«A new study, published in Nature this January, Schizophrenia risk from complex variation of complement component 4links , complement component 4 (C4) genes to schizophrenia. C4 genes are important in the major histocompatibility complex (MHC). C4 was found to mediate synapse elimination (called pruning) in development after birth, in mice. These findings might therefore help to explain the reduced number of synapses in brains of humans with schizophrenia.
(Sekar et al., 2016)
Lynn Marquardt
For å kunne hjelpe dem som har utfordringer, er det første vi må gjøre å anerkjenne at de trenger hjelp.
As the editor of one of the most prestigious peer-reviewed medical journals in the world (The Lancet) said, “the case against science is straightforward: much of the scientific literature, perhaps half, may simply be untrue.” 1 This is Science 2.0.
Science 2.0 does not bother with the old phenomena of sane hypotheses, experiments, interpretation of results or reasonable conclusions. Those are the limitations of Science 1.0, which prompted the development of the newer version of Science. Science 2.0 is easy to implement as it has the “advantages” of not being based on facts, the experiments being manipulated to support the conclusions and the time-consuming peer-reviews being omitted. In addition, Science 2.0 is also accepting “statistical fairy-tales” about significance1 and it does not care about negative findings (no matter how informative they may be).
Since 2015, we are even able to study human health in space as NASA has selected 10 scientists from 12 Universities to examine how zero-gravity may affect the human body (https://www.nasa.gov/twins-study/about;http://time.com/3843801/space-twins-science-kelly/). The concept of this study is very interesting, but it is based on 1 (one!) twin pair. So, there are 10 scientists and 2 participants. This may be the coolest twin study ever, but, most probably, the least statistically powered one in human history.
Science 2.0 is quite alarming: all of its studies are used to develop drugs/vaccines to supposedly help people, train medical staff, educate students and much more. “It is simply no longer possible to believe much of the clinical research that is published, or to rely on the judgment of trusted physicians or authoritative medical guidelines.”2
“In august 2015, the publisher Springer retracted 64 articles from 10 different subscription journals“3, after editorial checks uncovered peer-review fraud. Since 2012, “more than 250 articles have been retracted because of fake reviews — about 15% of the total number of retractions.”3 And there are also cases of data fabrication (http://retractionwatch.com/2015/06/17/columbia-biologists-deeply-regret-nature-retraction-after-postdoc-faked-74-panels-in-3-papers/).
Peter Higgs, who won the Nobel prize for physics in 2013, has famously said: “I wouldn’t be productive enough for today’s academic system.”4 “He would almost certainly have been sacked had he not been nominated for the Nobel in 1980”4 as the British physicist published less than 10 papers between 1964 and 2013.4 Despite such publication record, the University’s authorities decided to keep employing Peter Higgs, because he «might get a Nobel prize – and if he doesn’t” they “can always get rid of him.»4
So, why is it that “individual scientists, including their most senior leaders, do little to alter a research culture that occasionally veers close to misconduct”?1 “Can bad scientific practices be fixed?”1 “One of the most convincing proposals came from outside the biomedical community. Tony Weidberg is a Professor of Particle Physics at Oxford. Following several high-profile errors, the particle physics community now invests great effort into intensive checking and rechecking of data prior to publication. By filtering results through independent working groups, physicists are encouraged to criticise. Good criticism is rewarded.”1 Could good criticism save the science? Let us know your thoughts in the comments below!
1http://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736%2815%2960696-1.pdf
2http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2964337/pdf/pmed.1000355.pdf
3http://www.nejm.org/doi/pdf/10.1056/NEJMp1512330
4http://www.theguardian.com/science/2013/dec/06/peter-higgs-boson-academic-system
Tetyana Zayats
ADHD is a common (~3.5% in adulthood and ~5% in childhood) childhood onset neuropsychiatric condition, leading to high disability because of the frequent psychiatric co-morbidities such as substance abuse, major depression and learning disabilities. Thus, the treatment of ADHD is of high relevance to our society, especially as untreated ADHD has been linked to unemployment, criminality and suicidal attempts. To date, the most effective pharmacological therapy includes methylphenidate and atomoxetine, chemical compounds that affect dopaminergic and noradrenergic neurotransmission. But it is important to consider and study the alternative drugs as they may provide help in dealing with resistant ADHD symptoms and/or co-morbid conditions. The following article provides comprehensive overview of such alternatives: Alternative pharmacological strategies for adult ADHD treatment: a systematic review. In short, amphetamines, antidepressants and metadoxine may be considered suitable pharmacological treatments for symptoms of ADHD and its co-morbid conditions.
