I am however glad that the Windows version returned to its emulator-compatible state: Volume 11 — June 05, I hope this helps you with HydroBuddy: I think this pot is mine. I suppose the database is using ' as a separator. If too much water and not enough air surrounds the plants roots, it is possible to gradually lower the medium's water-retention capability by mixing in increasing quantities of perlite. In the formula I'm attempting to replicate I can tell I will need X amount of an acid to get to the required pH but HydroBuddy wants to use less of the acid and more of the salt with the same element.
Dr. Fuhrman’s Aggregate Nutrient Density Index (ANDI)
On the contrary, practice effects on IQ tests are caused by just seeing the items without awareness of which are the right answers. Of course, so what are we supposed to conclude from that? Whether the difference is large enough to be useful in some sense is immaterial to the statistician. I am curious what other people see given that I did my experiments with Google in a Chrome incognito window.
The best thing about statements like this is that no one is always right so everyone can tell just how full of BS you are. Thanks for making that clear. Still not sure how to do this for the genes that are in the recent paper. Very frustrating that full disclosure is not required in the article. Are we really supposed to reverse engineer it? How is not giving the results considered to be Science?
The Gini Index score of the United States has been steadily going up in tandem with the intensification of Financialization: I generally agree with you on China. To have a government that is so overwhelmingly dominated by people with a common training risks shutting out other ways of thinking about what our politics could be.
Anyone can be sued for anything, no matter how absurd or egregious. And everyone knows how expensive and overwhelming a legal assault can be. The rule of law is essential to a free and orderly society, but too much law and lawyering makes democratic self-rule impossible, and common sense legally precarious. One way to find them might be to go to the gene view page on dbsnp as above and then zoom out to a chromosome wide level.
You could then select the LOFs i,e. This would give 10, for Chromosome Then search by genes. Yet, perhaps the new paper is actually doing an even better job than dbsnp.
That link is a good example of what you can do, and perhaps a good model to follow e. Though there are quite a few blank fields. Doing a database join on that file with another SNP list by rsID might be a good start at what we are looking for depends on of SNPs which appear in both.
Spreadsheets are much better than text tables for doing further analysis. This is hard to imagine. How is that even science to publish the results and not provide the SNPs? Articles that merely hint at what the research has found might need to be withheld from publication until such findings are produced. Some people leave school, find a brainless job, and never read a book afterwards.
Others will not only find a challenging, intellectually stimulating work but also use their spare time to learn more. If that was even remotely true 50 points , the superior, old bookworm geezer caste would visibly run intellectual circles around everyone else since the dawn of man and everyone would be in awe.
I do suspect that IQ can be boosted through lifelong study but the IQ gain is probably less than 0. Frankly, these theories reek of SJW politics. Africans have the lowest frequency of the rare and ultra-rare variants. While the Finns and others have very high rates of these variants. It is almost as though the people who left African were the least favored. This would make sense as the most highly connected would probably want to remain at the center of humanity.
Similar situation when the new world was settled: Research into IQ is a great thing. Instead they foster emotionalism over reason. They glorify group work and group think. Not teaching, instead mind arson. Their products are human lemmings, easily stampeded by TPTB when desired. This is a feature not a bug. Check out the blog InvisibleSerfsCollar dot com. The ratio of deleterious to neutral alleles per individual increases as humans migrated out of Africa, consistent with negative selection against deleterious variants and serial founder effects that reduce the effective population size 9.
Here is a graphic showing effective population sizes for the Genomes populations over time. The Ashkenazi Jewish bottleneck was even greater. This page quotes an effective population of about years ago: For the Finns this article gives an effective population of 1, for generations ago at the founding: Figure 1B is the opposite of what I had expected.
If rare and ultra variants are typically detrimental, I was unsure why Finns and Ashkenazim both high IQ groups had so many while Africans not usually understood to constitute a high IQ group had so few. Especially since for high IQ to happen many things need to go right and few things can go wrong: Maybe it has Nothing to do with bottlenecks, my friend.
Every once in a while a few very intelligent people experience angelic inspiration, and that makes all the difference. That was, if not — to be fair — expected, not — to be accurate — surprising. NO, that was not angelic inspiration, that was just science chugging along in it usual way, where accuracy gets a little clearer after all the bumpy muddy roads of even the most naturally intelligent of the grinders, like even Einstein, have done their truck-driver best.
The only reason that one group of people is not marginally more clueless than another group — and all groups are fairly clueless, getting things right is a low-scoring game, year in, year out — beyond nutrition and a seasoning of Aspergerite suffering in the gene pool — is the miraculously aesthetic if one is a materialist or angelic if one understands how, as Umberto Eco used to say, between cigarettes inspiration that accords the humble young adult and once in a while the rare older adult in his or her thoughts with the much much much less humble but still, sometimes, measurable or describable world we assume we live in.
As Don Colacho humbly said, the rain it raineth every day… no, that was someone else. Don Colacho said something about order and disorder that is relevant …. It does not equate to memory, but it does rely on accessing information from long-term memory. And extra tuitions or hardworkings. PISA Maths tends to test the application of mathematical knowledge to solve problems set in real-world contexts. This had exposed the many lies told about rote learning of the high performing countries from the whinging lusers.
Interestingly there were seperate CPS data for crystallized IQ knowledge acquisition, knowledge utilization and the composite scores. A plot of the data is here http: It can be seen that the high performing countries have much better knowledge acquisition rate, either through more hardworking or through innate ability. This give them extra competitive advantage positive outliers further to the right even when their knowledge utilization rates are already much better than the rest.
There are also tests for handling vague problems where the students interactively have to know which questions to ask to get a full picture of the problems. Keep in mind that environment matters a lot. I also expect that you understand that this study makes HBD myths null and void. Athletic performance is a real and measurable variable.
We know how and why people are better than others, athletically speaking. Early humans were hunter-gatherer nomads. Arabia and India are closer to East Africa than West Africa, and people migrated over very long distances within Africa. Genetic bottlenecks and drift are enough to explain genetic load in non-Africans in my opinion. Except conservatives give more of their own money than liberals. More even if disregarding religious giving. They give more blood and volunteer their time more, too.
I have worked in a psychiatric hospital with overwhelmingly liberal staff for 40 years. They will tell you that they are more giving and caring than other people. In fact, they tell it to each other all the time. I had not expected this. My original narrative was that those who left Africa might have been more adventurous and perhaps of higher ability. In the journey to new lands various cognitive challenges would have arisen that would have exerted a selective force towards those with higher g.
In light of this new research, an alternative narrative could be that those leaving Africa were the less favored and less socially and politically entrenched. Leaving Africa at that time must have felt like an excommunication.
