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Mitral valve prolapse is a common valve disorder that usually has a benign prognosis unless there is significant regurgitation or LV impairment. However, a subset of patients are at an increased risk of ventricular arrhythmias and sudden cardiac death, which has led to the recognition of "arrhythmic mitral valve prolapse" as a clinical entity. Emerging risk factors include mitral annular disjunction and myocardial fibrosis. While echocardiography remains the primary method of evaluation, cardiac magnetic resonance has become crucial in managing this condition. Cine magnetic resonance sequences provide accurate characterization of prolapse and annular disjunction, assessment of ventricular volumes and function, identification of early dysfunction and remodeling, and quantitative assessment of mitral regurgitation when integrated with flow imaging. However, the unique strength of magnetic resonance lies in its ability to identify tissue changes. T1 mapping sequences identify diffuse fibrosis, in turn related to early ventricular dysfunction and remodeling. Late gadolinium enhancement sequences detect replacement fibrosis, an independent risk factor for ventricular arrhythmias and sudden cardiac death. There are consensus documents and reviews on the use of cardiac magnetic resonance specifically in arrhythmic mitral valve prolapse. However, in this article, we propose an algorithm for the broader use of cardiac magnetic resonance in managing this condition in various scenarios. Future advancements may involve implementing techniques for tissue characterization and flow analysis, such as 4D flow imaging, to identify patients with ventricular dysfunction and remodeling, increased arrhythmic risk, and more accurate grading of mitral regurgitation, ultimately benefiting patient selection for surgical therapy., (© 2024 Wiley Periodicals LLC.)

Background and Aims: Primary biliary cholangitis is an autoimmune biliary disease characterized by injury of bile ducts, eventually leading to cirrhosis and death. In most cases, anti-mitochondrial antibodies and persistently elevated serum alkaline phosphatase are the basis for the serological diagnosis. Anti-nuclear antibodies are also useful and may indicate a more aggressive diseases course. In patients in which anti-mitochondrial antibodies are not detected, an accurate diagnosis requires liver histology. This study aims at identifying specific biomarkers for the serological diagnosis of primary biliary cholangitis., Methods: Sera from patients affected by primary biliary cholangitis, primary sclerosing cholangitis, hepatitis C virus (with and without cryoglobulinemia), hepatocarcinoma and healthy donors were tested on a protein array representing 1658 human proteins. The most reactive autoantigens were confirmed by DELFIA analysis on expanded cohorts of the same mentioned serum classes, and on autoimmune hepatitis sera, using anti-PDC-E2 as reference biomarker., Results: Two autoantigens, SPATA31A3 and GARP, showed high reactivity with primary biliary cholangitis sera, containing or not anti-mitochondrial antibodies. Their combination with PDC-E2 allowed to discriminate primary biliary cholangitis from all tested control classes with high sensitivity and specificity. We found that GARP expression is upregulated upon exposure to biliary salts in human cholangiocytes, an event involving EGFR and insulin pathways. GARP expression was also detected in biliary duct cells of PBC patients., Conclusions: This study highlighted SPATA31A3 and GARP as new biomarkers for primary biliary cholangitis and unravelled molecular stimuli underlying GARP expression in human cholangiocytes., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

In this work, a simple approach to prepare luminescent poly(3-hexylthiophene)-CdS nanocomposites to be employed in organic light emitting devices (OLED) devices is reported. The nucleation and growth of CdS nanoparticles were obtained by the thermolysis of a single Cd and S precursor dispersed in the polymer at three different temperatures of annealing: 240, 265, and 300°C. In this way, it was possible to compare the properties of nanocomposites containing nanoparticles with different sizes. X-ray diffraction and transmission electron microscopy analyses confirmed the formation of CdS nanoparticles and gave information about the size, distribution, and morphology of the nanoparticles; monodispersive and very small nanoparticles with diameters below 2.5 nm were obtained at 240°C. The application of such nanocomposites as emitting layers in OLED devices is discussed. Enhanced electrooptical properties were observed for the device containing the nanocomposite annealed at 240°C with respect to the pure polymer based device. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011 [ABSTRACT FROM AUTHOR]

Posidonia oceanica (L) Delile, a seagrass endemic of the Mediterranean sea, provides food and shelter to marine organisms. As environment contamination and variation in physico-chemical parameters may compromise the survival of the few Posidonia genotypes living in the Mediterranean, comprehending the molecular mechanisms controlling Posidonia growth and development is increasingly important. In the present study the properties of ion channels in P. oceanica plasma membranes studied by the patch-clamp technique in protoplasts obtained from the young non-photosynthetic leaves were investigated. In protoplasts that were presumably originated from sheath cells surrounding the vascular bundles of the leaves, an outward-rectifying time-dependent channel with a single channel conductance of 58 ± 2 pS which did not inactivate, was selective for potassium and impermeable to monovalent cations such as Na+, Li+ and Cs+ was identified. In the same protoplasts, an inward-rectifying channel that has a time-dependent component with single channel conductance of the order of 10 pS, a marked selectivity for potassium and no permeation to sodium was also identified, as was a third type of channel that did not display any ionic selectivity and was reversibly inhibited by tetraethylammonium and lanthanum. A comparison of Posidonia channel characteristics with channels identified in terrestrial plants and other halophytic plants is included. [ABSTRACT FROM AUTHOR]

Recent studies have described chromosome 2p gain as a recurrent lesion in chronic lymphocytic leukemia (CLL). We investigated the 2p gain and its relationship with common prognostic biomarkers in a prospective series of 69 clinical monoclonal B-cell lymphocytosis (cMBL) and 218 early stage (Binet A) CLL patients. The 2p gain was detected by FISH in 17 patients (6%, 16 CLL, and 1 cMBL) and further characterized by single nucleotide polymorphism-array. Overall, unfavorable cytogenetic deletions, i.e., del(11)(q23) and del(17)(p13) (P = 0.002), were significantly more frequent in 2p gain cases, as well as unmutated status of IGHV (P < 1 × 10(-4) ) and CD38 (P < 1 × 10(-4) ) and ZAP-70 positive expression (P = 0.003). Furthermore, 2p gain patients had significantly higher utilization of stereotyped B-cell receptors compared with 2p negative patients (P = 0.009), and the incidence of stereotyped subset #1 in 2p gain patients was significantly higher than that found in the remaining CLLs (P = 0.031). Transcriptional profiling analysis identified several genes significantly upregulated in 2p gain CLLs, most of which mapped to 2p. Among these, NCOA1 and ROCK2 are known for their involvement in tumor progression in several human cancers, whereas among those located in different chromosomes, CAV1 at 7q31.1 has been recently identified to play a critical role in CLL progression. Thus, 2p gain can be present since the early stages of the disease, particularly in those cases characterized by other poor prognosis markers. The finding of genes upregulated in the cells with 2p gain provides new insights to define the pathogenic role of this lesion., (Copyright © 2012 Wiley Periodicals, Inc.)

