bluuebunny/crossref_metadata_2025 huggingface dataset:
Density-dependent selection at low food levels leads to the evolution of population stability in Drosophila melanogaster even without a clear r-K trade-off
Authors: Pandey Neha , Joshi Amitabh
Published: June 2022

Density-dependent selection, especially together with r-K trade-offs, has been one of the most plausible suggested mechanisms for the evolution of population stability. However, experimental support for this explanation has been both meagre and mixed. One study with Drosophila melanogaster yielded no evidence for populations adapted to chronic larval crowding having also evolved greater population stability. Another study, on D. ananassae, suggested that populations adapted to larval crowding evolved both greater constancy and persistence stability, and the data also suggested an r-K trade-off in those populations, though the evidence for the latter was not conclusive. Moreover, theoretical work suggested that density-dependent selection could result in the evolution of greater population stability, even in the absence of an r-K trade-off. Here, we show that populations of D. melanogaster, selected for adaptation to larval crowding at very low food amounts per vial, evolve enhanced constancy and persistence stability. The enhanced population stability in the crowding-adapted populations seems to have evolved through the increased equlibrium size (K) and reduced sensitivity of realized population growth rates to density (α).There was no clear evidence for reduced intrinsic population growth rate (r) in the more stable crowding-adapted populations. Our study adds to the growing evidence in support of the hypothesis that population stability can evolve in response to density-dependent selection through the evolution of certain life-history traits that are associated with higher K and less negative α. We discuss our results in the light of previous work, and suggest that a model-free framework might be of great heuristic value in understanding the evolution of population stability through changes in the density-sensitivity of life-history traits, whether or not these changes result from density-dependent selection.
Single cell RNA sequencing reveals mechanisms underlying a senescence-like phenotype of Alveolar Macrophages during Aging
Authors: Wu Yue , Zhu Bibo , Zhang Ruixuan , Goplen Nick P. , Gao Xiaochen , Narasimhan Harish , Shi Ao , Chen Yin , Li Ying , Dong Haidong , Braciale Thomas J. , Sun Jie
Published: June 2022

Alveolar Macrophages (AMs) are unique innate immune cells that reside in the alveolar space and accommodate the ever-changing needs of the lungs against internal and external challenges. During homeostasis, AMs maintain themselves through self-renewal without input from adult hematopoietic stem cells. Currently, little is known regarding the influence of aging on AM dynamics, heterogeneity and transcriptional profiles. Here, we identified CBFβ as an indispensable transcription factor that ensures AM self-renewal. Deficiency in CBFβ led to decreased proliferation and self-renewal ability of AMs. Moreover, with single cell RNA sequencing analysis of AMs from young and aged mice, we discovered that despite similarities in the transcriptome of proliferating cells, AMs from the aged mice exhibited reduced embryotic stem cell-like features. Aged AMs also showed diminished capacity for DNA repair, potentially contributing to impaired cell cycle progression and elevation of senescence markers. In accordance with the analysis, we observed reduced number of AMs in aged mice, which had defective self-renewal ability and were more sensitive to the reduction of GM-CSF. Interestingly, decreased CBFβ was observed in the cytosol of AMs from aged mice. A similar senescence-like phenotype was also found in human AMs. Taken together, we conclude that AMs in the aged host harbor a senescence-like phenotype, potentially mediated by the activity of CBFβ.

Highlights

scRNAseq revealed Alveolar Macrophage (AM) heterogeneity and self-renewal

CBFβ is associated with AM cell cycle and facilitate AM self-renewal

AMs displayed a senescence-like phenotype during physiological Aging

Aging impairs CBFβ expression in mouse and human AMs
Community science for enigmatic ecosystems: Using eBird to assess avian biodiversity on glaciers and snowfields
Authors: Brooks William E. , Boersma Jordan , Paprocki Neil , Wimberger Peter , Hotaling Scott
Published: June 2022

Aim

To quantify avian biodiversity and habitat preference and describe behavior in an enigmatic, understudied ecosystem: mountain glaciers and snowfields.

Location

Mountains in the Pacific Northwest of western North America: British Columbia (CA), Washington and Oregon (USA).

Taxon

Birds observed within our study area and focal habitat.

Methods

We used community science data from eBird—an online database of bird observations from around the world—to estimate bird biodiversity and abundance in glacier and snowfield ecosystems as well as nearby, ice-adjacent habitats. We used field notes from eBird users and breeding codes to extend our data set to include insight into habitat usage and behavior. Finally, we compared our community-science approach to previous studies that used traditional survey methods.

Results

We identified considerable avian biodiversity in glacier and snowfield habitat (46 species) with four specialists that appeared to prefer glaciers and snowfields over nearby, ice-adjacent habitat. Combined with field notes by eBird users, our efforts increased the known global total of avian species associated with ice and snow habitats by 14%. When community science data was compared to traditional methods, we found similar species diversity but differences in abundance.

