Perturbing cortical networks: in vivo electrophysiological consequences of pan-neuronal chemogenetic manipulations using deschloroclozapine.

Introduction: Chemogenetic techniques, specifically the use of Designer Receptors Exclusively Activated by Designer Drugs (DREADDs), have become invaluable tools in neuroscience research. Yet, the understanding of how Gq- and Gicoupled DREADDs alter local field potential (LFP) oscillations in vivo remains incomplete. Methods: This study investigates the in vivo electrophysiological effects of DREADD actuation by deschloroclozapine, on spontaneous firing rate and LFP oscillations recorded from the anterior cingulate cortex in lightly anesthetized male rats. Results: Unexpectedly, in response to the administration of deschloroclozapine, we observed inhibitory effects with pan-neuronal hM3D(Gq) stimulation, and excitatory effects with pan-neuronal hM4D(Gi) stimulation in a significant portion of neurons. These results emphasize the need to account for indirect perturbation effects at the local neuronal network level in vivo, particularly when not all neurons express the chemogenetic receptors uniformly. In the current study, for instance, the majority of cells that were transduced with both hM3D(Gq) and hM4D(Gi) were GABAergic. Moreover, we found that panneuronal cortical chemogenetic modulation can profoundly alter oscillatory neuronal activity, presenting a potential research tool or therapeutic strategy in several neuropsychiatric models and diseases. Discussion: These findings help to optimize the use of chemogenetic techniques in neuroscience research and open new possibilities for novel therapeutic strategies.

Intrinsic anticipatory motives in non-human primate food consumption behavior.

Future-oriented behavior is regarded as a cornerstone of human cognition. One key phenomenon through which future orientation can be studied is the delay of gratification, when consumption of an immediate reward is withstood to achieve a larger reward later. The delays used in animal delay of gratification paradigms are rather short to be considered relevant for studying human-like future orientation. Here, for the first time, we show that rhesus macaques exhibit human-relevant future orientation downregulating their operant food consumption in anticipation of a nutritionally equivalent but more palatable food with an unprecedentedly long delay of approximately 2.5 h. Importantly, this behavior is not a result of conditioning but intrinsic to the animals. Our results show that the cognitive time horizon of primates, when tested in ecologically valid foraging-like experiments, extends much further into the future than previously considered, opening up new avenues for translational biomedical research.

[The importance and areas of modern supportive and early integrated palliative care in the treatment of brain tumor patients]. / A korszeru szupportív ellátás és az integrált korai palliatív gondozás jelentosége és fontosabb területei agydaganatos betegek kezelése során.

During the care of brain tumor patients, supportive care and palliation are carried out in an individualized manner, accompanied by adequate communication, in a multidisciplinary professional environment. In the case of brain tumor patients, the burden of symptoms resulting from the progression of the disease and the complications of treatments occur in a particularly high proportion. The supportive care of patients in a modern approach covers the targeted treatment of physical and psychosocial problems and also includes integrated palliation. Palliative care is a form of care that can be used in addition to curative therapies, and it is advisable and necessary to introduce it as early as possible among brain tumor patients due to the significant deterioration of the quality of life. Dealing with seriously ill patients on a daily basis is also an emotional burden for the professional staff, and carries the risk of burnout. The support of the staff and family members, as well as the issues of adequate communication, are also part of the scope of the supportive care approach.

Variable Projection Support Vector Machines and Some Applications Using Adaptive Hermite Expansions.

In this paper, we develop the so-called variable projection support vector machine (VP-SVM) algorithm that is a generalization of the classical SVM. In fact, the VP block serves as an automatic feature extractor to the SVM, which are trained simultaneously. We consider the primal form of the arising optimization task and investigate the use of nonlinear kernels. We show that by choosing the so-called adaptive Hermite function system as the basis of the orthogonal projections in our classification scheme, several real-world signal processing problems can be successfully solved. In particular, we test the effectiveness of our method in two case studies corresponding to anomaly detection. First, we consider the detection of abnormal peaks in accelerometer data caused by sensor malfunction. Then, we show that the proposed classification algorithm can be used to detect abnormalities in ECG data. Our experiments show that the proposed method produces comparable results to the state-of-the-art while retaining desired properties of SVM classification such as light weight architecture and interpretability. We implement the proposed method on a microcontroller and demonstrate its ability to be used for real-time applications. To further minimize computational cost, discrete orthogonal adaptive Hermite functions are introduced for the first time.

