Respiratory Pathway Research Articles

Transcriptomic Analysis of the Amygdala in Subjects with Schizophrenia, Bipolar Disorder and Major Depressive Disorder Reveals Differentially Altered Metabolic Pathways.

The amygdala, crucial for mood, anxiety, fear, and reward regulation, shows neuroanatomical and molecular divergence in psychiatric disorders like schizophrenia, bipolar disorder and major depression. This region is also emerging as an important regulator of metabolic and immune pathways. The goal of this study is to address the paucity of molecular studies in the human amygdala. We hypothesize that diagnosis-specific gene expression alterations contribute to the unique pathophysiological profiles of these disorders. We used a cohort of subjects diagnosed with SCZ, BPD or MDD, and nonpsychiatrically ill control subjects (n = 15/group), together with our bioinformatic 3-pod analysis consisting of full transcriptome pathway analysis, targeted pathway analysis, leading-edge gene analysis and iLINCS perturbagen analysis. We identified altered expression of metabolic pathways in each disorder. Subjects with SCZ displayed downregulation of mitochondrial respiration and nucleotide metabolism pathways. In comparison, we observed upregulation of mitochondrial respiration pathways in subjects with MDD, while subjects with BPD displayed enrichment of pathways involved in carbohydrate metabolism. Several pathways associated with brain metabolism including immune system processes and calcium ion transport were also differentially altered between diagnosis groups. Our findings suggest metabolic pathways, including downregulation of energy metabolism pathways in SCZ and upregulation of energy metabolism pathways in MDD, are uniquely altered in the amygdala in these disorders, which may impact approaches for therapeutic strategies.

Preliminary Functional Analysis of the Gut Microbiome in Colic Horses

The gut microbiome plays a critical role in maintaining horse health, influencing digestion, immunity, and overall well-being. However, in certain conditions like colic, there is evidence of significant alterations in the microbial community. To analyze the composition of the fecal microbiome and the enriched predicted metabolic functions of horses with colic compared to a control group, 14 horses with colic and 14 control horses were recruited. From a stool sample, DNA extraction was carried out for subsequent 16S rRNA metagenomic analysis. The composition of the microbiome was analyzed from the sequences of each sample using the QIIME version 1.8.0 and DADA2 version 1.22 programs. PICRUSt2 was used to predict metabolic functions. Statistical analyses were performed with the Mann–Whitney U test from the Python scipy v1 package. The gut microbiomes of both groups were dominated by Firmicuteota, Bacteroidota, and Pseudomonadota phyla. Colic in horses was associated with reduced diversity, reduced abundance of Fibrobacter, and an increase in Streptococcus. The abundance of Firmicuteota was negatively correlated with Pseudomonadota and Actinobacteriota. The equine colic microbiome was predicted to be enriched in aerobic respiration pathways and fatty acid and amino acid degradation. These observations indicate discrete but important differences in the gut microbiome of colic horses.

Proteomics and Metabolomics Study on the Responses of Sertoli Cells Infected With Brucella and Its bvfA-Deletion Strains.

To investigate the potential effects of BvfA in reproductive system damage caused by Brucella. Brucella intracellular multiplication ability was determined by a gentamicin protection assay; the LDH method was used to determine the lethal effect of Brucella on TM4 cells. Afterward, Label-free proteomics and LC-MS/MS metabolomics assays were combined to reveal differential abundant proteins and metabolites of TM4 cells infected with bvfA-deletion strains and parental strains. Finally, PRM mass spectrometry and western blot analysis were carried out to confirm differential expression of proteins. This report demonstrated that bvfA-deletion strains failed to invade TM4 cells and reconstitution of invasion when a strain with gene bvfA was reintroduced to the deletion strain in 3 h. The bvfA-deletion exhibited weakened intracellular multiplication compared with parental strains in TM4 cells in 12 h; however, the death rate of TM4 cells infected with bvfA-deletion strains was higher than that of TM4 cells infected with parental strains. Combined proteomics and metabolomics analyses revealed that the differential abundant proteins and metabolites in TM4 cells infected with bvfA-deletion and parental strains mainly involved the mineral absorption-related pathway, NADH:ubiquinone oxidoreductase subunit-related mitochondrial respiratory signaling pathway, and sphingolipid signaling pathway of TM4 cells. These three signaling pathways were involved in expression changes of TRPM6/7, STEAP1, Gnaq, Trp53, Pbk, Tns2, Akt2, and the NADH:ubiquinone oxidoreductase subunit, as well as content changes of l-Valine, l-Isoleucine, l-Methionine, PC, PE DG, and SM metabolites. These results indicated that BvfA of Brucella abortus S19 affected the above proteins and metabolites in TM4 cells.