Main conclusions

Despite the imminent threat of glacier and snowfield melt due to climate change, species living in these habitats remain poorly studied, likely due to the remoteness and ruggedness of their terrain. Glaciers and snowfields hold notable bird diversity, however, with a specialized set of species appearing to preferentially forage in these habitats. Our results show that community science data can provide a valuable starting point for studying difficult to access areas, but traditional surveys are still useful for more rigorous quantification of avian biodiversity.
Accumulating waves of random mutations before fixation
Authors: Moeller Marius , Werner Benjamin , Huang Weini
Published: June 2022

Mutations provide variation for evolution to emerge. A quantitative analysis of how mutations arising in single individuals expand and possibly fixate in a population is essential for studying evolutionary processes. While it is intuitive to expect that a continuous influx of mutations will lead to a continuous flow of mutations fixating in a stable constant population, joint fixation of multiple mutations occur frequently in stochastic simulations even under neutral selection. We quantitatively measure and analyse the distribution of joint fixation events of neutral mutations in constant populations. We propose a new concept, the mutation “waves”, where multiple mutations reach given frequencies simultaneously. We show that all but the lowest frequencies of the variant allele frequency are dominated by single mutation “waves” that approximately follow an exponential distribution both in their size and the time between two “waves”. Consequently, large swaths of empty frequencies are observed in the variant allele frequency distributions, with a few frequencies having numbers of mutations far in excess of the expected average values. We further show that the discrete mutation waves average out to a continuous distribution named as the Wave Frequency Distribution (WFD), the shape of which is predictable based on few model parameters.
Sticker-and-Linker Model for Amyloid Beta Condensation and Fibrillation
Authors: Connor Jack P. , Quinn Steven D. , Schaefer Charley
Published: June 2022

A major pathogenic hallmark of Alzheimer’s disease is the presence of neurotoxic plaques composed of amyloid beta (Aβ) peptides in patients’ brains. The pathway of plaque formation remains elusive, though some clues appear to lie in the dominant presence of Aβ1–42in these plaques despite Aβ1–4making up approximately 90% of the Aβpool. We hypothesise that this asymmetry is driven by the hydrophobicity of the two extra amino acids that are incorporated in Aβ1–42. To investigate this hypothesis at the level of single molecules, we have developed a molecular ‘sticker-and-linker lattice model’ of unfolded Aβ. The model protein has a single sticker that may reversibly dimerise and elongate into semi-flexible linear oligomers. The growth is hampered by excluded-volume interactions that are encoded by the hydrophilic linkers but is rendered cooperative by the attractive interactions of hydrophobic linkers. For sufficiently strong hydrophobicity, the chains undergo liquid-liquid phase-separation (LLPS) into condensates that facilitate the nucleation of fibres. We find that a small fraction of Aβ1–40in a mixture of Aβ1–40and Aβ1–42shifts the critical concentration for LLPS to lower values. This study provides theoretical support for the hypothesis that LLPS condensates act as a precursors for aggregation and provides an explanation for the Aβ1–42-enrichment of aggregates in terms of hydrophobic interactions.
The Integrative Studies on the Functional A-to-I RNA Editing Events in Human Cancers
Authors: Wu Sijia , Fan Zhiwei , Kim Pora , Huang Liyu , Zhou Xiaobo
Published: June 2022

A-to-I RNA editing, constituting nearly 90% of all RNA editing events in human, has been reported to contribute to the tumorigenesis in diverse cancers. However, the comprehensive map for functional A-to-I RNA editing events in cancers is still insufficient. To fill this gap, we systematically and intensively analyzed multiple tumorigenic mechanisms of A-to-I RNA editing events in samples across 33 cancer types from The Cancer Genome Atlas. For individual candidate among ~ 1.5M quantified RNA editing events, we performed diverse types of down-stream functional annotations. Finally, we identified 24,236 potentially functional A-to-I RNA editing events, including the cases in APOL1, IGFBP3, GluA2, BLCAP, and miR-589-3p. These events showed significant results and might play crucial roles in the scenarios of tumorigenesis, due to their tumor-related editing frequencies or probable effects on altered expression profiles, protein functions, splicing patterns, and miRNA regulations of tumor genes. Our functional A-to-I RNA editing events (https://ccsm.uth.edu/CAeditome/) will help better understanding of cancer pathology from A-to-I RNA editing aspect.
Circadian Control of Pulmonary Endothelial Signaling occurs via the NADPH oxidase 2-NLRP3 pathway
Authors: Sengupta Shaon , Lee Yool , Tao Jian Qin , Sehgal Amita , Chatterjee Shampa
Published: June 2022

Circadian rhythms are endogenous oscillations that occur with a 24-hr periodicity. These rhythms are ubiquitous and thus, vascular endothelial cells that line the vascular bed are also subjected to circadian regulation. While the circadian control of vascular function has been demonstrated in the context of various pathologies, the relevance and functional implication of clock control over pulmonary vasculature has never been investigated. As the pulmonary endothelium is a crucial site for the host’s inflammatory response to a lung specific pathogen, we investigated the role of the circadian clock in mediation the response of the pulmonary endothelium to inflammation. We hypothesized that the pulmonary endothelium is under circadian control and that the clock serves to curb inflammatory signaling.

Methods

Circadian rhythms were monitored in pulmonary artery segments and endothelial cells isolated from mPer2luciferase transgenic mice in the presence of an inflammatory stimuli (LPS). Reactive oxygen species (ROS) production in LPS treated cells was measured by fluorescence microscopy using the cell permeant dye CellROX Green. NLRP3 inflammasome was monitored post-mortem (0-72 h post LPS instillation) by measuring the expression of the NLRP3 subunit in wild type and Bmal1−/− and Cry1/2−/− mice. Inflammation was quantified in these mice by measuring PMN adherence and intercellular adhesion molecule (ICAM-1).

