recombine

After Twitter bot makes death threat, its owner gets questioned by police – Fusion

Robots are starting to break the law, the law is trying to figure out what to do about it, and it all seems to be happening in Europe. Last month, Swiss authorities seized the Random Darknet Shopper art exhibit which included weekly purchases made by an automated bot given Bitcoin to surf a Dark Web marketplace. (It mainly bought drugs.) This week, police in the Netherlands are dealing with a robot miscreant. Amsterdam-based developer Jeffry van der Goot reports on Twitter that he was questioned by police because a Twitter bot he owned made a death threat.
Van der Goot’s bot used his own tweets as fodder, taking random chunks of them and trying to recombine them into new sentences that made sense. According to van der Goot, the bot tweeted something that sounded like a threat which mentioned an upcoming event in Amsterdam. Best of all, the bot was responding to another bot, according to van der Goot. He is not identifying the bot and says he has deleted it, per the request of the police. If this is not a hoax, this may be the first time police had to respond because of a robot-on-robot threat of violence.

The transgenic mice have been genetically modified so that they carry a green fluorescent protein which glows green under blue light. A transgenic animal is one that carries a foreign gene that has been deliberately inserted into its genome. The foreign gene is constructed using recombinant DNA methodology. In addition to the gene itself, the DNA usually includes other sequences to enable it. (Source)

Bacteriophages: Antibiotic Alternative or Just a Phase?

It is now clear that we are rapidly approaching a post-antibiotic era, and the need for an alternative is more vital than ever. The CDC estimates that approximately 2 million people are infected with antibiotic resistant bacteria each year, and of that 23 000 of them die as a result of the infection [1]. Our antibiotic pipeline is drying up and the development of new antibiotics is both slow and expensive, making antibiotics unappealing investments for pharmaceutical companies. Although alternatives to antibiotics are far from the market, the field is slowly expanding. Amongst the alternatives, bacteriophages (phages) are a potential candidate for both diagnostic and therapeutic medicine.

Quite simply, phages are viruses that infect bacteria. These are the most abundant biological entity on the planet and are thought to outnumber bacteria 10:1. Their sheer abundance has led to a vast diversity that has yet to be exploited by modern medicine. This is in part due to a number of problems with phages that haven’t made them ideal candidates for therapy. This article seeks to look at some of the problems with phages, and what steps are being taken to improve them for application in humans.

Rapid clearance from the host:

Delivery systems for phages have not been thoroughly assessed for systemic phage application. In other words we are still lacking a way of delivering a bacteriophage drug intravenously to ensure that phages have the maximal effect on the patient. Annoyingly, our immune systems are great at rapidly inactivating and removing them from our bodies [2], with animal studies showing that phage can be completely cleared within 24 hours [3]. Early work carried out in germ-free mice in the 70s showed that phages are passively collected in the mononuclear phagocyte system (MPS), where they remain viable until inactivated by immune cells [3].

There have been two solutions developed so far to amend this problem [2]. The first was developed in the late 90s by the National Institute of Health in the US, which involved the serial passage of phage through a living organism. It was hypothesised that some phage would have mutations in their coat proteins that would give them increased protection from the natural filtration systems in the body over wild type phage [3] and by selecting for these phage, you could gradually produce a population of long-circulating phage. When applied, these phage would have longer circulation times, and therefore a greater chance of colliding with their target bacteria. Animal studies have shown far better recovery of animals given long-circulating strains of virus over wild type, when presenting symptoms of otherwise fatal bacteraemia [4].

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Figure 1. Diagram showing a few of the possible receptors for Salmonella sp. phage [5]

Additionally, to prevent degradation or inactivation of phages, polymers can be added to the coatings of phages [1]. The polymer polyethylene glycol (PEG) has been shown to increase systematic circulation and decrease T-helper cell activation in response to phage. It is likely that a combination of these two methods may improve delivery strategies in the future of phage therapeutics.

Altering host range and preventing resistance:

Unlike antibiotics, phages have incredibly refined, narrow host-ranges. This property is in reality a double edged sword: in many cases, phages are only able to target a few strains of a single species, whereas antibiotics relentlessly target multiple branches of the bacterial phylogenetic tree. Antibiotic treatment can lead to disruption of the host’s own microbiota which can permit the colonisation of nastier and less cooperative microorganisms.

In contrast, phages can target their host whilst leaving the surrounding organisms in relative peace. When a patient presents symptoms of infection, the particular species or strain causing the infection would be unknown. Identifying the culprit before selecting the right phage would take time a patient may not have.

