The advent of molecular data has transformed the science of organizing and studying life on Earth. Genetics-based evidence provides fundamental insights into the diversity, ecology, and origins of ...many biological systems, including the mutualisms between metazoan hosts and their micro-algal partners. A well-known example is the dinoflagellate endosymbionts (“zooxanthellae”) that power the growth of stony corals and coral reef ecosystems. Once assumed to encompass a single panmictic species, genetic evidence has revealed a divergent and rich diversity within the zooxanthella genus Symbiodinium. Despite decades of reporting on the significance of this diversity, the formal systematics of these eukaryotic microbes have not kept pace, and a major revision is long overdue. With the consideration of molecular, morphological, physiological, and ecological data, we propose that evolutionarily divergent Symbiodinium “clades” are equivalent to genera in the family Symbiodiniaceae, and we provide formal descriptions for seven of them. Additionally, we recalibrate the molecular clock for the group and amend the date for the earliest diversification of this family to the middle of the Mesozoic Era (∼160 mya). This timing corresponds with the adaptive radiation of analogs to modern shallow-water stony corals during the Jurassic Period and connects the rise of these symbiotic dinoflagellates with the emergence and evolutionary success of reef-building corals. This improved framework acknowledges the Symbiodiniaceae’s long evolutionary history while filling a pronounced taxonomic gap. Its adoption will facilitate scientific dialog and future research on the physiology, ecology, and evolution of these important micro-algae.
•The micro-algal genus Symbiodinium is split into multiple genera•Seven of these genera are formally described based on genetics and ecology•Dinoflagellates in the family Symbiodiniaceae originated in the Jurassic Period•Symbiodiniaceae diversification coincided with the radiation of reef-building corals
Symbiodinium are micro-algal symbionts of reef-building corals. LaJeunesse et al. report new estimates from molecular dating, indicating that corals and Symbiodinium originated and diversified together ∼140–200 mya. Divergent Symbiodinium “clades” are now partitioned into multiple genera, better reflecting their long evolutionary history.
Maintaining cognitive function is essential for healthy aging and to function autonomously within society. White matter lesions (WMLs) are associated with reduced cognitive function in older adults. ...However, whether their anatomical location moderates these associations is not well-established. This review systematically evaluates peer-reviewed evidence on the role of anatomical location in the association between WMLs and cognitive function.
In accordance with the preferred reporting items for systematic reviews and meta-analysis (PRISMA) statement, databases of EMBASE, PUBMED, MEDLINE, and CINAHL, and reference lists of selected papers were searched. We limited our search results to adults aged 60 years and older, and studies published in the English language from 2000 to 2011. Studies that investigated the association between cognitive function and WML location were included. Two independent reviewers extracted: 1) study characteristics including sample size, sample characteristic, and study design; 2) WML outcomes including WML location, WML quantification method (scoring or volume measurement), strength of the MRI magnet in Tesla, and MRI sequence used for WML detection; and 3) cognitive function outcomes including cognitive tests for two cognitive domains of memory and executive function/processing speed.
Of the 14 studies included, seven compared the association of subcortical versus periventricular WMLs with cognitive function. Seven other studies investigated the association between WMLs in specific brain regions (e.g., frontal, parietal lobes) and cognitive function. Overall, the results show that a greater number of studies have found an association between periventricular WMLs and executive function/processing speed, than subcortical WMLs. However, whether WMLs in different brain regions have a differential effect on cognitive function remains unclear.
Evidence suggests that periventricular WMLs may have a significant negative impact on cognitive abilities of older adults. This finding may be influenced by study heterogeneity in: 1) MRI sequences, WML quantification methods, and neuropsychological batteries; 2) modifying effect of cardiovascular risk factors; and 3) quality of studies and lack of sample size calculation.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Experience alters cortical networks through neural plasticity mechanisms. During a developmental critical period, the most dramatic consequence of occluding vision through one eye (monocular ...deprivation) is a rapid loss of excitatory synaptic inputs to parvalbumin-expressing (PV) inhibitory neurons in visual cortex. Subsequent cortical disinhibition by reduced PV cell activity allows for excitatory ocular dominance plasticity. However, the molecular mechanisms underlying critical period synaptic plasticity are unclear. Here we show that brief monocular deprivation during the critical period downregulates neuregulin-1(NRG1)/ErbB4 signaling in PV neurons, causing retraction of excitatory inputs to PV neurons. Exogenous NRG1 rapidly restores excitatory inputs onto deprived PV cells through downstream PKC-dependent activation and AMPA receptor exocytosis, thus enhancing PV neuronal inhibition to excitatory neurons. NRG1 treatment prevents the loss of deprived eye visual cortical responsiveness in vivo. Our findings reveal molecular, cellular, and circuit mechanisms of NRG1/ErbB4 in regulating the initiation of critical period visual cortical plasticity.