Results

We observed that the circadian rhythm of the pulmonary vasculature was altered LPS. LPS also led to ROS production in these cells; ROS increased 3 h post LPS treatment, peaked by 36 h and returned to baseline values by 72 h. ROS were inhibited by pretreating the cells with the NADPH oxidase 2 (NOX2) inhibitor dipheneylene iodonium (DPI). Addition of DPI, prior to LPS pretreatment also restored the circadian rhythmicity of the pulmonary endothelium. The increase in NLRP3 along the vessel wall (post LPS treatment) was resolved by 72 h in lungs of wild type mice but not in Bmal1−/− and Cry1−/−Cry2−/− lungs. Inflammation (ICAM-1 and PMN) was also resolved in wild type but not in mice wherein the circadian clock had been disrupted genetically.

Conclusion

Our data indicate that pro-inflammatory stimuli reprogram circadian rhythms in the pulmonary endothelium via ROS via the NOX2-NLRP3 pathway. Disruption of the clock mediates a sustained increase in ROS via this Nox2-NLRP3 pathway in endothelial cells, thus offering a novel mechanism for mitigating the effects of clock disruption.
Contrasting autoimmune and treatment effects reveals baseline set points of immune toxicity following checkpoint inhibitor treatment
Authors: Zhao Chen , Mulè Matthew P. , Martins Andrew J. , Pinal-Fernandez Iago , Donahue Renee N. , Chen Jinguo , Schlom Jeffrey , Gulley James L. , Mammen Andrew , Tsang John S. , Rajan Arun
Published: June 2022

Immune checkpoint inhibitors (ICIs) have changed the cancer treatment landscape, but severe immune-related adverse events (irAEs) can be life-threatening or fatal and may prohibit patients from receiving further ICI treatment. While the clinical features of irAEs are well documented, molecular signatures, predictive biomarkers, and mechanisms of impending irAEs are largely unknown. In addition, the markers and mechanisms of ICI-induced antitumor immunity often overlap with those for irAEs. It is thus critical to uncover signatures associated specifically with irAEs but not with antitumor immunity. To identify circulating immune cell states associated with irAEs, we applied multimodal single cell analysis (CITE-seq) to simultaneously measure the transcriptome and surface proteins from peripheral blood mononuclear cells (PBMCs) collected before and after treatment with an anti-PD-L1 antibody (avelumab) in patients with thymic cancers (thymic epithelial tumors). All patients had an antitumor response, yet a subset developed muscle autoimmunity (myositis), a potentially life-threatening irAE. Mixed-effect modeling disentangled cell type-specific transcriptional states associated with ICI treatment responses from those of irAEs to identify temporally stable pre-treatment immune set points associated with irAEs only. These pre-treatment baseline signatures of irAE developed post-avelumab irAEs reflect correlated transcriptional states of multiple innate and adaptive immune cell populations, including elevation of metabolic genes downstream of mTOR signaling in T-cell subsets. Together these findings suggest putative pre-treatment biomarkers for irAEs following ICI therapy in thymic cancer patients and raise the prospect of therapeutically dampening autoimmunity while sparing antitumor activity in cancer patients treated with ICIs. Together, pre-treatment biomarkers and interventional therapeutics could help mitigate treatment discontinuation and improve clinical outcomes.
Arabidopsis MLO4 Functions as a Ca2+ Channel Essential for Mechanosensing in Root Tips
Authors: Zhang Zhengli , Sun Yujia , Lu Pengfei , Feng Changxin , Niu Qi , Lin Geng , Kong Dongdong , Liu Liangyu , Luan Sheng , Li Legong , Hou Congcong
Published: June 2022

Mechanical stimuli guide root growth to avoid obstacles in the soil. Although mechanisms underlying root mechanosensing remain largely unknown, calcium signaling is proposed to be an early event that proceeds directional root growth. In response to mechanical perturbations, root cells produce transient spikes in the cytosolic free Ca2+ levels. Loss-of-function mutations of MLOs cause root curling upon contact with hard surface of obstacles, the mechanism for MLOs action in root thigmomorphogenesis has been enigmatic. WT and mlo4 seedlings were grown on MS media containing gradient agar concentrations mimicking different levels of soil hardness and compared their root growth into the agar gradient mlo4 had much less roots penetrated the harder agar barrier as compared to WT roots. The channel activity of MLO4 was examined in Xenopus oocytes using the two-electrode voltage clamp (TEVC) method. The TEVC recording showed that the oocytes injected with MLO cRNA displayed large inward currents in the presence of Ca2+. MLO4 rescued the cch1/mid1 from growth arrest by the pheromone, these results indicate that MLO4 constitutes a novel Ca2+-permeable channel. Ca2+ spike was hardly detectable in mlo4/GCaMP6s seedings in response to a hard surface during root elongation. In summary, MLO4 functions as a typical Ca2+ channel that links touch stimulation to Ca2+ elevation in root tip cells.
Chromosomal conservatism vs chromosomal megaevolution: enigma of karyotypic evolution in Lepidoptera
Authors: Pazhenkova Elena A. , Lukhtanov Vladimir A.
Published: June 2022

