Long noncoding RNAs (lncRNAs) are often expressed in a development-specific manner, yet little is known about their roles in lineage commitment. Here, we identified Braveheart (Bvht), a ...heart-associated lncRNA in mouse. Using multiple embryonic stem cell (ESC) differentiation strategies, we show that Bvht is required for progression of nascent mesoderm toward a cardiac fate. We find that Bvht is necessary for activation of a core cardiovascular gene network and functions upstream of mesoderm posterior 1 (MesP1), a master regulator of a common multipotent cardiovascular progenitor. We also show that Bvht interacts with SUZ12, a component of polycomb-repressive complex 2 (PRC2), during cardiomyocyte differentiation, suggesting that Bvht mediates epigenetic regulation of cardiac commitment. Finally, we demonstrate a role for Bvht in maintaining cardiac fate in neonatal cardiomyocytes. Together, our work provides evidence for a long noncoding RNA with critical roles in the establishment of the cardiovascular lineage during mammalian development.
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► Braveheart (Bvht) is a heart-associated long noncoding RNA in the mouse ► In embryonic stem cells, Bvht is necessary for cardiovascular lineage commitment ► Bvht functions upstream of MesP1 to regulate a core cardiac gene network ► Bvht interacts with PRC2 to mediate epigenetic activation of the cardiac program
Braveheart (Bvht) is a heart-associated long noncoding RNA that is necessary for cardiovascular lineage commitment in embryonic stem cells. Its interaction with the polycomb complex suggests that it may regulate the cardiac program epigenetically.
The popularity of smartphones is undeniable in nearly all facets of society. Despite the many benefits attributed to the technology, concern has grown over the potential for excessive smartphone use ...to become problematic in nature. Due to the growing concerns surrounding the recognized and unrecognized implications of smartphone use, great efforts have been made through research to evaluate, label and identify problematic smartphone use mostly through the development and administration of scales assessing the behavior. This study examines 78 existing validated scales that have been developed over the past 13 years to measure, identify or characterize excessive or problematic smartphone use by evaluating their theoretical foundations and their psychometric properties. Our review determined that, despite an abundance of self-report scales examining the construct, many published scales lack sufficient internal consistency and test-retest reliability. Additionally, there is a lack of research supporting the theoretical foundation of many of the scales evaluated. Future research is needed to better characterize problematic smartphone use so that assessment tools can be more efficiently developed to evaluate the behavior in order to avoid the excessive publication of seemingly redundant assessment tools.
The three interacting components of the outer blood-retinal barrier are the retinal pigment epithelium (RPE), choriocapillaris, and Bruch's membrane, the extracellular matrix that lies between them. ...Although previously reviewed independently, this review integrates these components into a more wholistic view of the barrier and discusses reconstitution models to explore the interactions among them. After updating our understanding of each component's contribution to barrier function, we discuss recent efforts to examine how the components interact. Recent studies demonstrate that claudin-19 regulates multiple aspects of RPE's barrier function and identifies a barrier function whereby mutations of claudin-19 affect retinal development. Co-culture approaches to reconstitute components of the outer blood-retinal barrier are beginning to reveal two-way interactions between the RPE and choriocapillaris. These interactions affect barrier function and the composition of the intervening Bruch's membrane. Normal or disease models of Bruch's membrane, reconstituted with healthy or diseased RPE, demonstrate adverse effects of diseased matrix on RPE metabolism. A stumbling block for reconstitution studies is the substrates typically used to culture cells are inadequate substitutes for Bruch's membrane. Together with human stem cells, the alternative substrates that have been designed offer an opportunity to engineer second-generation culture models of the outer blood-retinal barrier.
Objective
This narrative review examines six important non‐nutritive substances in breast milk, many of which were thought to have little to no biological significance. The overall objective is to ...provide background on key bioactive factors in breast milk believed to have an effect on infant outcomes (growth and body composition).
Methods
The evidence for the effects of the following six bioactive compounds in breast milk on infant growth outcomes are reviewed: insulin, leptin, adiponectin, ghrelin, interleukin‐6, and tumor necrosis factor‐α.
Results
The existing literature on the effects of breast milk insulin, ghrelin, interleukin‐6, and tumor necrosis factor‐α and their associations with infant growth and adiposity is sparse. Of the bioactive compounds reviewed, leptin and adiponectin are the most researched. Data reveal that breast milk adiponectin has negative associations with growth in infancy.
