Phosphatidylinositol 3-kinase function at very early symbiont perception: a local nodulation control under stress conditions?

PubMed

Robert, Germán; Muñoz, Nacira; Alvarado-Affantranger, Xochitl; Saavedra, Laura; Davidenco, Vanina; Rodríguez-Kessler, Margarita; Estrada-Navarrete, Georgina; Sánchez, Federico; Lascano, Ramiro

2018-04-09

Root hair curling is an early and essential morphological change required for the success of the symbiotic interaction between legumes and rhizobia. At this stage rhizobia grow as an infection thread within root hairs and are internalized into the plant cells by endocytosis, where the PI3K enzyme plays important roles. Previous observations show that stress conditions affect early stages of the symbiotic interaction, from 2 to 30 min post-inoculation, which we term as very early host responses, and affect symbiosis establishment. Herein, we demonstrated the relevance of the very early host responses for the symbiotic interaction. PI3K and the NADPH oxidase complex are found to have key roles in the microsymbiont recognition response, modulating the apoplastic and intracellular/endosomal ROS induction in root hairs. Interestingly, compared with soybean mutant plants that do not perceive the symbiont, we demonstrated that the very early symbiont perception under sublethal saline stress conditions induced root hair death. Together, these results highlight not only the importance of the very early host-responses on later stages of the symbiont interaction, but also suggest that they act as a mechanism for local control of nodulation capacity, prior to the abortion of the infection thread, preventing the allocation of resources/energy for nodule formation under unfavorable environmental conditions.

The effect of timing of manipulation under anesthesia to improve range of motion and functional outcomes following total knee arthroplasty.

PubMed

Issa, Kimona; Banerjee, Samik; Kester, Mark A; Khanuja, Harpal S; Delanois, Ronald E; Mont, Michael A

2014-08-20

Manipulation under anesthesia has been reported to improve range of motion when other rehabilitative efforts fail to obtain adequate motion after total knee arthroplasty. The purpose of this study was to evaluate the effects of the timing of the manipulation on knee range of motion and clinical outcomes. All 2128 total knee arthroplasties performed at our institution from 2005 to 2011 were reviewed to determine the number of patients who had undergone manipulation under anesthesia. A total of 144 manipulations in eighty-eight women and forty-five men were reviewed. Manipulations under anesthesia that were performed within the first twelve weeks after total knee arthroplasty were considered early and those after that period were considered late. Patients were further substratified according to the timing of the manipulation: Group I included those who had the manipulation within six weeks; Group II, at seven to twelve weeks; Group III, at thirteen to twenty-six weeks; and Group IV, after twenty-six weeks. Outcomes evaluated included gains in flexion and final range of motion, and Knee Society objective and function scores between early and late manipulation, using various adjusted multivariable regression models and at a mean follow-up of fifty-one months (range, twelve to eighty-one months). Mediation analysis was used to investigate whether gains in range of motion from the manipulations under anesthesia alone had mediated the effect between the timing of the manipulation and the clinical outcomes. Patients who underwent early manipulation had a significantly higher mean gain in flexion (36.5° versus 17°), higher final range of motion (119° versus 95°), and higher Knee Society objective (89 versus 84 points) and function scores (88 versus 83 points) than those who had late manipulation under anesthesia. There were no significant differences in the outcomes of Groups I and II. Manipulations after twenty-six weeks resulted in unsatisfactory clinical outcomes. Multivariable regression analyses confirmed significantly better clinical outcomes with early manipulation. Mediation analysis showed that the timing of manipulation independently had significantly contributed to the outcomes. Orthopaedic surgeons should have a low threshold for performing early manipulations with the patient under anesthesia within twelve weeks after an arthroplasty, to achieve higher knee range of motion and improved clinical outcomes. Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence. Copyright © 2014 by The Journal of Bone and Joint Surgery, Incorporated.

Frodo proteins: modulators of Wnt signaling in vertebrate development.

PubMed

Brott, Barbara K; Sokol, Sergei Y

2005-09-01

The Frodo/dapper (Frd) proteins are recently discovered signaling adaptors, which functionally and physically interact with Wnt and Nodal signaling pathways during vertebrate development. The Frd1 and Frd2 genes are expressed in dynamic patterns in early embryos, frequently in cells undergoing epithelial-mesenchymal transition. The Frd proteins function in multiple developmental processes, including mesoderm and neural tissue specification, early morphogenetic cell movements, and organogenesis. Loss-of-function studies using morpholino antisense oligonucleotides demonstrate that the Frd proteins regulate Wnt signal transduction in a context-dependent manner and may be involved in Nodal signaling. The identification of Frd-associated factors and cellular targets of the Frd proteins should shed light on the molecular mechanisms underlying Frd functions in embryonic development and in cancer.

(Re)Landscaping Early Childhood Education in East Asia: A Neoliberal Economic and Political Imaginary

ERIC Educational Resources Information Center

Lee, I-Fang

2018-01-01

This article unpacks how neoliberal discourse functions as a dominant but problematic system of reasoning that changes and shifts the ways in which we come to think about early childhood education and care. A post-structuralist lens is deployed to understand the production of fears and hopes under the looming shadows of contemporary education…

Evaluating physical and behavioral changes in older adults.

PubMed

Walton, J C; Miller, J M

1998-04-01

In older adults, subtle and sometime not so subtle physical or behavior changes can act as early warning signs of changing status. Nonspecific signs and symptoms occurring in older adults such as decline in previous functional capacity, urinary incontinence, anorexia, confusion, or unexplained falls may be signs of infection, medication interaction, dehydration, constipation, or sleep deprivation. Nurses, by critically assessing the situation early, may identify a developing problem. Prompt and early diagnosis of the underlying problem may save costly extended hospitalization or even prevent life-threatening complications.

From Childhood Conduct Problems to Poor Functioning at Age 18 Years: Examining Explanations in a Longitudinal Cohort Study.

PubMed

Wertz, Jasmin; Agnew-Blais, Jessica; Caspi, Avshalom; Danese, Andrea; Fisher, Helen L; Goldman-Mellor, Sidra; Moffitt, Terrie E; Arseneault, Louise

2018-01-01

Childhood conduct problems are associated with poor functioning in early adulthood. We tested a series of hypotheses to understand the mechanisms underlying this association. We used data from the Environmental Risk (E-Risk) Longitudinal Twin Study, a birth cohort of 2,232 twins born in England and Wales in 1994 and 1995, followed up to age 18 years with 93% retention. Severe conduct problems in childhood were assessed at ages 5, 7, and 10 years using parent and teacher reports. Poor functioning at age 18 years, including cautions and convictions, daily cigarette smoking, heavy drinking, and psychosocial difficulties, was measured through interviews with participants and official crime record searches. Participants 18 years old with versus without a childhood history of severe conduct problems had greater rates of each poor functional outcome, and they were more likely to experience multiple poor outcomes. This association was partly accounted for by concurrent psychopathology in early adulthood, as well as by early familial risk factors, both genetic and environmental. Childhood conduct problems, however, continued to predict poor outcomes at age 18 years after accounting for these explanations. Children with severe conduct problems display poor functioning at age 18 years because of concurrent problems in early adulthood and familial risk factors originating in childhood. However, conduct problems also exert a lasting effect on young people's lives independent of these factors, pointing to early conduct problems as a target for early interventions aimed at preventing poor functional outcomes. Copyright © 2017 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

Changes in Frontal EEG Coherence across Infancy Predict Cognitive Abilities at Age 3: The Mediating Role of Attentional Control

ERIC Educational Resources Information Center

Whedon, Margaret; Perry, Nicole B.; Calkins, Susan D.; Bell, Martha Ann

2016-01-01

Theoretical perspectives of cognitive development have maintained that functional integration of the prefrontal cortex across infancy underlies the emergence of attentional control and higher cognitive abilities in early childhood. To investigate these proposed relations, we tested whether functional integration of prefrontal regions across the…

The role of early life nutrition in programming of reproductive function.

PubMed

Chadio, S; Kotsampasi, B

2014-02-01

Accumulating evidence suggest that the concept of programming can also be applied to reproductive development and function, representing an ever expanding research area. Recently issues such as peri- or even preconceptional nutrition, transgenerational effects and underlying mechanisms have received considerable attention. The present chapter presents the existed evidence and reviews the available data from numerous animal and human studies on the effects of early life nutritional environment on adult reproductive function. Specific outcomes depend on the severity, duration and stage of development when nutritional perturbations are imposed, while sex-specific effects are also manifested. Apart from undernutrition, effects of relative overnutrition as well as the complex interactions between pre- and postnatal nutrition is of high importance, especially in the context of our days obesity epidemic. Mechanisms underlying reproductive programming are yet unclear, but may include a role for epigenetic modifications. Epigenetic modulation of critical genes involved in the control of reproductive function and potential intergenerational effects represent an exciting area of interdisciplinary research toward the development of new nutritional approaches during pre- and postnatal periods to ensure reproductive health in later life.

Early-life nutritional effects on the female reproductive system.

PubMed

Chan, K A; Tsoulis, M W; Sloboda, D M

2015-02-01

There is now considerable epidemiological and experimental evidence indicating that early-life environmental conditions, including nutrition, affect subsequent development in later life. These conditions induce highly integrated responses in endocrine-related homeostasis, resulting in persistent changes in the developmental trajectory producing an altered adult phenotype. Early-life events trigger processes that prepare the individual for particular circumstances that are anticipated in the postnatal environment. However, where the intrauterine and postnatal environments differ markedly, such modifications to the developmental trajectory may prove maladaptive in later life. Reproductive maturation and function are similarly influenced by early-life events. This should not be surprising, because the primordial follicle pool is established early in life and is thus vulnerable to early-life events. Results of clinical and experimental studies have indicated that early-life adversity is associated with a decline in ovarian follicular reserve, changes in ovulation rates, and altered age at onset of puberty. However, the underlying mechanisms regulating the relationship between the early-life developmental environment and postnatal reproductive development and function are unclear. This review examines the evidence linking early-life nutrition and effects on the female reproductive system, bringing together clinical observations in humans and experimental data from targeted animal models. © 2015 Society for Endocrinology.

Relationship between macular pigment and visual function in subjects with early age-related macular degeneration.

PubMed

Akuffo, Kwadwo Owusu; Nolan, John M; Peto, Tunde; Stack, Jim; Leung, Irene; Corcoran, Laura; Beatty, Stephen

2017-02-01

To investigate the relationship between macular pigment (MP) and visual function in subjects with early age-related macular degeneration (AMD). 121 subjects with early AMD enrolled as part of the Central Retinal Enrichment Supplementation Trial (CREST; ISRCTN13894787) were assessed using a range of psychophysical measures of visual function, including best corrected visual acuity (BCVA), letter contrast sensitivity (CS), mesopic and photopic CS, mesopic and photopic glare disability (GD), photostress recovery time (PRT), reading performance and subjective visual function, using the National Eye Institute Visual Function Questionnaire-25 (NEI VFQ-25). MP was measured using customised heterochromatic flicker photometry. Letter CS, mesopic and photopic CS, photopic GD and mean reading speed were each significantly (p<0.05) associated with MP across a range of retinal eccentricities, and these statistically significant relationships persisted after controlling for age, sex and cataract grade. BCVA, NEI VFQ-25 score, PRT and mesopic GD were unrelated to MP after controlling for age, sex and cataract grade (p>0.05, for all). MP relates positively to many measures of visual function in unsupplemented subjects with early AMD. The CREST trial will investigate whether enrichment of MP influences visual function among those afflicted with this condition. ISRCTN13894787. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Are gains in decision-making autonomy during early adolescence beneficial for emotional functioning? The case of the United States and china.

PubMed

Qin, Lili; Pomerantz, Eva M; Wang, Qian

2009-01-01

This research examined the role of children's decision-making autonomy in their emotional functioning during early adolescence in the United States and China. Four times over the 7th and 8th grades, 825 American and Chinese children (M = 12.73 years) reported on the extent to which they versus their parents make decisions about issues children often deem as under their authority. Children also reported on their emotional functioning. American children made greater gains over time in decision-making autonomy than did Chinese children. Initial decision-making autonomy predicted enhanced emotional functioning similarly among American and Chinese children. However, gains over time in decision-making autonomy predicted enhanced emotional functioning more in the United States (vs. China) where such gains were normative.

[Early functional hemispherectomy in hemimegalencephaly associated to refractory epilepsy].

PubMed

Fonseca, Luiz Fernando; Melo, Renato Pacheco de; Cukiert, Arthur; Burattini, Jose Augusto; Mariani, Pedro Paulo; Brandão, Ródio; Ceda, Lauro; Baldauf, Cristine Mella; Argentoni, Meire; Forster, Cássio; Baise, Carla

2004-12-01

Hemimegalencephaly (HME) is a rare congenital brain malformation of unknown etiology. Patients with HME can present with an early onset epileptic syndrome which is often refractory to medical treatment and associated to impaired neurological development. Functional hemispherectomy (FH) has proven to be a valuable treatment alternative in patients with refractory epilepsy in this setting. Very few children operated under the age of 6 months and bearing HME and catastrophic epilepsy (CE) have been described in the literature. This study reports on 2 kids younger than 6 months with HME and CE submitted to FH with good clinical outcome.

Stimulation of functional vision in children with perinatal brain damage.

PubMed

Alimović, Sonja; Mejaski-Bosnjak, Vlatka

2011-01-01

Cerebral visual impairment (CVI) is one of the most common causes of bilateral visual loss, which frequently occurs due to perinatal brain injury. Vision in early life has great impact on acquisition of basic comprehensions which are fundamental for further development. Therefore, early detection of visual problems and early intervention is necessary. The aim of the present study is to determine specific visual functioning of children with perinatal brain damage and the influence of visual stimulation on development of functional vision at early age of life. We initially assessed 30 children with perinatal brain damage up to 3 years of age, who were reffered to our pediatric low vision cabinet in "Little house" from child neurologists, ophthalmologists Type and degree of visual impairment was determined according to functional vision assessment of each child. On the bases of those assessments different kind of visual stimulations were carried out with children who have been identified to have a certain visual impairment. Through visual stimulation program some of the children were stimulated with light stimulus, some with different materials under the ultraviolet (UV) light, and some with bright color and high contrast materials. Children were also involved in program of early stimulation of overall sensory motor development. Goals and methods of therapy were determined individually, based on observation of child's possibilities and need. After one year of program, reassessment was done. Results for visual functions and functional vision were compared to evaluate the improvement of the vision development. These results have shown that there was significant improvement in functional vision, especially in visual attention and visual communication.

Factors influencing speech and language outcomes of children with early identified severe/profound hearing loss: Clinician-identified facilitators and barriers.

PubMed

Fulcher, Anne Nivelles; Purcell, Alison; Baker, Elise; Munro, Natalie

2015-06-01

Early identification of severe/profound childhood hearing loss (HL) gives these children access to hearing devices and early intervention to facilitate improved speech and language outcomes. Predicting which infants will go on to achieve such outcomes remains difficult. This study describes clinician identified malleable and non-malleable factors that may influence speech and language outcomes for children with severe/profound HL. Semi-structured interviews were conducted with six experienced auditory verbal clinicians. A collective case study design was implemented. The interviews were transcribed and coded into themes using constant comparative analysis. Clinicians identified that, for children with severe/profound HL, early identification, early amplification and commencing auditory-verbal intervention under 6 months of age may facilitate child progress. Possible barriers were living in rural/remote areas, the clinicians' lack of experience and confidence in providing intervention for infants under age 6-months and belonging to a family with a culturally and linguistically diverse (CALD) background. The results indicate that multiple factors need to be considered by clinicians working with children with HL and their families to determine how each child functions within their own environment and personal contexts, consistent with the International Classification of Functioning, Disability and Health (ICF) framework. Such an approach is likely to empower clinicians to carefully balance potential barriers to, and facilitators of, optimal speech and language outcomes for all children with HL.

Cognitive load effects on early visual perceptual processing.

PubMed

Liu, Ping; Forte, Jason; Sewell, David; Carter, Olivia

2018-05-01

Contrast-based early visual processing has largely been considered to involve autonomous processes that do not need the support of cognitive resources. However, as spatial attention is known to modulate early visual perceptual processing, we explored whether cognitive load could similarly impact contrast-based perception. We used a dual-task paradigm to assess the impact of a concurrent working memory task on the performance of three different early visual tasks. The results from Experiment 1 suggest that cognitive load can modulate early visual processing. No effects of cognitive load were seen in Experiments 2 or 3. Together, the findings provide evidence that under some circumstances cognitive load effects can penetrate the early stages of visual processing and that higher cognitive function and early perceptual processing may not be as independent as was once thought.

Manipulation under anaesthetic for frozen shoulder using Codman's paradox: a safe and early return of function.

PubMed

Tsvieli, Oren; Atoun, Ehud; Consigliere, Paolo; Polyzois, Ioannis; Walecka, Joanna; Pradhan, Rajib; Ippolito, Giorgio; Rath, Ehud; Levy, Ofer

2018-02-01

Although previously frozen shoulder was thought to resolve by two to three years, recent studies demonstrated the symptoms can remain for much longer. Manipulation under anaesthetic (MUA) has been shown to be successful in relieving pain and restoring function. Yet, concerns have been raised regarding its safety and the risks of complications. We utilise Codman's paradox to manipulate the shoulder, avoiding rotational torque on the humerus. The aim of our study was to asses shoulder function in the early post MUA period. Two hundred twelve consecutive patients (224 shoulders) (mean age 52.4 years) underwent MUA using Codman's paradox for frozen shoulder as sole procedure between 2005 and 2013. All were evaluated clinically, preoperatively and postoperatively, at three weeks and three months, for Constant score (CS), pain, range of motion (ROM), patient satisfaction and subjective shoulder value (SSV). At three weeks and three months, a significant improvement was found in CS from 30.7 to 66 and 70 respectively. Forward elevation improved from 91° to 154° and 160 °, abduction from 69° to 150° and 156 °, internal rotation from 12° to 62° and 66 °, and external rotation from 10° to 46° and 50 °. Pain score improved from 4.4/15 to 9.6/15 and 10.4/15, SSV improved from 1.5/10 to 6.5/10 and 6.7/10. (p<0.001). Use of Codman's paradox provides a safe and efficient way to perform MUA for frozen shoulder. It results in dramatic early improvement in ROM, functional outcomes and high satisfaction, as early as three weeks post-operatively.

Plasticity following early-life brain injury: Insights from quantitative MRI.

PubMed

Fiori, Simona; Guzzetta, Andrea

2015-03-01

Over the last decade, the application of novel advanced neuroimaging techniques to study congenital brain damage has provided invaluable insights into the mechanisms underlying early neuroplasticity. The concept that is clearly emerging, both from human and nun-human studies, is that functional reorganization in the immature brain is substantially different from that of the more mature, developed brain. This applies to the reorganization of language, the sensorimotor system, and the visual system. The rapid implementation and development of higher order imaging methods will offer increased, currently unavailable knowledge about the specific mechanisms of cerebral plasticity in infancy, which is essential to support the development of early therapeutic interventions aimed at supporting and enhancing functional reorganization during a time of greatest potential brain plasticity. Copyright © 2015. Published by Elsevier Inc.

Cardioprotective effects of early and late aerobic exercise training in experimental pulmonary arterial hypertension.

PubMed

Moreira-Gonçalves, Daniel; Ferreira, Rita; Fonseca, Hélder; Padrão, Ana Isabel; Moreno, Nuno; Silva, Ana Filipa; Vasques-Nóvoa, Francisco; Gonçalves, Nádia; Vieira, Sara; Santos, Mário; Amado, Francisco; Duarte, José Alberto; Leite-Moreira, Adelino F; Henriques-Coelho, Tiago

2015-11-01

Clinical studies suggest that aerobic exercise can exert beneficial effects in pulmonary arterial hypertension (PAH), but the underlying mechanisms are largely unknown. We compared the impact of early or late aerobic exercise training on right ventricular function, remodeling and survival in experimental PAH. Male Wistar rats were submitted to normal cage activity (SED), exercise training in early (EarlyEX) and in late stage (LateEX) of PAH induced by monocrotaline (MCT, 60 mg/kg). Both exercise interventions resulted in improved cardiac function despite persistent right pressure-overload, increased exercise tolerance and survival, with greater benefits in EarlyEX+MCT. This was accompanied by improvements in the markers of cardiac remodeling (SERCA2a), neurohumoral activation (lower endothelin-1, brain natriuretic peptide and preserved vascular endothelial growth factor mRNA), metabolism and mitochondrial oxidative stress in both exercise interventions. EarlyEX+MCT provided additional improvements in fibrosis, tumor necrosis factor-alpha/interleukin-10 and brain natriuretic peptide mRNA, and beta/alpha myosin heavy chain protein expression. The present study demonstrates important cardioprotective effects of aerobic exercise in experimental PAH, with greater benefits obtained when exercise training is initiated at an early stage of the disease.

Impact of early childhood caries and its treatment under general anesthesia on orofacial function and quality of life : A prospective comparative study.

PubMed

Collado, V; Pichot, H; Delfosse, C; Eschevins, C; Nicolas, E; Hennequin, M

2017-05-01

Early Childhood Caries (ECC) has become a major public health concern worldwide, mostly affecting children from disadvantaged families in increasingly severe forms. This condition has been frequently reported to alter children's nutrition, growth and general development. It negatively impacts their quality of life, through painful episodes and severe eating difficulties. While this period is crucial for oral praxes development, the impact of dental state on oro-facial functions is poorly documented. This study evaluated the impact of ECC and its treatment under general anesthesia on oro-facial functions and quality of life in pre-school children. The dysfunction and quality of life scores from 25 children with ECC were evaluated before treatment (T0), one month (T1) and three months after treatment (T2), using the Nordic Orofacial Test-Screening (NOT-S) and the Early Childhood Oral Health Impact Scale (ECOHIS), respectively, in comparison with 16 caries-free children. The number and extent of inter-arch dental contacts were also observed. The pre-operative higher NOT-S score observed in children with ECC decreased to reach the control level at T2. The mastication item was the most affected in the ECC group throughout the study. Their mean ECOHIS score also significantly decreased post-operatively and differences remaining between both groups were no longer clinically relevant. In addition, in children with ECC, values of functional inter-arch surfaces tended to increase over the follow-up period. Oro-facial functions and quality of life, altered by ECC, could be restored through a conservative treatment approach. Relations between dental state, orofacial functions and particularly chewing, and nutrition should be investigated further.

20 CFR 631.30 - Designation or creation and functions of a State dislocated worker unit or office, and rapid...

Code of Federal Regulations, 2010 CFR

2010-04-01

... provision of early intervention services and other appropriate forms of immediate assistance in response to... Governor and the State Council to assist in providing an adequate information base for effective program... workers under the NAFTA Worker Security Act for which the Governor has made a finding under § 631.3(j...

Impaired theta phase-resetting underlying auditory N1 suppression in chronic alcoholism.

PubMed

Fuentemilla, Lluis; Marco-Pallarés, Josep; Gual, Antoni; Escera, Carles; Polo, Maria Dolores; Grau, Carles

2009-02-18

It has been suggested that chronic alcoholism may lead to altered neural mechanisms related to inhibitory processes. Here, we studied auditory N1 suppression phenomena (i.e. amplitude reduction with repetitive stimuli) in chronic alcoholic patients as an early-stage information-processing brain function involving inhibition by the analysis of the N1 event-related potential and time-frequency computation (spectral power and phase-resetting). Our results showed enhanced neural theta oscillatory phase-resetting underlying N1 generation in suppressed N1 event-related potential. The present findings suggest that chronic alcoholism alters neural oscillatory synchrony dynamics at very early stages of information processing.

Light quantity and photosystem function mediate host susceptibility to turnip mosaic virus via a salicylic acid-independent mechanism

USDA-ARS?s Scientific Manuscript database

Evidence going as far back as the early part of the 20th century suggests that both light and chloroplast function may play key roles in host susceptibility to viruses. Despite the long history of such work, confirmation of these phenomena and a determination of the underlying mechanisms remain elu...

Elucidation of Cross-Talk and Specificity of Early Response Mechanisms to Salt and PEG-Simulated Drought Stresses in Brassica napus Using Comparative Proteomic Analysis

PubMed Central

Luo, Junling; Tang, Shaohua; Peng, Xiaojue; Yan, Xiaohong; Zeng, Xinhua; Li, Jun; Li, Xiaofei; Wu, Gang

2015-01-01

To understand the cross-talk and specificity of the early responses of plants to salt and drought, we performed physiological and proteome analyses of Brassica napus seedlings pretreated with 245 mM NaCl or 25% polyethylene glycol (PEG) 6000 under identical osmotic pressure (-1.0 MPa). Significant decreases in water content and photosynthetic rate and excessive accumulation of compatible osmolytes and oxidative damage were observed in response to both stresses. Unexpectedly, the drought response was more severe than the salt response. We further identified 45 common differentially expressed proteins (DEPs), 143 salt-specific DEPs and 160 drought-specific DEPs by isobaric tags for relative and absolute quantitation (iTRAQ) analysis. The proteome quantitative data were then confirmed by multiple reaction monitoring (MRM). The differences in the proteomic profiles between drought-treated and salt-treated seedlings exceeded the similarities in the early stress responses. Signal perception and transduction, transport and membrane trafficking, and photosynthesis-related proteins were enriched as part of the molecular cross-talk and specificity mechanism in the early responses to the two abiotic stresses. The Ca2+ signaling, G protein-related signaling, 14-3-3 signaling pathway and phosphorylation cascades were the common signal transduction pathways shared by both salt and drought stress responses; however, the proteins with executive functions varied. These results indicate functional specialization of family proteins in response to different stresses, i.e., CDPK21, TPR, and CTR1 specific to phosphorylation cascades under early salt stress, whereas STN7 and BSL were specific to phosphorylation cascades under early drought stress. Only the calcium-binding EF-hand family protein and ZKT were clearly identified as signaling proteins that acted as cross-talk nodes for salt and drought signaling pathways. Our study provides new clues and insights for developing strategies to improve the tolerance of crops to complex, multiple environmental stresses. PMID:26448643

Prognostic importance of early worsening renal function after initiation of angiotensin-converting enzyme inhibitor therapy in patients with cardiac dysfunction.

PubMed

Testani, Jeffrey M; Kimmel, Stephen E; Dries, Daniel L; Coca, Steven G

2011-11-01

Worsening renal function (WRF) in the setting of heart failure has been associated with increased mortality. However, it is unclear if this decreased survival is a direct result of the reduction in glomerular filtration rate (GFR) or if the mechanism underlying the deterioration in GFR is driving prognosis. Given that WRF in the setting of angiotensin-converting enzyme inhibitor (ACE-I) initiation is likely mechanistically distinct from spontaneously occurring WRF, we investigated the relative early WRF-associated mortality rates in subjects randomized to ACE-I or placebo. Subjects in the Studies Of Left Ventricular Dysfunction (SOLVD) limited data set (n=6337) were studied. The interaction between early WRF (decrease in estimated GFR ≥20% at 14 days), randomization to enalapril, and mortality was the primary end point. In the overall population, early WRF was associated with increased mortality (adjusted hazard ratio [HR], 1.2; 95% CI, 1.0-1.4; P=0.037). When analysis was restricted to the placebo group, this association strengthened (adjusted HR, 1.4; 95% CI, 1.1-1.8; P=0.004). However, in the enalapril group, early WRF had no adverse prognostic significance (adjusted HR, 1.0; 95% CI, 0.8-1.3; P=1.0; P=0.09 for the interaction). In patients who continued to receive study drug despite early WRF, a survival advantage remained with enalapril therapy (adjusted HR, 0.66; 95% CI, 0.5-0.9; P=0.018). These data support the notion that the mechanism underlying WRF is important in determining its prognostic significance. Specifically, early WRF in the setting of ACE-I initiation appears to represent a benign event that is not associated with a loss of benefit from continued ACE-I therapy.

How the Timing and Quality of Early Experiences Influence the Development of Brain Architecture

PubMed Central

Fox, Sharon E.; Levitt, Pat; Nelson, Charles A.

2009-01-01

Early life events can exert a powerful influence on both the pattern of brain architecture and behavioral development. In this paper a conceptual framework is provided for considering how the structure of early experience gets “under the skin.” The paper begins with a description of the genetic framework that lays the foundation for brain development, and then to the ways experience interacts with and modifies the structures and functions of the developing brain. Much of the attention is focused on early experience and sensitive periods, although it is made clear that later experience also plays an important role in maintaining and elaborating this early wiring diagram, which is critical to establishing a solid footing for development beyond the early years. PMID:20331653

Mechanisms Underlying Latent Disease Risk Associated with Early-Life Arsenic Exposure: Current Research Trends and Scientific Gaps

PubMed Central

Bailey, Kathryn A.; Smith, Allan H.; Tokar, Erik J.; Graziano, Joseph H.; Kim, Kyoung-Woong; Navasumrit, Panida; Ruchirawat, Mathuros; Thiantanawat, Apinya; Suk, William A.; Fry, Rebecca C.

2015-01-01

Background Millions of individuals worldwide, particularly those living in rural and developing areas, are exposed to harmful levels of inorganic arsenic (iAs) in their drinking water. Inorganic As exposure during key developmental periods is associated with a variety of adverse health effects, including those that are evident in adulthood. There is considerable interest in identifying the molecular mechanisms that relate early-life iAs exposure to the development of these latent diseases, particularly in relationship to cancer. Objectives This work summarizes research on the molecular mechanisms that underlie the increased risk of cancer development in adulthood that is associated with early-life iAs exposure. Discussion Epigenetic reprogramming that imparts functional changes in gene expression, the development of cancer stem cells, and immunomodulation are plausible underlying mechanisms by which early-life iAs exposure elicits latent carcinogenic effects. Conclusions Evidence is mounting that relates early-life iAs exposure and cancer development later in life. Future research should include animal studies that address mechanistic hypotheses and studies of human populations that integrate early-life exposure, molecular alterations, and latent disease outcomes. Citation Bailey KA, Smith AH, Tokar EJ, Graziano JH, Kim KW, Navasumrit P, Ruchirawat M, Thiantanawat A, Suk WA, Fry RC. 2016. Mechanisms underlying latent disease risk associated with early-life arsenic exposure: current research trends and scientific gaps. Environ Health Perspect 124:170–175; http://dx.doi.org/10.1289/ehp.1409360 PMID:26115410

'What's up, (R)DoC?'--can identifying core dimensions of early functioning help us understand, and then reduce, developmental risk for mental disorders?

PubMed

Sonuga-Barke, Edmund J S

2014-08-01

In the U.S. the National Institute of Mental Health (NIMH), the main funder of mental health research in the world, has recently changed its funding model to promote a radically new perspective for mental health science. This bold, and for some controversial, initiative, termed the Research Diagnostic Criteria (or RDoC for short), intends to shift the focus of research, and eventually clinical practice, away from existing diagnostic categories, as recently updated in the DSM-5, towards 'new ways of classifying psychopathology based on dimensions of observable behavior and neurobiological measures.' This reorientation from discrete categorical disorder manifestations to underlying cross-cutting dimensions of individual functioning has generated considerable debate across the community of mental health researchers and clinicians (with strong views voiced both pro and con). Given its pivotal role in defining the research agenda globally, there is little doubt that this US science funding initiative will also have ramifications for researchers and clinicians worldwide. In this Editorial we focus specifically on the translational potential of the dimensional RDoC approach, properly extended to developmental models of early risk, in terms of its value as a potential driver of early intervention/prevention models; in the current issue of the JCPP this is exemplified by a number of papers thata address the mapping of underlying dimensions of core functioning to disorder risk, providing evidence for their potential predictive power as early markers of later disorder processes. © 2014 The Author. Journal of Child Psychology and Psychiatry. © 2014 Association for Child and Adolescent Mental Health.

Murine fetal echocardiography.

PubMed

Kim, Gene H

2013-02-15

Transgenic mice displaying abnormalities in cardiac development and function represent a powerful tool for the understanding the molecular mechanisms underlying both normal cardiovascular function and the pathophysiological basis of human cardiovascular disease. Fetal and perinatal death is a common feature when studying genetic alterations affecting cardiac development. In order to study the role of genetic or pharmacologic alterations in the early development of cardiac function, ultrasound imaging of the live fetus has become an important tool for early recognition of abnormalities and longitudinal follow-up. Noninvasive ultrasound imaging is an ideal method for detecting and studying congenital malformations and the impact on cardiac function prior to death. It allows early recognition of abnormalities in the living fetus and the progression of disease can be followed in utero with longitudinal studies. Until recently, imaging of fetal mouse hearts frequently involved invasive methods. The fetus had to be sacrificed to perform magnetic resonance microscopy and electron microscopy or surgically delivered for transillumination microscopy. An application of high-frequency probes with conventional 2-D and pulsed-wave Doppler imaging has been shown to provide measurements of cardiac contraction and heart rates during embryonic development with databases of normal developmental changes now available. M-mode imaging further provides important functional data, although, the proper imaging planes are often difficult to obtain. High-frequency ultrasound imaging of the fetus has improved 2-D resolution and can provide excellent information on the early development of cardiac structures.

Identification and functional analysis of long non-coding RNAs in human and mouse early embryos based on single-cell transcriptome data

PubMed Central

Qiu, Jia-jun; Ren, Zhao-rui; Yan, Jing-bin

2016-01-01

Epigenetics regulations have an important role in fertilization and proper embryonic development, and several human diseases are associated with epigenetic modification disorders, such as Rett syndrome, Beckwith-Wiedemann syndrome and Angelman syndrome. However, the dynamics and functions of long non-coding RNAs (lncRNAs), one type of epigenetic regulators, in human pre-implantation development have not yet been demonstrated. In this study, a comprehensive analysis of human and mouse early-stage embryonic lncRNAs was performed based on public single-cell RNA sequencing data. Expression profile analysis revealed that lncRNAs are expressed in a developmental stage–specific manner during human early-stage embryonic development, whereas a more temporal-specific expression pattern was identified in mouse embryos. Weighted gene co-expression network analysis suggested that lncRNAs involved in human early-stage embryonic development are associated with several important functions and processes, such as oocyte maturation, zygotic genome activation and mitochondrial functions. We also found that the network of lncRNAs involved in zygotic genome activation was highly preservative between human and mouse embryos, whereas in other stages no strong correlation between human and mouse embryo was observed. This study provides insight into the molecular mechanism underlying lncRNA involvement in human pre-implantation embryonic development. PMID:27542205

Chaotic home environment is associated with reduced infant processing speed under high task demands.

PubMed

Tomalski, Przemysław; Marczuk, Karolina; Pisula, Ewa; Malinowska, Anna; Kawa, Rafał; Niedźwiecka, Alicja

2017-08-01

Early adversity has profound long-term consequences for child development across domains. The effects of early adversity on structural and functional brain development were shown for infants under 12 months of life. However, the causal mechanisms of these effects remain relatively unexplored. Using a visual habituation task we investigated whether chaotic home environment may affect processing speed in 5.5 month-old infants (n=71). We found detrimental effects of chaos on processing speed for complex but not for simple visual stimuli. No effects of socio-economic status on infant processing speed were found although the sample was predominantly middle class. Our results indicate that chaotic early environment may adversely affect processing speed in early infancy, but only when greater cognitive resources need to be deployed. The study highlights an attractive avenue for research on the mechanisms linking home environment with the development of attention control. Copyright © 2017 Elsevier Inc. All rights reserved.

Developmental disruption of medial prefrontal cortical GABAergic function by non-contingent cocaine exposure during early adolescence

PubMed Central

Cass, Daryn K.; Thomases, Daniel R.; Caballero, Adriana; Tseng, Kuei Y.

2013-01-01

Background Drug experimentation during adolescence is associated with increased risk of drug addiction relative to any other age group. To further our understanding on the neurobiology underlying such liability, we investigate how early adolescent cocaine experience impacts the overall medial prefrontal cortex (mPFC) network function in adulthood. Methods A non-contingent administration paradigm was used to assess the impact of early adolescent cocaine treatment (rats; postnatal days -PD- 35-40) on the overall inhibitory regulation of mPFC activity in adulthood (PD65-75) by means of histochemical and in vivo electrophysiological measures combined with pharmacological manipulations. Results Cocaine exposure during early adolescence yields a distinctive hyper-metabolic PFC state that was not observed in adult (PD75-80)-treated rats. Local field potential recordings expand upon these findings by showing that early adolescent cocaine exposure is associated with an attenuation of mPFC GABAergic inhibition evoked by ventral hippocampal stimulation at beta and gamma frequencies that endures throughout adulthood. Such cocaine-induced mPFC disinhibition was not observed in adult-exposed animals. Furthermore, the normal developmental upregulation of parvalbumin immunoreactivity observed in the mPFC from PD35 to PD65 is lacking following early adolescent cocaine treatment. Conclusion Our data indicate that repeated cocaine exposure during early adolescence can elicit a state of mPFC disinhibition resulting from a functional impairment of the local prefrontal GABAergic network that endures through adulthood. A lack of acquisition of prefrontal GABAergic function during adolescence could trigger long-term deficits in the mPFC that may increase the susceptibility for the onset of substance abuse and related psychiatric disorders. PMID:23558299

Using cross-species comparisons and a neurobiological framework to understand early social deprivation effects on behavioral development.

PubMed

Brett, Zoë H; Humphreys, Kathryn L; Fleming, Alison S; Kraemer, Gary W; Drury, Stacy S

2015-05-01

Building upon the transactional model of brain development, we explore the impact of early maternal deprivation on neural development and plasticity in three neural systems: hyperactivity/impulsivity, executive function, and hypothalamic-pituitary-adrenal axis functioning across rodent, nonhuman primate, and human studies. Recognizing the complexity of early maternal-infant interactions, we limit our cross-species comparisons to data from rodent models of artificial rearing, nonhuman primate studies of peer rearing, and the relations between these two experimental approaches and human studies of children exposed to the early severe psychosocial deprivation associated with institutional care. In addition to discussing the strengths and limitations of these paradigms, we present the current state of research on the neurobiological impact of early maternal deprivation and the evidence of sensitive periods, noting methodological challenges. Integrating data across preclinical animal models and human studies, we speculate about the underlying biological mechanisms; the differential impact of deprivation due to temporal factors including onset, offset, and duration of the exposure; and the possibility and consequences of reopening of sensitive periods during adolescence.

Using cross-species comparisons and a neurobiological framework to understand early social deprivation effects on behavioral development

PubMed Central

BRETT, ZOË H.; HUMPHREYS, KATHRYN L.; FLEMING, ALISON S.; KRAEMER, GARY W.; DRURY, STACY S.

2017-01-01

Building upon the transactional model of brain development, we explore the impact of early maternal deprivation on neural development and plasticity in three neural systems: hyperactivity/impulsivity, executive function, and hypothalamic–pituitary–adrenal axis functioning across rodent, nonhuman primate, and human studies. Recognizing the complexity of early maternal–infant interactions, we limit our cross-species comparisons to data from rodent models of artificial rearing, nonhuman primate studies of peer rearing, and the relations between these two experimental approaches and human studies of children exposed to the early severe psychosocial deprivation associated with institutional care. In addition to discussing the strengths and limitations of these paradigms, we present the current state of research on the neurobiological impact of early maternal deprivation and the evidence of sensitive periods, noting methodological challenges. Integrating data across preclinical animal models and human studies, we speculate about the underlying biological mechanisms; the differential impact of deprivation due to temporal factors including onset, offset, and duration of the exposure; and the possibility and consequences of reopening of sensitive periods during adolescence. PMID:25997759

Learning-Induced Suboptimal Compensation for PKCι/λ Function in Mutant Mice.

PubMed

Sheng, Tao; Wang, Shaoli; Qian, Dandan; Gao, Jun; Ohno, Shigeo; Lu, Wei

2017-06-01

PKCι/λ has been proposed to be crucial in the early expression of long-term potentiation (LTP). Here, we further investigate the potential role of PKCι/λ in learning and memory by generating PKCι/λ conditional knockout mice specifically lacking PKCι/λ in the hippocampal CA1 pyramidal cells. Surprisingly, PKCι/λ cKO mice show normal hippocampal LTP and memory. Further close-up observation reveals compensation for PKCι/λ expression by PKMζ in PKCι/λ cKO mice. This compensation was not observed under basal conditions, but was detected either after LTP induction or learning-associated behavioral training. Accordingly, in the early stage of LTP expression, a switch from PKCι/λ- to PKMζ-dependent molecular mechanisms was detected in PKCι/λ cKO mice. Notably, when cKO mice were challenged with more difficult hippocampus-dependent learning tasks, moderate learning deficits were detected, suggesting a suboptimal compensation for PKCι/λ's function in PKCι/λ cKO mice. Thus, under physiological conditions, PKCι/λ is essential for hippocampal early-LTP and long-term memory (LTM). © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Initiation of ART during Early Acute HIV Infection Preserves Mucosal Th17 Function and Reverses HIV-Related Immune Activation

PubMed Central

Schuetz, Alexandra; Deleage, Claire; Sereti, Irini; Rerknimitr, Rungsun; Phanuphak, Nittaya; Phuang-Ngern, Yuwadee; Estes, Jacob D.; Sandler, Netanya G.; Sukhumvittaya, Suchada; Marovich, Mary; Jongrakthaitae, Surat; Akapirat, Siriwat; Fletscher, James L. K.; Kroon, Eugene; Dewar, Robin; Trichavaroj, Rapee; Chomchey, Nitiya; Douek, Daniel C.; O′Connell, Robert J.; Ngauy, Viseth; Robb, Merlin L.; Phanuphak, Praphan; Michael, Nelson L.; Excler, Jean-Louis; Kim, Jerome H.; de Souza, Mark S.; Ananworanich, Jintanat

2014-01-01

Mucosal Th17 cells play an important role in maintaining gut epithelium integrity and thus prevent microbial translocation. Chronic HIV infection is characterized by mucosal Th17 cell depletion, microbial translocation and subsequent immune-activation, which remain elevated despite antiretroviral therapy (ART) correlating with increased mortality. However, when Th17 depletion occurs following HIV infection is unknown. We analyzed mucosal Th17 cells in 42 acute HIV infection (AHI) subjects (Fiebig (F) stage I-V) with a median duration of infection of 16 days and the short-term impact of early initiation of ART. Th17 cells were defined as IL-17+ CD4+ T cells and their function was assessed by the co-expression of IL-22, IL-2 and IFNγ. While intact during FI/II, depletion of mucosal Th17 cell numbers and function was observed during FIII correlating with local and systemic markers of immune-activation. ART initiated at FI/II prevented loss of Th17 cell numbers and function, while initiation at FIII restored Th17 cell numbers but not their polyfunctionality. Furthermore, early initiation of ART in FI/II fully reversed the initially observed mucosal and systemic immune-activation. In contrast, patients treated later during AHI maintained elevated mucosal and systemic CD8+ T-cell activation post initiation of ART. These data support a loss of Th17 cells at early stages of acute HIV infection, and highlight that studies of ART initiation during early AHI should be further explored to assess the underlying mechanism of mucosal Th17 function preservation. PMID:25503054

Abscisic Acid Regulates Early Seed Development in Arabidopsis by ABI5-Mediated Transcription of SHORT HYPOCOTYL UNDER BLUE1[C][W][OPEN

PubMed Central

Cheng, Zhi Juan; Zhao, Xiang Yu; Shao, Xing Xing; Wang, Fei; Zhou, Chao; Liu, Ying Gao; Zhang, Yan; Zhang, Xian Sheng

2014-01-01

Seed development includes an early stage of endosperm proliferation and a late stage of embryo growth at the expense of the endosperm in Arabidopsis thaliana. Abscisic acid (ABA) has known functions during late seed development, but its roles in early seed development remain elusive. In this study, we report that ABA-deficient mutants produced seeds with increased size, mass, and embryo cell number but delayed endosperm cellularization. ABSCISIC ACID DEFICIENT2 (ABA2) encodes a unique short-chain dehydrogenase/reductase that functions in ABA biosynthesis, and its expression pattern overlaps that of SHORT HYPOCOTYL UNDER BLUE1 (SHB1) during seed development. SHB1 RNA accumulation was significantly upregulated in the aba2-1 mutant and was downregulated by the application of exogenous ABA. Furthermore, RNA accumulation of the basic/region leucine zipper transcription factor ABSCISIC ACID-INSENSITIVE5 (ABI5), involved in ABA signaling, was decreased in aba2-1. Consistent with this, seed size was also increased in abi5. We further show that ABI5 directly binds to two discrete regions in the SHB1 promoter. Our results suggest that ABA negatively regulates SHB1 expression, at least in part, through the action of its downstream signaling component ABI5. Our findings provide insights into the molecular mechanisms by which ABA regulates early seed development. PMID:24619610

Executive functioning and reading achievement in school: a study of Brazilian children assessed by their teachers as "poor readers".

PubMed

Engel de Abreu, Pascale M J; Abreu, Neander; Nikaedo, Carolina C; Puglisi, Marina L; Tourinho, Carlos J; Miranda, Mônica C; Befi-Lopes, Debora M; Bueno, Orlando F A; Martin, Romain

2014-01-01

This study examined executive functioning and reading achievement in 106 6- to 8-year-old Brazilian children from a range of social backgrounds of whom approximately half lived below the poverty line. A particular focus was to explore the executive function profile of children whose classroom reading performance was judged below standard by their teachers and who were matched to controls on chronological age, sex, school type (private or public), domicile (Salvador/BA or São Paulo/SP) and socioeconomic status. Children completed a battery of 12 executive function tasks that were conceptual tapping cognitive flexibility, working memory, inhibition and selective attention. Each executive function domain was assessed by several tasks. Principal component analysis extracted four factors that were labeled "Working Memory/Cognitive Flexibility," "Interference Suppression," "Selective Attention," and "Response Inhibition." Individual differences in executive functioning components made differential contributions to early reading achievement. The Working Memory/Cognitive Flexibility factor emerged as the best predictor of reading. Group comparisons on computed factor scores showed that struggling readers displayed limitations in Working Memory/Cognitive Flexibility, but not in other executive function components, compared to more skilled readers. These results validate the account that working memory capacity provides a crucial building block for the development of early literacy skills and extends it to a population of early readers of Portuguese from Brazil. The study suggests that deficits in working memory/cognitive flexibility might represent one contributing factor to reading difficulties in early readers. This might have important implications for how educators might intervene with children at risk of academic under achievement.

Capturing structure and function in an embryonic heart with biophotonic tools

PubMed Central

Karunamuni, Ganga H.; Gu, Shi; Ford, Matthew R.; Peterson, Lindsy M.; Ma, Pei; Wang, Yves T.; Rollins, Andrew M.; Jenkins, Michael W.; Watanabe, Michiko

2014-01-01

Disturbed cardiac function at an early stage of development has been shown to correlate with cellular/molecular, structural as well as functional cardiac anomalies at later stages culminating in the congenital heart defects (CHDs) that present at birth. While our knowledge of cellular and molecular steps in cardiac development is growing rapidly, our understanding of the role of cardiovascular function in the embryo is still in an early phase. One reason for the scanty information in this area is that the tools to study early cardiac function are limited. Recently developed and adapted biophotonic tools may overcome some of the challenges of studying the tiny fragile beating heart. In this chapter, we describe and discuss our experience in developing and implementing biophotonic tools to study the role of function in heart development with emphasis on optical coherence tomography (OCT). OCT can be used for detailed structural and functional studies of the tubular and looping embryo heart under physiological conditions. The same heart can be rapidly and quantitatively phenotyped at early and again at later stages using OCT. When combined with other tools such as optical mapping (OM) and optical pacing (OP), OCT has the potential to reveal in spatial and temporal detail the biophysical changes that can impact mechanotransduction pathways. This information may provide better explanations for the etiology of the CHDs when interwoven with our understanding of morphogenesis and the molecular pathways that have been described to be involved. Future directions for advances in the creation and use of biophotonic tools are discussed. PMID:25309451

Nuclear Translocation of MEK1 Triggers a Complex T cell Response through the Co-repressor Silencing Mediator of Retinoid and Thyroid Hormone Receptor (SMRT)

PubMed Central

Guo, Lei; Chen, Chaoyu; Liang, Qiaoling; Karim, Md. Zunayet; Gorska, Magdalena M.; Alam, Rafeul

2012-01-01

MEK1 phosphorylates ERK1/2 and regulates T cell generation, differentiation and function. MEK1 has recently been shown to translocate to the nucleus. Its nuclear function is largely unknown. By studying human CD4 T cells we demonstrate that a low level of MEK1 is present in the nucleus of CD4 T cells under basal conditions. T cell activation further increases the nuclear translocation of MEK1. MEK1 interacts with the nuclear receptor co-repressor SMRT. MEK1 reduces the nuclear level of SMRT in an activation-dependent manner. MEK1 is recruited to the promoter of c-Fos upon TCR stimulation. Conversely, SMRT is bound to the c-Fos promoter under basal conditions and is removed upon TCR stimulation. We examined the role of SMRT in regulation of T cell function. siRNA-mediated knockdown of SMRT results in a biphasic effect on cytokine production. The production of the cytokines—IL2, IL4, IL10 and IFNγ increases in the early phase (8 hr) and then decreases in the late phase (48 hr). The late phase decrease is associated with inhibition of T cell proliferation. The late phase inhibition of T cell activation is, in part, mediated by IL10 that is produced in the early phase, and in part, by β-catenin signaling. Thus, we have identified a novel nuclear function of MEK1. MEK1 triggers a complex pattern of early T cell activation followed by a late inhibition through its interaction with SMRT. This biphasic dual effect likely reflects a homeostatic regulation of T cell function by MEK1. PMID:23225884

FKBP5 genotype interacts with early life trauma to predict heavy drinking in college students.

PubMed

Lieberman, Richard; Armeli, Stephen; Scott, Denise M; Kranzler, Henry R; Tennen, Howard; Covault, Jonathan

2016-09-01

Alcohol use disorder (AUD) is debilitating and costly. Identification and better understanding of risk factors influencing the development of AUD remain a research priority. Although early life exposure to trauma increases the risk of adulthood psychiatric disorders, including AUD, many individuals exposed to early life trauma do not develop psychopathology. Underlying genetic factors may contribute to differential sensitivity to trauma experienced in childhood. The hypothalamic-pituitary-adrenal (HPA) axis is susceptible to long-lasting changes in function following childhood trauma. Functional genetic variation within FKBP5, a gene encoding a modulator of HPA axis function, is associated with the development of psychiatric symptoms in adulthood, particularly among individuals exposed to trauma early in life. In the current study, we examined interactions between self-reported early life trauma, past-year life stress, past-year trauma, and a single nucleotide polymorphism (rs1360780) in FKBP5 on heavy alcohol consumption in a sample of 1,845 college students from two university settings. Although we found no effect of early life trauma on heavy drinking in rs1360780*T-allele carriers, rs1360780*C homozygotes exposed to early life trauma had a lower probability of heavy drinking compared to rs1360780*C homozygotes not exposed to early life trauma (P < 0.01). The absence of an interaction between either current life stress or past-year trauma, and FKBP5 genotype on heavy drinking suggests that there exists a developmental period of susceptibility to stress that is moderated by FKBP5 genotype. These findings implicate interactive effects of early life trauma and FKBP5 genetic variation on heavy drinking. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Functionally Redundant RXLR Effectors from Phytophthora infestans Act at Different Steps to Suppress Early flg22-Triggered Immunity

PubMed Central

Fraiture, Malou; Liu, Xiaoyu; Boevink, Petra C.; Gilroy, Eleanor M.; Chen, Ying; Kandel, Kabindra; Sessa, Guido; Birch, Paul R. J.; Brunner, Frédéric

2014-01-01

Genome sequences of several economically important phytopathogenic oomycetes have revealed the presence of large families of so-called RXLR effectors. Functional screens have identified RXLR effector repertoires that either compromise or induce plant defense responses. However, limited information is available about the molecular mechanisms underlying the modes of action of these effectors in planta. The perception of highly conserved pathogen- or microbe-associated molecular patterns (PAMPs/MAMPs), such as flg22, triggers converging signaling pathways recruiting MAP kinase cascades and inducing transcriptional re-programming, yielding a generic anti-microbial response. We used a highly synchronizable, pathogen-free protoplast-based assay to identify a set of RXLR effectors from Phytophthora infestans (PiRXLRs), the causal agent of potato and tomato light blight that manipulate early stages of flg22-triggered signaling. Of thirty-three tested PiRXLR effector candidates, eight, called Suppressor of early Flg22-induced Immune response (SFI), significantly suppressed flg22-dependent activation of a reporter gene under control of a typical MAMP-inducible promoter (pFRK1-Luc) in tomato protoplasts. We extended our analysis to Arabidopsis thaliana, a non-host plant species of P. infestans. From the aforementioned eight SFI effectors, three appeared to share similar functions in both Arabidopsis and tomato by suppressing transcriptional activation of flg22-induced marker genes downstream of post-translational MAP kinase activation. A further three effectors interfere with MAMP signaling at, or upstream of, the MAP kinase cascade in tomato, but not in Arabidopsis. Transient expression of the SFI effectors in Nicotiana benthamiana enhances susceptibility to P. infestans and, for the most potent effector, SFI1, nuclear localization is required for both suppression of MAMP signaling and virulence function. The present study provides a framework to decipher the molecular mechanisms underlying the manipulation of host MAMP-triggered immunity (MTI) by P. infestans and to understand the basis of host versus non-host resistance in plants towards P. infestans. PMID:24763622

Cutaneous consequences of accelerated thyroid function.

PubMed

Mullin, G E; Eastern, J S

1986-02-01

General and specific cutaneous findings associated with hyperthyroidism are reviewed. Familiarity with these findings may aid the practitioner in the early diagnosis of thyroid diseases. Several normally idiopathic cutaneous diseases can occasionally be controlled if underlying thyroid disease is considered as a cause, and appropriate testing performed.

Attention Measures of Accuracy, Variability, and Fatigue Detect Early Response to Donepezil in Alzheimer's Disease: A Randomized, Double-blind, Placebo-Controlled Pilot Trial.

PubMed

Vila-Castelar, Clara; Ly, Jenny J; Kaplan, Lillian; Van Dyk, Kathleen; Berger, Jeffrey T; Macina, Lucy O; Stewart, Jennifer L; Foldi, Nancy S

2018-04-09

Donepezil is widely used to treat Alzheimer's disease (AD), but detecting early response remains challenging for clinicians. Acetylcholine is known to directly modulate attention, particularly under high cognitive conditions, but no studies to date test whether measures of attention under high load can detect early effects of donepezil. We hypothesized that load-dependent attention tasks are sensitive to short-term treatment effects of donepezil, while global and other domain-specific cognitive measures are not. This longitudinal, randomized, double-blind, placebo-controlled pilot trial (ClinicalTrials.gov Identifier: NCT03073876) evaluated 23 participants newly diagnosed with AD initiating de novo donepezil treatment (5 mg). After baseline assessment, participants were randomized into Drug (n = 12) or Placebo (n = 11) groups, and retested after approximately 6 weeks. Cognitive assessment included: (a) attention tasks (Foreperiod Effect, Attentional Blink, and Covert Orienting tasks) measuring processing speed, top-down accuracy, orienting, intra-individual variability, and fatigue; (b) global measures (Alzheimer's Disease Assessment Scale-Cognitive Subscale, Mini-Mental Status Examination, Dementia Rating Scale); and (c) domain-specific measures (memory, language, visuospatial, and executive function). The Drug but not the Placebo group showed benefits of treatment at high-load measures by preserving top-down accuracy, improving intra-individual variability, and averting fatigue. In contrast, other global or cognitive domain-specific measures could not detect treatment effects over the same treatment interval. The pilot-study suggests that attention measures targeting accuracy, variability, and fatigue under high-load conditions could be sensitive to short-term cholinergic treatment. Given the central role of acetylcholine in attentional function, load-dependent attentional measures may be valuable cognitive markers of early treatment response.

Acid stress mediated adaptive divergence in ion channel function during embryogenesis in Rana arvalis

PubMed Central

Shu, Longfei; Laurila, Anssi; Räsänen, Katja

2015-01-01

Ion channels and pumps are responsible for ion flux in cells, and are key mechanisms mediating cellular function. Many environmental stressors, such as salinity and acidification, are known to severely disrupt ionic balance of organisms thereby challenging fitness of natural populations. Although ion channels can have several vital functions during early life-stages (e.g. embryogenesis), it is currently not known i) how developing embryos maintain proper intracellular conditions when exposed to environmental stress and ii) to what extent environmental stress can drive intra-specific divergence in ion channels. Here we studied the moor frog, Rana arvalis, from three divergent populations to investigate the role of different ion channels and pumps for embryonic survival under acid stress (pH 4 vs 7.5) and whether populations adapted to contrasting acidities differ in the relative role of different ion channel/pumps. We found that ion channels that mediate Ca2+ influx are essential for embryonic survival under acidic pH, and, intriguingly, that populations differ in calcium channel function. Our results suggest that adaptive divergence in embryonic acid stress tolerance of amphibians may in part be mediated by Ca2+ balance. We suggest that ion flux may mediate adaptive divergence of natural populations at early life-stages in the face of environmental stress. PMID:26381453

A Functional Neuroimaging Study of Sound Localization: Visual Cortex Activity Predicts Performance in Early-Blind Individuals

PubMed Central

Gougoux, Frédéric; Zatorre, Robert J; Lassonde, Maryse; Voss, Patrice

2005-01-01

Blind individuals often demonstrate enhanced nonvisual perceptual abilities. However, the neural substrate that underlies this improved performance remains to be fully understood. An earlier behavioral study demonstrated that some early-blind people localize sounds more accurately than sighted controls using monaural cues. In order to investigate the neural basis of these behavioral differences in humans, we carried out functional imaging studies using positron emission tomography and a speaker array that permitted pseudo-free-field presentations within the scanner. During binaural sound localization, a sighted control group showed decreased cerebral blood flow in the occipital lobe, which was not seen in early-blind individuals. During monaural sound localization (one ear plugged), the subgroup of early-blind subjects who were behaviorally superior at sound localization displayed two activation foci in the occipital cortex. This effect was not seen in blind persons who did not have superior monaural sound localization abilities, nor in sighted individuals. The degree of activation of one of these foci was strongly correlated with sound localization accuracy across the entire group of blind subjects. The results show that those blind persons who perform better than sighted persons recruit occipital areas to carry out auditory localization under monaural conditions. We therefore conclude that computations carried out in the occipital cortex specifically underlie the enhanced capacity to use monaural cues. Our findings shed light not only on intermodal compensatory mechanisms, but also on individual differences in these mechanisms and on inhibitory patterns that differ between sighted individuals and those deprived of vision early in life. PMID:15678166

Gender comparisons in children with ASD entering early intervention.

PubMed

Fulton, Alexandra M; Paynter, Jessica M; Trembath, David

2017-09-01

Males are diagnosed with Autism Spectrum Disorder (ASD) approximately four times as often as females. This has led to interest in recent years of potential under-diagnosis of females, as well as negative consequences for females with ASD due to under-identification. A number of potential explanations for gender bias in diagnosis are discussed including that females and males may present differently despite showing the same core symptoms. Previous research has shown inconsistent findings in comparisons between genders in young children with ASD for whom early intervention is vital. Thus, the aim of the present study was to investigate the social, communication, and cognitive functioning, as well as level of ASD symptoms, in a cohort of children who presented for early intervention to inform understanding of gender differences in this population, as well as to inform understanding of the mechanisms by which gender bias may occur. Participants included 254 children (42 females) aged 29-74 months who completed measures of cognition, communication skills, adaptive behaviour, and ASD symptoms on entry to early intervention. Consistent with hypotheses, no significant gender differences were found both overall, and when split by functioning level. However, a similar ratio of males and females was found in both high- and low-functioning groups contrary to predictions. These results are consistent with some of the previous research that suggests gender differences may not be apparent in clinical samples at this young age. We highlight a need for further research that may use universal screening or longitudinal methods to understand the trajectory of development for females with ASD specifically. Such research could better inform timely and tailored intervention from the preschool years onwards. Copyright © 2017 Elsevier Ltd. All rights reserved.

Functional interplay of top-down attention with affective codes during visual short-term memory maintenance.

PubMed

Kuo, Bo-Cheng; Lin, Szu-Hung; Yeh, Yei-Yu

2018-06-01

Visual short-term memory (VSTM) allows individuals to briefly maintain information over time for guiding behaviours. Because the contents of VSTM can be neutral or emotional, top-down influence in VSTM may vary with the affective codes of maintained representations. Here we investigated the neural mechanisms underlying the functional interplay of top-down attention with affective codes in VSTM using functional magnetic resonance imaging. Participants were instructed to remember both threatening and neutral objects in a cued VSTM task. Retrospective cues (retro-cues) were presented to direct attention to the hemifield of a threatening object (i.e., cue-to-threat) or a neutral object (i.e., cue-to-neutral) during VSTM maintenance. We showed stronger activity in the ventral occipitotemporal cortex and amygdala for attending threatening relative to neutral representations. Using multivoxel pattern analysis, we found better classification performance for cue-to-threat versus cue-to-neutral objects in early visual areas and in the amygdala. Importantly, retro-cues modulated the strength of functional connectivity between the frontoparietal and early visual areas. Activity in the frontoparietal areas became strongly correlated with the activity in V3a-V4 coding the threatening representations instructed to be relevant for the task. Together, these findings provide the first demonstration of top-down modulation of activation patterns in early visual areas and functional connectivity between the frontoparietal network and early visual areas for regulating threatening representations during VSTM maintenance. Copyright © 2018 Elsevier Ltd. All rights reserved.

How age of bilingual exposure can change the neural systems for language in the developing brain: a functional near infrared spectroscopy investigation of syntactic processing in monolingual and bilingual children.

PubMed

Jasinska, K K; Petitto, L A

2013-10-01

Is the developing bilingual brain fundamentally similar to the monolingual brain (e.g., neural resources supporting language and cognition)? Or, does early-life bilingual language experience change the brain? If so, how does age of first bilingual exposure impact neural activation for language? We compared how typically-developing bilingual and monolingual children (ages 7-10) and adults recruit brain areas during sentence processing using functional Near Infrared Spectroscopy (fNIRS) brain imaging. Bilingual participants included early-exposed (bilingual exposure from birth) and later-exposed individuals (bilingual exposure between ages 4-6). Both bilingual children and adults showed greater neural activation in left-hemisphere classic language areas, and additionally, right-hemisphere homologues (Right Superior Temporal Gyrus, Right Inferior Frontal Gyrus). However, important differences were observed between early-exposed and later-exposed bilinguals in their earliest-exposed language. Early bilingual exposure imparts fundamental changes to classic language areas instead of alterations to brain regions governing higher cognitive executive functions. However, age of first bilingual exposure does matter. Later-exposed bilinguals showed greater recruitment of the prefrontal cortex relative to early-exposed bilinguals and monolinguals. The findings provide fascinating insight into the neural resources that facilitate bilingual language use and are discussed in terms of how early-life language experiences can modify the neural systems underlying human language processing. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

Early disrupted neurovascular coupling and changed event level hemodynamic response function in type 2 diabetes: an fMRI study.

PubMed

Duarte, João V; Pereira, João M S; Quendera, Bruno; Raimundo, Miguel; Moreno, Carolina; Gomes, Leonor; Carrilho, Francisco; Castelo-Branco, Miguel

2015-10-01

Type 2 diabetes (T2DM) patients develop vascular complications and have increased risk for neurophysiological impairment. Vascular pathophysiology may alter the blood flow regulation in cerebral microvasculature, affecting neurovascular coupling. Reduced fMRI signal can result from decreased neuronal activation or disrupted neurovascular coupling. The uncertainty about pathophysiological mechanisms (neurodegenerative, vascular, or both) underlying brain function impairments remains. In this cross-sectional study, we investigated if the hemodynamic response function (HRF) in lesion-free brains of patients is altered by measuring BOLD (Blood Oxygenation Level-Dependent) response to visual motion stimuli. We used a standard block design to examine the BOLD response and an event-related deconvolution approach. Importantly, the latter allowed for the first time to directly extract the true shape of HRF without any assumption and probe neurovascular coupling, using performance-matched stimuli. We discovered a change in HRF in early stages of diabetes. T2DM patients show significantly different fMRI response profiles. Our visual paradigm therefore demonstrated impaired neurovascular coupling in intact brain tissue. This implies that functional studies in T2DM require the definition of HRF, only achievable with deconvolution in event-related experiments. Further investigation of the mechanisms underlying impaired neurovascular coupling is needed to understand and potentially prevent the progression of brain function decrements in diabetes.

Early stages of functional diversification in the Rab GTPase gene family revealed by genomic and localization studies in Paramecium species.

PubMed

Bright, Lydia J; Gout, Jean-Francois; Lynch, Michael

2017-04-15

New gene functions arise within existing gene families as a result of gene duplication and subsequent diversification. To gain insight into the steps that led to the functional diversification of paralogues, we tracked duplicate retention patterns, expression-level divergence, and subcellular markers of functional diversification in the Rab GTPase gene family in three Paramecium aurelia species. After whole-genome duplication, Rab GTPase duplicates are more highly retained than other genes in the genome but appear to be diverging more rapidly in expression levels, consistent with early steps in functional diversification. However, by localizing specific Rab proteins in Paramecium cells, we found that paralogues from the two most recent whole-genome duplications had virtually identical localization patterns, and that less closely related paralogues showed evidence of both conservation and diversification. The functionally conserved paralogues appear to target to compartments associated with both endocytic and phagocytic recycling functions, confirming evolutionary and functional links between the two pathways in a divergent eukaryotic lineage. Because the functionally diversifying paralogues are still closely related to and derived from a clade of functionally conserved Rab11 genes, we were able to pinpoint three specific amino acid residues that may be driving the change in the localization and thus the function in these proteins. © 2017 Bright et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

Functional mobility in a divided attention task in older adults with cognitive impairment.

PubMed

Borges, Sheila de Melo; Radanovic, Márcia; Forlenza, Orestes Vicente

2015-01-01

Motor disorders may occur in mild cognitive impairment (MCI) and at early stages of Alzheimer's disease (AD), particularly under divided attention conditions. We examined functional mobility in 104 older adults (42 with MCI, 26 with mild AD, and 36 cognitively healthy) using the Timed Up and Go test (TUG) under 4 experimental conditions: TUG single task, TUG plus a cognitive task, TUG plus a manual task, and TUG plus a cognitive and a manual task. Statistically significant differences in mean time of execution were found in all four experimental conditions when comparing MCI and controls (p < .001), and when comparing MCI and AD patients (p < .05). Receiver-operating characteristic curve analyses showed that all four testing conditions could differentiate the three groups (area under the curve > .8, p < .001 for MCI vs. controls; area under the curve > .7, p < .001 for MCI vs. AD). The authors conclude that functional motor deficits occurring in MCI can be assessed by the TUG test, in single or dual task modality.

H2S Regulates Hypobaric Hypoxia-Induced Early Glio-Vascular Dysfunction and Neuro-Pathophysiological Effects

PubMed Central

Kumar, Gaurav; Chhabra, Aastha; Mishra, Shalini; Kalam, Haroon; Kumar, Dhiraj; Meena, Ramniwas; Ahmad, Yasmin; Bhargava, Kalpana; Prasad, Dipti N.; Sharma, Manish

2016-01-01

Hypobaric Hypoxia (HH) is an established risk factor for various neuro-physiological perturbations including cognitive impairment. The origin and mechanistic basis of such responses however remain elusive. We here combined systems level analysis with classical neuro-physiological approaches, in a rat model system, to understand pathological responses of brain to HH. Unbiased ‘statistical co-expression networks’ generated utilizing temporal, differential transcriptome signatures of hippocampus—centrally involved in regulating cognition—implicated perturbation of Glio-Vascular homeostasis during early responses to HH, with concurrent modulation of vasomodulatory, hemostatic and proteolytic processes. Further, multiple lines of experimental evidence from ultra-structural, immuno-histological, substrate-zymography and barrier function studies unambiguously supported this proposition. Interestingly, we show a significant lowering of H2S levels in the brain, under chronic HH conditions. This phenomenon functionally impacted hypoxia-induced modulation of cerebral blood flow (hypoxic autoregulation) besides perturbing the strength of functional hyperemia responses. The augmentation of H2S levels, during HH conditions, remarkably preserved Glio-Vascular homeostasis and key neuro-physiological functions (cerebral blood flow, functional hyperemia and spatial memory) besides curtailing HH-induced neuronal apoptosis in hippocampus. Our data thus revealed causal role of H2S during HH-induced early Glio-Vascular dysfunction and consequent cognitive impairment. PMID:27211559

Epigenetic Programming of Synthesis, Release, and/or Receptor Expression of Common Mediators Participating in the Risk/Resilience for Comorbid Stress-Related Disorders and Coronary Artery Disease.

PubMed

Zapata-Martín Del Campo, Carlos Manuel; Martínez-Rosas, Martín; Guarner-Lans, Verónica

2018-04-18

Corticotrophin releasing factor, vasopressin, oxytocin, natriuretic hormones, angiotensin, neuregulins, some purinergic substances, and some cytokines contribute to the long-term modulation and restructuring of cardiovascular regulation networks and, at the same time, have relevance in situations of comorbid abnormal stress responses. The synthesis, release, and receptor expression of these mediators seem to be under epigenetic control since early stages of life, possibly underlying the comorbidity to coronary artery disease (CAD) and stress-related disorders (SRD). The exposure to environmental conditions, such as stress, during critical periods in early life may cause epigenetic programming modifying the development of pathways that lead to stable and long-lasting alterations in the functioning of these mediators during adulthood, determining the risk of or resilience to CAD and SRD. However, in contrast to genetic information, epigenetic marks may be dynamically altered throughout the lifespan. Therefore, epigenetics may be reprogrammed if the individual accepts the challenge to undertake changes in their lifestyle. Alternatively, epigenetics may remain fixed and/or even be inherited in the next generation. In this paper, we analyze some of the common neuroendocrine functions of these mediators in CAD and SRD and summarize the evidence indicating that they are under early programming to put forward the theoretical hypothesis that the comorbidity of these diseases might be epigenetically programmed and modified over the lifespan of the individual.

Epigenetic Programming of Synthesis, Release, and/or Receptor Expression of Common Mediators Participating in the Risk/Resilience for Comorbid Stress-Related Disorders and Coronary Artery Disease

PubMed Central

Zapata-Martín del Campo, Carlos Manuel; Martínez-Rosas, Martín

2018-01-01

Corticotrophin releasing factor, vasopressin, oxytocin, natriuretic hormones, angiotensin, neuregulins, some purinergic substances, and some cytokines contribute to the long-term modulation and restructuring of cardiovascular regulation networks and, at the same time, have relevance in situations of comorbid abnormal stress responses. The synthesis, release, and receptor expression of these mediators seem to be under epigenetic control since early stages of life, possibly underlying the comorbidity to coronary artery disease (CAD) and stress-related disorders (SRD). The exposure to environmental conditions, such as stress, during critical periods in early life may cause epigenetic programming modifying the development of pathways that lead to stable and long-lasting alterations in the functioning of these mediators during adulthood, determining the risk of or resilience to CAD and SRD. However, in contrast to genetic information, epigenetic marks may be dynamically altered throughout the lifespan. Therefore, epigenetics may be reprogrammed if the individual accepts the challenge to undertake changes in their lifestyle. Alternatively, epigenetics may remain fixed and/or even be inherited in the next generation. In this paper, we analyze some of the common neuroendocrine functions of these mediators in CAD and SRD and summarize the evidence indicating that they are under early programming to put forward the theoretical hypothesis that the comorbidity of these diseases might be epigenetically programmed and modified over the lifespan of the individual. PMID:29670001

Functional identity and functional structure change through succession in a rocky intertidal marine herbivore assemblage.

PubMed

Aguilera, Moisés A; Navarrete, Sergio A

2012-01-01

Despite the great interest in characterizing the functional structure and resilience of functional groups in natural communities, few studies have examined in which way the roles and relationships of coexisting species change during community succession, a fundamental and natural process that follows the release of new resources in terrestrial and aquatic ecosystems. Variation in algal traits that characterize different phases and stages of community succession on rocky shores are likely to influence the magnitude, direction of effects, and the level of redundancy and complementarity in the diverse assemblage of herbivores. Two separate field experiments were conducted to quantify per capita and population effects and the functional relationship (i.e., redundancy or complementarity) of four herbivore species found in central Chile during early and late algal succession. The first experiment examined grazer effects on the colonization and establishment of early-succession algal species. The second experiment examined effects on the late-successional, dominant corticated alga Mazzaella laminarioides. Complementary laboratory experiments with all species and under natural environmental conditions allowed us to further characterize the collective effects of these species. We found that, during early community succession, all herbivore species had similar effects on the ephemeral algae, ulvoids, but only during the phase of colonization. Once these algae were established, only a subset of the species was able to control their abundance. During late succession, only the keyhole limpet Fissurella crassa could control corticated Mazzaella. The functional relationships among these species changed dramatically from redundant effects on ephemeral algae during early colonization, to a more complementary role on established early-successional algae, to a dominant (i.e., keystone) effect on late succession. This study highlights that functional relationship within consumer assemblages can vary at different phases and times of community succession. Differentiation in herbivore roles emphasizes the need to evaluate consumer's impacts through different times of community succession, and through experimental manipulations to make even broad predictions about the resilience or vulnerability of diverse intertidal assemblages to human disturbances.

Perioperative echocardiography-derived right ventricle function parameters and early outcomes after tetralogy of Fallot repair in mid-childhood: a single-center, prospective observational study.

PubMed

Raj, Ravi; Puri, Goverdhan Dutt; Jayant, Aveek; Thingnam, Shyam Kumar Singh; Singh, Rana Sandip; Rohit, Manoj Kumar

2016-11-01

Right ventricular (RV) function alterations are invariably present in all patients after tetralogy of Fallot (TOF) repair. Unlike the developed world where most of the patients with TOF are corrected in infancy, average age of presentation and thus surgery for these patients in the developing world may be higher. We aimed to study the correlation between RV function parameters such as tricuspid annular peak systolic excursion (TAPSE), fractional area change (FAC), and tricuspid annular peak systolic velocity (S') with early outcome variables after intracardiac repair for TOF. Fifty patients with a preoperative diagnosis of tetralogy of Fallot scheduled for corrective surgery were included in this single-center, prospective observational study. A preoperative transthoracic echocardiogram was performed to measure RV function parameters (FAC0, TAPSE0, S'0). Transthoracic echocardiography was repeated postoperatively to measure FAC1, TAPSE1, S'1 (day 1) and FAC2, TAPSE2, and S'2 (day 3). The relationship between preoperative and postoperative RV function parameters with in-hospital mortality, duration of mechanical ventilation, and intensive care unit stay was studied. The median age of patients was 6 years (range 1-14 years). Multiple stepwise logistic regression analysis showed RV FAC as best predictor of clinical outcome. Area under the receiver operating characteristic curve for postoperative RV function parameters, that is, FAC, TAPSE, and S' to predict early or delayed recovery was 0.944, 0.875, and 0.655, respectively. Among the RV function parameters studied, RV FAC best predicted the early outcome variables after TOF repair, followed by TAPSE while lateral tricuspid annular velocity S' being the least predictive. © 2016, Wiley Periodicals, Inc.

Executive functioning and reading achievement in school: a study of Brazilian children assessed by their teachers as “poor readers”

PubMed Central

Engel de Abreu, Pascale M. J.; Abreu, Neander; Nikaedo, Carolina C.; Puglisi, Marina L.; Tourinho, Carlos J.; Miranda, Mônica C.; Befi-Lopes, Debora M.; Bueno, Orlando F. A.; Martin, Romain

2014-01-01

This study examined executive functioning and reading achievement in 106 6- to 8-year-old Brazilian children from a range of social backgrounds of whom approximately half lived below the poverty line. A particular focus was to explore the executive function profile of children whose classroom reading performance was judged below standard by their teachers and who were matched to controls on chronological age, sex, school type (private or public), domicile (Salvador/BA or São Paulo/SP) and socioeconomic status. Children completed a battery of 12 executive function tasks that were conceptual tapping cognitive flexibility, working memory, inhibition and selective attention. Each executive function domain was assessed by several tasks. Principal component analysis extracted four factors that were labeled “Working Memory/Cognitive Flexibility,” “Interference Suppression,” “Selective Attention,” and “Response Inhibition.” Individual differences in executive functioning components made differential contributions to early reading achievement. The Working Memory/Cognitive Flexibility factor emerged as the best predictor of reading. Group comparisons on computed factor scores showed that struggling readers displayed limitations in Working Memory/Cognitive Flexibility, but not in other executive function components, compared to more skilled readers. These results validate the account that working memory capacity provides a crucial building block for the development of early literacy skills and extends it to a population of early readers of Portuguese from Brazil. The study suggests that deficits in working memory/cognitive flexibility might represent one contributing factor to reading difficulties in early readers. This might have important implications for how educators might intervene with children at risk of academic under achievement. PMID:24959155

LSD alters eyes-closed functional connectivity within the early visual cortex in a retinotopic fashion.

