Brain-Derived CCN3 Is An Osteoanabolic Hormone That Sustains Bone in Lactating Females.

In lactating mothers, the high calcium (Ca 2+ ) demand for milk production triggers significant bone resorption. While estrogen would normally counteract excessive bone loss and maintain sufficient bone formation during this postpartum period, this sex steroid drops precipitously after giving birth. Here, we report that brain-derived CCN3 (Cellular Communication Network factor 3) secreted from KISS1 neurons of the arcuate nucleus (ARC KISS1 ) fills this void and functions as a potent osteoanabolic factor to promote bone mass in lactating females. Using parabiosis and bone transplant methods, we first established that a humoral factor accounts for the female-specific, high bone mass previously observed by our group after deleting estrogen receptor alpha (ER α ) from ARC KISS1 neurons 1 . This exceptional bone phenotype in mutant females can be traced back to skeletal stem cells (SSCs), as reflected by their increased frequency and osteochondrogenic potential. Based on multiple assays, CCN3 emerged as the most promising secreted pro-osteogenic factor from ARC KISS1 neurons, acting on mouse and human SSCs at low subnanomolar concentrations independent of age or sex. That brain-derived CCN3 promotes bone formation was further confirmed by in vivo gain- and loss-of-function studies. Notably, a transient rise in CCN3 appears in ARC KISS1 neurons in estrogen-depleted lactating females coincident with increased bone remodeling and high calcium demand. Our findings establish CCN3 as a potentially new therapeutic osteoanabolic hormone that defines a novel female-specific brain-bone axis for ensuring mammalian species survival.

Metal nanowires grown in situ on polymeric fibres for electronic textiles.

A key aspect of the use of conventional fabrics as smart textiles and wearable electronics is to incorporate a means of electrical conductivity into single polymer fibres. We present the transformation of thin polymer fibres and fabrics into conductive materials by in situ growth of a thin, optically transparent gold-silver nanowire (NW) mesh with a relatively low metal loading directly on the surface of polymer fibres. Demonstrating the method on poly(lactic-co-glycolic) acid and nylon microfibres, we show that the NW network morphology depends on the diameter of the polymer fibres, where at small diameters (1-2 µm), the NWs form a randomly oriented network, but for diameters above several micrometers, the NWs wrap around the fibres transversally. This phenomenon is associated with the stiffness of the surfactant templates used for the NW formation. The NW-decorated fibres exhibit a significant increase in conductivity. Moreover, single fibres can be stretched up to ∼15% before losing the electrical conductivity, while non-woven meshes could be stretched by about 25% before losing the conductivity. We believe that the approach demonstrated here can be extended to other polymeric fibres and that these flexible and transparent metal-coated polymer fibres could be useful for various smart electronic textile applications.

No Evidence of Association Between Undercarboxylated Osteocalcin and Incident Type 2 Diabetes.

Mouse models suggest that undercarboxylated osteocalcin (ucOC), produced by the skeleton, protects against type 2 diabetes development, whereas human studies have been inconclusive. We aimed to determine if ucOC or total OC is associated with incident type 2 diabetes or changes in fasting glucose, insulin resistance (HOMA-IR), or beta-cell function (HOMA-Beta). A subcohort (n = 338; 50% women; 36% black) was identified from participants without diabetes at baseline in the Health, Aging, and Body Composition Study. Cases of incident type 2 diabetes (n = 137) were defined as self-report at an annual follow-up visit, use of diabetes medication, or elevated fasting glucose during 8 years of follow-up. ucOC and total OC were measured in baseline serum. Using a case-cohort design, the association between biomarkers and incident type 2 diabetes was assessed using robust weighted Cox regression. In the subcohort, linear regression models analyzed the associations between biomarkers and changes in fasting glucose, HOMA-IR, and HOMA-Beta over 9 years. Higher levels of ucOC were not statistically associated with increased risk of incident type 2 diabetes (adjusted hazard ratio = 1.06 [95% confidence interval, 0.84-1.34] per 1 standard deviation [SD] increase in ucOC). Results for %ucOC and total OC were similar. Adjusted associations of ucOC, %ucOC, and total OC with changes in fasting glucose, HOMA-IR, and HOMA-Beta were modest and not statistically significant. We did not find evidence of an association of baseline undercarboxylated or total osteocalcin with risk of incident type 2 diabetes or with changes in glucose metabolism in older adults. © 2022 American Society for Bone and Mineral Research (ASBMR).

