Cognitive predictors of shallow-orthography spelling speed and accuracy in 6th grade children

Spelling accuracy and time course was investigated in a sample of 100 Norwegian 6th grade students completing a standardized spelling-to-dictation task. Students responded by keyboard with accurate recordings of response-onset latency (RT) and inter-keypress interval (IKI). We determined effects of a number of child-level cognitive ability factors, and of word-level factors—particularly the location within the word of a spelling challenge (e.g., letter doubling), if present. Spelling accuracy was predicted by word reading (word split) performance, non-word spelling accuracy, keyboard key-finding speed and short-term memory span. Word reading performance predicted accuracy just for words with spelling challenges. For correctly spelled words, RT was predicted by non-word spelling response time and by speed on a key-finding task, and mean IKI by non-verbal cognitive ability, word reading, non-word spelling response time, and key-finding speed. Compared to words with no challenge, mean IKI was shorter for words with an initial challenge and longer for words with a mid-word challenge. These findings suggest that spelling is not fully planned when typing commences, a hypothesis that is confirmed by the fact that IKI immediately before within word challenges were reliably longer than elsewhere within the same word. Taken together our findings imply that routine classroom spelling tests better capture student competence if they focus not only on accuracy but also on production time course

Macrophage-Specific ApoE Gene Repair Reduces Diet-Induced Hyperlipidemia and Atherosclerosis in Hypomorphic Apoe Mice

Apolipoprotein (apo) E is best known for its ability to lower plasma cholesterol and protect against atherosclerosis. Although the liver is the major source of plasma apoE, extra-hepatic sources of apoE, including from macrophages, account for up to 10% of plasma apoE levels. This study examined the contribution of macrophage-derived apoE expression levels in diet-induced hyperlipidemia and atherosclerosis.Hypomorphic apoE (Apoe(h/h)) mice expressing wildtype mouse apoE at ∼2-5% of physiological levels in all tissues were derived by gene targeting in embryonic stem cells. Cre-mediated gene repair of the Apoe(h/h) allele in Apoe(h/h)LysM-Cre mice raised apoE expression levels by 26 fold in freshly isolated peritoneal macrophages, restoring it to 37% of levels seen in wildtype mice. Chow-fed Apoe(h/h)LysM-Cre and Apoe(h/h) mice displayed similar plasma apoE and cholesterol levels (55.53±2.90 mg/dl versus 62.70±2.77 mg/dl, n = 12). When fed a high-cholesterol diet (HCD) for 16 weeks, Apoe(h/h)LysM-Cre mice displayed a 3-fold increase in plasma apoE and a concomitant 32% decrease in plasma cholesterol when compared to Apoe(h/h) mice (602.20±22.30 mg/dl versus 888.80±24.99 mg/dl, n = 7). On HCD, Apoe(h/h)LysM-Cre mice showed increased apoE immunoreactivity in lesional macrophages and liver-associated Kupffer cells but not hepatocytes. In addition, Apoe(h/h)LysM-Cre mice developed 35% less atherosclerotic lesions in the aortic root than Apoe(h/h) mice (167×10(3)±16×10(3) µm(2) versus 259×10(3)±56×10(3) µm(2), n = 7). This difference in atherosclerosis lesions size was proportional to the observed reduction in plasma cholesterol.Macrophage-derived apoE raises plasma apoE levels in response to diet-induced hyperlipidemia and by such reduces atherosclerosis proportionally to the extent to which it lowers plasma cholesterol levels

Stem cells and other innovative intra-articular therapies for osteoarthritis: what does the future hold?

Osteoarthritis (OA), the most common type of arthritis in the world, is associated with suffering due to pain, productivity loss, decreased mobility and quality of life. Systemic therapies available for OA are mostly symptom modifying and have potential gastrointestinal, renal, hepatic, and cardiac side effects. BMC Musculoskeletal Disorders recently published a study showing evidence of reparative effects demonstrated by homing of intra-articularly injected autologous bone marrow stem cells in damaged cartilage in an animal model of OA, along with clinical and radiographic benefit. This finding adds to the growing literature showing the potential benefit of intra-articular (IA) bone marrow stem cells. Other emerging potential IA therapies include IL-1 receptor antagonists, conditioned autologous serum, botulinum toxin, and bone morphogenetic protein-7. For each of these therapies, trial data in humans have been published, but more studies are needed to establish that they are safe and effective. Several additional promising new OA treatments are on the horizon, but challenges remain to finding safe and effective local and systemic therapies for OA

Barriers to adequate follow-up during adjuvant therapy may be important factors in the worse outcome for Black women after breast cancer treatment