PubMed

Roseman, Leor; Sereno, Martin I; Leech, Robert; Kaelen, Mendel; Orban, Csaba; McGonigle, John; Feilding, Amanda; Nutt, David J; Carhart-Harris, Robin L

2016-08-01

The question of how spatially organized activity in the visual cortex behaves during eyes-closed, lysergic acid diethylamide (LSD)-induced "psychedelic imagery" (e.g., visions of geometric patterns and more complex phenomena) has never been empirically addressed, although it has been proposed that under psychedelics, with eyes-closed, the brain may function "as if" there is visual input when there is none. In this work, resting-state functional connectivity (RSFC) data was analyzed from 10 healthy subjects under the influence of LSD and, separately, placebo. It was suspected that eyes-closed psychedelic imagery might involve transient local retinotopic activation, of the sort typically associated with visual stimulation. To test this, it was hypothesized that, under LSD, patches of the visual cortex with congruent retinotopic representations would show greater RSFC than incongruent patches. Using a retinotopic localizer performed during a nondrug baseline condition, nonadjacent patches of V1 and V3 that represent the vertical or the horizontal meridians of the visual field were identified. Subsequently, RSFC between V1 and V3 was measured with respect to these a priori identified patches. Consistent with our prior hypothesis, the difference between RSFC of patches with congruent retinotopic specificity (horizontal-horizontal and vertical-vertical) and those with incongruent specificity (horizontal-vertical and vertical-horizontal) increased significantly under LSD relative to placebo, suggesting that activity within the visual cortex becomes more dependent on its intrinsic retinotopic organization in the drug condition. This result may indicate that under LSD, with eyes-closed, the early visual system behaves as if it were seeing spatially localized visual inputs. Hum Brain Mapp 37:3031-3040, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Adaptive neuroplastic responses in early and late hemispherectomized monkeys.

PubMed

Burke, Mark W; Kupers, Ron; Ptito, Maurice

2012-01-01

Behavioural recovery in children who undergo medically required hemispherectomy showcase the remarkable ability of the cerebral cortex to adapt and reorganize following insult early in life. Case study data suggest that lesions sustained early in childhood lead to better recovery compared to those that occur later in life. In these children, it is possible that neural reorganization had begun prior to surgery but was masked by the dysfunctional hemisphere. The degree of neural reorganization has been difficult to study systematically in human infants. Here we present a 20-year culmination of data on our nonhuman primate model (Chlorocebus sabeus) of early-life hemispherectomy in which behavioral recovery is interpreted in light of plastic processes that lead to the anatomical reorganization of the early-damaged brain. The model presented here suggests that significant functional recovery occurs after the removal of one hemisphere in monkeys with no preexisting neurological dysfunctions. Human and primate studies suggest a critical role for subcortical and brainstem structures as well as corticospinal tracts in the neuroanatomical reorganization which result in the remarkable behavioral recovery following hemispherectomy. The non-human primate model presented here offers a unique opportunity for studying the behavioral and functional neuroanatomical reorganization that underlies developmental plasticity.

A relative L-arginine deficiency contributes to endothelial dysfunction across the stages of the menopausal transition.

PubMed

Klawitter, Jelena; Hildreth, Kerry L; Christians, Uwe; Kohrt, Wendy M; Moreau, Kerrie L

2017-09-01

Vascular endothelial function declines across the menopause transition in women. We tested the hypothesis that reduced availability of the endothelial nitric oxide synthase [eNOS] substrate L-arginine is an underlying mechanism to vascular endothelial dysfunction across menopause stages. Endothelial function (brachial artery flow-mediated dilation [FMD]) and plasma markers of L-arginine metabolism (citrulline, N G -mono-methyl-ւ-arginine [L-NMMA] asymmetric dimethylarginine [ADMA] and N G -N 'G -dimethyl-l-arginine [SDMA]), were measured in 129 women: 36 premenopausal (33 ± 7 years), 16 early- (49 ± 3 years) or 21 late- (50 ± 4 years) perimenopausal, and 21 early- (55 ± 3 years) or 35 late- (61 ± 4 years) postmenopausal. FMD was progressively reduced across menopause stages ( P  < 0.001). Menopause stage was associated with L-arginine concentrations ( P  = 0.012), with higher levels in early postmenopausal compared to early and late perimenopausal women ( P  < 0.05). The methylarginine and eNOS inhibitor L-NMMA was higher in early and late postmenopausal women compared to premenopausal and early and late perimenopausal women (all P  < 0.001), and was inversely correlated with FMD ( r  = -0.30, P  = 0.001). The L-arginine/L-NMMA ratio, a potential biomarker of relative L-arginine levels, was lower in postmenopausal compared to either premenopausal or perimenopausal women (both P  < 0.001), and was positively correlated with FMD ( r  = 0.33, P  < 0.001). There were no differences in plasma citrulline, ADMA or SDMA across groups. These data suggest that a relative L-arginine deficiency may be a mechanism underlying the decline in endothelial function with the menopause transition in women. The relative L-arginine deficiency may be related to elevated levels of the methylarginine L-NMMA, which would compete with L-arginine for eNOS and for intracellular transport, reducing NO biosynthesis. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Linking Executive Function and Peer Problems from Early Childhood Through Middle Adolescence.

PubMed

Holmes, Christopher J; Kim-Spoon, Jungmeen; Deater-Deckard, Kirby

2016-01-01

Peer interactions and executive function play central roles in the development of healthy children, as peer problems have been indicative of lower cognitive competencies such as self-regulatory behavior and poor executive function has been indicative of problem behaviors and social dysfunction. However, few studies have focused on the relation between peer interactions and executive function and the underlying mechanisms that may create this link. Using a national sample (n = 1164, 48.6% female) from the Study of Early Child Care and Youth Development (SECCYD), we analyzed executive function and peer problems (including victimization and rejection) across three waves within each domain (executive function or peer problems), beginning in early childhood and ending in middle adolescence. Executive function was measured as a multi-method, multi-informant composite including reports from parents on the Children's Behavior Questionnaire and Child Behavior Checklist and child's performance on behavioral tasks including the Continuous Performance Task, Woodcock-Johnson, Tower of Hanoi, Operation Span Task, Stroop, and Tower of London. Peer problems were measured as a multi-informant composite including self, teacher, and afterschool caregiver reports on multiple peer-relationship scales. Using a cross-lagged design, our Structural Equation Modeling findings suggested that experiencing peer problems contributed to lower executive function later in childhood and better executive function reduced the likelihood of experiencing peer problems later in childhood and middle adolescence, although these relations weakened as a child moves into adolescence. The results highlight that peer relationships are involved in the development of strengths and deficits in executive function and vice versa.

Linking Executive Function and Peer Problems from Early Childhood through Middle Adolescence

PubMed Central

Holmes, Christopher J.; Kim-Spoon, Jungmeen; Deater-Deckard, Kirby

2015-01-01

Peer interactions and executive function play central roles in the development of healthy children, as peer problems have been indicative of lower cognitive competencies such as self-regulatory behavior and poor executive function has been indicative of problem behaviors and social dysfunction. However, few studies have focused on the relation between peer interactions and executive function and the underlying mechanisms that may create this link. Using a national sample (n = 1,164, 48.6% female) from the Study of Early Child Care and Youth Development (SECCYD), we analyzed executive function and peer problems (including victimization and rejection) across three waves within each domain (executive function or peer problems), beginning in early childhood and ending in middle adolescence. Executive function was measured as a multi-method, multi-informant composite including reports from parents on the Children’s Behavior Questionnaire and Child Behavior Checklist and child’s performance on behavioral tasks including the Continuous Performance Task, Woodcock-Johnson, Tower of Hanoi, Operation Span Task, Stroop, and Tower of London. Peer problems were measured as a multi-informant composite including self, teacher, and after school caregiver reports on multiple peer-relationship scales. Using a cross-lagged design, our Structural Equation Modeling findings suggested that experiencing peer problems contributed to lower executive function later in childhood and better executive function reduced the likelihood of experiencing peer problems later in childhood and middle adolescence, although these relations weakened as a child moves into adolescence. The results highlight that peer relationships are involved in the development of strengths and deficits in executive function and vice versa. PMID:26096194

Toward Understanding How Early-Life Stress Reprograms Cognitive and Emotional Brain Networks.

PubMed

Chen, Yuncai; Baram, Tallie Z

2016-01-01

Vulnerability to emotional disorders including depression derives from interactions between genes and environment, especially during sensitive developmental periods. Adverse early-life experiences provoke the release and modify the expression of several stress mediators and neurotransmitters within specific brain regions. The interaction of these mediators with developing neurons and neuronal networks may lead to long-lasting structural and functional alterations associated with cognitive and emotional consequences. Although a vast body of work has linked quantitative and qualitative aspects of stress to adolescent and adult outcomes, a number of questions are unclear. What distinguishes 'normal' from pathologic or toxic stress? How are the effects of stress transformed into structural and functional changes in individual neurons and neuronal networks? Which ones are affected? We review these questions in the context of established and emerging studies. We introduce a novel concept regarding the origin of toxic early-life stress, stating that it may derive from specific patterns of environmental signals, especially those derived from the mother or caretaker. Fragmented and unpredictable patterns of maternal care behaviors induce a profound chronic stress. The aberrant patterns and rhythms of early-life sensory input might also directly and adversely influence the maturation of cognitive and emotional brain circuits, in analogy to visual and auditory brain systems. Thus, unpredictable, stress-provoking early-life experiences may influence adolescent cognitive and emotional outcomes by disrupting the maturation of the underlying brain networks. Comprehensive approaches and multiple levels of analysis are required to probe the protean consequences of early-life adversity on the developing brain. These involve integrated human and animal-model studies, and approaches ranging from in vivo imaging to novel neuroanatomical, molecular, epigenomic, and computational methodologies. Because early-life adversity is a powerful determinant of subsequent vulnerabilities to emotional and cognitive pathologies, understanding the underlying processes will have profound implications for the world's current and future children.

Prognostic Importance of Early Worsening Renal Function Following Initiation of Angiotensin Converting Enzyme Inhibitor Therapy in Patients with Cardiac Dysfunction

PubMed Central

Testani, Jeffrey M.; Kimmel, Stephen E.; Dries, Daniel L.; Coca, Steven G.

2011-01-01

Background Worsening renal function (WRF) in the setting of heart failure has been associated with increased mortality. However, it is unclear if this decreased survival is a direct result of the reduction in glomerular filtration rate (GFR) or if the mechanism underlying the deterioration in GFR is driving prognosis. Given that WRF in the setting of angiotensin converting enzyme inhibitor (ACE-I) initiation is likely mechanistically distinct from spontaneously occurring WRF, we sought to investigate the relative early WRF associated mortality rates in subjects randomized to ACE-I or placebo. Methods and Results Subjects in the Studies Of Left Ventricular Dysfunction limited data set were studied (6,377 patients). The interaction between early WRF (decrease in estimated GFR ≥20% at 14 days), randomization to enalapril, and mortality was the primary endpoint. In the overall population, early WRF was associated with increased mortality (adjusted HR=1.2, 95% CI 1.0–1.4, p=0.037). When analysis was restricted to the placebo group, this association strengthened (adjusted HR=1.4, 95% CI 1.1–1.8, p=0.004). However, in the enalapril group, early WRF had no adverse prognostic significance (adjusted HR=1.0, 95% CI 0.8–1.3, p=1.0, p interaction=0.09). In patients that continued study drug despite early WRF, a survival advantage remained with enalapril therapy (adjusted HR=0.66, 95% CI 0.5–0.9, p=0.018). Conclusions These data support the notion that the mechanism underlying WRF is important in determining its prognostic significance. Specifically, early WRF in the setting of ACE-I initiation appears to represent a benign event which is not associated with a loss of benefit from continued ACE-I therapy. PMID:21903907

Pathways to Arithmetic Fact Retrieval and Percentage Calculation in Adolescents

ERIC Educational Resources Information Center

Träff, Ulf; Skagerlund, Kenny; Olsson, Linda; Östergren, Rickard

2017-01-01

Background: Developing sufficient mathematical skills is a prerequisite to function adequately in society today. Given this, an important task is to increase our understanding regarding the cognitive mechanisms underlying young people's acquisition of early number skills and formal mathematical knowledge. Aims: The purpose was to examine whether…

Biomarker for early renal microvascular and diabetic kidney diseases.

PubMed

Futrakul, Narisa; Futrakul, Prasit

2017-11-01

Recognition of early stage of diabetic kidney disease, under common practice using biomarkers, namely microalbuminuria, serum creatinine level above 1 mg/dL and accepted definition of diabetic kidney disease associated with creatinine clearance value below 60 mL/min/1.73 m 2 , is unlikely. This would lead to delay treatment associated with therapeutic resistance to vasodilator due to a defective vascular homoeostasis. Other alternative biomarkers related to the state of microalbuminuria is not sensitive to screen for early diabetic kidney disease (stages I, II). In this regard, a better diagnostic markers to serve for this purpose are creatinine clearance, fractional excretion of magnesium (FE Mg), cystatin C. Recently, renal microvascular disease and renal ischemia have been demonstrated to correlate indirectly with the development of diabetic kidney disease and its function. Among these are angiogenic and anti-angiogenic factors, namely VEGF, VEGF receptors, angiopoietins and endostatin. With respect to therapeutic prevention, implementation of treatment at early stage of diabetic and nondiabetic kidney disease is able to restore renal perfusion and function.

Early adaption to the antarctic environment at dome C: consequences on stress-sensitive innate immune functions.

PubMed

Feuerecker, Matthias; Crucian, Brian; Salam, Alex P; Rybka, Ales; Kaufmann, Ines; Moreels, Marjan; Quintens, Roel; Schelling, Gustav; Thiel, Manfred; Baatout, Sarah; Sams, Clarence; Choukèr, Alexander

2014-09-01

Abstract Feuerecker, Matthias, Brian Crucian, Alex P. Salam, Ales Rybka, Ines Kaufmann, Marjan Moreels, Roel Quintens, Gustav Schelling, Manfred Thiel, Sarah Baatout, Clarence Sams, and Alexander Choukèr. Early adaption in the Antarctic environment at Dome C: Consequences on stress-sensitive innate immune functions. High Alt Med Biol 15:341-348, 2014.-Purpose/Aims: Medical reports of Antarctic expeditions indicate that health is affected under these extreme conditions. The present study at CONCORDIA-Station (Dome C, 3233 m) seeks to investigate the early consequences of confinement and hypobaric hypoxia on the human organism. Nine healthy male participants were included in this study. Data collection occurred before traveling to Antarctica (baseline), and at 1 week and 1 month upon arrival. Investigated parameters included basic physiological variables, psychological stress tests, cell blood count, stress hormones, and markers of innate immune functions in resting and stimulated immune cells. By testing for the hydrogen peroxide (H2O2) production of stimulated polymorphonuclear leukocytes (PMNs), the effects of the hypoxia-adenosine-sensitive immune modulatory pathways were examined. As compared to baseline data, reduced oxygen saturation, hemoconcentration, and an increase of secreted catecholamines was observed, whereas no psychological stress was seen. Upon stimulation, the activity of PMNs and L-selectin shedding was mitigated after 1 week. Endogenous adenosine concentration was elevated during the early phase. In summary, living conditions at high altitude influence the innate immune system's response. After 1 month, some of the early effects on the human organism were restored. As this early adaptation is not related to psychological stress, the changes observed are likely to be induced by environmental stressors, especially hypoxia. As hypoxia is triggering ATP-catabolism, leading to elevated endogenous adenosine concentrations, this and the increased catecholamine concentration might contribute to the early, but reversible downregulation of innate immune functions. This indicates the slope of innate immune adaptation to hypoxia.

Motivational deficits in early schizophrenia: prevalent, persistent, and key determinants of functional outcome.

PubMed

Fervaha, Gagan; Foussias, George; Agid, Ofer; Remington, Gary

2015-08-01

Negative symptoms, in particular motivational deficits, are reported as impediments to functional recovery in patients with schizophrenia. This study examined the prevalence of motivational deficits in patients early in the illness, and the impact these deficits have on community functioning. Patients with schizophrenia between the ages of 18 and 35years, and within 5years of initiating antipsychotic treatment were included in the present investigation (N=166). The impact of motivation and cognition on concurrent and longitudinal functioning was evaluated. Motivational impairments were found in more than 75% of participants, and were not associated with receipt of social support. These deficits served as the most robust and reliable predictor of functional outcome, while neurocognition demonstrated significantly weaker associations with outcome. When considered together, motivational deficits demonstrated a reliable link with concurrent and longitudinal functioning, with cognition not offering any independent predictive value. Moreover, motivation was found to mediate the relationship between cognition and outcome. Changes in motivation were linked to changes in functioning; however, this was not the case for changes in cognitive performance. Motivation emerged as a significant predictor of functioning even after selected demographic and clinical characteristics (e.g., positive symptoms) were accounted for. These data indicate that motivational deficits are prevalent in patients with schizophrenia, even in the early stages of the illness, and these deficits stand as one of the most robust barriers to people with schizophrenia achieving functional recovery. Greater understanding of the mechanisms underlying these deficits is critical to effective treatment innovation. Copyright © 2015 Elsevier B.V. All rights reserved.

Development under elevated pCO2 conditions does not affect lipid utilization and protein content in early life-history stages of the purple sea urchin, Strongylocentrotus purpuratus.

PubMed

Matson, Paul G; Yu, Pauline C; Sewell, Mary A; Hofmann, Gretchen E

2012-12-01

Ocean acidification (OA) is expected to have a major impact on marine species, particularly during early life-history stages. These effects appear to be species-specific and may include reduced survival, altered morphology, and depressed metabolism. However, less information is available regarding the bioenergetics of development under elevated CO(2) conditions. We examined the biochemical and morphological responses of Strongylocentrotus purpuratus during early development under ecologically relevant levels of pCO(2) (365, 1030, and 1450 μatm) that may occur during intense upwelling events. The principal findings of this study were (1) lipid utilization rates and protein content in S. purpuratus did not vary with pCO(2); (2) larval growth was reduced at elevated pCO(2) despite similar rates of energy utilization; and (3) relationships between egg phospholipid content and larval length were found under control but not high pCO(2) conditions. These results suggest that this species may either prioritize endogenous energy toward development and physiological function at the expense of growth, or that reduced larval length may be strictly due to higher costs of growth under OA conditions. This study highlights the need to further expand our knowledge of the physiological mechanisms involved in OA response in order to better understand how present populations may respond to global environmental change.

CMV colitis in early HIV infection.

PubMed

Smith, P R; Glynn, M; Sheaff, M; Aitken, C

2000-11-01

Cytomegalovirus (CMV) colitis is a well recognized complication of advanced HIV disease and is only rarely diagnosed in patients with normal immune function. A case of CMV colitis occurring in early HIV infection is described. Although CMV infection is normally confined to patients with advanced HIV disease, it is possible that a number of contributing factors may have led to clinical disease in this patient. CMV colitis is an important diagnosis to consider in all patients who present with a diarrhoeal illness associated with systemic features, regardless of underlying immunosuppression.

The role of early visual cortex in visual short-term memory and visual attention.

PubMed

Offen, Shani; Schluppeck, Denis; Heeger, David J

2009-06-01

We measured cortical activity with functional magnetic resonance imaging to probe the involvement of early visual cortex in visual short-term memory and visual attention. In four experimental tasks, human subjects viewed two visual stimuli separated by a variable delay period. The tasks placed differential demands on short-term memory and attention, but the stimuli were visually identical until after the delay period. Early visual cortex exhibited sustained responses throughout the delay when subjects performed attention-demanding tasks, but delay-period activity was not distinguishable from zero when subjects performed a task that required short-term memory. This dissociation reveals different computational mechanisms underlying the two processes.

Effects of Neonatal Dexamethasone Exposure on Adult Neuropsychiatric Traits in Rats

PubMed Central

Robertson, Donald; Rodger, Jennifer; Martin-Iverson, Mathew T.

2016-01-01

The effects of early life stress in utero or in neonates has long-term consequences on hypothalamic-pituitary-adrenal (HPA) stress axis function and neurodevelopment. These effects extend into adulthood and may underpin a variety of mental illnesses and be related to various developmental and cognitive changes. We examined the potential role of neonatal HPA axis activation on adult psychopathology and dopamine sensitivity in the mature rat using neonatal exposure to the synthetic glucocorticoid receptor agonist and stress hormone, dexamethasone. We utilized a comprehensive battery of assessments for behaviour, brain function and gene expression to determine if elevated early life HPA activation is associated with adult-onset neuropsychiatric traits. Dexamethasone exposure increased startle reactivity under all conditions tested, but decreased sensitivity of sensorimotor gating to dopaminergic disruption–contrasting with what is observed in several neuropsychiatric diseases. Under certain conditions there also appeared to be mild long-term changes in stress and anxiety-related behaviours with neonatal dexamethasone exposure. Electrophysiology revealed that there were no consistent neuropsychiatric abnormalities in auditory processing or resting state brain function with dexamethasone exposure. However, neonatal dexamethasone altered auditory cortex glucocorticoid activation, and auditory cortex synchronization. Our results indicate that neonatal HPA axis activation by dexamethasone alters several aspects of adult brain function and behaviour and may induce long-term changes in emotional stress-reactivity. However, neonatal dexamethasone exposure is not specifically related to any particular neuropsychiatric disease. PMID:27936175

Studying Individual Plant AOX Gene Functionality in Early Growth Regulation: A New Approach.

PubMed

Arnholdt-Schmitt, Birgit; Patil, Vinod Kumar

2017-01-01

AOX1 and AOX2 genes are thought to play different physiological roles. Whereas AOX1 is typically expected to associate to stress and growth responses, AOX2 was more often found to be linked to development and housekeeping functions. However, this view is questioned by several adverse observations. For example, co-regulated expression for DcAOX1 and DcAOX2a genes was recently reported during growth induction in carrot (Daucus carota L.). Early expression peaks for both genes during the lag phase of growth coincided with a critical time point for biomass prediction, a result achieved by applying calorespirometry. The effect of both AOX family member genes cannot easily be separated. However, separate functional analysis is required in order to identify important gene-specific polymorphisms or patterns of polymorphisms for functional marker development and its use in breeding. Specifically, a methodology is missing that enables studying functional effects of individual genes or polymorphisms/polymorphic patterns on early growth regulation.This protocol aims to provide the means for identifying plant alternative oxidase (AOX) gene variants as functional markers for early growth regulation. Prerequisite for applying this protocol is available Schizosaccharomyces pombe strains that were transformed with individual AOX genes following published protocols from Anthony Moore's group (Albury et al., J Biol Chem 271:17062-17066, 1996; Affourtit et al., J Biol Chem 274:6212-6218, 1999). The novelty of the present protocol comes by modifying yeast cell densities in a way that allows studying critical qualitative and quantitative effects of AOX gene variants (isoenzymes or polymorphic genes) during the early phase of growth. Calorimetry is used as a novel tool to confirm differences obtained by optical density measurements in early growth regulation by metabolic phenotyping (released heat rates). This protocol enables discriminating between AOX genes that inhibit growth and AOX genes that enhance growth under comparable conditions. It also allows studying dependency of AOX gene effects on gene copy number. The protocol can also be combined with laser microdissection of individual cells from target tissues for specified breeding traits.

Alterations of functional connectivities from early to middle adulthood: Clues from multivariate pattern analysis of resting-state fMRI data.

PubMed

Tian, Lixia; Ma, Lin; Wang, Linlin

2016-04-01

In contrast to extended research interests in the maturation and aging of human brain, alterations of brain structure and function from early to middle adulthood have been much less studied. The aim of the present study was to investigate the extent and pattern of the alterations of functional interactions between brain regions from early to middle adulthood. We carried out the study by multivariate pattern analysis of resting-state fMRI (RS-fMRI) data of 63 adults aged 18 to 45 years. Specifically, using elastic net, we performed brain age estimation and age-group classification (young adults aged 18-28 years vs. middle-aged adults aged 35-45 years) based on the resting-state functional connectivities (RSFCs) between 160 regions of interest (ROIs) evaluated on the RS-fMRI data of each subject. The results indicate that the estimated brain ages were significantly correlated with the chronological age (R=0.78, MAE=4.81), and a classification rate of 94.44% and area under the receiver operating characteristic curve (AUC) of 0.99 were obtained when classifying the young and middle-aged adults. These results provide strong evidence that functional interactions between brain regions undergo notable alterations from early to middle adulthood. By analyzing the RSFCs that contribute to brain age estimation/age-group classification, we found that a majority of the RSFCs were inter-network, and we speculate that inter-network RSFCs might mature late but age early as compared to intra-network ones. In addition, the strengthening/weakening of the RSFCs associated with the left/right hemispheric ROIs, the weakening of cortico-cerebellar RSFCs and the strengthening of the RSFCs between the default mode network and other networks contributed much to both brain age estimation and age-group classification. All these alterations might reflect that aging of brain function is already in progress in middle adulthood. Overall, the present study indicated that the RSFCs undergo notable alterations from early to middle adulthood and highlighted the necessity of careful considerations of possible influences of these alterations in related studies. Copyright © 2016 Elsevier Inc. All rights reserved.

Revisiting Hemicraniectomy: Late Decompressive Hemicraniectomy for Malignant Middle Cerebral Artery Stroke and the Role of Infarct Growth Rate

PubMed Central

Akhtar, Naveed; Salam, Abdul; Alboudi, Ayman; Kamran, Kainat; Ahmed, Arsalan; Khan, Rabia A.; Mirza, Mohsin K.; Inshasi, Jihad

2017-01-01

Objective and Methods. The outcome in late decompressive hemicraniectomy in malignant middle cerebral artery stroke and the optimal timings of surgery has not been addressed by the randomized trials and pooled analysis. Retrospective, multicenter, cross-sectional study to measure outcome following DHC under 48 or over 48 hours using the modified Rankin scale [mRS] and dichotomized as favorable ≤4 or unfavorable >4 at three months. Results. In total, 137 patients underwent DHC. Functional outcome analyzed as mRS 0–4 versus mRS 5-6 showed no difference in this split between early and late operated on patients [P = 0.140] and mortality [P = 0.975]. Multivariate analysis showed that age ≥ 55 years, MCA with additional infarction, septum pellucidum deviation ≥1 cm, and uncal herniation were independent predictors of poor functional outcome at three months. In the “best” multivariate model, second infarct growth rate [IGR2] >7.5 ml/hr, MCA with additional infarction, and patients with temporal lobe involvement were independently associated with surgery under 48 hours. Both first infarct growth rate [IGR1] and second infarct growth rate [IGR2] were nearly double [P < 0.001] in patients with early surgery [under 48 hours]. Conclusions. The outcome and mortality in malignant middle cerebral artery stroke patients operated on over 48 hours of stroke onset were comparable to those of patients operated on less than 48 hours after stroke onset. Our data identifies IGR, temporal lobe involvement, and middle cerebral artery with additional infarct as independent predictors for early surgery. PMID:28409051

Revisiting Hemicraniectomy: Late Decompressive Hemicraniectomy for Malignant Middle Cerebral Artery Stroke and the Role of Infarct Growth Rate.

PubMed

Kamran, Saadat; Akhtar, Naveed; Salam, Abdul; Alboudi, Ayman; Kamran, Kainat; Ahmed, Arsalan; Khan, Rabia A; Mirza, Mohsin K; Inshasi, Jihad; Shuaib, Ashfaq

2017-01-01

Objective and Methods. The outcome in late decompressive hemicraniectomy in malignant middle cerebral artery stroke and the optimal timings of surgery has not been addressed by the randomized trials and pooled analysis. Retrospective, multicenter, cross-sectional study to measure outcome following DHC under 48 or over 48 hours using the modified Rankin scale [mRS] and dichotomized as favorable ≤4 or unfavorable >4 at three months. Results. In total, 137 patients underwent DHC. Functional outcome analyzed as mRS 0-4 versus mRS 5-6 showed no difference in this split between early and late operated on patients [ P = 0.140] and mortality [ P = 0.975]. Multivariate analysis showed that age ≥ 55 years, MCA with additional infarction, septum pellucidum deviation ≥1 cm, and uncal herniation were independent predictors of poor functional outcome at three months. In the "best" multivariate model, second infarct growth rate [IGR2] >7.5 ml/hr, MCA with additional infarction, and patients with temporal lobe involvement were independently associated with surgery under 48 hours. Both first infarct growth rate [IGR1] and second infarct growth rate [IGR2] were nearly double [ P < 0.001] in patients with early surgery [under 48 hours]. Conclusions. The outcome and mortality in malignant middle cerebral artery stroke patients operated on over 48 hours of stroke onset were comparable to those of patients operated on less than 48 hours after stroke onset. Our data identifies IGR, temporal lobe involvement, and middle cerebral artery with additional infarct as independent predictors for early surgery.

Integration of functional safety systems on the Daniel K. Inouye Solar Telescope

NASA Astrophysics Data System (ADS)

Williams, Timothy R.; Hubbard, Robert P.; Shimko, Steve

2016-07-01

The Daniel K. Inouye Solar Telescope (DKIST) was envisioned from an early stage to incorporate a functional safety system to ensure the safety of personnel and equipment within the facility. Early hazard analysis showed the need for a functional safety system. The design used a distributed approach in which each major subsystem contains a PLC-based safety controller. This PLC-based system complies with the latest international standards for functional safety. The use of a programmable controller also allows for flexibility to incorporate changes in the design of subsystems without adversely impacting safety. Various subsystems were built by different contractors and project partners but had to function as a piece of the overall control system. Using distributed controllers allows project contractors and partners to build components as standalone subsystems that then need to be integrated into the overall functional safety system. Recently factory testing was concluded on the major subsystems of the facility. Final integration of these subsystems is currently underway on the site. Building on lessons learned in early factory tests, changes to the interface between subsystems were made to improve the speed and ease of integration of the entire system. Because of the distributed design each subsystem can be brought online as it is delivered and assembled rather than waiting until the entire facility is finished. This enhances safety during the risky period of integration and testing. The DKIST has implemented a functional safety system that has allowed construction of subsystems in geographically diverse locations but that function cohesively once they are integrated into the facility currently under construction.

On the causes of early life experience effects: evaluating the role of mom.

PubMed

Tang, Akaysha C; Reeb-Sutherland, Bethany C; Romeo, Russell D; McEwen, Bruce S

2014-04-01

Early life experiences are thought to have long-lasting effects on cognitive, emotional, and social function during adulthood. Changes in neuroendocrine function, particularly the hypothalamic-pituitary-adrenal (HPA) axis, contribute to these systems-level behavioral effects. In searching for causal mechanisms underlying these early experience effects, pioneering research has demonstrated an important role for maternal care in offspring development, and this has led to two persistent ideas that permeate current research and thinking: first, environmental impact on the developing infant is mediated through maternal care behavior; second, the more care that a mother provides, the better off her offspring. While a good beginning, the reality is likely more complex. In this review, we critically examine these ideas and propose a computationally-motivated theoretical framework, and within this framework, we consider evidence supporting a hypothesis of maternal modulation. These findings may inform policy decisions in the context of child health and development. Copyright © 2013 Elsevier Inc. All rights reserved.

Infants and adults have similar regional functional brain organization for the perception of emotions.

PubMed

Rotem-Kohavi, N; Oberlander, T F; Virji-Babul, N

2017-05-22

An infant's ability to perceive emotional facial expressions is critical for developing social skills. Infants are tuned to faces from early in life, however the functional organization of the brain that supports the processing of emotional faces in infants is still not well understood. We recorded electroencephalography (EEG) brain responses in 8-10 month old infants and adults and applied graph theory analysis on the functional connections to compare the network organization at the global and the regional levels underlying the perception of negative and positive dynamic facial expressions (happiness and sadness). We first show that processing of dynamic emotional faces occurs across multiple brain regions in both infants and adults. Across all brain regions, at the global level, network density was higher in the infant group in comparison with adults suggesting that the overall brain organization in relation to emotion perception is still immature in infancy. In contrast, at the regional levels, the functional characteristics of the frontal and parietal nodes were similar between infants and adults, suggesting that functional regional specialization for emotion perception is already established at this age. In addition, in both groups the occipital, parietal and temporal nodes appear to have the strongest influence on information flow within the network. These results suggest that while the global organization for the emotion perception of sad and happy emotions is still under development, the basic functional network organization at the regional level is already in place early in infancy. Copyright © 2017 Elsevier B.V. All rights reserved.

Easy as AcHGzrjq: the Quick Letter Name Knowledge Assessment

ERIC Educational Resources Information Center

Tortorelli, Laura S.; Bowles, Ryan P.; Skibbe, Lori E.

2017-01-01

A firm foundation in alphabet knowledge is critical for children learning to read. Under new literacy standards, letter name knowledge in preschool and kindergarten can function as a gatekeeper to the rest of the curriculum. Teachers need data about their students' alphabet knowledge early and often to plan differentiated instruction that moves…

Outcomes for Children Served through IDEA's Early Childhood Programs: 2014-15

ERIC Educational Resources Information Center

Early Childhood Technical Assistance Center, 2016

2016-01-01

In 2014-2015, children with delays or disabilities who received services under the Individuals with Disabilities Act (IDEA) showed greater than expected developmental progress. Many children exited the program functioning within age expectations, and most made progress. States' Part C and Part B Preschool programs report data annually on three…

Predict the neurological recovery under hypothermia after cardiac arrest using C0 complexity measure of EEG signals.

PubMed

Lu, Yueli; Jiang, Dineng; Jia, Xiaofeng; Qiu, Yihong; Zhu, Yisheng; Thakor, Nitish; Tong, Shanbao

2008-01-01

Clinical trials have proven the efficacy of therapeutic hypothermia in improving the functional outcome after cardiac arrest (CA) compared with the normothermic controls. Experimental researches also demonstrated quantitative electroencephalogram (qEEG) analysis was associated with the long-term outcome of the therapeutic hypothermia in brain injury. Nevertheless, qEEG has not been able to provide a prediction earlier than 6h after the return of spontaneous circulation (ROSC). In this study, we use C0 complexity to analyze the nonlinear characteristic of EEG, which could predict the neurological recovery under therapeutic hypothermia during the early phase after asphyxial cardiac arrest in rats. Twelve Wistar rats were randomly assigned to 9-min asphyxia injury under hypothermia (33 degrees C, n=6) or normothermia (37 degrees C, n=6). Significantly greater C0 complexity was found in hypothermic group than that in normothermic group as early as 4h after the ROSC (P0.05). C0 complexity at 4h correlated well with the 72h neurodeficit score (NDS) (Pearson's correlation = 0.882). The results showed that the C0 complexity could be an early predictor of the long-term neurological recovery from cardiac arrest.

ICF-CY code set for infants with early delay and disabilities (EDD Code Set) for interdisciplinary assessment: a global experts survey.

PubMed

Pan, Yi-Ling; Hwang, Ai-Wen; Simeonsson, Rune J; Lu, Lu; Liao, Hua-Fang

2015-01-01

Comprehensive description of functioning is important in providing early intervention services for infants with developmental delay/disabilities (DD). A code set of the International Classification of Functioning, Disability and Health: Children and Youth Version (ICF-CY) could facilitate the practical use of the ICF-CY in team evaluation. The purpose of this study was to derive an ICF-CY code set for infants under three years of age with early delay and disabilities (EDD Code Set) for initial team evaluation. The EDD Code Set based on the ICF-CY was developed on the basis of a Delphi survey of international professionals experienced in implementing the ICF-CY and professionals in early intervention service system in Taiwan. Twenty-five professionals completed the Delphi survey. A total of 82 ICF-CY second-level categories were identified for the EDD Code Set, including 28 categories from the domain Activities and Participation, 29 from body functions, 10 from body structures and 15 from environmental factors. The EDD Code Set of 82 ICF-CY categories could be useful in multidisciplinary team evaluations to describe functioning of infants younger than three years of age with DD, in a holistic manner. Future validation of the EDD Code Set and examination of its clinical utility are needed. The EDD Code Set with 82 essential ICF-CY categories could be useful in the initial team evaluation as a common language to describe functioning of infants less than three years of age with developmental delay/disabilities, with a more holistic view. The EDD Code Set including essential categories in activities and participation, body functions, body structures and environmental factors could be used to create a functional profile for each infant with special needs and to clarify the interaction of child and environment accounting for the child's functioning.

The effects of early life adversity on the immune system.

PubMed

Elwenspoek, Martha M C; Kuehn, Annette; Muller, Claude P; Turner, Jonathan D

2017-08-01

Early life adversity (ELA) is associated with a higher risk for diseases in adulthood. Although the pathophysiological effects of ELA are varied, there may be a unifying role for the immune system in all of the long-term pathologies such as chronic inflammatory disorders (autoimmune diseases, allergy, and asthma). Recently, significant efforts have been made to elucidate the long-term effects ELA has on immune function, as well as the mechanisms underlying these immune changes. In this review, we focus on data from human studies investigating immune parameters in relation to post-natal adverse experiences. We describe the current understanding of the 'ELA immune phenotype', characterized by inflammation, impairment of the cellular immune system, and immunosenescence. However, at present, data addressing specific immune functions are limited and there is a need for high-quality, well powered, longitudinal studies to unravel cause from effect. Besides the immune system, also the stress system and health behaviors are altered in ELA. We discuss probable underlying mechanisms based on epigenetic programming that could explain the ELA immune phenotype and whether this is a direct effect of immune programming or an indirect consequence of changes in behavior or stress reactivity. Understanding the underlying mechanisms will help define effective strategies to prevent or counteract negative ELA-associated outcomes. Copyright © 2017 Elsevier Ltd. All rights reserved.

Functional weight-bearing mobilization after Achilles tendon rupture enhances early healing response: a single-blinded randomized controlled trial.

PubMed

Valkering, Kars P; Aufwerber, Susanna; Ranuccio, Francesco; Lunini, Enricomaria; Edman, Gunnar; Ackermann, Paul W

2017-06-01

Functional weight-bearing mobilization may improve repair of Achilles tendon rupture (ATR), but the underlying mechanisms and outcome were unknown. We hypothesized that functional weight-bearing mobilization by means of increased metabolism could improve both early and long-term healing. In this prospective randomized controlled trial, patients with acute ATR were randomized to either direct post-operative functional weight-bearing mobilization (n = 27) in an orthosis or to non-weight-bearing (n = 29) plaster cast immobilization. During the first two post-operative weeks, 15°-30° of plantar flexion was allowed and encouraged in the functional weight-bearing mobilization group. At 2 weeks, patients in the non-weight-bearing cast immobilization group received a stiff orthosis, while the functional weight-bearing mobilization group continued with increased range of motion. At 6 weeks, all patients discontinued immobilization. At 2 weeks, healing metabolites and markers of procollagen type I (PINP) and III (PIIINP) were examined using microdialysis. At 6 and 12 months, functional outcome using heel-rise test was assessed. Healing tendons of both groups exhibited increased levels of metabolites glutamate, lactate, pyruvate, and of PIIINP (all p < 0.05). Patients in functional weight-bearing mobilization group demonstrated significantly higher concentrations of glutamate compared to the non-weight-bearing cast immobilization group (p = 0.045).The upregulated glutamate levels were significantly correlated with the concentrations of PINP (r = 0.5, p = 0.002) as well as with improved functional outcome at 6 months (r = 0.4; p = 0.014). Heel-rise tests at 6 and 12 months did not display any differences between the two groups. Functional weight-bearing mobilization enhanced the early healing response of ATR. In addition, early ankle range of motion was improved without the risk of Achilles tendon elongation and without altering long-term functional outcome. The relationship between functional weight-bearing mobilization-induced upregulation of glutamate and enhanced healing suggests novel opportunities to optimize post-operative rehabilitation.

Proteomic profiling in MPTP monkey model for early Parkinson disease biomarker discovery

PubMed Central

Lin, Xiangmin; Shi, Min; Gunasingh Masilamoni, Jeyaraj; Dator, Romel; Movius, James; Aro, Patrick; Smith, Yoland; Zhang, Jing

2015-01-01

Identification of reliable and robust biomarkers is crucial to enable early diagnosis of Parkinson disease (PD) and monitoring disease progression. While imperfect, the slow, chronic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced non-human primate animal model system of parkinsonism is an abundant source of pre-motor or early stage PD biomarker discovery. Here, we present a study of a MPTP rhesus monkey model of PD that utilizes complementary quantitative iTRAQ-based proteomic, glycoproteomics and phosphoproteomics approaches. We compared the glycoprotein, non-glycoprotein, and phosphoprotein profiles in the putamen of asymptomatic and symptomatic MPTP-treated monkeys as well as saline injected controls. We identified 86 glycoproteins, 163 non-glycoproteins, and 71 phosphoproteins differentially expressed in the MPTP-treated groups. Functional analysis of the data sets inferred the biological processes and pathways that link to neurodegeneration in PD and related disorders. Several potential biomarkers identified in this study have already been translated for their usefulness in PD diagnosis in human subjects and further validation investigations are currently under way. In addition to providing potential early PD biomarkers, this comprehensive quantitative proteomic study may also shed insights regarding the mechanisms underlying early PD development. This article is part of a Special Issue entitled: Neuroproteomics: Applications in neuroscience and neurology. PMID:25617661

Craniofacial form and function in Metriorhynchidae (Crocodylomorpha: Thalattosuchia): modelling phenotypic evolution with maximum-likelihood methods.

PubMed

Young, Mark T; Bell, Mark A; Brusatte, Stephen L

2011-12-23

Metriorhynchid crocodylomorphs were the only group of archosaurs to fully adapt to a pelagic lifestyle. During the Jurassic and Early Cretaceous, this group diversified into a variety of ecological and morphological types, from large super-predators with a broad short snout and serrated teeth to specialized piscivores/teuthophages with an elongate tubular snout and uncarinated teeth. Here, we use an integrated repertoire of geometric morphometric (form), biomechanical finite-element analysis (FEA; function) and phylogenetic data to examine the nature of craniofacial evolution in this clade. FEA stress values significantly correlate with morphometric values representing skull length and breadth, indicating that form and function are associated. Maximum-likelihood methods, which assess which of several models of evolution best explain the distribution of form and function data on a phylogenetic tree, show that the two major metriorhynchid subclades underwent different evolutionary modes. In geosaurines, both form and function are best explained as evolving under 'random' Brownian motion, whereas in metriorhynchines, the form metrics are best explained as evolving under stasis and the function metric as undergoing a directional change (towards most efficient low-stress piscivory). This suggests that the two subclades were under different selection pressures, and that metriorhynchines with similar skull shape were driven to become functionally divergent.

Interocular suppression in strabismic amblyopia results in an attenuated and delayed hemodynamic response function in early visual cortex.

PubMed

Farivar, Reza; Thompson, Benjamin; Mansouri, Behzad; Hess, Robert F

2011-12-20

Factors such as strabismus or anisometropia during infancy can disrupt normal visual development and result in amblyopia, characterized by reduced visual function in an otherwise healthy eye and often associated with persistent suppression of inputs from the amblyopic eye by those from the dominant eye. It has become evident from fMRI studies that the cortical response to stimulation of the amblyopic eye is also affected. We were interested to compare the hemodynamic response function (HRF) of early visual cortex to amblyopic vs. dominant eye stimulation. In the first experiment, we found that stimulation of the amblyopic eye resulted in a signal that was both attenuated and delayed in its time to peak. We postulated that this delay may be due to suppressive effects of the dominant eye and, in our second experiment, measured the cortical response of amblyopic eye stimulation under two conditions--where the dominant eye was open and seeing a static pattern (high suppression) or where the dominant eye was patched and closed (low suppression). We found that the HRF in response to amblyopic eye stimulation depended on whether the dominant eye was open. This effect was manifested as both a delayed HRF under the suppressed condition and an amplitude reduction.

Transcriptional signature associated with early rheumatoid arthritis and healthy individuals at high risk to develop the disease

PubMed Central

Macías-Segura, N.; Bastian, Y.; Santiago-Algarra, D.; Castillo-Ortiz, J. D.; Alemán-Navarro, A. L.; Jaime-Sánchez, E.; Gomez-Moreno, M.; Saucedo-Toral, C. A.; Lara-Ramírez, Edgar E.; Zapata-Zuñiga, M.; Enciso-Moreno, L.; González-Amaro, R.; Ramos-Remus, C.; Enciso-Moreno, J. A.

2018-01-01

Background Little is known regarding the mechanisms underlying the loss of tolerance in the early and preclinical stages of autoimmune diseases. The aim of this work was to identify the transcriptional profile and signaling pathways associated to non-treated early rheumatoid arthritis (RA) and subjects at high risk. Several biomarker candidates for early RA are proposed. Methods Whole blood total RNA was obtained from non-treated early RA patients with <1 year of evolution as well as from healthy first-degree relatives of patients with RA (FDR) classified as ACCP+ and ACCP- according to their antibodies serum levels against cyclic citrullinated peptides. Complementary RNA (cRNA) was synthetized and hybridized to high-density microarrays. Data was analyzed in Genespring Software and functional categories were assigned to a specific transcriptome identified in subjects with RA and FDR ACCP positive. Specific signaling pathways for genes associated to RA were identified. Gene expression was evaluated by qPCR. Receiver operating characteristic (ROC) analysis was used to evaluate these genes as biomarkers. Results A characteristic transcriptome of 551 induced genes and 4,402 repressed genes were identified in early RA patients. Bioinformatics analysis of the data identified a specific transcriptome in RA patients. Moreover, some overlapped transcriptional profiles between patients with RA and ACCP+ were identified, suggesting an up-regulated distinctive transcriptome from the preclinical stages up to progression to an early RA state. A total of 203 pathways have up-regulated genes that are shared between RA and ACCP+. Some of these genes show potential to be used as progression biomarkers for early RA with area under the curve of ROC > 0.92. These genes come from several functional categories associated to inflammation, Wnt signaling and type I interferon pathways. Conclusion The presence of a specific transcriptome in whole blood of RA patients suggests the activation of a specific inflammatory transcriptional signature in early RA development. The set of overexpressed genes in early RA patients that are shared with ACCP+ subjects but not with ACCP- subjects, can represent a transcriptional signature involved with the transition of a preclinical to a clinical RA stage. Some of these particular up-regulated and down-regulated genes are related to inflammatory processes and could be considered as biomarker candidates for disease progression in subjects at risk to develop RA. PMID:29584756

Early organ-specific mitochondrial dysfunction of jejunum and lung found in rats with experimental acute pancreatitis

PubMed Central

Mittal, Anubhav; Hickey, Anthony JR; Chai, Chau C; Loveday, Benjamin PT; Thompson, Nichola; Dare, Anna; Delahunt, Brett; Cooper, Garth JS; Windsor, John A; Phillips, Anthony RJ

2011-01-01

Introduction Multiple organ dysfunction is the main cause of death in severe acute pancreatitis. Primary mitochondrial dysfunction plays a central role in the development and progression of organ failure in critical illness. The present study investigated mitochondrial function in seven tissues during early experimental acute pancreatitis. Methods Twenty-eight male Wistar rats (463 ± 2 g; mean ± SEM) were studied. Group 1 (n = 8), saline control; Group 2 (n = 6), caerulein-induced mild acute pancreatitis; Group 3 (n = 7) sham surgical controls; and Group 4 (n = 7), taurocholate-induced severe acute pancreatitis. Animals were euthanased at 6 h from the induction of acute pancreatitis and mitochondrial function was assessed in the heart, lung, liver, kidney, pancreas, duodenum and jejunum by mitochondrial respirometry. Results Significant early mitochondrial dysfunction was present in the pancreas, lung and jejunum in both models of acute pancreatitis, however, the Heart, liver, kidney and duodenal mitochondria were unaffected. Conclusions The present study provides the first description of early organ-selective mitochondrial dysfunction in the lung and jejunum during acute pancreatitis. Research is now needed to identify the underlying pathophysiology behind the organ selective mitochondrial dysfunction, and the potential benefits of early mitochondrial-specific therapies in acute pancreatitis. PMID:21492333

Reactive Oxygene Species and Thioredoxin Activity in Plants at Development of Hypergravity and Oxidative Stresses

NASA Astrophysics Data System (ADS)

Jadko, Sergiy

Early increasing of reactive oxygen species (ROS) content, including H2O2, occurs in plant cells under various impacts and than these ROS can function as signaling molecules in starting of cell stress responses. At the same time thioredoxins (TR) are significant ROS and H2O2 sensors and transmitters to activation of various redox sensitive proteins, transcription factors and MAP kinases. This study was aimed to investigate early increasing of ROS and H2O2 contents and TR activity in the pea roots and in tissue culture under hypergravity and oxidative stresses. Pea roots of 3-5 days old seedlings and 12-14 days old tissue culture of Arabidopsis thaliana were studied. The pea seedlings were grown on wet filter paper and the tissue culture was grown on MS medium in dark conditions under 24oC. Hypergravity stress was induced by centrifugation at 10 and 15 g. Chemiluminescence (ChL) intensity for ROS concentration, H2O2 content and TR activity were determined. All experiments were repeated by 3-5 times. Early and reliable increasing of ChL intensity and H2O2 contents in the pea roots and in the tissue culture took place under hypergravity and oxidative stresses to 30, 60 and 90 min. At the same time TR activity increased on 11 and 19 percents only to 60 and 90 min. Thus under hypergravity and oxidative stresses in both investigated plants take place early increasing of ROS and H2O2 contents which as second messengers lead to increasing of TR activity with creating of ROS-TR stress signaling pathway.

Early detection of schizophrenia: current evidence and future perspectives

PubMed Central

HÄFNER, HEINZ; MAURER, KURT

2006-01-01

Research into the early course of schizophrenia has identified a prepsychotic prodromal stage (mean duration: 4.8 years) and a psychotic prephase (mean duration: 1.3 years). Comparisons of individually matched samples have demonstrated prodromal symptoms common to schizophrenia and moderate to severe depression. It is not until positive symptoms emerge that psychosis and mood disorders become distinguishable from each other. In both disorders the prodromal stage early produces functional impairment and related social consequences. Hence, early intervention is of great public health relevance. This intervention is targeted at manifest symptoms and not at the underlying, still unknown disease process. Cognitive-behavioural therapy at the prepsychotic prodromal stage seems to favourably influence the short-term illness course. In the psychotic prephase, a combination with low-dose antipsychotics seems to have some efficacy. The aim of early recognition by the instruments discussed in this paper is to permit the identification of the largest possible proportion of at-risk persons as early as possible and their referral to appropriate treatment. PMID:17139339

Scotopic vision deficits in young monkeys exposed to lead.

PubMed

Bushnell, P J; Bowman, R E; Allen, J R; Marlar, R J

1977-04-15

Rhesus monkeys were reared on diets designed to produce blood lead concentrations of 14 (untreated), 55, or 85 micrograms per 100 milliliters for the first year of life. Eighteen months later, blood lead levels were normal in all animals. At this time, however, visual discrimination performance in the 85-microgram group was impaired under dim light relative both to their own performance under bright light and to the performance of the other groups under all light levels used. We interpret these results to reflect a deleterious, enduring impairment of scotopic visual function (night blindness) as a result of early lead intoxication.

The Cerebellum and Neurodevelopmental Disorders.

PubMed

Stoodley, Catherine J

2016-02-01

Cerebellar dysfunction is evident in several developmental disorders, including autism, attention deficit-hyperactivity disorder (ADHD), and developmental dyslexia, and damage to the cerebellum early in development can have long-term effects on movement, cognition, and affective regulation. Early cerebellar damage is often associated with poorer outcomes than cerebellar damage in adulthood, suggesting that the cerebellum is particularly important during development. Differences in cerebellar development and/or early cerebellar damage could impact a wide range of behaviors via the closed-loop circuits connecting the cerebellum with multiple cerebral cortical regions. Based on these anatomical circuits, behavioral outcomes should depend on which cerebro-cerebellar circuits are affected. Here, we briefly review cerebellar structural and functional differences in autism, ADHD, and developmental dyslexia, and discuss clinical outcomes following pediatric cerebellar damage. These data confirm the prediction that abnormalities in different cerebellar subregions produce behavioral symptoms related to the functional disruption of specific cerebro-cerebellar circuits. These circuits might also be crucial to structural brain development, as peri-natal cerebellar lesions have been associated with impaired growth of the contralateral cerebral cortex. The specific contribution of the cerebellum to typical development may therefore involve the optimization of both the structure and function of cerebro-cerebellar circuits underlying skill acquisition in multiple domains; when this process is disrupted, particularly in early development, there could be long-term alterations of these neural circuits, with significant impacts on behavior.

The cerebellum and neurodevelopmental disorders

PubMed Central

Stoodley, Catherine J.

2015-01-01

Cerebellar dysfunction is evident in several developmental disorders, including autism, attention deficit hyperactivity disorder (ADHD), and developmental dyslexia, and damage to the cerebellum early in development can have long-term effects on movement, cognition, and affective regulation. Early cerebellar damage is often associated with poorer outcomes than cerebellar damage in adulthood, suggesting that the cerebellum is particularly important during development. Differences in cerebellar development and/or early cerebellar damage could impact a wide range of behaviors via the closed-loop circuits connecting the cerebellum with multiple cerebral cortical regions. Based on these anatomical circuits, behavioral outcomes should depend on which cerebro-cerebellar circuits are affected. Here, we briefly review cerebellar structural and functional differences in autism, ADHD, and developmental dyslexia, and discuss clinical outcomes following pediatric cerebellar damage. These data confirm the prediction that abnormalities in different cerebellar subregions produce behavioral symptoms related to the functional disruption of specific cerebro-cerebellar circuits. These circuits might also be crucial to structural brain development, as peri-natal cerebellar lesions have been associated with impaired growth of the contralateral cerebral cortex. The specific contribution of the cerebellum to typical development may therefore involve the optimization of both the structure and function of cerebro-cerebellar circuits underlying skill acquisition in multiple domains; when this process is disrupted, particularly in early development, there could be long-term alterations of these neural circuits, with significant impacts on behavior. PMID:26298473

Dual function of CD70 in viral infection: modulator of early cytokine responses and activator of adaptive responses1

PubMed Central

Allam, Atef; Swiecki, Melissa; Vermi, William; Ashwell, Jonathan D.; Colonna, Marco

2014-01-01

The role of the tumor necrosis factor family member CD70 in adaptive T cell responses has been intensively studied but its function in innate responses is still under investigation. Here we show that CD70 inhibits the early innate response to murine cytomegalovirus (MCMV) but is essential for the optimal generation of virus-specific CD8 T cells. CD70-/- mice reacted to MCMV infection with a robust type I interferon and proinflammatory cytokine response. This response was sufficient for initial control of MCMV, although at later time points, CD70-/- mice became more susceptible to MCMV infection. The heightened cytokine response during the early phase of MCMV infection in CD70-/- mice was paralleled by a reduction in regulatory T cells (Treg). Treg from naïve CD70-/- mice were not as efficient at suppressing T cell proliferation compared to Treg from naïve WT mice and depletion of Treg during MCMV infection in Foxp3-DTR mice or in WT mice recapitulated the phenotype observed in CD70-/- mice. Our study demonstrates that while CD70 is required for the activation of the antiviral adaptive response, it has a regulatory role in early cytokine responses to viruses such as MCMV, possibly through maintenance of Treg survival and function. PMID:24913981

Effects of therapeutic interventions for foster children on behavioral problems, caregiver attachment, and stress regulatory neural systems.

PubMed

Fisher, Philip A; Gunnar, Megan R; Dozier, Mary; Bruce, Jacqueline; Pears, Katherine C

2006-12-01

Young children in foster care are exposed to high levels of stress. These experiences place foster children at risk for poor social, academic, and mental heath outcomes. The role of adverse events in stimulating neurobiological stress responses presumably plays a role in shaping neural systems that contribute to these problems. Systematic and developmentally well-timed interventions might have the potential to change developmental trajectories and promote resilience. Moreover, understanding how specific dimensions of early adversity affect underlying stress response systems and how alterations in these systems are related to later psychosocial outcomes might facilitate more precise and targeted interventions. Data are drawn from two ongoing randomized trials involving foster infants/toddlers and preschoolers. Consistent with prior animal models of early adversity, these studies have shown that early adversity-particularly neglect, younger age at first foster placement, and higher number of placements-is associated with altered hypothalamic-pituitary-adrenal (HPA) axis function. The interventions under investigation have produced evidence that it is possible to impact many areas that have been negatively affected by early stress, including HPA axis activity, behavior, and attachment to caregivers.

Daidzein Augments Cholesterol Homeostasis via ApoE to Promote Functional Recovery in Chronic Stroke

PubMed Central

Kim, Eunhee; Woo, Moon-Sook; Qin, Luye; Ma, Thong; Beltran, Cesar D.; Bao, Yi; Bailey, Jason A.; Corbett, Dale; Ratan, Rajiv R.; Lahiri, Debomoy K.

2015-01-01

Stroke is the world's leading cause of physiological disability, but there are currently no available agents that can be delivered early after stroke to enhance recovery. Daidzein, a soy isoflavone, is a clinically approved agent that has a neuroprotective effect in vitro, and it promotes axon growth in an animal model of optic nerve crush. The current study investigates the efficacy of daidzein on neuroprotection and functional recovery in a clinically relevant mouse model of stroke recovery. In light of the fact that cholesterols are essential lipid substrates in injury-induced synaptic remodeling, we found that daidzein enhanced the cholesterol homeostasis genetic program, including Lxr and downstream transporters, Apoe, Abca1, and Abcg1 genes in vitro. Daidzein also elevated the cholesterol homeostasis genes in the poststroke brain with Apoe, the highest expressing transporter, but did not affect infarct volume or hemispheric swelling. Despite the absence of neuroprotection, daidzein improved motor/gait function in chronic stroke and elevated synaptophysin expression. However, the daidzein-enhanced functional benefits and synaptophysin expression were abolished in Apoe-knock-out mice, suggesting the importance of daidzein-induced ApoE upregulation in fostering stroke recovery. Dissociation between daidzein-induced functional benefits and the absence of neuroprotection further suggest the presence of nonoverlapping mechanisms underlying recovery processes versus acute pathology. With its known safety in humans, early and chronic use of daidzein aimed at augmenting ApoE may serve as a novel, translatable strategy to promote functional recovery in stroke patients without adverse acute effect. SIGNIFICANCE STATEMENT There have been recurring translational failures in treatment strategies for stroke. One underlying issue is the disparity in outcome analysis between animal and clinical studies. The former mainly depends on acute infarct size, whereas long-term functional recovery is an important outcome in patients. In an attempt to identify agents that promote functional recovery, we discovered that an FDA-approved soy isoflavone, daidzein, improved stroke-induced behavioral deficits via enhancing cholesterol homeostasis in chronic stroke, and this occurs without causing adverse effects in the acute phase. With its known safety in humans, the study suggests that the early and chronic use of daidzein serves as a potential strategy to promote functional recovery in stroke patients. PMID:26558782

Daidzein Augments Cholesterol Homeostasis via ApoE to Promote Functional Recovery in Chronic Stroke.

PubMed

Kim, Eunhee; Woo, Moon-Sook; Qin, Luye; Ma, Thong; Beltran, Cesar D; Bao, Yi; Bailey, Jason A; Corbett, Dale; Ratan, Rajiv R; Lahiri, Debomoy K; Cho, Sunghee

2015-11-11

Stroke is the world's leading cause of physiological disability, but there are currently no available agents that can be delivered early after stroke to enhance recovery. Daidzein, a soy isoflavone, is a clinically approved agent that has a neuroprotective effect in vitro, and it promotes axon growth in an animal model of optic nerve crush. The current study investigates the efficacy of daidzein on neuroprotection and functional recovery in a clinically relevant mouse model of stroke recovery. In light of the fact that cholesterols are essential lipid substrates in injury-induced synaptic remodeling, we found that daidzein enhanced the cholesterol homeostasis genetic program, including Lxr and downstream transporters, Apoe, Abca1, and Abcg1 genes in vitro. Daidzein also elevated the cholesterol homeostasis genes in the poststroke brain with Apoe, the highest expressing transporter, but did not affect infarct volume or hemispheric swelling. Despite the absence of neuroprotection, daidzein improved motor/gait function in chronic stroke and elevated synaptophysin expression. However, the daidzein-enhanced functional benefits and synaptophysin expression were abolished in Apoe-knock-out mice, suggesting the importance of daidzein-induced ApoE upregulation in fostering stroke recovery. Dissociation between daidzein-induced functional benefits and the absence of neuroprotection further suggest the presence of nonoverlapping mechanisms underlying recovery processes versus acute pathology. With its known safety in humans, early and chronic use of daidzein aimed at augmenting ApoE may serve as a novel, translatable strategy to promote functional recovery in stroke patients without adverse acute effect. There have been recurring translational failures in treatment strategies for stroke. One underlying issue is the disparity in outcome analysis between animal and clinical studies. The former mainly depends on acute infarct size, whereas long-term functional recovery is an important outcome in patients. In an attempt to identify agents that promote functional recovery, we discovered that an FDA-approved soy isoflavone, daidzein, improved stroke-induced behavioral deficits via enhancing cholesterol homeostasis in chronic stroke, and this occurs without causing adverse effects in the acute phase. With its known safety in humans, the study suggests that the early and chronic use of daidzein serves as a potential strategy to promote functional recovery in stroke patients. Copyright © 2015 the authors 0270-6474/15/3515113-14$15.00/0.

MRI uncovers disrupted hippocampal microstructure that underlies memory impairments after early-life adversity.

PubMed

Molet, Jenny; Maras, Pamela M; Kinney-Lang, Eli; Harris, Neil G; Rashid, Faisal; Ivy, Autumn S; Solodkin, Ana; Obenaus, Andre; Baram, Tallie Z

2016-12-01

Memory and related cognitive functions are progressively impaired in a subgroup of individuals experiencing childhood adversity and stress. However, it is not possible to identify vulnerable individuals early, a crucial step for intervention. In this study, high-resolution magnetic resonance imaging (MRI) and intra-hippocampal diffusion tensor imaging (DTI) were employed to examine for structural signatures of cognitive adolescent vulnerabilities in a rodent model of early-life adversity. These methods were complemented by neuroanatomical and functional assessments of hippocampal network integrity during adolescence, adulthood and middle-age. The high-resolution MRI identified selective loss of dorsal hippocampal volume, and intra-hippocampal DTI uncovered disruption of dendritic structure, consistent with disrupted local connectivity, already during late adolescence in adversity-experiencing rats. Memory deteriorated over time, and stunting of hippocampal dendritic trees was apparent on neuroanatomical analyses. Thus, disrupted hippocampal neuronal structure and connectivity, associated with cognitive impairments, are detectable via non-invasive imaging modalities in rats experiencing early-life adversity. These high-resolution imaging approaches may constitute promising tools for prediction and assessment of at-risk individuals in the clinic. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Approach to the critically ill camelid.

PubMed

Bedenice, Daniela

2009-07-01

The estimation of fluid deficits in camelids is challenging. However, early recognition and treatment of shock and hypovolemia is instrumental to improve morbidity and mortality of critically ill camelids. Early goal-directed fluid therapy requires specific knowledge of clinical indicators of hypovolemia and assessment of resuscitation endpoints, but may significantly enhance the understanding, monitoring, and safety of intravenous fluid therapy in South American camelids (SAC). It is important to recognize that over-aggressive fluid resuscitation is just as detrimental as under resuscitation. Nonetheless, a protocol of conservative fluid management is often indicated in the treatment of camelids with pulmonary inflammation, to counteract edema formation. The early recognition of lung dysfunction is often based on advanced diagnostic techniques, including arterial blood gas analysis, diagnostic imaging, and noninvasive pulmonary function testing.

Caregiver Ratings of Long-term Executive Dysfunction and Attention Problems After Early Childhood Traumatic Brain Injury: Family Functioning Is Important

PubMed Central

Kurowski, Brad G.; Taylor, H. Gerry; Yeates, Keith Owen; Walz, Nicolay C.; Stancin, Terry; Wade, Shari L.

2013-01-01

Objective To evaluate the relationship of family and parenting factors to long-term executive dysfunction and attention problems after early childhood traumatic brain injury (TBI). We hypothesized that the magnitude of executive dysfunction and attention problems would be moderated by family and parenting factors. Design A multicenter, prospective cohort study that included an orthopedic injury (OI) reference group. Setting Three tertiary academic children’s hospital medical centers and one general medical center. Participants Children, ages 3–7 years, hospitalized for OI, moderate TBI, or severe TBI. Methods and Outcome Measurements Parental ratings of family functioning and parenting styles were obtained 18 months after the injury occurred. The main outcome measurements, which were parental ratings of children’s executive function and attention, were performed at least 24 months after the injury occurred (mean, 39 months; range, 25–63 months). Analysis Group comparisons were conducted with use of t-tests, χ2 analysis, analysis of variance, and Pearson and Spearman correlations. Regression analysis was used to examine associations of the outcomes with family functioning and parenting styles and to test moderating effects of these factors on group differences. Results Participants with severe TBI demonstrated increased executive dysfunction and attention problems compared with those who sustained moderate TBI or OI. Lower levels of family dysfunction were associated with better executive function and attention across groups but did not moderate group differences. However, attention deficits after severe TBI were exacerbated under conditions of more permissive parenting relative to attention deficits after OIs. Conclusions Executive function and attention problems persisted on a long-term basis (>24 months) after early childhood TBI, and positive global family functioning and nonpermissive parenting were associated with better outcomes. Better characterization of the optimal family environment for recovery from early childhood TBI could help target future interventions. PMID:21944301

Caregiver ratings of long-term executive dysfunction and attention problems after early childhood traumatic brain injury: family functioning is important.

PubMed

Kurowski, Brad G; Taylor, H Gerry; Yeates, Keith Owen; Walz, Nicolay C; Stancin, Terry; Wade, Shari L

2011-09-01

To evaluate the relationship of family and parenting factors to long-term executive dysfunction and attention problems after early childhood traumatic brain injury (TBI). We hypothesized that the magnitude of executive dysfunction and attention problems would be moderated by family and parenting factors. A multicenter, prospective cohort study that included an orthopedic injury (OI) reference group. Three tertiary academic children's hospital medical centers and one general medical center. Children, ages 3-7 years, hospitalized for OI, moderate TBI, or severe TBI. METHODS AND OUTCOME MEASUREMENTS: Parental ratings of family functioning and parenting styles were obtained 18 months after the injury occurred. The main outcome measurements, which were parental ratings of children's executive function and attention, were performed at least 24 months after the injury occurred (mean, 39 months; range, 25-63 months). Group comparisons were conducted with use of t-tests, χ(2) analysis, analysis of variance, and Pearson and Spearman correlations. Regression analysis was used to examine associations of the outcomes with family functioning and parenting styles and to test moderating effects of these factors on group differences. Participants with severe TBI demonstrated increased executive dysfunction and attention problems compared with those who sustained moderate TBI or OI. Lower levels of family dysfunction were associated with better executive function and attention across groups but did not moderate group differences. However, attention deficits after severe TBI were exacerbated under conditions of more permissive parenting relative to attention deficits after OIs. Executive function and attention problems persisted on a long-term basis (>24 months) after early childhood TBI, and positive global family functioning and nonpermissive parenting were associated with better outcomes. Better characterization of the optimal family environment for recovery from early childhood TBI could help target future interventions. Copyright © 2011 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.

Relation of Perinatal Risk and Early Parenting to Executive Control at the Transition to School

ERIC Educational Resources Information Center

Clark, Caron A. C.; Woodward, Lianne J.

2015-01-01

Executive control (EC) develops rapidly during the preschool years and is central to academic achievement and functional outcome. Although children with perinatal adversity are at known risk for EC impairments, little is known about the underlying nature of these impairments or the mechanisms that contribute to their development over time. Drawing…

Types and status of high reliability practices in the federal fire community (Abstract)

Treesearch

Anne Black; Brooke McBride

2012-01-01

Since emerging in the late 1980s, the paradigm of High Reliability Organizing (HRO) has sought to describe how and why certain organizations consistently function safely under hazardous conditions. Researchers have explored a variety of industrial situations, from the early observations of nuclear aircraft carrier operations to nursing units and even high-tech IPOs....

Functional Brain Organization for Number Processing in Pre-Verbal Infants

ERIC Educational Resources Information Center

Edwards, Laura A.; Wagner, Jennifer B.; Simon, Charline E.; Hyde, Daniel C.

2016-01-01

Humans are born with the ability to mentally represent the approximate numerosity of a set of objects, but little is known about the brain systems that sub-serve this ability early in life and their relation to the brain systems underlying symbolic number and mathematics later in development. Here we investigate processing of numerical magnitudes…

Neural Connectivity Patterns Underlying Symbolic Number Processing Indicate Mathematical Achievement in Children

ERIC Educational Resources Information Center

Park, Joonkoo; Li, Rosa; Brannon, Elizabeth M.

2014-01-01

In early childhood, humans learn culturally specific symbols for number that allow them entry into the world of complex numerical thinking. Yet little is known about how the brain supports the development of the uniquely human symbolic number system. Here, we use functional magnetic resonance imaging along with an effective connectivity analysis…

Functional Hemispheric Asymmetries of Global/Local Processing Mirrored by the Steady-State Visual Evoked Potential

ERIC Educational Resources Information Center

Martens, Ulla; Hubner, Ronald

2013-01-01

While hemispheric differences in global/local processing have been reported by various studies, it is still under dispute at which processing stage they occur. Primarily, it was assumed that these asymmetries originate from an early perceptual stage. Instead, the content-level binding theory (Hubner & Volberg, 2005) suggests that the hemispheres…

Associating Neural Alterations and Genotype in Autism and Fragile X Syndrome: Incorporating Perceptual Phenotypes in Causal Modeling

ERIC Educational Resources Information Center

Bertone, Armando; Hanck, Julie; Kogan, Cary; Chaudhuri, Avi; Cornish, Kim

2010-01-01

We have previously described (see companion paper, this issue) the utility of using perceptual signatures for defining and dissociating condition-specific neural functioning underlying early visual processes in autism and FXS. These perceptually-driven hypotheses are based on differential performance evidenced only at the earliest stages of visual…

[Treatment of metaphyseal fractures of shin bones by the method of blocking osteosynthesis].

PubMed

Neverov, V A; Khromov, A A; Cherniaev, S N; Egorov, K S; Shebarshov, A L

2008-01-01

The proposed method of reposition and polyaxial stabilization of fragments for intramedullary meallosynthesis of fractures of long tubular bones allows blocking osteosynthesis to be successfully used in treatment of complex metaphyseal fractures of shin bones. It results in strong fixation of the fragments, makes it possible to successfully eliminate residual deformities after introduction of the nail and to avoid the development of them in future under the influence of loading. The method provides early functioning of the interfacing joints, early axial loading, shorter period of disability, the absence of external immobilization.

Initial home health outcomes under prospective payment.

PubMed

Schlenker, Robert E; Powell, Martha C; Goodrich, Glenn K

2005-02-01

To assess initial changes in home health patient outcomes under Medicare's home health Prospective Payment System (PPS), implemented by the Centers for Medicare and Medicaid Services (CMS) in October 2000. Pre-PPS and early PPS data were obtained from CMS Outcome and Assessment Information Set (OASIS) and Medicare claims files. Regression analysis was applied to national random samples (n=164,810) to estimate pre-PPS/PPS outcome and visit-per-episode changes. Outcome episodes were constructed from OASIS data and linked with Medicare claims data on visits. Outcome changes (risk adjusted) were mixed and generally modest. Favorable changes included higher improvement rates under PPS for functioning and dyspnea, higher community discharge rates, and lower hospitalization and emergent care rates. Most stabilization (nonworsening) outcome rates also increased. However, improvement rates were lower under PPS for wounds, incontinence, and cognitive and emotional/behavioral outcomes. Total visits per episode (case-mix adjusted) declined 16.6 percent although therapy visits increased by 8.4 percent. The outcome and visit results suggest improved system efficiency under PPS (fewer visits, similar outcomes). However, declines in several improvement rates merit ongoing monitoring, as do subsequent (posthome health) hospitalization and emergent care use. Since only the early PPS period was examined, longer-term analyses are needed.

Validation of the Early Functional Abilities scale: An assessment of four dimensions in early recovery after traumatic brain injury.

PubMed

Poulsen, Ingrid; Kreiner, Svend; Engberg, Aase W

2018-02-13

The Early Functional Abilities scale assesses the restoration of brain function after brain injury, based on 4 dimensions. The primary objective of this study was to evaluate the validity, objectivity, reliability and measurement precision of the Early Functional Abilities scale by Rasch model item analysis. A secondary objective was to examine the relationship between the Early Functional Abilities scale and the Functional Independence Measurement™, in order to establish the criterion validity of the Early Functional Abilities scale and to compare the sensitivity of measurements using the 2 instruments. The Rasch analysis was based on the assessment of 408 adult patients at admission to sub-acute rehabilitation in Copenhagen, Denmark after traumatic brain injury. The Early Functional Abilities scale provides valid and objective measurement of vegetative (autonomic), facio-oral, sensorimotor and communicative/cognitive functions. Removal of one item from the sensorimotor scale confirmed unidimensionality for each of the 4 subscales, but not for the entire scale. The Early Functional Abilities subscales are sensitive to differences between patients in ranges in which the Functional Independence Measurement™ has a floor effect. The Early Functional Abilities scale assesses the early recovery of important aspects of brain function after traumatic brain injury, but is not unidimensional. We recommend removal of the "standing" item and calculation of summary subscales for the separate dimensions.

Trans-Golgi network/early endosome: a central sorting station for cargo proteins in plant immunity.

PubMed

LaMontagne, Erica D; Heese, Antje

2017-12-01

In plants, the trans-Golgi network (TGN) functionally overlaps with the early endosome (EE), serving as a central sorting hub to direct newly synthesized and endocytosed cargo to the cell surface or vacuole. Here, we focus on the emerging role of the TGN/EE in sorting of immune cargo proteins for effective plant immunity against pathogenic bacteria and fungi. Specific vesicle coat and regulatory components at the TGN/EE ensure that immune cargoes are correctly sorted and transported to the location of their cellular functions. Our understanding of the identity of immune cargoes and the underlying cellular mechanisms regulating their sorting are still rudimentary, but this knowledge is essential to understanding the physiological contribution of the TGN/EE to effective immune responses. Copyright © 2017. Published by Elsevier Ltd.

The distinct emotional flavor of Gnostic writings from the early Christian era.

PubMed

Whissell, Cynthia

2008-02-01

More than 500,000 scored words in 83 documents were used to conclude that it is possible to identify the source of documents (proto-orthodox Christian versus early Gnostic) on the basis of the emotions underlying the words. Twenty-seven New Testament works and seven Gnostic documents (including the gospels of Thomas, Judas, and Mary [Magdalene]) were scored with the Dictionary of Affect in Language. Patterns of emotional word use focusing on eight types of extreme emotional words were employed in a discriminant function analysis to predict source. Prediction was highly successful (canonical r = .81, 97% correct identification of source). When the discriminant function was tested with more than 30 additional Gnostic and Christian works including a variety of translations and some wisdom books, it correctly classified all of them. The majority of the predictive power of the function (97% of all correct categorizations, 70% of the canonical r2) was associated with the preferential presence of passive and passive/pleasant words in Gnostic documents.

Functional roles of flavonoids in photoprotection: new evidence, lessons from the past.

PubMed

Agati, Giovanni; Brunetti, Cecilia; Di Ferdinando, Martina; Ferrini, Francesco; Pollastri, Susanna; Tattini, Massimiliano

2013-11-01

We discuss on the relative significance of different functional roles potentially served by flavonoids in photoprotection, with special emphasis to their ability to scavenge reactive oxygen species (ROS) and control the development of individual organs and whole plant. We propose a model in which chloroplast-located flavonoids scavenge H2O2 and singlet oxygen generated under excess light-stress, thus avoiding programmed cell death. We also draw a picture in which vacuolar flavonoids in conjunction with peroxidases and ascorbic acid constitute a secondary antioxidant system aimed at detoxifying H2O2, which may diffuse out of the chloroplast at considerable rates and enter the vacuole following excess light stress-induced depletion of ascorbate peroxidase. We hypothesize for flavonols key roles as developmental regulators in early and current-day land-plants, based on their ability to modulate auxin movement and auxin catabolism. We show that antioxidant flavonoids display the greatest capacity to regulate key steps of cell growth and differentiation in eukaryotes. These regulatory functions of flavonoids, which are shared by plants and animals, are fully accomplished in the nM concentration range, as likely occurred in early land plants. We therefore conclude that functions of flavonoids as antioxidants and/or developmental regulators flavonoids are of great value in photoprotection. We also suggest that UV-B screening was just one of the multiple functions served by flavonoids when early land-plants faced an abrupt increase in sunlight irradiance. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Contextual modulation revealed by optical imaging exhibits figural asymmetry in macaque V1 and V2.

PubMed

Zarella, Mark D; Ts'o, Daniel Y

2017-01-01

Neurons in early visual cortical areas are influenced by stimuli presented well beyond the confines of their classical receptive fields, endowing them with the ability to encode fine-scale features while also having access to the global context of the visual scene. This property can potentially define a role for the early visual cortex to contribute to a number of important visual functions, such as surface segmentation and figure-ground segregation. It is unknown how extraclassical response properties conform to the functional architecture of the visual cortex, given the high degree of functional specialization in areas V1 and V2. We examined the spatial relationships of contextual activations in macaque V1 and V2 with intrinsic signal optical imaging. Using figure-ground stimulus configurations defined by orientation or motion, we found that extraclassical modulation is restricted to the cortical representations of the figural component of the stimulus. These modulations were positive in sign, suggesting a relative enhancement in neuronal activity that may reflect an excitatory influence. Orientation and motion cues produced similar patterns of activation that traversed the functional subdivisions of V2. The asymmetrical nature of the enhancement demonstrated the capacity for visual cortical areas as early as V1 to contribute to figure-ground segregation, and the results suggest that this information can be extracted from the population activity constrained only by retinotopy, and not the underlying functional organization.

