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What is life? The physicist who sparked a revolution in biology | Matthew Cobb

What is life? The physicist who sparked a revolution in biology | Matthew Cobb | Metabolomics and Disease | Scoop.it
Matthew Cobb: Erwin Schrödinger introduced some of the most important concepts in biology, including the idea of a 'code' of life

Via Ben van Lier, Aviva Lev-Ari, PhD, RN
Larry Bernstein's insight:

The idea of a code of life was perhaps not his most important contribution. He might well have influenced the later emergence of molecular biology as a member of the Bohr-network. The later outcome was the James Watson (Franklin, Crick) search for the genetic code with Pauling in pursuit, and the Cold Spring Harbor meetings.

 

However, his book, "What is Life", is much more than that.  He also posed the dilemma that the complexity of life is not to be resolved by any mathematical formulation. The code itself is important, but not sufficient. The code has to be translated, so it is of evolutionary significance. There are archaic codes that may not even be expressed. Life involves the interaction of a living organism with an external environment that it has to engage in. It becomes a difference exercise for a multicellular, and multiorgan creature than for unicellular life. The environmental concerns are not minimal either - mountains, the deep sea, and sea level.  There was much of physiology and biochemistry that was yet to be learned at the time he wrote.

 

Jose Eduardo de Salle Rosalino has made exceptionally astute comments on this...and related thoughts...

 

Frequently, I prefer to present my thoughts based upon a historical perspective the reason for that is not to present myself as a academic-peacock proud of its tail on the contrary is to use this perspective to indicate when scientific thoughts were moved away from previous track. 
I cannot see energetic regulation in mammals as something that could be tackled without restoring correct understanding of homeostasis that is a regulation that has extracellular aspects in its regulatory mechanisms to be taken into account. Those external (extracellular) aspects are linked with the cell differentiated function while pure energetics is linked to intracellular aspects of regulation. 
This is the main form to address differences found when muscles (heart, skeletal smooth) are compared or heart and liver are compared. Eventually, this are also the major reason why tumors are rare in one tissue and most common in others…

 

Larry H. Bernstein, MD, FCAP 
http://pharmaceuticalinnovations.com

 

Metabolic Genomics & Pharmaceutics2015http://www.amazon.com/dp/B012BB0ZF0

 

Author, Curator and EditorLarry H Bernstein, MD, FCAP

Chief Scientific Officer

Leaders in Pharmaceutical Business Intelligence

Larry.bernstein@gmail.com


http://www.amazon.com/dp/B012BB0ZF0

 

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Ebola and ZMapp: What is the 'Secret Serum' That 'Cured' American Doctor Kent Brantly?


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Kenzibit's curator insight, August 5, 2014 3:24 PM

"ZMapp is composed of three 'humanised' monoclonal antibodies manufactured in plants, specifically Nicotiana. It is an optimised cocktail combining the best components of MB-003 and ZMAb.

Kenzibit's curator insight, August 5, 2014 3:25 PM

"ZMapp is composed of three 'humanised' monoclonal antibodies manufactured in plants, specifically Nicotiana. It is an optimised cocktail combining the best components of MB-003 and ZMAb.

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Boost Your NAD And Fix It All? - Corante

Boost Your NAD And Fix It All? - Corante | Metabolomics and Disease | Scoop.it
Boost Your NAD And Fix It All?
Corante
It's a key regulatory switch for a number of metabolic pathways under those conditions, but there's no obvious reason for it to be getting more active just because you're getting older.
Larry Bernstein's insight:

Boosting NAD - the nicotinamiide adenine diphosphate might tie in with increased energy availability because of the tie in with energy utilization both through the pyruvate forward reaction, which would also be wasteful if there was muscle proteolysis to provide gluconeogenic precursors.  That would signal a change favorable to cancer, which relies on anaerobic glycolysis under aerobic conditions.  NADP, which has an additional phosphate is more tied in with the citric acic cycle, and it is actually critical in synthetic functions.  You have to look at this by organ systems, except for the hepatocyte.

