478 research outputs found
Nonselective Wiring Accounts for Red-Green Opponency in Midget Ganglion Cells of the Primate Retina
In primate retina, “red-green” color coding is initiated when signals originating in long (L) and middle (M) wavelength-sensitive cone photoreceptors interact antagonistically. The center-surround receptive field of “midget” ganglion cells provides the neural substrate for L versus M cone-opponent interaction, but the underlying circuitry remains unsettled, centering around the longstanding question of whether specialized cone wiring is present. To address this question, we measured the strength, sign, and spatial tuning of L- and M-cone input to midget receptive fields in the peripheral retina of macaque primates of either sex. Consistent with previous work, cone opponency arose when one of the cone types showed a stronger connection to the receptive field center than to the surround. We implemented a difference-of-Gaussians spatial receptive field model, incorporating known biology of the midget circuit, to test whether physiological responses we observed in real cells could be captured entirely by anatomical nonselectivity. When this model sampled nonselectively from a realistic cone mosaic, it accurately reproduced key features of a cone-opponent receptive field structure, and predicted both the variability and strength of cone opponency across the retina. The model introduced here is consistent with abundant anatomical evidence for nonselective wiring, explains both local and global properties of the midget population, and supports a role in their multiplexing of spatial and color information. It provides a neural basis for human chromatic sensitivity across the visual field, as well as the maintenance of normal color vision despite significant variability in the relative number of L and M cones across individuals
Travels in Architectural History
Travel is a powerful force in shaping the perception of the modern world and plays an ever-growing role within architectural and urban cultures. Inextricably linked to political and ideological issues, travel redefines places and landscapes through new transport infrastructures and buildings. Architecture, in turn, is reconstructed through visual and textual narratives produced by scores of modern travellers — including writers and artists along with architects themselves. In the age of the camera, travel is bound up with new kinds of imaginaries; private records and recollections often mingle with official, stereotyped views, as the value of architectural heritage increasingly rests on the mechanical reproduction of its images. Whilst students often learn about architectural history through image collections, the place of the journey in the formation of the architect itself shifts. No longer a lone and passionate antiquarian or an itinerant designer, the modern architect eagerly hops on buses, trains, and planes in pursuit of personal as well as professional interests. Increasingly built on a presumption of mobility, architectural culture integrates travel into cultural debates and design experiments. By addressing such issues from a variety of perspectives, this collection, a special Architectural Histories issue on travel, prompts us to rethink the mobile conditions in which architecture has historically been produced and received
Global Genomic Epidemiology of <i>Salmonella enterica</i> Serovar Typhimurium DT104
International audienceIt has been 30 years since the initial emergence and subsequent rapid global spread of multidrug-resistant Salmonella entericaserovar Typhimurium DT104 (MDR DT104). Nonetheless, its origin and transmission route have never been revealed. We used whole-genome sequencing (WGS) and temporally structured sequence analysis within a Bayesian framework to reconstruct temporal and spatial phylogenetic trees and estimate the rates of mutation and divergence times of 315S Typhimurium DT104 isolates sampled from 1969 to 2012 from 21 countries on six continents. DT104 was estimated to have emerged initially as antimicrobial susceptible in ∼1948 (95% credible interval [CI], 1934 to 1962) and later became MDR DT104 in ∼1972 (95% CI, 1972 to 1988) through horizontal transfer of the 13-kb Salmonella genomic island 1 (SGI1) MDR region into susceptible strains already containing SGI1. This was followed by multiple transmission events, initially from central Europe and later between several European countries. An independent transmission to the United States and another to Japan occurred, and from there MDR DT104 was probably transmitted to Taiwan and Canada. An independent acquisition of resistance genes took place in Thailand in ∼1975 (95% CI, 1975 to 1990). In Denmark, WGS analysis provided evidence for transmission of the organism between herds of animals. Interestingly, the demographic history of Danish MDR DT104 provided evidence for the success of the program to eradicate Salmonellafrom pig herds in Denmark from 1996 to 2000. The results from this study refute several hypotheses on the evolution of DT104 and suggest that WGS may be useful in monitoring emerging clones and devising strategies for prevention of Salmonella infections
The role of ongoing dendritic oscillations in single-neuron dynamics
The dendritic tree contributes significantly to the elementary computations a neuron performs while converting its synaptic inputs into action potential output. Traditionally, these computations have been characterized as temporally local, near-instantaneous mappings from the current input of the cell to its current output, brought about by somatic summation of dendritic contributions that are generated in spatially localized functional compartments. However, recent evidence about the presence of oscillations in dendrites suggests a qualitatively different mode of operation: the instantaneous phase of such oscillations can depend on a long history of inputs, and under appropriate conditions, even dendritic oscillators that are remote may interact through synchronization. Here, we develop a mathematical framework to analyze the interactions of local dendritic oscillations, and the way these interactions influence single cell computations. Combining weakly coupled oscillator methods with cable theoretic arguments, we derive phase-locking states for multiple oscillating dendritic compartments. We characterize how the phase-locking properties depend on key parameters of the oscillating dendrite: the electrotonic properties of the (active) dendritic segment, and the intrinsic properties of the dendritic oscillators. As a direct consequence, we show how input to the dendrites can modulate phase-locking behavior and hence global dendritic coherence. In turn, dendritic coherence is able to gate the integration and propagation of synaptic signals to the soma, ultimately leading to an effective control of somatic spike generation. Our results suggest that dendritic oscillations enable the dendritic tree to operate on more global temporal and spatial scales than previously thought
