal did not diminish proton conductivity. The findings lay the groundwork for more detailed studies into the specific interactions of molecules inside AoL gel at the nanoscale.