Contact-free conductivity probing of metal nanowire films using THz reflection spectroscopy.

We utilize time-domain Terahertz (THz) reflectivity measurements for characterizing the surface conductivity of Polyethylene-terephthalate coated with nanowire (NW) films to form novel transparent electrodes (TE). We find good correspondence between the film conductivity and the THz-field reflectivity that provide uniquely desirable means for non-destructive, contactless conductivity measurements of large area NW-based-TEs. We demonstrate the robustness of THz reflectivity measurements to deviations invoked on NW film composition and film uniformity. The dependence of THz reflectivity on area NW coverage follows an anisotropic effective medium model for the dielectric constant.

Patterning Metal Nanowire-Based Transparent Electrodes by Seed Particle Printing.

This article describes a unique combination of inkjet printing of functional materials with an intricate self-assembly process. Gold-silver nanowire (NW) mesh films were produced by a sequential deposition process, in which small metal seed nanoparticle film was deposited at desired areas by inkjet printing, followed by coating with a thin film of NW growth solution. Two different types of NW growth solutions were used: the first, based on benzylhexadecyldimethylammonium chloride, exhibited a bulk solution growth mode and was thus suitable for coverage of large uniform areas. The second type was based on hexadecyltrimethylammonium bromide, which induced NW growth confined to the substrate-solution interface and thus enabled patterning of small transparent electrode features, which have the same dimensions as the deposited seed droplets. A selective silver plating bath was used to thicken the ultrathin NWs, stabilize them, and reduce the sheet resistance, resulting in films with sheet resistance in the range of 20-300 Ω/sq, 86-95% light transmission, and a relatively low haze. This simple patterning method of the NW film works at ambient conditions on many different types of substrates and has the potential to replace the conventional photolithography used for indium tin oxide patterning for applications such as touch sensors and flexible/stretchable electronics.

Analysis of disease activity and response to treatment in a large Spanish cohort of patients with systemic lupus erythematosus.

OBJECTIVES: The objectives of this paper are to study the impact of disease activity in a large cohort of patients with systemic lupus erythematosus (SLE) and estimate the rate of response to therapies. METHODS: We conducted a nationwide, retrospective, multicenter, cross-sectional cohort study of 3658 SLE patients. Data on demographics, disease characteristics: activity (SELENA-SLEDAI), damage, severity, hospitalizations and therapies were collected. Factors associated with refractory disease were identified by logistic regression. RESULTS: A total of 3658 patients (90% female; median SLE duration (interquartile range): 10.4 years (5.3-17.1)) were included. At the time of their last evaluation, 14.7% of the patients had moderate-severe SLE (SELENA-SLEDAI score ≥6). There were 1954 (53.4%) patients who were hospitalized for activity at least once over the course of the disease. At some stage, 84.6% and 78.8% of the patients received glucocorticoids and antimalarials, respectively, and 51.3% of the patients received at least one immunosuppressant. Owing to either toxicity or ineffectiveness, cyclophosphamide was withdrawn in 21.5% of the cases, mycophenolate mofetil in 24.9%, azathioprine in 40.2% and methotrexate in 46.8%. At some stage, 7.3% of the patients received at least one biologic. A total of 898 (24.5%) patients had refractory SLE at some stage. Renal, neuropsychiatric, vasculitic, hematological and musculoskeletal involvement, a younger age at diagnosis and male gender were associated with refractory disease. CONCLUSIONS: A significant percentage of patients have moderately-to-severely active SLE at some stage. Disease activity has a big impact in terms of need for treatment and cause of hospitalization. The effectiveness of the standard therapies for reducing disease activity is clearly insufficient. Some clinical features are associated with refractory SLE.

A Communicative Analysis of a Sexual Health Screening Intervention Conducted in a Low-income Housing Complex.