Multi-decadal trends in large-bodied fish populations in the New South Wales Murray-Darling Basin, Australia
Context: Native fish populations in Australia's Murray-Darling Basin (MDB) have experienced severe declines since European settlement. Information on their status is needed to guide management and recovery. Aims: To quantify trends in MDB fish populations in New South Wales (NSW) from 1994 to 2022. Methods: Relative abundance, biomass, and size structure were examined using generalised additive mixed models at NSW MDB and river catchment (valley) scales for five native species (Murray cod, Maccullochella peelii, golden perch, Macquaria ambigua, silver perch, Bidyanus bidyanus, Macquarie perch, Macquaria australasica, freshwater catfish, Tandanus tandanus) and one alien species (common carp, Cyprinus carpio). Key results: There was strong inter-annual variation in relative abundance, biomass and population structure for all species. At the Basin scale, relative abundance of Murray cod, golden perch and common carp increased across the time series, with no clear trends for silver perch, Macquarie perch or freshwater catfish. Patterns in relative abundance, biomass, and population structure were variable among valleys for most species. Conclusions and implications: Although native fish populations in the MDB remain degraded and face escalating threats, recent increases in the abundance of some native species are an encouraging sign that integrated restoration efforts can improve the outlook for native fish
Rifampicin resistant 'Mycobacterium tuberculosis' in Vietnam, 2020–2022
Objective: We conducted a descriptive analysis of multi-drug resistant tuberculosis (MDR-TB) in Vietnam’s two largest cities, Hanoi and Ho Chi Minh city.
Methods: All patients with rifampicin resistant tuberculosis were recruited from Hanoi and surrounding provinces between 2020 and 2022. Additional patients were recruited from Ho Chi Minh city over the same time period. Demographic data were recorded from all patients, and samples collected, cultured, whole genome sequenced and analysed for drug resistance mutations. Genomic susceptibility predictions were made on the basis of the World Health Organization’s catalogue of mutations in Mycobacterium tuberculosis associated with drug resistance, version 2. Comparisons were made against phenotypic drug susceptibility test results where these were available. Multivariable logistic regression was used to assess risk factors for previous episodes of tuberculosis.
Results: 233/265 sequenced isolates were of sufficient quality for analysis, 146 (63 %) from Ho Chi Minh City and 87 (37 %) from Hanoi. 198 (85 %) were lineage 2, 20 (9 %) were lineage 4, and 15 (6 %) were lineage 1. 17/211 (8 %) for whom HIV status was known were infected, and 109/214 (51 %) patients had had a previous episode of tuberculosis. The main risk factor for a previous episode was HIV infection (odds ratio 5.1 (95 % confidence interval 1.3–20.0); p = 0.021). Sensitivity for predicting first-line drug resistance from whole genome sequencing data was over 90 %, with the exception of pyrazinamide (85 %). For moxifloxacin and amikacin it was 50 % or less. Among rifampicin-resistant isolates, prevalence of resistance to each non-first-line drug was < 20 %.
Conclusions: Drug resistance among most MDR-TB strains in Vietnam’s two largest cities is confined largely to first-line drugs. Living with HIV is the main risk factor among patients with MDR-TB for having had a previous episode of tuberculosis
Harmonizing semantic annotations for computational models in biology
Life science researchers use computational models to articulate and test hypotheses about the behavior of biological systems. Semantic annotation is a critical component for enhancing the interoperability and reusability of such models as well as for the integration of the data needed for model parameterization and validation. Encoded as machine-readable links to knowledge resource terms, semantic annotations describe the computational or biological meaning of what models and data represent. These annotations help researchers find and repurpose models, accelerate model composition and enable knowledge integration across model repositories and experimental data stores. However, realizing the potential benefits of semantic annotation requires the development of model annotation standards that adhere to a community-based annotation protocol.Without such standards, tool developers must account for a variety of annotation formats and approaches, a situation that can become prohibitively cumbersome and which can defeat the purpose of linking model elements to controlled knowledge resource terms. Currently, no consensus protocol for semantic annotation exists among the larger biological modeling community. Here, we report on the landscape of current annotation practices among the Computational Modeling in BIology NEtwork community and provide a set of recommendations for building a consensus approach to semantic annotation
Desglycinamide-(ARG8)-vasopressin in five trials with memory-disturbed patients
A series of five consecutive clinical trials were performed in which the neuropeptide desglycinamide‐(Arg8)‐vasopressin (DGAVP) was administered to human subjects suffering from cognitive and memory complaints. The patients selected for the study were carefully screened with the aid of neuropsychological assessment procedures. The trials were conducted according to a structured design in which the variables ‘dose’, ‘route of administration’, ‘treatment schedule’, ‘diagnostic group’, and ‘severity of deficit’ were varied from trial to trial in order to find optimal conditions for the possible expression of a peptide effect. The results indicate a statistically significant effect of DGAVP on word list learning in patients with mild brain trauma, suggesting that learning performance and memory retrieval are improved after peptide treatment in these patients. Patients with more severe brain trauma did not respond to peptide treatment. Some DGAVP effects, e.g. increased speed of memory search, were observed in patients with age‐associated memory deficits
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