<p>Abstract</p> <p>Introduction</p> <p>Black women appear to have worse outcome after diagnosis and treatment of breast cancer. It is still unclear if this is because Black race is more often associated with known negative prognostic indicators or if it is an independent prognostic factor. To study this, we analyzed a patient cohort from an urban university medical center where these women made up the majority of the patient population.</p> <p>Methods</p> <p>We used retrospective analysis of a prospectively collected database of breast cancer patients seen from May 1999 to June 2006. Time to recurrence and survival were analyzed using the Kaplan-Meier method, with statistical analysis by chi-square, log rank testing, and the Cox regression model.</p> <p>Results</p> <p>265 female patients were diagnosed with breast cancer during the time period. Fifty patients (19%) had pure DCIS and 215 patients (81%) had invasive disease. Racial and ethnic composition of the entire cohort was as follows: Black (N = 150, 56.6%), Hispanic (N = 83, 31.3%), Caucasian (N = 26, 9.8%), Asian (N = 4, 1.5%), and Arabic (N = 2, 0.8%). For patients with invasive disease, independent predictors of poor disease-free survival included tumor size, node-positivity, incompletion of adjuvant therapy, and Black race. Tumor size, node-positivity, and Black race were independently associated with disease-specific overall survival.</p> <p>Conclusion</p> <p>Worse outcome among Black women appears to be independent of the usual predictors of survival. Further investigation is necessary to identify the cause of this survival disparity. Barriers to completion of standard post-operative treatment regimens may be especially important in this regard.</p

Models of Neocortical Layer 5b Pyramidal Cells Capturing a Wide Range of Dendritic and Perisomatic Active Properties

The thick-tufted layer 5b pyramidal cell extends its dendritic tree to all six layers of the mammalian neocortex and serves as a major building block for the cortical column. L5b pyramidal cells have been the subject of extensive experimental and modeling studies, yet conductance-based models of these cells that faithfully reproduce both their perisomatic Na+-spiking behavior as well as key dendritic active properties, including Ca2+ spikes and back-propagating action potentials, are still lacking. Based on a large body of experimental recordings from both the soma and dendrites of L5b pyramidal cells in adult rats, we characterized key features of the somatic and dendritic firing and quantified their statistics. We used these features to constrain the density of a set of ion channels over the soma and dendritic surface via multi-objective optimization with an evolutionary algorithm, thus generating a set of detailed conductance-based models that faithfully replicate the back-propagating action potential activated Ca2+ spike firing and the perisomatic firing response to current steps, as well as the experimental variability of the properties. Furthermore, we show a useful way to analyze model parameters with our sets of models, which enabled us to identify some of the mechanisms responsible for the dynamic properties of L5b pyramidal cells as well as mechanisms that are sensitive to morphological changes. This automated framework can be used to develop a database of faithful models for other neuron types. The models we present provide several experimentally-testable predictions and can serve as a powerful tool for theoretical investigations of the contribution of single-cell dynamics to network activity and its computational capabilities

Modes of Gene Duplication Contribute Differently to Genetic Novelty and Redundancy, but Show Parallels across Divergent Angiosperms

BACKGROUND: Both single gene and whole genome duplications (WGD) have recurred in angiosperm evolution. However, the evolutionary effects of different modes of gene duplication, especially regarding their contributions to genetic novelty or redundancy, have been inadequately explored. RESULTS: In Arabidopsis thaliana and Oryza sativa (rice), species that deeply sample botanical diversity and for which expression data are available from a wide range of tissues and physiological conditions, we have compared expression divergence between genes duplicated by six different mechanisms (WGD, tandem, proximal, DNA based transposed, retrotransposed and dispersed), and between positional orthologs. Both neo-functionalization and genetic redundancy appear to contribute to retention of duplicate genes. Genes resulting from WGD and tandem duplications diverge slowest in both coding sequences and gene expression, and contribute most to genetic redundancy, while other duplication modes contribute more to evolutionary novelty. WGD duplicates may more frequently be retained due to dosage amplification, while inferred transposon mediated gene duplications tend to reduce gene expression levels. The extent of expression divergence between duplicates is discernibly related to duplication modes, different WGD events, amino acid divergence, and putatively neutral divergence (time), but the contribution of each factor is heterogeneous among duplication modes. Gene loss may retard inter-species expression divergence. Members of different gene families may have non-random patterns of origin that are similar in Arabidopsis and rice, suggesting the action of pan-taxon principles of molecular evolution. CONCLUSION: Gene duplication modes differ in contribution to genetic novelty and redundancy, but show some parallels in taxa separated by hundreds of millions of years of evolution

Leukocyte Telomere Length in Major Depression: Correlations with Chronicity, Inflammation and Oxidative Stress - Preliminary Findings

