The emergence of synaesthesia in a Neuronal Network Model via changes in perceptual sensitivity and plasticity

Synaesthesia is an unusual perceptual experience in which an inducer stimulus triggers a percept in a different domain in addition to its own. To explore the conditions under which synaesthesia evolves, we studied a neuronal network model that represents two recurrently connected neural systems. The interactions in the network evolve according to learning rules that optimize sensory sensitivity. We demonstrate several scenarios, such as sensory deprivation or heightened plasticity, under which synaesthesia can evolve even though the inputs to the two systems are statistically independent and the initial cross-talk interactions are zero. Sensory deprivation is the known causal mechanism for acquired synaesthesia and increased plasticity is implicated in developmental synaesthesia. The model unifies different causes of synaesthesia within a single theoretical framework and repositions synaesthesia not as some quirk of aberrant connectivity, but rather as a functional brain state that can emerge as a consequence of optimising sensory information processing

Human Cytomegalovirus UL29/28 Protein Interacts with Components of the NuRD Complex Which Promote Accumulation of Immediate-Early RNA

Histone deacetylation plays a pivotal role in regulating human cytomegalovirus gene expression. In this report, we have identified candidate HDAC1-interacting proteins in the context of infection by using a method for rapid immunoisolation of an epitope-tagged protein coupled with mass spectrometry. Putative interactors included multiple human cytomegalovirus-coded proteins. In particular, the interaction of pUL38 and pUL29/28 with HDAC1 was confirmed by reciprocal immunoprecipitations. HDAC1 is present in numerous protein complexes, including the HDAC1-containing nucleosome remodeling and deacetylase protein complex, NuRD. pUL38 and pUL29/28 associated with the MTA2 component of NuRD, and shRNA-mediated knockdown of the RBBP4 and CHD4 constituents of NuRD inhibited HCMV immediate-early RNA and viral DNA accumulation; together this argues that multiple components of the NuRD complex are needed for efficient HCMV replication. Consistent with a positive acting role for the NuRD elements during viral replication, the growth of pUL29/28- or pUL38-deficient viruses could not be rescued by treating infected cells with the deacetylase inhibitor, trichostatin A. Transient expression of pUL29/28 enhanced activity of the HCMV major immediate-early promoter in a reporter assay, regardless of pUL38 expression. Importantly, induction of the major immediate-early reporter activity by pUL29/28 required functional NuRD components, consistent with the inhibition of immediate-early RNA accumulation within infected cells after knockdown of RBBP4 and CHD4. We propose that pUL29/28 modifies the NuRD complex to stimulate the accumulation of immediate-early RNAs

Trait phenomenological control predicts experience of mirror synaesthesia and the rubber hand illusion

In hypnotic responding, expectancies arising from imaginative suggestion drive striking experiential changes (e.g., hallucinations) — which are experienced as involuntary — according to a normally distributed and stable trait ability (hypnotisability). Such experiences can be triggered by implicit suggestion and occur outside the hypnotic context. In large sample studies (of 156, 404 and 353 participants), we report substantial relationships between hypnotisability and experimental measures of experiential change in mirror-sensory synaesthesia and the rubber hand illusion comparable to relationships between hypnotisability and individual hypnosis scale items. The control of phenomenology to meet expectancies arising from perceived task requirements can account for experiential change in psychological experiments

All-sky, all-frequency directional search for persistent gravitational waves from Advanced LIGO’s and Advanced Virgo’s first three observing runs

We present the first results from an all-sky all-frequency (ASAF) search for an anisotropic stochastic gravitational-wave background using the data from the first three observing runs of the Advanced LIGO and Advanced Virgo detectors. Upper limit maps on broadband anisotropies of a persistent stochastic background were published for all observing runs of the LIGO-Virgo detectors. However, a broadband analysis is likely to miss narrowband signals as the signal-to-noise ratio of a narrowband signal can be significantly reduced when combined with detector output from other frequencies. Data folding and the computationally efficient analysis pipeline, {\tt PyStoch}, enable us to perform the radiometer map-making at every frequency bin. We perform the search at 3072 {\tt{HEALPix}} equal area pixels uniformly tiling the sky and in every frequency bin of width $1/32$~Hz in the range $20-1726$~Hz, except for bins that are likely to contain instrumental artefacts and hence are notched. We do not find any statistically significant evidence for the existence of narrowband gravitational-wave signals in the analyzed frequency bins. Therefore, we place $95\%$ confidence upper limits on the gravitational-wave strain for each pixel-frequency pair, the limits are in the range $(0.030 - 9.6) \times10^{-24}$. In addition, we outline a method to identify candidate pixel-frequency pairs that could be followed up by a more sensitive (and potentially computationally expensive) search, e.g., a matched-filtering-based analysis, to look for fainter nearly monochromatic coherent signals. The ASAF analysis is inherently independent of models describing any spectral or spatial distribution of power. We demonstrate that the ASAF results can be appropriately combined over frequencies and sky directions to successfully recover the broadband directional and isotropic results

Search for gravitational waves associated with gamma-ray bursts detected by Fermi and Swift during the LIGO–Virgo run O3b