Whatever existed of human civilization would have been almost entirely concentrated in Africa. Africa would have been THE happening place. By comparison the frontier must have felt barren. In some places of the world, it still does. For those migrating out of Africa, near family mating would become almost inevitable.
There is evidence that early peoples were aware of the dangers of family members intermarrying, though in small bands of people there often would seem to be few other options. There might have been a sense that the purging of deleterious alleles was impossible; people just made do as best they could. Yet, within the African context, society would be more fully formed and such selection against certain alleles would be more possible.
These pieces of contrary evidence usually fall from the sky without warning which then a just so workaround to fit everything back into place again. Even the IQ idea was like finding a sea shell on the sea shore.
Would be so much better if we could be a few more steps ahead of these finds and not a few steps behind. From my latest comment in the other thread, which might interest you. Check out the astonishing and eye-opening stats and graphs there:. This is another amazing figure. I tried to find religious demographics for the U. It would be interesting to see how many of them are Protestant, Catholic, Jewish, Muslim, etc.
And of course, it is a necessary consequence of the great over-representation of Jews in our trade that all other ethnic groups are under-represented. According to Wikipedia they are now 4. Is this discrimination, reverse discrimination, or just what happens as people seek work that suits them? And then there are ethnic groups that have virtually no representation at all in these big firm partnerships.
Middle-Eastern muslims come to mind. Nobody who was there what now we call Africa knew they were in Africa or anywhere. People were going left or right back and forth. Some were going West, some were going East, North or South. Some where going in circles clock wise and some counter clock wise.
Some ended up against the ocean, some against a river, some against mountains. Some stayed and some moved along the river. It was more of a Brownian motion than any journey that you can imagine. Nobody had any map to know where they were and where they were going. They did not have destination, they did not have plans. Some were escaping and some were chasing something or looking for something. They did not keep diaries and did not take selfies.
They did not have any sense where they had been or where were they coming from. If the totality of people in Africa had a given genetic diversity it meant that there were many families and groups that different from each other.
Any subset that is spatially limited will have smaller diversity than the total set. This is the reason why the genetic diversity of people who ended up away from Africa is smaller that the total diversity of Africans.
It does not mean that genetic diversity of Norwegian is smaller than diversity of Pygmy or some tribe in Nigeria. The great diversity of Africa only means that there more tribes and sub races that can hate each other more than Swedes can hate Norwegians because they are more different form each other than Swedes and Norwegians.
The only thing they have in common is their dark skin and few other physical features which does not prevent Hutus form killing Tutsis. In term of genes responsible for skin color they are no more diverse than Europeans or Asians.
Lots of ignorant Blacks and Africans take a misguided pride in the genetic diversity of Africa. They are not aware that genetic diversity is not defined on individual level. Neither Afrosapience nor you can claim having greater genetic diversity. Because you and him have none. Greater diversity of Africa means that if some plague is going to come as a result of dancing with dead corpses in Madagascar or eating humans in Botswana for some medical purposes that is going to wipe out a lot of people it is possible it will wipe out all Nigerians and Kenyans but there might be a chance that Pygmy will survive because they are sufficiently more different from Nigerians and Kenyans.
Only in this sense some Africans may survive. It does not mean that Afrosapience will survive. But there are some genes that Europeans are more diverse. One day we will not for sure but in the meantime there is zero evidence that Africans are smarter than Europeans or Asians.
Yes, I met some Blacks for whom the fact of not having Neanderthal genes gives them some sense of superiority. I wonder how widely this meme is spread among AA Blacks and Africans? They were not like trekkers migrating over long distances on purpose, they were just nomads seizing hunting and gathering opportunities.
They had no maps, no awareness of landforms, they were moving in random directions, which lead some to leave Africa to Arabia and then the rest of Eurasia and the Americas, others moved to Western Africa, by chance. I doubt the supremacy of lawyers over American policies causes the inequalities. A large share of the whites oppose social programs for fear that it benefits blacks and immigrants.
Race struggle took over class struggle. Diversity means that there are more variants which are unique to Africans than to non-Africans. It also means that Africans are more often heterozygote, which protects against harmful recessive alleles. The Republicans will occasionally put up someone who has scientific training, but not often. I use an incognito window for the search completion test not for my typical browsing because Google customizes its completion results. That way I get a result that is more likely to be representative of what others see.
That sentence is almost true. Every lawyer is not always right, just like you. I suppose I should realize that anyone who would write a sentence like yours is an idiot who does not deserve to be taken seriously.
Given that I supplied you with a link to the full text for the paper underlying my argument as you requested I am surprised not to see a response. See Table 1 in https: Look, I have wasted enough time with you and your cold winters fantasy tales. The evidence that Africans have less genetic load, cognition genes included, is here and all we have to do is to deal with the facts whether we like it or not.
Some people want to be proud of something. I do not think that pride is a necessary ingredient for a human soul that everybody needs. Happy well adjusted people do not need pride. In fact pride is a toxic ingredient. After all superbia pride is the seventh mortal sin for a good reason. From the psychological angle one can see that pride serves to compensate or mask some perceived deficits in other areas.
When I was growing up in Europe utterances using this pattern were completely unknown. Did it come from the special education classes to make the special kids feel good? Is that where Blacks are getting it from?
Anyway, I felt kind of sorry as well as embarrassed for the Black guy I met who felt proud that he did not have Neanderthal genes unlike me. Likewise I should feel sorry for A-something or O-something when they clearly derive some degree of pride from the fact that Africa has larger genetic diversity than Europe or Asia. It is interesting because it is clearly an expression of continental nationalism if not chauvinism. What about galactic pride? What is the common denominator of Africa to them?
If Africa is so diverse A-something or O-something might be more distant from each other than say from some southern Europeans in some genetic respects.
So, the common denominator must be the external phenotype, i. And this you get from people who will fight you tooth and nail that race does not exist. And then you hear this: To quote from the report,. These problem-solving skills are key to success in all pursuits, and can be developed in school through curricular subjects. Can memory and rote learning solve non-traditional problems? Results show that students in Singapore and Korea, followed by students in Japan, score higher in problem solving than students in all other participating countries and economies.
This topic can be a major study by itself, but here only the relative results are shown. The general results for creative problem solving on static and vague interactive problems are the same. Thus only the results of interactively solving the ill defined problems are shown here. The extreme cases considered were from PISA the percentages of students in each country who have more than 4 hours of off-school Maths lessons per week. There was no data for Singapore. First beside Korea at rank 2 with Now in real life students normally will stop having extra tuitions if they are not effective.
Thus it is normally because of poor performance that requires tuition, otherwise there could be the interpretation of extra tuitions dumbing down the students.