Benefits of Blastocyst Transfer With at Least Three Good-Quality Cleavage-stage Embryos in Women of Advanced Maternal Age: A Retrospective Analysis.

OBJECTIVES: Limited studies on the benefits of blastocyst transfer in advanced maternal age (AMA) (≥40 years) have been reported. Our objective was to find whether blastocyst-stage embryo transfer improves pregnancy and live birth rates in women ≥40 years who have 3 or more good-quality cleavage-stage embryos. METHODS: All fresh in vitro fertilization-intracytoplasmic sperm injection cycles performed from January 2020 to December 2021 in AMA women that progressed to transfer were considered for analysis. We compared fresh and cumulative ongoing pregnancy rates in AMA women of those who had a cleavage-stage transfer, while meeting the criteria for extended culture (≥3 high-quality embryos, group 1), and those who underwent blastocyst transfer (group 2). Demographic parameters, stimulation, embryology, fresh and cumulative ongoing pregnancy rates, and clinical miscarriage rates were compared. RESULTS: During the study period, 255 cycles were analyzed including group 1 (n = 99) and group 2 (n = 156). Group 1 participants were older and had a greater number of embryos for transfer. Fresh and cumulative ongoing pregnancy rates per transfer were higher in group 2 compared to group 1 (23.4% vs. 13.1%, P = 0.04; 25.5% vs. 14.1%, P = 0.03), while overall miscarriage rates were higher in group 1 than group 2 (51.7% vs. 25%, P = 0.01). CONCLUSIONS: Blastocyst culture provides a benefit to AMA women who have at least 3 good-quality embryos on day 3 resulting in significantly higher fresh and cumulative ongoing pregnancy rates and lower miscarriage compared to cleavage-stage transfers.

The Role of Phosphatidylethanolamine N-Methyltransferase (PEMT) and Its Waist-Hip-Ratio-Associated Locus rs4646404 in Obesity-Related Metabolic Traits and Liver Disease.

In previous genome-wide association studies (GWAS), genetic loci associated with obesity and impaired fat distribution (FD) have been identified. In the present study, we elucidated the role of the PEMT gene, including the waist-hip-ratio-associated single nucleotide polymorphism rs4646404, and its influence on obesity-related metabolic traits. DNA from 2926 metabolically well-characterized subjects was used for genotyping. PEMT expression was analyzed in paired visceral (vis) and subcutaneous (sc) adipose tissue (AT) from a subset of 574 individuals. Additionally, PEMT expression was examined in vis, sc AT and liver tissue in a separate cohort of 64 patients with morbid obesity and liver disease. An in vitro Pemt knockdown was conducted in murine epididymal and inguinal adipocytes. Our findings highlight tissue-specific variations in PEMT mRNA expression across the three studied tissues. Specifically, vis PEMT mRNA levels correlated significantly with T2D and were implicated in the progression of non-alcoholic steatohepatitis (NASH), in contrast to liver tissue, where no significant associations were found. Moreover, sc PEMT expression showed significant correlations with several anthropometric- and metabolic-related parameters. The rs4646404 was associated with vis AT PEMT expression and also with diabetes-related traits. Our in vitro experiments supported the influence of PEMT on adipogenesis, emphasizing its role in AT biology. In summary, our data suggest that PEMT plays a role in regulating FD and has implications in metabolic diseases.

Cattle manure application for 12 and 17 years enhanced depth distribution of soil organic carbon and X-ray computed tomography-derived pore characteristics.