•NRG1/ErbB4 signaling shows developmental and experience-dependent regulation•NRG1 restores excitation to deprived PV neurons to enhance cortical inhibition•NRG1/ErbB4 signaling in PV neurons is coupled to AMPA receptor response modulation•NRG1 treatment suppresses critical period ocular dominance plasticity in vivo
Sun et al. finds that NRG1/ErbB4 signaling regulates the initiation of critical period visual cortical plasticity by rapidly controlling excitatory synaptic inputs onto PV neurons and thus PV-cell-mediated cortical inhibition in response to visual deprivation.
The segmented structure of the influenza virus genome plays a pivotal role in its adaptation to new hosts and the emergence of pandemics. Despite concerns about the pandemic threat posed by highly ...pathogenic avian influenza H5N1 viruses, little is known about the biological properties of H5N1 viruses that may emerge following reassortment with contemporary human influenza viruses. In this study, we used reverse genetics to generate the 63 possible virus reassortants derived from H5N1 and H3N2 viruses, containing the H5N1 surface protein genes, and analyzed their viability, replication efficiency, and mouse virulence. Specific constellations of avian-human viral genes proved deleterious for viral replication in cell culture, possibly due to disruption of molecular interaction networks. In particular, striking phenotypes were noted with heterologous polymerase subunits, as well as NP and M, or NS. However, nearly one-half of the reassortants replicated with high efficiency in vitro, revealing a high degree of compatibility between avian and human virus genes. Thirteen reassortants displayed virulent phenotypes in mice and may pose the greatest threat for mammalian hosts. Interestingly, one of the most pathogenic reassortants contained avian PB1, resembling the 1957 and 1968 pandemic viruses. Our results reveal the broad spectrum of phenotypes associated with H5N1/H3N2 reassortment and a possible role for the avian PB1 in the emergence of pandemic influenza. These observations have important implications for risk assessment of H5N1 reassortant viruses detected in surveillance programs.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The H1 subtype of influenza A viruses (IAVs) has been circulating in swine since the 1918 human influenza pandemic. Over time, and aided by further introductions from nonswine hosts, swine H1 viruses ...have diversified into three genetic lineages. Due to limited global data, these H1 lineages were named based on colloquial context, leading to a proliferation of inconsistent regional naming conventions. In this study, we propose rigorous phylogenetic criteria to establish a globally consistent nomenclature of swine H1 virus hemagglutinin (HA) evolution. These criteria applied to a data set of 7,070 H1 HA sequences led to 28 distinct clades as the basis for the nomenclature. We developed and implemented a web-accessible annotation tool that can assign these biologically informative categories to new sequence data. The annotation tool assigned the combined data set of 7,070 H1 sequences to the correct clade more than 99% of the time. Our analyses indicated that 87% of the swine H1 viruses from 2010 to the present had HAs that belonged to 7 contemporary cocirculating clades. Our nomenclature and web-accessible classification tool provide an accurate method for researchers, diagnosticians, and health officials to assign clade designations to HA sequences. The tool can be updated readily to track evolving nomenclature as new clades emerge, ensuring continued relevance. A common global nomenclature facilitates comparisons of IAVs infecting humans and pigs, within and between regions, and can provide insight into the diversity of swine H1 influenza virus and its impact on vaccine strain selection, diagnostic reagents, and test performance, thereby simplifying communication of such data.
A fundamental goal in the biological sciences is the definition of groups of organisms based on evolutionary history and the naming of those groups. For influenza A viruses (IAVs) in swine, understanding the hemagglutinin (HA) genetic lineage of a circulating strain aids in vaccine antigen selection and allows for inferences about vaccine efficacy. Previous reporting of H1 virus HA in swine relied on colloquial names, frequently with incriminating and stigmatizing geographic toponyms, making comparisons between studies challenging. To overcome this, we developed an adaptable nomenclature using measurable criteria for historical and contemporary evolutionary patterns of H1 global swine IAVs. We also developed a web-accessible tool that classifies viruses according to this nomenclature. This classification system will aid agricultural production and pandemic preparedness through the identification of important changes in swine IAVs and provides terminology enabling discussion of swine IAVs in a common context among animal and human health initiatives.
In 2016, a total of 18 human infections with influenza A(H3N2) virus occurred after exposure to influenza-infected swine at 7 agricultural fairs. Sixteen of these cases were the result of infection ...by a reassorted virus with increasing prevalence among US swine containing a hemagglutinin gene from 2010-11 human seasonal H3N2 strains.
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DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Low-pathogenicity avian influenza A(H9N2) viruses, enzootic in poultry populations in Asia, are associated with fewer confirmed human infections but higher rates of seropositivity compared to A(H5) ...or A(H7) subtype viruses. Cocirculation of A(H5) and A(H7) viruses leads to the generation of reassortant viruses bearing A(H9N2) internal genes with markers of mammalian adaptation, warranting continued surveillance in both avian and human populations. Here, we describe active surveillance efforts in live poultry markets in Vietnam in 2018 and compare representative viruses to G1 and Y280 lineage viruses that have infected humans. Receptor binding properties, pH thresholds for HA activation,
replication in human respiratory tract cells, and
mammalian pathogenicity and transmissibility were investigated. While A(H9N2) viruses from both poultry and humans exhibited features associated with mammalian adaptation, one human isolate from 2018, A/Anhui-Lujiang/39/2018, exhibited increased capacity for replication and transmission, demonstrating the pandemic potential of A(H9N2) viruses.
