Journal of nature and science最新文献

Efficient overcoming of the nucleosomal barrier and accurate maintenance of associated histone marks during chromatin replication are essential for normal functioning of the cell. Recent studies revealed new protein factors and histone modifications contributing to overcoming the nucleosomal barrier, and suggested an important role for DNA looping in survival of the original histones during replication. These studies suggest new possible mechanisms for transmitting the histone code to next generations of cells.

Clinicians have been aware that posterior dental particulate-filled composites (PFCs) have many placement disadvantages and indeed fail clinically at an average rate faster than amalgam alloys. Secondary caries is most commonly identified as the chief failure mechanism for both dental PFCs and amalgam. In terms of a solution, fiber-reinforced composites (FRCs) above critical length (L_c) can provide mechanical property safety factors with compound molding packing qualities to reduce many problems associated with dental PFCs. Discontinuous chopped fibers above the necessary L_c have been incorporated into dental PFCs to make consolidated molding compounds that can be tested for comparisons with PFC controls on mechanical properties, wear resistance, void-defect occurrence and packing ability to reestablish the interproximal contact. Further, imaging characterizations can aid in providing comparisons for FRCs with other materials using scanning electron microscopy, atomic force microscopy and photographs. Also, the amalgam filling material has finally been tested by appropriate ASTM flexural bending methods that eliminate shear failure associated with short span lengths in dental standards for comparison with dental PFCs to best explain increased longevity for the amalgam when compared to dental PFCs. Accurate mechanical tests also provide significant proof for superior advantages with FRCs. Mechanical properties tested included flexural strength, yield strength, modulus, resilience, work of fracture, critical strain energy release and critical stress intensity factor. FRC molding compounds with fibers above L_c extensively improve all mechanical properties over PFC dental paste and over the amalgam for all mechanical properties except modulus. The dental PFC also demonstrated superior mechanical properties over the amalgam except modulus to provide a better explanation for increased PFC failure due to secondary caries. With lower PFC modulus, increased adhesive bond breakage is expected from greater interlaminar shearing as the PFC accentuates straining deflections compared to amalgam at the higher modulus tooth enamel margins during loading. Preliminary testing for experimental FRCs with fibers above L_c demonstrated three-body wear even less than enamel to reduce the possibility of marginal ditching as a factor in secondary caries seen with both PFCs and amalgam. Further, FRC molding compounds with chopped fibers above L_c properly impregnated with photocure resin can pack with condensing forces higher than the amalgam to eliminate voids in the proximal box commonly seen with dental PFCs and reestablish interproximal contacts better than amalgam. Subsequent higher FRC packing forces can aid in squeezing monomer, resin, particulate and nanofibers deeper into adhesive mechanical bond retention sites and then leave a higher concentration of insoluble fibers and particulate as moisture barriers

Objectives: Exaggerated reflex responses to passive stretch and shortening contribute to parkinsonian rigidity. Studies have reported medication-induced reductions in rigidity in the absence of attenuated reflex magnitudes. The purpose of this study was to determine if normalization procedures mask medication-induced reductions in reflex responses in Parkinson's disease.

Methods: Twelve participants with PD performed passive wrist flexion and extension movements after a 12-hour withdrawal from dopaminergic medication and 60 minutes after medication was administered. EMG was recorded from wrist flexors and extensors. Raw EMG signals were conditioned and normalized to mean background EMG amplitudes collected 100 ms prior to the onset of passive movement by division and by subtraction.

Results: Raw EMG amplitudes were significantly reduced. No medication-related reductions were observed during passive flexion or extension when EMG amplitudes were normalized by division. When EMG amplitudes were normalized by subtraction, significant reductions were observed following administration of dopaminergic medication during flexion and extension. Dopaminergic medication was associated with significant reductions in rigidity work scores and significant increases in moment-angle slope plots.

