Dynamic genetic adaptation of Bacteroides thetaiotaomicron during murine gut colonization.

To understand how a bacterium ultimately succeeds or fails in adapting to a new host, it is essential to assess the temporal dynamics of its fitness over the course of colonization. Here, we introduce a human-derived commensal organism, Bacteroides thetaiotaomicron (Bt), into the guts of germ-free mice to determine whether and how the genetic requirements for colonization shift over time. Combining a high-throughput functional genetics assay and transcriptomics, we find that gene usage changes drastically during the first days of colonization, shifting from high expression of amino acid biosynthesis genes to broad upregulation of diverse polysaccharide utilization loci. Within the first week, metabolism becomes centered around utilization of a predominant dietary oligosaccharide, and these changes are largely sustained through 6 weeks of colonization. Spontaneous mutations in wild-type Bt also evolve around this locus. These findings highlight the importance of considering temporal colonization dynamics in developing more effective microbiome-based therapies.

A novel correlation Gaussian process regression-based extreme learning machine.

An obvious defect of extreme learning machine (ELM) is that its prediction performance is sensitive to the random initialization of input-layer weights and hidden-layer biases. To make ELM insensitive to random initialization, GPRELM adopts the simple an effective strategy of integrating Gaussian process regression into ELM. However, there is a serious overfitting problem in kernel-based GPRELM (kGPRELM). In this paper, we investigate the theoretical reasons for the overfitting of kGPRELM and further propose a correlation-based GPRELM (cGPRELM), which uses a correlation coefficient to measure the similarity between two different hidden-layer output vectors. cGPRELM reduces the likelihood that the covariance matrix becomes an identity matrix when the number of hidden-layer nodes is increased, effectively controlling overfitting. Furthermore, cGPRELM works well for improper initialization intervals where ELM and kGPRELM fail to provide good predictions. The experimental results on real classification and regression data sets demonstrate the feasibility and superiority of cGPRELM, as it not only achieves better generalization performance but also has a lower computational complexity.

Preoperative Radiomics Nomogram Based on CT Image Predicts Recurrence-Free Survival After Surgical Resection of Hepatocellular Carcinoma.

RATIONALE AND OBJECTIVES: To construct preoperative models based on CT radiomics, radiologic and clinical features to predict recurrence-free survival (RFS) after liver resection (LR) of BCLC 0 to B stage hepatocellular carcinoma (HCC) and to classify the prognosis. MATERIALS AND METHODS: This study retrospectively analyzed 161 HCC patients who underwent radical LR. Two methods, the least absolute shrinkage and selection operator and random survival forest analysis, were performed for radiomics signature (RS) construction. Univariate and multivariate stepwise Cox regression analyses were performed to establish a combined nomogram (RCN) of RS and clinical parameters and a clinical nomogram (CN). The performance of the models was assessed comprehensively using Harrell's concordance index (C-index), the calibration curve, and decision curve analysis. The discrimination accuracy of the models was compared using integrated discrimination improvement index (IDI). The risk stratification effect was assessed with Kaplan-Meier survival analysis and subgroup analysis. RESULTS: The RCN achieved a C-index of 0.792/0.758 in the training/validation set, which was higher than the CN, RS, and BCLC stage system. The discriminatory accuracy of the RCN was improved when compared to the CN, RS, and BCLC staging systems (IDI > 0). Decision curve analysis reflected the clinical net benefit of the RCN. The RCN allows risk stratification of patients in different clinical subgroups. CONCLUSION: The integrated model combining RS and clinical factors can more effectively predict RFS after LR of BCLC 0 to B stage HCC patients and can effectively stratify the prognostic risk.

Recent Advances of Magnetic Resonance Neuroimaging in Trigeminal Neuralgia.

Trigeminal neuralgia (TN) is a disease of unclear pathogenesis. It has a low incidence and is not fatal, but it can cause afflicted patients' depression or suicide. In the past, neurovascular compression was considered to be the main cause of TN, but recent studies have found that neurovascular contact is also common in asymptomatic patients and the asymptomatic side in symptomatic patients. This indicates that the neurovascular contact is not, or is only to a lesser extent, a factor in the development of TN. Thus, the study of the peripheral branches of the trigeminal nerve is necessary to understand the etiology of TN. With the development of imaging technology and the emergence of various imaging modalities, it is possible to study the etiology of TN and the pathological changes of related structures by magnetic resonance neuroimaging. This article reviews the recent advances in magnetic resonance neuroimaging of the trigeminal nerve.

