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The mutation profile of the SARS-CoV-2 Omicron (lineage BA.1) variant posed a concern for naturally acquired and vaccine-induced immunity. We investigated the ability of prior infection with an early SARS-CoV-2 ancestral isolate (Australia/VIC01/2020, VIC01) to protect against disease caused by BA.1. We established that BA.1 infection in naïve Syrian hamsters resulted in a less severe disease than a comparable dose of the ancestral virus, with fewer clinical signs including less weight loss. We present data to show that these clinical observations were almost absent in convalescent hamsters challenged with the same dose of BA.1 50 days after an initial infection with ancestral virus. These data provide evidence that convalescent immunity against ancestral SARS-CoV-2 is protective against BA.1 in the Syrian hamster model of infection. Comparison with published pre-clinical and clinical data supports consistency of the model and its predictive value for the outcome in humans. Further, the ability to detect protection against the less severe disease caused by BA.1 demonstrates continued value of the Syrian hamster model for evaluation of BA.1-specific countermeasures.

Lambe, Spencer, Thomas, Gilbert and colleagues report on the detailed immune profile of rhesus macaques and ferrets vaccinated against SARS-CoV-2 under high dose challenge. Their findings indicate that the ChAdOx1 nCoV-19 (AZD1222) the vaccine induces immune responses and reduces disease symptoms in both models, including SARS-CoV-2 mediated pneumonia and virus shedding.

Non-human primates are important animal models for studying SARS-CoV-2 infection. Here, Salguero et al. directly compare rhesus and cynomolgus macaques and show that both species represent COVID-19 disease of mild clinical cases, and provide a lung histopathology scoring system.

SARS-CoV-2 induces mild infection in ferret model. Here, Ryan et al. characterise optimal infection dosage inducing upper respiratory tract (UTR) viral shedding, progression time of viral shedding, and pathology in ferrets and finally provide evidence for protection after re-challenge.

Background: The novel human coronavirus SARS-CoV-2 is a major ongoing global threat with huge economic burden. Like all respiratory viruses, SARS-CoV-2 initiates infection in the upper respiratory tract (URT). Infected individuals are often asymptomatic, yet highly infectious and readily transmit virus. A therapy that restricts initial replication in the URT has the potential to prevent progression of severe lower respiratory tract disease as well as limiting person-to-person transmission. Methods: SARS-CoV-2 Victoria/01/2020 was passaged in Vero/hSLAM cells and virus titre determined by plaque assay. Challenge virus was delivered by intranasal instillation to female ferrets at 5.0 × 106 pfu/ml. Treatment groups received intranasal INNA-051, developed by Ena Respiratory. SARS-CoV-2 RNA was detected using the 2019-nCoV CDC RUO Kit and QuantStudio™ 7 Flex Real-Time PCR System. Histopathological analysis was performed using cut tissues stained with haematoxylin and eosin (H&E). Findings: We show that prophylactic intra-nasal administration of the TLR2/6 agonist INNA-051 in a SARS-CoV-2 ferret infection model effectively reduces levels of viral RNA in the nose and throat. After 5 days post-exposure to SARS-CoV-2, INNA-051 significantly reduced virus in throat swabs (p=

Despite high vaccination coverage, Bordetella pertussis the causative agent of whooping cough is still a health concern worldwide. A resurgence of pertussis cases has been reported, particularly in countries using acellular vaccines with waning immunity and pathogen adaptation thought to be responsible. A better understanding of protective immune responses is needed for the development of improved vaccines. In our study, B. pertussis strain B1917 variants presenting a single gene deletion were generated to analyze the role of vaccine components or candidate vaccine antigens as targets for bactericidal antibodies generated after acellular vaccination or natural infection. Our results show that acellular vaccination generates bactericidal antibodies that are only directed against pertactin. Serum bactericidal assay performed with convalescent samples show that disease induces bactericidal antibodies against Prn but against other antigen(s) as well. Four candidate vaccine antigens (CyaA, Vag8, BrkA, and TcfA) have been studied but were not targets for complement-mediated bactericidal antibodies after natural infection. We confirm that Vag8 and BrkA are involved in complement resistance and would be targeted by blocking antibodies. Our study suggests that the emergence and the widespread circulation of Prn-deficient strains is driven by acellular vaccination and the generation of bactericidal antibodies targeting Prn.

