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Ant nest beetles (Paussus L.) are ecologically fascinating and phenotypically bizarre. Obligate myrmecophiles, Paussus have undergone extreme adaptations for life with ants and their profound range ...of phenotypic diversity has been difficult to reconcile in a systematic framework. We conducted a detailed morphological study of Paussus utilizing novel techniques and character systems in order to discover anatomical apomorphies diagnostic of the major clades of Paussus strongly supported by molecular data. Bayesian inference (BI) of molecules alone, morphology alone and varying combinations of the two data types reveal that morphology is informative for placing Paussus species, despite the extreme phenotypic diversity and convergence prevalent in the group. We propose a new classification for Paussus based on this phylogeny. The genus Paussus is revised to include all genera, subgenera and species formerly classified as Paussus by Nagel (2003) in addition to Hylopaussus syn.n., Hylotorus syn.n. and Granulopaussus syn.n. The following species are transferred to Paussus: Paussus sebakuanus (Péringuey) comb.n., Paussus gracilis (Reichensperger) comb.n., Paussus bucephalus Gyllenhal, Paussus caroli (Reichensperger) comb.n., Paussus uelensis (Reichensperger) comb.n., Paussus hottentottus (Westwood) comb.n., Paussus blanchardi (Raffray) comb.n., Paussus basilewskyi (Luna de Carvalho) comb.n., Paussus granulatus Westwood, Paussus sankuruensis Reichensperger, Paussus leleupi (Reichensperger) comb.n., Paussus reichenspergeri (Luna de Carvalho) comb.n. We formally delineate and diagnose the following major subgroups of Paussus: Paussus I series, comprising the subgenera Bohemanipaussus Luna de Carvalho stat. rev. sensu n., Bathypaussus Wasmann stat. rev. sensu n., and Edaphopaussus Kolbe stat. rev. sensu n.; the Paussus II series comprising the subgenera Paussus L. stat. rev. sensu n., Klugipaussus Kolbe stat. rev. sensu n., Scaphipaussus Fowler stat. rev. sensu n., Hylotorus Dalman stat.n. sensu n., and Anapaussus Wasmann stat. rev. sensu n.; and the Paussus III series comprising the subgenera Lineatopaussus Kolbe stat. rev. sensu n. and Shuckardipaussus Kolbe stat. rev. sensu n.
Here we present a phylogeny of beetles (Insecta: Coleoptera) based on DNA sequence data from eight nuclear genes, including six single‐copy nuclear protein‐coding genes, for 367 species representing ...172 of 183 extant families. Our results refine existing knowledge of relationships among major groups of beetles. Strepsiptera was confirmed as sister to Coleoptera and each of the suborders of Coleoptera was recovered as monophyletic. Interrelationships among the suborders, namely Polyphaga (Adephaga (Archostemata, Myxophaga)), in our study differ from previous studies. Adephaga comprised two clades corresponding to Hydradephaga and Geadephaga. The series and superfamilies of Polyphaga were mostly monophyletic. The traditional Cucujoidea were recovered in three distantly related clades. Lymexyloidea was recovered within Tenebrionoidea. Several of the series and superfamilies of Polyphaga received moderate to maximal clade support in most analyses, for example Buprestoidea, Chrysomeloidea, Coccinelloidea, Cucujiformia, Curculionoidea, Dascilloidea, Elateroidea, Histeroidea and Hydrophiloidea. However, many of the relationships within Polyphaga lacked compatible resolution under maximum‐likelihood and Bayesian inference, and/or lacked consistently strong nodal support. Overall, we recovered slightly younger estimated divergence times than previous studies for most groups of beetles. The ordinal split between Coleoptera and Strepsiptera was estimated to have occurred in the Early Permian. Crown Coleoptera appeared in the Late Permian, and only one or two lineages survived the end‐Permian mass extinction, with stem group representatives of all four suborders appearing by the end of the Triassic. The basal split in Polyphaga was estimated to have occurred in the Triassic, with the stem groups of most series and superfamilies originating during the Triassic or Jurassic. Most extant families of beetles were estimated to have Cretaceous origins. Overall, Coleoptera experienced an increase in diversification rate compared to the rest of Neuropteroidea. Furthermore, 10 family‐level clades, all in suborder Polyphaga, were identified as having experienced significant increases in diversification rate. These include most beetle species with phytophagous habits, but also several groups not typically or primarily associated with plants. Most of these groups originated in the Cretaceous, which is also when a majority of the most species‐rich beetle families first appeared. An additional 12 clades showed evidence for significant decreases in diversification rate. These clades are species‐poor in the Modern fauna, but collectively exhibit diverse trophic habits. The apparent success of beetles, as measured by species numbers, may result from their associations with widespread and diverse substrates – especially plants, but also including fungi, wood and leaf litter – but what facilitated these associations in the first place or has allowed these associations to flourish likely varies within and between lineages. Our results provide a uniquely well‐resolved temporal and phylogenetic framework for studying patterns of innovation and diversification in Coleoptera, and a foundation for further sampling and resolution of the beetle tree of life.
