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Anatomy of the first flying feathered dinosaurs, modern birds and crocodylians, proposes an ancestral flight system divided between shoulder and chest muscles, before the upstroke muscles migrated beneath the body. This ancestral flight system featured the dorsally positioned deltoids and supracoracoideus controlling the upstroke and the chest-bound pectoralis controlling the downstroke. Preserved soft anatomy is needed to contextualize the origin of the modern flight system, but this has remained elusive. Here we reveal the soft anatomy of the earliest theropod flyers preserved as residual skin chemistry covering the body and delimiting its margins. These data provide preserved soft anatomy that independently validate the ancestral theropod flight system. The heavily constructed shoulder and more weakly constructed chest in the early pygostylian Confuciusornis indicated by a preserved body profile, proposes the first upstroke-enhanced flight stroke. Slender ventral body profiles in the early-diverging birds Archaeopteryx and Anchiornis suggest habitual use of the pectoralis could not maintain the sternum through bone functional adaptations. Increased wing-assisted terrestrial locomotion potentially accelerated sternum loss through higher breathing requirements. Lower expected downstroke requirements in the early thermal soarer Sapeornis could have driven sternum loss through bone functional adaption, possibly encouraged by the higher breathing demands of a Confuciusornis -like upstroke. Both factors are supported by a slender ventral body profile. These data validate the ancestral shoulder/chest flight system and provide insights into novel upstroke-enhanced flight strokes and early sternum loss, filling important gaps in our understanding of the appearance of modern flight.

To explore synergistic effects related to skin regeneration, peptides with distinct biological mechanisms of action were evaluated in combination with different skin cell lines in the presence or absence of niacinamide (Nam). Furthermore, the synergistic responses of peptide combinations on global gene expression were compared with the changes that occur with fractional laser resurfacing treatment, a gold standard approach for skin rejuvenation, to further define optimal peptide combinations.Microarray profiling was used to characterize the biological responses of peptide combinations (+/- Nam) relative to the individual components in epidermal keratinocyte and dermal fibroblast cell lines. Cellular functional assays were utilized to confirm the synergistic effects of peptide combinations. Bioinformatics approaches were used to link the synergistic effects of peptide combinations on gene expression to the transcriptomics of the skin rejuvenation response from fractional laser treatment.Microarray analysis of skin cells treated with peptide combinations revealed synergistic changes in gene expression compared with individual peptide controls. Bioinformatic analysis of synergy genes in keratinocytes revealed the activation of NRF2-mediated oxidative stress responses by a combination of Ac-PPYL, Pal-KTTKS and Nam. Additional analysis revealed direct downstream transcriptional targets of NRF2/ARE exhibiting synergistic regulation by this combination of materials, which was corroborated by a cellular reporter assay. NRF2-mediated oxidative stress response pathways were also found to be activated in the transcriptomics of the early skin rejuvenation response to fractional laser treatment, suggesting the importance of this biology in the early stages of tissue repair. Additionally, the second combination of peptides (pal-KT and Ac-PPYL) was found to synergistically restore cellular ATP levels that had been depleted due to the presence of ROS, indicating an additional mechanism, whereby peptide synergies may accelerate skin repair.Through combinatorial synergy studies, we have identified additional in vitro skin repair mechanisms beyond the previously described functions of individual peptides and correlated these to the transcriptomics of the skin rejuvenation response of fractional laser treatment. These findings suggest that specific peptides can act together, via complementary and synergistic mechanisms, to holistically enhance the regenerative capacity of in vitro skin cells.Pour explorer les effets synergiques liés à la régénération cutanée, les peptides ayant des mécanismes d’action biologiques distincts ont été évalués en association dans différentes lignées cellulaires cutanées en présence ou en l’absence de niacinamide (Nam). De plus, les réponses synergiques des associations de peptides sur l’expression des gènes globale ont été comparées aux changements qui surviennent avec le traitement de resurfaçage au laser fractionné, une approche de référence pour le rajeunissement de la peau, afin de définir davantage les associations optimales de peptides. MÉTHODES: Le profilage de micro-réseau a été utilisé pour caractériser les réponses biologiques des combinaisons de peptides (+/-Nam) par rapport aux composants individuels dans les lignées cellulaires de kératinocytes épidermiques et de fibroblastes dermiques. Des tests fonctionnels cellulaires ont été réalisés pour confirmer les effets synergiques des associations de peptides. Des approches bio-informatiques ont été utilisées pour mettre en lien les effets synergiques des associations de peptides sur l’expression des gènes à la transcriptomique de la réponse de rajeunissement de la peau du traitement au laser fractionné. RÉSULTATS: L’analyse par micro-réseau des cellules cutanées traitées par des combinaisons de peptides a révélé des changements synergiques dans l’expression des gènes par rapport aux contrôles peptidiques individuels. L’analyse bio-informatique des gènes de synergie dans les kératinocytes a révélé une activation des réponses au stress oxydatif médiées par NRF2 par une association d’Ac-PPYL, de Pal-KTTKS et de Nam. Une analyse supplémentaire a révélé des cibles transcriptionnelles directes en aval de NRF2/ARE présentant une régulation synergique par cette combinaison de matériaux, qui a été corroborée par un test de gène rapporteur. Les voies de réponses au stress oxydatif médiées par NRF2 se sont également révélées activées dans la transcriptomique de la réponse précoce de rajeunissement cutané au traitement au laser fractionné, ce qui suggère l’importance de cette biologie dans les stades précoces de la réparation des tissus. De plus, une deuxième association de peptides (pal-KT et Ac-PPYL) s’est avérée restaurer de manière synergique les taux d’ATP cellulaire qui avaient été épuisés en raison de la présence de ROS, indiquant un mécanisme supplémentaire par lequel les synergies de peptides pourraient accélérer la réparation cutanée.Grâce à des études de synergie combinatoire, nous avons identifié des mécanismes de réparation cutanés in vitro supplémentaires au-delà des fonctions précédemment décrites des peptides individuels et les avons corrélés à la transcriptomique de la réponse de rajeunissement de la peau au traitement au laser fractionné. Ces résultats suggèrent que des peptides spécifiques peuvent agir ensemble, par le biais de mécanismes complémentaires et synergiques, pour améliorer de manière globale la capacité régénérative des cellules cutanées in vitro.