Study of the Microbiological Efficiency of a Hospital Ventilation System With Hepa Filtration in the Prevention of Airborne Pathogens

Objective: To evaluate the microbiological efficiency in air conditioning systems with HEPA filtration in an infectious disease hospital. Theoretical Framework: Air conditioning in intensive care units and wards must consider the spread of microorganisms through respiratory pathways, as both patients and healthcare professionals are exposed to infectious agents transmitted by bioaerosols. Due to the possibility of environmental infection, there is a growing recognition that poorly designed air conditioning systems enhance the transmission of pathogens in areas with constant flow of individuals, particularly immunocompromised patients, who are more susceptible to infections. Air conditioning with HEPA filtration is a hospital engineering technique that shows great potential for filtering airborne contaminants, thereby reducing their dispersion in the environment. Method: Air samples were collected using the active impaction method over a 32-week period in the intensive care unit and wards of a reference hospital for infectious diseases. Results and Discussion: In the hospital environment, 67% of fungi and 33% of bacteria were identified, along with their respective subcategories. The colony-forming unit count exceeded the standards established by current regulations. The study highlights that hospital air is a pathway for the transmission and persistence of pathogenic microorganisms. Research Implications: The importance of ensuring a safe and healthy hospital environment is emphasized. Originality/Value: There are few studies addressing pathogens transmitted by bioaerosols. This study contributes to expanding knowledge on this topic and suggests the need for a review of current regulatory standards.

Mitochondrial respiratory pathways in immature rat heart tissue using different cardioplegic solutions.

Minor defects in the mitochondrial ATP-generating system and post-cardioplegia oxidative phosphorylation can negatively impact cardiac function in immature hearts. This study aimed to examine the mitochondrial respiratory pathway using three different cardioplegic solutions (Custodiol HTK, St. Thomas, and Del Nido) during moderate (1h) and long (3h) ischemic periods. A total of 41 male Wistar albino rats were utilized in this study. Five experiments were conducted without the use of any cardioplegic solution (CP0 group). To assess both moderate and prolonged ischemic periods, six experiments were carried out in each of the following groups: CP1 group (St. Thomas solution), CP2 group (Custodiol HTK solution), and CP3 group (Del Nido solution). After 1h, the highest mitochondrial respiration rate was observed in the CP3 group and the lowest in the CP1 group (p = 0.006). After adding ADP substrate, the highest mitochondrial ATP-production-coupled respiration was recorded in the CP3 group, which was similar to the control group CP0. After 3h, while evaluating the ratio between mitochondrial respiration ATP-production coupled and basal respiration, significant differences were found between CP1 group and CP3 group (p = 0.035), as well as between the CP1 and CP0 groups (p = 0.045). Additionally, by assessing the condition of the outer mitochondrial membrane using the Cyt C effect (Cyt/Phos [ADP]), significant differences were observed between the CP1 and CP3 group (p = 0.004), as well as between CP1 and CP0 groups (p = 0.003). Del Nido cardioplegic solution provided optimal mitochondrial protection under moderate and long myocardial ischemia conditions.

