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IScience Aug 2023Individuals with Down syndrome (DS) clinically manifest severe respiratory illnesses; however, there is a paucity of data on how DS influences homeostatic physiology of...
Individuals with Down syndrome (DS) clinically manifest severe respiratory illnesses; however, there is a paucity of data on how DS influences homeostatic physiology of lung airway, and its reactive responses to pulmonary pathogens. We generated well-differentiated ciliated airway epithelia using tracheas from wild-type and Dp(16)1/Yey mice , and discovered that Dp(16)1/Yey epithelia have significantly lower abundance of ciliated cells, an altered ciliary beating profile, and reduced mucociliary transport. Interestingly, both sets of differentiated epithelia released similar quantities of viral particles after infection with influenza A virus (IAV). However, RNA-sequencing and proteomic analyses revealed an immune hyperreactive phenotype particularly for monocyte-recruiting chemokines in Dp(16)1/Yey epithelia. Importantly, when we challenged mice with IAV, we observed immune hyper-responsiveness in Dp(16)1/Yey mice, evidenced by higher quantities of lung airway infiltrated monocytes, and elevated levels of pro-inflammatory cytokines in bronchoalveolar lavage fluid. Our findings illuminate mechanisms underlying DS-mediated pathophysiological changes in airway epithelium.
PubMed: 37554445
DOI: 10.1016/j.isci.2023.107361 -
Frontiers in Plant Science 2024Abiotic and biotic stresses globally constrain plant growth and impede the optimization of crop productivity. The phytohormone auxin is involved in nearly every aspect... (Review)
Review
Abiotic and biotic stresses globally constrain plant growth and impede the optimization of crop productivity. The phytohormone auxin is involved in nearly every aspect of plant development. Auxin acts as a chemical messenger that influences gene expression through a short nuclear pathway, mediated by a family of specific DNA-binding transcription factors known as Auxin Response Factors (ARFs). ARFs thus act as effectors of auxin response and translate chemical signals into the regulation of auxin responsive genes. Since the initial discovery of the first ARF in Arabidopsis, advancements in genetics, biochemistry, genomics, and structural biology have facilitated the development of models elucidating ARF action and their contributions to generating specific auxin responses. Yet, significant gaps persist in our understanding of ARF transcription factors despite these endeavors. Unraveling the functional roles of ARFs in regulating stress response, alongside elucidating their genetic and molecular mechanisms, is still in its nascent phase. Here, we review recent research outcomes on ARFs, detailing their involvement in regulating leaf, flower, and root organogenesis and development, as well as stress responses and their corresponding regulatory mechanisms: including gene expression patterns, functional characterization, transcriptional, post-transcriptional and post- translational regulation across diverse stress conditions. Furthermore, we delineate unresolved questions and forthcoming challenges in ARF research.
PubMed: 38903418
DOI: 10.3389/fpls.2024.1398818 -
BMC Immunology Oct 2023Leptospirosis is a zoonotic disease caused by Leptospira species. Variations in lipopolysaccharide (LPS) structure in Leptospira are known to be associated with the...
BACKGROUND
Leptospirosis is a zoonotic disease caused by Leptospira species. Variations in lipopolysaccharide (LPS) structure in Leptospira are known to be associated with the serovar diversity and antigenicity. Development of immunodiagnostics for early detection of leptospirosis based on immune responses against different pathogenic antigens as well as development of vaccines are important. Hence, this study has assessed the immune response generated against leptospiral LPS and whole antigen preparations of pathogenic and saprophytic Leptospira and specific changes in peritoneal cells was also studied to elucidate the cellular responses associated with immune response of Wistar rats.
METHODS
During the study, immune response induced by two types of Leptospira antigen preparations of two selected serovars was compared. Changes in the specific peritoneal cell subpopulations following immunizations of rats were analyzed using flow cytometry.
