Neurodevelopmental Changes in Social Reinforcement Processing: A Functional Magnetic Resonance Imaging Study.

ObjectiveIn the current study we investigated neurodevelopmental changes in response to social and non-social reinforcement.MethodsFifty-three healthy participants including 16 early adolescents (age, 10-15 years), 16 late adolescents (age, 15-18 years), and 21 young adults (age, 21-25 years) completed a social/non-social reward learning task while undergoing functional magnetic resonance imaging. Participants responded to fractal image stimuli and received social or non-social reward/non-rewards according to their accuracy. ANOVAs were conducted on both the blood oxygen level dependent response data and the product of a context-dependent psychophysiological interaction (gPPI) analysis involving ventromedial prefrontal cortex (vmPFC) and bilateral insula cortices as seed regions.ResultsEarly adolescents showed significantly increased activation in the amygdala and anterior insula cortex in response to non-social monetary rewards relative to both social reward/non-reward and monetary non-rewards compared to late adolescents and young adults. In addition, early adolescents showed significantly more positive connectivity between the vmPFC/bilateral insula cortices seeds and other regions implicated in reinforcement processing (the amygdala, posterior cingulate cortex, insula cortex, and lentiform nucleus) in response to non-reward and especially social non-reward, compared to late adolescents and young adults.ConclusionIt appears that early adolescence may be marked by: (i) a selective increase in responsiveness to non-social, relative to social, rewards; and (ii) enhanced, integrated functioning of reinforcement circuitry for non-reward, and in particular, with respect to posterior cingulate and insula cortices, for social non-reward

Raging Hormones: Why Age-Based Etiological Conceptualizations of the Development of Antisocial Behavior Are Insufficient

Developmental science, particularly developmental neuroscience, has substantially influenced the modern legal system. However, this science has typically failed to consider the role of puberty and pubertal hormones on development when considering antisocial behavior. This review describes major theoretical positions on the developmental neuroscience of antisocial behavior and highlights where basic developmental neuroscience suggests that the role of puberty and pubertal hormones should be considered. The implications of the current state of the science with respect to developmental neuroscience is considered, particularly what is known in light of development beyond puberty. This review shows that development continues to an older age for many youth than the legal system typically acknowledges. The plasticity of the brain that this continued development implies has implications for the outcome of interventions in the legal system in ways that have not been explored. Future directions for both developmental scientists and legal professions are recommended

CRISPR antiphage defence mediated by the cyclic nucleotide-binding membrane protein Csx23

Biotechnology and Biological Sciences Research Council [BB/T004789/1 to M.F.W., T.M.G.]; European Research Council Advanced Grant [101018608 to M.F.W.]; Engineering and Physical Sciences Research Council [EP/X016455/1 to K.A., B.E.B., M.F.W.]; BBSRC equipment grants [BB/R013780/1, BB/T017740/1 to B.E.B.]. Funding for open access charge: University of St Andrews block grant.CRISPR-Cas provides adaptive immunity in prokaryotes. Type III CRISPR systems detect invading RNA and activate the catalytic Cas10 subunit, which generates a range of nucleotide second messengers to signal infection. These molecules bind and activate a diverse range of effector proteins that provide immunity by degrading viral components and/or by disturbing key aspects of cellular metabolism to slow down viral replication. Here, we focus on the uncharacterised effector Csx23, which is widespread in Vibrio cholerae. Csx23 provides immunity against plasmids and phage when expressed in Escherichia coli along with its cognate type III CRISPR system. The Csx23 protein localises in the membrane using an N-terminal transmembrane α-helical domain and has a cytoplasmic C-terminal domain that binds cyclic tetra-adenylate (cA4), activating its defence function. Structural studies reveal a tetrameric structure with a novel fold that binds cA4 specifically. Using pulse EPR, we demonstrate that cA4 binding to the cytoplasmic domain of Csx23 results in a major perturbation of the transmembrane domain, consistent with the opening of a pore and/or disruption of membrane integrity. This work reveals a new class of cyclic nucleotide binding protein and provides key mechanistic detail on a membrane-associated CRISPR effector.Many anti-viral defence systems generate a cyclic nucleotide signal that activates cellular defences in response to infection. Type III CRISPR systems use a specialised polymerase to make cyclic oligoadenylate (cOA) molecules from ATP. These can bind and activate a range of effector proteins that slow down viral replication. In this study, we focussed on the Csx23 effector from the human pathogen Vibrio cholerae – a trans-membrane protein that binds a cOA molecule, leading to anti-viral immunity. Structural studies revealed a new class of nucleotide recognition domain, where cOA binding is transmitted to changes in the trans-membrane domain, most likely resulting in membrane depolarisation. This study highlights the diversity of mechanisms for anti-viral defence via nucleotide signalling.Peer reviewe

Dairy Farm Business Summary: Southeastern New York Region 1990

A.E. Ext. 91-17Dairy farmers throughout New York State have been participating in Cornell Cooperative Extension's farm business summary and analysis program since the early 1950's. Each participating farmer receives a comprehensive business summary and analysis of his or her farm business. The information in this report represents an average of the data submitted from farms in the Southeastern New York region