Extreme Antagonism Arising from Gene-Environment Interactions.

Antagonistic interactions in biological systems, which occur when one perturbation blunts the effect of another, are typically interpreted as evidence that the two perturbations impact the same cellular pathway or function. Yet, this interpretation ignores extreme antagonistic interactions wherein an otherwise deleterious perturbation compensates for the function lost because of a prior perturbation. Here, we report on gene-environment interactions involving genetic mutations that are deleterious in a permissive environment but beneficial in a specific environment that restricts growth. These extreme antagonistic interactions constitute gene-environment analogs of synthetic rescues previously observed for gene-gene interactions. Our approach uses two independent adaptive evolution steps to address the lack of experimental methods to systematically identify such extreme interactions. We apply the approach to Escherichia coli by successively adapting it to defined glucose media without and with the antibiotic rifampicin. The approach identified multiple mutations that are beneficial in the presence of rifampicin and deleterious in its absence. The analysis of transcription shows that the antagonistic adaptive mutations repress a stringent response-like transcriptional program, whereas nonantagonistic mutations have an opposite transcriptional profile. Our approach represents a step toward the systematic characterization of extreme antagonistic gene-drug interactions, which can be used to identify targets to select against antibiotic resistance.

A genetic strategy for probing the functional diversity of magnetosome formation.

Model genetic systems are invaluable, but limit us to understanding only a few organisms in detail, missing the variations in biological processes that are performed by related organisms. One such diverse process is the formation of magnetosome organelles by magnetotactic bacteria. Studies of model magnetotactic α-proteobacteria have demonstrated that magnetosomes are cubo-octahedral magnetite crystals that are synthesized within pre-existing membrane compartments derived from the inner membrane and orchestrated by a specific set of genes encoded within a genomic island. However, this model cannot explain all magnetosome formation, which is phenotypically and genetically diverse. For example, Desulfovibrio magneticus RS-1, a δ-proteobacterium for which we lack genetic tools, produces tooth-shaped magnetite crystals that may or may not be encased by a membrane with a magnetosome gene island that diverges significantly from those of the α-proteobacteria. To probe the functional diversity of magnetosome formation, we used modern sequencing technology to identify hits in RS-1 mutated with UV or chemical mutagens. We isolated and characterized mutant alleles of 10 magnetosome genes in RS-1, 7 of which are not found in the α-proteobacterial models. These findings have implications for our understanding of magnetosome formation in general and demonstrate the feasibility of applying a modern genetic approach to an organism for which classic genetic tools are not available.

Rare giant secondary cutis verticis gyrata.

We report a case of cerebriform intradermal naevus (CIN) of the scalp in a 17-year-old girl. The clinical and histopathological presentations of the case are described and the diagnostic and therapeutic aspects presented.

[Preparation of decellularized carotids and its biocompatibility].

OBJECTIVE: To study the preparation method for acellular vascular matrix and to evaluate its biocompatibility and safety so as to afford an ideal scaffold for tissue engineered blood vessel. METHODS: Fresh caprine carotids (length 50 mm) were harvested and treated with repeated frozen (-80 degrees C)/thawing (37 degrees C), cold isostatic pressing (506 (MPa, 4 degrees C), and 0.125% sodium dodecyl sulfate separately for preparation of acellular vascular matrix. Fluorescence staining and DNA remain test were used to assess the cell extracting results. Biological characteristics were compared with the raw caprine carotids using HE staining, Masson staining, scanning electron microscope (SEM), and mechanical test. Biocompatibility was detected using cell adhesion test, MTT assay, and subcutaneously embedding test. Ten SD rats were divided in 2 groups (n = 5). In experimental group, acellular vascular matrix preserved by the combination of repeated frozen/thawing, ultrahigh pressure treatment and chemical detergent was subcutaneously embedded; and in control group, acellular vascular matrix preserved only by repeated frozen/thawing and ultrahigh pressure treatment was subcutaneously embedded. RESULTS: HE staining and Masson staining revealed that no nucleus was detected in the acellular vascular matrix. SEM demonstrated that a lot of collagen fibers were preserved which were beneficial for cell adhesion. Fluorescence staining and DNA remain test showed that the cells were removed completely. There was no significant difference in stress and strain under the maximum load between before and after treatment. Mechanical test revealed that the acellular vascular matrix reserved mechanical properties of the raw caprine carotids. Cell adhesion test and MTT assay confirmed that cytotoxicity was grade 0-1, and the acellular vascular matrix had good compatibility to endothelial cells. After subcutaneously embedding for 8 weeks, negligible lymphocyte infiltration was observed in experimental group but obvious lymphocyte infiltration in control group. CONCLUSION: The acellular vascular matrix, which is well-preserved by the combination of repeated frozen/thawing, ultrahigh pressure treatment, and chemical detergent, is an ideal scaffold for tissue engineered blood vessel.