Providing free HIV screening within public housing sites offers the potential for increased participation of at-risk populations. Residential-based screening, however, raises concerns about privacy because of the stigma attached to HIV/AIDS and even to the testing for HIV. This study examined the effectiveness of offering HIV screening within a public housing high-rise in upstate New York. Through interviews with both women who obtained testing and those who did not, this study explored the tension between convenience and privacy concerns. The findings suggest that offering HIV screening where people live could encourage participation in the screenings, as well as lead to a destigmatization of HIV testing over time. Some women chose to eschew the convenience of on-site testing in favor of a more private venue for screening, whereas some women responded positively to the accessibility of on-site testing, using communicative strategies to manage privacy concerns.

Transcriptional responses indicate attenuated oxidative stress in the springtail Folsomia candida exposed to mixtures of cadmium and phenanthrene.

Since the 'omics revolution', the assessment of toxic chemical mixtures has incorporated approaches where phenotypic endpoints are connected to a mechanistic understanding of toxicity. In this study we determined the effect of binary mixtures of cadmium and phenanthrene on the reproduction of Folsomia candida and investigated the cellular mechanisms underlying this response. Mixture toxicity modeling showed an antagonistic deviation from concentration addition for reproduction effects of the mixtures. Subsequent transcriptional response analysis was done using five mixtures at the modeled 50 % effect level for reproduction. The transcription profiles of 86 high throughput RT-qPCR assays were studied by means of partial least squares regression analysis. The first and second principal components (PCs) were correlated with global responses to cadmium and phenanthrene, while correlations with the mixture treatments were found in the higher PCs. Specifically associated with the mixture treatments were a biotransformation phase II gene, four mitochondrial related genes and a gene involved in the biosynthesis of antioxidant selenoproteins. Membrane integrity related gene inductions were correlated with the single phenanthrene treatment but not with the mixtures. Immune and inflammatory response assays did not correlate with any of the mixtures. These results suggest moderated oxidative stress, a higher mitochondrial maintenance and less compromised membrane function in the mixture exposed samples compared to the separate cadmium or phenanthrene exposures. The antagonism found for inhibition of reproduction may partially originate from these differences. Mechanistic studies on mixture toxicity can ultimately aid risk assessment by defining relevant toxicity pathways in organisms exposed to real-world mixture exposures present in the field.

Schistosomiasis collection at NHM (SCAN).

BACKGROUND: The Natural History Museum (NHM) is developing a repository for schistosomiasis-related material, the Schistosomiasis Collection at NHM (SCAN) as part of its existing Wolfson Wellcome Biomedical Laboratory (WWBL). This is timely because a major research and evaluation effort to understand control and move towards elimination of schistosomiasis in Africa has been initiated by the Schistosomiasis Consortium for Operational Research and Evaluation (SCORE), resulting in the collection of many important biological samples, including larval schistosomes and snails. SCAN will collaborate with a number of research groups and control teams and the repository will acquire samples relevant to both immediate and future research interest. The samples collected through ongoing research and field activities, WWBL's existing collections, and other acquisitions will be maintained over the long term and made available to the global research community for approved research purposes. Goals include: ·Consolidation of the existing NHM schistosome and snail collections and transfer of specimens into suitable long-term storage systems for DNA retrieval, ·Long-term and stable storage of specimens collected as part of on going field programmes initially in Africa especially relating to the SCORE research programmes, ·Provision of access to snail and schistosome collections for approved research activities.

A cautionary tale of technology: not a substitute for careful collaboration and effective communication.

This is an original case study highlighting the importance of careful collaboration and effective communication among healthcare providers. Amid the chaos of a new year, implementing a new healthcare act with an entirely new system of coding, patients are informed consumers interconnected through enhanced technological advances. This article describes a complicated situation involving long-term follow-up of a patient with a history of previous surgical removal of a rare tumor. The problem is one in which the patient is given exclusive access to a newly implemented electronic medical record system that has not fully completed the transition, including all healthcare specialties in the new system. What results is unnecessary, weeklong emotional turmoil, where the patient's health status is misinterpreted and miscommunicated. The challenge is helping patients become aggressive advocates and consumers of quality care, without breaching confidentiality. How much access is too much and what can happen if patients are given full disclosure and access to the electronic medical record? Fortunately, in this case, the problem is solved when the main provider returns from out-of-town, and multiple providers unite, carefully collaborate, and effectively communicate with the patient.

