Intrinsic activity in the fly brain gates visual information during behavioral choices

The small insect brain is often described as an input/output system that executes reflex-like behaviors. It can also initiate neural activity and behaviors intrinsically, seen as spontaneous behaviors, different arousal states and sleep. However, less is known about how intrinsic activity in neural circuits affects sensory information processing in the insect brain and variability in behavior. Here, by simultaneously monitoring Drosophila's behavioral choices and brain activity in a flight simulator system, we identify intrinsic activity that is associated with the act of selecting between visual stimuli. We recorded neural output (multiunit action potentials and local field potentials) in the left and right optic lobes of a tethered flying Drosophila, while its attempts to follow visual motion (yaw torque) were measured by a torque meter. We show that when facing competing motion stimuli on its left and right, Drosophila typically generate large torque responses that flip from side to side. The delayed onset (0.1-1 s) and spontaneous switch-like dynamics of these responses, and the fact that the flies sometimes oppose the stimuli by flying straight, make this behavior different from the classic steering reflexes. Drosophila, thus, seem to choose one stimulus at a time and attempt to rotate toward its direction. With this behavior, the neural output of the optic lobes alternates; being augmented on the side chosen for body rotation and suppressed on the opposite side, even though the visual input to the fly eyes stays the same. Thus, the flow of information from the fly eyes is gated intrinsically. Such modulation can be noise-induced or intentional; with one possibility being that the fly brain highlights chosen information while ignoring the irrelevant, similar to what we know to occur in higher animals

Risk preference and choice stochasticity during decisions for other people

In several contexts, such as finance and politics, people make choices that are relevant for others but irrelevant for oneself. Focusing on decision-making under risk, we compared monetary choices made for one’s own interest with choices made on behalf of an anonymous individual. Consistent with the previous literature, other-interest choices were characterized by an increased gambling propensity. We also investigated choice stochasticity, which captures how much decisions vary in similar conditions. An aspect related to choice stochasticity is how much decisions are tuned to the option values, and we found that this was higher during self-interest than during other-interest choices. This effect was observed only in individuals who reported a motivation to distribute rewards unequally, suggesting that it may (at least partially) depend on a motivation to make accurate decisions for others. Our results indicate that, during decision-making under risk, choices for other people are characterized by a decreased tuning to the values of the options, in addition to enhanced risk seeking

Vaccines as alternatives to antibiotics for food producing animals. Part 1:challenges and needs

Vaccines and other alternative products can help minimize the need for antibiotics by preventing and controlling infectious diseases in animal populations, and are central to the future success of animal agriculture. To assess scientific advancements related to alternatives to antibiotics and provide actionable strategies to support their development, the United States Department of Agriculture, with support from the World Organisation for Animal Health, organized the second International Symposium on Alternatives to Antibiotics. It focused on six key areas: vaccines; microbial-derived products; non-nutritive phytochemicals; immune-related products; chemicals, enzymes, and innovative drugs; and regulatory pathways to enable the development and licensure of alternatives to antibiotics. This article, part of a two-part series, synthesizes and expands on the expert panel discussions regarding opportunities, challenges and needs for the development of vaccines that may reduce the need for use of antibiotics in animals; new approaches and potential solutions will be discussed in part 2 of this series. Vaccines are widely used to prevent infections in food animals. Various studies have demonstrated that their animal agricultural use can lead to significant reductions in antibiotic consumption, making them promising alternatives to antibiotics. To be widely used in food producing animals, vaccines have to be safe, effective, easy to use, and cost-effective. Many current vaccines fall short in one or more of these respects. Scientific advancements may allow many of these limitations to be overcome, but progress is funding-dependent. Research will have to be prioritized to ensure scarce public resources are dedicated to areas of potentially greatest impact first, and private investments into vaccine development constantly compete with other investment opportunities. Although vaccines have the potential to improve animal health, safeguard agricultural productivity, and reduce antibiotic consumption and resulting resistance risks, targeted research and development investments and concerted efforts by all affected are needed to realize that potential

Functional impact and evolution of a novel human polymorphic inversion that disrupts a gene and creates a fusion transcript

Since the discovery of chromosomal inversions almost 100 years ago, how they are maintained in natural populations has been a highly debated issue. One of the hypotheses is that inversion breakpoints could affect genes and modify gene expression levels, although evidence of this came only from laboratory mutants. In humans, a few inversions have been shown to associate with expression differences, but in all cases the molecular causes have remained elusive. Here, we have carried out a complete characterization of a new human polymorphic inversion and determined that it is specific to East Asian populations. In addition, we demonstrate that it disrupts the ZNF257 gene and, through the translocation of the first exon and regulatory sequences, creates a previously nonexistent fusion transcript, which together are associated to expression changes in several other genes. Finally, we investigate the potential evolutionary and phenotypic consequences of the inversion, and suggest that it is probably deleterious. This is therefore the first example of a natural polymorphic inversion that has position effects and creates a new chimeric gene, contributing to answer an old question in evolutionary biology