Background: We clinically and genetically evaluated a Taiwanese boy presenting with developmental delay, organomegaly, hypogammaglobulinemia and hypopigmentation without osteopetrosis. Whole‐exome sequencing revealed a de novo gain‐of‐function variant, p.Tyr715Cys, in the C‐terminal domain of ClC‐7 encoded by CLCN7. Methods: Nicoli et al. (2019) assessed the functional impact of p.Tyr715Cys by heterologous expression in Xenopus oocytes and evaluating resulting currents. Results: The variant led to increased outward currents, indicating it underlies the patient's phenotype of lysosomal hyperacidity, storage defects and vacuolization. This demonstrates the crucial physiological role of ClC‐7 antiporter activity in maintaining appropriate lysosomal pH. Conclusion: Elucidating mechanisms by which CLCN7 variants lead to lysosomal dysfunction will advance understanding of genotype–phenotype correlations. Identifying modifier genes and compensatory pathways may reveal therapeutic targets. Ongoing functional characterization of variants along with longitudinal clinical evaluations will continue advancing knowledge of ClC‐7's critical roles and disease mechanisms resulting from its dysfunction. Expanded cohort studies are warranted to delineate the full spectrum of associated phenotypes. [ABSTRACT FROM AUTHOR]

COVID‐19 is heterogeneous; therefore, it is crucial to identify early biomarkers for adverse outcomes. Extracellular vesicles (EV) are involved in the pathophysiology of COVID‐19 and have both negative and positive effects. The objective of this study was to identify the potential role of EV in the prognostic stratification of COVID‐19 patients. A total of 146 patients with severe or critical COVID‐19 were enrolled. Demographic and comorbidity characteristics were collected, together with routine haematology, blood chemistry and lymphocyte subpopulation data. Flow cytometric characterization of the dimensional and antigenic properties of COVID‐19 patients' plasma EVs was conducted. Elastic net logistic regression with cross‐validation was employed to identify the best model for classifying critically ill patients. Features of smaller EVs (i.e. the fraction of EVs smaller than 200 nm expressing either cluster of differentiation [CD] 31, CD 140b or CD 42b), albuminemia and the percentage of monocytes expressing human leukocyte antigen DR (HLA‐DR) were associated with a better outcome. Conversely, the proportion of larger EVs expressing N‐cadherin, CD 34, CD 56, CD31 or CD 45, interleukin 6, red cell width distribution (RDW), N‐terminal pro‐brain natriuretic peptide (NT‐proBNP), age, procalcitonin, Charlson Comorbidity Index and pro‐adrenomedullin were associated with disease severity. Therefore, the simultaneous assessment of EV dimensions and their antigenic properties complements laboratory workup and helps in patient stratification. [ABSTRACT FROM AUTHOR]

The production of high‐quality recombinant proteins is critical to maintaining a continuous supply of biopharmaceuticals, such as therapeutic antibodies. Engineering mammalian cell factories presents a number of limitations typically associated with the proteotoxic stress induced upon aberrant accumulation of off‐pathway protein folding intermediates, which eventually culminate in the induction of apoptosis. In this review, we will discuss advances in cell engineering and their applications at different hierarchical levels of control of the expression of recombinant proteins, from transcription and translational to posttranslational modifications and subcellular trafficking. We also highlight challenges and unique opportunities to apply modern synthetic biology tools to the design of programmable cell factories for improved biomanufacturing of therapeutic proteins. [ABSTRACT FROM AUTHOR]

Reorganization of cell organelle‐deprived host red blood cells by the apicomplexan malaria parasite Plasmodium falciparum enables their cytoadherence to endothelial cells that line the microvasculature. This increases the time red blood cells infected with mature developmental stages remain within selected organs such as the brain to avoid the spleen passage, which can lead to severe complications and cumulate in patient death. The Maurer's clefts are a novel secretory organelle of parasite origin established by the parasite in the cytoplasm of the host red blood cell in order to facilitate the establishment of cytoadherence by conducting the trafficking of immunovariant adhesins to the host cell surface. Another important function of the organelle is the sorting of other proteins the parasite traffics into its host cell. Although the organelle is of high importance for the pathology of malaria, additional putative functions, structure, and genesis remain shrouded in mystery more than a century after its discovery. In this review, we highlight our current knowledge about the Maurer's clefts and other novel secretory organelles established within the host cell cytoplasm by human‐pathogenic malaria parasites and other parasites that reside within human red blood cells. [ABSTRACT FROM AUTHOR]

Objective: This study investigates the relations of resilience with coping, personality traits, emotional intelligence, sense of coherence and maladaptive personality traits. Method: The study employs network analysis techniques to the study of resilience, showcasing how these methods can estimate a model that is simple to interpret while still retaining the most important relations and that can even suggest the direction of causality despite using a cross‐sectional design (N = 305). Results: The results highlight several important variables that should be considered for fostering resilience, foremost among them the use of positive reappraisal coping, sense of coherence, and the social management aspect of emotional intelligence. Conclusions: The results successfully replicated known associations between resilience and other psychological constructs (emotional intelligence, personality, sense of coherence, coping) and shed light on relations between resilience and maladaptive personality traits. Network analysis considered all these constructs together, so as to take into account the complex pattern of relations between them and offer a bird's eye view of the whole network of associations centred on resilience. The resulting model is parsimonious and easy to interpret while still striving to preserve the complexity of the variables' interrelations. [ABSTRACT FROM AUTHOR]

Summary: PIN‐FORMED auxin efflux transporters, a subclass of which is plasma membrane‐localised, mediate a variety of land‐plant developmental processes via their polar localisation and subsequent directional auxin transport. We provide the first characterisation of PIN proteins in liverworts using Marchantia polymorpha as a model system. Marchantia polymorpha possesses a single PIN‐FORMED gene, whose protein product is predicted to be plasma membrane‐localised, MpPIN1.To characterise MpPIN1, we created loss‐of‐function alleles and produced complementation lines in both M. polymorpha and Arabidopsis. In M. polymorpha, gene expression and protein localisation were tracked using an MpPIN1 transgene encoding a translationally fused fluorescent protein.Overexpression of MpPIN1 can partially complement loss of an orthologous gene, PIN‐FORMED1, in Arabidopsis. In M. polymorpha, MpPIN1 influences development in numerous ways throughout its life cycle. Most notably, MpPIN1 is required to establish gemmaling dorsiventral polarity and for orthotropic growth of gametangiophore stalks, where MpPIN1 is basally polarised.PIN activity is largely conserved within land plants, with PIN‐mediated auxin flow providing a flexible mechanism to organise growth. Specifically, PIN is fundamentally linked to orthotropism and to the establishment of de novo meristems, the latter potentially involving the formation of both auxin biosynthesis maxima and auxin‐signalling minima. [ABSTRACT FROM AUTHOR]

