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PubMed2003

Bronchodilation and bronchoprotection by deep inspiration and their relationship to bronchial hyperresponsiveness.

Bronchial hyperresponsiveness (BHR) is a cardinal feature of asthma. Airway inflammation and BHR are probably linked, but the mechanisms underlying this relationship remain elusive. BHR is closely associated with defects in the beneficial responses to lung inflation. These responses, which become apparent by the fact that healthy individuals can develop severe airway obstruction if they are exposed to methacholine in the absence of deep inspirations, include bronchodilation and bronchoprotection. Bronchodilation refers to the effect of lung inflation after the induction of airway smooth muscle tone, while bronchoprotection is used to indicate the effect prior to inhalation of a spasmogen. Mild asthmatics who manifest BHR lack bronchoprotection by lung inflation. In contrast, many of them are able to bronchodilate. In more severe disease, both functions are impaired. The lack of bronchoprotection is also found in individuals with rhinitis and BHR, but no asthma. These and other observations suggest that the mechanisms of bronchodilation and bronchoprotection may be distinct, although overlap is possible. We believe that the loss of bronchoprotection is pertinent to the phenomenon of hyperresponsiveness, but that both the bronchodilatory and bronchoprotective functions of deep inspiration interact to produce the asthmatic phenotype. In this review, we describe the phenomena of lung inflation-induced bronchodilation and bronchoprotection and detail potential mechanical and neurohumoral mechanisms accounting for these physiologic functions. In addition, possible mechanisms leading to the impairment of these functions in subjects with BHR are discussed.

Animals↗
PubMed1986

Terminal erythroid differentiation in the K-562 cell line by 1-beta-D-arabinofuranosylcytosine: accompaniment by c-myc messenger RNA decrease.

Two erythroid markers, acetylcholinesterase and hemoglobin, can be reversibly induced in the K-562 cell line after sodium butyrate treatment. In the present paper we show that 1-beta-D-arabinofuranosylcytosine (ara-C), induces the coordinate, irreversible expression of these two erythroid markers. This induction occurs at an ara-C concentration (0.05 mM) that results in K-562 cytostasis and is accompanied by deep morphological changes of cells. The differentiated phenotype is independent of the K-562 cell clone used [K-562, K-562 (S), K-562 (S)P] and is associated with the loss of cell renewal capacity. Continuous presence of the inducer is not necessary to achieve terminal differentiation. In contrast to what is seen for other inducers (sodium butyrate and hemin), one of the early effects of ara-C treatment is the marked decrease of c-myc mRNA expression after the first 4 hours of induction, whereas N-ras and histone 4 expression remain constant during the first 48 h. Our results suggest that ara-C treatment can irreversibly activate the erythroid differentiative program of K-562 cells.

Acetylcholinesterase↗
PubMed2026

Mul-PheG2P: decoupled learning and prediction-space fusion enables robust and interpretable multi-phenotype genomic prediction.

Genomic prediction of multiple phenotypes is crucial in modern plant breeding; however, existing methods struggle with negative transfer and lack interpretability, particularly across high-dimensional small-sample data and diverse species. To address this, we propose Mul-PheG2P, a novel paradigm based on decoupled learning and predictive space fusion. It employs a two-stage design: first training phenotype-specific encoders using genetic data, then decoupling phenotype-specific learning from cross-phenotype aggregation via an interpretable prediction layer. Mul-PheG2P outperforms existing methods across diverse crop datasets, including maize (Zea mays), wheat (Triticum aestivum), and tomato (Solanum lycopersicum). It provides a multi-scale interpretability chain: at the macro level, it quantifies phenotypic contributions via attention-based weighting; at the micro level, Integrated Gradients reveal the genetic basis of predictions. Notably, the model successfully identified the CCT (CONSTANS, CO-like, and TOC) motif regulating photoperiodism and the SQUAMOSA (SQUAMOSA promoter binding protein) promoter for inflorescence development, confirming its ability to capture functional biological mechanisms. These results highlight the high performance and interpretability of Mul-PheG2P, showcasing its value for low-cost, large-scale screening to advance precision breeding.