Despite traditional prenatal interventions, the incidence of low birth weight and prematurity in the United States have not significantly decreased. Interconception care for women between pregnancies has been proposed as a method of improving various perinatal outcomes. Although broadly advocated by national groups, interconception care (ICC) has not been widely implemented. We describe best practices for an ICC model based on screening mothers for tobacco use, depression, folic acid intake, and inter-pregnancy interval at well child visits. Because of the model's flexibility, sites can readily customize implementation by incorporating the questions directly into existing workflows and using local service providers already working in maternal-child health. This model has demonstrated promising results and ease of implementation thus far, and offers great potential for improved perinatal outcomes and promotion of health equity.

Background Macromolecules in skin cells are damaged when exposed to environmental stressors, leading to disrupted cellular function and homeostasis. While epidermal turnover can eliminate some of this damage, autophagy can rapidly remove these defective components. Niacinamide (Nam) is known to induce autophagy and optimizing formulations to maximize this response could provide improved homeostasis in stressed skin. Objective To determine (i) whether Nam can induce autophagy related 5 (ATG5), an autophagy marker, in human keratinocytes and (ii) whether optimized low pH Nam formulations can enhance the response in 3D skin models. Methods Human keratinocytes treated with Nam were evaluated for autophagosome accumulation and induction of ATG5 by gene expression, immunoblotting and immune-fluorescence microscopy. 3D skin equivalents were topically treated with Nam formulations at pH 5.8 and 3.8. Gene expression profiling and immunoblot analysis of ATG5 were performed. Results Nam treatment of keratinocytes led to an accumulation of autophagosomes with a maximal signal at 48 h. Gene expression of ATG5 was induced by Nam, and immunoblots stained for ATG5 showed a significant increase after 6 h of treatment. Gene expression profiling of 3D epidermal skin equivalents treated with Nam at pH 3.8 showed stronger induction of autophagy-related genes, including ATG5, compared with pH 5.8 formulas. Enrichment for gene ontology terms on autophagy showed an increased linkage with Nam formulas at pH 3.8. Conclusions We found that Nam induces autophagosome accumulation and ATG5 levels in keratinocytes. We also discovered that a Nam formulation at pH 3.8 can further increase levels of ATG5 in 3D skin models when compared to Nam at pH 5.8. These data support that Nam can induce autophagy in keratinocytes and formulations at pH 3.8 can enhance the impact. We hypothesize that optimized formulations at pH 3.8 can improve skin ageing appearance via autophagy induction.