Eukaryotic initiation factor 6 (eIF6) is necessary for ribosome biogenesis and translation, but eIF6 has been poorly elucidated in insects. Phylogenetic analysis demonstrated that eIF6 originated from one ancestral gene among animals and exhibited specific duplication in Tribolium, yielding three homologues in Tribolium castaneum, eIF6, eIF6‐like 1 (eIF6l1), and eIF6‐like 2 (eIF6l2). It was found that eIF6 was highly expressed in the embryonic and early adult stages, eIF6l1 had peak expression at the adult stage, and eIF6l2 showed peak expression in late adults of T. castaneum. Tissue‐specific analyses in late‐stage larvae demonstrated that eIF6 was abundantly expressed in all tissues, while eIF6l1 and eIF6l2 had the highest expression in the gut and the lowest expression in the head of T. castaneum. Knockdown of eIF6 caused precocious pupation and eclosion, impaired ovary and testis development and completely repressed egg production. The expression levels of vitellogenin 1 (Vg1), Vg2 and Vg receptor (VgR) significantly decreased in ds‐eIF6 females 5 days post‐adult emergence. Silencing eIF6 activated ecdysteroid biosynthesis and juvenile hormone degradation but reduced the activity of insulin signalling in T. castaneum, which might mediate its roles in metamorphosis, reproduction and gene expression regulation. However, silence of eIF6l1 or eIF6l2 had no effects on metamorphosis and reproduction in T. castaneum. This study provides comprehensive information for eIF6 evolution and function in the insect. [ABSTRACT FROM AUTHOR]

Background and Purpose: Pharmacological inhibitors of TMEM16A (ANO1), a Ca2+‐activated Cl− channel, are important tools of research and possible therapeutic agents acting on smooth muscle, airway epithelia and cancer cells. We tested a panel of TMEM16A inhibitors, including CaCCinh‐A01, niclosamide, MONNA, Ani9 and niflumic acid, to evaluate their possible effect on intracellular Ca2+. Experimental Approach: We recorded cytosolic Ca2+ increase elicited with UTP, ionomycin or IP3 uncaging. Key Results: Unexpectedly, we found that all compounds, except for Ani9, markedly decreased intracellular Ca2+ elevation induced by stimuli acting on intracellular Ca2+ stores. These effects were similarly observed in cells with and without TMEM16A expression. We investigated in more detail the mechanism of action of niclosamide and CaCCinh‐A01. Acute addition of niclosamide directly increased intracellular Ca2+, an activity consistent with inhibition of the SERCA pump. In contrast to niclosamide, CaCCinh‐A01 did not elevate intracellular Ca2+, thus implying a different mechanism of action, possibly a block of inositol triphosphate receptors. Conclusions and Implications: Most TMEM16A inhibitors are endowed with indirect effects mediated by alteration of intracellular Ca2+ handling, which may in part preclude their use as TMEM16A research tools. [ABSTRACT FROM AUTHOR]

We review recent literature that proposes to adapt ideas from classical model based optimal design of experiments to problems of data selection of large datasets. Special attention is given to bias reduction and to protection against confounders. Some new results are presented. Theoretical and computational comparisons are made. [ABSTRACT FROM AUTHOR]

Background: Maternal-fetal immunology is intricate, and the effects of mRNA-S maternal vaccination on immune regulation at the maternal-fetal interface require further investigation. Our study endeavors to elucidate these immunological changes, enhancing our comprehension of maternal and fetal health outcomes. By analyzing immune profiles and cytokine responses, we aim to provide valuable insights into the impact of mRNA-S vaccination on the delicate balance of immune regulation during pregnancy, addressing critical questions in the field of reproductive pharmacology., Objectives: This investigation sought to examine the prospective influence of mRNA-S-based vaccines and extracellular vesicles (EVs) containing the Spike (S) protein at the maternal-fetal interface. Our primary emphasis was on evaluating their effects on maternal decidua cells and fetal chorion trophoblast cells (hFM-CTCs)., Methods: We validated the generation of EVs containing the S protein from small human airway epithelial cell lines (HSAECs) following mRNA-S vaccine exposure. We assessed the expression of angiotensin-converting enzyme 2 (ACE2) gene and protein in fetal membranes and the placenta, with specific attention to decidual cells and fetal membrane chorion cells. To assess cellular functionality, these cells were exposed to both recombinant S protein and EVs loaded with S proteins (eSPs)., Results: Our findings revealed that cells and EVs subjected to mRNA-S-based vaccination exhibited altered protein expression levels of S proteins. At the feto-maternal interface, both placental and fetal membrane tissues demonstrated similar ACE-2 expression levels. Among individual cellular layers, syncytiotrophoblast cells in the placenta and chorion cells in the fetal membrane exhibited elevated ACE-2 expression. Notably, EVs derived from HSAECs activated the MAPK pathway in decidual cells. Additionally, decidual cells displayed a substantial increase in gene expression of chemokines like CXCL-10 and CXCL-11, as well as proinflammatory cytokines such as IL-6 in response to eSPs. However, the levels of Ccl-2 and IL-1β remained unchanged in decidual cells under the same conditions. Conversely, hFM-CTCs demonstrated significant alterations in the proinflammatory cytokines and chemokines with respect to eSPs., Conclusion: In conclusion, our study indicates that mRNA-S-based maternal vaccination during pregnancy may influence the maternal-fetal interface's COVID-19 interaction and immune regulation. Further investigation is warranted to assess safety and implications., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Adult neural progenitor cells (aNPCs) ensure lifelong neurogenesis in the mammalian hippocampus. Proper regulation of aNPC fate has thus important implications for brain plasticity and healthy aging. Piwi proteins and the small noncoding RNAs interacting with them (piRNAs) have been proposed to control memory and anxiety, but the mechanism remains elusive. Here, we show that Piwil2 (Mili) is essential for proper neurogenesis in the postnatal mouse hippocampus. RNA sequencing of aNPCs and their differentiated progeny reveal that Mili and piRNAs are dynamically expressed in neurogenesis. Depletion of Mili and piRNAs in the adult hippocampus impairs aNPC differentiation toward a neural fate, induces senescence, and generates reactive glia. Transcripts modulated upon Mili depletion bear sequences complementary or homologous to piRNAs and include repetitive elements and mRNAs encoding essential proteins for proper neurogenesis. Our results provide evidence of a critical role for Mili in maintaining fitness and proper fate of aNPCs, underpinning a possible involvement of the piRNA pathway in brain plasticity and successful aging. Synopsis: Functions of the Piwi proteins and Piwi‐interacting RNAs have been related to memory and neurodegeneration, but mechanisms remain elusive. This study reports that Piwil2 safeguards aNPC fitness and proper neurogenesis in the postnatal mouse hippocampus. Piwil2 and piRNAs are present in adult neural progenitor cells (aNPCs) of the postnatal mouse hippocampus, and their expression is reduced in neurons.Depletion of Piwil2 in aNPCs induces senescence, impairs neurogenesis, and increases the generation of reactive glia.Depletion of Piwil2 occurs in aged aNPCs and upon induction of aNPC reactivity.The piRNA pathway in neurogenesis targets transcripts from repetitive elements and genes encoding regulators of senescence, neuroinflammation, oxidative stress, and circadian mechanism. [ABSTRACT FROM AUTHOR]