Receptors on the bacterial cell surface are what determine which phage are able to bind to the cell. A wide variety of receptors are used by phage, but many still remain a mystery. To curtail these issues and ensure that as many receptors can be targeted for a particular bacterium, phage cocktails are used [6]. These are mixtures containing a number of different phage strains. In theory, the cocktail should be designed so that the phages together should be able to target all the known clinically relevant strains of a particular species of bacteria.

Creating phage cocktails from natural sources can be laborious [7], however viral DNA provides a platform for genetically engineering phages with desired properties. Improving phage cocktails with modified phages expressing structures that could target a wide variety of receptors on a bacterial cell could ensure that a cocktail could target the maximum number of strains, whilst reducing the selection pressure on a sole receptor. Resistance to the phage cocktail would then also be avoided.

Much of this work looks at genetically engineering phage tail fibres [7, 8]. These ‘spider-leg’ like components regulate the initial binding step between a phage and a target cell. It has been shown by Mahichi et al, 2009 and Ando et al, 2015 that switching tail fibres between phages with different host ranges can confer host-range specificity from one phage to another. Hopefully, modular engineering of phages will push phage technology forwards, offering new strategies for developing phages for therapeutic purposes.

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Figure 2. Diagram showing how the modular shuffling of tail fibres between viral strains can confer host range of parental strain [7].

Preventing the release of cellular toxins

A major health risk of phage, is that like β-lactam antibiotics, they interfere with the bacterial cell wall integrity and ultimately lead to cell lysis. Lysing cells prevents further replication, but also releases all the cell’s content. This may include but not be limited to superantigens and lipopolysaccharides (LPS) [2]. These toxins will trigger the inflammatory response, and in extreme cases cause organ failure and death.

Phages have a simple dual-lysis system consisting of a holin and endolysin. The holin is a pore-forming membrane protein that creates an exit from the cytoplasm for the endolysin. The endolysin is then able to attack the peptidoglycan of the bacterial cell wall, resulting in its rupture. To generate phage incapable of lysing a cell, the dual lysis system simply needs to be inactivated.

To restore killing power to the phage in the absense of the dual lysis system, a bacterial toxin needs to be incorporated into the phage genome. Hagens et al, 2004 has shown that by engineering the filamentous phage M13 to encode a non-native restriction enzyme, antimicrobial activity can be restored through the generation of double stranded breaks in chromosomal DNA. Upon infecting Psuedomonas aeruginosa with this phage, there was a 99% drop in viable cell counts over the time course [9]. Other research has looked into other uses for the non-lytic killing of bacteria, including proteins that interfere with regulatory systems and other bacterial toxins.

Conclusions:

Phage therapy has shown promise in recent years as being a good candidate for either working in synergy with or replacing antibiotics. The appalling lack of human based clinical trials haven’t helped to expose their potential for human use. Although this is the case, a significant amount of work has been done on improving phage therapy in preparation for further studies with human application. The past 15 years have seen an improved outcome for this technology as obstacles with phages are gradually manoeuvred by intelligent reengineering. With hindsight we have now acquired through our experiences with antibiotics, hopefully we will not make the same mistakes with phages as we have done with antibiotics.

1. CDC (2013) Antibiotic resistance threats. US Dep Heal Hum Serv 22–50

2. Lu TK, Koeris MS (2011) The next generation of bacteriophage therapy. Curr Opin Microbiol 14:524–531

3. Carlton RM (1999) Phage therapy: past history and future prospects. Arch Immunol Ther Exp (Warsz) 47:267–274

4. Merril CR, Biswas B, Carlton R, Jensen NC, Creed GJ, Zullo S, Adhya S (1996) Long-circulating bacteriophage as antibacterial agents. Proc Natl Acad Sci U S A 93:3188–3192

5. Chaturongakul S, Ounjai P (2014) Phage host interplay: examples from tailed phages and Gram-negative bacterial pathogens. Front Microbiol 5:1–8

6. Moradpour Z, Ghasemian A (2011) Modified phages: Novel antimicrobial agents to combat infectious diseases. Biotechnol Adv 29:732–738

7. Ando H, Lemire S, Pires DP, Lu TK (2015) Engineering Modular Viral Scaffolds for Targeted Bacterial Population Editing. Cell Syst 1:187–196

8. Mahichi F, Synnott AJ, Yamamichi K, Osada T, Tanji Y (2009) Site-specific recombination of T2 phage using IP008 long tail fiber genes provides a targeted method for expanding host range while retaining lytic activity. FEMS Microbiol Lett 295:211–217

9. Hagens S, Habel A, Ahsen U Von, Gabain A Von (2004) Therapy of Experimental Pseudomonas Infections with a Nonreplicating Genetically Modified Phage Therapy of Experimental Pseudomonas Infections with a Nonreplicating Genetically Modified Phage. Antimicrob Agents Chemother 46:3817–3822

The Fourier series

Used in Physics, a Fourier series is a way to represent wave-like functions as the sum of simple sine waves. the fourier series breaks down any periodic function into the sum of an infinite set of simple oscillating functions of sines and cosines.