The use of dentin matrix scaffold and dental follicle cells for dentin regeneration.

Scaffold and inductive microenvironment are the two most important factors for dentin regeneration. They have been addressed with hydroxyapatite, tricalcium phosphate, polyglycolic acid, calcined bovine bone, and collagen, among other things. However, as of yet, no scaffold and inductive microenvironment combination has been shown to contribute to the regeneration of complete and prefabricated-shaped dentin tissues that include dentin, predentin and odontoblasts. To test the supporting and inductive effects of treated dentin matrix (TDM) on complete and prefabricated-shaped dentin regeneration, dental follicle cells (DFCs) were seeded onto TDM and further incubated for 1 and 2 weeks in vitro and for 2 and 4 weeks in vivo. The results show that in vitro, in addition to dentin sialoprotein (DSP) and dentin matrix protein 1 (DMP1) (regarded as identifying markers of odontoblasts), DFCs induced by TDM expressed osteocalcin, bone sialoprotein, type I collagen, osteopontin, osteonectin and alkaline phosphatase (all expressed by odontoblasts), and that complete and prefabricated-shaped dentin was successfully regenerated. Most importantly, it was found that in vivo TDM supports and induces regeneration of complete and prefabricated-shaped dentin, and regenerated dentin expresses DSP and DMP1, which are identifying dentin markers. Taken together, these results suggest that, for dentin regeneration, TDM is a suitable scaffold and inductive microenvironment and DFCs are a suitable cell type. The combination of TDM and DFCs may constitute a promising approach for future clinical dentin regeneration.

Could cells from menstrual blood be a new source for cell-based therapies?

Human endometrium is a highly regenerative tissue and contains a low number of cells which have high replicative ability and differentiation efficiency. This has been identified by many scientists. When the fresh growth of tissue and blood vessels is shed during each menstrual cycle, some cells with regenerative capabilities are present. Reports have also indicated that these cells possess the capacity to trans-differentiate into mesodermal, ectodermal and endodermal lineages by using standard commercially available culture reagents and methodologies. Given the ease of extraction and pluripotency of this cell population, we propose it as a novel alternative to current cells sources for cell-based therapies.

Possibilities and potential roles of estrogen in the pathogenesis of proliferation hemangiomas formation.

Hemangiomas, often categorized as angiogenic diseases, are the most common tumors of infancy, the life span of which is generally divided into proliferating phase, involuting phase, and involuted phase. Despite their high prevalence, the mechanism leading to proliferation hemangiomas formation is poorly understood and the best approach to their management remains controversial. None of the current therapeutic modalities is ideal, partly because the pathogenesis of hemangioma and the mechanism of its proliferation are far from clear. Many clues reveal that estrogen has an important role in developing the vascular system, experimental and clinical evidences accumulated in recent years also suggest the potential for estrogen to influence neovascularization. Based on those, we hypothesize that estrogen play a potential role in the development of hemangiomas, mainly by regulating some key angiogenic factors, including MMP-9, EPCs, VEGF, NO, etc. Accepting the hypothesis to be correct, a therapy that identify estrogen as a potential target for the design of new, more specific treatments can be used to prevent the proliferation hemangiomas formation. The hypothesis may lead a new direction in the study of mechanisms for proliferation hemangiomas formation, and further study of the precise mechanisms for estrogen-induced hemangiomas will produce effective antiestrogens and estrogen receptor antagonists as new medication for the very difficult problem.