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Life Science Paradigms and Foundations
Aims to enumerate novel life science paradigms and theories. All views presented here are completely my own and do not reflect those of anyone else.  Don't take anything here too seriously. It's just brainstorming. Skim all the pages.
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Physical Review Letters: Could Humans Recognize Odor by Phonon Assisted Tunneling?

Physical Review Letters: Could Humans Recognize Odor by Phonon Assisted Tunneling? | Life Science Paradigms and Foundations | Scoop.it
Our sense of smell relies on sensitive, selective atomic-scale processes that occur when a scent molecule meets specific receptors in the nose. The physical mechanisms of detection are unclear: odorant shape and size are important, but experiment shows them insufficient. One novel proposal suggests receptors are actuated by inelastic electron tunneling from a donor to an acceptor mediated by the odorant, and provides critical discrimination. We test the physical viability of this mechanism using a simple but general model. With parameter values appropriate for biomolecular systems, we find the proposal consistent both with the underlying physics and with observed features of smell. This mechanism suggests a distinct paradigm for selective molecular interactions at receptors (the swipe card model): recognition and actuation involve size and shape, but also exploit other processes.
Colbert Sesanker's insight:

more corroboration of luca turin's vibrational theory of smell

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Nature News: Flies sniff out heavy hydrogen

Nature News: Flies sniff out heavy hydrogen | Life Science Paradigms and Foundations | Scoop.it
Skoulakis and his colleagues say that the results offer strong support to a controversial theory of how olfaction works; a theory proposed previously by one of the report's co-authors, Luca Turin at the Massachusetts Institute of Technology in Cambridge. According to Turin, odorants are identified not according to their molecular shape, but their atomic vibrations.

"This is an important paper, and offers very strong evidence in favour of the vibrational theory of olfaction," says materials physicist Andrew Horsfield of Imperial College London.
Colbert Sesanker's insight:

corroboration of luca turin's vibration theory of smell

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Current Opinion in Structural Biology: Electrostatic aspects of protein–protein interactions

Structural and mutational analyses reveal a central role for electrostatic interactions in protein–protein association. Experiment and theory both demonstrate that clusters of charged and polar residues that are located on protein–protein interfaces may enhance complex stability, although the total effect of electrostatics is generally net destabilizing. The past year also witnessed significant progress in our understanding of the effect of electrostatics on protein association kinetics, specifically in the characterization of a partially desolvated encounter complex.
Colbert Sesanker's insight:

The induced fit model considers local protein deformations and local electrostatic interactions but denies long range coulomb interactions generated by an excited protein.

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Science: Probing Allostery Through DNA

Allostery is well documented for proteins but less recognized for DNA-protein interactions. Here, we report that specific binding of a protein on DNA is substantially stabilized or destabilized by another protein bound nearby. The ternary complex's free energy oscillates as a function of the separation between the two proteins with a periodicity of ~10 base pairs, the helical pitch of B-form DNA, and a decay length of ~15 base pairs. The binding affinity of a protein near a DNA hairpin is similarly dependent on their separation, which—together with molecular dynamics simulations—suggests that deformation of the double-helical structure is the origin of DNA allostery. The physiological relevance of this phenomenon is illustrated by its effect on gene expression in live bacteria and on a transcription factor's affinity near nucleosomes.
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Is there any unreasonable effectiveness of mathematics in biology? - Dominique Lambert

basonAn open lecture of Professor Dominique Lambert (University of Namur, Belgium), a renowned expert in the field of theoretical physics and philosophy of scienc...

Colbert Sesanker's insight:

best people for unreasonable effectiveness arguments are Penrose and Tegmark. One caution is that the mathematics described here is being fit to really high level properties like observed 'shapes' and 'patterns' 

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Physics: QBism puts the scientist back into science

Physics: QBism puts the scientist back into science | Life Science Paradigms and Foundations | Scoop.it
Schrödinger wrote in a little-known 1931 letter2 to German physicist Arnold Sommerfeld that quantum mechanics “deals only with the object–subject relation”. Another founder of quantum mechanics, Danish physicist Niels Bohr, insisted in a 1929 essay3 that the purpose of science was not to reveal “the real essence of the phenomena” but only to find “relations between the manifold aspects of our experience”
Colbert Sesanker's insight:

the moral interpretation 

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Freeman Dyson - Where Do the Laws of Nature Come From?

