Effective connectivity measured using optogenetically evoked hemodynamic signals exhibits topography distinct from resting state functional connectivity in the mouse

Brain connectomics has expanded from histological assessment of axonal projection connectivity (APC) to encompass resting state functional connectivity (RS-FC). RS-FC analyses are efficient for whole-brain mapping, but attempts to explain aspects of RS-FC (e.g., interhemispheric RS-FC) based on APC have been only partially successful. Neuroimaging with hemoglobin alone lacks specificity for determining how activity in a population of cells contributes to RS-FC. Wide-field mapping of optogenetically defined connectivity could provide insights into the brain\u27s structure-function relationship. We combined optogenetics with optical intrinsic signal imaging to create an efficient, optogenetic effective connectivity (Opto-EC) mapping assay. We examined EC patterns of excitatory neurons in awake, Thy1-ChR2 transgenic mice. These Thy1-based EC (Thy1-EC) patterns were evaluated against RS-FC over the cortex. Compared to RS-FC, Thy1-EC exhibited increased spatial specificity, reduced interhemispheric connectivity in regions with strong RS-FC, and appreciable connection strength asymmetry. Comparing the topography of Thy1-EC and RS-FC patterns to maps of APC revealed that Thy1-EC more closely resembled APC than did RS-FC. The more general method of Opto-EC mapping with hemoglobin can be determined for 100 sites in single animals in under an hour, and is amenable to other neuroimaging modalities. Opto-EC mapping represents a powerful strategy for examining evolving connectivity-related circuit plasticity

Evasion of anti-growth signaling: a key step in tumorigenesis and potential target for treatment and prophylaxis by natural compounds

The evasion of anti-growth signaling is an important characteristic of cancer cells. In order to continue to proliferate, cancer cells must somehow uncouple themselves from the many signals that exist to slow down cell growth. Here, we define the anti-growth signaling process, and review several important pathways involved in growth signaling: p53, phosphatase and tensin homolog (PTEN), retinoblastoma protein (Rb), Hippo, growth differentiation factor 15 (GDF15), AT-rich interactive domain 1A (ARID1A), Notch, insulin-like growth factor (IGF), and Krüppel-like factor 5 (KLF5) pathways. Aberrations in these processes in cancer cells involve mutations and thus the suppression of genes that prevent growth, as well as mutation and activation of genes involved in driving cell growth. Using these pathways as examples, we prioritize molecular targets that might be leveraged to promote anti-growth signaling in cancer cells. Interestingly, naturally-occurring phytochemicals found in human diets (either singly or as mixtures) may promote anti-growth signaling, and do so without the potentially adverse effects associated with synthetic chemicals. We review examples of naturally-occurring phytochemicals that may be applied to prevent cancer by antagonizing growth signaling, and propose one phytochemical for each pathway. These are: epigallocatechin-3-gallate (EGCG) for the Rb pathway, luteolin for p53, curcumin for PTEN, porphyrins for Hippo, genistein for GDF15, resveratrol for ARID1A, withaferin A for Notch and diguelin for the IGF1-receptor pathway. The coordination of anti-growth signaling and natural compound studies will provide insight into the future application of these compounds in the clinical setting

A conceptual scheme of knowledge systems for MS/OR

This paper suggests a conceptual scheme to represent the knowledge base of Management Science/Operations Research (MS/OR). Such a scheme could be utilized within the framework of a Decision Support System (DSS). Its purpose is to facilitate expansion of knowledge. An illustrative example is provided to indicate the potential of a DSS with the scheme suggested. Finally, some of the issues of development and implementation of the suggested DSS are discussed.

Using cell phones to collect postpartum hemorrhage outcome data in rural Ghana

ObjectiveTo evaluate the use of cell phones by professional and traditional birth attendants in rural Africa for reporting postpartum hemorrhage (PPH) data.MethodsTen birth attendants from the remote Sene District of Ghana participated in the study. Subjects were trained to send Short Message Service text messages from cell phones using a simple numeric protocol to report data regarding PPH: maternal age; PPH; use of bimanual uterine compression; maternal and neonatal mortality; and prenatal care. Participants sent texts to a pre‐programmed number to report data for all births they attended over a 90‐day period.ResultsIn total, 425 births and 13 (3.1%) cases of PPH were reported during the 90‐day period after training. All attendants followed the reporting protocol correctly, although with uncertain data integrity.ConclusionThe results indicate that it is possible to train professional and traditional birth attendants to use cell phones to report health‐related outcome data via a specified protocol. Reporting from rural‐based providers may present a more accurate picture of what occurs in remote communities because it happens in real time. These findings could be exportable to other program evaluation or population‐monitoring applications (healthcare and other) where rural outcome tracking is necessary.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/135243/1/ijgo148.pd