Role of CBP and SATB-1 in Aging, Dietary Restriction, and Insulin-Like Signaling

Increased transcriptional complex activity, or pharmacological mimics of increased complex activity, predict lifespan in mice and mediate the protective effects of dietary restriction during aging

Biopsy confirmation of metastatic sites in breast cancer patients:clinical impact and future perspectives

Determination of hormone receptor (estrogen receptor and progesterone receptor) and human epidermal growth factor receptor 2 status in the primary tumor is clinically relevant to define breast cancer subtypes, clinical outcome,and the choice of therapy. Retrospective and prospective studies suggest that there is substantial discordance in receptor status between primary and recurrent breast cancer. Despite this evidence and current recommendations,the acquisition of tissue from metastatic deposits is not routine practice. As a consequence, therapeutic decisions for treatment in the metastatic setting are based on the features of the primary tumor. Reasons for this attitude include the invasiveness of the procedure and the unreliable outcome of biopsy, in particular for biopsies of lesions at complex visceral sites. Improvements in interventional radiology techniques mean that most metastatic sites are now accessible by minimally invasive methods, including surgery. In our opinion, since biopsies are diagnostic and changes in biological features between the primary and secondary tumors can occur, the routine biopsy of metastatic disease needs to be performed. In this review, we discuss the rationale for biopsy of suspected breast cancer metastases, review issues and caveats surrounding discordance of biomarker status between primary and metastatic tumors, and provide insights for deciding when to perform biopsy of suspected metastases and which one (s) to biopsy. We also speculate on the future translational implications for biopsy of suspected metastatic lesions in the context of clinical trials and the establishment of bio-banks of biopsy material taken from metastatic sites. We believe that such bio-banks will be important for exploring mechanisms of metastasis. In the future,advances in targeted therapy will depend on the availability of metastatic tissue

You turn me cold: evidence for temperature contagion

Introduction During social interactions, our own physiological responses influence those of others. Synchronization of physiological (and behavioural) responses can facilitate emotional understanding and group coherence through inter-subjectivity. Here we investigate if observing cues indicating a change in another's body temperature results in a corresponding temperature change in the observer. Methods Thirty-six healthy participants (age; 22.9±3.1 yrs) each observed, then rated, eight purpose-made videos (3 min duration) that depicted actors with either their right or left hand in visibly warm (warm videos) or cold water (cold videos). Four control videos with the actors' hand in front of the water were also shown. Temperature of participant observers' right and left hands was concurrently measured using a thermistor within a Wheatstone bridge with a theoretical temperature sensitivity of <0.0001°C. Temperature data were analysed in a repeated measures ANOVA (temperature × actor's hand × observer's hand). Results Participants rated the videos showing hands immersed in cold water as being significantly cooler than hands immersed in warm water, F(1,34) = 256.67, p0.1). There was however no evidence of left-right mirroring of these temperature effects p>0.1). Sensitivity to temperature contagion was also predicted by inter-individual differences in self-report empathy. Conclusions We illustrate physiological contagion of temperature in healthy individuals, suggesting that empathetic understanding for primary low-level physiological challenges (as well as more complex emotions) are grounded in somatic simulation

The Shift from Local to Global Visual Processing in 6-Year-Old Children Is Associated with Grey Matter Loss

International audienceBackground: A real-world visual scene consists of local elements (e.g. trees) that are arranged coherently into a global configuration (e.g. a forest). Children show psychological evolution from a preference for local visual information to an adult-like preference for global visual information, with the transition in visual preference occurring around 6 years of age. The brain regions involved in this shift in visual preference have not been described. Methods and Results: We used voxel-based morphometry (VBM) to study children during this developmental window to investigate changes in gray matter that underlie the shift from a bias for local to global visual information. Six-year-old children were assigned to groups according to their judgment on a global/local task. The first group included children who still presented with local visual processing biases, and the second group included children who showed global visual processing biases. VBM results indicated that compared to children with local visual processing biases, children with global visual processing biases had a loss of gray matter in the right occipital and parietal visuospatial areas. Conclusions: These anatomical findings are in agreement with previous findings in children with neurodevelopmental disorders and represent the first structural identification of brain regions that allow healthy children to develop a global perception of the visual world

Elemental and configural olfactory coding by antennal lobe neurons of the honeybee (Apis mellifera)

When smelling an odorant mixture, olfactory systems can be analytical (i.e. extract information about the mixture elements) or synthetic (i.e. creating a configural percept of the mixture). Here, we studied elemental and configural mixture coding in olfactory neurons of the honeybee antennal lobe, local neurons in particular. We conducted intracellular recordings and stimulated with monomolecular odorants and their coherent or incoherent binary mixtures to reproduce a temporally dynamic environment. We found that about half of the neurons responded as ‘elemental neurons’, i.e. responses evoked by mixtures reflected the underlying feature information from one of the components. The other half responded as ‘configural neurons’, i.e. responses to mixtures were clearly different from responses to their single components. Elemental neurons divided in late responders (above 60 ms) and early responder neurons (below 60 ms), whereas responses of configural coding neurons concentrated in-between these divisions. Latencies of neurons with configural responses express a tendency to be faster for coherent stimuli which implies employment in different processing circuits

