Biology subjects

Beatty, J. A.

Publications and source records attributed to Beatty, J. A..

5 recordsLinked to original sources

bioRxiv2025

The hemagglutinin proteins of clades 1 and 2.3.4.4b H5N1 highly pathogenic avian influenza viruses exhibit comparable attachment patterns to avian and mammalian tissues

The global spread of the A/goose/Guangdong/1/96-lineage H5N1 highly pathogenic avian influenza (HPAI) viruses is accompanied by an expanded host range and the establishment of sustained viral transmission among dairy cattle. To evaluate if the evolving H5N1 viruses have changed tissue tropism over time, we compared the binding patterns of recombinant hemagglutinin (HA) proteins derived from clade 1 (A/Vietnam/1203/04, H5VN) and circulating clade 2.3.4.4b viruses detected from a wild bird (A/Eurasian Teal/Hong Kong/AFCD-HKU-23- 14009-01020/2023, H5HK) and dairy cattle (A/bovine/Ohio/B24OSU-439/2024, H5OH). The HA protein of A(H1N1)pdm09 virus was included for comparison. Using bio-layer interferometry, H1 protein preferentially bound to the 2,6-linked sialoside 6SLNLN while H5 proteins preferentially bound to the 2,3-linked sialoside 3SLN. H5OH showed higher binding affinity to 3SLN than H5HK and H5VN. The attachment pattern of H1 and H5 proteins to the respiratory tissues of different species and dairy cattle mammary glands were evaluated. Compared to the H1 protein, H5 proteins showed stronger binding to the lung epithelial cells of cat, cattle, chicken, ferret, human, and pig, and the clade 2.3.4.4b H5 proteins exhibited increased binding to pig and cattle bronchial epithelial cells. All H5 proteins attached to the alveolar and cistern epithelial cells in mammary glands where 2,3-linked and 2,6-linked sialyl glycans were detected by Maackia amurensis lectin II and Sambucus Nigra Lectin, respectively. Taken together, the HA proteins of clade 1 and 2.3.4.4b H5N1 viruses generally share comparable attachment patterns to avian and mammalian tissues, despite of evolving into antigenically distinct clades over the past 3 decades. IMPORTANCEThe outbreaks of H5N1 HPAI among US dairy cattle since 2024 have raised concerns of the potential changes in HA receptor binding specificity and tissue tropism. Using insect-cell expressed recombinant HA proteins derived from clade 1 and circulating clade 2.3.4.4b H5N1 viruses, we showed that the dairy cattle H5 protein retained binding specificity for the avian-like 2,3-linked sialoside 3SLN over the human-like 2,6-linked sialoside 6SLNLN, with higher binding affinity to 3SLN than the other H5 proteins. Clade 1 and 2.3.4.4b H5 proteins showed comparable attachment patterns to the mammary tissues of lactating dairy cattle, which showed high expression of 2,3-linked and 2,6-linked sialyl glycans. All H5 proteins also showed comparable attachment patterns to the lungs of cat, cattle, chicken, ferret, human, and pig. Our results suggest that the recent H5N1 outbreaks in dairy cattle may be related to ecological factors rather than changes in HA receptor binding specificity.

microbiology↗

bioRxiv2024

Meta-transcriptomic analysis of companion animal infectomes reveals their diversity and potential roles in animal and human disease

Companion animals such as cats and dogs harbor diverse microbial communities that can potentially impact human health due to close and frequent contact. To better characterize their total infectomes and assess zoonotic risks, we performed meta-transcriptomic profiling on 239 samples from cats and dogs collected across China, comparing the similarities and differences between animal species (cats or dogs), sampling sites (rectal or oropharyngeal), and health status (healthy or diseased). We identified 24 viral species, 270 bacterial genera, and two fungal genera, including many known pathogens such as canine parvovirus, Clostridium difficile, and Candida albicans, as well as opportunistic pathogens such as canine vesivirus. Microbial compositions differed mainly according to sampling site (i.e., rectal and oropharyngeal swabs), and less so between host species and health status. Notably, we detected 27 potential zoonotic pathogens, such as alphacoronavirus 1, among all sampling sites, hosts, and health status, underscoring substantial zoonotic risks requiring surveillance. Overall, our meta-transcriptomic analysis reveals a landscape of actively transcribing microorganisms in major companion animals, including key pathogens, those with the potential for cross-species transmission, and possible zoonotic threats.