Background: Fragile X syndrome, with an approximate incidence rate of 1 in 4000 males to 1 in 8000 females, is the most prevalent genetic cause of heritable intellectual disability and the most common monogenic cause of autism spectrum disorder. The full mutation of the Fragile X Messenger Ribonucleoprotein-1 gene, characterized by an expansion of CGG trinucleotide repeats (>200 CGG repeats), leads to fragile X syndrome. Currently, there are no targeted treatments available for fragile X syndrome. In a recent large multi-site trial, FXLEARN, the effects of the mGluR5 negative allosteric modulator, AFQ056 (mavoglurant), were investigated, but did not show a significant impact of AFQ056 on language development in children with fragile X syndrome aged 3-6 years., Objectives: The current analyses from biospecimens collected in the FXLEARN study aimed to determine whether AFQ056 affects the level of potential biomarkers associated with Akt/mTOR and matrix metalloproteinase 9 signaling in young individuals with fragile X syndrome. Previous research has indicated that these biomarkers play crucial roles in the pathophysiology of fragile X syndrome., Design: A double-blind placebo-controlled parallel-group flexible-dose forced titration design., Methods: Blood samples for biomarkers were collected during the FXLEARN at baseline and subsequent visits (1- and 8-month visits). Biomarker analyses included fragile X messenger ribonucleoprotein-1 genotyping by Southern blot and PCR approaches, fragile X messenger ribonucleoprotein-1 mRNA levels determined by PCR, matrix metalloproteinase 9 levels' detection using a magnetic bead panel, and targets of the Akt/mTOR signaling pathway with their phosphorylation levels detected., Results: This research revealed that administering AFQ056 does not affect the expression levels of the investigated blood biomarkers in young children with fragile X syndrome., Conclusion: Our findings of the lack of association between clinical improvement and biomarkers' levels in the treatment group are in line with the lack of benefit observed in the FXLEARN study. These findings indicate that AFQ056 does not provide benefits as assessed by primary or secondary endpoints., Registration: ClincalTrials.gov NCT02920892., Competing Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dragana Protic has received funding from The Science Fund of the Republic of Serbia and the FRAXA Research Foundation for carrying out studies on Fragile X Syndrome. Flora Tassone has received funding from Zynerba and Azrieli Foundation for carrying out studies on Fragile X Syndrome. Elizabeth Berry-Kravis has received funding from Acadia, Biogen, BioMarin, Erydel, GeneTx/Ultragenyx, Ionis, Jaguar, Kisbee, Neuren, Neurogene, Orphazyme/Kempharm/Zevra, PTC Therapeutics, Roche, Taysha, Tetra/Shionogi, Yamo, Zynerba, and Mallinckrodt Pharmaceuticals, for consulting or on clinical trials in genetic neurological disorders, all funds directed to Rush University Medical Center. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© The Author(s) 2024.)

Imaging plant embryos at the cellular level over time is technically challenging, since the embryo, once its protective seed coat is removed, must be kept viable and unstressed on a microscope slide for the duration of the experiment. Here we describe a procedure and suitable apparatus for the visualization, over several days, of changes in endoplasmic reticulum (ER) morphology associated with the process of germination in Arabidopsis thaliana seeds. Moreover, we also present a user-friendly image analysis tool, which enables subtle perturbations in the ER network to be measured., (© 2024. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

The plant endoplasmic reticulum forms a network of tubules connected by three-way junctions or sheet-like cisternae. Although the network is three-dimensional, in many plant cells, it is constrained to thin volume sandwiched between the vacuole and plasma membrane, effectively restricting it to a 2-D planar network. The structure of the network, and the morphology of the tubules and cisternae can be automatically extracted following intensity-independent edge-enhancement and various segmentation techniques to give an initial pixel-based skeleton, which is then converted to a graph representation. ER dynamics can be determined using optical flow techniques from computer vision or persistency analysis. Collectively, this approach yields a wealth of quantitative metrics for ER structure and can be used to describe the effects of pharmacological treatments or genetic manipulation. The software is publicly available., (© 2024. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

