Cells require mechanical forces for their physiological functions. The forces are generated mainly from molecular interactions between actin filaments, cross-linking proteins, and myosin motors in ...the actin cytoskeleton. To better understand the molecular interactions, many studies employed myosin motility assays with actin filaments propelled by myosin heads fixed on a surface. Various interesting behaviors of actin filaments have been observed in the motility assay experiments. Despite the popularity of the motility assays, there were only a few computational models designed for simulating the motility assay systems. Most of the previous models have limitations which precluded full understanding of molecular origins for behaviors of actin filaments. In this study, we used an agent-based computational model based on Brownian dynamics for simulating the motility assay system. Our model rigorously describes the mechanics, dynamics, and interactions of actin filaments, cross-linking proteins, and molecular motors. Using the model, we first investigated how properties of actin filaments and motors affect gliding motions of actin filaments without volume-exclusion effects as a base study. We found that actin filaments can continuously glide at relative fast speed only when they are sufficiently longer than the average spacing between neighboring motors and that the gliding speed of F-actins shows a biphasic dependence on processivity of motors. Then, we showed that volume-exclusion effects between actin filaments can induce diverse collective movements and alignment of actin filaments, thus creating thick bundles and ring-like structures in the absence of cross-linking proteins. Lastly, we demonstrated that cross-linking proteins can lead to distinct contractile behaviors of actin networks depending on the density and kinetics of the cross-linking proteins. Results from our study show the ability of our model to simulate the motility assay system under various conditions and provide insights into understanding of different behaviors of actin filaments.
Epithelial invagination is one of the fundamental deformation modes during morphogenesis, and is essential for deriving the three‐dimensional shapes of organs from a flat epithelial sheet. ...Invagination occurs in an orderly manner according to the spatial pattern of the contractile cells; however, it remains elusive how tissue deformation can be caused by cellular activity in the patterned region. In this study, we investigated the mechanical role of the spatial patterns of the contractile cells in invagination of growing tissue using multicellular dynamics simulations. We found that cell proliferation and apical constriction were responsible for expanding the degree of tissue deformation and determining the location of the deformation, respectively. The direction of invagination depended on the spatial pattern of the contractile cells. Further, comparing the simulation results of surface and line contractions as possible modes of apical constriction, we found that the direction of invagination differed between these two modes even if the spatial pattern was the same. These results indicate that the buckling of the epithelial cell sheet caused by cell proliferation causes the invagination, with the direction and location determined by the configuration of the wedge‐shaped cells given by the spatial pattern of the contractile cells.
The buckling of the epithelial cell sheet caused by cell proliferation causes the epithelial invagination, with the direction and location determined by the configuration of the wedge‐shaped cells given by the spatial pattern of the contractile cells.
We designed two novel primer sets based on the sequence of the
hrpZ
gene to detect
Pseudomonas syringae
pv.
syringae
, the causal agent of bacterial black node in barley and wheat. A conventional PCR ...using these primers amplified only
P
.
syringae
group III strains. The result of a nested PCR with the novel primers showed that
P
.
syringae
pv.
syringae
was detectible even when only one culturable cell was used as the PCR template. This highly sensitive PCR detected
P
.
syringae
in diseased parts of wheat and barley plants and in asymptomatic plants.
Culturable bacteria were isolated from tomato seeds using media selective for the canker pathogen Clavibacter michiganensis subsp. michiganensis. Clustering analysis (>99% identity) revealed the ...presence of 16 operational taxonomic units (OTUs) among isolates detected on semi-selective media. Three OTUs belonged to the phylum Actinobacteria, including those of Micrococcus and Dermacoccus, and 13 OTUs belonged to the phylum Firmicutes, including Bacillus and related genera. These Gram-positive endophytic bacteria have the potential to provide false-positive results in seed health tests using media considered semi-selective for the cancer pathogen.
The treatment of metastatic gastric cancer is not uniform, and the prognostic factors and indications for surgery are currently unclear. This retrospective study aimed to identify the prognostic ...factors and clinical indications for surgery in patients with metastatic gastric cancer.