RESULTS
Of the two antigen preparations tested, the LPS extract induced a higher IgM immune response as opposed to the sonicated antigen preparation. Of the two serovars tested, L. interrogans serovar Pyrogenes had induced a higher IgM response compared to that by L. biflexa serovar Patoc. Considering the IgG titers, equivalent responses were observed with all four antigen preparations. Significant increases in lymphocytes were observed following immunization with LPS of both serovars. Interestingly, the B2 cell percentages increased significantly during the immunization period. Further, significant correlations were observed with both IgM and IgG responses and percentage of B2 cells in the peritoneal cavity (PC).
CONCLUSION
LPS extract of L. interrogans serovar Pyrogenes induced higher IgM response while the IgG response was equivalent among the four antigen preparations tested. Significant increase of B2 cell percentage in the peritoneal cavity during the immunization reflects the accumulation of B2 cells in the PC which may play considerable role in generating humoral response against Leptospira antigens.
Topics: Rats; Animals; Leptospira; Serogroup; Immunity, Humoral; Lipopolysaccharides; Rats, Wistar; Leptospirosis; Antigens, Bacterial; Immunoglobulin G; Immunoglobulin M
PubMed: 37848809
DOI: 10.1186/s12865-023-00574-z -
Gels (Basel, Switzerland) May 2024Human defense against infection remains a global topic. In addition to developing novel anti-infection drugs, therapeutic drug delivery strategies are also crucial to... (Review)
Review
Human defense against infection remains a global topic. In addition to developing novel anti-infection drugs, therapeutic drug delivery strategies are also crucial to achieving a higher efficacy and lower toxicity of these drugs for treatment. The application of hydrogels has been proven to be an effective localized drug delivery approach to treating infections without generating significant systemic adverse effects. The recent emerging dynamic hydrogels further show power as injectable formulations, giving new tools for clinical treatments. In this review, we delve into the potential applications of dynamic hydrogels in antibacterial and antiviral treatments and elaborate on their molecular designs and practical implementations. By outlining the chemical designs underlying these hydrogels, we discuss how the choice of dynamic chemical bonds affects their stimulus responsiveness, self-healing capabilities, and mechanical properties. Afterwards, we focus on how to endow dynamic hydrogels with anti-infection properties. By comparing different drug-loading methods, we highlight the advantages of dynamic chemical bonds in achieving sustained and controlled drug release. Moreover, we also include the design principles and uses of hydrogels that possess inherent anti-infective properties. Furthermore, we explore the design principles and applications of hydrogels with inherent anti-infective properties. Finally, we briefly summarize the current challenges faced by dynamic hydrogels and present a forward-looking vision for their future development. Through this review, we expect to draw more attention to these therapeutic strategies among scientists working with chemistry, materials, as well as pharmaceutics.
PubMed: 38786248
DOI: 10.3390/gels10050331 -
Science Advances Oct 2023Early-life adversities are associated with altered defensive responses. Here, we demonstrate that the repeated cross-fostering (RCF) paradigm of early maternal...
Early-life adversities are associated with altered defensive responses. Here, we demonstrate that the repeated cross-fostering (RCF) paradigm of early maternal separation is associated with enhancements of distinct homeostatic reactions: hyperventilation in response to hypercapnia and nociceptive sensitivity, among the first generation of RCF-exposed animals, as well as among two successive generations of their normally reared offspring, through matrilineal transmission. Parallel enhancements of acid-sensing ion channel 1 (ASIC1), ASIC2, and ASIC3 messenger RNA transcripts were detected transgenerationally in central neurons, in the medulla oblongata, and in periaqueductal gray matter of RCF-lineage animals. A single, nebulized dose of the ASIC-antagonist amiloride renormalized respiratory and nociceptive responsiveness across the entire RCF lineage. These findings reveal how, following an early-life adversity, a biological memory reducible to a molecular sensor unfolds, shaping adaptation mechanisms over three generations. Our findings are entwined with multiple correlates of human anxiety and pain conditions and suggest nebulized amiloride as a therapeutic avenue.