 

But if in aging you observe a change in the ratio of NAD/NADP, then I would want to see the tie in with the transhydrogenase.  I'm not sure it is a metabolic switch.  There has to be cell renewal, and the garbage is removed by the ubiquitin system.  Where does the balance come in?  We know that diet and exercise can be helpful, and if we look there we have omega-3 PUFA/n-6 ratio/and we also have an inportant arguable situation with S-adenosyl methionine for maintenance of LBM.  If that is compromized, you get degenerative diseases.  Then we have to look at how these are related.

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eLife: Fungal effector Ecp6 outcompetes host immune receptor for chitin binding through intrachain LysM dimerization (2013)

eLife: Fungal effector Ecp6 outcompetes host immune receptor for chitin binding through intrachain LysM dimerization (2013) | Metabolomics and Disease | Scoop.it

While host immune receptors detect pathogen-associated molecular patterns to activate immunity, pathogens attempt to deregulate host immunity through secreted effectors. Fungi employ LysM effectors to prevent recognition of cell wall-derived chitin by host immune receptors, although the mechanism to compete for chitin binding remained unclear. Structural analysis of the LysM effector Ecp6 of the fungal tomato pathogen Cladosporium fulvum reveals a novel mechanism for chitin binding, mediated by intrachain LysM dimerization, leading to a chitin-binding groove that is deeply buried in the effector protein. This composite binding site involves two of the three LysMs of Ecp6 and mediates chitin binding with ultra-high (pM) affinity. Intriguingly, the remaining singular LysM domain of Ecp6 binds chitin with low micromolar affinity but can nevertheless still perturb chitin-triggered immunity. Conceivably, the perturbation by this LysM domain is not established through chitin sequestration but possibly through interference with the host immune receptor complex.


Via Kamoun Lab @ TSL, Loiret David
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Twenty%20Tips%20for%20Senior%20Thesis%20Writers%20Revised%20August%202012.pdf

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Researchers sequence the genome of global deep ocean

Researchers sequence the genome of global deep ocean | Metabolomics and Disease | Scoop.it
Biologists have started to sequence the genome of the global deep ocean. They are using more than 2,000 samples of microorganisms collected in the Atlantic, Indian and Pacific Oceans during the Malaspina Expedition.  

This collection of marine microbial genomic, the first in the world on a global scale, will provide new clues about a reservoir of biodiversity yet to explore, considering that it could imply the discovery of tens of millions of new genes in the coming years.

The works of sequencing (framed in the Malaspinomics project) focus on the viruses, bacteria and protists that inhabit the ocean to 4,000 meters deep. Most of the biomass of marine organisms is composed of microorganism. Of these, a 72% inhabit the dark ocean, from 200 meters deep. However, so far, the DNA or RNA sequencing had been almost exclusively limited to the ocean surface waters.

Malaspinomics preliminary results reveal a wealth of unknown species of microorganisms in the deep ocean, characterized by an intense biological activity. Specifically, 60% of the bacterial species of the deep ocean detected by massive sequencing techniques are unknown.


Via Ed Rybicki, Loiret David
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Ed Rybicki's curator insight, August 12, 2013 3:35 AM

Viruses: they'll find lots of viruses.  But they may well miss the ssRNA and small ssDNA viruses - and it'll have to be done again....

Gretel Posadas's curator insight, August 23, 2013 8:19 AM

#Malaspinomics preliminary results reveal a wealth of unknown species of microorganisms in the deep ocean, characterized by an intense #biologicalactivity. Specifically, 60% of the bacterial species of the deep ocean detected by massive sequencing techniques are unknown.