A total of 123 consecutive patients with gastric cancer and synchronous distant metastasis treated between January 1999 and December 2011 were reviewed. Patient, tumor, laboratory, surgical, and chemotherapy factors were analyzed, with overall survival as the endpoint. Univariate analyses were performed using the log-rank test, multivariate analyses were performed using the Cox proportional hazards model, and Kaplan-Meier curves were used to estimate survival. Significance was set at p<0.05.
The median overall survival time was 13.1 months. Ninety-eight patients received chemotherapy. Twenty-eight patients underwent gastrectomy with metastasectomy and 55 underwent gastrectomy without metastasectomy. The median overall survival time for patients who underwent gastrectomy with metastasectomy, gastrectomy without metastasectomy, and no surgical intervention was 21.9 months, 12.5 months, and 7.2 months, respectively (p<0.001). Multivariate analysis identified gastrectomy with or without metastasectomy, performance status (PS) ≥ 3, neutrophil-to-lymphocyte ratio (NLR) >3.1, and carbohydrate antigen 19-9 (CA19-9) level >37 U/mL as predictors of poor survival. NLR and CA19-9 level were also independent prognostic factors in the group of patients who underwent surgery.
High pretreatment NLR, CA19-9 level, and PS are predictors of poor prognosis in patients with metastatic gastric cancer. In selected patients, gastrectomy can be performed safely, and may be associated with longer survival.
Background
Ceftriaxone, a third-generation cephalosporin antibiotic with a long plasma half-life, is widely used to treat various infections. The use of ceftriaxone can sometimes induce biliary ...sludge or stone formation. Although most cases of ceftriaxone-induced pseudolithiasis are asymptomatic or mild and resolve with discontinuation of the drug, we experienced an elderly case of severe acute necrotizing calculous cholecystitis after administration of ceftriaxone.
Case presentation
A 72-year-old male patient was admitted to our hospital because of acute diverticulitis in ascending colon. Ceftriaxone was administered at a dose of 2 g/day for 6 days. Although he recovered after therapy, he was readmitted about 2 weeks later because of severe pain with rebound tenderness in the right upper quadrant. An abdominal imaging study revealed stones and sludge in the gallbladder that were not observed before starting ceftriaxone therapy. Therefore, antibiotic treatment with flomoxef 2 g/day was indicated. However, on the fifth day of readmission, the peritoneal irritation symptoms in the right upper quadrant worsened, and elevated inflammatory response and liver dysfunction were observed. Cholecystectomy was performed based on these findings. The resected inflamed gallbladder showed acute necrotizing cholecystitis with sand granular gallstones. A comparative analysis of the infrared spectroscopic pattern of the composition of gallstones collected during surgery with that of the ceftriaxone powder revealed that both have very similar infrared spectroscopic patterns.
Conclusions
Ceftriaxone-related pseudolithiasis is generally reversible and mainly observed in children. Here, we report a rare case of ceftriaxone-related acute necrotizing cholecystitis in an elderly patient. We confirmed that the stones in the gallbladder are composed of ceftriaxone. The older age, dehydration, fasting, and long-time bed rest during the administration of high-dose ceftriaxone were the potential risk factors for gallstone formation.
Objectives: This retrospective study was conducted to clarify the morphological characteristics of colorectal cancer (CRC) in Japanese familial adenomatous polyposis (FAP) patients.Methods: This ...study was carried out by the study group for FAP of the Japanese Society for Cancer of the Colon and Rectum. FAP patients who underwent surgical resection between 2000 and 2012 were included in the study.Results: Of the 303 patients enrolled, 119 patients without CRC were excluded. Of 523 lesions, 49 lesions with missing morphological information were excluded; hence, only 474 CRC lesions in 178 patients (328 superficial lesions in 122 patients and 146 non-superficial lesions in 92 patients) were included in the study. Depressed lesions accounted for 3.0% of superficial lesions and ulcerated lesions accounted for 84.9% of non-superficial lesions. The depressed superficial lesions were observed only in patients with sparse and attenuated FAP (P = 0.003). The age of the patients at surgery differed between the two groups, with patients with depressed superficial lesions being significantly older than those with non-depressed superficial lesions (P = 0.009). Moreover, the age of the patients at FAP diagnosis differed between the two groups, with patients with ulcerated non-superficial lesions being significantly older than those with protruded non-superficial lesions (P = 0.006).Conclusions: In patients with FAP, depressed superficial CRC lesions rarely developed but were detected in our study group, and ulcerated non-superficial CRC lesions were also present with similar ratios. Clinicians should pay attention to depressed superficial lesions during endoscopic surveillance of FAP patients.
