A Role for Strain Differences in Waveforms of Ultrasonic Vocalizations during Male–Female Interaction

Male mice emit ultrasonic vocalizations (USVs) towards females during male–female interaction. It has been reported that USVs of adult male mice have the capability of attracting females. Although the waveform pattern of USVs is affected by genetic background, differences among strains with respect to USV and the effects of these differences on courtship behavior have not been analyzed fully. We analyzed USV patterns, as well as actual social behavior during USV recording, in 13 inbred mouse strains, which included laboratory and wild-derived strains. Significant effects of strain were observed for the frequency of USV emission, duration, and frequency of the waveform category. Principal component (PC) analysis showed that PC1 was related to frequency and duration, and PC2–4 were related to each waveform. In the comparison of USV patterns and behaviors among strains, wild-derived KJR mice displayed the highest scores for PC2–4, and female mice paired with KJR males did not emit rejection-related click sounds. It is assumed that the waveforms emitted by KJR males have a positive effect in male–female interaction. Therefore, we extracted waveforms in PC2–4 from the USV recordings of KJR mice to produce a sound file, "HIGH2-4". As a negative control, another sound file ("LOW2-4") was created by extracting waveforms in PC2-4 from strains with low scores for these components. In the playback experiments using these sound files, female mice were attracted to the speaker that played HIGH2-4 but not the speaker that played LOW2-4. These results highlight the role of strain differences in the waveforms of male USVs during male–female interaction. The results indicated that female mice use male USVs as information when selecting a suitable mate

Multiple mechanisms mediating carbon monoxide inhibition of the voltage-gated K+ channel Kv1.5

The voltage-gated K+ channel plays key roles in the vasculature and in atrial excitability, and contributes to apoptosis in various tissues. In this study, we have explored its regulation by carbon monoxide (CO), a product of the cytoprotective heme oxygenase enzymes, and a recognized toxin. CO inhibited recombinant Kv1.5 expressed in HEK293 cells in a concentration-dependent manner which involved multiple signalling pathways. CO inhibition was partially reversed by superoxide dismutase mimetics, and by suppression of mitochondrial reactive oxygen species. CO also elevated intracellular nitric oxide (NO) levels. Prevention of NO formation also partially reversed CO inhibition of Kv1.5, as did inhibition of soluble guanylyl cyclase. CO also elevated intracellular peroxynitrite levels, and a peroxynitrite scavenger markedly attenuated the ability of CO to inhibit Kv1.5. CO caused nitrosylation of Kv1.5, an effect which was also observed in C331A and C346A mutant forms of the channel, which had previously been suggested as nitrosylation sites within Kv1.5. Augmentation of Kv1.5 via exposure to hydrogen peroxide was fully reversed by CO. Native Kv1.5 recorded in HL-1 murine atrial cells was also inhibited by CO. Action potentials recorded in HL-1 cells were increased in amplitude and duration by CO, an effect mimicked and occluded by pharmacological inhibition of Kv1.5. Our data indicate that Kv1.5 is a target for modulation by CO via multiple mechanisms. This regulation has important implications for diverse cellular functions, including excitability, contractility and apoptosis

Patterns of Chemical Diversity in the Mediterranean Sponge Spongia lamella

The intra-specific diversity in secondary metabolites can provide crucial information for understanding species ecology and evolution but has received limited attention in marine chemical ecology. The complex nature of diversity is partially responsible for the lack of studies, which often target a narrow number of major compounds. Here, we investigated the intra-specific chemical diversity of the Mediterranean sponge Spongia lamella. The chemical profiles of seven populations spreading over 1200 km in the Western Mediterranean were obtained by a straightforward SPE-HPLC-DAD-ELSD process whereas the identity of compounds was assessed by comparison between HPLC-MS spectra and literature data. Chemical diversity calculated by richness and Shannon indexes differed significantly between sponge populations but not at a larger regional scale. We used factor analysis, analysis of variance, and regression analysis to examine the chemical variability of this sponge at local and regional scales, to establish general patterns of variation in chemical diversity. The abundance of some metabolites varied significantly between sponge populations. Despite these significant differences between populations, we found a clear pattern of increasing chemical dissimilarity with increasing geographic distance. Additional large spatial scale studies on the chemical diversity of marine organisms will validate the universality or exclusivity of this pattern

