Friday, 30 August 2013

Psychological manipulation - Wikipedia

Psychological manipulation - Wikipedia, the free encyclopedia


Psychological manipulation is a type of social influence that aims to change the perception or behavior of others through underhanded, deceptive, or even abusive tactics.[1] By advancing the interests of the manipulator, often at another's expense, such methods could be considered exploitative, abusive, devious and deceptive. Social influence is not necessarily negative. For example, doctors can try to persuade patients to change unhealthy habits. Social influence is generally perceived to be harmless when it respects the right of the influenced to accept or reject and is not unduly coercive. Depending on the context and motivations, social influence may constitute underhanded manipulation.
Manipulators may have any of the following psychological conditions:[1]
See also

▶ Science Of Persuasion - Dr. Robert Cialdini, Professor Emeritus of Psychology and Marketing, Arizona State University



Published on 26 Nov 2012
For more visit our blog at www.insideinfluence.com

Animation describing the Universal Principles of Persuasion based on the research of Dr. Robert Cialdini, Professor Emeritus of Psychology and Marketing, Arizona State University.

Dr. Robert Cialdini & Steve Martin are co-authors (together with Dr. Noah Goldstein) of the New York Times, Wall Street Journal and Business Week International Bestseller Yes! 50 Scientifically Proven Ways to be Persuasive.

US Amazon http://tinyurl.com/afbam9g
UK Amazon http://tinyurl.com/adxrp6c

IAW USA: www.influenceatwork.com
IAW UK: www.influenceatwork.co.uk/

Monday, 26 August 2013

What Learning Cursive Does for Your Brain | Psychology Today

What Learning Cursive Does for Your Brain | Psychology Today

Cursive Writing Makes Kids Smarter 
 

Ever try to read your physician’s prescriptions? Children increasingly print their writing because they don’t know cursive or theirs is unreadable. I have a middle-school grandson who has trouble reading his own cursive. Grandparents may find that their grandchildren can’t read the notes they send. Our new U.S. Secretary of the Treasury can’t (or won’t) write his own name on the new money being printed.

When we adults went to school, one of the first things we learned was how to write the alphabet, in caps and lower case, and then to hand-write words, sentences, paragraphs, and essays. Some of us were lucky enough to have penmanship class where we learned how to make our writing pretty and readable. Today, keyboarding is in, the Common Core Standards no longer require elementary students to learn cursive, and some schools are dropping the teaching of cursive, dismissing it as an “ancient skill.”[1]

 
The primary schools that teach handwriting spend only just over an hour a week, according to Zaner-Bloser Inc., one of the nation's largest handwriting-curriculum publishers. Cursive is not generally taught after the third grade (my penmanship class was in the 7th grade; maybe its just coincidence, but the 7th grade was when I was magically transformed from a poor student into an exceptional student).
Yet scientists are discovering that learning cursive is an important tool for cognitive development, particularly in training the brain to learn “functional specialization,”[2] that is capacity for optimal efficiency. In the case of learning cursive writing, the brain develops functional specialization that integrates both sensation, movement control, and thinking. Brain imaging studies reveal that multiple areas of brain become co-activated during learning of cursive writing of pseudo-letters, as opposed to typing or just visual practice.

There is spill-over benefit for thinking skills used in reading and writing. To write legible cursive, fine motor control is needed over the fingers. Students have to pay attention and think about what and how they are doing it. They have to practice. Brain imaging studies show that cursive activates areas of the brain that do not participate in keyboarding.

Much of the benefit of hand writing in general comes simply from the self-generated mechanics of drawing letters. During one study at Indiana University to be published this year,[3] researchers conducted brain scans on pre-literate 5-year olds before and after receiving different letter-learning instruction. In children who had practiced self-generated printing by hand, the neural activity was far more enhanced and "adult-like" than in those who had simply looked at letters. The brain’s “reading circuit” of linked regions that are activated during reading was activated during hand writing, but not during typing. This lab has also demonstrated that writing letters in meaningful context, as opposed to just writing them as drawing objects, produced much more robust activation of many areas in both hemispheres.

In learning to write by hand, even if it is just printing, a child’s brain must:
  • Locate each stroke relative to other strokes.
  • Learn and remember appropriate size, slant of global form, and feature detail characteristic of each letter.
  • Develop categorization skills.
Cursive writing, compared to printing, is even more beneficial because the movement tasks are more demanding, the letters are less stereotypical, and the visual recognition requirements create a broader repertoire of letter representation. Cursive is also faster and more likely to engage students by providing a better sense of personal style and ownership.