Long-term fertilizer application in row crops may influence soil pore characteristics, thereby impacting soil aggregation and structure. Therefore, understanding the influences on soil pore characteristics is useful for adopting suitable conservation practices. However, the impact of cattle manure and inorganic fertilizer application at varied rates on soil pore characteristics in the soil profile at a microscale level remains limited. This study quantifies the impacts of manure and inorganic fertilizer amendments under a corn (Zea mays L.)-soybean (Glycine max L.)-spring wheat (Triticum aestivum) rotation system on soil pore characteristics using the X-ray computed tomography (XCT). Treatments included: low manure (LM; 4.4 and 3.3 Mg ha-1), medium manure (MM; 27.4 and 18.7 Mg ha-1), high manure (HM; 54.8 and 37.4 Mg ha-1), medium fertilizer (MF; 136 kg N ha-1, 49 kg P2O5 ha-1, and 91.5 kg K2O ha-1), high fertilizer (HF; 204 kg N ha-1, 73.5 kg P2O5 ha-1, and 137.3 kg K2O ha-1), and control (CK), respectively, at Brookings (initiated in 2008) and Beresford (2003) in South Dakota. Four intact soil cores were collected from each treatment at 0-10, 10-20, 20-30, and 30-40 cm depths. Results showed that the HM treatment increased the SOC by 8-68% compared to the CK and MF at 0-20 cm at the study sites. Both HM and MM treatments increased the macroporosity and mesoporosity in 0-20 cm soil depths at both study sites. Treatment did not always improve soil pore characteristics below 20 cm soil depth. Additionally, a positive correlation was observed between the XCT-derived macroporosity, total number of macropores, and SOC for all the treatments. Therefore, this study encourages the adoption of the XCT technique in quantifying soil pore characteristics and suggests that long-term medium manure application enhances soil structure as compared to an equivalent inorganic fertilizer application.

Origin of the success of mGGAs for bandgaps.

One of the well-known limitations of Kohn-Sham density functional theory is the tendency to strongly underestimate bandgaps. Meta-generalized gradient approximations (mGGAs), which include the kinetic energy density in the functional form, have been shown to significantly alleviate this deficiency. In this study, we explore the mechanisms responsible for this improvement from the angle of the underlying local densities. We find that the highest occupied and lowest unoccupied states are distinct in the space of the underlying descriptors. The gap opening is compared to a simple scaling of the local density approximation, and two mechanisms responsible for opening the mGGA gaps are identified. First of all, the relatively large negative derivative of the functional form with respect to reduced kinetic energy tends to elevate the lowest unoccupied state. Second, the curvature of functional, which ensures that it is bounded, tends to lower the highest occupied state. Remarkably, these two mechanisms are found to be transferable over a large and diverse database of compounds.

Investigation of the Tensile Strength of Adhesive-Bonded Steels Using Surface Treatments.

This study explores the tensile strength of adhesive joints in steel, focusing on the influence of heat treatment and diverse surface modifications. Results indicate a notable relationship between annealing temperature and tensile strength, with the most favorable outcomes identified at 90 min and 165 °C. Particularly, surfaces treated through turning, sandblasting, and plasma treatment (type C) consistently outperformed other methods. A standout revelation emerged from the turned, sandblasted, and plasma-treated surface (C), showcasing an exceptional tensile strength of 69.06 MPa. Load-holding tests underscored its resilience under diverse load conditions. Surface analyses, including roughness measurements, wetting characteristics, and Scanning Electron Microscope imaging, provided valuable insights into structural transformations induced by different treatments. Chemical composition examinations unveiled significant alterations post-plasma treatment, impacting surface chemistry and contributing to an outstanding tensile strength of 67.63 MPa. In essence, this research offers a glimpse into the nuanced factors influencing adhesive joint strength in steel. The turned, sandblasted, and plasma-treated surface emerges as a promising avenue, sparking further curiosity into the underlying mechanisms propelling superior tensile strength in adhesive joints.

Chromosome genomics facilitates the marker development and selection of wheat-Aegilops biuncialis addition, substitution and translocation lines.

The annual goatgrass, Aegilops biuncialis is a rich source of genes with considerable agronomic value. This genetic potential can be exploited for wheat improvement through interspecific hybridization to increase stress resistance, grain quality and adaptability. However, the low throughput of cytogenetic selection hampers the development of alien introgressions. Using the sequence of flow-sorted chromosomes of diploid progenitors, the present study enabled the development of chromosome-specific markers. In total, 482 PCR markers were validated on wheat (Mv9kr1) and Ae. biuncialis (MvGB642) crossing partners, and 126 on wheat-Aegilops additions. Thirty-two markers specific for U- or M-chromosomes were used in combination with GISH and FISH for the screening of 44 Mv9kr1 × Ae. biuncialis BC3F3 genotypes. The predominance of chromosomes 4M and 5M, as well as the presence of chromosomal aberrations, may indicate that these chromosomes have a gametocidal effect. A new wheat-Ae. biuncialis disomic 4U addition, 4M(4D) and 5M(5D) substitutions, as well as several introgression lines were selected. Spike morphology and fertility indicated that the Aegilops 4M or 5M compensated well for the loss of 4D and 5D, respectively. The new cytogenetic stocks represent valuable genetic resources for the introgression of key genes alleles into wheat.