Phenotype↗
PubMed2025

Predicting emergent phenotypes from single cell populations using CELLECTION.

Biological systems exhibit emergent phenotypes that arise from the collective behavior of individual components, such as whole-organ functions that arise from the coordinated activity of its individual cells, or organism-level phenotypes that result from the functional interplay of collections of genes in the genome. We present CELLECTION, a deep learning framework that learns to associate subgroups of instances with different emergent phenotypes. We show CELLECTION enables interpretable predictions for heterogeneous tasks, including disease classification, identification of disease-associated cell subtypes, alignment of developmental stages between human model systems, and even predicting relative hand-wing indices across the avian lineage. CELLECTION therefore provides a scalable and flexible framework for identifying key cellular or genetic signatures underlying complex traits in development, disease, and evolution.

Journal Article↗
PubMed2005

Phylogenetic resolution and habitat specificity of members of the Photobacterium phosphoreum species group.

Substantial ambiguity exists regarding the phylogenetic status of facultatively psychrophilic luminous bacteria identified as Photobacterium phosphoreum, a species thought to be widely distributed in the world's oceans and believed to be the specific bioluminescent light-organ symbiont of several deep-sea fishes. Members of the P. phosphoreum species group include luminous and non-luminous strains identified phenotypically from a variety of different habitats as well as phylogenetically defined lineages that appear to be evolutionarily distinct. To resolve this ambiguity and to begin developing a meaningful knowledge of the geographic distributions, habitats and symbiotic relationships of bacteria in the P. phosphoreum species group, we carried out a multilocus, fine-scale phylogenetic analysis based on sequences of the 16S rRNA, gyrB and luxABFE genes of many newly isolated luminous strains from symbiotic and saprophytic habitats, together with previously isolated luminous and non-luminous strains identified as P. phosphoreum from these and other habitats. Parsimony analysis unambiguously resolved three evolutionarily distinct clades, phosphoreum, iliopiscarium and kishitanii. The tight phylogenetic clustering within these clades and the distinct separation between them indicates they are different species, P. phosphoreum, Photobacterium iliopiscarium and the newly recognized 'Photobacterium kishitanii'. Previously reported non-luminous strains, which had been identified phenotypically as P. phosphoreum, resolved unambiguously as P. iliopiscarium, and all examined deep-sea fishes (specimens of families Chlorophthalmidae, Macrouridae, Moridae, Trachichthyidae and Acropomatidae) were found to harbour 'P. kishitanii', not P. phosphoreum, in their light organs. This resolution revealed also that 'P. kishitanii' is cosmopolitan in its geographic distribution. Furthermore, the lack of phylogenetic variation within 'P. kishitanii' indicates that this facultatively symbiotic bacterium is not cospeciating with its phylogenetically divergent host fishes. The results of this fine-scale phylogenetic analysis support the emerging view that bacterial species names should designate singular historical entities, i.e. discrete lineages diagnosed by a significant divergence of shared derived nucleotide characters.

Animals↗
PubMed2002

Mapping QTLs for root morphology of a rice population adapted to rainfed lowland conditions.

