GoMiner: a resource for biological interpretation of genomic and proteomic data

We have developed GoMiner, a program package that organizes lists of 'interesting' genes (for example, under- and overexpressed genes from a microarray experiment) for biological interpretation in the context of the Gene Ontology. GoMiner provides quantitative and statistical output files and two useful visualizations. The first is a tree-like structure analogous to that in the AmiGO browser and the second is a compact, dynamically interactive 'directed acyclic graph'. Genes displayed in GoMiner are linked to major public bioinformatics resources

Observable Effects of Scalar Fields and Varying Constants

We show by using the method of matched asymptotic expansions that a sufficient condition can be derived which determines when a local experiment will detect the cosmological variation of a scalar field which is driving the spacetime variation of a supposed constant of Nature. We extend our earlier analyses of this problem by including the possibility that the local region is undergoing collapse inside a virialised structure, like a galaxy or galaxy cluster. We show by direct calculation that the sufficient condition is met to high precision in our own local region and we can therefore legitimately use local observations to place constraints upon the variation of "constants" of Nature on cosmological scales.Comment: Invited Festscrift Articl

Subcortical Source and Modulation of the Narrowband Gamma Oscillation in Mouse Visual Cortex

Primary visual cortex exhibits two types of gamma rhythm: broadband activity in the 30-90 Hz range and a narrowband oscillation seen in mice at frequencies close to 60 Hz. We investigated the sources of the narrowband gamma oscillation, the factors modulating its strength, and its relationship to broadband gamma activity. Narrowband and broadband gamma power were uncorrelated. Increasing visual contrast had opposite effects on the two rhythms: it increased broadband activity, but suppressed the narrowband oscillation. The narrowband oscillation was strongest in layer 4 and was mediated primarily by excitatory currents entrained by the synchronous, rhythmic firing of neurons in the lateral geniculate nucleus (LGN). The power and peak frequency of the narrowband gamma oscillation increased with light intensity. Silencing the cortex optogenetically did not abolish the narrowband oscillation in either LGN firing or cortical excitatory currents, suggesting that this oscillation reflects unidirectional flow of signals from thalamus to cortex

Terrestrial Very-Long-Baseline Atom Interferometry:Workshop Summary

This document presents a summary of the 2023 Terrestrial Very-Long-Baseline Atom Interferometry Workshop hosted by CERN. The workshop brought together experts from around the world to discuss the exciting developments in large-scale atom interferometer (AI) prototypes and their potential for detecting ultralight dark matter and gravitational waves. The primary objective of the workshop was to lay the groundwork for an international TVLBAI proto-collaboration. This collaboration aims to unite researchers from different institutions to strategize and secure funding for terrestrial large-scale AI projects. The ultimate goal is to create a roadmap detailing the design and technology choices for one or more km-scale detectors, which will be operational in the mid-2030s. The key sections of this report present the physics case and technical challenges, together with a comprehensive overview of the discussions at the workshop together with the main conclusions

Impact of Optimized Breastfeeding on the Costs of Necrotizing Enterocolitis in Extremely Low Birthweight Infants

To estimate risk of NEC for ELBW infants as a function of preterm formula and maternal milk (MM) intake and calculate the impact of suboptimal feeding on NEC incidence and costs