Depression is associated with an unusually high rate of aging-related illnesses and early mortality. One aspect of “accelerated aging” in depression may be shortened leukocyte telomeres. When telomeres critically shorten, as often occurs with repeated mitoses or in response to oxidation and inflammation, cells may die. Indeed, leukocyte telomere shortening predicts early mortality and medical illnesses in non-depressed populations. We sought to determine if leukocyte telomeres are shortened in Major Depressive Disorder (MDD), whether this is a function of lifetime depression exposure and whether this is related to putative mediators, oxidation and inflammation.Leukocyte telomere length was compared between 18 unmedicated MDD subjects and 17 controls and was correlated with lifetime depression chronicity and peripheral markers of oxidation (F2-isoprostane/Vitamin C ratio) and inflammation (IL-6). Analyses were controlled for age and sex.The depressed group, as a whole, did not differ from the controls in telomere length. However, telomere length was significantly inversely correlated with lifetime depression exposure, even after controlling for age (p<0.05). Average telomere length in the depressed subjects who were above the median of lifetime depression exposure (≥9.2 years' cumulative duration) was 281 base pairs shorter than that in controls (p<0.05), corresponding to approximately seven years of “accelerated cell aging.” Telomere length was inversely correlated with oxidative stress in the depressed subjects (p<0.01) and in the controls (p<0.05) and with inflammation in the depressed subjects (p<0.05).These preliminary data indicate that accelerated aging at the level of leukocyte telomeres is proportional to lifetime exposure to MDD. This might be related to cumulative exposure to oxidative stress and inflammation in MDD. This suggest that telomere shortening does not antedate depression and is not an intrinsic feature. Rather, telomere shortening may progress in proportion to lifetime depression exposure

Ageing vision and falls: a review

Background: Falls are the leading cause of accidental injury and death among older adults. One of three adults over the age of 65 years falls annually. As the size of elderly population increases, falls become a major concern for public health and there is a pressing need to understand the causes of falls thoroughly. Main body of the abstract: While it is well documented that visual functions such as visual acuity, contrast sensitivity, and stereo acuity are correlated with fall risks, little attention has been paid to the relationship between falls and the ability of the visual system to perceive motion in the environment. The omission of visual motion perception in the literature is a critical gap because it is an essential function in maintaining balance. In the present article, we first review existing studies regarding visual risk factors for falls and the effect of ageing vision on falls. We then present a group of phenomena such as vection and sensory reweighting that provide information on how visual motion signals are used to maintain balance. Conclusion: We suggest that the current list of visual risk factors for falls should be elaborated by taking into account the relationship between visual motion perception and balance control

Cellular binding partners of the human papillomavirus E6 protein

The high-risk strains of human papillomavirus (HR-HPV) are known to be causative agents of cervical cancer and have recently also been implicated in cancers of the oropharynx. E6 is a potent oncogene of HR-HPVs, and its role in the progression to malignancy has been and continues to be explored. E6 is known to interact with and subsequently inactivate numerous cellular proteins pivotal in the mediation of apoptosis, transcription of tumor suppressor genes, maintenance of epithelial organization, and control of cell proliferation. Binding of E6 to these proteins cumulatively contributes to the oncogenic potential of HPV. This paper provides an overview of these cellular protein partners of HR-E6, the motifs known to mediate oncoprotein binding, and the agents that have the potential to interfere with E6 expression and activity and thus prevent the subsequent progression to oncogenesis

Molecular marks for epigenetic identification of developmental and cancer stem cells

Epigenetic regulations of genes by reversible methylation of DNA (at the carbon-5 of cytosine) and numerous reversible modifications of histones play important roles in normal physiology and development, and epigenetic deregulations are associated with developmental disorders and various disease states, including cancer. Stem cells have the capacity to self-renew indefinitely. Similar to stem cells, some malignant cells have the capacity to divide indefinitely and are referred to as cancer stem cells. In recent times, direct correlation between epigenetic modifications and reprogramming of stem cell and cancer stem cell is emerging. Major discoveries were made with investigations on reprogramming gene products, also known as master regulators of totipotency and inducer of pluoripotency, namely, OCT4, NANOG, cMYC, SOX2, Klf4, and LIN28. The challenge to induce pluripotency is the insertion of four reprogramming genes (Oct4, Sox2, Klf4, and c-Myc) into the genome. There are always risks of silencing of these genes by epigenetic modifications in the host cells, particularly, when introduced through retroviral techniques. In this contribution, we will discuss some of the major discoveries on epigenetic modifications within the chromatin of various genes associated with cancer progression and cancer stem cells in comparison to normal development of stem cell. These modifications may be considered as molecular signatures for predicting disorders of development and for identifying disease states