Motivation: Medical image analysis involves a series of tasks used to assist physicians in qualitative and quantitative analyses of lesions or anatomical structures which can significantly improve the accuracy and reliability of medical diagnoses and prognoses. Traditionally, these tedious tasks were finished by experienced physicians or medical physicists and were marred with two major problems, low efficiency and bias. In the past decade, many machine learning methods have been applied to accelerate and automate the image analysis process. Compared to the enormous deployments of supervised and unsupervised learning models, attempts to use reinforcement learning in medical image analysis are still scarce. We hope that this review article could serve as the stepping stone for related research in the future. Significance: We found that although reinforcement learning has gradually gained momentum in recent years, many researchers in the medical analysis field still find it hard to understand and deploy in clinical settings. One possible cause is a lack of well‐organized review articles intended for readers without professional computer science backgrounds. Rather than to provide a comprehensive list of all reinforcement learning models applied in medical image analysis, the aim of this review is to help the readers formulate and solve their medical image analysis research through the lens of reinforcement learning. Approach & Results: We selected published articles from Google Scholar and PubMed. Considering the scarcity of related articles, we also included some outstanding newest preprints. The papers were carefully reviewed and categorized according to the type of image analysis task. In this article, we first reviewed the basic concepts and popular models of reinforcement learning. Then, we explored the applications of reinforcement learning models in medical image analysis. Finally, we concluded the article by discussing the reviewed reinforcement learning approaches' limitations and possible future improvements. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID‐19), caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), has wrought havoc on the world economy and people's daily lives. The inability to comprehensively control COVID‐19 is due to the difficulty of early and timely diagnosis, the lack of effective therapeutic drugs, and the limited effectiveness of vaccines. The body contains billions of extracellular vesicles (EVs), which have shown remarkable potential in disease diagnosis, drug development, and vaccine carriers. Recently, increasing evidence has indicated that EVs may participate or assist the body in defence, antagonism, recovery and acquired immunity against SARS‐CoV‐2. On the one hand, intercepting and decrypting the general intelligence carried in circulating EVs from COVID‐19 patients will provide an important hint for diagnosis and treatment; on the other hand, engineered EVs modified by gene editing in the laboratory will amplify the effectiveness of inhibiting infection, replication and destruction of ever‐mutating SARS‐CoV‐2, facilitating tissue repair and making a better vaccine. To comprehensively understand the interaction between EVs and SARS‐CoV‐2, providing new insights to overcome some difficulties in the diagnosis, prevention and treatment of COVID‐19, we conducted a rounded review in this area. We also explain numerous critical challenges that these tactics face before they enter the clinic, and this work will provide previous 'meet change with constancy' lessons for responding to future similar public health disasters. Extracellular vesicles (EVs) provide a 'meet changes with constancy' strategy to combat SARS‐CoV‐2 that spans defence, antagonism, recovery, and acquired immunity.Targets for COVID‐19 diagnosis, therapy, and prevention of progression may be found by capture of the message decoding in circulating EVs.Engineered and biomimetic EVs can boost effects of the natural EVs, especially anti‐SARS‐CoV‐2, targeted repair of damaged tissue, and improvement of vaccine efficacy. [ABSTRACT FROM AUTHOR]

Summary: While recent studies on automated multilabel chest X‐ray (CXR) images classification have shown remarkable progress in leveraging complicated network and attention mechanisms, the automated detection on chest radiographs is still challenging because the pathological patterns are usually highly diverse in their sizes and locations. The CNN model will suffer from the complicated background and high diversity of diseases, which reduce the generalization and performance of the model. To solve these problems, we propose a dual‐distribution consistency (DDC) model, which increases the consistency from two aspects, that is, feature‐level and label‐level. This model integrates two novel loss functions: multilabel response consistency (MRC) loss and distribution consistency (DC) loss. Specifically, we use the original image and its transformed image as inputs to imitate different views of CXR images. The MRC loss encourages the multilabel‐wise attention maps to be consistent between the original CXR image and its transformed counterpart. And the DC loss can force their output probability distributions to be uniform. In this manner, we can make sure that the model can learn discriminative features by using a different view of CXR images. Experiments conducted on the ChestX‐ray14 dataset show the effectiveness of the proposed method. [ABSTRACT FROM AUTHOR]

A key feature of C4 Kranz anatomy is the presence of an enlarged, photosynthetically highly active bundle sheath whose cells contain large numbers of chloroplasts. With the aim to identify novel candidate regulators of C4 bundle sheath development, we performed an activation tagging screen with Arabidopsis thaliana. The reporter gene used encoded a chloroplast‐targeted GFP protein preferentially expressed in the bundle sheath, and the promoter of the C4 phosphoenolpyruvate carboxylase gene from Flaveria trinervia served as activation tag because of its activity in all chlorenchymatous tissues of A. thaliana. Primary mutants were selected based on their GFP signal intensity, and one stable mutant named kb‐1 with a significant increase in GFP fluorescence intensity was obtained. Despite the increased GFP signal, kb‐1 showed no alterations to bundle sheath anatomy. The causal locus, AT1G29480, is specific to the Brassicaceae with its second exon being conserved. Overexpression and reconstitution studies confirmed that AT1G29480, and specifically its second exon, were sufficient for the enhanced GFP phenotype, which was not dependent on translation of the locus or its parts into protein. We conclude, therefore, that the AT1G29480 locus enhances the GFP reporter gene activity via an RNA‐based mechanism. [ABSTRACT FROM AUTHOR]

Abnormal glycoconjugates have distinctly been recognized as potential biomarkers for cancer diagnosis. A great deal of attention has been focused on Tn antigen, an oversimplified mucin‐1 O‐glycan, over‐expressed in different cancers. Herein, we investigate the possibility to replace the use of anti‐Tn monoclonal antibodies with an innovative class of catecholamine‐based Molecularly Imprinted Polymers (MIPs), emerging in recent years as promising tools for bioanalytical applications. MIPs are synthetic receptors characterized by high sensitivity and specificity towards the imprinted target. Here, original polynorepinephrine‐based MIPs coupled to Surface Plasmon Resonance biosensing for Tn antigen recognition are reported. We have verified the imprinting and binding capacity of these MIPs towards very small antigenic entities, represented by the natural Tn antigen and the TnThr mimetic 1 (conjugated to BSA or linked to a MUC1 hexapeptide analogue), and compared the biosensor performances with an anti‐Tn monoclonal antibody. The results clearly display the effectiveness of the pursued imprinting strategies. [ABSTRACT FROM AUTHOR]

Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection is persistently threatening the lives of thousands of individuals globally. It triggers pulmonary oedema, driving to dyspnoea and lung failure. Viral infectivity of coronavirus disease 2019 (COVID‐19) is a genuine challenge due to the mutagenic genome and mysterious immune‐pathophysiology. Early reports highlighted that extracellular vesicles (exosomes, Exos) work to enhance COVID‐19 progression by mediating viral transmission, replication and mutations. Furthermore, recent studies revealed that Exos derived from immune cells play an essential role in the promotion of immune cell exhaustion by transferring regulatory lncRNAs and miRNAs from exhausted cells to the active cells. Fortunately, there are great chances to modulate the immune functions of Exos towards a sustained repression of COVID‐19. Engineered Exos hold promising immunotherapeutic opportunities for remodelling cytotoxic T cells' function. Immune cell‐derived Exos may trigger a stable epigenetic repression of viral infectivity, restore functional cytokine‐producing T cells and rebalance immune response in severe infections by inducing functional T regulatory cells (Tregs). This review introduces a view on the current outcomes of immunopathology, and immunotherapeutic applications of immune cell‐derived Exos in COVID‐19, besides new perspectives to develop novel patterns of engineered Exos triggering novel anti‐SARS‐CoV‐2 immune responses. [ABSTRACT FROM AUTHOR]

Background: Total lung volume is an important quantitative biomarker and is used for the assessment of restrictive lung diseases. Purpose: In this study, we investigate the performance of several deep‐learning approaches for automated measurement of total lung volume from chest radiographs. Methods: About 7621 posteroanterior and lateral view chest radiographs (CXR) were collected from patients with chest CT available. Similarly, 928 CXR studies were chosen from patients with pulmonary function test (PFT) results. The reference total lung volume was calculated from lung segmentation on CT or PFT data, respectively. This dataset was used to train deep‐learning architectures to predict total lung volume from chest radiographs. The experiments were constructed in a stepwise fashion with increasing complexity to demonstrate the effect of training with CT‐derived labels only and the sources of error. The optimal models were tested on 291 CXR studies with reference lung volume obtained from PFT. Mean absolute error (MAE), mean absolute percentage error (MAPE), and Pearson correlation coefficient (Pearson's r) were computed. Results: The optimal deep‐learning regression model showed an MAE of 408 ml and an MAPE of 8.1% using both frontal and lateral chest radiographs as input. The predictions were highly correlated with the reference standard (Pearson's r = 0.92). CT‐derived labels were useful for pretraining but the optimal performance was obtained by fine‐tuning the network with PFT‐derived labels. Conclusion: We demonstrate, for the first time, that state‐of‐the‐art deep‐learning solutions can accurately measure total lung volume from plain chest radiographs. The proposed model is made publicly available and can be used to obtain total lung volume from routinely acquired chest radiographs at no additional cost. This deep‐learning system can be a useful tool to identify trends over time in patients referred regularly for chest X‐ray. [ABSTRACT FROM AUTHOR]

The pandemic of COVID‐19 caused worldwide concern. Due to the lack of appropriate medications and the inefficiency of commercially available vaccines, lots of efforts are being made to develop de novo therapeutic modalities. Besides this, the possibility of several genetic mutations in the viral genome has led to the generation of resistant strains such as Omicron against neutralizing antibodies and vaccines, leading to worsening public health status. Exosomes (Exo), nanosized vesicles, possess several therapeutic properties that participate in intercellular communication. The discovery and application of Exo in regenerative medicine have paved the way for the alleviation of several pathologies. These nanosized particles act as natural bioshuttles and transfer several biomolecules and anti‐inflammatory cytokines. To date, several approaches are available for the administration of Exo into the targeted site inside the body, although the establishment of standard administration routes remains unclear. As severe acute respiratory syndrome coronavirus 2 primarily affects the respiratory system, we here tried to highlight the transplantation of Exo in the alleviation of COVID‐19 pathologies. Significance statement: Exosomes (Exo) are nanosized vesicles that are released from each cell type and can transfer therapeutic molecules to the injured sites. It has been shown that Exo therapy circumvents difficulties that are associated with whole cell‐based therapies. Due to recent advances in the field of Exo‐based therapies, the current review article highlighted recent data and the applicability of Exo during viral diseases such as COVID‐19. The mechanism action and superiority of Exo were also debated in detail. [ABSTRACT FROM AUTHOR]

Ribosomes coordinate spatiotemporal control of gene expression, contributing to the acquisition and maintenance of cancer phenotype. The link between ribosomes and cancer is found in the roles of individual ribosomal proteins in tumorigenesis and cancer progression, including the ribosomal protein, receptor for activated C kinase 1 (RACK1). RACK1 regulates cancer cell invasion and is localized in spreading initiation centres, structural adhesion complexes containing RNA binding proteins and poly‐adenylated mRNAs that suggest a local translation process. As RACK1 is a ribosomal protein directly involved in translation and in breast cancer progression, we propose a new molecular mechanism for breast cancer cell migration and invasion, which considers the molecular differences between epithelial and mesenchymal cell profiles in order to characterize and provide novel targets for therapeutic strategies. Hence, we provide an analysis on how ribosomes translate cancer progression with a final focus on the ribosomal protein RACK1 in breast cancer. LINKED ARTICLES: This article is part of a themed issue on New avenues in cancer prevention and treatment (BJP 75th Anniversary). To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.12/issuetoc [ABSTRACT FROM AUTHOR]

Objective: As SARS‐CoV‐2 is known to invade neural cell mitochondria, a plasma system for quantifying central nervous system proteins in living humans was used to investigate neuropathogenic mechanisms of long‐COVID‐19. Methods: SARS‐CoV‐2 proteins and mitochondrial proteins (MPs) in enriched plasma neuron‐derived extracellular vesicles (NDEVs) and astrocyte‐derived EVs (ADEVs) were quantified in resolved acute COVID‐19 without post‐acute sequelae of SARS‐CoV‐2 (PASC), PASC without neuropsychiatric manifestations (NP), PASC with NP and healthy controls. Results: NDEV and ADEV mean levels of SARS‐CoV‐2 S1 and nucleocapsid (N) proteins were higher in all PASC sub‐groups than controls, but only N levels were higher in PASC with than without NP. Exosome marker CD81‐normalized NDEV mean levels of subunit 6 of MP respiratory chain complex I and subunit 10 of complex III, and neuroprotective MPs Humanin and mitochondrial open‐reading frame of the 12S rRNA‐c (MOTS‐c) all were decreased significantly in PASC with NP but not in PASC without NP relative to controls. NDEV levels of MPs voltage‐dependent anion‐selective channel protein 1 (VDAC1) and N‐methyl‐D‐aspartate receptor 1 (NMDAR1) were decreased in PASC without and with NP, whereas those of calcium channel MPs mitochondrial calcium uniporter (MCU), sodium/calcium exchanger (NCLX) and leucine zipper EF‐hand containing transmembrane 1 protein (LETM1) were decreased only in PASC with NP. ADEV levels of MCU and NCLX only were increased in PASC without and with NP. Interpretation: Abnormal NDEV and ADEV levels of SARS‐CoV‐2 N and S1 protein and MPs correlate with NP and may be biomarkers for long‐COVID prognostics and therapeutic trials. ANN NEUROL 2022;91:772–781 [ABSTRACT FROM AUTHOR]