Genetics and Epigenetics in Obesity: What Do We Know so Far?

PURPOSE OF REVIEW: Enormous progress has been made in understanding the genetic architecture of obesity and the correlation of epigenetic marks with obesity and related traits. This review highlights current research and its challenges in genetics and epigenetics of obesity. RECENT FINDINGS: Recent progress in genetics of polygenic traits, particularly represented by genome-wide association studies, led to the discovery of hundreds of genetic variants associated with obesity, which allows constructing polygenic risk scores (PGS). In addition, epigenome-wide association studies helped identifying novel targets and methylation sites being important in the pathophysiology of obesity and which are essential for the generation of methylation risk scores (MRS). Despite their great potential for predicting the individual risk for obesity, the use of PGS and MRS remains challenging. Future research will likely discover more loci being involved in obesity, which will contribute to better understanding of the complex etiology of human obesity. The ultimate goal from a clinical perspective will be generating highly robust and accurate prediction scores allowing clinicians to predict obesity as well as individual responses to body weight loss-specific life-style interventions.

Genetic dissection of serum vaspin highlights its causal role in lipid metabolism.

OBJECTIVE: Vaspin (visceral adipose tissue derived serine protease inhibitor, SERPINA12) is associated with obesity-related metabolic traits, but its causative role is still elusive. The role of genetics in serum vaspin variability to establish its causal relationship with metabolically relevant traits was investigated. METHODS: A meta-analysis of genome-wide association studies for serum vaspin from six independent cohorts (N = 7446) was conducted. Potential functional variants of vaspin were included in Mendelian randomization (MR) analyses to assess possible causal pathways between vaspin and homeostasis model assessment and lipid traits. To further validate the MR analyses, data from Genotype-Tissue Expression (GTEx) were analyzed, db/db mice were treated with vaspin, and serum lipids were measured. RESULTS: A total of 468 genetic variants represented by five independent variants (rs7141073, rs1956709, rs4905216, rs61978267, rs73338689) within the vaspin locus were associated with serum vaspin (all p < 5×10-8 , explained variance 16.8%). MR analyses revealed causal relationships between serum vaspin and triglycerides, low-density lipoprotein, and total cholesterol. Gene expression correlation analyses suggested that genes, highly correlated with vaspin expression in adipose tissue, are enriched in lipid metabolic processes. Finally, in vivo vaspin treatment reduced serum triglycerides in obese db/db mice. CONCLUSIONS: The data show that serum vaspin is strongly determined by genetic variants within vaspin, which further highlight vaspin's causal role in lipid metabolism.

The effect of polyphenols on DNA methylation-assessed biological age attenuation: the DIRECT PLUS randomized controlled trial.