Conclusions: These findings demonstrate that EMG normalization techniques may hinder data interpretation in studies of altered reflex responses in individuals with Parkinson's disease following the administration of dopaminergic medication.

The retina is a light sensitive tissue that contains specialized photoreceptor cells called rods and cones which process visual signals. These signals are relayed to the brain through interneurons and the fibers of the optic nerve. The retina is susceptible to a variety of degenerative diseases, including age-related macular degeneration (AMD), diabetic retinopathy (DR), retinitis pigmentosa (RP) and other inherited retinal degenerations. In order to reveal the mechanism underlying these diseases and to find methods for the prevention/treatment of retinal degeneration, animal models have been generated to mimic human eye diseases. In this paper, several well-characterized and commonly used animal models are reviewed. Of particular interest are the contributions of these models to our understanding of the mechanisms of retinal degeneration and thereby providing novel treatment options including gene therapy, stem cell therapy, nanomedicine, and CRISPR/Cas9 genome editing. Role of newly-identified adaptor protein epsins from our laboratory is discussed in retinal angiogenesis and VEGFR2 signaling.

Group I metabotropic glutamate receptors (mGluR1 and mGluR5 subtypes) are regulated by protein kinases. A recent focus is mitogen-activated protein kinases (MAPK). A prototypic subclass of MAPKs, extracellular signal-regulated kinases (ERK), is densely expressed in adult brain postmitotic neurons. This kinase resides in not only the cytoplasm around the nucleus, also the neuronal peripheral structures such as synapses. Recombinant ERK2 binds to C terminal tails of mGluR1a in vitro and native ERK1/2 forms complexes with mGluR1/5 in neurons in vivo. Association of ERK with mGluR1/5 enables the kinase to phosphorylate mGluR1/5 at a cluster of serine sites in the distal C terminus, including a serine residue within the Homer binding site. The ERK-mediated phosphorylation of mGluR1/5 promotes surface expression of mGluR1a in cerebellar neurons. ERK also regulates mGluR1/5 signaling and functions. Among different functional outputs surveyed, ERK exerts an output-specific role in either potentiating or inhibiting their activities. In sum, synaptic group I mGluRs are sufficient substrates of MAPK/ERK. Phosphorylation of mGluR1/5 by ERK has a significant impact on subcellular expression and function of phospho-modified receptors.

The relationship between presence or absence of Attention Deficit Hyperactivity Disorder (ADHD) in persisting developmental dysgraphia (impaired handwriting) and brain connectivity during writing tasks was investigated. Thirteen participants (6 males, 1 female with ADHD; 4 males, 2 females without ADHD) in upper elementary or middle school grades performed four fMRI writing tasks-two cognitive (mind wandering and planning to compose) and two transcription (handwriting and spelling). Presence or absence of ADHD was correlated with brain connectivity on all four fMRI writing tasks during scanning, rather than just on the fMRI handwriting task as predicted based on prior research. However, the nature of the fMRI functional connectivity (from which of four seeds with which of eight brain regions) for the four fMRI writing tasks varied as a function of presence or absence of ADHD. The significance of these findings is discussed for both understanding the invisible biological bases of co-occurring ADHD and persisting developmental dysgraphia and teaching students with developmental dysgraphia and co-occurring ADHD.

Objectives: Statins partially block the production of coenzyme Q10 (CoQ10), an essential component for mitochondrial function. Reduced skeletal muscle mitochondrial oxidative capacity has been proposed to be a cause of statin myalgia and can be measured using ³¹phosphorus magnetic resonance spectroscopy (³¹P-MRS). The purpose of this study is to assess the effect of CoQ10 oral supplementation on mitochondrial function in statin users using ³¹P-MRS.

Design/setting: In this randomized, double-blind, placebo-controlled pilot study, 21 adults aged 47-73 were randomized to statin+placebo (n=9) or statin+CoQ10 (n=12). Phosphocreatine (PCr) recovery kinetics of calf muscles were assessed at baseline (off statin and CoQ10) and 4 weeks after randomization to either statin+CoQ10 or statin+placebo.

