Abstract The mechanisms underlying cerebellar learning are reviewed with an emphasis on old arguments and new perspectives on eyeblink conditioning. Eyeblink conditioning has been used for decades a ...model system for elucidating cerebellar learning mechanisms. The standard model of the mechanisms underlying eyeblink conditioning is that there two synaptic plasticity processes within the cerebellum that are necessary for acquisition of the conditioned response: (1) long-term depression (LTD) at parallel fiber-Purkinje cell synapses and (2) long-term potentiation (LTP) at mossy fiber-interpositus nucleus synapses. Additional Purkinje cell plasticity mechanisms may also contribute to eyeblink conditioning including LTP, excitability, and entrainment of deep nucleus activity. Recent analyses of the sensory input pathways necessary for eyeblink conditioning indicate that the cerebellum regulates its inputs to facilitate learning and maintain plasticity. Cerebellar learning during eyeblink conditioning is therefore a dynamic interactive process which maximizes responding to significant stimuli and suppresses responding to irrelevant or redundant stimuli. This article is part of a Special Issue entitled SI: Brain and Memory.
Abstract We have calculated six-locus high resolution HLA A∼C∼B∼DRB3/4/5∼DRB1∼DQB1 haplotype frequencies using all Be The Match® Registry volunteer donors typed by DNA methods at recruitment. Mixed ...resolution HLA typing data was inputted to a modified expectation–maximization (EM) algorithm in the form of genotype lists generated by interpretation of primary genomic typing data to the IMGT/HLA v3.4.0 allele list. The full cohort consists of 6.59 million subjects categorized at a broad race level. Overall 25.8% of the individuals were typed at the C locus, and 5.2% typed at the DQB1 locus, while all individuals were typed for A, B, DRB1. We also present a subset of 2.90 million subjects with detailed race/ethnic information mapped to 21 population subgroups, 64.1% of which have primary DNA typing data across at least A, B, and DRB1 loci. Sample sizes at the detailed race level range from 1,242,890 for European Caucasian to 1,376 Alaskan Native or Aleut. Genetic distance measurements show high levels of HLA genetic divergence among the 21 detailed race categories, especially among the eight Asian–American populations. These haplotype frequencies will be used to improve match predictions for donor selection algorithms for hematopoietic stem cell transplantation and improve the accuracy in modeling registry match rates.
Communication between the cerebellum and forebrain structures is necessary for motor learning and has been implicated in a variety of cognitive functions. The exact nature of cerebellar-forebrain ...interactions supporting behavior and cognition is not known. We examined how local and network activity support learning by simultaneously recording neural activity in the cerebellum, amygdala, and anterior cingulate cortex while male and female rats were trained in trace eyeblink conditioning. Initially, the cerebellum and forebrain signal the contingency between external stimuli through increases in theta power and synchrony. Neuronal activity driving expression of the learned response was observed in the cerebellum and became evident in the anterior cingulate and amygdala as learning progressed. Aligning neural activity to the training stimuli or learned response provided a way to differentiate between learning-related activity driven by different mechanisms. Stimulus and response-related increases in theta power and coherence were observed across all three areas throughout learning. However, increases in slow gamma power and coherence were only observed when oscillations were aligned to the cerebellum-driven learned response. Percentage of learned responses, learning-related local activity, and slow gamma communication from cerebellum to forebrain all progressively increased during training. The relatively fast frequency of slow gamma provides an ideal mechanism for the cerebellum to communicate learned temporal information to the forebrain. This cerebellar response-aligned slow gamma then provides enrichment of behavior-specific temporal information to local neuronal activity in the forebrain. These dynamic network interactions likely support a wide range of behaviors and cognitive tasks that require coordination between the forebrain and cerebellum.
This study presents new evidence for how dynamic learning-related changes in single neurons and neural oscillations in a cerebellar-forebrain network support associative motor learning. The current results provide an integrated mechanism for how bidirectional communication between the cerebellum and forebrain represents important external events and internal neural drive. This bidirectional communication between the cerebellum and forebrain likely supports a wide range of behaviors and cognitive tasks that require temporal precision.