In the rainfed lowlands, rice ( Oryza sativa L.) develops roots under anaerobic soil conditions with ponded water, prior to exposure to water stress and aerobic soil conditions that arise later in the season. Constitutive root system development in anaerobic soil conditions has been reported to have a positive effect on subsequent expression of adaptive root traits and water extraction during progressive water stress in aerobic soil conditions. We examined quantitative trait loci (QTLs) for constitutive root morphology traits using a mapping population derived from a cross between two rice lines which were well-adapted to rainfed lowland conditions. The effects of phenotyping environment and genetic background on QTLs identification were examined by comparing the experimental data with published results from four other populations. One hundred and eighty-four recombinant inbred lines (RILs) from a lowland indica cross (IR58821/IR52561) were grown under anaerobic conditions in two experiments. Seven traits, categorized into three groups (shoot biomass, deep root morphology, root thickness) were measured during the tillering stage. Though parental lines showed consistent differences in shoot biomass and root morphology traits across the two seasons, genotype-by-environment interaction (GxE) and QTL-by-environment interaction were significant among the progeny. Two, twelve, and eight QTLs for shoot biomass, deep root morphology, and root thickness, respectively, were identified, with LOD scores ranging from 2.0 to 12.8. Phenotypic variation explained by a single QTL ranged from 6% to 30%. Only two QTLs for deep root morphology, in RG256-RG151 in chromosome 2 and in PC75M3-PC11M4 in chromosome 4, were identified in both experiments. Comparison of positions of QTLs across five mapping populations (the current population plus populations from four other studies) revealed that these two QTLs for deep root morphology were only identified in populations that were phenotyped under anaerobic conditions. Fourteen and nine chromosome regions overlapped across different populations as putative QTLs for deep root morphology and root thickness, respectively. PC41M2-PC173M5 in chromosome 2 was identified as an interval that had QTLs for deep root morphology in four mapping populations. The PC75M3-PC11M4 interval in chromosome 4 was identified as a QTL for root thickness in three mapping populations with phenotypic variation explained by a single QTL consistently as large as 20-30%. Three QTLs for deep root morphology were found only in japonica/indica populations but not in IR58821/IR52561. The results identifying chromosome regions that had putative QTLs for deep root morphology and root thickness over different mapping populations indicate potential for marker-assisted selection for these traits.

Journal Article↗
PubMed2001

Effect of chronic uncontrollable stress on myosin heavy chain expression in rat masseter muscle.

This study has evaluated the influence of chronic uncontrollable painless stress on the expression of myosin heavy chain (MyHC) isoforms in deep and superficial parts of the rat masseter muscle. Muscle cross sections of three month old Wistar rats were processed for immunohistochemical staining. In control muscle the three adult fast MyHC isoforms (-2a, -2x/d, -2b), were nonhomogenously distributed: in the smaller anterior part of the muscle only fast MyHC isoforms were expressed. The major superficial and posterior part of the muscle fibres also contained MyHC-1 (10%) and only 7% expressed of MyHC-2b. Psychological stress significantly modified the expression of particular MyHC isoforms in both parts of the muscle. In the anterior part of the experimental masseter the proportion of MyHC-2b expressing fibres decreased and 10% of the muscle fibres expressed MyHC-1. The superficial and posterior part of the experimental muscle contained significantly more muscle fibres expressing MyHC-2b isoforms. Regarding whole cross-sectional area transition towards faster phenotype was evident due to a higher percentage of either pure MyHC-2b containing fibres or hybrid MyHC-2x/d and -2b expressing fibres. The results of this study demonstrate that psychological stress is accompanied by a modification of muscle phenotype which is region specific. Opposite changes in deep and superficial part of the muscle could be ascribed to differences in genetic programme, function or susceptibility to hormones in both parts of masseter.

Animals↗
PubMed2025

Phenotypic pleiotropy of missense variants in human B cell confinement receptor P2RY8.

Missense variants can have pleiotropic effects on protein function, and predicting these effects can be difficult. We performed near-saturation deep mutational scanning of P2RY8, a G protein-coupled receptor that promotes germinal center B cell confinement. We assayed the effect of each variant on surface expression, migration, and proliferation. We delineated variants that affected both expression and function, affected function independently of expression, and discrepantly affected migration and proliferation. We also used cryo-electron microscopy to determine the structure of activated, ligand-bound P2RY8, providing structural insights into the effects of variants on ligand binding and signal transmission. We applied the deep mutational scanning results to both improve computational variant effect predictions and to characterize the phenotype of germline variants and lymphoma-associated variants. Together, our results demonstrate the power of integrating deep mutational scanning, structure determination, and in silico prediction to advance the understanding of a receptor important in human health.