Other research highlights the hand's unique relationship with the brain when it comes to composing thoughts and ideas. Virginia Berninger, a professor at the University of Washington, reported her study of children in grades two, four and six that revealed they wrote more words, faster, and expressed more ideas when writing essays by hand versus with a keyboard.[4]

There is a whole field of research known as “haptics,” which includes the interactions of touch, hand movements, and brain function.[5] Cursive writing helps train the brain to integrate visual, and tactile information, and fine motor dexterity. School systems, driven by ill-informed ideologues and federal mandate, are becoming obsessed with testing knowledge at the expense of training kids to develop better capacity for acquiring knowledge.

The benefits to brain development are similar to what you get with learning to play a musical instrument. Not everybody can afford music lessons, but everybody has access to pencil and paper. Not everybody can afford a computer for their kids−maybe such kids are not as deprived as we would think.

Take heart. Some schools just celebrated National Handwriting Day on Jan. 23. Cursive is not dead yet. Parents need to insist that cursive be maintained in their local school.


Readers who want an easy way to acquire a neuroscience background will want to know about the 2nd Edition of my e-book, “Core Ideas in Neuroscience.” Check my web site for available formats and sources (http://thankyoubrain.com/neurobook).

Also check out the Neuro-education discussion group I just created on Linkedin (type “Neuro-education in Linkedin’s search field).

[1] Slape, L. “Cursive Giving Way to Other Pursuits as Educators Debate Its Value.” The Daily News, Feb. 4, 2012. http://tdn.com/news/local/cursive-giving-way-to-other-pursuits-as...

[2] James, Karin H. an Atwood, Thea P. (2009).The role of sensorimotor learning in the perception of letter-like forms: Tracking the causes of neural specialization for letters. Cognitive Neuropsychology.26 (1), 91-100.

[3] James, K.H. and Engelhardt, L. (2013). The effects of handwriting experience on functional brain development in pre-literate children. Trends in Neuroscience and Education. Article in press.

[4] Berninger, V. “Evidence-Based, Developmentally Appropriate Writing Skills K–5: Teaching the Orthographic Loop of Working Memory to Write Letters So Developing Writers Can Spell Words and Express Ideas.” Presented at Handwriting in the 21st Century?: An Educational Summit, Washington, D.C., January 23, 2012.

[5] Mangen, A., and Velay, J. –L. (2010). Digitizing literacy: reflections on the haptics of writing. In Advances in Haptics, edited by M. H. Zadeh. http://www.intechopen.com/books/advances-in-haptics/digitizing-li....

Friday, 9 August 2013

Therapeutic Potential of D-Amino Acid Oxidase (DAAO) Inhibitors

The Therapeutic Potential of D-Amino Acid Oxidase (DAAO) Inhibitors

Abstract

D-amino acid oxidase (DAAO) is a flavoenzyme that degrades D-amino acids through the process of oxidative deamination. DAAO regulation of D-amino acid levels has been associated with several physiological processes ranging from hormone secretion to synaptic transmission and cognition. Recent genetic studies have identified a mutation on chromosome 13 in schizophrenia patients that encodes two gene products (G30 and G72) that are associated with DAAO. Furthermore, DAAO expression and enzyme activity has been reported to be increased in post mortem brain tissue samples from patients with schizophrenia compared to healthy controls. 

D-serine, a D-amino acid that is regulated by DAAO, is a potent, endogenous co-agonist of the N-methyl-D-aspartic acid (NMDA) receptor. Because NMDA receptor dysfunction is thought to be involved in the positive (psychotic), negative and cognitive symptoms in schizophrenia, there has been much interest in developing potent and selective DAAO inhibitors for the treatment of this disease. Several research reports have been published that describe the synthesis and biological effects of novel, selective, small molecule inhibitors of DAAO. 

Many of these compounds have been shown, when given systemically, to increase D-serine concentrations in the blood and brain. However, the efficacy of these compounds in behavioral assays that measure antipsychotic potential and pro-cognitive effects in laboratory animals has been inconsistent. This article highlights and reviews research advances for DAAO inhibitors published in peer reviewed journals.

Keywords: D-serine. D-amino acid oxidase, schizophrenia, NMDA receptor.

D-Amino acid oxidase and serine racemase in human brain: Normal distribution and altered expression in schizophrenia — NDCN

D-Amino acid oxidase and serine racemase in human brain: Normal distribution and altered expression in schizophrenia — NDCN

The N-methyl-D-aspartate receptor co-agonist d-serine is synthesized by serine racemase and degraded by D-amino acid oxidase. Both D-serine and its metabolizing enzymes are implicated in N-methyl-D-aspartate receptor hypofunction thought to occur in schizophrenia. We studied D-amino acid oxidase and serine racemase immunohistochemically in several brain regions and compared their immunoreactivity and their mRNA levels in the cerebellum and dorsolateral prefrontal cortex in schizophrenia.