Maternity care access in the United States is in crisis. The American Congress of Obstetrics and Gynecology projects that by 2030 there will be a nationwide shortage of 9,000 obstetrician-gynecologists (OB/GYNs). Midwives and OB/GYNs have been called upon to address this crisis, yet in underserved areas, family physicians are often providing a majority of this care. Family medicine maternity care, a natural fit for the discipline, has been on sharp decline in recent years for many reasons including difficulties cultivating interdisciplinary relationships, navigating privileging, developing and maintaining adequate volume/competency, and preventing burnout. In 2016 and 2017, workshops were held among family medicine educators with resultant recommendations for essential strategies to support family physician maternity care providers. This article summarizes these strategies, provides guidance, and highlights the role family physicians have in addressing maternity care access for the underserved as well as presenting innovative ideas to train and retain rural family physician maternity care providers.

Niacinamide has been suggested to impact hair biology via stimulation of VEGF synthesis. Testing in an in vitro VEGF synthesis assay, it was found that niacinamide cannot stimulate VEGF synthesis across a broad dose-response range.

We employed the widely-tested biophysiological modeling software, Niche Mapper™ to investigate the metabolic function of Late Triassic dinosaursPlateosaurusandCoelophysisduring global greenhouse conditions. We tested them under a variety of assumptions about resting metabolic rate, evaluated within six microclimate models that bound paleoenvironmental conditions at 12° N paleolatitude, as determined by sedimentological and isotopic proxies for climate within the Chinle Formation of the southwestern United States. Sensitivity testing of metabolic variables and simulated “metabolic chamber” analyses support elevated “ratite-like” metabolic rates and intermediate “monotreme-like” core temperature ranges in these species of early saurischian dinosaur. Our results suggest small theropods may have needed partial to full epidermal insulation in temperate environments, while fully grown prosauropods would have likely been heat stressed in open, hot environments and should have been restricted to cooler microclimates such as dense forests (under any vegitative cover) or those seen at higher latitudes and elevations. This is in agreement with the Late Triassic fossil record and may have contributed to the latitudinal gap in the Triassic prosauropod record.

Introduction: Short interpregnancy periods increase the likelihood of preterm delivery and low birth weight,1 both of which are significant causes of infant morbidity and mortality.2 Since nearly half of pregnancies in the United States are unplanned,3 opportunities exist to better understand barriers to contraceptive services. Studying these barriers as perceived by clinical staff can better guide programs to improve interpregnancy spacing. Methods: Between September and November 2017, 76 staff and 95 primary care clinicians from two family medicine residency practices (Highland Family Medicine (HFM) in Rochester, New York and St Margaret Family Medicine (SM) in Pittsburgh, Pennsylvania) completed surveys. Questions assessed perceived barriers to providing contraceptive services, contraception knowledge, and opportunities for improvement. Survey-based analysis focused on comparative descriptive statistics between staff and provider responses. Results: Clinicians ranked side effects and patient lack of awareness and misconceptions about contraceptive methods more highly than staff (P=0.0073 and P=0.0001, respectively). Staff identified childcare and work absence as more significant barriers (P=0.0114 and P=0.0380, respectively). Providers felt appointment timing was the largest constraint to contraceptive care. Staff perceived financial limitations and scheduling to be the top barriers. Nonclinician staff exhibited significant knowledge gaps regarding contraception. Conclusions: Numerous modifiable barriers contribute to difficulty providing contraceptive services. Providers and staff largely agree on the perceived barriers, but there is a significant gap in nonclinician staff knowledge of contraception. Education can address one of the leading concerns, but improvement efforts should also address areas such as availability of devices, scheduling issues, and resident supervision.