Contextual modulation revealed by optical imaging exhibits figural asymmetry in macaque V1 and V2

PubMed Central

Zarella, Mark D; Ts’o, Daniel Y

2017-01-01

Neurons in early visual cortical areas are influenced by stimuli presented well beyond the confines of their classical receptive fields, endowing them with the ability to encode fine-scale features while also having access to the global context of the visual scene. This property can potentially define a role for the early visual cortex to contribute to a number of important visual functions, such as surface segmentation and figure–ground segregation. It is unknown how extraclassical response properties conform to the functional architecture of the visual cortex, given the high degree of functional specialization in areas V1 and V2. We examined the spatial relationships of contextual activations in macaque V1 and V2 with intrinsic signal optical imaging. Using figure–ground stimulus configurations defined by orientation or motion, we found that extraclassical modulation is restricted to the cortical representations of the figural component of the stimulus. These modulations were positive in sign, suggesting a relative enhancement in neuronal activity that may reflect an excitatory influence. Orientation and motion cues produced similar patterns of activation that traversed the functional subdivisions of V2. The asymmetrical nature of the enhancement demonstrated the capacity for visual cortical areas as early as V1 to contribute to figure–ground segregation, and the results suggest that this information can be extracted from the population activity constrained only by retinotopy, and not the underlying functional organization. PMID:28761385

Age-related functional brain changes in young children.

PubMed

Long, Xiangyu; Benischek, Alina; Dewey, Deborah; Lebel, Catherine

2017-07-15

Brain function and structure change significantly during the toddler and preschool years. However, most studies focus on older or younger children, so the specific nature of these changes is unclear. In the present study, we analyzed 77 functional magnetic resonance imaging datasets from 44 children aged 2-6 years. We extracted measures of both local (amplitude of low frequency fluctuation and regional homogeneity) and global (eigenvector centrality mapping) activity and connectivity, and examined their relationships with age using robust linear correlation analysis and strict control for head motion. Brain areas within the default mode network and the frontoparietal network, such as the middle frontal gyrus, the inferior parietal lobule and the posterior cingulate cortex, showed increases in local and global functional features with age. Several brain areas such as the superior parietal lobule and superior temporal gyrus presented opposite development trajectories of local and global functional features, suggesting a shifting connectivity framework in early childhood. This development of functional connectivity in early childhood likely underlies major advances in cognitive abilities, including language and development of theory of mind. These findings provide important insight into the development patterns of brain function during the preschool years, and lay the foundation for future studies of altered brain development in young children with brain disorders or injury. Copyright © 2017 Elsevier Inc. All rights reserved.

Computer codes developed and under development at Lewis

NASA Technical Reports Server (NTRS)

Chamis, Christos C.

1992-01-01

The objective of this summary is to provide a brief description of: (1) codes developed or under development at LeRC; and (2) the development status of IPACS with some typical early results. The computer codes that have been developed and/or are under development at LeRC are listed in the accompanying charts. This list includes: (1) the code acronym; (2) select physics descriptors; (3) current enhancements; and (4) present (9/91) code status with respect to its availability and documentation. The computer codes list is grouped by related functions such as: (1) composite mechanics; (2) composite structures; (3) integrated and 3-D analysis; (4) structural tailoring; and (5) probabilistic structural analysis. These codes provide a broad computational simulation infrastructure (technology base-readiness) for assessing the structural integrity/durability/reliability of propulsion systems. These codes serve two other very important functions: they provide an effective means of technology transfer; and they constitute a depository of corporate memory.

Poverty, physical stature, and cognitive skills: Mechanisms underlying children's school enrollment in Zambia.

PubMed

McCoy, Dana Charles; Zuilkowski, Stephanie Simmons; Fink, Günther

2015-05-01

Past research suggests robust positive associations between household socioeconomic status and children's early cognitive development in Western countries. Relatively little is known about these relations in low-income country settings characterized by economic adversity, high prevalence of malnutrition and infectious disease, and relatively lower school enrollment. The present study develops and empirically evaluates an adapted model of early childhood development using a sample of 2,711 Zambian 6-year-olds. Early learning in and out of the home was found to explain much of the relation between socioeconomic status and children's cognitive skills, including language, nonverbal reasoning, and executive function. Child height-for-age (a proxy for overall nutritional status and health) was also predictive of children's cognitive skills and both early and on-time school enrollment. Implications for global child development, intervention, and future work are discussed. (c) 2015 APA, all rights reserved).

Blood-brain barrier and its function during inflammation and autoimmunity.

PubMed

Sonar, Sandip Ashok; Lal, Girdhari

2018-05-01

The blood-brain barrier (BBB) is an important physiologic barrier that separates CNS from soluble inflammatory mediators and effector immune cells from peripheral circulation. The optimum function of the BBB is necessary for the homeostasis, maintenance, and proper neuronal function. The clinical and experimental findings have shown that BBB dysfunction is an early hallmark of various neurologic disorders ranging from inflammatory autoimmune, neurodegenerative, and traumatic diseases to neuroinvasive infections. Significant progress has been made in the understanding of the regulation of BBB function under homeostatic and neuroinflammatory conditions. Several neurologic disease-modifying drugs have shown to improve the BBB function. However, they have a broad-acting immunomodulatory function and can increase the risk of life-threatening infections. The recent development of in vitro multicomponent 3-dimensional BBB models coupled with fluidics chamber as well as a cell-type specific reporter and knockout mice gave a new boost to our understanding of the dynamics of the BBB. In the review, we discuss the current understanding of BBB composition and recent findings that illustrate the critical regulatory elements of the BBB function under physiologic and inflammatory conditions, and also suggested the strategies to control BBB structure and function. ©2018 Society for Leukocyte Biology.

What has fMRI told us about the Development of Cognitive Control through Adolescence?

PubMed Central

Luna, Beatriz; Padmanabhan, Aarthi; O’Hearn, Kirsten

2009-01-01

Cognitive control, the ability to voluntarily guide our behavior, continues to improve throughout adolescence. Below we review the literature on age-related changes in brain function related to response inhibition and working memory, which support cognitive control. Findings from studies using functional magnetic imaging (fMRI) indicate that processing errors, sustaining a cognitive control state, and reaching adult levels of precision, persist through adolescence. Developmental changes in patterns of brain function suggest that core regions of the circuitry underlying cognitive control are on-line early in development. However, age-related changes in localized processes across the brain and in establishing long range connections that support top-down modulation of behavior may support more effective neural processing for optimal mature executive function. While great progress has been made in understanding the age-related changes in brain processes underlying cognitive development, there are still important challenges in developmental neuroimaging methods and the interpretation of data that need to be addressed. PMID:19765880

Understanding early elementary children's conceptual knowledge of plant structure and function through drawings.

PubMed

Anderson, Janice L; Ellis, Jane P; Jones, Alan M

2014-01-01

This study examined children's drawings to explain children's conceptual understanding of plant structure and function. The study explored whether the children's drawings accurately reflect their conceptual understanding about plants in a manner that can be interpreted by others. Drawing, survey, interview, and observational data were collected from 182 students in grades K and 1 in rural southeastern United States. Results demonstrated the children held a wide range of conceptions concerning plant structure and function. These young children held very simple ideas about plants with respect to both their structure and function. Consistent with the drawings, the interviews presented similar findings. © 2014 J. L. Anderson et al. CBE—Life Sciences Education © 2014 The American Society for Cell Biology. This article is distributed by The American Society for Cell Biology under license from the author(s). It is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

Patterns of Spontaneous Local Network Activity in Developing Cerebral Cortex: Relationship to Adult Cognitive Function.

PubMed

Peinado, Alejandro; Abrams, Charles K

2015-01-01

Detecting neurodevelopμental disorders of cognition at the earliest possible stages could assist in understanding them mechanistically and ultimately in treating them. Finding early physiological predictors that could be visualized with functional neuroimaging would represent an important advance in this regard. We hypothesized that one potential source of physiological predictors is the spontaneous local network activity prominent during specific periods in development. To test this we used calcium imaging in brain slices and analyzed variations in the frequency and intensity of this early activity in one area, the entorhinal cortex (EC), in order to correlate early activity with level of cognitive function later in life. We focused on EC because of its known role in different types of cognitive processes and because it is an area where spontaneous activity is prominent during early postnatal development in rodent models of cortical development. Using rat strains (Long-Evans, Wistar, Sprague-Dawley and Brattleboro) known to differ in cognitive performance in adulthood we asked whether neonatal animals exhibit corresponding strain-related differences in EC spontaneous activity. Our results show significant differences in this activity between strains: compared to a high cognitive-performing strain, we consistently found an increase in frequency and decrease in intensity in neonates from three lower performing strains. Activity was most different in one strain considered a model of schizophrenia-like psychopathology. While we cannot necessarily infer a causal relationship between early activity and adult cognition our findings suggest that the pattern of spontaneous activity in development could be an early predictor of a developmental trajectory advancing toward sub-optimal cognitive performance in adulthood. Our results further suggest that the strength of dopaminergic signaling, by setting the balance between excitation and inhibition, is a potential underlying mechanism that could explain the observed differences in early spontaneous activity patterns.

Types and status of high reliability practices in the US federal wildland fire community

Treesearch

Anne E. Black

2012-01-01

Since emerging in the late 1980s, the paradigm of High Reliability Organizing (HRO) has sought to describe how and why certain organizations consistently function safely under hazardous conditions. Researchers have explored a variety of industrial situations, from the early observations of nuclear aircraft carrier operations to nursing units and even high-tech IPOs....

Functional Dyspepsia: Advances in Diagnosis and Therapy

PubMed Central

Talley, Nicholas J.

2017-01-01

Functional dyspepsia (FD) is a common but under-recognized syndrome comprising bothersome recurrent postprandial fullness, early satiety, or epigastric pain/burning. Epidemiologically, there are two clinically distinct FD syndromes (although these often overlap clinically): postprandial distress syndrome (PDS; comprising early satiety or meal-related fullness) and epigastric pain syndrome. Symptoms of gastroesophageal reflux disease overlap with FD more than expected by chance; a subset has pathological acid reflux. The pre-test probability of FD in a patient who presents with classical FD symptoms and no alarm features is high, approximately 0.7. Coexistent heartburn should not lead to the exclusion of FD as a diagnosis. One of the most exciting observations in FD has been the consistent finding of increased duodenal eosinophilia, notably in PDS. Small bowel homing T cells, signaling intestinal inflammation, and increased cytokines have been detected in the circulation, and elevated tumor necrosis factor-α levels have been significantly correlated with increased anxiety. Postinfectious gastroenteritis is a risk factor for FD. Therapeutic options remain limited and provide only symptomatic benefit in most cases. Only one therapy is known to change the natural history of FD–Helicobacter pylori eradication. Treatment of duodenal eosinophilia is under investigation. PMID:28452210

The evolutionary origin of jaw yaw in mammals

PubMed Central

Grossnickle, David M.

2017-01-01

Theria comprises all but three living mammalian genera and is one of the most ecologically pervasive clades on Earth. Yet, the origin and early history of therians and their close relatives (i.e., cladotherians) remains surprisingly enigmatic. A critical biological function that can be compared among early mammal groups is mastication. Morphometrics and modeling analyses of the jaws of Mesozoic mammals indicate that cladotherians evolved musculoskeletal anatomies that increase mechanical advantage during jaw rotation around a dorsoventrally-oriented axis (i.e., yaw) while decreasing the mechanical advantage of jaw rotation around a mediolaterally-oriented axis (i.e., pitch). These changes parallel molar transformations in early cladotherians that indicate their chewing cycles included significant transverse movement, likely produced via yaw rotation. Thus, I hypothesize that cladotherian molar morphologies and musculoskeletal jaw anatomies evolved concurrently with increased yaw rotation of the jaw during chewing cycles. The increased transverse movement resulting from yaw rotation may have been a crucial evolutionary prerequisite for the functionally versatile tribosphenic molar morphology, which underlies the molars of all therians and is retained by many extant clades. PMID:28322334

Temporal variation in phenotypic gender and expected functional gender within and among individuals in an annual plant.

PubMed

Austen, Emily J; Weis, Arthur E

2014-07-01

Adaptive explanations for variation in sex allocation centre on variation in resource status and variation in the mating environment. The latter can occur when dichogamy causes siring opportunity to vary across the flowering season. In this study, it is hypothesized that the widespread tendency towards declining fruit-set from first to last flowers on plants can similarly lead to a varying mating environment by causing a temporal shift in the quality (not quantity) of siring opportunities. A numerical model was developed to examine the effects of declining fruit-set on the expected male versus female reproductive success (functional gender) of first and last flowers on plants, and of early- and late-flowering plants. Within- and among-plant temporal variation in pollen production, ovule production and fruit-set in 70 Brassica rapa plants was then characterized to determine if trends in male and female investment mirror expected trends in functional gender. Under a wide range of model conditions, functional femaleness decreased sharply in the last flowers on plants, and increased from early- to late-flowering plants in the population. In B. rapa, pollen production decreased more rapidly than ovule production from first to last flowers, leading to a within-plant increase in phenotypic femaleness. Among plants, ovule production decreased from early- to late-flowering plants, causing a temporal decrease in phenotypic femaleness. The numerical model confirmed that declining fruit-set can drive temporal variation in functional gender, especially among plants. The discrepancy between observed trends in phenotypic gender in B. rapa and expected functional gender predicted by the numerical model does not rule out the possibility that male reproductive success decreases with later flowering onset. If so, plants may experience selection for early flowering through male fitness. © The Author 2014. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

The effect of cannabis use on memory function: an update.

PubMed

Schoeler, Tabea; Bhattacharyya, Sagnik

2013-01-01

Investigating the effects of cannabis use on memory function appears challenging. While early observational investigations aimed to elucidate the longer-term effects of cannabis use on memory function in humans, findings remained equivocal and pointed to a pattern of interacting factors impacting on the relationship between cannabis use and memory function, rather than a simple direct effect of cannabis. Only recently, a clearer picture of the chronic and acute effects of cannabis use on memory function has emerged once studies have controlled for potential confounding factors and started to investigate the acute effects of delta-9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD), the main ingredients in the extract of the cannabis plant in pharmacological challenge experiments. Relatively consistent findings have been reported regarding the acute impairments induced by a single dose of Δ9-THC on verbal and working memory. It is unclear whether they may persist beyond the intoxication state. In the long-term, these impairments seem particularly likely to manifest and may also persist following abstinence if regular and heavy use of cannabis strains high in Δ9-THC is started at an early age. Although still at an early stage, studies that employed advanced neuroimaging techniques have started to model the neural underpinnings of the effects of cannabis use and implicate a network of functional and morphological alterations that may moderate the effects of cannabis on memory function. Future experimental and epidemiological studies that take into consideration individual differences, particularly previous cannabis history and demographic characteristics, but also the precise mixture of the ingredients of the consumed cannabis are necessary to clarify the magnitude and the mechanisms by which cannabis-induced memory impairments occur and to elucidate underlying neurobiological mechanisms.

The effect of cannabis use on memory function: an update

PubMed Central

Schoeler, Tabea; Bhattacharyya, Sagnik

2013-01-01

Investigating the effects of cannabis use on memory function appears challenging. While early observational investigations aimed to elucidate the longer-term effects of cannabis use on memory function in humans, findings remained equivocal and pointed to a pattern of interacting factors impacting on the relationship between cannabis use and memory function, rather than a simple direct effect of cannabis. Only recently, a clearer picture of the chronic and acute effects of cannabis use on memory function has emerged once studies have controlled for potential confounding factors and started to investigate the acute effects of delta-9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD), the main ingredients in the extract of the cannabis plant in pharmacological challenge experiments. Relatively consistent findings have been reported regarding the acute impairments induced by a single dose of Δ9-THC on verbal and working memory. It is unclear whether they may persist beyond the intoxication state. In the long-term, these impairments seem particularly likely to manifest and may also persist following abstinence if regular and heavy use of cannabis strains high in Δ9-THC is started at an early age. Although still at an early stage, studies that employed advanced neuroimaging techniques have started to model the neural underpinnings of the effects of cannabis use and implicate a network of functional and morphological alterations that may moderate the effects of cannabis on memory function. Future experimental and epidemiological studies that take into consideration individual differences, particularly previous cannabis history and demographic characteristics, but also the precise mixture of the ingredients of the consumed cannabis are necessary to clarify the magnitude and the mechanisms by which cannabis-induced memory impairments occur and to elucidate underlying neurobiological mechanisms. PMID:24648785

Impact of an Early Invasive Strategy versus Conservative Strategy for Unstable Angina and Non-ST Elevation Acute Coronary Syndrome in Patients with Chronic Kidney Disease: A Systematic Review

PubMed Central

Shaw, Catriona; Nitsch, Dorothea; Lee, Jasmine; Fogarty, Damian; Sharpe, Claire C.

2016-01-01

Background Clinical practice guidelines support an early invasive approach after NSTE-ACS in patients with chronic kidney disease (CKD). There is no direct randomised controlled trial evidence in the CKD population, and whether the benefit of an early invasive approach is maintained across the spectrum of severity of CKD remains controversial. Methods We conducted a systematic review to evaluate the association between an early invasive approach and all-cause mortality in patients with CKD. We searched MEDLINE and EMBASE (1990-May 2015) and article reference lists. Data describing study design, participants, invasive management strategies, renal function, all-cause mortality and risk of bias were extracted. Results 3,861 potentially relevant studies were identified. Ten studies, representing data on 147,908 individuals with NSTE-ACS met the inclusion criteria. Qualitative heterogeneity in the definitions of early invasive approach, comparison groups and renal dysfunction existed. Meta-analysis of the RCT derived and observational data were generally supportive of an early invasive approach in CKD (RR0.76 (95% CI 0.49–1.17) and RR0.50 (95%CI 0.42–0.59) respectively). Meta-analysis of the observational studies demonstrated a large degree of heterogeneity (I2 79%) driven in part by study size and heterogeneity across various kidney function levels. Conclusions The observational data support that an early invasive approach after NSTE-ACS confers a survival benefit in those with early-moderate CKD. Local opportunities for quality improvement should be sought. Those with severe CKD and the dialysis population are high risk and under-studied. Novel and inclusive approaches for CKD and dialysis patients in cardiovascular clinical trials are needed. PMID:27195786

The combination of indocyanine green clearance test and model for end-stage liver disease score predicts early graft outcome after liver transplantation.

PubMed

Yunhua, Tang; Weiqiang, Ju; Maogen, Chen; Sai, Yang; Zhiheng, Zhang; Dongping, Wang; Zhiyong, Guo; Xiaoshun, He

2018-06-01

Early allograft dysfunction (EAD) and early postoperative complications are two important clinical endpoints when evaluating clinical outcomes of liver transplantation (LT). We developed and validated two ICGR15-MELD models in 87 liver transplant recipients for predicting EAD and early postoperative complications after LT by incorporating the quantitative liver function tests (ICGR15) into the MELD score. Eighty seven consecutive patients who underwent LT were collected and divided into a training cohort (n = 61) and an internal validation cohort (n = 26). For predicting EAD after LT, the area under curve (AUC) for ICGR15-MELD score was 0.876, with a sensitivity of 92.0% and a specificity of 75.0%, which is better than MELD score or ICGR15 alone. The recipients with a ICGR15-MELD score ≥0.243 have a higher incidence of EAD than those with a ICGR15-MELD score <0.243 (P <0.001). For predicting early postoperative complications, the AUC of ICGR15-MELD score was 0.832, with a sensitivity of 90.9% and a specificity of 71.0%. Those recipients with an ICGR15-MELD score ≥0.098 have a higher incidence of early postoperative complications than those with an ICGR15-MELD score <0.098 (P < 0.001). Finally, application of the two ICGR15-MELD models in the validation cohort still gave good accuracy (AUC, 0.835 and 0.826, respectively) in predicting EAD and early postoperative complications after LT. The combination of quantitative liver function tests (ICGR15) and the preoperative MELD score is a reliable and effective predictor of EAD and early postoperative complications after LT, which is better than MELD score or ICGR15 alone.

Reduced resistance to oxidative stress during reproduction as a cost of early-life stress.

PubMed

Zimmer, Cédric; Spencer, Karen A

2015-05-01

Stress exposure during early-life development can have long-term consequences for a variety of biological functions including oxidative stress. The link between early-life stress and oxidative balance is beginning to be explored and previous studies have focused on this link in adult non-breeding or immature individuals. However, as oxidative stress is considered as the main physiological mechanism underlying the trade-off between self-maintenance and investment in reproduction, it is necessary to look at the consequences of early-life stress on oxidative status during reproduction. Here, we investigated the effects of exposure to pre- and/or post-natal stress on oxidative balance during reproduction under benign or stressful environmental conditions in an avian model species, the Japanese quail. We determined total antioxidant status (TAS), total oxidant status (TOS) and resistance to a free-radical attack in individual exposed to pre-natal stress, post-natal stress or both and in control individuals exposed to none of the stressors. TAS levels decreased over time in all females that reproduced under stressful conditions. TOS decreased between the beginning and the end of reproductive period in pre-natal control females. In all females, resistance to a free-radical attack decreased over the reproductive event but this decrease was more pronounced in females from a pre-natal stress development. Our results suggest that pre-natal stress may be associated with a higher cost of reproduction in terms of oxidative stress. These results also confirm that early-life stress can be associated with both benefits and costs depending of the life-history stage or environmental context. Copyright © 2014 Elsevier Inc. All rights reserved.

Joint Attention and Brain Functional Connectivity in Infants and Toddlers.

PubMed

Eggebrecht, Adam T; Elison, Jed T; Feczko, Eric; Todorov, Alexandre; Wolff, Jason J; Kandala, Sridhar; Adams, Chloe M; Snyder, Abraham Z; Lewis, John D; Estes, Annette M; Zwaigenbaum, Lonnie; Botteron, Kelly N; McKinstry, Robert C; Constantino, John N; Evans, Alan; Hazlett, Heather C; Dager, Stephen; Paterson, Sarah J; Schultz, Robert T; Styner, Martin A; Gerig, Guido; Das, Samir; Kostopoulos, Penelope; Schlaggar, Bradley L; Petersen, Steven E; Piven, Joseph; Pruett, John R

2017-03-01

Initiating joint attention (IJA), the behavioral instigation of coordinated focus of 2 people on an object, emerges over the first 2 years of life and supports social-communicative functioning related to the healthy development of aspects of language, empathy, and theory of mind. Deficits in IJA provide strong early indicators for autism spectrum disorder, and therapies targeting joint attention have shown tremendous promise. However, the brain systems underlying IJA in early childhood are poorly understood, due in part to significant methodological challenges in imaging localized brain function that supports social behaviors during the first 2 years of life. Herein, we show that the functional organization of the brain is intimately related to the emergence of IJA using functional connectivity magnetic resonance imaging and dimensional behavioral assessments in a large semilongitudinal cohort of infants and toddlers. In particular, though functional connections spanning the brain are involved in IJA, the strongest brain-behavior associations cluster within connections between a small subset of functional brain networks; namely between the visual network and dorsal attention network and between the visual network and posterior cingulate aspects of the default mode network. These observations mark the earliest known description of how functional brain systems underlie a burgeoning fundamental social behavior, may help improve the design of targeted therapies for neurodevelopmental disorders, and, more generally, elucidate physiological mechanisms essential to healthy social behavior development. © The Author 2017. Published by Oxford University Press.

Joint Attention and Brain Functional Connectivity in Infants and Toddlers

PubMed Central

Eggebrecht, Adam T.; Elison, Jed T.; Feczko, Eric; Todorov, Alexandre; Wolff, Jason J.; Kandala, Sridhar; Adams, Chloe M.; Snyder, Abraham Z.; Lewis, John D.; Estes, Annette M.; Zwaigenbaum, Lonnie; Botteron, Kelly N.; McKinstry, Robert C.; Constantino, John N.; Evans, Alan; Hazlett, Heather C.; Dager, Stephen; Paterson, Sarah J.; Schultz, Robert T.; Styner, Martin A.; Gerig, Guido; Das, Samir; Kostopoulos, Penelope; Schlaggar, Bradley L.; Petersen, Steven E.; Piven, Joseph; Pruett, John R.

2017-01-01

Abstract Initiating joint attention (IJA), the behavioral instigation of coordinated focus of 2 people on an object, emerges over the first 2 years of life and supports social-communicative functioning related to the healthy development of aspects of language, empathy, and theory of mind. Deficits in IJA provide strong early indicators for autism spectrum disorder, and therapies targeting joint attention have shown tremendous promise. However, the brain systems underlying IJA in early childhood are poorly understood, due in part to significant methodological challenges in imaging localized brain function that supports social behaviors during the first 2 years of life. Herein, we show that the functional organization of the brain is intimately related to the emergence of IJA using functional connectivity magnetic resonance imaging and dimensional behavioral assessments in a large semilongitudinal cohort of infants and toddlers. In particular, though functional connections spanning the brain are involved in IJA, the strongest brain-behavior associations cluster within connections between a small subset of functional brain networks; namely between the visual network and dorsal attention network and between the visual network and posterior cingulate aspects of the default mode network. These observations mark the earliest known description of how functional brain systems underlie a burgeoning fundamental social behavior, may help improve the design of targeted therapies for neurodevelopmental disorders, and, more generally, elucidate physiological mechanisms essential to healthy social behavior development. PMID:28062515

Inflammatory Bowel Disease in Primary Immunodeficiencies.

PubMed

Kelsen, Judith R; Sullivan, Kathleen E

2017-08-01

Inflammatory bowel disease is most often a polygenic disorder with contributions from the intestinal microbiome, defects in barrier function, and dysregulated host responses to microbial stimulation. There is, however, increasing recognition of single gene defects that underlie a subset of patients with inflammatory bowel disease, particularly those with early-onset disease, and this review focuses on the primary immunodeficiencies associated with early-onset inflammatory bowel disease. The advent of next-generation sequencing has led to an improved recognition of single gene defects underlying some cases of inflammatory bowel disease. Among single gene defects, immune response genes are the most frequent category identified. This is also true of common genetic variants associated with inflammatory bowel disease, supporting a pivotal role for host responses in the pathogenesis. This review focuses on practical aspects related to diagnosis and management of children with inflammatory bowel disease who have underlying primary immunodeficiencies.

Hepatic Shock Differential Diagnosis and Risk Factors: A Review Article.

PubMed

Soleimanpour, Hassan; Safari, Saeid; Rahmani, Farzad; Nejabatian, Arezu; Alavian, Seyed Moayed

2015-10-01

Liver as an important organ has a vital role in physiological processes in the body. Different causes can disrupt normal function of liver. Factors such as hypo-perfusion, hypoxemia, infections and some others can cause hepatic injury and hepatic shock. Published research resources from 2002 to May 2015 in some databases (PubMed, Scopus, Index Copernicus, DOAJ, EBSCO-CINAHL, Science direct, Cochrane library and Google scholar and Iranian search database like SID and Iranmedex) were investigated for the present study. Different causes can lead to hepatic shock. Most of these causes can be prevented by early resuscitation and treatment of underlying factors. Hepatic shock is detected in ill patients, especially those with hemodynamic disorders. It can be prevented by early treatment of underlying disease. There is no definite treatment for hepatic shock and should be managed conservatively. Hepatic shock in patients can increase the mortality rate.

Hepatic Shock Differential Diagnosis and Risk Factors: A Review Article

PubMed Central

Soleimanpour, Hassan; Safari, Saeid; Rahmani, Farzad; Nejabatian, Arezu; Alavian, Seyed Moayed

2015-01-01

Context: Liver as an important organ has a vital role in physiological processes in the body. Different causes can disrupt normal function of liver. Factors such as hypo-perfusion, hypoxemia, infections and some others can cause hepatic injury and hepatic shock. Evidence Acquisition: Published research resources from 2002 to May 2015 in some databases (PubMed, Scopus, Index Copernicus, DOAJ, EBSCO-CINAHL, Science direct, Cochrane library and Google scholar and Iranian search database like SID and Iranmedex) were investigated for the present study. Results: Different causes can lead to hepatic shock. Most of these causes can be prevented by early resuscitation and treatment of underlying factors. Conclusions: Hepatic shock is detected in ill patients, especially those with hemodynamic disorders. It can be prevented by early treatment of underlying disease. There is no definite treatment for hepatic shock and should be managed conservatively. Hepatic shock in patients can increase the mortality rate. PMID:26587034

Estimation of abbreviated mycophenolic acid area under the concentration-time curve during early posttransplant period by limited sampling strategy.

PubMed

Mohammadpour, A-H; Nazemian, F; Abtahi, B; Naghibi, M; Gholami, K; Rezaee, S; Nazari, M-R A; Rajabi, O

2008-12-01

Area under the concentration curve (AUC) of mycophenolic acid (MPA) could help to optimize therapeutic drug monitoring during the early post-renal transplant period. The aim of this study was to develop a limited sampling strategy to estimate an abbreviated MPA AUC within the first month after renal transplantation. In this study we selected 19 patients in the early posttransplant period with normal renal graft function (glomerular filtration rate > 70 mL/min). Plasma MPA concentrations were measured using reverse-phase high-performance liquid chromatography. MPA AUC(0-12h) was calculated using the linear trapezoidal rule. Multiple stepwise regression analysis was used to determine the minimal and convenient time points of MPA levels that could be used to derive model equations best fitted to MPA AUC(0-12h). The regression equation for AUC estimation that gave the best performance was AUC = 14.46 C(10) + 15.547 (r(2) = .882). The validation of the method was performed using the jackknife method. Mean prediction error of this model was not different from zero (P > .05) and had a high root mean square prediction error (8.06). In conclusion, this limited sampling strategy provided an effective approach for therapeutic drug monitoring during the early posttransplant period.

A prospective cohort study among new Chinese coal miners: the early pattern of lung function change.

PubMed

Wang, M-L; Wu, Z-E; Du, Q-G; Petsonk, E L; Peng, K-L; Li, Y-D; Li, S-K; Han, G-H; Atffield, M D

2005-11-01

To investigate the early pattern of longitudinal change in forced expiratory volume in 1 second (FEV1) among new Chinese coal miners, and the relation between coal mine dust exposure and the decline of lung function. The early pattern of lung function changes in 317 newly hired Chinese underground coal miners was compared to 132 referents. This three year prospective cohort study involved a pre-employment and 15 follow up health surveys, including a questionnaire and spirometry tests. Twice a month, total and respirable dust area sampling was done. The authors used a two stage analysis and a linear mixed effects model approach to analyse the longitudinal spirometry data, and to investigate the changes in FEV1 over time, controlling for age, height, pack years of smoking, mean respirable dust concentration, the room temperature during testing, and the groupxtime interaction terms. FEV1 change over time in new miners is non-linear. New miners experience initial rapid FEV1 declines, primarily during the first year of mining, little change during the second year, and partial recovery during the third year. Both linear and quadratic time trends in FEV1 change are highly significant. Smoking miners lost more FEV1 than non-smokers. Referents, all age less than 20 years, showed continued lung growth, whereas the miners who were under age 20 exhibited a decline in FEV1. Dust and smoking affect lung function in young, newly hired Chinese coal miners. FEV1 change over the first three years of employment is non-linear. The findings have implications for both methods and interpretation of medical screening in coal mining and other dusty work: during the first several years of employment more frequent testing may be desirable, and caution is required in interpreting early FEV1 declines.

Gestalten of today: early processing of visual contours and surfaces.

PubMed

Kovács, I

1996-12-01

While much is known about the specialized, parallel processing streams of low-level vision that extract primary visual cues, there is only limited knowledge about the dynamic interactions between them. How are the fragments, caught by local analyzers, assembled together to provide us with a unified percept? How are local discontinuities in texture, motion or depth evaluated with respect to object boundaries and surface properties? These questions are presented within the framework of orientation-specific spatial interactions of early vision. Key observations of psychophysics, anatomy and neurophysiology on interactions of various spatial and temporal ranges are reviewed. Aspects of the functional architecture and possible neural substrates of local orientation-specific interactions are discussed, underlining their role in the integration of information across the visual field, and particularly in contour integration. Examples are provided demonstrating that global context, such as contour closure and figure-ground assignment, affects these local interactions. It is illustrated that figure-ground assignment is realized early in visual processing, and that the pattern of early interactions also brings about an effective and sparse coding of visual shape. Finally, it is concluded that the underlying functional architecture is not only dynamic and context dependent, but the pattern of connectivity depends as much on past experience as on actual stimulation.

Experience-dependent development of spinal motor neurons

NASA Technical Reports Server (NTRS)

Inglis, F. M.; Zuckerman, K. E.; Kalb, R. G.; Walton, K. D. (Principal Investigator)

2000-01-01

Locomotor activity in many species undergoes pronounced alterations in early postnatal life, and environmental cues may be responsible for modifying this process. To determine how these events are reflected in the nervous system, we studied rats reared under two different conditions-the presence or absence of gravity-in which the performance of motor operations differed. We found a significant effect of rearing environment on the size and complexity of dendritic architecture of spinal motor neurons, particularly those that are likely to participate in postural control. These results provide evidence that neurons subserving motor function undergo activity-dependent maturation in early postnatal life in a manner analogous to sensory systems.

Mitochondrial functionality in reproduction: from gonads and gametes to embryos and embryonic stem cells.

PubMed

Ramalho-Santos, João; Varum, Sandra; Amaral, Sandra; Mota, Paula C; Sousa, Ana Paula; Amaral, Alexandra

2009-01-01

Mitochondria are multitasking organelles involved in ATP synthesis, reactive oxygen species (ROS) production, calcium signalling and apoptosis; and mitochondrial defects are known to cause physiological dysfunction, including infertility. The goal of this review was to identify and discuss common themes in mitochondrial function related to mammalian reproduction. The scientific literature was searched for studies reporting on the several aspects of mitochondrial activity in mammalian testis, sperm, oocytes, early embryos and embryonic stem cells. ATP synthesis and ROS production are the most discussed aspects of mitochondrial function. Metabolic shifts from mitochondria-produced ATP to glycolysis occur at several stages, notably during gametogenesis and early embryo development, either reflecting developmental switches or substrate availability. The exact role of sperm mitochondria is especially controversial. Mitochondria-generated ROS function in signalling but are mostly described when produced under pathological conditions. Mitochondria-based calcium signalling is primarily important in embryo activation and embryonic stem cell differentiation. Besides pathologically triggered apoptosis, mitochondria participate in apoptotic events related to the regulation of spermatogonial cell number, as well as gamete, embryo and embryonic stem cell quality. Interestingly, data from knock-out (KO) mice is not always straightforward in terms of expected phenotypes. Finally, recent data suggests that mitochondrial activity can modulate embryonic stem cell pluripotency as well as differentiation into distinct cellular fates. Mitochondria-based events regulate different aspects of reproductive function, but these are not uniform throughout the several systems reviewed. Low mitochondrial activity seems a feature of 'stemness', being described in spermatogonia, early embryo, inner cell mass cells and embryonic stem cells.

Occupational pesticide exposure in early pregnancy associated with sex-specific neurobehavioral deficits in the children at school age.

PubMed

Andersen, Helle R; Debes, Fróði; Wohlfahrt-Veje, Christine; Murata, Katsuyuki; Grandjean, Philippe

2015-01-01

Prenatal exposure to pesticides may affect neurodevelopment, while the impact of modern pesticides is unclear. From 1997-2001, women working in greenhouse horticultures were recruited at the beginning of their pregnancy. Based on detailed interview of the women and their employers, those categorized as occupationally exposed to pesticides were moved to unexposed work functions or went on paid leave, while women without any exposure were considered unexposed controls. Of the resulting birth cohort of 203 children, 133 (65%) were examined at age 6 to 11 years together with 44 newly recruited children of same age whose mothers were not occupationally exposed to pesticides in pregnancy. All children underwent a standardized examination including a battery of neurodevelopmental tests. Maternal occupational pesticide exposure in early pregnancy was associated with prolonged brainstem auditory evoked potential latencies in the children as a whole and with impaired neuropsychological function in girls, while no effect was apparent in boys. In girls, language and motor speed functions were significantly inversely associated with prenatal exposure, and a non-significant tendency toward decreased function was also seen for other neuropsychological outcomes. A structural equation model that combined all these test results showed an overall impaired neuropsychological function in girls prenatally exposed to pesticides. Thus, our findings suggest an adverse effect of maternal occupational pesticide exposure on their children's neurodevelopment, despite the fact that the exposures occurred solely during early pregnancy and under well regulated working conditions, where special measures to protect pregnant women were applied. Copyright © 2014 Elsevier Inc. All rights reserved.

Role of reactive oxygene species, peroxiredoxins and thioredoxins in reaction of plants to hypergravity and oxidative stresses

NASA Astrophysics Data System (ADS)

Jadko, Sergiy

Early increasing of reactive oxygen species (ROS) concentration, including H2O2, occur in plant cells under various impacts and these ROS can function as signaling molecules in starting of cell stress responses. Peroxiredoxins (Prx) and thioredoxins (Trx) are significant cell ROS/H2O2 sensors and transmitters. Prx besides its antioxidant activity, participate in creating of stress redox signals by destroying of H2O2 and reducing of Trx. Than these reduced Trx lead to activation of various redox sensitive proteins, transcription factors and MAP kinases. This study aimed to investigate early increasing of ROS and H2O2 contents and Prx and Trx activities in pea roots and arabidopsis tissue culture cells under hypergravity and oxidative stresses. Pea roots of 3-5 days old seedlings and 12 days old tissue culture of Arabidopsis thaliana from leaves were studied. Pea seedlings were grown on wet filter paper and the tissue culture was grown on MS medium in dark conditions under 24oC. Hypergravity stress was induced by centrifugation at 15 g. Chemiluminescence (ChL) intensity for ROS concentration, H2O2 content and Prx and Trx activities were determined. All experiments were repeated by 3-4 times. Early increasing of ChL intensity and H2O2 content in the pea roots and arabidopsis tissue culture cells took place under hypergravity and oxidative stresses and its were higher corresponding controls on average on 25, 21 and 17 percents to 30, 60 and 90 min. At the same time Prx and Trx activities increased on 7, 13 and 16 percents. Thus under hypergravity and oxidative stresses in both investigated plants take place early increasing of ROS and H2O2 contents which as second messengers can lead to ROS/H2O2-dependent increasing of Prx and Trx activities with creating of H2O2-Prx-Trx signaling pathway.

Functional Differentiation of Uterine Stromal Cells Involves Cross-regulation between Bone Morphogenetic Protein 2 and Kruppel-like Factor (KLF) Family Members KLF9 and KLF13

USDA-ARS?s Scientific Manuscript database

The inability of the uterine epithelium to enter a state of receptivity for the embryo to implant is a significant underlying cause of early pregnancy loss. We previously showed that mice null for the Progesterone Receptor (PGR)-interacting protein Kruppel-like Factor (KLF) 9 are subfertile and exhi...

Regenerative Medicine and Restoration of Joint Function

DTIC Science & Technology

2014-12-01

to resist fracture and excessive deformation under antici- pated mechanical loading conditions both during the early healing process and for longer...per sample type), the results sug- gest a correlation between percent fractured sinter neck area and mechanical properties with the lowest bending...joint replacement are used to treat a joint with an intra-articular fracture or destroyed by a combat injury. Generation of personalized, anatomically

Early Functional Connectome Integrity and 1-Year Recovery in Comatose Survivors of Cardiac Arrest.

PubMed

Sair, Haris I; Hannawi, Yousef; Li, Shanshan; Kornbluth, Joshua; Demertzi, Athena; Di Perri, Carol; Chabanne, Russell; Jean, Betty; Benali, Habib; Perlbarg, Vincent; Pekar, James; Luyt, Charles-Edouard; Galanaud, Damien; Velly, Lionel; Puybasset, Louis; Laureys, Steven; Caffo, Brian; Stevens, Robert D

2018-04-01

Purpose To assess whether early brain functional connectivity is associated with functional recovery 1 year after cardiac arrest (CA). Materials and Methods Enrolled in this prospective multicenter cohort were 46 patients who were comatose after CA. Principal outcome was cerebral performance category at 12 months, with favorable outcome (FO) defined as cerebral performance category 1 or 2. All participants underwent multiparametric structural and functional magnetic resonance (MR) imaging less than 4 weeks after CA. Within- and between-network connectivity was measured in dorsal attention network (DAN), default-mode network (DMN), salience network (SN), and executive control network (ECN) by using seed-based analysis of resting-state functional MR imaging data. Structural changes identified with fluid-attenuated inversion recovery and diffusion-weighted imaging sequences were analyzed by using validated morphologic scales. The association between connectivity measures, structural changes, and the principal outcome was explored with multivariable modeling. Results Patients underwent MR imaging a mean 12.6 days ± 5.6 (standard deviation) after CA. At 12 months, 11 patients had an FO. Patients with FO had higher within-DMN connectivity and greater anticorrelation between SN and DMN and between SN and ECN compared with patients with unfavorable outcome, an effect that was maintained after multivariable adjustment. Anticorrelation of SN-DMN predicted outcomes with higher accuracy than fluid-attenuated inversion recovery or diffusion-weighted imaging scores (area under the receiver operating characteristic curves, respectively, 0.88, 0.74, and 0.71). Conclusion MR imaging-based measures of cerebral functional network connectivity obtained in the acute phase of CA were independently associated with FO at 1 year, warranting validation as early markers of long-term recovery potential in patients with anoxic-ischemic encephalopathy. © RSNA, 2017.

Control of Retrograde Signaling by Rapid Turnover of GENOMES UNCOUPLED11[OPEN

PubMed Central

Chalvin, Camille; Wu, Xu Na

2018-01-01

The exchange of signals between cellular compartments coordinates development and differentiation, modulates metabolic pathways, and triggers responses to environmental conditions. The proposed central regulator of plastid-to-nucleus retrograde signaling, GENOMES UNCOUPLED1 (GUN1), is present at very low levels, which has hampered the discovery of its precise molecular function. Here, we show that the Arabidopsis (Arabidopsis thaliana) GUN1 protein accumulates to detectable levels only at very early stages of leaf development, where it functions in the regulation of chloroplast biogenesis. GUN1 mRNA is present at high levels in all tissues, but GUN1 protein undergoes rapid degradation (with an estimated half-life of ∼4 h) in all tissues where chloroplast biogenesis has been completed. The rapid turnover of GUN1 is controlled mainly by the chaperone ClpC1, suggesting degradation of GUN1 by the Clp protease. Degradation of GUN1 slows under stress conditions that alter retrograde signaling, thus ensuring that the plant has sufficient GUN1 protein. We also find that the pentatricopeptide repeat motifs of GUN1 are important determinants of GUN1 stability. Moreover, overexpression of GUN1 causes an early flowering phenotype, suggesting a function of GUN1 in developmental phase transitions beyond chloroplast biogenesis. Taken together, our results provide new insight into the regulation of GUN1 by proteolytic degradation, uncover its function in early chloroplast biogenesis, and suggest a role in developmental phase transitions. PMID:29367233

Real-Time Strategy Video Game Experience and Visual Perceptual Learning.

PubMed

Kim, Yong-Hwan; Kang, Dong-Wha; Kim, Dongho; Kim, Hye-Jin; Sasaki, Yuka; Watanabe, Takeo

2015-07-22

Visual perceptual learning (VPL) is defined as long-term improvement in performance on a visual-perception task after visual experiences or training. Early studies have found that VPL is highly specific for the trained feature and location, suggesting that VPL is associated with changes in the early visual cortex. However, the generality of visual skills enhancement attributable to action video-game experience suggests that VPL can result from improvement in higher cognitive skills. If so, experience in real-time strategy (RTS) video-game play, which may heavily involve cognitive skills, may also facilitate VPL. To test this hypothesis, we compared VPL between RTS video-game players (VGPs) and non-VGPs (NVGPs) and elucidated underlying structural and functional neural mechanisms. Healthy young human subjects underwent six training sessions on a texture discrimination task. Diffusion-tensor and functional magnetic resonance imaging were performed before and after training. VGPs performed better than NVGPs in the early phase of training. White-matter connectivity between the right external capsule and visual cortex and neuronal activity in the right inferior frontal gyrus (IFG) and anterior cingulate cortex (ACC) were greater in VGPs than NVGPs and were significantly correlated with RTS video-game experience. In both VGPs and NVGPs, there was task-related neuronal activity in the right IFG, ACC, and striatum, which was strengthened after training. These results indicate that RTS video-game experience, associated with changes in higher-order cognitive functions and connectivity between visual and cognitive areas, facilitates VPL in early phases of training. The results support the hypothesis that VPL can occur without involvement of only visual areas. Significance statement: Although early studies found that visual perceptual learning (VPL) is associated with involvement of the visual cortex, generality of visual skills enhancement by action video-game experience suggests that higher-order cognition may be involved in VPL. If so, real-time strategy (RTS) video-game experience may facilitate VPL as a result of heavy involvement of cognitive skills. Here, we compared VPL between RTS video-game players (VGPs) and non-VGPs (NVGPs) and investigated the underlying neural mechanisms. VGPs showed better performance in the early phase of training on the texture discrimination task and greater level of neuronal activity in cognitive areas and structural connectivity between visual and cognitive areas than NVGPs. These results support the hypothesis that VPL can occur beyond the visual cortex. Copyright © 2015 the authors 0270-6474/15/3510485-08$15.00/0.

Early diagnosis of asthma in young children by using non-invasive biomarkers of airway inflammation and early lung function measurements: study protocol of a case-control study

PubMed Central

van de Kant, Kim DG; Klaassen, Ester MM; Jöbsis, Quirijn; Nijhuis, Annedien J; van Schayck, Onno CP; Dompeling, Edward

2009-01-01

Background Asthma is the most common chronic disease in childhood, characterized by chronic airway inflammation. There are problems with the diagnosis of asthma in young children since the majority of the children with recurrent asthma-like symptoms is symptom free at 6 years, and does not have asthma. With the conventional diagnostic tools it is not possible to differentiate between preschool children with transient symptoms and children with asthma. The analysis of biomarkers of airway inflammation in exhaled breath is a non-invasive and promising technique to diagnose asthma and monitor inflammation in young children. Moreover, relatively new lung function tests (airway resistance using the interrupter technique) have become available for young children. The primary objective of the ADEM study (Asthma DEtection and Monitoring study), is to develop a non-invasive instrument for an early asthma diagnosis in young children, using exhaled inflammatory markers and early lung function measurements. In addition, aetiological factors, including gene polymorphisms and gene expression profiles, in relation to the development of asthma are studied. Methods/design A prospective case-control study is started in 200 children with recurrent respiratory symptoms and 50 control subjects without respiratory symptoms. At 6 years, a definite diagnosis of asthma is made (primary outcome measure) on basis of lung function assessments and current respiratory symptoms ('golden standard'). From inclusion until the definite asthma diagnosis, repeated measurements of lung function tests and inflammatory markers in exhaled breath (condensate), blood and faeces are performed. The study is registered and ethically approved. Discussion This article describes the study protocol of the ADEM study. The new diagnostic techniques applied in this study could make an early diagnosis of asthma possible. An early and reliable asthma diagnosis at 2–3 years will have consequences for the management of the large group of young children with asthma-like symptoms. It will avoid both over-treatment of children with transient wheeze and under-treatment of children with asthma. This might have a beneficial influence on the prognosis of asthma in these young children. Besides, insight into the pathophysiology and aetiology of asthma will be obtained. TRIAL REGISTRATION This study is registered by clinicaltrials.gov (NCT00422747). PMID:19563637

Comparison between the story recall test and the word-list learning test in Korean patients with mild cognitive impairment and early stage of Alzheimer's disease.

PubMed

Baek, Min Jae; Kim, Hyun Jung; Kim, Sangyun

2012-01-01

Among verbal memory tests, two that are commonly used to measure the ability of verbal memory function in cognitive impairment are story recall tests and word-list learning tests. However, research is limited regarding which test might be more sensitive in discriminating between normal cognitive aging and patients with Alzheimer's disease (AD) in the Korean population. The purpose of the current study was to compare the word-list learning test (Seoul Verbal Learning Test; SVLT) and the story recall test (Korean Story Recall Test; KSRT) to determine which test is more sensitive in discriminating between individuals with normal cognitive aging and patients with mild cognitive impairment (MCI) and early stage of AD in Korea. A total of 53 healthy adults, 127 patients with MCI, and 72 patients with early stage of AD participated in this study. The receiver-operating characteristic (ROC) curve and area under the curve (AUC) were evaluated to compare these two tests. The results showed that the AUC of the SVLT was significantly larger than the AUC of the KSRT in all three groups (healthy adults vs. MCI and early stage of AD; healthy adults vs. MCI; healthy adults vs. early stage of AD). However, in comparison of patients with MCI and early stage of AD, the AUC of SVLT and the AUC of KSRT were not significant. The word-list learning test is a more useful tool for examining verbal memory function for older adults in Korea than the story recall test.

Effect of bed exercises and gum chewing on abdominal sounds, flatulence and early discharge in the early period after caesarean section.

PubMed

Çevik, Semra Akköz; Başer, Mürüvvet

2016-05-01

The purpose of this study was to determine the effects of bed exercises and gum chewing on abdominal sounds, flatulence and early discharge on women who have given birth at the Cengiz Gökçek Gynecology and Obstetrics Hospital surgery services in Gaziantep city centre. Caesarean operation is the most significant surgical intervention that affects central nervous system and decelerates bowel movements in the postoperative period. Conducted studies show that practices such as gum chewing ensure that bowel functions start in a short time through early feeding and mobilisation and shorten the duration of hospital stay. A randomised controlled experimental was used. A total of 120 women participated in the study in three groups of 40 for gum, exercise and control groups. Gum was given to the groups in the gum section two hours after the ceasarean, the women chewed gum for the first eight hours until flatulence for 15 minutes every two hours. However, the women in the exercise group started moving two hours after the caesarean for the first eight hours until flatulence for five minutes every two hours. The control group consisted of women under routine treatment and care of the hospital. All women were hourly evaluated in terms of abdominal sounds, flatulence and defaecation. It was determined that following caesarean, bowel functions started in three groups at the same time, there was no significant difference between three groups. It was determined that the gum group, exercise group and the control group were discharged earlier, there was no significant difference between three groups The study results show that spinal anaesthesia have positive effects on discharge time after caesarean section operation. This study provides useful information to clinician and researchers when determining practices such as postoperative standing up in early period, gum chewing and early liquid intake related to postoperative bowel functions after abdominal operations. © 2016 John Wiley & Sons Ltd.

E-Index for Differentiating Complex Dynamic Traits

PubMed Central

Qi, Jiandong; Sun, Jianfeng; Wang, Jianxin

2016-01-01

While it is a daunting challenge in current biology to understand how the underlying network of genes regulates complex dynamic traits, functional mapping, a tool for mapping quantitative trait loci (QTLs) and single nucleotide polymorphisms (SNPs), has been applied in a variety of cases to tackle this challenge. Though useful and powerful, functional mapping performs well only when one or more model parameters are clearly responsible for the developmental trajectory, typically being a logistic curve. Moreover, it does not work when the curves are more complex than that, especially when they are not monotonic. To overcome this inadaptability, we therefore propose a mathematical-biological concept and measurement, E-index (earliness-index), which cumulatively measures the earliness degree to which a variable (or a dynamic trait) increases or decreases its value. Theoretical proofs and simulation studies show that E-index is more general than functional mapping and can be applied to any complex dynamic traits, including those with logistic curves and those with nonmonotonic curves. Meanwhile, E-index vector is proposed as well to capture more subtle differences of developmental patterns. PMID:27064292

Story time turbocharger? Child engagement during shared reading and cerebellar activation and connectivity in preschool-age children listening to stories.

PubMed

Hutton, John S; Phelan, Kieran; Horowitz-Kraus, Tzipi; Dudley, Jonathan; Altaye, Mekibib; DeWitt, Thomas; Holland, Scott K

2017-01-01

Expanding behavioral and neurobiological evidence affirms benefits of shared (especially parent-child) reading on cognitive development during early childhood. However, the majority of this evidence involves factors under caregiver control, the influence of those intrinsic to the child, such as interest or engagement in reading, largely indirect or unclear. The cerebellum is increasingly recognized as playing a "smoothing" role in higher-level cognitive processing and learning, via feedback loops with language, limbic and association cortices. We utilized functional MRI to explore the relationship between child engagement during a mother-child reading observation and neural activation and connectivity during a story listening task, in a sample of 4-year old girls. Children exhibiting greater interest and engagement in the narrative showed increased activation in right-sided cerebellar association areas during the task, and greater functional connectivity between this activation cluster and language and executive function areas. Our findings suggest a potential cerebellar "boost" mechanism responsive to child engagement level that may contribute to emergent literacy development during early childhood, and synergy between caregiver and child factors during story sharing.

Early intervention for psychotic disorders: Real-life implementation in Hong Kong.

PubMed

Wong, Gloria H Y; Hui, Christy L M; Tang, Jennifer Y M; Chang, Wing-Chung; Chan, Sherry K W; Xu, Jia-Qi; Lin, Jessie J X; Lai, Dik-Chee; Tam, Wendy; Kok, Joy; Chung, Dicky; Hung, S F; Chen, Eric Y H

2012-03-01

Hong Kong is among the first few cities in Asia to have implemented early intervention for psychosis in 2001. Substantial changes in psychosis service have since taken place. We reviewed available outcome data in Hong Kong, with reference to the philosophy of early intervention in psychosis, discussing experience and lessons learned from the implementation process, and future opportunities and challenges. Data accumulated in the past decade provided evidence for the benefits and significance of early intervention programmes: patients under the care of early intervention service showed improved functioning, milder symptoms, and fewer hospitalizations and suicides. Early intervention is more cost-effective compared with standard care. Stigma and misconception remains an issue, and public awareness campaigns are underway. In recent years, a critical mass is being formed, and Hong Kong has witnessed the unfolding of public service extension, new projects and organizations, and increasing interest from the community. Several major platforms are in place for coherent efforts, including the public Early Assessment Service for Young people with psychosis (EASY) programme, the Psychosis Studies and Intervention (PSI) research unit, the independent Hong Kong Early Psychosis Intervention Society (EPISO), the Jockey Club Early Psychosis (JCEP) project, and the postgraduate Psychological Medicine (Psychosis Studies) programme. The first decade of early intervention work has been promising; consolidation and further development is needed on many fronts of research, service and education. Copyright © 2012 Elsevier B.V. All rights reserved.

Neutrophils in Homeostasis, Immunity, and Cancer.

PubMed

Nicolás-Ávila, José Ángel; Adrover, José M; Hidalgo, Andrés

2017-01-17

Neutrophils were among the first leukocytes described and visualized by early immunologists. Prominent effector functions during infection and sterile inflammation classically placed them low in the immune tree as rapid, mindless aggressors with poor regulatory functions. This view is currently under reassessment as we uncover new aspects of their life cycle and identify transcriptional and phenotypic diversity that endows them with regulatory properties that extend beyond their lifetime in the circulation. These properties are revealing unanticipated roles for neutrophils in supporting homeostasis, as well as complex disease states such as cancer. We focus this review on these emerging functions in order to define the true roles of neutrophils in homeostasis, immunity, and disease. Copyright © 2017 Elsevier Inc. All rights reserved.

Multiple imputation methods for nonparametric inference on cumulative incidence with missing cause of failure

PubMed Central

Lee, Minjung; Dignam, James J.; Han, Junhee

2014-01-01

We propose a nonparametric approach for cumulative incidence estimation when causes of failure are unknown or missing for some subjects. Under the missing at random assumption, we estimate the cumulative incidence function using multiple imputation methods. We develop asymptotic theory for the cumulative incidence estimators obtained from multiple imputation methods. We also discuss how to construct confidence intervals for the cumulative incidence function and perform a test for comparing the cumulative incidence functions in two samples with missing cause of failure. Through simulation studies, we show that the proposed methods perform well. The methods are illustrated with data from a randomized clinical trial in early stage breast cancer. PMID:25043107

Individual Pressure Vessel (PV) and Common Pressure Vessel (CPV) Nickel-Hydrogen Battery Performance Under LEO Cycling Conditions

NASA Technical Reports Server (NTRS)

Miller, Thomas B.; Lewis, Harlan L.

2004-01-01

LEO life cycle testing of Individual Pressure Vessel (PV) and Common Pressure Vessel (CPV) nickel-hydrogen cell packs have been sponsored by the NASA Aerospace Flight Battery Program. The cell packs have cycled under both 35% and 60% depth-of- discharge and temperature conditions of -5 C and +lO C. The packs have been on test since as early as 1992 and have generated a substantial database. This report will provide insight into performance trends as a function of the specific cell configuration and manufacturer for eight separate nickel-hydrogen battery cell packs.

[Seeking the aetiology of autistic spectrum disorder. Part 2: Functional neuroimaging].

PubMed

Bryńska, Anita

2012-01-01

Multiple functional imaging techniques help to a better understanding of the neurobiological basis of autism-spectrum disorders (ASD). The early functional imaging studies on ASD focused on task-specific methods related to core symptom domains and explored patterns of activation in response to face processing, theory of mind tasks, language processing and executive function tasks. On the other hand, fMRI research in ASD focused on the development of functional connectivity methods and has provided evidence of alterations in cortical connectivity in ASD and establish autism as a disorder of under-connectivity among the brain regions participating in cortical networks. This atypical functional connectivity in ASD results in inefficiency and poor integration of processing in network connections to achieve task performance. The goal of this review is to summarise the actual neuroimaging functional data and examine their implication for understanding of the neurobiology of ASD.

Adverse and adaptive childhood experiences are associated with parental reflective functioning in mothers with substance use disorder.

PubMed

Håkansson, Ulrika; Watten, Reidulf; Söderström, Kerstin; Skårderud, Finn; Øie, Merete Glenne

2018-07-01

Mothers with a substance use disorder (SUD) are at risk for maladaptive parenting practices, and have heightened likelihood of having experienced childhood adversity themselves. In addition, parental reflective functioning (PRF), a capacity underlying sensitive caregiving, is often low in mothers with SUD. This study examines the relationship between PRF and aversive (emotional, physical, sexual abuse and neglect) and adaptive (safety and competence) experiences, in different developmental phases (early childhood, latency, and adolescence) in mothers with a SUD. A sample of 43 mothers with small children were interviewed with the Parental Developmental Interview to assess PRF, and they completed the Traumatic Antecedents Questionnaire regarding aversive and adaptive experiences. In addition, we used the Hopkins Symptoms Checklist-10 to control for mental health status and a battery of neuropsychological tests to control for executive functions. Results indicated that adaptive experiences in early childhood were positively related to PRF, and that experience of emotional abuse was negatively related to PRF. When separating the group of mothers in two sub-groups based on PRF level, results showed that mothers with negative to low PRF had significantly more experiences of adversities in early childhood and latency, and significantly less adaptive experiences in early childhood, latency and adolescence, compared to mothers with moderate to high PRF. In addition, mothers with adequate to high PRF reported experiencing significantly more types of adaptive experiences, and significantly less adversities compared to mothers with negative to low PRF. Results are discussed in relation to developmental trauma, resilience, epistemic trust and mistrust. Copyright © 2018 Elsevier Ltd. All rights reserved.

Motivational impairment predicts functional remission in first-episode psychosis: 3-Year follow-up of the randomized controlled trial on extended early intervention.

PubMed

Chang, Wing Chung; Kwong, Vivian Wing Yan; Or Chi Fai, Philip; Lau, Emily Sin Kei; Chan, Gloria Hoi Kei; Jim, Olivia Tsz Ting; Hui, Christy Lai Ming; Chan, Sherry Kit Wa; Lee, Edwin Ho Ming; Chen, Eric Yu Hai

2018-02-01

Functional remission represents an intermediate functional milestone toward recovery. Differential relationships of negative symptom sub-domains with functional remission in first-episode psychosis are understudied. We aimed to examine rate and predictors of functional remission in people with first-episode psychosis in the context of a 3-year follow-up of a randomized controlled trial comparing 1-year extension of early intervention (i.e. 3-year early intervention) with step-down psychiatric care (i.e. 2-year early intervention). A total of 160 participants were recruited upon completion of a 2-year specialized early intervention program for first-episode psychosis in Hong Kong and underwent a 1-year randomized controlled trial comparing 1-year extended early intervention with step-down care. Participants were followed up and reassessed 3 years after inclusion to the trial (i.e. 3-year follow-up). Functional remission was operationalized as simultaneous fulfillment of attaining adequate functioning (measured by Social and Occupational Functioning Scale and Role Functioning Scale) at 3-year follow-up and sustained employment in the last 6 months of 3-year study period. Negative symptom measure was delineated into amotivation (i.e. motivational impairment) and diminished expression (i.e. reduced affect and speech output). Data analysis was based on 143 participants who completed follow-up functional assessments. A total of 31 (21.7%) participants achieved functional remission status at 3-year follow-up. Multivariate regression analysis showed that lower levels of amotivation ( p = 0.010) and better functioning at study intake ( p = 0.004) independently predicted functional remission (Final model: Nagelkerke R 2  = 0.40, χ 2  = 42.9, p < 0.001). Extended early intervention, duration of untreated psychosis and diminished expression did not predict functional remission. Only approximately one-fifths of early psychosis patients were found to achieve functional remission. Functional impairment remains an unmet treatment need in the early stage of psychotic illness. Our results further suggest that amotivation may represent a critical therapeutic target for functional remission attainment in early psychosis.

The Role of Inhibitory Control in Behavioral and Physiological Expressions of Toddler Executive Function

PubMed Central

Morasch, Katherine C.; Bell, Martha Ann

2010-01-01

Eighty-one toddlers (ranging from 24 to 27 months) participated in a biobehavioral investigation of inhibitory control. Maternal-report measures of inhibitory control were related to laboratory tasks assessing inhibitory abilities under conditions of conflict, delay, and compliance challenge as well as toddler verbal ability. Additionally, unique variance in inhibitory control was explained by task-related changes in brain electrical activity at lateral frontal scalp sites as well as concurrent inhibitory task performance. Implications regarding neural correlates of executive function in early development and a central, organizing role of inhibitory processing in toddlerhood are discussed. PMID:20719337

Preparation and characterization of polyclonal antibodies against human chaperonin 10

PubMed Central

Somodevilla-Torres, Maria J.; Hillyard, Narelle C.; Morton, Halle; Alewood, Dianne; Halliday, Judy A.; Alewood, Paul F.; Vesey, David A.; Walsh, Michael D.; Cavanagh, Alice C.

2000-01-01

Abstract Early pregnancy factor (EPF) has been identified as an extracellular homologue of chaperonin 10 (Cpn10), a heat shock protein that functions within the cell as a molecular chaperone. Here, we report the production of polyclonal antibodies directed against several different regions of the human Cpn10 molecule and their application to specific protein quantitation and localization techniques. These antibodies will be valuable tools in further studies to elucidate the mechanisms underlying the differential spatial and temporal localization of EPF and Cpn10 and in studies to elucidate structure and function. PMID:10701835

Delayed degradation of chlorophylls and photosynthetic proteins in Arabidopsis autophagy mutants during stress-induced leaf yellowing

PubMed Central

Sakuraba, Yasuhito; Lee, Sang-Hwa; Kim, Ye-Sol; Park, Ohkmae K.; Hörtensteiner, Stefan; Paek, Nam-Chon

2014-01-01

Plant autophagy, one of the essential proteolysis systems, balances proteome and nutrient levels in cells of the whole plant. Autophagy has been studied by analysing Arabidopsis thaliana autophagy-defective atg mutants, but the relationship between autophagy and chlorophyll (Chl) breakdown during stress-induced leaf yellowing remains unclear. During natural senescence or under abiotic-stress conditions, extensive cell death and early yellowing occurs in the leaves of atg mutants. A new finding is revealed that atg5 and atg7 mutants exhibit a functional stay-green phenotype under mild abiotic-stress conditions, but leaf yellowing proceeds normally in wild-type leaves under these conditions. Under mild salt stress, atg5 leaves retained high levels of Chls and all photosystem proteins and maintained a normal chloroplast structure. Furthermore, a double mutant of atg5 and non-functional stay-green nonyellowing1-1 (atg5 nye1-1) showed a much stronger stay-green phenotype than either single mutant. Taking these results together, it is proposed that autophagy functions in the non-selective catabolism of Chls and photosynthetic proteins during stress-induced leaf yellowing, in addition to the selective degradation of Chl–apoprotein complexes in the chloroplasts through the senescence-induced STAY-GREEN1/NYE1 and Chl catabolic enzymes. PMID:24510943

[Influence of factors on independence of patients after stroke in early rehabilitation stage].

PubMed

Petruseviciene, Daiva; Krisciūnas, Aleksandras

2005-01-01

Brain stroke is the main cause of disability starting from age of 40 years. Due to this disability, a person loses his ability to work because of long-lasting disorders of biosocial functions. According to literature, occupational therapy for such patients, taking regard to their social, cultural and economic background, significantly increases their self-care and independence and helps to educate working skills. OBJECTIVE. To evaluate conditional disorders of patients with stroke under rehabilitation and to establish the influence of extent of brain damage, localization, age and gender on effectiveness of occupational therapy. Study included 47 men and 53 women diagnosed with brain ischemia or hemorrhage (ischemic or hemorrhagic stroke). Out of them, 30 were of working age (18-59 years old) and 70 of non-working age (more than 60 years old). The mean age was 63.4+/-1.2 years. In order to assess the functional status of patients, they were tested using the Functional Independence Measure (FIM). At the start of rehabilitation, the mean FIM score was 47.4+/-16.1 (48.9+/-15.6 for men and 46.3+/-16.6 for women, p>0.05). At the end of early rehabilitation, the mean FIM score reached up to 89.9+/-22.3 (94.7+/-18.9 for men and 85.7+/-24.3 for women, p<0.05). Evaluation of functional status showed that at the start of rehabilitation functional status was worse in women than men, nevertheless, women's functional status improved during rehabilitation, though the difference between men and women still remained. Occupational therapy was less effective for patients who suffered from hemiplegia than for patients with hemiparesis (p<0.01). Older patients (more than 60 years) had more expressed functional disorders, and worse functional recovery comparing with younger, working age patients (18-59 years old). Evaluation of occupational therapy effectiveness at the end of early rehabilitation showed that extent of brain damage influences independence of patients suffering from brain stroke (p<0.01).

Intrauterine and early postnatal exposure to outdoor air pollution and lung function at preschool age.

PubMed

Morales, Eva; Garcia-Esteban, Raquel; de la Cruz, Oscar Asensio; Basterrechea, Mikel; Lertxundi, Aitana; de Dicastillo, Maria D Martinez López; Zabaleta, Carlos; Sunyer, Jordi

2015-01-01

Effects of prenatal and postnatal exposure to air pollution on lung function at preschool age remain unexplored. We examined the association of exposure to air pollution during specific trimesters of pregnancy and postnatal life with lung function in preschoolers. Lung function was assessed with spirometry in preschoolers aged 4.5 years (n=620) participating in the INfancia y Medio Ambiente (INMA) cohort. Temporally adjusted land use regression (LUR) models were applied to estimate individual residential exposures to benzene and nitrogen dioxide (NO₂) during specific trimesters of pregnancy and early postnatal life (the first year of life). Recent and current (1 year and 1 week before lung function testing, respectively) exposures to NO₂ and nitrogen oxides (NOx) were also assessed. Exposure to higher levels of benzene and NO₂ during pregnancy was associated with reduced lung function. FEV1 estimates for an IQR increase in exposures during the second trimester of pregnancy were -18.4 mL, 95% CI -34.8 to -2.1 for benzene and -28.0 mL, 95% CI -52.9 to -3.2 for NO₂. Relative risk (RR) of low lung function (<80% of predicted FEV1) for an IQR increase in benzene and NO₂ during the second trimester of pregnancy were 1.22, 95% CI 1.02 to 1.46 and 1.30, 95% CI 0.97 to 1.76, respectively. Associations for early postnatal, recent and current exposures were not statistically significant. Stronger associations appeared among allergic children and those of lower social class. Prenatal exposure to residential traffic-related air pollution may result in long-term lung function deficits at preschool age. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Potential economic value of drought information to support early warning in Africa

NASA Astrophysics Data System (ADS)

Quiroga, S.; Iglesias, A.; Diz, A.; Garrote, L.

2012-04-01

We present a methodology to estimate the economic value of advanced climate information for food production in Africa under climate change scenarios. The results aim to facilitate better choices in water resources management. The methodology includes 4 sequential steps. First two contrasting management strategies (with and without early warning) are defined. Second, the associated impacts of the management actions are estimated by calculating the effect of drought in crop productivity under climate change scenarios. Third, the optimal management option is calculated as a function of the drought information and risk aversion of potential information users. Finally we use these optimal management simulations to compute the economic value of enhanced water allocation rules to support stable food production in Africa. Our results show how a timely response to climate variations can help reduce loses in food production. The proposed framework is developed within the Dewfora project (Early warning and forecasting systems to predict climate related drought vulnerability and risk in Africa) that aims to improve the knowledge on drought forecasting, warning and mitigation, and advance the understanding of climate related vulnerability to drought and to develop a prototype operational forecasting.

Early-\\x90stage Electrical Breakdown involving Tunneling

NASA Astrophysics Data System (ADS)

Hjalmarson, Harold; Moore, Chris; Schultz, Peter; Bussman, Ezra; Scrymgeour, David; Hopkins, Matt

The early stage of electrical breakdown from a surface is assumed to involve field emission. In real-world applications, the electrical field is often assumed to be increased by geometrical effects. In addition to these enhancement effects, contamination by adsorbates can lead to reductions in the effective work functions. To develop a physics-based understanding beyond the use of these empirical effects, the field emission currents at early times are being computed and measured. The calculations involve a solution of the Boltzmann equation, and the measurements involve a scanning tunneling microscope. Early results from this collaborative theoretical-experimental project will be described in this presentation. The presentation will focus on results for an ideal system with an absence of geometrical effects. Sandia National Laboratories is a multi-mission laboratory managed and operated by Sandia Corporation, a wholly owned subsidiary of Lockheed Martin Corporation, for the U.S. Department of Energy's National Nuclear Security Administration under contract DE-AC04-94AL85000.

Swimming speed alteration in the early developmental stages of Paracentrotus lividus sea urchin as ecotoxicological endpoint.

PubMed

Morgana, Silvia; Gambardella, Chiara; Falugi, Carla; Pronzato, Roberto; Garaventa, Francesca; Faimali, Marco

2016-04-01

Behavioral endpoints have been used for decades to assess chemical impacts at concentrations unlikely to cause mortality. With recently developed techniques, it is possible to investigate the swimming behavior of several organisms under laboratory conditions. The aims of this study were: i) assessing for the first time the feasibility of swimming speed analysis of the early developmental stage sea urchin Paracentrotus lividus by an automatic recording system ii) investigating any Swimming Speed Alteration (SSA) on P. lividus early stages exposed to a chemical reference; iii) identifying the most suitable stage for SSA test. Results show that the swimming speed of all the developmental stages was easily recorded. The swimming speed was inhibited as a function of toxicant concentration. Pluteus were the most appropriate stage for evaluating SSA in P. lividus as ecotoxicological endpoint. Finally, swimming of sea urchin early stages represents a sensitive endpoint to be considered in ecotoxicological investigations. Copyright © 2016 Elsevier Ltd. All rights reserved.

Successional changes in trophic interactions support a mechanistic model of post-fire population dynamics.

PubMed

Smith, Annabel L

2018-01-01

Models based on functional traits have limited power in predicting how animal populations respond to disturbance because they do not capture the range of demographic and biological factors that drive population dynamics, including variation in trophic interactions. I tested the hypothesis that successional changes in vegetation structure, which affected invertebrate abundance, would influence growth rates and body condition in the early-successional, insectivorous gecko Nephrurus stellatus. I captured geckos at 17 woodland sites spanning a succession gradient from 2 to 48 years post-fire. Body condition and growth rates were analysed as a function of the best-fitting fire-related predictor (invertebrate abundance or time since fire) with different combinations of the co-variates age, sex and location. Body condition in the whole population was positively affected by increasing invertebrate abundance and, in the adult population, this effect was most pronounced for females. There was strong support for a decline in growth rates in weight with time since fire. The results suggest that increased early-successional invertebrate abundance has filtered through to a higher trophic level with physiological benefits for insectivorous geckos. I integrated the new findings about trophic interactions into a general conceptual model of mechanisms underlying post-fire population dynamics based on a long-term research programme. The model highlights how greater food availability during early succession could drive rapid population growth by contributing to previously reported enhanced reproduction and dispersal. This study provides a framework to understand links between ecological and physiological traits underlying post-fire population dynamics.

Human immune cells' behavior and survival under bioenergetically restricted conditions in an in vitro fracture hematoma model

PubMed Central

Hoff, Paula; Maschmeyer, Patrick; Gaber, Timo; Schütze, Tabea; Raue, Tobias; Schmidt-Bleek, Katharina; Dziurla, René; Schellmann, Saskia; Lohanatha, Ferenz Leonard; Röhner, Eric; Ode, Andrea; Burmester, Gerd-Rüdiger; Duda, Georg N; Perka, Carsten; Buttgereit, Frank

2013-01-01

The initial inflammatory phase of bone fracture healing represents a critical step for the outcome of the healing process. However, both the mechanisms initiating this inflammatory phase and the function of immune cells present at the fracture site are poorly understood. In order to study the early events within a fracture hematoma, we established an in vitro fracture hematoma model: we cultured hematomas forming during an osteotomy (artificial bone fracture) of the femur during total hip arthroplasty (THA) in vitro under bioenergetically controlled conditions. This model allowed us to monitor immune cell populations, cell survival and cytokine expression during the early phase following a fracture. Moreover, this model enabled us to change the bioenergetical conditions in order to mimic the in vivo situation, which is assumed to be characterized by hypoxia and restricted amounts of nutrients. Using this model, we found that immune cells adapt to hypoxia via the expression of angiogenic factors, chemoattractants and pro-inflammatory molecules. In addition, combined restriction of oxygen and nutrient supply enhanced the selective survival of lymphocytes in comparison with that of myeloid derived cells (i.e., neutrophils). Of note, non-restricted bioenergetical conditions did not show any similar effects regarding cytokine expression and/or different survival rates of immune cell subsets. In conclusion, we found that the bioenergetical conditions are among the crucial factors inducing the initial inflammatory phase of fracture healing and are thus a critical step for influencing survival and function of immune cells in the early fracture hematoma. PMID:23396474

Development of a long-term ovine model of cutaneous burn and smoke inhalation injury and the effects of early excision and skin autografting

PubMed Central

Yamamoto, Yusuke; Enkhbaatar, Perenlei; Sakurai, Hiroyuki; Rehberg, Sebastian; Asmussen, Sven; Ito, Hiroshi; Sousse, Linda E.; Cox, Robert A.; Deyo, Donald J.; Traber, Lillian D.; Traber, Maret G.; Herndon, David N.; Traber, Daniel L.

2013-01-01

Smoke inhalation injury frequently increases the risk of pneumonia and mortality in burn patients. The pathophysiology of acute lung injury secondary to burn and smoke inhalation is well studied, but long-term pulmonary function, especially the process of lung tissue healing following burn and smoke inhalation, has not been fully investigated. By contrast, early burn excision has become the standard of care in the management of major burn injury. While many clinical studies and small-animal experiments support the concept of early burn wound excision, and show improved survival and infectious outcomes, we have developed a new chronic ovine model of burn and smoke inhalation injury with early excision and skin grafting that can be used to investigate lung pathophysiology over a period of 3 weeks. Materials and methods Eighteen female sheep were surgically prepared for this study under isoflurane anesthesia. The animals were divided into three groups: an Early Excision group (20% TBSA, third-degree cutaneous burn and 36 breaths of cotton smoke followed by early excision and skin autografting at 24 h after injury, n = 6), a Control group (20% TBSA, third-degree cutaneous burn and 36 breaths of cotton smoke without early excision, n = 6) and a Sham group (no injury, no early excision, n = 6). After induced injury, all sheep were placed on a ventilator and fluid-resuscitated with Lactated Ringers solution (4 mL/% TBS/kg). At 24 h post-injury, early excision was carried out to fascia, and skin grafting with meshed autografts (20/1000 in., 1:4 ratio) was performed under isoflurane anesthesia. At 48 h post-injury, weaning from ventilator was begun if PaO2/FiO2 was above 250 and sheep were monitored for 3 weeks. Results At 96 h post-injury, all animals were weaned from ventilator. There are no significant differences in PaO2/FiO2 between Early Excision and Control groups at any points. All animals were survived for 3 weeks without infectious complication in Early Excision and Sham groups, whereas two out of six animals in the Control group had abscess in lung. The percentage of the wound healed surviving area (mean ± SD) was 74.7 ± 7.8% on 17 days post-surgery in the Early Excision group. Lung wet-to-dry weight ratio (mean ± SD) was significantly increased in the Early Excision group vs. Sham group (p < 0.05). The calculated net fluid balance significantly increased in the early excision compared to those seen in the Sham and Control groups. Plasma protein, oncotic pressure, hematocrit of % baseline, hemoglobin of % baseline, white blood cell and neutrophil were significantly decreased in the Early Excision group vs. Control group. Conclusions The early excision model closely resembles practice in a clinical setting and allows long-term observations of pulmonary function following burn and smoke inhalation injury. Further studies are warranted to assess lung tissue scarring and measuring collagen deposition, lung compliance and diffusion capacity. PMID:22459154

Genome-wide Fitness Profiles Reveal a Requirement for Autophagy During Yeast Fermentation

PubMed Central

Piggott, Nina; Cook, Michael A.; Tyers, Mike; Measday, Vivien

2011-01-01

The ability of cells to respond to environmental changes and adapt their metabolism enables cell survival under stressful conditions. The budding yeast Saccharomyces cerevisiae (S. cerevisiae) is particularly well adapted to the harsh conditions of anaerobic wine fermentation. However, S. cerevisiae gene function has not been previously systematically interrogated under conditions of industrial fermentation. We performed a genome-wide study of essential and nonessential S. cerevisiae gene requirements during grape juice fermentation to identify deletion strains that are either depleted or enriched within the viable fermentative population. Genes that function in autophagy and ubiquitin-proteasome degradation are required for optimal survival during fermentation, whereas genes that function in ribosome assembly and peroxisome biogenesis impair fitness during fermentation. We also uncover fermentation phenotypes for 139 uncharacterized genes with no previously known cellular function. We demonstrate that autophagy is induced early in wine fermentation in a nitrogen-replete environment, suggesting that autophagy may be triggered by other forms of stress that arise during fermentation. These results provide insights into the complex fermentation process and suggest possible means for improvement of industrial fermentation strains. PMID:22384346

Taurine flux in chicken erythrocytes.