D-Amino acid oxidase immunoreactivity was abundant in glia, especially Bergmann glia, of the cerebellum, whereas in prefrontal cortex, hippocampus and substantia nigra, it was predominantly neuronal. Serine racemase was principally glial in all regions examined and demonstrated prominent white matter staining. In schizophrenia, D-amino acid oxidase mRNA was increased in the cerebellum, and as a trend for protein.

Serine racemase was increased in schizophrenia in the dorsolateral prefrontal cortex but not in cerebellum, while serine racemase mRNA was unchanged in both regions. Administration of haloperidol to rats did not significantly affect serine racemase or D-amino acid oxidase levels.

These findings establish the major cell types wherein serine racemase and D-amino acid oxidase are expressed in human brain and provide some support for aberrant D-serine metabolism in schizophrenia. However, they raise further questions as to the roles of D-amino acid oxidase and serine racemase in both physiological and pathophysiological processes in the brain.

D-amino acid oxidase activator (DAOA), a candidate schizophrenia gene - TBioMed

TBioMed | Full text | Structural, phylogenetic and docking studies of D-amino acid oxidase activator (DAOA), a candidate schizophrenia gene

Sheikh Arslan Sehgal1, Naureen Aslam Khattak2 and Asif Mir1*

The electronic version of this article is the complete one and can be found online at: http://www.tbiomed.com/content/10/1/3

Received:17 December 2012
Accepted:2 January 2013
Published:4 January 2013
© 2013 Sehgal et al.; licensee BioMed Central Ltd.


This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background

Schizophrenia is a neurodegenerative disorder that occurs worldwide and can be difficult to diagnose. It is the foremost neurological disorder leading to suicide among patients in both developed and underdeveloped countries. D-amino acid oxidase activator (DAOA), also known as G72, is directly implicated in the glutamateric hypothesis of schizophrenia. It activates D-amino acid oxidase, which oxidizes D-serine, leading to modulation of the N-methyl-D-aspartate receptor.

Methods

MODELLER (9v10) was utilized to generate three dimensional structures of the DAOA candidate gene. The HOPE server was used for mutational analysis. The Molecular Evolutionary Genetics Analysis (MEGA5) tool was utilized to reconstruct the evolutionary history of the candidate gene DAOA. AutoDock was used for protein-ligand docking and Gramm-X and PatchDock for protein-protein docking.

Results

A suitable template (1ZCA) was selected by employing BLASTp on the basis of 33% query coverage, 27% identity and E-value 4.9. The Rampage evaluation tool showed 91.1% favored region, 4.9% allowed region and 4.1% outlier region in DAOA. ERRAT demonstrated that the predicted model had a 50.909% quality factor. Mutational analysis of DAOA revealed significant effects on hydrogen bonding and correct folding of the DAOA protein, which in turn affect protein conformation. Ciona was inferred as the outgroup. Tetrapods were in their appropriate clusters with bifurcations. Human amino acid sequences are conserved, with chimpanzee and gorilla showing more than 80% homology and bootstrap value based on 1000 replications. Molecular docking analysis was employed to elucidate the binding mode of the reported ligand complex for DAOA. The docking experiment demonstrated that DAOA is involved in major amino acid interactions: the residues that interact most strongly with the ligand C28H28N3O5PS2 are polar but uncharged (Gln36, Asn38, Thr 122) and non-polar hydrophobic (Ile119, Ser171, Ser21, Ala31). Protein-protein docking simulation demonstrated two ionic bonds and one hydrogen bond involving DAOA. Lys-7 of the receptor protein interacted with Lys-163 and Asp-2037. Tyr-03 interacted with Arg-286 of the ligand protein and formed a hydrogen bond.

Conclusion

The predicted interactions might serve to inhibit the disease-related allele. It is assumed that current bioinformatics methods will contribute significantly to identifying, analyzing and curing schizophrenia. There is an urgent need to develop effective drugs for schizophrenia, and tools for examining candidate genes more accurately and efficiently are required.
Keywords:
Schizophrenia; Bioinformatics; Modeling; Docking; DAOA; Phylogenetic analysis

Background

The nature of a human medical disorder is often elucidated through biological markers and behavioral studies. Diagnosis of mental disorders is very difficult because it primarily relies on behavioral markers. An example of a complex mental disorder is schizophrenia (SZ), diagnosis of which depends on abnormal behavior such as paranoia, dampening of emotions and auditory hallucinations. Genome-wide studies have attained a major role in SZ research because high-throughput technologies are valuable for discovering relevant genes. SZ is a psychiatric disorder with severe manifestations - abnormal behavior, disorganized speech and figments of the imagination - and an estimated heritability of about 80% [1]. Negative symptoms can also include affective flattening, avolition, and alogia. Approximately 1% of the population is affected during the course of life. The effects of SZ usually start during the patient’s late teens to early twenties; females have an age of onset five years later than males [2]. A recent meta-data analysis estimated the risk of SZ in males to be about 40% higher than in females [3]. Epidemiological studies of SZ have shown that it occurs in all populations with a prevalence of approximately 1.5-4.5 per thousand and an incidence of 0.17-0.43 per thousand [4].
According to analysis of gene linkage data and meta-analysis of genome scans [5], highly vulnerable genes on chromosomes 1q, 3p, 5q, 6p, 8p, 11q, 14p, 20q and 22q [6,7] contribute to SZ. Both functional and positional candidate SZ genes have been studied and various promising candidates that might be involved in risk for the disease have been identified. 