High throughput nano-liter RT-qPCR to classify soil contamination using a soil arthropod.

BACKGROUND: To incorporate genomics data into environmental assessments a mechanistic perspective of interactions between chemicals and induced biological processes needs to be developed. Since chemical compounds with structural similarity often induce comparable biological responses in exposed animals, gene expression signatures can serve as a starting point for the assessment of chemicals and their toxicity, but only when relevant and stable gene panels are available. To design such a panel, we isolated differentially expressed gene fragments from the soil arthropod Folsomia candida, a species often used for ecotoxicological testing. Animals were exposed to two chemically distinct compounds, being a metal (cadmium) and a polycyclic aromatic hydrocarbon (phenanthrene). We investigated the affected molecular responses resulting from either treatment and developed and validated 44 qPCR assays for their responses using a high throughput nano-liter RT-qPCR platform for the analysis of the samples. RESULTS: Suppressive subtractive hybridization (SSH) was used to retrieve stress-related gene fragments. SSH libraries revealed pathways involved in mitochondrial dysfunction and protein degradation for cadmium and biotransformation for phenanthrene to be overrepresented. Amongst a small cluster of SSH-derived cadmium responsive markers were an inflammatory response protein and an endo-glucanase. Conversely, cytochrome P450 family 6 or 9 was specifically induced by phenanthrene. Differential expressions of these candidate biomarkers were also highly significant in the independently generated test sample set. Toxicity levels in different training samples were not reflected by any of the markers' intensity of expressions. Though, a model based on partial least squares differential analysis (PLS-DA) (with RMSEPs between 9 and 22% and R(2)s between 0.82 and 0.97) using gene expressions of 25 important qPCR assays correctly predicted the nature of exposures of test samples. CONCLUSIONS: For the application of molecular bio-indication in environmental assessments, multivariate analyses obviously have an added value over univariate methods. Our results suggest that compound discrimination can be achieved by PLS-DA, based on a hard classification of the within-class rankings of samples from a test set. This study clearly shows that the use of high throughput RT-qPCR could be a valuable tool in ecotoxicology combining high throughput with analytical sensitivity.

Reference genes for QRT-PCR tested under various stress conditions in Folsomia candida and Orchesella cincta (Insecta, Collembola).

BACKGROUND: Genomic studies measuring transcriptional responses to changing environments and stress currently make their way into the field of evolutionary ecology and ecotoxicology. To investigate a small to medium number of genes or to confirm large scale microarray studies, Quantitative Reverse Transcriptase PCR (QRT-PCR) can achieve high accuracy of quantification when key standards, such as normalization, are carefully set. In this study, we validated potential reference genes for their use as endogenous controls under different chemical and physical stresses in two species of soil-living Collembola, Folsomia candida and Orchesella cincta. Treatments for F. candida were cadmium exposure, phenanthrene exposure, desiccation, heat shock and pH stress, and for O. cincta cadmium, desiccation, heat shock and starvation. RESULTS: Eight potential reference genes for F. candida and seven for O. cincta were ranked by their stability per stress factor using the programs geNorm and Normfinder. For F. candida the succinate dehydrogenase (SDHA) and eukaryotic transcription initiation factor 1A (ETIF) genes were found the most stable over the different treatments, while for O. cincta, the beta actin (ACTb) and tyrosine 3-monooxygenase (YWHAZ) genes were the most stable. CONCLUSION: We present a panel of reference genes for two emerging ecological genomic model species tested under a variety of treatments. Within each species, different treatments resulted in differences in the top stable reference genes. Moreover, the two species differed in suitable reference genes even when exposed to similar stresses. This might be attributed to dissimilarity of physiology. It is vital to rigorously test a panel of reference genes for each species and treatment, in advance of relative quantification of QRT-PCR gene expression measurements.