PubMed

Porter, D W; Martin, W G

1992-05-01

1. The intracellular taurine concentration in chick erythrocytes increased with age. 2. Erythrocyte taurine influx and efflux rates increased with age. 3. Erythrocyte taurine influx decreased when the extracellular sodium concentration was below normal physiological concentrations. 4. Under hypo-osmotic conditions, taurine efflux from erythrocytes increased. 5. The data suggest that chick erythrocyte taurine metabolism changes during early post-hatch development and that one taurine function may be as an osmoregulator.

The density management and riparian buffer study: a large-scale silviculture experiment informing riparian management in the Pacific Northwest, USA

Treesearch

Paul D. Anderson; Nathan J. Poage

2014-01-01

The advent of the Northwest Forest Plan (NWFP) in the early 1990s signaled a new paradigm for management of 9.9 million ha of federal forest lands in western Washington and Oregon, USA. The emphasis shifted from commodity timber production to ensuring sustained ecological functioning to meet a broad array of ecosystem services including economic benefits. Under interim...

Motion Direction Biases and Decoding in Human Visual Cortex

PubMed Central

Wang, Helena X.; Merriam, Elisha P.; Freeman, Jeremy

2014-01-01

Functional magnetic resonance imaging (fMRI) studies have relied on multivariate analysis methods to decode visual motion direction from measurements of cortical activity. Above-chance decoding has been commonly used to infer the motion-selective response properties of the underlying neural populations. Moreover, patterns of reliable response biases across voxels that underlie decoding have been interpreted to reflect maps of functional architecture. Using fMRI, we identified a direction-selective response bias in human visual cortex that: (1) predicted motion-decoding accuracy; (2) depended on the shape of the stimulus aperture rather than the absolute direction of motion, such that response amplitudes gradually decreased with distance from the stimulus aperture edge corresponding to motion origin; and 3) was present in V1, V2, V3, but not evident in MT+, explaining the higher motion-decoding accuracies reported previously in early visual cortex. These results demonstrate that fMRI-based motion decoding has little or no dependence on the underlying functional organization of motion selectivity. PMID:25209297

Tumor-associated macrophages as a paradigm of macrophage plasticity, diversity, and polarization: lessons and open questions.

PubMed

Mantovani, Alberto; Locati, Massimo

2013-07-01

Macrophages are present in all body compartments, including cancerous tissues, and their functions are profoundly affected by signals from the microenvironment under homeostatic and pathological conditions. Tumor-associated macrophages are a major cellular component of cancer-related inflammation and have served as a paradigm for the plasticity and functional polarization of mononuclear phagocytes. Tumor-associated macrophages can exert dual influence of cancer depending on the activation state, with classically activated (M1) and alternatively activated (M2) cells generally exerting antitumoral and protumoral functions, respectively. These are extremes in a continuum of polarization states in a universe of diversity. Tumor-associated macrophages affect virtually all aspects of tumor tissues, including stem cells, metabolism, angiogenesis, invasion, and metastasis. Progress has been made in defining signaling molecules, transcription factors, epigenetic changes, and repertoire of microRNAs underlying macrophage polarization. Preclinical and early clinical data suggest that macrophages may serve as tools for the development of innovative diagnostic and therapeutic strategies in cancer and chronic nonresolving inflammatory diseases.

Impaired early visual response modulations to spatial information in chronic schizophrenia

PubMed Central

Knebel, Jean-François; Javitt, Daniel C.; Murray, Micah M.

2011-01-01

Early visual processing stages have been demonstrated to be impaired in schizophrenia patients and their first-degree relatives. The amplitude and topography of the P1 component of the visual evoked potential (VEP) are both affected; the latter of which indicates alterations in active brain networks between populations. At least two issues remain unresolved. First, the specificity of this deficit (and suitability as an endophenotype) has yet to be established, with evidence for impaired P1 responses in other clinical populations. Second, it remains unknown whether schizophrenia patients exhibit intact functional modulation of the P1 VEP component; an aspect that may assist in distinguishing effects specific to schizophrenia. We applied electrical neuroimaging analyses to VEPs from chronic schizophrenia patients and healthy controls in response to variation in the parafoveal spatial extent of stimuli. Healthy controls demonstrated robust modulation of the VEP strength and topography as a function of the spatial extent of stimuli during the P1 component. By contrast, no such modulations were evident at early latencies in the responses from patients with schizophrenia. Source estimations localized these deficits to the left precuneus and medial inferior parietal cortex. These findings provide insights on potential underlying low-level impairments in schizophrenia. PMID:21764264

Dermatoglyphic asymmetries and fronto-striatal dysfunction in young-adults reporting non-clinical psychosis

PubMed Central

Mittal, Vijay A.; Dean, Derek J.; Pelletier, Andrea

2012-01-01

Objective Growing evidence indicates that non-clinical psychotic-like experiences occur in otherwise healthy individuals, suggesting that psychosis may occur on a continuum. However, little is know about how the diathesis for formal psychosis maps on to individuals at the non-clinical side of this continuum. Our current understanding of the pathophysiology of schizophrenia implicates certain key factors such as early developmental abnormalities and fronto-striatal dysfunction. To date, no studies have examined these core factors in the context of non-clinical psychosis. Method A total of 221 young adults were assessed for distressing attenuated positive symptoms (DAPS), dermatoglyphic asymmetries (a marker of early developmental insult), and procedural memory (a proxy for fronto-striatal function). Results Participants reporting DAPS (n=16; 7.2%) and no-DAPS (n=205; 92.7%) were split into two groups. The DAPS group showed significantly elevated depression, elevated dermatoglyphic asymmetries, and a pattern of procedural learning consistent with other studies with formally psychotic patients. Conclusion The results indicate that the non-clinical side of the psychosis continuum also shares key vulnerability factors implicated in schizophrenia, suggesting that both early developmental disruption and abnormalities in fronto-striatal function are core aspects underlying the disorder. PMID:22519833

Mitochondrial Reactive Oxygen Species and Kidney Hypoxia in the Development of Diabetic Nephropathy

PubMed Central

Schiffer, Tomas A.; Friederich-Persson, Malou

2017-01-01

The underlying mechanisms in the development of diabetic nephropathy are currently unclear and likely consist of a series of dynamic events from the early to late stages of the disease. Diabetic nephropathy is currently without curative treatments and it is acknowledged that even the earliest clinical manifestation of nephropathy is preceded by an established morphological renal injury that is in turn preceded by functional and metabolic alterations. An early manifestation of the diabetic kidney is the development of kidney hypoxia that has been acknowledged as a common pathway to nephropathy. There have been reports of altered mitochondrial function in the diabetic kidney such as altered mitophagy, mitochondrial dynamics, uncoupling, and cellular signaling through hypoxia inducible factors and AMP-kinase. These factors are also likely to be intertwined in a complex manner. In this review, we discuss how these pathways are connected to mitochondrial production of reactive oxygen species (ROS) and how they may relate to the development of kidney hypoxia in diabetic nephropathy. From available literature, it is evident that early correction and/or prevention of mitochondrial dysfunction may be pivotal in the prevention and treatment of diabetic nephropathy. PMID:28443030

Mitochondrial Reactive Oxygen Species and Kidney Hypoxia in the Development of Diabetic Nephropathy.

PubMed

Schiffer, Tomas A; Friederich-Persson, Malou

2017-01-01

The underlying mechanisms in the development of diabetic nephropathy are currently unclear and likely consist of a series of dynamic events from the early to late stages of the disease. Diabetic nephropathy is currently without curative treatments and it is acknowledged that even the earliest clinical manifestation of nephropathy is preceded by an established morphological renal injury that is in turn preceded by functional and metabolic alterations. An early manifestation of the diabetic kidney is the development of kidney hypoxia that has been acknowledged as a common pathway to nephropathy. There have been reports of altered mitochondrial function in the diabetic kidney such as altered mitophagy, mitochondrial dynamics, uncoupling, and cellular signaling through hypoxia inducible factors and AMP-kinase. These factors are also likely to be intertwined in a complex manner. In this review, we discuss how these pathways are connected to mitochondrial production of reactive oxygen species (ROS) and how they may relate to the development of kidney hypoxia in diabetic nephropathy. From available literature, it is evident that early correction and/or prevention of mitochondrial dysfunction may be pivotal in the prevention and treatment of diabetic nephropathy.

[Quantitative histoenzymatic analysis of the adenohypophysis and adrenal cortex during the early stages of involution].

PubMed

Prochukhanov, R A; Rostovtseva, T I

1977-11-01

A method of quantitative histenzymatic analysis was applied for determination of the involution changes of the neuroendocrine system. The activity of NAD- and NADP-reductases, acid and alkaline phosphatases, glucose-6-phosphoric dehydrogenase, 3-OH-steroid-dehydrogenase, 11-hydroxysteroid dehydrogenases was investigated in the adenohypophysis and in the adrenal cortex of rats aged 4 and 12 months. There were revealed peculiarities attending the structural-metabolic provision of physiological reconstructions of the neuro-endocrine system under conditions of the estral cycle at the early involution stages. An initial reduction of the cell ular-vascular transport with the retention of the functional activity of the intracellular organoids was demonstrated in ageing animals.

Transient times in linear metabolic pathways under constant affinity constraints.

PubMed

Lloréns, M; Nuño, J C; Montero, F

1997-10-15

In the early seventies, Easterby began the analytical study of transition times for linear reaction schemes [Easterby (1973) Biochim. Biophys. Acta 293, 552-558]. In this pioneer work and in subsequent papers, a state function (the transient time) was used to measure the period before the stationary state, for systems constrained to work under both constant and variable input flux, was reached. Despite the undoubted usefulness of this quantity to describe the time-dependent features of these kinds of systems, its application to the study of chemical reactions under other constraints is questionable. In the present work, a generalization of these magnitudes to linear metabolic pathways functioning under a constant-affinity constraint is carried out. It is proved that classical definitions of transient times do not reflect the actual properties of the transition to the steady state in systems evolving under this restriction. Alternatively, a more adequate framework for interpretation of the transient times for systems with both constant and variable input flux is suggested. Within this context, new definitions that reflect more accurately the transient characteristics of constant affinity systems are stated. Finally, the meaning of these transient times is discussed.

Practical applications of trace minerals for dairy cattle.

PubMed

Overton, T R; Yasui, T

2014-02-01

Trace minerals have critical roles in the key interrelated systems of immune function, oxidative metabolism, and energy metabolism in ruminants. To date, the primary trace elements of interest in diets for dairy cattle have included Zn, Cu, Mn, and Se although data also support potentially important roles of Cr, Co, and Fe in diets. Trace minerals such as Zn, Cu, Mn, and Se are essential with classically defined roles as components of key antioxidant enzymes and proteins. Available evidence indicates that these trace minerals can modulate aspects of oxidative metabolism and immune function in dairy cattle, particularly during the transition period and early lactation. Chromium has been shown to influence both immune function and energy metabolism of cattle; dairy cows fed Cr during the transition period and early lactation have evidence of improved immune function, increased milk production, and decreased cytological endometritis. Factors that complicate trace mineral nutrition at the farm level include the existence of a large number of antagonisms affecting bioavailability of individual trace minerals and uncertainty in terms of requirements under all physiological and management conditions; therefore, determining the optimum level and source of trace minerals under each specific situation continues to be a challenge. Typical factorial approaches to determine requirements for dairy cattle do not account for nuances in biological function observed with supplementation with various forms and amounts of trace minerals. Trace mineral nutrition modulates production, health, and reproduction in cattle although both formal meta-analysis and informal survey of the literature reveal substantial heterogeneity of response in these outcome variables. The industry has largely moved away from oxide-based programs toward sulfate-based programs; however, some evidence favors shifting supplementation strategies further toward more bioavailable forms of inorganic and organic trace minerals. Furthermore, opportunities for specific modulation of aspects of health, milk production, and reproduction through supplementation strategies for diets of transition dairy cows are attractive because of the known dynamics of energy metabolism, immune function, and oxidative metabolism during this timeframe.

34 CFR 303.211 - State option to make services under this part available to children ages three and older.

Code of Federal Regulations, 2013 CFR

2013-07-01

... EDUCATION EARLY INTERVENTION PROGRAM FOR INFANTS AND TODDLERS WITH DISABILITIES State Application and... eligible for preschool services under section 619 of the Act and who previously received early intervention services under this part, may choose the continuation of early intervention services under this part for...

34 CFR 303.211 - State option to make services under this part available to children ages three and older.

Code of Federal Regulations, 2014 CFR

2014-07-01

... EDUCATION EARLY INTERVENTION PROGRAM FOR INFANTS AND TODDLERS WITH DISABILITIES State Application and... eligible for preschool services under section 619 of the Act and who previously received early intervention services under this part, may choose the continuation of early intervention services under this part for...

34 CFR 303.211 - State option to make services under this part available to children ages three and older.

Code of Federal Regulations, 2012 CFR

2012-07-01

... EDUCATION EARLY INTERVENTION PROGRAM FOR INFANTS AND TODDLERS WITH DISABILITIES State Application and... eligible for preschool services under section 619 of the Act and who previously received early intervention services under this part, may choose the continuation of early intervention services under this part for...

Different Cortical Dynamics in Face and Body Perception: An MEG study

PubMed Central

Meeren, Hanneke K. M.; de Gelder, Beatrice; Ahlfors, Seppo P.; Hämäläinen, Matti S.; Hadjikhani, Nouchine

2013-01-01

Evidence from functional neuroimaging indicates that visual perception of human faces and bodies is carried out by distributed networks of face and body-sensitive areas in the occipito-temporal cortex. However, the dynamics of activity in these areas, needed to understand their respective functional roles, are still largely unknown. We monitored brain activity with millisecond time resolution by recording magnetoencephalographic (MEG) responses while participants viewed photographs of faces, bodies, and control stimuli. The cortical activity underlying the evoked responses was estimated with anatomically-constrained noise-normalised minimum-norm estimate and statistically analysed with spatiotemporal cluster analysis. Our findings point to distinct spatiotemporal organization of the neural systems for face and body perception. Face-selective cortical currents were found at early latencies (120–200 ms) in a widespread occipito-temporal network including the ventral temporal cortex (VTC). In contrast, early body-related responses were confined to the lateral occipito-temporal cortex (LOTC). These were followed by strong sustained body-selective responses in the orbitofrontal cortex from 200–700 ms, and in the lateral temporal cortex and VTC after 500 ms latency. Our data suggest that the VTC region has a key role in the early processing of faces, but not of bodies. Instead, the LOTC, which includes the extra-striate body area (EBA), appears the dominant area for early body perception, whereas the VTC contributes to late and post-perceptual processing. PMID:24039712

m-AAA Complexes Are Not Crucial for the Survival of Arabidopsis Under Optimal Growth Conditions Despite Their Importance for Mitochondrial Translation.

PubMed

Kolodziejczak, Marta; Skibior-Blaszczyk, Renata; Janska, Hanna

2018-05-01

For optimal mitochondrial activity, the mitochondrial proteome must be properly maintained or altered in response to developmental and environmental stimuli. Based on studies of yeast and humans, one of the key players in this control are m-AAA proteases, mitochondrial inner membrane-bound ATP-dependent metalloenzymes. This study focuses on the importance of m-AAA proteases in plant mitochondria, providing their first experimentally proven physiological substrate. We found that the Arabidopsis m- AAA complexes composed of AtFTSH3 and/or AtFTSH10 are involved in the proteolytic maturation of ribosomal subunit L32. Consequently, in the double Arabidopsis ftsh3/10 mutant, mitoribosome biogenesis, mitochondrial translation and functionality of OXPHOS (oxidative phosphorylation) complexes are impaired. However, in contrast to their mammalian or yeast counterparts, plant m-AAA complexes are not critical for the survival of Arabidopsis under optimal conditions; ftsh3/10 plants are only slightly smaller in size at the early developmental stage compared with plants containing m-AAA complexes. Our data suggest that a lack of significant visible morphological alterations under optimal growth conditions involves mechanisms which rely on existing functional redundancy and induced functional compensation in Arabidopsis mitochondria.

The influence of pericardial fat upon left ventricular function in obese females: evidence of a site-specific effect

PubMed Central

2014-01-01

Background Although increased volume of pericardial fat has been associated with decreased cardiac function, it is unclear whether this association is mediated by systemic overall obesity or direct regional fat interactions. We hypothesized that if local effects dominate, left ventricular (LV) function would be most strongly associated with pericardial fat that surrounds the left rather than the right ventricle (RV). Methods Female obese subjects (n = 60) had cardiovascular magnetic resonance (CMR) scans to obtain measures of LV function and pericardial fat volumes. LV function was obtained using the cine steady state free precession imaging in short axis orientation. The amount of pericardial fat was determined volumetrically by the cardiac gated T1 black blood imaging and normalized to body surface area. Results In this study cohort, LV fat correlated with several LV hemodynamic measurements including cardiac output (r = -0.41, p = 0.001) and stroke volume (r = -0.26, p = 0.05), as well as diastolic functional parameters including peak-early-filling rate (r = -0.38, p = 0.01), early late filling ratio (r = -0.34, p = 0.03), and time to peak-early-filling (r = 0.34, p = 0.03). These correlations remained significant even after adjusting for the body mass index and the blood pressure. However, similar correlations became weakened or even disappeared between RV fat and LV function. LV function was not correlated with systemic plasma factors, such as C-reactive protein (CRP), B-type natriuretic peptide (BNP), Interleukin-6 (IL-6), resistin and adiponectin (all p > 0.05). Conclusions LV hemodynamic and diastolic function was associated more with LV fat as compared to RV or total pericardial fat, but not with systemic inflammatory markers or adipokines. The correlations between LV function and pericardial fat remained significant even after adjusting for systemic factors. These findings suggest a site-specific influence of pericardial fat on LV function, which could imply local secretion of molecules into the underlying tissue or an anatomic effect, both mechanisms meriting future evaluation. PMID:24884541

Temporal Expression Profiling Identifies Pathways Mediating Effect of Causal Variant on Phenotype

PubMed Central

Gupta, Saumya; Radhakrishnan, Aparna; Raharja-Liu, Pandu; Lin, Gen; Steinmetz, Lars M.; Gagneur, Julien; Sinha, Himanshu

2015-01-01

Even with identification of multiple causal genetic variants for common human diseases, understanding the molecular processes mediating the causal variants’ effect on the disease remains a challenge. This understanding is crucial for the development of therapeutic strategies to prevent and treat disease. While static profiling of gene expression is primarily used to get insights into the biological bases of diseases, it makes differentiating the causative from the correlative effects difficult, as the dynamics of the underlying biological processes are not monitored. Using yeast as a model, we studied genome-wide gene expression dynamics in the presence of a causal variant as the sole genetic determinant, and performed allele-specific functional validation to delineate the causal effects of the genetic variant on the phenotype. Here, we characterized the precise genetic effects of a functional MKT1 allelic variant in sporulation efficiency variation. A mathematical model describing meiotic landmark events and conditional activation of MKT1 expression during sporulation specified an early meiotic role of this variant. By analyzing the early meiotic genome-wide transcriptional response, we demonstrate an MKT1-dependent role of novel modulators, namely, RTG1/3, regulators of mitochondrial retrograde signaling, and DAL82, regulator of nitrogen starvation, in additively effecting sporulation efficiency. In the presence of functional MKT1 allele, better respiration during early sporulation was observed, which was dependent on the mitochondrial retrograde regulator, RTG3. Furthermore, our approach showed that MKT1 contributes to sporulation independent of Puf3, an RNA-binding protein that steady-state transcription profiling studies have suggested to mediate MKT1-pleiotropic effects during mitotic growth. These results uncover interesting regulatory links between meiosis and mitochondrial retrograde signaling. In this study, we highlight the advantage of analyzing allele-specific transcriptional dynamics of mediating genes. Applications in higher eukaryotes can be valuable for inferring causal molecular pathways underlying complex dynamic processes, such as development, physiology and disease progression. PMID:26039065

The Fantasmatic and Imaginary Child of the Pregnant Woman

PubMed Central

SETTERBERG, Simone

2017-01-01

Background Pregnancy is a period of transition, which makes women more vulnerable and in unfavorable conditions may lead to psychopathology in both mother and infant. It is essential to outline factors adversely affecting the resolution of this period. Early interventions and why they matter: Interventions during pregnancy can provide important improvement in the outcome for both maternal and infant mental health. Aim The aim of the study is to evaluate the risk factors of antenatal anxiety and depression focusing particularly on maternal representations of the relationship towards the fetus and her own parents during pregnancy and the early postpartum period. Methods The study is outlined using a quantifiable interview during pregnancy to evaluate the woman’s ability to keep her child in mind, measured by reflective functioning. Reflective functioning provides information regarding the pregnant woman’s relationship quality to her fetus and important people in her life. Primiparae in Stockholm around gestation week 20 are asked about their experience with respect to pregnancy, their relationship to their family, partner, and their unborn child. The women selected to the study are an at risk population, with high levels of stress, childhood adversity, and/or history of mental health. These women are more vulnerable to develop perinatal anxiety and depression. Results The pregnancy interview provides valuable insight into the pregnant women’s psychic constitution. The quantifiable measure of their mental state, reflective functioning, serves as measure of quality of the mother’s parenting capacity. The countertransference and transference of the interviewer towards the women during the interview enables a more profound understanding of the underlying dynamics and constructs of repression, aggression, mourning, and narcissistic defenses. Conclusion A better understanding of the underlying mechanisms of the pregnant women’s intrapsychic reorganization of motherhood and her relation to the unborn child shall facilitate specific early interventions. These interventions shall be targeted to specific risk groups and enable the prevention of adverse child outcomes. PMID:28904511

Attentional avoidance of fearful facial expressions following early life stress is associated with impaired social functioning.

PubMed

Humphreys, Kathryn L; Kircanski, Katharina; Colich, Natalie L; Gotlib, Ian H

2016-10-01

Early life stress is associated with poorer social functioning. Attentional biases in response to threat-related cues, linked to both early experience and psychopathology, may explain this association. To date, however, no study has examined attentional biases to fearful facial expressions as a function of early life stress or examined these biases as a potential mediator of the relation between early life stress and social problems. In a sample of 154 children (ages 9-13 years) we examined the associations among interpersonal early life stressors (i.e., birth through age 6 years), attentional biases to emotional facial expressions using a dot-probe task, and social functioning on the Child Behavior Checklist. High levels of early life stress were associated with both greater levels of social problems and an attentional bias away from fearful facial expressions, even after accounting for stressors occurring in later childhood. No biases were found for happy or sad facial expressions as a function of early life stress. Finally, attentional biases to fearful faces mediated the association between early life stress and social problems. Attentional avoidance of fearful facial expressions, evidenced by a bias away from these stimuli, may be a developmental response to early adversity and link the experience of early life stress to poorer social functioning. © 2016 Association for Child and Adolescent Mental Health.

Specialised dental care for children with complex disabilities focusing on child's functioning and need for general anaesthesia.

PubMed

Norderyd, Johanna; Klingberg, Gunilla; Faulks, Denise; Granlund, Mats

2017-12-01

To describe and analyse dental care and treatment modalities for children with complex disabilities from a biopsychosocial perspective, with special focus on dental treatment under general anaesthesia (GA) and its relationship to child's functioning. An ICF-CY Checklist for Oral Health was completed using structured interview, direct observations, and dental records for patients attending a specialist paediatric dentistry clinic. Descriptive and comparative data analysis was performed. Performance qualifiers from the ICF-CY component Activities and participation were used to calculate functional factors. Median referral age was 1.5 years and the majority were referred by their paediatrician. Almost all visited a dental hygienist regularly. Dental treatment under GA was common and was combined in 78% of sessions with medical treatment. Children with limitations in their interpersonal interactions and relationships were most likely to have dental GA. Children without caries experience had been referred for specialist dental care at an earlier age than children with caries experience. GA was a common treatment modality and dental and medical treatments were coordinated under the same GA for a majority of children. By using the ICF-CY, it was possible to identify functional limitations characterising children with disabilities that require dental treatment under GA. Implications for Rehabilitation Early referral to a specialist in paediatric dentistry is valuable for oral disease prevention in children with disabilities. Availability of dental treatment under general anaesthesia (GA) is also important. Combining dental and medical interventions during the same GA session optimises resources both for the individual and for the health organisation. Children with limitations in interpersonal interactions and relationships are more likely to need dental treatment under GA than other children.

Trithorax Group Protein Oryza sativa Trithorax1 Controls Flowering Time in Rice via Interaction with Early heading date31[W][OPEN

PubMed Central

Choi, Sang Chul; Lee, Shinyoung; Kim, Sung-Ryul; Lee, Yang-Seok; Liu, Chunyan; Cao, Xiaofeng; An, Gynheung

2014-01-01

Trithorax group proteins are chromatin-remodeling factors that activate target gene expression by antagonistically functioning against the Polycomb group. In Arabidopsis (Arabidopsis thaliana), Arabidopsis Trithorax protein1 (ATX1) regulates flowering time and floral organ identity. Here, we observed that suppression of Oryza sativa Trithorax1 (OsTrx1), an ortholog of ATX1, delayed flowering time in rice (Oryza sativa). Because the delay occurred only under long-day conditions, we evaluated the flowering signal pathways that specifically function under long-day conditions. Among them, the OsMADS50 and Heading date1 pathways were not affected by the mutation. However, the Grain number, plant height, and heading date7 (Ghd7) pathway was altered in ostrx1. Transcript levels of OsGI, phytochrome genes, and Early heading date3 (Ehd3), which function upstream of Ghd7, were unchanged in the mutant. Because Trx group proteins form a complex with other proteins to modify the chromatin structure of target genes, we investigated whether OsTrx1 interacts with a previously identified protein that functions upstream of Ghd7. We demonstrated that the plant homeodomain motif of OsTrx1 binds to native histone H3 from the calf thymus and that OsTrx1 binds to Ehd3 through the region between the plant homeodomain and SET domains. Finally, we showed that the SET domain at the C-terminal end of OsTrx1 has histone H3 methyltransferase activity when incubated with oligonucleosomes. Our results suggest that OsTrx1 plays an important role in regulating flowering time in rice by modulating chromatin structure. PMID:24420930

Language Outcomes at 7 Years: Early Predictors and Co-Occurring Difficulties.

PubMed

McKean, Cristina; Reilly, Sheena; Bavin, Edith L; Bretherton, Lesley; Cini, Eileen; Conway, Laura; Cook, Fallon; Eadie, Patricia; Prior, Margot; Wake, Melissa; Mensah, Fiona

2017-03-01

To examine at 7 years the language abilities of children, the salience of early life factors and language scores as predictors of language outcome, and co-occurring difficulties METHODS: A longitudinal cohort study of 1910 infants recruited at age 8 to 10 months. Exposures included early life factors (sex, prematurity, birth weight/order, twin birth, socioeconomic status, non-English speaking background,family history of speech/language difficulties); maternal factors (mental health, vocabulary, education, and age); and child language ability at 2 and 4 years. Outcomes were 7-year standardized receptive or expressive language scores (low language: ≥1.25 SD below the mean), and co-occurring difficulties (autism, literacy, social, emotional, and behavioral adjustment, and health-related quality of life). Almost 19% of children (22/1204;18.9%) met criteria for low language at 7 years. Early life factors explained 9-13% of variation in language scores, increasing to 39-58% when child language scores at ages 2 and 4 were included. Early life factors moderately discriminated between children with and without low language (area under the curve: 0.68-0.72), strengthening to good discrimination with language scores at ages 2 and 4 (area under the curve: 0.85-0.94). Low language at age 7 was associated with concurrent difficulties in literacy, social-emotional and behavioral difficulties, and limitations in school and psychosocial functioning. Child language ability at 4 years more accurately predicted low language at 7 than a range of early child, family, and environmental factors. Low language at 7 years was associated with a higher prevalence of co-occurring difficulties. Copyright © 2017 by the American Academy of Pediatrics.

Early detection of probable idiopathic Parkinson's disease: I. development of a diagnostic test battery.

PubMed

Montgomery, Erwin B; Koller, William C; LaMantia, Theodora J K; Newman, Mary C; Swanson-Hyland, Elizabeth; Kaszniak, Alfred W; Lyons, Kelly

2000-05-01

We developed a test battery as an inexpensive and objective aid for the early diagnosis of idiopathic Parkinson's disease (iPD) and its differential diagnoses. The test battery incorporates tests of motor function, olfaction, and mood. In the motor task, a wrist flexion-and-extension task to different targets, movement velocities were recorded. Olfaction was tested with the University of Pennsylvania Smell Identification Test. Mood was assessed with the Beck Depression Inventory. An initial regression model was developed from the results of 19 normal control subjects and 18 patients with early, mild, probable iPD. Prospective application to an independent validation set of 122 normal control subjects and 103 patients resulted in an 88% specificity rate and 69% sensitivity rate, with an area under the Receiver Operator Characteristic curve of 0.87. Copyright © 2000 Movement Disorder Society.

Mismatch Negativity with Visual-only and Audiovisual Speech

PubMed Central

Ponton, Curtis W.; Bernstein, Lynne E.; Auer, Edward T.

2009-01-01

The functional organization of cortical speech processing is thought to be hierarchical, increasing in complexity and proceeding from primary sensory areas centrifugally. The current study used the mismatch negativity (MMN) obtained with electrophysiology (EEG) to investigate the early latency period of visual speech processing under both visual-only (VO) and audiovisual (AV) conditions. Current density reconstruction (CDR) methods were used to model the cortical MMN generator locations. MMNs were obtained with VO and AV speech stimuli at early latencies (approximately 82-87 ms peak in time waveforms relative to the acoustic onset) and in regions of the right lateral temporal and parietal cortices. Latencies were consistent with bottom-up processing of the visible stimuli. We suggest that a visual pathway extracts phonetic cues from visible speech, and that previously reported effects of AV speech in classical early auditory areas, given later reported latencies, could be attributable to modulatory feedback from visual phonetic processing. PMID:19404730

Leukemic gingival enlargement: Report of a rare case with review of literature

PubMed Central

Hasan, Shamimul; Khan, Nabeel Ishrat; Reddy, L Bhaskar

2015-01-01

Oral cavity functions as an early indicator for a variety of systemic diseases. Early and accurate diagnosis of these underlying systemic disorders entails thorough examination of the oral mucosa, gingiva, teeth, tongue and other oral tissues. Although gingival changes may be related to local factors in the oral cavity, it can also be an expression of systemic conditions such as blood dyscrasias, endocrinal imbalance, and nutritional deficiencies. Leukemia, a malignancy of white blood cells is a dreadful disease, which, if not diagnosed properly and treated early may result in significant morbidity and mortality. Oral changes may be the first and only presenting signs in leukemic patients. This paper aims to throw light on an interesting case of acute leukemia diagnosed on the basis of oral signs and emphasizes the importance of thorough oral examination to identify the threatening condition. PMID:25664273

Early dynamic fate changes in haemogenic endothelium characterized at the single-cell level

NASA Astrophysics Data System (ADS)

Swiers, Gemma; Baumann, Claudia; O'Rourke, John; Giannoulatou, Eleni; Taylor, Stephen; Joshi, Anagha; Moignard, Victoria; Pina, Cristina; Bee, Thomas; Kokkaliaris, Konstantinos D.; Yoshimoto, Momoko; Yoder, Mervin C.; Frampton, Jon; Schroeder, Timm; Enver, Tariq; Göttgens, Berthold; de Bruijn, Marella F. T. R.

2013-12-01

Haematopoietic stem cells (HSCs) are the founding cells of the adult haematopoietic system, born during ontogeny from a specialized subset of endothelium, the haemogenic endothelium (HE) via an endothelial-to-haematopoietic transition (EHT). Although recently imaged in real time, the underlying mechanism of EHT is still poorly understood. We have generated a Runx1 +23 enhancer-reporter transgenic mouse (23GFP) for the prospective isolation of HE throughout embryonic development. Here we perform functional analysis of over 1,800 and transcriptional analysis of 268 single 23GFP+ HE cells to explore the onset of EHT at the single-cell level. We show that initiation of the haematopoietic programme occurs in cells still embedded in the endothelial layer, and is accompanied by a previously unrecognized early loss of endothelial potential before HSCs emerge. Our data therefore provide important insights on the timeline of early haematopoietic commitment.

The effect of childhood trauma on spatial cognition in adults: a possible role of sex.

PubMed

Syal, Supriya; Ipser, Jonathan; Phillips, Nicole; Thomas, Kevin G F; van der Honk, Jack; Stein, Dan J

2014-06-01

Although animal evidence indicates that early life trauma results in pervasive hippocampal deficits underlying spatial and cognitive impairment, visuo-spatial data from adult humans with early childhood adversity are lacking. We administered 4 tests of visuo-spatial ability from the Cambridge Neuorpsychological Test Automated Battery (CANTAB) to adults with a history of childhood trauma (measured by the Childhood Trauma Questionnaire) and a matched sample of healthy controls (trauma/control = 27/28). We observed a significant effect of trauma history on spatial/pattern learning. These effects could not be accounted for by adverse adult experiences, and were sex-specific, with prior adversity improving performance in men but worsening performance in women, relative to controls. Limitations include the small sample size and reliance of our study design on a retrospective, self report measure. Our results suggest that early adversity can lead to specific and pervasive deficits in adult cognitive function.

 Rapid identification system of frontal dysfunction in subclinical hepatic encephalopathy.

PubMed

Moretti, Rita; Gazzin, Silvia; Crocè, Lory Saveria; Baso, Beatrice; Masutti, Flora; Bedogni, Giorgio; Tiribelli, Claudio

2016-01-01

 Introduction and aim. Liver disease is associated with cognitive dysfunction also at early stages, and minimal hepatic encephalopathy, affecting 20-70% of patients, is frequently under-recognized. The main purpose of this work was to demonstrate that a substantial number of patients, enrolled due to an acute confusional state in absence of a diagnosis of liver disease, suffers of hepatic encephalopathy. Before a diagnosis of a well-compensated liver diseases was performed, 410 patients with an acute confusional state were enrolled in this study. Even in the presence of minimal alterations of hepatic function, the psychometric tests applied demonstrated early signs of cerebral frontal alteration. The alteration was associated with the severity of liver disease, paralleling the progression of the patient to minimal hepatic failure or chronic liver disease. These psychometric tests are essential to detect early and subclinical frontal failure. Frontal dysfunction may be a useful tool in the follow-up of these patients.

Suppression Subtractive Hybridization Analysis of Genes Regulated by Application of Exogenous Abscisic Acid in Pepper Plant (Capsicum annuum L.) Leaves under Chilling Stress.

PubMed

Guo, Wei-Li; Chen, Ru-Gang; Gong, Zhen-Hui; Yin, Yan-Xu; Li, Da-Wei

2013-01-01

Low temperature is one of the major factors limiting pepper (Capsicum annuum L.) production during winter and early spring in non-tropical regions. Application of exogenous abscisic acid (ABA) effectively alleviates the symptoms of chilling injury, such as wilting and formation of necrotic lesions on pepper leaves; however, the underlying molecular mechanism is not understood. The aim of this study was to identify genes that are differentially up- or downregulated in ABA-pretreated hot pepper seedlings incubated at 6°C for 48 h, using a suppression subtractive hybridization (SSH) method. A total of 235 high-quality ESTs were isolated, clustered and assembled into a collection of 73 unigenes including 18 contigs and 55 singletons. A total of 37 unigenes (50.68%) showed similarities to genes with known functions in the non-redundant database; the other 36 unigenes (49.32%) showed low similarities or unknown functions. Gene ontology analysis revealed that the 37 unigenes could be classified into nine functional categories. The expression profiles of 18 selected genes were analyzed using quantitative RT-PCR; the expression levels of 10 of these genes were at least two-fold higher in the ABA-pretreated seedlings under chilling stress than water-pretreated (control) plants under chilling stress. In contrast, the other eight genes were downregulated in ABA-pretreated seedlings under chilling stress, with expression levels that were one-third or less of the levels observed in control seedlings under chilling stress. These results suggest that ABA can positively and negatively regulate genes in pepper plants under chilling stress.

Big Data in the SHELA Field: Investigating Galaxy Quenching at High Redshifts

NASA Astrophysics Data System (ADS)

Stevans, Matthew L.; Finkelstein, Steven L.; Wold, Isak; Kawinwanichakij, Lalitwadee; Sherman, Sydney; Gebhardt, Karl; Jogee, Shardha; Papovich, Casey J.; Ciardullo, Robin; Gronwall, Caryl; Gawiser, Eric J.; Acquaviva, Viviana; Casey, Caitlin; Florez, Jonathan; HETDEX Team

2017-06-01

We present a measurement of the z ~ 4 Lyman break galaxy (LBG) rest-frame UV luminosity function to investigate the onset of quenching in the early universe. The bright-end of the galaxy luminosity function typically shows an exponential decline far steeper than that of the underlying halo mass function. This is typically attributed to negative feedback from past active galactic nuclei (AGN) activity as well as dust attenuation. Constraining the abundance of bright galaxies at early times (z > 3) can provide a key insight into the mechanisms regulating star formation in galaxies. However, existing studies suffer from low number statistics and/or the inability to robustly remove stellar and AGN contaminants. In this study we take advantage of the unprecedentedly large (24 deg^2) Spitzer/HETDEX Exploratory Large Area (SHELA) field and its deep multi-wavelength photometry, which includes DECam ugriz, NEWFIRM K-band, Spitzer/IRAC, Herschel/SPIRE, and X-ray from XMM-Newton and Chandra. With SHELA’s deep imaging over a large area we are uniquely positioned to study statistically significant samples of massive galaxies at high redshifts (z > 3) when the first massive galaxies began quenching. We select our sample using photometric redshifts from the EAZY software package (Brammer et al. 2008) based on the optical and far-infrared imaging. We directly identify and remove stellar contaminants and AGN with IRAC colors and X-ray detections, respectively. By pinning down the exact shape of the bright-end of the z ~ 4 LBG luminosity function, we provide the deepest probe yet into the baryonic physics dominating star formation and quenching in the early universe.

Early Evolution of Vertebrate Mybs: An Integrative Perspective Combining Synteny, Phylogenetic, and Gene Expression Analyses

PubMed Central

Campanini, Emeline B.; Vandewege, Michael W.; Pillai, Nisha E.; Tay, Boon-Hui; Jones, Justin L.; Venkatesh, Byrappa; Hoffmann, Federico G.

2015-01-01

Abstract The genes in the Myb superfamily encode for three related transcription factors in most vertebrates, A-, B-, and c-Myb, with functionally distinct roles, whereas most invertebrates have a single Myb. B-Myb plays an essential role in cell division and cell cycle progression, c-Myb is involved in hematopoiesis, and A-Myb is involved in spermatogenesis and regulating expression of pachytene PIWI interacting RNAs, a class of small RNAs involved in posttranscriptional gene regulation and the maintenance of reproductive tissues. Comparisons between teleost fish and tetrapods suggest that the emergence and functional divergence of the Myb genes were linked to the two rounds of whole-genome duplication early in vertebrate evolution. We combined phylogenetic, synteny, structural, and gene expression analyses of the Myb paralogs from elephant shark and lampreys with data from 12 bony vertebrates to reconstruct the early evolution of vertebrate Mybs. Phylogenetic and synteny analyses suggest that the elephant shark and Japanese lamprey have copies of the A-, B-, and c-Myb genes, implying their origin could be traced back to the common ancestor of lampreys and gnathostomes. However, structural and gene expression analyses suggest that their functional roles diverged between gnathostomes and cyclostomes. In particular, we did not detect A-Myb expression in testis suggesting that the involvement of A-Myb in the pachytene PIWI interacting RNA pathway is probably a gnathostome-specific innovation. We speculate that the secondary loss of a central domain in lamprey A-Myb underlies the functional differences between the cyclostome and gnathostome A-Myb proteins. PMID:26475318

Morphometric analysis of Martian valley network basins using a circularity function

NASA Astrophysics Data System (ADS)

Luo, Wei; Howard, Alan D.

2005-12-01

This paper employs a circularity function to quantify the internal morphology of Martian watershed basins in Margaritifer Sinus region and to infer the primary erosional processes that led to their current geomorphologic characteristics and possible climatic conditions under which these processes operated. The circularity function describes the elongation of a watershed basin at different elevations. We have used the circularity functions of terrestrial basins that were interpreted as having been modified by (1) erosion related to primarily groundwater sapping and (2) erosion related to primarily rainfall and surface run-off, as well as the circularity functions of cratering basins on the Moon, in order to formulate discriminant functions that are able to separate the three types of landforms. The spatial pattern of the classification of Martian basins based on discriminant functions shows that basins that look morphologically similar to terrestrial fluvial basins are mostly clustered near the mainstream at low elevation, while those that look morphologically similar to terrestrial basins interpreted as groundwater sapping origin are located near the tributaries and at higher elevation. There are more of the latter than the former. This spatial distribution is inconsistent with a continuous Earth-like warm and wet climate for early Mars. Instead, it is more aligned with an overall early dry climate punctuated with episodic wet periods. Alternatively, the concentrated erosion in the mainstream could also be caused by a change of water source from rainfall to snowfall or erosion cut through a duricrust layer.

HvLUX1 is a candidate gene underlying the early maturity 10 locus in barley: phylogeny, diversity, and interactions with the circadian clock and photoperiodic pathways

PubMed Central

Campoli, Chiara; Pankin, Artem; Drosse, Benedikt; Casao, Cristina M; Davis, Seth J; von Korff, Maria

2013-01-01

Photoperiodic flowering is a major factor determining crop performance and is controlled by interactions between environmental signals and the circadian clock. We proposed Hvlux1, an ortholog of the Arabidopsis circadian gene LUX ARRHYTHMO, as a candidate underlying the early maturity 10 (eam10) locus in barley (Hordeum vulgare L.). The link between eam10 and Hvlux1 was discovered using high-throughput sequencing of enriched libraries and segregation analysis. We conducted functional, phylogenetic, and diversity studies of eam10 and HvLUX1 to understand the genetic control of photoperiod response in barley and to characterize the evolution of LUX-like genes within barley and across monocots and eudicots. We demonstrate that eam10 causes circadian defects and interacts with the photoperiod response gene Ppd-H1 to accelerate flowering under long and short days. The results of phylogenetic and diversity analyses indicate that HvLUX1 was under purifying selection, duplicated at the base of the grass clade, and diverged independently of LUX-like genes in other plant lineages. Taken together, these findings contribute to improved understanding of the barley circadian clock, its interaction with the photoperiod pathway, and evolution of circadian systems in barley and across monocots and eudicots. PMID:23731278

Social recovery therapy in combination with early intervention services for enhancement of social recovery in patients with first-episode psychosis (SUPEREDEN3): a single-blind, randomised controlled trial.

PubMed

Fowler, David; Hodgekins, Jo; French, Paul; Marshall, Max; Freemantle, Nick; McCrone, Paul; Everard, Linda; Lavis, Anna; Jones, Peter B; Amos, Tim; Singh, Swaran; Sharma, Vimal; Birchwood, Max

2018-01-01

Provision of early intervention services has increased the rate of social recovery in patients with first-episode psychosis; however, many individuals have continuing severe and persistent problems with social functioning. We aimed to assess the efficacy of early intervention services augmented with social recovery therapy in patients with first-episode psychosis. The primary hypothesis was that social recovery therapy plus early intervention services would lead to improvements in social recovery. We did this single-blind, phase 2, randomised controlled trial (SUPEREDEN3) at four specialist early intervention services in the UK. We included participants who were aged 16-35 years, had non-affective psychosis, had been clients of early intervention services for 12-30 months, and had persistent and severe social disability, defined as engagement in less than 30 h per week of structured activity. Participants were randomly assigned (1:1), via computer-generated randomisation with permuted blocks (sizes of four to six), to receive social recovery therapy plus early intervention services or early intervention services alone. Randomisation was stratified by sex and recruitment centre (Norfolk, Birmingham, Lancashire, and Sussex). By necessity, participants were not masked to group allocation, but allocation was concealed from outcome assessors. The primary outcome was time spent in structured activity at 9 months, as measured by the Time Use Survey. Analysis was by intention to treat. This trial is registered with ISRCTN, number ISRCTN61621571. Between Oct 1, 2012, and June 20, 2014, we randomly assigned 155 participants to receive social recovery therapy plus early intervention services (n=76) or early intervention services alone (n=79); the intention-to-treat population comprised 154 patients. At 9 months, 143 (93%) participants had data for the primary outcome. Social recovery therapy plus early intervention services was associated with an increase in structured activity of 8·1 h (95% CI 2·5-13·6; p=0·0050) compared with early intervention services alone. No adverse events were deemed attributable to study therapy. Our findings show a clinically important benefit of enhanced social recovery on structured activity in patients with first-episode psychosis who received social recovery therapy plus early intervention services. Social recovery therapy might be useful in improving functional outcomes in people with first-episode psychosis, particularly in individuals not motivated to engage in existing psychosocial interventions targeting functioning, or who have comorbid difficulties preventing them from doing so. National Institute for Health Research. Copyright © 2017 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.

Not all emotions are created equal: The negativity bias in social-emotional development

PubMed Central

Vaish, Amrisha; Grossmann, Tobias; Woodward, Amanda

2013-01-01

There is ample empirical evidence for an asymmetry in the way that adults use positive versus negative information to make sense of their world; specifically, across an array of psychological situations and tasks, adults display a negativity bias, or the propensity to attend to, learn from, and use negative information far more than positive information. This bias is argued to serve critical evolutionarily adaptive functions, but its developmental presence and ontogenetic emergence have never seriously been considered. Here, we argue for the existence of the negativity bias in early development, evident especially in research on infant social referencing but also in other developmental domains. We discuss ontogenetic mechanisms underlying the emergence of this bias, and explore not only its evolutionary but also its developmental functions and consequences. Throughout, we suggest ways to further examine the negativity bias in infants and older children, and we make testable predictions that would help clarify the nature of the negativity bias during early development. PMID:18444702

Clonal analysis of Notch1-expressing cells reveals the existence of unipotent stem cells that retain long-term plasticity in the embryonic mammary gland.

PubMed

Lilja, Anna M; Rodilla, Veronica; Huyghe, Mathilde; Hannezo, Edouard; Landragin, Camille; Renaud, Olivier; Leroy, Olivier; Rulands, Steffen; Simons, Benjamin D; Fre, Silvia

2018-06-01

Recent lineage tracing studies have revealed that mammary gland homeostasis relies on unipotent stem cells. However, whether and when lineage restriction occurs during embryonic mammary development, and which signals orchestrate cell fate specification, remain unknown. Using a combination of in vivo clonal analysis with whole mount immunofluorescence and mathematical modelling of clonal dynamics, we found that embryonic multipotent mammary cells become lineage-restricted surprisingly early in development, with evidence for unipotency as early as E12.5 and no statistically discernable bipotency after E15.5. To gain insights into the mechanisms governing the switch from multipotency to unipotency, we used gain-of-function Notch1 mice and demonstrated that Notch activation cell autonomously dictates luminal cell fate specification to both embryonic and basally committed mammary cells. These functional studies have important implications for understanding the signals underlying cell plasticity and serve to clarify how reactivation of embryonic programs in adult cells can lead to cancer.

Emotional learning, stress, and development: An ever-changing landscape shaped by early-life experience.

PubMed

Pattwell, Siobhan S; Bath, Kevin G

2017-09-01

The capacity to learn to associate cues with negative outcomes is a highly adaptive process that appears to be conserved across species. However, when the cue is no longer a valid predictor of danger, but the emotional response persists, this can result in maladaptive behaviors, and in humans contribute to debilitating emotional disorders. Over the past several decades, work in neuroscience, psychiatry, psychology, and biology have uncovered key processes underlying, and structures governing, emotional responding and learning, as well as identified disruptions in the structural and functional integrity of these brain regions in models of pathology. In this review, we highlight some of this elegant body of work as well as incorporate emerging findings from the field of developmental neurobiology to emphasize how development contributes to changes in the ability to learn and express emotional responses, and how early experiences, such as stress, shape the development and functioning of these circuits. Copyright © 2017 Elsevier Inc. All rights reserved.

Information Fusion for Hypothesis Generation under Uncertain and Partial Information Access Situation

DTIC Science & Technology

2006-07-21

This fundermental architecture can be illustrated as bow-tie architeture , that is claimed to be the fundermenal architecture of robust systems (Fig...sequenced genomes86,87. The Gene Ontology’s biological process hierarchy88 was used to annotate functional categories to each gene, and proportions of... proportions in the early Drosophila embryo. Nature 415, 798-802 (2002). 14. Kitano, H. Cancer robustness: tumour tactics. Nature 426, 125 (2003). 15

Information Fusion for Hypothesis Generation under Uncertain and Partial Information Access Situation

DTIC Science & Technology

2008-07-21

size. This fundermental architecture can be illustrated as bow-tie architeture , that is claimed to be the fundermenal architecture of robust systems...sequenced genomes86,87. The Gene Ontology’s biological process hierarchy88 was used to annotate functional categories to each gene, and proportions ...and proportions in the early Drosophila embryo. Nature 415, 798-802 (2002). 14. Kitano, H. Cancer robustness: tumour tactics. Nature 426, 125 (2003

Biomarkers for Early Detection of Clinically Relevant Prostate Cancer: A Multi-Institutional Validation Trial

DTIC Science & Technology

2015-10-01

Suzanne Kolb 12 Project Role: Project Coordinator Researcher Identifier (e.g. ORCID ID): N/A Nearest person month worked: 5 person months...Contribution to Project: Ms. Kolb works under the direction of Drs. Lin and Newcomb to fulfill daily fiscal and administrative functions of the...program. She monitors subaward budgets, provides logistical support. Ms. Kolb works closely with the PASS Deputy Director to maintain IRB files

Biomarkers for Early Detection of Clinically Relevant Prostate Cancer: A Multi-Institutional Validation Trial

DTIC Science & Technology

2015-10-01

Name: Suzanne Kolb 12 Project Role: Project Coordinator Researcher Identifier (e.g. ORCID ID): N/A Nearest person month worked: 5 person...months Contribution to Project: Ms. Kolb works under the direction of Drs. Lin and Newcomb to fulfill daily fiscal and administrative functions of the...program. She monitors subaward budgets, provides logistical support. Ms. Kolb works closely with the PASS Deputy Director to maintain IRB files

34 CFR 303.420 - Parental consent and ability to decline services.

Code of Federal Regulations, 2014 CFR

2014-07-01

... decline any early intervention service under this part at any time, in accordance with State law; and (2...) OFFICE OF SPECIAL EDUCATION AND REHABILITATIVE SERVICES, DEPARTMENT OF EDUCATION EARLY INTERVENTION... conducted under § 303.321; (3) Early intervention services are provided to the child under this part; (4...

34 CFR 303.420 - Parental consent and ability to decline services.

Code of Federal Regulations, 2013 CFR

2013-07-01

... decline any early intervention service under this part at any time, in accordance with State law; and (2...) OFFICE OF SPECIAL EDUCATION AND REHABILITATIVE SERVICES, DEPARTMENT OF EDUCATION EARLY INTERVENTION... conducted under § 303.321; (3) Early intervention services are provided to the child under this part; (4...

34 CFR 303.420 - Parental consent and ability to decline services.

Code of Federal Regulations, 2012 CFR

2012-07-01

... decline any early intervention service under this part at any time, in accordance with State law; and (2...) OFFICE OF SPECIAL EDUCATION AND REHABILITATIVE SERVICES, DEPARTMENT OF EDUCATION EARLY INTERVENTION... conducted under § 303.321; (3) Early intervention services are provided to the child under this part; (4...

Impact of early applied upper limb stimulation: the EXPLICIT-stroke programme design.

PubMed

Kwakkel, Gert; Meskers, Carel G M; van Wegen, Erwin E; Lankhorst, Guus J; Geurts, Alexander C H; van Kuijk, Annet A; Lindeman, Eline; Visser-Meily, Anne; de Vlugt, Erwin; Arendzen, J Hans

2008-12-17

Main claims of the literature are that functional recovery of the paretic upper limb is mainly defined within the first month post stroke and that rehabilitation services should preferably be applied intensively and in a task-oriented way within this particular time window. EXplaining PLastICITy after stroke (acronym EXPLICIT-stroke) aims to explore the underlying mechanisms of post stroke upper limb recovery. Two randomized single blinded trials form the core of the programme, investigating the effects of early modified Constraint-Induced Movement Therapy (modified CIMT) and EMG-triggered Neuro-Muscular Stimulation (EMG-NMS) in patients with respectively a favourable or poor probability for recovery of dexterity. 180 participants suffering from an acute, first-ever ischemic stroke will be recruited. Functional prognosis at the end of the first week post stroke is used to stratify patient into a poor prognosis group for upper limb recovery (N = 120, A2 project) and a group with a favourable prognosis (N = 60, A1 project). Both groups will be randomized to an experimental arm receiving respectively modified CIMT (favourable prognosis) or EMG-NMS (poor prognosis) for 3 weeks or to a control arm receiving usual care. Primary outcome variable will be the Action Research Arm Test (ARAT), assessed at 1,2,3,4,5, 8, 12 and 26 weeks post stroke. To study the impact of modified CIMT or EMG-NMS on stroke recovery mechanisms i.e. neuroplasticity, compensatory movements and upper limb neuromechanics, 60 patients randomly selected from projects A1 and A2 will undergo TMS, kinematical and haptic robotic measurements within a repeated measurement design. Additionally, 30 patients from the A1 project will undergo fMRI at baseline, 5 and 26 weeks post stroke. EXPLICIT stroke is a 5 year translational research programme which main aim is to investigate the effects of early applied intensive intervention for regaining dexterity and to explore the underlying mechanisms that are involved in regaining upper limb function after stroke. EXPLICIT-stroke will provide an answer to the key question whether therapy induced improvements are due to either a reduction of basic motor impairment by neural repair i.e. restitution of function and/or the use of behavioural compensation strategies i.e. substitution of function.

Early Childhood Education and Care Policy in England under the Coalition Government

ERIC Educational Resources Information Center

Lloyd, Eva

2015-01-01

This paper reviews developments in policy on early childhood education and care--early years--under the Coalition Government in England. Three factors came to define the Coalition's performance and record in this area: ambivalence about the rationales for the two areas of early education and childcare; a disconnect between early years and other…

Computer-controlled stimulation for functional magnetic resonance imaging studies of the neonatal olfactory system

PubMed Central

Arichi, T; Gordon-Williams, R; Allievi, A; Groves, AM; Burdet, E; Edwards, AD

2013-01-01

Aim Olfactory sensation is highly functional early in human neonatal life, with studies suggesting that odours can influence behaviour and infant–mother bonding. Due to its good spatial properties, blood oxygen level–dependent (BOLD) contrast functional magnetic resonance imaging (fMRI) has the potential to rapidly advance our understanding of the neural activity which underlies the development of olfactory perception in this key period. We aimed to design an ‘olfactometer’ specifically for use with neonatal subjects for fMRI studies of odour perception. Methods We describe a fully automated and programmable, fMRI compatible system capable of presenting odorant liquids. To prevent contamination of the system and minimize between-subject infective risk, the majority of the olfactometer is constructed from single-use, readily available clinical equipment. The system was used to present the odour of infant formula milk in a validation group of seven neonatal subjects at term equivalent postmenstrual age (median age 40 weeks). Results A safe, reliable and reproducible pattern of stimulation was delivered leading to well-localized positive BOLD functional responses in the piriform cortex, amygdala, thalamus, insular cortex and cerebellum. Conclusions The described system is therefore suitable for detailed studies of the ontology of olfactory sensation and perception during early human brain development. PMID:23789919

Shaping Early Reorganization of Neural Networks Promotes Motor Function after Stroke

PubMed Central

Volz, L. J.; Rehme, A. K.; Michely, J.; Nettekoven, C.; Eickhoff, S. B.; Fink, G. R.; Grefkes, C.

2016-01-01

Neural plasticity is a major factor driving cortical reorganization after stroke. We here tested whether repetitively enhancing motor cortex plasticity by means of intermittent theta-burst stimulation (iTBS) prior to physiotherapy might promote recovery of function early after stroke. Functional magnetic resonance imaging (fMRI) was used to elucidate underlying neural mechanisms. Twenty-six hospitalized, first-ever stroke patients (time since stroke: 1–16 days) with hand motor deficits were enrolled in a sham-controlled design and pseudo-randomized into 2 groups. iTBS was administered prior to physiotherapy on 5 consecutive days either over ipsilesional primary motor cortex (M1-stimulation group) or parieto-occipital vertex (control-stimulation group). Hand motor function, cortical excitability, and resting-state fMRI were assessed 1 day prior to the first stimulation and 1 day after the last stimulation. Recovery of grip strength was significantly stronger in the M1-stimulation compared to the control-stimulation group. Higher levels of motor network connectivity were associated with better motor outcome. Consistently, control-stimulated patients featured a decrease in intra- and interhemispheric connectivity of the motor network, which was absent in the M1-stimulation group. Hence, adding iTBS to prime physiotherapy in recovering stroke patients seems to interfere with motor network degradation, possibly reflecting alleviation of post-stroke diaschisis. PMID:26980614

Rapid Blood Pressure Lowering According to Recovery at Different Time Intervals after Acute Intracerebral Hemorrhage: Pooled Analysis of the INTERACT Studies.

PubMed

Wang, Xia; Arima, Hisatomi; Al-Shahi Salman, Rustam; Woodward, Mark; Heeley, Emma; Stapf, Christian; Lavados, Pablo M; Robinson, Thompson; Huang, Yining; Wang, Jiguang; Delcourt, Candice; Anderson, Craig S

2015-01-01

Early intensive blood pressure (BP) lowering has been shown to improve functional outcome in acute intracerebral hemorrhage (ICH), but the treatment effect is modest and without a clearly defined underlying explanatory mechanism. We aimed at more reliably quantifying the benefits of this treatment according to different time periods in the recovery of participants in the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial (INTERACT) studies. Pooled analysis of the pilot INTERACT1 (n = 404) and main INTERACT2 (n = 2,839) involving patients with spontaneous ICH (<6 h) and elevated systolic BP (SBP 150-220 mm Hg) who were randomized to intensive (target SBP <140 mm Hg) or guideline-recommended (target SBP <180 mm Hg) BP lowering treatment. Treatment effects were examined according to repeated measures analysis of an ordinal ('shift') across all 7 levels of the modified Rankin Scale (mRS) assessed during follow-up at 7, 28, and 90 days, post-randomization. http://www.clinicaltrials.gov, NCT00226096 and NCT00716079. Intensive BP lowering resulted in a significant favorable distribution of mRS scores for better functioning (odds ratio 1.13, 95% confidence interval 1.00-1.26; p = 0.042) over 7, 28 and 90 days, and the effect was consistency for early (7-28 days) and later (28-90 days) time periods (p homogeneity 0.353). Treatment effects were also consistent across several pre-specified patient characteristic subgroups, with trends favoring those randomized early, and with higher SBP and milder neurological severity at baseline. Intensive BP lowering provides beneficial effects on physical functioning that manifests consistently through the early and later phases of recovery from ICH. © 2015 S. Karger AG, Basel.

Relationship between cardiovascular system response and adrenocortical glucocorticoid function on exposure to diffuse, low-intensity helium-neon laser emission

NASA Astrophysics Data System (ADS)

Ushkova, I. N.; Pokrovskaya, L. A.; Stepanov, G. S.; Suvorov, I. M.; Kogan, M. Y.; Grishina, Y. F.

1984-06-01

The effect of light from a low intensity helium neon laser on the formation of a series of adaptive processes in the body is investigated. The study is carried out on 32 chinchilla rabbits, weighing from two to two point five kilograms. The right eyes of the creatures were subjected to diffuse laser radiation, for 30 days, 14 minutes per day, under conditions of low illumination. Controls are rabbits under the same conditions, but not exposed to laser radiation. In order to isolate the early glucocorticoid response to the treatment, the hydrocortisone content of the blood is determined which permitted judgment on presence of a functional cumulation effect. The body developed an adaptive/compensatory reaction to the laser radiation so that hydrocortisone levels and the system's hemodynamics and nervous system returned to normal.

[Principles of changes of structural organization of cell membranes and functional properties of erythrocytes in neurotic disorders].

PubMed

Riazantseva, N V; Novitskiĭ, V V

2003-02-01

Investigation into structural, metabolic, and functional conditions of red blood cells was performed in 24 patients with a neurosis (neurasthenia, disturbance of asaptation) with the aid of electrophoretic division of proteins of the erythrocyte membrane, thin-layer chromatography, fluorescent probing of membranes, evaluation of peroxidative oxidation process, scanning and transmission electron microscopy, laser diphractometry, photometry. The patients with neurotic disorders at the early period after the influence of psychogenic factors (up to 3 months) revealed disorganization of lipid and protein composition of the red cell membrane, increase in microviscosity of its lipid phase, impairment of surface architectonics and ultrastructure of red cells, decrease of a deformation ability and increase of aggregate properties of erythrocytes. The authors treat stability of erythrocytes' homeostasis under the long-term influence of psychogenic factors from a viewpoint of adaptive changes in organism under the influence of neurogenic factors.

Biomechanical Analysis of the Efficacy of Locking Plates during Cyclic Loading in Metacarpal Fractures

PubMed Central

Meffert, Rainer H.; Raschke, Michael J.; Blunk, Torsten; Ochman, Sabine

2014-01-01

Purpose. To analyse the biomechanical characteristics of locking plates under cyclic loading compared to a nonlocking plate in a diaphyseal metacarpal fracture. Methods. Oblique diaphyseal shaft fractures in porcine metacarpal bones were created in a biomechanical fracture model. An anatomical reduction and stabilization with a nonlocking and a comparable locking plate in mono- or bicortical screw fixation followed. Under cyclic loading, the displacement, and in subsequent load-to-failure tests, the maximum load and stiffness were measured. Results. For the monocortical screw fixation of the locking plate, a similar displacement, maximum load, and stiffness could be demonstrated compared to the bicortical screw fixation of the nonlocking plate. Conclusions. Locking plates in monocortical configuration may function as a useful alternative to the currently common treatment with bicortical fixations. Thereby, irritation of the flexor tendons would be avoided without compromising the stability, thus enabling the necessary early functional rehabilitation. PMID:24757429

Targeting aspirin in acute disabling ischemic stroke: an individual patient data meta-analysis of three large randomized trials.

PubMed

Thompson, Douglas D; Murray, Gordon D; Candelise, Livia; Chen, Zhengming; Sandercock, Peter A G; Whiteley, William N

2015-10-01

Aspirin is of moderate overall benefit for patients with acute disabling ischemic stroke. It is unclear whether functional outcome could be improved after stroke by targeting aspirin to patients with a high risk of recurrent thrombosis or a low risk of haemorrhage. We aimed to determine whether patients at higher risk of thrombotic events or poor functional outcome, or lower risk of major haemorrhage had a greater absolute risk reduction of poor functional outcome with aspirin than the average patient. We used data on individual ischemic stroke patients from three large trials of aspirin vs. placebo in acute ischemic stroke: the first International Stroke Trial (n = 18,372), the Chinese Acute Stroke Trial (n = 20,172) and the Multicentre Acute Stroke Trial (n = 622). We developed and evaluated clinical prediction models for the following: early thrombotic events (myocardial infarction, ischemic stroke, deep vein thrombosis and pulmonary embolism); early haemorrhagic events (significant intracranial haemorrhage, major extracranial haemorrhage, or haemorrhagic transformation of an infarct); and late poor functional outcome. We calculated the absolute risk reduction of poor functional outcome (death or dependence) at final follow-up in: quartiles of early thrombotic risk; quartiles of early haemorrhagic risk; and deciles of poor functional outcome risk. Ischemic stroke patients who were older, had lower blood pressure, computerized tomography evidence of infarct or more severe deficits due to stroke had increased risk of thrombotic and haemorrhagic events and poor functional outcome. Prediction models built with all baseline variables (including onset to treatment time) discriminated weakly between patients with and without recurrent thrombotic events (area under the receiver operating characteristic curve 0·56, 95% CI:0·53-0·59) and haemorrhagic events (0·57, 0·52-0·64), though well between patients with and without poor functional outcome (0·77, 0·76-0·78) in the International Stroke Trial. We found no evidence that the net benefit of aspirin increased with increasing risk of thrombosis, haemorrhage or poor functional outcome in all three trials. Using simple clinical variables to target aspirin to patients after acute disabling stroke by risk of thrombosis, haemorrhage or poor functional outcome does not lead to greater net clinical benefit. We suggest future risk stratification schemes include new risk factors for thrombosis and intracranial haemorrhage. © 2015 The Authors. International Journal of Stroke published by John Wiley & Sons Ltd on behalf of World Stroke Organization.

Neonatal Lipopolysaccharide Exposure Gender-Dependently Increases Heart Susceptibility to Ischemia/Reperfusion Injury in Male Rats.

PubMed

Zhang, Peng; Lv, Juanxiu; Li, Yong; Zhang, Lubo; Xiao, Daliao

2017-01-01

Background: Adverse stress exposure during the early neonatal period has been shown to cause aberrant development, resulting in an increased risk of adult disease. We tested the hypothesis that neonatal exposure to lipopolysaccharide (LPS) does not alter heart function at rest condition but causes heart dysfunction under stress stimulation later in life. Methods: Saline control or LPS were administered to neonatal rats via intraperitoneal injection. Experiments were conducted in 6 week-old male and female rats. Isolated hearts were perfused in a Langendorff preparation. Results: Neonatal LPS exposure exhibited no effects on the body weight of the developing rats, but induced decreases in the left ventricle (LV) to the body weight ratio in male rats. Neonatal LPS exposure showed no effects on the baseline heart function determined by in vivo and ex vivo experiments, but caused decreases in the post-ischemic recovery of the LV function in male but not female rats. Neonatal LPS-mediated LV dysfunction was associated with an increase in myocardial infarct size and the LDH release in the male rats. Conclusion: The present study provides novel evidence that neonatal immune challenges could induce gender-dependent long-term effects on cardiac development and heart function, which reinforces the notion that adverse stress exposure during the early neonatal period can aggravate heart functions and the development of a heart ischemia-sensitive phenotype later in life.

Cyclic-glycine-proline accelerates mammary involution by promoting apoptosis and inhibiting IGF-1 function.

PubMed

Singh-Mallah, Gagandeep; McMahon, Christopher D; Guan, Jian; Singh, Kuljeet

2017-12-01

In rodents, post-lactational involution of mammary glands is characterized by the loss of mammary epithelial cells via apoptosis, which is associated with a decline in the expression of insulin-like growth factor-1 (IGF-1). Overexpression of IGF-1 delays involution by inhibiting apoptosis of epithelial cells and preserving the remaining secretory alveoli. Cyclic-glycine-proline (cGP), a metabolite of IGF-1, normalizes IGF-1 function under pathological conditions by regulating the bioavailability of IGF-1. The present study investigated the effect of cGP on the physiological decline in IGF-1 function during post-lactational mammary involution. Rat dams were gavaged with either cGP (3 mg/kg) or saline once per day from post-natal d8-22. Before collecting tissue on post-natal d23, a pair of mammary glands were sealed on d20 (72 hr-engorgement, thus representative of late-involution) and d22 (24 hr-engorgement, thus representative of mid-involution), while the remaining glands were allowed to involute naturally (early-involution). During early-involution, cGP accelerated the loss of mammary cells through apoptosis, resulting in an earlier clearance of intact secretory alveoli compared with the control group. This coincided with an earlier up-regulation of the cell survival factors, Bcl-xl and IGF-1R, in the early-involution cGP glands compared with the control glands. During late-involution, cGP reduced the bioactivity of IGF-1, which was evident through decreased phosphorylation of IGF-1R in the regressed alveoli. Maternal administration of cGP did not alter milk production and composition during early-, peak-, or late-stage of lactation. These data show that cGP accelerates post-lactational involution by promoting apoptosis and the physiological decline in IGF-1 function. © 2017 Wiley Periodicals, Inc.

Kindler syndrome pathogenesis and fermitin family homologue 1 (kindlin-1) function.

PubMed

D'Souza, Maria-Anna M A; Kimble, Roy M; McMillan, James R

2010-01-01

Kindler syndrome is caused by genetic defects in the focal contact-associated protein, fermitin family homologue 1 (FFH1), encoded by the gene FERMT1 (known as KIND1). Defects in FFH1 lead to abnormal integrin activation and loss of keratinocyte epidermal adhesion to the underlying basal lamina, disruption in normal cell cytoskeleton within keratinocytes, and altered signaling pathways, leading to increased extracellular matrix production. Null mutations in FERMT1 result in skin blistering from birth and early childhood progressive poikiloderma, mucosal fragility, and increased risk of cancer. The complete range of FFH1 functions in skin and other epithelia has yet to be determined.

Regulation and functional diversification of root hairs.

PubMed

Cui, Songkui; Suzaki, Takuya; Tominaga-Wada, Rumi; Yoshida, Satoko

2017-10-13

Root hairs result from the polar outgrowth of root epidermis cells in vascular plants. Root hair development processes are regulated by intrinsic genetic programs, which are flexibly modulated by environmental conditions, such as nutrient availability. Basic programs for root hair development were present in early land plants. Subsequently, some plants developed the ability to utilize root hairs for specific functions, in particular, for interactions with other organisms, such as legume-rhizobia and host plants-parasites interactions. In this review, we summarize the molecular regulation of root hair development and the modulation of root hairs under limited nutrient supply and during interactions with other organisms. Copyright © 2017 Elsevier Ltd. All rights reserved.

Physiotherapy in pauciarticular juvenile idiopathic arthritis. Case study.

PubMed

Zuk, Beata; Kaczor, Zofia; Zuk-Drążyk, Berenika; Księżopolska-Orłowska, Krystyna

2014-01-01

Juvenile idiopathic arthritis (JIA) is the most common arthropathy of childhood and adolescence. This term encompasses a group of chronic systemic inflammatory diseases of the connective tissue which cause arthritis in patients under 16 years of age lasting at least 6 weeks. The authors presented the characteristic features of physiotherapy based on functional examination results on the basis of two cases of girls with pauciarticular JIA treated according to an established pharmacological regimen. Physiotherapy should be introduced at an early stage of the disease. Kinesiotherapy preceded by history-taking and a functional examination of the patient, has to focus on both primary and secondary joint lesions.

The versatility of a truss mounted mobile transporter for in-space construction

NASA Technical Reports Server (NTRS)

Bush, Harold G.; Lake, Mark S.; Watson, Judith J.; Heard, Walter L., Jr.

1988-01-01

The Mobile Transporter (MT) evolution from early erectable structures assembly activities is detailed. The MT operational features which are required to support astronauts performing on-orbit structure construction or spacecraft assembly functions are presented and discussed. Use of the MT to perform a variety of assembly functions is presented. Estimated EVA assembly times for a precision segmented reflector approximately 20 m in diameter are presented. The EVA/MT technique under study for construction of the reflector (and the entire spacecraft) is illustrated. Finally, the current status of development activities and test results involving the MT and Space Station structural assembly are presented.

Acupuncture-induced changes in functional connectivity of the primary somatosensory cortex varied with pathological stages of Bell's palsy.

PubMed

He, Xiaoxuan; Zhu, Yifang; Li, Chuanfu; Park, Kyungmo; Mohamed, Abdalla Z; Wu, Hongli; Xu, Chunsheng; Zhang, Wei; Wang, Linying; Yang, Jun; Qiu, Bensheng

2014-10-01

Bell's palsy is the most common cause of acute facial nerve paralysis. In China, Bell's palsy is frequently treated with acupuncture. However, its efficacy and underlying mechanism are still controversial. In this study, we used functional MRI to investigate the effect of acupuncture on the functional connectivity of the brain in Bell's palsy patients and healthy individuals. The patients were further grouped according to disease duration and facial motor performance. The results of resting-state functional MRI connectivity show that acupuncture induces significant connectivity changes in the primary somatosensory region of both early and late recovery groups, but no significant changes in either the healthy control group or the recovered group. In the recovery group, the changes also varied with regions and disease duration. Therefore, we propose that the effect of acupuncture stimulation may depend on the functional connectivity status of patients with Bell's palsy.

34 CFR 300.226 - Early intervening services.

Code of Federal Regulations, 2010 CFR

2010-07-01

... CHILDREN WITH DISABILITIES Local Educational Agency Eligibility § 300.226 Early intervening services. (a... annually report to the SEA on— (1) The number of children served under this section who received early intervening services; and (2) The number of children served under this section who received early intervening...

78 FR 13294 - Enhanced Prudential Standards and Early Remediation Requirements for Foreign Banking...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-27

... Prudential Standards and Early Remediation Requirements for Foreign Banking Organizations and Foreign Nonbank... under section 165 of the Dodd-Frank Act and the early remediation requirements established under section... Prudential Standards and Early Remediation Requirements for Foreign Banking Organizations and Foreign Nonbank...

RAGE-dependent potentiation of TRPV1 currents in sensory neurons exposed to high glucose.

PubMed

Lam, Doris; Momeni, Zeinab; Theaker, Michael; Jagadeeshan, Santosh; Yamamoto, Yasuhiko; Ianowski, Juan P; Campanucci, Verónica A

2018-01-01

Diabetes mellitus is associated with sensory abnormalities, including exacerbated responses to painful (hyperalgesia) or non-painful (allodynia) stimuli. These abnormalities are symptoms of diabetic peripheral neuropathy (DPN), which is the most common complication that affects approximately 50% of diabetic patients. Yet, the underlying mechanisms linking hyperglycemia and symptoms of DPN remain poorly understood. The transient receptor potential vanilloid 1 (TRPV1) channel plays a central role in such sensory abnormalities and shows elevated expression levels in animal models of diabetes. Here, we investigated the function of TRPV1 channels in sensory neurons cultured from the dorsal root ganglion (DRG) of neonatal mice, under control (5mM) and high glucose (25mM) conditions. After maintaining DRG neurons in high glucose for 1 week, we observed a significant increase in capsaicin (CAP)-evoked currents and CAP-evoked depolarizations, independent of TRPV1 channel expression. These functional changes were largely dependent on the expression of the receptor for Advanced Glycation End-products (RAGE), calcium influx, cytoplasmic ROS accumulation, PKC, and Src kinase activity. Like cultured neurons from neonates, mature neurons from adult mice also displayed a similar potentiation of CAP-evoked currents in the high glucose condition. Taken together, our data demonstrate that under the diabetic condition, DRG neurons are directly affected by elevated levels of glucose, independent of vascular or glial signals, and dependent on RAGE expression. These early cellular and molecular changes to sensory neurons in vitro are potential mechanisms that might contribute to sensory abnormalities that can occur in the very early stages of diabetes.

RAGE-dependent potentiation of TRPV1 currents in sensory neurons exposed to high glucose

PubMed Central

Lam, Doris; Momeni, Zeinab; Theaker, Michael; Jagadeeshan, Santosh; Yamamoto, Yasuhiko; Ianowski, Juan P.

2018-01-01

Diabetes mellitus is associated with sensory abnormalities, including exacerbated responses to painful (hyperalgesia) or non-painful (allodynia) stimuli. These abnormalities are symptoms of diabetic peripheral neuropathy (DPN), which is the most common complication that affects approximately 50% of diabetic patients. Yet, the underlying mechanisms linking hyperglycemia and symptoms of DPN remain poorly understood. The transient receptor potential vanilloid 1 (TRPV1) channel plays a central role in such sensory abnormalities and shows elevated expression levels in animal models of diabetes. Here, we investigated the function of TRPV1 channels in sensory neurons cultured from the dorsal root ganglion (DRG) of neonatal mice, under control (5mM) and high glucose (25mM) conditions. After maintaining DRG neurons in high glucose for 1 week, we observed a significant increase in capsaicin (CAP)-evoked currents and CAP-evoked depolarizations, independent of TRPV1 channel expression. These functional changes were largely dependent on the expression of the receptor for Advanced Glycation End-products (RAGE), calcium influx, cytoplasmic ROS accumulation, PKC, and Src kinase activity. Like cultured neurons from neonates, mature neurons from adult mice also displayed a similar potentiation of CAP-evoked currents in the high glucose condition. Taken together, our data demonstrate that under the diabetic condition, DRG neurons are directly affected by elevated levels of glucose, independent of vascular or glial signals, and dependent on RAGE expression. These early cellular and molecular changes to sensory neurons in vitro are potential mechanisms that might contribute to sensory abnormalities that can occur in the very early stages of diabetes. PMID:29474476

Does skeletal muscle have an 'epi'-memory? The role of epigenetics in nutritional programming, metabolic disease, aging and exercise.