In the main the plot supported this reasoning. From the plot it become clear there might not be much values for Koreans, Turks, Isrealis, HongKongers, Macaoists and Taiwaneses to have too much extra tuitions, they were more or less locked into arm races which they could not jump out and without much value addition.
Japanese with little extra tuitions was performing better than them. Elsewhere in the PISA report asserted that most of the East Asians gained their knowledge during regular school hours. The data have to be extracted from the questionaires dataset and this might not worth the effort. The relationship TuteGt4 and CPS scores is statistically significant only when those outliers are removed.
So why are all those whinges when extra tuitions do not seem to have conferred much extra advantages? So no response to that paper I gave you in response to your request.
Now we know what you do when you are wrong. All these enormous resources invested into raising intelligence and we wind up talking about 1 IQ point? How many trillions of dollars of year does this cost? Of course, with genetic enhancement it is already clear that we could increase human IQ over points, and the intelligence increasing benefits would continue generation after generation for eternity.
Cost estimates for increasing IQ by points already appear to be within range of middle income families in developed nations. When the technology is introduced the IQ gap between nations with economic resources and those without could become at least temporarily overwhelming.
If increasing intelligence through genetic enhancement is thought of being so morally reprehensible, then why do we spend all those trillions of dollars a year and spend all those decades of our lives learning in order to increase our IQs?
Is there research into the possibility of increasing intelligence past adolescence or early adulthood? From what I understand the literature suggests that brain development continues perhaps into the mids, though I would think that life-long brain development is a possibility. The evidence that learning helps prevent dementia has been accumulating for some time. Enriched environment as a technique to positively change neuroanatomy has been ongoing for a very long time.
Why were the SNP not identified and included in the article? He pathetically missed his target because no matter who is genetically advantaged, I do not believe in genetic determinism. I have not figured it out. The idea of whiteness is a recent and primarily American construct. But you sure as hell have always been proud of your various tribes, nationalities, ethnicities and religious traditions. Similarly, black conscientiousness is an alien concept in Africa with the exception of those areas where white supremacists constructed a caste system with themselves on top.
Obviously, you could never have black power fist pumpers like Stephen Biko or Nelson Mandela in Nigeria. You can have all the races you want. But nobody has butchered each other more than than the relatively inbred and bottlenecked Europeans. I have very dark almost black and very light almost white people in my immediate family. And, of course, a wide spectrum in between. I have more skin color diversity in my family alone than exists in all of white Europe.
Previous studies of genetic and craniometric traits have found higher levels of within-population diversity in sub-Saharan Africa compared to other geographic regions. This study examines regional differences in within-population diversity of human skin color.
Published data on skin reflectance were collected for 98 male samples from eight geographic regions: Regional differences in local within-population diversity were examined using two measures of variability: For both measures, the average level of within-population diversity is higher in sub-Saharan Africa than in other geographic regions. This difference persists even after adjusting for a correlation between within-population diversity and distance from the equator.
Though affected by natural selection, skin color variation shows the same pattern of higher African diversity as found with other traits. Most people associate Africans with dark skin. But different groups of people in Africa have almost every skin color on the planet, from deepest black in the Dinka of South Sudan to beige in the San of South Africa.
Now, researchers have discovered a handful of new gene variants responsible for this palette of tones. The study, published online this week in Science, traces the evolution of these genes and how they traveled around the world. While the dark skin of some Pacific Islanders can be traced to Africa, gene variants from Eurasia also seem to have made their way back to Africa. And surprisingly, some of the mutations responsible for lighter skin in Europeans turn out to have an ancient African origin.
In South Africa, a rare group of children unknowingly find themselves resistant to the effects of HIV. Even without antiretroviral treatment, they will never develop AIDS, or so scientists believe.
Unlike adults and other children who succumb to the virus if not treated — enabling it to attack their immune cells and weakening their immunity to disease — these kids harbor huge amounts of HIV within their blood but remain unscathed. Diversity … It also means that Africans are more often heterozygote, which protects against harmful recessive alleles. Africans are diverse because their social and political arrangements have, until very recent times, been organized on a tribal basis.
Africa, the least urbanized continent, has a population comprising many relatively homogeneous inbreeding groups, which are less, not more, heterzygous than the population of the European and North American cities now filled with immigrants from throughout the world. Thus most Africans still possess a genetic constitution representative of a tribe, rather than a continental or transcontinental outbred population.
Belonging to inbreeding tribes, i. Inbreeding limits the frequency of detrimental genes, i. Outbreeding increases the genetic load because detrimental recessive genes are more likely to be masked by good alleles. However, that means that the genetic load in outbreeding populations increases over time.
Outbreeding populations thus go through a period of hybrid vigor, evident in the early stages of urbanization first in Europe, then the Americas, Japan, the Asian Tigers, now China and in the future, presumably, Africa. A downside to outbreeding is that desirable gene groupings, resulting from various selective pressures, e. A further downside to outbreeding is that the hybrid vigor that characterizes outbreeding populations initially, gradually fades, leaving a population lacking either unique local adaptation or unusual energy, but possessing a higher genetic load than the inbred populations from which it has been derived.
The impact of inbreeding on reproduction, childhood mortality, and Mendelian disorders is well documented. This is despite the fact that inbreeding may have a greater influence on late onset traits than on traits that are subject to early selection. Characterization of Greater Middle Eastern genetic variation for enhanced disease gene discovery Here we generated a whole-exome GME variome from 1, unrelated subjects.
We detected substantial diversity and admixture in continental and subregional populations, corresponding to several ancient founder populations with little evidence of bottlenecks. Despite millennia of elevated rates of consanguinity in the GME, we detected no evidence for purging of recessive alleles. Instead, we detected large, rare homozygous blocks, distinct from the small homozygous blocks found in other populations , supporting the occurrence of recent consanguineous matings and allowing the identification of genes harboring putatively high-impact homozygous variants in healthy humans from this population.
If you have inbreeding, you bring together deleterious recessive alleles, and so they get exposed to selection. In this way you can purge the segregating genetic load. It works with plants. But humans, and complex animals in general, are not plants. Middle Easterners should stop marrying cousins to reduce the disease load. Some of these nations, like Qatar, have a lot of money to throw at Mendelian diseases. A heterozygote advantage describes the case in which the heterozygous genotype has a higher relative fitness than either the homozygous dominant or homozygous recessive genotype.
The specific case of heterozygote advantage due to a single locus is known as overdominance. Polymorphism can be maintained by selection favoring the heterozygote, and this mechanism is used to explain the occurrence of some kinds of genetic variability.
