Stimulus pauses and perturbations differentially delay or promote the segregation of auditory objects: psychoacoustics and modeling

This Provisional PDF corresponds to the article as it appeared upon acceptance, after peer-review. The final publisher formatted version is available from the publisher via the DOI in this record.Segregating distinct sound sources is fundamental for auditory perception, as in the cocktail party problem. In a process called the build-up of stream segregation, distinct sound sources that are perceptually integrated initially can be segregated into separate streams after several seconds. Previous research concluded that abrupt changes in the incoming sounds during build-up --- for example, a step change in location, loudness or timing --- reset the percept to integrated. Following this reset, the multisecond build-up process begins again. Neurophysiological recordings in auditory cortex (A1) show fast (subsecond) adaptation, but unified mechanistic explanations for the bias toward integration, multisecond build-up and resets remain elusive. Combining psychoacoustics and modeling, we show that initial unadapted A1 responses bias integration, that the slowness of build-up arises naturally from competition downstream, and that recovery of adaptation can explain resets. An early bias toward integrated perceptual interpretations arising from primary cortical stages that encode low-level features and feed into competition downstream could also explain similar phenomena in vision. Further, we report a previously overlooked class of perturbations that promote segregation rather than integration. Our results challenge current understanding for perturbation effects on the emergence of sound source segregation, leading to a new hypothesis for differential processing downstream of A1. Transient perturbations can momentarily redirect A1 responses as input to downstream competition units that favor segregation

Recently evolved combination of unique sulfatase and amidase genes enables bacterial degradation of the wastewater micropollutant acesulfame worldwide

Xenobiotics often challenge the principle of microbial infallibility. One example is acesulfame introduced in the 1980s as zero-calorie sweetener, which was recalcitrant in wastewater treatment plants until the early 2010s. Then, efficient removal has been reported with increasing frequency. By studying acesulfame metabolism in alphaproteobacterial degraders of the genera Bosea and Chelatococcus, we experimentally confirmed the previously postulated route of two subsequent hydrolysis steps via acetoacetamide-N-sulfonate (ANSA) to acetoacetate and sulfamate. Genome comparison of wildtype Bosea sp. 100-5 and an acesulfame degradation-defective mutant revealed the involvement of two plasmid-borne gene clusters. The acesulfame-hydrolyzing sulfatase is strictly manganese-dependent and belongs to the metallo beta-lactamase family. In all degraders analyzed, it is encoded on a highly conserved gene cluster embedded in a composite transposon. The ANSA amidase, on the other hand, is an amidase signature domain enzyme encoded in another gene cluster showing variable length among degrading strains. Transposition of the sulfatase gene cluster between chromosome and plasmid explains how the two catabolic gene clusters recently combined for the degradation of acesulfame. Searching available genomes and metagenomes for the two hydrolases and associated genes indicates that the acesulfame plasmid evolved and spread worldwide in short time. While the sulfatase is unprecedented and unique for acesulfame degraders, the amidase occurs in different genetic environments and likely evolved for the degradation of other substrates. Evolution of the acesulfame degradation pathway might have been supported by the presence of structurally related natural and anthropogenic compounds, such as aminoacyl sulfamate ribonucleotide or sulfonamide antibiotics

Genome-wide RNA-Sequencing analysis reveals a distinct fibrosis gene signature in the conjunctiva after glaucoma surgery

Fibrosis-related events play a part in most blinding diseases worldwide. However, little is known about the mechanisms driving this complex multifactorial disease. Here we have carried out the first genome-wide RNA-Sequencing study in human conjunctival fibrosis. We isolated 10 primary fibrotic and 7 non-fibrotic conjunctival fibroblast cell lines from patients with and without previous glaucoma surgery, respectively. The patients were matched for ethnicity and age. We identified 246 genes that were differentially expressed by over two-fold and p < 0.05, of which 46 genes were upregulated and 200 genes were downregulated in the fibrotic cell lines compared to the non-fibrotic cell lines. We also carried out detailed gene ontology, KEGG, disease association, pathway commons, WikiPathways and protein network analyses, and identified distinct pathways linked to smooth muscle contraction, inflammatory cytokines, immune mediators, extracellular matrix proteins and oncogene expression. We further validated 11 genes that were highly upregulated or downregulated using real-time quantitative PCR and found a strong correlation between the RNA-Seq and qPCR results. Our study demonstrates that there is a distinct fibrosis gene signature in the conjunctiva after glaucoma surgery and provides new insights into the mechanistic pathways driving the complex fibrotic process in the eye and other tissues

