Depth perception in disparity-defined objects: finding the balance between averaging and segregation

Deciding what constitutes an object, and what background, is an essential task for the visual system. This presents a conundrum: averaging over the visual scene is required to obtain a precise signal for object segregation, but segregation is required to define the region over which averaging should take place. Depth, obtained via binocular disparity (the differences between two eyes’ views), could help with segregation by enabling identification of object and background via differences in depth. Here, we explore depth perception in disparity-defined objects. We show that a simple object segregation rule, followed by averaging over that segregated area, can account for depth estimation errors. To do this, we compared objects with smoothly varying depth edges to those with sharp depth edges, and found that perceived peak depth was reduced for the former. A computational model used a rule based on object shape to segregate and average over a central portion of the object, and was able to emulate the reduction in perceived depth. We also demonstrated that the segregated area is not predefined but is dependent on the object shape. We discuss how this segregation strategy could be employed by animals seeking to deter binocular predators.This article is part of the themed issue ‘Vision in our three-dimensional world’.     

Cortical circuits: finding balance in the brain

Maintaining the right balance between excitation and inhibition is crucial to healthy brain function. A recent study has used optogenetics to show how quickly and effectively inhibition clamps down a novel burst of excitation in the neocortex.     

Regulating the balance between symmetric and asymmetric stem cell division in the developing brain

Stem cells proliferate through symmetric division or self-renew through asymmetric division whilst generating differentiating cell types. The balance between symmetric and asymmetric division requires tight control to either expand a stem cell pool or to generate cell diversity. In the Drosophila optic lobe, symmetrically dividing neuroepithelial cells transform into asymmetrically dividing neuroblasts. The switch from neuroepithelial cells to neuroblasts is triggered by a proneural wave that sweeps across the neuroepithelium. Here we review recent findings showing that the orchestrated action of the Notch, EGFR, Fat-Hippo, and JAK/STAT signalling pathways controls the progression of the proneural wave and the sequential transition from symmetric to asymmetric division. The neuroepithelial to neuroblast transition in the optic lobe bears many similarities to the switch from neuroepithelial cell to radial glial cell in the developing mammalian cerebral cortex. The Notch signalling pathway has a similar role in the transition from proliferating to differentiating stem cell pools in the developing vertebrate retina and in the neural tube. Therefore, findings in the Drosophila optic lobe provide insights into the transitions between proliferative and differentiative division in the stem cell pools of higher organisms.     

Regulating the balance between symmetric and asymmetric stem cell division in the developing brain

Stem cells proliferate through symmetric division or self-renew through asymmetric division whilst generating differentiating cell types. The balance between symmetric and asymmetric division requires tight control to either expand a stem cell pool or to generate cell diversity. In the Drosophila optic lobe, symmetrically dividing neuroepithelial cells transform into asymmetrically dividing neuroblasts. The switch from neuroepithelial cells to neuroblasts is triggered by a proneural wave that sweeps across the neuroepithelium. Here we review recent findings showing that the orchestrated action of the Notch, EGFR, Fat-Hippo, and JAK/STAT signalling pathways controls the progression of the proneural wave and the sequential transition from symmetric to asymmetric division. The neuroepithelial to neuroblast transition in the optic lobe bears many similarities to the switch from neuroepithelial cell to radial glial cell in the developing mammalian cerebral cortex. The Notch signalling pathway has a similar role in the transition from proliferating to differentiating stem cell pools in the developing vertebrate retina and in the neural tube. Therefore, findings in the Drosophila optic lobe provide insights into the transitions between proliferative and differentiative division in the stem cell pools of higher organisms.     