A common example is the case where the heterozygote conveys both advantages and disadvantages, while both homozygotes convey a disadvantage. A well-established case of heterozygote advantage is that of the gene involved in sickle cell anaemia.
Often, the advantages and disadvantages conveyed are rather complicated, because more than one gene may influence a given trait or morph. Major genes almost always have multiple effects pleiotropism , which can simultaneously convey separate advantageous traits and disadvantageous traits upon the same organism.
Previous research, comparing measures of dominance, overdominance and epistasis mostly in plants , found that the majority of cases of heterozygote advantage were due to complementation or dominance , the masking of deleterious recessive alleles by wild-type alleles, as discussed in the articles Heterosis and Complementation genetics , but there were also findings of overdominance, especially in rice. Genomic Patterns of Homozygosity in Worldwide Human Populations Per-individual total lengths of class A and class B ROH that reflect LD patterns are lowest in populations from Africa, rising in a stepwise fashion in successive continental groups and having relatively similar values within continents.
This finding can be explained as a consequence of a serial-migration model outward from Africa; each migration decreases effective population size, generating LD, reducing haplotype diversity, and increasing the probability that identical copies of the same long haplotype will pair together in the same individual. The per-individual total lengths of class C ROH, which result largely from inbreeding, do not follow such a pattern and are instead most frequent in populations where isolation and consanguineous unions are more common.
The different continental patterns observed for different ROH classes therefore reflect the distinct forces generating ROH of different sizes. It is outbreeding among formerly inbreeding populations that results in to high heterozygosity. So yes, where Africans from all over the continent get together and interbreed you have high heterozygosity. But most Africans are still visibly members of distinct tribes. I seem to remember receiving an A or maybe it was an A minus — memory is said to be untrustworthy on such details for an essay I wrote, God knows how long ago, that dealt with this question.
What I concluded, based on some rough and ready calculations, was that inbreeding does not purge lethal recessive genes entirely, although it must obviously keep the frequency in check since the homozygote is, well, lethal. The Passenger pigeon, of which there were several billions in North America prior to the arrival of the white man, was highly genetically homogeneous.
That, it has been postulated, was the reason it failed to survive the presence of men with guns. It had one genetically determined mode of existence, with no options to survive a change in environment. Humanity, under the whip of the globalist elite seems headed the way of the Passenger pigeon: To mention the undesirability of the ongoing globalist project for the genocide of national groups particularly the Europeans is, of course taboo, and will generate a paeon of contemptuous ridicule and hate speech from brainwashed biological illiterates.
Such was the confusion that existed with humans after leaving Africa for tens of thousands of years. The humans that left Africa were essentially exiles. They had been evicted from the Promised Land.
The vast void that they confronted once leaving would have felt infinite. The one organizing force would have been to diffuse to lower density as would occur with Brownian motion. Such random low density particles do not congeal into anything more interesting. Neither did humans for tens of thousands of years.
Your depiction of the random Brownian motion of the first humans Out of Africa was very compelling for me. I think that such a description has substantial explanatory power for much of how human history has unfolded over the last , or more years. As humans gradually journeyed out of Africa, there would have been this enormous almost endless landscape to fill. Just imagine what it must have been like! Whenever any population density arose some of the people would likely have decided to pack up and move on.
Such an environment would have made almost any sense of community or the state essentially impossible. There are many barren polar regions of the world that have never managed to establish any meaningful social cohesion. Consider what happens on a crowded bus.
As soon as someone gets off, someone standing will take the seat. Once everyone standing is seated people will start moving as far away from others as they can. Something similar would have happened with humans over the last many tens of thousands of years. Under such a scenario it is not surprising in the least that we only see the emergence of any meaningful degree of social organization starting about 10, years ago.
This is a testable idea as genetic samples from humans years ago have been found. Yet with Africa a meaningful density effect has probably been operating for upwards of 50, years. There should exist deep cultural traditions that have developed possibly over the span of tens of thousands of years.
Leaving such a homeland for the barrens must have been difficult. Africa has its dangers though think of all the entirely novel dangers that would be encountered when leaving and think of leaving what would have been the center of human culture and technology. Encountering other humanoids with possibly higher cognitive ability would have been one such surprise faced by those leaving Africa.
The problem time and time again in psychometrics is that by only looking at a very brief interval of time the powerful role of the environment can be ignored which then transfers the load to genetics. This would all to obvious if one were to jump into a time machine and go back in time or years. As we move to an idealized future of a constant environment everything could be loaded on genetics.
In that book the author suggests that what we understand as human consciousness Theory of Mind emerges only relatively recently perhaps years ago. If the nature of human contact has been as limited as the above discussion suggests then such a recent emergence of humanness might not be so far fetched. In fact when first contact was made with some isolated human populations even a few centuries ago one might have observed such an absence of a Theory of Mind in these peoples.
Many on this blog are likely not big fans of big government or the deep state, though imagine what life would be like without it. Before about years ago, there are no constructions of collective human effort that can be found. It took humans almost 50, years to get it together! It is only after we organized and systematized our world that we have been able to make any forward progress. I suppose, though that the counter argument would be that the state is not so much an instrument of progress as a parasite living off the benefits that accrue from human civilization.
You keep getting your metaphors wrong. If anything they got evicted from the Eden and they went to the Promised Land. The ones who remained in the Eden did so because they remained ignorant, they did not eat the fruit from the Tree of Knowledge. Sexual selection presumably continues to play some role in human evolution, although cosmetic surgery, acquisition of wealth, and other factors may relax this as well. For example, although it has been argued that female choice for healthy males may aid in reducing the mutation load Whitlock and Agrawal , the strength of such reinforcement would also be diminished in human populations where suboptimal male phenotypes are hidden by various medical procedures.
Thus, without any compelling counterarguments at this time, it remains difficult to escape the conclusion that numerous physical and psychological attributes are likely to slowly deteriorate in technologically advanced societies, with notable changes in average preintervention phenotypes expected on a timescale of a few generations, i.
The following nutrients were included in the evaluation: For consistency, nutrient quantities were converted from their typical measurement conventions mg, mcg, IU to a percentage of their Dietary Reference Intake DRI. For nutrients that have no DRI, goals were established based on available research and current understanding of the benefits of these factors. To make it easier to compare foods, the raw point totals were converted multiplied by the same number so that the highest ranking foods leafy green vegetables received a score of , and the other foods received lower scores accordingly.
For over 25 years, Dr. Fuhrman has shown that it is possible to achieve sustainable weight loss and reverse heart disease, diabetes and many other illnesses using smart nutrition. In his medical practice, and through his books and PBS television specials, he continues to bring this life-saving message to hundreds of thousands of people around the world. All material provided on the DrFuhrman.
