Design of more efficient luminescent solar concentrators by using peripherally dye-doped stacked optical fibers.

Ways of improving the optical efficiency of luminescent solar concentrators based on multiple poly(methyl methacrylate) plastic optical fibers peripherally doped with two promising types of dyes are analyzed by means of a Monte-Carlo computational model developed by us. By comparing the performance of optical fibers doped with lumogen red and lumogen yellow, or combinations of them at several concentrations, this work clarifies how to achieve a better compromise between the trapping efficiency of the sunlight and the reabsorption of the light emitted by the mixture in stacked optical fibers connected to a photovoltaic solar cell.

[Infective endocarditis with bivalvular involvement due to Erysipelothrix rhusiopathiae. Report of one case]. / Endocarditis infecciosa con compromiso bivalvular por Erysipelothrix rhusiopathiae.

The microbiology of infective endocarditis (IE) varies in different populations and depends on public health conditions and socioeconomic status. In low-income countries, oral Streptococci affect hearts with rheumatic valve disease in patients with poor dentition. In high-income countries, Staphylococci are the most common cause, affecting elderly and immunocompromised patients, or those with invasive devices. Gram - positive bacili as IE pathogens are unusual. Erysipelothrix rhusiopathiae is a Gram positive bacili. It causes skin diseases in domestic and farm animals, but in humans, is a very unusual pathogen. This infection is considered a zoonosis, since most cases are linked to direct contact with vector animals. We report a 62 year-old male patient with a history of exposure to animals, who developed an infective endocarditis with severe bivalve regurgitation and septic shock, requiring antimicrobials and surgical resolution. Erysipelothrix rhusiopathiae was isolated from blood and valve vegetation cultures. The patient had a successful evolution and was discharged from the hospital.

Peroxisome proliferator-activated receptor-γ signalling protects hair follicle stem cells from chemotherapy-induced apoptosis and epithelial-mesenchymal transition.

BACKGROUND: Permanent chemotherapy-induced alopecia (pCIA), for which preventive interventions remain limited, can manifest with scarring. While the underlying pathomechanisms of pCIA are unclear, depletion of epithelial hair follicle (HF) stem cells (eHFSCs) is likely to play a role. OBJECTIVES: To explore the hypothesis that, besides apoptosis, eHFSCs undergo pathological epithelial-mesenchymal transition (EMT) in pCIA, thus explaining the scarring phenotype. Furthermore, we tested whether a peroxisome proliferator-activated receptor (PPAR)-γ modulator could prevent pCIA-associated pathomechanisms. METHODS: Organ-cultured human scalp HFs were treated with the cyclophosphamide metabolite 4-hydroperoxycyclophosphamide (4-HC). Additionally, HFs were pretreated with the agonistic PPAR-γ modulator N-acetyl-GED-0507-34-Levo (NAGED), which has previously been shown to promote K15 expression and antagonize EMT in eHFSCs. RESULTS: In accordance with anticipated hair bulb cytotoxicity, dystrophy and catagen induction, 4-HC promoted apoptosis along with increased p53 expression, DNA damage and pathological EMT in keratin 15+ (K15) eHFSCs, as evidenced by decreased E-cadherin expression and the appearance of fibronectin+ and vimentin+ cells in the hair bulge. Pretreatment with NAGED protected against 4-HC-induced hair bulb cytotoxicity/dystrophy, and apoptosis, p53 upregulation and EMT in the bulge, thereby significantly preventing depletion of K15+ human eHFSCs ex vivo. CONCLUSIONS: Since a key cyclophosphamide metabolite alone suffices to damage and deplete human scalp eHFSCs by promoting apoptosis, DNA damage and EMT ex vivo, strategies to prevent pCIA need to target these pathomechanisms. Given the ability of NAGED to prevent chemotherapy-induced eHFSCs damage ex vivo, our study introduces the stimulation of PPAR-γ signalling as a novel intervention strategy for the prevention of pCIA.

Citellinema (Nematoda: Heligmosomidae) from North America with descriptions of 2 new species from the red squirrel Tamiasciurus hudsonicus and 1 from the Canadian woodchuck, Marmota monax.

