Dissecting the sources of gene expression variation in a pan-cancer analysis identifies novel regulatory mutations.

Although the catalog of cancer-associated mutations in protein-coding regions is nearly complete for all major cancer types, an assessment of regulatory changes in cancer genomes and their clinical significance remain largely preliminary. Adopting bottom-up approach, we quantify the effects of different sources of gene expression variation in a cohort of 3899 samples from 10 cancer types. We find that copy number alterations, epigenetic changes, transcription factors and microRNAs collectively explain, on average, only 31-38% and 18-26% expression variation for cancer-associated and other genes, respectively, and that among these factors copy number alteration has the highest effect.

Naturally Occurring Amino Acids in Helix 10 of the Thyroid Hormone Receptor Mediate Isoform-Specific TH Gene Regulation.

Thyroid hormone (TH) action is mediated by the products of two genes, TH receptor (THR)α (THRA) and THRβ (THRB) that encode several closely related receptor isoforms with differing tissue distributions. The vast majority of THR isoform-specific effects are thought to be due to tissue-specific differences in THR isoform expression levels. We investigated the alternative hypothesis that intrinsic functional differences among THR isoforms mediate these tissue-specific effects.

Immune response cytokines as potential biomarkers for DDT induced neurodegeneration.

Background: The world incidence rate of Alzheimer’s Disease (AD) is 64 cases per 1,000 individuals. Due to the aging population, the prevalence of AD is however increasing and yet, little remains known about the etiology of AD.

Objective: Previous studies suggested relationships between AD, neuro-inflammation and organochloride pesticide exposures, therefore, we aimed to study the association between DDT and possible biomarkers of AD.

The Behavioral Effects of the Antidepressant Tianeptine Require the Mu-Opioid Receptor.

Depression is a debilitating chronic illness that affects around 350 million people worldwide. Current treatments, such as selective serotonin reuptake inhibitors, are not ideal because only a fraction of patients achieve remission. Tianeptine is an effective antidepressant with a previously unknown mechanism of action.

Weakening Impact of Excessive Human Serum Albumin (eHSA) on Cisplatin and Etoposide Anticancer Effect in C57BL/6 Mice with Tumor and in Human NSCLC A549 Cells.

Excessive human serum albumin (eHSA) impact on anticancer effects is inconsistent. We explored the outcome of cisplatin (DDP)/etoposide (VP-16) plus eHSA and . C57BL/6 mice with tumor were used to compare the efficacy of DDP/VP-16 alone and DDP/VP-16+eHSA.

Chesapeake Bay nitrogen fluxes derived from a land-estuarine ocean biogeochemical modeling system: Model description, evaluation, and nitrogen budgets.

The Chesapeake Bay plays an important role in transforming riverine nutrients before they are exported to the adjacent continental shelf. Although the mean nitrogen budget of the Chesapeake Bay has been previously estimated from observations, uncertainties associated with interannually varying hydrological conditions remain. In this study, a land-estuarine-ocean biogeochemical modeling system is developed to quantify Chesapeake riverine nitrogen inputs, within-estuary nitrogen transformation processes and the ultimate export of nitrogen to the coastal ocean.

Transcriptional and Physiological Changes during Mycobacterium tuberculosis Reactivation from Non-replicating Persistence.

Mycobacterium tuberculosis can persist for years in the hostile environment of the host in a non-replicating or slowly replicating state. While active disease predominantly results from reactivation of a latent infection, the molecular mechanisms of M. tuberculosis reactivation are still poorly understood.

Characterization of the Statistical Signatures of Micro-Movements Underlying Natural Gait Patterns in Children with Phelan McDermid Syndrome: Towards Precision-Phenotyping of Behavior in ASD.

Background: There is a critical need for precision phenotyping across neurodevelopmental disorders, especially in individuals who receive a clinical diagnosis of autism spectrum disorder (ASD). Phelan-McDermid deletion syndrome (PMS) is one such example, as it has a high penetrance of ASD. At present, no biometric characterization of the behavioral phenotype within PMS exists.

Box-Counting Dimension Revisited: Presenting an Efficient Method of Minimizing Quantization Error and an Assessment of the Self-Similarity of Structural Root Systems.

Fractal dimension (FD), estimated by box-counting, is a metric used to characterize plant anatomical complexity or space-filling characteristic for a variety of purposes. The vast majority of published studies fail to evaluate the assumption of statistical self-similarity, which underpins the validity of the procedure. The box-counting procedure is also subject to error arising from arbitrary grid placement, known as quantization error (QE), which is strictly positive and varies as a function of scale, making it problematic for the procedure's slope estimation step.

Functional Identification and Characterization of Genes Cloned from Halophyte Seashore Paspalum Conferring Salinity and Cadmium Tolerance.

Salinity-affected and heavy metal-contaminated soils limit the growth of glycophytic plants. Identifying genes responsible for superior tolerance to salinity and heavy metals in halophytes has great potential for use in developing salinity- and Cd-tolerant glycophytes. The objective of this study was to identify salinity- and Cd-tolerance related genes in seashore paspalum (Paspalum vaginatum), a halophytic perennial grass species, using yeast cDNA expression library screening method.

Sensory Cortical Plasticity Participates in the Epigenetic Regulation of Robust Memory Formation.