Tetyana Zayats
Ved foten av Alpene i den franske byen Grenoble, ble «European Nanomedicine Meeting» arrangert. Konferansen samlet forskere innen medisin, nanoteknologi, farmasi og biokjemi. De fleste kom fra Europa, men noen var også invitert fra USA. Mange interessante foredrag ble holdt, og temaene spredte seg fra utviklingen av nanomaterialer til kliniske studier av nanoprodukter. Arwyn Jones fortalte om hvordan cellene i kroppen tar opp nanopartikler og hvordan celle-penetrerende peptider (CPP) kan forbedre opptaket slik at legemiddelet, som nanopartiklene bærer på, kan leveres til riktig sted inni cellene.
Vi var en gjeng på fire som reiste fra Bergen, Maite Bezem og Fredrik G. Johannessen fra Biogjenkjenning, og presenterte våre prosjekter på poster. Våre postere handlet om biologisk nedbrytbare nanopartikler som brukes til å pakke inn tyrosin hydroksylase, også kalt TH. TH er et enzym og kan beskrives som en molekylær maskin. Kroppen trenger det til å produsere lykkemolekylet dopamin. Dopamin er også et signalstoff som hjernen trenger for å kunne styre kroppens bevegelser. Dopaminnivået kan være påvirket i noen sykdommer, blant annet Parkinsons sykdom og ADHD.
Tekst: Maite (Maria Teresa) Bezem (stipendiat, Biogjenkjenning)
30. oktober til 1. november ble medisinstudentenes årlige forskningskonferanse, Frampeik, avholdt. De fire byene Oslo, Bergen, Trondheim og Tromsø veksler på å avholde arrangementet, og i år var det idylliske Tromsø sin tur.
Elisabet Kvadsheim, forskerlinjestudent ved UiB og medlem av KGJN, deltok på konferansen. Forskerlinjen gir medisinstudenter mulighet til å arbeide i en forskningsgruppe parallelt med studiene, og i år har Kvadsheim fulltidspermisjon for å fokusere på forskningen. Hun undersøker hvordan det autonome (ikke-viljestyrte) nervesystemet fungerer hos barn og ungdom med ADHD og angst, ved bruk av et mål kalt hjerteratevariabilitet.
Frampeik gir medisinstudenter som forsker muligheten til å presentere sine prosjekter. Det var et stort spenn i tematikken – alt fra biomarkører og medikamentutprøving til Kvadsheims forskning på ADHD. Kvadsheim fikk flere spørsmål fra salen etter presentasjonen, som kan tyde på at deltakerne syntes dette er et viktig og interessant forskningsområde.
Daniel Jensen
During this year, I’ve spent two fortnights at BROAD Institute of MIT and Harvard (https://www.broadinstitute.org) to work on the genetics of ADHD. The first fortnight was in February of 2015, when I was working on the rare variant associations (exome chip content) in adult ADHD. This project is a collaborative effort within IMpACT consortium (http://www.webdesign-rijen.nl/impact/ ) led by our group at Jebsen center. The work has since been finished and we are in the process of publishing the manuscript.
The second fortnight was spent at BROAD in November 2015. This time I was working on the identification of copy number variations (CNVs) related to ADHD. Similarly to the previous project, this is a collaborative effort within Psychiatric Genomics Consortium (PGC, https://www.med.unc.edu/pgc ) that our group is leading. This is the largest CNV study in ADHD, involving over 5.000 cases and 10.000 controls. Future plans of this project involve further work at BROAD in 2016.
Tetyana Zayats
Kerstin J. Plessen, MD, PhD; Elena A. Allen, PhD; Heike Eichele, MD; Heidi van Wageningen, Phd; Marie Farstad Høvik, MD; Lin Sørensen, PhD; Marius Kalsås Worren, MD; Kenneth Hugdahl, PhD; Tom Eichele, MD,PhD
Background:
We examined the blood-oxygen level–dependent (BOLD) activation in brain regions that signal errors and their association with intraindividual behavioural variability and adaptation to errors in children with attention-deficit/hyperactivity disorder (ADHD).