PubMed

Sharples, Adam P; Stewart, Claire E; Seaborne, Robert A

2016-08-01

Skeletal muscle mass, quality and adaptability are fundamental in promoting muscle performance, maintaining metabolic function and supporting longevity and healthspan. Skeletal muscle is programmable and can 'remember' early-life metabolic stimuli affecting its function in adult life. In this review, the authors pose the question as to whether skeletal muscle has an 'epi'-memory? Following an initial encounter with an environmental stimulus, we discuss the underlying molecular and epigenetic mechanisms enabling skeletal muscle to adapt, should it re-encounter the stimulus in later life. We also define skeletal muscle memory and outline the scientific literature contributing to this field. Furthermore, we review the evidence for early-life nutrient stress and low birth weight in animals and human cohort studies, respectively, and discuss the underlying molecular mechanisms culminating in skeletal muscle dysfunction, metabolic disease and loss of skeletal muscle mass across the lifespan. We also summarize and discuss studies that isolate muscle stem cells from different environmental niches in vivo (physically active, diabetic, cachectic, aged) and how they reportedly remember this environment once isolated in vitro. Finally, we will outline the molecular and epigenetic mechanisms underlying skeletal muscle memory and review the epigenetic regulation of exercise-induced skeletal muscle adaptation, highlighting exercise interventions as suitable models to investigate skeletal muscle memory in humans. We believe that understanding the 'epi'-memory of skeletal muscle will enable the next generation of targeted therapies to promote muscle growth and reduce muscle loss to enable healthy aging. © 2016 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Perceptual Learning Improves Contrast Sensitivity of V1 Neurons in Cats

PubMed Central

Hua, Tianmiao; Bao, Pinglei; Huang, Chang-Bing; Wang, Zhenhua; Xu, Jinwang

2010-01-01

Summary Background Perceptual learning has been documented in adult humans over a wide range of tasks. Although the often observed specificity of learning is generally interpreted as evidence for training-induced plasticity in early cortical areas, physiological evidence for training-induced changes in early visual cortical areas is modest, despite reports of learning-induced changes of cortical activities in fMRI studies. To reveal the physiological bases of perceptual learning, we combined psychophysical measurements with extracellular single-unit recording under anesthetized preparations, and examined the effects of training in grating orientation identification on both perceptual and neuronal contrast sensitivity functions of cats. Results We have found that training significantly improved perceptual contrast sensitivity of the cats to gratings with the spatial frequencies near the ‘trained’ spatial frequency, with stronger effects in the trained eye. Consistent with behavioral assessments, the mean contrast sensitivity of neurons recorded from V1 of the trained cats was significantly higher than that of neurons recorded from the untrained cats. Furthermore, in the trained cats, the contrast sensitivity of V1 neurons responding preferentially to stimuli presented via the trained eyes was significantly greater than that of neurons responding preferentially to stimuli presented via the ‘untrained’ eyes. The effect was confined to the trained spatial frequencies. In both trained and untrained cats, the neuronal contrast sensitivity functions derived from the contrast sensitivity of the individual neurons were highly correlated with behaviorally determined perceptual contrast sensitivity functions. Conclusions We suggest that training-induced neuronal contrast-gain in area V1 underlies behaviorally determined perceptual contrast sensitivity improvements. PMID:20451388

10 CFR 52.24 - Issuance of early site permit.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 2 2010-01-01 2010-01-01 false Issuance of early site permit. 52.24 Section 52.24 Energy... Early Site Permits § 52.24 Issuance of early site permit. (a) After conducting a hearing under § 52.21 and receiving the report to be submitted by the ACRS under § 52.23, the Commission may issue an early...

10 CFR 52.24 - Issuance of early site permit.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 2 2011-01-01 2011-01-01 false Issuance of early site permit. 52.24 Section 52.24 Energy... Early Site Permits § 52.24 Issuance of early site permit. (a) After conducting a hearing under § 52.21 and receiving the report to be submitted by the ACRS under § 52.23, the Commission may issue an early...

Evaluation of renal allografts function early after transplantation using intravoxel incoherent motion and arterial spin labeling MRI.

PubMed

Ren, Tao; Wen, Cheng-Long; Chen, Li-Hua; Xie, Shuang-Shuang; Cheng, Yue; Fu, Ying-Xin; Oesingmann, Niels; de Oliveira, Andre; Zuo, Pan-Li; Yin, Jian-Zhong; Xia, Shuang; Shen, Wen

2016-09-01

To evaluate renal allografts function early after transplantation using intravoxel incoherent motion (IVIM) and arterial spin labeling (ASL) MRI. This prospective study was approved by the local ethics committee, and written informed consent was obtained from all participants. A total of 82 participants with 62 renal allograft recipients (2-4weeks after kidney transplantation) and 20 volunteers were enrolled to be scanned using IVIM and ASL MRI on a 3.0T MR scanner. Recipients were divided into two groups with either normal or impaired function according to the estimated glomerular filtration rate (eGFR) with a threshold of 60ml/min/1.73m(2). The apparent diffusion coefficient (ADC) of pure diffusion (ADCslow), the ADC of pseudodiffusion (ADCfast), perfusion fraction (PF), and renal blood flow (RBF) of cortex were compared among three groups. The correlation of ADCslow, ADCfast, PF and RBF with eGFR was evaluated. The receiver operating characteristic (ROC) curve and binary logistic regression analyses were performed to assess the diagnostic efficiency of using IVIM and ASL parameters to discriminate allografts with impaired function from normal function. P<0.05 was considered statistically significant. In allografts with normal function, no significant difference of mean cortical ADCslow, ADCfast, and PF was found compared with healthy controls (P>0.05). Cortical RBF in allografts with normal function was statistically lower than that of healthy controls (P<0.001). Mean cortical ADCslow, ADCfast, PF and RBF were lower for allografts with impaired function than that with normal function (P<0.05). Mean cortical ADCslow, ADCfast, PF and RBF showed a positive correlation with eGFR (all P<0.01) for recipients. The combination of IVIM and ASL MRI showed a higher area under the ROC curve (AUC) (0.865) than that of ASL MRI alone (P=0.02). Combined IVIM and ASL MRI can better evaluate the diffusion and perfusion properties for allografts early after kidney transplantation. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Disrupted progression of the intestinal microbiota with age in children with cystic fibrosis.

PubMed

Nielsen, Shaun; Needham, Bronwen; Leach, Steven T; Day, Andrew S; Jaffe, Adam; Thomas, Torsten; Ooi, Chee Y

2016-05-04

Cystic fibrosis (CF) is a genetic disorder that leads to formation of thick epithelial secretions in affected organs. Chronic microbial infections associated with thick mucus secretions are the hallmarks of lung disease in CF. Despite similar conditions existing in the gastrointestinal tract, it is much less studied. We therefore examined the microbial communities within the gastrointestinal tract of children with and without CF (either pancreatic sufficient or insufficient) across a range of childhood ages (0.87-17 years). We observed a substantial reduction in the richness and diversity of gut bacteria associated with CF from early childhood (2 years) until late adolescence (17 years). A number of bacteria that establish themselves in the gut of healthy children were unable to do so in children with CF. In contrast, a few bacteria dominated the gut microbiota in children with CF and are unlikely to be beneficial for the metabolic function of the gut. A functioning pancreas (pancreatic sufficient) under a CF lifestyle showed little effect on microbial communities. Our results argue that any attempts to rectify the loss of bacterial diversity and provide normal bacterial function in the gut of CF patients should be conducted no later than early childhood.

Story time turbocharger? Child engagement during shared reading and cerebellar activation and connectivity in preschool-age children listening to stories

PubMed Central

Phelan, Kieran; Horowitz-Kraus, Tzipi; Dudley, Jonathan; Altaye, Mekibib; DeWitt, Thomas; Holland, Scott K.

2017-01-01

Expanding behavioral and neurobiological evidence affirms benefits of shared (especially parent-child) reading on cognitive development during early childhood. However, the majority of this evidence involves factors under caregiver control, the influence of those intrinsic to the child, such as interest or engagement in reading, largely indirect or unclear. The cerebellum is increasingly recognized as playing a “smoothing” role in higher-level cognitive processing and learning, via feedback loops with language, limbic and association cortices. We utilized functional MRI to explore the relationship between child engagement during a mother-child reading observation and neural activation and connectivity during a story listening task, in a sample of 4-year old girls. Children exhibiting greater interest and engagement in the narrative showed increased activation in right-sided cerebellar association areas during the task, and greater functional connectivity between this activation cluster and language and executive function areas. Our findings suggest a potential cerebellar “boost” mechanism responsive to child engagement level that may contribute to emergent literacy development during early childhood, and synergy between caregiver and child factors during story sharing. PMID:28562619

Long-term effects of early life exposure to environmental estrogens on ovarian function: Role of epigenetics

PubMed Central

Cruz, Gonzalo; Foster, Warren; Paredes, Alfonso; Yi, Kun Don; Uzumcu, Mehmet

2014-01-01

Estrogens play an important role in development and function of the brain and reproductive tract. Accordingly, it is thought that developmental exposure to environmental estrogens can disrupt neural and reproductive tract development potentially resulting in long-term alterations in neurobehavior and reproductive function. Many chemicals have been shown to have estrogenic activity whereas others affect estrogen production and turnover resulting in disruption of estrogen signaling pathways. However, these mechanisms and the concentrations required to induce these effects cannot account for the myriad adverse effects of environmental toxicants on estrogen sensitive target tissues. Hence, alternative mechanisms are thought to underlie the adverse effects documented in experimental animal models and thus could be important to human health. In this review, the epigenetic regulation of gene expression is explored as a potential target of environmental toxicants including estrogenic chemicals. We suggest that toxicant-induced changes in epigenetic signatures are important mechanisms underlying disruption of ovarian follicular development. In addition, we discuss how exposure to environmental estrogens during early life can alter gene expression through effects on epigenetic control potentially leading to permanent changes in ovarian physiology. PMID:25040227

Long-term effects of early-life exposure to environmental oestrogens on ovarian function: role of epigenetics.

PubMed

Cruz, G; Foster, W; Paredes, A; Yi, K D; Uzumcu, M

2014-09-01

Oestrogens play an important role in development and function of the brain and reproductive tract. Accordingly, it is considered that developmental exposure to environmental oestrogens can disrupt neural and reproductive tract development, potentially resulting in long-term alterations in neurobehaviour and reproductive function. Many chemicals have been shown to have oestrogenic activity, whereas others affect oestrogen production and turnover, resulting in the disruption of oestrogen signalling pathways. However, these mechanisms and the concentrations required to induce these effects cannot account for the myriad adverse effects of environmental toxicants on oestrogen-sensitive target tissues. Hence, alternative mechanisms are assumed to underlie the adverse effects documented in experimental animal models and thus could be important to human health. In this review, the epigenetic regulation of gene expression is explored as a potential target of environmental toxicants including oestrogenic chemicals. We suggest that toxicant-induced changes in epigenetic signatures are important mechanisms underlying the disruption of ovarian follicular development. In addition, we discuss how exposure to environmental oestrogens during early life can alter gene expression through effects on epigenetic control potentially leading to permanent changes in ovarian physiology. © 2014 British Society for Neuroendocrinology.

Stimulation targeting higher motor areas in stroke rehabilitation: A proof-of-concept, randomized, double-blinded placebo-controlled study of effectiveness and underlying mechanisms

PubMed Central

Cunningham, David A.; Varnerin, Nicole; Machado, Andre; Bonnett, Corin; Janini, Daniel; Roelle, Sarah; Potter-Baker, Kelsey; Sankarasubramanian, Vishwanath; Wang, Xiaofeng; Yue, Guang; Plow, Ela B.

2016-01-01

Purpose To demonstrate, in a proof-of-concept study, whether potentiating ipsilesional higher motor areas (premotor cortex and supplementary motor area) augments and accelerates recovery associated with constraint induced movement. Methods In a randomized, double-blinded pilot clinical study, 12 patients with chronic stroke were assigned to receive anodal transcranial direct current stimulation (tDCS) (n = 6) or sham (n = 6) to the ipsilesional higher motor areas during constraint-induced movement therapy. We assessed functional and neurophysiologic outcomes before and after 5 weeks of therapy. Results Only patients receiving tDCS demonstrated gains in function and dexterity. Gains were accompanied by an increase in excitability of the contralesional rather than the ipsilesional hemisphere. Conclusions Our proof-of-concept study provides early evidence that stimulating higher motor areas can help recruit the contralesional hemisphere in an adaptive role in cases of greater ipsilesional injury. Whether this early evidence of promise translates to remarkable gains in functional recovery compared to existing approaches of stimulation remains to be confirmed in large-scale clinical studies that can reasonably dissociate stimulation of higher motor areas from that of the traditional primary motor cortices. PMID:26484700

Effects of Anesthetics on Brain Circuit Formation

PubMed Central

Wagner, Meredith; Ryu, Yun Kyoung; Smith, Sarah C.; Mintz, C. David

2014-01-01

The results of several retrospective clinical studies suggest that exposure to anesthetic agents early in life is correlated with subsequent learning and behavioral disorders. While ongoing prospective clinical trials may help to clarify this association, they remain confounded by numerous factors. Thus, some of the most compelling data supporting the hypothesis that a relatively short anesthetic exposure can lead to a long-lasting change in brain function are derived from animal models. The mechanism by which such changes could occur remains incompletely understood. Early studies identified anesthetic-induced neuronal apoptosis as a possible mechanism of injury, and more recent work suggests that anesthetics may interfere with several critical processes in brain development. The function of the mature brain requires the presence of circuits, established during development, that perform the computations underlying learning and cognition. In this review we examine the mechanisms by which anesthetics could disrupt brain circuit formation, including effects on neuronal survival and neurogenesis, neurite growth and guidance, formation of synapses, and function of supporting cells. There is evidence that anesthetics can disrupt aspects of all of these processes, and further research is required to elucidate which are most relevant to pediatric anesthetic neurotoxicity. PMID:25144504

A method of determining where to target surveillance efforts in heterogeneous epidemiological systems

PubMed Central

van den Bosch, Frank; Gottwald, Timothy R.; Alonso Chavez, Vasthi

2017-01-01

The spread of pathogens into new environments poses a considerable threat to human, animal, and plant health, and by extension, human and animal wellbeing, ecosystem function, and agricultural productivity, worldwide. Early detection through effective surveillance is a key strategy to reduce the risk of their establishment. Whilst it is well established that statistical and economic considerations are of vital importance when planning surveillance efforts, it is also important to consider epidemiological characteristics of the pathogen in question—including heterogeneities within the epidemiological system itself. One of the most pronounced realisations of this heterogeneity is seen in the case of vector-borne pathogens, which spread between ‘hosts’ and ‘vectors’—with each group possessing distinct epidemiological characteristics. As a result, an important question when planning surveillance for emerging vector-borne pathogens is where to place sampling resources in order to detect the pathogen as early as possible. We answer this question by developing a statistical function which describes the probability distributions of the prevalences of infection at first detection in both hosts and vectors. We also show how this method can be adapted in order to maximise the probability of early detection of an emerging pathogen within imposed sample size and/or cost constraints, and demonstrate its application using two simple models of vector-borne citrus pathogens. Under the assumption of a linear cost function, we find that sampling costs are generally minimised when either hosts or vectors, but not both, are sampled. PMID:28846676

Increased gibberellin contents contribute to accelerated growth and development of transgenic tobacco overexpressing a wheat ubiquitin gene.

PubMed

Wang, Guo-Kun; Zhang, Meng; Gong, Jiang-Feng; Guo, Qi-Fang; Feng, Ya-Nan; Wang, Wei

2012-12-01

Overexpressing TaUb2 promoted stem growth and resulted in early flowering in transgenic tobacco plants. Ubiquitin are involved in the production, metabolism and proper function of gibberellin. The ubiquitin-26S proteasome system (UPS), in which ubiquitin (Ub) functions as a marker, is a post-translational regulatory system that plays a prominent role in various biological processes. To investigate the impact of different Ub levels on plant growth and development, transgenic tobacco (Nicotiana tabacum L.) plants were engineered to express an Ub gene (TaUb2) from wheat (Triticum aestivum L.) under the control of cauliflower mosaic virus 35S promoter. Transgenic tobacco plants overexpressing TaUb2 demonstrated an accelerated growth rate at early stage and an early flowering phenotype in development. The preceding expression of MADS-box genes also corresponded to the accelerated developmental phenotypes of the transgenic tobacco plants compared to that of wild-type (WT). Total gibberellin (GA) and active GA contents in transgenic tobacco plants were higher than those in WT at the corresponding developmental stages, and some GA metabolism genes were upregulated. Treatment with GA(3) conferred a similarly accelerated grown rate in WT plants to that of transgenic tobacco plants, while growth was inhibited when transgenic tobacco plants were treated with a GA biosynthesis inhibitor. Thus, the results suggest that Ub are involved in the production, metabolism and proper function of GA, which is important in the regulation of plant growth and development.

Spreading the Clinical Window for Diagnosing Fetal-Onset Hypogonadism in Boys

PubMed Central

Grinspon, Romina P.; Loreti, Nazareth; Braslavsky, Débora; Valeri, Clara; Schteingart, Helena; Ballerini, María Gabriela; Bedecarrás, Patricia; Ambao, Verónica; Gottlieb, Silvia; Ropelato, María Gabriela; Bergadá, Ignacio; Campo, Stella M.; Rey, Rodolfo A.

2014-01-01

In early fetal development, the testis secretes – independent of pituitary gonadotropins – androgens and anti-Müllerian hormone (AMH) that are essential for male sex differentiation. In the second half of fetal life, the hypothalamic–pituitary axis gains control of testicular hormone secretion. Follicle-stimulating hormone (FSH) controls Sertoli cell proliferation, responsible for testis volume increase and AMH and inhibin B secretion, whereas luteinizing hormone (LH) regulates Leydig cell androgen and INSL3 secretion, involved in the growth and trophism of male external genitalia and in testis descent. This differential regulation of testicular function between early and late fetal periods underlies the distinct clinical presentations of fetal-onset hypogonadism in the newborn male: primary hypogonadism results in ambiguous or female genitalia when early fetal-onset, whereas it becomes clinically undistinguishable from central hypogonadism when established later in fetal life. The assessment of the hypothalamic–pituitary–gonadal axis in male has classically relied on the measurement of gonadotropin and testosterone levels in serum. These hormone levels normally decline 3–6 months after birth, thus constraining the clinical evaluation window for diagnosing male hypogonadism. The advent of new markers of gonadal function has spread this clinical window beyond the first 6 months of life. In this review, we discuss the advantages and limitations of old and new markers used for the functional assessment of the hypothalamic–pituitary–testicular axis in boys suspected of fetal-onset hypogonadism. PMID:24847309

Functional Recovery in Major Depressive Disorder: Focus on Early Optimized Treatment.

PubMed

Habert, Jeffrey; Katzman, Martin A; Oluboka, Oloruntoba J; McIntyre, Roger S; McIntosh, Diane; MacQueen, Glenda M; Khullar, Atul; Milev, Roumen V; Kjernisted, Kevin D; Chokka, Pratap R; Kennedy, Sidney H

2016-09-01

This article presents the case that a more rapid, individualized approach to treating major depressive disorder (MDD) may increase the likelihood of achieving full symptomatic and functional recovery for individual patients and that studies show it is possible to make earlier decisions about appropriateness of treatment in order to rapidly optimize that treatment. A PubMed search was conducted using terms including major depressive disorder, early improvement, predictor, duration of untreated illness, and function. English-language articles published before September 2015 were included. Additional studies were found within identified research articles and reviews. Thirty antidepressant studies reporting predictor criteria and outcome measures are included in this review. Studies were reviewed to extract definitions of predictors, outcome measures, and results of the predictor analysis. Results were summarized separately for studies reporting effects of early improvement, baseline characteristics, and duration of untreated depression. Shorter duration of the current depressive episode and duration of untreated depression are associated with better symptomatic and functional outcomes in MDD. Early improvement of depressive symptoms predicts positive symptomatic outcomes (response and remission), and early functional improvement predicts an increased likelihood of functional remission. The approach to treatment of depression that exhibits the greatest potential for achieving full symptomatic and functional recovery is early optimized treatment: early diagnosis followed by rapid individualized treatment. Monitoring symptoms and function early in treatment is crucial to ensuring that patients do not remain on ineffective or poorly tolerated treatment, which may delay recovery and heighten the risk of residual functional deficits. © Copyright 2016 Physicians Postgraduate Press, Inc.

Maternal sensitivity, infant limbic structure volume and functional connectivity: a preliminary study

PubMed Central

Rifkin-Graboi, A; Kong, L; Sim, L W; Sanmugam, S; Broekman, B F P; Chen, H; Wong, E; Kwek, K; Saw, S-M; Chong, Y-S; Gluckman, P D; Fortier, M V; Pederson, D; Meaney, M J; Qiu, A

2015-01-01

Mechanisms underlying the profound parental effects on cognitive, emotional and social development in humans remain poorly understood. Studies with nonhuman models suggest variations in parental care affect the limbic system, influential to learning, autobiography and emotional regulation. In some research, nonoptimal care relates to decreases in neurogenesis, although other work suggests early-postnatal social adversity accelerates the maturation of limbic structures associated with emotional learning. We explored whether maternal sensitivity predicts human limbic system development and functional connectivity patterns in a small sample of human infants. When infants were 6 months of age, 20 mother–infant dyads attended a laboratory-based observational session and the infants underwent neuroimaging at the same age. After considering age at imaging, household income and postnatal maternal anxiety, regression analyses demonstrated significant indirect associations between maternal sensitivity and bilateral hippocampal volume at six months, with the majority of associations between sensitivity and the amygdala demonstrating similar indirect, but not significant results. Moreover, functional analyses revealed direct associations between maternal sensitivity and connectivity between the hippocampus and areas important for emotional regulation and socio-emotional functioning. Sensitivity additionally predicted indirect associations between limbic structures and regions related to autobiographical memory. Our volumetric results are consistent with research indicating accelerated limbic development in response to early social adversity, and in combination with our functional results, if replicated in a larger sample, may suggest that subtle, but important, variations in maternal care influence neuroanatomical trajectories important to future cognitive and emotional functioning. PMID:26506054

Cannabis use and memory brain function in adolescent boys: a cross-sectional multicenter functional magnetic resonance imaging study.

PubMed

Jager, Gerry; Block, Robert I; Luijten, Maartje; Ramsey, Nick F

2010-06-01

Early-onset cannabis use has been associated with later use/abuse, mental health problems (psychosis, depression), and abnormal development of cognition and brain function. During adolescence, ongoing neurodevelopmental maturation and experience shape the neural circuitry underlying complex cognitive functions such as memory and executive control. Prefrontal and temporal regions are critically involved in these functions. Maturational processes leave these brain areas prone to the potentially harmful effects of cannabis use. We performed a two-site (United States and The Netherlands; pooled data) functional magnetic resonance imaging (MRI) study with a cross-sectional design, investigating the effects of adolescent cannabis use on working memory (WM) and associative memory (AM) brain function in 21 abstinent but frequent cannabis-using boys (13-19) years of age and compared them with 24 nonusing peers. Brain activity during WM was assessed before and after rule-based learning (automatization). AM was assessed using a pictorial hippocampal-dependent memory task. Cannabis users performed normally on both memory tasks. During WM assessment, cannabis users showed excessive activity in prefrontal regions when a task was novel, whereas automatization of the task reduced activity to the same level in users and controls. No effect of cannabis use on AM-related brain function was found. In adolescent cannabis users, the WM system was overactive during a novel task, suggesting functional compensation. Inefficient WM recruitment was not related to a failure in automatization but became evident when processing continuously changing information. The results seem to confirm the vulnerability of still developing frontal lobe functioning for early-onset cannabis use. 2010 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

Effectiveness and feasibility of early physical rehabilitation programs for geriatric hospitalized patients: a systematic review

PubMed Central

2013-01-01

Background Old adults admitted to the hospital are at severe risk of functional loss during hospitalization. Early in-hospital physical rehabilitation programs appear to prevent functional loss in geriatric patients. The first aim of this review was to investigate the effect of early physical rehabilitation programs on physical functioning among geriatric patients acutely admitted to the hospital. The second aim was to evaluate the feasibility of early physical rehabilitation programs. Methods Two searches, one for physical functioning and one for feasibility, were conducted in PubMed, CINAHL, and EMBASE. Additional studies were identified through reference and citation tracking. To be included articles had to report on in-hospital early physical rehabilitation of patients aged 65 years and older with an outcome measure of physical functioning. Studies were excluded when the treatment was performed on specialized units other than geriatric units. Randomized controlled trials were included to examine the effect of early physical rehabilitation on physical functioning, length of stay and discharge destination. To investigate feasibility also non randomized controlled trials were added. Results Fifteen articles, reporting on 13 studies, described the effect on physical functioning. The early physical rehabilitation programs were classified in multidisciplinary programs with an exercise component and usual care with an exercise component. Multidisciplinary programs focussed more on facilitating discharge home and independent ADL, whereas exercise programs aimed at improving functional outcomes. At time of discharge patients who had participated in a multidisciplinary program or exercise program improved more on physical functional tests and were less likely to be discharged to a nursing home compared to patients receiving only usual care. In addition, multidisciplinary programs reduced the length of hospital stay significantly. Follow-up interventions improved physical functioning after discharge. The feasibility search yielded four articles. The feasibility results showed that early physical rehabilitation for acutely hospitalized old adults was safe. Adherence rates differed between studies and the recruitment of patients was sometimes challenging. Conclusions Early physical rehabilitation care for acutely hospitalized old adults leads to functional benefits and can be safely executed. Further research is needed to specifically quantify the physical component in early physical rehabilitation programs. PMID:24112948

Effectiveness and feasibility of early physical rehabilitation programs for geriatric hospitalized patients: a systematic review.

PubMed

Kosse, Nienke M; Dutmer, Alisa L; Dasenbrock, Lena; Bauer, Jürgen M; Lamoth, Claudine J C

2013-10-10

Old adults admitted to the hospital are at severe risk of functional loss during hospitalization. Early in-hospital physical rehabilitation programs appear to prevent functional loss in geriatric patients. The first aim of this review was to investigate the effect of early physical rehabilitation programs on physical functioning among geriatric patients acutely admitted to the hospital. The second aim was to evaluate the feasibility of early physical rehabilitation programs. Two searches, one for physical functioning and one for feasibility, were conducted in PubMed, CINAHL, and EMBASE. Additional studies were identified through reference and citation tracking. To be included articles had to report on in-hospital early physical rehabilitation of patients aged 65 years and older with an outcome measure of physical functioning. Studies were excluded when the treatment was performed on specialized units other than geriatric units. Randomized controlled trials were included to examine the effect of early physical rehabilitation on physical functioning, length of stay and discharge destination. To investigate feasibility also non randomized controlled trials were added. Fifteen articles, reporting on 13 studies, described the effect on physical functioning. The early physical rehabilitation programs were classified in multidisciplinary programs with an exercise component and usual care with an exercise component. Multidisciplinary programs focussed more on facilitating discharge home and independent ADL, whereas exercise programs aimed at improving functional outcomes. At time of discharge patients who had participated in a multidisciplinary program or exercise program improved more on physical functional tests and were less likely to be discharged to a nursing home compared to patients receiving only usual care. In addition, multidisciplinary programs reduced the length of hospital stay significantly. Follow-up interventions improved physical functioning after discharge. The feasibility search yielded four articles. The feasibility results showed that early physical rehabilitation for acutely hospitalized old adults was safe. Adherence rates differed between studies and the recruitment of patients was sometimes challenging. Early physical rehabilitation care for acutely hospitalized old adults leads to functional benefits and can be safely executed. Further research is needed to specifically quantify the physical component in early physical rehabilitation programs.

[THE OPTIMIZATION OF NUTRITION FUNCTION UNDER SYNDROME OF RESISTANCE TO INSULIN, DISORDER OF FATTY ACIDS' METABOLISM AND ABSORPTION OF GLUCOSE BY CELLS (A LECTURE)].

PubMed

Titov, V N

2016-01-01

The phylogenetic processes continue to proceed in Homo Sapiens. At the very early stages ofphylogenesis, the ancient Archaea that formed mitochondria under symbiotic interaction with later bacterial cells conjointly formed yet another system. In this system, there are no cells' absorption of glucose if it is possible to absorb fatty acids from intercellular medium in the form of unesterfied fatty acids or ketonic bodies--metabolites of fatty acids. This is caused by objectively existed conditions and subsequent availability of substrates at the stages ofphylogenesis: acetate, ketonic bodies, fatty acids and only later glucose. The phylogenetically late insulin used after billions years the same dependencies at formation of regulation ofmetabolism offatty acids and cells' absorption of glucose. In order that syndrome ofresistance ceased to exist as afoundation of metabolic pandemic Homo Sapiens has to understand the following. After successful function ofArchaea+bacterial cells and considered by biology action of insulin for the third time in phylogenesis and using biological function of intelligence the content ofphylogenetically earlier palmitic saturated fatty acid infood can't to exceed possibilities of phylogenetically late lipoproteins to transfer it in intercellular medium and blood and cells to absorb it. It is supposed that at early stages of phylogenesis biological function of intelligence is primarily formed to bring into line "unconformities" of regulation of metabolism against the background of seeming relative biological "perfection". These unconformities were subsequently and separately formed at the level of cells in paracrin regulated cenosises of cells and organs and at the level of organism. The prevention of resistance to insulin basically requires biological function of intelligence, principle of self-restraint, bringing into line multiple desires of Homo Sapiens with much less extensive biological possibilities. The "unconformities" of regulation of metabolism in vivo are etiological factors of all metabolic pandemics including atherosclerosis, metabolic arterial hypertension, obesity and metabolic syndrome Tertiannondatum.

Ecosystem function and the net benefit of services provided by three land-use types under variable management in northwestern Virginia

NASA Astrophysics Data System (ADS)

Huelsman, K. S.; Epstein, H. E.

2017-12-01

The concept of Ecosystem Services (ES) has become more interdisciplinary and influential in policy decision-making, but there are two major shortcomings in recent ES conversations: the resource inputs required by highly managed systems in order to provide material goods are not widely considered, and the distinction between ecosystem function and service is not always made. Supporting and regulating ES were examined for three land-use types with variable human management within the same mesoclimate: farmland, native prairie, and non-native early successional field. In situ soil moisture readings and soil nitrogen (N) transformation incubations, biodiversity surveys, vegetation harvesting, and soil sampling in each land-use type were used to determine the following ES: habitat, productivity, soil fertility, nutrient cycling, and water retention. If the provision of a particular ES required human inputs or interference, its overall value was reduced by the environmental cost of management. Non-native early successional field is not valued for the provision of any particular ES, as native prairie and farmland are, but it provides supporting and regulating ES without the requirement of human intervention, making it valuable in different ways. Likewise, any ecosystem functions with negative ecological side effects were considered ecosystem disservices and reduced the overall value of ES provided by the system. For example, the function of net nitrogen mineralization, generally defined as a service, is a disservice under N-saturated conditions, as additional N could be lost via leaching or gaseous forms. This research is valuable in the context of the current trend of increasing farmland abandonment and land use conversions. By considering the cost of human management for the provision of certain ES, as well as potential disservices associated with function, the overall net benefits of these three land-use types can be compared to improve land-use decision-making.

State-of-the-Art Review of Echocardiographic Imaging in the Evaluation and Treatment of Functional Tricuspid Regurgitation.

PubMed

Hahn, Rebecca T

2016-12-01

Functional or secondary tricuspid regurgitation (TR) is the most common cause of severe TR in the Western world. The presence of functional TR, either isolated or in combination with left heart disease, is associated with unfavorable natural history. Surgical mortality for isolated tricuspid valve interventions remains higher than for any other single valve surgery, and surgical options for repair do not have consistent long-term durability. In addition, as more patients undergo transcatheter left valve interventions, developing transcatheter solutions for functional TR has gained greater momentum. Numerous transcatheter devices are currently in early clinical trials. All patients require an assessment of valve morphology and function, and transcatheter devices typically require intraprocedural guidance by echocardiography. The following review will describe tricuspid anatomy, define echocardiographic views for evaluating tricuspid valve morphology and function, and discuss imaging requirements for the current transcatheter devices under development for the treatment of functional TR. © 2016 American Heart Association, Inc.

34 CFR 694.14 - What requirements apply to a State that served students under the National Early Intervention...

Code of Federal Regulations, 2010 CFR

2010-07-01

... 34 Education 3 2010-07-01 2010-07-01 false What requirements apply to a State that served students under the National Early Intervention Scholarship and Partnership program (NEISP) and that receives a... students under the National Early Intervention Scholarship and Partnership program (NEISP) and that...

Modeling and Circumventing the Effect of Sediments and Water Column on Receiver Functions

NASA Astrophysics Data System (ADS)

Audet, P.

2017-12-01

Teleseismic P-wave receiver functions are routinely used to resolve crust and mantle structure in various geologic settings. Receiver functions are approximations to the Earth's Green's functions and are composed of various scattered phase arrivals, depending on the complexity of the underlying Earth structure. For simple structure, the dominant arrivals (converted and back-scattered P-to-S phases) are well separated in time and can be reliably used in estimating crustal velocity structure. In the presence of sedimentary layers, strong reverberations typically produce high-amplitude oscillations that contaminate the early part of the wave train and receiver functions can be difficult to interpret in terms of underlying structure. The effect of a water column also limits the interpretability of under-water receiver functions due to the additional acoustic wave propagating within the water column that can contaminate structural arrivals. We perform numerical modeling of teleseismic Green's functions and receiver functions using a reflectivity technique for a range of Earth models that include thin sedimentary layers and overlying water column. These modeling results indicate that, as expected, receiver functions are difficult to interpret in the presence of sediments, but the contaminating effect of the water column is dependent on the thickness of the water layer. To circumvent these effects and recover source-side structure, we propose using an approach based on transfer function modeling that bypasses receiver functions altogether and estimates crustal properties directly from the waveforms (Frederiksen and Delayney, 2015). Using this approach, reasonable assumptions about the properties of the sedimentary layer can be included in forward calculations of the Green's functions that are convolved with radial waveforms to predict vertical waveforms. Exploration of model space using Monte Carlo-style search and least-square waveform misfits can be performed to estimate any model parameter of interest, including those of the sedimentary or water layer. We show how this method can be applied to OBS data using broadband stations from the Cascadia Initiative to recover oceanic plate structure.

Evaluation of Early and Prolonged Effects of Acute Neurotoxicity and Neuroprotection Using Novel Functional Imaging Techniques

DTIC Science & Technology

2004-08-01

Mutual Information (NMI) voxel match algorithm of the ANALYZE software package and cubic spline interpolation (Brownell et al. 2003, Appendix). 2...nuclear inclusion and cell survival. Materials and Methods Animals: Male transgenic R6/2 mice, which depict many clinical features of juvenile HD were...purchased from the Jackson Laboratories (Bar Harbor, ME). The mice were housed 3-4 per cage under standard conditions with free access to food and water

[The importance of the thermometric method for assessing the function of mucoperiosteal flaps in uranostaphyloplasty with/without transection of the neurovascular bundles in the rehabilitation of patients with congenital cleft palate].

PubMed

Bernadskiĭ, Iu I; Khar'kov, L V; Prudnikov, V M

1990-01-01

The nature and degree of reflow to the mucoperiosteal flaps was evaluated using a distant thermometry of the cleft palate in 67 children under uranostaphyloplasty and in early postsurgical period. In extracting the neurovascular bundles from their channels heat reflow to the palate was more fast and pronounced than with the bundles sectioned.

Clinical symptoms predict concurrent social and global functioning in an early psychosis sample.

PubMed

Cacciotti-Saija, Cristina; Langdon, Robyn; Ward, Philip B; Hickie, Ian B; Guastella, Adam J

2018-04-01

Although well established in chronic schizophrenia, the key determinants of functioning remain unknown during the early phase of a psychotic disorder. The aim of this study was to comprehensively examine the social cognitive, basic neurocognitive and clinical predictors of concurrent social functioning and global functioning in an early psychosis sample. This study examined the relationship between social cognition, basic neurocognition and clinical symptoms with concurrent functioning in 51 early psychosis individuals. Assessments included a range of self-report, observational and clinician-rated measures of cognitive, symptom severity and functioning domains. Results revealed a significant association between self-reported social function and lower levels of both social interaction anxiety and negative psychotic symptoms. A significant association was also observed between lower levels of negative psychotic symptoms and observed social functioning. Lastly, results demonstrated a significant association between reduced negative psychotic symptoms and clinician-rated global functioning. Clinical domains such as negative symptoms and social interaction anxiety significantly contribute to an optimal model predicting outcome during the early phase of a psychotic disorder. These clinical features may also provide useful markers of an individual's capacity for social participation. Clinical implications include the need for early targeted intervention to address social anxiety and negative psychotic symptoms to facilitate optimum patient outcome. © 2015 Wiley Publishing Asia Pty Ltd.

The Typical Developmental Trajectory of Social and Executive Functions in Late Adolescence and Early Adulthood

ERIC Educational Resources Information Center

Taylor, Sophie Jane; Barker, Lynne Ann; Heavey, Lisa; McHale, Sue

2013-01-01

Executive functions and social cognition develop through childhood into adolescence and early adulthood and are important for adaptive goal-oriented behavior (Apperly, Samson, & Humphreys, 2009; Blakemore & Choudhury, 2006). These functions are attributed to frontal networks known to undergo protracted maturation into early adulthood…

How Homes Influence Schools: Early Parenting Predicts African American Children's Classroom Social-Emotional Functioning

ERIC Educational Resources Information Center

Baker, Claire E.; Rimm-Kaufman, Sara E.

2014-01-01

Data from the Early Childhood Longitudinal Study, Kindergarten Cohort were used to examine the extent to which early parenting predicted African American children's kindergarten social-emotional functioning. Teachers rated children's classroom social-emotional functioning in four areas (i.e., approaches to learning, self-control, interpersonal…

Impaired Voluntary Movement Control and Its Rehabilitation in Cerebral Palsy.

PubMed

Gordon, Andrew M

2016-01-01

Cerebral palsy is caused by early damage to the developing brain, as the most common pediatric neurological disorder. Hemiplegia (unilateral spastic cerebral palsy) is the most common subtype, and the resulting impairments, lateralized to one body side, especially affect the upper extremity, limiting daily function. This chapter first describes the pathophysiology and mechanisms underlying impaired upper extremity control of cerebral palsy. It will be shown that the severity of impaired hand function closely relates to the integrity of the corticospinal tract innervating the affected hand. It will also shown that the developing corticospinal tract can reorganize its connectivity depending on the timing and location of CNS injury, which also has implications for the severity of hand impairments and rehabilitation. The mechanisms underlying impaired motor function will be highlighted, including deficits in movement execution and planning and sensorimotor integration. It will be shown that despite having unimanual hand impairments, bimanual movement control deficits and mirror movements also impact function. Evidence for motor learning-based therapies including Constraint-Induced Movement Therapy and Bimanual Training, and the possible pathophysiological predictors of treatment outcome and plasticity will be described. Finally, future directions for rehabilitations will be presented.

On the Evolution of the Cardiac Pacemaker

PubMed Central

Burkhard, Silja; van Eif, Vincent; Garric, Laurence; Christoffels, Vincent M.; Bakkers, Jeroen

2017-01-01

The rhythmic contraction of the heart is initiated and controlled by an intrinsic pacemaker system. Cardiac contractions commence at very early embryonic stages and coordination remains crucial for survival. The underlying molecular mechanisms of pacemaker cell development and function are still not fully understood. Heart form and function show high evolutionary conservation. Even in simple contractile cardiac tubes in primitive invertebrates, cardiac function is controlled by intrinsic, autonomous pacemaker cells. Understanding the evolutionary origin and development of cardiac pacemaker cells will help us outline the important pathways and factors involved. Key patterning factors, such as the homeodomain transcription factors Nkx2.5 and Shox2, and the LIM-homeodomain transcription factor Islet-1, components of the T-box (Tbx), and bone morphogenic protein (Bmp) families are well conserved. Here we compare the dominant pacemaking systems in various organisms with respect to the underlying molecular regulation. Comparative analysis of the pathways involved in patterning the pacemaker domain in an evolutionary context might help us outline a common fundamental pacemaker cell gene programme. Special focus is given to pacemaker development in zebrafish, an extensively used model for vertebrate development. Finally, we conclude with a summary of highly conserved key factors in pacemaker cell development and function. PMID:29367536

Age of language acquisition and cortical language organization in multilingual patients undergoing awake brain mapping.

PubMed

Fernández-Coello, Alejandro; Havas, Viktória; Juncadella, Montserrat; Sierpowska, Joanna; Rodríguez-Fornells, Antoni; Gabarrós, Andreu

2017-06-01

OBJECTIVE Most knowledge regarding the anatomical organization of multilingualism is based on aphasiology and functional imaging studies. However, the results have still to be validated by the gold standard approach, namely electrical stimulation mapping (ESM) during awake neurosurgical procedures. In this ESM study the authors describe language representation in a highly specific group of 13 multilingual individuals, focusing on how age of acquisition may influence the cortical organization of language. METHODS Thirteen patients who had a high degree of proficiency in multiple languages and were harboring lesions within the dominant, left hemisphere underwent ESM while being operated on under awake conditions. Demographic and language data were recorded in relation to age of language acquisition (for native languages and early- and late-acquired languages), neuropsychological pre- and postoperative language testing, the number and location of language sites, and overlapping distribution in terms of language acquisition time. Lesion growth patterns and histopathological characteristics, location, and size were also recorded. The distribution of language sites was analyzed with respect to age of acquisition and overlap. RESULTS The functional language-related sites were distributed in the frontal (55%), temporal (29%), and parietal lobes (16%). The total number of native language sites was 47. Early-acquired languages (including native languages) were represented in 97 sites (55 overlapped) and late-acquired languages in 70 sites (45 overlapped). The overlapping distribution was 20% for early-early, 71% for early-late, and 9% for late-late. The average lesion size (maximum diameter) was 3.3 cm. There were 5 fast-growing and 7 slow-growing lesions. CONCLUSIONS Cortical language distribution in multilingual patients is not homogeneous, and it is influenced by age of acquisition. Early-acquired languages have a greater cortical representation than languages acquired later. The prevalent native and early-acquired languages are largely represented within the perisylvian left hemisphere frontoparietotemporal areas, and the less prevalent late-acquired languages are mostly overlapped with them.

Early-life stress links 5-hydroxymethylcytosine to anxiety-related behaviors

PubMed Central

Papale, Ligia A.; Madrid, Andy; Li, Sisi; Alisch, Reid S.

2017-01-01

ABSTRACT Environmental stress contributes to the development of psychiatric disorders, including posttraumatic stress disorder and anxiety. While even acute stress alters gene expression, the molecular mechanisms underlying these changes remain largely unknown. 5-hydroxymethylcytosine (5hmC) is a novel environmentally sensitive DNA modification that is highly enriched in the brain and is associated with active transcription of neuronal genes. Here we examined behavioral and molecular alterations in adult mice that experienced an early-life stress before weaning (postnatal day 12 to 18) and found anxiety-like behaviors in adult female mice that were accompanied by correlated disruptions of hypothalamic 5hmC and gene expression in 118 genes, revealing potentially functional 5hmC (i.e., gene regulation). These genes are known and potentially novel stress-related targets, including Nr3c2, Nrxn1, Nfia, and Clip1, that have a significant enrichment for neuronal ontological functions, such as neuronal development and differentiation. Sequence motif predictions indicated that 5hmC may regulate gene expression by mediating transcription factor binding and alternative splicing of many of these transcripts. Together, these findings represent a critical step toward understanding the effects of early environment on the neuromolecular mechanisms that underlie the risk to develop anxiety disorders. PMID:28128679

Two functions of early language experience.

PubMed

Arshavsky, Yuri I

2009-05-01

The unique human ability of linguistic communication, defined as the ability to produce a practically infinite number of meaningful messages using a finite number of lexical items, is determined by an array of "linguistic" genes, which are expressed in neurons forming domain-specific linguistic centers in the brain. In this review, I discuss the idea that infants' early language experience performs two complementary functions. In addition to allowing infants to assimilate the words and grammar rules of their mother language, early language experience initiates genetic programs underlying language production and comprehension. This hypothesis explains many puzzling characteristics of language acquisition, such as the existence of a critical period for acquiring the first language and the absence of a critical period for the acquisition of additional language(s), a similar timetable for language acquisition in children belonging to families of different social and cultural status, the strikingly similar timetables in the acquisition of oral and sign languages, and the surprisingly small correlation between individuals' final linguistic competence and the intensity of their training. Based on the studies of microcephalic individuals, I argue that genetic factors determine not only the number of neurons and organization of interneural connections within linguistic centers, but also the putative internal properties of neurons that are not limited to their electrophysiological and synaptic properties.

Serum cystatin C level is associated with locomotive syndrome risk and can be an early predictor in community-living people: The Yakumo study.

PubMed

Tanaka, Satoshi; Ando, Kei; Kobayashi, Kazuyoshi; Hida, Tetsuro; Ito, Kenyu; Tsushima, Mikito; Morozumi, Masayoshi; Machino, Masaaki; Ota, Kyotaro; Seki, Taisuke; Suzuki, Koji; Nishida, Yoshihiro; Ishiguro, Naoki; Hasegawa, Yukiharu; Imagama, Shiro

2018-03-02

The locomotive syndrome (LS) risk has been recently proposed as a criterion for evaluating physical ability. Serum cystatin C level is an early renal function marker and a cardiovascular disease predictor. This study aimed to evaluate the relationship between serum cystatin C level and LS risk. We enrolled 54 participants and conducted the two-step test, stand-up test, 25-question geriatric locomotive function scale, LS risk test, Timed Up and Go test, back muscle strength, grip strength, blood test and serum cystatin C level measurement. A comparative study was conducted in participants with and without LS risk and in subgroups aged <60 and ≥60 years. No significant difference was found in the serum cystatin C level in subgroups aged <60 years and without LS risk. However, it was significantly higher in subjects with LS risk and aged ≥60 years. The area under the curve of the serum cystatin C level for LS risk was 0.824. The serum cystatin C level is significantly related to LS risk and can be an early predictor. In middle-aged and elderly people with high serum cystatin C levels, it is strongly recommended to enforce LS risk test and intervention.

[A Comparison Study on Early Damage Detection of Left Ventricular Function Based on Doppler Imaging Method for Children with Tumor].

PubMed

Liu, Ying; Zhang, Haowei; Zhang, Hang

2015-12-01

The early damage detection and evaluation are of great significance in treatment and prognosis to the left ventricular function for children with tumor. In this paper, it is reported that the early damage of the left ventricular function was observed by pulsed wave Doppler (PWD) and tissue Doppler imaging (TDI) in our laboratory. Eighty children half a year to fourteen years old were included in this study. The cardiac function indices in chemotherapy group and control group were measured and compared. The results showed that there was significant difference in mitral and tricuspid annulus flow spectrum between the two groups. Compared with PWD,TDI is more prompt, objective and accurate in detecting early damage of left ventricular function in children with tumor. And TDI is a good method for early identification of ventricular function damage in children with tumor.

A cosmological solution to the Impossibly Early Galaxy Problem

NASA Astrophysics Data System (ADS)

Yennapureddy, Manoj K.; Melia, Fulvio

2018-06-01

To understand the formation and evolution of galaxies at redshifts 0 ≲ z ≲ 10, one must invariably introduce specific models (e.g., for the star formation) in order to fully interpret the data. Unfortunately, this tends to render the analysis compliant to the theory and its assumptions, so consensus is still somewhat elusive. Nonetheless, the surprisingly early appearance of massive galaxies challenges the standard model, and the halo mass function estimated from galaxy surveys at z ≳ 4 appears to be inconsistent with the predictions of ΛCDM, giving rise to what has been termed "The Impossibly Early Galaxy Problem" by some workers in the field. A simple resolution to this question may not be forthcoming. The situation with the halos themselves, however, is more straightforward and, in this paper, we use linear perturbation theory to derive the halo mass function over the redshift range 0 ≲ z ≲ 10 for the Rh = ct universe. We use this predicted halo distribution to demonstrate that both its dependence on mass and its very weak dependence on redshift are compatible with the data. The difficulties with ΛCDM may eventually be overcome with refinements to the underlying theory of star formation and galaxy evolution within the halos. For now, however, we demonstrate that the unexpected early formation of structure may also simply be due to an incorrect choice of the cosmology, rather than to yet unknown astrophysical issues associated with the condensation of mass fluctuations and subsequent galaxy formation.

Leu72Met408 Polymorphism of the Ghrelin Gene Is Associated With Early Phase of Gastric Emptying in the Patients With Functional Dyspepsia in Japan

PubMed Central

Yamawaki, Hiroshi; Futagami, Seiji; Shimpuku, Mayumi; Shindo, Tomotaka; Maruki, Yuuta; Nagoya, Hiroyuki; Kodaka, Yasuhiro; Sato, Hitomi; Gudis, Katya; Kawagoe, Tetsuro; Sakamoto, Choitsu

2015-01-01

Background/Aims There are no available data about the relationship between ghrelin gene genotypes and early phase of gastric emptying in functional dyspepsia (FD) as defined by Rome III classification. Methods We enrolled 74 patients presenting with typical symptoms of FD and 64 healthy volunteers. Gastric motility was evaluated using the 13C-acetate breath test. We used Rome III criteria to evaluate upper abdominal symptoms and self-rating questionnaires for depression (SRQ-D) scores to determine status of depression. The Arg51Gln (346G>A), preproghrelin (3056T>C), Leu72Met (408C>A), Gln90Leu (3412T>A) and G-protein β3 (825C>T) polymorphisms were analyzed in the DNA from blood samples of enrolled subjects. Genotyping was performed by polymerase chain reaction. Results There was a significant relationship between the Gln90Leu3412 genotype and SRQ-D score in FD patients (P = 0.009). Area under the curve at 15 minutes (AUC15) value was significantly associated with the Leu72Met408 genotype (P = 0.015) but not with entire gastric emptying. Conclusions The Leu72Met (408C>A) single nucleotide polymorphism was significantly associated with early phase of gastric emptying in FD patients. Further studies will be necessary to clarify the association between ghrelin gene single nucleotide polymorphisms and early phase of gastric emptying in FD patients. PMID:25540946

Leu72Met408 Polymorphism of the Ghrelin Gene Is Associated With Early Phase of Gastric Emptying in the Patients With Functional Dyspepsia in Japan.

PubMed

Yamawaki, Hiroshi; Futagami, Seiji; Shimpuku, Mayumi; Shindo, Tomotaka; Maruki, Yuuta; Nagoya, Hiroyuki; Kodaka, Yasuhiro; Sato, Hitomi; Gudis, Katya; Kawagoe, Tetsuro; Sakamoto, Choitsu

2015-01-01

There are no available data about the relationship between ghrelin gene genotypes and early phase of gastric emptying in functional dyspepsia (FD) as defined by Rome III classification. We enrolled 74 patients presenting with typical symptoms of FD and 64 healthy volunteers. Gastric motility was evaluated using the 13C-acetate breath test. We used Rome III criteria to evaluate upper abdominal symptoms and self-rating questionnaires for depression (SRQ-D) scores to determine status of depression. The Arg51Gln (346G->A), preproghrelin (3056T->C), Leu72Met (408C->A), Gln90Leu (3412T->A) and G-protein 3 (825C->T) polymorphisms were analyzed in the DNA from blood samples of enrolled subjects. Genotyping was performed by polymerase chain reaction. There was a significant relationship between the Gln90Leu3412 genotype and SRQ-D score in FD patients (P = 0.009). Area under the curve at 15 minutes (AUC15) value was significantly associated with the Leu72Met408 genotype (P = 0.015) but not with entire gastric emptying. The Leu72Met (408C->A) single nucleotide polymorphism was significantly associated with early phase of gastric emptying in FD patients. Further studies will be necessary to clarify the association between ghrelin gene single nucleotide polymorphisms and early phase of gastric emptying in FD patients.

Impact of early diagnosis on functional disability in rheumatoid arthritis

PubMed Central

Kim, Dam; Choi, Chan-Bum; Lee, Jiyoung; Cho, Soo-Kyung; Won, Soyoung; Bang, So-Young; Cha, Hoon-Suk; Choe, Jung-Yoon; Chung, Won Tae; Hong, Seung-Jae; Jun, Jae-Bum; Jung, Young Ok; Kim, Jinseok; Kim, Seong-Kyu; Kim, Tae-Hwan; Kim, Tae-Jong; Koh, Eunmi; Lee, Hye-Soon; Lee, Jaejoon; Lee, Jisoo; Lee, Sang-Heon; Lee, Shin-Seok; Lee, Sung Won; Shim, Seung-Cheol; Yoo, Dae-Hyun; Yoon, Bo Young; Sung, Yoon-Kyoung; Bae, Sang-Cheol

2017-01-01

Background/Aims To determine whether early diagnosis is beneficial for functional status of various disease durations in rheumatoid arthritis (RA) patients. Methods A total of 4,540 RA patients were enrolled as part of the Korean Observational Study Network for Arthritis (KORONA). We defined early diagnosis as a lag time between symptom onset and RA diagnosis of ≤ 12 months, whereas patients with a longer lag time comprised the delayed diagnosis group. Demographic characteristics and outcomes were compared between early and delayed diagnosis groups. Logistic regression analyses were performed to identify the impact of early diagnosis on the development of functional disability in RA patients. Results A total of 2,597 patients (57.2%) were included in the early diagnosis group. The average Health Assessment Questionnaire-Disability Index (HAQ-DI) score was higher in the delayed diagnosis group (0.64 ± 0.63 vs. 0.70 ± 0.66, p < 0.01), and the proportion of patients with no functional disability (HAQ = 0) was higher in the early diagnosis group (22.9% vs. 20.0%, p = 0.02). In multivariable analyses, early diagnosis was independently associated with no functional disability (odds ratio [OR], 1.19; 95% confidence interval [CI], 1.01 to 1.40). In a subgroup analysis according to disease duration, early diagnosis was associated with no functional disability in patients with disease duration < 5 years (OR, 1.37; 95% CI, 1.09 to 1.72) but not in patients with longer disease duration (for 5 to 10 years: OR, 1.07; 95% CI, 0.75 to 1.52; for ≥ 10 years: OR, 0.92; 95% CI, 0.65 to 1.28). Conclusions Early diagnosis is associated with no functional disability, especially in patients with shorter disease duration. PMID:27618867

Suppression Subtractive Hybridization Analysis of Genes Regulated by Application of Exogenous Abscisic Acid in Pepper Plant (Capsicum annuum L.) Leaves under Chilling Stress

PubMed Central

Gong, Zhen-Hui; Yin, Yan-Xu; Li, Da-Wei

2013-01-01

Low temperature is one of the major factors limiting pepper (Capsicum annuum L.) production during winter and early spring in non-tropical regions. Application of exogenous abscisic acid (ABA) effectively alleviates the symptoms of chilling injury, such as wilting and formation of necrotic lesions on pepper leaves; however, the underlying molecular mechanism is not understood. The aim of this study was to identify genes that are differentially up- or downregulated in ABA-pretreated hot pepper seedlings incubated at 6°C for 48 h, using a suppression subtractive hybridization (SSH) method. A total of 235 high-quality ESTs were isolated, clustered and assembled into a collection of 73 unigenes including 18 contigs and 55 singletons. A total of 37 unigenes (50.68%) showed similarities to genes with known functions in the non-redundant database; the other 36 unigenes (49.32%) showed low similarities or unknown functions. Gene ontology analysis revealed that the 37 unigenes could be classified into nine functional categories. The expression profiles of 18 selected genes were analyzed using quantitative RT-PCR; the expression levels of 10 of these genes were at least two-fold higher in the ABA-pretreated seedlings under chilling stress than water-pretreated (control) plants under chilling stress. In contrast, the other eight genes were downregulated in ABA-pretreated seedlings under chilling stress, with expression levels that were one-third or less of the levels observed in control seedlings under chilling stress. These results suggest that ABA can positively and negatively regulate genes in pepper plants under chilling stress. PMID:23825555

Functional Development of the Circadian Clock in the Zebrafish Pineal Gland

PubMed Central

Ben-Moshe, Zohar; Foulkes, Nicholas S.

2014-01-01

The zebrafish constitutes a powerful model organism with unique advantages for investigating the vertebrate circadian timing system and its regulation by light. In particular, the remarkably early and rapid development of the zebrafish circadian system has facilitated exploring the factors that control the onset of circadian clock function during embryogenesis. Here, we review our understanding of the molecular basis underlying functional development of the central clock in the zebrafish pineal gland. Furthermore, we examine how the directly light-entrainable clocks in zebrafish cell lines have facilitated unravelling the general mechanisms underlying light-induced clock gene expression. Finally, we summarize how analysis of the light-induced transcriptome and miRNome of the zebrafish pineal gland has provided insight into the regulation of the circadian system by light, including the involvement of microRNAs in shaping the kinetics of light- and clock-regulated mRNA expression. The relative contributions of the pineal gland central clock and the distributed peripheral oscillators to the synchronization of circadian rhythms at the whole animal level are a crucial question that still remains to be elucidated in the zebrafish model. PMID:24839600

Sensitivity of newly defined impulse oscillometry indices in preschool children.

PubMed

Knihtilä, Hanna; Kotaniemi-Syrjänen, Anne; Pelkonen, Anna S; Kalliola, Satu; Mäkelä, Mika J; Malmberg, L Pekka

2017-05-01

Early origins of chronic obstructive pulmonary disease have been recognized. Impulse oscillometry (IOS) is suitable for assessment of lung function also in preschool children, and some novel indices have been connected to assessment of small airway function. However, limited data exist on the sensitivity of these new indices to detect lung function deficits in young symptomatic children. IOS measurements of 103 healthy preschool children were evaluated to establish reference equations for the difference between respiratory resistance at 5 and 20 Hz (R5-20), the relative difference of R5-20 (R5-20%), and area under the reactance curve (AX). Thereafter, IOS results of children with late-onset troublesome lung symptoms (n = 20), a history of early wheeze (n = 37), or a history of bronchopulmonary dysplasia (BPD, n = 8) were compared to healthy children. None of the patient groups differed from healthy regarding respiratory resistance at 5 Hz (R5), and only children with a history of BPD differed from healthy regarding respiratory reactance at 5 Hz (X5). In contrast, z-scores of R5-20, R5-20%, and AX were significantly higher in all patient groups than in healthy children (P < 0.001), showing improved sensitivity (20-55%) compared to R5 and X5 (5-6%). R5-20, R5-20%, and AX are superior to conventional IOS parameters in distinguishing children with current or past lower respiratory tract symptoms from healthy, and may prove valuable for screening early lung function deficits. Pediatr Pulmonol. 2017;52:598-605. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Genome-wide study of the adaptation of Saccharomyces cerevisiae to the early stages of wine fermentation.

PubMed

Novo, Maite; Mangado, Ana; Quirós, Manuel; Morales, Pilar; Salvadó, Zoel; Gonzalez, Ramon

2013-01-01

This work was designed to identify yeast cellular functions specifically affected by the stress factors predominating during the early stages of wine fermentation, and genes required for optimal growth under these conditions. The main experimental method was quantitative fitness analysis by means of competition experiments in continuous culture of whole genome barcoded yeast knockout collections. This methodology allowed the identification of haploinsufficient genes, and homozygous deletions resulting in growth impairment in synthetic must. However, genes identified as haploproficient, or homozygous deletions resulting in fitness advantage, were of little predictive power concerning optimal growth in this medium. The relevance of these functions for enological performance of yeast was assessed in batch cultures with single strains. Previous studies addressing yeast adaptation to winemaking conditions by quantitative fitness analysis were not specifically focused on the proliferative stages. In some instances our results highlight the importance of genes not previously linked to winemaking. In other cases they are complementary to those reported in previous studies concerning, for example, the relevance of some genes involved in vacuolar, peroxisomal, or ribosomal functions. Our results indicate that adaptation to the quickly changing growth conditions during grape must fermentation require the function of different gene sets in different moments of the process. Transport processes and glucose signaling seem to be negatively affected by the stress factors encountered by yeast in synthetic must. Vacuolar activity is important for continued growth during the transition to stationary phase. Finally, reduced biogenesis of peroxisomes also seems to be advantageous. However, in contrast to what was described for later stages, reduced protein synthesis is not advantageous for the early (proliferative) stages of the fermentation process. Finally, we found adenine and lysine to be in short supply for yeast growth in some natural grape musts.

40 CFR 124.66 - Special procedures for decisions on thermal variances under section 316(a).

Code of Federal Regulations, 2010 CFR

2010-07-01

... the best available technology under section 316(b). Permit applicants who wish an early decision on... filed under § 122.21. The Regional Administrator will then decide whether or not to make an early decision. If it is granted, both the early decision on CWA section 316 (a) or (b) issues and the grant of...

40 CFR 124.66 - Special procedures for decisions on thermal variances under section 316(a).

Code of Federal Regulations, 2013 CFR

2013-07-01

... the best available technology under section 316(b). Permit applicants who wish an early decision on... filed under § 122.21. The Regional Administrator will then decide whether or not to make an early decision. If it is granted, both the early decision on CWA section 316 (a) or (b) issues and the grant of...

40 CFR 124.66 - Special procedures for decisions on thermal variances under section 316(a).

Code of Federal Regulations, 2012 CFR

2012-07-01

... the best available technology under section 316(b). Permit applicants who wish an early decision on... filed under § 122.21. The Regional Administrator will then decide whether or not to make an early decision. If it is granted, both the early decision on CWA section 316 (a) or (b) issues and the grant of...

40 CFR 124.66 - Special procedures for decisions on thermal variances under section 316(a).

Code of Federal Regulations, 2011 CFR

2011-07-01

... the best available technology under section 316(b). Permit applicants who wish an early decision on... filed under § 122.21. The Regional Administrator will then decide whether or not to make an early decision. If it is granted, both the early decision on CWA section 316 (a) or (b) issues and the grant of...

40 CFR 124.66 - Special procedures for decisions on thermal variances under section 316(a).

Code of Federal Regulations, 2014 CFR

2014-07-01

... the best available technology under section 316(b). Permit applicants who wish an early decision on... filed under § 122.21. The Regional Administrator will then decide whether or not to make an early decision. If it is granted, both the early decision on CWA section 316 (a) or (b) issues and the grant of...

34 CFR 694.11 - Under what conditions may a Partnership that does not participate in the GEAR UP scholarship...

Code of Federal Regulations, 2010 CFR

2010-07-01

... for postsecondary education to students under the GEAR UP early intervention component? 694.11 Section... education to students under the GEAR UP early intervention component? A GEAR UP Partnership that does not... early intervention component of GEAR UP if— (a) The financial assistance is directly related to, and in...

Cerebellum tunes the excitability of the motor system: evidence from peripheral motor axons.

PubMed

Nodera, Hiroyuki; Manto, Mario

2014-12-01

Cerebellum is highly connected with the contralateral cerebral cortex. So far, the motor deficits observed in acute focal cerebellar lesions in human have been mainly explained on the basis of a disruption of the cerebello-thalamo-cortical projections. Cerebellar circuits have also numerous anatomical and functional interactions with brainstem nuclei and projects also directly to the spinal cord. Cerebellar lesions alter the excitability of peripheral motor axons as demonstrated by peripheral motor threshold-tracking techniques in cerebellar stroke. The biophysical changes are correlated with the functional scores. Nerve excitability measurements represent an attractive tool to extract the rules underlying the tuning of excitability of the motor pathways by the cerebellum and to discover the contributions of each cerebellar nucleus in this key function, contributing to early plasticity and sensorimotor learning.

Ocean Warming Enhances Malformations, Premature Hatching, Metabolic Suppression and Oxidative Stress in the Early Life Stages of a Keystone Squid

PubMed Central

Rosa, Rui; Pimentel, Marta S.; Boavida-Portugal, Joana; Teixeira, Tatiana; Trübenbach, Katja; Diniz, Mário

2012-01-01

Background The knowledge about the capacity of organisms’ early life stages to adapt to elevated temperatures is very limited but crucial to understand how marine biota will respond to global warming. Here we provide a comprehensive and integrated view of biological responses to future warming during the early ontogeny of a keystone invertebrate, the squid Loligo vulgaris. Methodology/Principal Findings Recently-spawned egg masses were collected and reared until hatching at present day and projected near future (+2°C) temperatures, to investigate the ability of early stages to undergo thermal acclimation, namely phenotypic altering of morphological, behavioural, biochemical and physiological features. Our findings showed that under the projected near-future warming, the abiotic conditions inside the eggs promoted metabolic suppression, which was followed by premature hatching. Concomitantly, the less developed newborns showed greater incidence of malformations. After hatching, the metabolic burst associated with the transition from an encapsulated embryo to a planktonic stage increased linearly with temperature. However, the greater exposure to environmental stress by the hatchlings seemed to be compensated by physiological mechanisms that reduce the negative effects on fitness. Heat shock proteins (HSP70/HSC70) and antioxidant enzymes activities constituted an integrated stress response to ocean warming in hatchlings (but not in embryos). Conclusions/Significance The stressful abiotic conditions inside eggs are expected to be aggravated under the projected near-future ocean warming, with deleterious effects on embryo survival and growth. Greater feeding challenges and the lower thermal tolerance limits of the hatchlings are strictly connected to high metabolic demands associated with the planktonic life strategy. Yet, we found some evidence that, in the future, the early stages might support higher energy demands by adjusting some cellular functional properties to increase their thermal tolerance windows. PMID:22701620

Effect of Early Referral to Specialist in Dementia on Institutionalization and Functional Decline: Findings from a Population-Based Study.

PubMed

Pimouguet, Clément; Le-Goff, Mélanie; Rizzuto, Debora; Berr, Claudine; Leffondré, Karen; Pérès, Karine; Dartigues, Jean FranÇois; Helmer, Catherine

2016-01-01

Although early diagnosis has been hypothesized to benefit both patients and caregivers, until now studies evaluating the effect of early dementia diagnosis are lacking. To investigate the influence of early specialist referral for dementia on the risk of institutionalization and functional decline in Activity of Daily Living (ADL). Incident dementia cases were screened in a prospective population-based cohort, the Three-City Study, and initial specialist consultation for cognitive complaint was assessed at dementia diagnosis. Proportional hazard regression and illness-death models were used to test the association between specialist referral and, respectively, institutionalization and functional decline. Only one third of the incident individuals with dementia had consulted a specialist for cognitive problems early (36%). After adjustment on potential confounders (including cognitive and functional decline) and competing risk of death, participants who had consulted a specialist early in the disease course presented a higher rate of being institutionalized than those who did not (Hazard Ratio = 2.00, 95% Confidence Interval (CI): 1.09- 3.64). But early specialist referral was not associated with further functional decline (HR = 1.09, 95% CI: 0.71- 1.67). Early specialist referral in dementia is associated with increased risk of institutionalization but not with functional decline in ADL. These findings suggest that early care referral in dementia may be a marker of concern for patients and/or caregivers; subsequent medical and social care could be suboptimal or inappropriate to allow patients to stay longer at home.

Attention and executive functions in the early course of pediatric epilepsy.

PubMed

Reuner, Gitta; Kadish, Navah Esther; Doering, Jan Henje; Balke, Doreen; Schubert-Bast, Susanne

2016-07-01

Our prospective study aimed at exploring attention and executive functions in children with new-onset epilepsy prior to and during the early course of antiepileptic treatment. Sociodemographic and epilepsy-related factors were analyzed as potential predictors both of impaired cognitive functions as well as for changes in cognitive functioning in the early course of illness. From a total group of 115 children aged six to 17years without major disabilities, 76 children were assessed longitudinally with a screening tool for attention and executive functions (EpiTrack Junior®). Sociodemographic variables (gender, age at epilepsy onset, need of special education) and epilepsy-related variables (etiology of epilepsy, semiology of seizures, number of seizures) were considered as potential predictors for impaired functions prior to treatment and for deterioration/amelioration in cognitive functions in the early course. Attention and executive functions of children with new-onset epilepsy were significantly more often impaired when compared with a healthy population, but less often when compared with children with chronic epilepsy. The majority of children showed stable cognitive functioning in the early course of treatment. The risk of impaired cognitive functions was significantly heightened when etiology of epilepsy was unknown or not classifiable. The chance for improvement of functioning was lowered by having a genetic epilepsy, or an unknown semiology of seizures. Children with new-onset epilepsy are at high risk for impaired attention and executive functions even prior to antiepileptic treatment, especially when etiology of their epilepsy remains unclear. The high stability of cognitive functioning in the early course can be used in counseling of families who worry about negative side effects of drug treatment. Finally, a systematic assessment of cognitive functions in children with new-onset epilepsy is necessary to detect subtle deficits in the early course and adjust treatment accordingly. Copyright © 2016 Elsevier Inc. All rights reserved.

Peritransplant Soluble CD30 as a Risk Factor for Slow Kidney Allograft Function, Early Acute Rejection, Worse Long-Term Allograft Function, and Patients' Survival.

PubMed

Trailin, Andriy V; Ostapenko, Tetyana I; Nykonenko, Tamara N; Nesterenko, Svitlana N; Nykonenko, Olexandr S

2017-01-01

We aimed to determine whether serum soluble CD30 (sCD30) could identify recipients at high risk for unfavorable early and late kidney transplant outcomes. Serum sCD30 was measured on the day of kidney transplantation and on the 4th day posttransplant. We assessed the value of these measurements in predicting delayed graft function, slow graft function (SGF), acute rejection (AR), pyelonephritis, decline of allograft function after 6 months, and graft and patient survival during 5 years of follow-up in 45 recipients. We found the association between low pretransplant serum levels of sCD30 and SGF. The absence of significant decrease of sCD30 on the 4th day posttransplant was characteristic for SGF, early AR (the 8th day-6 months), late AR (>6 months), and early pyelonephritis (the 8th day-2 months). Lower pretransplant and posttransplant sCD30 predicted worse allograft function at 6 months and 2 years, respectively. Higher pretransplant sCD30 was associated with higher frequency of early AR, and worse patients' survival, but only in the recipients of deceased-donor graft. Pretransplant sCD30 also allowed to differentiate patients with early pyelonephritis and early AR. Peritransplant sCD30 is useful in identifying patients at risk for unfavorable early and late transplant outcomes.

Early and sustained exposure to high-sucrose diet triggers hippocampal ER stress in young rats.

PubMed

Pinto, Bruno Araújo Serra; Melo, Thamys Marinho; Flister, Karla Frida Torres; França, Lucas Martins; Kajihara, Daniela; Tanaka, Leonardo Yuji; Laurindo, Francisco Rafael Martins; Paes, Antonio Marcus de Andrade

2016-08-01

Early-life environmental insults have been shown to promote long-term development of chronic non-communicable diseases, including metabolic disturbances and mental illnesses. As such, premature consumption of high-sugar foods has been associated to early onset of detrimental outcomes, whereas underlying mechanisms are still poorly understood. In the present study, we sought to investigate whether early and sustained exposure to high-sucrose diet promotes metabolic disturbances that ultimately might anticipate neurological injuries. At postnatal day 21, weaned male rats started to be fed a standard chow (10 % sucrose, CTR) or a high-sucrose diet (25 % sucrose, HSD) for 9 weeks prior to euthanasia at postnatal day 90. HSD did not alter weight gain and feed efficiency between groups, but increased visceral, non-visceral and brown adipose tissue accumulation. HSD rats demonstrated elevated blood glucose levels in both fasting and fed states, which were associated to impaired glucose tolerance. Peripheral insulin sensitivity did not change, whereas hepatic insulin resistance was supported by increased serum triglyceride levels, as well as higher TyG index values. Assessment of hippocampal gene expression showed endoplasmic reticulum (ER) stress pathways were activated in HSD rats, as compared to CTR. HSD rats had overexpression of unfolded protein response sensors, PERK and ATF6; ER chaperone, PDIA2 and apoptosis-related genes, CHOP and Caspase 3; but decreased expression of chaperone GRP78. Finally, HSD rats demonstrated impaired neuromuscular function and anxious behavior, but preserved cognitive parameters. In conclusion, our data indicate that early exposure to HSD promote metabolic disturbances, which disrupt hippocampus homeostasis and might precociously affect its neurobehavioral functions.

Multimodal MRI for early diabetic mild cognitive impairment: study protocol of a prospective diagnostic trial.

PubMed

Yu, Ying; Sun, Qian; Yan, Lin-Feng; Hu, Yu-Chuan; Nan, Hai-Yan; Yang, Yang; Liu, Zhi-Cheng; Wang, Wen; Cui, Guang-Bin

2016-08-24

Type 2 diabetes mellitus (T2DM) is a risk factor for dementia. Mild cognitive impairment (MCI), an intermediary state between normal cognition and dementia, often occurs during the prodromal diabetic stage, making early diagnosis and intervention of MCI very important. Latest neuroimaging techniques revealed some underlying microstructure alterations for diabetic MCI, from certain aspects. But there still lacks an integrated multimodal MRI system to detect early neuroimaging changes in diabetic MCI patients. Thus, we intended to conduct a diagnostic trial using multimodal MRI techniques to detect early diabetic MCI that is determined by the Montreal Cognitive Assessment (MoCA). In this study, healthy controls, prodromal diabetes and diabetes subjects (53 subjects/group) aged 40-60 years will be recruited from the physical examination center of Tangdu Hospital. The neuroimaging and psychometric measurements will be repeated at a 0.5 year-interval for 2.5 years' follow-up. The primary outcome measures are 1) Microstructural and functional alterations revealed with multimodal MRI scans including structure magnetic resonance imaging (sMRI), resting state functional magnetic resonance imaging (rs-fMRI), diffusion kurtosis imaging (DKI), and three-dimensional pseudo-continuous arterial spin labeling (3D-pCASL); 2) Cognition evaluation with MoCA. The second outcome measures are obesity, metabolic characteristics, lifestyle and quality of life. The study will provide evidence for the potential use of multimodal MRI techniques with psychometric evaluation in diagnosing MCI at prodromal diabetic stage so as to help decision making in early intervention and improve the prognosis of T2DM. This study has been registered to ClinicalTrials.gov ( NCT02420470 ) on April 2, 2015 and published on July 29, 2015.

Reactivity of airway phagocytes during the development of acute pneumonia under conditions of stimulation of mononuclear phagocyte system with zymosan.

PubMed

Makarova, O P

2008-12-01

Pneumonia was induced in (CBA x C57Bl)F1 mice under conditions of stimulation of the mononuclear phagocyte system with zymosan. The number of neutrophils in airways increased after 3 days; by day 14, the number of cells in the bronchoalveolar lavage fluid further increased due to migration of macrophages. After zymosan prestimulation, the number and functional activity of neutrophils during the early period of inflammation (3 days) did not change, but the increase in phagocytic activity of macrophages was inhibited by 20%. By day 14, the effect of prestimulation manifested in 4.5-fold decreased capacity of neutrophils and macrophages to reduce NBT.

Sensorimotor Functional and Structural Networks after Intracerebral Stem Cell Grafts in the Ischemic Mouse Brain.

PubMed

Green, Claudia; Minassian, Anuka; Vogel, Stefanie; Diedenhofen, Michael; Beyrau, Andreas; Wiedermann, Dirk; Hoehn, Mathias

2018-02-14

Past investigations on stem cell-mediated recovery after stroke have limited their focus on the extent and morphological development of the ischemic lesion itself over time or on the integration capacity of the stem cell graft ex vivo However, an assessment of the long-term functional and structural improvement in vivo is essential to reliably quantify the regenerative capacity of cell implantation after stroke. We induced ischemic stroke in nude mice and implanted human neural stem cells (H9 derived) into the ipsilateral cortex in the acute phase. Functional and structural connectivity changes of the sensorimotor network were noninvasively monitored using magnetic resonance imaging for 3 months after stem cell implantation. A sharp decrease of the functional sensorimotor network extended even to the contralateral hemisphere, persisting for the whole 12 weeks of observation. In mice with stem cell implantation, functional networks were stabilized early on, pointing to a paracrine effect as an early supportive mechanism of the graft. This stabilization required the persistent vitality of the stem cells, monitored by bioluminescence imaging. Thus, we also observed deterioration of the early network stabilization upon vitality loss of the graft after a few weeks. Structural connectivity analysis showed fiber-density increases between the cortex and white matter regions occurring predominantly on the ischemic hemisphere. These fiber-density changes were nearly the same for both study groups. This motivated us to hypothesize that the stem cells can influence, via early paracrine effect, the functional networks, while observed structural changes are mainly stimulated by the ischemic event. SIGNIFICANCE STATEMENT In recent years, research on strokes has made a shift away from a focus on immediate ischemic effects and towards an emphasis on the long-range effects of the lesion on the whole brain. Outcome improvements in stem cell therapies also require the understanding of their influence on the whole-brain networks. Here, we have longitudinally and noninvasively monitored the structural and functional network alterations in the mouse model of focal cerebral ischemia. Structural changes of fiber-density increases are stimulated in the endogenous tissue without further modulation by the stem cells, while functional networks are stabilized by the stem cells via a paracrine effect. These results will help decipher the underlying networks of brain plasticity in response to cerebral lesions and offer clues to unravelling the mystery of how stem cells mediate regeneration. Copyright © 2018 the authors 0270-6474/18/381648-14$15.00/0.