Age-Related Impairment of Ultrasonic Vocalization in Tau.P301L Mice: Possible Implication for Progressive Language Disorders

Tauopathies, including Alzheimer's Disease, are the most frequent neurodegenerative diseases in elderly people and cause various cognitive, behavioural and motor defects, but also progressive language disorders. For communication and social interactions, mice produce ultrasonic vocalization (USV) via expiratory airflow through the larynx. We examined USV of Tau.P301L mice, a mouse model for tauopathy expressing human mutant tau protein and developing cognitive, motor and upper airway defects.At age 4-5 months, Tau.P301L mice had normal USV, normal expiratory airflow and no brainstem tauopathy. At age 8-10 months, Tau.P301L mice presented impaired USV, reduced expiratory airflow and severe tauopathy in the periaqueductal gray, Kolliker-Fuse and retroambiguus nuclei. Tauopathy in these nuclei that control upper airway function and vocalization correlates well with the USV impairment of old Tau.P301L mice.In a mouse model for tauopathy, we report for the first time an age-related impairment of USV that correlates with tauopathy in midbrain and brainstem areas controlling vocalization. The vocalization disorder of old Tau.P301L mice could be, at least in part, reminiscent of language disorders of elderly suffering tauopathy

Recurrent SARS-CoV-2 mutations in immunodeficient patients

Long-term severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in immunodeficient patients are an important source of variation for the virus but are understudied. Many case studies have been published which describe one or a small number of long-term infected individuals but no study has combined these sequences into a cohesive dataset. This work aims to rectify this and study the genomics of this patient group through a combination of literature searches as well as identifying new case series directly from the COVID-19 Genomics UK (COG-UK) dataset. The spike gene receptor-binding domain and N-terminal domain (NTD) were identified as mutation hotspots. Numerous mutations associated with variants of concern were observed to emerge recurrently. Additionally a mutation in the envelope gene, T30I was determined to be the second most frequent recurrently occurring mutation arising in persistent infections. A high proportion of recurrent mutations in immunodeficient individuals are associated with ACE2 affinity, immune escape, or viral packaging optimisation.There is an apparent selective pressure for mutations that aid cell–cell transmission within the host or persistence which are often different from mutations that aid inter-host transmission, although the fact that multiple recurrent de novo mutations are considered defining for variants of concern strongly indicates that this potential source of novel variants should not be discounted

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

Lawson criterion for ignition exceeded in an inertial fusion experiment

For more than half a century, researchers around the world have been engaged in attempts to achieve fusion ignition as a proof of principle of various fusion concepts. Following the Lawson criterion, an ignited plasma is one where the fusion heating power is high enough to overcome all the physical processes that cool the fusion plasma, creating a positive thermodynamic feedback loop with rapidly increasing temperature. In inertially confined fusion, ignition is a state where the fusion plasma can begin "burn propagation" into surrounding cold fuel, enabling the possibility of high energy gain. While "scientific breakeven" (i.e., unity target gain) has not yet been achieved (here target gain is 0.72, 1.37 MJ of fusion for 1.92 MJ of laser energy), this Letter reports the first controlled fusion experiment, using laser indirect drive, on the National Ignition Facility to produce capsule gain (here 5.8) and reach ignition by nine different formulations of the Lawson criterion