In the evolution of many organisms, periods of very slow genome reorganization (=chromosomal conservatism) are interrupted by bursts of numerous chromosomal changes (=chromosomal megaevolution). However, the patterns, mechanisms, and consequences of conservative and rapid chromosomal evolution are still poorly understood and widely discussed. Here we show that in blue butterflies (Lepidoptera: Lycaenidae), the periods of chromosome number conservatism are characterized by the real stability of most autosomes and the highly dynamic evolution of the sex chromosome Z, which, due to autosome-sex chromosome fusions and fissions, is carried out according to the cycle Z=>NeoZ1=>Z=>NeoZ2=>Z=>NeoZ3. These fusions and fissions result in a fluctuation of chromosomal number (±1) around the ancestral value, a phenomenon previously observed (but not explained) in numerous groups of Lepidoptera. In the phase of chromosomal megaevolution, the explosive increase in the chromosome number occurs mainly due to simple chromosomal fissions, in some cases complicated by autosomal translocations. Interestingly, these translocations are not random and found to occur only between fragmented chromosomes originated from the same primary linkage group. We also found that the Z chromosomes of two closely related Lysandra species are differentiated by a large inversion. We argue that the special role of sex chromosomes in speciation can be reinforced via sex chromosome – autosome fusion. The cycles of fusions and fissions of sex chromosomes with autosomes, such as those found in the blue butterflies, indicate that the species divergence driven by neo-Z chromosome formation is widely distributed in Lepidoptera.
Simultaneously cholinergic projection in Ascending and Descending Circuits from Midbrain
Authors: Zhao Peilin , Jiang Tao , Wang Huading , Jia Xueyan , Li Anan , Yuan Jing , Luo Qingming , Li Xiangning , Gong Hui
Published: June 2022

The midbrain participates in complex neural information processing in the ascending and descending circuits, but their organization remains unclear due to the lack of comprehensive dissection of the characterization of individual neurons. Combining fluorescent micro-optical sectional tomography with sparse labeling, we acquired the whole-brain dataset with high resolution and reconstructed the detailed morphology of the pontine-tegmental cholinergic neurons (PTCNs). As the main cholinergic system of the midbrain, the individual PTCNs own abundant axons with length up to 60 cm and 5000 terminal branches and innervate multiple brain regions from the spinal cord to cortex in both hemispheres. According to various targeting regions in the ascending and descending circuits, individual PTCNs could be grouped into four types and the axonal fibers of cholinergic neurons in the pedunculopontine nucleus present more divergent while neurons in the laterodorsal tegmental nucleus contain richer axonal fibers and dendrites. In the axonal targeting nuclei, such as in the thalamus or cortex, the individual neurons innervate multiple sub-regions with separate pathways. These results provide the detailed organization characterization of the cholinergic neurons to understand the connection logic of the midbrain.
Statistical Methods for Detecting Circadian Rhythmicity and Differential Circadian Patterns with Repeated Measurement in Transcriptomic Applications
Authors: Ding Haocheng , Meng Lingsong , Xing Chengguo , Esser Karyn A. , Huo Zhiguang
Published: June 2022

Circadian analysis via transcriptomic data has been successful in revealing the clock output changes underlying many diseases and physiological processes. Repeated measurement design in a circadian study is prevalent, in which the same subject is repeatedly measured over time. Several methods are currently available to perform circadian analysis, however, none of them take advantage of the repeated measurement design. And ignoring the within-subject correlation from the repeated measurement could result in lower statistical power. To address this issue, we developed linear mixed model based methods to detect (i) circadian rhythmicity (i.e., Rpt_rhythmicity) and (ii) differential circadian patterns comparing two experimental conditions (i.e., Rpt_diff). Our model includes a subject-specific random effect, which will account for the within-subject correlation. Via simulations, we showed our method not only could control the type I error rate around the nominal level, but also achieve higher statistical power compared to other methods that cannot model repeated measurement. The superior performance of Rpt_rhythmicity and Rpt_diff were also demonstrated in two real data applications, including a human restricted feeding data and a human sleep restriction data. An R package for our methods is publicly available on GitHub to promote the application of our methods.
Pathobionts from chemically disrupted gut microbiota induce insulin-dependent diabetes in mice
Authors: Yang Xin , Wang Zhiyi , Niu Junling , Zhai Rui , Xue Xinhe , Wu Guojun , Meng Guangxun , Yuan Huijuan , Zhao Liping , Zhang Chenhong
Published: June 2022

Background

Dysbiotic gut microbiome, genetically predisposed or chemically disrupted, has been linked with insulin-dependent diabetes (IDD) including autoimmune type 1 diabetes (T1D) in both humans and animal models. However, specific IDD-inducing gut bacteria remain to be identified and their casual role in disease development demonstrated via experiments that can fulfill Koch’s postulates.

