Parcellation of the Primary Cerebral Cortices based on Local Connectivity Profiles

Primary cerebral cortices are of great importance for our understanding of the human brain. Although their functions are relatively monomodal, primary cerebral cortices have been suggested to compromise structurally and functionally distinct subregions from many evidences, for example, cytoarchitectionics, myeloarchitectonics and functional brain imaging. In recent years, structural connectivity-based parcellation using diffusion MRI has been extensively used to do parcellation of subcortical areas and association cortex. However, it has rarely been employed to primary cerebral cortices. In connectivity-based parcellation, connectivity profiles are very vital. Different researchers used different information of connectivity profiles, such as global connectivity profiles (the connectivity information from seed to the whole brain) and long connectivity profiles (the connectivity information from seed to other brain regions after excluding the seed). Given that primary cerebral cortices are rich of local hierarchical connections and possess high local functional connectivity profiles, we proposed that local connectivity profiles (the connectivity information in the seed region of interest (ROI)) might be used for parcellating primary cerebral cortices. Global, long and local connectivity profiles were compared on M1, A1, S1 and V1. We found that results using the three were all in good consistency with cytoarchitectonic results. More importantly, results using local connectivity profiles showed less inter-subject variability than results using the other two. This suggests that for parcellation of primary cerebral cortices local connectivity profiles are superior to global and long connectivity profiles. This also infers us that different connectivity profiles should be adopted according to the characteristics of the cerebral cortices

Distinct changes in functional connectivity in posteromedial cortex subregions during the progress of Alzheimer’s disease

Alzheimer’s disease is a progressive neurodegenerative disorder which causes dementia, especially in the elderly. The posteromedial cortex, which consists of several subregions involved in distinct functions, is one of the critical regions associated with the progression and severity of Alzheimer’s disease. However, previous studies always ignored the heterogeneity of the posteromedial cortex and focused on one stage of Alzheimer’s disease. Using resting-state functional magnetic resonance imaging, we studied the respective alterations of each subregion within the posteromedial cortex along the progression of Alzheimer’s disease. Our data set consisted of 21 healthy controls, 18 patients with mild cognitive impairment, 17 patients with mild Alzheimer’s disease, and 18 patients with severe Alzheimer’s disease. We investigated the functional alterations of each subregion within the posteromedial cortex in different stages of Alzheimer’s disease. We found that subregions within the posteromedial cortex have differential vulnerability in Alzheimer’s disease. Disruptions in functional connectivity began in the transition area between the precuneus and the posterior cingulate cortex and then extended to other subregions of the posteromedial cortex. In addition, each of these subregions was associated with distinct alterations in the functional networks that we were able to relate to Alzheimer’s disease. Our research demonstrated functional changes within the posteromedial cortex in the progression of Alzheimer’s disease and may elucidate potential biomarkers for clinical applications

The broad-host-range plasmid pSFA231 isolated from petroleum-contaminated sediment represents a new member of the PromA plasmid family

A self-transmissible broad-host-range (BHR) plasmid pSFA231 was isolated from petroleum-contaminated sediment in Shen-fu wastewater irrigation zone, China, using the triparental mating exogenous plasmid capture method. Based on its complete sequence the plasmid has a size of 41.5 kb and codes for 50 putative open reading frames (orfs), 28 of which represent genes involved in replication, partitioning and transfer functions of the plasmid. Phylogenetic analysis grouped pSFA231 into the newly defined PromA plasmid family, which currently includes five members. Further comparative genomic analysis shows that pSFA231 shares the common backbone regions with the other PromA plasmids, i.e., genes involved in replication, maintenance and control, and conjugative transfer. Nevertheless, phylogenetic divergence was found in specific gene products. We propose to divide the PromA group into two subgroups, PromA-α (pMRAD02, pSB102) and PromA-β (pMOL98, pIPO2T, pSFA231, pTer331), based on the splits network analysis of the RepA protein. Interestingly, a cluster of hypothetical orfs located between parA and traA of pSFA231 shows high similarity with the corresponding regions on pMOL98, pIPO2T and pTer331, suggesting these hypothetical orfs may represent ‘‘essential’’ plasmid backbone genes for the PromA-β subgroup. Alternatively, they may also be accessory genes that were first acquired and then stayed as the plasmid diverged. Our study increases the available collection of complete genome sequences of BHR plasmids, and since pSFA231 is the only characterized PromA plasmid from China, our findings also enhance our understanding of the genetic diversity of this plasmid group in different parts of the world

Ovarian tumor attachment, invasion and vascularization reflect unique microenvironments in the peritoneum:Insights from xenograft and mathematical models

Ovarian cancer relapse is often characterized by metastatic spread throughout the peritoneal cavity with tumors attached to multiple organs. In this study, interaction of ovarian tumor cells with the peritoneal tumor microenvironment was evaluated in a xenograft model based on intraperitoneal injection of fluorescent SKOV3.ip1 ovarian cancer cells. Intra-vital microscopy of mixed GFP-RFP cell populations injected into the peritoneum demonstrated that tumor cells aggregate and attach as mixed spheroids, emphasizing the importance of homotypic adhesion in tumor formation. Electron microscopy provided high resolution structural information about local attachment sites. Experimental measurements from the mouse model were used to build a three-dimensional cellular Potts ovarian tumor model (OvTM) that examines ovarian tumor cell attachment, chemotaxis, growth and vascularization. OvTM simulations provide insight into the relative influence of tumor cell-cell adhesion, oxygen availability, and local architecture on tumor growth and morphology. Notably, tumors on the mesentery, omentum or spleen readily invade the open architecture, while tumors attached to the gut encounter barriers that restrict invasion and instead rapidly expand into the peritoneal space. Simulations suggest that rapid neovascularization of SKOV3.ip1 tumors is triggered by constitutive release of angiogenic factors in the absence of hypoxia. This research highlights the importance of cellular adhesion and tumor microenvironment in the seeding of secondary ovarian tumors on diverse organs within the peritoneal cavity. Results of the OvTM simulations indicate that invasion is strongly influenced by features underlying the mesothelial lining at different sites, but is also affected by local production of chemotactic factors. The integrated in vivo mouse model and computer simulations provide a unique platform for evaluating targeted therapies for ovarian cancer relapse