We search for gravitational-wave signals associated with gamma-ray bursts (GRBs) detected by the Fermi and Swift satellites during the second half of the third observing run of Advanced LIGO and Advanced Virgo (2019 November 1 15:00 UTC–2020 March 27 17:00 UTC). We conduct two independent searches: a generic gravitational-wave transients search to analyze 86 GRBs and an analysis to target binary mergers with at least one neutron star as short GRB progenitors for 17 events. We find no significant evidence for gravitational-wave signals associated with any of these GRBs. A weighted binomial test of the combined results finds no evidence for subthreshold gravitational-wave signals associated with this GRB ensemble either. We use several source types and signal morphologies during the searches, resulting in lower bounds on the estimated distance to each GRB. Finally, we constrain the population of low-luminosity short GRBs using results from the first to the third observing runs of Advanced LIGO and Advanced Virgo. The resulting population is in accordance with the local binary neutron star merger rate

Human cytomegalovirus pUL29/28 and pUL38 repression of p53-regulated p21CIP1 and caspase 1 promoters during infection.

During infection by human cytomegalovirus (HCMV), the tumor suppressor protein p53, which promotes efficient viral gene expression, is stabilized. However, the expression of numerous p53-responsive cellular genes is not upregulated. The molecular mechanism used to manipulate the transcriptional activity of p53 during infection remains unclear. The HCMV proteins IE1, IE2, pUL44, and pUL84 likely contribute to the regulation of p53. In this study, we used a discovery-based approach to identify the protein targets of the HCMV protein pUL29/28 during infection. Previous studies have demonstrated that pUL29/28 regulates viral gene expression by interacting with the chromatin remodeling complex NuRD. Here, we observed that pUL29/28 also associates with p53, an additional deacetylase complex, and several HCMV proteins, including pUL38. We confirmed the interaction between p53 and pUL29/28 in both the presence and absence of infection. HCMV pUL29/28 with pUL38 altered the activity of the 53-regulatable p21CIP1 promoter. During infection, pUL29/28 and pUL38 contributed to the inhibition of p21CIP1 as well as caspase 1 expression. The expression of several other p53-regulating genes was not altered. Infection using a UL29-deficient virus resulted in increased p53 binding and histone H3 acetylation at the responsive promoters. Furthermore, expression of pUL29/28 and its interacting partner pUL38 contributed to an increase in the steady-state protein levels of p53. This study identified two additional HCMV proteins, pUL29/28 and pUL38, which participate in the complex regulation of p53 transcriptional activity during infection

Discovery of Host–Viral Protein Complexes During Infection

Viruses have co-evolved with their hosts, developing effective approaches for hijacking and manipulating host cellular processes. Therefore, for their efficient replication and spread, viruses depend on dynamic and temporally-regulated interactions with host proteins. The rapid identification of host proteins targeted by viral proteins during infection provides significant insights into mechanisms of viral protein function. The resulting discoveries often lead to unique and innovative hypotheses on viral protein function. Here, we describe a robust method for identifying virus-host protein interactions and protein complexes, which we have successfully utilized to characterize spatial-temporal protein interactions during infections with either DNA or RNA viruses, including human cytomegalovirus (HCMV), herpes simplex virus type 1 (HSV-1), pseudorabies virus (PRV), human immunodeficiency virus (HIV-1), Sindbis, and West Nile virus (WNV). This approach involves cryogenic cell lysis, rapid immunoaffinity purification targeting a virus or host protein, followed by identification of associated proteins using mass spectrometry. Like most proteomic approaches, this methodology has evolved over the past few years and continues to evolve. We are presenting here the updated approaches for each step, and discuss alternative strategies allowing for the protocol to be optimized for different biological systems

The herpevac trial for women: Sequence analysis of glycoproteins from viruses obtained from infected subjects

<div><p>The Herpevac Trial for Women revealed that three dose HSV-2 gD vaccine was 58% protective against culture-positive HSV-1 genital disease, but it was not protective against HSV-2 infection or disease. To determine whether vaccine-induced immune responses had selected for a particular gD sequence in strains infecting vaccine recipients compared with viruses infecting control subjects, genetic sequencing studies were carried out on viruses isolated from subjects infected with HSV-1 or HSV-2. We identified naturally occurring variants among the gD sequences obtained from 83 infected subjects. Unique or low frequency amino acid substitutions in the ectodomain of gD were found in 6 of 39 HSV-1-infected subjects and in 7 of 44 HSV-2-infected subjects. However, no consistent amino acid change was identified in isolates from gD-2 vaccine recipients compared with infected placebo recipients. gC and gE surround and partially shield gD from neutralizing antibody, and gB also participates closely in the viral entry process. Therefore, these genes were sequenced from a number of isolates to assess whether sequence variation may alter protein conformation and influence the virus strain’s capacity to be neutralized by vaccine-induced antibody. gC and gE genes sequenced from HSV-1-infected subjects showed more variability than their HSV-2 counterparts. The gB sequences of HSV-1 oral isolates resembled each other more than they did gB sequences rom genital isolates. Overall, however, comparison of glycoprotein sequences of viral isolates obtained from infected subjects did not reveal any singular selective pressure on the viral cell attachment protein or surrounding glycoproteins due to administration of gD-2 vaccine.</p></div