Results

Here, we show that novel gut pathobionts in the Muribaculaceae family, enriched by a low-dose dextran sulfate sodium (DSS) treatment, translocated to the pancreas and caused local inflammation, beta cell destruction and IDD in C57BL/6 mice. Antibiotic removal and transplantation of gut microbiota showed that this low DSS disrupted gut microbiota was both necessary and sufficient to induce IDD. Reduced butyrate content in the gut and decreased gene expression levels of an antimicrobial peptide in the pancreas allowed for the enrichment of members in the Muribaculaceae family in the gut and their translocation to the pancreas. Pure isolate of one such members induced IDD in wildtype germ-free mice on normal diet either alone or in combination with normal gut microbiome after gavaged into stomach and translocated to pancreas.

Conclusion

The pathobionts that are chemically enriched in dysbiotic gut microbiota are sufficient to induce insulin-dependent diabetes after translocation to the pancreas. This indicates that IDD can be mainly a microbiome-dependent disease, inspiring the need to search for novel pathobionts for IDD development in humans.
The magnocellular division of the human medial geniculate nucleus preferentially responds to auditory transients
Authors: Meng Qianli , Schneider Keith A.
Published: June 2022

The medial geniculate nucleus (MGN), the auditory relay in the thalamus, is composed of three anatomical subdivisions: the ventral, dorsal and medial or magnocellular division. The functional differences among these nuclei have not been studied in humans, and in particular, the function of the magnocellular division is poorly understood in mammals in general. We anatomically segmented the MGN using proton-density-weighted magnetic resonance images (MRI) and measured the functional responses of the MGN to sustained and transient sounds, using functional MRI (fMRI). We observed that voxels in the ventromedial portion of the MGN, corresponding to the magnocellular division, exhibited a strong preference to transient sounds, whereas the remainder of the MGN showed no preference between sustained and transient sounds. We concluded that the magnocellular neurons in the MGN parallel the magnocellular neurons in its visual counterpart, the lateral geniculate nucleus (LGN), and constitute an information stream specialized for encoding stimuli dynamics.

Significance statement

The medial geniculate nucleus is the auditory relay in the thalamus. It is composed of three anatomical divisions, of which the function of the magnocellular division is poorly understood. We show, using functional magnetic resonance imaging (fMRI) in humans, that the magnocellular neurons are strongly activated by transient auditory stimuli, similar to the magnocellular neurons in the lateral geniculate nucleus, the visual thalamic relay, which are rapidly adapting and specialized to encode visual transients. These results confirm that the auditory system represents stimuli using parallel information streams, employing similar encoding strategies as in other sensory modalities.
Widespread epistasis among beneficial genetic variants revealed by high-throughput genome editing
Authors: Ang Roy Moh Lik , Chen Shi-An Anderson , Kern Alexander F. , Xie Yihua , Fraser Hunter B.
Published: June 2022

Genetic interactions occur when a variant’s phenotypic effect is altered by variation at other genomic loci. Also known as epistasis, these interactions shape the genetic architecture of complex traits and modify phenotypes across genetic backgrounds. However, the factors associated with their occurrence remain poorly understood. To investigate this, we employed high-throughput genome editing to measure the fitness effects of 1,826 naturally polymorphic variants in four genetically diverse strains of Saccharomyces cerevisiae. About 31% of variants affect fitness in a common laboratory environment, of which 24% have strain-specific fitness effects indicative of epistasis. We found that beneficial variants are more likely to exhibit genetic interactions, and that genetic interactions are depleted among variants at higher allele frequencies. In addition, we demonstrate that these epistatic interactions for fitness can be mediated by specific traits such as flocculation ability. This work suggests that adaptive evolution from standing variation will often involve trade-offs where a variant is only beneficial in some genetic backgrounds, potentially explaining why many beneficial variants remain polymorphic. In sum, we provide a framework to understand the factors influencing epistasis in natural genetic variants with single-nucleotide resolution, revealing widespread epistasis among beneficial variants.
Effectiveness of BNT162b2 booster doses in England: an observational study in OpenSAFELY-TPP
Authors: Hulme William J , Williamson Elizabeth J , Horne Elsie , Green Amelia , Nab Linda , Keogh Ruth , Parker Edward PK , Walker Venexia , Palmer Tom , Curtis Helen , Wiedemann Milan , Cunningham Christine , Walker Alex J , Fisher Louis , MacKenna Brian , Rentsch Christopher T , Schultze Anna , Bhaskaran Krishnan , Tazare John , Tomlinson Laurie , McDonald Helen I , Morton Caroline E , Croker Richard , Andrews Colm , Parks Robin , Hopcroft Lisa , Massey Jon , Morley Jessica , Mehrkar Amir , Bacon Seb , Evans Dave , Inglesby Peter , Hickman George , Davy Simon , Dillingham Iain , Ward Tom , Mahalingasivam Viyasaan , Zheng Bang , Douglas Ian J , Evans Stephen JW , Bates Chris , Sterne Jonathan AC , Hernán Miguel A , Goldacre Ben
Published: June 2022

Background

The UK COVID-19 vaccination programme delivered its first “booster” doses in September 2021, initially in groups at high risk of severe disease then across the adult population. The BNT162b2 Pfizer-BioNTech vaccine was used initially, with Moderna mRNA-1273 subsequently also used.