Using molecular modeling, we predicted the 3-D structure of the mAB B2 active center and analyzed the characteristics of its interaction with different polycyclic aromatic hydrocarbons, as well as with the benzo[a]pyrene immunomimetic peptide. Thus, a comprehensive analysis of the results of the obtainment of hapten-specific components of anticarcinogenic vaccines allowed us to outline a strategy for future development in this direction.
Marshak 2 , D. Mukha 1 , A. The results presented allow for the consideration of the chromatin diminution as a mechanism of rDNA copy number regulation. Chernorizov 1 , V. ABSTRACT Hsp70 is a chaperone protein that participates in the folding of de novo synthesized proteins, protection of the hydrophobic regions of denaturated proteins, the regulation of apoptosis, the immune response, and several other cellular processes.
Despite the large number of publications devoted to the functioning and structure of Hsp70, a reliable full-size 3D structure of this protein remains currently unavailable. Several probable full-size models of human Hsp70 have been constructed based on the structures of individual domains and their components from different organisms and using molecular modeling methodology.
The stability of the obtained structures was studied using molecular dynamics. As a result of such an analysis, the most adequate model was selected. The model was built on the basis of Hsp70 elements from Bos Taurus and Caenorhabditis elegans. Using the method of steered molecular dynamics, the key salt bridges responsible for the interdomain interactions were identified: Based on the performed molecular modeling, the scheme of the mechanism triggering ATP hydrolysis and leading to the separation of ATPase and the substrate-binding domains was proposed.
Kovalyov 1 , M. Kovalyova 1 , K. Lisitskaya 1 , L. Eremina 1 , A. Ivanov 1 , E. Gerasimov 1 , E. Sadykhov 1 , N. Ulasova 2 , O. Sokolova 2 , I. Toropygin 3 , V. PCP consists of 7 interrelated modules, each containing four levels of proteomic and biomedical data on the proteins in corresponding tissues or cells. The first data level, onto which each module is based, is a 2DE proteomic reference map where proteins separated by 2D electrophoresis, and subsequently identified by mass-spectrometry, are marked.
The results of proteomic experiments form the second data level. The third level contains protein data from published articles and existing databases. The database will be useful in a wide range of applications, including studies of molecular mechanisms of the aetiology and pathogenesis of prostate diseases, finding new diagnostic markers, etc. Logunov 1 , I.
Gitlin 2 , M. Shmarov 1 , P. Adzhieva 1 , A. Moroz 1 , N. Kostyukova 1 , L. Burdelya 2 , B. Naroditsky 1 , A. Gintsburg 1 , A. The activation of PRR by specific, highly conserved pathogen-associated molecular patterns PAMPs induces numerous immune reactions related both to innate and adaptive immunity. Makarycheva 1 , E.
Tsareva 1,2 , M. Sudomoina 1,2 , O. Kulakova 1,2 , B. Titov 1,2 , O. Bykova 3 , N. Kuzenkova 3 , A. Boiko 2 , O. Proteins of the immune system, as well as proteins that are involved in the infiltration of activated immune cells in the CNS, play an important role in the pathogenesis of MS.
We investigated the association and linkage with MS of the following immune-system genes polymorphisms: For this purpose we used the transmission disequilibrium test TDT.
The group investigated was comprised of nuclear families of Russian ethnicity, each consisting of an affected offspring and his nonaffected parents. Suplatov 1,2 , V.
However, numerous enzymes that derive from a common ancestor and have undergone substantial functional alterations during natural selection appear not to have a sequence similarity acceptable for a statistically reliable comparative analysis.
At the same time, their active site structures, in general, can be conserved, while other parts may largely differ. Therefore, it sounds both plausible and appealing to implement a comparative analysis of the most functionally important structural elements — the active site structures; that is, the amino acid residues involved in substrate binding and the catalytic mechanism.
A computer algorithm has been developed to create a library of enzyme active site structures based on the use of the PDB database, together with programs of structural analysis and identification of functionally important amino acid residues and cavities in the enzyme structure.
The insight has revealed a high structural similarity of catalytic site areas, including the conservative organization of a catalytic triad and oxyanion hole residues, despite the wide functional diversity among the remote homologues compared. Gusev 2 , O. Zaitseva 2 , E. Lazareva 1 , G. Onishchenko 1 , E. Kuznetsova 3 , A. Tkachev 4 , A. Feofanov 1,5 , M. ABSTRACT Engineered nanoparticles ENPs are now being used in many sectors of industry; however, the impact of ENPs on the environment still requires further study, since their use, recycling, and accidental spill can result in the accumulation of nanoparticles in the atmosphere, soil, and water.
Plants are an integral part of ecosystems; hence their interaction with ENPs is inevitable. It is important to understand the consequences of this interaction and assess its potential effects. The present research is focused on studying the effects of the industrial material Taunit, containing multi-walled carbon nanotubes MWNTs , on plants, and testing of its ability to penetrate into plant cells and tissues.
Taunit has been found to stimulate the growth of roots and stems and cause an increase in peroxidase activity in Onobrychis arenaria seedlings. MWNTs from Taunit were detected in the cells and tissues of seedling roots and leaves, implying the ability of MWNTs to penetrate into roots and accumulate there, as well as their ability to be transported into seedling leaves.
Thus, the changes in the physiological parameters of plants are associated not only with MWNT adsorption on the root surface, as previously believed, but also with their penetration, uptake and accumulation in the plant cells and tissues. Ovsepyan 4 , D.
Panchenkov 1,3 , E. Telegin 4 , N. Zhigalova 1 , E. Golubev 2 , T. Sviridova 5 , S. Matskeplishvili 2 , K. Skryabin 1 , U. In this work, a minimally invasive method for simulating myocardial infarction in mice is described in the Russian Federation for the very first time; the procedure is carried out by ligation of the coronary heart artery or by controlled electrocoagulation.
As a part of the methodology, a series of anesthetic, microsurgical and revival protocols are designed, owing to which a decrease in the postoperational mortality from the initial ECG confirms the development of large-focal or surface myocardial infarction.
Postmortal histological examination confirms the presence of necrosis foci in the heart muscles of Altogether, the medical data allow us to conclude that an adequate mouse model for myocardial infarction was generated. A further study is focused on the standardization of the experimental procedure and the use of genetically modified mouse strains, with the purpose of finding the most efficient therapeutic approaches for this disease.
The living cell is a relatively simple, but at the same time very sophisticated biological system. After the sequencing of the human genome, molecular physiology has endeavored to investigate the systems of cellular interactions at a completely new level based on knowledge of the spatial organization and functions of receptors, their ligands, and protein-protein interactions. In recent years, the achievements in molecular physiology have centered on the study of sensor reception mechanisms and intercellular data transfer, as well as the immune system physiology, amongst other processes.