The aggregation of proteins into inclusions or plaques is a prominent hallmark of a diverse range of pathologies including neurodegenerative diseases. The quantification of such inclusions in Caenorhabditis elegans models of aggregation is usually achieved by fluorescence microscopy or other techniques involving biochemical fractionation of worm lysates. Here, we describe a simple and rapid flow cytometry‐based approach that allows fluorescently tagged inclusions to be enumerated in whole worm lysate in a quantitative and unbiased fashion. We demonstrate that this technique is applicable to multiple C. elegans models of aggregation and importantly, can be used to monitor the dynamics of inclusion formation in response to heat shock and during ageing. This includes the characterisation of physicochemical properties of inclusions, such as their apparent size, which may reveal how aggregate formation is distinct in different tissues or at different stages of pathology or ageing. This new method can be used as a powerful technique for the medium‐ to high‐throughput quantification of inclusions in future studies of genetic or chemical modulators of aggregation in C. elegans. [ABSTRACT FROM AUTHOR]

In mountain ecosystems, it is crucial to identify conservation strategies to avoid local extinctions mainly due to agropastoral abandonment. For this purpose, identifying appropriate system indicators is required, for example, butterflies, which respond precisely and quickly to environmental changes. Zerynthia polyxena is an ecotonal species of butterfly, and thus, through its conservation it could be possible to protect clearing and ecotonal species. To develop conservation measures, we set up a hierarchical investigation that characterizes the ecological preferences of the adult and larval Z. polyxena, and host plant—Aristolochia pallida—by collecting data on the butterfly abundance (adult and larvae), tree cover, and litter plant features and by phytosociological surveys. Adult preferences change along an altitudinal gradient; the highest butterfly presence is at sites with medium elevation (1100 m above sea level [asl]) with high presence of forest, but even sites at low elevation (975 m asl), a high presence of forest favors butterfly abundance. Larvae prefer partially shaded ecotone plots with abundant host plants and low management intensity (corresponding to abundant litter) and with heterogeneous tree cover. High tree cover (70%) at low altitude and low tree cover (<20%) at high altitude favor larval presence. Larvae prefer plants with large leaves. Host plants were more abundant at low elevation where tree cover was low (<20%). We found that the optimal ecological niches of host plant and larvae have a spatial mismatch. By analyzing vegetation dynamics and butterfly monitoring during one field season, we are able to describe current and past (about 10–50 years ago) management pressures, in order to identify butterfly ecological preferences in relation to local features and therefore to suggest local conservation actions that might support Z. polyxena, as well as other butterflies and insects. Specifically, management measures should prevent afforestation (e.g., through irregular mowing) and favor the presence of small clearings and of ecotonal habitats in relation to elevation. Our study suggests that a new multifunctional approach that combines local entomological and vegetational surveys could be applied to define species optimal habitat features and, thus, to address appropriate conservation measures. [ABSTRACT FROM AUTHOR]

Dysfunction of the epithelial anion channel cystic fibrosis transmembrane conductance regulator (CFTR) causes a wide spectrum of disease, including cystic fibrosis (CF) and CFTR‐related diseases (CFTR‐RDs). Here, we investigate genotype–phenotype–CFTR function relationships using human nasal epithelial (hNE) cells from a small cohort of non‐CF subjects and individuals with CF and CFTR‐RDs and genotypes associated with either residual or minimal CFTR function using electrophysiological techniques. Collected hNE cells were either studied directly with the whole‐cell patch‐clamp technique or grown as primary cultures at an air–liquid interface after conditional reprogramming. The properties of cAMP‐activated whole‐cell Cl− currents in freshly isolated hNE cells identified them as CFTR‐mediated. Their magnitude varied between hNE cells from individuals within the same genotype and decreased in the rank order: non‐CF > CFTR residual function > CFTR minimal function. CFTR‐mediated whole‐cell Cl− currents in hNE cells isolated from fully differentiated primary cultures were identical to those in freshly isolated hNE cells in both magnitude and behaviour, demonstrating that conditional reprogramming culture is without effect on CFTR expression and function. For the cohort of subjects studied, CFTR‐mediated whole‐cell Cl− currents in hNE cells correlated well with CFTR‐mediated transepithelial Cl− currents measured in vitro with the Ussing chamber technique, but not with those determined in vivo with the nasal potential difference assay. Nevertheless, they did correlate with the sweat Cl− concentration of study subjects. Thus, this study highlights the complexity of genotype–phenotype–CFTR function relationships, but emphasises the value of conditionally reprogrammed hNE cells in CFTR research and therapeutic testing. Key points: The genetic disease cystic fibrosis is caused by pathogenic variants in the cystic fibrosis transmembrane conductance regulator (CFTR), an ion channel, which controls anion flow across epithelia lining ducts and tubes in the body.This study investigated CFTR function in nasal epithelial cells from people with cystic fibrosis and CFTR variants with a range of disease severity.CFTR function varied widely in nasal epithelial cells depending on the identity of CFTR variants, but was unaffected by conditional reprogramming culture, a cell culture technique used to grow large numbers of patient‐derived cells.Assessment of CFTR function in vitro in nasal epithelial cells and epithelia, and in vivo in the nasal epithelium and sweat gland highlights the complexity of genotype–phenotype–CFTR function relationships. [ABSTRACT FROM AUTHOR]

In the respiratory analysis of human beings, lungs play an important role and can be used to find several associated diseases. One of such conditions is called pneumothorax which occurs due to leaking of air into pleural space and results in lungs collapse. The traditional methodology uses chest radiography with the manual intervention of radiologists for the detection and segmentation of the affected areas. This paper introduces a deep neural network based methodology for the automatic localization and segmentation of the proper region‐of‐interest (RoI). The proposed approach is based on transfer learning where the existing UNet model is extended and redesigned to a new architecture named PTXNet for RoI segmentation. In PTXNet, the traditional encoder is redesigned with the use of EfficientNet, SE‐ResNeXt50 and Xception convolutional neural network (CNN) architectures. Furthermore, residual blocks are introduced in the decoder phase and concatenation of the previous decoder stage feature maps in addition to standard global skip connections is performed. The PTXNet is trained on a dataset of more than 15,000 chest radiography and resulted in the mean dice coefficient of 84.89%. It is found that the proposed approach provides superior results than the UNet model with an increase in the mean dice coefficient of 18.76%. [ABSTRACT FROM AUTHOR]