Despite the lack of substantial evidence for improvement in the quality of teaching and learning with information and communication technology (ICT), governmental organizations have pushed ICT as a ...means of providing broad-scale training to meet the demand for a skilled workforce, centred upon a hypothesized ICT–scientific literacy relationship. To better understand this possible association, this study used data from the 2006 administration of the Programme for International Student Assessment (PISA 2006) to determine the extent to which scientific literacy is predicted by a host of ICT-related variables, after adjusting for student demographic characteristics. The findings suggest that, once demographic characteristics have been accounted for, students with prior experience with ICT, who browse the Internet more frequently, and who are confident with basic ICT tasks earned higher scientific literacy scores. Gender differences existed with respect to types of productivity and entertainment software used; this difference may be attributed to personal choice and initiative to learn ICT. Furthermore, the way in which students are using computers in schools, towards attaining learning outcomes, may have a stronger effect on scientific literacy than how often computers are accessed.
►Use of ICT for productivity, but not entertainment, beneficial to science achievement. ►ICT use at home positively related to science achievement but may be related with SES. ►Mean SES explained much of the school-level variance in science achievement scores.
Pavlovian eyeblink conditioning has been used extensively as a model system for examining the neural mechanisms underlying associative learning. Delay eyeblink conditioning depends on the ...intermediate cerebellum ipsilateral to the conditioned eye. Evidence favors a two-site plasticity model within the cerebellum with long-term depression of parallel fiber synapses on Purkinje cells and long-term potentiation of mossy fiber synapses on neurons in the anterior interpositus nucleus. Conditioned stimulus and unconditioned stimulus inputs arise from the pontine nuclei and inferior olive, respectively, converging in the cerebellar cortex and deep nuclei. Projections from subcortical sensory nuclei to the pontine nuclei that are necessary for eyeblink conditioning are beginning to be identified, and recent studies indicate that there are dynamic interactions between sensory thalamic nuclei and the cerebellum during eyeblink conditioning. Cerebellar output is projected to the magnocellular red nucleus and then to the motor nuclei that generate the blink response(s). Tremendous progress has been made toward determining the neural mechanisms of delay eyeblink conditioning but there are still significant gaps in our understanding of the necessary neural circuitry and plasticity mechanisms underlying cerebellar learning.
Hematopoietic stem-cell transplantation (HSCT) is a potentially lifesaving therapy for several blood cancers and other diseases. For patients without a suitable related HLA-matched donor, ...unrelated-donor registries of adult volunteers and banked umbilical cord-blood units, such as the Be the Match Registry operated by the National Marrow Donor Program (NMDP), provide potential sources of donors. Our goal in the present study was to measure the likelihood of finding a suitable donor in the U.S. registry.
Using human HLA data from the NMDP donor and cord-blood-unit registry, we built population-based genetic models for 21 U.S. racial and ethnic groups to predict the likelihood of identifying a suitable donor (either an adult donor or a cord-blood unit) for patients in each group. The models incorporated the degree of HLA matching, adult-donor availability (i.e., ability to donate), and cord-blood-unit cell dose.
Our models indicated that most candidates for HSCT will have a suitable (HLA-matched or minimally mismatched) adult donor. However, many patients will not have an optimal adult donor--that is, a donor who is matched at high resolution at HLA-A, HLA-B, HLA-C, and HLA-DRB1. The likelihood of finding an optimal donor varies among racial and ethnic groups, with the highest probability among whites of European descent, at 75%, and the lowest probability among blacks of South or Central American descent, at 16%. Likelihoods for other groups are intermediate. Few patients will have an optimal cord-blood unit--that is, one matched at the antigen level at HLA-A and HLA-B and matched at high resolution at HLA-DRB1. However, cord-blood units mismatched at one or two HLA loci are available for almost all patients younger than 20 years of age and for more than 80% of patients 20 years of age or older, regardless of racial and ethnic background.