Results: Baseline and post-treatment PCr recovery kinetics were assessed for 19 participants. After 4 weeks of statin+ CoQ10 or statin+placebo, the overall relative percentage change (100*(baseline-follow up)/baseline) in PCr recovery time was -15.1% compared with baseline among all participants, (p-value=0.258). Participants randomized to statin+placebo (n=9) had a relative percentage change in PCr recovery time of -18.9%, compared to -7.7% among participants (n=10) receiving statin+CoQ10 (p-value=0.448).

Conclusions: In this pilot study, there was no significant change in mitochondrial function in patients receiving 4 weeks of statin+CoQ10 oral therapy when compared to patients on statin+placebo.

The objective of the study was to investigate the pharmacokinetics and efficacy of 5-FU entrapped pH-sensitive liposomal nanoparticles with surface-modified anti-epidermal growth factor receptor (EGFR) antibody (pHLNps-5-FU) delivery system. Cytotoxicity of 5-FU and pHLNps-5-FU was determined in vitro against HCT-116 cells. The biodistribution and pharmacokinetic parameters of the administered 5-FU and pHLNps-5-FU as well as efficacy of 5-FU and pHLNps-5-FU were determined in HCT-116 subcutaneous mouse model. Mean size of pHLNp-5-FU was 164.3 ± 8.4 nm with entrapment efficiency (E.E) of 54.17%. While cytotoxicity of 5-FU and pHLNps-5-FU showed a strong dose-dependent, pHLNps-5-FU proved to be more effective (2-3 fold high) than that of 5-FU against HCT-116 cells. Pharmacokinetic study showed a prolonged plasma circulation of pHLNps-5-FU and a more significant body exposure while accumulation of pHLNps-5-FU in tumor was significantly higher than that of free 5-FU. Further, the efficacy of pHLNps-5-FU, was greater than free 5-FU at equivalent 5-FU dose. The study suggests that pHLNps may be an effective drug delivery system to enhance the anticancer activity of 5-FU against colorectal tumor growth.

Malnutrition is prevalent in patients undergoing elective total joint arthroplasty (TJA). Malnutrition has been shown to be an independent risk factor for multiple postsurgical complications following TJA in addition to increasing postoperative mortality. In the current healthcare environment, it is important to recognize and correct modifiable risk factors preoperatively to minimize perioperative complications and improve patient outcomes. Recently, multiple studies have been published focusing on the association between malnutrition and perioperative complications following TJA. The findings of these studies are summarized in this review. Further research is required to determine if optimization of nutritional status preoperatively influence surgical outcomes in the elective TJA patient.

Objective: Elevated systemic stress is a predictor of adverse health outcomes, and stress can be objectively quantified by cortisol concentration. Despite its utility, such testing is rarely performed in otolaryngology. This manuscript provides details on the principles, methodology, and feasibility of performing laboratory assessments of hair and salivary cortisol to inform researchers wishing to incorporate these novel tests in future otolaryngologic studies.

Methods: Participants were older adults with hearing impairment. One hair sample and eight saliva samples were collected. Feasibility of study design was assessed through rates of participation in hair and saliva sampling and protocol adherence for saliva collection. Area under the curve (AUC) was used to evaluate overall secretion, and cortisol awakening response (CAR) was used to evaluate the dynamic secretion response.

Results: From 9/1/2013 to 12/31/2013, 26/30 (86.7%) eligible participants agreed to hair sampling. All 30 subjects agreed to collect saliva, with 29 (96.7%) adhering to the collection protocol. Mean AUC was 401.2 nmol/L per hour, and CAR was 4.5 nmol/L.

Conclusions: Evaluating systemic stress in an otolaryngologic population using hair and saliva is feasible with acceptable participation and adherence. Repeat measurements over time will allow for evaluation of changes in systemic stress in relation to treatment.