Morphological, physiological, and biochemical responses of rice (Oryza sativa L.) varieties to drought stress via regulating respiration and ROS metabolism during germination

Germination marks a pivotal and sensitive phase in the life cycle of crops, with drought stress, precipitated by water scarcity, posing a significant impediment to the germination process in rice. Despite this, the regulation mechanism of respiratory and reactive oxygen species (ROS) metabolism during rice germination under drought stress remains to be fully elucidated. This manuscript presents an integrative analysis encompassing morphological, physiological, biochemical, and molecular attributes of germinated seeds from a cultivated drought-sensitive rice variety (JN10) and a drought-resistant rice variety (NG36). Our findings revealed that drought stress adversely affected the germination of both rice varieties, with NG36 exhibiting a more rapid germination rate compared to JN10 under such stress conditions. This differential response was attributed to the heightened activity of key enzymes, elevated levels of metabolic intermediates, and upregulated expression of genes encoding enzymes involved in ROS and respiratory metabolic pathways in NG36. To further dissect the interplay between these metabolic pathways, we selected specific enzyme activities for detailed examination. Notably, a robust positive linear correlation was established among phosphofructokinase (PFK), α-ketoglutarate dehydrogenase (KGDH), citrate synthase (CS), and isocitrate dehydrogenase (ICDH) in NG36. This correlation underscores the pivotal role of glycolytic pathways, particularly the tricarboxylic acid (TCA) cycle, in conferring drought resistance to NG36 during the germination phase under drought stress. To encapsulate our findings, the results of this investigation suggest that the rice cultivar NG36 manifests a heightened degree of drought tolerance relative to JN10. This is primarily achieved through the adept modulation of its respiratory metabolic pathways and the stringent preservation of ROS homeostasis during the germination phase under conditions of water deficit. These revelations provide unprecedented insights into the intricate regulatory mechanisms that subserve rice's drought resistance, potentially paving the way for the development of novel strategies in the breeding of rice cultivars with improved drought resilience.

Alternative oxidase of plants mitochondria is related with increased resistance of tomato mtDNA to the difenoconazole exposure

It is known that plant mitochondria and mitochondrial DNA (mtDNA) are more resistant to damage than animal mitochondria. We hypothesized that this phenomenon may be related to alternative respiratory pathways in plants mitochondria, in particular alternative oxidase (AOX). The results of a pot experiment demonstrated that the application of the fungicide difenoconazole at concentrations that were 3-, 5-, and 10-times higher than the recommended dosage resulted in a 106 %, 76 %, and 90 % increase in mitochondrial DNA damage in tomato shoots, respectively, in comparison to the shoots treated with difenoconazole at the dosage recommended by the manufacturer . Inhibition of shoot growth was observed in response to treatment with difenoconazole at a dose 10times higher than recommended. It is noteworthy that when tomatoes were treated with difenoconazole at this concentration, there was a tendency for the expression of inducible aox1a. In a field experiment, difenoconazole at a concentration of 5 times higher than recommended resulted in a 10 % increase in mtDNA damage in the fruits compared to the control. Similar results were obtained in an in vitro experiment. The addition of low doses of difenoconazole to intact tomato mitochondria did not cause mtDNA damage. The observed damages occured only when 200 μM difenoconazole was added. In contrast, incubation of 20 μM difenoconazole with SHAM, which inhibits AOX, resulted in a 115 % increase in mtDNA damage compared to the use of the same concentration without difenoconazole. This finding is consistent with the damaging effect induced by 200 μM difenoconazole. The increase in difenoconazole toxicity induced by SHAM and the elevation in aox1a gene expression resulting from the treatment with a 10 times higher than the recommended dose of difenoconazole may signify a pivotal function of AOX in the increased resistance of plant mtDNA to the pesticide exposure.

Phosphoketolase and KDPG aldolase metabolisms modulate photosynthetic carbon yield in cyanobacteria.

