robert Padilla

Recent reports have suggested that the reactivation of otherwise transcriptionally silent transposable elements (TEs) might induce brain degeneration, either by dysregulating the expression of genes and pathways implicated in cognitive decline and dementia or through the induction of immune-mediated neuroinflammation resulting in the elimination of neural and glial cells. In the work we present here, we test the hypothesis that differentially expressed TEs in blood could be used as biomarkers of cognitive decline and development of AD. To this aim, we used a sample of aging subjects (age > 70) that developed late-onset Alzheimer’s disease (LOAD) over a relatively short period of time (12–48 months), for which blood was available before and after their phenoconversion, and a group of cognitive stable subjects as controls. We applied our developed and validated customized pipeline that allows the identification, characterization, and quantification of the differentially expressed (...

Objective: We recently defined that a critical mechanism of IVIG therapy in KD patients is the activation and expansion of natural regulatory T cells (nTreg) that recognize the heavy constant region (Fc) of IgG1. Lack of circulating Fc-specific nTreg in the sub-acute phase of KD strongly correlates with arterial complications. Notably, Fc-specific nTreg are always detectable in circulation in healthy donors, suggesting their importance in maintaining vascular homeostasis. Here we aim at the characterization of the fine specificity of these nTreg by testing the immunogenicity of synthetic peptides (> 97% purity) 15 amino acid long, overlapping 10 amino acids, spanning the whole Fc protein. Methods: To define the immunodominat Fc sequences for nTreg expansion, T cell lines have been established with pools of two consecutive overlapping peptides been generated from PBMC ex vivo from: 1) healthy donors, 2) sub-acute KD subjects (2 weeks after IVIG), and 3) KD subjects that received I...

The reach of the Rio Grande from San Acacia Diversion Dam downstream to the Narrows of Elephant Butte Reservoir, a distance of about 70 miles, has changed significantly through recorded history from the early 1900's to the present. Many significant changes occurred during the period from the 1980's to 2008. Because of high water years beginning in 1979, Elephant Butte Reservoir filled to capacity in 1985. This led to delta sediments being deposited (aggradation) in the channel for a distance of about 40 miles upstream of the full reservoir pool location. Aggradation at the USGS San Marcial Gage amounted to about 15 ft during this period. The river channel and riparian zone in many reaches is perched above the valley floor. During this same period, the reach from San Acacia Diversion Dam downstream for about 12-13 miles has experienced bed lowering (degradation). Maximum degradation or bed lowering has been about 12 ft. Bed level profiles, discharge, peak flows, reservoir con...

We have studied the effects of the vasoactive agents phorbol 12-myristate 13-acetate (PMA) and vasopressin (VP) on phosphatidylcholine metabolism in cultured rat glomerular mesangial cells. PMA and VP stimulate the incorporation of [3H]choline into phosphatidylcholine and the release of [3H]choline into the culture medium. VP, but not PMA, also increases the release of phosphorylcholine into the medium. This suggests that PMA specifically stimulates phospholipase D, whereas VP stimulates phospholipases C and D. Experiments were also conducted to look for production of phosphatidic acid and diacylglycerol, products of phospholipase D- and C-mediated breakdown of phosphatidylcholine. Treatment of cells prelabeled with [3H]myristic acid for 2.5 min with PMA or VP increases the content of [3H]myristic acid in diacylglycerol and phosphatidic acid. A dual labeling study ([3H]myristic acid and [14C]arachidonic acid) suggests that phosphatidylcholine is an important source of diacylglycerol...

Contemporary metabolomics experiments generate a rich array of complex high-dimensional data. Consequently, there have been concurrent efforts to develop methodological standards and analytical workflows to streamline the generation of meaningful biochemical and clinical inferences from raw data generated using an analytical platform like mass spectrometry. While such considerations have been frequently addressed in untargeted metabolomics (i.e., the broad survey of all distinguishable metabolites within a sample of interest), this methodological scrutiny has seldom been applied to data generated using commercial, targeted metabolomics kits. We suggest that this may, in part, account for past and more recent incomplete replications of previously specified biomarker panels. Herein, we identify common impediments challenging the analysis of raw, targeted metabolomic abundance data from a commercial kit and review methods to remedy these issues. In doing so, we propose an analytical pi...