Cystic fibrosis (CF) is a lethal autosomal recessive disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The common ΔF508‐CFTR mutation results in protein misfolding and proteasomal degradation. If ΔF508‐CFTR trafficks to the cell surface, its anion channel function may be partially restored. Several in vitro strategies can partially correct ΔF508‐CFTR trafficking and function, including low‐temperature, small molecules, overexpression of miR‐138, or knockdown of SIN3A. The challenge remains to translate such interventions into therapies and to understand their mechanisms. One approach for connecting such interventions to small molecule therapies that has previously succeeded for CF and other diseases is via mRNA expression profiling and iterative searches of small molecules with similar expression signatures. Here, we query the Library of Integrated Network‐based Cellular Signatures using transcriptomic signatures from previously generated CF expression data, including RNAi‐ and low temperature‐based rescue signatures. This LINCS in silico screen prioritized 135 small molecules that mimicked our rescue interventions based on their genomewide transcriptional perturbations. Functional screens of these small molecules identified eight compounds that partially restored ΔF508‐CFTR function, as assessed by cAMP‐activated chloride conductance. Of these, XL147 rescued ΔF508‐CFTR function in primary CF airway epithelia, while also showing cooperativity when administered with C18. Improved CF corrector therapies are needed and this integrative drug prioritization approach offers a novel method to both identify small molecules that may rescue ΔF508‐CFTR function and identify gene networks underlying such rescue. [ABSTRACT FROM AUTHOR]

Emerging studies corroborate the importance of neuroimaging biomarkers and machine learning to improve diagnostic classification of amyotrophic lateral sclerosis (ALS). While most studies focus on structural data, recent studies assessing functional connectivity between brain regions by linear methods highlight the role of brain function. These studies have yet to be combined with brain structure and nonlinear functional features. We investigate the role of linear and nonlinear functional brain features, and the benefit of combining brain structure and function for ALS classification. ALS patients (N = 97) and healthy controls (N = 59) underwent structural and functional resting state magnetic resonance imaging. Based on key hubs of resting state networks, we defined three feature sets comprising brain volume, resting state functional connectivity (rsFC), as well as (nonlinear) resting state dynamics assessed via recurrent neural networks. Unimodal and multimodal random forest classifiers were built to classify ALS. Out‐of‐sample prediction errors were assessed via five‐fold cross‐validation. Unimodal classifiers achieved a classification accuracy of 56.35–61.66%. Multimodal classifiers outperformed unimodal classifiers achieving accuracies of 62.85–66.82%. Evaluating the ranking of individual features' importance scores across all classifiers revealed that rsFC features were most dominant in classification. While univariate analyses revealed reduced rsFC in ALS patients, functional features more generally indicated deficits in information integration across resting state brain networks in ALS. The present work undermines that combining brain structure and function provides an additional benefit to diagnostic classification, as indicated by multimodal classifiers, while emphasizing the importance of capturing both linear and nonlinear functional brain properties to identify discriminative biomarkers of ALS. [ABSTRACT FROM AUTHOR]

Objectives: Post‐infectious bronchiolitis obliterans (PiBO) is a rare, chronic disease initiated by severe infection and followed by perpetuating inflammation and obliteration of the small airways. MicroRNAs (miRNAs) have been proposed to play a central role as epigenetic regulators, which control resolution and prevent the uncontrolled progress of inflammation. The aim of this study was to define biomarkers on the level of post‐transcriptional gene regulation in order to characterise PiBO. Methods: A total of 39 patients with well‐defined PiBO and 31 controls from two centres, Barcelona, Spain, and Frankfurt, Germany, were analysed by next‐generation sequencing (NGS). The evaluation of the biological targets of the miRNAs was performed by pathway enrichment analysis and protein–protein interaction network analysis respectively. Results: Patients with PiBO had significantly lower lung function values and increased airway inflammation in induced sputum as indicated by total cell counts, neutrophils, IL‐1β, IL‐6, IL‐8 and TGF‐β compared to controls. Next‐generation sequencing analysis revealed a total of 22 dysregulated miRNAs, which passed significance threshold for Padj ≤ 0.001 with 17 being upregulated and 5 being downregulated. Of these dysregulated miRNAs, miR‐335‐5p, miR‐186‐5p, miR‐30b‐5p and miR‐30c‐5p were further validated using qRT‐PCR. Interestingly, these miRNAs are functionally implicated in cytokine–cytokine receptor interaction, TGF‐β signalling and FoxO signalling pathway and significantly correlated with lung function values (FEV1). Conclusion: Our results demonstrate an aberrant miRNA expression profile in PiBO, which impacts pathways responsible for the regulation of inflammation and fibrosis. The defined miRNAs are useful biomarkers and should be assessed as potential target in the field of miRNA therapeutics. [ABSTRACT FROM AUTHOR]

The development of medical imaging artificial intelligence (AI) systems for evaluating COVID‐19 patients has demonstrated potential for improving clinical decision making and assessing patient outcomes during the recent COVID‐19 pandemic. These have been applied to many medical imaging tasks, including disease diagnosis and patient prognosis, as well as augmented other clinical measurements to better inform treatment decisions. Because these systems are used in life‐or‐death decisions, clinical implementation relies on user trust in the AI output. This has caused many developers to utilize explainability techniques in an attempt to help a user understand when an AI algorithm is likely to succeed as well as which cases may be problematic for automatic assessment, thus increasing the potential for rapid clinical translation. AI application to COVID‐19 has been marred with controversy recently. This review discusses several aspects of explainable and interpretable AI as it pertains to the evaluation of COVID‐19 disease and it can restore trust in AI application to this disease. This includes the identification of common tasks that are relevant to explainable medical imaging AI, an overview of several modern approaches for producing explainable output as appropriate for a given imaging scenario, a discussion of how to evaluate explainable AI, and recommendations for best practices in explainable/interpretable AI implementation. This review will allow developers of AI systems for COVID‐19 to quickly understand the basics of several explainable AI techniques and assist in the selection of an approach that is both appropriate and effective for a given scenario. [ABSTRACT FROM AUTHOR]

Renovation of host erythrocytes is vital for pathogenesis by Plasmodium falciparum. These changes are mediated by parasite proteins that translocate beyond the parasitophorous vacuolar membrane in an unfolded state, suggesting protein folding by chaperones is imperative for the functionality of exported proteins. We report a type IV P. falciparum heat‐shock protein 40, PF11_0034, that localizes to the cytoplasmic side of J‐dots and interacts with the erythrocyte cytoskeleton, and therefore named eCiJp (erythrocyte cytoskeleton‐interacting J protein). Recombinant eCiJp binds to the human heat‐shock protein 70 HsHSPA1 and promotes its ATPase activity. In addition, eCiJp could suppress protein aggregation. Our data suggest that eCiJp recruits HsHSPA1 to the host erythrocyte cytoskeleton, where it may become involved in remodeling of the erythrocyte cytoskeleton and/or folding of exported parasite proteins. [ABSTRACT FROM AUTHOR]

The immune system is composed of immune organs, immune cells, and immunoactive substances, which plays a vital role in antitumor immunity in cancer immunotherapy. During the process of the antitumor immune response, many factors are involved in the cancer immune cycle. Therefore, developing intelligent strategies based on the steps of the cancer immune cycle to elicit the immune responses for enhanced cancer immunotherapy is of great significance. In this review, the key factors in each step of the cancer immune cycle are discussed, and then, the intelligent therapeutic strategies for modulating the immune surveillance against cancer are highlighted. Considering the demand for cancer immunotherapy in clinic, some suggestions for constructing new intelligent strategies are also put forward, which will make antitumor immunity more effective and advance the development of cancer immunotherapy. [ABSTRACT FROM AUTHOR]