Cyanobacteria contribute to roughly a quarter of global net carbon fixation. During diel light/dark growth, dark respiration substantially lowers the overall photosynthetic carbon yield in cyanobacteria and other phototrophs. How respiratory pathways participate in carbon resource allocation at night to optimize dark survival and support daytime photosynthesis remains unclear. Here, using the cyanobacterium Synechococcus elongatus PCC 7942, we show that phosphoketolase integrates into a respiratory network in the dark to best allocate carbon resources for amino acid biosynthesis and to prepare for photosynthesis reinitiation upon photoinduction. Moreover, we show that the respiratory Entner-Doudoroff (ED) pathway in S. elongatus is incomplete, with its key enzyme 2-keto-3-deoxy-6-phosphogluconate (KDPG) aldolase exhibiting alternative oxaloacetate decarboxylation activity that modulates daytime photosynthesis. This activity allows for the bypassing of the tricarboxylic acid (TCA) cycle when ATP and NADPH consumption for biosynthesis is excessive and imbalanced relative to their production by the light reactions, thereby preventing relative NADPH accumulation and ensuring optimal photosynthetic carbon yield. Optimizing these metabolic processes offers opportunities to enhance photosynthetic carbon yield in cyanobacteria and other photosynthetic organisms under diel light/dark cycles.

Patient referral pathways to leisure providers: impacts on physical activity and falls risk

Abstract Background Physical activity aids prevention and management of noncommunicable diseases. Yet many UK adults, particularly those with long-term health conditions, do not meet recommended activity levels. In 2021, West Suffolk Foundation Trust commissioned local leisure provider Abbeycroft to offer 24 week tailored physical activity programs as part of respiratory and frailty patient pathways. Objectives Evaluation of activity and outcome data for all 1670 individuals referred between January - December 2023 to determine future commissioning decisions. Results 256 participants had completed a 24 week pathway by the time of analysis. Compared to baseline, they demonstrated statistically significant (p < 0.05) self-reported improvements on the Short Warwick Edinburgh Mental Well-being Scale (median 25 to 27) amongst 68.9% of participants; and on the self-reported International Physical Activity Questionnaire 62.1% reduced time spent sitting (average 436 to 300 minutes/ week), 75% increased metabolically active minutes (average 955 to 2632 minutes/week) and the proportion of participants with a low (inactive) score decreased by 61%. Of 40 frailty patients, 87.5% lowered their self-reported Short Falls Efficacy Scale Score (14.6 to 10.4) and observed Timed Get up and Go (13.55 to 9.53 seconds), indicative of moving from a higher risk to lower falls risk (p < 0.05). 24 week retention exceeded 80% for all ages except 16-20 years. 17.8% of participants were >75 years. Lessons Both pathways have been recommissioned and new tailored pathways for Parkinson’s disease, COPD and cancer are planned. This partnership working is a sustainable, integrated way to embed prevention in the community but needs time to build relationships and streamline data sharing. Key messages • Hospital and community referral pathways to leisure providers significantly improve patient well-being, physical activity and falls risk. • These pathways are affordable, adaptable across conditions and show high retention.

Excess Potassium Promotes Autophagy to Maintain the Immunosuppressive Capacity of Myeloid-Derived Suppressor Cells Independent of Arginase 1.

Potassium ions (K+) are critical electrolytes that regulate multiple functions in immune cells. Recent studies have shown that the elevated concentration of extracellular potassium in the tumor interstitial fluid limits T cell effector function and suppresses the anti-tumor capacity of tumor-associated macrophages (TAMs). The effect of excess potassium on the biology of myeloid-derived suppressor cells (MDSCs), another important immune cell component of the tumor microenvironment (TME), is unknown. Here, we present data showing that increased concentrations of potassium chloride (KCl), as the source of K+ ions, facilitate autophagy by increasing the expression of the autophagosome marker LC3β. Simultaneously, excess potassium ions significantly decrease the expression of arginase I (Arg I) and inducible nitric oxide synthase (iNOS) without reducing the ability of MDSCs to suppress T cell proliferation. Further investigation reveals that excess K+ ions decrease the expression of the transcription factor C/EBP-β and alter the expression of phosphorylated kinases. While excess K+ ions downregulated the expression levels of phospho-AMPKα (pAMPKα), it increased the levels of pAKT and pERK. Additionally, potassium increased mitochondrial respiration as measured by the oxygen consumption rate (OCR). Interestingly, all these alterations induced by K+ ions were abolished by the autophagy inhibitor 3-methyladenine (3-MA). Our results suggest that hyperosmotic stress caused by excess K+ ions regulate the mitochondrial respiration and signaling pathways in MDSCs to trigger the process of autophagy to support MDSCs' immunosuppressive function by mechanisms independent of Arg I and iNOS. Overall, our in vitro and ex vivo findings offer valuable insights into the adaptations of MDSCs within the K+ ion-rich TME, which has important implications for MDSCs-targeted therapies.