Cortical Dynamics in Visual Processing

Recurrent circuits are a hallmark of mammalian sensory cortex. How they impact dynamics of sensory representation is not understood. Because recurrent circuits provide a majority of the synaptic excitation to cortical neurons in response to sensory stimulation, the intrinsic dynamics of these cortical recurrent circuits are expected to be a critical determinant of the timing of the sensory response in cortex. Previous methods could not isolate dynamics of these intra-cortical recurrent circuits from those of thalamic afferents during sensory processing. I now accomplish this by developing an approach to optogenetically silence thalamus in a model system: the mouse visual pathway. Silencing thalamus revealed the time course over which visually evoked activity in visual cortex was maintained by the intra-cortical recurrent circuits themselves, in isolation from thalamic input. I found that, at all time points during the cortical sensory-evoked response, optogenetically silencing thalamus led to a fast decay of sensory-evoked activity in cortical recurrent circuits. This activity decay time course was fit by a 10 ms network time constant, similar to a neuron’s integration time window. This decay time course was invariant across all tested visual stimulation conditions and behavioral states but depended on cortical inhibition. In awake mice, the dynamics of this time course predicted the time-locking of cortical activity to thalamic input at frequencies <15 Hz and the attenuation of the cortical response to higher frequencies. Under anesthesia, however, dynamics of depression at thalamocortical synapses disrupted the fidelity of sensory transmission. Thus, I determine sensory-evoked dynamics intrinsic to the intra-cortical recurrent circuits in isolation from thalamus and show how these dynamics transform afferent input in time

Cortical Dynamics in Visual Processing

Recurrent circuits are a hallmark of mammalian sensory cortex. How they impact dynamics of sensory representation is not understood. Because recurrent circuits provide a majority of the synaptic excitation to cortical neurons in response to sensory stimulation, the intrinsic dynamics of these cortical recurrent circuits are expected to be a critical determinant of the timing of the sensory response in cortex. Previous methods could not isolate dynamics of these intra-cortical recurrent circuits from those of thalamic afferents during sensory processing. I now accomplish this by developing an approach to optogenetically silence thalamus in a model system: the mouse visual pathway. Silencing thalamus revealed the time course over which visually evoked activity in visual cortex was maintained by the intra-cortical recurrent circuits themselves, in isolation from thalamic input. I found that, at all time points during the cortical sensory-evoked response, optogenetically silencing thalamus led to a fast decay of sensory-evoked activity in cortical recurrent circuits. This activity decay time course was fit by a 10 ms network time constant, similar to a neuron’s integration time window. This decay time course was invariant across all tested visual stimulation conditions and behavioral states but depended on cortical inhibition. In awake mice, the dynamics of this time course predicted the time-locking of cortical activity to thalamic input at frequencies <15 Hz and the attenuation of the cortical response to higher frequencies. Under anesthesia, however, dynamics of depression at thalamocortical synapses disrupted the fidelity of sensory transmission. Thus, I determine sensory-evoked dynamics intrinsic to the intra-cortical recurrent circuits in isolation from thalamus and show how these dynamics transform afferent input in time

Hypersensitivity to mGluR5 and ERK1/2 Leads to Excessive Protein Synthesis in the Hippocampus of a Mouse Model of Fragile X Syndrome

Fragile X syndrome (FXS) is caused by loss of the FMR1 gene product FMRP (fragile X mental retardation protein), a repressor of mRNA translation. According to the metabotropic glutamate receptor (mGluR) theory of FXS, excessive protein synthesis downstream of mGluR5 activation causes the synaptic pathophysiology that underlies multiple aspects of FXS. Here, we use an in vitro assay of protein synthesis in the hippocampus of male Fmr1 knock-out (KO) mice to explore the molecular mechanisms involved in this core biochemical phenotype under conditions where aberrant synaptic physiology has been observed. We find that elevated basal protein synthesis in Fmr1 KO mice is selectively reduced to wild-type levels by acute inhibition of mGluR5 or ERK1/2, but not by inhibition of mTOR (mammalian target of rapamycin). The mGluR5-ERK1/2 pathway is not constitutively overactive in the Fmr1 KO, however, suggesting that mRNA translation is hypersensitive to basal ERK1/2 activation in the absence of FMRP. We find that hypersensitivity to ERK1/2 pathway activation also contributes to audiogenic seizure susceptibility in the Fmr1 KO. These results suggest that the ERK1/2 pathway, and other neurotransmitter systems that stimulate protein synthesis via ERK1/2, represent additional therapeutic targets for FXS.FRAXA Research FoundationSimons FoundationNational Institute of Mental Health (U.S.)Eunice Kennedy Shriver National Institute of Child Health and Human Development (U.S.)Hilibrand Foundatio