microbiology↗

bioRxiv2022

Heterogeneity of burst firing in mouse thalamic reticular nucleus neurons

The thalamic reticular nucleus (TRN) sits at the interface of the thalamus and neocortex and provides the majority of inhibition to thalamic relay nuclei. Functionally, the activity of TRN neurons can impact sensory processing and may influence arousal states. TRN neurons discharge action potentials in two distinct output modes: tonic or burst firing. Burst output, a transient high frequency discharge of action potentials, is dependent on the activation of transient low-threshold voltage-dependent T-type calcium current (IT). In our current study, we identify a broad range of burst firing frequencies in TRN neurons, which depend on the activation of IT. The amplitude of the low-threshold calcium spike (LTS) underlying the burst positively correlated with burst frequency and number of action potentials per burst. Activation of small conductance calcium-activated potassium (SK) channels on TRN neurons can impact burst discharge. Attenuation of SK channels increased TRN neuron burst frequency through an increase in LTS duration, but not magnitude. The broad range of burst firing frequencies could provide distinct downstream inhibition within thalamic nuclei.

neuroscience↗

bioRxiv2022

Structural and functional changes of pyramidal neurons at the site of an implanted microelectrode array in rat primary motor cortex

Devices capable of recording or stimulating neuronal signals have created new opportunities to understand normal physiology and treat sources of pathology in the brain. However, it is possible that the initial surgical insertion and subsequent tissue response to implanted electrodes may influence the nature of the signals detected or stimulated. In this study, we characterized structural and functional changes in pyramidal neurons surrounding silicon or polyimide-based electrodes implanted in the motor cortex of rats. Devices were captured in 300 m-thick tissue slices collected at the 1 or 6 week time point post-implantation, and individual neurons were assessed using a combination of whole-cell electrophysiology and 2-photon imaging. We observed disruption of the dendritic arbor of neurons near (<100 m) the device surface at both time points, as well as a significant reduction in spine densities. These effects were accompanied by a decrease in the frequency of spontaneous excitatory post-synaptic currents (sEPSCs), a loss in sag amplitude, and an increase in spike frequency adaptation at the 6 week time point. Interestingly, we also noted a significant increase in filopodial density in neurons surrounding devices. Results were similar for polyimide and silicon-based electrodes. We hypothesize that the effects observed in this study may contribute to the signal loss and instability that often accompany chronically implanted electrodes.

bioengineering↗

bioRxiv2022

Faecal virome of the Australian grey-headed flying fox from urban/suburban environments contains novel coronaviruses, retroviruses and sapoviruses

Bats are important reservoirs for viruses of public health and veterinary concern. Virus studies in Australian bats usually target the families Paramyxoviridae, Coronaviridae and Rhabdoviridae, with little known about their overall virome composition. We used metatranscriptomic sequencing to characterise the faecal virome of grey-headed flying foxes from three colonies in urban/suburban locations from two Australian states. We identified viruses from three mammalian-infecting (Coronaviridae, Caliciviridae, Retroviridae) and one possible mammalian-infecting (Birnaviridae) family. Of particular interest were a novel bat betacoronavirus (subgenus Nobecovirus) and a novel bat sapovirus (Caliciviridae), the first identified in Australian bats, as well as a potentially exogenous retrovirus. The novel betacoronavirus was detected in two sampling locations 1,375 km apart and falls in a viral lineage likely with a long association with bats. This study highlights the utility of unbiased sequencing of faecal samples for identifying novel viruses and revealing broad-scale patterns of virus ecology and evolution.

microbiology↗