SynopsisTyrannosaurid dinosaurs had large preserved leg muscle attachments and low rotational inertia relative to their body mass, indicating that they could turn more quickly than other large theropods.MethodsTo compare turning capability in theropods, we regressed agility estimates against body mass, incorporating superellipse-based modeled mass, centers of mass, and rotational inertia (mass moment of inertia). Muscle force relative to body mass is a direct correlate of agility in humans, and torque gives potential angular acceleration. Agility scores therefore include rotational inertia values divided by proxies for (1) muscle force (ilium area and estimates of m. caudofemoralis longus cross-section), and (2) musculoskeletal torque. Phylogenetic ANCOVA (phylANCOVA) allow assessment of differences in agility between tyrannosaurids and non-tyrannosaurid theropods (accounting for both ontogeny and phylogeny). We applied conditional error probabilitiesa(p) to stringently test the null hypothesis of equal agility.ResultsTyrannosaurids consistently have agility index magnitudes twice those of allosauroids and some other theropods of equivalent mass, turning the body with both legs planted or pivoting over a stance leg. PhylANCOVA demonstrates definitively greater agilities in tyrannosaurids, and phylogeny explains nearly all covariance. Mass property results are consistent with those of other studies based on skeletal mounts, and between different figure-based methods (our main mathematical slicing procedures, lofted 3D computer models, and simplified graphical double integration).ImplicationsThe capacity for relatively rapid turns in tyrannosaurids is ecologically intriguing in light of their monopolization of large (>400 kg), toothed dinosaurian predator niches in their habitats.

The last two decades have seen a remarkable increase in the known diversity of basal avialans and their paravian relatives. The lack of resolution in the relationships of these groups combined with attributing the behavior of specialized taxa to the base of Paraves has clouded interpretations of the origin of avialan flight. Here, we describeHesperornithoides miesslerigen. et sp. nov., a new paravian theropod from the Morrison Formation (Late Jurassic) of Wyoming, USA, represented by a single adult or subadult specimen comprising a partial, well-preserved skull and postcranial skeleton. Limb proportions firmly establishHesperornithoidesas occupying a terrestrial, non-volant lifestyle. Our phylogenetic analysis emphasizes extensive taxonomic sampling and robust character construction, recovering the new taxon most parsimoniously as a troodontid close toDaliansaurus,Xixiasaurus, andSinusonasus. Multiple alternative paravian topologies have similar degrees of support, but proposals of basal paravian archaeopterygids, avialan microraptorians, andRahonavisbeing closer to Pygostylia than archaeopterygids or unenlagiines are strongly rejected. All parsimonious results support the hypothesis that each early paravian clade was plesiomorphically flightless, raising the possibility that avian flight originated as late as the Late Jurassic or Early Cretaceous.

Multiple studies have demonstrated improved perinatal outcomes for group prenatal care (GPC) when compared to traditional prenatal care. Benefits of GPC include lower rates of prematurity and low birth weight, fewer cesarean deliveries, improved breastfeeding outcomes and improved maternal satisfaction with care. However, the outpatient financial costs of running a GPC program are not well established. This study involved the creation of a financial model that forecasted costs and revenues for prenatal care groups with various numbers of participants based on numerous variables, including patient population, payor mix, patient show rates, staffing mix, supply usage and overhead costs. The model was developed for use in an urban underserved practice. Adjusted revenue per pregnancy in this model was found to be $989.93 for traditional care and $1080.69 for GPC. Cost neutrality for GPC was achieved when each group enrolled an average of 10.652 women with an enriched staffing model or 4.801 women when groups were staffed by a single nurse and single clinician. Mathematical cost-benefit modeling in an urban underserved practice demonstrated that GPC can be not only financially sustainable but possibly a net income generator for the outpatient clinic. Use of this model could offer maternity care practices an important tool for demonstrating the financial practicality of GPC.

