Journal of nature and science最新文献

Oxygen saturation targets in premature infants have been investigated in multiple international randomized controlled trials. Some trials have shown increased mortality with targeting lower (85% to 89%) compared to higher (91% to 95%) oxygen saturation ranges, while others have not. We will review the mortality outcomes of the largest multi-centered trials and a post hoc study that observed increased mortality at lower target ranges among small for gestational age infants. The planned Neonatal Oxygen Prospective Meta-analysis (NeOProM) collaborative will hopefully provide further insight into patient-specific risks, which include growth status.

This brief research report examines brain-behavioral relationships specific to levels of language in the complex reading brain. The first specific aim was to examine prior findings for significant fMRI connectivity from four seeds (left precuneus, left occipital temporal, left supramarginal, left inferior frontal) for each of four levels of language-subword, word (word-specific spelling or affixed words), syntax (with and without homonym foils or affix foils), and multi-sentence text to identify significant fMRI connectivity (a) unique to the lower level of language when compared to the immediately higher adjacent level of language across subword-word, word-syntax, and syntax-text comparisons; and (b) involving a brain region associated with executive functions. The second specific aim was to correlate the magnitude of that connectivity with standard scores on tests of Focused Attention (D-K EFS Color Word Form Inhibition) and Switching Attention (Wolf & Denckla Rapid Automatic Switching). Seven correlations were significant. Focused Attention was significantly correlated with the word level (word-specific spellings of real words) fMRI task in left cingulum from left inferior frontal seed. Switching Attention was significantly correlated with the (a) subword level (grapheme-phoneme correspondence) fMRI task in left and right Cerebellum V from left supramarginal seed; (b) the word level (word-specific spelling) fMRI task in right Cerebellum V from left precuneus seed; (c) the syntax level (with and without homonym foils) fMRI task in right Cerebellum V from left precuneus seed and from left supramarginal seed; and (d) syntax level (with and without affix foils) fMRI task in right Cerebellum V from left precuneus seed. Results are discussed in reference to neuropsychological assessment of supervisory attention (focused and switching) for specific levels of language related to reading acquisition in students with and without language-related specific learning disabilities and self-regulation of the complex reading brain.

Cancer is traditionally considered a genetic disease. It starts with a gene mutation, often caused by environmental carcinogens that are enzymatically activated to metabolites that covalently bind to DNA. If these now-damaged carcinogen-DNA adducts are not repaired before the cell replicates, they result in a mutation, which is inherited by daughter cells and their subsequent progeny. Still more mutations are added that are thought to advance cellular independence, metastasis, and drug resistance, among other characteristics typically observed for advanced cancer. The stages of initiation, promotion and progression of cancer by mutations infer irreversibility because back mutations are exceedingly rare. Thus, treatment protocols typically are designed to remove or kill cancer cells by surgery, chemotherapy, immunotherapy and/or radiotherapy. However, empirical evidence has existed to show a fundamentally different treatment option. For example, the promotion of cancer growth and development in laboratory animals initiated by a powerful mutagen/carcinogen can be repetitively turned on and off by non-mutagenic mechanisms, even completely, by modifying the consumption of protein at relevant levels of intake. Similar but less substantiated evidence also exists for other nutrients and other cancer types. This suggests that ultimate cancer development is primarily a nutrition-responsive disease rather than a genetic disease, with the understanding that nutrition is a comprehensive, wholistic biological effect that reflects the natural contents of nutrients and related substances in whole, intact food. This perspective sharply contrasts with the contemporary inference that nutrition is the summation of individual nutrients acting independently. The spelling of 'holism' with the 'w' is meant to emphasize the empirical basis for this function. The proposition that wholistic nutrition controls and even reverses disease development suggests that cancer may be treated by nutritional intervention.