We examined how set-volume equated resistance training using either the back squat (SQ) or hip thrust (HT) affected hypertrophy and various strength outcomes. Untrained college-aged participants were randomized into HT (n = 18) or SQ (n = 16) groups. Surface electromyograms (sEMG) from the right gluteus maximus and medius muscles were obtained during the first training session. Participants completed 9 weeks of supervised training (15-17 sessions), before and after which gluteus and leg muscle cross-sectional area (mCSA) was assessed via magnetic resonance imaging. Strength was also assessed prior to and after the training intervention via three-repetition maximum (3RM) testing and an isometric wall push test. Gluteus mCSA increases were similar across both groups. Specifically, estimates [(-) favors HT (+) favors SQ] modestly favored the HT versus SQ for lower [effect ±SE, -1.6 ± 2.1 cm 2 ; CI 95% (-6.1, 2.0)], mid [-0.5 ± 1.7 cm 2 ; CI 95% (-4.0, 2.6)], and upper [-0.5 ± 2.6 cm 2 ; CI 95% (-5.8, 4.1)] gluteal mCSAs but with appreciable variance. Gluteus medius + minimus [-1.8 ± 1.5 cm 2 ; CI 95% (-4.6, 1.4)] and hamstrings [0.1 ± 0.6 cm 2 ; CI 95% (-0.9, 1.4)] mCSA demonstrated little to no growth with small differences between groups. mCSA changes were greater in SQ for the quadriceps [3.6 ± 1.5 cm 2 ; CI 95% (0.7, 6.4)] and adductors [2.5 ± 0.7 cm 2 ; CI 95% (1.2, 3.9)]. Squat 3RM increases favored SQ [14 ± 2 kg; CI 95% (9, 18),] and hip thrust 3RM favored HT [-26 ± 5 kg; CI 95% (-34, -16)]. 3RM deadlift [0 ± 2 kg; CI 95% (-4, 3)] and wall push strength [-7 ± 12N; CI 95% (-32, 17)] similarly improved. All measured gluteal sites showed greater mean sEMG amplitudes during the first bout hip thrust versus squat set, but this did not consistently predict gluteal hypertrophy outcomes. Squat and hip thrust training elicited similar gluteal hypertrophy, greater thigh hypertrophy in SQ, strength increases that favored exercise allocation, and similar deadlift and wall push strength increases., Competing Interests: BC and MH disclose that they sell exercise-related products and services. However, neither was involved in any aspect of the study beyond assisting with the study design and providing funds to partially cover participant and MRI costs through a gift to the laboratory of MR. The results of the study are presented clearly, honestly, and without fabrication, falsification, or inappropriate data manipulation. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Plotkin, Rodas, Vigotsky, McIntosh, Breeze, Ubrik, Robitzsch, Agyin-Birikorang, Mattingly, Michel, Kontos, Lennon, Frugé, Wilburn, Weimar, Bashir, Beyers, Henselmans, Contreras and Roberts.)

The endoplasmic reticulum (ER) is the entry point to the secretory pathway and, as such, is critical for adaptive responses to biotic stress, when the demand for de novo synthesis of immunity-related proteins and signalling components increases significantly. Successful phytopathogens have evolved an arsenal of small effector proteins which collectively reconfigure multiple host components and signalling pathways to promote virulence; a small, but important, subset of which are targeted to the endomembrane system including the ER. We identified and validated a conserved C-terminal tail-anchor motif in a set of pathogen effectors known to localize to the ER from the oomycetes Hyaloperonospora arabidopsidis and Plasmopara halstedii (downy mildew of Arabidopsis and sunflower, respectively) and used this protein topology to develop a bioinformatic pipeline to identify putative ER-localized effectors within the effectorome of the related oomycete, Phytophthora infestans, the causal agent of potato late blight. Many of the identified P. infestans tail-anchor effectors converged on ER-localized NAC transcription factors, indicating that this family is a critical host target for multiple pathogens., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Society for Experimental Biology.)

Background: Since the era of smartphones started in early 2007, they have steadily turned into an accepted part of our lives. Poor sleep is a health problem that needs to be closely monitored before it causes severe mental health problems, such as anxiety or depression. Sleep disorders (eg, acute insomnia) can also develop to chronic insomnia if not treated early. More specifically, mental health problems have been recognized to have casual links to anxiety, depression, heart disease, obesity, dementia, diabetes, and cancer. Several researchers have used mobile sensors to monitor sleep and to study changes in individual mood that may cause depression and anxiety., Objective: Extreme sleepiness and insomnia not only influence physical health, they also have a significant impact on mental health, such as by causing depression, which has a prevalence of 18% to 21% among young adults aged 16 to 24 in the United Kingdom. The main body of this narrative review explores how passive data collection through smartphone sensors can be used in predicting anxiety and depression., Methods: A narrative review of the English language literature was performed. We investigated the use of smartphone sensors as a method of collecting data from individuals, regardless of whether the data source was active or passive. Articles were found from a search of Google Scholar records (from 2013 to 2020) with keywords including "mobile phone," "mobile applications," "health apps," "insomnia," "mental health," "sleep monitoring," "depression," "anxiety," "sleep disorder," "lack of sleep," "digital phenotyping," "mobile sensing," "smartphone sensors," and "sleep detector.", Results: The 12 articles presented in this paper explain the current practices of using smartphone sensors for tracking sleep patterns and detecting changes in mental health, especially depression and anxiety over a period of time. Several researchers have been exploring technological methods to detect sleep using smartphone sensors. Researchers have also investigated changes in smartphone sensors and linked them with mental health and well-being., Conclusions: The conducted review provides an overview of the possibilities of using smartphone sensors unobtrusively to collect data related to sleeping pattern, depression, and anxiety. This provides a unique research opportunity to use smartphone sensors to detect insomnia and provide early detection or intervention for mental health problems such as depression and anxiety if insomnia is detected., (©Doaa Alamoudi, Emma Breeze, Esther Crawley, Ian Nabney. Originally published in JMIR mHealth and uHealth (https://mhealth.jmir.org), 17.02.2023.)