What's real? What's fundamental? There are regularities in nature, things that are or work the same—always, everywhere, across the universe just like across your kitchen. Down deep, what are the laws of nature?
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Masao Ito: The Cerebellum: Brain for an Implicit Self

Leading neuroscientist Dr. Masao Ito advances a detailed and fascinating view of what the cerebellum contributes to brain function.  The cerebellum has been seen as primarily involved in coordination of body movement control, facilitating the learning of motor skills such as those involved in walking, riding a bicycle, or playing a piano. The cerebellum is now viewed as an assembly of numerous neuronal machine modules, each of which provides an implicit learning capability to various types of motor control. The cerebellum enables us to unconsciously learn motor skills through practice by forming internal models simulating control system properties of the body parts.
 
Based on these remarkable advances in our understanding of motor control mechanisms of the cerebellum, Ito presents a still larger view of the cerebellum as serving a higher level of brain functions beyond movements, including the implicit part of the thought and cognitive processes that manipulate knowledge. Ito extends his investigation of the cerebellum to discuss neural processes that may be involved implicitly in such complex mental actions as having an intuition, imagination, hallucination, or delusion.
Colbert Sesanker's insight:

What is the cerebellum, really?

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Child prodigy: A novel cognitive profile places elevated general intelligence, exceptional working memory and attention to detail at the root of prodigiousness

The collected data reveals a startling picture. While each of the prodigies demonstrated an at least moderately elevated level of intelligence, the prodigies' full scale IQ scores were not consistently on the extreme end of the spectrum. What was consistently extraordinary, however, was the child prodigies' working memory scores—a category in which every prodigy tested in the 99th percentile. Additional results suggest a previously unknown connection between child prodigies and autism. The prodigies' family histories yielded an unlikely number of autistic relatives. And the child prodigies received elevated AQ scores with respect to attention to detail, a trait associated with autism. The prodigies did not, however, display many of the other traits typically associated with autism.
Colbert Sesanker's insight:

"What was consistently extraordinary, however, was the child prodigies' working memory scores—a category in which every prodigy tested in the 99th percentile. "  Supports Vandervert's proposal?

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Subcortical Structures and Cognition - Implications for Neuropsychological Assessment

Subcortical Structures and Cognition - Implications for Neuropsychological Assessment | Life Science Paradigms and Foundations | Scoop.it

"The study of neuropsychology traditionally begins with geography: the neocortex as the seat of cognition and behavior, and the subcortical regions coordinating movement. Subcortical Structures and Cognition breaks with this traditional view, arguing for a practice-oriented rethinking of brain organization"

Colbert Sesanker's insight:

The sections on the cerebellum are very good. Again, was there any scientific reason to assume sub-cortical structures are not involved in higher order cognition? 
 

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Cell (Current Biology): Rapid Evolution of the Cerebellum in Humans and Other Great Apes

Humans’ unique cognitive abilities are usually attributed to a greatly expanded neocortex, which has been described as “the crowning achievement of evolution and the biological substrate of human mental prowess” [ 1 ]. The human cerebellum, however, contains four times more neurons than the neocortex [ 2 ] and is attracting increasing attention for its wide range of cognitive functions. Using a method for detecting evolutionary rate changes along the branches of phylogenetic trees, we show that the cerebellum underwent rapid size increase throughout the evolution of apes, including humans, expanding significantly faster than predicted by the change in neocortex size. As a result, humans and other apes deviated significantly from the general evolutionary trend for neocortex and cerebellum to change in tandem, having significantly larger cerebella relative to neocortex size than other anthropoid primates. These results suggest that cerebellar specialization was a far more important component of human brain evolution than hitherto recognized and that technical intelligence was likely to have been at least as important as social intelligence in human cognitive evolution. Given the role of the cerebellum in sensory-motor control and in learning complex action sequences, cerebellar specialization is likely to have underpinned the evolution of humans’ advanced technological capacities, which in turn may have been a preadaptation for language.
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The Atlantic: Secrets of the Creative Brain

The Atlantic: Secrets of the Creative Brain | Life Science Paradigms and Foundations | Scoop.it
A leading neuroscientist who has spent decades studying creativity shares her research on where genius comes from, whether it is dependent on high IQ—and why it is so often accompanied by mental illness. 
Colbert Sesanker's insight:

Excellent overview on the relationship between mental illness and creativity 

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The Dynamics of DNA Methylation in Schizophrenia and Related Psychiatric Disorders (Nature, Neuropsychopharmacology)

The Dynamics of DNA Methylation in Schizophrenia and Related Psychiatric Disorders (Nature, Neuropsychopharmacology) | Life Science Paradigms and Foundations | Scoop.it
Major psychiatric disorders such as schizophrenia (SZ) and bipolar disorder (BP) with psychosis (BP+) express a complex symptomatology characterized by positive symptoms, negative symptoms, and cognitive impairment. Postmortem studies of human SZ and BP+ brains show considerable alterations in the transcriptome of a variety of cortical structures, including multiple mRNAs that are downregulated in both inhibitory GABAergic and excitatory pyramidal neurons compared with non-psychiatric subjects (NPS). Several reports show increased expression of DNA methyltransferases in telencephalic GABAergic neurons. Accumulating evidence suggests a critical role for altered DNA methylation processes in the pathogenesis of SZ and related psychiatric disorders. The establishment and maintenance of CpG site methylation is essential during central nervous system differentiation and this methylation has been implicated in synaptic plasticity, learning, and memory. Atypical hypermethylation of candidate gene promoters expressed in GABAergic neurons is associated with transcriptional downregulation of the corresponding mRNAs, including glutamic acid decarboxylase 67 (GAD67) and reelin (RELN). Recent reports indicate that the methylation status of promoter proximal CpG dinucleotides is in a dynamic balance between DNA methylation and DNA hydroxymethylation. Hydroxymethylation and subsequent DNA demethylation is more complex and involves additional proteins downstream of 5-hydroxymethylcytosine, including members of the base excision repair (BER) pathway. Recent advances in our understanding of altered CpG methylation, hydroxymethylation, and active DNA demethylation provide a framework for the identification of new targets, which may be exploited for the pharmacological intervention of the psychosis associated with SZ and possibly BP+.
Colbert Sesanker's insight:

Molecular Markers of Schizophrenia and psychosis 

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How our microbes make us who we are (TED, Rob Knight)

How our microbes make us who we are (TED, Rob Knight) | Life Science Paradigms and Foundations | Scoop.it
Rob Knight is a pioneer in studying human microbes, the community of tiny single-cell organisms living inside our bodies that have a huge — and largely unexplored — role in our health. “The three pounds of microbes that you carry around with you might be more important than every single gene you carry around in your genome,” he says. Find out why.
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Luca Turin (MIT): A Quantum of Solace - Molecular Electronics of Benzodiazepines

"Benzodiazepines and related drugs modulate the activity of GABA-A receptors, the main inhibitory receptor of the central nervous system. The prevailing view is that these drugs bind at the interface between two receptor subunits and allosterically modulate the response to GABA. In this talk I shall present evidence that benzodiazepines work instead by facilitating electron transport from the cytoplasm to a crucial redox-sensitive group in the gamma subunit. If this idea is correct, benzodiazepines should not only be regarded as keys fitting into a lock, but also as one-electron chemical field-effect transistors fitting into an electronic circuit. "

Colbert Sesanker's insight:

Luca Turin describing benzodiazepines binding to GABA-A receptors via resonance. Similar to his theory of smell. Distinct from the lock and key model.  

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Oxford Journals (PEDS): The investigation of the effects of counterions in protein dynamics simulations

Electrostatic effects not only play an important role in stabilizing proteins' compact structures (Wada and Nakamura, 1981) but the specificity of structure recognition is also determined to a significant extent by electrostatics (Nakamura and Wada, 1985; Jug and Gerwens, 1998).
Colbert Sesanker's insight:

May be related to coherent excitations as these can excite proteins and increase their affinities towards their substrates 

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Earth Talk: Fritjof Capra - The Systems View of Life

"A talk given at Schumacher College (UK), Dartington on May 7th 2014.

The great challenge of our time is to build and nurture sustainable communities, designed in such a manner that their ways of life, physical structures, and technologies do not interfere with nature's inherent ability to sustain life. To do so, requires a new ecological understanding of life, as well as a new kind of "systemic" thinking.

