Short-term acclimation in adults does not predict offspring acclimation potential to hypoxia

Abstract The prevalence of hypoxic areas in coastal waters is predicted to increase and lead to reduced biodiversity. While the adult stages of many estuarine invertebrates can cope with short periods of hypoxia, it remains unclear whether that ability is present if animals are bred and reared under chronic hypoxia. We firstly investigated the effect of moderate, short-term environmental hypoxia (40% air saturation for one week) on metabolic performance in adults of an estuarine amphipod, and the fitness consequences of prolonged exposure. We then reared the offspring of hypoxia-exposed parents under hypoxia, and assessed their oxyregulatory ability under declining oxygen tensions as juveniles and adults. Adults from the parental generation were able to acclimate their metabolism to hypoxia after one week, employing mechanisms typically associated with prolonged exposure. Their progeny, however, did not develop the adult pattern of respiratory regulation when reared under chronic hypoxia, but instead exhibited a poorer oxyregulatory ability than their parents. We conclude that species apparently hypoxia-tolerant when tested in short-term experiments, could be physiologically compromised as adults if they develop under hypoxia. Consequently, we propose that the increased prevalence of hypoxia in coastal regions will have marked effects in some species currently considered hypoxia tolerant

Dissociating Object Directed and Non-Object Directed Action in the Human Mirror System; Implications for Theories of Motor Simulation

Mirror neurons are single cells found in macaque premotor and parietal cortices that are active during action execution and observation. In non-human primates, mirror neurons have only been found in relation to object-directed movements or communicative gestures, as non-object directed actions of the upper limb are not well characterized in non-human primates. Mirror neurons provide important evidence for motor simulation theories of cognition, sometimes referred to as the direct matching hypothesis, which propose that observed actions are mapped onto associated motor schemata in a direct and automatic manner. This study, for the first time, directly compares mirror responses, defined as the overlap between action execution and observation, during object directed and meaningless non-object directed actions. We present functional MRI data that demonstrate a clear dissociation between object directed and non-object directed actions within the human mirror system. A premotor and parietal network was preferentially active during object directed actions, whether observed or executed. Moreover, we report spatially correlated activity across multiple voxels for observation and execution of an object directed action. In contrast to predictions made by motor simulation theory, no similar activity was observed for non-object directed actions. These data demonstrate that object directed and meaningless non-object directed actions are subserved by different neuronal networks and that the human mirror response is significantly greater for object directed actions. These data have important implications for understanding the human mirror system and for simulation theories of motor cognition. Subsequent theories of motor simulation must account for these differences, possibly by acknowledging the role of experience in modulating the mirror response

fMRI Supports the Sensorimotor Theory of Motor Resonance

The neural mechanisms mediating the activation of the motor system during action observation, also known as motor resonance, are of major interest to the field of motor control. It has been proposed that motor resonance develops in infants through Hebbian plasticity of pathways connecting sensory and motor regions that fire simultaneously during imitation or self movement observation. A fundamental problem when testing this theory in adults is that most experimental paradigms involve actions that have been overpracticed throughout life. Here, we directly tested the sensorimotor theory of motor resonance by creating new visuomotor representations using abstract stimuli (motor symbols) and identifying the neural networks recruited through fMRI. We predicted that the network recruited during action observation and execution would overlap with that recruited during observation of new motor symbols. Our results indicate that a network consisting of premotor and posterior parietal cortex, the supplementary motor area, the inferior frontal gyrus and cerebellum was activated both by new motor symbols and by direct observation of the corresponding action. This tight spatial overlap underscores the importance of sensorimotor learning for motor resonance and further indicates that the physical characteristics of the perceived stimulus are irrelevant to the evoked response in the observer

Identifying and evaluating field indicators of urogenital schistosomiasis-related morbidity in preschool-aged children

BACKGROUND:Several studies have been conducted quantifying the impact of schistosome infections on health and development in school-aged children. In contrast, relatively little is known about morbidity levels in preschool-aged children (≤ 5 years) who have been neglected in terms of schistosome research and control. The aim of this study was to compare the utility of available point-of-care (POC) morbidity diagnostic tools in preschool versus primary school-aged children (6-10 years) and determine markers which can be used in the field to identify and quantify Schistosoma haematobium-related morbidity. METHODS/PRINCIPAL FINDINGS:A comparative cross-sectional study was conducted to evaluate the performance of currently available POC morbidity diagnostic tools on Zimbabwean children aged 1-5 years (n=104) and 6-10 years (n=194). Morbidity was determined using the POC diagnostics questionnaire-based reporting of haematuria and dysuria, clinical examination, urinalysis by dipsticks, and urine albumin-to-creatinine ratio (UACR). Attributable fractions were used to quantify the proportion of morbidity attributable to S. haematobium infection. Based on results of attributable fractions, UACR was identified as the most reliable tool for detecting schistosome-related morbidity, followed by dipsticks, visual urine inspection, questionnaires, and lastly clinical examination. The results of urine dipstick attributes showed that proteinuria and microhaematuria accounted for most differences between schistosome egg-positive and negative children (T=-50.1; p<0.001). These observations were consistent in preschool vs. primary school-aged children. CONCLUSIONS/SIGNIFICANCE:Preschool-aged children in endemic areas can be effectively screened for schistosome-related morbidity using the same currently available diagnostic tools applicable to older children. UACR for detecting albuminuria is recommended as the best choice for rapid assessment of morbidity attributed to S. haematobium infection in children in the field. The use of dipstick microhaematuria and proteinuria as additional indicators of schistosome-related morbidity would improve the estimation of disease burden in young children

Comprehensive molecular characterization of the hippo signaling pathway in cancer

Hippo signaling has been recognized as a key tumor suppressor pathway. Here, we perform a comprehensive molecular characterization of 19 Hippo core genes in 9,125 tumor samples across 33 cancer types using multidimensional “omic” data from The Cancer Genome Atlas. We identify somatic drivers among Hippo genes and the related microRNA (miRNA) regulators, and using functional genomic approaches, we experimentally characterize YAP and TAZ mutation effects and miR-590 and miR-200a regulation for TAZ. Hippo pathway activity is best characterized by a YAP/TAZ transcriptional target signature of 22 genes, which shows robust prognostic power across cancer types. Our elastic-net integrated modeling further reveals cancer-type-specific pathway regulators and associated cancer drivers. Our results highlight the importance of Hippo signaling in squamous cell cancers, characterized by frequent amplification of YAP/TAZ, high expression heterogeneity, and significant prognostic patterns. This study represents a systems-biology approach to characterizing key cancer signaling pathways in the post-genomic era