BACKGROUND: Epigenetic age is an estimator of biological age based on DNA methylation; its discrepancy from chronologic age warrants further investigation. We recently reported that greater polyphenol intake benefitted ectopic fats, brain function, and gut microbiota profile, corresponding with elevated urine polyphenols. The effect of polyphenol-rich dietary interventions on biological aging is yet to be determined. METHODS: We calculated different biological aging epigenetic clocks of different generations (Horvath2013, Hannum2013, Li2018, Horvath skin and blood2018, PhenoAge2018, PCGrimAge2022), their corresponding age and intrinsic age accelerations, and DunedinPACE, all based on DNA methylation (Illumina EPIC array; pre-specified secondary outcome) for 256 participants with abdominal obesity or dyslipidemia, before and after the 18-month DIRECT PLUS randomized controlled trial. Three interventions were assigned: healthy dietary guidelines, a Mediterranean (MED) diet, and a polyphenol-rich, low-red/processed meat Green-MED diet. Both MED groups consumed 28 g walnuts/day (+ 440 mg/day polyphenols). The Green-MED group consumed green tea (3-4 cups/day) and Mankai (Wolffia globosa strain) 500-ml green shake (+ 800 mg/day polyphenols). Adherence to the Green-MED diet was assessed by questionnaire and urine polyphenols metabolomics (high-performance liquid chromatography quadrupole time of flight). RESULTS: Baseline chronological age (51.3 ± 10.6 years) was significantly correlated with all methylation age (mAge) clocks with correlations ranging from 0.83 to 0.95; p < 2.2e - 16 for all. While all interventions did not differ in terms of changes between mAge clocks, greater Green-Med diet adherence was associated with a lower 18-month relative change (i.e., greater mAge attenuation) in Li and Hannum mAge (beta = - 0.41, p = 0.004 and beta = - 0.38, p = 0.03, respectively; multivariate models). Greater Li mAge attenuation (multivariate models adjusted for age, sex, baseline mAge, and weight loss) was mostly affected by higher intake of Mankai (beta = - 1.8; p = 0.061) and green tea (beta = - 1.57; p = 0.0016) and corresponded with elevated urine polyphenols: hydroxytyrosol, tyrosol, and urolithin C (p < 0.05 for all) and urolithin A (p = 0.08), highly common in green plants. Overall, participants undergoing either MED-style diet had ~ 8.9 months favorable difference between the observed and expected Li mAge at the end of the intervention (p = 0.02). CONCLUSIONS: This study showed that MED and green-MED diets with increased polyphenols intake, such as green tea and Mankai, are inversely associated with biological aging. To the best of our knowledge, this is the first clinical trial to indicate a potential link between polyphenol intake, urine polyphenols, and biological aging. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03020186.

An atlas of genome-wide gene expression and metabolite associations and possible mediation effects towards body mass index.

Investigating the cross talk of different omics layers is crucial to understand molecular pathomechanisms of metabolic diseases like obesity. Here, we present a large-scale association meta-analysis of genome-wide whole blood and peripheral blood mononuclear cell (PBMC) gene expressions profiled with Illumina HT12v4 microarrays and metabolite measurements from dried blood spots (DBS) characterized by targeted liquid chromatography tandem mass spectrometry (LC-MS/MS) in three large German cohort studies with up to 7706 samples. We found 37,295 associations comprising 72 amino acids (AA) and acylcarnitine (AC) metabolites (including ratios) and 8579 transcripts. We applied this catalogue of associations to investigate the impact of associating transcript-metabolite pairs on body mass index (BMI) as an example metabolic trait. This is achieved by conducting a comprehensive mediation analysis considering metabolites as mediators of gene expression effects and vice versa. We discovered large mediation networks comprising 27,023 potential mediation effects within 20,507 transcript-metabolite pairs. Resulting networks of highly connected (hub) transcripts and metabolites were leveraged to gain mechanistic insights into metabolic signaling pathways. In conclusion, here, we present the largest available multi-omics integration of genome-wide transcriptome data and metabolite data of amino acid and fatty acid metabolism and further leverage these findings to characterize potential mediation effects towards BMI proposing candidate mechanisms of obesity and related metabolic diseases. KEY MESSAGES: Thousands of associations of 72 amino acid and acylcarnitine metabolites and 8579 genes expand the knowledge of metabolome-transcriptome associations. A mediation analysis of effects on body mass index revealed large mediation networks of thousands of obesity-related gene-metabolite pairs. Highly connected, potentially mediating hub genes and metabolites enabled insight into obesity and related metabolic disease pathomechanisms.

Implication of DNA methylation during lifestyle mediated weight loss.

Over the past 50 years, the number of overweight/obese people increased significantly, making obesity a global public health challenge. Apart from rare monogenic forms, obesity is a multifactorial disease, most likely resulting from a concerted interaction of genetic, epigenetic and environmental factors. Although recent studies opened new avenues in elucidating the complex genetics behind obesity, the biological mechanisms contributing to individual's risk to become obese are not yet fully understood. Non-genetic factors such as eating behaviour or physical activity are strong contributing factors for the onset of obesity. These factors may interact with genetic predispositions most likely via epigenetic mechanisms. Epigenome-wide association studies or methylome-wide association studies are measuring DNA methylation at single CpGs across thousands of genes and capture associations to obesity phenotypes such as BMI. However, they only represent a snapshot in the complex biological network and cannot distinguish between causes and consequences. Intervention studies are therefore a suitable method to control for confounding factors and to avoid possible sources of bias. In particular, intervention studies documenting changes in obesity-associated epigenetic markers during lifestyle driven weight loss, make an important contribution to a better understanding of epigenetic reprogramming in obesity. To investigate the impact of lifestyle in obesity state specific DNA methylation, especially concerning the development of new strategies for prevention and individual therapy, we reviewed 19 most recent human intervention studies. In summary, this review highlights the huge potential of targeted interventions to alter disease-associated epigenetic patterns. However, there is an urgent need for further robust and larger studies to identify the specific DNA methylation biomarkers which influence obesity.