[The ontogeny of the mirror neuron system].

PubMed

Myowa-Yamakoshi, Masako

2014-06-01

Abstract Humans utilize the mirror neuron system to understand and predict others' actions. However, the ontogeny of the mirror neuron system remains unknown. Whether mirror neuron function is an innate trait or whether mirror neurons acquire their sensorimotor matching properties ontogenetically remains to be clarified. In this paper, I review the ontogenetic theory of the mirror neuron system. I then discuss the functioning of the mirror neuron system in the context of social cognitive abilities, which are unique to humans. Recently, some researchers argue that it is too early to interpret the function of mirror neurons as an understanding of the underlying psychological states of others. They imply that such functioning would require inferential cognitive processes that are known to involve areas outside the mirror neuron system. Filling in this missing link may be the key to elucidating the unique ability of humans to understand others' actions.

Roles for Msx and Dlx homeoproteins in vertebrate development.

PubMed

Bendall, A J; Abate-Shen, C

2000-04-18

This review provides a comparative analysis of the expression patterns, functions, and biochemical properties of Msx and Dlx homeobox genes. These comprise multi-gene families that are closely related with respect to sequence features as well as expression patterns during vertebrate development. Thus, members of the Msx and Dlx families are expressed in overlapping, but distinct, patterns and display complementary or antagonistic functions, depending upon the context. A common theme shared among Msx and Dlx genes is that they are required during early, middle, and late phases of development where their differential expression mediates patterning, morphogenesis, and histogenesis of tissues in which they are expressed. With respect to their biochemical properties, Msx proteins function as transcriptional repressors, while Dlx proteins are transcriptional activators. Moreover, their ability to oppose each other's transcriptional actions implies a mechanism underlying their complementary or antagonistic functions during development.

Functional requirements for an intelligent RPC. [remote power controller for spaceborne electrical distribution system

NASA Technical Reports Server (NTRS)

Aucoin, B. M.; Heller, R. P.

1990-01-01

An intelligent remote power controller (RPC) based on microcomputer technology can implement advanced functions for the accurate and secure detection of all types of faults on a spaceborne electrical distribution system. The intelligent RPC will implement conventional protection functions such as overcurrent, under-voltage, and ground fault protection. Advanced functions for the detection of soft faults, which cannot presently be detected, can also be implemented. Adaptive overcurrent protection changes overcurrent settings based on connected load. Incipient and high-impedance fault detection provides early detection of arcing conditions to prevent fires, and to clear and reconfigure circuits before soft faults progress to a hard-fault condition. Power electronics techniques can be used to implement fault current limiting to prevent voltage dips during hard faults. It is concluded that these techniques will enhance the overall safety and reliability of the distribution system.

Dissociable Effects of Aging and Mild Cognitive Impairment on Bottom-Up Audiovisual Integration.

PubMed

Festa, Elena K; Katz, Andrew P; Ott, Brian R; Tremont, Geoffrey; Heindel, William C

2017-01-01

Effective audiovisual sensory integration involves dynamic changes in functional connectivity between superior temporal sulcus and primary sensory areas. This study examined whether disrupted connectivity in early Alzheimer's disease (AD) produces impaired audiovisual integration under conditions requiring greater corticocortical interactions. Audiovisual speech integration was examined in healthy young adult controls (YC), healthy elderly controls (EC), and patients with amnestic mild cognitive impairment (MCI) using McGurk-type stimuli (providing either congruent or incongruent audiovisual speech information) under conditions differing in the strength of bottom-up support and the degree of top-down lexical asymmetry. All groups accurately identified auditory speech under congruent audiovisual conditions, and displayed high levels of visual bias under strong bottom-up incongruent conditions. Under weak bottom-up incongruent conditions, however, EC and amnestic MCI groups displayed opposite patterns of performance, with enhanced visual bias in the EC group and reduced visual bias in the MCI group relative to the YC group. Moreover, there was no overlap between the EC and MCI groups in individual visual bias scores reflecting the change in audiovisual integration from the strong to the weak stimulus conditions. Top-down lexicality influences on visual biasing were observed only in the MCI patients under weaker bottom-up conditions. Results support a deficit in bottom-up audiovisual integration in early AD attributable to disruptions in corticocortical connectivity. Given that this deficit is not simply an exacerbation of changes associated with healthy aging, tests of audiovisual speech integration may serve as sensitive and specific markers of the earliest cognitive change associated with AD.

Unexpected high vulnerability of functions in wilderness areas: evidence from coral reef fishes.

PubMed

D'agata, Stéphanie; Vigliola, Laurent; Graham, Nicholas A J; Wantiez, Laurent; Parravicini, Valeriano; Villéger, Sébastien; Mou-Tham, Gerard; Frolla, Philippe; Friedlander, Alan M; Kulbicki, Michel; Mouillot, David

2016-12-14

High species richness is thought to support the delivery of multiple ecosystem functions and services under changing environments. Yet, some species might perform unique functional roles while others are redundant. Thus, the benefits of high species richness in maintaining ecosystem functioning are uncertain if functions have little redundancy, potentially leading to high vulnerability of functions. We studied the natural propensity of assemblages to be functionally buffered against loss prior to fishing activities, using functional trait combinations, in coral reef fish assemblages across unfished wilderness areas of the Indo-Pacific: Chagos Archipelago, New Caledonia and French Polynesia. Fish functional diversity in these wilderness areas is highly vulnerable to fishing, explained by species- and abundance-based redundancy packed into a small combination of traits, leaving most other trait combinations (60%) sensitive to fishing, with no redundancy. Functional vulnerability peaks for mobile and sedentary top predators, and large species in general. Functional vulnerability decreases for certain functional entities in New Caledonia, where overall functional redundancy was higher. Uncovering these baseline patterns of functional vulnerability can offer early warning signals of the damaging effects from fishing, and may serve as baselines to guide precautionary and even proactive conservation actions. © 2016 The Author(s).

Unexpected high vulnerability of functions in wilderness areas: evidence from coral reef fishes

PubMed Central

Vigliola, Laurent; Graham, Nicholas A. J.; Wantiez, Laurent; Parravicini, Valeriano; Villéger, Sébastien; Mou-Tham, Gerard; Frolla, Philippe; Friedlander, Alan M.; Kulbicki, Michel; Mouillot, David

2016-01-01

High species richness is thought to support the delivery of multiple ecosystem functions and services under changing environments. Yet, some species might perform unique functional roles while others are redundant. Thus, the benefits of high species richness in maintaining ecosystem functioning are uncertain if functions have little redundancy, potentially leading to high vulnerability of functions. We studied the natural propensity of assemblages to be functionally buffered against loss prior to fishing activities, using functional trait combinations, in coral reef fish assemblages across unfished wilderness areas of the Indo-Pacific: Chagos Archipelago, New Caledonia and French Polynesia. Fish functional diversity in these wilderness areas is highly vulnerable to fishing, explained by species- and abundance-based redundancy packed into a small combination of traits, leaving most other trait combinations (60%) sensitive to fishing, with no redundancy. Functional vulnerability peaks for mobile and sedentary top predators, and large species in general. Functional vulnerability decreases for certain functional entities in New Caledonia, where overall functional redundancy was higher. Uncovering these baseline patterns of functional vulnerability can offer early warning signals of the damaging effects from fishing, and may serve as baselines to guide precautionary and even proactive conservation actions. PMID:27928042

Analysis of the Developmental Functioning of Early Intervention and Early Childhood Special Education Populations in Oregon. Issues & Answers. REL 2009-078

ERIC Educational Resources Information Center

Nave, Gary; Nishioka, Vicki; Burke, Arthur

2009-01-01

This study reports on the developmental functioning levels of children from birth through age 2 in early intervention services and children ages 3-5 in early childhood special education services at the time of entry into services, using data from the Oregon Early Childhood Assessment System. The assessment system contains data on the assessed…

Does early communication mediate the relationship between motor ability and social function in children with cerebral palsy?

PubMed

Lipscombe, Belinda; Boyd, Roslyn N; Coleman, Andrea; Fahey, Michael; Rawicki, Barry; Whittingham, Koa

2016-01-01

Children diagnosed with neurodevelopmental conditions such as cerebral palsy (CP) are at risk of experiencing restrictions in social activities negatively impacting their subsequent social functioning. Research has identified motor and communication ability as being unique determinants of social function capabilities in children with CP, to date, no research has investigated whether communication is a mediator of the relationship between motor ability and social functioning. To investigate whether early communication ability at 24 months corrected age (ca.) mediates the relationship between early motor ability at 24 months ca. and later social development at 60 months ca. in a cohort of children diagnosed with cerebral palsy (CP). A cohort of 71 children (43 male) diagnosed with CP (GMFCS I=24, 33.8%, II=9, 12.7%, III=12, 16.9%, IV=10, 14.1%, V=16, 22.5%) were assessed at 24 and 60 months ca. Assessments included the Gross Motor Function Measure (GMFM), the Communication and Symbolic Behaviour Scales-Developmental Profile (CSBS-DP) Infant-Toddler Checklist and the Paediatric Evaluation of Disability Inventory (PEDI). A mediation model was examined using bootstrapping. Early communication skills mediated the relationship between early motor abilities and later social functioning, b=0.24 (95% CI=0.08-0.43 and the mediation model was significant, F (2, 68)=32.77, p<0.001, R(2)=0.49. Early communication ability partially mediates the relationship between early motor ability and later social function in children with CP. This demonstrates the important role of early communication in ongoing social development. Early identification of communication delay and enriched language exposure is crucial in this population. Copyright © 2016 Elsevier Ltd. All rights reserved.

Distracted and confused?: selective attention under load.

PubMed

Lavie, Nilli

2005-02-01

The ability to remain focused on goal-relevant stimuli in the presence of potentially interfering distractors is crucial for any coherent cognitive function. However, simply instructing people to ignore goal-irrelevant stimuli is not sufficient for preventing their processing. Recent research reveals that distractor processing depends critically on the level and type of load involved in the processing of goal-relevant information. Whereas high perceptual load can eliminate distractor processing, high load on "frontal" cognitive control processes increases distractor processing. These findings provide a resolution to the long-standing early and late selection debate within a load theory of attention that accommodates behavioural and neuroimaging data within a framework that integrates attention research with executive function.

Prevalence and Psychosocial Correlates of After-School Activities among Chinese Adolescents in Hong Kong

PubMed Central

Ma, Cecilia M. S.; Shek, Daniel Tan Lei

2014-01-01

Using a cross-sectional design, this study (a) explores the prevalence of after-school activities among Chinese early adolescents and (b) assesses the relationships between participation in after-school activities, personal well-being, and family functioning. A total of 3,328 Grade 7 students (mean age = 12.59 years, SD = 0.74) completed a self-administered questionnaire. Results showed that the majority of adolescents returned home under adult supervision. Further analyses showed the associations between after-school activities, positive youth development qualities, academic and school competence, family functioning, and risky behavior. Implications regarding efforts aimed at designing high quality and structured after-school youth programs are discussed. PMID:25309895

Integrated controls for a new aircraft generation

NASA Technical Reports Server (NTRS)

Mace, W. D.; Howell, W. E.

1978-01-01

Many of the commercial aircraft now flying will have to be phased out in the early 1980s because of fuel inefficiency and unacceptable noise levels. This paper discusses the role of new digital technology in making aircraft more fuel efficient, more reliable, and quieter. Attention is given to the integration of sensing and control functions in an aircraft in order to provide a simple, lightweight, and high-redundancy system. Technology under development now is expected to come on-line in the 1990s.

Identification of Pro-Differentiation p53 Target Genes and Evaluation of Expression in Normal and Malignant Mammary Gland

DTIC Science & Technology

2009-04-01

progenitor cells ’ ability to survive under non-attachment culture conditions, which is composed of primary mammoshpere and secondary mammosphere. Both... cell lineages in early mouse development depend on SOX2 function. Genes Dev, 17: 126-140, 2003 8. Chambers, I., Colby, D., Robertson, M., Nichols, J...Rivett, D., Jones, K., and Dalton, S. LIF/STAT3 controls ES cell self-renewal and pluripotency by a Myc-dependent mechanism. Development , 132: 885-896

Lost Toy? Monsters Under the Bed? Contributions of Temperament and Family Factors to Early Internalizing Problems in Boys and Girls

PubMed Central

Marakovitz, Susan E.; Wagmiller, Robert L.; Mian, Nicholas D.; Briggs-Gowan, Margaret J.; Carter, Alice S.

2016-01-01

This study was designed to examine the contribution of multiple risk factors to early internalizing problems and to investigate whether family and ecological context moderated the association between child temperament and internalizing outcomes. A sample of 1,202 mothers of 2- and 3-year-old children completed a survey of child social-emotional functioning, family environment, and violence exposure. Child temperament, maternal affective symptoms, and family expressiveness were associated with child anxiety and depression problems. Violence exposure was related only to child anxiety. When maternal affective symptoms were elevated, inhibited girls but not boys were rated as more anxious and youngsters with heightened negative emotionality were rated as more depressed. Family expressiveness moderated the association between inhibited temperament and anxiety symptoms. PMID:21391020

Recessive Twinkle mutations in early onset encephalopathy with mtDNA depletion.

PubMed

Hakonen, Anna H; Isohanni, Pirjo; Paetau, Anders; Herva, Riitta; Suomalainen, Anu; Lönnqvist, Tuula

2007-11-01

Twinkle is a mitochondrial replicative helicase, the mutations of which have been associated with autosomal dominant progressive external ophthalmoplegia (adPEO), and recessively inherited infantile onset spinocerebellar ataxia (IOSCA). We report here a new phenotype in two siblings with compound heterozygous Twinkle mutations (A318T and Y508C), characterized by severe early onset encephalopathy and signs of liver involvement. The clinical manifestations included hypotonia, athetosis, sensory neuropathy, ataxia, hearing deficit, ophthalmoplegia, intractable epilepsy and elevation of serum transaminases. The liver showed mtDNA depletion, whereas the muscle mtDNA was only slightly affected. Alpers-Huttenlocher syndrome has previously been associated with mutations of polymerase gamma, a replicative polymerase of mtDNA. We show here that recessive mutations of the close functional partner of the polymerase, the Twinkle helicase, can also manifest as early encephalopathy with liver involvement, a phenotype reminiscent of Alpers syndrome, and are a new genetic cause underlying tissue-specific mtDNA depletion.

To Stroop or Not to Stroop: Sex-Related Differences in Brain-Behavior Associations During Early Childhood

PubMed Central

Cuevas, Kimberly; Calkins, Susan D.; Bell, Martha Ann

2015-01-01

Executive functions (EFs) are linked with optimal cognitive and social-emotional development. Despite behavioral evidence of sex differences in early childhood EF, little is known about potential sex differences in corresponding brain-behavior associations. The present study examined changes in 4-year-olds’ 6–9 Hz EEG power in response to increased executive processing demands (i.e., “Stroop-like” vs. “non-Stroop” day-night tasks). Although there were no sex differences in task performance, an examination of multiple scalp electrode sites revealed that boys exhibited more widespread changes in EEG power as compared to girls. Further, multiple regression analyses controlling for maternal education and non-EF performance indicated that individual differences in boys’ and girls’ EF performance were associated with different frontal neural correlates (i.e., different frontal scalp sites and different measures of EEG power). These data reveal valuable information concerning sex differences in the neural systems underlying executive processing during early childhood. PMID:26681615

Extra-embryonic tissue spreading directs early embryo morphogenesis in killifish

PubMed Central

Reig, Germán; Cerda, Mauricio; Sepúlveda, Néstor; Flores, Daniela; Castañeda, Victor; Tada, Masazumi; Härtel, Steffen; Concha, Miguel L.

2017-01-01

The spreading of mesenchymal-like cell layers is critical for embryo morphogenesis and tissue repair, yet we know little of this process in vivo. Here we take advantage of unique developmental features of the non-conventional annual killifish embryo to study the principles underlying tissue spreading in a simple cellular environment, devoid of patterning signals and major morphogenetic cell movements. Using in vivo experimentation and physical modelling we reveal that the extra-embryonic epithelial enveloping cell layer, thought mainly to provide protection to the embryo, directs cell migration and the spreading of embryonic tissue during early development. This function relies on the ability of embryonic cells to couple their autonomous random motility to non-autonomous signals arising from the expansion of the extra-embryonic epithelium, mediated by cell membrane adhesion and tension. Thus, we present a mechanism of extra-embryonic control of embryo morphogenesis that couples the mechanical properties of adjacent tissues in the early killifish embryo. PMID:28580937

Influences of maternal nutritional status on vascular function in the offspring.

PubMed

Poston, Lucilla

2007-08-01

Fetal growth restriction leading to low birthweight is associated with increased risk of ischaemic heart disease and hypertension in later life. Increasingly, it is recognised that cardiovascular risk may also be initiated in early life when the fetus and neonate are exposed to maternal nutritional excess. This review summarises the studies in man and animals that have investigated the potential role of vascular disorders in the aetiology of atherosclerosis and hypertension arising from early life nutritional deprivation or excess. Malfunction of the arterial endothelial cell layer in the offspring has been frequently described in association with both maternal under and overnutritional states and may play a permissive role in the origin of these disorders. Also prevalent is evidence for increased stiffness of the large arteries which may contribute to systolic hypertension. Further investigation is required into the intriguing suggestion that early life nutritional imbalance may adversely influence vascular angiogenesis leading to rarefaction and increased peripheral vascular resistance.

Relationship between histopathological changes in post partum renal biopsies and renal function tests of African women with early onset pre-eclampsia.

PubMed

Khedun, S M; Naicker, T; Moodley, J

2000-05-01

To improve the diagnostic accuracy of concurrent renal disease in hypertension of pregnancy, biopsy evaluation is essential. In addition, establishing underlying renal disease is important for prognosis on future pregnancies. We therefore designed a study to determine the diagnostic yield of postpartum renal biopsy and the nature and frequency of complications associated with this procedure. Also, to determine relationships, if any, between renal function tests and ultrastructural and histopathological findings. Fifty renal biopsies were performed in the immediate postpartum period in black African women with early onset pre-eclampsia. Each biopsy specimen was placed in a separate container and coded so that sampling was unknown to the electron microscopist. Each biopsy specimen was divided into three parts, and processed and stained for light, fluorescent and transmission electron microscopy using conventional techniques. Renal tissue biopsies were adequate for diagnostic purposes in all cases. There were no complications in any of the 50 patients studied. Ultrastructural examination confirmed the light microscopy findings. In addition the ultrastructural findings showed intramembranous deposits, foot process fusion and mesangial deposits. In 16 patients with normal renal function tests; the biopsies evaluation from these patients showed ultrastructural changes. In the remaining 34 patients with abnormal renal function tests of varying severity; biopsy evaluation from these patients showed both ultrastructural and histopathological changes. Renal biopsy procedure is safe, and ultrastructural and histological findings obtained from postpartum renal biopsies are more informative than the routine renal function tests.

Functional outcomes following lesions in visual cortex: Implications for plasticity of high-level vision.

PubMed

Liu, Tina T; Behrmann, Marlene

2017-10-01

Understanding the nature and extent of neural plasticity in humans remains a key challenge for neuroscience. Importantly, however, a precise characterization of plasticity and its underlying mechanism has the potential to enable new approaches for enhancing reorganization of cortical function. Investigations of the impairment and subsequent recovery of cognitive and perceptual functions following early-onset cortical lesions in humans provide a unique opportunity to elucidate how the brain changes, adapts, and reorganizes. Specifically, here, we focus on restitution of visual function, and we review the findings on plasticity and re-organization of the ventral occipital temporal cortex (VOTC) in published reports of 46 patients with a lesion to or resection of the visual cortex early in life. Findings reveal that a lesion to the VOTC results in a deficit that affects the visual recognition of more than one category of stimuli (faces, objects and words). In addition, the majority of pediatric patients show limited recovery over time, especially those in whom deficits in low-level vision also persist. Last, given that neither the equipotentiality nor the modularity view on plasticity was clearly supported, we suggest some intermediate possibilities in which some plasticity may be evident but that this might depend on the area that was affected, its maturational trajectory as well as its structural and functional connectivity constraints. Finally, we offer suggestions for future research that can elucidate plasticity further. Copyright © 2017 Elsevier Ltd. All rights reserved.

Doppler echocardiographic myocardial stunning index predicts recovery of left ventricular systolic function after primary percutaneous coronary intervention.

PubMed

Sharif, Dawod; Matanis, Wisam; Sharif-Rasslan, Amal; Rosenschein, Uri

2016-10-01

Myocardial stunning is responsible for partially reversible left ventricular (LV) systolic dysfunction after successful primary percutaneous coronary intervention (PPCI) in patients with acute ST-elevation myocardial infarction (STEMI). To test the hypothesis that early coronary blood flow (CBF) to LV systolic function ratios, as an equivalent to LV stunning index (SI), predict recovery of LV systolic function after PPCI in patients with acute STEMI. Twenty-four patients with acute anterior STEMI who had successful PPCI were evaluated and compared to 96 control subjects. Transthoracic echocardiography with measurement of LV ejection fraction (EF), LV, and left anterior descending (LAD) coronary artery area wall-motion score index (WMSI) as well as Doppler sampling of LAD blood velocities, early after PPCI and 5 days later, were performed. SI was evaluated as the early ratio of CBF parameters in the LAD to LV systolic function parameters. Early SI-LVEF well predicted late LVEF (r=.51, P<.01) and the change in LVEF (r=.48, P<.017). Early SI-LVMSI predicted well late LVEF (r=.56, P<.006) and the change in LVEF (r=.46, P<.028). Early SI-LADWMSI predicted late LVEF (r=.44, P<.028). Other SI indices measured as other LAD-CBF to LV systolic function parameters were not predictive of late LV systolic function. LV stunning indices measured as early LAD flow to LVEF, LVWMSI, and LADWMSI ratios well predicted late LVEF and the change in LVEF. Thus, greater early coronary artery flow to LV systolic function parameter ratios predict a better improvement in late LV systolic function after PPCI. © 2016, Wiley Periodicals, Inc.

Interhemispheric Functional Brain Connectivity in Neonates with Prenatal Alcohol Exposure: Preliminary Findings.

PubMed

Donald, Kirsten A; Ipser, Jonathan C; Howells, Fleur M; Roos, Annerine; Fouche, Jean-Paul; Riley, Edward P; Koen, Nastassja; Woods, Roger P; Biswal, Bharat; Zar, Heather J; Narr, Katherine L; Stein, Dan J

2016-01-01

Children exposed to alcohol in utero demonstrate reduced white matter microstructural integrity. While early evidence suggests altered functional brain connectivity in the lateralization of motor networks in school-age children with prenatal alcohol exposure (PAE), the specific effects of alcohol exposure on the establishment of intrinsic connectivity in early infancy have not been explored. Sixty subjects received functional imaging at 2 to 4 weeks of age for 6 to 8 minutes during quiet natural sleep. Thirteen alcohol-exposed (PAE) and 14 age-matched control (CTRL) participants with usable data were included in a multivariate model of connectivity between sensorimotor intrinsic functional connectivity networks. Seed-based analyses of group differences in interhemispheric connectivity of intrinsic motor networks were also conducted. The Dubowitz neurological assessment was performed at the imaging visit. Alcohol exposure was associated with significant increases in connectivity between somatosensory, motor networks, brainstem/thalamic, and striatal intrinsic networks. Reductions in interhemispheric connectivity of motor and somatosensory networks did not reach significance. Although results are preliminary, findings suggest PAE may disrupt the temporal coherence in blood oxygenation utilization in intrinsic networks underlying motor performance in newborn infants. Studies that employ longitudinal designs to investigate the effects of in utero alcohol exposure on the evolving resting-state networks will be key in establishing the distribution and timing of connectivity disturbances already described in older children. Copyright © 2016 by the Research Society on Alcoholism.

Sudden early-morning awakening impairs immediate tactical planning in a changing 'emergency' scenario.

PubMed

Horne, Jim; Moseley, Robert

2011-06-01

This was a realistic military-type exercise assessing unexpected, abrupt early-morning awakening effects on immediate 'executive function' and the ability to comprehend and deal with a sudden emergency under a changing situation. Twenty (average age 21years) healthy, highly motivated junior officer reservists were assigned randomly to two equal, independent groups, unforewarned as to what would happen. The experimental group was woken abruptly at 03:00h (<3h sleep) and confronted immediately with a 'paper exercise' of an enemy attack, requiring a feasible plan of engagement with minimal loss of resources, to be completed within 15min. A control group slept until 07:30h; they were then presented with the identical emergency 1h later. Participants worked individually, under time pressure, receiving written information, map and other details, all containing relevant, irrelevant and misleading information. Halfway through, they were given (unexpectedly) a critical update necessitating a change of tactics. Performance was scored blind by instructors, under five categories. Eight of the experimental group versus three controls failed overall, with significant group differences on three specific categories relying on flexible decision-making: 'identification of available cover', 'use of available assets' and 'extraction of relevant from irrelevant information'. Other, logical and highly trained skills were unimpaired. Ours was a 'worst case scenario', combining short sleep, circadian 'trough' and sleep inertia, all of which differentiated the two groups, unlike typical laboratory studies. Nevertheless, it was relevant to real-life situations involving highly motivated, trained individuals making critical innovative decisions in the early morning versus the normal waking day. © 2010 European Sleep Research Society.

Development and Application of a Tendon Prosthesis for Early Functional Restoration of the Hand.

DTIC Science & Technology

1975-09-01

AD-ARSA 323 JEFFERSON MEDICAL COLL PHILADELP HIA PA F/6 6/5 DEVELOFHNT AND APPLICATION OF A TENDON PROSTHESIS FOR EARLY FU--ETCU, SEP 75 .1 M HUNTER...THIS SHEET S LEVELINETR S DEVELOPEN AND APPLICATION OF A TENDON PROSTESIS FOR EARLY FUNCTIONAL RTORATION OF THE HAND DOCUMENT IDENTIFICATION...OF A TENDON PROSTHESIS * (B.l FOR EARLY FUNCTIONAL RESTORATION OF THE HArD ANNUAL REPORT by James M. Hunter, M.D. September 1975 (For the period 1 July

Trial-Based Functional Analysis and Functional Communication Training in an Early Childhood Setting

ERIC Educational Resources Information Center

Lambert, Joseph M.; Bloom, Sarah E.; Irvin, Jennifer

2012-01-01

Problem behavior is common in early childhood special education classrooms. Functional communication training (FCT; Carr & Durand, 1985) may reduce problem behavior but requires identification of its function. The trial-based functional analysis (FA) is a method that can be used to identify problem behavior function in schools. We conducted…

Distributed and opposing effects of incidental learning in the human brain.

PubMed

Hall, Michelle G; Naughtin, Claire K; Mattingley, Jason B; Dux, Paul E

2018-06-01

Incidental learning affords a behavioural advantage when sensory information matches regularities that have previously been encountered. Previous studies have taken a focused approach by probing the involvement of specific candidate brain regions underlying incidentally acquired memory representations, as well as expectation effects on early sensory representations. Here, we investigated the broader extent of the brain's sensitivity to violations and fulfilments of expectations, using an incidental learning paradigm in which the contingencies between target locations and target identities were manipulated without participants' overt knowledge. Multivariate analysis of functional magnetic resonance imaging data was applied to compare the consistency of neural activity for visual events that the contingency manipulation rendered likely versus unlikely. We observed widespread sensitivity to expectations across frontal, temporal, occipital, and sub-cortical areas. These activation clusters showed distinct response profiles, such that some regions displayed more reliable activation patterns under fulfilled expectations, whereas others showed more reliable patterns when expectations were violated. These findings reveal that expectations affect multiple stages of information processing during visual decision making, rather than early sensory processing stages alone. Copyright © 2018 Elsevier Inc. All rights reserved.

Sex-dependent effects of periadolescent exposure to the cannabinoid agonist CP-55,940 on morphine self-administration behaviour and the endogenous opioid system.

PubMed

Biscaia, Miguel; Fernández, Beatriz; Higuera-Matas, Alejandro; Miguéns, Miguel; Viveros, Maria-Paz; García-Lecumberri, Carmen; Ambrosio, Emilio

2008-04-01

Early cannabinoid consumption may predispose individuals to the misuse of addictive drugs later in life. However, there is a lack of experimental evidence as to whether cannabinoid exposure during adolescence might differently affect opiate reinforcing efficacy and the opioid system in adults of both sexes. Our aim was to examine whether periadolescent chronic exposure to the cannabinoid agonist CP-55,940 could exert sex-dependent effects on morphine reinforcing and the opioid system in adulthood. Morphine reinforcing was studied under a progressive ratio (PR) reinforcement schedule in adult male and female rats that previously acquired morphine self-administration under a fixed ratio 1 (FR1) schedule. Binding levels and functionality of mu-opioid receptors were also evaluated. Periadolescent cannabinoid exposure altered morphine self-administration and the opioid system in adult rats in a sex-dependent manner. CP-55,940-exposed males exhibited higher self-administration rates under a FR1, but not under a PR schedule. In females, CP-55,940 did not modify morphine self-administration under either schedule. Moreover, CP-55,940 also increased mu-opioid receptor levels in the subcallosal streak of pre-treated animals and decreased mu-opioid receptor functionality in the nucleus accumbens shell but again, only in males. Our data indicate that adult male rats exposed to the cannabinoid in adolescence self-administer more morphine than females, but only when the demands required by the schedule of reinforcement are low, which might be related to the decrease in mu-opioid receptor functionality in the NAcc-shell observed in these animals.

Implications for psychedelic-assisted psychotherapy: functional magnetic resonance imaging study with psilocybin.

PubMed

Carhart-Harris, R L; Leech, R; Williams, T M; Erritzoe, D; Abbasi, N; Bargiotas, T; Hobden, P; Sharp, D J; Evans, J; Feilding, A; Wise, R G; Nutt, D J

2012-03-01

Psilocybin is a classic psychedelic drug that has a history of use in psychotherapy. One of the rationales for its use was that it aids emotional insight by lowering psychological defences. To test the hypothesis that psilocybin facilitates access to personal memories and emotions by comparing subjective and neural responses to positive autobiographical memories under psilocybin and placebo. Ten healthy participants received two functional magnetic resonance imaging scans (2 mg intravenous psilocybin v. intravenous saline), separated by approximately 7 days, during which they viewed two different sets of 15 positive autobiographical memory cues. Participants viewed each cue for 6 s and then closed their eyes for 16 s and imagined re-experiencing the event. Activations during this recollection period were compared with an equivalent period of eyes-closed rest. We split the recollection period into an early phase (first 8 s) and a late phase (last 8 s) for analysis. Robust activations to the memories were seen in limbic and striatal regions in the early phase and the medial prefrontal cortex in the late phase in both conditions (P<0.001, whole brain cluster correction), but there were additional visual and other sensory cortical activations in the late phase under psilocybin that were absent under placebo. Ratings of memory vividness and visual imagery were significantly higher after psilocybin (P<0.05) and there was a significant positive correlation between vividness and subjective well-being at follow-up (P<0.01). Evidence that psilocybin enhances autobiographical recollection implies that it may be useful in psychotherapy either as a tool to facilitate the recall of salient memories or to reverse negative cognitive biases.

Alterations in Sociability and Functional Brain Connectivity Caused by Early-Life Seizures is Reversed by Bumetanide

PubMed Central

Holmes, Gregory L.; Tian, Chengju; Hernan, Amanda E.; Flynn, Sean; Camp, Devon; Barry, Jeremy

2015-01-01

There is a well-described association between infantile epilepsy and pervasive cognitive and behavioral deficits, including a high incidence of autism spectrum disorders. Despite the robustness of the relationship between early-life seizures and the development of autism, the pathophysiological mechanism by which this occurs has not been explored. As a result of increasing evidence that autism is a disorder of brain connectivity we hypothesized that early-life seizures would interrupt normal brain connectivity during brain maturation and result in an autistic phenotype. Normal rat pups underwent recurrent flurothyl-induced seizures from postnatal (P) day 5-14 and then tested, along with controls, for developmental alterations of development brain oscillatory activity from P18-25. Specifically we wished to understand how normal changes in rhythmicity in and between brain regions change as a function of age and if this rhythmicity is altered or interrupted by early life seizures. In rat pups with early-life seizures, field recordings from dorsal and ventral hippocampus and prefrontal cortex demonstrated marked increase in coherence as well as a decrease in voltage correlation at all bandwidths compared to controls while there were minimal differences in total power and relative power spectral densities. Rats with early-life seizures had resulting impairment in the sociability and social novelty tests but demonstrated no evidence of increased activity or generalized anxiety as measured in the open field. In addition, rats with early-life seizures had lower seizure thresholds than controls, indicating long-standing alterations in the excitatory/inhibition balance. Bumetanide, a pharmacological agent that blocks the activity of NKCC1 and induces a significant shift of ECl toward more hyperpolarized values, administration at the time of the seizures precluded the subsequent abnormalities in coherence and voltage correlation and resulted in normal sociability and seizure threshold. Taken together these findings indicate that early-life seizures alter the development of oscillations and result in autistic-like behaviors. The altered communication between these brain regions could reflect the physiological underpinnings underlying social cognitive deficits seen in autism spectrum disorders. PMID:25766676

Functional Trait Trade-Offs for the Tropical Montane Rain Forest Species Responding to Light from Simulating Experiments

PubMed Central

Mao, Peili; Zang, Runguo; Shao, Hongbo; Yu, Junbao

2014-01-01

Differences among tropical tree species in survival and growth to light play a key role in plant competition and community composition. Two canopy species with contrasting functional traits dominating early and late successional stages, respectively, in a tropical montane rain forest of Hainan Island, China, were selected in a pot experiment under 4 levels of light intensity (full, 50%, 30%, and 10%) in order to explore the adaptive strategies of tropical trees to light conditions. Under each light intensity level, the pioneer species, Endospermum chinense (Euphorbiaceae), had higher relative growth rate (RGR), stem mass ratio (SMR), specific leaf area (SLA), and morphological plasticity while the shade tolerant climax species, Parakmeria lotungensis (Magnoliaceae), had higher root mass ratio (RMR) and leaf mass ratio (LMR). RGR of both species was positively related to SMR and SLA under each light level but was negatively correlated with RMR under lower light (30% and 10% full light). The climax species increased its survival by a conservative resource use strategy through increasing leaf defense and root biomass investment at the expense of growth rate in low light. In contrast, the pioneer increased its growth by an exploitative resource use strategy through increasing leaf photosynthetic capacity and stem biomass investment at the expense of survival under low light. There was a trade-off between growth and survival for species under different light conditions. Our study suggests that tree species in the tropical rainforest adopt different strategies in stands of different successional stages. Species in the earlier successional stages have functional traits more advantageous to grow faster in the high light conditions, whereas species in the late successional stages have traits more favorable to survive in the low light conditions. PMID:25019095

Age and Early Graft Function Relate With Risk-Benefit Ratio of Allogenic Islet Transplantation Under Antithymocyte Globulin-Mycophenolate Mofetil-Tacrolimus Immune Suppression.

PubMed

Lee, DaHae; Keymeulen, Bart; Hilbrands, Robert; Ling, Zhidong; Van de Velde, Ursule; Jacobs-Tulleneers-Thevissen, Daniel; Maleux, Geert; Lapauw, Bruno; Crenier, Laurent; De Block, Christophe; Mathieu, Chantal; Pipeleers, Daniel; Gillard, Pieter

2017-09-01

Induction therapy with a T cell-depleting agent followed by mycophenolate mofetil and tacrolimus is presently the most frequently used immune suppression (IS) regimen in islet transplantation. This study assesses its safety and tolerability in nonuremic type 1 diabetic recipients. Fifty-one patients (age, between 29 and 63 years) with high glycemic variability and problematic hypoglycemia received intraportal islet grafts under anti-thymocyte globulin-mycophenolate mofetil-tacrolimus protocol. They were followed up for over 48 months for function of the implant and adverse events. Severe hypoglycemia and diabetic ketoacidosis were absent in patients with functioning graft. Immune suppressive therapy was maintained for 48 months in 29 recipients with sustained function (group A), whereas 16 patients stopped earlier due to graft failure (group B) and in 6 for other reasons. Group A was significantly older at the time of implantation and achieved higher graft function at posttransplantation month 6 under similar dose of IS. Prevalence of IS-related side effects was similar in groups A and B, occurring predominantly during the first year posttransplantation. IS-related serious adverse events (SAE) were reported in 47% of patients, with 4 presenting with cytomegalovirus infection and 4 (age, 42-59 years) diagnosed with cancer. Except in 1 patient with cancer, all SAEs resolved after appropriate treatment. These risk/benefit data serve as a basis for clinical decision-making before entering an intraportal islet transplantation protocol. A longer benefit is observed in recipients of higher age (≥40 years), but it is not associated with more side effects and SAE.

The Formation of Fe/Mg Smectite Under Mildly Acidic Conditions on Early Mars

NASA Technical Reports Server (NTRS)

Sutter, B.; Golden, D. C.; Ming, Douglas W.; Niles, P. B.

2011-01-01

The detection of Fe/Mg smectites and carbonate in Noachian and early Hesperian terrain of Mars suggests that neutral to mildly alkaline conditions prevailed during the early history of Mars. If early Mars surface geochemical conditions were neutral to moderately alkaline with a denser CO2 atmosphere than today, then large carbonates deposits should be more widely detected in Noachian terrain. Why have so few carbonate deposits been detected compared to Fe/Mg smectites? Fe/Mg smectites on early Mars formed under mildly acidic conditions, which would preclude the extensive formation of carbonate deposits. The goal of the proposed work is to evaluate the formation of Fe/Mg smectites under mildly acidic conditions.

Development of Effective Connectivity during Own- and Other-Race Face Processing: A Granger Causality Analysis

PubMed Central

Zhou, Guifei; Liu, Jiangang; Ding, Xiao Pan; Fu, Genyue; Lee, Kang

2016-01-01

Numerous developmental studies have suggested that other-race effect (ORE) in face recognition emerges as early as in infancy and develops steadily throughout childhood. However, there is very limited research on the neural mechanisms underlying this developmental ORE. The present study used Granger causality analysis (GCA) to examine the development of children's cortical networks in processing own- and other-race faces. Children were between 3 and 13 years. An old-new paradigm was used to assess their own- and other-race face recognition with ETG-4000 (Hitachi Medical Co., Japan) acquiring functional near infrared spectroscopy (fNIRS) data. After preprocessing, for each participant and under each face condition, we obtained the causal map by calculating the weights of causal relations between the time courses of [oxy-Hb] of each pair of channels using GCA. To investigate further the differential causal connectivity for own-race faces and other-race faces at the group level, a repeated measure analysis of variance (ANOVA) was performed on the GCA weights for each pair of channels with the face race task (own-race face vs. other-race face) as the within-subject variable and the age as a between-subject factor (continuous variable). We found an age-related increase in functional connectivity, paralleling a similar age-related improvement in behavioral face processing ability. More importantly, we found that the significant differences in neural functional connectivity between the recognition of own-race faces and that of other-race faces were modulated by age. Thus, like the behavioral ORE, the neural ORE emerges early and undergoes a protracted developmental course. PMID:27713696

Novel Mahalanobis-based feature selection improves one-class classification of early hepatocellular carcinoma.

PubMed

Thomaz, Ricardo de Lima; Carneiro, Pedro Cunha; Bonin, João Eliton; Macedo, Túlio Augusto Alves; Patrocinio, Ana Claudia; Soares, Alcimar Barbosa

2018-05-01

Detection of early hepatocellular carcinoma (HCC) is responsible for increasing survival rates in up to 40%. One-class classifiers can be used for modeling early HCC in multidetector computed tomography (MDCT), but demand the specific knowledge pertaining to the set of features that best describes the target class. Although the literature outlines several features for characterizing liver lesions, it is unclear which is most relevant for describing early HCC. In this paper, we introduce an unconstrained GA feature selection algorithm based on a multi-objective Mahalanobis fitness function to improve the classification performance for early HCC. We compared our approach to a constrained Mahalanobis function and two other unconstrained functions using Welch's t-test and Gaussian Data Descriptors. The performance of each fitness function was evaluated by cross-validating a one-class SVM. The results show that the proposed multi-objective Mahalanobis fitness function is capable of significantly reducing data dimensionality (96.4%) and improving one-class classification of early HCC (0.84 AUC). Furthermore, the results provide strong evidence that intensity features extracted at the arterial to portal and arterial to equilibrium phases are important for classifying early HCC.

Interactome disassembly during apoptosis occurs independent of caspase cleavage.

PubMed

Scott, Nichollas E; Rogers, Lindsay D; Prudova, Anna; Brown, Nat F; Fortelny, Nikolaus; Overall, Christopher M; Foster, Leonard J

2017-01-12

Protein-protein interaction networks (interactomes) define the functionality of all biological systems. In apoptosis, proteolysis by caspases is thought to initiate disassembly of protein complexes and cell death. Here we used a quantitative proteomics approach, protein correlation profiling (PCP), to explore changes in cytoplasmic and mitochondrial interactomes in response to apoptosis initiation as a function of caspase activity. We measured the response to initiation of Fas-mediated apoptosis in 17,991 interactions among 2,779 proteins, comprising the largest dynamic interactome to date. The majority of interactions were unaffected early in apoptosis, but multiple complexes containing known caspase targets were disassembled. Nonetheless, proteome-wide analysis of proteolytic processing by terminal amine isotopic labeling of substrates (TAILS) revealed little correlation between proteolytic and interactome changes. Our findings show that, in apoptosis, significant interactome alterations occur before and independently of caspase activity. Thus, apoptosis initiation includes a tight program of interactome rearrangement, leading to disassembly of relatively few, select complexes. These early interactome alterations occur independently of cleavage of these protein by caspases. © 2017 The Authors. Published under the terms of the CC BY 4.0 license.

Behavior as a sentry of metal toxicity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Weiss, B.

1978-01-01

Many of the toxic properties of metals are expressed as behavioral aberrations. Some of these arise from direct actions on the central nervous system. Others arise from primary events elsewhere, but still influence behavior. Toxicity may be expressed either as objectively measurable phenomena, such as ataxia, or as subjective complaints, such as depression. In neither instance is clinical medicine equipped to provide assessments of subtle, early indices of toxicity. Reviewers of visual disturbances, paresthesia, and mental retardation exemplify the potential contribution of psychology to the toxicology of metals. Behavior and nervous system functions act as sensitive mirrors of metal toxicity.more » Sensitivity is the prime aim in environmental health assessments. Early detection of adverse effects, before they progress to irreversibility, underlies the strategy for optimal health protection. Some of the toxic actions of metals originate in direct nervous system dysfunction. Others may reflect disturbances of systems less directly linked to behavior than the central nervous system. But behavior, because it expresses the integrated functioning of the organism, can indicate flaws in states and processes outside the nervous system.« less

Skin transcriptome reveals the intrinsic molecular mechanisms underlying hair follicle cycling in Cashmere goats under natural and shortened photoperiod conditions.

PubMed

Yang, Min; Song, Shen; Dong, Kunzhe; Chen, XiaoFei; Liu, Xuexue; Rouzi, Marhaba; Zhao, Qianjun; He, Xiaohong; Pu, Yabin; Guan, Weijun; Ma, Yuehui; Jiang, Lin

2017-10-18

The growth of cashmere exhibits a seasonal pattern arising from photoperiod change. However, the underlying molecular mechanism remains unclear. We profiled the skin transcriptome of six goats at seven time points during hair follicle cycling via RNA-seq. The six goats comprised three goats exposed to a natural photoperiod and three exposed to a shortened photoperiod. During hair cycle transition, 1713 genes showed differential expression, and 332 genes showed a pattern of periodic expression. Moreover, a short photoperiod induced the hair follicle to enter anagen early, and 246 genes overlapped with the periodic genes. Among these key genes, cold-shock domain containing C2 (CSDC2) was highly expressed in the epidermis and dermis of Cashmere goat skin, although its function in hair-follicle development remains unknown. CSDC2 silencing in mouse fibroblasts resulted in the decreased mRNA expression of two key hair-follicle factors, leading to reduced cell numbers and a lower cell density. Cashmere growth or molting might be controlled by a set of periodic regulatory genes. The appropriate management of short light exposure can induce hair follicles to enter full anagen early through the activation of these regulators. The CSDC2 gene is a potentially important transcription factor in the hair growth cycle.

Mechanisms and genetic factors underlying co-use of nicotine and alcohol or other drugs of abuse.

PubMed

Cross, Sarah J; Lotfipour, Shahrdad; Leslie, Frances M

2017-03-01

Concurrent use of tobacco and alcohol or psychostimulants represents a major public health concern, with use of one substance influencing consumption of the other. Co-abuse of these drugs leads to substantial negative health outcomes, reduced cessation, and high economic costs, but the underlying mechanisms are poorly understood. Epidemiological data suggest that tobacco use during adolescence plays a particularly significant role. Adolescence is a sensitive period of development marked by major neurobiological maturation of brain regions critical for reward processing, learning and memory, and executive function. Nicotine exposure during this time produces a unique and long-lasting vulnerability to subsequent substance use, likely via actions at cholinergic, dopaminergic, and serotonergic systems. In this review, we discuss recent clinical and preclinical data examining the genetic factors and mechanisms underlying co-use of nicotine and alcohol or cocaine and amphetamines. We evaluate the critical role of nicotinic acetylcholine receptors throughout, and emphasize the dearth of preclinical studies assessing concurrent drug exposure. We stress important age and sex differences in drug responses, and highlight a brief, low-dose nicotine exposure paradigm that may better model early use of tobacco products. The escalating use of e-cigarettes among youth necessitates a closer look at the consequences of early adolescent nicotine exposure on subsequent alcohol and drug abuse.

Early-life inflammation, immune response and ageing.

PubMed

Khan, Imroze; Agashe, Deepa; Rolff, Jens

2017-03-15

Age-related diseases are often attributed to immunopathology, which results in self-damage caused by an inappropriate inflammatory response. Immunopathology associated with early-life inflammation also appears to cause faster ageing, although we lack direct experimental evidence for this association. To understand the interactions between ageing, inflammation and immunopathology, we used the mealworm beetle Tenebrio molitor as a study organism. We hypothesized that phenoloxidase, an important immune effector in insect defence, may impose substantial immunopathological costs by causing tissue damage to Malpighian tubules (MTs; functionally equivalent to the human kidney), in turn accelerating ageing. In support of this hypothesis, we found that RNAi knockdown of phenoloxidase (PO) transcripts in young adults possibly reduced inflammation-induced autoreactive tissue damage to MTs, and increased adult lifespan. Our work thus suggests a causative link between immunopathological costs of early-life inflammation and faster ageing. We also reasoned that if natural selection weakens with age, older individuals should display increased immunopathological costs associated with an immune response. Indeed, we found that while old infected individuals cleared infection faster than young individuals, possibly they also displayed exacerbated immunopathological costs (larger decline in MT function) and higher post-infection mortality. RNAi-mediated knockdown of PO response partially rescued MTs function in older beetles and resulted in increased lifespan after infection. Taken together, our data are consistent with a direct role of immunopathological consequences of immune response during ageing in insects. Our work is also the first report that highlights the pervasive role of tissue damage under diverse contexts of ageing and immune response. © 2017 The Author(s).

Ebstein's anomaly in children: a single-center study in Angola.

PubMed

Manuel, Valdano; Morais, Humberto; Magalhães, Manuel Pedro; Nunes, Maria Ana Sampaio; Leon, Gilberto; Ferreira, Manuel; Filipe Júnior, António Pedro

2015-10-01

Ebstein's anomaly is a rare complex congenital heart defect of the tricuspid valve. We aimed to describe the frequency, clinical profile, and early and short-term post-operative results in patients under the age of 18 years operated for this anomaly in a tertiary center in Angola. A retrospective cross-sectional study was conducted over a period of 37 months. We analyzed all patients diagnosed with congenital heart defects. Of the 1362 patients studied, eight (0.6%) had Ebstein's anomaly; six patients (75%) were female. Mean age was 69±59 months. Five patients were in NYHA functional class III or IV. Mean cardiothoracic index was 0.72. Seven patients (87.5%) had severe tricuspid regurgitation and five (62.5%) had another associated congenital heart defect. All patients were operated: two had complications and one (12.5%) died in the early post-operative period. The mean follow-up time was 1.22±0.6 years, and mortality during follow-up was 12.5% (n=1). At the end of the study, of the five patients in whom cone reconstruction was performed, four (80%) were in functional class I. Mean cardiothoracic index decreased to 0.64. Three patients had mild and two had moderate tricuspid regurgitation. The patient who underwent cone reconstruction and a Glenn procedure was in functional class I. The frequency of Ebstein's anomaly was similar to that in other centers. Cone reconstruction was viable in the majority of patients, with good early and short-term results. Copyright © 2015 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

Early-life inflammation, immune response and ageing

PubMed Central

2017-01-01

Age-related diseases are often attributed to immunopathology, which results in self-damage caused by an inappropriate inflammatory response. Immunopathology associated with early-life inflammation also appears to cause faster ageing, although we lack direct experimental evidence for this association. To understand the interactions between ageing, inflammation and immunopathology, we used the mealworm beetle Tenebrio molitor as a study organism. We hypothesized that phenoloxidase, an important immune effector in insect defence, may impose substantial immunopathological costs by causing tissue damage to Malpighian tubules (MTs; functionally equivalent to the human kidney), in turn accelerating ageing. In support of this hypothesis, we found that RNAi knockdown of phenoloxidase (PO) transcripts in young adults possibly reduced inflammation-induced autoreactive tissue damage to MTs, and increased adult lifespan. Our work thus suggests a causative link between immunopathological costs of early-life inflammation and faster ageing. We also reasoned that if natural selection weakens with age, older individuals should display increased immunopathological costs associated with an immune response. Indeed, we found that while old infected individuals cleared infection faster than young individuals, possibly they also displayed exacerbated immunopathological costs (larger decline in MT function) and higher post-infection mortality. RNAi-mediated knockdown of PO response partially rescued MTs function in older beetles and resulted in increased lifespan after infection. Taken together, our data are consistent with a direct role of immunopathological consequences of immune response during ageing in insects. Our work is also the first report that highlights the pervasive role of tissue damage under diverse contexts of ageing and immune response. PMID:28275145

Improvement of mitochondrial function and dynamics by the metabolic enhancer piracetam.

PubMed

Stockburger, Carola; Kurz, Christopher; Koch, Konrad A; Eckert, Schamim H; Leuner, Kristina; Müller, Walter E

2013-10-01

The metabolic enhancer piracetam is used in many countries to treat cognitive impairment in aging, brain injuries, as well as dementia such as AD (Alzheimer's disease). As a specific feature of piracetam, beneficial effects are usually associated with mitochondrial dysfunction. In previous studies we were able to show that piracetam enhanced ATP production, mitochondrial membrane potential as well as neurite outgrowth in cell and animal models for aging and AD. To investigate further the effects of piracetam on mitochondrial function, especially mitochondrial fission and fusion events, we decided to assess mitochondrial morphology. Human neuroblastoma cells were treated with the drug under normal conditions and under conditions imitating aging and the occurrence of ROS (reactive oxygen species) as well as in stably transfected cells with the human wild-type APP (amyloid precursor protein) gene. This AD model is characterized by expressing only 2-fold more human Aβ (amyloid β-peptide) compared with control cells and therefore representing very early stages of AD when Aβ levels gradually increase over decades. Interestingly, these cells exhibit an impaired mitochondrial function and morphology under baseline conditions. Piracetam is able to restore this impairment and shifts mitochondrial morphology back to elongated forms, whereas there is no effect in control cells. After addition of a complex I inhibitor, mitochondrial morphology is distinctly shifted to punctate forms in both cell lines. Under these conditions piracetam is able to ameliorate morphology in cells suffering from the mild Aβ load, as well as mitochondrial dynamics in control cells.

Marginal eyespots on butterfly wings deflect bird attacks under low light intensities with UV wavelengths.

PubMed

Olofsson, Martin; Vallin, Adrian; Jakobsson, Sven; Wiklund, Christer

2010-05-24

Predators preferentially attack vital body parts to avoid prey escape. Consequently, prey adaptations that make predators attack less crucial body parts are expected to evolve. Marginal eyespots on butterfly wings have long been thought to have this deflective, but hitherto undemonstrated function. Here we report that a butterfly, Lopinga achine, with broad-spectrum reflective white scales in its marginal eyespot pupils deceives a generalist avian predator, the blue tit, to attack the marginal eyespots, but only under particular conditions-in our experiments, low light intensities with a prominent UV component. Under high light intensity conditions with a similar UV component, and at low light intensities without UV, blue tits directed attacks towards the butterfly head. In nature, birds typically forage intensively at early dawn, when the light environment shifts to shorter wavelengths, and the contrast between the eyespot pupils and the background increases. Among butterflies, deflecting attacks is likely to be particularly important at dawn when low ambient temperatures make escape by flight impossible, and when insectivorous birds typically initiate another day's search for food. Our finding that the deflective function of eyespots is highly dependent on the ambient light environment helps explain why previous attempts have provided little support for the deflective role of marginal eyespots, and we hypothesize that the mechanism that we have discovered in our experiments in a laboratory setting may function also in nature when birds forage on resting butterflies under low light intensities.

Structural and Functional Evaluations for the Early Detection of Glaucoma.

PubMed

Lucy, Katie A; Wollstein, Gadi

2016-01-01

The early detection of glaucoma is imperative in order to preserve functional vision. Structural and functional methods are utilized to detect and monitor glaucomatous damage and the vision loss it causes. The relationship between these detection measures is complex and differs between individuals, especially in early glaucoma. Using both measures together is advised in order to ensure the highest probability of glaucoma detection, and new testing methods are continuously developed with the goals of earlier disease detection and improvement of disease monitoring. The purpose of this review is to explore the relationship between structural and functional glaucoma detection and discuss important technological advances for early glaucoma detection.

Structural and Functional Evaluations for the Early Detection of Glaucoma

PubMed Central

Lucy, Katie A.; Wollstein, Gadi

2016-01-01

The early detection of glaucoma is imperative in order to preserve functional vision. Structural and functional methods are utilized to detect and monitor glaucomatous damage and the vision loss it causes. The relationship between these detection measures is complex and differs between individuals, especially in early glaucoma. Using both measures together is advised in order to ensure the highest probability of glaucoma detection, and new testing methods are continuously developed with the goals of earlier disease detection and improvement of disease monitoring. The purpose of this review is to explore the relationship between structural and functional glaucoma detection and discuss important technological advances for early glaucoma detection. PMID:28603546

Association of Adiposity and Mental Health Functioning across the Lifespan: Findings from Understanding Society (The UK Household Longitudinal Study).

PubMed

Davillas, Apostolos; Benzeval, Michaela; Kumari, Meena

2016-01-01

Evidence on the adiposity-mental health associations is mixed, with studies finding positive, negative or no associations, and less is known about how these associations may vary by age. To examine the association of adiposity -body mass index (BMI), waist circumference (WC) and percentage body fat (BF%)- with mental health functioning across the adult lifespan. Data from 11,257 participants (aged 18+) of Understanding Society: the UK Household Longitudinal Study (waves 2 and 3, 5/2010-7/2013) were employed. Regressions of mental health functioning, assessed by the Mental Component Summary (MCS-12) and the General Health Questionnaire (GHQ-12), on adiposity measures (continuous or dichotomous indicators) were estimated adjusted for covariates. Polynomial age-adiposity interactions were estimated. Higher adiposity was associated with poorer mental health functioning. This emerged in the 30s, increased up to mid-40s (all central adiposity and obesity-BF% measures) or early 50s (all BMI measures) and then decreased with age. Underlying physical health generally accounted for these associations except for central adiposity, where associations remained statistically significant from the mid-30s to 50s. Cardiovascular, followed by arthritis and endocrine, conditions played the greatest role in attenuating the associations under investigation. We found strong age-specific patterns in the adiposity-mental health functioning association that varied across adiposity measures. Underlying physical health had the dominant role in attenuating these associations. Policy makers and health professionals should target increased adiposity, mainly central adiposity, as it is a risk factor for poor mental health functioning in those aged between mid-30s to 50 years.

Association of Adiposity and Mental Health Functioning across the Lifespan: Findings from Understanding Society (The UK Household Longitudinal Study)

PubMed Central

2016-01-01

Background Evidence on the adiposity-mental health associations is mixed, with studies finding positive, negative or no associations, and less is known about how these associations may vary by age. Objective To examine the association of adiposity -body mass index (BMI), waist circumference (WC) and percentage body fat (BF%)- with mental health functioning across the adult lifespan. Methods Data from 11,257 participants (aged 18+) of Understanding Society: the UK Household Longitudinal Study (waves 2 and 3, 5/2010-7/2013) were employed. Regressions of mental health functioning, assessed by the Mental Component Summary (MCS-12) and the General Health Questionnaire (GHQ-12), on adiposity measures (continuous or dichotomous indicators) were estimated adjusted for covariates. Polynomial age-adiposity interactions were estimated. Results Higher adiposity was associated with poorer mental health functioning. This emerged in the 30s, increased up to mid-40s (all central adiposity and obesity-BF% measures) or early 50s (all BMI measures) and then decreased with age. Underlying physical health generally accounted for these associations except for central adiposity, where associations remained statistically significant from the mid-30s to50s. Cardiovascular, followed by arthritis and endocrine, conditions played the greatest role in attenuating the associations under investigation. Conclusions We found strong age-specific patterns in the adiposity-mental health functioning association that varied across adiposity measures. Underlying physical health had the dominant role in attenuating these associations. Policy makers and health professionals should target increased adiposity, mainly central adiposity, as it is a risk factor for poor mental health functioning in those aged between mid-30s to 50 years. PMID:26849046

Peritransplant Soluble CD30 as a Risk Factor for Slow Kidney Allograft Function, Early Acute Rejection, Worse Long-Term Allograft Function, and Patients' Survival

PubMed Central

Ostapenko, Tetyana I.; Nykonenko, Tamara N.; Nesterenko, Svitlana N.; Nykonenko, Olexandr S.

2017-01-01

Background We aimed to determine whether serum soluble CD30 (sCD30) could identify recipients at high risk for unfavorable early and late kidney transplant outcomes. Methods Serum sCD30 was measured on the day of kidney transplantation and on the 4th day posttransplant. We assessed the value of these measurements in predicting delayed graft function, slow graft function (SGF), acute rejection (AR), pyelonephritis, decline of allograft function after 6 months, and graft and patient survival during 5 years of follow-up in 45 recipients. Results We found the association between low pretransplant serum levels of sCD30 and SGF. The absence of significant decrease of sCD30 on the 4th day posttransplant was characteristic for SGF, early AR (the 8th day–6 months), late AR (>6 months), and early pyelonephritis (the 8th day–2 months). Lower pretransplant and posttransplant sCD30 predicted worse allograft function at 6 months and 2 years, respectively. Higher pretransplant sCD30 was associated with higher frequency of early AR, and worse patients' survival, but only in the recipients of deceased-donor graft. Pretransplant sCD30 also allowed to differentiate patients with early pyelonephritis and early AR. Conclusions Peritransplant sCD30 is useful in identifying patients at risk for unfavorable early and late transplant outcomes. PMID:28694560

Elevated pretransplantation soluble CD30 is associated with decreased early allograft function after human lung transplantation.

PubMed

Shah, Ashish S; Leffell, M Sue; Lucas, Donna; Zachary, Andrea A

2009-02-01

Early allograft function after lung transplantation is variable. Clinical criteria have limited predictive value for early graft function. Recipient immunologic state before LTx may affect early lung function. We investigated the association between pretransplantation soluble CD30 (sCD30), a marker of Th2-type T-cell activation, and early clinical parameters of allograft function. Between September 2002 and January 2007, a total of 80 transplantations were performed at Johns Hopkins Hospital. Of the patients, 43 had a pretransplantation sCD30 level determined. Pre- and postoperative patient variables were collected, and patients were stratified into two groups: sCD30 <20 (low sCD30) and >20 (high sCD30). High sCD30 (n = 26) and low sCD30 (n = 17) groups were similar in age, gender, and ischemia time. In the high sCD30 group, a higher percentage of patients had pulmonary fibrosis and a lower percentage had emphysema. Oxygenation at 48 hours was significantly worse in the high sCD30 group as compared with the low sCD30 (p = 0.003). Moreover, prolonged intubation and 90-day mortality were greater in the high sCD30 group. This represents the first report of the use of sCD30 as a marker for early allograft function in human lung transplanation. Increased pretransplantation recipient sCD30 appears to be associated with decreased early post-transplantation gas exchange, prolonged intubation, and early mortality.

Organic haze on Titan and the early Earth

PubMed Central

Trainer, Melissa G.; Pavlov, Alexander A.; DeWitt, H. Langley; Jimenez, Jose L.; McKay, Christopher P.; Toon, Owen B.; Tolbert, Margaret A.

2006-01-01

Recent exploration by the Cassini/Huygens mission has stimulated a great deal of interest in Saturn's moon, Titan. One of Titan's most captivating features is the thick organic haze layer surrounding the moon, believed to be formed from photochemistry high in the CH4/N2 atmosphere. It has been suggested that a similar haze layer may have formed on the early Earth. Here we report laboratory experiments that demonstrate the properties of haze likely to form through photochemistry on Titan and early Earth. We have used a deuterium lamp to initiate particle production in these simulated atmospheres from UV photolysis. Using a unique analysis technique, the aerosol mass spectrometer, we have studied the chemical composition, size, and shape of the particles produced as a function of initial trace gas composition. Our results show that the aerosols produced in the laboratory can serve as analogs for the observed haze in Titan's atmosphere. Experiments performed under possible conditions for early Earth suggest a significant optical depth of haze may have dominated the early Earth's atmosphere. Aerosol size measurements are presented, and implications for the haze layer properties are discussed. We estimate that aerosol production on the early Earth may have been on the order of 1014 g·year−1 and thus could have served as a primary source of organic material to the surface. PMID:17101962

Mental health functioning (SF-36) and intentions to retire early among ageing municipal employees: the Helsinki Health Study.

PubMed

Harkonmäki, Karoliina; Lahelma, Eero; Martikainen, Pekka; Rahkonen, Ossi; Silventoinen, Karri

2006-01-01

To examine the associations of mental health functioning with intentions to retire early among ageing municipal employees. Cross-sectional survey data (n = 7,765) from the Helsinki Health Study in 2000, 2001, and 2002 were used. Intentions to retire early were sought with a question: "Have you considered retiring before normal retirement age?" The dependent variable was divided into three categories: 1 = no intentions to retire early; 2 = weak intentions; 3 = strong intentions. Mental health functioning was measured by the Short Form 36 (SF-36) mental component summary (MCS). Other variables included age, sex, physical health functioning (SF-36), limiting longstanding illness, socioeconomic status, and spouse's employment status. Multinomial regression analysis was used to examine the association of mental health functioning with intentions to retire early. Employees with the poorest mental health functioning were much more likely to report strong intentions to retire early (OR 6.09, 95% CI 4.97-7.47) than those with the best mental health functioning. Adjustments for physical health, socioeconomic status, and spouse's employment status did not substantially affect this association. The findings highlight the importance of mental health for intentions to retire early. Strategies aimed at keeping people at work for longer should emphasize the importance of mental well-being and the prevention of poor mental health. More evidence is needed on why mental problems among ageing baby-boomer employees are giving rise to increasing social consequences, although the overall prevalence of mental problems has not increased.

β-Amyloid Deposition Is Associated with Decreased Right Prefrontal Activation during Task Switching among Cognitively Normal Elderly

PubMed Central

Steffener, Jason; Razlighi, Qolamreza R.; Habeck, Christian; Stern, Yaakov

2016-01-01

The accumulation of β-amyloid (Aβ) peptides, a pathological hallmark of Alzheimer's disease (AD), has been associated with functional alterations, often in an episodic memory system with a particular emphasis on medial temporal lobe function. The topography of Aβ deposition, however, largely overlaps with frontoparietal control (FPC) regions implicated in cognitive control that has been shown to be impaired in early mild AD. To understand the neural mechanism underlying early changes in cognitive control with AD, we examined the impact of Aβ deposition on task-evoked FPC activation using functional magnetic resonance imaging (fMRI) in humans. Forty-three young and 62 cognitively normal older adults underwent an fMRI session during an executive contextual task in which task difficulty varied: single (either letter case or vowel/consonant judgment task) vs dual (switching between letter case and vowel/consonant decisions) task. Older subjects additionally completed 18F-florbetaben positron emission tomography scans and were classified as either amyloid positive (Aβ+) or negative (Aβ−). Consistent with previous reports, age-related increases in brain activity were found in FPC regions commonly identified across groups. For both task conditions, Aβ-related increases in brain activity were found compared with baseline activity. For higher cognitive control load, however, Aβ+ elderly showed reduced task-switching activation in the right inferior frontal cortex. Our findings suggest that with Aβ deposition, brain activation in the cognitive control region reaches a maximum with lower control demand and decreases with higher control demand, which may underlie early impairment in cognitive control with AD progression. SIGNIFICANCE STATEMENT The accumulation of β-amyloid (Aβ) peptides, a pathological hallmark of Alzheimer's disease, spatially overlaps with frontoparietal control (FPC) regions implicated in cognitive control, but the impact of Aβ deposition on FPC regions is largely unknown. Using functional magnetic resonance imaging with a task-switching task, we found Aβ-related increases in FPC regions compared with baseline activity. For higher cognitive control load, however, Aβ-related hypoactivity was found in the right inferior frontal cortex, a region highly implicated in cognitive control. The findings suggest that with Aβ deposition, task-related brain activity may reach a plateau early and undergo downstream pathways of neural dysfunction, which may relate to the early impairment of cognitive control seen in the progression of Aβ pathology. PMID:26865619

Alterations of the Lipid Metabolome in Dairy Cows Experiencing Excessive Lipolysis Early Postpartum

PubMed Central

Humer, Elke; Khol-Parisini, Annabella; Metzler-Zebeli, Barbara U.; Gruber, Leonhard; Zebeli, Qendrim

2016-01-01

A decrease in insulin sensitivity enhances adipose tissue lipolysis helping early lactation cows counteracting their energy deficit. However, excessive lipolysis poses serious health risks for cows, and its underlying mechanisms are not clearly understood. The present study used targeted ESI-LC-MS/MS-based metabolomics and indirect insulin sensitivity measurements to evaluate metabolic alterations in the serum of dairy cows of various parities experiencing variable lipolysis early postpartum. Thirty (12 primiparous and 18 multiparous) cows of Holstein Friesian and Simmental breeds, fed the same diet and kept under the same management conditions, were sampled at d 21 postpartum and classified as low (n = 10), medium (n = 8), and high (n = 12) lipolysis groups, based on serum concentration of nonesterified fatty acids. Overall, excessive lipolysis in the high group came along with impaired estimated insulin sensitivity and characteristic shifts in acylcarnitine, sphingomyelin, phosphatidylcholine and lysophospholipid metabolome profiles compared to the low group. From the detected phosphatidylcholines mainly those with diacyl-residues showed differences among lipolysis groups. Furthermore, more than half of the detected sphingomyelins were increased in cows experiencing high lipomobilization. Additionally, strong differences in serum acylcarnitines were noticed among lipolysis groups. The study suggests an altered serum phospholipidome in dairy cows associated with an increase in certain long-chain sphingomyelins and the progression of disturbed insulin function. In conclusion, the present study revealed 37 key metabolites as part of alterations in the synthesis or breakdown of sphingolipids and phospholipids associated with lowered estimated insulin sensitivity and excessive lipolysis in early-lactating cows. PMID:27383746

Alterations of the Lipid Metabolome in Dairy Cows Experiencing Excessive Lipolysis Early Postpartum.

PubMed

Humer, Elke; Khol-Parisini, Annabella; Metzler-Zebeli, Barbara U; Gruber, Leonhard; Zebeli, Qendrim

2016-01-01

A decrease in insulin sensitivity enhances adipose tissue lipolysis helping early lactation cows counteracting their energy deficit. However, excessive lipolysis poses serious health risks for cows, and its underlying mechanisms are not clearly understood. The present study used targeted ESI-LC-MS/MS-based metabolomics and indirect insulin sensitivity measurements to evaluate metabolic alterations in the serum of dairy cows of various parities experiencing variable lipolysis early postpartum. Thirty (12 primiparous and 18 multiparous) cows of Holstein Friesian and Simmental breeds, fed the same diet and kept under the same management conditions, were sampled at d 21 postpartum and classified as low (n = 10), medium (n = 8), and high (n = 12) lipolysis groups, based on serum concentration of nonesterified fatty acids. Overall, excessive lipolysis in the high group came along with impaired estimated insulin sensitivity and characteristic shifts in acylcarnitine, sphingomyelin, phosphatidylcholine and lysophospholipid metabolome profiles compared to the low group. From the detected phosphatidylcholines mainly those with diacyl-residues showed differences among lipolysis groups. Furthermore, more than half of the detected sphingomyelins were increased in cows experiencing high lipomobilization. Additionally, strong differences in serum acylcarnitines were noticed among lipolysis groups. The study suggests an altered serum phospholipidome in dairy cows associated with an increase in certain long-chain sphingomyelins and the progression of disturbed insulin function. In conclusion, the present study revealed 37 key metabolites as part of alterations in the synthesis or breakdown of sphingolipids and phospholipids associated with lowered estimated insulin sensitivity and excessive lipolysis in early-lactating cows.

Delineation of early brain development from fetuses to infants with diffusion MRI and beyond.

PubMed

Ouyang, Minhui; Dubois, Jessica; Yu, Qinlin; Mukherjee, Pratik; Huang, Hao

2018-04-12

Dynamic macrostructural and microstructural changes take place from the mid-fetal stage to 2 years after birth. Delineating structural changes of the brain during early development provides new insights into the complicated processes of both typical development and the pathological mechanisms underlying various psychiatric and neurological disorders including autism, attention deficit hyperactivity disorder and schizophrenia. Decades of histological studies have identified strong spatial and functional maturation gradients in human brain gray and white matter. The recent improvements in magnetic resonance imaging (MRI) techniques, especially diffusion MRI (dMRI), relaxometry imaging, and magnetization transfer imaging (MTI) have provided unprecedented opportunities to non-invasively quantify and map the early developmental changes at whole brain and regional levels. Here, we review the recent advances in understanding early brain structural development during the second half of gestation and the first two postnatal years using modern MR techniques. Specifically, we review studies that delineate the emergence and microstructural maturation of white matter tracts, as well as dynamic mapping of inhomogeneous cortical microstructural organization unique to fetuses and infants. These imaging studies converge into maturational curves of MRI measurements that are distinctive across different white matter tracts and cortical regions. Furthermore, contemporary models offering biophysical interpretations of the dMRI-derived measurements are illustrated to infer the underlying microstructural changes. Collectively, this review summarizes findings that contribute to charting spatiotemporally heterogeneous gray and white matter structural development, offering MRI-based biomarkers of typical brain development and setting the stage for understanding aberrant brain development in neurodevelopmental disorders. Copyright © 2018 Elsevier Inc. All rights reserved.

Abnormal early brain responses during visual search are evident in schizophrenia but not bipolar affective disorder.

PubMed

VanMeerten, Nicolaas J; Dubke, Rachel E; Stanwyck, John J; Kang, Seung Suk; Sponheim, Scott R

2016-01-01

People with schizophrenia show deficits in processing visual stimuli but neural abnormalities underlying the deficits are unclear and it is unknown whether such functional brain abnormalities are present in other severe mental disorders or in individuals who carry genetic liability for schizophrenia. To better characterize brain responses underlying visual search deficits and test their specificity to schizophrenia we gathered behavioral and electrophysiological responses during visual search (i.e., Span of Apprehension [SOA] task) from 38 people with schizophrenia, 31 people with bipolar disorder, 58 biological relatives of people with schizophrenia, 37 biological relatives of people with bipolar disorder, and 65 non-psychiatric control participants. Through subtracting neural responses associated with purely sensory aspects of the stimuli we found that people with schizophrenia exhibited reduced early posterior task-related neural responses (i.e., Span Endogenous Negativity [SEN]) while other groups showed normative responses. People with schizophrenia exhibited longer reaction times than controls during visual search but nearly identical accuracy. Those individuals with schizophrenia who had larger SENs performed more efficiently (i.e., shorter reaction times) on the SOA task suggesting that modulation of early visual cortical responses facilitated their visual search. People with schizophrenia also exhibited a diminished P300 response compared to other groups. Unaffected first-degree relatives of people with bipolar disorder and schizophrenia showed an amplified N1 response over posterior brain regions in comparison to other groups. Diminished early posterior brain responses are associated with impaired visual search in schizophrenia and appear to be specifically associated with the neuropathology of schizophrenia. Published by Elsevier B.V.

DEVELOPMENTAL CHANGES IN SEROTONIN SIGNALING: IMPLICATIONS FOR EARLY BRAIN FUNCTION, BEHAVIOR AND ADAPTATION

PubMed Central

BRUMMELTE, S.; GLANAGHY, E. MC; BONNIN, A.; OBERLANDER, T. F.

2017-01-01

The neurotransmitter serotonin (5-HT) plays a central role in brain development, regulation of mood, stress reactivity and risk of psychiatric disorders, and thus alterations in 5-HT signaling early in life have critical implications for behavior and mental health across the life span. Drawing on preclinical and emerging human evidence this narrative review paper will examine three key aspects when considering the consequences of early life changes in 5-HT: (1) developmental origins of variations of 5-HT signaling; (2) influence of genetic and epigenetic factors; and (3) preclinical and clinical consequences of 5-HT-related changes associated with antidepressant exposure (SSRIs). The developmental consequences of altered prenatal 5-HT signaling varies greatly and outcomes depend on an ongoing interplay between biological (genetic/epigenetic variations) and environmental factors, both pre and postnatally. Emerging evidence suggests that variations in 5-HT signaling may increase sensitivity to risky home environments, but may also amplify a positive response to a nurturing environment. In this sense, factors that change central 5-HT levels may act as ‘plasticity’ rather than ‘risk’ factors associated with developmental vulnerability. Understanding the impact of early changes in 5-HT levels offers critical insights that might explain the variations in early typical brain development that underlies behavioral risk. PMID:26905950

Association of early National Institutes of Health Stroke Scale improvement with vessel recanalization and functional outcome after intravenous thrombolysis in ischemic stroke.

PubMed

Kharitonova, Tatiana; Mikulik, Robert; Roine, Risto O; Soinne, Lauri; Ahmed, Niaz; Wahlgren, Nils

2011-06-01

Early neurological improvement (ENI) after thrombolytic therapy of acute stroke has been linked with recanalization and favorable outcome, although its definition shows considerable variation. We tested the ability of ENI, as defined in previous publications, to predict vessel recanalization and 3-month functional outcome after intravenous thrombolysis recorded in an extensive patient cohort in the Safe Implementation of Thrombolysis in Stroke-International Stroke Thrombolysis Register (SITS-ISTR). Of 21,534 patients registered between December 2002 and December 2008, 798 patients (3.7%) had CT- or MR angiography-documented baseline vessel occlusion and also angiography data at 22 to 36 hours post-treatment. ENI definitions assessed at 2 hours and 24 hours post-treatment were (1) National Institutes of Health Stroke Scale (NIHSS) score improvement ≥4 points from baseline; (2) NIHSS 0, 1, or improvement ≥8; (3) NIHSS ≤3 or improvement ≥10; (4) improvement by 20%; (5) 40% from baseline; or (6) NIHSS score 0 to 1. Receiver operating curve analysis and multiple logistic regression were performed to evaluate the association of ENI with vessel recanalization and favorable functional outcome (modified Rankin Scale score 0 to 2 at 3 months). ENI at 2 hours had fair accuracy to diagnose recanalization as derived from receiver operating curve analysis. Definitions of improvement based on percent of NIHSS score change from baseline demonstrate better accuracy to diagnose recanalization at 2 hours and 24 hours than the definitions based on NIHSS cutoffs (the best performance at 2 hours was area under the curve 0.633, sensitivity 58%, specificity 69%, positive predictive value 68%, and negative predictive value 59% for 20% improvement; and area under the curve 0.692, sensitivity 69%, specificity 70%, positive predictive value 70%, and negative predictive value 62% for 40% improvement at 24 hours). ENI-predicted functional outcome with OR 2.8 to 6.0 independently from recanalization in the angiography cohort (n=695) and with OR of 6.9 to 9.7 in the whole cohort (n=18 181). Early 20% neurological improvement at 2 hours was the best predictor of 3-month functional outcome and recanalization after thrombolysis, although fairly accurate, and may serve as a surrogate marker of recanalization if only imaging evaluation of vessel status is not available. If recanalization status is required after intravenous thrombolysis, vascular imaging is recommended despite ENI.