Gene expression analysis of collembola in cadmium containing soil.

Increasing concern about pollution of our environment calls for advanced and rapid methods to estimate ecological toxicity. The use of gene expression microarrays in environmental studies can potentially meet this challenge. We present a novel method to examine soil toxicity. We exposed the collembolan Folsomia candida to soil containing an ecologically relevant cadmium concentration, and found a cumulative total of 1586 differentially expressed transcripts across three exposure durations, including transcripts involved in stress response, detoxification, and hypoxia. Additional enrichment analysis of gene ontology (GO) terms revealed that antibiotic biosynthesis is important at all time points examined. Interestingly, genes involved in the "penicillin and cephalosporin biosynthesis pathway" have never been identified in animals before, but are expressed in F. candida's tissue. The synthesis of antibiotics can possibly be a response to increased cadmium-induced susceptibility to invading pathogens, which might be caused by repression of genes involved in the immune-system (C-type lectins and Toll receptor). This study presents a first global view on the environmental stress response of an arthropod species exposed to contaminated soil, and provides a mechanistic basis for the development of a gene expression soil quality test.

The age incidence of childhood B-cell precursor acute lymphoblastic leukemia in Mexico City.

The objective of this population-based survey was to assess the peak age of incidence of B-cell precursor acute lymphoblastic leukemia (ALL) in children in Mexico City (MC). All patients were classified according to their immunophenotype, and only B-cell precursor and T-lineage were analyzed. Rates of incidence were calculated x10 children. Of the 364 children from MC who were included in this study, immunophenotyping had been performed for 81.6%. The frequency of B-cell precursor ALL was 76.1%, whereas T lineage ALL showed a frequency of 23.6%. Peak age for ALL was 2 to 3 years of age. B-cell precursor ALL was the major contributor to peak age; T lineage ALL showed a peak among 1 and 3 years of age. We conclude that the age peak for children with ALL in MC is within the ranges reported for developed countries and that B-cell precursor ALL is the main contributor to these peak.

Comparison of different methods for total lipid quantification in meat and meat products.

This study was aimed to evaluate the efficiency of six extraction methods for the quantification of total lipid content in meat and meat products: standard Soxhlet method (with and without previous acid hydrolysis), continuous Soxhlet method (with and without previous acid hydrolysis), and those methods based in the use of a mixture of chloroform and methanol, and described by Folch, Less, and Sloane (1957) and Bligh and Dyer (1959). Lipid content was determined in nine different meat products with different fat contents and physico-chemical features: cooked turkey breast, fresh pork loin, cooked ham, dry-cured ham, mortadella, beef burger, fresh sausage, dry-cured sausage and salami. The most effective methods for determining fat content in the studied meat products were the method described by Folch et al. (1957) and the Soxhlet with previous acid hydrolysis method. The Soxhlet method without previous acid hydrolysis adequately extracted lipids only in those meat products with very high fat content. The use of the method described by Bligh and Dyer (1959) gave rise to the lowest lipid contents in all the studied meat products.

Collembase: a repository for springtail genomics and soil quality assessment.

BACKGROUND: Environmental quality assessment is traditionally based on responses of reproduction and survival of indicator organisms. For soil assessment the springtail Folsomia candida (Collembola) is an accepted standard test organism. We argue that environmental quality assessment using gene expression profiles of indicator organisms exposed to test substrates is more sensitive, more toxicant specific and significantly faster than current risk assessment methods. To apply this species as a genomic model for soil quality testing we conducted an EST sequencing project and developed an online database. DESCRIPTION: Collembase is a web-accessible database comprising springtail (F. candida) genomic data. Presently, the database contains information on 8686 ESTs that are assembled into 5952 unique gene objects. Of those gene objects approximately 40% showed homology to other protein sequences available in GenBank (blastx analysis; non-redundant (nr) database; expect-value < 10-5). Software was applied to infer protein sequences. The putative peptides, which had an average length of 115 amino-acids (ranging between 23 and 440) were annotated with Gene Ontology (GO) terms. In total 1025 peptides (approximately 17% of the gene objects) were assigned at least one GO term (expect-value < 10-25). Within Collembase searches can be conducted based on BLAST and GO annotation, cluster name or using a BLAST server. The system furthermore enables easy sequence retrieval for functional genomic and Quantitative-PCR experiments. Sequences are submitted to GenBank (Accession numbers: EV473060 - EV481745). CONCLUSION: Collembase http://www.collembase.org is a resource of sequence data on the springtail F. candida. The information within the database will be linked to a custom made microarray, based on the Agilent platform, which can be applied for soil quality testing. In addition, Collembase supplies information that is valuable for related scientific disciplines such as molecular ecology, ecogenomics, molecular evolution and phylogenetics.