Petrin 1 , S. Arutyunov 1 , V. Tsarev 1 , L. Akulenko 1 , A. Zorina 2 , D. Rebrikov 3,4 , A. Rubanovich 3,4 , S.
Borinskaya 1,4 , N. ABSTRACT Gingivitis and periodontitis are chronic inflammatory diseases of the periodontal tissue in humans caused by both environmental and genetic factors.
The human cytokine genes that regulate the immune response may play an important role in the development of these chronic inflammatory diseases. The aim of this study is to analyze the allele status of eight human cytokine genes and to associate it with the inflammation of periodontal tissue in humans.
A total of unrelated males of Russian origin were studied. The influence of genetic factors on gingivitis may contribute to the understanding of the mechanisms of interaction between genetic and environmental factors in periodontal conditions, and to the identification of risk groups for effective prevention and treatment. ABSTRACT Semiconductor quantum dots QDs are a new class of fluorophores with unique physical and chemical properties, which allow to appreciably expand the possibilities for the current methods of fluorescent imaging and optical diagnostics.
Here we discuss the prospects of QD application for molecular diagnostics of tumors ranging from cancer-specific marker detection on microplates to non-invasive tumor imaging in vivo. We also point out the essential problems that require resolution in order to clinically promote QD, and we indicate innovative approaches to oncology which are implementable using QD. ABSTRACT Progressive loss of the telomeric ends of chromosomes caused by the semi-conservative mechanism of DNA replication is an important timing mechanism which controls the number of cells doubling.
Telomerase is an enzyme which elongates one chain of the telomeric DNA and compensates for its shortening during replication. Therefore, telomerase activity serves as a proliferation marker. Telomerase activity is not detected in most somatic cells, with the exception of embryonic tissues, stem cells, and reproductive organs. This is the primary reason why assays regarding the development of telomerase activity have attracted the attention of researchers. Telomerase activity testing may be useful in the search for telomerase inhibitors, which have the potential to be anti-cancer drugs.
Moreover, telomerase activation may play a positive role in tissue regeneration; e. All telomerase activity detection assays can be divided into two large groups: The methods discussed in this review are suitable for testing telomerase activity in different samples: An adequate study of the disease requires essential understanding of the molecular fundamentals of the pathogenesis. In the present study, the structure and dynamics of the recombinant peptide corresponding to the APP fragment, GlnLys, which comprises the APP transmembrane domain with an adjacent N-terminal juxtamembrane sequence, were determined in the membrane mimetic environment composed of detergent micelles using NMR spectroscopy.
Alekseenko 1,2 , M. Zinovyeva 1 , T. Vinogradova 1 , E. It develops from pigment-forming cells melanocytes and results in a high number of lethal outcomes.
The use of genetic constructs with the ability to specifically kill melanoma cells, but not normal cells, might increase the lifespan of patients, as well as improve their quality of life. One of the methods to achieve a selective impact for therapeutic genes on cancer cells is to utilize a transcriptional control mechanism using promoters that are specifically activated only in cancerous cells. In this review, promoters of the genes that are preferentially expressed in melanoma cells are described.
These promoters, and other highly melanoma-specific regulatory elements, reduce the unspecific expression of therapeutic genes in normal tissues. Moreover, cancer-specific promoters and their elements are advantageous for the development of universal anticancer drugs.
Examples of the use of double promoters that have a high potential as instruments in cancer gene therapy are also given in this review. Dykman 1 , N. ABSTRACT Functionalized gold nanoparticles with controlled geometrical and optical properties are the subject of intensive studies and biomedical applications, including genomics, biosensorics, immunoassays, clinical chemistry, laser phototherapy of cancer cells and tumors, the targeted delivery of drugs, DNA and antigens, optical bioimaging and the monitoring of cells and tissues with the use of state-of-the-art detection systems.
This work will provide an overview of the recent advances and current challenges facing the biomedical application of gold nanoparticles of various sizes, shapes, and structures. The review is focused on the application of gold nanoparticle conjugates in biomedical diagnostics and analytics, photothermal and photodynamic therapies, as a carrier for delivering target molecules, and on the immunological and toxicological properties.
KEYWORDS gold nanoparticles; plasmon resonance; biosensors; biomedical diagnostics; photothermal and photodynamic therapy; targeted drug delivery; nanotoxicology. Balanovsky 2,5 , A. Melnikov 3 , A.
Lash-Zavada 3 , V. Tyazhelova 2 , V. Akhmetova 4 , O. Zhukova 2 , Yu. Shneider 2 , I. Borinskaya 2 , A. Marusin 1 , M. Spiridonova 1 , K. Simonova 1 , I. Khitrinskaya 1 , M. Radzhabov 7 , A. Romanov 5 , O. Shtygasheva 8 , S. Balanovskaya 5 , A. Rybakova 3 , E. Khusnutdinova 4 , V. Puzyrev 1 , N. The degree of polymorphism and population diversity of microsatellite loci within the Power Plex system Promega in Russian populations; the distribution of alleles and genotypes within the populations of six cities and 11 ethnic groups of the Russian Federation; the levels of intra- and interpopulation genetic differentiation of population; genetic relations between populations; and the identification and forensic medical characteristics of the system of markers under study were determined.
Significant differences were revealed between the Russian populations and the U. A database of the allelic frequencies of 15 microsatellite loci that are used for DNA identification and forensic medical examination was created; the database has the potential of becoming the reference for performing forensic medical examinations in Russia.
The spatial organization of genetic diversity over the panel of the STR markers that are used for DNA identification was revealed. It represents the general regularities of geographical clusterization of human populations over various types of genetic markers.
Samsonova 1,2 , K. Kudryashova 1 , A. ABSTRACT The antimicrobial peptide Ltc1-K and its derivates without one, two, then three N-terminal amino acid residues were studied based on the hypothesis backed by some experimental data that the hydrophobic N-terminal moiety of linear cationic antimicrobial peptides defines their haemolytic activity.
The synthesis of AICAR in Bacillus subtilis cells is controlled by the enzymes of purine biosynthesis; their genes constituting purine operon pur -operon. Reconstruction of purine metabolism in B. An insertion inactivating the gene purR that encodes the negative transcriptional regulator of the purine biosynthesis operon was introduced into the B.