Citellinema Hall, 1918 includes 6 valid species of gastrointestinal nematodes of sciurids. Two species occur in the Palearctic and 4 in the Nearctic, 3 of which occur minimally across Colorado, Idaho and Oregon and 1, Citellinema bifurcatum, has a wide distribution across North America. Members of the genus are didelphic, possess a cephalic vesicle, a terminal spine-like process in females and feature robust spicules, consisting of a proximal end fused and semicylindrical shaft connected to a lamina supported by 2 terminal filiform processes. Typically, the size of the spicules is used to differentiate species. As part of the Beringian Coevolution Project, specimens provisionally identified as C. bifurcatum were collected through intensive field sampling of mammals and associated parasites from across localities spanning the Holarctic. These specimens revealed considerable genetic variability at both mitochondrial and nuclear loci, supporting the identification of deeply divergent clades. Examination of these new specimens, along with the holotypes of C. bifurcatum and Citellinema quadrivittati indicates that Citellinema monacis (previously synonymized with C. bifurcatum) should be resurrected and 3 additional species described. We suggest that the apparent bifurcated nature of the spicule should be considered a generic diagnostic trait, while the proportional length of the lamina relative to that of the spicule is used as a specific character. We demonstrate the critical need for continued inventory of often poorly known assemblages of hosts and parasites, contributing to a growing baseline of archival specimens, collections and information that make explorations of faunal structure and diversity possible.

Assessment of a computed tomography imaging spectrometer using an optimized expectation-maximization algorithm.

We designed and built a homemade computed tomography imaging spectrometer (CTIS) of 250×250pixels of spatial resolution and 2 nm spectral resolution. The optical design considers a CTIS optical array coupled to a digital reflex camera. We reconstructed the intensity spectra of a fluorescent source, the diffuse reflectance of a ColorChecker, and samples of Capsicum annuum of three different colors, using the expectation-maximization sequential algorithm, optimized utilizing an array of indices to reduce the reconstruction time. The results obtained with a ColorChecker indicate a high positive correlation of 0.9745 with an average residual difference of 1.31% concerning the spectra obtained with a commercial integrating sphere spectrometer. The feasibility of the proposed CTIS system shows how to detect and evaluate the physiological changes resulting from the decomposition of the green fruit of the Capsicum annuum in a range from 500 to 650 nm.

Space colonization by branching trachea explains the morphospace of a simple respiratory organ.

Branching morphogenesis helps increase the efficiency of gas and liquid transport in many animal organs. Studies in several model organisms have highlighted the molecular and cellular complexity behind branching morphogenesis. To understand this complexity, computational models have been developed with the goal of identifying the "major rules" that globally explain the branching patterns. These models also guide further experimental exploration of the biological processes that execute and maintain these rules. In this paper we introduce the tracheal gills of mayfly (Ephemeroptera) larvae as a model system to study the generation of branched respiratory patterns. First, we describe the gills of the mayfly Cloeon dipterum, and quantitatively characterize the geometry of its branching trachea. We next extend this characterization to those of related species to generate the morphospace of branching patterns. Then, we show how an algorithm based on the "space colonization" concept (SCA) can generate this branching morphospace via growth towards a hypothetical attractor molecule (M). SCA differs from other branch-generating algorithms in that the geometry generated depends to a great extent on its perception of the "external" space available for branching, uses few rules and, importantly, can be easily translated into a realistic "biological patterning algorithm". We identified a gene in the C. dipterum genome (Cd-bnl) that is orthologous to the fibroblast growth factor branchless (bnl), which stimulates growth and branching of embryonic trachea in Drosophila. In C. dipterum, this gene is expressed in the gill margins and areas of finer tracheolar branching from thicker trachea. Thus, Cd-bnl may perform the function of M in our model. Finally, we discuss this general mechanism in the context of other branching pattern-generating algorithms.

Deciphering the molecular morphology of the human hair cycle: Wnt signalling during the telogen-anagen transformation.