The symptoms of SZ have different dimensions that usually occur together and can reflect substantial variation among patient phenotypes [8-10]. Different researchers have formulated various models of these dimensions but the most widely appreciated 3D models were first proposed by Bilder et al. and Liddle [9,11]. These authors concluded that the main symptoms are poverty of speech, formal thought disorder, decreased voluntary movement, psychomotor impairment, bizarre behavior, hallucinations, abnormal acts, inappropriate affects, flat affects, flattening, avolition, and alogia. 

A genome-wide association study (GWAS) for SZ was conducted in 2008 but no significant loci were reported, though 7000 samples were used [12,13]. 

The gene DAOA, located on chromosome 13q3, encodes the D-amino acid oxidase activator protein, as shown by functional and expression studies. It is significantly associated with SZ and is also known as G72. The D-amino acid oxidase activator (DAOA) is directly implicated in the glutamateric hypothesis of SZ [14]. When D-amino acid oxidase is activated, D-serine is oxidized and the product modulates the N-methyl-D-aspartate receptor. Modulation of this receptor leads to the cause of SZ; glutamate signaling is involved in important pathways directly linked to SZ [15]. 

DAOA is also involved in other psychotic disorders and can modify the cognitive and negative symptoms of mood. It could be the primary genetic cause of the observed overlap of phenotypes between bipolar disorder and SZ [16]. 

Bioinformatics has been used for in silico analysis of biological queries using mathematical and statistical techniques. X-ray and NMR techniques are expensive and time-consuming for structural modeling of proteins. Screening of small chemical compounds against target receptors by high throughput screening (HTS) is very expensive. 

In this work, we predicted the 3D structure and the protein-ligand and protein-protein docking of DAOA using different bioinformatics strategies. The main aim of our research was to predict the 3D structure and docking. The objective of the present study was to elucidate the interactions of DAOA protein with ligands and other proteins and to identify the connection of DAOA to SZ. Protein-protein docking and interaction simulations reveal hydrogen and ionic bonds. The present work was conducted to provide molecular insights into the structure of the protein and to find its most plausible function.

Results

This paper describes the implementation of an in silico technique to recruit and analyze DAOA, the most likely candidate gene for SZ. The direct involvement of DAOA in disease pathogencity has already been reported in several research studies on SZ. 

Initially, a literature search was conducted to explore the most likely candidate gene involved in SZ. A comparative modeling technique (MODELER 9v10) was adopted to predict the three dimensional structure of the protein encoded by the selected gene. The protein data bank (PDB) was checked for the 3D structure of the selected protein, and it was confirmed that no 3D structure had been predicted to date. To check the quality and reliability of the predicted model, the evaluation tools ERRAT and Rampage were used. 

Protein-ligand and protein-protein docking of DAOA were simulated. The ZINC and PubChem databases were used to retrieve the ligand and STRING was used to identify protein interactions [17].
DAOA has been mapped on chromosome 13, with starting and ending base pairs 06118216 and 10143383 respectively. Homology modeling was implemented to generate the 3D structure of the encoded protein. MODELER 9v10 was used to construct the protein model. A basic local alignment technique (BLAST) was utilized to identify the homology between the target protein and its template. 

The lowest energy minimization value for the predicted structure was selected for further analysis.
The 3D structure or modeling of DAOA is not known and no structural information can be found for the templates. The amino acid sequence of DAOA in FASTA format was retrieved from Uniprot with accession number A2T115. Table 1 lists the three templates 1ZCA, 1V30 and 2E5K with optimal alignment of the first template and good alignment for the others, sorted by overall quality, query coverage, similarity and E-values. 

The structure predicted by MODELLER 9v10 with the alpha helices and beta-pleated sheets visualized by Chimera 1.6 is illustrated in Figure 1(A). Figure 1(B) demonstrates a superimposition of structure and template. The predicted structure is evaluated in Figures 2 and 3.

1 Department of Bioinformatics and Biotechnology, International Islamic University, H-10 Sector, Islamabad, Pakistan
2 Institute of Biochemistry and Biotechnology, Department of Biochemistry, Arid Agriculture University Rawalpindi Pakistan, Rawalpindi, Pakistan
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Theoretical Biology and Medical Modelling 2013, 10:3 doi:10.1186/1742-4682-10-3