Topics: Animals; Humans; Amiloride; Maternal Deprivation; RNA, Messenger; Anxiety
PubMed: 37792939
DOI: 10.1126/sciadv.adi8750 -
Journal of Affective Disorders Sep 2023Patients with Post-traumatic stress disorder (PTSD) exposed to traumatic reminders show hyperreactivity in brain areas (e.g., amygdala) belonging or related to the... (Meta-Analysis)
Meta-Analysis Review
Patients with Post-traumatic stress disorder (PTSD) exposed to traumatic reminders show hyperreactivity in brain areas (e.g., amygdala) belonging or related to the Innate Alarm System (IAS), allowing the rapid processing of salient stimuli. Evidence that IAS is activated by subliminal trauma-reminders could shed a new light on the factors precipitating and perpetuating PTSD symptomatology. Thus, we systematically reviewed studies investigating neuroimaging correlates of subliminal stimulation in PTSD. Twenty-three studies were selected from the MEDLINE and Scopus® databases for a qualitative synthesis, 5 of which allowed a further meta-analysis of fMRI data. The intensity of IAS responses to subliminal trauma-related reminders ranged from a minimum in healthy controls to a maximum in the PTSD patients with the most severe (e.g., dissociative) symptoms or the least responsiveness to treatment. Comparisons with other disorders (e.g., phobias) revealed contrasting results. Our findings demonstrate the hyperactivation of areas belonging or related to IAS in response to unconscious threats that should be integrated in diagnostic as well as in therapeutic protocols.
Topics: Humans; Stress Disorders, Post-Traumatic; Subliminal Stimulation; Brain; Amygdala; Brain Mapping; Magnetic Resonance Imaging
PubMed: 37236272
DOI: 10.1016/j.jad.2023.05.047 -
BioRxiv : the Preprint Server For... Nov 2023Changes in the intracellular concentration of free calcium (Ca) underpin egg activation and initiation of development in animals and plants. In mammals, the Ca release...
Changes in the intracellular concentration of free calcium (Ca) underpin egg activation and initiation of development in animals and plants. In mammals, the Ca release is periodical, known as Ca oscillations, and mediated by the type 1 inositol 1,4,5-trisphosphate receptor (IPR1). Another divalent cation, zinc (Zn), increases exponentially during oocyte maturation and is vital for meiotic transitions, arrests, and polyspermy prevention. It is unknown if these pivotal cations interplay during fertilization. Here, using mouse eggs, we showed that basal concentrations of labile Zn are indispensable for sperm-initiated Ca oscillations because Zn-deficient conditions induced by cell-permeable chelators abrogated Ca responses evoked by fertilization and other physiological and pharmacological agonists. We also found that chemically- or genetically generated eggs with lower levels of labile Zn displayed reduced IPR1 sensitivity and diminished ER Ca leak despite the stable content of the stores and IPR1 mass. Resupplying Zn restarted Ca oscillations, but excessive Zn prevented and terminated them, hindering IPR1 responsiveness. The findings suggest that a window of Zn concentrations is required for Ca responses and IPR1 function in eggs, ensuring optimal response to fertilization and egg activation.
PubMed: 37131581
DOI: 10.1101/2023.04.13.536745 -
Frontiers in Plant Science 2024Plants have evolved distinct defense strategies in response to a diverse range of chewing and sucking insect herbivory. While chewing insect herbivores, exemplified by... (Review)
Review
Plants have evolved distinct defense strategies in response to a diverse range of chewing and sucking insect herbivory. While chewing insect herbivores, exemplified by caterpillars and beetles, cause visible tissue damage and induce jasmonic acid (JA)-mediated defense responses, sucking insects, such as aphids and whiteflies, delicately tap into the phloem sap and elicit salicylic acid (SA)-mediated defense responses. This review aims to highlight the specificity of defense strategies in plants and associated underlying molecular mechanisms when challenged by herbivorous insects from different feeding guilds (i.e., chewing and sucking insects). To establish such an understanding in plants, the typical defense responses were categorized into physical, chemical, and metabolic adjustments. Further, the impact of contrasting feeding patterns on is discussed in context to unique biochemical and molecular that governs the resistance against chewing and sucking insect pests. Grasping these interactions is crucial to developing innovative and targeted pest management approaches to ensure ecosystem sustainability and productivity.