In this lecture, Fritjof Capra describes that such a new understanding of life in terms of complexity, networks, and patterns of organization, has recently emerged at the forefront of science. He will emphasize, in particular, the new conception of the nature of mind and consciousness, which is one of the most radical philosophical implications of the systemic understanding of life; and the urgency of this new understanding for dealing with our global ecological crisis and protecting the continuation and flourishing of life on Earth.

Fritjof Capra was speaking as part of his short course running at Schumacher College."

Colbert Sesanker's insight:

In the book systemic thinking is described as if it is  non-mechanistic and somehow makes room for qualia, social and political issues. There is nothing presented to suggest living organisms are more than 'machines'.  Also implicitly assumes that systemic thinking is what allowed us to break off Cartesian dualism and into panpsychism. 

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Bayesian Interpretation of Quantum Mechanics (Christopher A. Fuchs)

Bayesian Interpretation of Quantum Mechanics (Christopher A. Fuchs) | Life Science Paradigms and Foundations | Scoop.it

"The world we live in is well-described by quantum mechanics. What should we make of that? In a way, the answer to this question was once less positive than it is today. For although quantum theory is a tool of unprecedented accuracy in predicting and controlling the phenomena about us---and by way of that is the basis of our technological society---the intellectual lesson we have come to derive from it has been one largely of limitations. The best place to see this attitude at work is in a standard presentation of the Heisenberg uncertainty relations. It is almost as if the world were holding something back that we really had every right to possess: the task of physics, or so it was believed, is simply to sober up to this fact and make the best of it.

 

In contrast to this textbook lesson, the last five years have seen the start of a significantly more positive, almost intoxicating, attitude about the basic role of quantum mechanics. This is evidenced no more clearly than within the small, but growing, community of workers in Quantum Information Theory and Quantum Computing. The point of departure in both these disciplines is not to ask what limits quantum mechanics places upon us, but instead what novel, productive things we can do in the quantum world that we could not have done otherwise. In what ways can we say that the quantum world is fantastically better than the classical world?"

Colbert Sesanker's insight:

"QBism would say, it’s not that the world is built up from stuff on “the outside” as the Greeks would have had it. Nor is it built up from stuff on “the inside” as the idealists, like George Berkeley and Eddington, would have it. Rather, the stuff of the world is in the character of what each of us encounters every living moment — stuff that is neither inside nor outside, but prior to the very notion of a cut between the two at all."

 

sounds very non-dual and idealistic.. 

 

from the quanta magazine article: https://www.quantamagazine.org/20150604-quantum-bayesianism-qbism/

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Masao Ito (RIKEN Brain Science Institute)

Masao Ito (RIKEN Brain Science Institute) | Life Science Paradigms and Foundations | Scoop.it

"Masao Ito is Special Advisor to the RIKEN Brain Science Institute, Japan.  He received the Fujiwara Prize (1981), the Academy Prize and Imperial Prize (1986), the Robert Dow Neuroscience Award (1993), the IPSEN Foundation Award (1993), the Person of Cultural Merit (1994), the Japan Prize (1996), Order of Culture (1996), and an Honorary Degree of Science from The University of Southern California (1995) and from Torino University (1996).  Dr. Ito's field is neuroscience. He discovered the inhibitory action of cerebellar Purkinje cells, and the characteristic synaptic plasticity, long-term depression (LTD), in these cells. Based upon these findings, he developed a theory that the cerebellum is a general learning machine for acquiring not only motor skills, but also implicit memory in thought."

 

Colbert Sesanker's insight:

Do some research on Ito's views on the cerebellum's role in cognition. Too interesting to spell out here.

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Cognitive functions of the cerebellum explain how Ericsson's deliberate practice produces giftedness

 

"To get at the details of the subtle effects of deliberate practice, Hesheng Liu1 and I recently proposed a thoroughgoing neurophysiological explanation of the child prodigy (Vandervert & Liu, in press). Our explanation is based upon the collaboration of working memory and cognitive functions of the cerebellum (Ito, 1997, 2005; Vandervert, 2003a, b; Vandervert et al., 2007). In our approach all repetitive working memory processes taking place in the cerebral cortex (e.g., in deliberate practice) are adaptively modeled in the cerebellum (see Ito, 1997, 2005; Chein et al., 2003; Vandervert et al., 2007). When the resulting cerebellar control models are fed back to working memory areas of the cortex, the thought processes of working memory become faster, higher in attentional control, and more appropriately and optimally timed (Akshoomoff et al., 1997; Ito, 1997, 2005; Ivry, 1997).