Methods:
We acquired functional MRI data during a Flanker task in medication-naive children with ADHD and healthy controls aged 8–12 years and analyzed the data using independent component analysis. For components corresponding to performance monitoring networks, we compared activations across groups and conditions and correlated them with reaction times (RT). Additionally, we analyzed post-error adaptations in behaviour and motor component activations.
Results:
We included 25 children with ADHD and 29 controls in our analysis. Children with ADHD displayed reduced activation to errors in cingulo-opercular regions and higher RT variability, but no differences of interference control. Larger BOLD amplitude to error trials significantly predicted reduced RT variability across all participants. Neither group showed evidence of post-error response slowing; however, post-error adaptation in motor networks was significantly reduced in children with ADHD. This adaptation was inversely related to activation of the right-lateralized ventral attention network (VAN) on error trials and to taskdriven connectivity between the cingulo-opercular system and the VAN.
Limitations:
Our study was limited by the modest sample size and imperfect matching across groups.
Conclusion:
Our findings show a deficit in cingulo-opercular activation in children with ADHD that could relate to reduced signalling for errors. Moreover, the reduced orienting of the VAN signal may mediate deficient post-error motor adaptions. Pinpointing general performance monitoring problems to specific brain regions and operations in error processing may help to guide the targets of future treatments for ADHD.
Read the article here:
Every year, millions of people consume tons of dietary supplements. In particular, the claimed ergogenic properties of β-alanine and taurine (2-amino-ethanesulfonic acid) have made these amino acids extremely popular particularly among young people and they are widely used by athletes world-wide. Taurine is abundant in many mammalian tissues and has been implicated in a range of different physiological functions. It has a well-documented regulatory role in maintenance of osmotic pressure and preservation of structural integrity of biological membranes. In the nervous system, taurine may modulate protein phosphorylation, serve as a trophic factor, or act as a neurotransmitter / neuromodulator. In several species, taurine deficiency has been linked with specific disease states and also in humans altered levels of taurine has been reported in different conditions, including ADHD and autism. The related amino acid β-alanine, generated from aspartate, and its dipeptide derivative carnosine have also been proposed to have many health benefits.
In this article we have tried to expand the knowledge base for these substances by provide new fundamental insights into the biosynthesis of these amino acids and their derivatives in mice and man, in particular regarding the roles of the biosynthetic enzymes CSAD and GADL1 at the cellular and organ level and determine their expression levels during pre/postnatal development.
In the present study, we compared the catalytic properties, inhibitor sensitivity and expression profiles of GADL1 and CSAD in brain tissue. In mouse and human brain we observed distinct patterns of expression of the PLP-dependent decarboxylases CSAD, GADL1 and glutamic acid decarboxylase 67 (GAD67). CSAD levels were highest during prenatal and early postnatal development; GADL1 peaked early in prenatal development, while GAD67 increased rapidly after birth. Both CSAD and GADL1 are being expressed in neurons, whereas only CSAD mRNA was detected in astrocytes. Cysteine sulfinic acid was the preferred substrate for both mouse CSAD and GADL1, although both enzymes also decarboxylated cysteic acid and aspartate.
In silico screening and molecular docking using the crystal structure of CSAD and in vitro assays led to the discovery of eight new enzyme inhibitors with partial selectivity for either CSAD or GADL1. Lithium had minimal effect on their enzyme activities. In conclusion, taurine biosynthesis in vertebrates involves two structurally related PLP-dependent decarboxylases (CSAD and GADL1) that have partially overlapping catalytic properties but different tissue distribution, indicating divergent physiological roles. Development of selective enzyme inhibitors targeting these enzymes is important to further dissect their (patho)physiological roles.
Mammalian CSAD and GADL1 have distinct biochemical properties and patterns of brain expression
The research groups of Aurora Martinez and Jan Haavik at the KGJN and Department of Biomedicine have recently published their results in a leading journal in the field of proteomics – Molecular and Cellular Protemics. The work presents novel findings on the protein complex between Tyrosine Hydroxylase (TH) and 14-3-3 proteins, and has been performed in close collaboration with international experts within the field of native mass spectrometry (Utrecht University, Netherlands) and in electron microscopy of protein complexes (Centro Nacional de Biotecnologia, Spain). This protein complex is important for regulation of the neurotransmitters dopamine and norepinephrine and the study provides a breakthrough in our understanding of the protein complex and its functions.
The article: Phosphorylation dependence and stoichiometry of the complex formed by tyrosine hydroxylase and 14-3-3γ
Rune Kleppe