Lipolytic and oxidative changes in Iberian dry-cured loin.

This study was conducted using 61 Iberian pigs from four different genetic lines fattened under two different rearing systems. Fatty acid composition of neutral lipids (NL), polar lipids (PL) and free fatty acids (FFA) of the 61 fresh loins and their corresponding dry-cured loins and indices of lipid oxidation (hexanal, TBARS and rancid flavour) of the dry-cured loins were analyzed. Although the total amount of fatty acids from PL decreased most (89.77%), the fatty acid profile of FFA from dry-cured loin was more similar to that of NL from fresh loins. Monounsaturated fatty acids (MUFA) were the most abundant FFA type (260mg/100g muscle dry matter) followed by saturated fatty acid (SFA) (256mg/100g muscle dry matter) and polyunsaturated fatty acids (PUFA) (148mg/100g muscle dry matter). Neither genetic line nor rearing system showed any significant (P>0.05) effect on the decrease of fatty acids in the lipid fractions studied. The important decrease in PUFA from NL (43.70%) and PL (89%) was not reflected in higher oxidative indices in dry-cured loin. Neither PCA nor Pearson's correlation showed any clear relationships between lipolytic changes and oxidative indices.

Study of the branched hydrocarbon fraction of intramuscular lipids from Iberian dry-cured ham.

Branched hydrocarbons from the unsaponifiable lipid fraction of intramuscular fat from Iberian dry-cured hams were analyzed. Thirty-four hams were distributed into four groups according to the feed system of the pigs (extensive system "Montanera" and intensive system "Pienso") and genotype (Iberian and Iberian×Duroc). A total of 35 different hydrocarbons were identified in this study. Some differences were found in the levels of branched, cyclical and unsaturated hydrocarbons as a function of the diet of the pigs (3-hexyl-1,1-dimethyl cyclopentane, p<0.05; 3-octadecene, p<0.01; neophytadiene, p<0.001; 1-ethylundecyl benzene, p<0.01; cyclohexadecane, p<0.001; cyclotriacontane, p<0.05). However, the genotype had a limited effect in the level of branched hydrocarbons found. The study of branched hydrocarbons in intramuscular fat from dry-cured Iberian ham allows differentiation between the pigs management systems.

Fatty acids and triacylglycerols profiles from different types of Iberian dry-cured hams.

Thirty hams were allotted into four groups according to fattening diet ("Montanera" - acorns and pasture; and "Pienso" - concentrated diet) and genotype of pigs (Iberian and Iberian×Duroc pigs). Total lipids, triacylglycerol composition and fatty acids from neutral lipids fraction were measured in biceps femoris muscle. Fattening diet largely affected lipid composition of hams. Total intramuscular lipids and triacylglycerols content were higher in Montanera hams than in Pienso hams. In Montanera hams, triacylglycerols contained more oleic acid (C18:1) and less stearic (C18:0) and palmitic (C16:0) acids (p<0.001) and accordingly less PSO, PPL, PPO, PPS, SSO (p<0.001) and more OLL, OOL, OOO triacylglycerols compared to Pienso hams (p<0.001). Genotype of pigs has an important effect in triacylglycerols composition but only a limited effect on their fatty acids composition. So, Iberian hams contained more of PLLn, PLL, POLn and POL+SLL compared to Iberian×Duroc hams (p<0.001) and POO and SOO were present in a higher quantity in Iberian×Duroc hams (p<0.01).