BACKGROUND: The signals that induce anagen (growth) in 'quiescent' human telogen hair follicles (HFs) are as yet unknown. Their identification promises better targeted therapeutic hair growth interventions. OBJECTIVES: Recognizing the central role of Wnt signalling in hair biology, the aim was to delineate the differential expression of key agonists, antagonists and target genes of this pathway during the telogen-to-anagen transformation of human scalp HFs. METHODS: This differential expression was studied by in situ hybridization in human telogen and early-anagen scalp HF sections. RESULTS: On anagen induction, gene expression of the Wnt ligands WNT3, WNT4 and WNT10B, the Wnt ligand secretion regulator WLS, and the Wnt target genes AXIN2 and LEF1, is significantly increased within the secondary hair germ and the dermal papilla. Conversely, expression of the secreted Wnt inhibitor SFRP1 (secreted frizzled-related protein 1) is reduced. Human epithelial HF stem cells upregulate WNT4 and WNT10A expression, suggesting that these Wnt agonists are important for stem cell activation. CONCLUSIONS: We provide the first evidence that key changes in Wnt signalling that drive murine anagen induction also occur in human scalp HFs, yet with notable differences. This provides a rational basis for Wnt-targeting therapeutic interventions to manipulate human hair growth disorders. What's already known about this topic? Upregulation of Wnt agonists and downregulation of Wnt antagonists in the secondary hair germ and/or dermal papilla drives hair growth (anagen) induction in mice. Autocrine Wnt signalling in murine epithelial hair follicle stem cells is required to maintain their stem cell function. Reduction of Wnt ligands or increased expression of Wnt antagonists induces dysregulation of the murine hair follicle cycle and causes alopecia. What does this study add? This study demonstrates for the first time that key Wnt pathway regulatory agonists, antagonists and target genes, are expressed in the human telogen-to-early-anagen transformation. On human anagen induction the Wnt ligands WNT3, WNT4 and WNT10B are increased in the regenerating epithelium, whereas the Wnt antagonist, SFRP1 (secreted frizzled-related protein 1), is reduced. Human anagen induction has fundamental differences in the expression of Wnt ligands compared with the murine system. What is the translational message? Regulation of these Wnt ligands permits targeted therapeutic interventions in human hair growth disorders and informs development of new drugs that promote or suppress anagen induction.

Cerebrospinal and blood levels of amino acids as potential biomarkers for Parkinson's disease: review and meta-analysis.

BACKGROUND AND PURPOSE: The present systematic review and meta-analysis aims to establish the possible value of cerebrospinal fluid (CSF) and serum/plasma levels of amino acids as markers of Parkinson's disease (PD). METHODS: This is a review of four databases (PubMed, Embase, MEDLINE and Web of Science - Core Collection) from 1966 to 14 March 2020, with identification of references of interest for the topic. The meta-analysis of eligible studies was done using R software package meta, following the PRISMA and MOOSE guidelines. RESULTS: Compared with age- and sex-matched controls, PD patients showed decreased CSF levels of glutamate and taurine and increased CSF levels of tyrosine; decreased serum/plasma levels of aspartate, serine, tryptophan and lysine, and increased serum/plasma proline and homocysteine levels. CONCLUSION: Despite the limitations of this study due to the important variability of results between different series, our findings suggest the value of CSF or serum/plasma levels of several amino acids in the discrimination of PD patients from healthy subjects, related to the levels of some amino acids.

Hydrocarbon Contamination Patterns in the Cenotes of the Mexican Caribbean: The Application of Principal Component Analysis.

Cenotes are naturally occurring flooded caves that are frequent in Mexico's Yucatan Peninsula; they result from the collapse of limestone bedrock into the regional groundwater table. Cenotes in Quintana Roo are important ecological and economic hot spots but are susceptible to anthropogenic pollution. In this study, we collected water samples from 11 cenotes over multiple years to evaluate polycyclic aromatic hydrocarbon (PAH) concentrations and patterns as associated with tourist traffic. The primary PAHs detected in samples included fluoranthene, anthracene, phenanthrene and naphthalene, with total PAH concentrations increasing almost fivefold for cenotes sampled from 2016 to 2017. This is compared to only a 7% increase in tourist traffic during these years. Multivariate statistical analysis of the PAH concentration data suggests that diesel, gasoline and asphalt are the most likely pollution sources and that they are associated with periods of increased tourist traffic.

Short Review: Investigating ARSACS: models for understanding cerebellar degeneration.

Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is an early-onset neurodegenerative disease that includes progressive cerebellar dysfunction. ARSACS is caused by an autosomal recessive loss-of-function mutation in the SACS gene, which encodes for SACSIN. Although animal models are still necessary to investigate the role of SACSIN in the pathology of this disease, more reliable human cellular models need to be generated to better understand the cerebellar pathophysiology of ARSACS. The discovery of human induced pluripotent stem cells (hiPSC) has permitted the derivation of patient-specific cells. These cells have an unlimited self-renewing capacity and the ability to differentiate into different neural cell types, allowing studies of disease mechanism, drug discovery and cell replacement therapies. In this study, we discuss how the hiPSC-derived cerebellar organoid culture offers novel strategies for targeting the pathogenic mutations related to ARSACS. We also highlight the advantages and challenges of this 3D cellular model, as well as the questions that still remain unanswered.