Microbe-associated molecular pattern (MAMP)-triggered immunity (MTI) research has traditionally centred around signal transduction pathways originating from activated membrane-localized pattern recognition receptors (PRRs), culminating in nuclear transcription and posttranslational modifications. More recently, chloroplasts have emerged as key immune signalling hubs, playing a central role in integrating environmental signals. Notably, MAMP recognition induces chloroplastic reactive oxygen species (cROS) that is suppressed by pathogen effectors, which also modify the balance of chloroplast-synthesized precursors of the defence hormones, jasmonic acid, salicylic acid (SA) and abscisic acid. This study focuses on how well-characterized PRRs and coreceptors modulate chloroplast physiology, examining whether diverse signalling pathways converge to similarly modulate chloroplast function. Pretreatment of receptor mutant plants with MAMP and D(Damage)AMP peptides usually protect against effector modulation of chlorophyll fluorescence and prevent Pseudomonas syringae effector-mediated quenching of cROS and suppression of maximum dark-adapted quantum efficiency (the ratio of variable/maximum fluorescence [F v /F m ]). The MTI coreceptor double mutant, bak1-5/bkk1-1, exhibits a remarkable decrease in F v /F m compared to control plants during infection, underlining the importance of MTI-mediated signalling in chloroplast immunity. Further probing the role of the chloroplast in immunity, we unexpectedly found that even moderate changes in light intensity can uncouple plant immune signalling., (© 2022 The Authors. Plant, Cell & Environment published by John Wiley & Sons Ltd.)

The response of chloroplasts to adverse environmental cues, principally increases in light intensity, stimulates chloroplast-to-nucleus retrograde signalling, which leads to the induction of immediate protective responses and longer-term acclimation. Hydrogen peroxide (H 2 O 2 ), generated during photosynthesis, is proposed to both initiate and transduce a retrograde signal in response to photoinhibitory light intensities. Signalling specificity achieved by chloroplast-sourced H 2 O 2 for signal transduction may be dependent upon the oft-observed close association of a proportion of these organelles with the nucleus. In this review, we consider more precisely the nature of the close association between a chloroplast appressed to the nucleus and the requirement for H 2 O 2 to cross both the double membranes of the chloroplast and nuclear envelopes. Of particular relevance is that the endoplasmic reticulum (ER) has close physical contact with chloroplasts and is contiguous with the nuclear envelope. Therefore, the perinuclear space, which transducing H 2 O 2 molecules would have to cross, may have an oxidising environment the same as the ER lumen. Based on studies in animal cells, the ER lumen may be a significant source of H 2 O 2 in plant cells arising from the oxidative folding of proteins. If this is the case, then there is potential for the ER lumen/perinuclear space to be an important location to modify chloroplast-to-nucleus H 2 O 2 signal transduction and thereby introduce modulation of it by additional different environmental cues. These would include for example, heat stress and pathogen infection, which induce the unfolded protein response characterised by an increased H 2 O 2 level in the ER lumen.

Leaf senescence is an important developmental process for the plant life cycle. It is controlled by endogenous and environmental factors and can be positively or negatively affected by plant growth regulators. It is characterised by major and significant changes in the patterns of gene expression. Auxin, especially indole-3-acetic acid (IAA), is a plant growth hormone that affects plant growth and development. The effect of IAA on leaf senescence is still unclear. In this study, we performed microarray analysis to investigate the role of IAA on gene expression during senescence in Arabidopsis thaliana . We sprayed IAA on plants at 3 different time points (27, 31 or 35 days after sowing). Following spraying, PSII activity of the eighth leaf was evaluated daily by measurement of chlorophyll fluorescence parameters. Our results show that PSII activity decreased following IAA application and the IAA treatment triggered different gene expression responses in leaves of different ages., (© Prof. H.S. Srivastava Foundation for Science and Society 2020.)