Humans↗
PubMed1996

Biology and the measurement problem.

Present-day molecular biology, despite its name, is almost entirely committed to a macroscopic, classical picture of the organism; one in which quantum aspects play no role, except as a source of noise. Particularly is this true when dealing with informational aspects; especially "genetic information". The pervading metaphor here is an identification of "genetic information" with DNA sequence, and thence with program or software. We take a quite different view herein. If we presume, to the contrary, that microphysical processes play a role in primary genetic processes, then the "information" they can convey consists of observables evaluated on states. It is then natural to analogize a complex, consisting of (observed system + observer) with the biological partition between genome (observed system) and phenotype (observer). Such a picture immediately raises the deep issues surrounding "the measurement problem" in quantum mechanics. In our brief consideration of such matters, we suggest that standard quantum mechanics is too narrow to deal with the biological pictures, because it is inexorably tied to quantifications of classical, conservative systems; there is no such for an organism. Rather, we are led to consider subsystems we call "sites", for which there is in principle no Hamiltonian. We then query the extent to which such "genetic information" is already subsumed in traditional observables a physicist would measure in vitro in a laboratory. We suggest there is no reason to believe that "genetic information", manifested in bioactivities, is reducible to these. Finally, we contrast this view of "genetic information" with more traditional ideas of program and computability. We argue that computability (algorithms) are entirely classical concepts, in a physical sense, and quite inadequate for a biology (or even a physics) in which quantum measurement processes are important.

Computational Biology↗
PubMed1993

Variations in the distribution, frequency, and phenotype of Langerhans cells during the evolution of malignant melanoma of the skin.

We examined the frequency, distribution, and immunophenotype (S-100 protein, CD1) of epidermal Langerhans cells (LC) in the epidermis overlying primary melanoma, and dermal dendritic cells (DC) in the dermis deep to melanoma, and in adjacent normal skin. There is a substantial reduction in S-100+ LC and a lesser decline in CD1+ LC in the epidermis over melanoma. There is a simultaneous increase in the frequency of cells expressing these phenotypes in the dermis deep to tumor. Double-staining studies in progress show coexpression of S-100 and CD1 in most of these cells. The depletion of S-100+/CD1+ DC from the peritumoral epidermis is maximum in deeper (Clark level III-V) and thicker (> 0.76 mm) tumors. The reduction in total DC in peritumoral epidermis is, however, proportionally less than the reduction in S-100+/CD1+ DC owing to an increase in cells that are S-100-/CD1+. The proportion of S-100+/CD1+ dermal DC deep to tumor is similar to that in normal epidermis and dermis, suggesting that there is no increased migration of S-100-/CD1+ DC from tumor-associated epidermis to subjacent dermis. Non-dendritic leukocytes in the dermis deep to tumor were increased in frequency, maximally in the dermis deep to thinner and more superficial melanomas. Most such cells were T lymphocytes with helper/inducer cells predominating. The data presented show substantial alterations in the frequency, distribution, and phenotype of LC/DC as melanoma evolves, alterations that may be critical for development of effective tumor-directed immunity.

Antigens, CD↗
PubMed2006

Friedreich's ataxia: clinical heterogeneity in two sisters.

Diagnostic evaluation of two sisters affected by ataxia, with similar age of onset, revealed a characteristic trinucleotide expansion in the Friedreich's ataxia (FRDA) locus and two different phenotypic presentations. At onset the elder sister had retained deep tendon reflexes (FARR), while the younger sister presented classic FRDA. The GAA expansion in the patients' alleles proved to be similar in both siblings, ruling out that age at onset and clinical heterogeneity could be due to different FRDA mutations. On the whole, clinical and genetic data on these patients confirmed that FARR is a variant phenotype of FRDA.

Adult↗
PubMed1988

In vitro percutaneous absorption in mouse skin: influence of skin appendages.