[Effectiveness of psychotherapeutic interventions: the potentials of professional guidelines - a methodological consensus proposal].

Psychotherapeutic interventions diff er from other health care interventions in many ways, thus the indicators of evidence-based medicine should be used with modifications when necessary. Implementation of a unified evaluation and quality assurance framework would aid the psychotherapy scene in having their intervention methods acknowledged by other medical specialties as an equal healthcare intervention. Professional recommendations regarding the interventions and methods used in clinical care in the field of psychotherapy can be laid down in specific professional guidelines of the domestic healthcare regulatory practice. A professional guideline is both a starting point and a practical guide for (planning to train, in training, or trained) professionals, as well as for the healthcare funder(s). In addition, a fixed professional framework would provide a consistent and accountable reference for quality assurance for patients who wish to recover and for those consider receiving psychotherapy. Evidence-based recommendations for the practice of the profession 1) can validate the applied care practice through findings supported from a scientific point of view, 2) can consensually resolve the specific contradictions of the field through definitions 3) can also provide a basis for transparent training, administrative and financing aspects. Consistent professional decision-making must be carried out according to a uniform ranking system. The reliability of the evidence is also very important in terms of clinical applicability of a psychotherapy method.

Genome-wide association study and functional characterization identifies candidate genes for insulin-stimulated glucose uptake.

Distinct tissue-specific mechanisms mediate insulin action in fasting and postprandial states. Previous genetic studies have largely focused on insulin resistance in the fasting state, where hepatic insulin action dominates. Here we studied genetic variants influencing insulin levels measured 2 h after a glucose challenge in >55,000 participants from three ancestry groups. We identified ten new loci (P < 5 × 10-8) not previously associated with postchallenge insulin resistance, eight of which were shown to share their genetic architecture with type 2 diabetes in colocalization analyses. We investigated candidate genes at a subset of associated loci in cultured cells and identified nine candidate genes newly implicated in the expression or trafficking of GLUT4, the key glucose transporter in postprandial glucose uptake in muscle and fat. By focusing on postprandial insulin resistance, we highlighted the mechanisms of action at type 2 diabetes loci that are not adequately captured by studies of fasting glycemic traits.

Overexpressing high levels of human vaspin limits high fat diet-induced obesity and enhances energy expenditure in a transgenic mouse.

Adipose tissue inflammation and insulin resistance are hallmarks in the development of metabolic diseases resulting from overweight and obesity, such as type 2 diabetes and non-alcoholic fatty liver disease. In obesity, adipocytes predominantly secrete proinflammatory adipokines that further promote adipose tissue dysfunction with negative effects on local and systemic insulin sensitivity. Expression of the serpin vaspin (SERPINA12) is also increased in obesity and type 2 diabetes, but exhibits compensatory roles in inflammation and insulin resistance. This has in part been demonstrated using vaspin-transgenic mice. We here report a new mouse line (h-vaspinTG) with transgenic expression of human vaspin in adipose tissue that reaches vaspin concentrations three orders of magnitude higher than wild type controls (>200 ng/ml). Phenotyping under chow and high-fat diet conditions included glucose-tolerance tests, measurements of energy expenditure and circulating parameters, adipose tissue and liver histology. Also, ex vivo glucose uptake in isolated adipocytes and skeletal muscle was analyzed in h-vaspinTG and littermate controls. The results confirmed previous findings, revealing a strong reduction in diet-induced weight gain, fat mass, hyperinsulinemia, -glycemia and -cholesterolemia as well as fatty liver. Insulin sensitivity in adipose tissue and muscle was not altered. The h-vaspinTG mice showed increased energy expenditure under high fat diet conditions, that may explain reduced weight gain and overall metabolic improvements. In conclusion, this novel human vaspin-transgenic mouse line will be a valuable research tool to delineate whole-body, tissue- and cell-specific effects of vaspin in health and disease.