Association of adiposity, telomere length and mortality: data from the NHANES 1999-2002.

BACKGROUND/OBJECTIVES: Telomere shortening is associated with age and risk of medical comorbidity. We assessed the relationship between measures of adiposity, leukocyte telomere length, and mortality and whether it is modified by age. SUBJECTS/METHODS: Subjects with dual-energy X-ray absorptiometry measures were identified using the National Health and Nutrition Examination Survey 1999-2002. Obesity was categorized using two body fat definitions (BF1%: men ⩾25%; females ⩾35%; BF2% ⩾28% and ⩾38%, respectively), body mass index (BMI) and waist circumference (WC; men ⩾102 cm; females ⩾88 cm). Telomere length relative to standard reference DNA (T/S ratio) was assessed using quantitative PCR. Weighted multivariable regression models evaluated the association of telomere length with adiposity, both continuously and categorically (low/normal BF%, low/high WC and standard BMI categories). Differences in telomere length by age and adiposity were ascertained and subsequent models were stratified by age. Proportional hazard models assessed the risk of mortality by adiposity status. A telomere by adiposity interaction was tested in the entire cohort and by age category (<60 vs ⩾60 years; <70 vs ⩾70 years). RESULTS: We identified 7827 subjects. Mean age was 46.1 years. Overall telomere length was 1.05±0.01 (s.e.) that differed by BF1% (low/high: 1.12±0.02 vs 1.03±0.02; P<0.001), BF2% (1.02±0.02 vs 1.11±0.02; P<0.001), BMI (underweight 1.08±0.03; normal 1.09±0.02; overweight 1.04±0.02; and obese 1.03±0.02;P<0.001) and WC (low/high 1.09±0.02 vs 1.02±0.02; P<0.001). Adjusted ß-coefficients evaluating the relationship between telomere length and adiposity (measured continuously) were as follows: BF1% (ß=-0.0033±0.0008; P<0.001), BF2% (-0.041±0.008; P<0.001), BMI (ß=-0.025±0.0008; P=0.005) and WC (ß=-0.0011±0.0004; P=0.007). High BF% (BF1%: ß=-0.035±0.011; P=0.002; BF2%: ß=-0.041±0.008; P<0.001) and WC (ß=-0.035±0.011; P=0.008) were inversely related to telomere length (TL). Stratifying by age, high BF1% (-0.061±0.013), BF2% (-0.065±0.01), BMI-obesity (-0.07±0.015) and high WC (-0.048±0.013) were significant (all P<0.001). This association diminished with increasing age. In older participants, TL was inversely related to mortality (hazard ratio 0.36 (0.27, 0.49)), as were those classified by BF1% (0.68 (0.56, 0.81)), BF2% (0.75 (0.65, 0.80)), BMI (0.50 (0.42, 0.60)) and WC (0.72 (0.63, 0.83)). No interaction was observed between adiposity status, telomere length and mortality. CONCLUSIONS: Obesity is associated with shorter telomere length in young participants, a relationship that diminishes with increasing age. It does not moderate the relationship with mortality.

Eccrine sweat glands associate with the human hair follicle within a defined compartment of dermal white adipose tissue.

BACKGROUND: Eccrine sweat glands (ESGs) are critical for thermoregulation and are involved in wound healing. ESGs have traditionally been considered as separate skin appendages without connection to the pilosebaceous unit (PSU). However, recent preliminary evidence has encouraged the hypothesis that the PSU and ESG are more interconnected than previously thought. OBJECTIVES: To re-evaluate the morphology of human skin adnexa with an integrated three-dimensional (3D) perspective in order to explore the possible interconnections that the PSU and the ESG may form. METHODS: A systematic 3D reconstruction method of skin sections, direct visualization of human scalp follicular unit transplant grafts and a scalp strip ex vivo were used to validate and further explore the hypothesis. RESULTS: We demonstrate that the coiled portion of most ESGs is morphologically integrated into the PSU of human scalp skin and forms a structural unit that is embedded into a specific, hair follicle-associated region of dermal white adipose tissue (dWAT). This newly recognized unit is easily accessible and experimentally tractable by organ culture of follicular units and can be visualized intravitally. CONCLUSIONS: We propose a model of functional human skin anatomy in which ESGs are closely associated with the PSU and the dWAT to form a common homeostatic tissue environment, which may best be encapsulated in the term 'adnexal skin unit'. The challenge now is to dissect how each component of this superstructure of human skin functionally cooperates with and influences the other under physiological conditions, during regeneration and repair and in selected skin diseases.