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Priming with Recombinant Auxotrophic BCG Expressing HIV-1 Gag, RT and Gp120 and Boosting with Recombinant MVA Induces a Robust T Cell Response in Mice

Priming with Recombinant Auxotrophic BCG Expressing HIV-1 Gag, RT and Gp120 and Boosting with Recombinant MVA Induces a Robust T Cell Response in Mice | Metabolomics and Disease | Scoop.it

In previous studies we have shown that a pantothenate auxotroph of Myocbacterium bovis BCG (BCGΔpanCD) expressing HIV-1 subtype C Gag induced Gag-specific immune responses in mice and Chacma baboons after prime-boost immunization in combination with matched rMVA and VLP vaccines respectively. In this study recombinant BCG (rBCG) expressing HIV-1 subtype C reverse transcriptase and a truncated envelope were constructed using both the wild type BCG Pasteur strain as a vector and the pantothenate auxotroph. Mice were primed with rBCG expressing Gag and RT and boosted with a recombinant MVA, expressing a polyprotein of Gag, RT, Tat and Nef (SAAVI MVA-C). Priming with rBCGΔpanCD expressing Gag or RT rather than the wild type rBCG expressing Gag or RT resulted in higher frequencies of total HIV-specific CD8+ T cells and increased numbers of T cells specific to the subdominant Gag and RT epitopes. Increasing the dose of rBCG from 105 cfu to 107 cfu also led to an increase in the frequency of responses to subdominant HIV epitopes. A mix of the individual rBCGΔpanCDvaccines expressing either Gag, RT or the truncated Env primed the immune system for a boost with SAAVI MVA-C and generated five-fold higher numbers of HIV-specific IFN-γ-spot forming cells than mice primed with rBCGΔpanCD containing an empty vector control. Priming with the individual rBCGΔpanCD vaccines or the mix and boosting with SAAVI MVA-C also resulted in the generation of HIV-specific CD4+ and CD8+ T cells producing IFN-γ and TNF-α and CD4+ cells producing IL-2. The rBCG vaccines tested in this study were able to prime the immune system for a boost with rMVA expressing matching antigens, inducing robust, HIV-specific T cell responses to both dominant and subdominant epitopes in the individual proteins when used as individual vaccines or in a mix.

 

Disclaimer: married to the last author....B-)

 


Via Ed Rybicki
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HLA targeting efficiency correlates with human T-cell response magnitude and with mortality from influenza A infection

Experimental and computational evidence suggests that HLAs preferentially bind conserved regions of viral proteins, a concept we term “targeting efficiency,” and that this preference may provide improved clearance of infection in several viral systems. To test this hypothesis, T-cell responses to A/H1N1 (2009) were measured from peripheral blood mononuclear cells obtained from a household cohort study performed during the 2009–2010 influenza season. We found that HLA targeting efficiency scores significantly correlated with IFN-γ enzyme-linked immunosorbent spot responses (P = 0.042, multiple regression). A further population-based analysis found that the carriage frequencies of the alleles with the lowest targeting efficiencies, A*24, were associated with pH1N1 mortality (r = 0.37, P = 0.031) and are common in certain indigenous populations in which increased pH1N1 morbidity has been reported. HLA efficiency scores and HLA use are associated with CD8 T-cell magnitude in humans after influenza infection. The computational tools used in this study may be useful predictors of potential morbidity and identify immunologic differences of new variant influenza strains more accurately than evolutionary sequence comparisons. Population-based studies of the relative frequency of these alleles in severe vs. mild influenza cases might advance clinical practices for severe H1N1 infections among genetically susceptible populations.


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Responsible Conduct in Synthetic Biology

Terry Johnson of UC Berkeley and Synberc provides a perspective on the unique features of synthetic biology that require special consideration above and beyo...

Via Gerd Moe-Behrens, Loiret David
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Gerd Moe-Behrens's curator insight, August 16, 2013 5:59 PM

Responsible Conduct in Synthetic Biology http://bit.ly/13FZcQm

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BMC Genomics | Full text | Web-based visual analysis for high-throughput genomics

Visualization plays an essential role in genomics research by making it possible to observe correlations and trends in large datasets as well as communicate findings to others.