Although lignin has been negatively correlated with neutral-detergent fibre (NDF) digestibility (NDFD) in ruminants and used to predict potential extent of NDF digestion of forages, selection of an ...analysis, Klason lignin (KL) or acid-detergent lignin (ADL), to describe that the nutritionally relevant lignin has not been resolved. Dismissed as an artifact is the difference between KL and ADL (ΔL). A question is whether ΔL influences NDFD. We evaluated the relationships of ΔL, KL and ADL with NDFD in order to determine the nutritionally homogeneous or heterogeneous nature of KL. Data sets from two laboratories (DS1 and DS2) were used that included ADL, KL and in vitro NDFD at 48 h (NDFD48). DS1 contained seven C3 grasses, seventeen C4 maize forages and nineteen alfalfas, and DS2 had fifteen C3 grasses, eight C4 forages and six alfalfas. Mean ΔL was greater than ADL in C3 and C4 samples and less in alfalfas. Within forage type and laboratory, ΔL was not correlated with NDFD48 (r -0·34-0·49; all P > 0·17). ADL was more consistently correlated with NDFD48 (r -0·47--0·95; P < 0·01-0·21) than with KL (r 0·03--0·91; P < 0·01-0·94). ΔL as a proportion of KL was correlated with NDFD48 in C3 and C4 samples (r 0·44-0·76; P < 0·01-0·08). The differing behaviours of ΔL and ADL relative to NDFD48 indicate that KL is a nutritionally heterogeneous fraction, the behaviour of which may vary by forage type and ratios of ADL and ΔL present.
The aim of this study was to assess the transmission of the ultraviolet (UV) radiation (200–400 nm) through intact enucleated globes of different species (dogs, cats, pigs, rabbits, horses, and ...humans) using spectrophotometry. Globes of cats (n = 6), dogs (n = 18), pigs (n = 10), rabbits (n = 6), horses (n = 10), and humans (n = 4) were analyzed. A 5–10 mm circular area of sclera and choroid from the posterior aspect of the globe was removed under a surgical microscope, leaving the retina intact in all species except the horse. Glass coverslips were added in horses and rabbits due to retinal and globe fragility. The %T of wavelengths from 200 to 800 nm were measured through the ocular media (cornea, aqueous humor, lens, and vitreous humor) and retina, and compared between species. The globes of cats and dogs allowed the most amount of UV radiation transmission, while those of pigs and humans allowed the least amount of UV radiation transmission. A small amount of UV radiation transmission through the ocular media was detected in the rabbit and horse. Results from this study will support further vision research that may be used to train companion, working, and service animals.
•Dogs and cats transmit the most UV radiation through the ocular media.•Pigs and humans allowed the least amount of UV radiation transmission through the ocular media.•Dogs with nuclear sclerosis transmitted significantly less UV radiation.
Enzymes catalyze multistep chemical reactions and achieve phenomenal rate accelerations by matching protein and substrate chemical groups in the transition state. Inhibitors that take advantage of ...these chemical interactions are among the most potent and effective drugs known. Recently, three new enzyme targets have been validated by FDA approval of new enzyme inhibitor drugs. These include mitogen-activated protein kinase, renin, and dipeptidyl peptidase IV. The drugs against these enzymes engage important enzyme functional groups, such as the active site serine in dipeptidyl peptidase IV. Clinical and pre-clinical discovery programs also demonstrate the same theme, as evidenced by pM and fM transition state inhibitors of purine nucleoside phosphorylase, methylthioadenosine phosphorylase, and 5-methylthioadenosine/
S-adenosylhomocysteine nucleosidase, and covalent substrate trapping in leu-tRNA synthetase. The catalytic chemistry of enzymes is the key to designing potent inhibitors and makes them a special class of drug target.