 

The above newer role of the ‘cognitive cerebellum’ (see Schmahmann, 1997; Ramnani, 2006) offers needed detailed support for Ericsson et al.’s proposal. In addition to the cerebellum constructing adaptive models of mental activity occurring in working memory, it has been convincingly argued that the cerebellum does this in the form of multi-pairs of models that constitute complex modular architectures for mental processes that when fed to working memory functions in the cerebral cortex act to facilitate the development of new, higher levels of performance (Haruno et al., 1999; Wolpert et al., 2003)."

 

 

Colbert Sesanker's insight:

The conception of the "Urge to Master" is still completely open.

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Vandervert, L. (2011). The evolution of language: The cerebro-cerebellar blending of visual-spatial working memory with vocalizations. The Journal of Mind and Behavior, 32, 317-331.

Vandervert, L. (2011). The evolution of language: The cerebro-cerebellar blending of visual-spatial working memory with vocalizations. The Journal of Mind and Behavior, 32, 317-331. | Life Science Paradigms and Foundations | Scoop.it
Leiner, Leiner, and Dow proposed that the co-evolution of cerebral cortex and the cerebellum over the last million years gave rise to the unique cognitive capacities and language of humans. Following the findings of recent imaging studies by Imamizu and his colleagues, it is proposed that over the last million or so years language evolved from the blending of (1) decomposed/re-composed contexts or “moments” of visual-spatial experience with (2) those of sound patterns decomposed/re-composed from parallel context-appropriate vocalizations (calls or previously acquired “words”). It is further proposed that the adaptive value of this blending was the progressively rapid access to the control of detailed cause-and-effect relationships in working memory as it entered new and challenging environments. Employing the complex syntactical sequence of nut-cracking among capuchin monkeys, it is proposed how cerebro-cerebellar blending of low-volume vocalization and visual-spatial working memory could have produced the beginnings of the phonological loop as proposed by Baddeley, Gathercole, and Papagno. It is concluded that the blending of cerebellar internal models in the cerebral cortex can explain the evolution of human advancements in the manipulation of cause-and-effect ideas in working memory, and, therefore, the emergence of the distinctive “cognitive niche” of humans proposed by Tooby and DeVore and supportively elaborated by Pinker.
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Economist: Who wants to be a genius?

"This is a much more contentious point. Twenty years ago, Dr Ericsson tried to prove it by training some ordinary laboratory volunteers up to prodigy-level performance in a number-memory task. Average people tend to have a “digit-span” of seven—in other words they can recall a string of seven random digits after hearing it read out once. But after a year's practice, two of his particularly dedicated subjects were able to increase their digit-spans to lengths of 80 and 100."


"Dr Ericsson does not believe that the exceptional abilities of such people are due to their innate talent. Rather, he explains their performance by pointing out that they have developed powerful memories for storing information about particular topics. Psychologists recognise (and brain-science confirms) a distinction between short-term “working” memory and long-term memory. Dr Ericsson believes that prodigies get such impressive mileage out of their working memories by placing important pieces of information into their long-term memories in a way that makes them accessible to working-memory processes. According to Dr Ericsson, this “long-term working memory” is the essential ingredient for expert performance in any field, from chess to typing to golf, and can be developed at will."

 "Mr Gamm appeared to be using his long-term memory to store the working results that he needed to complete his calculations—for example, all the dividends and remainders of a division sum. His use of this extra memory space meant that he could circumvent that perennial pitfall of mental arithmetic, losing one's place. In other respects, Mr Gamm's brain does not appear notably unusual. Nor does he perform with exceptional aptitude on tests of skills that lie outside his area of expertise, such as verbal recall. Moreover, Mr Gamm, who is now 26, was not born with this computing ability. He developed his skills, through four hours of practising memorisation daily, only after he had passed the ripe old age of 20."