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The anti-HBV effect mediated by a novel recombinant eukaryotic expression vector for IFN-alpha

The anti-HBV effect mediated by a novel recombinant eukaryotic expression vector for IFN-alpha | Metabolomics and Disease | Scoop.it

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Candidate microRNA biomarkers in human epithelial ovarian cancer: systematic ... - 7thSpace Interactive (press release)

Candidate microRNA biomarkers in human epithelial ovarian cancer: systematic ...
7thSpace Interactive (press release)
There is an urgent need to search for specific and sensitive biomarkers for early diagnosis of EOC.
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Regular cigarette smoking influences the transsulfuration pathway, endothelial function, and inflammation biomarkers in a sex-gender specific manner in healthy young humans

Regular cigarette smoking influences the transsulfuration pathway, endothelial function, and inflammation biomarkers in a sex-gender specific manner in healthy young humans | Metabolomics and Disease | Scoop.it
@PHCL3700 Use of biomarkers suggests female smokers are at earlier risk than male smokers to cardiovascular problems http://t.co/X453S7IRXX
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All Ashkenazi Jews alive today can trace their roots to a group of just 350 people who lived 600 to 800 years ago

All Ashkenazi Jews alive today can trace their roots to a group of just 350 people who lived 600 to 800 years ago | Metabolomics and Disease | Scoop.it

Ashkenazi Jews (AJ), identified as Jewish individuals of Central- and Eastern European ancestry, form the largest genetic isolate in the United States. AJ demonstrate distinctive genetic characteristics1, 2, including high prevalence of autosomal recessive diseases and relatively high frequency of alleles that confer a strong risk of common diseases, such as Parkinson’s disease3and breast and ovarian cancer4. Several recent studies have employed common polymorphisms5,-13 to characterize AJ as a genetically distinct population, close to other Jewish populations as well as to present-day Middle Eastern and European populations. Previous analyses of recent AJ history highlighted a narrow population bottleneck of only hundreds of individuals in late medieval times, followed by rapid expansion12, 14.

 

The AJ population is much larger and/or experienced a more severe bottleneck than other founder populations, such as Amish, Hutterites or Icelanders15, whose demographic histories facilitated a steady stream of genetic discoveries. This suggests the potential for cataloguing nearly all founder variants in a large extant population by sequencing a limited number of samples, who represent the diversity in the founding group (for example, ref. 16). Such a catalogue of variants can make a threefold contribution: First, it will enable clinical interpretation of personal genomes in the sizeable AJ population by distinguishing between background variation and recent, potentially more deleterious mutations. Second, it will improve disease mapping in AJ by increasing the accuracy of imputation. Third, the ability to extensively sample a population with ancient roots in the Levant is expected to provide insights regarding the histories of both Middle Eastern and European populations.

 

Now a team of scientists report high-depth sequencing of 128 complete genomes of AJ controls. Compared with European samples, our AJ panel has 47% more novel variants per genome and is eightfold more effective at filtering benign variants out of AJ clinical genomes. Reconstruction of recent AJ history from such data confirms a recent bottleneck of merely ≈350 individuals. Modeling of ancient histories for AJ and European populations using their joint allele frequency spectrum determines AJ to be an even admixture of European and likely Middle Eastern origins. The researchers date the split between the two ancestral populations to ≈12–25 Kyr, suggesting a predominantly Near Eastern source for the repopulation of Europe after the Last Glacial Maximum.


Via Dr. Stefan Gruenwald, Aviva Lev-Ari, PhD, RN
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Lake Erie Algae Bloom Matches Climate Change Projections

The bloom that poisoned Toledo's waters may become more common as the waters of the Great Lakes warm
-- Read more on ScientificAmerican.com

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Software upgrades to bionic eye enable color recognition, improve resolution, image focus, zooming

Software upgrades to bionic eye enable color recognition, improve resolution, image focus, zooming | Metabolomics and Disease | Scoop.it

The first bionic eye to be approved for patients in the U.S. is getting software upgrades. The FDA-approved Argus II Retinal Prosthesis System from Second Sight Medical Products transmits images from a small, eye-glass-mounted camera wirelessly to a microelectrode array implanted on a patient’s damaged retina. The array sends electrical signals via the optic nerve, and the brain interprets a visual image.