S100A7, a Novel Alzheimer's Disease Biomarker with Non-Amyloidogenic α-Secretase Activity Acts via Selective Promotion of ADAM-10

Alzheimer's disease (AD) is the most common cause of dementia among older people. At present, there is no cure for the disease and as of now there are no early diagnostic tests for AD. There is an urgency to develop a novel promising biomarker for early diagnosis of AD. Using surface-enhanced laser desorption ionization-mass spectrometry SELDI-(MS) proteomic technology, we identified and purified a novel 11.7-kDa metal- binding protein biomarker whose content is increased in the cerebrospinal fluid (CSF) and in the brain of AD dementia subjects as a function of clinical dementia. Following purification and protein-sequence analysis, we identified and classified this biomarker as S100A7, a protein known to be involved in immune responses. Using an adenoviral-S100A7 expression system, we continued to examine the potential role of S100A7 in AD amyloid neuropathology in in vitro model of AD. We found that the expression of exogenous S100A7 in primary cortico-hippocampal neuron cultures derived from Tg2576 transgenic embryos inhibits the generation of β-amyloid (Aβ)1–42 and Aβ1–40 peptides, coincidental with a selective promotion of “non- amyloidogenic” α-secretase activity via promotion of ADAM (a disintegrin and metalloproteinase)-10. Finally, a selective expression of human S100A7 in the brain of transgenic mice results in significant promotion of α-secretase activity. Our study for the first time suggests that S100A7 may be a novel biomarker of AD dementia and supports the hypothesis that promotion of S100A7 expression in the brain may selectively promote α-secretase activity in the brain of AD precluding the generation of amyloidogenic peptides. If in the future we find that S1000A7 protein content in CSF is sensitive to drug intervention experimentally and eventually in the clinical setting, S100A7 might be developed as novel surrogate index (biomarker) of therapeutic efficacy in the characterization of novel drug agents for the treatment of AD

Using social and behavioural science to support COVID-19 pandemic response

The COVID-19 pandemic represents a massive global health crisis. Because the crisis requires large-scale behaviour change and places significant psychological burdens on individuals, insights from the social and behavioural sciences can be used to help align human behavior with the recommendations of epidemiologists and public health experts. Here we review experimental and correlational data from a selection of research topics relevant to pandemics, including work on navigating threats, social and cultural influences on behaviour, science communication, moral decision-making, leadership, and stress and coping. In each section, we note the nature and quality of prior research, including uncertainty and unsettled issues. We identify several insights for effective response to the COVID-19 pandemic, and also highlight important gaps researchers should move quickly to fill in the coming weeks and months

Imidacloprid-Induced Impairment of Mushroom Bodies and Behavior of the Native Stingless Bee Melipona quadrifasciata anthidioides

Declines in pollinator colonies represent a worldwide concern. The widespread use of agricultural pesticides is recognized as a potential cause of these declines. Previous studies have examined the effects of neonicotinoid insecticides such as imidacloprid on pollinator colonies, but these investigations have mainly focused on adult honey bees. Native stingless bees (Hymenoptera: Apidae: Meliponinae) are key pollinators in neotropical areas and are threatened with extinction due to deforestation and pesticide use. Few studies have directly investigated the effects of pesticides on these pollinators. Furthermore, the existing impact studies did not address the issue of larval ingestion of contaminated pollen and nectar, which could potentially have dire consequences for the colony. Here, we assessed the effects of imidacloprid ingestion by stingless bee larvae on their survival, development, neuromorphology and adult walking behavior. Increasing doses of imidacloprid were added to the diet provided to individual worker larvae of the stingless bee Melipona quadrifasciata anthidioides throughout their development. Survival rates above 50% were only observed at insecticide doses lower than 0.0056 µg active ingredient (a.i.)/bee. No sublethal effect on body mass or developmental time was observed in the surviving insects, but the pesticide treatment negatively affected the development of mushroom bodies in the brain and impaired the walking behavior of newly emerged adult workers. Therefore, stingless bee larvae are particularly susceptible to imidacloprid, as it caused both high mortality and sublethal effects that impaired brain development and compromised mobility at the young adult stage. These findings demonstrate the lethal effects of imidacloprid on native stingless bees and provide evidence of novel serious sublethal effects that may compromise colony survival. The ecological and economic importance of neotropical stingless bees as pollinators, their susceptibility to insecticides and the vulnerability of their larvae to insecticide exposure emphasize the importance of studying these species

Neurobiology of social behavior abnormalities in autism and Williams syndrome

Social behavior is a basic behavior mediated by multiple brain regions and neural circuits, and is crucial for the survival and development of animals and humans. Two neuropsychiatric disorders that have prominent social behavior abnormalities are autism spectrum disorders (ASD), which is characterized mainly by hyposociability, and Williams syndrome (WS), whose subjects exhibit hypersociability. Here we review the unique properties of social behavior in ASD and WS, and discuss the major theories in social behavior in the context of these disorders. We conclude with a discussion of the research questions needing further exploration to enhance our understanding of social behavior abnormalities