Premyelinated central axons express neurotoxic NMDA receptors: relevance to early developing white-matter injury

PubMed Central

Huria, Tahani; Beeraka, Narasimha Murthy; Al-Ghamdi, Badrah; Fern, Robert

2015-01-01

Ischemic-type injury to developing white matter is associated with the significant clinical condition cerebral palsy and with the cognitive deficits associated with premature birth. Premyelinated axons are the major cellular component of fetal white matter and loss of axon function underlies the disability, but the cellular mechanisms producing ischemic injury to premyelinated axons have not previously been described. Injury was found to require longer periods of modelled ischemia than at latter developmental points. Ischemia produced initial hyperexcitability in axons followed by loss of function after Na+ and Ca2+ influx. N-methyl-D-aspartate- (NMDA) type glutamate receptor (GluR) agonists potentiated axon injury while antagonists were protective. The NMDA GluR obligatory Nr1 subunit colocalized with markers of small premyelinated axons and expression was found at focal regions of axon injury. Ischemic injury of glial cells present in early developing white matter was NMDA GluR independent. Axons in human postconception week 18 to 23 white matter had a uniform prediameter expansion phenotype and postembedded immuno-gold labelling showed Nr1 subunit expression on the membrane of these axons, demonstrating a shared key neuropathologic feature with the rodent model. Premyelinated central axons therefore express high levels of functional NMDA GluRs that confer sensitivity to ischemic injury. PMID:25515212

Functional Traits and Water Transport Strategies in Lowland Tropical Rainforest Trees.

PubMed

Apgaua, Deborah M G; Ishida, Françoise Y; Tng, David Y P; Laidlaw, Melinda J; Santos, Rubens M; Rumman, Rizwana; Eamus, Derek; Holtum, Joseph A M; Laurance, Susan G W

2015-01-01

Understanding how tropical rainforest trees may respond to the precipitation extremes predicted in future climate change scenarios is paramount for their conservation and management. Tree species clearly differ in drought susceptibility, suggesting that variable water transport strategies exist. Using a multi-disciplinary approach, we examined the hydraulic variability in trees in a lowland tropical rainforest in north-eastern Australia. We studied eight tree species representing broad plant functional groups (one palm and seven eudicot mature-phase, and early-successional trees). We characterised the species' hydraulic system through maximum rates of volumetric sap flow and velocities using the heat ratio method, and measured rates of tree growth and several stem, vessel, and leaf traits. Sap flow measures exhibited limited variability across species, although early-successional species and palms had high mean sap velocities relative to most mature-phase species. Stem, vessel, and leaf traits were poor predictors of sap flow measures. However, these traits exhibited different associations in multivariate analysis, revealing gradients in some traits across species and alternative hydraulic strategies in others. Trait differences across and within tree functional groups reflect variation in water transport and drought resistance strategies. These varying strategies will help in our understanding of changing species distributions under predicted drought scenarios.

Functional Traits and Water Transport Strategies in Lowland Tropical Rainforest Trees

PubMed Central

Apgaua, Deborah M. G.; Ishida, Françoise Y.; Tng, David Y. P.; Laidlaw, Melinda J.; Santos, Rubens M.; Rumman, Rizwana; Eamus, Derek; Holtum, Joseph A. M.; Laurance, Susan G. W.

2015-01-01

Understanding how tropical rainforest trees may respond to the precipitation extremes predicted in future climate change scenarios is paramount for their conservation and management. Tree species clearly differ in drought susceptibility, suggesting that variable water transport strategies exist. Using a multi-disciplinary approach, we examined the hydraulic variability in trees in a lowland tropical rainforest in north-eastern Australia. We studied eight tree species representing broad plant functional groups (one palm and seven eudicot mature-phase, and early-successional trees). We characterised the species’ hydraulic system through maximum rates of volumetric sap flow and velocities using the heat ratio method, and measured rates of tree growth and several stem, vessel, and leaf traits. Sap flow measures exhibited limited variability across species, although early-successional species and palms had high mean sap velocities relative to most mature-phase species. Stem, vessel, and leaf traits were poor predictors of sap flow measures. However, these traits exhibited different associations in multivariate analysis, revealing gradients in some traits across species and alternative hydraulic strategies in others. Trait differences across and within tree functional groups reflect variation in water transport and drought resistance strategies. These varying strategies will help in our understanding of changing species distributions under predicted drought scenarios. PMID:26087009

An experimental manipulation of life-history trajectories and resistance to oxidative stress.

PubMed

Alonso-Alvarez, Carlos; Bertrand, Sophie; Devevey, Godefroy; Prost, Josiane; Faivre, Bruno; Chastel, Olivier; Sorci, Gabriele

2006-09-01

Optimal investment into life-history traits depends on the environmental conditions that organisms are likely to experience during their life. Evolutionary theory tells us that optimal investment in reproduction versus maintenance is likely to shape the pattern of age-associated decline in performance, also known as aging. The currency that is traded against different vital functions is, however, still debated. Here, we took advantage of a phenotypic manipulation of individual quality in early life to explore (1) long-term consequences on life-history trajectories, and (2) the possible physiological mechanism underlying the life-history adjustments. We manipulated phenotypic quality of a cohort of captive zebra finches (Taeniopygia guttata) by assigning breeding pairs to either an enlarged or a reduced brood. Nestlings raised in enlarged broods were in poorer condition than nestlings raised in reduced broods. Interestingly, the effect of environmental conditions experienced during early life extended to the age at first reproduction. Birds from enlarged broods delayed reproduction. Birds that delayed reproduction produced less offspring but lived longer, although neither fecundity nor longevity were directly affected by the experimental brood size. Using the framework of the life-table response experiment modeling, we also explored the effect of early environmental condition on population growth rate and aging. Birds raised in reduced broods tended to have a higher population growth rate, and a steeper decrease of reproductive value with age than birds reared in enlarged broods. Metabolic resources necessary to fight off the damaging effect of reactive oxygen species (ROS) could be the mechanism underlying the observed results, as (1) birds that engaged in a higher number of breeding events had a weaker red blood cell resistance to oxidative stress, (2) red blood cell resistance to oxidative stress predicted short-term mortality (but not longevity), and (3) was related with a parabolic function to age. Overall, these results highlight that early condition can have long-term effects on life-history trajectories by affecting key life-history traits such as age at first reproduction, and suggest that the trade-off between reproduction and self-maintenance might be mediated by the cumulative deleterious effect of ROS.

Emergence of biological organization through thermodynamic inversion.

PubMed

Kompanichenko, Vladimir

2014-01-01

Biological organization arises under thermodynamic inversion in prebiotic systems that provide the prevalence of free energy and information contribution over the entropy contribution. The inversion might occur under specific far-from-equilibrium conditions in prebiotic systems oscillating around the bifurcation point. At the inversion moment, (physical) information characteristic of non-biological systems acquires the new features: functionality, purposefulness, and control over the life processes, which transform it into biological information. Random sequences of amino acids and nucleotides, spontaneously synthesized in the prebiotic microsystem, in the primary living unit (probiont) re-assemble into functional sequences, involved into bioinformation circulation through nucleoprotein interaction, resulted in the genetic code emergence. According to the proposed concept, oscillating three-dimensional prebiotic microsystems transformed into probionts in the changeable hydrothermal medium of the early Earth. The inversion concept states that spontaneous (accidental, random) transformations in prebiotic systems cannot produce life; it is only non-spontaneous (perspective, purposeful) transformations, which are the result of thermodynamic inversion, that lead to the negentropy conversion of prebiotic systems into initial living units.

Music listening after stroke: beneficial effects and potential neural mechanisms.

PubMed

Särkämö, Teppo; Soto, David

2012-04-01

Music is an enjoyable leisure activity that also engages many emotional, cognitive, and motor processes in the brain. Here, we will first review previous literature on the emotional and cognitive effects of music listening in healthy persons and various clinical groups. Then we will present findings about the short- and long-term effects of music listening on the recovery of cognitive function in stroke patients and the underlying neural mechanisms of these music effects. First, our results indicate that listening to pleasant music can have a short-term facilitating effect on visual awareness in patients with visual neglect, which is associated with functional coupling between emotional and attentional brain regions. Second, daily music listening can improve auditory and verbal memory, focused attention, and mood as well as induce structural gray matter changes in the early poststroke stage. The psychological and neural mechanisms potentially underlying the rehabilitating effect of music after stroke are discussed. © 2012 New York Academy of Sciences.

Behavioral alterations of zebrafish larvae after early embryonic exposure to ketamine.

PubMed

Félix, Luís M; Antunes, Luís M; Coimbra, Ana M; Valentim, Ana M

2017-02-01

Ketamine has been associated with pediatric risks that include neurocognitive impairment and long-term behavioral disorders. However, the neurobehavioral effects of ketamine exposure in early development remain uncertain. This study aimed to test stage- and dose-dependent effects of ketamine exposure on certain brain functions by evaluating alterations in locomotion, anxiety-like and avoidance behaviors, as well as socialization. Embryos were exposed to different concentrations of ketamine (0, 0.2, 0.4, and 0.8 mg mL -1 ) for 20 min during the 256-cell (2.5 h post fertilization-hpf), 50% epiboly (5.5 hpf), and 1-4 somites (10.5 hpf) stages. General exploratory activities, natural escape-like responses, and social interactions were analyzed under continuous light or under a moving light stimulus. A dose-dependent decrease in the overall mean speed was perceived in the embryos exposed during the 256-cell stage. These results were related to previously observed head and eye malformations, following ketamine exposure at this stage and may indicate possible neurobehavioral disorders when ketamine exposure is performed at this stage. Results also showed that ketamine exposure during the 50% epiboly and 1-4 somites stages induced a significant increment of the anxiety-like behavior and a decrease in avoidance behavior in all exposed groups. Overall, the results validate the neurodevelopmental risks of early-life exposure to ketamine.

Advances in asthma 2015: Across the lifespan.

PubMed

Liu, Andrew H; Anderson, William C; Dutmer, Cullen M; Searing, Daniel A; Szefler, Stanley J

2016-08-01

In 2015, progress in understanding asthma ranged from insights to asthma inception, exacerbations, and severity to advancements that will improve disease management throughout the lifespan. 2015's insights to asthma inception included how the intestinal microbiome affects asthma expression with the identification of specific gastrointestinal bacterial taxa in early infancy associated with less asthma risk, possibly by promoting regulatory immune development at a critical early age. The relevance of epigenetic mechanisms in regulating asthma-related gene expression was strengthened. Predicting and preventing exacerbations throughout life might help to reduce progressive lung function decrease and disease severity in adulthood. Although allergy has long been linked to asthma exacerbations, a mechanism through which IgE impairs rhinovirus immunity and underlies asthma exacerbations was demonstrated and improved by anti-IgE therapy (omalizumab). Other key molecular pathways underlying asthma exacerbations, such as cadherin-related family member 3 (CDHR3) and orosomucoid like 3 (ORMDL3), were elucidated. New anti-IL-5 therapeutics, mepolizumab and reslizumab, were US Food and Drug Administration approved for the treatment of patients with severe eosinophilic asthma. In a clinical trial the novel therapeutic inhaled GATA3 mRNA-specific DNAzyme attenuated early- and late-phase allergic responses to inhaled allergen. These current findings are significant steps toward addressing unmet needs in asthma prevention, severity modification, disparities, and lifespan outcomes. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Associations between and development of cool and hot executive functions across early childhood.

PubMed

O'Toole, Sarah; Monks, Claire P; Tsermentseli, Stella

2018-03-01

This study explored the development of cool and hot EF skills across early childhood. Children 4.5- to 5.5-years-old (N = 80) completed performance-based assessments of cool EF (inhibition and working memory), hot EF (affective decision-making and delay of gratification) at three time points across 12 months. Cool EF task performance was consistently correlated with early childhood, but hot EF task performance was not. Performance on cool EF tasks showed significant improvements over early childhood, but performance on hot EF tasks did not. During early childhood performance on delay of gratification and affective decision-making tasks may therefore be unrelated and show limited sensitivity to improvement. Statement of contribution What is already known about cool and hot EF An EF model has been proposed that distinguishes between cool-cognitive and hot-affective skills. Findings regarding whether cool and hot EF are distinct in early childhood are mixed. Hot EF skills, compared to cool EF abilities, are thought to develop more gradually. What the present study adds to understanding of cool and hot EF Performance on cool EF tasks and hot delay of gratification were associated in early childhood. Performance on hot EF tasks was not related, meaning they do not tap the same underlying factor. Age related gains in hot EF were not found, but 5-year-olds had better hot EF than 4-year-olds. © 2017 The British Psychological Society.

Linguistic ability in early life and cognitive function and Alzheimer's disease in late life. Findings from the Nun Study.

PubMed

Snowdon, D A; Kemper, S J; Mortimer, J A; Greiner, L H; Wekstein, D R; Markesbery, W R

1996-02-21

To determine if linguistic ability in early life is associated with cognitive function and Alzheimer's disease in late life. Two measures of linguistic ability in early life, idea density and grammatical complexity, were derived from autobiographies written at a mean age of 22 years. Approximately 58 years later, the women who wrote these autobiographies participated in an assessment of cognitive function, and those who subsequently died were evaluated neuropathologically. Convents in the United States participating in the Nun Study; primarily convents in the Milwaukee, Wis, area. Cognitive function was investigated in 93 participants who were aged 75 to 95 years at the time of their assessments, and Alzheimer's disease was investigated in the 14 participants who died at 79 to 96 years of age. Seven neuropsychological tests and neuropathologically confirmed Alzheimer's disease. Low idea density and low grammatical complexity in autobiographies written in early life were associated with low cognitive test scores in late life. Low idea density in early life had stronger and more consistent associations with poor cognitive function than did low grammatical complexity. Among the 14 sisters who died, neuropathologically confirmed Alzheimer's disease was present in all of those with low idea density in early life and in none of those with high idea density. Low linguistic ability in early life was a strong predictor of poor cognitive function and Alzheimer's disease in late life.

GPR30 Activation Opposes Estrogen-Dependent Uterine Growth via Inhibition of Stromal ERK1/2 and Estrogen Receptor Alpha (ERα) Phosphorylation Signals

PubMed Central

Gao, Fei; Ma, Xinghong; Ostmann, Alicia B.

2011-01-01

Although estradiol-17β (E2)-regulated early and late phase uterine responses have been well defined, the molecular mechanisms linking the phases remain poorly understood. We have previously shown that E2-regulated early signals mediate cross talk with estrogen receptor (ER)-α to elicit uterine late growth responses. G protein-coupled receptor (GPR30) has been implicated in early nongenomic signaling mediated by E2, although its role in E2-dependent uterine biology is unclear. Using selective activation of GPR30 by G-1, we show here a new function of GPR30 in regulating early signaling events, including the inhibition of ERK1/2 and ERα (Ser118) phosphorylation signals and perturbation of growth regulation under the direction of E2 in the mouse uterus. We observed that GPR30 primarily localizes in the uterine epithelial cells, and its activation alters gene expression and mediates inhibition of ERK1/2 and ERα (Ser118) phosphorylation signals in the stromal compartment, suggesting a paracrine signaling is involved. Importantly, viral-driven manipulation of GPR30 or pharmacological inhibition of ERK1/2 activation effectively alters E2-dependent uterine growth responses. Overall, GPR30 is a negative regulator of ERα-dependent uterine growth in response to E2. Our work has uncovered a novel GPR30-regulated inhibitory event, which may be physiologically relevant in both normal and pathological situations to negatively balance ERα-dependent uterine growth regulatory functions induced by E2. PMID:21303939

Soft Functionals for Hard Matter

NASA Astrophysics Data System (ADS)

Cooper, Valentino R.; Yuk, Simuck F.; Krogel, Jaron T.

Theory and computation are critical to the materials discovery process. While density functional theory (DFT) has become the standard for predicting materials properties, it is often plagued by inaccuracies in the underlying exchange-correlation functionals. Using high-throughput DFT calculations we explore the accuracy of various exchange-correlation functionals for modeling the structural and thermodynamic properties of a wide range of complex oxides. In particular, we examine the feasibility of using the nonlocal van der Waals density correlation functional with C09 exchange (C09x), which was designed for sparsely packed soft matter, for investigating the properties of hard matter like bulk oxides. Preliminary results show unprecedented performance for some prototypical bulk ferroelectrics, which can be correlated with similarities between C09x and PBEsol. This effort lays the groundwork for understanding how these soft functionals can be employed as general purpose functionals for studying a wide range of materials where strong internal bonds and nonlocal interactions coexist. Research was sponsored by the US DOE, Office of Science, BES, MSED and Early Career Research Programs and used resources at NERSC.

Dominant Species in Subtropical Forests Could Decrease Photosynthetic N Allocation to Carboxylation and Bioenergetics and Enhance Leaf Construction Costs during Forest Succession

PubMed Central

Xiao, Yihua; Liu, Shirong; Tong, Fuchun; Chen, Bufeng; Kuang, Yuanwen

2018-01-01

It is important to understand how eco-physiological characteristics shift in forests when elucidating the mechanisms underlying species replacement and the process of succession and stabilization. In this study, the dominant species at three typical successional stages (early-, mid-, and late-succession) in the subtropical forests of China were selected. At each stage, we compared the leaf construction costs (CC), payback time (PBT), leaf area based N content (NA), maximum CO2 assimilation rate (Pmax), specific leaf area (SLA), photosynthetic nitrogen use efficiency (PNUE), and leaf N allocated to carboxylation (NC), and to bioenergetics (NB). The relationships between these leaf functional traits were also determined. The results showed that the early-succession forest is characterized with significantly lower leaf CC, PBT, NA, but higher Pmax, SLA, PNUE, NC, and NB, in relation to the late-succession forest. From the early- to the late-succession forests, the relationship between Pmax and leaf CC strengthened, whereas the relationships between NB, NC, PNUE, and leaf CC weakened. Thus, the dominant species are able to decrease the allocation of the photosynthetic N fraction to carboxylation and bioenergetics during forest succession. The shift in these leaf functional traits and their linkages might represent a fundamental physiological mechanism that occurs during forest succession and stabilization. PMID:29472939

Dominant Species in Subtropical Forests Could Decrease Photosynthetic N Allocation to Carboxylation and Bioenergetics and Enhance Leaf Construction Costs during Forest Succession.

PubMed

Xiao, Yihua; Liu, Shirong; Tong, Fuchun; Chen, Bufeng; Kuang, Yuanwen

2018-01-01

It is important to understand how eco-physiological characteristics shift in forests when elucidating the mechanisms underlying species replacement and the process of succession and stabilization. In this study, the dominant species at three typical successional stages (early-, mid-, and late-succession) in the subtropical forests of China were selected. At each stage, we compared the leaf construction costs (CC), payback time (PBT), leaf area based N content ( N A ), maximum CO 2 assimilation rate ( P max ), specific leaf area (SLA), photosynthetic nitrogen use efficiency (PNUE), and leaf N allocated to carboxylation ( N C ), and to bioenergetics ( N B ). The relationships between these leaf functional traits were also determined. The results showed that the early-succession forest is characterized with significantly lower leaf CC, PBT, N A , but higher P max , SLA, PNUE, N C , and N B , in relation to the late-succession forest. From the early- to the late-succession forests, the relationship between P max and leaf CC strengthened, whereas the relationships between N B , N C , PNUE, and leaf CC weakened. Thus, the dominant species are able to decrease the allocation of the photosynthetic N fraction to carboxylation and bioenergetics during forest succession. The shift in these leaf functional traits and their linkages might represent a fundamental physiological mechanism that occurs during forest succession and stabilization.

Bryophyte-dominated biological soil crusts mitigate soil erosion in an early successional Chinese subtropical forest

NASA Astrophysics Data System (ADS)

Seitz, Steffen; Nebel, Martin; Goebes, Philipp; Käppeler, Kathrin; Schmidt, Karsten; Shi, Xuezheng; Song, Zhengshan; Webber, Carla L.; Weber, Bettina; Scholten, Thomas

2017-12-01

This study investigated the development of biological soil crusts (biocrusts) in an early successional subtropical forest plantation and their impact on soil erosion. Within a biodiversity and ecosystem functioning experiment in southeast China (biodiversity and ecosystem functioning (BEF) China), the effect of these biocrusts on sediment delivery and runoff was assessed within micro-scale runoff plots under natural rainfall, and biocrust cover was surveyed over a 5-year period. Results showed that biocrusts occurred widely in the experimental forest ecosystem and developed from initial light cyanobacteria- and algae-dominated crusts to later-stage bryophyte-dominated crusts within only 3 years. Biocrust cover was still increasing after 6 years of tree growth. Within later-stage crusts, 25 bryophyte species were determined. Surrounding vegetation cover and terrain attributes significantly influenced the development of biocrusts. Besides high crown cover and leaf area index, the development of biocrusts was favoured by low slope gradients, slope orientations towards the incident sunlight and the altitude of the research plots. Measurements showed that bryophyte-dominated biocrusts strongly decreased soil erosion, being more effective than abiotic soil surface cover. Hence, their significant role in mitigating sediment delivery and runoff generation in mesic forest environments and their ability to quickly colonise soil surfaces after disturbance are of particular interest for soil erosion control in early-stage forest plantations.

High-Resolution Tissue Doppler Imaging of the Zebrafish Heart During Its Regeneration

PubMed Central

Su, Ta-Han; Shih, Cho-Chiang

2015-01-01

Abstract The human heart cannot regenerate after injury, whereas the adult zebrafish can fully regenerate its heart even after 20% of the ventricle is amputated. Many studies have begun to reveal the cellular and molecular mechanisms underlying this regenerative process, which have exciting implications for human cardiac diseases. However, the dynamic functions of the zebrafish heart during regeneration are not yet understood. This study established a high-resolution echocardiography for tissue Doppler imaging (TDI) of the zebrafish heart to explore the cardiac functions during different regeneration phases. Experiments were performed on AB-line adult zebrafish (n=40) in which 15% of the ventricle was surgically removed. An 80-MHz ultrasound TDI based on color M-mode imaging technology was employed. The cardiac flow velocities and patterns from both the ventricular chamber and myocardium were measured at different regeneration phases relative to the day of amputation. The peak velocities of early diastolic inflow, early diastolic myocardial motion, late diastolic myocardial motion, early diastolic deceleration slope, and heart rate were increased at 3 days after the myocardium amputation, but these parameters gradually returned to close to their baseline values for the normal heart at 7 days after amputation. The peak velocities of late diastolic inflow, ventricular systolic outflow, and systolic myocardial motion did not significantly differ during the heart regeneration. PMID:25517185

Impaired GABAergic inhibition in the prefrontal cortex of early postnatal phencyclidine (PCP)-treated rats.

PubMed

Kjaerby, Celia; Broberg, Brian V; Kristiansen, Uffe; Dalby, Nils Ole

2014-09-01

A compromised γ-aminobutyric acid (GABA)ergic system is hypothesized to be part of the underlying pathophysiology of schizophrenia. N-methyl-D-aspartate (NMDA) receptor hypofunction during neurodevelopment is proposed to disrupt maturation of interneurons causing an impaired GABAergic transmission in adulthood. The present study examines prefrontal GABAergic transmission in adult rats administered with the NMDA receptor channel blocker, phencyclidine (PCP), for 3 days during the second postnatal week. Whole-cell patch-clamp recordings from pyramidal cells in PCP-treated rats showed a 22% reduction in the frequency of miniature inhibitory postsynaptic currents in layer II/III, but not in layer V pyramidal neurons of the prefrontal cortex. Furthermore, early postnatal PCP treatment caused insensitivity toward effects of the GABA transporter 1 (GAT-1) inhibitor, 1,2,5,6-tetrahydro-1-[2-[[(diphenyl-methylene)amino]oxy]ethyl]-3-pyridinecarboxylic acid, and also diminished currents passed by δ-subunit-containing GABAA receptors in layer II/III pyramidal neurons. The observed impairments in GABAergic function are compatible with the alteration of GABAergic markers as well as cognitive dysfunction observed in early postnatal PCP-treated rats and support the hypothesis that PCP administration during neurodevelopment affects the functionality of interneurons in later life. © The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Sex differences during humor appreciation in child-sibling pairs.

PubMed

Vrticka, Pascal; Neely, Michelle; Walter Shelly, Elizabeth; Black, Jessica M; Reiss, Allan L

2013-01-01

The developmental origin of sex differences in adult brain function is poorly understood. Elucidating neural mechanisms underlying comparable cognitive functionality in both children and adults is required to address this gap. Humor appreciation represents a particularly relevant target for such developmental research because explanatory theories apply across the life span, and underlying neurocircuitry shows sex differences in adults. As a positive mood state, humor is also of interest due to sex differences in rates of depression, a disorder afflicting twice as many women as men. In this study, we employed functional magnetic resonance imaging (fMRI) to investigate brain responses to funny versus positive (and neutral) video clips in 22 children, ages 6-13 years, including eight sibling-pairs. Our data revealed increased activity to funny clips in bilateral temporo-occipital cortex, midbrain, and amygdala in girls. Conversely, we found heightened activation to positive clips in bilateral inferior parietal lobule, fusiform gyrus, inferior frontal gyrus, amygdala, and ventromedial prefrontal cortex in boys. Many of these effects persisted when looking at sibling-pairs only. We interpret such findings as reflecting the presence of early sex divergence in reward saliency or expectation and stimulus relevance attribution. These findings are discussed in the context of evolutionary and developmental theories of humor function.

Reconstructing the Evolutionary History of Paralogous APETALA1/FRUITFULL-Like Genes in Grasses (Poaceae)

PubMed Central

Preston, Jill C.; Kellogg, Elizabeth A.

2006-01-01

Gene duplication is an important mechanism for the generation of evolutionary novelty. Paralogous genes that are not silenced may evolve new functions (neofunctionalization) that will alter the developmental outcome of preexisting genetic pathways, partition ancestral functions (subfunctionalization) into divergent developmental modules, or function redundantly. Functional divergence can occur by changes in the spatio-temporal patterns of gene expression and/or by changes in the activities of their protein products. We reconstructed the evolutionary history of two paralogous monocot MADS-box transcription factors, FUL1 and FUL2, and determined the evolution of sequence and gene expression in grass AP1/FUL-like genes. Monocot AP1/FUL-like genes duplicated at the base of Poaceae and codon substitutions occurred under relaxed selection mostly along the branch leading to FUL2. Following the duplication, FUL1 was apparently lost from early diverging taxa, a pattern consistent with major changes in grass floral morphology. Overlapping gene expression patterns in leaves and spikelets indicate that FUL1 and FUL2 probably share some redundant functions, but that FUL2 may have become temporally restricted under partial subfunctionalization to particular stages of floret development. These data have allowed us to reconstruct the history of AP1/FUL-like genes in Poaceae and to hypothesize a role for this gene duplication in the evolution of the grass spikelet. PMID:16816429

Genetic dyslexia risk variant is related to neural connectivity patterns underlying phonological awareness in children.

PubMed

Skeide, Michael A; Kirsten, Holger; Kraft, Indra; Schaadt, Gesa; Müller, Bent; Neef, Nicole; Brauer, Jens; Wilcke, Arndt; Emmrich, Frank; Boltze, Johannes; Friederici, Angela D

2015-09-01

Phonological awareness is the best-validated predictor of reading and spelling skill and therefore highly relevant for developmental dyslexia. Prior imaging genetics studies link several dyslexia risk genes to either brain-functional or brain-structural factors of phonological deficits. However, coherent evidence for genetic associations with both functional and structural neural phenotypes underlying variation in phonological awareness has not yet been provided. Here we demonstrate that rs11100040, a reported modifier of SLC2A3, is related to the functional connectivity of left fronto-temporal phonological processing areas at resting state in a sample of 9- to 12-year-old children. Furthermore, we provide evidence that rs11100040 is related to the fractional anisotropy of the arcuate fasciculus, which forms the structural connection between these areas. This structural connectivity phenotype is associated with phonological awareness, which is in turn associated with the individual retrospective risk scores in an early dyslexia screening as well as to spelling. These results suggest a link between a dyslexia risk genotype and a functional as well as a structural neural phenotype, which is associated with a phonological awareness phenotype. The present study goes beyond previous work by integrating genetic, brain-functional and brain-structural aspects of phonological awareness within a single approach. These combined findings might be another step towards a multimodal biomarker for developmental dyslexia. Copyright © 2015 Elsevier Inc. All rights reserved.

Modulation of early functional recovery of Achilles tendon to bone unit after transection by BPC 157 and methylprednisolone.

PubMed

Krivic, A; Majerovic, M; Jelic, I; Seiwerth, S; Sikiric, P

2008-05-01

In the presented study we compared the effect of stable peptide BPC 157 and methylprednisolone on early functional recovery after Achilles tendon to bone transection in a rat model before collagen healing started. Surgical transection of the right Achilles tendon to bone area was performed in seventy two Wistar Albino male rats. Healing Achilles tendon edges were harvested at days 1-4 following the transection. Using Achilles functional index (AFI), myeloperoxidase activity, histological inflammatory cell influx and vascular index early functional recovery was evaluated. Agents (stable peptide BPC 157 10 microg methylprednisolone 5 mg, normal saline 5 ml) were given alone (/kg b.w., intraperitoneally, once daily, first 30 min after surgery, last 24 h before analysis). Control group received normal saline 5 ml/kg. BPC 157 improved functional recovery (AFI values increased at all time points, p <0.05) by anti-inflammatory (decreased myeloperoxidase (MPO) activity and histological inflammatory cell influx, p <0.05) and increased new blood vessel formation (increased vascular index, p <0.05). Methyprednisolone decreased MPO activity and histological inflammatory cell influx, (p <0.05) but also decreased new blood vessel formation and did not affect early functional recovery. Stable peptide BPC 157 with combined anti-inflammatory action and induction of early new blood vessel formation facilitates early functional recovery in Achilles tendon to bone healing.

10 CFR 50.81 - Creditor regulations.

Code of Federal Regulations, 2014 CFR

2014-01-01

... provided by law. (d) As used in this section: (1) License includes any license under this chapter, any construction permit under this part, and any early site permit under part 52 of this chapter, which may be... limited to, a site which is the subject of an early site permit under subpart A of part 52 of this chapter...

10 CFR 50.81 - Creditor regulations.

Code of Federal Regulations, 2010 CFR

2010-01-01

... provided by law. (d) As used in this section: (1) License includes any license under this chapter, any construction permit under this part, and any early site permit under part 52 of this chapter, which may be... limited to, a site which is the subject of an early site permit under subpart A of part 52 of this chapter...

10 CFR 50.81 - Creditor regulations.

Code of Federal Regulations, 2012 CFR

2012-01-01

... provided by law. (d) As used in this section: (1) License includes any license under this chapter, any construction permit under this part, and any early site permit under part 52 of this chapter, which may be... limited to, a site which is the subject of an early site permit under subpart A of part 52 of this chapter...

10 CFR 50.81 - Creditor regulations.

Code of Federal Regulations, 2011 CFR

2011-01-01

... provided by law. (d) As used in this section: (1) License includes any license under this chapter, any construction permit under this part, and any early site permit under part 52 of this chapter, which may be... limited to, a site which is the subject of an early site permit under subpart A of part 52 of this chapter...

10 CFR 50.81 - Creditor regulations.

Code of Federal Regulations, 2013 CFR

2013-01-01

... provided by law. (d) As used in this section: (1) License includes any license under this chapter, any construction permit under this part, and any early site permit under part 52 of this chapter, which may be... limited to, a site which is the subject of an early site permit under subpart A of part 52 of this chapter...

Protein Delivery into Plant Cells: Toward In vivo Structural Biology

PubMed Central

Cedeño, Cesyen; Pauwels, Kris; Tompa, Peter

2017-01-01

Understanding the biologically relevant structural and functional behavior of proteins inside living plant cells is only possible through the combination of structural biology and cell biology. The state-of-the-art structural biology techniques are typically applied to molecules that are isolated from their native context. Although most experimental conditions can be easily controlled while dealing with an isolated, purified protein, a serious shortcoming of such in vitro work is that we cannot mimic the extremely complex intracellular environment in which the protein exists and functions. Therefore, it is highly desirable to investigate proteins in their natural habitat, i.e., within live cells. This is the major ambition of in-cell NMR, which aims to approach structure-function relationship under true in vivo conditions following delivery of labeled proteins into cells under physiological conditions. With a multidisciplinary approach that includes recombinant protein production, confocal fluorescence microscopy, nuclear magnetic resonance (NMR) spectroscopy and different intracellular protein delivery strategies, we explore the possibility to develop in-cell NMR studies in living plant cells. While we provide a comprehensive framework to set-up in-cell NMR, we identified the efficient intracellular introduction of isotope-labeled proteins as the major bottleneck. Based on experiments with the paradigmatic intrinsically disordered proteins (IDPs) Early Response to Dehydration protein 10 and 14, we also established the subcellular localization of ERD14 under abiotic stress. PMID:28469623

Diagnostic uncertainty in a severely demented male patient: a case report

PubMed Central

Maiovis, Pantelis; Gavopoulou, Evgenia; Eleftheriou, Marina; Tsokanari, Ioanna; Tsolaki, Magda

2008-01-01

Introduction Current trends in dementia research focus on early and accurate diagnosis. In clinical practice however, this is not always possible, as multiple underlying pathologies produce mixed dementia syndromes. Furthermore, patients with severe dementia are often underestimated. Case presentation We present a case of a 71 year old Caucasian male with severe Alzheimer's Disease, bedridden and fully dependent in activities of everyday living, whose general cognitive function is almost intact. We emphasize on the diverse underlying pathologies contributing to this intriguing clinical presentation and to diagnostic uncertainty. Conclusion Understanding the complexity of the dementia process in every patient using a multidimensional approach, contributes to more rational management strategies and finally to high quality care for patients and caregivers. PMID:18928571

Peritoneal Dialysis in Diabetics: There Is Room for More

PubMed Central

Cotovio, P.; Rocha, A.; Rodrigues, A.

2011-01-01

End stage renal disease diabetic patients suffer from worse clinical outcomes under dialysis-independently of modality. Peritoneal dialysis offers them the advantages of home therapy while sparing their frail vascular capital and preserving residual renal function. Other benefits and potential risks deserve discussion. Predialysis intervention with early nephrology referral, patient education, and multidisciplinary support are recommended. Skilled and updated peritoneal dialysis protocols must be prescribed to assure better survival. Optimized volume control, glucose-sparing peritoneal dialysis regimens, and elective use of icodextrin are key therapy strategies. Nutritional evaluation and support, preferential use of low-glucose degradation products solutions, and prescription of renin-angiotensin-aldosterone system acting drugs should also be part of the panel to improve diabetic care under peritoneal dialysis. PMID:22013524

Associations of SF-36 mental health functioning and work and family related factors with intentions to retire early among employees.

PubMed

Harkonmäki, K; Rahkonen, O; Martikainen, P; Silventoinen, K; Lahelma, E

2006-08-01

To examine the associations of mental health functioning (SF-36) and work and family related psychosocial factors with intentions to retire early. Cross sectional survey data (n = 5037) from the Helsinki Health Study occupational cohort in 2001 and 2002 were used. Intentions to retire early were inquired with a question: "Have you considered retiring before normal retirement age?" Mental health functioning was measured by the Short Form 36 (SF-36) mental component summary (MCS). Work and family related psychosocial factors included job demands and job control, procedural and relational justice, conflicts between work and family, and social network size. Multinomial regression models were used to analyse the data. Poor mental health functioning, unfavourable psychosocial working conditions, and conflicts between work and family were individually related to intentions to retire early. After adjustments for all work and family related factors the odds ratio for low mental health functioning was halved (from OR = 6.05 to 3.67), but nevertheless the association between poor mental health functioning and strong intentions to retire early remained strong. These findings highlight not only the importance of low mental health and unfavourable working conditions but also the simultaneous impact of conflicts between work and family to employees' intentions to retire early.

The Paradox of Isochrony in the Evolution of Human Rhythm

PubMed Central

Ravignani, Andrea; Madison, Guy

2017-01-01

Isochrony is crucial to the rhythm of human music. Some neural, behavioral and anatomical traits underlying rhythm perception and production are shared with a broad range of species. These may either have a common evolutionary origin, or have evolved into similar traits under different evolutionary pressures. Other traits underlying rhythm are rare across species, only found in humans and few other animals. Isochrony, or stable periodicity, is common to most human music, but isochronous behaviors are also found in many species. It appears paradoxical that humans are particularly good at producing and perceiving isochronous patterns, although this ability does not conceivably confer any evolutionary advantage to modern humans. This article will attempt to solve this conundrum. To this end, we define the concept of isochrony from the present functional perspective of physiology, cognitive neuroscience, signal processing, and interactive behavior, and review available evidence on isochrony in the signals of humans and other animals. We then attempt to resolve the paradox of isochrony by expanding an evolutionary hypothesis about the function that isochronous behavior may have had in early hominids. Finally, we propose avenues for empirical research to examine this hypothesis and to understand the evolutionary origin of isochrony in general. PMID:29163252

Child maltreatment and trajectories of personality and behavioral functioning: Implications for the development of personality disorder

PubMed Central

Kim, Jungmeen; Cicchetti, Dante; Rogosch, Fred A.; Manly, Jody Todd

2009-01-01

This study investigated the longitudinal impact of maltreatment parameters on personality processes and maladjustment and prospective relationships between personality trajectory classes and subsequent maladjustment outcomes. The sample involved maltreated (n = 249) and nonmaltreated (n = 200) children followed longitudinally between ages 6 – 10. Growth mixture modeling indicated multifinality in personality development depending on the risk status (i.e., maltreated vs. nonmaltreated). Two trajectory classes of ego resiliency were identified for maltreated children; those who showed a declining trajectory exhibited greater maladjustment. In contrast, three trajectory classes of ego control were identified for nonmaltreated children; the subgroups showing increases in ego under-control or dramatic changes from high ego under-control to high ego over-control exhibited poor adjustment. Experiencing multiple maltreatment subtypes and physical/sexual abuse were related to higher levels of ego under-control and externalizing symptomatology, whereas early onset of maltreatment was associated with the low and decreasing trajectory of ego resiliency and higher levels of internalizing symptomatology. The findings suggest that ego resiliency and ego control – personality processes related to self-regulation – may be important factors in identifying distinct pathways to later personality disorders as well as pathways to resilient functioning. PMID:19583889

The Curious Relation between Theory of Mind and Sharing in Preschool Age Children

PubMed Central

Cowell, Jason M.; Samek, Anya; List, John; Decety, Jean

2015-01-01

Young children have long been known to act selfishly and gradually appear to become more generous across middle childhood. While this apparent change has been well documented, the underlying mechanisms supporting this remain unclear. The current study examined the role of early theory of mind and executive functioning in facilitating sharing in a large sample (N = 98) of preschoolers. Results reveal a curious relation between early false-belief understanding and sharing behavior. Contrary to many commonsense notions and predominant theories, competence in this ability is actually related to less sharing. Thus, the relation between developing theory of mind and sharing may not be as straightforward as it seems in preschool age children. It is precisely the children who can engage in theory of mind that decide to share less with others. PMID:25658696

The curious relation between theory of mind and sharing in preschool age children.

PubMed

Cowell, Jason M; Samek, Anya; List, John; Decety, Jean

2015-01-01

Young children have long been known to act selfishly and gradually appear to become more generous across middle childhood. While this apparent change has been well documented, the underlying mechanisms supporting this remain unclear. The current study examined the role of early theory of mind and executive functioning in facilitating sharing in a large sample (N = 98) of preschoolers. Results reveal a curious relation between early false-belief understanding and sharing behavior. Contrary to many commonsense notions and predominant theories, competence in this ability is actually related to less sharing. Thus, the relation between developing theory of mind and sharing may not be as straightforward as it seems in preschool age children. It is precisely the children who can engage in theory of mind that decide to share less with others.

Early Hormonal Influences on Cognitive Functioning in Congenital Adrenal Hyperplasia.

ERIC Educational Resources Information Center

Resnick, Susan M.; And Others

1986-01-01

Reports the results of cognitive test performance and early childhood activities in individuals with congenital adrenal hyperplasia, an autosomal recessive disorder associated with elevated prenatal adrenal androgen levels, demonstrating the effects of early exposure to excess androgenizing hormones on sexually dimorphic cognitive functioning.…

Genetic, environmental, and epigenetic factors in the development of personality disturbance.

PubMed

Depue, Richard A

2009-01-01

A dimensional model of personality disturbance is presented that is defined by extreme values on interacting subsets of seven major personality traits. Being at the extreme has marked effects on the threshold for eliciting those traits under stimulus conditions: that is, the extent to which the environment affects the neurobiological functioning underlying the traits. To explore the nature of development of extreme values on these traits, each trait is discussed in terms of three major issues: (a) the neurobiological variables associated with the trait, (b) individual variation in this neurobiology as a function of genetic polymorphisms, and (c) the effects of environmental adversity on these neurobiological variables through the action of epigenetic processes. It is noted that gene-environment interaction appears to be dependent on two main factors: (a) both genetic and environmental variables appear to have the most profound and enduring effects when they exert their effects during early postnatal periods, times when the forebrain is undergoing exuberant experience-expectant dendritic and axonal growth; and (b) environmental effects on neurobiology are strongly modified by individual differences in "traitlike" functioning of neurobiological variables. A model of the nature of the interaction between environmental and neurobiological variables in the development of personality disturbance is presented.

Usher syndrome (sensorineural deafness and retinitis pigmentosa): pathogenesis, molecular diagnosis and therapeutic approaches.

PubMed

Bonnet, Crystel; El-Amraoui, Aziz

2012-02-01

Usher syndrome (USH) is the most prevalent cause of hereditary deafness-blindness in humans. In this review, we pinpoint new insights regarding the molecular mechanisms defective in this syndrome, its molecular diagnosis and prospective therapies. Animal models wherein USH proteins were targeted at different maturation stages of the auditory hair cells have been engineered, shedding new light on the development and functioning of the hair bundle, the sound receptive structure. Improved protocols and guidelines for early molecular diagnosis of USH (USH genotyping microarrays, otochips and complete Sanger sequencing of the 366 coding exons of identified USH genes) have been developed. Approaches to alleviate or cure hearing and visual impairments have been initiated, leading to various degrees of functional rescuing. Whereas the mechanisms underlying hearing impairment in USH patients are being unraveled, showing in particular that USH1 proteins are involved in the shaping of the hair bundle and the functioning of the mechanoelectrical transduction machinery, the mechanisms underlying the retinal defects are still unclear. Efforts to improve clinical diagnosis have been successful. Yet, despite some encouraging results, further development of therapeutic approaches is necessary to ultimately treat this dual sensory defect.

Differential Proteomic Analysis Reveals the Effect of Calcium on Malus baccata Borkh. Leaves under Temperature Stress.

PubMed

Li, Lijie; Su, Hong; Ma, Huaiyu; Lyu, Deguo

2017-08-11

In the cool apple-producing areas of northern China, air temperature during early spring changes in a rapid and dramatic manner, which affects the growth and development of apple trees at the early stage of the growing season. Previous studies have shown that the treatment of calcium can increase the cold tolerance of Malus baccata Borkh., a widely-used rootstock apple tree in northern China. To better understand the physiological function of calcium in the response of M. baccata to temperature stress, we analyzed the effect of calcium treatment (2% CaCl₂) on M. baccata leaves under temperature stress. Physiological analysis showed that temperature stress aggravated membrane lipid peroxidation, reduced chlorophyll content and induced photo-inhibition in leaves, whereas these indicators of stress injuries were alleviated by the application of calcium. An isobaric tags for relative and absolute quantitation (iTRAQ)-based proteomics approach was used in this study. Among the 2114 proteins that were detected in M. baccata leaves, 41, 25, and 34 proteins were differentially regulated by the increasing, decreasing, and changing temperature treatments, respectively. Calcium treatment induced 9 and 15 proteins after increasing and decreasing temperature, respectively, in comparison with non-treated plants. These calcium-responsive proteins were mainly related to catalytic activity, binding, and structural molecule activity. Hierarchical cluster analysis indicated that the changes in abundance of the proteins under increasing temperature and changing temperature treatments were similar, and the changes in protein abundance under decreasing temperature and increasing temperature with calcium treatment were similar. The findings of this study will allow a better understanding of the mechanisms underlying the role of calcium in M. baccata leaves under temperature stress.

Differential Proteomic Analysis Reveals the Effect of Calcium on Malus baccata Borkh. Leaves under Temperature Stress

PubMed Central

Li, Lijie; Su, Hong; Ma, Huaiyu; Lyu, Deguo

2017-01-01

In the cool apple-producing areas of northern China, air temperature during early spring changes in a rapid and dramatic manner, which affects the growth and development of apple trees at the early stage of the growing season. Previous studies have shown that the treatment of calcium can increase the cold tolerance of Malus baccata Borkh., a widely-used rootstock apple tree in northern China. To better understand the physiological function of calcium in the response of M. baccata to temperature stress, we analyzed the effect of calcium treatment (2% CaCl2) on M. baccata leaves under temperature stress. Physiological analysis showed that temperature stress aggravated membrane lipid peroxidation, reduced chlorophyll content and induced photo-inhibition in leaves, whereas these indicators of stress injuries were alleviated by the application of calcium. An isobaric tags for relative and absolute quantitation (iTRAQ)-based proteomics approach was used in this study. Among the 2114 proteins that were detected in M. baccata leaves, 41, 25, and 34 proteins were differentially regulated by the increasing, decreasing, and changing temperature treatments, respectively. Calcium treatment induced 9 and 15 proteins after increasing and decreasing temperature, respectively, in comparison with non-treated plants. These calcium-responsive proteins were mainly related to catalytic activity, binding, and structural molecule activity. Hierarchical cluster analysis indicated that the changes in abundance of the proteins under increasing temperature and changing temperature treatments were similar, and the changes in protein abundance under decreasing temperature and increasing temperature with calcium treatment were similar. The findings of this study will allow a better understanding of the mechanisms underlying the role of calcium in M. baccata leaves under temperature stress. PMID:28800123

Early sex work initiation and condom use among alcohol-using female sex workers in Mombasa, Kenya: a cross-sectional analysis.

PubMed

Parcesepe, Angela M; L'Engle, Kelly L; Martin, Sandra L; Green, Sherri; Suchindran, Chirayath; Mwarogo, Peter

2016-12-01

Early initiation of sex work is prevalent among female sex workers (FSWs) worldwide. The objectives of this study were to investigate if early initiation of sex work was associated with: (1) consistent condom use, (2) condom negotiation self-efficacy or (3) condom use norms among alcohol-using FSWs in Mombasa, Kenya. In-person interviews were conducted with 816 FSWs in Mombasa, Kenya. Sample participants were: recruited from HIV prevention drop-in centres, 18 years or older and moderate risk drinkers. Early initiation was defined as first engaging in sex work at 17 years or younger. Logistic regression modelled outcomes as a function of early initiation, adjusting for drop-in centre, years in sex work, supporting others and HIV status. FSWs who initiated sex work early were significantly less likely to report consistent condom use with paying sex partners compared with those who initiated sex work in adulthood. There was no significant difference between groups in consistent condom use with non-paying sex partners. FSWs who initiated sex work early endorsed less condom negotiation self-efficacy with paying sex partners compared with FSWs who did not initiate sex work early. Findings highlight a need for early intervention for at-risk youth and adolescent FSWs, particularly in relation to HIV sexual risk behaviours. Evidence-based interventions for adolescent FSWs or adult FSWs who began sex work in adolescence should be developed, implemented and evaluated. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Do Children's Executive Functions Account for Associations Between Early Autonomy-Supportive Parenting and Achievement Through High School?

PubMed Central

Bindman, Samantha W.; Pomerantz, Eva M.; Roisman, Glenn I.

2015-01-01

This study evaluated whether the positive association between early autonomy-supportive parenting and children's subsequent achievement is mediated by children's executive functions. Using observations of mothers’ parenting from the NICHD Study of Early Child Care and Youth Development (N = 1,306), analyses revealed that mothers’ autonomy support over the first 3 years of life predicted enhanced executive functions (i.e., inhibition, delay of gratification, and sustained attention) during the year prior to kindergarten and academic achievement in elementary and high school even when mothers’ warmth and cognitive stimulation, as well as other factors (e.g., children's early general cognitive skills and mothers’ educational attainment) were covaried. Mediation analyses demonstrated that over and above other attributes (e.g., temperament), children's executive functions partially accounted for the association between early autonomy-supportive parenting and children's subsequent achievement. PMID:26366009

Do Children's Executive Functions Account for Associations Between Early Autonomy-Supportive Parenting and Achievement Through High School?

PubMed

Bindman, Samantha W; Pomerantz, Eva M; Roisman, Glenn I

2015-08-01

This study evaluated whether the positive association between early autonomy-supportive parenting and children's subsequent achievement is mediated by children's executive functions. Using observations of mothers' parenting from the NICHD Study of Early Child Care and Youth Development ( N = 1,306), analyses revealed that mothers' autonomy support over the first 3 years of life predicted enhanced executive functions (i.e., inhibition, delay of gratification, and sustained attention) during the year prior to kindergarten and academic achievement in elementary and high school even when mothers' warmth and cognitive stimulation, as well as other factors (e.g., children's early general cognitive skills and mothers' educational attainment) were covaried. Mediation analyses demonstrated that over and above other attributes (e.g., temperament), children's executive functions partially accounted for the association between early autonomy-supportive parenting and children's subsequent achievement.

Dynamic range of Nef-mediated evasion of HLA class II-restricted immune responses in early HIV-1 infection.

PubMed

Mahiti, Macdonald; Brumme, Zabrina L; Jessen, Heiko; Brockman, Mark A; Ueno, Takamasa

2015-07-31

HLA class II-restricted CD4(+) T lymphocytes play an important role in controlling HIV-1 replication, especially in the acute/early infection stage. But, HIV-1 Nef counteracts this immune response by down-regulating HLA-DR and up-regulating the invariant chain associated with immature HLA-II (Ii). Although functional heterogeneity of various Nef activities, including down-regulation of HLA class I (HLA-I), is well documented, our understanding of Nef-mediated evasion of HLA-II-restricted immune responses during acute/early infection remains limited. Here, we examined the ability of Nef clones from 47 subjects with acute/early progressive infection and 46 subjects with chronic progressive infection to up-regulate Ii and down-regulate HLA-DR and HLA-I from the surface of HIV-infected cells. HLA-I down-regulation function was preserved among acute/early Nef clones, whereas both HLA-DR down-regulation and Ii up-regulation functions displayed relatively broad dynamic ranges. Nef's ability to down-regulate HLA-DR and up-regulate Ii correlated positively at this stage, suggesting they are functionally linked in vivo. Acute/early Nef clones also exhibited higher HLA-DR down-regulation and lower Ii up-regulation functions compared to chronic Nef clones. Taken together, our results support enhanced Nef-mediated HLA class II immune evasion activities in acute/early compared to chronic infection, highlighting the potential importance of these functions following transmission. Copyright © 2015 Elsevier Inc. All rights reserved.

Biomechanical analysis of intramedullary vs. superior plate fixation of transverse midshaft clavicle fractures.

PubMed

Wilson, David J; Scully, William F; Min, Kyong S; Harmon, Tess A; Eichinger, Josef K; Arrington, Edward D

2016-06-01

Middle-third clavicle fractures represent 2% to 4% of all skeletal trauma in the United States. Treatment options include intramedullary (IM) as well as plate and screw (PS) constructs. The purpose of this study was to analyze the biomechanical stability of a specific IM system compared with nonlocking PS fixation under low-threshold physiologic load. Twenty fourth-generation Sawbones (Pacific Research Laboratories, Vashon, WA, USA) with a simulated middle-third fracture pattern were repaired with either an IM device (n = 10) or superiorly positioned nonlocking PS construct (n = 10). Loads were modeled to simulate physiologic load. Combined axial compression and torsion forces were sequentially increased until failure. Data were analyzed on the basis of loss of rotational stability using 3 criteria: early (10°), clinical (30°), and terminal (120°). No significant difference was noted between constructs in early loss of rotational stability (P > .05). The PS group was significantly more rotationally stable than the IM group on the basis of clinical and terminal criteria (P < .05 for both). All test constructs failed in rotational stability. When tested under physiologic load, fixation failure occurred from loss of rotational stability. No statistical difference was seen between groups under early physiologic loads. However, during load to failure, the PS group was statistically more rotationally stable than the IM group. Given the clavicle's function as a bony strut for the upper extremity and the biomechanical results demonstrated, rotational stability should be carefully considered during surgical planning and postoperative advancement of activity in patients undergoing operative fixation of middle-third clavicle fractures. Basic Science Study; Biomechanics. Published by Elsevier Inc.

Genetics Home Reference: early-onset primary dystonia

MedlinePlus

... such as seizures or a loss of intellectual function (dementia). Early-onset primary dystonia does not affect a person's intelligence. On ... of torsinA. The altered protein's effect on the function of nerve cells in the brain ... with early-onset primary dystonia do not have a loss of nerve ...

Association of subjective memory complaint and depressive symptoms with objective cognitive functions in prodromal Alzheimer's disease including pre-mild cognitive impairment.

PubMed

Seo, Eun Hyun; Kim, Hoowon; Choi, Kyu Yeong; Lee, Kun Ho; Choo, Il Han

2017-08-01

Subjective memory complaints (SMC) and depressive symptoms (SDS) are common in the elderly population. However, the relationship among SMC, SDS, and cognitive function remains unclear. We investigated these associations in the elderly from cognitively normal (CN), pre-mild cognitive impairment (MCI), and amnestic MCI (aMCI) groups. Participants (CN, 299; pre-MCI, 106; aMCI, 267) underwent comprehensive clinical and neuropsychological assessment. and self-report SMC and SDS questionnaires. SMC and SDS were administered in a self-report format. For each neuropsychological test z-score, stepwise multiple linear regressions were performed to assess the relative contribution of SMC, SDS, and their interactions. SMC are associated with lower objective memory, while SDS are associated with lower psychomotor speed. Interactions between SMC and SDS were significant for tests of memory, executive function, psychomotor speed, and global cognition. Additional analyses revealed that SDS moderated the SMC-cognition relationship such that only individuals with higher SDS showed significant SMC-cognition associations. Due to the cross-sectional design, associations among SMC, SDS, and cognitive function was rather weak, albeit significant. Additionally, future biomarker studies, such as those assessing amyloid burden, are needed to explore the mechanisms underlying the relationship among SMC, SDS, and cognitive function. Early identification of individuals at risk for developing abnormal cognitive changes is critical. Our findings from the study involving a large sample of carefully selected participants suggest that SMC and SDS could be used as early detection markers of Alzheimer's disease. Copyright © 2017. Published by Elsevier B.V.

Early Childhood Practitioner Involvement in Functional Behavioral Assessment and Function-Based Interventions: A Literature Review

ERIC Educational Resources Information Center

Wood, Brenna K.; Drogan, Robin R.; Janney, Donna M.

2014-01-01

Reviewers analyzed studies published from 1990 to 2012 to determine early childhood practitioner involvement in functional behavioral assessment (FBA) and function-based behavioral intervention plans (BIP) for children with challenging behavior, age 6 and younger. Coding of 30 studies included practitioner involvement in FBA and BIP processes,…

Early Cellular Changes in the Ascending Aorta and Myocardium in a Swine Model of Metabolic Syndrome.

PubMed

Saraf, Rabya; Huang, Thomas; Mahmood, Feroze; Owais, Khurram; Bardia, Amit; Khabbaz, Kamal R; Liu, David; Senthilnathan, Venkatachalam; Lassaletta, Antonio D; Sellke, Frank; Matyal, Robina

2016-01-01

Metabolic syndrome is associated with pathological remodeling of the heart and adjacent vessels. The early biochemical and cellular changes underlying the vascular damage are not fully understood. In this study, we sought to establish the nature, extent, and initial timeline of cytochemical derangements underlying reduced ventriculo-arterial compliance in a swine model of metabolic syndrome. Yorkshire swine (n = 8 per group) were fed a normal diet (ND) or a high-cholesterol (HCD) for 12 weeks. Myocardial function and blood flow was assessed before harvesting the heart. Immuno-blotting and immuno-histochemical staining were used to assess the cellular changes in the myocardium, ascending aorta and left anterior descending artery (LAD). There was significant increase in body mass index, blood glucose and mean arterial pressures (p = 0.002, p = 0.001 and p = 0.024 respectively) in HCD group. At the cellular level there was significant increase in anti-apoptotic factors p-Akt (p = 0.007 and p = 0.002) and Bcl-xL (p = 0.05 and p = 0.01) in the HCD aorta and myocardium, respectively. Pro-fibrotic markers TGF-β (p = 0.01), pSmad1/5 (p = 0.03) and MMP-9 (p = 0.005) were significantly increased in the HCD aorta. The levels of pro-apoptotic p38MAPK, Apaf-1 and cleaved Caspase3 were significantly increased in aorta of HCD (p = 0.03, p = 0.04 and p = 0.007 respectively). Similar changes in coronary arteries were not observed in either group. Functionally, the high cholesterol diet resulted in significant increase in ventricular end systolic pressure and-dp/dt (p = 0.05 and p = 0.007 respectively) in the HCD group. Preclinical metabolic syndrome initiates pro-apoptosis and pro-fibrosis pathways in the heart and ascending aorta, while sparing coronary arteries at this early stage of dietary modification.

New biomarkers of post-settlement growth in the sea urchin Strongylocentrotus purpuratus.

PubMed

Fadl, Alyaa Elsaid Abdelaziz; Mahfouz, Magdy Elsayed; El-Gamal, Mona Mabrouk Taha; Heyland, Andreas

2017-10-01

Some sea urchins, including the purple sea urchin Strongylocentrotus purpuratus, have been successfully used in aquaculture, but their slow growth and late reproduction are challenging to overcome when developing efficient aquaculture production techniques. S. purpuratus develops via an indirect life history that is characterized by a drastic settlement process at the end of a larval period that lasts for several weeks. During this transition, the bilateral larva is transformed into a pentaradial juvenile, which will start feeding and growing in the benthic habitat. Due to predation and other ecological factors, settlement is typically associated with high mortality rates in juvenile populations. Additionally, juveniles require several days to develop a functional mouth and digestive system. During this perimetamorphic period, juveniles use up larval resources until they are capable to digest adult food. Mechanisms underlying the onset of juvenile feeding and metabolism have implications for the recruitment of natural populations as well as aquaculture and are relatively poorly understood in S. purpuratus . The insulin/insulin-like growth factor signalling (IIS)/Target of Rapamycin (TOR) pathway (IIS/TOR) is well conserved among animal phyla and regulates physiological and developmental functions, such as growth, reproduction, aging and nutritional status. We analyzed the expression of FoxO, TOR, and ILPs in post-settlement juveniles in conjunction with their early growth trajectories. We also tested how pre-settlement starvation affected post-settlement expression of IIS. We found that FoxO provides a useful molecular marker in early juveniles as its expression is strongly correlated with juvenile growth. We also found that pre-settlement starvation affects juvenile growth trajectories as well as IIS. Our findings provide preliminary insights into the mechanisms underlying post-settlement growth and metabolism in S. purpuratus . They also have important implications for sea urchin aquaculture, as they show that pre-settlement nutrient environment significantly affects both early growth trajectories and gene expression. This information can be used to develop new biomarkers for juvenile health in sea urchin population ecology and aquaculture aquaculture.

Defects in Mitochondrial Dynamics and Metabolomic Signatures of Evolving Energetic Stress in Mouse Models of Familial Alzheimer's Disease

PubMed Central

Trushina, Eugenia; Nemutlu, Emirhan; Zhang, Song; Christensen, Trace; Camp, Jon; Mesa, Janny; Siddiqui, Ammar; Tamura, Yasushi; Sesaki, Hiromi; Wengenack, Thomas M.; Dzeja, Petras P.; Poduslo, Joseph F.

2012-01-01

Background The identification of early mechanisms underlying Alzheimer's Disease (AD) and associated biomarkers could advance development of new therapies and improve monitoring and predicting of AD progression. Mitochondrial dysfunction has been suggested to underlie AD pathophysiology, however, no comprehensive study exists that evaluates the effect of different familial AD (FAD) mutations on mitochondrial function, dynamics, and brain energetics. Methods and Findings We characterized early mitochondrial dysfunction and metabolomic signatures of energetic stress in three commonly used transgenic mouse models of FAD. Assessment of mitochondrial motility, distribution, dynamics, morphology, and metabolomic profiling revealed the specific effect of each FAD mutation on the development of mitochondrial stress and dysfunction. Inhibition of mitochondrial trafficking was characteristic for embryonic neurons from mice expressing mutant human presenilin 1, PS1(M146L) and the double mutation of human amyloid precursor protein APP(Tg2576) and PS1(M146L) contributing to the increased susceptibility of neurons to excitotoxic cell death. Significant changes in mitochondrial morphology were detected in APP and APP/PS1 mice. All three FAD models demonstrated a loss of the integrity of synaptic mitochondria and energy production. Metabolomic profiling revealed mutation-specific changes in the levels of metabolites reflecting altered energy metabolism and mitochondrial dysfunction in brains of FAD mice. Metabolic biomarkers adequately reflected gender differences similar to that reported for AD patients and correlated well with the biomarkers currently used for diagnosis in humans. Conclusions Mutation-specific alterations in mitochondrial dynamics, morphology and function in FAD mice occurred prior to the onset of memory and neurological phenotype and before the formation of amyloid deposits. Metabolomic signatures of mitochondrial stress and altered energy metabolism indicated alterations in nucleotide, Krebs cycle, energy transfer, carbohydrate, neurotransmitter, and amino acid metabolic pathways. Mitochondrial dysfunction, therefore, is an underlying event in AD progression, and FAD mouse models provide valuable tools to study early molecular mechanisms implicated in AD. PMID:22393443

78 FR 31568 - Ryan White HIV/AIDS Program, Part C Early Intervention Services Grant Under the Ryan White HIV...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-24

... HIV/AIDS Program, Part C Early Intervention Services Grant Under the Ryan White HIV/AIDS Program.... ACTION: Notice of Ryan White HIV/AIDS Program Part C Early Intervention Services One-Time Noncompetitive Award to Ensure Continued HIV Primary Medical Care. SUMMARY: To prevent a lapse in comprehensive primary...

78 FR 10183 - Ryan White HIV/AIDS Program, Part C Early Intervention Services Grant Under the Ryan White HIV...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-13

... HIV/AIDS Program, Part C Early Intervention Services Grant Under the Ryan White HIV/AIDS Program.... ACTION: Notice of Ryan White HIV/AIDS Program Part C Early Intervention Services One-Time Noncompetitive Award to Ensure Continued HIV Primary Medical Care. SUMMARY: To prevent a lapse in comprehensive primary...

78 FR 10182 - Ryan White HIV/AIDS Program, Part C Early Intervention Services Grant Under the Ryan White HIV...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-13

... HIV/AIDS Program, Part C Early Intervention Services Grant Under the Ryan White HIV/AIDS Program.... ACTION: Notice of Ryan White HIV/AIDS Program (Part C) Early Intervention Services One-Time Noncompetitive Award to Ensure Continued HIV Primary Medical Care. SUMMARY: To prevent a lapse in comprehensive...

Kidney Dysfunction in Adult Offspring Exposed In Utero to Type 1 Diabetes Is Associated with Alterations in Genome-Wide DNA Methylation

PubMed Central

Gautier, Jean-François; Porcher, Raphaël; Abi Khalil, Charbel; Bellili-Munoz, Naima; Fetita, Lila Sabrina; Travert, Florence; Choukem, Simeon-Pierre; Riveline, Jean-Pierre; Hadjadj, Samy; Larger, Etienne; Boudou, Philippe; Blondeau, Bertrand; Roussel, Ronan; Ferré, Pascal; Ravussin, Eric; Rouzet, François; Marre, Michel

2015-01-01

Background Fetal exposure to hyperglycemia impacts negatively kidney development and function. Objective Our objective was to determine whether fetal exposure to moderate hyperglycemia is associated with epigenetic alterations in DNA methylation in peripheral blood cells and whether those alterations are related to impaired kidney function in adult offspring. Design Twenty nine adult, non-diabetic offspring of mothers with type 1 diabetes (T1D) (case group) were matched with 28 offspring of T1D fathers (control group) for the study of their leukocyte genome-wide DNA methylation profile (27,578 CpG sites, Human Methylation 27 BeadChip, Illumina Infinium). In a subset of 19 cases and 18 controls, we assessed renal vascular development by measuring Glomerular Filtration Rate (GFR) and Effective Renal Plasma Flow (ERPF) at baseline and during vasodilatation produced by amino acid infusion. Results Globally, DNA was under-methylated in cases vs. controls. Among the 87 CpG sites differently methylated, 74 sites were less methylated and 13 sites more methylated in cases vs. controls. None of these CpG sites were located on a gene known to be directly involved in kidney development and/or function. However, the gene encoding DNA methyltransferase 1 (DNMT1)—a key enzyme involved in gene expression during early development–was under-methylated in cases. The average methylation of the 74 under-methylated sites differently correlated with GFR in cases and controls. Conclusion Alterations in methylation profile imprinted by the hyperglycemic milieu of T1D mothers during fetal development may impact kidney function in adult offspring. The involved pathways seem to be a nonspecific imprinting process rather than specific to kidney development or function. PMID:26258530

Kidney Dysfunction in Adult Offspring Exposed In Utero to Type 1 Diabetes Is Associated with Alterations in Genome-Wide DNA Methylation.

PubMed

Gautier, Jean-François; Porcher, Raphaël; Abi Khalil, Charbel; Bellili-Munoz, Naima; Fetita, Lila Sabrina; Travert, Florence; Choukem, Simeon-Pierre; Riveline, Jean-Pierre; Hadjadj, Samy; Larger, Etienne; Boudou, Philippe; Blondeau, Bertrand; Roussel, Ronan; Ferré, Pascal; Ravussin, Eric; Rouzet, François; Marre, Michel

2015-01-01

Fetal exposure to hyperglycemia impacts negatively kidney development and function. Our objective was to determine whether fetal exposure to moderate hyperglycemia is associated with epigenetic alterations in DNA methylation in peripheral blood cells and whether those alterations are related to impaired kidney function in adult offspring. Twenty nine adult, non-diabetic offspring of mothers with type 1 diabetes (T1D) (case group) were matched with 28 offspring of T1D fathers (control group) for the study of their leukocyte genome-wide DNA methylation profile (27,578 CpG sites, Human Methylation 27 BeadChip, Illumina Infinium). In a subset of 19 cases and 18 controls, we assessed renal vascular development by measuring Glomerular Filtration Rate (GFR) and Effective Renal Plasma Flow (ERPF) at baseline and during vasodilatation produced by amino acid infusion. Globally, DNA was under-methylated in cases vs. controls. Among the 87 CpG sites differently methylated, 74 sites were less methylated and 13 sites more methylated in cases vs. controls. None of these CpG sites were located on a gene known to be directly involved in kidney development and/or function. However, the gene encoding DNA methyltransferase 1 (DNMT1)--a key enzyme involved in gene expression during early development--was under-methylated in cases. The average methylation of the 74 under-methylated sites differently correlated with GFR in cases and controls. Alterations in methylation profile imprinted by the hyperglycemic milieu of T1D mothers during fetal development may impact kidney function in adult offspring. The involved pathways seem to be a nonspecific imprinting process rather than specific to kidney development or function.

Cocaine-Induced Neurodevelopmental Deficits and Underlying Mechanisms

PubMed Central

Martin, Melissa M.; Graham, Devon L.; McCarthy, Deirdre M.; Bhide, Pradeep G.; Stanwood, Gregg D.

2017-01-01

Exposure to drugs early in life has complex and long-lasting implications for brain structure and function. This review summarizes work to date on the immediate and long-term effects of prenatal exposure to cocaine. In utero cocaine exposure produces disruptions in brain monoamines, particularly dopamine, during sensitive periods of brain development, and leads to permanent changes in specific brain circuits, molecules, and behavior. Here, we integrate clinical studies and significance with mechanistic preclinical studies, to define our current knowledge base and identify gaps for future investigation. PMID:27345015

[Significance of roentgen cinematography in the diagnosis of functional disorders of the pharyngo-esophageal junction].

PubMed

Augustiny, N; wolfensberger, M; Brühlmann, W

1984-12-01

Dysfunction of the pharyngo-oesophageal sphincter may escape detection by clinical examination, endoscopy, and routine barium studies. Cineradiographic examination of 300 patients with unexplained dysphagia revealed 57 cases of pharyngo-oesophageal dysfunction. In 25 cases an underlying disorder could be found, and 32 cases were considered idiopathic. Radiologically 3 types of dysfunction may be distinguished, namely late opening, incomplete relaxation, and early contraction of the pharyngo-oesophageal sphincter. Cineradiography was found to be an easy and reliable method of detecting pharyngo-oesophageal sphincter dysfunction.

Update on the Role of Extracorporeal CO2 Removal as an Adjunct to Mechanical Ventilation in ARDS

DTIC Science & Technology

2015-03-16

alveoli, atelectotrauma, and increased in- flammatory mediator levels [7]. The ARDSNet study re- ported a reduction in mortality with a ventilation... mortality rates [6]. Impaired RV function in early stage ARDS may be under- diagnosed and yet it might be the harbinger of a down- ward spiral in the ...them according to the ARDSNet protocol for 72 h, at which point the tidal volume was reduced from 6 to 4 ml/kg in all patients (n = 10) who had a plateau

Early Functional Treatment of Proximal Phalanx Fractures in Children: A Case Series Study.

PubMed

Bohr, Stefan; Mammadli, Toghrul

2018-05-23

The objective of this study was to assess proper indications a nonsurgical treatment regime for pediatric fractures of the proximal phalanx based on principles of early functional treatment. A case series (evidence level 4) of 30 pediatric patients with fractures of the proximal phalanx were treated nonsurgically using protective dynamic splinting techniques and fiberglass casting material. Assessments were performed clinically and by x-ray within 4 to 8 weeks of commencement of treatment. Outcome measures included Disabilities of the Arm, Shoulder, and Hand score questionnaire as well as fingertip palm distance (cm) and dynamic pain interval assessments. All fractures healed without any clinically apparent bony deformities. Disabilities of the Arm, Shoulder, and Hand scores were of 25.17 ± 5.29 (mean ± SD), which indicated good functional results usually within 2 weeks of removal of dynamic splints. Fingertip palm distance measurements at endpoints were of 0.17 ± 0.27 cm (mean ± SD), which indicated an almost free range of finger motion. Absence of pain perception under active finger motion (dynamic pain interval) was noted at 14.10 ± 6.79 days (mean ± SD). Well-established criteria for surgical treatment of phalangeal fractures exist. However, in our experience, a majority of pediatric fractures of the proximal phalanx can be safely treated nonsurgically with dynamic splinting along with shorter intervals of immobilization of the affected fingers and faster restoration of overall hand function compared to surgical treatment.

Low-dose atorvastatin improves dyslipidemia and vascular function in patients with primary biliary cirrhosis after one year of treatment.

PubMed

Stojakovic, Tatjana; Claudel, Thierry; Putz-Bankuti, Csilla; Fauler, Günter; Scharnagl, Hubert; Wagner, Martin; Sourij, Harald; Stauber, Rudolf E; Winkler, Karl; März, Winfried; Wascher, Thomas C; Trauner, Michael

2010-03-01

Primary biliary cirrhosis (PBC) is frequently associated with hypercholesterolemia and with an increased cardiovascular morbidity and mortality. Statins lower serum cholesterol levels and may thus improve the cardiovascular risk in PBC patients. The aim of our study was to prospectively examine the efficacy of low-dose atorvastatin on cholestasis as well as cardiovascular risk markers such as dyslipidemia and vascular function in patients with PBC. Nineteen patients with early-stage (biopsy proven and AMA positive) PBC and low-density lipoprotein cholesterol (LDL-C) above 130mg/dL were included in this single-center study and treated with atorvastatin 10mg per day for one year. Concentrations of total cholesterol, LDL-C, LDL triglycerides, oxLDL, IgG and sVCAM-1 decreased significantly after 48 weeks of atorvastatin treatment. Flow-mediated dilation (FMD) of the brachial artery as an indicator of vascular function significantly increased, while carotid artery intima-media thickness and vascular wall stiffness did not progress under treatment. No statistical differences in liver enzymes were observed except a transient increase of alkaline phosphatase. Treatment with low-dose atorvastatin is safe in early-stage PBC, effectively reduces total cholesterol, LDL-C, LDL triglycerides, oxLDL and sVCAM-1 and improves vascular function as reflected by FMD, without affecting cholestasis progression. Therefore, statin therapy should be considered in PBC patients with additional risk factors for cardiovascular disease.

Magnetic resonance imaging reveals elevated aortic pulse wave velocity in obese and overweight adolescents.

PubMed

Caterini, J E; Banks, L; Wells, G D; Cifra, B; Slorach, C; McCrindle, B W; Seed, M

2017-12-01

The aortic pulse wave velocity (PWV) measured via cardiac magnetic resonance (CMR) can be used to non-invasively assess changes in arterial stiffness and potential underlying vascular dysfunction. This technique could unmask early arterial dysfunction in overweight and obese youth at risk for cardiovascular disease. We sought to determine the association between vascular stiffness, percentage body fat, body mass index (BMI), and cardiac function in adolescents across the weight spectrum through both CMR and standard applanation tonometry (AT)-based PWV measurements. PWV and left-ventricular cardiac function were assessed using 3.0 T CMR in obese and overweight (OB/OW) participants (n = 12) and controls (n = 7). PWV was also estimated via carotid-femoral AT. OB/OW participants did not differ from healthy-weight controls regarding cardiometabolic risk factors or physical activity levels, but there was a trend towards higher levels of triglycerides in obese/overweight participants (P = 0.07). Mean PWV was higher in obese participants when corrected for age and sex (P = 0.01), and was positively associated with BMI (β = 0.51, P = 0.02). PWV estimated through AT was not significantly different between groups. Cardiac function measured by left-ventricular ejection fraction z-score was inversely associated with mean PWV (β = -0.57, P = 0.026). Increasing arterial stiffness and decreasing cardiac function were evident among our overweight and obese cohort. PWV estimated by CMR could detect early increases in arterial stiffness vs. traditional AT measurements of PWV. © 2017 World Obesity Federation.

Scents and Nonsense: Olfactory Dysfunction in Schizophrenia

PubMed Central

Turetsky, Bruce I.; Hahn, Chang-Gyu; Borgmann-Winter, Karin; Moberg, Paul J.

2009-01-01

Among the sensory modalities, olfaction is most closely associated with the frontal and temporal brain regions that are implicated in schizophrenia and most intimately related to the affective and mnemonic functions that these regions subserve. Olfactory probes may therefore be ideal tools through which to assess the structural and functional integrity of the neural substrates that underlie disease-related cognitive and emotional disturbances. Perhaps more importantly, to the extent that early sensory afferents are also disrupted in schizophrenia, the olfactory system—owing to its strategic anatomic location—may be especially vulnerable to such disruption. Olfactory dysfunction may therefore be a sensitive indicator of schizophrenia pathology and may even serve as an “early warning” sign of disease vulnerability or onset. In this article, we review the evidence supporting a primary olfactory sensory disturbance in schizophrenia. Convergent data indicate that structural and functional abnormalities extend from the cortex to the most peripheral elements of the olfactory system. These reflect, in part, a genetically mediated neurodevelopmental etiology. Gross structural and functional anomalies are mirrored by cellular and molecular abnormalities that suggest decreased or faulty innervation and/or dysregulation of intracellular signaling. A unifying mechanistic hypothesis may be the epigenetic regulation of gene expression. With the opportunity to obtain olfactory neural tissue from live patients through nasal epithelial biopsy, the peripheral olfactory system offers a uniquely accessible window through which the pathophysiological antecedents and sequelae of schizophrenia may be observed. This could help to clarify underlying brain mechanisms and facilitate identification of clinically relevant biomarkers. PMID:19793796

Early Child Care and Adolescent Functioning at the End of High School: Results from the NICHD Study of Early Child Care and Youth Development

ERIC Educational Resources Information Center

Vandell, Deborah Lowe; Burchinal, Margaret; Pierce, Kim M.

2016-01-01

Relations between early child care and adolescent functioning at the end of high school (EOHS; M age = 18.3 years) were examined in a prospective longitudinal study of 1,214 children. Controlling for extensive measures of family background, early child care was associated with academic standing and behavioral adjustment at the EOHS. More…

Thermal and fluid simulation of the environment under the dashboard, compared with measurement data

NASA Astrophysics Data System (ADS)

Popescu, C. S.; Sirbu, G. M.; Nita, I. C.

2017-10-01

The development of vehicles during the last decade is related to the evolution of electronic systems added in order to increase the safety and the number of services available on board, such as advanced driver-assistance systems (ADAS). Cars already have a complex computer network, with electronic control units (ECUs) connected to each other and receiving information from many sensors. The ECUs transfer an important heat power to the environment, while proper operating conditions need to be provided to ensure their reliability at high and low temperature, vibration and humidity. In a car cabin, electronic devices are usually placed in the compartment under the dashboard, an enclosed space designed for functional purposes. In the early stages of the vehicle design it has become necessary to analyse the environment under dashboard, by the use of Computational Fluid Dynamics (CFD) simulations and measurements. This paper presents the cooling of heat sinks by natural convection, a thermal and fluid simulation of the environment under the dashboard compared with test data.

Timing of myocardial trpm7 deletion during cardiogenesis variably disrupts adult ventricular function, conduction, and repolarization.