Furthermore, the expression integrative vector carrying a strong promoter of the rpsF gene encoding the ribosomal protein S6 was designed. The modified purF and prs genes were inserted into the chromosome of the B. Extra amino acid residues are added to protein S6. The functional significance of these modifications has remained unclear. These modifications are not vital to the cells, and it is likely that they have regulatory functions. This paper reviews all the known posttranslational modifications of ribosomal proteins in Escherichia coli.
Certain enzymes responsible for the modifications and mechanisms of enzymatic reactions are also discussed. Various membrane-like media, partially those mimicking the conditions of multicomponent biological membranes, are used to study the structural and thermodynamic features that define the character of oligomerization of transmembrane helical segments. The choice of the composition of the membrane-mimicking medium is conducted in an effort to obtain a biologically relevant conformation of the protein complex and a sample that would be stable enough to allow to perform a series of long-term experiments with its use.
However, a number of peculiarities place lipid bicelles closer to natural lipid bilayers in terms of their physical properties. Kulakov 1 , O. Boriskina 1 , D. ABSTRACT Periodontitis is a common disease that is considered to be a manifestation of the distortion of the ratio between the normal and conditionally pathogenic microflora of periodontal pockets.
In this study, the ratio between the six most important periodontal pathogens and the total microflora of the periodontal pocket in healthy individuals and patients with varying severity of periodontitis was ascertained by quantitative real-time PCR. It was ascertained that the relative content of Porphyromonas gingivalis, Prevotella intermedia, and Tannerella forsythensis Bacteroides forsythus persistently develops in the total microflora of the periodontal pocket upon progressing periodontitis; this value is higher than that in the control group by more than two orders of magnitude upon a severe degree of chronic generalized periodontitis.
KEYWORDS ecosystem; habitat; periodontitis; periodontopathogenic microflora of periodontal pockets; quantitative polymerase chain reaction. However, after 20 min, the production of NO decreases; while the amplitude of Ca-signals remains high.
Arkhipenko 1 , E. Petrova 1 , N. Nikitin 1 , A. Protopopova 2,3 , E. Dubrovin 3 , I. Yaminskii 2,3 , N. Rodionova 1 , O. Fedichev 1 , A. Vinnik 1 , J. Testa 3 , O. In vitro tests of the 14 top-rated ligands showed that compound Q12 displays the best ability to inhibit the proliferation of Dlx5 positive mouse lymphoma cells, which correlates with the down-regulation of c-myc expression.
Compound Q12 has low toxicity on normal human ovarian epithelial cells and mouse lymphoma cells with absent expression of Dlx5 , and can be used for further chemical optimization and for the development of novel, highly efficient cancer treatments.
Gribova 1 , S. Tillib 2 , I. Shmarov 1 , D. Logunov 1 , L. Verkhovskaya 1 , B. ABSTRACT The present study is devoted to the feasibility of expressing the single-domain mini-antibody nanoantibody selected from the library of sequences of the variable domains of special single-stranded antibodies derived from an immunized camel, a gene of which was introduced into eukaryotic cells within a recombinant adenoviral vector.
A vector bearing the gene of a single-domain nanoantibody was obtained using the AdEasy Adenoviral Vector System Stratagene. This method of delivering the nanoantibody gene facilitates efficient expression of this gene and functional activity of the nanoantibody. The results obtained can be used to produce passive immunizing tools against pathogens or new-generation immunobiological antitoxic medication. Favorova 1 , E. Goncharuk 1,2 , M. Mayzel 1 , D.
Lesovoy 1 , V. Chupin 1 , E. Bocharov 1 , A. Arseniev 1 , M. FGFR3 plays an important role in human skeletal development.
Mutations in this protein, including GlyArg or AlaGlu substitutions in the transmembrane TM region, can cause different disorders in bone development. The determination of the spatial structure of the FGFR3 TM domain in a normal protein and in a protein with single GlyArg and AlaGlu mutations is essential in order to understand the mechanisms that control dimerization and signal transduction by receptor tyrosine kinases.
The effective system of expression of eukaryotic genes in bacteria and the purification protocol for the production of milligram amounts of both normal TM fragments of FGFR3 and those with single pathogenic mutations GlyArg and AlaGlu, as well as their 15 N- and [ 15 N, 13 C]-isotope-labelled derivatives, were described.
The purification protocol involved immobilized metal affinity chromatography and cation- and anion-exchange chromatography, as well as the fusion protein cleavage with the light subunit of human enterokinase.
Koliasnikov 1,2 , V. Egorov 2 , S. Lange 3 , R. ABSTRACT Recombinant immunoconjugates of marker enzymes with antigens or antibodies present considerably more advantages than those obtained by conventional methods of chemical synthesis; i. Based on the pPICZ? B shuttle vector, we first managed to obtain a recombinant conjugate of key marker enzyme horseradish peroxidase HRP with Fab fragments of antibodies against atrazine.
The resulting genetic construction allows us to switch to any other antibody sequence, via the simple re-cloning of variable parts and an additional reporter enzyme. Conjugates were successfully produced in the Pichia pastoris methylotrophic yeast expression system.
The target activity of the conjugates both enzymatic and antigen-binding has been demonstrated by ELISA method. Dzyubenko 1,2 , D.
Bagrov 1 , G. Maksimov 1 , S. Shram 2 , K. The present work describes an examination of the arrangement and mechanical properties of cytoskeleton of living astrocytes using atomic force microscopy AFM. The experiments were performed with an organotypic culture of dorsal root ganglia DRG obtained from a chicken embryo. The cells were cultivated on a gelatinous substrate and showed strong adhesion.
AFM allows one to observe cytoskeleton fibers, which are interpreted as actin filaments and microtubules. This assumption is supported by confocal microscopy fluorescence imaging of? Thus, the data obtained indicate that AFM is a promising method to study neural cells cytoskeleton integrity and arrangement in in vitro models of neurodegeneration.
Logunov 1 , D. Shchebliakov 1 , M. Shmarov 1 , E. Khodunova 3 , I. Galtseva 3 , R. Belousova 2 , B. As a result of the fiber modification, the adenovirus can efficiently deliver the genetic information to bone marrow leukocytes and the tumor blood cells KG-1A human myeloblastic leukemia cells and U human histiocytic lymphoma cells , which are normally resistant to Ad5 infection.
The expression of interleukin-2 in CAR-negative bone marrow leukocytes The fiber-modified adenovirus can be used as a vector for the efficient gene delivery of interleukin-2 to human normal and tumor hematopoietic cells. Agapkina 1 , M. Inhibitors of HIV-1 integration have been under development for over 10 years; yet, only one integration inhibitor, raltegravir, has been approved for clinical use so far.