Methods

We used the OpenSAFELY-TPP database, covering 40% of English primary care practices and linked to national coronavirus surveillance, hospital episodes, and death registry data, to estimate the effectiveness of boosting with BNT162b2 compared with no boosting in eligible adults who had received two primary course vaccine doses between 16 September and 16 December 2021 when the Delta variant of SARS-CoV-2 was dominant. Follow up was for up to 10 weeks. Each booster recipient was matched with an unboosted control on factors relating to booster priority status and prior immunisation. Additional factors were adjusted for in Cox models estimating hazard ratios (HRs). Outcomes were positive SARS-CoV-2 test, COVID-19 hospitalisation, COVID-19 death and non-COVID-9 death. Booster vaccine effectiveness was defined as 1−HR.

Results

Among 4,352,417 BNT162b2 booster recipients matched with unboosted controls, estimated effectiveness of a booster dose compared with two doses only was 50.7% (95% CI 50.1-51.3) for positive SARS-CoV-2 test, 80.1% (78.3-81.8) for COVID-19 hospitalisation, 88.5% (85.0-91.1) for COVID-19 death, and 80.3% (79.0-81.5) for non-COVID-19 death.

Estimated effectiveness was similar among those who had received a BNT162b2 or ChAdOx1-S two-dose primary vaccination course, but effectiveness against severe COVID-19 was slightly lower in those classified as clinically extremely vulnerable (76.3% (73.1-79.1) for COVID-19 hospitalisation, and 85.1% (79.6-89.1) for COVID-19 death). Estimated effectiveness against each outcome was lower in those aged 18-65 years than in those aged 65 and over.

Conclusion

Our findings are consistent with strong protection of BNT162b2 boosting against positive SARS-CoV-2 test, COVID-19 hospitalisation, and COVID-19 death.
Understanding COVID-19 admissions in the UK; Analysis of Freedom of Information Requests
Authors: Jefferson T. , Brassey J , Heneghan C
Published: June 2022

Background

The progression and severity of the COVID 19 pandemic have been measured based on the daily and total numbers of cases, hospitalisations and deaths. We focused on the nature of hospitalisations from 2020 to 2022.

Methods

We analysed the role played by SARS-CoV-2 in the pandemic in the UK; we lodged FOI requests to Public Health Wales (PHW), Scotland (PHS), and Northern Ireland (PHA NI), the UK Health Security Agency (UKHSA) and NHS England. We asked for all-cause hospital admission monthly numbers reported by days of positivity to SARS-CoV-2 since admission from March 2020. We grouped replies by respondents. We considered any positive tests acquired from day 8 post admission as evidence of in hospital transmission.

Results

PHW, PHS and PHA NI, provided data within two months. The proportion of people admitted who became positive after eight or more days was 33% in Northern Ireland, 24% in Scotland and 45% in Wales. There are seasonal fluctuations reflecting community admissions but no evidence that the proportion of those infected in hospitals reduced over time. No authorities had viral load or symptoms data relating to their datasets. Given the limitations in PCR reporting, it is impossible to know how many “positive” cases were active. UKHSA did not hold the data, and NHS England did not clarify the content of its website.

Conclusion

Aggregate data of “cases of Covid” in hospitals should not be used to inform policy of decision-makers until coordination, and proper interpretation of the dataset are instigated.
Chronic activation of Toll-like receptor 2 induces an ichthyotic skin phenotype
Authors: Tagoe Hephzi , Hassan Sakinah , Youssef Gehad , Heywood Wendy , Mills Kevin , Harper John I. , O’Shaughnessy Ryan F.L.
Published: June 2022

Ichthyosis defines a group of chronic conditions that manifest phenotypically as a thick layer of fish-like scales in response to disorders of cornification and often affects the entire skin. While the gene mutations that lead to ichthyosis are well documented, the actual signalling mechanisms that lead to scaling are poorly characterised, however recent publications suggest that there are common mechanisms active in ichthyotic tissue, and in analogous models of ichthyosis. Combining gene expression analysis of gene-specific shRNA knockdowns of more severe autosomal recessive congenital ichthyoses (ARCI) and proteomic analysis of skin scale from ARCI patients, we identified a common activation of the Toll-like receptor (TLR) 2 pathway. Exogenous activation of TLR2 led to increased expression of important cornified envelope genes and in organotypic culture caused hyperkeratosis. Conversely blockade of TLR2 signalling in ichthyosis patient keratinocytes and our shRNA models reduced the expression of keratin 1, a structural protein overexpressed in ichthyosis scale. A time-course of Tlr2 activation in rat epidermal keratinocytes revealed that although there was rapid initial activation of innate immune pathways, this was rapidly superseded by widespread up-regulation of epidermal differentiation related proteins. Both NFκβ phosphorylation and the Gata3 up-regulation was associated with this switch and Gata3 overexpression was sufficient to increase Keratin 1 expression. Taken together, these data define a dual role for Tlr2 during epidermal barrier repair, that may be a useful therapeutic modality in treating diseases of epidermal barrier dysfunction.
Projecting the futures of plant traits across habitats in Central Europe
Authors: Golivets Marina , Knapp Sonja , Essl Franz , Lenzner Bernd , Latombe Guillaume , Leung Brian , Kühn Ingolf
Published: June 2022