Skin appendages are often envisaged as channels that bypass the stratum corneum barrier and are generally thought to facilitate the dermal absorption of topical agents. However, the significance of this transappendageal pathway in percutaneous absorption remains to be assessed experimentally. With the use of a skin organ culture penetration chamber system, the influence of skin appendages on the in vitro permeation of topically applied benzo[a]pyrene and testosterone (5 micrograms/2 cm2) was examined in skin preparations from both haired and hairless mice. Haired mice examined included the C57BL6, C3H, DBA2, Balbc, and Sencar strains and the hairless mice were the HRS and SKH. In all mouse strains examined, the overall permeation of testosterone (greater than 65% of applied dose) 16 hr following in vitro topical application was greater than that of benzo[a]pyrene (less than 10%). No strain differences were observed with respect to the percutaneous permeation of testosterone; however, percutaneous permeation of benzo[a]pyrene in the haired mice (7-10% of applied dose) was higher than that in the hairless mice (2%). In an in-house derived mouse strain which showed three phenotypic variants due to hair densities, the permeability to both compounds was highest in the skin of the haired phenotype (testosterone 67%, benzo[a]pyrene 7%), lowest in the hairless phenotype (35 and 1%, respectively) and intermediate in the fuzzy-haired animal (57 and 3%, respectively). Examination by fluorescence microscopy of cryosections of skin, prepared 1 hr after topical benzo[a]pyrene, showed areas of intense fluorescence deep within the nonfluorescing dermis of skin from the haired phenotype. These fluorescent areas were correlated with follicular ducts and sebaceous glands. In contrast, skin from the hairless phenotype showed no evidence of fluorescence in the dermis and intermediate was the fluorescence observed in the skin from the fuzzy-haired animal. These observations showed that transappendageal penetration could contribute significantly to the overall skin absorption of topical agents. They also suggest that regional distribution of skin appendages could influence the percutaneous fate of topically applied chemicals.

Animals↗
PubMed2006

Prader-Willi-like phenotype: investigation of 1p36 deletion in 41 patients with delayed psychomotor development, hypotonia, obesity and/or hyperphagia, learning disabilities and behavioral problems.

Monosomy 1p36 is one of the most commonly observed mental retardation (MR) syndromes that results in a clinically recognizable phenotype including delayed psychomotor development and/or MR, hypotonia, epilepsy, hearing loss, growth delay, microcephaly, deep-set eyes, flat nasal bridge and pointed chin. Besides, a Prader-Willi syndrome (PWS)-like phenotype has been described in patients with 1p36 monosomy. Forty-one patients presenting hypotonia, developmental delay, obesity and/or hyperphagia and behavioral problems who tested negative for PWS were investigated by FISH and/or microsatellite markers. Twenty-six were analyzed with a 1p-specific subtelomeric probe, and one terminal deletion was identified. Thirty patients (15 of which also studied by FISH) were investigated by microsatellite markers, and no interstitial 1p36 deletion was found. Our patient presenting the 1p36 deletion did not have the striking features of this monosomy, but her clinical and behavioral features were quite similar to those observed in patients with PWS, except for the presence of normal sucking at birth. The extent of the deletion could be limited to the most terminal 2.5 Mb of 1p36, within the chromosomal region 1p36.33-1p36.32, that is smaller than usually seen in monosomy 1p36 patients. Therefore, chromosome 1p36.33 deletion should be investigated in patients with hypotonia, developmental delay, obesity and/or hyperphagia and behavioral problems who test negative for PWS.

Adolescent↗
PubMed1997

HECA-452+ T cells migrate through superficial vascular plexus but not through deep vascular plexus endothelium.

