The Proteomic Signature of Intestinal Acute Rejection in the Mouse

Intestinal acute rejection (AR) lacks a reliable non-invasive biomarker and AR surveillance is conducted through frequent endoscopic biopsies. Although citrulline and calprotectin have been suggested as AR biomarkers, these have limited clinical value. Using a mouse model of intestinal transplantation (ITx), we performed a proteome-wide analysis and investigated rejection-related proteome changes that may eventually be used as biomarkers. ITx was performed in allogenic (Balb/C to C57Bl) and syngeneic (C57Bl) combinations. Graft samples were obtained three and six days after transplantation (n = 4/time point) and quantitative proteomic analysis with iTRAQ-labeling and mass spectrometry of whole tissue homogenates was performed. Histology showed moderate AR in all allografts post-transplantation at day six. Nine hundred and thirty-eight proteins with at least three unique peptides were identified in the intestinal grafts. Eighty-six proteins varying by >20% between time points and/or groups had an alteration pattern unique to the rejecting allografts: thirty-seven proteins and enzymes (including S100-A8 and IDO-1) were significantly upregulated whereas forty-nine (among other chromogranin, ornithine aminotransferase, and arginase) were downregulated. Numerous proteins showed altered expression during intestinal AR, several of which were previously identified to be involved in acute rejection, although our results also identified previously unreported proteome changes. The metabolites and downstream metabolic pathways of some of these proteins and enzymes may become potential biomarkers for intestinal AR.

Gray Matter Deterioration Pattern During Alzheimer's Disease Progression: A Regions-of-Interest Based Surface Morphometry Study

Accurate detection of the regions of Alzheimer's disease (AD) lesions is critical for early intervention to effectively slow down the progression of the disease. Although gray matter volumetric abnormalities are commonly detected in patients with mild cognition impairment (MCI) and patients with AD, the gray matter surface-based deterioration pattern associated with the progression of the disease from MCI to AD stages is largely unknown. To identify group differences in gray matter surface morphometry, including cortical thickness, the gyrification index (GI), and the sulcus depth, 80 subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database were split into healthy controls (HCs; N = 20), early MCIs (EMCI; N = 20), late MCIs (LMCI; N = 20), and ADs (N = 20). Regions-of-interest (ROI)-based surface morphometry was subsequently studied and compared across the four stage groups to characterize the gray matter deterioration during AD progression. Co-alteration patterns (Spearman's correlation coefficient) across the whole brain were also examined. Results showed that patients with MCI and AD exhibited a significant reduction in cortical thickness (p < 0.001) mainly in the cingulate region (four subregions) and in the temporal (thirteen subregions), parietal (five subregions), and frontal (six subregions) lobes compared to HCs. The sulcus depth of the eight temporal, four frontal, four occipital, and eight parietal subregions were also significantly affected (p < 0.001) by the progression of AD. The GI was shown to be insensitive to AD progression (only three subregions were detected with a significant difference, p < 0.001). Moreover, Spearman's correlation analysis confirmed that the co-alteration pattern of the cortical thickness and sulcus depth indices is predominant during AD progression. The findings highlight the relevance between gray matter surface morphometry and the stages of AD, laying the foundation for in vivo tracking of AD progression. The co-alteration pattern of surface-based morphometry would improve the researchers' knowledge of the underlying pathologic mechanisms in AD.