Unfortunately, the clinical use of raltegravir results in the development of viral resistance among some patients. Several more HIV-1 integration inhibitors are undergoing clinical trials at the moment. However, the structure and mechanism of action of those are similar to raltegravir, which results in the emergence of cross resistance with raltegravir. The present review is focused on the history of the development and clinical trials of raltegravir and its analogues, the problems connected with the emergence of viral resistance to integration inhibitors, and the prospect of their future clinical use.
ABSTRACT Deregulation of the expression of the genes that are involved in the control of the cell cycle impairs cellular differentiation and leads to cell death. This process can result in uncontrollable cell proliferation and, subsequently, cancer development. The obtained data indicate that the CCNB1 and PKC genes can be used as targets in the development of drugs for neuroblastoma treatment.
Posukh 2 , N. Barashkov 3 , S. Fedorova 3 , F. Teryutin 3 , V. Akhmetova 1 , I. Khidiyatova 1 , R. Khusainova 1 , S. Lobov 1 , E. The spectrum and prevalence of the GJB2 gene mutations are specific to populations of different ethnic origins. The prevalence of the c. The haplotype analysis of chromosomes with the c. The peculiarities of the selection of escort aptamers are discussed in this review.
The methods used in selection of escort aptamers via the SELEX technique are considered, including selection against isolated cell-surface proteins, cell fragments, living eukaryotic cells, and bacteria. Particular attention is given to the design and chemical modification of escort aptamers. The different fields of application of escort aptamers are described, including the targeted delivery of siRNAs, nanoparticles, toxins, and photoagents, as well as the identification of specific cell markers and the detection or isolation of cells of a definite type.
The potential for the application of escort aptamers in the development of new therapeutic agents and diagnostic systems is also discussed. Mesenchymal stem cells MSCs are part of the most important population of adult stem cells.
Bone marrow-derived MSCs have been believed to play the role of a source of cells for the renewal and repair of connective tissues, including bone, cartilage and adipose tissues. Cells similar to bone marrow-derived MSCs have now been identified in all postnatal tissues. In our opinion, MSCs provide the connection between the blood-vascular, immune, endocrine, and nervous systems and tissue-specific stem cells in the body.
Alekseeva 1,2,3 , S. Savin 2,3 , V. FDH consists of two identical subunits and contains neither prosthetic groups nor metal ions. This type of FDH was found in different microorganisms including pathogenic ones , such as bacteria, yeasts, fungi, and plants. Formate dehydrogenase activity was first discovered as early as in in plant; however, until the past decade FDHs from plants had been considerably less studied than the enzymes from microorganisms.
This review summarizes the recent results on studying the physiological role, properties, structure, and protein engineering of plant formate dehydrogenases. Khramova 1 , M. L Semenova 1 , I. Saburina 2 , N. Nowadays, numerous protocols exist which provide a neural differentiation of the stem cells transplanted into the retina. However, questions concerning the functional replacement of the missing retinal neurons by transplanted cells thus far remain unanswered.
This technique enables a detailed characterization of cell behavior post-transplantation. MMSCs are also shown to form synapses up to 2. Following electrical stimulation 20V, 0. Shmigol 1 , V.
Sysolyatina 2 , E. Nagurskaya 2 , S. Ermolaeva 2 , A. The following is already known about MC Secondly, singlet oxygen can only be photogenerated by MC monomers. In the present work, we studied the effect of MC in the aggregated state on the rate of photosensitized inactivation of Staphylococcus aureus and Pseudomonas aeruginosa.
To this end, bacteria either in MCcontaining distilled water or in a 0. The results show that, in the presence of salt, the aggregation of MC greatly increases the efficiency of the MCphotosensitized inactivation of P.
In the presence of salt, the rates of P. Our results suggest that a salt-induced photosensitization mechanism can switch from the singlet oxygen to the free-radical pathway. Suzdaltseva 2 , K. Goryunov 1 , N.
Kalinina 1 , V. Sysoeva 1 , V. Control of immune cell activation could be of significant benefit for regenerative medicine and the treatment of patients with autoimmune and degenerative diseases.
It is a proven fact that MCSs multipotent mesenchymal stromal cells are capable of suppressing immune responses via the inhibition of dendritic cell maturation and via the restraining of the T, B, and NK cell function in the course of autoimmune diseases and various forms of inflammation. MSCs can be isolated easily from almost every type of tissue or organ and subsequently expanded in vitro. These cells are self-renewable and can be differentiated into various cell types of mesenchymal lineage.
The current review contains a collection and critical analysis of data regarding the molecular mechanisms responsible for cross-talk between immune cells and MSCs. Some of these mechanisms can be used for the development of new practical approaches for the treatment of autoimmune diseases.
Prokofjeva 1 , P. Spirin 1 , D. Yanvarev 1 , A. Ivanov 1 , M. Novikov 2 , O. Stepanov 1 , M. Gottikh 3 , S. Kochetkov 1 , B. Fehse 4 , C. Stocking 5 , V. We have described in detail a system we designed that is based on lentiviral vectors Prokofjeva et. The system enables one to test the efficiency of the inhibitory activity of compounds whose action is directed towards either wild-type HIV-1 reverse transcriptase or integrase, or mutant enzymes corresponding to the drug-resistant virus form.
Application of this system substantially broadens the possibilities of preclinical anti-HIV drugs testing. Tyulkina 1 , E. Skurat 1 , O. Frolova 2 , T. Komarova 2 , E. Karger 2 , I. The expression, based on the hybrid viral vectors, is genetically safe, since the systemic transport and formation of infective viral particles are blocked. The vectors can be used for the presentation of foreign peptides including epitopes of human pathogens on the surface of the VLP.
The epitopes of the M2 influenza virus protein were not eliminated during the process of accumulation, polymerization and purification of chimeric VLP AltMV, providing evidence of the stability of chimeric VLP with C-terminal heterologous epitopes.
It is shown that TLRs play an essential role in the immune resistance of an organism to bacterial and viral infections. The binding of TLR to its own ligands results in the activation of several adapter molecules and kinases, inducing the activation of the main pro-inflammatory transcriptional factors, which in turn induce the activation of the main pro-inflammatory transcriptional factors. This activation results in the development of both the innate immune response triggered by the enhanced expression of a number of pro-inflammatory cytokines and antimicrobial peptides and that of the adaptive immune response, via the activation of dendritic cells and enhancement of antigen presentation, etc.
The ability of TLR agonists to bolster the immune reaction makes them promising for use in the therapy of infectious diseases and in the chemotherapy of malignant neoformations. However, different TLR ligands may have either antitumor activity lipopolysaccharide, imiquimod, CpG or, conversely, could beef up the resistance of tumor cells to apoptosis, stimulating their proliferation under certain conditions lipopolysaccharide, lipopeptide.