Conclusions
There is a need for innovative, well‐designed studies to improve causal inference and advance our understanding in the effects of breast milk and its components on offspring growth and body composition. The recommendations provided, along with careful consideration of both known and unknown factors that affect breast milk composition, will help improve, standardize, and ultimately advance this emergent field.
Cognitive impairment and neuropsychiatric symptoms affect a substantial number of individuals with Parkinson's disease (PD). These non-motor changes can occur at all stages of disease, often years ...before motor symptoms manifest in some patients while occurring much later in the disease process for others. Lewy bodies are the hallmark of PD, yet not all patients with PD follow the same course or present in the same way clinically, either from a motor or non-motor standpoint. This has implications on assessment, intervention, and planning for the future. This review will focus on the cognitive and neuropsychiatric features of Parkinson's disease dementia (PDD) and dementia with Lewy bodies (DLB), with emphasis on neuropsychological findings. Differentiation between these dementia syndromes and other atypical parkinsonian syndromes will be mentioned only briefly, as the latter are covered in detail elsewhere in this issue. Neuropathologic, laboratory and radiographic findings will be presented, and recommendations for neurobehavioral assessment and treatment will be provided.
Agitation after general anaesthesia can lead to self-harm, violence against staff, and increased resource utilisation. We aimed to assess patient and procedural characteristics associated with this ...complication in adults.
We identified cases of agitation (Richmond Agitation–Sedation Scale score +3 or +4, or administration of haloperidol) in patients after general anaesthesia in the PACU from July 1, 2010 to September 30, 2016. The cases were matched 1:1 with control patients without agitation by age, sex, and procedure. Potential clinical associations were assessed with a multivariable analysis.
We identified agitation in 510 patients incidence: 2.5 cases/1000 patients; 95% confidence interval (CI): 2.3–2.7. Variables associated with agitation were substance misuse odds ratio (OR): 6.77; 95% CI: 1.23–37.2; P=0.03, cognitive impairment (OR: 4.66; 95% CI: 1.79–12.1; P=0.002), obesity (OR: 2.49; 95% CI: 1.66–3.73; P<0.001), psychiatric problems (OR: 2.05; 95% CI: 1.32–3.19; P=0.002), fall risk (OR: 1.66; 95% CI: 1.02–2.70; P=0.04), postoperative presence of a tracheal tube (OR: 16.6; 95% CI: 7.25–38.2; P<0.001), urine catheter (OR: 7.25; 95% CI: 4.31–12.2; P<0.001), nasogastric tube (OR: 4.06; 95% CI: 1.51–10.9; P=0.006), or chest tube (OR: 3.46; 95% CI: 1.07–11.2; P=0.006). Compared with control patients, more agitated patients had postoperative delirium (16.1% vs 6.3%; P<0.001) and pulmonary complications (9.8% vs 4.7%; P=0.002).
Agitation after general anaesthesia was associated with postoperative indwelling catheters, tracheal intubation and patient features suggestive of pre-existing mental health problems. Anticipation of high-risk patients could allow allocation of staffing resources to provide a safe environment for anaesthetic recovery.
Body composition assessment in the infant Demerath, Ellen W.; Fields, David A.
American journal of human biology,
May/June 2014, Volume:
26, Issue:
3
Journal Article
Chlamydia spp. utilize multiple secretion systems, including the type III secretion system (T3SS), to deploy host-interactive effector proteins into infected host cells. Elucidation of secreted ...proteins has traditionally required ectopic expression in a surrogate T3SS followed by immunolocalization of endogenous candidate effectors to confirm secretion by chlamydiae. The ability to transform Chlamydia and achieve stable expression of recombinant gene products has enabled a more direct assessment of secretion. We adapted TEM-1 β-lactamase as a reporter system for assessment of chlamydial protein secretion. We provide evidence that this system facilitates visualization of secretion in the context of infection. Specifically, our findings provide definitive evidence that C. trachomatis CT695 is secreted during infection. Follow-up indirect immunofluorescence studies confirmed CT695 secretion and indicate that this effector can be secreted at multiple points during the chlamydial developmental cycle. Our results indicate that the BlaM-fusion reporter assay will allow efficacious identification of novel secreted proteins. Moreover, this approach can easily be adapted to enable more sophisticated studies of the secretion process in Chlamydia.