A(H9N2) influenza viruses are widespread in poultry in many parts of the world and for over 20 years have sporadically jumped species barriers to cause human infection. As these viruses continue to diversify genetically and antigenically, it is critical to closely monitor viruses responsible for human infections, to ascertain if A(H9N2) viruses are acquiring properties that make them better suited to infect and spread among humans. In this study, we describe an active poultry surveillance system established in Vietnam to identify the scope of influenza viruses present in live bird markets and the threat they pose to human health. Assessment of a recent A(H9N2) virus isolated from an individual in China in 2018 is also reported, and it was found to exhibit properties of adaptation to humans and, importantly, it shows similarities to strains isolated from the live bird markets of Vietnam.
Pimodivir exerts an antiviral effect on the early stages of influenza A virus replication by inhibiting the cap-binding function of polymerase basic protein 2 (PB2). In this study, we used a ...combination of sequence analysis and phenotypic methods to evaluate pimodivir susceptibility of influenza A viruses collected from humans and other hosts. Screening PB2 sequences for substitutions previously associated with reduced pimodivir susceptibility revealed a very low frequency among seasonal viruses circulating in the U.S. during 2015–2020 (<0.03%; 3/11,934) and among non-seasonal viruses collected in various countries during the same period (0.2%; 18/8971). Pimodivir potently inhibited virus replication in two assays, a single-cycle HINT and a multi-cycle FRA, with IC50 values in a nanomolar range. Median IC50 values determined by HINT were similar for both subtypes of seasonal viruses, A(H1N1)pdm09 and A(H3N2), across three seasons. Human seasonal viruses with PB2 substitutions S324C, S324R, or N510K displayed a 27-317-fold reduced pimodivir susceptibility by HINT. In addition, pimodivir was effective at inhibiting replication of a diverse group of animal-origin viruses that have pandemic potential, including avian viruses of A(H5N6) and A(H7N9) subtypes. A rare PB2 substitution H357N was identified in an A(H4N2) subtype poultry virus that displayed >100-fold reduced pimodivir susceptibility. Our findings demonstrate a broad inhibitory activity of pimodivir and expand the existing knowledge of amino acid substitutions that can reduce susceptibility to this investigational antiviral.
•PB2 sequence analysis and phenotypic assays were used to assess pimodivir susceptibility of influenza A viruses.•Naturally occurring resistance to pimodivir is low in seasonal and non-seasonal influenza A viruses.•Pimodivir potently inhibited replication of widely diverse viruses in a single-cycle HINT or a multi-cycle FRA assays.•Pimodivir was effective against pandemic potential avian A(H5N6) and A(H7N9) viruses.•A rare substitution PB2–H357N conferring >100-fold reduced drug susceptibility was identified in an A(H4N2) poultry virus.
Full-genome analysis was conducted on the first isolate of a highly pathogenic avian influenza A(H5N1) virus from a human in North America. The virus has a hemagglutinin gene of clade 2.3.2.1c and is ...a reassortant with an H9N2 subtype lineage polymerase basic 2 gene. No mutations conferring resistance to adamantanes or neuraminidase inhibitors were found.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The COVID-19 pandemic and subsequent implementation of nonpharmaceutical interventions (e.g., cessation of global travel, mask use, physical distancing, and staying home) reduced transmission of some ...viral respiratory pathogens (1). In the United States, influenza activity decreased in March 2020, was historically low through the summer of 2020 (2), and remained low during October 2020-May 2021 (<0.4% of respiratory specimens with positive test results for each week of the season). Circulation of other respiratory pathogens, including respiratory syncytial virus (RSV), common human coronaviruses (HCoVs) types OC43, NL63, 229E, and HKU1, and parainfluenza viruses (PIVs) types 1-4 also decreased in early 2020 and did not increase until spring 2021. Human metapneumovirus (HMPV) circulation decreased in March 2020 and remained low through May 2021. Respiratory adenovirus (RAdV) circulated at lower levels throughout 2020 and as of early May 2021. Rhinovirus and enterovirus (RV/EV) circulation decreased in March 2020, remained low until May 2020, and then increased to near prepandemic seasonal levels. Circulation of respiratory viruses could resume at prepandemic levels after COVID-19 mitigation practices become less stringent. Clinicians should be aware of increases in some respiratory virus activity and remain vigilant for off-season increases. In addition to the use of everyday preventive actions, fall influenza vaccination campaigns are an important component of prevention as COVID-19 mitigation measures are relaxed and schools and workplaces resume in-person activities.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, ODKLJ, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
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