Many plant traits covary with environmental gradients, reflecting shifts in adaptive strategies under changing conditions and thus providing information about potential consequences of future environmental change for vegetation and ecosystem functioning. Despite extensive efforts to map trait–environment relationships, the evidence remains heterogeneous and often conflicting, partially because of insufficient consideration of distinct trait syndromes for certain growth forms and habitats. Moreover, it is unclear whether traits of non-native and native plant taxa respond similarly to environmental gradients, limiting our ability to assess the consequences of future plant invasions. Here, using comprehensive data for Germany and the Czech Republic and a Bayesian multilevel modeling framework, we assessed relationships between three major plant traits (maximum height,Hmax; specific leaf area,SLA; and seed mass,SM) and environmental factors (7 climate variables and percentage of urban land cover) for native and non-native woody and herbaceous plant assemblages across six broad habitat types. We projected the trait change in these assemblages under future environmental change scenarios until 2081–2100 and quantified the change in trait difference between native and non-native plants. Our models depicted multiple trait–environment relationships, with several important differences attributed to biogeographical status and woodiness within and across habitat types. The overall magnitude of trait change is projected to be greater for non-native than native taxa and to increase under more extreme scenarios. Native woody plant assemblages may generally experience an increase across all three traits, whereas woody non-natives may decline inHmaxand increase inSLAandSM. HerbaceousHmaxis expected to increase andSLAto decrease in most habitats. The obtained trait projections highlight the conditions under which non-native plants may prevail over natives and vice versa and can serve as a starting point for projecting future changes in ecosystem functions and services.
Is the production of reactive oxygen and nitrogen species by macrophages associated with better infectious control in the experimental disseminated and pulmonary mucormycosis?
Authors: dos Santos Amanda Ribeiro , Fraga-Silva Thais Fernanda , Almeida Donanzam Débora de Fátima , Finatto Angela Carolina , Marchetti Camila , Andrade Maria Izilda , de Arruda Olavo Speranza , de Arruda Maria Sueli Parreira , Venturini James
Published: June 2022

Different levels of resistance againstRhizopus oryzaeinfection have been observed between inbred (BALB/c) and outbred (Swiss) mice, with is associated with the genetic background of each mouse strain. Considering that macrophages play an important role in host resistance toRhizopusspecies, we use the different infectious outcomes observed in experimental mucormycosis to identify the most efficient macrophages responses pattern againstR. oryzae in vitroandin vivo. For this, we compared BALB/c and Swiss macrophage activity pre-and-post intravenous or intratrachealR. oryzaeinfections. Production of hydrogen peroxide (H2O2) and nitric oxide (NO) was determined in cultures of peritoneal (PMΦ) or alveolar macrophages (AMΦ) challenged, or not, with heat-killed spores ofR. oryzae. Levels of TNF-α and IL-10 were also measured to enhance our findings. Naïve PMΦ from BALB/c increased the production of H2O2, TNF-α, and IL-10 in the presence of heat-killed spores ofR. oryzae, while naïve PMΦ from Swiss mice was less responsive. Naïve AMΦ from two strains of mice were less reactive to heat-killed spores ofR. oryzaethan PMΦ. On 30 days ofR. oryzaeintravenous infection, lower fungal load in BALB/c strain of mice was accompanied by higher production of H2O2by PMΦ when compared with Swiss mice. Differently, AMΦ from BALB/c mice showed higher production of NO, TNF-α, and IL-10 after 7 days of intratracheal infection and after 30 days, lower fungal load, when compared with Swiss mice. According to the set of experiments performed, our findings reveal that independently of mice strain, PMΦ is more reactive againstR. oryzaein the first contact than AMΦ. In addition, increased PMΦ production of H2O2at the end of disseminated infection is related to efficient fungal clearance observed in resistant (BALB/c). Our findings provide new evidence to understand the parasite-hosts relationship in mucormycosis.
A novel event-triggered adaptive tracking control framework for a manipulator with aperiodic neural network estimation
Authors: Gao Jie
Published: June 2022

Purpose

The purpose of this study is developing the minimum parameter learning law for the weight updating, which reduces the updating of neural network (NN) weight only at triggering instants and makes a trade-off between the estimation accuracy and triggering frequency such that the computing complexity can be decreased. Besides that, a novel “soft” method is first constructed for the control updating at the triggered instants, to reduce the chattering effect of discontinued renewal of control. Addressing to the proposed control and updating method, a novel dead-zone condition with variable boundary about the triggered control signal is derived to ensure the positivity of adjacent execution intervals.

Design/methodology/approach

In this paper, to achieve the motion tracking of manipulator with uncertainty of system dynamics and the communication constraints in the control-execution channel, an adaptive event-triggered controller with NN identification is constructed to improve the transmission efficiency of control on the premise of the guaranteed performance. In the proposed method, the NN with intermittent updating is proposed to perform the uncertain approximation with the saved computation, and the triggered mechanism is constructed to regulate the transportation of the signal in the channel of controller-to-actuator.

Findings

According to the impulsive Lyapunov function, it can be proved that all the signals are semi-global uniformly ultimately bounded, and the positivity of adjacent execution intervals is also guaranteed by the proposed method. In addition, the chattering effect of control updating at the jumping instants can be relieved by the proposed “soft” mechanism, such that the control accuracy and stability can be guaranteed. Experiments on the JACO2 real manipulator are carried out to verify the effectiveness of the proposed scheme.