Evidence linking breastfeeding to reduced risk of developing childhood obesity is inconclusive, yet previous studies have not considered variation in specific components of breast milk that may ...affect early development.
We examined whether differences in the composition of human milk oligosaccharides (HMOs) correlate with infant growth and body composition at 1 and 6 mo of age.
Twenty-five mother-infant dyads were recruited from the University Hospital at the University of Oklahoma Health Sciences Center. Infants were breastfed for 6 mo. Breast-milk and infant measures were obtained at 1 and 6 mo of infant age. HMO composition was analyzed by high-pressure liquid chromatography, and infant growth (length and weight) and body composition (percentage fat, total fat, lean mass) were measured by dual-energy X-ray absorptiometry. Relations between HMOs and infant growth and body composition were examined by using multiple linear regression. A priori covariates included maternal prepregnancy body mass index, pregnancy weight gain, and infant age and sex.
Higher HMO diversity and evenness at 1 mo were associated with lower total and percentage fat mass at 1 mo. At 1 mo, each 1-μg/mL increase in lacto-N-fucopentaose (LNFP) I was associated with a 0.40-kg lower infant weight (P = 0.03). At 6 mo, each 1-μg/mL increase in LNFPI was associated with a 1.11-kg lower weight (P = 0.03) and a 0.85-g lower lean mass (P = 0.01). At 6 mo, each 1-μg/mL increase in LNFPI was associated with a 0.79-g lower fat mass (P = 0.02), whereas disialyl-lacto-N-tetraose and LNFPII were associated with a 1.92-g (P = 0.02) and 0.42-g (P = 0.02) greater fat mass, respectively. At 6 mo, each 1-μg/mL increase in fucosyl-disialyl-lacto-N-hexaose and lacto-N-neotetraose was associated with 0.04% higher (P = 0.03) and 0.03% lower (P < 0.01) body fat, respectively.
These findings support the hypothesis that differences in HMO composition in mother's milk are associated with infant growth and body composition. This trial was registered at clinicaltrials.gov as NCT02535637.
Au nanoparticles (NPs) with protecting organothiolate ligands and core diameters smaller than 2 nm are interesting materials because their size-dependent properties range from metal-like to ...molecule-like. This Account focuses on the most thoroughly investigated of these NPs, Au25L18. Future advances in nanocluster catalysis and electronic miniaturization and biological applications such as drug delivery will depend on a thorough understanding of nanoscale materials in which molecule-like characteristics appear. This Account tells the story of Au25L18 and its associated synthetic, structural, mass spectrometric, electron transfer, optical spectroscopy, and magnetic resonance results. We also reference other Au NP studies to introduce helpful synthetic and measurement tools. Historically, nanoparticle sizes have been described by their diameters. Recently, researchers have reported actual molecular formulas for very small NPs, which is chemically preferable to solely reporting their size. Au25L18 is a success story in this regard; however, researchers initially mislabeled this NP as Au28L16 and as Au38L24 before correctly identifying it by electrospray-ionization mass spectrometry. Because of its small size, this NP is amenable to theoretical investigations. In addition, Au25L18’s accessibility in pure form and molecule-like properties make it an attractive research target. The properties of this NP include a large energy gap readily seen in cyclic voltammetry (related to its HOMO−LUMO gap), a UV−vis absorbance spectrum with step-like fine structure, and NIR fluorescence emission. A single crystal structure and theoretical analysis have served as important steps in understanding the chemistry of Au25L18. Researchers have determined the single crystal structure of both its “native” as-prepared form, a N((CH2)7CH3)4 1+Au25(SCH2CH2Ph)18 1− salt, and of the neutral, oxidized form Au25(SCH2CH2Ph)18 0. A density functional theory (DFT) analysis correctly predicted essential elements of the structure. The NP is composed of a centered icosahedral Au13 core stabilized by six Au2(SR)3 semirings. These semirings present interesting implications regarding other small Au nanoparticle clusters. Many properties of the Au25 NP result from these semiring structures. This overview of the identification, structure determination, and analytical properties of perhaps the best understood Au nanoparticle provides results that should be useful for further analyses and applications. We also hope that the story of this nanoparticle will be useful to those who teach about nanoparticle science.
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