Neural responses underlying extraordinary altruists' generosity for socially distant others.

Most people are much less generous toward strangers than close others, a bias termed social discounting. But people who engage in extraordinary real-world altruism, like altruistic kidney donors, show dramatically reduced social discounting. Why they do so is unclear.

Introducing an adolescent cognitive maturity index.

Children show substantial variation in the rate of physical, cognitive, and social maturation as they traverse adolescence and enter adulthood. Differences in developmental paths are thought to underlie individual differences in later life outcomes, however, there remains a lack of consensus on the normative trajectory of cognitive maturation in adolescence. To address this problem, we derive a Cognitive Maturity Index (CMI), to estimate the difference between chronological and cognitive age predicted with latent factor estimates of inhibitory control, risky decision-making and emotional processing measured with standard neuropsychological instruments.

Baseline brain and behavioral factors distinguish adolescent substance initiators and non-initiators at follow-up.

Background: Earlier substance use (SU) initiation is associated with greater risk for the development of SU disorders (SUDs), while delays in SU initiation are associated with a diminished risk for SUDs. Thus, identifying brain and behavioral factors that are markers of enhanced risk for earlier SU has major public health import. Heightened reward-sensitivity and risk-taking are two factors that confer risk for earlier SU.

Low glutamate diet improves working memory and contributes to altering BOLD response and functional connectivity within working memory networks in Gulf War Illness.

Gulf War Illness is a chronic multi-symptom disorder with severe cognitive impairments which may be related to glutamate excitotoxicity and central nervous system dysfunction. The low glutamate diet has been proposed as a comprehensive intervention for Gulf War Illness. We examined the effects of the low glutamate diet on verbal working memory using a fMRI N-back task.

The effectiveness of a brief intervention to increase the likelihood of advance care planning among college students.

Advance care planning (ACP) is atypical in the United States, especially among young adults. We designed and evaluated the effectiveness of a brief intervention about the benefits of perceived control and planning for end-of-life. Participants ( = 188) were randomized into three conditions and completed a cross-sectional questionnaire.

Reverse Phase Protein Microarrays.

While genes and RNA encode information about cellular status, proteins are considered the engine of the cellular machine, as they are the effective elements that drive all cellular functions including proliferation, migration, differentiation, and apoptosis. Consequently, investigations of the cellular protein network are considered a fundamental tool for understanding cellular functions.Alteration of the cellular homeostasis driven by elaborate intra- and extracellular interactions has become one of the most studied fields in the era of personalized medicine and targeted therapy.

Tobacco mosaic virus-based protein nanoparticles and nanorods for chemotherapy delivery targeting breast cancer.

Drug delivery systems are required for drug targeting to avoid adverse effects associated with chemotherapy treatment regimes. Our approach is focused on the study and development of plant virus-based materials as drug delivery systems; specifically, this work focuses on the tobacco mosaic virus (TMV). Native TMV forms a hollow, high aspect-ratio nanotube measuring 300×18nm with a 4nm-wide central channel.

Molecular mapping of five soybean genes involved in male-sterility, female-sterility.

In soybean, asynaptic and desynaptic mutants lead to abnormal meiosis and fertility reduction. Several male-sterile, female-sterile mutants have been identified and studied in soybean, however, some of these mutants have not been mapped to locations on soybean chromosomes. The objectives of this study were to molecularly map five male-sterile, female-sterile genes (st2, st4, st5, st6, and st7) in soybean and compare the map locations of these genes with already mapped sterility genes.

Nanomanufacturing of Tobacco Mosaic Virus-Based Spherical Biomaterials Using a Continuous Flow Method.

Nanomanufacturing of nanoparticles is critical for potential translation and commercialization. Continuous flow devices can alleviate this need through unceasing production of nanoparticles. Here we demonstrate the scaled-up production of spherical nanoparticles functionalized with biomedical cargos from the rod-shaped plant virus tobacco mosaic virus (TMV) using a mesofluidic, continued flow method.

Biodistribution, pharmacokinetics, and blood compatibility of native and PEGylated tobacco mosaic virus nano-rods and -spheres in mice.

Understanding the pharmacokinetics, blood compatibility, biodistribution and clearance properties of nanoparticles is of great importance to their translation to clinical application. In this paper we report the biodistribution and pharmacokinetic properties of tobacco mosaic virus (TMV) in the forms of 300×18nm(2) rods and 54nm-sized spheres. The availability of rods and spheres made of the same protein provides a unique scaffold to study the effect of nanoparticle shape on in vivo fate.

Serum low-molecular-weight protein fractionation for biomarker discovery.

Protein biomarkers provide the key diagnostic information for the detection of disease, risk of disease progression, and a patient's likely response to drug therapy. Potential biomarkers exist in biofluids, such as serum, urine, and cerebrospinal fluid. Unfortunately, discovering and validating protein biomarkers are hindered by the presence of high-molecular-weight proteins, such as serum albumin and immunoglobulins, which comprise 90% of the proteins present in these samples.

Reverse-phase protein microarrays.

Cancer is the consequence of intra- and extracellular signaling network deregulation that derives from alteration of genetic and proteomic cellular homeostasis. Mapping the individual molecular circuitry of a patient's tumor cells is the starting point for rational personalized therapy.While genes and RNA encode information about cellular status, proteins are considered the engine of the cellular machine, as they are the effective elements that drive cellular functions, such as proliferation, migration, differentiation, and apoptosis.

Phosphoproteomic analysis of signaling pathways in head and neck squamous cell carcinoma patient samples.