Ultraviolet radiation inhibits mitochondrial bioenergetics activity.

Mitochondria play an important role in cellular function, not only as a major site of adenosine triphosphate (ATP) production but also by regulating energy expenditure, apoptosis signaling, control of the cell cycle, cellular growth, cell differentiation, transportation of metabolites, and production of reactive oxygen species. Interaction with electromagnetic waves can lead to dysregulation or alterations in the patterns of energy activities in the mitochondria. Ultraviolet light (UV) can be found in sunlight and artificial sources, such as lamps. UV radiation can cause damage to DNA, proteins, and lipids. Besides that, UV radiation is largely used in microorganism disinfection. To establish possible alterations in mitochondrial bioenergetics, this study proposes to investigate the UV (at two distinct intervals) effects on isolated mitochondria from mice liver to obtain direct responses and selective permeability of the internal membrane information. UVA-371 and UVC-255 nm lamps were used to irradiate, at different doses varying from 22.5 to 756 mJ/cm2, isolated mitochondria samples. Mitochondrial respiration pathways were investigated by high-resolution respirometry, and possible mitochondrial membrane damages were evaluated by mitochondrial swelling by spectrophotometer analysis. UVC irradiation results (in the higher dose) indicate decrease in 75% of mitochondrial bioenergetics capacity, such as limitation of oxidative phosphorylation in 60% and increased energy dissipation in 30%. Mitochondrial swelling experiments (spectrophotometer) indicated inner membrane damage, and consequently a loss of selective permeability. Direct correlation between irradiation and effect responses was observed, mitochondrial bioenergetics is severely affected by UVC radiation, but (UVA) radiation did not present bioenergetic alterations. These alterations can contribute to improving the knowledge behind the cell death mechanism in disinfection UV light and UV therapy such as phototherapy.

Alternative oxidase affects ascorbate metabolism in Arabidopsis thaliana plants under high-light conditions: possible links between respiratory electron transport pathways in mitochondria

Alternative oxidase affects ascorbate metabolism in Arabidopsis thaliana plants under high-light conditions: possible links between respiratory electron transport pathways in mitochondria

Interactions of Polychlorinated Biphenyls and Their Metabolites with the Brain and Liver Transcriptome of Female Mice.

Exposure to polychlorinated biphenyls (PCBs) is linked to neurotoxic effects. This study aims to close knowledge gaps regarding the specific modes of action of PCBs in female C57BL/6J mice (>6 weeks) orally exposed for 7 weeks to a human-relevant PCB mixture (MARBLES mix) at 0, 0.1, 1, and 6 mg/kg body weight/day. PCB and hydroxylated PCB (OH-PCBs) levels were quantified in the brain, liver, and serum; RNA sequencing was performed in the striatum, prefrontal cortex, and liver, and metabolomic analyses were performed in the striatum. Profiles of PCBs but not their hydroxylated metabolites were similar in all tissues. In the prefrontal cortex, PCB exposure activated the oxidative phosphorylation respiration pathways, while suppressing the axon guidance pathway. PCB exposure significantly changed the expression of genes associated with neurodevelopmental and neurodegenerative diseases in the striatum, impacting pathways like growth hormone synthesis and dendrite development. PCBs did not affect the striatal metabolome. In contrast to the liver, which showed activation of metabolic processes following PCB exposure and the induction of cytochrome P450 enzymes, the expression of xenobiotic processing genes was not altered by PCB exposure in either brain region. Network analysis revealed complex interactions between individual PCBs (e.g., PCB28 [2,4,4'-trichlorobiphenyl]) and their hydroxylated metabolites and specific differentially expressed genes (DEGs), underscoring the need to characterize the association between specific PCBs and DEGs. These findings enhance the understanding of PCB neurotoxic mechanisms and their potential implications for human health.

New approach methodologies (NAMs) for the in vitro assessment of cleaning products for respiratory irritation: workshop report.