 

Colbert Sesanker's insight:

More evidence for the role of Long Term Working Memory (LTM) 

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Play: How it Shapes the Brain, Opens the Imagination, and Invigorates the Soul: Stuart Brown, Christopher Vaughan:

Play: How it Shapes the Brain, Opens the Imagination, and Invigorates the Soul

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"From a leading expert, a groundbreaking book on the science of play, and its essential role in fueling our happiness and intelligence throughout our lives 

We've all seen the happiness on the face of a child while playing in the school yard. Or the blissful abandon of a golden retriever racing across a lawn. This is the joy of play. By definition, play is purposeless, all-consuming, and fun. But as Dr. Stuart Brown illustrates, play is anything but trivial. It is a biological drive as integral to our health as sleep or nutrition. We are designed by nature to flourish through play. 

Dr. Brown has spent his career studying animal behavior and conducting more than six-thousand "play histories" of humans from all walks of life-from serial murderers to Nobel Prize winners. Backed by the latest research, Play(20,000 copies in print) explains why play is essential to our social skills, adaptability, intelligence, creativity, ability to problem solve and more. Particularly in tough times, we need to play more than ever, as it's the very means by which we prepare for the unexpected, search out new solutions, and remain optimistic. A fascinating blend of cutting-edge neuroscience, biology, psychology, social science, and inspiring human stories of the transformative power of play, this book proves why play just might be the most important work we can ever do."

Colbert Sesanker's insight:

The sections describing the physiology of play have a lot of overlap with Vandervert's theories. Special attention given to the cerebellum's role of coordinating and integrating activity across the entire brain. 

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Colbert Sesanker's curator insight, March 19, 10:05 PM

The sections describing the physiology of play have a lot of overlap with Vandervert's theories. Special attention given to the cerebellum's role of coordinating and integrating activity across the entire brain. 

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PLOS ONE: Spectral Signatures of Reorganised Brain Networks in Disorders of Consciousness

PLOS ONE: Spectral Signatures of Reorganised Brain Networks in Disorders of Consciousness | Life Science Paradigms and Foundations | Scoop.it
What are the neural signatures of consciousness? This is an elusive yet fascinating challenge to current cognitive neuroscience, but it takes on an immediate clinical and societal significance in patients diagnosed as vegetative and minimally conscious. In these patients, it leads us to ask whether we can test for the presence of these signatures in the absence of any external signs of awareness. Recent conceptual advances suggest that consciousness requires a dynamic balance between integrated and differentiated networks of information exchange between brain regions. Here we apply this insight to study such networks in patients and compare them to healthy adults. Using the science of graph theory, we show that the rich and diversely connected networks that support awareness are characteristically impaired in patients, lacking the ability to efficiently integrate information across disparate regions via well-connected hubs. We find that the quality of patients' networks also correlates well with their degree of behavioural responsiveness, and some vegetative patients who show signs of hidden awareness have remarkably well-preserved networks similar to healthy adults.
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Potential metabolite markers of schizophrenia (Nature, Molecular Psychiatry)

Potential metabolite markers of schizophrenia (Nature, Molecular Psychiatry) | Life Science Paradigms and Foundations | Scoop.it
Schizophrenia is a severe mental disorder that affects 0.5–1% of the population worldwide. Current diagnostic methods are based on psychiatric interviews, which are subjective in nature. The lack of disease biomarkers to support objective laboratory tests has been a long-standing bottleneck in the clinical diagnosis and evaluation of schizophrenia. Here we report a global metabolic profiling study involving 112 schizophrenic patients and 110 healthy subjects, who were divided into a training set and a test set, designed to identify metabolite markers. A panel of serum markers consisting of glycerate, eicosenoic acid, β-hydroxybutyrate, pyruvate and cystine was identified as an effective diagnostic tool, achieving an area under the receiver operating characteristic curve (AUC) of 0.945 in the training samples (62 patients and 62 controls) and 0.895 in the test samples (50 patients and 48 controls). Furthermore, a composite panel by the addition of urine β-hydroxybutyrate to the serum panel achieved a more satisfactory accuracy, which reached an AUC of 1 in both the training set and the test set. Multiple fatty acids and ketone bodies were found significantly (P<0.01) elevated in both the serum and urine of patients, suggesting an upregulated fatty acid catabolism, presumably resulting from an insufficiency of glucose supply in the brains of schizophrenia patients.
Colbert Sesanker's insight:

recent work (2013) on metabolic markers for schizophrenia 

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