DNA methylation, the early-life social environment and behavioral disorders

One of the outstanding questions in behavioral disorders is untangling the complex relationship between nurture and nature. Although epidemiological data provide evidence that there is an interaction between genetics (nature) and the social and physical environments (nurture) in a spectrum of behavioral disorders, the main open question remains the mechanism. Emerging data support the hypothesis that DNA methylation, a covalent modification of the DNA molecule that is a component of its chemical structure, serves as an interface between the dynamic environment and the fixed genome. We propose that modulation of DNA methylation in response to environmental cues early in life serves as a mechanism of life-long genome adaptation. Under certain contexts, this adaptation can turn maladaptive resulting in behavioral disorders. This hypothesis has important implications on understanding, predicting, preventing, and treating behavioral disorders including autism that will be discussed

Asymmetrical Gene Flow in a Hybrid Zone of Hawaiian Schiedea (Caryophyllaceae) Species with Contrasting Mating Systems

Asymmetrical gene flow, which has frequently been documented in naturally occurring hybrid zones, can result from various genetic and demographic factors. Understanding these factors is important for determining the ecological conditions that permitted hybridization and the evolutionary potential inherent in hybrids. Here, we characterized morphological, nuclear, and chloroplast variation in a putative hybrid zone between Schiedea menziesii and S. salicaria, endemic Hawaiian species with contrasting breeding systems. Schiedea menziesii is hermaphroditic with moderate selfing; S. salicaria is gynodioecious and wind-pollinated, with partially selfing hermaphrodites and largely outcrossed females. We tested three hypotheses: 1) putative hybrids were derived from natural crosses between S. menziesii and S. salicaria, 2) gene flow via pollen is unidirectional from S. salicaria to S. menziesii and 3) in the hybrid zone, traits associated with wind pollination would be favored as a result of pollen-swamping by S. salicaria. Schiedea menziesii and S. salicaria have distinct morphologies and chloroplast genomes but are less differentiated at the nuclear loci. Hybrids are most similar to S. menziesii at chloroplast loci, exhibit nuclear allele frequencies in common with both parental species, and resemble S. salicaria in pollen production and pollen size, traits important to wind pollination. Additionally, unlike S. menziesii, the hybrid zone contains many females, suggesting that the nuclear gene responsible for male sterility in S. salicaria has been transferred to hybrid plants. Continued selection of nuclear genes in the hybrid zone may result in a population that resembles S. salicaria, but retains chloroplast lineage(s) of S. menziesii

DNA glycosylases: in DNA repair and beyond

The base excision repair machinery protects DNA in cells from the damaging effects of oxidation, alkylation, and deamination; it is specialized to fix single-base damage in the form of small chemical modifications. Base modifications can be mutagenic and/or cytotoxic, depending on how they interfere with the template function of the DNA during replication and transcription. DNA glycosylases play a key role in the elimination of such DNA lesions; they recognize and excise damaged bases, thereby initiating a repair process that restores the regular DNA structure with high accuracy. All glycosylases share a common mode of action for damage recognition; they flip bases out of the DNA helix into a selective active site pocket, the architecture of which permits a sensitive detection of even minor base irregularities. Within the past few years, it has become clear that nature has exploited this ability to read the chemical structure of DNA bases for purposes other than canonical DNA repair. DNA glycosylases have been brought into context with molecular processes relating to innate and adaptive immunity as well as to the control of DNA methylation and epigenetic stability. Here, we summarize the key structural and mechanistic features of DNA glycosylases with a special focus on the mammalian enzymes, and then review the evidence for the newly emerging biological functions beyond the protection of genome integrity

25th Annual Computational Neuroscience Meeting: CNS-2016

Abstracts of the 25th Annual Computational Neuroscience Meeting: CNS-2016 Seogwipo City, Jeju-do, South Korea. 2–7 July 201

Do recipient country characteristics affect international spillovers of CO2-efficiency via trade and foreign direct investment?

Although there is evidence that CO2-efficiency enhancing innovations in one country diffuse into other countries to contribute to the goals of climate change mitigation, very little is known about the conditions under which such international spillovers are most likely to take place. Our contribution in the present article seeks to address this gap by examining whether the strength of cross-border CO2-efficiency spatial dependence working through import ties and inward foreign direct investment (FDI) stocks is greater in (a) countries with lower existing levels of domestic CO2-efficiency and (b) countries with greater social capabilities in terms of a better educated workforce and higher institutional quality. We find that less CO2-efficient countries and countries with higher institutional quality experience stronger FDI-weighted CO2-efficiency spillovers, whereas a higher level of human capital increases receptivity to import-weighted international spillovers