Short-Lived Trace Gases in the Surface Ocean and the Atmosphere

The two-way exchange of trace gases between the ocean and the atmosphere is important for both the chemistry and physics of the atmosphere and the biogeochemistry of the oceans, including the global cycling of elements. Here we review these exchanges and their importance for a range of gases whose lifetimes are generally short compared to the main greenhouse gases and which are, in most cases, more reactive than them. Gases considered include sulphur and related compounds, organohalogens, non-methane hydrocarbons, ozone, ammonia and related compounds, hydrogen and carbon monoxide. Finally, we stress the interactivity of the system, the importance of process understanding for modeling, the need for more extensive field measurements and their better seasonal coverage, the importance of inter-calibration exercises and finally the need to show the importance of air-sea exchanges for global cycling and how the field fits into the broader context of Earth System Science

A paediatric bone index derived by automated radiogrammetry

Hand radiographs are obtained routinely to determine bone age of children. This paper presents a method that determines a Paediatric Bone Index automatically from such radiographs. The Paediatric Bone Index is designed to have minimal relative standard deviation (7.5%), and the precision is determined to be 1.42%. Introduction We present a computerised method to determine bone mass of children based on hand radiographs, including a reference database for normal Caucasian children. Methods Normal Danish subjects (1,867), of ages 7-17, and 531 normal Dutch subjects of ages 5-19 were included. Historically, three different indices of bone mass have been used in radiogrammetry all based on A = pi TW(1 - T/W), where T is the cortical thickness and W the bone width. The indices are the metacarpal index A/W-2, DXR-BMD=A/W, and Exton-Smith's index A/(WL), where L is the length of the bone. These indices are compared with new indices of the form A/((WLb)-L-a), and it is argued that the preferred index has minimal SD relative to the mean value at each bone age and sex. Finally, longitudinal series of X-rays of 20 Japanese children are used to derive the precision of the measurements. Results The preferred index is A/((WL0.33)-L-1.33), which is named the Paediatric Bone Index, PBI. It has mean relative SD 7.5% and precision 1.42%. Conclusions As part of the BoneXpert method for automated bone age determination, our method facilitates retrospective research studies involving validation of the proposed index against fracture incidence and adult bone mineral densit

In-depth clinical and biological exploration of DNA Damage Immune Response (DDIR) as a biomarker for oxaliplatin use in colorectal cancer

PURPOSE: The DNA Damage Immune Response (DDIR) assay was developed in breast cancer (BC) based on biology associated with deficiencies in homologous recombination and Fanconi Anemia (HR/FA) pathways. A positive DDIR call identifies patients likely to respond to platinum-based chemotherapies in breast and oesophageal cancers. In colorectal cancer (CRC) there is currently no biomarker to predict response to oxaliplatin. We tested the ability of the DDIR assay to predict response to oxaliplatin-based chemotherapy in CRC and characterised the biology in DDIR-positive CRC. METHODS: Samples and clinical data were assessed according to DDIR status from patients who received either 5FU or FOLFOX within the FOCUS trial (n=361, stage 4), or neo-adjuvant FOLFOX in the FOxTROT trial (n=97, stage 2/3). Whole transcriptome, mutation and immunohistochemistry data of these samples were used to interrogate the biology of DDIR in CRC. RESULTS: Contrary to our hypothesis, DDIR negative patients displayed a trend towards improved outcome for oxaliplatin-based chemotherapy compared to DDIR positive patients. DDIR positivity was associated with Microsatellite Instability (MSI) and Colorectal Molecular Subtype 1 (CMS1). Refinement of the DDIR signature, based on overlapping interferon-related chemokine signalling associated with DDIR positivity across CRC and BC cohorts, further confirmed that the DDIR assay did not have predictive value for oxaliplatin-based chemotherapy in CRC. CONCLUSIONS: DDIR positivity does not predict improved response following oxaliplatin treatment in CRC. However, data presented here suggests the potential of the DDIR assay in identifying immune-rich tumours that may benefit from immune checkpoint blockade, beyond current use of MSI status

The Association of Depressive Symptoms with Inflammatory Factors and Adipokines in Middle-Aged and Older Chinese

Studies in Western populations find that depression is associated with inflammation and obesity. The present study aimed to evaluate the relation of depressive symptoms with inflammatory factors and adipose-derived adipokines in middle-aged and older Chinese.Data were from 3289 community residents aged 50-70 from Beijing and Shanghai who participated in the Nutrition and Health of Aging Population in China project. Depressive symptoms were defined as a Center for Epidemiological Studies of Depression Scale (CES-D) score of 16 or higher. Plasma concentrations of C-reactive protein (CRP), interleukin-6 (IL-6), adiponectin, resistin, plasminogen activator inhibitor-1 (PAI-1) and retinol binding protein 4 (RBP4) were measured. Of the 3289 participants, 312 (9.5%) suffered from current depressive symptoms. IL-6 level was higher in participants with depressive symptoms compared to their counterparts in the crude analyses (1.17 vs. 1.05 pg/mL, p = 0.023) and this association lost statistical significance after multiple adjustments (1.13 vs. 1.10 pg/mL, p = 0.520). Depressive symptoms were not associated with increased mean levels of any other inflammatory factors or adipokines in the unadjusted or adjusted analyses.We found no evidence that depressive symptoms were associated with inflammatory factors and adipokines in the middle-aged and older Chinese populations. Prospective studies and studies in clinically diagnosed patients are needed to confirm our results and clarify the relation of depression with inflammatory factors and adipokines