Replication-deficient adenoviral vectors have been under investigation as a platform technology for vaccine development for several years and have recently been successfully deployed as an effective ...COVID-19 counter measure. A replication-deficient adenoviral vector based on the simian adenovirus type Y25 and named ChAdOx1 has been evaluated in several clinical trials since 2012.
The Brighton Collaboration Benefit-Risk Assessment of VAccines by TechnolOgy (BRAVATO) was formed to evaluate the safety and other key features of new platform technology vaccines. This manuscript reviews key features of the ChAdOx1-vectored vaccines.
The simian adenovirus Y25 was chosen as a strategy to circumvent pre-existing immunity to common human adenovirus serotypes which could impair immune responses induced by adenoviral vectored vaccines. Deletion of the E1 gene renders the ChAdOx1 vector replication incompetent and further genetic engineering of the E3 and E4 genes allows for increased insertional capability and optimizes vaccine manufacturing processes. ChAdOx1 vectored vaccines can be manufactured in E1 complementing cell lines at scale and are thermostable. The first ChAdOx1 vectored vaccines approved for human use, against SARS-CoV-2, received emergency use authorization in the UK on 30th December 2020, and is now approved in more than 180 countries.
Safety data were compiled from phase I-III clinical trials of ChAdOx1 vectored vaccines expressing different antigens (influenza, tuberculosis, malaria, meningococcal B, prostate cancer, MERS-CoV, Chikungunya, Zika and SARS-CoV-2), conducted by the University of Oxford, as well as post marketing surveillance data for the COVID-19 Oxford-AstraZeneca vaccine. Overall, ChAdOx1 vectored vaccines have been well tolerated. Very rarely, thrombosis with thrombocytopenia syndrome (TTS), capillary leak syndrome (CLS), immune thrombocytopenia (ITP), and Guillain-Barre syndrome (GBS) have been reported following mass administration of the COVID-19 Oxford-AstraZeneca vaccine. The benefits of this COVID-19 vaccination have outweighed the risks of serious adverse events in most settings, especially with mitigation of risks when possible.
Extensive immunogenicity clinical evaluation of ChAdOx1 vectored vaccines reveal strong, durable humoral and cellular immune responses to date; studies to refine the COVID-19 protection (e.g., via homologous/heterologous booster, fractional dose) are also underway.
New prophylactic and therapeutic vaccines based on the ChAdOx1 vector are currently undergoing pre-clinical and clinical assessment, including vaccines against viral hemorrhagic fevers, Nipah virus, HIV, Hepatitis B, amongst others.
Abstract Cells within the astroglial lineage are proposed as the origin of human brain evolution. It is now widely accepted that they direct mammalian fetal neurogenesis, gliogenesis, laminar ...cytoarchitectonics, synaptic connectivity and neuronal network formation. Furthermore, genetic, anatomical and functional studies have recently identified multiple astrocyte exaptations that strongly suggest a direct relation to the increased size and complexity of the human brain.
Background
Urethral sphincter mechanism incompetence (USMI) is a common problem in female dogs, but some dogs fail to achieve continence with standard treatment. Urethral submucosal injection of ...autologous skeletal muscle progenitor cells (skMPCs) previously has been shown to restore urethral function in a canine model of USMI.
Hypothesis/Objective
To determine if urethral submucosal injection of skMPC alters continence in dogs with USMI that had previously failed standard medical management. We hypothesized that the injections would lead to improved continence.
Animals
Fifteen client‐owned dogs with USMI that had failed standard medical management.
Methods
Dogs were prospectively enrolled into a single‐armed clinical trial. Once enrolled, a triceps muscle of each dog was biopsied; the tissue specimens were digested, cultured, and expanded to 100 million cells before injection into the urethral submucosa using a surgical approach. Continence was assessed at baseline and 3, 6, 12, and 24 months post‐injection using continence scores and urethral pressure profilometry.