Resistant hypertension (RHTN) is relatively common with an estimated prevalence of 10-20% of treated hypertensive patients. It is defined as blood pressure (BP) >140/90 mmHg treated with ≥3 antihypertensive medications, including a diuretic, if tolerated. Refractory hypertension is a novel phenotype of severe antihypertensive treatment failure. The proposed definition for refractory hypertension, i.e. BP >140/90 mmHg with use of ≥5 different antihypertensive medications, including a diuretic and a mineralocorticoid receptor antagonist (MRA) has been applied inconsistently. In comparison to RHTN, refractory hypertension seems to be less prevalent than RHTN. This review focuses on current knowledge about this novel phenotype compared with RHTN including definition, prevalence, mechanisms, characteristics and comorbidities, including cardiovascular risk. In patients with RHTN excess fluid retention is thought to be a common mechanism for the development of RHTN. Recently, evidence has emerged suggesting that refractory hypertension may be more of neurogenic etiology due to increased sympathetic activity as opposed to excess fluid retention. Treatment recommendations for RHTN are generally based on use and intensification of diuretic therapy, especially with the combination of a long-acting thiazide-like diuretic and an MRA. Based on findings from available studies, such an approach does not seem to be a successful strategy to control BP in patients with refractory hypertension and effective sympathetic inhibition in such patients, either with medications and/or device based approaches may be needed.

Large-scale epigenetic changes take place when epithelial cells with cell-cell adhesion and apical-basal polarity transition into invasive, individual, mesenchymal cells through a process known as epithelial to mesenchymal transition (EMT). Importantly, cancers with stem cell properties disseminate and form distant metastases by reactivating the developmental EMT program. Recent studies have demonstrated that the epigenetic histone modification, H2BK5 acetylation (H2BK5Ac), is important in the regulation of EMT. For example, in trophoblast stem (TS) cells, H2BK5Ac promotes the expression of genes important to the maintenance of an epithelial phenotype. This finding led to the discovery that TS cells and stem-like claudin-low breast cancer cells share similar H2BK5Ac-regulated gene expression, linking developmental and cancer cell EMT. An improved understanding of the role of H2BK5Ac in developmental EMT and stemness will further our understanding of epigenetics in EMT-related pathologies. Here, we examine the binders and regulators of H2BK5Ac and discuss the roles of H2BK5Ac in stemness and EMT.

Down's syndrome (DS) is the most common genetic cause of intellectual disability and cognitive deficit attributable to a naturally-occurring abnormality of gene dosage. DS is caused by a triplication of all or part of human chromosome 21 (chr21) and currently there are no effective treatments for this incapacitating disorder of neurodevelopment. First described by the English physician John Langdon Down in 1862, propelled by the invention of karyotype analytical techniques in the early 1950s and the discovery in 1959 by the French geneticist Jerome Lejune that DS resulted from an extra copy of chr21, DS was the first neurological disorder linking a chromosome dosage imbalance to a defect in intellectual development with ensuing cognitive disruption. Especially over the last 60 years, it has been repeatedly demonstrated that DS is not an easily defined disease entity but rather possesses a remarkably wide variability in the 'phenotypic spectrum' associated with this trisomic disorder. This commentary describes the presence of a 5 member cluster of chr21-encoded microRNAs (miRNAs) that includes let-7c, miRNA-99a, miRNA-125b, miRNA-155 and miRNA-802 located on the long arm of human chr21, spanning the chr21q21.1-chr21q21.3 region and flanking the beta amyloid precursor (βAPP) gene, and reviews the potential contribution of these 5 miRNAs to the remarkably diverse DS phenotype.