The use of in vitro new approach methodologies (NAMs) to assess respiratory irritation depends on several factors, including the specifics of exposure methods and cell/tissue-based test systems. This topic was examined in the context of human health risk assessment for cleaning products at a 1-day public workshop held on 2 March 2023, organized by the American Cleaning Institute® (ACI). The goals of this workshop were to (1) review in vitro NAMs for evaluation of respiratory irritation, (2) examine different perspectives on current challenges and suggested solutions, and (3) publish a manuscript of the proceedings. Targeted sessions focused on exposure methods, in vitro cell/tissue test systems, and application to human health risk assessment. The importance of characterization of assays and development of reporting standards was noted throughout the workshop. The exposure methods session emphasized that the appropriate exposure system design depends on the purpose of the assessment. This is particularly important given the many dosimetry and technical considerations affecting relevance and translation of results to human exposure scenarios. Discussion in the in vitro cell/tissue test systems session focused on the wide variety of cell systems with varying suitability for evaluating key mechanistic steps, such as molecular initiating events (MIEs) and key events (KEs) likely present in any putative respiratory irritation adverse outcome pathway (AOP). This suggests the opportunity to further develop guidance around in vitro cell/tissue test system endpoint selection, assay design, characterization and validation, and analytics that provide information about a given assay's utility. The session on applications for human health protection emphasized using mechanistic understanding to inform the choice of test systems and integration of NAMs-derived data with other data sources (e.g., physicochemical properties, exposure information, and existing in vivo data) as the basis for in vitro to in vivo extrapolation. In addition, this group noted a need to develop procedures to align NAMs-based points of departure (PODs) and uncertainty factor selection with current human health risk assessment methods, together with consideration of elements unique to in vitro data. Current approaches are described and priorities for future characterization of in vitro NAMs to assess respiratory irritation are noted.

9227 Haptoglobin-related protein (HPR) new role as insulin secretion enhancer

Abstract Disclosure: Carlos Viesi, Ph.D.[1], Ian Tamburini, BS[1], Hosung Bae, Ph.D[1]., Erwin Ilegems, Ph.D.[2], Leandro Velez, Ph.D. [1], Mingqi Zhou, BS[1], Christy Nguyen, Ph.D.[1], Casey Johnson, Ph.D.[1], Cholsoon Jang, Ph.D[1]., Erika Nishimura[2] and Marcus Seldin, Ph.D.[1]. [1]Department of Biological Chemistry, Center for Epigenetics and Metabolism, University of California, Irvine, CA, USA, [2]Departments of Diabetes Protein Engineering, Diabetes Biology & Pharmacology, Medicinal Chemistry, Protein Engineering, Novo Nordisk A/S, Novo Nordisk Park, DK-2760 Måløv, Denmark. Type 2 Diabetes (T2D) affects over 530 million people around the globe. Insulin resistance, encompassing tissues such as muscle, adipose, and liver, is the initial step hallmarked by hyperinsulinemia. Coupled with β-cell failure, these coordinated responses progress to T2D, becoming irreversible and medically challenging. Despite the well-established requirement for communication between pancreas and peripheral tissues in T2D progression, this area remains almost entirely unexplored. Here, we performed a human population genetic screening across 310 individuals to search for new endocrine regulators of pancreas function. Specifically, global gene expression from 18 peripheral tissues was analyzed to identify potential endocrine regulators of insulin secretion. This analysis prioritized liver-specific Haptoglobin-related protein (HPR) as genetically-enriched with islet insulin responses. Mouse models using AAV technology and acute protein administration of HPR showed that this newly secreted protein is sufficient to prevent diet-induced insulin resistance through enhanced beta-cell respiration. When mice were administered soluble HPR, then pancreatic tissue subjected to global RNA-sequencing, enhanced respiration pathways were observed. Next, we generated hepatocyte-specific overexpression models using AAV, which were sufficient to rescue whole-body glucose disposal profiles and weight gain in diet-induced insulin-resistant mice. Altogether, these findings highlight HPR as a novel soluble protein which signals from liver to pancreatic islets. Presentation: 6/3/2024