Rare recessive loss-of-function methionyl-tRNA synthetase mutations presenting as a multi-organ phenotype

BACKGROUND: Methionyl-tRNA synthetase (MARS) catalyzes the ligation of methionine to its cognate transfer RNA and therefore plays an essential role in protein biosynthesis. METHODS: We used exome sequencing, aminoacylation assays, homology modeling, and immuno-isolation of transfected MARS to identify and characterize mutations in the methionyl-tRNA synthetase gene (MARS) in an infant with an unexplained multi-organ phenotype. RESULTS: We identified compound heterozygous mutations (F370L and I523T) in highly conserved regions of MARS. The parents were each heterozygous for one of the mutations. Aminoacylation assays documented that the F370L and I523T MARS mutants had 18 ± 6% and 16 ± 6%, respectively, of wild-type activity. Homology modeling of the human MARS sequence with the structure of E. coli MARS showed that the F370L and I523T mutations are in close proximity to each other, with residue I523 located in the methionine binding pocket. We found that the F370L and I523T mutations did not affect the association of MARS with the multisynthetase complex. CONCLUSION: This infant expands the catalogue of inherited human diseases caused by mutations in aminoacyl-tRNA synthetase genes

Ariel - Volume 10 Number 3

Executive Editors Madalyn Schaefgen David Reich Business Manager David Reich News Editors Medical College Edward Zurad CAHS John Guardiani World Mark Zwanger Features Editors Meg Trexler Jim O\u27Brien Editorials Editor Jeffrey Banyas Photography and Sports Editor Stuart Singer Commons Editor Brenda Peterso

The Density Matrix Renormalization Group for finite Fermi systems

The Density Matrix Renormalization Group (DMRG) was introduced by Steven White in 1992 as a method for accurately describing the properties of one-dimensional quantum lattices. The method, as originally introduced, was based on the iterative inclusion of sites on a real-space lattice. Based on its enormous success in that domain, it was subsequently proposed that the DMRG could be modified for use on finite Fermi systems, through the replacement of real-space lattice sites by an appropriately ordered set of single-particle levels. Since then, there has been an enormous amount of work on the subject, ranging from efforts to clarify the optimal means of implementing the algorithm to extensive applications in a variety of fields. In this article, we review these recent developments. Following a description of the real-space DMRG method, we discuss the key steps that were undertaken to modify it for use on finite Fermi systems and then describe its applications to Quantum Chemistry, ultrasmall superconducting grains, finite nuclei and two-dimensional electron systems. We also describe a recent development which permits symmetries to be taken into account consistently throughout the DMRG algorithm. We close with an outlook for future applications of the method.Comment: 48 pages, 17 figures Corrections made to equation 19 and table

Redox-engineering enhances maize thermotolerance and grain yield in the field

Contains fulltext : 252904.pdf (Publisher’s version ) (Open Access)08 juli 202

Early Cenozoic denudation of central west Britain in response to transient and permanent uplift above a mantle plume

Upwelling mantle plumes beneath continental crust are predicted to produce difficult to quantify, modest uplift and denudation. The contribution of permanent and transient components to the uplift is also difficult to distinguish. A pulse of denudation in Britain in the Early Paleogene has been linked, although with some controversy, with the arrival of the proto-Iceland mantle plume. In this contribution we show that combining apatite and zircon (U-Th-Sm)/He and apatite fission track analyses from central west Britain with numerical modeling clearly identifies a pulse of early Cenozoic denudation. The data indicate that rock uplift and denudation were centered on the northern East Irish Sea Basin and 1.0–2.4 km of rocks were removed during the latest Cretaceous-early Paleogene. Uplift and erosion appears to have started a few million years before the earliest magmatism in the region. The regional denudation pattern mirrors the distribution of low-density magmatic rocks that has been imaged in the deep crust. However, the injection of the underplating melt is not enough to account for the total denudation. An additional regional uplift of at least 300 m is required, which is consistent with a transient thermal effect from the hot mantle plume. The rapid exhumation event ceased by ~40 Ma and the data do not require significant Neogene exhumation

Is youth unemployment really the major worry? (AOM)

Youth unemployment is neither the only nor the basic problem of the European labour market. The comparative analysis of unemployment data demonstrates that the unemployment of older people is even more serious. The article proves that the weight of young people in total unemployment has as a tendency been declining in the “inner periphery” of the EU, among them in Central and Eastern European member states (CEECs). The trend is just the opposite in the developed or “core” countries of the Union where youngsters took a higher share in total unemployment in 2012 than 10-12 years ago. In Europe there are millions of young people beyond the active unemployed who do not want to work or think they cannot find a job that fulfils their expectations and refuse to take part in any kind of education or training (NEETs-“Not in Employment, Education or Training”). By estimating the rate of NEETs in the adult population the article claims that the NEETs-phenomenon is not the differentia specifica of the youth. At the end the article details two suggestions for the mitigation of the problem. It concludes that the joblessness in Europe is an old and tendencially worsening problem that cannot be solved by particular policies