Influence of pH on the balance between methanogenesis and iron reduction

Methanogenesis and iron reduction play major roles in determining global fluxes of greenhouse gases. Despite their importance, environmental factors that influence their interactions are poorly known. Here, we present evidence that pH significantly influences the balance between each reaction in anoxic environments that contain ferric (oxyhydr)oxide minerals. In sediment bioreactors that contained goethite as a source of ferric iron, both iron reduction and methanogenesis occurred but the balance between them varied significantly with pH. Compared to bioreactors receiving acidic media (pH 6), electron donor oxidation was 85% lower for iron reduction and 61% higher for methanogenesis in bioreactors receiving alkaline media (pH 7.5). Thus, methanogenesis displaced iron reduction considerably at alkaline pH. Geochemistry data collected from U.S. aquifers demonstrate that a similar pattern also exists on a broad spatial scale in natural settings. In contrast, in bioreactors that were not augmented with goethite, clay minerals served as the source of ferric iron and the balance between each reaction did not vary significantly with pH. We therefore conclude that pH can regulate the relative contributions of microbial iron reduction and methanogenesis to carbon fluxes from terrestrial environments. We further propose that the availability of ferric (oxyhydr)oxide minerals influences the extent to which the balance between each reaction is sensitive to pH. The results of this study advance our understanding of environmental controls on microbial methane generation and provide a basis for using pH and the occurrence of ferric minerals to refine predictions of greenhouse gas fluxes.     

Native-like cyclic peptide models of a viral antigenic site: finding a balance between rigidity and flexibility

Antigenic site A of foot-and-mouth disease virus (serotype C) has been reproduced by means of cyclic versions of peptide A15, YTASARGDLAHLTTT, corresponding to residues 136-150 of envelope protein VP1. A structural basis for the design of the cyclic peptides is provided by crystallographic data from complexes between the Fab fragments of anti-site A monoclonal antibodies and A15, in which the bound peptide is folded into a quasi-cyclic pattern. Head-to-tail cyclizations of A15 do not provide peptides of superior antigenicity. Internal disulfide cyclization, however, leads to analogs which are recognized as one to two orders of magnitude better than linear A15 in both ELISA and biosensor experiments. CD and NMR studies show that the best antigen, CTASARGDLAHLTT-Ahx-C (disulfide), is very insensitive to environment-induced conformational change, suggesting that cyclization helps to stabilize a bioactive-like structure.     

Relationship between atorvastatin dose and the harm caused by torcetrapib

Development of the cholesteryl ester transfer protein (CETP) inhibitor, torcetrapib, was halted after the ILLUMINATE trial revealed an increase in both all-cause mortality (ACM) and major cardiovascular events (MCVEs) associated with its use. We now report that the harm caused by torcetrapib was confined to those in the 10 mg atorvastatin subgroup for both ACM [hazard ratio (HR) = 2.68, 95% CI (1.58, 4.54), P < 0.0001] and MCVEs [HR = 1.41, 95% CI (1.14, 1.74), P = 0.002], with no evidence of harm when torcetrapib was coadministered with higher doses of atorvastatin. In the atorvastatin 10 mg subgroup, age, prior heart failure and stroke were significantly associated with ACM, independent of torcetrapib treatment, whereas low apoA-I, smoking, hypertension, heart failure, myocardial infarction, and stroke were independently associated with MCVEs. After adjusting for these factors, the HR associated with torcetrapib treatment in the 10 mg atorvastatin subgroup remained elevated for both ACM [HR = 2.67, 95% CI (1.57, 4.54), P < 0.001] and MCVE [HR = 1.36, 95% CI (1.10, 1.69), P = 0.005]. Thus, the harm caused by torcetrapib was confined to individuals taking atorvastatin 10 mg. The harm could not be explained by torcetrapib-induced changes in lipid levels, blood pressure, or electrolytes. It is conceivable that higher doses of atorvastatin protected against the harm caused by torcetrapib.     

Interaction between anticoagulants and contraceptives: an unsuspected finding.

To assess the effects of oral contraceptives on anticoagulant treatment the prothrombin times of 12 patients were measured while they were taking both drugs simultaneously and while they were taking only anticoagulants. The mean prothrombin time ratio was significantly higher when patients were taking both drugs than when they were taking only anticoagulants and their doses of anticoagulant were significantly lower. During both periods most of the prothrombin values remained in the therapeutic range. These findings suggest that, contrary to the common belief that oral contraceptives diminish the effects of anticoagulants, contraceptives in fact potentiate the action of the anticoagulants.     