Abstract : This paper presents a summary of the results of the Apparel Research Networks (ARN) installation providing for the development and implementation of the Integrated Retail Module (IRM) at Lackland Air Force Base San Antonio Texas to support the Lackland Air Force Clothing Initial Issue Flight (LAFB AFCIIF). Implementation of ARN IRM at Lackland AFCIIF was completed as part of the research into methods to enhance the ARN Supply Chain Management (SCM) systems for achieving reduced military clothing inventories though automated systems providing asset visibility at the wholesale retail and manufacturing levels and balanced flow replenishment. The IRM solution ties together: (1) the Virtual Item Manager-Wholesale Local (VIM-WL) web based inventory management application; (2) both a wired and wireless network outside the Ft. Jackson Army firewall; (3) electronic forms filing and management with CabinetNG; (4) RF applications with handheld terminals for warehousing data capture; and ultimately (5) optical character recognition automated issue capture system known as the IRM Control Panel. IRM is part of the ARN solution to reduce military clothing inventories through automated systems for asset visibility at the wholesale, retail and manufacturing levels and balanced flow replenishment.

The activation of natural regulatory T cells (nTreg) recognizing the heavy constant region (Fc) of IgG is an important mechanism of action of intravenous immunoglobulin (IVIG) therapy in Kawasaki disease (KD). Lack of circulating Fc-specific nTreg in the sub-acute phase of KD is correlated with the development of coronary artery abnormalities (CAA). Here, we characterize the fine specificity of nTreg in sub-acute (2- to 8-week post-IVIG) and convalescent (1- to 10-year post-IVIG) KD subjects by testing the immunogenicity of 64 peptides, 15 amino acids in length with a 10 amino acid-overlap spanning the entire Fc protein. About 12 Fc peptides (6 pools of 2 consecutive peptides) were recognized by nTreg in the cohorts studied, including two patients with CAA. To test whether IVIG expands the same nTreg populations that maintain vascular homeostasis in healthy subjects, we compared these results with results obtained in healthy adult controls. Similar nTreg fine specificities were obse...

The Middle Rio Grande is a complex and changing river system which presents many maintenance challenges. The need was identified for a comprehensive assessment to provide a foundation of information for planning and implementing Middle Rio Grande River Maintenance Program activities. Steps in this appraisal level assessment begin with identifying the current geomorphic trends and important characteristics of each reach. Reach-based strategies were defined to address trends of interest. If a strategy would not meet the trends of concern in a reach, it was screened out from further analysis. The geomorphic effects of strategy implementation were then described. Next, strategies were scored for engineering effectiveness, ecosystem function, and economics (in terms of implementation cost). Effectiveness to cost ratios were developed and strategies with high ratios were recommended for further study at the feasibility level. BACKGROUND The Middle Rio Grande is a complex and changing river system which presents many maintenance challenges. The need was identified for a comprehensive assessment to provide a foundation of information for planning and implementing Middle Rio Grande River Maintenance Program activities. Strong consideration was given to the current and future geomorphic processes and trends occurring in the Middle Rio Grande for the current flow and sediment regimes. Future river maintenance strategy implementation is planned to be as compatible as possible with these geomorphic processes and trends as well as the ecosystem function needs identified. This robust approach seeks to understand and treat the causes of channel instability rather than the trending symptoms as much as is practical. Adaptive management is already a part of river maintenance, and these efforts will continue in the future. River Maintenance Goals have been redefined to reflect the evolution of practices of river engineering and management and the changing river conditions within the context of the Middle Rio Grande Project authorization. The updated goals are Support Channel Sustainability, Protect Riverside Infrastructure and Resources, Be Ecosystem Compatible, and Provide Effective Water Delivery. Data was examined to define a set of geomorphic trends of importance to river maintenance and to examine the reaches based on the observed trends. These trends are Channel Narrowing, Vegetation Encroachment, Degradation, Increased Bank Height, Bank Erosion, Coarsening of Bed Material, Aggradation, Channel Plugging with Sediment, and Perched Channel Conditions. The fundamental cause of the

To investigate the effectiveness of this methodology, operations of the S-3A copilot Integrated Control System (INCOS) panel, involving procedural and simple perceptual motor skills, were selected for subject matter. Computerbased training (CBT) materials used consisted of interactive ...