 

Now, to speed up the development process, Second Sight is working on a software platform called Acuboost that would make updating previously manufactured Argus models as easy as updating your computer’s operating system. This is especially important because the Argus is an implanted device, and installing it inside a patient’s eye requires pretty invasive surgery. So software upgrades would benefit both new patients and patients who already have the device implanted.

 

The company is currently developing algorithms to improve resolution, image focus and zooming. Their latest software can also automate brightness adjustments and enable color recognition.

 

Thus far, scientists at Second Sight have been able to produce the perception of multiple colors in the lab by sending different patterns of stimulation to each electrode in the retinal implant. When the Argus camera picks up red or green, that information would be encoded through different patterns of electrical activity, which would be sent to the electrodes in the patient’s eye, creating the perception of color.


Via Dr. Stefan Gruenwald, Loiret David
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The Hitchhiker’s Guide to Python! — The Hitchhiker's Guide to Python

The Hitchhiker’s Guide to Python! — The Hitchhiker's Guide to Python | Metabolomics and Disease | Scoop.it

This opinionated guide exists to provide both novice and expert Python developers a best-practice handbook to the installation, configuration, and usage of Python on a daily basis.


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Mutated Genes in Schizophrenia Map to Brain Networks

Mutated Genes in Schizophrenia Map to Brain Networks | Metabolomics and Disease | Scoop.it
People with schizophrenia have a high number of spontaneous mutations in genes that form a network in the front region of the brain. The findings reveal new clues about the disorder.

 

Researchers found that people with schizophrenia have a high number of spontaneous mutations in genes that form a network in the front region of the brain. The findings reveal further clues about the causes of the disorder.

 

Schizophrenia networks in the prefrontal cortex area of the brain.Image courtesy of Dr. Mary-Claire King, University of Washington.

 

Schizophrenia is a chronic, severe brain disorder. People with schizophrenia may hear voices or see things that aren’t there. They may believe that people are reading their minds or controlling their thoughts.

 

The disorder occurs in 1% of the general population. However, it occurs in 10% of people who have a parent, brother or sister with the disorder, indicating that genetics plays a role in its cause.

 

Previous studies have shown that many people with schizophrenia have de novo, or new, genetic mutations. These misspellings in a gene’s DNA sequence occur spontaneously and so aren’t shared by their close relatives.

 

Dr. Mary-Claire King of the University of Washington in Seattle and colleagues set out to identify spontaneous genetic mutations in people with schizophrenia and to assess where and when in the brain these misspelled genes are turned on, or expressed. The researchers sequenced the exomes (protein-coding DNA regions) of 399 people—105 with schizophrenia plus their unaffected parents and siblings. Gene variations that were found in a person with schizophrenia but not in either parent were considered spontaneous.

 

The likelihood of having a spontaneous mutation was associated with the age of the father in both affected and unaffected siblings. Significantly more mutations were found in people whose fathers were 33-45 years at the time of conception compared to 19-28 years.

 

Among people with schizophrenia, the scientists identified 54 genes with spontaneous mutations predicted to cause damage to the function of the protein they encode. The researchers used newly available database resources that show where in the brain and when during development genes are expressed. The genes, they found, form an interconnected expression network with many more connections than that of the genes with spontaneous damaging mutations in unaffected siblings.

 

The spontaneously mutated genes in people with schizophrenia were expressed in the prefrontal cortex, a region in the front of the brain. The genes are known to be involved in important pathways in brain development. Fifty of these genes were active mainly during the period of fetal development.

“Processes critical for the brain’s development can be revealed by the mutations that disrupt them,” King says. “Mutations can lead to loss of integrity of a whole pathway, not just of a single gene.”