Observation of Two New Excited Ξb0 States Decaying to Λb0 K-π+

Two narrow resonant states are observed in the Λb0K-π+ mass spectrum using a data sample of proton-proton collisions at a center-of-mass energy of 13 TeV, collected by the LHCb experiment and corresponding to an integrated luminosity of 6 fb-1. The minimal quark content of the Λb0K-π+ system indicates that these are excited Ξb0 baryons. The masses of the Ξb(6327)0 and Ξb(6333)0 states are m[Ξb(6327)0]=6327.28-0.21+0.23±0.12±0.24 and m[Ξb(6333)0]=6332.69-0.18+0.17±0.03±0.22 MeV, respectively, with a mass splitting of Δm=5.41-0.27+0.26±0.12 MeV, where the uncertainties are statistical, systematic, and due to the Λb0 mass measurement. The measured natural widths of these states are consistent with zero, with upper limits of Γ[Ξb(6327)0]<2.20(2.56) and Γ[Ξb(6333)0]<1.60(1.92) MeV at a 90% (95%) credibility level. The significance of the two-peak hypothesis is larger than nine (five) Gaussian standard deviations compared to the no-peak (one-peak) hypothesis. The masses, widths, and resonant structure of the new states are in good agreement with the expectations for a doublet of 1D Ξb0 resonances

The impact of viral mutations on recognition by SARS-CoV-2 specific T cells.

We identify amino acid variants within dominant SARS-CoV-2 T cell epitopes by interrogating global sequence data. Several variants within nucleocapsid and ORF3a epitopes have arisen independently in multiple lineages and result in loss of recognition by epitope-specific T cells assessed by IFN-γ and cytotoxic killing assays. Complete loss of T cell responsiveness was seen due to Q213K in the A∗01:01-restricted CD8+ ORF3a epitope FTSDYYQLY207-215; due to P13L, P13S, and P13T in the B∗27:05-restricted CD8+ nucleocapsid epitope QRNAPRITF9-17; and due to T362I and P365S in the A∗03:01/A∗11:01-restricted CD8+ nucleocapsid epitope KTFPPTEPK361-369. CD8+ T cell lines unable to recognize variant epitopes have diverse T cell receptor repertoires. These data demonstrate the potential for T cell evasion and highlight the need for ongoing surveillance for variants capable of escaping T cell as well as humoral immunity.This work is supported by the UK Medical Research Council (MRC); Chinese Academy of Medical Sciences(CAMS) Innovation Fund for Medical Sciences (CIFMS), China; National Institute for Health Research (NIHR)Oxford Biomedical Research Centre, and UK Researchand Innovation (UKRI)/NIHR through the UK Coro-navirus Immunology Consortium (UK-CIC). Sequencing of SARS-CoV-2 samples and collation of data wasundertaken by the COG-UK CONSORTIUM. COG-UK is supported by funding from the Medical ResearchCouncil (MRC) part of UK Research & Innovation (UKRI),the National Institute of Health Research (NIHR),and Genome Research Limited, operating as the Wellcome Sanger Institute. T.I.d.S. is supported by a Well-come Trust Intermediate Clinical Fellowship (110058/Z/15/Z). L.T. is supported by the Wellcome Trust(grant number 205228/Z/16/Z) and by theUniversity of Liverpool Centre for Excellence in Infectious DiseaseResearch (CEIDR). S.D. is funded by an NIHR GlobalResearch Professorship (NIHR300791). L.T. and S.C.M.are also supported by the U.S. Food and Drug Administration Medical Countermeasures Initiative contract75F40120C00085 and the National Institute for Health Research Health Protection Research Unit (HPRU) inEmerging and Zoonotic Infections (NIHR200907) at University of Liverpool inpartnership with Public HealthEngland (PHE), in collaboration with Liverpool School of Tropical Medicine and the University of Oxford.L.T. is based at the University of Liverpool. M.D.P. is funded by the NIHR Sheffield Biomedical ResearchCentre (BRC – IS-BRC-1215-20017). ISARIC4C is supported by the MRC (grant no MC_PC_19059). J.C.K.is a Wellcome Investigator (WT204969/Z/16/Z) and supported by NIHR Oxford Biomedical Research Centreand CIFMS. The views expressed are those of the authors and not necessarily those of the NIHR or MRC