Maternal vaccination as a Salmonella Typhimurium reduction strategy on pig farms.

AIMS: The control of Salmonella in pig production is necessary for public and animal health, and vaccination was evaluated as a strategy to decrease pig prevalence. METHODS AND RESULTS: The study examined the efficacy of a live Salmonella Typhimurium vaccine, administered to sows on eight commercial farrow-to-finish herds experiencing clinical salmonellosis or Salmonella carriage associated with S. Typhimurium or its monophasic variants. Results of longitudinal Salmonella sampling were compared against eight similarly selected and studied control farms. At the last visit (~14 months after the start of vaccination), when all finishing stock had been born to vaccinated sows, both faecal shedding and environmental prevalence of Salmonella substantially declined on the majority of vaccinated farms in comparison to the controls. A higher proportion of vaccine farms resolved clinical salmonellosis than controls. However, Salmonella counts in positive faeces samples were similar between nonvaccinated and vaccinated herds. CONCLUSIONS: The results suggest that maternal vaccination is a suitable option for a Salmonella Typhimurium reduction strategy in farrow-to-finish pig herds. SIGNIFICANCE AND IMPACT OF THE STUDY: Salmonella vaccines have the potential to reduce the prevalence of Salmonella in pigs and result in a reduction of human cases attributed to pork.

Association between eating time interval and frequency with ideal cardiovascular health: Results from a random sample Czech urban population.

BACKGROUND AND AIMS: The frequency and timing of meals may affect cardiovascular health (CVH) outcomes, but large-scale epidemiological studies are lacking. The aim of this study was to understand the relationship between eating time interval and frequency, and measures of ideal CVH in the Kardiovize Brno cohort study, a random urban sample population in Central Europe. METHODS AND RESULTS: 1659 members of the Kardiovize Brno 2030 cohort were included in a cross-sectional study (mean age = 46.86 years; 44.6% male). Exposure variables were eating time interval and frequency, and skipping meals. Primary outcomes were indices of CVH, including body mass index, diet, physical activity, smoking, blood pressure, glucose and cholesterol, and the composite CVH score. Cluster analysis and binary logistic regression analysis were used to evaluate eating habits and the association between variables. After adjustment for well-known risk factors, subjects who skipped breakfast or the afternoon snack had a higher risk of poor CVH (OR = 1.613; 95%CI = 1.121-2.320; p = 0.010; OR = 1.409; 95%CI = 1.110-1.788; p = 0.005, respectively). Moreover, we identified three clusters of individuals based on eating habits; from cluster 1 to cluster 3, eating time interval and frequency increased and this was associated with increases in CVH score from 8.70 (SEM = 0.10) in cluster 1, and 9.06 (SEM = 0.08) in cluster 2 to 9.42 (SEM = 0.09) in cluster 3 (p-trend = 0.019). CONCLUSIONS: Our findings suggest that skipping breakfast or the afternoon snack are risk factors for poor CVH, while higher eating time interval and frequency may promote ideal CVH.

Feed restriction regime in a rabbit line selected for growth rate alters oocyte maturation manifested by alteration in MSY2 gene expression.

Young rabbit females selected for growth rate may have nutritional needs, which may not be met with the common practice of feed restriction during rearing in commercial rabbit production. The aim of this study was to analyse whether two different feeding programmes: ad libitum or restricted (130 g/day) feeding, applied in young rabbit females for 1 month at the end of rearing, could modulate the origin of ovulation process and the quality of the oocytes. At 16 weeks of age, 34 females were randomly assigned to restricted or ad libitum feeding, maintaining these conditions for a month. Then, in an initial experiment, transcriptional profiling of hypothalamus-hypophysis tissue was performed to assess failure to ovulate. In the second experiment, the gene expression analysis of some candidate genes related to oocytes quality was performed. Our results demonstrated that neither of the two feeding programmes modified the transcription of hypothalamus-hypophysis tissue, while the only differences in MSYR expression were found in in vivo mature oocytes ready for successful fertilization. Specifically, MSYR was over-expressed in oocytes from females fed ad libitum. MSYR is one of the most abundant proteins in the oocyte and has proven to be a key regulator of maternal RNA transcription and translation. This finding suggests that MSYR gene is a promising gene in our understanding of the relationship between high growth rate and reproductive performance decline.