 

These findings support the concept that schizophrenia may result, in part, from disruptions in development in the prefrontal cortex during fetal development.


Via Agãpe Lenõre, Dr. Stefan Gruenwald, Loiret David
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Linus Ridge's comment, August 15, 2013 5:08 AM
Thanks for this.
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Plant J: Resistance gene enrichment sequencing (RenSeq) enables re-annotation of the NB-LRR gene family from sequenced plant genomes and rapid mapping of resistance loci in segregating populations ...

Plant J: Resistance gene enrichment sequencing (RenSeq) enables re-annotation of the NB-LRR gene family from sequenced plant genomes and rapid mapping of resistance loci in segregating populations ... | Metabolomics and Disease | Scoop.it

RenSeq is a NB-LRR gene-targeted, Resistance gene enrichment and sequencing method that enables discovery and annotation of pathogen resistance gene family members in plant genome sequences. We successfully applied RenSeq to the sequenced potatoSolanum tuberosum clone DM, and increased the number of identified NB-LRRs from 438 to 755. The majority of these identified R gene loci reside in poorly- or previous un-annotated regions of the genome. Sequence and positional details on the twelve chromosomes have been established for 704 NB-LRRs and can be accessed through a genome browser that we provide. We compared these NB-LRR genes and the corresponding oligonucleotide baits with the highest sequence similarity and demonstrated that ~80% sequence identity is sufficient for enrichment. Analysis of the sequenced tomato S. lycopersicum extended the NB-LRR complement to 394 loci. We further describe a methodology that applies RenSeq to rapidly identify molecular markers that co-segregate with a trait of interest. In two independent segregating populations involving the wild Solanum species S. berthaultii (Rpi-ber2) and S. ruiz-ceballosii (Rpi-rzc1), we were able to apply RenSeq to successfully identify markers that co-segregate with resistance towards the late blight pathogenPhytophthora infestans. These SNP identification workflows were designed as easy-to-adapt Galaxy pipelines.


Via The Sainsbury Lab, Kamoun Lab @ TSL, Loiret David
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MIT: How to make big things out of small interlocking composite components

MIT: How to make big things out of small interlocking composite components | Metabolomics and Disease | Scoop.it

MIT researchers have developed a lightweight structure whose tiny blocks can be snapped together much like the bricks of a child’s construction toy. The new material, the researchers say, could revolutionize the assembly of airplanes, spacecraft, and even larger structures, such as dikes and levees.

 

Neil Gershenfeld, director of MIT’s Center for Bits and Atoms, likens the structure — which is made from tiny, identical, interlocking parts — to chainmail. The parts, based on a novel geometry that Cheung developed with Gershenfeld, form a structure that is 10 times stiffer for a given weight than existing ultralight materials. But this new structure can also be disassembled and reassembled easily — such as to repair damage, or to recycle the parts into a different configuration.

 

The individual parts can be mass-produced; Gershenfeld and Cheung are developing a robotic system to assemble them into wings, airplane fuselages, bridges or rockets — among many other possibilities.

The new design combines three fields of research, Gershenfeld says: fiber composites, cellular materials (those made with porous cells) and additive manufacturing (such as 3-D printing, where structures are built by depositing rather than removing material).

With conventional composites — now used in everything from golf clubs and tennis rackets to the components of Boeing’s new 787 airplane — each piece is manufactured as a continuous unit. Therefore, manufacturing large structures, such as airplane wings, requires large factories where fibers and resins can be wound and parts heat-cured as a whole, minimizing the number of separate pieces that must be joined in final assembly. That requirement meant, for example, Boeing’s suppliers have had to build enormous facilities to make parts for the 787.

 

Pound for pound, the new technique allows much less material to carry a given load. This could not only reduce the weight of vehicles, for example — which could significantly lower fuel use and operating costs — but also reduce the costs of construction and assembly, while allowing greater design flexibility. The system is useful for “anything you need to move, or put in the air or in space,” says Cheung, who will begin work this fall as an engineer at NASA’s Ames Research Center. 