Neuroplasticity remodels sensory cortex across the lifespan. A function of adult sensory cortical plasticity may be capturing available information during perception for memory formation. The degree of experience-dependent remodeling in sensory cortex appears to determine memory strength and specificity for important sensory signals.

Rumination in major depressive disorder is associated with impaired neural activation during conflict monitoring.

Individuals with major depressive disorder (MDD) often ruminate about past experiences, especially those with negative content. These repetitive thoughts may interfere with cognitive processes related to attention and conflict monitoring. However, the temporal nature of these processes as reflected in event-related potentials (ERPs) has not been well-described.

Hippocampal developmental vulnerability to methylmercury extends into prepubescence.

The developing brain is sensitive to environmental toxicants such as methylmercury (MeHg), to which humans are exposed via contaminated seafood. Prenatal exposure in children is associated with learning, memory and IQ deficits, which can result from hippocampal dysfunction. To explore underlying mechanisms, we have used the postnatal day (P7) rat to model the third trimester of human gestation.

Objective and personalized longitudinal assessment of a pregnant patient with post severe brain trauma.

Background: Following severe trauma to the brain (whether internally generated by seizures, tumors or externally caused by collision with or penetration of objects) individuals may experience initial coma state followed by slow recovery and rehabilitation treatment. At present there is no objective biometric to track the daily progression of the person for extended periods of time.

Objective: We introduce new analytical techniques to process data from physically wearable sensors and help track the longitudinal progression of motions and physiological states upon the brain trauma.

Pathologic findings in patients who underwent robot-assisted radical prostatectomy following active surveillance: a prospective study in a single center.

Aim: Active surveillance is the recommended treatment of option for men with very low-risk prostate cancer. In this study, the clinicopathological results of patients who were initially treated with active surveillance and subsequently underwent robot-assisted radical prostatectomy during follow-up are described.

Methods: A prospective cohort of 106 men enrolled in active surveillance was reviewed.

Novel and enhanced anti-melanoma DNA vaccine targeting the tyrosinase protein inhibits myeloid-derived suppressor cells and tumor growth in a syngeneic prophylactic and therapeutic murine model.

Melanoma is the most deadly type of skin cancer, constituting annually ∼ 75% of all cutaneous cancer-related deaths due to metastatic spread. Currently, because of metastatic spread, there are no effective treatment options for late-stage metastatic melanoma patients. Studies over the past two decades have provided insight into several complex molecular mechanisms as to how these malignancies evade immunological control, indicating the importance of immune escape or suppression for tumor survival.

A Domain Constrained Deformable (DoCD) Model for Co-registration of Pre- and Post-Radiated Prostate MRI.

External beam radiation treatment (EBRT) is a popular method for treating prostate cancer (CaP) involving destroying tumor cells with ionizing radiation. Following EBRT, biochemical failure has been linked with disease recurrence. However, there is a need for methods for evaluating early treatment related changes to allow for an early intervention in case of incomplete disease response.

Decoding the role of chromatin architecture in development: coming closer to the end of the tunnel.

Form and function in biology are intimately related aspects that are often difficult to untangle. While the structural aspects of chromatin organization were apparent from early cytological observations long before the molecular details of chromatin functions were deciphered, the extent to which genome architecture may impact its output remains unclear. A major roadblock to resolve this issue is the divergent scales, both temporal and spatial, of the experimental approaches for examining these facets of chromatin biology.

Predictors of Infant Feeding Frequency by Mexican Immigrant Mothers.

With an increase in the prevalence of overweight being seen as early as infancy, it is essential that the factors which account for early excess weight gain be identified. In this study, maternal and infant characteristics were examined to determine their relation to the frequency of infants being fed. A cohort of 67 low-educated Mexican mothers who formula-fed their infants were recruited at a WIC Center and home-visited when their infants were 6-months-old.

Immunological challenge modulates brain orphanin FQ/nociceptin and nociceptive behavior.

Orphanin FQ/Nociceptin (OFQ/N), an endogenous peptide found throughout the central nervous system, has been attributed with a wide range of functions, including modulation of motivational and emotional behavior, but most prominently, facilitation of hyperalgesia. It has also been shown that brain OFQ/N is stimulated during locally-induced peripheral inflammation, a condition well known to increase pain sensitivity. However, few studies have addressed whether specific immunological challenge using T-cell dependent and independent stimuli alters OFQ/N gene activation in the brain.

Anaerobic degradation and dehalogenation of chlorosalicylates and salicylate under four reducing conditions.

The anaerobic biodegradability and transformation of the mono-and dichlorinated salicylates (2-hydroxybenzoates) was examined under denitrifying, Fe (III) reducing, sulfate reducing and methanogenic conditions. 3,6-Dichlorosalicylate and 6-chlorosalicylate are anaerobic microbial metabolites of dicamba, a widely used herbicide. Anaerobic microcosms were established with dicamba treated soil from Wyoming, and golf course drainage stream sediments from New Jersey, which were each spiked with salicylate, 3,6-dichlorosalicylate or one of the four monochlorosalicylate isomers.

Peekaboo: a new look at infants' perception of emotion expressions.

Infants' responsiveness to others' affective expressions was investigated in the context of a peekaboo game. Forty 4-month-olds participated in a peekaboo game in which the typical happy/surprised expression was systematically replaced with a different emotion, depending on group assignment. Infants viewed three typical peekaboo trials followed by a change (anger, fear, or sadness) or no-change (happiness/surprise) trial, repeated over two blocks.