Olfaction is an ancient sensory modality which is heavily involved in viscerally-important tasks like finding food and identifying mates. Olfactory processing involves interpreting stimuli from a non-continuous odor space, and translating them into an organized pattern of neuronal activity in the olfactory bulb. Additionally, olfactory processing is rapidly modulated by behavioral states and vice versa. This implies strong bidirectional neuromodulation between the olfactory bulb and other brain regions that include the cortex, hippocampus, and basal forebrain. Intriguingly, the olfactory bulb is one of the only brain regions where adult-born neurons are integrated into existing networks throughout life. The ongoing integration of adult-born neurons is known to be important for olfactory processing, odor discrimination, and odor learning. Furthermore, the survival and integration of the adult-born neurons is regulated by neuromodulatory signaling, sensory experience, and olfactory learning. Studies making use of new genetic markers to label and manipulate immature adult-born neurons reveal an increase in their population response to odors as they mature. Importantly, this reflects a period of developmental plasticity where adult-born neurons are especially sensitive to sensory experience and olfactory learning. In this review, we discuss the contribution of adult neurogenesis to olfactory bulb plasticity and information processing, with a focus on the developmental plasticity of adult born neurons, and how it is influenced by sensory experience and olfactory learning. Ultimately, recent studies raise important questions about behavioral-state-dependent effects on adult-born neurons, and the consequences of neuromodulation on the developmental plasticity of newborn neurons in the olfactory bulb.

This review describes the important functional implications of TCL1A single nucleotide polymorphisms (SNPs) discovered during pharmacogenomic studies of aromatase inhibitor-induced musculoskeletal adverse events that were subsequently shown to influence the expression of cytokines, chemokines, toll-like receptors (TLR), and NF-κB in a SNP and estrogen-dependent fashion. Functional genomic studies of these SNPs led to the discovery of novel mechanisms that may contribute to disease pathophysiology and which may also increase our understanding of pharmacogenomic aspects of regulation of the expression of inflammatory mediators. Specifically, TCL1A expression was induced by estrogens in a SNP-dependent fashion, resulting in downstream effects on the expression of immune mediators that included IL17RA, IL17A, CCR6, CCL20 TLR2, TLR7, TLR9, TLR10 and NF-κB. These observations have potential implications for inflammatory diseases such as rheumatoid arthritis-a disease for which two thirds of patients are women. Strikingly, this genomic phenomenon could be "reversed" by estrogen receptor antagonist treatment-once again in a SNP-dependent, i.e., in a pharmacogenomic fashion. Specifically, differential SNP-dependent effects on estrogen receptor binding to estrogen response elements before and after estrogen receptor blockade might be associated with mechanisms underlying the SNP genotype and estrogen-dependent regulation of TCL1A and the expression of downstream immune mediators. Furthermore, this SNP and estrogen-dependent phenotypic response could be "reversed" by SERM treatment. These observations could potentially open the way to understand, predict and even pharmacologically manipulate the expression of selected immune mediators in a SNP-dependent fashion.

Corneal stroma plays a pivotal role in normal visual function. Anatomically, it is located between the outer epithelium and the inner endothelium and is the thickest layer of the cornea. Keratocytes in the stroma produce a variety of cellular products, including growth factors/cytokines, extracellular matrix (ECM) components, and kinases. These products support normal corneal development and homeostasis.

Sadly many military veterans, who left home to serve their country honorably, return from service with permanent life-changing injuries. It is easy to remember our debt to those who have incurred such visible injuries, and all too easy to forget the invisible wounds that afflict so many of our military servicemen and women. Brain injuries can be invisible during initial medical evaluations and are often caused by military explosives that create blast shockwaves of varying intensity. One of the most common types of traumatic brain injury (TBI) linked to military service is blast-induced neurotrauma. To better understand this type of injury, a recently published study subjected rat brain slice cultures to detonations of RDX military explosives, resulting in reduced levels of specific synaptic markers. Such alterations have in fact been linked to depressive behavior, anxiety, and cognitive rigidity, and the blast-induced synaptic modifications may underlie the behavioral changes in those TBI sufferers who do not exhibit measurable brain damage. This research has the potential to improve diagnoses by identifying indicators of synapse integrity for the assessment of subtle synaptopathogenesis linked to blast-induced neurotrauma.