Excellent levels of enantiorecognition are displayed by tert-butyl (RS)-6-n-alkyl-cyclohex-1-ene-carboxylates in mutual kinetic resolutions with lithium (RS)-N-benzyl-N-(α-methylbenzyl)amide. Therefore a 50:50 pseudoenantiomeric mixture of lithium (S)-N-benzyl-N-(α-methylbenzyl)amide and lithium (R)-N-3,4-dimethoxybenzyl-N-(α-methylbenzyl)amide allows their efficient parallel kinetic resolution, affording differentially protected 6-n-alkyl-cishexacin derivatives in high yield and >95% de. N-Debenzylation and ester hydrolysis give access to the corresponding homochiral 6-n-alkyl-substituted cishexacin derivatives. © 2008 Elsevier Ltd. All rights reserved.

We describe the tenth skeletal specimen of the Upper Jurassic Archaeopterygidae. The almost complete and well-preserved skeleton is assigned to Archaeopteryx siemensii Dames, 1897 and provides significant new information on the osteology of the Archaeopterygidae. As is evident from the new specimen, the palatine of Archaeopteryx was tetraradiate as in non-avian theropods, and not triradiate as in other avians. Also with respect to the position of the ectopterygoid, the data obtained from the new specimen lead to a revision of a previous reconstruction of the palate of Archaeopteryx. The morphology of the coracoid and that of the proximal tarsals is, for the first time, clearly visible in the new specimen. The new specimen demonstrates the presence of a hyperextendible second toe in Archaeopteryx. This feature is otherwise known only from the basal avian Rahonavis and deinonychosaurs (Dromaeosauridae and Troodontidae), and its presence in Archaeopteryx provides additional evidence for a close relationship between deinonychosaurs and avians. The new specimen also shows that the first toe of Archaeopteryx was not fully reversed but spread medially, supporting previous assumptions that Archaeopteryx was only facultatively arboreal. Finally, we comment on the taxonomic composition of the Archaeopterygidae and conclude that Archaeopteryx bavarica Wellnhofer, 1993 is likely to be a junior synonym of A. siemensii, and Wellnhoferia grandis Elzanowski, 2001 a junior synonym of A. lithographica von Meyer, 1861. © 2007 The Linnean Society of London, Zoological Journal of the Linnean Society, 2007, 149, 97–116.

When small biological samples are collected by microdissection or other methods, amplification techniques are required to provide sufficient target for hybridization to expression arrays. One such technique is to perform two successive rounds of T7-based in vitro transcription. However, the use of random primers, required to regenerate cDNA from the first round of transcription, results in shortened copies of cDNA from which the 5′ end is missing. In this paper we describe an experiment designed to compare the quality of data obtained from labeling small RNA samples using the Affymetrix Two-Cycle Eukaryotic Target Labeling procedure to that of data obtained using the One-Cycle Eukaryotic Target Labeling protocol. We utilized different preprocessing algorithms to compare the data generated using both labeling methods and present a new algorithm that improves upon existing ones in this setting.

This study demonstrates the synthesis and release of prolactin (PRL) from dermal fibroblasts (98%) in vitro, suggesting a potential local source of PRL in skin. PRL release was first detected in confluent cultures (0.25 x 10(6) plated cells) on or before day 18 and increased to a maximal level of 2 ng/72 h by day 30. Medroxyprogesterone acetate and estradiol (E2) had no effect on PRL release, but prostaglandin E2 (PGE2) reduced the time required for PRL induction to 6-9 days. The steroids and PGE2 together were synergistic, reaching maximal values of approximately 10 ng/72 h after 2 or more weeks of treatment. Dibutyryl-cyclic AMP, a second messenger in prostaglandin signal transduction, was also synergistic with medroxyprogesterone acetate and E2, but induced significant PRL expression in the absence of the steroids (28 and 12 ng/72 h, respectively). The increase in PRL release was not a result of increased cell proliferation, because the PRL-secreting cultures had 32.2 +/- 8.8% less DNA (N = 3 individuals, 93% confidence limit) than control cultures after 3 weeks of treatment with dibutyryl-cyclic AMP, medroxyprogesterone acetate, and E2. Dermal fibroblast PRL was immunologically and electrophoretically identical to decidual and pituitary PR-Ls, and Northern blot analysis demonstrated a PRL mRNA size of 1.15 kb. Maximal PRL release from fibroblast cells was 32.0 +/- 6.1 ng/72 h (mean +/- SD at 95% confidence limit) for a donor population representing both males (n = 15) and females (n = 7) between the ages of 20-week gestation to 52 years. In contrast to term decidual fibroblast cells that also express PRL, dermal fibroblasts did not co-express insulin-like growth factor-binding protein-1.