PubMed

Sah, Rajan; Mesirca, Pietro; Mason, Xenos; Gibson, William; Bates-Withers, Christopher; Van den Boogert, Marjolein; Chaudhuri, Dipayan; Pu, William T; Mangoni, Matteo E; Clapham, David E

2013-07-09

Transient receptor potential (TRP) channels are a superfamily of broadly expressed ion channels with diverse physiological roles. TRPC1, TRPC3, and TRPC6 are believed to contribute to cardiac hypertrophy in mouse models. Human mutations in TRPM4 have been linked to progressive familial heart block. TRPM7 is a divalent-permeant channel and kinase of unknown function, recently implicated in the pathogenesis of atrial fibrillation; however, its function in ventricular myocardium remains unexplored. We generated multiple cardiac-targeted knockout mice to test the hypothesis that TRPM7 is required for normal ventricular function. Early cardiac Trpm7 deletion (before embryonic day 9; TnT/Isl1-Cre) results in congestive heart failure and death by embryonic day 11.5 as a result of hypoproliferation of the compact myocardium. Remarkably, Trpm7 deletion late in cardiogenesis (about embryonic day 13; αMHC-Cre) produces viable mice with normal adult ventricular size, function, and myocardial transcriptional profile. Trpm7 deletion at an intermediate time point results in 50% of mice developing cardiomyopathy associated with heart block, impaired repolarization, and ventricular arrhythmias. Microarray analysis reveals elevations in transcripts of hypertrophy/remodeling genes and reductions in genes important for suppressing hypertrophy (Hdac9) and for ventricular repolarization (Kcnd2) and conduction (Hcn4). These transcriptional changes are accompanied by action potential prolongation and reductions in transient outward current (Ito; Kcnd2). Similarly, the pacemaker current (If; Hcn4) is suppressed in atrioventricular nodal cells, accounting for the observed heart block. Trpm7 is dispensable in adult ventricular myocardium under basal conditions but is critical for myocardial proliferation during early cardiogenesis. Loss of Trpm7 at an intermediate developmental time point alters the myocardial transcriptional profile in adulthood, impairing ventricular function, conduction, and repolarization.

Spaceflight and simulated microgravity cause a significant reduction of key gene expression in early T-cell activation

PubMed Central

Martinez, Emily M.; Yoshida, Miya C.; Candelario, Tara Lynne T.

2015-01-01

Healthy immune function depends on precise regulation of lymphocyte activation. During the National Aeronautics and Space Administration (NASA) Apollo and Shuttle eras, multiple spaceflight studies showed depressed lymphocyte activity under microgravity (μg) conditions. Scientists on the ground use two models of simulated μg (sμg): 1) the rotating wall vessel (RWV) and 2) the random positioning machine (RPM), to study the effects of altered gravity on cell function before advancing research to the true μg when spaceflight opportunities become available on the International Space Station (ISS). The objective of this study is to compare the effects of true μg and sμg on the expression of key early T-cell activation genes in mouse splenocytes from spaceflight and ground animals. For the first time, we compared all three conditions of microgravity spaceflight, RPM, and RWV during immune gene activation of Il2, Il2rα, Ifnγ, and Tagap; moreover, we confirm two new early T-cell activation genes, Iigp1 and Slamf1. Gene expression for all samples was analyzed using quantitative real-time PCR (qRT-PCR). Our results demonstrate significantly increased gene expression in activated ground samples with suppression of mouse immune function in spaceflight, RPM, and RWV samples. These findings indicate that sμg models provide an excellent test bed for scientists to develop baseline studies and augment true μg in spaceflight experiments. Ultimately, sμg and spaceflight studies in lymphocytes may provide insight into novel regulatory pathways, benefiting both future astronauts and those here on earth suffering from immune disorders. PMID:25568077

Spaceflight and simulated microgravity cause a significant reduction of key gene expression in early T-cell activation.

PubMed

Martinez, Emily M; Yoshida, Miya C; Candelario, Tara Lynne T; Hughes-Fulford, Millie

2015-03-15

Healthy immune function depends on precise regulation of lymphocyte activation. During the National Aeronautics and Space Administration (NASA) Apollo and Shuttle eras, multiple spaceflight studies showed depressed lymphocyte activity under microgravity (μg) conditions. Scientists on the ground use two models of simulated μg (sμg): 1) the rotating wall vessel (RWV) and 2) the random positioning machine (RPM), to study the effects of altered gravity on cell function before advancing research to the true μg when spaceflight opportunities become available on the International Space Station (ISS). The objective of this study is to compare the effects of true μg and sμg on the expression of key early T-cell activation genes in mouse splenocytes from spaceflight and ground animals. For the first time, we compared all three conditions of microgravity spaceflight, RPM, and RWV during immune gene activation of Il2, Il2rα, Ifnγ, and Tagap; moreover, we confirm two new early T-cell activation genes, Iigp1 and Slamf1. Gene expression for all samples was analyzed using quantitative real-time PCR (qRT-PCR). Our results demonstrate significantly increased gene expression in activated ground samples with suppression of mouse immune function in spaceflight, RPM, and RWV samples. These findings indicate that sμg models provide an excellent test bed for scientists to develop baseline studies and augment true μg in spaceflight experiments. Ultimately, sμg and spaceflight studies in lymphocytes may provide insight into novel regulatory pathways, benefiting both future astronauts and those here on earth suffering from immune disorders.

Adenoviral bcl-2 transfer improves survival and early graft function after ischemia and reperfusion in rat liver transplantation.

PubMed

Rentsch, Markus; Kienle, Klaus; Mueller, Thomas; Vogel, Mandy; Jauch, Karl Walter; Püllmann, Kerstin; Obed, Aiman; Schlitt, Hans J; Beham, Alexander

2005-11-27

Primary graft dysfunction due to ischemia and reperfusion injury represents a major problem in liver transplantation. The related cell stress may induce apoptosis, which can be suppressed by bcl-2. The purpose of the study was to investigate the effect of adenoviral bcl-2 gene transfer on early graft function and survival in rat liver transplantation. An adenoviral construct that transfers bcl-2 under the control of a tetracycline inducible promoter was generated (advTetOn bcl-2) and used with a second adenovirus that transfers the repressor protein (advCMV Rep). Forty-eight hours before explantation, donor rats were treated with advTetOn bcl-2/ advCMV Rep (n=7) and doxycyclin, with the control adenoviral construct advCMV GFP (n=8) or with doxycyclin alone (n=8). Liver transplantation was performed following 16 hours of cold storage (UW). Bcl-2 expression and intrahepatic apoptosis was assessed. Bile flow was monitored 90 min posttransplantation. The endpoint for survival was 7 days. Bcl-2 was expressed in hepatocytes and sinusoidal lining cells. This was associated with a significant reduction of apoptotic sinusoidal lining cells and hepatocytes after 24 hours and 7 days. Bile production was significantly higher following bcl-2 pretreatment. Furthermore, bcl-2 transfer resulted in significantly improved survival (100% vs. 50% both control groups). Adenoviral bcl-2 transfer results in protein expression in hepatocytes and sinusoidal lining cells resulting in early graft function and survival enhancement after prolonged ischemia and reperfusion injury. The inhibition of apoptosis in the context of liver transplantation might be a reasonable approach in the treatment of graft dysfunction.

The lower airway microbiota in early cystic fibrosis lung disease: a longitudinal analysis.

PubMed

Frayman, Katherine B; Armstrong, David S; Carzino, Rosemary; Ferkol, Thomas W; Grimwood, Keith; Storch, Gregory A; Teo, Shu Mei; Wylie, Kristine M; Ranganathan, Sarath C

2017-12-01

In infants and young children with cystic fibrosis, lower airway infection and inflammation are associated with adverse respiratory outcomes. However, the role of lower airway microbiota in the pathogenesis of early cystic fibrosis lung disease remains uncertain. To assess the development of the lower airway microbiota over time in infants and young children with cystic fibrosis, and to explore its association with airway inflammation and pulmonary function at age 6 years. Serial, semi-annual bronchoscopies and bronchoalveolar lavage (BAL) procedures were performed in infants newly diagnosed with cystic fibrosis following newborn screening. Quantitative microbiological cultures and inflammatory marker (interleukin 8 and neutrophil elastase) measurements were undertaken contemporaneously. 16S ribosomal RNA gene sequencing was conducted on stored BAL samples. Spirometry results recorded at 6 years of age were extracted from medical records. Ninety-five BAL samples provided 16S ribosomal RNA gene data. These were collected from 48 subjects aged 1.2-78.3 months, including longitudinal samples from 27 subjects and 13 before age 6 months. The lower airway microbiota varied, but diversity decreased with advancing age. Detection of recognised cystic fibrosis bacterial pathogens was associated with reduced microbial diversity and greater lower airway inflammation. There was no association between the lower airway microbiota and pulmonary function at age 6 years. In infants with cystic fibrosis, the lower airway microbiota is dynamic. Dominance of the microbiota by recognised cystic fibrosis bacterial pathogens is associated with increased lower airway inflammation, however early microbial diversity is not associated with pulmonary function at 6 years of age. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Hydration status and diurnal trophic interactions shape microbial community function in desert biocrusts

NASA Astrophysics Data System (ADS)

Kim, Minsu; Or, Dani

2017-12-01

Biological soil crusts (biocrusts) are self-organised thin assemblies of microbes, lichens, and mosses that are ubiquitous in arid regions and serve as important ecological and biogeochemical hotspots. Biocrust ecological function is intricately shaped by strong gradients of water, light, oxygen, and dynamics in the abundance and spatial organisation of the microbial community within a few millimetres of the soil surface. We report a mechanistic model that links the biophysical and chemical processes that shape the functioning of biocrust representative microbial communities that interact trophically and respond dynamically to cycles of hydration, light, and temperature. The model captures key features of carbon and nitrogen cycling within biocrusts, such as microbial activity and distribution (during early stages of biocrust establishment) under diurnal cycles and the associated dynamics of biogeochemical fluxes at different hydration conditions. The study offers new insights into the highly dynamic and localised processes performed by microbial communities within thin desert biocrusts.

CHIP as a membrane-shuttling proteostasis sensor

PubMed Central

Kopp, Yannick; Martínez-Limón, Adrián; Hofbauer, Harald F; Ernst, Robert; Calloni, Giulia

2017-01-01

Cells respond to protein misfolding and aggregation in the cytosol by adjusting gene transcription and a number of post-transcriptional processes. In parallel to functional reactions, cellular structure changes as well; however, the mechanisms underlying the early adaptation of cellular compartments to cytosolic protein misfolding are less clear. Here we show that the mammalian ubiquitin ligase C-terminal Hsp70-interacting protein (CHIP), if freed from chaperones during acute stress, can dock on cellular membranes thus performing a proteostasis sensor function. We reconstituted this process in vitro and found that mainly phosphatidic acid and phosphatidylinositol-4-phosphate enhance association of chaperone-free CHIP with liposomes. HSP70 and membranes compete for mutually exclusive binding to the tetratricopeptide repeat domain of CHIP. At new cellular locations, access to compartment-specific substrates would enable CHIP to participate in the reorganization of the respective organelles, as exemplified by the fragmentation of the Golgi apparatus (effector function). PMID:29091030

[Principles of organization and evolution of systems of regulation of functions].

PubMed

Veselkin, N P; Natochin, Iu V

2010-01-01

Evolution of living organisms is closely connected with evolution of structure of the system of regulations and its mechanisms. The functional ground of regulations is chemical signalization. As early as in unicellular organisms there is a set of signal mechanisms providing their life activity and orientation in space and time. Subsequent evolution of ways of chemical signalization followed the way of development of ways of delivery of chemical signal and development of mechanisms of its regulation. The mechanisms of chemical regulation of the signal interaction is discussed by the example of the specialized system of transduction of signal from neuron to neuron, of effect of hormone on the epithelial cell and modulation of this effect. These mechanisms are considered as the most important ways of the fine and precise adaptation of chemical signalization underlying functioning of physiological systems and organs of the living organism.

BDNF in fragile X syndrome.

PubMed

Castrén, Maija L; Castrén, Eero

2014-01-01

Fragile X syndrome (FXS) is a monogenic disorder that is caused by the absence of FMR1 protein (FMRP). FXS serves as an excellent model disorder for studies investigating disturbed molecular mechanisms and synapse function underlying cognitive impairment, autism, and behavioral disturbance. Abnormalities in dendritic spines and synaptic transmission in the brain of FXS individuals and mouse models for FXS indicate perturbations in the development, maintenance, and plasticity of neuronal network connectivity. However, numerous alterations are found during the early development in FXS, including abnormal differentiation of neural progenitors and impaired migration of newly born neurons. Several aspects of FMRP function are modulated by brain-derived neurotrophic factor (BDNF) signaling. Here, we review the evidence of the role for BDNF in the developing and adult FXS brain. This article is part of the Special Issue entitled 'BDNF Regulation of Synaptic Structure, Function, and Plasticity'. Copyright © 2013 Elsevier Ltd. All rights reserved.

Basic science for the clinician 53: mast cells.

PubMed

Sigal, Leonard H

2011-10-01

Mast cells stand at the interface between the innate immune system and the acquired (adaptive) immune response, serving as sentinels detecting invaders and directing a concerted and coordinated response. Mast cells reside immediately under body surfaces and within lymph nodes, near blood vessels and nerves, perfectly situated to for early detection and defense. They secrete a wide array of prostanoids, cytokines, chemokines, and other proteins mediators and modifiers of a variety of immune and inflammatory functions and bear surface markers suggesting broad functions, including as antigen-presenting cells. Although usually not given their due in medical school lectures, there is great likelihood that mast cells will be implicated in the pathogenesis of rheumatoid arthritis, scleroderma, multiple sclerosis, and perhaps cancer. Thus, better insights into mast cell functions and mast cell-derived effector molecules should command our attention as we move forward in better understanding disease immunopathogenesis and directed intelligent therapeutics development.

A Jurassic stem pleurodire sheds light on the functional origin of neck retraction in turtles

PubMed Central

Anquetin, Jérémy; Tong, Haiyan; Claude, Julien

2017-01-01

Modern turtles are composed of two monophyletic groups, notably diagnosed by divergent neck retraction mechanisms. Pleurodires (side-necked turtles) bend their neck sideways and protect their head under the anterior margin of the carapace. Cryptodires (hidden-necked turtles) withdraw their neck and head in the vertical plane between the shoulder girdles. These two mechanisms of neck retraction appeared independently in the two lineages and are usually assumed to have evolved for protective reasons. Here we describe the neck of Platychelys oberndorferi, a Late Jurassic early stem pleurodire, and find remarkable convergent morphological and functional similarities with modern cryptodires. Partial vertical neck retraction in this taxon is interpreted to have enabled fast forward projection of the head during underwater prey capture and offers a likely explanation to the functional origin of neck retraction in modern cryptodires. Complete head withdrawal for protection may therefore have resulted from an exaptation in that group. PMID:28206991

Understanding the Contribution of Zinc Transporters in the Function of the Early Secretory Pathway

PubMed Central

Matsunaga, Mayu; Takeda, Taka-aki

2017-01-01

More than one-third of newly synthesized proteins are targeted to the early secretory pathway, which is comprised of the endoplasmic reticulum (ER), Golgi apparatus, and other intermediate compartments. The early secretory pathway plays a key role in controlling the folding, assembly, maturation, modification, trafficking, and degradation of such proteins. A considerable proportion of the secretome requires zinc as an essential factor for its structural and catalytic functions, and recent findings reveal that zinc plays a pivotal role in the function of the early secretory pathway. Hence, a disruption of zinc homeostasis and metabolism involving the early secretory pathway will lead to pathway dysregulation, resulting in various defects, including an exacerbation of homeostatic ER stress. The accumulated evidence indicates that specific members of the family of Zn transporters (ZNTs) and Zrt- and Irt-like proteins (ZIPs), which operate in the early secretory pathway, play indispensable roles in maintaining zinc homeostasis by regulating the influx and efflux of zinc. In this review, the biological functions of these transporters are discussed, focusing on recent aspects of their roles. In particular, we discuss in depth how specific ZNT transporters are employed in the activation of zinc-requiring ectoenzymes. The means by which early secretory pathway functions are controlled by zinc, mediated by specific ZNT and ZIP transporters, are also subjects of this review. PMID:29048339

Understanding the Contribution of Zinc Transporters in the Function of the Early Secretory Pathway.

PubMed

Kambe, Taiho; Matsunaga, Mayu; Takeda, Taka-Aki

2017-10-19

More than one-third of newly synthesized proteins are targeted to the early secretory pathway, which is comprised of the endoplasmic reticulum (ER), Golgi apparatus, and other intermediate compartments. The early secretory pathway plays a key role in controlling the folding, assembly, maturation, modification, trafficking, and degradation of such proteins. A considerable proportion of the secretome requires zinc as an essential factor for its structural and catalytic functions, and recent findings reveal that zinc plays a pivotal role in the function of the early secretory pathway. Hence, a disruption of zinc homeostasis and metabolism involving the early secretory pathway will lead to pathway dysregulation, resulting in various defects, including an exacerbation of homeostatic ER stress. The accumulated evidence indicates that specific members of the family of Zn transporters (ZNTs) and Zrt- and Irt-like proteins (ZIPs), which operate in the early secretory pathway, play indispensable roles in maintaining zinc homeostasis by regulating the influx and efflux of zinc. In this review, the biological functions of these transporters are discussed, focusing on recent aspects of their roles. In particular, we discuss in depth how specific ZNT transporters are employed in the activation of zinc-requiring ectoenzymes. The means by which early secretory pathway functions are controlled by zinc, mediated by specific ZNT and ZIP transporters, are also subjects of this review.

Variable corneal compensation improves discrimination between normal and glaucomatous eyes with the scanning laser polarimeter.

PubMed

Tannenbaum, Dana P; Hoffman, Douglas; Lemij, Hans G; Garway-Heath, David F; Greenfield, David S; Caprioli, Joseph

2004-02-01

The presently available scanning laser polarimeter (SLP) has a fixed corneal compensator (FCC) that neutralizes corneal birefringence only in eyes with birefringence that matches the population mode. A prototype variable corneal compensator (VCC) provides neutralization of individual corneal birefringence based on individual macular retardation patterns. The aim of this study was to evaluate the relative ability of the SLP with the FCC and with the VCC to discriminate between normal and glaucomatous eyes. Prospective, nonrandomized, comparative case series. Algorithm-generating set consisting of 56 normal eyes and 55 glaucomatous eyes and an independent data set consisting of 83 normal eyes and 56 glaucomatous eyes. Sixteen retardation measurements were obtained with the SLP with the FCC and the VCC from all subjects. Dependency of parameters on age, gender, ethnic origin, and eye side was sought. Logistic regression was used to evaluate how well the various parameters could detect glaucoma. Discriminant functions were generated, and the area under the receiver operating characteristic (ROC) curve was determined. Discrimination between normal and glaucomatous eyes on the basis of single parameters was significantly better with the VCC than with the FCC for 6 retardation parameters: nasal average (P = 0.0003), superior maximum (P = 0.0003), ellipse average (P = 0.002), average thickness (P = 0.003), superior average (P = 0.010), and inferior average (P = 0.010). Discriminant analysis identified the optimal combination of parameters for the FCC and for the VCC. When the discriminant functions were applied to the independent data set, areas under the ROC curve were 0.84 for the FCC and 0.90 for the VCC (P<0.021). When the discriminant functions were applied to a subset of patients with early visual field loss, areas under the ROC curve were 0.82 for the FCC and 0.90 for the VCC (P<0.016). Individual correction for corneal birefringence with the VCC significantly improved the ability of the SLP to distinguish between normal and glaucomatous eyes and enabled detection of patients with early glaucoma.

The investigation of CD4+T-cell functions in primary HIV infection with antiretroviral therapy

PubMed Central

Sun, Yu; Fu, Yajing; Zhang, Zining; Tang, Tian; Liu, Jing; Ding, Haibo; Han, Xiaoxu; Xu, Junjie; Chu, Zhenxing; Shang, Hong; Jiang, Yongjun

2017-01-01

Abstract Human immunodeficiency virus (HIV) infection leads to reduced CD4+T-cell counts and immune dysfunction. Initiation of antiretroviral therapy (ART) in HIV primary infection has been recommended to achieve an optimal clinical outcome, but a comprehensive study on restoration of CD4+T-cell function in primary HIV-infected individuals with ART still needs to be eluciated. We investigated longitudinal changes in the CD4+T-cell counts, phenotypes, and functions in HIV-infected individuals with early ART (initiated within 6 months after HIV infection) or later ART (initiated more than 12 months after HIV infection). Patients from early ART and later ART groups had received ART for at least 1 year. Individuals with early ART had more CD4+T cells, a faster rate of CD4+T-cell recovery than those receiving later ART; the levels of CD4+T-cell activation and senescence were lower in early ART compared to those with later ART (P = .031; P = .016), but the activation was higher than normal controls (NC) (P = .001); thymic emigrant function was more upregulated in early ART than in later ART (P = .015), but still lower than NC (P = .027); proliferative capacity and interferon-γ secretion of CD4+T cells were significantly decreased in primary infection (P < .001; P = .029), and early ART restored these CD4+T-cell functions, there is no difference with NC, later ART could partially restore the functions of CD4+T cells, but it remained lower than that of NC (P = .005; P = .019). Early ART could better improve CD4+T-cell function. PMID:28700479

Effects of age and sex on developmental neural networks of visual-spatial attention allocation.

PubMed

Rubia, Katya; Hyde, Zoe; Halari, Rozmin; Giampietro, Vincent; Smith, Anna

2010-06-01

Compared to our understanding of the functional maturation of brain networks underlying complex cognitive abilities, hardly anything is known of the neurofunctional development of simpler cognitive abilities such as visuo-spatial attention allocation. Furthermore, nothing is known on the effect of gender on the functional development of attention allocation. This study employed event related functional magnetic resonance imaging to investigate effects of age, sex, and sex by age interactions on the brain activation of 63 males and females, between 13 to 38years, during a visual-spatial oddball task. Behaviourally, with increasing age, speed was traded for accuracy, indicative of a less impulsive performance style in older subjects. Increasing age was associated with progressively increased activation in typical areas of selective attention of lateral fronto-striatal and temporo-parietal brain regions. Sex difference analysis showed enhanced activation in right-hemispheric inferior frontal and superior temporal regions in females, and in left-hemispheric inferior temporo-parietal regions in males. Importantly, the age by sex interaction findings showed that these sex-dimorphic patterns of brain activation may be the result of underlying sex differences in the functional maturation of these brain regions, as females had sex-specific progressive age-correlations in the same right inferior fronto-striato-temporal areas, while male-specific age-correlations were in left medial temporal and parietal areas. The findings demonstrate progressive functional maturation of fronto-striato-parieto-temporal networks of the relatively simple function of attention allocation between early adolescence and mid-adulthood. They furthermore show that sex-dimorphic patterns of enhanced reliance on right inferior frontal, striatal and superior temporal regions in females and of left temporo-parietal regions in males during attention allocation may be the result of underlying sex differences in the functional maturation of these brain regions. Copyright 2010 Elsevier Inc. All rights reserved.

Early visual experience and the recognition of basic facial expressions: involvement of the middle temporal and inferior frontal gyri during haptic identification by the early blind

PubMed Central

Kitada, Ryo; Okamoto, Yuko; Sasaki, Akihiro T.; Kochiyama, Takanori; Miyahara, Motohide; Lederman, Susan J.; Sadato, Norihiro

2012-01-01

Face perception is critical for social communication. Given its fundamental importance in the course of evolution, the innate neural mechanisms can anticipate the computations necessary for representing faces. However, the effect of visual deprivation on the formation of neural mechanisms that underlie face perception is largely unknown. We previously showed that sighted individuals can recognize basic facial expressions by haptics surprisingly well. Moreover, the inferior frontal gyrus (IFG) and posterior superior temporal sulcus (pSTS) in the sighted subjects are involved in haptic and visual recognition of facial expressions. Here, we conducted both psychophysical and functional magnetic-resonance imaging (fMRI) experiments to determine the nature of the neural representation that subserves the recognition of basic facial expressions in early blind individuals. In a psychophysical experiment, both early blind and sighted subjects haptically identified basic facial expressions at levels well above chance. In the subsequent fMRI experiment, both groups haptically identified facial expressions and shoe types (control). The sighted subjects then completed the same task visually. Within brain regions activated by the visual and haptic identification of facial expressions (relative to that of shoes) in the sighted group, corresponding haptic identification in the early blind activated regions in the inferior frontal and middle temporal gyri. These results suggest that the neural system that underlies the recognition of basic facial expressions develops supramodally even in the absence of early visual experience. PMID:23372547

Early visual experience and the recognition of basic facial expressions: involvement of the middle temporal and inferior frontal gyri during haptic identification by the early blind.

PubMed

Kitada, Ryo; Okamoto, Yuko; Sasaki, Akihiro T; Kochiyama, Takanori; Miyahara, Motohide; Lederman, Susan J; Sadato, Norihiro

2013-01-01

Face perception is critical for social communication. Given its fundamental importance in the course of evolution, the innate neural mechanisms can anticipate the computations necessary for representing faces. However, the effect of visual deprivation on the formation of neural mechanisms that underlie face perception is largely unknown. We previously showed that sighted individuals can recognize basic facial expressions by haptics surprisingly well. Moreover, the inferior frontal gyrus (IFG) and posterior superior temporal sulcus (pSTS) in the sighted subjects are involved in haptic and visual recognition of facial expressions. Here, we conducted both psychophysical and functional magnetic-resonance imaging (fMRI) experiments to determine the nature of the neural representation that subserves the recognition of basic facial expressions in early blind individuals. In a psychophysical experiment, both early blind and sighted subjects haptically identified basic facial expressions at levels well above chance. In the subsequent fMRI experiment, both groups haptically identified facial expressions and shoe types (control). The sighted subjects then completed the same task visually. Within brain regions activated by the visual and haptic identification of facial expressions (relative to that of shoes) in the sighted group, corresponding haptic identification in the early blind activated regions in the inferior frontal and middle temporal gyri. These results suggest that the neural system that underlies the recognition of basic facial expressions develops supramodally even in the absence of early visual experience.

Early life influences on emotional reactivity: evidence that social enrichment has greater effects than handling on anxiety-like behaviors, neuroendocrine responses to stress and central BDNF levels.

PubMed

Cirulli, Francesca; Berry, Alessandra; Bonsignore, Luca Tommaso; Capone, Francesca; D'Andrea, Ivana; Aloe, Luigi; Branchi, Igor; Alleva, Enrico

2010-05-01

During the early post-natal phases the brain is experience-seeking and provided by a considerable plasticity which allows a fine tuning between the external environment and the developing organism. Since the early work of Seymour Levine, an impressive amount of research has clearly shown that stressful experiences exert powerful effects on the brain and body development. These effects can last throughout the entire life span influencing brain function and increasing the risk for depression and anxiety disorders. The mechanisms underlying the effects of early stress on the developing organism have been widely studied in rodents through experimental manipulations of the post-natal environment, such as handling, which have been shown to exert important effects on the emotional phenotype and the response to stress. In the present paper we review the relevant literature and present some original data indicating that, compared to handling, which imposes an external manipulation on the mother-infant relationship, social enrichment, in the form of communal rearing, in mice has very profound effects on animal's emotionality and the response to stress. These effects are also accompanied by important changes in central levels of brain-derived neurotrophic factor. The present data indicate that communal rearing has more pervasive effects than handling, strengthening previous data suggesting that it is a good animal model of reduced susceptibility to depression-like behavior. Overall, the availability of ever more sophisticated animal models represents a fundamental tool to translate basic research data into appropriate interventions for humans raised under traumatic or impoverished situations. (c) 2010 Elsevier Ltd. All rights reserved.

Intradermal microneedle delivery of insulin lispro achieves faster insulin absorption and insulin action than subcutaneous injection.

PubMed

Pettis, Ronald J; Ginsberg, Barry; Hirsch, Laurence; Sutter, Diane; Keith, Steven; McVey, Elaine; Harvey, Noel G; Hompesch, Marcus; Nosek, Leszek; Kapitza, Christoph; Heinemann, Lutz

2011-04-01

This study compared insulin lispro (IL) pharmacokinetics (PK) and pharmacodynamics (PD) delivered via microneedle intradermal (ID) injection with subcutaneous (SC) injection under euglycemic glucose clamp conditions. Ten healthy male volunteers were administered 10 international units (IU) of IL at 3 microneedle lengths (1.25, 1.50, or 1.75 mm) in a randomized, crossover fashion on Days 1-3 followed by a repetitive ID 1.5-mm microneedle dose (Day 4) and an SC dose (Day 5). Microneedle ID delivery resulted in more rapid absorption of IL, with decreased time to maximum insulin concentration (ID vs. SC: 36.0-46.4 vs. 64.3 min, P < 0.05) and higher fractional availability at early postinjection times. ID produced more rapid effects on glucose uptake with shorter times to maximal and early half-maximal glucose infusion rates (GIRs) (ID vs. SC: time to maximum GIR, 106-112 vs. 130 min, P < 0.05; early half-maximal GIR, 29-35 vs. 42 min), increased early GIR area under the curve (AUC), and faster offset of insulin action (shorter time to late half-maximal GIR: 271-287 vs. 309 min). Relative total insulin bioavailability (AUC to 360 min and AUC to infinite measurement) did not significantly differ between administration routes. ID PK/PD parameters showed some variation as a function of needle length. Delivery of ID IL was generally well tolerated, although transient, localized wheal formation and redness were observed at injection sites. Microneedle ID insulin lispro delivery enables more rapid onset and offset of metabolic effect than SC therapy and is safe and well tolerated; further study for insulin therapy is warranted.

The Development of Executive Function and Language Skills in the Early School Years

ERIC Educational Resources Information Center

Gooch, Debbie; Thompson, Paul; Nash, Hannah M.; Snowling, Margaret J.; Hulme, Charles

2016-01-01

Background: The developmental relationships between executive functions (EF) and early language skills are unclear. This study explores the longitudinal relationships between children's early EF and language skills in a sample of children with a wide range of language abilities including children at risk of dyslexia. In addition, we investigated…

Transactional relations between caregiving stress, executive functioning, and problem behavior from early childhood to early adolescence

PubMed Central

LaGasse, Linda L.; Conradt, Elisabeth; Karalunas, Sarah L.; Dansereau, Lynne M.; Butner, Jonathan E.; Shankaran, Seetha; Bada, Henrietta; Bauer, Charles R.; Whitaker, Toni M.; Lester, Barry M.

2016-01-01

Developmental psychopathologists face the difficult task of identifying the environmental conditions that may contribute to early childhood behavior problems. Highly stressed caregivers can exacerbate behavior problems, while children with behavior problems may make parenting more difficult and increase caregiver stress. Unknown is: (1) how these transactions originate, (2) whether they persist over time to contribute to the development of problem behavior and (3) what role resilience factors, such as child executive functioning, may play in mitigating the development of problem behavior. In the present study, transactional relations between caregiving stress, executive functioning, and behavior problems were examined in a sample of 1,388 children with prenatal drug exposures at three developmental time points: early childhood (birth-age 5), middle childhood (ages 6 to 9), and early adolescence (ages 10 to 13). Transactional relations differed between caregiving stress and internalizing versus externalizing behavior. Targeting executive functioning in evidence-based interventions for children with prenatal substance exposure who present with internalizing problems and treating caregiving psychopathology, depression, and parenting stress in early childhood may be particularly important for children presenting with internalizing behavior. PMID:27427803

Cognitive rehabilitation for patients with schizophrenia in Korea.

PubMed

Lee, Won Hye; Lee, Woo Kyeong

2017-02-01

Psychosocial rehabilitation programs received mental health professional support in addition to traditional medication therapy. Many psychosocial programs were developed since the 1990s, including cognitive remediation therapy. In this review, we focus on cognitive remediation therapy in Korea since the 1990s. We review several cognitive rehabilitation programs developed in Korea and their outcome studies and suggest future research directions and prospects. We reviewed cognitive rehabilitation programs including social cognitive training as well as more recent forms of computerized cognitive rehabilitation. Although there are differences in cognitive domains by training targets, almost all neurocognitive remediation trainings in Korea have beneficial effects on early visual processing, various attention types, and executive function. Future studies need to investigate the mechanisms and various mediators underlying the relationships between cognitive functions and functional outcomes. With more comprehensive cognitive and social cognitive programs, we can enhance both cognition and functional outcomes of the patients with schizophrenia. Copyright © 2016 Elsevier B.V. All rights reserved.

Parallel, exhaustive processing underlies logarithmic search functions: Visual search with cortical magnification.

PubMed

Wang, Zhiyuan; Lleras, Alejandro; Buetti, Simona

2018-04-17

Our lab recently found evidence that efficient visual search (with a fixed target) is characterized by logarithmic Reaction Time (RT) × Set Size functions whose steepness is modulated by the similarity between target and distractors. To determine whether this pattern of results was based on low-level visual factors uncontrolled by previous experiments, we minimized the possibility of crowding effects in the display, compensated for the cortical magnification factor by magnifying search items based on their eccentricity, and compared search performance on such displays to performance on displays without magnification compensation. In both cases, the RT × Set Size functions were found to be logarithmic, and the modulation of the log slopes by target-distractor similarity was replicated. Consistent with previous results in the literature, cortical magnification compensation eliminated most target eccentricity effects. We conclude that the log functions and their modulation by target-distractor similarity relations reflect a parallel exhaustive processing architecture for early vision.

Amotivation and functional outcomes in early schizophrenia.

PubMed

Fervaha, Gagan; Foussias, George; Agid, Ofer; Remington, Gary

2013-12-15

Negative symptoms, particularly amotivation/apathy, are intimately tied to functional outcomes. In the present study, apathy strongly predicted psychosocial functioning in a sample of early course schizophrenia patients. This relationship remained robust even after controlling for other clinical variables. These data suggest amotivation is core to functioning across the disease course. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Maternal work early in the lives of children and its distal associations with achievement and behavior problems: a meta-analysis.

PubMed

Lucas-Thompson, Rachel G; Goldberg, Wendy A; Prause, JoAnn

2010-11-01

This meta-analysis of 69 studies (1,483 effect sizes) used random effects models to examine maternal employment during infancy/early childhood in relation to 2 major domains of child functioning: achievement and behavior problems. Analyses of studies that spanned 5 decades indicated that, with a few exceptions, early employment was not significantly associated with later achievement or internalizing/externalizing behaviors. The exceptions were for teacher ratings of achievement and internalizing behaviors: Employment was associated with higher achievement and fewer internalizing behaviors. Substantial heterogeneity among the effect sizes prompted examination of moderators. Sample-level moderator analyses pointed to the importance of socioeconomic and contextual variables, with early employment most beneficial when families were challenged by single parenthood or welfare status. Maternal employment during Years 2 and 3 was associated with higher achievement. Some moderator analyses indicated negative effects of employment for middle-class and 2-parent families and for very early employment (child's first year). Associations also differed depending on whether effect sizes were adjusted for contextual variables. Only 1 study-level moderator (sex of first author) was significant after adjusting for other moderators. The small effect size and primarily nonsignificant results for main effects of early maternal employment should allay concerns about mothers working when children are young. However, negative findings associated with employment during the child's first year are compatible with calls for more generous maternal leave policies. Results highlight the importance of social context for identifying under which conditions and for which subgroups early maternal employment is associated with positive or negative child outcomes.

Dysfunction of cortical synapse-specific mitochondria in developing rats exposed to lead and its amelioration by ascorbate supplementation.

PubMed

Ahmad, Faraz; Salahuddin, Mohammad; Alamoudi, Widyan; Acharya, Sadananda

2018-01-01

Lead (Pb) is a widespread environmental neurotoxin and its exposure even in minute quantities can lead to compromised neuronal functions. A developing brain is particularly vulnerable to Pb mediated toxicity and early-life exposure leads to permanent alterations in brain development and neuronal signaling and plasticity, culminating into cognitive and behavioral dysfunctions and elevated risk of neuropsychiatric disorders later in life. Nevertheless, the underlying biochemical mechanisms have not been completely discerned. Because of their ability to fulfill high energy needs and to act as calcium buffers in events of high intensity neuronal activity as well as their adaptive regulatory capability to match the requirements of the dynamicity of synaptic signaling, synapse-specific or synaptic mitochondria (SM) are critical for synaptic development, function and plasticity. Our aim for the present study hence was to characterize the effects of early-life Pb exposure on the functions of SM of prepubertal rats. For this purpose, employing a chronic model of Pb neurotoxicity, we exposed rat pups perinatally and postnatally to Pb and used a plethora of colorimetric and fluorometric assays for assessing redox and bioenergetic properties of SM. In addition, taking advantage of its ability as an antioxidant and as a metal chelator, we employed ascorbic acid (vitamin C) supplementation as an ameliorative therapeutic strategy against Pb-induced neurotoxicity and dysfunction of SM. Our results suggest that early-life exposure to Pb leads to elevated oxidative stress in cortical SM with consequent compromises in its energy metabolism activity. Ascorbate supplementation resulted in significant recovery of Pb-induced oxidative stress and functional compromise of SM. Alterations in redox status and bioenergetic properties of SM could potentially contribute to the synaptic dysfunction observed in events of Pb neurotoxicity. Additionally, our study provides evidence for suitability of ascorbate as a significant ameliorative agent in tacking Pb neurotoxicity.

Early-life perturbations in glucocorticoid activity impacts on the structure, function and molecular composition of the adult zebrafish (Danio rerio) heart.

PubMed

Wilson, K S; Baily, J; Tucker, C S; Matrone, G; Vass, S; Moran, C; Chapman, K E; Mullins, J J; Kenyon, C; Hadoke, P W F; Denvir, M A

2015-10-15

Transient early-life perturbations in glucocorticoids (GC) are linked with cardiovascular disease risk in later life. Here the impact of early life manipulations of GC on adult heart structure, function and gene expression were assessed. Zebrafish embryos were incubated in dexamethasone (Dex) or injected with targeted glucocorticoid receptor (GR) morpholino knockdown (GR Mo) over the first 120 h post fertilisation (hpf); surviving embryos (>90%) were maintained until adulthood under normal conditions. Cardiac function, heart histology and cardiac genes were assessed in embryonic (120 hpf) and adult (120 days post fertilisation (dpf)) hearts. GR Mo embryos (120 hpf) had smaller hearts with fewer cardiomyocytes, less mature striation pattern, reduced cardiac function and reduced levels of vmhc and igf mRNA compared with controls. GR Mo adult hearts were smaller with diminished trabecular network pattern, reduced expression of vmhc and altered echocardiographic Doppler flow compared to controls. Dex embryos had larger hearts at 120 hpf (Dex 107.2 ± 3.1 vs. controls 90.2 ± 1.1 μm, p < 0.001) with a more mature trabecular network and larger cardiomyocytes (1.62 ± 0.13 cells/μm vs control 2.18 ± 0.13 cells/μm, p < 0.05) and enhanced cardiac performance compared to controls. Adult hearts were larger (1.02 ± 0.07 μg/mg vs controls 0.63 ± 0.06 μg/mg, p = 0.0007), had increased vmhc and gr mRNA levels. Perturbations in GR activity during embryonic development results in short and long-term alterations in the heart. Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Randomized Trial of Intelligent Sensor System for Early Illness Alerts in Senior Housing.

PubMed

Rantz, Marilyn; Phillips, Lorraine J; Galambos, Colleen; Lane, Kari; Alexander, Gregory L; Despins, Laurel; Koopman, Richelle J; Skubic, Marjorie; Hicks, Lanis; Miller, Steven; Craver, Andy; Harris, Bradford H; Deroche, Chelsea B

2017-10-01

Measure the clinical effectiveness and cost effectiveness of using sensor data from an environmentally embedded sensor system for early illness recognition. This sensor system has demonstrated in pilot studies to detect changes in function and in chronic diseases or acute illnesses on average 10 days to 2 weeks before usual assessment methods or self-reports of illness. Prospective intervention study in 13 assisted living (AL) communities of 171 residents randomly assigned to intervention (n=86) or comparison group (n=85) receiving usual care. Intervention participants lived with the sensor system an average of one year. Continuous data collected 24 hours/7 days a week from motion sensors to measure overall activity, an under mattress bed sensor to capture respiration, pulse, and restlessness as people sleep, and a gait sensor that continuously measures gait speed, stride length and time, and automatically assess for increasing fall risk as the person walks around the apartment. Continuously running computer algorithms are applied to the sensor data and send health alerts to staff when there are changes in sensor data patterns. The randomized comparison group functionally declined more rapidly than the intervention group. Walking speed and several measures from GaitRite, velocity, step length left and right, stride length left and right, and the fall risk measure of functional ambulation profile (FAP) all had clinically significant changes. The walking speed increase (worse) and velocity decline (worse) of 0.073 m/s for comparison group exceeded 0.05 m/s, a value considered to be a minimum clinically important difference. No differences were measured in health care costs. These findings demonstrate that sensor data with health alerts and fall alerts sent to AL nursing staff can be an effective strategy to detect and intervene in early signs of illness or functional decline. Copyright © 2017 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.

Brachial-ankle pulse wave velocity predicts decline in renal function and cardiovascular events in early stages of chronic kidney disease.

PubMed

Yoon, Hye Eun; Shin, Dong Il; Kim, Sung Jun; Koh, Eun Sil; Hwang, Hyeon Seok; Chung, Sungjin; Shin, Seok Joon

2013-01-01

In this study, we investigated the predictive capacity of the brachial-ankle aortic pulse wave velocity (baPWV), a marker of arterial stiffness, for the decline in renal function and for cardiovascular events in the early stages of chronic kidney disease (CKD). Two hundred forty-one patients who underwent a comprehensive check-up were included and were divided into two groups according to their estimated glomerular filtration rates (eGFR): patients with CKD categories G2, G3a and G3b (30 ≤ eGFR < 90 ml/min/1.73m(2), eGFR < 90 group; n=117) and those with eGFR ≥ 90 ml/min/1.73 m(2) (eGFR ≥ 90 group; n=124). The change in renal function, the eGFR change, was determined by the slope of eGFR against time. We analysed whether baPWV was associated with eGFR change or predicted cardiovascular events. baPWV was independently associated with eGFR change in a multivariate analysis of the total patients (β=-0.011, p=0.011) and remained significantly associated with eGFR change in a subgroup analysis of the eGFR < 90 group (β=-0.015, p=0.035). baPWV was independently associated with cardiovascular events (odds ratio=1.002, p=0.048) in the eGFR < 90 group, but not in the eGFR ≥ 90 group. The receiver operative characteristic curve analysis showed that 1,568 cm/sec was the cut-off value of baPWV for predicting CV events in the eGFR < 90 group (area under curve=0.691, p=0.03) CONCLUSIONS: In patients with early stages of CKD, baPWV was independently associated with the decline in renal function and short-term cardiovascular events.

Early-life perturbations in glucocorticoid activity impacts on the structure, function and molecular composition of the adult zebrafish (Danio rerio) heart

PubMed Central

Wilson, K.S.; Baily, J.; Tucker, C.S.; Matrone, G.; Vass, S.; Moran, C.; Chapman, K.E.; Mullins, J.J.; Kenyon, C.; Hadoke, P.W.F.; Denvir, M.A.

2015-01-01

Background Transient early-life perturbations in glucocorticoids (GC) are linked with cardiovascular disease risk in later life. Here the impact of early life manipulations of GC on adult heart structure, function and gene expression were assessed. Methods and results Zebrafish embryos were incubated in dexamethasone (Dex) or injected with targeted glucocorticoid receptor (GR) morpholino knockdown (GR Mo) over the first 120 h post fertilisation (hpf); surviving embryos (>90%) were maintained until adulthood under normal conditions. Cardiac function, heart histology and cardiac genes were assessed in embryonic (120 hpf) and adult (120 days post fertilisation (dpf)) hearts. GR Mo embryos (120 hpf) had smaller hearts with fewer cardiomyocytes, less mature striation pattern, reduced cardiac function and reduced levels of vmhc and igf mRNA compared with controls. GR Mo adult hearts were smaller with diminished trabecular network pattern, reduced expression of vmhc and altered echocardiographic Doppler flow compared to controls. Dex embryos had larger hearts at 120 hpf (Dex 107.2 ± 3.1 vs. controls 90.2 ± 1.1 μm, p < 0.001) with a more mature trabecular network and larger cardiomyocytes (1.62 ± 0.13 cells/μm vs control 2.18 ± 0.13 cells/μm, p < 0.05) and enhanced cardiac performance compared to controls. Adult hearts were larger (1.02 ± 0.07 μg/mg vs controls 0.63 ± 0.06 μg/mg, p = 0.0007), had increased vmhc and gr mRNA levels. Conclusion Perturbations in GR activity during embryonic development results in short and long-term alterations in the heart. PMID:26219824

Accessing Autonomic Function Can Early Screen Metabolic Syndrome

PubMed Central

Dai, Meng; Li, Mian; Yang, Zhi; Xu, Min; Xu, Yu; Lu, Jieli; Chen, Yuhong; Liu, Jianmin; Ning, Guang; Bi, Yufang

2012-01-01

Background Clinical diagnosis of the metabolic syndrome is time-consuming and invasive. Convenient instruments that do not require laboratory or physical investigation would be useful in early screening individuals at high risk of metabolic syndrome. Examination of the autonomic function can be taken as a directly reference and screening indicator for predicting metabolic syndrome. Methodology and Principal Findings The EZSCAN test, as an efficient and noninvasive technology, can access autonomic function through measuring electrochemical skin conductance. In this study, we used EZSCAN value to evaluate autonomic function and to detect metabolic syndrome in 5,887 participants aged 40 years or older. The EZSCAN test diagnostic accuracy was analyzed by receiver operating characteristic curves. Among the 5,815 participants in the final analysis, 2,541 were diagnosed as metabolic syndrome and the overall prevalence was 43.7%. Prevalence of the metabolic syndrome increased with the elevated EZSCAN risk level (p for trend <0.0001). Moreover, EZSCAN value was associated with an increase in the number of metabolic syndrome components (p for trend <0.0001). Compared with the no risk group (EZSCAN value 0–24), participants at the high risk group (EZSCAN value: 50–100) had a 2.35 fold increased risk of prevalent metabolic syndrome after the multiple adjustments. The area under the curve of the EZSCAN test was 0.62 (95% confidence interval [CI], 0.61–0.64) for predicting metabolic syndrome. The optimal operating point for the EZSCAN value to detect a high risk of prevalent metabolic syndrome was 30 in this study, while the sensitivity and specificity were 71.2% and 46.7%, respectively. Conclusions and Significance In conclusion, although less sensitive and accurate when compared with the clinical definition of metabolic syndrome, we found that the EZSCAN test is a good and simple screening technique for early predicting metabolic syndrome. PMID:22916265

Data-model integration to interpret connectivity between biogeochemical cycling, and vegetation phenology and productivity in mountainous ecosystems under changing hydrologic regimes

NASA Astrophysics Data System (ADS)

Brodie, E.; Arora, B.; Beller, H. R.; Bill, M.; Bouskill, N.; Chakraborty, R.; Conrad, M. E.; Dafflon, B.; Enquist, B. J.; Falco, N.; Henderson, A.; Karaoz, U.; Polussa, A.; Sorensen, P.; Steltzer, H.; Wainwright, H. M.; Wang, S.; Williams, K. H.; Wilmer, C.; Wu, Y.

2017-12-01

In mountainous systems, snow-melt is associated with a large pulse of nutrients that originates from under-snow microbial mineralization of organic matter and microbial biomass turnover. Vegetation phenology in these systems is regulated by environmental cues such as air temperature ranges and photoperiod, such that, under typical conditions, vegetation greening and nutrient uptake occur in sync with microbial biomass turnover and nutrient release, closing nutrient cycles and enhancing nutrient retention. However, early snow-melt has been observed with increasing frequency in the mountainous west and is hypothesized to disrupt coupled plant-microbial behavior, potentially resulting in a temporal discontinuity between microbial nutrient release and vegetation greening. As part of the Watershed Function Scientific Focus Area (SFA) at Berkeley Lab we are quantifying below-ground biogeochemistry and above-ground phenology and vegetation chemistry and their relationships to hydrologic events at a lower montane hillslope in the East River catchment, Crested Butte, CO. This presentation will focus on data-model integration to interpret connectivity between biogeochemical cycling of nitrogen and vegetation nitrogen demand. Initial model results suggest that early snow-melt will result in an earlier accumulation and leaching loss of nitrate from the upper soil depths but that vegetation productivity may not decline as traits such as greater rooting depth and resource allocation to stems are favored.

Cognitive advantages and disadvantages in early and late bilinguals.

PubMed

Pelham, Sabra D; Abrams, Lise

2014-03-01

Previous research has documented advantages and disadvantages of early bilinguals, defined as learning a 2nd language by school age and using both languages since that time. Relative to monolinguals, early bilinguals manifest deficits in lexical access but benefits in executive function. We investigated whether becoming bilingual after childhood (late bilinguals) can produce the cognitive advantages and disadvantages typical of early bilinguals. Participants were 30 monolingual English speakers, 30 late English-Spanish bilinguals, and 30 early Spanish-English bilinguals who completed a picture naming task (lexical access) and an attentional network task (executive function). Late and early bilinguals manifested equivalent cognitive effects in both tasks, demonstrating lexical access deficits and executive function benefits. These findings provide support for the hypothesis that cognitive effects associated with bilingualism arise as the result of proficient, habitual use of 2 languages and not of developmental changes associated with becoming bilingual during childhood.

34 CFR 694.2 - Which students must a Partnership, or a State that chooses to use the cohort approach in its...

Code of Federal Regulations, 2010 CFR

2010-07-01

... chooses to use the cohort approach in its project, serve under the program's early intervention component... cohort approach in its project, serve under the program's early intervention component? A Partnership, or a State that chooses to use a cohort approach in its GEAR UP early intervention component, must...

34 CFR 694.2 - Which students must a Partnership, or a State that chooses to use the cohort approach in its...

Code of Federal Regulations, 2013 CFR

2013-07-01

... chooses to use the cohort approach in its project, serve under the program's early intervention component... chooses to use the cohort approach in its project, serve under the program's early intervention component? A Partnership, or a State that chooses to use a cohort approach in its GEAR UP early intervention...

34 CFR 694.2 - Which students must a Partnership, or a State that chooses to use the cohort approach in its...

Code of Federal Regulations, 2012 CFR

2012-07-01

... chooses to use the cohort approach in its project, serve under the program's early intervention component... chooses to use the cohort approach in its project, serve under the program's early intervention component? A Partnership, or a State that chooses to use a cohort approach in its GEAR UP early intervention...

34 CFR 694.2 - Which students must a Partnership, or a State that chooses to use the cohort approach in its...

Code of Federal Regulations, 2014 CFR

2014-07-01

... chooses to use the cohort approach in its project, serve under the program's early intervention component... chooses to use the cohort approach in its project, serve under the program's early intervention component? A Partnership, or a State that chooses to use a cohort approach in its GEAR UP early intervention...

34 CFR 694.2 - Which students must a Partnership, or a State that chooses to use the cohort approach in its...

Code of Federal Regulations, 2011 CFR

2011-07-01

... chooses to use the cohort approach in its project, serve under the program's early intervention component... chooses to use the cohort approach in its project, serve under the program's early intervention component? A Partnership, or a State that chooses to use a cohort approach in its GEAR UP early intervention...

78 FR 10183 - Ryan White HIV/AIDS Program, Part C Early Intervention Services Grant Under the Ryan White HIV...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-13

... HIV/AIDS Program, Part C Early Intervention Services Grant Under the Ryan White HIV/AIDS Program... persons living with HIV/AIDS, HRSA will be providing a one-time noncompetitive Part C funds award to DFHS... provided critical Ryan White HIV/AIDS Program (Part C) Early Intervention Services for over 427 persons...

78 FR 78976 - Ryan White HIV/AIDS Program Part C Early Intervention Services Grant Under the Ryan White HIV...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-27

... HIV/AIDS Program Part C Early Intervention Services Grant Under the Ryan White HIV/AIDS Program AGENCY...: Notice of Ryan White HIV/AIDS Program Part C Early Intervention Services One-Time Noncompetitive Award To Ensure Continued HIV Primary Medical Care. SUMMARY: To prevent a lapse in comprehensive primary care...

The Transient High Energy Sky and Early Universe Surveyor (THESEUS)

NASA Astrophysics Data System (ADS)

Amati, Lorenzo; O'Brien, Paul T.; Götz, Diego

2016-07-01

The Transient High Energy Sky and Early Universe Surveyor (THESEUS) is a mission concept under development by a large international collaboration aimed at exploiting gamma-ray bursts for investigating the early Universe. The main scientific objectives of THESEUS include: investigating the star formation rate and metallicity evolution of the ISM and IGM up to redshift 9-10, detecting the first generation (pop III) of stars, studying the sources and physics of re-ionization, detecting the faint end of galaxies luminosity function. These goals will be achieved through a unique combination of instruments allowing GRB detection and arcmin localization over a broad FOV (more than 1sr) and an energy band extending from several MeVs down to 0.3 keV with unprecedented sensitivity, as well as on-board prompt (few minutes) follow-up with a 0.6m class IR telescope with both imaging and spectroscopic capabilities. Such instrumentation will also allow THESEUS to unveil and study the population of soft and sub-energetic GRBs, and, more in general, to perform monitoring and survey of the X-ray sky with unprecedented sensitivity.

Age effects on preattentive and early attentive auditory processing of redundant stimuli: is sensory gating affected by physiological aging?

PubMed

Gmehlin, Dennis; Kreisel, Stefan H; Bachmann, Silke; Weisbrod, Matthias; Thomas, Christine

2011-10-01

The frontal hypothesis of aging predicts an age-related decline in cognitive functions requiring inhibitory or attentional regulation. In Alzheimer's disease, preattentive gating out of redundant information is impaired. Our study aimed to examine changes associated with physiological aging in both pre- and early attentive inhibition of recurrent acoustic information. Using a passive double-click paradigm, we recorded mid-latency (P30-P50) and late-latency (N100 and P200) evoked potentials in healthy young (26 ± 5 years) and healthy elderly subjects (72 ± 5 years). Physiological aging did not affect auditory gating in amplitude measures. Both age groups exhibited clear inhibition in preattentive P50 and attention-modulated (N100) components, whereas P30 was not attenuated. Irrespective of age, the magnitude of inhibition differed significantly, being most pronounced for N100 gating. Inhibition of redundant information seems to be preserved with physiological aging. Early attentive N100 gating showed the maximum effect. Further studies are warranted to evaluate sensory gating as a suitable biomarker of underlying neurodegenerative disease.

Quality of life in breast cancer sufferers.

PubMed

Shouman, Ahmed Essmat; Abou El Ezz, Nahla Fawzy; Gado, Nivine; Ibrahim Goda, Amal Mahmoud

2016-08-08

Purpose - The purpose of this paper is to measure health-related quality of life (QOL) among patients with early stage cancer breast under curative treatment at department of oncology and nuclear medicine at Ain Shams University Hospitals. Identify factors affecting QOL among these patients. Design/methodology/approach - A cross-sectional study measured QOL among early stage female breast cancer (BC) patients and determined the main factors affecting their QOL. Three interviewer administered questionnaires were used. Findings - The physical domain mostly affected in BC patients and the functional domain least. Socio-demographic factors that significantly affected BC patients QOL scores were patient age, education, having children and family income. Specific patient characteristics include caregiver presence - a factor that affected different QOL scores. Age at diagnosis, affection in the side of the predominant hand, post-operative chemotherapy and difficulty in obtaining the medication were the disease-related factors that affected QOL scores. Originality/value - The final model predicting QOL for early stage female BC patients included age, education and difficulty in obtaining the medication as determinants for total QOL score. Carer presence was the specific patient characteristic that affected different QOL scores.

Future perspectives toward the early definition of a multivariate decision-support scheme employed in clinical decision making for senior citizens.

PubMed

Frantzidis, Christos A; Gilou, Sotiria; Billis, Antonis; Karagianni, Maria; Bratsas, Charalampos D; Bamidis, Panagiotis

2016-03-01

Recent neuroscientific studies focused on the identification of pathological neurophysiological patterns (emotions, geriatric depression, memory impairment and sleep disturbances) through computerised clinical decision-support systems. Almost all these research attempts employed either resting-state condition (e.g. eyes-closed) or event-related potentials extracted during a cognitive task known to be affected by the disease under consideration. This Letter reviews existing data mining techniques and aims to enhance their robustness by proposing a holistic decision framework dealing with comorbidities and early symptoms' identification, while it could be applied in realistic occasions. Multivariate features are elicited and fused in order to be compared with average activities characteristic of each neuropathology group. A proposed model of the specific cognitive function which may be based on previous findings (a priori information) and/or validated by current experimental data should be then formed. So, the proposed scheme facilitates the early identification and prevention of neurodegenerative phenomena. Neurophysiological semantic annotation is hypothesised to enhance the importance of the proposed framework in facilitating the personalised healthcare of the information society and medical informatics research community.

Brain network informed subject community detection in early-onset schizophrenia.

PubMed

Yang, Zhi; Xu, Yong; Xu, Ting; Hoy, Colin W; Handwerker, Daniel A; Chen, Gang; Northoff, Georg; Zuo, Xi-Nian; Bandettini, Peter A

2014-07-03

Early-onset schizophrenia (EOS) offers a unique opportunity to study pathophysiological mechanisms and development of schizophrenia. Using 26 drug-naïve, first-episode EOS patients and 25 age- and gender-matched control subjects, we examined intrinsic connectivity network (ICN) deficits underlying EOS. Due to the emerging inconsistency between behavior-based psychiatric disease classification system and the underlying brain dysfunctions, we applied a fully data-driven approach to investigate whether the subjects can be grouped into highly homogeneous communities according to the characteristics of their ICNs. The resultant subject communities and the representative characteristics of ICNs were then associated with the clinical diagnosis and multivariate symptom patterns. A default mode ICN was statistically absent in EOS patients. Another frontotemporal ICN further distinguished EOS patients with predominantly negative symptoms. Connectivity patterns of this second network for the EOS patients with predominantly positive symptom were highly similar to typically developing controls. Our post-hoc functional connectivity modeling confirmed that connectivity strength in this frontotemporal circuit was significantly modulated by relative severity of positive and negative syndromes in EOS. This study presents a novel subtype discovery approach based on brain networks and proposes complex links between brain networks and symptom patterns in EOS.

Circadian Desynchrony Promotes Metabolic Disruption in a Mouse Model of Shiftwork

PubMed Central

Barclay, Johanna L.; Husse, Jana; Bode, Brid; Naujokat, Nadine; Meyer-Kovac, Judit; Schmid, Sebastian M.; Lehnert, Hendrik; Oster, Henrik

2012-01-01

Shiftwork is associated with adverse metabolic pathophysiology, and the rising incidence of shiftwork in modern societies is thought to contribute to the worldwide increase in obesity and metabolic syndrome. The underlying mechanisms are largely unknown, but may involve direct physiological effects of nocturnal light exposure, or indirect consequences of perturbed endogenous circadian clocks. This study employs a two-week paradigm in mice to model the early molecular and physiological effects of shiftwork. Two weeks of timed sleep restriction has moderate effects on diurnal activity patterns, feeding behavior, and clock gene regulation in the circadian pacemaker of the suprachiasmatic nucleus. In contrast, microarray analyses reveal global disruption of diurnal liver transcriptome rhythms, enriched for pathways involved in glucose and lipid metabolism and correlating with first indications of altered metabolism. Although altered food timing itself is not sufficient to provoke these effects, stabilizing peripheral clocks by timed food access can restore molecular rhythms and metabolic function under sleep restriction conditions. This study suggests that peripheral circadian desynchrony marks an early event in the metabolic disruption associated with chronic shiftwork. Thus, strengthening the peripheral circadian system by minimizing food intake during night shifts may counteract the adverse physiological consequences frequently observed in human shift workers. PMID:22629359

76 FR 77537 - Early Retiree Reinsurance Program

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-13

... Early Retiree Reinsurance Program (ERRP), is exercising its authority under the ERRP regulations at 45... for ERRP as of May 6, 2011. II. Provisions of This Notice CMS is exercising our authority under 45 CFR...

[Disorders of higher mental functions in the early stages of hydrocephalus].

PubMed

Simernitskaia, E G; Simernitskiĭ, B P

1981-01-01

The authors have carried out neuropsychological examinations of 32 children operated for hydrocephalus on the first year of the life. A syndrome of the higher psychic function disturbances characteristics for children with early hydrocephalus is described, and the results of the neuropsychological function examinations were compared with the character, etiology, and gravity of the hydrocephalus. In the children with the early hydrocephalus a high incidence of sinistrality was revealed, the fact, that gives one grounds to explain the peculiarities of the syndrome observed in them by an anomaly of the development of the brain functional asymmetry.

An early warning and control system for urban, drinking water quality protection: China's experience.

PubMed

Hou, Dibo; Song, Xiaoxuan; Zhang, Guangxin; Zhang, Hongjian; Loaiciga, Hugo

2013-07-01

An event-driven, urban, drinking water quality early warning and control system (DEWS) is proposed to cope with China's urgent need for protecting its urban drinking water. The DEWS has a web service structure and provides users with water quality monitoring functions, water quality early warning functions, and water quality accident decision-making functions. The DEWS functionality is guided by the principles of control theory and risk assessment as applied to the feedback control of urban water supply systems. The DEWS has been deployed in several large Chinese cities and found to perform well insofar as water quality early warning and emergency decision-making is concerned. This paper describes a DEWS for urban water quality protection that has been developed in China.

Early postnatal exposure to isoflurane causes cognitive deficits and disrupts development of newborn hippocampal neurons via activation of the mTOR pathway

PubMed Central

Lim, Sanghee; Kwak, Minhye; Gray, Christy D.; Xu, Michael; Choi, Jun H.; Junn, Sue; Kim, Jieun; Xu, Jing; Schaefer, Michele; Johns, Roger A.; Song, Hongjun; Ming, Guo-Li; Mintz, C. David

2017-01-01

Clinical and preclinical studies indicate that early postnatal exposure to anesthetics can lead to lasting deficits in learning and other cognitive processes. The mechanism underlying this phenomenon has not been clarified and there is no treatment currently available. Recent evidence suggests that anesthetics might cause persistent deficits in cognitive function by disrupting key events in brain development. The hippocampus, a brain region that is critical for learning and memory, contains a large number of neurons that develop in the early postnatal period, which are thus vulnerable to perturbation by anesthetic exposure. Using an in vivo mouse model we demonstrate abnormal development of dendrite arbors and dendritic spines in newly generated dentate gyrus granule cell neurons of the hippocampus after a clinically relevant isoflurane anesthesia exposure conducted at an early postnatal age. Furthermore, we find that isoflurane causes a sustained increase in activity in the mechanistic target of rapamycin pathway, and that inhibition of this pathway with rapamycin not only reverses the observed changes in neuronal development, but also substantially improves performance on behavioral tasks of spatial learning and memory that are impaired by isoflurane exposure. We conclude that isoflurane disrupts the development of hippocampal neurons generated in the early postnatal period by activating a well-defined neurodevelopmental disease pathway and that this phenotype can be reversed by pharmacologic inhibition. PMID:28683067

Trajectories of positive, negative and general psychopathology symptoms in first episode psychosis and their relationship with functioning over a 2-year follow-up period.

PubMed

Abdin, Edimansyah; Chong, Siow Ann; Vaingankar, Janhavi Ajit; Peh, Chao Xu; Poon, Lye Yin; Rao, Sujatha; Verma, Swapna; Subramaniam, Mythily

2017-01-01

Few studies have examined the trajectories of symptom severity in first episode psychosis (FEP) and their impact on functioning. This study aimed to identify discrete trajectories of positive, negative and general psychopathological symptoms and functioning, determine predictors of the identified symptom trajectories and subsequently investigate the relationship between symptom and functioning trajectories over the 2-year follow-up period. Data were extracted from the Singapore Early Psychosis Intervention Programme clinical database. Trajectories of the Positive and Negative Syndrome Scale and Global Assessment of Functioning (GAF) scale over the two-year follow up were modelled using latent class growth curve modelling. Two distinct trajectories (early response and stable trajectory and delayed response trajectory) for positive symptoms, four distinct trajectories (early response and stable trajectory, early response and relapse trajectory, slower response and no response trajectory and delayed response trajectory) for negative and general psychopathology symptoms and three distinct trajectories for functioning (high functioning trajectory, moderately stable functioning trajectory and deterioration in functioning trajectory) were identified in our sample. Compared to individuals in the early response and stable trajectory, those in the delayed response trajectory for positive and negative symptoms, early response and relapse for negative and general psychopathology symptoms and slower response and no response trajectories for general psychopathology symptoms were significantly associated with higher odds of having deterioration in functioning over time. Poor symptom trajectories were also significantly predicted by younger age, male gender, unemployed and economically inactive status, lower education, longer duration of untreated psychosis and diagnosis of schizophrenia spectrum and delusional disorders. The results confirm that the symptoms trajectories among patients with FEP are heterogeneous and suggest that a small group of patients may be at higher risk of deterioration in symptom severity and functioning over the 2-year follow-up.

Form, function and environments of the early angiosperms: merging extant phylogeny and ecophysiology with fossils.

PubMed

Feild, Taylor S; Arens, Nan Crystal

2005-05-01

The flowering plants--angiosperms--appeared during the Early Cretaceous period and within 10-30 Myr dominated the species composition of many floras worldwide. Emerging insights into the phylogenetics of development and discoveries of early angiosperm fossils are shedding increased light on the patterns and processes of early angiosperm evolution. However, we also need to integrate ecology, in particular how early angiosperms established a roothold in pre-existing Mesozoic plant communities. These events were critical in guiding subsequent waves of angiosperm diversification during the Aptian-Albian. Previous pictures of the early flowering plant ecology have been diverse, ranging from large tropical rainforest trees, weedy drought-adapted and colonizing shrubs, disturbance- and sun-loving rhizomatous herbs, and, more recently, aquatic herbs; however, none of these images were tethered to a robust hypothesis of angiosperm phylogeny. Here, we synthesize our current understanding of early angiosperm ecology, focusing on patterns of functional ecology, by merging recent molecular phylogenetic studies and functional studies on extant 'basal angiosperms' with the picture of early angiosperm evolution drawn by the fossil record.

Functional analysis of a tyrosinase gene involved in early larval shell biogenesis in Crassostrea angulata and its response to ocean acidification.

PubMed

Yang, Bingye; Pu, Fei; Li, Lingling; You, Weiwei; Ke, Caihuan; Feng, Danqing

2017-04-01

The formation of the primary shell is a vital process in marine bivalves. Ocean acidification largely influences shell formation. It has been reported that enzymes involved in phenol oxidation, such as tyrosinase and phenoloxidases, participate in the formation of the periostracum. In the present study, we cloned a tyrosinase gene from Crassostrea angulata named Ca-tyrA1, and its potential function in early larval shell biogenesis was investigated. The Ca-tyrA1 gene has a full-length cDNA of 2430bp in size, with an open reading frame of 1896bp in size, which encodes a 631-amino acid protein that includes a 24-amino acid putative signal peptide. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analysis revealed that Ca-tyrA1 transcription mainly occurs at the trochophore stage, and the Ca-tyrA1 mRNA levels in the 3000ppm treatment group were significantly upregulated in the early D-veliger larvae. WMISH and electron scanning microscopy analyses showed that the expression of Ca-tyrA1 occurs at the gastrula stage, thereby sustaining the early D-veliger larvae, and the shape of its signal is saddle-like, similar to that observed under an electron scanning microscope. Furthermore, the RNA interference has shown that the treatment group has a higher deformity rate than that of the control, thereby indicating that Ca-tyrA1 participates in the biogenesis of the primary shell. In conclusion, and our results indicate that Ca-tyrA1 plays a vital role in the formation of the larval shell and participates in the response to larval shell damages in Crassostrea angulata that were induced by ocean acidification. Copyright © 2017 Elsevier Inc. All rights reserved.

Patterns of neural connectivity during an attention bias task moderate associations between early childhood temperament and internalizing symptoms in young adulthood.

PubMed

Hardee, Jillian E; Benson, Brenda E; Bar-Haim, Yair; Mogg, Karin; Bradley, Brendan P; Chen, Gang; Britton, Jennifer C; Ernst, Monique; Fox, Nathan A; Pine, Daniel S; Pérez-Edgar, Koraly

2013-08-15

Biased attention to threat is found in both individuals with anxiety symptoms and children with the childhood temperament of behavioral inhibition (BI). Although perturbed fronto-amygdala function is implicated in biased attention among anxious individuals, no work has examined the neural correlates of attention biases in BI. Work in this area might clarify underlying mechanisms for anxiety in a sample at risk for internalizing disorders. We examined the relations among early childhood BI, fronto-amygdala connectivity during an attention bias task in young adulthood, and internalizing symptoms, assessed in young adulthood. Children were assessed for BI at multiple age points from infancy through age seven. On the basis of a composite of observational and maternal report data, we selected 21 young adults classified as having a history of BI and 23 classified as non-BI for this study (n = 44). Participants completed an event-related functional magnetic resonance imaging attention-bias task involving threat (angry faces) and neutral trials. Internalizing symptoms were assessed by self-report and diagnostic interviews. The young adults characterized in childhood with BI exhibited greater strength in threat-related connectivity than non-behaviorally inhibited young adults. Between-group differences manifested in connections between the amygdala and two frontal regions: dorsolateral prefrontal cortex and anterior insula. Amygdala-insula connectivity also interacted with childhood BI to predict young adult internalizing symptoms. Behavioral inhibition during early childhood predicts differences as young adults in threat and attention-related fronto-amygdala connectivity. Connectivity strength, in turn, moderated the relations between early BI and later psychopathology. Copyright © 2013 Society of Biological Psychiatry. All rights reserved.

Liver Dysfunction and Phosphatidylinositol-3-Kinase Signalling in Early Sepsis: Experimental Studies in Rodent Models of Peritonitis

PubMed Central

Westermann, Martin; Lambeck, Sandro; Lupp, Amelie; Rudiger, Alain; Dyson, Alex; Carré, Jane E.; Kortgen, Andreas; Krafft, Christoph; Popp, Jürgen; Sponholz, Christoph; Fuhrmann, Valentin; Hilger, Ingrid; Claus, Ralf A.; Riedemann, Niels C.; Wetzker, Reinhard; Singer, Mervyn; Trauner, Michael; Bauer, Michael

2012-01-01

Background Hepatic dysfunction and jaundice are traditionally viewed as late features of sepsis and portend poor outcomes. We hypothesized that changes in liver function occur early in the onset of sepsis, yet pass undetected by standard laboratory tests. Methods and Findings In a long-term rat model of faecal peritonitis, biotransformation and hepatobiliary transport were impaired, depending on subsequent disease severity, as early as 6 h after peritoneal contamination. Phosphatidylinositol-3-kinase (PI3K) signalling was simultaneously induced at this time point. At 15 h there was hepatocellular accumulation of bilirubin, bile acids, and xenobiotics, with disturbed bile acid conjugation and drug metabolism. Cholestasis was preceded by disruption of the bile acid and organic anion transport machinery at the canalicular pole. Inhibitors of PI3K partially prevented cytokine-induced loss of villi in cultured HepG2 cells. Notably, mice lacking the PI3Kγ gene were protected against cholestasis and impaired bile acid conjugation. This was partially confirmed by an increase in plasma bile acids (e.g., chenodeoxycholic acid [CDCA] and taurodeoxycholic acid [TDCA]) observed in 48 patients on the day severe sepsis was diagnosed; unlike bilirubin (area under the receiver-operating curve: 0.59), these bile acids predicted 28-d mortality with high sensitivity and specificity (area under the receiver-operating curve: CDCA: 0.77; TDCA: 0.72; CDCA+TDCA: 0.87). Conclusions Liver dysfunction is an early and commonplace event in the rat model of sepsis studied here; PI3K signalling seems to play a crucial role. All aspects of hepatic biotransformation are affected, with severity relating to subsequent prognosis. Detected changes significantly precede conventional markers and are reflected by early alterations in plasma bile acids. These observations carry important implications for the diagnosis of liver dysfunction and pharmacotherapy in the critically ill. Further clinical work is necessary to extend these concepts into clinical practice. Please see later in the article for the Editors' Summary PMID:23152722

Sustained Attention and Age Predict Inhibitory Control during Early Childhood

ERIC Educational Resources Information Center

Reck, Sarah G.; Hund, Alycia M.

2011-01-01

Executive functioning skills develop rapidly during early childhood. Recent research has focused on specifying this development, particularly predictors of executive functioning skills. Here we focus on sustained attention as a predictor of inhibitory control, one key executive functioning component. Although sustained attention and inhibitory…

A novel redox method for rapid production of functional bi-specific antibodies for use in early pilot studies.

PubMed

Carlring, Jennifer; De Leenheer, Evy; Heath, Andrew William

2011-01-01

We demonstrate here a rapid alternative method for the production of functional bi-specific antibodies using the mild reducing agent 2-mercaptoethanesulfonic acid sodium salt (MESNA). Following reduction of a mixture of two monoclonal antibodies with MESNA to break inter heavy chain bonds, this solution is dialysed under oxidising conditions and antibodies are allowed to reform. During this reaction a mixture of antibodies is formed, including parental antibodies and bi-specific antibody. Bi-specific antibodies are purified over two sequential affinity columns. Following purification, bi-specificity of antibodies is determined in enzyme-linked immunosorbent assays and by flow cytometry. Using this redox method we have been successful in producing hybrid and same-species bi-specific antibodies in a time frame of 6-10 working days, making this production method a time saving alternative to the time-consuming traditional heterohybridoma technology for the production of bi-specific antibodies for use in early pilot studies. The use of both rat and mouse IgG antibodies forming a rat/mouse bi-specific antibody as well as producing a pure mouse bi-specific antibody and a pure rat bi-specific antibody demonstrates the flexibility of this production method.

Rats with ventral hippocampal damage are impaired at various forms of learning including conditioned inhibition, spatial navigation, and discriminative fear conditioning to similar contexts.

PubMed

McDonald, Robert J; Balog, R J; Lee, Justin Q; Stuart, Emily E; Carrels, Brianna B; Hong, Nancy S

2018-10-01

The ventral hippocampus (vHPC) has been implicated in learning and memory functions that seem to differ from its dorsal counterpart. The goal of this series of experiments was to provide further insight into the functional contributions of the vHPC. Our previous work implicated the vHPC in spatial learning, inhibitory learning, and fear conditioning to context. However, the specific role of vHPC on these different forms of learning are not clear. Accordingly, we assessed the effects of neurotoxic lesions of the ventral hippocampus on retention of a conditioned inhibitory association, early versus late spatial navigation in the water task, and discriminative fear conditioning to context under high ambiguity conditions. The results showed that the vHPC was necessary for the expression of conditioned inhibition, early spatial learning, and discriminative fear conditioning to context when the paired and unpaired contexts have high cue overlap. We argue that this pattern of effects, combined with previous work, suggests a key role for vHPC in the utilization of broad contextual representations for inhibition and discriminative memory in high ambiguity conditions. Copyright © 2018 Elsevier B.V. All rights reserved.

Design and evaluation of NEUROBike: a neurorehabilitative platform for bedridden post-stroke patients.

PubMed

Monaco, Vito; Galardi, Giuseppe; Coscia, Martina; Martelli, Dario; Micera, Silvestro

2012-11-01

Over the past decades, a large number of robotic platforms have been developed which provide rehabilitative treatments aimed at recovering walking abilities in post-stroke patients. Unfortunately, they do not significantly influence patients' performance after three months from the accident. One of the main reasons underlying this result seems to be related to the time of intervention. Specifically, although experimental evidences suggest that early (i.e., first days after the injury) and intense neuro-rehabilitative treatments can significantly favor the functional recovery of post-stroke patients, robots require patients to be verticalized. Consequently, this does not allow them to be treated immediately after the trauma. This paper introduces a new robotic platform, named NEUROBike, designed to provide neuro-rehabilitative treatments to bedridden patients. It was designed to provide an early and well-addressed rehabilitation therapy, in terms of kinesiology, efforts, and fatigue, accounting for exercises functionally related to daily motor tasks. For this purpose, kinematic models of leg-joint angular excursions during both walking and sit-to-stand were developed and implemented in control algorithms leading both passive and active exercises. Finally, a set of pilot tests was carried out to evaluate the performance of the robotic platform on healthy subjects.

Live imaging of rat embryos with Doppler swept-source optical coherence tomography

NASA Astrophysics Data System (ADS)

Larina, Irina V.; Furushima, Kenryo; Dickinson, Mary E.; Behringer, Richard R.; Larin, Kirill V.

2009-09-01

The rat has long been considered an excellent system to study mammalian embryonic cardiovascular physiology, but has lacked the extensive genetic tools available in the mouse to be able to create single gene mutations. However, the recent establishment of rat embryonic stem cell lines facilitates the generation of new models in the rat embryo to link changes in physiology with altered gene function to define the underlying mechanisms behind congenital cardiovascular birth defects. Along with the ability to create new rat genotypes there is a strong need for tools to analyze phenotypes with high spatial and temporal resolution. Doppler OCT has been previously used for 3-D structural analysis and blood flow imaging in other model species. We use Doppler swept-source OCT for live imaging of early postimplantation rat embryos. Structural imaging is used for 3-D reconstruction of embryo morphology and dynamic imaging of the beating heart and vessels, while Doppler-mode imaging is used to visualize blood flow. We demonstrate that Doppler swept-source OCT can provide essential information about the dynamics of early rat embryos and serve as a basis for a wide range of studies on functional evaluation of rat embryo physiology.