 

The concept, Gershenfeld says, arose in response to the question, “Can you 3-D print an airplane?” While he and Cheung realized that 3-D printing was an impractical approach at such a large scale, they wondered if it might be possible instead to use the discrete “digital” materials that they were studying.

“This satisfies the spirit of the question,” Gershenfeld says, “but it’s assembled rather than printed.” The team is now developing an assembler robot that can crawl, insectlike, over the surface of a growing structure, adding pieces one by one to the existing structure.


Via Dr. Stefan Gruenwald, Loiret David
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Ruth Obadia's curator insight, August 17, 2013 1:51 PM

MIT researchers have developed a lightweight structure whose tiny blocks can be snapped together much like the bricks of a child’s construction toy.

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Gut Immunity: brilliant educational animation from Nature Immunology › In Sciento Veritas

Gut Immunity: brilliant educational animation from Nature Immunology › In Sciento Veritas | Metabolomics and Disease | Scoop.it
It is well-said that a picture is worth a thousand words. I have always found that a good, illustrative graphic can make a great impact ...
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Priming with Recombinant Auxotrophic BCG Expressing HIV-1 Gag, RT and Gp120 and Boosting with Recombinant MVA Induces a Robust T Cell Response in Mice

Priming with Recombinant Auxotrophic BCG Expressing HIV-1 Gag, RT and Gp120 and Boosting with Recombinant MVA Induces a Robust T Cell Response in Mice | Metabolomics and Disease | Scoop.it

In previous studies we have shown that a pantothenate auxotroph of Myocbacterium bovis BCG (BCGΔpanCD) expressing HIV-1 subtype C Gag induced Gag-specific immune responses in mice and Chacma baboons after prime-boost immunization in combination with matched rMVA and VLP vaccines respectively. In this study recombinant BCG (rBCG) expressing HIV-1 subtype C reverse transcriptase and a truncated envelope were constructed using both the wild type BCG Pasteur strain as a vector and the pantothenate auxotroph. Mice were primed with rBCG expressing Gag and RT and boosted with a recombinant MVA, expressing a polyprotein of Gag, RT, Tat and Nef (SAAVI MVA-C). Priming with rBCGΔpanCD expressing Gag or RT rather than the wild type rBCG expressing Gag or RT resulted in higher frequencies of total HIV-specific CD8+ T cells and increased numbers of T cells specific to the subdominant Gag and RT epitopes. Increasing the dose of rBCG from 105 cfu to 107 cfu also led to an increase in the frequency of responses to subdominant HIV epitopes. A mix of the individual rBCGΔpanCDvaccines expressing either Gag, RT or the truncated Env primed the immune system for a boost with SAAVI MVA-C and generated five-fold higher numbers of HIV-specific IFN-γ-spot forming cells than mice primed with rBCGΔpanCD containing an empty vector control. Priming with the individual rBCGΔpanCD vaccines or the mix and boosting with SAAVI MVA-C also resulted in the generation of HIV-specific CD4+ and CD8+ T cells producing IFN-γ and TNF-α and CD4+ cells producing IL-2. The rBCG vaccines tested in this study were able to prime the immune system for a boost with rMVA expressing matching antigens, inducing robust, HIV-specific T cell responses to both dominant and subdominant epitopes in the individual proteins when used as individual vaccines or in a mix.

 

Disclaimer: married to the last author....B-)

 


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Researchers develop compilation of protein interaction data ...

Researchers have created a platform detailing all atomic data on protein structures and protein interactions for eight organisms.

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Novel Biomarkers for Diagnosing and Managing Heart Failure Patients

Novel Biomarkers for Diagnosing and Managing Heart Failure Patients | Metabolomics and Disease | Scoop.it
Novel Biomarkers for Diagnosing and Managing Heart Failure Patients. This program is part of AACC’s “Cutting Edge Technologies, Common Sense Solutions” webinar series. Dr.
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