Results
Median continence scores increased significantly from baseline at 3, 6, 12, and 24 months. Increases were seen in 14 of 15 dogs with 7, 6 or 1 dog achieving scores of 5, 4 or 3, respectively. Additional medication was required to achieve continence in all but 2 dogs.
Conclusions and Clinical Importance
Urethral submucosal injection of skMPC can be used adjunctively to improve continence in dogs with difficult to manage USMI. The procedure is labor intensive but well tolerated; most dogs will require continued medication to remain continent.
Previous studies on influenza A(H1N1)pdm09 candidate vaccine viruses (CVVs) that had adapted to growth in embryonated chicken eggs by the acquisition of amino acid substitutions at HA positions 222 ...or 223 showed that improved protein yield could be conferred by additional amino acid substitutions in the haemagglutinin (HA) that arose naturally during passaging of the virus in eggs. In this study we investigated, by means of reverse genetics, the ability of a non-egg adapted (cell-like) A(H1N1)pdm09 virus to egg-adapt at HA loci other than 222/223, introducing amino acid substitutions previously identified as egg adaptations in pre-H1N1pdm09 H1N1 viruses and assessing their effect on protein yield and antigenicity. We also investigated the effect on the protein yield of these substitutions in viruses that had A(H1N1)pdm09 internal genes rather than the traditional PR8 internal genes of a CVV. The data show that a cell-like A/Christchurch/16/2010 can be egg-adapted via amino acid substitutions in at least three alternative HA loci (187, 190 and 216), in viruses with either PR8 or A/California/7/2009 internal genes, but that the effects on protein yield vary depending on the amino acid substitution and the internal genes of the virus. Since CVVs need to produce high protein yields to be suitable for vaccine manufacture, the findings of this study will assist in the future characterisation of both wild type viruses and lab-derived CVVs for vaccine use.
The phasmatodeans or stick and leaf insects are considered to be a mesodiverse insect order with more than 3000 species reported mainly from the tropics. The stick insect subfamily Necrosciinae ...comprises approximately 700 described species in more than 60 genera from the Oriental and Australian region, forming the most species‐rich subfamily traditionally recognized within Phasmatodea. However, the monophyly of this taxon has never been thoroughly tested and the evolutionary relationships among its members are unknown. We analyse three nuclear (18S and 28S rDNA, histone 3) and three mitochondrial (CO II, 12S and 16S rDNA) genes to infer the phylogeny of 60 species of stick insects that represent all recognized families and major subfamilies sensu Günther and the remarkable diversity within Necrosciinae. Maximum parsimony, maximum likelihood and Bayesian techniques largely recover the same substantial clades, albeit with highly discordant relationships between them. Most members of the subfamily Necrosciinae form a clade. However, the genus Neohirasea – currently classified within Lonchodinae – is strongly supported as subordinate to Necrosciinae, whereas Baculofractum, currently classified within Necrosciinae, is strongly supported within Lonchodinae. Accordingly, we formally transfer Neohirasea and allied taxa (namely Neohiraseini) to Necrosciinae sensu nova (s.n.) and Baculofractum to Lonchodinae s.n. We also provide further evidence that Leprocaulinus, until recently recognized as Necrosciinae, belongs to Lonchodinae, and forms the sister taxon of Baculofractum. Furthermore, Lonchodinae is paraphyletic under exclusion of Eurycantha and Neopromachus. We reinstate the traditional view that Neopromachus and related taxa (Neopromachini sensu Günther) are a subgroup of Lonchodinae and transfer those taxa + the New Guinean Eurycanthinae accordingly. Morphological evidence largely corroborates our molecular‐based findings and also reveals that Menexenus fruhstorferi is a member of the genus Neohirasea and is thus transferred from Menexenus (Lonchodinae) to Neohirasea, as Neohirasea fruhstorferi comb.n. (Necrosciinae s.n.). Other phylogenetic results include Areolatae and Anareolatae each supported as polyphyletic, Heteropteryginae and Lanceocercata (Bayesian analysis) are monophyletic, albeit with low support, and Necrosciinae s.n. and Lonchodinae s.n. are recovered as sister taxa (Bayesian analysis).
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