The skin is nourished by two interconnected vascular systems, the superficial vascular plexus coursing just beneath the epidermis and the deep vascular plexus located above the subcutaneous tissue. Skin inflammatory T cells in diseases, such as psoriasis or dermatitis, strikingly aim for the superficial vascular plexus without involving the deep vascular plexus, and the infiltrating T cells bear a distinct phenotype expressing the cutaneous lymphocyte-associated antigen, which is recognized by mAb HECA-452. We wanted to know whether HECA-452+ lymphocytes indeed are able to distinguish between superficial and deep vascular plexus homing sites. Employing the hu-SCID mouse model grafted with human skin and human T cells, as described previously, we developed a new skin-grafting strategy providing superficial and deep vascular plexus skin specimens placed separately onto the same mouse. Fourteen days after allogeneic human T cell grafting, both human skin sites were densely infiltrated by human T cells, but only T cells within the superficial vascular plexus, but not within the deep vascular plexus, expressed the cutaneous lymphocyte-associated antigen. IL-2 and IFN-gamma expression and allogeneic vessel destruction were present within both superficial and deep vascular plexus skin. This model provides direct evidence that expression of a specific homing receptor is indeed able to direct lymphocyte traffic, not only to a distinct organ but also to a distinct vascular bed within one organ.

Animals↗
PubMed1994

Mutation in blood coagulation factor V associated with resistance to activated protein C.

Activated protein C (APC) is a serine protease with potent anticoagulant properties, which is formed in blood on the endothelium from an inactive precursor. During normal haemostasis, APC limits clot formation by proteolytic inactivation of factors Va and VIIIa (ref. 2). To do this efficiently the enzyme needs a nonenzymatic cofactor, protein S (ref. 3). Recently it was found that the anticoagulant response to APC (APC resistance) was very weak in the plasma of 21% of unselected consecutive patients with thrombosis and about 50% of selected patients with a personal or family history of thrombosis; moreover, 5% of healthy individuals show APC resistance, which is associated with a sevenfold increase in the risk for deep vein thrombosis. Here we demonstrate that the phenotype of APC resistance is associated with heterozygosity or homozygosity for a single point mutation in the factor V gene (at nucleotide position 1,691, G-->A substitution) which predicts the synthesis of a factor V molecule (FV Q506, or FV Leiden) that is not properly inactivated by APC. The allelic frequency of the mutation in the Dutch population is approximately 2% and is at least tenfold higher than that of all other known genetic risk factors for thrombosis (protein C (ref. 8), protein S (ref. 9), antithrombin10 deficiency) together.

Amino Acid Sequence↗
PubMed2026

Cryptic serpentine divergence and substrate adaptation of Cardamine glauca in the Balkan Peninsula.

BACKGROUND AND AIMS: Serpentine soils represent one of the most challenging substrates for plant life due to skewed ratios of essential nutrients and toxic concentrations of metals. Plant adaptation to such conditions may lead to locally adapted edaphic ecotypes or, when reproductive barriers evolve, to distinct serpentine endemics. However, a third scenario may occur: cryptic edaphic divergence, where phenotypically similar lineages adapted to contrasting substrates exhibit deep genetic divergence. Here, we tested whether substrate-associated divergence reflects repeated serpentine adaptation or cryptic edaphic lineage divergence in Cardamine glauca (Brassicaceae) in Balkan peninsula - a hotspot of serpentine endemism in Europe. METHODS: We sampled and sequenced genomes of 43 individuals of C. glauca together with four individuals representing closely related taxa, C. plumieri and C. pancicii, from variable substrates across the Balkans. We combined phylogenomics, population genomic analyses of selection and a reciprocal transplant experiment to infer the most likely evolutionary scenario. KEY RESULTS: Phylogenomic analysis of 941 loci confirmed monophyly of C. glauca, including the local endemic C. pancicii, but revealed deep splits (∼2.2-3.2 Mya) between co-occurring serpentine and non-serpentine lineages. Population genomic analyses of replicated geographically proximate serpentine-non-serpentine population pairs demonstrated strong genome-wide differentiation and limited gene flow between edaphic types. Window-based analyses of local genomic divergence and tests for positive selection revealed candidate genes involved in ion transport, membrane transporter activity and metal homeostasis, consistent with the hypothesis of substrate-driven ecological adaptation. This was further supported by a significant substrate-of-origin fitness advantage in a reciprocal transplant experiment. CONCLUSIONS: Altogether, our results demonstrate that edaphic preferences may correspond with deep genetic divergence between similar-looking yet differently adapted lineages. The presence of cryptic edaphic lineages suggests that plant diversity may still be underestimated in genomically underexplored but edaphically diverse hotspots such as the Balkans.