Big forensic data reduction: digital forensic images and electronic evidence

An issue that continues to impact digital forensics is the increasing volume of data and the growing number of devices. One proposed method to deal with the problem of “big digital forensic data”: the volume, variety, and velocity of digital forensic data, is to reduce the volume of data at either the collection stage or the processing stage. We have developed a novel approach which significantly improves on current practice, and in this paper we outline our data volume reduction process which focuses on imaging a selection of key files and data such as: registry, documents, spreadsheets, email, internet history, communications, logs, pictures, videos, and other relevant file types. When applied to test cases, a hundredfold reduction of original media volume was observed. When applied to real world cases of an Australian Law Enforcement Agency, the data volume further reduced to a small percentage of the original media volume, whilst retaining key evidential files and data. The reduction process was applied to a range of real world cases reviewed by experienced investigators and detectives and highlighted that evidential data was present in the data reduced forensic subset files. A data reduction approach is applicable in a range of areas, including: digital forensic triage, analysis, review, intelligence analysis, presentation, and archiving. In addition, the data reduction process outlined can be applied using common digital forensic hardware and software solutions available in appropriately equipped digital forensic labs without requiring additional purchase of software or hardware. The process can be applied to a wide variety of cases, such as terrorism and organised crime investigations, and the proposed data reduction process is intended to provide a capability to rapidly process data and gain an understanding of the information and/or locate key evidence or intelligence in a timely manner.     

Keeping the balance between proliferation and differentiation: the primary cilium

Primary cilia are post-mitotic cellular organelles that are present in the vast majority of cell types in the human body. An extensive body of data gathered in recent years is demonstrating a crucial role for this organelle in a number of cellular processes that include mechano and chemo-sensation as well as the transduction of signaling cascades critical for the development and maintenance of different tissues and organs. Consequently, cilia are currently viewed as cellular antennae playing a critical role at the interphase between cells and their environment, integrating a range of stimuli to modulate cell fate decisions including cell proliferation, migration and differentiation. Importantly, this regulatory role is not just a consequence of their participation in signal transduction but is also the outcome of both the tight synchronization/regulation of ciliogenesis with the cell cycle and the role of individual ciliary proteins in cilia-dependent and independent processes. Here we review the role of primary cilia in the regulation of cell proliferation and differentiation and illustrate how this knowledge has provided insight to understand the phenotypic consequences of ciliary dysfunction.     

High-throughput phenotyping of multicellular organisms: finding the link between genotype and phenotype

High-throughput phenotyping approaches (phenomics) are being combined with genome-wide genetic screens to identify alterations in phenotype that result from gene inactivation. Here we highlight promising technologies for 'phenome-scale' analyses in multicellular organisms.     

Alcohol,tobacco and cannabis use among Nova Scotia adolescents: implications for prevention and harm reduction

OBJECTIVE: To characterize adolescent drug use in terms of a risk continuum and to explore the rationale for harm reduction as a potential approach for school-based drug prevention. DESIGN: Self-reported surveys, in 1991 and 1996, of adolescent students concerning their use of drugs, especially alcohol, tobacco and cannabis, and the harmful consequences of such use. SETTING: Nova Scotia. PARTICIPANTS: A total of 3452 (in 1991) and 3790 (in 1996) junior and high school students in randomly selected classes in the public school system. OUTCOME MEASURES: Prevalence of drug use and patterns of multiple drug use and of alcohol- and drug-related problems; independent risk factors for multiple drug use. The risk continuum for the response to alcohol problems was used as a policy framework. RESULTS: The prevalence of cigarette smoking and the use of hallucinogens and stimulants was markedly higher in 1996 than in 1991. Over one-fifth (21.9%) of the students reported multiple drug use of alcohol and tobacco and cannabis in the 12 months before the 1996 survey. The 3 main subgroups--nonusers, users of alcohol only and users of multiple drugs--had distinct patterns of use, numbers of problems and risk factors. In all, 27.1% of the students had experienced at least 1 alcohol-related problem and 6% had experienced at least 1 drug-related problem in the 12 months before the 1996 survey. CONCLUSION: There is a need for integrated school- and community-based drug prevention programs, with goals, strategies and outcome measures capturing the full spectrum of patterns of use and levels of risk among subgroups of the adolescent student population.