Originality/value

To the best of the author’s knowledge, this study is firstly to propose a “soft” method to reduce the chattering effect caused by discontinuous updating. Addressing to the updating method designed above, a novel dead-zone condition with variable threshold and boundary is first constructed to ensure the positivity of execution intervals.
Implementing halal logistics in a non-Muslim-dominant environment: a proposal for reengineering the business processes in two stages
Authors: Ziegler Yvonne , Uli Vincenzo , Tatari Mahmoud
Published: June 2022

Purpose

The purpose of this paper, positioned in the halal logistics research domain, is to bridge the gap between the theory of halal logistics and halal logistics' empirical implementation through a business process reengineering (BPR) project in the context of a major European airport (i.e. Frankfurt Airport, Fraport AG).

Design/methodology/approach

An in-depth case study approach has been adopted in the authors' business processes reengineering proposal. Prior investigations on the topic maintained that “business process analysis and activity elimination” (BP and AE) and “problem analysis” (PA) are the most widespread approaches when the prominent business reengineering dimension under analysis is the specific process/task. Consistently, the authors adopted a six-step BP&AE-based model in order to implement the halal logistics requirements in the context of an air cargo supply chain.

Findings

This paper addresses fundamental issues about the analysis and the redesign of air cargo processes when halal shipments are taken into account. Conceptual breakthroughs of new processes are suggested. The paper sheds light on potential issues which may arise when adapting the extant air cargo processes to halal logistics guidelines. In addition, the paper suggests an appropriate resolution scheme articulated in two stages of progressively higher compliance to halal logistics according to the Malaysian standards (MS).

Research limitations/implications

The outcome of this work has implications for practitioners, researchers, and transport associations. For practitioners, the study offers an immediately applicable implementation plan which is ready to be discussed with all agents involved in the business reengineering (BR) process. For researchers, the study offers a basis for future halal logistics reengineering projects, both from a theoretical and from an empirical standpoint. Finally, the collaboration of transport associations will become mandatory due to an update of the International Air Transport Association (IATA) code system that includes a dedicated halal code, “HAL”, for halal air cargo shipments.

Originality/value

The concept of halal logistics is still in the infant stage and there is a complete lack of academic publications, especially empirical implementations of halal logistics principles. The authors' project provides detailed guidelines to help air cargo operators operating in non-Muslim-dominant countries to reengineer their internal processes and, in doing so, to comply with halal logistics and principles.
How do human relationships change in the digital environment after COVID-19 pandemic? The road towards agility
Authors: Bellis Paola , Trabucchi Daniel , Buganza Tommaso , Verganti Roberto
Published: June 2022

Purpose

The coronavirus disease 2019 (COVID-19) pandemic has led to a global digitalization of organizational activities: the pandemic forced people and organizations to profoundly review values, purposes and norms. However, the research on how digital technologies impact human relationships and interactions at work results fragmented. Still, the importance of understanding which behaviors and norms enhance social interactions and organizational performances in digital environments remains critical, especially after COVID-19 advent. Therefore, this study explores how human relationships change in a wholly digital environment and what to expect for the new normal.

Design/methodology/approach

The study first explores the research gap through a systematic literature review to clearly understand what emerged so far. Second, through semi-structured interviews and a focus group, an empirical analysis was conducted.

Findings

Findings suggest that both work and emotional dimensions are crucial to nurturing human relationships in a digital environment. More precisely, the study unveils the need for innovative leaders to review their approaches to communication and the work experience and consider the emotional dimension in terms of community purpose and individual well-being, while identifying rituals as an overlapping tool. Finally, the authors propose a parallelism between these results and the agile revolution to inspire leaders to rethink their leadership and behaviors getting closer to the agile approach, which may represent a valuable way to rethink human relations in our professional environment.

Originality/value

The paper sheds light on an ongoing phenomenon that touches the lives of each organizational actor. The two-step structure hopes to provide both a structured base of the knowledge developed to date, proposing a systematic view of what has been studied since the outbreak of the pandemic to date and to provide insights for future developments.
(No) country for old men? Intergenerational welfare distribution across welfare state regimes
Authors: Chybalski Filip , Orosz Agnes , Kurach Radosław
Published: June 2022

Purpose

The article examines the interplay between welfare state regimes and the distribution of welfare between generations.

Design/methodology/approach

Using data from 2017 for 24 European countries on six standard of living dimensions, the authors investigate the intergenerational welfare distribution in a two-stage procedure: (1) the authors compare the intergenerational welfare distribution across welfare state regimes using their existing typologies and find a moderate nexus. Therefore, (2) the authors employ clustering procedure to look for a new classification that would better reflect the cross-country variation in the intergenerational welfare division.

Findings

The authors find a complex relationship between the welfare state model and welfare distribution across generations and identify the policy patterns that shape it. Continental and liberal regimes are quite similar in these terms and favour the elderly generation. Social-democratic and CEE regimes seem to be a bit more balanced. COVID-19 pandemic will probably increase the intergenerational imbalance in terms of welfare distribution in favour of the elderly.

Originality/value

In contrast to the majority of previous studies, which employ inputs (social expenditures) or outputs (benefits, incomes), the authors use intergenerational balance indicators reflecting living conditions of a given generation as compared to the reference point defined as an average situation of all generations.