Most patients likely to benefit from HSCT will have a donor. Public investment in donor recruitment and cord-blood banks has expanded access to HSCT. (Funded by the Office of Naval Research, Department of the Navy, and the Health Resources and Services Administration, Department of Health and Human Services.).
•Demonstrated Se-hyperaccumulator plants can be used as organic Se fertilizer.•Demonstrated increasing amounts of Se in vegetables grown with more organic Se.•Identified extractable Se species in ...broccoli and carrots grown in Se amended soil.•Plants used for Se phytoremediation can biofortify vegetables with Se.
Amending soils with Se-hyperaccumulator plant derived sources of selenium (Se) may be useful for increasing the Se content in food crops in Se-deficient regions of the world. In this study we evaluated total Se and the different chemical species of Se in broccoli and carrots grown in soils amended with ground shoots of the Se-hyperaccumulator Stanleyapinnata. With increasing application rates of S. pinnata, total plant Se concentrations increased to nutritionally ideal levels inside edible parts. Selenium compounds in aqueous extracts were analyzed by SAX-HPLC-ICPMS and identified as a variety of mainly organic-Se forms. Together with bulk Se K-edge X-ray absorption near-edge structure (XANES) analysis performed on broccoli florets, carrot roots and shoots, dried ground S. pinnata, and the amended soil at post-plant, we demonstrate that Se-enriched S. pinnata is valuable as a soil amendment for enriching broccoli and carrots with healthful forms of organic-Se.
•Central amygdala inhibition during the CS impairs cerebellar learning.•Central amygdala excitation during the CS facilitates cerebellar learning.•Central amygdala inhibition before the CS also ...impairs cerebellar learning.•Central amygdala contributes to CS facilitation and vigilance in cerebellar learning.
Our previous studies found that the central amygdala (CeA) modulates cerebellum-dependent eyeblink conditioning (EBC) using muscimol inactivation. We also found that CeA inactivation decreases cerebellar neuronal activity during the conditional stimulus (CS) from the start of training. Based on these findings, we hypothesized that the CeA facilitates CS input to the cerebellum. The current study tested the CS facilitation hypothesis using optogenetic inhibition with archaerhodopsin (Arch) and excitation with channelrhodopsin (ChR2) of the CeA during EBC in male rats. Optogenetic manipulations were administered during the 400 ms tone CS or during a 400 ms pre-CS period. As predicted by the CS facilitation hypothesis CeA inhibition during the CS impaired EBC and CeA excitation during the CS facilitated EBC. Unexpectedly, CeA inhibition just prior to the CS also impaired EBC, while CeA excitation during the pre-CS pathway did not facilitate EBC. The results suggest that the CeA contributes to CS facilitation and vigilance during the pre-CS period. These putative functions of the CeA may be mediated through separate output pathways from the CeA to the cerebellum.
Abstract Purspose The prevention of youth violence is a public health priority in many countries. We examined the prevalence of bullying victimization and physical fighting in youths in 79 high- and ...low-income countries and the relations between structural determinants of adolescent health (country wealth, income inequality, and government spending on education) and international differences in youth violence. Methods Cross-sectional surveys were administered in schools between 2003 and 2011. These surveys provided national prevalence rates of bullying victimization (n = 334,736) and four or more episodes of physical fighting in the past year (n = 342,312) in eligible and consenting 11–16 year olds. Contextual measures included per capita income, income inequality, and government expenditures on education. We used meta-regression to examine relations between country characteristics and youth violence. Results Approximately 30% of adolescents reported bullying victimization and 10.7% of males and 2.7% of females were involved in frequent physical fighting. More youth were exposed to violence in African and Eastern Mediterranean countries than in Europe and Asia. Violence directly related to country wealth; a 1 standard deviation increase in per capita income corresponded to less bullying (−3.9% in males and −4.2% in females) and less fighting (−2.9% in males and −1.0% in females). Income inequality and education spending modified the relation between country wealth and fighting; where inequality was high, country wealth related more closely to fighting if education spending was also high. Conclusions Country wealth is a robust determinant of youth violence. Fighting in affluent but economically unequal countries might be reduced through increased government spending on education.
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