Cardamine glauca↗
PubMed2025

Automated Deep Learning-Based Detection of Early Atherosclerotic Plaques in Carotid Ultrasound Imaging.

BACKGROUND: Carotid plaque presence is associated with cardiovascular risk, even among asymptomatic individuals. While deep learning has shown promise for carotid plaque phenotyping in patients with advanced atherosclerosis, its application in population-based settings of asymptomatic individuals remains unexplored. METHODS: We developed a YOLOv8-based model for plaque detection using carotid ultrasound images from 19,499 participants of the population-based UK Biobank (UKB) and fine-tuned it for external validation in the BiDirect study (N = 2,105). Cox regression was used to estimate the impact of plaque presence and count on major cardiovascular events. To explore the genetic architecture of carotid atherosclerosis, we conducted a genome-wide association study (GWAS) meta-analysis of the UKB and CHARGE cohorts. Mendelian randomization (MR) assessed the effect of genetic predisposition to vascular risk factors on carotid atherosclerosis. RESULTS: Our model demonstrated high performance with accuracy, sensitivity, and specificity exceeding 85%, enabling identification of carotid plaques in 45% of the UKB population (aged 47-83 years). In the external BiDirect cohort, a fine-tuned model achieved 86% accuracy, 78% sensitivity, and 90% specificity. Plaque presence and count were associated with risk of major adverse cardiovascular events (MACE) over a follow-up of up to seven years, improving risk reclassification beyond the Pooled Cohort Equations. A GWAS meta-analysis of carotid plaques uncovered two novel genomic loci, with downstream analyses implicating targets of investigational drugs in advanced clinical development. Observational and MR analyses showed associations between smoking, LDL cholesterol, hypertension, and odds of carotid atherosclerosis. CONCLUSIONS: Our model offers a scalable solution for early carotid plaque detection, potentially enabling automated screening in asymptomatic individuals and improving plaque phenotyping in population-based cohorts. This approach could advance large-scale atherosclerosis research.

atherosclerosis↗
PubMed2002

Differential CO(2)-induced c-fos gene expression in the nucleus tractus solitarii of inbred mouse strains.

Genetic determinants confer variation between inbred mouse strains with respect to the magnitude and pattern of ventilation during hypercapnic challenge. Specifically, inheritance patterns derived from low-responsive C3H/HeJ (C3) and high-responsive C57BL/6J (B6) mouse strains suggest that differential hypercapnic ventilatory sensitivity (HCVS) is controlled by two independent genes. The present study also tests whether differential neuronal activity in respiratory control regions of the brain is positively associated with strain variation in HCVS. With the use of whole body plethysmography, ventilation was assessed in C3 and B6 strains at baseline and during 30 min of hypercapnia (inspired CO(2) fraction = 0.15, inspired O(2) fraction = 0.21 in N(2)). Subsequently, in situ hybridization histochemistry was performed to determine changes in c-fos gene expression in the commissural subnucleus of the nucleus tractus solitarius (NTS). During hypercapnia, breathing frequency and tidal volume were significantly (P < 0.01) different between strains: C3 mice showed a slow, deep-breathing pattern relative to a rapid, shallow phenotype of B6 mice. CO(2)-induced increase in c-fos gene expression was significantly (P < 0.01) greater in NTS regions of B6 compared with C3 mice. In this genetic model of differential HCVS, the results suggest that a genomic basis for varied hypercapnic chemoreception or transduction confers greater afferent neuronal activity in the caudal NTS for high-responsive B6 mice compared with low-responsive C3 mice.

Animals↗