PubMed: 38645389
DOI: 10.3389/fpls.2024.1376917 -
The Plant Cell Sep 2023The kinases SNF1-RELATED KINASE 1 (SnRK1) and TARGET OF RAPAMYCIN (TOR) are central sensors of the energy status, linking this information via diverse regulatory...
The kinases SNF1-RELATED KINASE 1 (SnRK1) and TARGET OF RAPAMYCIN (TOR) are central sensors of the energy status, linking this information via diverse regulatory mechanisms to plant development and stress responses. Despite the well-studied functions of SnRK1 and TOR under conditions of limited or ample energy availability, respectively, little is known about the extent to which the 2 sensor systems function and how they are integrated in the same molecular process or physiological context. Here, we demonstrate that both SnRK1 and TOR are required for proper skotomorphogenesis in etiolated Arabidopsis (Arabidopsis thaliana) seedlings, light-induced cotyledon opening, and regular development in light. Furthermore, we identify SnRK1 and TOR as signaling components acting upstream of light- and sugar-regulated alternative splicing events, expanding the known action spectra for these 2 key players in energy signaling. Our findings imply that concurring SnRK1 and TOR activities are required throughout various phases of plant development. Based on the current knowledge and our findings, we hypothesize that turning points in the activities of these sensor kinases, as expected to occur upon illumination of etiolated seedlings, instead of signaling thresholds reflecting the nutritional status may modulate developmental programs in response to altered energy availability.
Topics: Arabidopsis; Seedlings; Arabidopsis Proteins; Sirolimus; Gene Expression Regulation, Plant; Protein Serine-Threonine Kinases
PubMed: 37338062
DOI: 10.1093/plcell/koad168 -
The Journal of Clinical Endocrinology... Jul 2023Humans respond profoundly to changes in diet, while nutrition and environment have a great impact on population health. It is therefore important to deeply characterize...
CONTEXT
Humans respond profoundly to changes in diet, while nutrition and environment have a great impact on population health. It is therefore important to deeply characterize the human nutritional responses.
OBJECTIVE
Endocrine parameters and the metabolome of human plasma are rapidly responding to acute nutritional interventions such as caloric restriction or a glucose challenge. It is less well understood whether the plasma proteome would be equally dynamic, and whether it could be a source of corresponding biomarkers.
METHODS
We used high-throughput mass spectrometry to determine changes in the plasma proteome of i) 10 healthy, young, male individuals in response to 2 days of acute caloric restriction followed by refeeding; ii) 200 individuals of the Ely epidemiological study before and after a glucose tolerance test at 4 time points (0, 30, 60, 120 minutes); and iii) 200 random individuals from the Generation Scotland study. We compared the proteomic changes detected with metabolome data and endocrine parameters.
RESULTS
Both caloric restriction and the glucose challenge substantially impacted the plasma proteome. Proteins responded across individuals or in an individual-specific manner. We identified nutrient-responsive plasma proteins that correlate with changes in the metabolome, as well as with endocrine parameters. In particular, our study highlights the role of apolipoprotein C1 (APOC1), a small, understudied apolipoprotein that was affected by caloric restriction and dominated the response to glucose consumption and differed in abundance between individuals with and without type 2 diabetes.
CONCLUSION
Our study identifies APOC1 as a dominant nutritional responder in humans and highlights the interdependency of acute nutritional response proteins and the endocrine system.
Topics: Humans; Male; Proteome; Diabetes Mellitus, Type 2; Proteomics; Glucose; Caloric Restriction
PubMed: 36658456
DOI: 10.1210/clinem/dgad031