Molecular targeted therapy represents a promising new strategy for treating cancers because many small-molecule inhibitors targeting protein kinases have recently become available. Reverse-phase protein microarrays (RPPAs) are a useful platform for identifying dysregulated signaling pathways in tumors and can provide insight into patient-specific differences. In the present study, RPPAs were used to examine 60 protein end points (predominantly phosphoproteins) in matched tumor and nonmalignant biopsy specimens from 23 patients with head and neck squamous cell carcinoma to characterize the cancer phosphoproteome.

Functional protein network activation mapping reveals new potential molecular drug targets for poor prognosis pediatric BCP-ALL.

Background: In spite of leukemia therapy improvements obtained over the last decades, therapy is not yet effective in all cases. Current approaches in Acute Lymphoblastic Leukemia (ALL) research focus on identifying new molecular targets to improve outcome for patients with a dismal prognosis. In this light phosphoproteomics seems to hold great promise for the identification of proteins suitable for targeted therapy.

The heme degradation pathway is a promising serum biomarker source for the early detection of Alzheimer's disease.

One of the remaining challenges in Alzheimer's disease (AD) research is the establishment of biomarkers for early disease detection. As part of a prospective study spanning a period of five years, we have collected serial serum samples from cognitively normal, mild cognitively impaired (MCI), and mild AD participants, including same patient samples before and after cognitive decline. Using mass spectrometry we identified several promising leads for biomarker development, such as prosaposin, phospholipase D1, biliverdin reductase B, and S100 calcium binding protein A7.

An initial characterization of the serum phosphoproteome.

Phosphorylation is a dynamic post-translational protein modification that is the basis of a general mechanism for maintaining and regulating protein structure and function, and of course underpins key cellular processes through signal transduction. In the last several years, many studies of large-scale profiling of phosphoproteins and mapping phosphorylation sites from cultured human cells or tissues by mass spectrometry technique have been published; however, there is little information on general (or global) phosphoproteomic characterization and description of the content of phosphoprotein analytes within the circulation. Circulating phosphoproteins and phosphopeptides could represent important disease biomarkers because of their well-known importance in cellular function, and these analytes frequently are mutated and activated in human diseases such as cancer.

Laser capture microdissection and protein microarray analysis of human non-small cell lung cancer: differential epidermal growth factor receptor (EGPR) phosphorylation events associated with mutated EGFR compared with wild type.

Little is known about lung carcinoma epidermal growth factor (EGF) kinase pathway signaling within the context of the tissue microenvironment. We quantitatively profiled the phosphorylation and abundance of signal pathway proteins relevant to the EGF receptor within laser capture microdissected untreated, human non-small cell lung cancer (NSCLC) (n = 25) of known epidermal growth factor receptor (EGFR) tyrosine kinase domain mutation status. We measured six phosphorylation sites on EGFR to evaluate whether EGFR mutation status in vivo was associated with the coordinated phosphorylation of specific multiple phosphorylation sites on the EGFR and downstream proteins.

A portrait of tissue phosphoprotein stability in the clinical tissue procurement process.

Little is known about the preanalytical fluctuations of phosphoproteins during tissue procurement for molecular profiling. This information is crucial to establish guidelines for the reliable measurement of these analytes. To develop phosphoprotein profiles of tissue subjected to the trauma of excision, we measured the fidelity of 53 signal pathway phosphoproteins over time in tissue specimens procured in a community clinical practice.

Reverse-phase protein microarrays: application to biomarker discovery and translational medicine.

Mapping of protein signaling networks within tumors can identify new targets for therapy and provide a means to stratify patients for individualized therapy. Kinases are important drug targets, as such kinase network information could become the basis for development of therapeutic strategies for improving treatment outcome. An urgent clinical goal is to identify functionally important molecular networks associated with subpopulations of patients that may not respond to conventional combination chemotherapy.

Laser-capture microdissection.

Deciphering the cellular and molecular interactions that drive disease within the tissue microenvironment holds promise for discovering drug targets of the future. In order to recapitulate the in vivo interactions thorough molecular analysis, one must be able to analyze specific cell populations within the context of their heterogeneous tissue microecology. Laser-capture microdissection (LCM) is a method to procure subpopulations of tissue cells under direct microscopic visualization.

A genomic and proteomic study of the spectrum of nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, and some of its forms are progressive. This study describes the profiling of hepatic gene expression and serum protein content in patients with different subtypes of NAFLD. Liver biopsy specimens from 98 bariatric surgery patients were classified as normal, steatosis alone, steatosis with nonspecific inflammation, and nonalcoholic steatohepatitis (NASH).

Identification of thioredoxin reductase 1-regulated genes using small interference RNA and cDNA microarray.

Thioredoxin reductase 1 (TrxR1) is a cytosolic enzyme that plays a central role in controlling cellular redox homeostasis. TrxR1 can transduce regulatory redox signals through NADPH-dependent reduction of thioredoxin (Trx), which is able to reduce a broad spectrum of target enzymes and regulate the activity of several transcription factors (e.g.

Development of a new reference standard for microarray experiments.

Often microarray studies require a reference to indirectly compare the samples under observation. References based on pooled RNA from different cell lines have already been described (here referred to as RNA-R), but they usually do not exhaustively represent the set of genes printed on a chip, thus requiring many adjustments during the analyses. A reference could also be generated in vitro transcribing the collection of cDNA clones printed on the microarray in use (here referred to as T3-R).

Aged lymphocyte proliferation following incorporation and retention of dietary omega-3 fatty acids.

T cell activation involves events at the plasma membrane; therefore, molecules such as long chain omega-3 fatty acids that alter the structure of the plasma membrane may affect the activation of aged T cells. In this project we investigated whether the incorporation of omega-3 fatty acids (from fish oil), in the presence of vitamin E, improves age-diminished T cell proliferation. Young and old mice were fed diets rich in either fish (menhaden) oil or saturated fat for various lengths of time.