Neural progenitors exhibit cell cycle-dependent interkinetic nuclear migration (INM) along the apicobasal axis. Despite recent advances in understanding its underlying molecular mechanisms, the ...processes to which INM contributes mechanically and the regulation of INM by the apicobasally elongated morphology of progenitors remain unclear. We found that knockdown of the cell-surface molecule TAG-1 resulted in retraction of neocortical progenitors' basal processes. Highly shortened stem-like progenitors failed to undergo basalward INM and became overcrowded in the periventricular (subapical) space. Surprisingly, the overcrowded progenitors left the apical surface and migrated into basal neuronal territories. These observations, together with the results of in toto imaging and physical tests, suggest that progenitors may sense and respond to excessive mechanical stress. Although, unexpectedly, the heterotopic progenitors remained stem-like and continued to sequentially produce neurons until the late embryonic period, histogenesis was severely disrupted. Thus, INM is essential for preventing overcrowding of nuclei and their somata, thereby ensuring normal brain histogenesis.
During morphogenesis in development, multicellular tissues deform by mechanical forces induced by spatiotemporally regulated cellular activities, such as cell proliferation and constriction. Various ...morphologies are formed because of various spatiotemporal combinations and sequences of multicellular activities. Despite its potential to variations, morphogenesis is a surprisingly robust process, in which qualitatively similar morphologies are reproducibly formed even under spatiotemporal fluctuation of multicellular activities. To understand these essential characteristics of tissue morphogenesis, which involves the coexistence of various morphologies and robustness of the morphogenetic process, in this study, we propose a novel approach to capture the overall view of morphogenesis from mechanical viewpoints. This approach will enable visualization of the energy landscape, which includes morphogenetic processes induced by admissible histories of cellular activities. This approach was applied to investigate the morphogenesis of a sheet-like tissue with curvature, where it deformed to a concave or convex morphology depending on the history of growth and constriction. Qualitatively different morphologies were produced by bifurcation of the valley in the energy landscape. The depth and steepness of the valley near the stable states represented the degree of robustness to fluctuations of multicellular activities. Furthermore, as a realistic example, we showed an application of this approach to luminal folding observed in the initial stage of intestinal villus formation. This approach will be helpful to understand the mechanism of how various morphologies are formed and how tissues reproducibly achieve specific morphologies.
MicroRNAs (miRNAs) are a class of small, endogenous, non-coding, single-stranded RNAs that act as post-transcriptional regulators. Their discovery has provided new avenues for the diagnosis and ...treatment of cancer. The expression of both oncogenic and tumor suppressor miRNAs can be aberrantly either up- or down-regulated in cancer cells. These miRNAs target mRNAs of genes that either promote or inhibit tumor growth, and are one of several epigenetic factors that control the initiation and progression of colorectal cancer (CRC) and other cancers. Investigations of miRNAs as CRC biomarkers have employed the expression profiling of traditional tissue samples and, more recently, non-invasive samples, such as feces and body fluids, have been analyzed. MiRNAs may also be able to predict responses to chemo- and radiotherapy, and may be manipulated to modify CRC characteristics. We herein discuss the use of circulating miRNAs as possible non-invasive biomarkers of early CRC onset, relapse, or response to treatment. We also discuss the obstacles that currently limit the routine use of epigenetic biomarkers in clinical settings.
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