8258 Haptoglobin-related protein (HPR) new role as insulin secretion enhancer

Abstract Disclosure: C. Viesi: None. Type 2 Diabetes (T2D) affects over 530 million people around the globe. Insulin resistance, encompassing tissues such as muscle, adipose, and liver, is the initial step hallmarked by hyperinsulinemia. Coupled with β-cell failure, these coordinated responses progress to T2D, becoming irreversible and medically challenging. Despite the well-established requirement for communication between pancreas and peripheral tissues in T2D progression, this area remains almost entirely unexplored. Here, we performed a human population genetic screening across 310 individuals to search for new endocrine regulators of pancreas function. Specifically, global gene expression from 18 peripheral tissues was analyzed to identify potential endocrine regulators of insulin secretion. This analysis prioritized liver-specific Haptoglobin-related protein (HPR) as genetically-enriched with islet insulin responses. Mouse models using AAV technology and acute protein administration of HPR showed that this newly secreted protein is sufficient to prevent diet-induced insulin resistance through enhanced beta-cell respiration. When mice were administered soluble HPR, then pancreatic tissue subjected to global RNA-sequencing, enhanced respiration pathways were observed. Next, we generated hepatocyte-specific overexpression models using AAV, which were sufficient to rescue whole-body glucose disposal profiles and weight gain in diet-induced insulin-resistant mice. Altogether, these findings highlight HPR as a novel soluble protein which signals from liver to pancreatic islets. Presentation: 6/3/2024

Evaluating the hypoxic tolerance of two maturity stages of Antarctic krill (Euphausia superba) at its range edge

AbstractThe South Georgia region of the Southern Ocean represents the northernmost range edge for Antarctic krill. Of concern is the extent to which rapid warming of surface water temperatures and reduced oxygen contents around this region might challenge the physiological tolerance of krill, particularly the later maturity stages. Hypoxia is generally considered to be less than 30 to 20% of air saturation, hereafter as threshold hypoxia, while less than 10% of air saturation would qualify as severe hypoxia. These levels are unlikely to occur in the Southern Ocean but might happen in the middle of dense krill swarms. We investigated gene expression and biochemical markers related to aerobic metabolism, antioxidant defence, and heat-shock response under 6-h threshold (4 kPa; TH) and 1-h severe (0.6 kPa; SH) hypoxia exposure, to understand how hypoxia might alter respiratory and biochemical pathways in adult and subadult krill. After 6-h TH, subadults induced expression of citrate synthase (CS), and mitochondrial superoxide dismutase (also after 1-h SH) over normoxic expression levels. The maturity stages responded differently in glutathione peroxidase (1-h SH; lower in subadults and higher in adults), and CS (6-h TH; higher in subadults and lower in adults) activities as for the oxidative damage marker to lipids (6-h TH; lower in subadults and higher in adults). Subadults had a greater capacity than adults to deal with hypoxic conditions. This may be a strategy allowing them to exist in larger swarms to reduce predation pressure before reaching reproductive condition.

Low Magnetic Field Exposure Alters Prostate Cancer Cell Properties.