An Efficient In Vitro Culture System To Amplify Spermatogonia Stem Cell Markers

Introduction: Proliferation of spermatogonial stem cells (SSCs) can be a treatment for infertile men. Here, we design an efficient method based on culturing in the presence of Sertoli cells to improve the expression level of some specific spermatogonia stem cell genes during two weeks post culture. Materials and Methods: Cells were derived from neonatal (2-6 days old) mice testes and were cultured in DMEM medium with FBS. The colonization of cultured SSCs in days 4, 7, and 14 of culture was counted via phase-contrast microscope and Image J software. Methyl thiazolyl tetrazolium (MTT) test was performed to evaluate the viability of cultured SSCs in days 3, 7, and 14 of culture. The expression level and the alteration pattern of specific spermatogonial markers, i.e., Stra8, DAZL, and Piwill2 was examined via real-time polymerase chain reaction (PCR) during two weeks post culture. Results: The number and the diameters of colonies showed a significant increase in cultured cells. MTT results proved the higher viability of testicular cells during the culture period. The results of ALP staining detected a positive reaction in spermatogonia colonies. Real-time PCR data showed that culturing SSCs in the presence of interstitial cells of the testis, amplified the level and alteration pattern of specific spermatogonia stem cells genes beneficial in the enrichment of SSCs propagation. Conclusion: Providing a similar culture environment to testicular niche increases viability, forms SSCs colonies, and regulates the level and alteration pattern of spermatogonia stem cell genes.

Mangrove Forest Cover Change Detection Along the Coastline of Trincomalee District, Sri Lanka Using GIS and Remote Sensing Techniques

Mangroves provide valuable services to the coastal community in Trincomalee District despite they distributed in the small area. The objectives of this research are to map out the distribution of the mangroves and to detect the change in mangroves in Trincomalee District during the last 20 years. According to this study the reduction in the extent of mangroves caused by clearance for alternative land use including aquaculture, tourism. The total extent of mangroves in Trincomalee district was estimated using Landsat satellite imageries 1997 and 2017. The medium resolution of Landsat imageries may lead to underestimating relatively small, linear mangroves in coastal line of Trincomalee district. The occurrence of clouds in the coastal area can cause data gaps during analysis. This study estimated total mangroves in Trincomalee district was 20.26km2 and 15.07 km2 in 1997 and 2017 respectively and representing a loss of 5.19 km2 in the 20 years (1997-2017). Mangroves loss in the study area varied both spatially and temporally due to differences in habitat alteration pattern. However, Landsat images adequately aided to detect changes in mangroves in Trincomalee district which shows the rate of decline in mangroves.

Addressing reverse inference in structural brain alterations

In neuroimaging with reverse inferences we can infer the involvement of cognitive processes from certain patterns of brain activity. Still, the same reasoning holds if we substitute “brain activity” with “brain alteration” and “cognitive process” with “brain disorder”. To assess the involvement of a certain alteration pattern in a brain disorder we used the Bayes’ factor technique on voxel-based morphometry data of schizophrenia and Alzheimer’s disease. This technique allows to calculate the ratio between the likelihoods of two alternative hypotheses (in our case, that the alteration of the voxel is specific for the brain disorder under scrutiny or that the alteration is not specific). We then performed temporal simulations of the alteration spread associated with different pathologies. The Bayes’ factor values calculated on these simulated data were able to reveal that the areas which are more specific to a certain disease are also the ones to be early altered.

Similarities in Blood Mononuclear Cell Membrane Phospholipid Profiles During Malignancy

Phospholipids (PLs), key elements of cellular membranes, are regulated reciprocally with membrane proteins and can act as sensors for alterations in physiological or pathological states of cells including initiation and development of cancer. On the other hand, peripheral blood mononuclear cells (MNCs) play an important role in antitumor immune response by reacting to cancerous modifications in distant organs. In the current study, we tested the hypothesis that tumor initiation and development are reflected in the alteration pattern of the MNC PL component. We analyzed MNC membrane PL fractions in samples from healthy individuals and from patients with diverse types of cancers to reveal possible alterations induced by malignancy. Compared to healthy controls, the cancer samples demonstrated shifts in several membrane PL profiles. In particular, when analyzing cancer data pooled together, there were significantly higher levels in lysophosphatidylcholine, phosphatidylcholine, and phosphatidylethanolamine fractions, and significantly lower quantities in phosphatidylinositol, phosphatidylserine, and phosphatidic acid fractions in cancer samples compared to controls. The levels of sphingomyelins and diphosphatidylglycerols were relatively unaffected. Most of the differences in PLs were sustained during the analysis of individual cancers such as breast cancer and chronic lymphocytic leukemia. Our findings suggest the presence of a common pattern of changes in MNC PLs during malignancy.