Diagnostic accuracy of body mass index to identify obesity in older adults: NHANES 1999-2004.

BACKGROUND: Body composition changes with aging lead to increased adiposity and decreased muscle mass, making the diagnosis of obesity challenging. Conventional anthropometry, including body mass index (BMI), while easy to use clinically may misrepresent adiposity. We determined the diagnostic accuracy of BMI using dual-energy X-ray absorptiometry (DEXA) in assessing the degree of obesity in older adults. METHODS: The National Health and Nutrition Examination Surveys 1999-2004 were used to identify adults aged ⩾60 years with DEXA measures. They were categorized (yes/no) as having elevated body fat by gender (men: ⩾25%; women ⩾35%) and by BMI ⩾25 and ⩾30 kg m(-)(2). The diagnostic performance of BMI was assessed. Metabolic characteristics were compared in discordant cases of BMI/body fat. Weighting and analyses were performed per NHANES (National Health and Nutrition Examination Survey) guidelines. RESULTS: We identified 4984 subjects (men: 2453; women: 2531). Mean BMI and % body fat was 28.0 kg m(-2) and 30.8% in men, and 28.5 kg m(-)(2) and 42.1% in women. A BMI ⩾30 kg m(-)(2) had a low sensitivity and moderately high specificity (men: 32.9 and 80.8%, concordance index 0.66; women: 38.5 and 78.5%, concordance 0.69) correctly classifying 41.0 and 45.1% of obese subjects. A BMI ⩾25 kg m(-2) had a moderately high sensitivity and specificity (men: 80.7 and 99.6%, concordance 0.81; women: 76.9 and 98.8%, concordance 0.84) correctly classifying 80.8 and 78.5% of obese subjects. In subjects with BMI <30 kg m(-)(2), body fat was considered elevated in 67.1% and 61.5% of men and women, respectively. For a BMI ⩾30 kg m(-)(2), sensitivity drops from 40.3% to 14.5% and 44.5% to 23.4%, whereas specificity remains elevated (>98%), in men and women, respectively, in those 60-69.9 years to subjects aged ⩾80 years. Correct classification of obesity using a cutoff of 30 kg m(-)(2) drops from 48.1 to 23.9% and 49.0 to 19.6%, in men and women in these two age groups. CONCLUSIONS: Traditional measures poorly identify obesity in the elderly. In older adults, BMI may be a suboptimal marker for adiposity.

Differential effects of leptin on adiponectin expression with weight gain versus obesity.

BACKGROUND/OBJECTIVE: Adiponectin exerts beneficial effects by reducing inflammation and improving lipid metabolism and insulin sensitivity. Although the adiponectin level is lower in obese individuals, whether weight gain reduces adiponectin expression in humans is controversial. We sought to investigate the role of weight gain, and consequent changes in leptin, on altering adiponectin expression in humans. METHODS/RESULTS: Forty-four normal-weight healthy subjects were recruited (mean age 29 years; 14 women) and randomized to either gain 5% of body weight by 8 weeks of overfeeding (n=34) or maintain weight (n=10). Modest weight gain of 3.8±1.2 kg resulted in increased adiponectin level (P=0.03), whereas weight maintenance resulted in no changes in adiponectin. Further, changes in adiponectin correlated positively with changes in leptin (P=0.0085). In-vitro experiments using differentiated human white preadipocytes showed that leptin increased adiponectin mRNA and protein expression, whereas a leptin antagonist had opposite effects. To understand the role of leptin in established obesity, we compared adipose tissue samples obtained from normal-weight versus obese subjects. We noted, first, that leptin activated cellular signaling pathways and increased adiponectin mRNA in the adipose tissue from normal-weight participants, but did not do so in the adipose tissue from obese participants. Second, we noted that obese subjects had increased caveolin-1 expression, which attenuates leptin-dependent increases in adiponectin. CONCLUSIONS: Modest weight gain in healthy individuals is associated with increases in adiponectin levels, which correlate positively with changes in leptin. In vitro, leptin induces adiponectin expression, which is attenuated by increased caveolin-1 expression. In addition, the adipose tissue from obese subjects shows increased caveolin-1 expression and impaired leptin signaling. This leptin signal impairment may prevent concordant increases in adiponectin levels in obese subjects despite their high levels of leptin. Therefore, impaired leptin signaling may contribute to low adiponectin expression in obesity and may provide a target for increasing adiponectin expression, hence improving insulin sensitivity and cardio-metabolic profile in obesity.