Term decidual tissue consists of terminally differentiated decidual cells, bone marrow-derived cells, and fibroblast cells. Since undifferentiated decidual cells are fibroblast-like cells of the endometrial stroma, the possibility exists that the fibroblast cells in term decidua are undifferentiated decidual cells. To test this hypothesis, a purified population of fibroblast cells was isolated from term decidua and treated under conditions that are known to induce differentiation of endometrial stromal cells. By flow cytometry and immunocytochemistry, the fibroblast cells from term decidua were shown to be free of cells expressing bone marrow-derived cell-surface antigens and the epithelial cell marker cytokeratin. In addition, they tested positive for the cytoskeletal protein vimentin, thus establishing that they were mesenchymal cells. As with endometrial stromal cells, continuous treatment of the decidual fibroblast cells with the progesterone analog medroxyprogesterone acetate and estradiol in combination with either dibutyryl-cAMP or prostaglandin E2 induced cell aggregation and the expression of prolactin (PRL) and insulin-like growth factor-binding protein-1 (IGFBP-1). When cells were plated at an initial cell density of 0.25 x 10(6) cells/well in a 24-well culture dish with medium changes every three days, PRL was first detected on Days 4-6, and the peak of averaged 24 h-PRL release (30 ng/well) occurred on Days 26-28. The mRNA for decidual fibroblast PRL followed a temporal pattern corresponding to that of the released hormone. The size of the PRL mRNA was 1.15 kb, corresponding to the alternately spliced PRL mRNA reported for decidualized endometrial stromal cells and other extrapituitary sources of PRL.(ABSTRACT TRUNCATED AT 250 WORDS)

Item does not contain fulltext It has been demonstrated previously that the exposure to 7,12-dimethyl[a]benzanthracene (DMBA) and UVB radiation leads to the development of epidermal cysts, squamous cell carcinomas (SCC), melanocytic hyperplasia and melanoma in human foreskins from newborns grafted to immunodeficient mice. Improved techniques in grafting full-thickness skin from adults have enabled us to study photocarcinogenesis in human skin from different body sites and from older donors. One hundred and fifty-five normal white skin specimens from the trunk and face of 53 adult individuals were grafted onto severe combined immunodeficient (SCID) and recombinase activating gene-1 (Rag-1) knockout mice and irradiated two to three times weekly with 40 mJ/cm(2) UVB or solar-simulated UV (SSUV) over a period of up to 10 months with or without one prior topical application of DMBA. Over an observation period of 2-22 months, histopathological and immunohistochemical analyses of 134 specimens revealed actinic keratoses in 30% of the DMBA- + UV-treated grafts, in 18% of the grafts exposed to SSUV only, and in 10% of the grafts exposed to UVB only. Actinic keratoses were absent in grafts treated with DMBA only. One SCC was found in an abdominal skin graft 3 months after exposure to DMBA followed by UVB. Point mutations in codon 61 of the human Ha-ras gene were detected in the SCC, five of six analyzed actinic keratoses and in non-lesional epidermis of DMBA- and UVB-treated grafts, indicating that DMBA as well as UVB alone can induce these mutations in human skin. In contrast to the previous experience with neonatal foreskin grafts, melanocytic lesions were not found except for mild hyperplasia in few cases. The data suggest that melanocytes from young individuals are more susceptible to the transforming effects of genotoxic agents than melanocytes from adults.