Prostate cancer is the second most common neoplasia and fifth-leading cause of cancer death in men worldwide. Electromagnetic and magnetic fields have been classified as possible human carcinogens, but current understanding of molecular and cellular pathways involved is very limited. Effects due to extremely low magnetic/hypomagnetic fields (LMF) are furthermore poorly understood. Extracellular vesicles (EVs) are crucial mediators of cellular communication with multifaceted roles in cancer progression, including via transport and uptake of various protein and microRNA (miRNA) EV-cargoes. miRNAs regulate gene expression and are implicated in cancer-related processes such as proliferation, metastasis, and chemoresistance. This study investigated the effects of LMF exposure (20 nT) by magnetic shielding on the prostate cancer cell line PC3 compared to the prostate epithelial cell line PNT2 under short-term (4 h) conditions. We examined EV profiles following a 4 h LMF exposure alongside associated functional enrichment KEGG and GO pathways for the EV proteomes. The 4 h LMF exposure significantly reduced cellular EV release and modified PC3 EV cargoes to a more inflammatory and metastatic profile, with 16 Disease Pathways and 95 Human Phenotypes associated specifically with the LMF-treated PC3 EV proteomes. These included cancerous, metabolic, blood, skin, cardiac and skeletal Disease Pathways, as well as pain and developmental disorders. In the normal PNT2 cells, less EV protein cargo was observed following LMF exposure compared with cells not exposed to LMF, and fewer associated functional enrichment pathways were identified. This pointed to some differences in various cellular functions, ageing, defence responses, oxidative stress, and disease phenotypes, including respiratory, digestive, immune, and developmental pathways. Furthermore, we analysed alterations in matrix metalloproteinases (MMPs) and miRNAs linked to metastasis, as this is crucial in cancer aggressiveness. The 4 h LMF exposure caused a significant increase in MMP2 and MMP9, as well as in onco-miRs miR-155, miR-210, miR-21, but a significant reduction in tumour-suppressor miRs (miR-200c and miR-126) in the metastatic PC3 cells, compared with normal PNT2 cells. In addition, 4 h LMF exposure significantly induced cellular invasion of PC3 cells. Overall, our findings suggest that changes in magnetic field exposures modulate EV-mediated and miR-regulatory processes in PCa metastasis, providing a basis for exploring novel therapeutic strategies.

EHealth in pediatric respiratory allergy.

This review explores the relevance of eHealth technologies to address unmet needs in pediatric respiratory allergies, particularly allergic rhinitis (AR) and asthma. Given the increasing burden of these conditions, there is a pressing need for effective solutions to enhance disease surveillance, diagnosis, and management. Recent literature highlights the potential of eHealth tools to transform pediatric respiratory allergy care. The use of digital data for infodemiology, application of machine learning models to improve diagnostic sensitivity, smartphone apps with digital patient reported outcome measure (PROMs) and embedded sensors to monitor disease, healthcare professional dashboards with real-time data monitoring and clinical decision support systems (CDSS) are advances emerging to optimize pediatric respiratory allergy care. Integrating eHealth technologies into the pediatric respiratory allergy care pathway is a potential solution for current healthcare challenges to better meet the needs of children with AR and asthma. However, while the potential of eHealth is evident, its widespread implementation in real-world practice requires continued research, collaboration, and efforts to overcome existing barriers.

Genome-Wide Identification and Characterization of Alternative Oxidase (AOX) Genes in Foxtail Millet (Setaria italica): Insights into Their Abiotic Stress Response.

Alternative oxidase (AOX) serves as a critical terminal oxidase within the plant respiratory pathway, playing a significant role in cellular responses to various stresses. Foxtail millet (Setaria italica), a crop extensively cultivated across Asia, is renowned for its remarkable tolerance to abiotic stresses and minimal requirement for fertilizer. In this study, we conducted a comprehensive genome-wide identification of AOX genes in foxtail millet genome, discovering a total of five SiAOX genes. Phylogenetic analysis categorized these SiAOX members into two subgroups. Prediction of cis-elements within the promoter regions, coupled with co-expression network analysis, intimated that SiAOX proteins are likely involved in the plant's adaptive response to abiotic stresses. Employing RNA sequencing (RNA-seq) and real-time quantitative PCR (RT-qPCR), we scrutinized the expression patterns of the SiAOX genes across a variety of tissues and under multiple abiotic stress conditions. Specifically, our analysis uncovered that SiAOX1, SiAOX2, SiAOX4, and SiAOX5 display distinct tissue-specific expression profiles. Furthermore, SiAOX2, SiAOX3, SiAOX4, and SiAOX5 exhibit responsive expression patterns under abiotic stress conditions, with significant differences in expression levels observed between the shoot and root tissues of foxtail millet seedlings. Haplotype analysis of SiAOX4 and SiAOX5 revealed that these genes are in linkage disequilibrium, with Hap_2 being the superior haplotype for both, potentially conferring enhanced cold stress tolerance in the cultivar group. These findings suggest that both SiAOX4 and SiAOX5 may be targeted for selection in future breeding programs aimed at improving foxtail millet's resilience to cold stress.