In Arabidopsis thaliana, the epidermis is the outermost cell layer composed of many specialized types of epidermal cells, such as pavement cells, trichomes, and guard cells. The homeodomain‐leucine zipper (HD‐ZIP) class Ⅳ transcription factors (TFs), which are unique to the plant kingdom, have been recognized as key regulators of epidermis development. Unlike animal HD proteins, which can bind to DNA as monomers, plant HD‐ZIP class Ⅳ TFs bind to DNA as dimers, although little is known about the regulation of their dimerization process. Here, we show that the homodimerization of ARABIDOPSIS THALIANA MERISTEM LAYER 1 (ATML1) — HD‐ZIP class Ⅳ TF that is required for protoderm development — is regulated by the lipid‐binding steroidogenic acute regulatory protein‐related lipid transfer (START) domain. We found that ATML1 forms homodimer through interaction via its ZIP motif in yeast and plant cells, although the interaction is abolished by generating a mutation into the lipid‐binding START domain to disrupt the lipid‐binding ability. These results suggest that lipidic ligands function as key regulators of protoderm development via modulating the dimerization of ATML1. [ABSTRACT FROM AUTHOR]

The recently emerging stem‐cell artificial niche engineering in induced pluripotent stem cell (iPSCs) 3D cultures has provided enormous opportunities to fully utilize the potential of these cells in biomedical applications. Although a fully chemically defined niche environment can supply cells with desirable safety for clinical use, establishing an artificial degradable niche environment for the controlled release of proliferated cells under mild conditions is still a big challenge. Here, an advanced controlled releasable iPSC 3D artificial niche is reported based on dendritic polyglycerol and poly(N‐isopropylacrylamide)‐co‐polyethylene glycol polymers via a physical–chemical cogelation strategy. Benefiting from the chemically defined synthetic materials and their precise cooperation by covalent cross‐linking and physical phase transition, the cogelation‐based artificial niche system can be adjusted with optimal parameters and owns high cell biocompatibility to support the robust production of high quality iPSCs with an excellent expansion efficiency. Moreover, the expanded cells can be released out of their niche environment controllably only by adjusting the temperature. Overall, this controlled release hydrogel scaffold shows great promise in iPSC 3D culture for downstream applications. [ABSTRACT FROM AUTHOR]

Loss of function of the cystic fibrosis transmembrane conductance regulator (CFTR) causes cystic fibrosis (CF). In the lungs, this manifests as immune cell infiltration and bacterial infections, leading to tissue destruction. Previous work has determined that acute bacterial sphingomyelinase (SMase) decreases CFTR function in bronchial epithelial cells from individuals without CF (nHBEs) and with CF (cfHBEs, homozygous ΔF508‐CFTR mutation). This study focuses on exploring the mechanisms underlying this effect. SMase increased the abundance of dihydroceramides, a result mimicked by blockade of ceramidase enzyme using ceranib‐1, which also decreased CFTR function. The SMase‐mediated inhibitory mechanism did not involve the reduction of cellular CFTR abundance or removal of CFTR from the apical surface, nor did it involve the activation of 5′ adenosine monophosphate‐activated protein kinase. In order to determine the pathological relevance of these sphingolipid imbalances, we evaluated the sphingolipid profiles of cfHBEs and cfHNEs (nasal) as compared to non‐CF controls. Sphingomyelins, ceramides, and dihydroceramides were largely increased in CF cells. Correction of ΔF508‐CFTR trafficking with VX445 + VX661 decreased some sphingomyelins and all ceramides, but exacerbated increases in dihydroceramides. Additional treatment with the CFTR potentiator VX770 did not affect these changes, suggesting rescue of misfolded CFTR was sufficient. We furthermore determined that cfHBEs express more acid‐SMase protein than nHBEs. Lastly, we determined that airway‐like neutrophils, which are increased in the CF lung, secrete acid‐SMase. Identifying the mechanism of SMase‐mediated inhibition of CFTR will be important, given the imbalance of sphingolipids in CF cells and the secretion of acid‐SMase from cell types relevant to CF. [ABSTRACT FROM AUTHOR]

However CT chest may be useful in patients with moderate to severe respiratory symptoms and to determine the pre-test probability of the COVID-19 infection. H Abbouchie, SP 1 sp A Lamanna, SP 1 sp G Mitreski, SP 1 sp J Maingard, SP 2 sp H Kuan Kok, SP 3 sp C Barras, SP 4 sp V Thijs, SP 1 sp M Brooks SP 1 sp and H Asadi SP 1 sp I SP 1 sp Austin Health, Melbourne, Victoria, Australia, SP 2 sp Monash Health, Melbourne, Victoria, Australia, SP 3 sp Northern Health, Melbourne, Victoria, Australia, SP 4 sp South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia i B Purpose: b Emergent carotid artery stenting (eCAS) with endovascular clot retrieval (ECR) is an effective treatment in patients with tandem occlusion ischaemic stroke. An analysis of the CT findings was conducted by comparing CT findings based on the positivity or negativity of the RT-PCR results. [Extracted from the article]

Summary: Characterising the processes that control auxin dynamics is essential to understanding how auxin regulates plant development. Over recent years, several studies have investigated auxin diffusion through plasmodesmata, characterising this cell‐to‐cell diffusion and demonstrating that it affects auxin distributions. Furthermore, studies have shown that plasmodesmatal auxin diffusion affects developmental processes, including phototropism, lateral root emergence and leaf hyponasty. This short Tansley Insight review describes how these studies have contributed to our understanding of auxin dynamics and discusses potential future directions in this area. [ABSTRACT FROM AUTHOR]

Methyltransferase Set2‐mediated methylation of histone H3 lysine 36 (H3K36), which involves the addition of up to three methyl groups at this site, has been demonstrated to function in many chromatin‐coupled events. The methylation of H3K36 is known to recruit different chromatin effector proteins, affecting transcription, mRNA splicing and DNA repair. In this study, we engineered two yeast set2 mutants that lack H3K36 mono/dimethylation (H3K36me1/2) and trimethylation (H3K36me3), respectively, and characterized their roles in the production of antisense transcripts under nutrient‐rich conditions. Using our new bioinformatics identification pipeline analysis, we are able to identify a larger number of antisense transcripts in set2∆ cells than has been published previously. We further show that H3K36me1/2 or H3K36me3 redundantly repressed the production of antisense transcripts. Moreover, gene ontology (GO) analysis implies that H3K36me3‐mediated antisense transcription might play a role in DNA replication and DNA damage repair, which is independent of regulation of the corresponding sense gene expression. Overall, our results validate a coregulatory mechanism of different H3K36 methylation states, particularly in the repression of antisense transcription. [ABSTRACT FROM AUTHOR]