“A Fourier series is an expansion of a periodic function  in terms of an infinite sum of sines and cosines. Fourier series make use of the orthogonality relationships of the sine and cosine functions. The computation and study of Fourier series is known as harmonic analysis and is extremely useful as a way to break up an arbitrary periodic function into a set of simple terms that can be plugged in, solved individually, and then recombined to obtain the solution to the original problem or an approximation to it to whatever accuracy is desired or practical.“ - wolfram alpha

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The California Nebula : Whats California doing in space? Drifting through the Orion Arm of the spiral Milky Way Galaxy, this cosmic cloud by chance echoes the outline of California on the west coast of the United States. Our own Sun also lies within the Milky Ways Orion Arm, only about 1,500 light-years from the California Nebula. Also known as NGC 1499, the classic emission nebula is around 100 light-years long. On the featured image, the most prominent glow of the California Nebula is the red light characteristic of hydrogen atoms recombining with long lost electrons, stripped away by energetic starlight. The star most likely providing the energetic starlight that ionizes much of the nebular gas is the bright, hot, bluish Xi Persei just to the right of the nebula. A regular target for astrophotographers, the California Nebula can be spotted with a wide-field telescope under a dark sky toward the constellation of Perseus, not far from the Pleiades. via NASA

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The Colorful Clouds of Rho Ophiuchi : The many spectacular colors of the Rho Ophiuchi clouds highlight the many processes that occur there. The blue regions shine primarily by reflected light. Blue light from the star Rho Ophiuchi and nearby stars reflects more efficiently off this portion of the nebula than red light. The Earths daytime sky appears blue for the same reason. The red and yellow regions shine primarily because of emission from the nebulas atomic and molecular gas. Light from nearby blue stars - more energetic than the bright star Antares - knocks electrons away from the gas, which then shines when the electrons recombine with the gas. The dark brown regions are caused by dust grains - born in young stellar atmospheres - which effectively block light emitted behind them. The Rho Ophiuchi star clouds, well in front of the globular cluster M4 visible here on the upper right, are even more colorful than humans can see - the clouds emits light in every wavelength band from the radio to the gamma-ray. via NASA

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Cognitive Function definitions

Perception Functions:

Originally posted by mirayama

Extroverted Sensing / Se: The awareness and external observation of space and the environment. A person or an object can only be influenced in actual reality (an external perception of tangible surrounding). The goal of using force and willpower to affect people/objects in the surrounding space. Ideas are only useful if they will impact the external environment with force.

Introverted Sensing / Si: Maintaining a relaxed and stable inner state, through collecting and gathering sensory experience. Comparing past experience of sensation to the current moment. Physical external sensations that affect the internal state of an individual through a sense of comfort or routine.

Extroverted Intuition / Ne: Seeing the potential energy of a situation, and the potential of a person by identifying their strengths and attributes, thinking of various possibilities during discussion, juxtaposing the seemingly unrelated; the recombination of ideas and concepts, innovative ideas and techniques as an alternative solution, and seeing an opportunity. The connecting of concepts and ideas and perceiving objective possibility.

Introverted Intuition / Ni: Where an event has come from and where it is going - cause and effect. Having an awareness of time and understanding the processes between external events. The focus of where events come from also leads to learning from mistakes through memory to apply to the present moment. Can sometimes have the ability to predict the consequences and outcome of a situation. This anticipation of events is disconnected from the present moment and results in an apparent inactivity. Perceived the underlying meaning of symbolism and abstract concepts, which appear detached from the physical realm.

Judgement Functions:

Originally posted by imperfect--impostors

Extroverted Thinking / Te: Directly accesses people and events from a logical perspective. Aims to be productive and strives for efficiency and usefulness. Makes rational decisions. Direction of the most logical course of action, wants to achieve a logical result through action and production.

Introverted Thinking / Ti: Has an analytical state of mind. Recognizes nonsensical flaws or mistakes from a whole logical system. Validates correctness and consistency based on internal constructs of logic. The analysis of logical processes and clarification rather than gaining a productive result.  

Extroverted Feeling / Fe: Gaining an sense of external emotions and the emotional atmosphere, expressing feelings and experiences outwardly and openly, using words and gestures to impact the emotional space.Feeling values are developed from the environment, can recognize shared values and may adhere to them to reach a goal.

Introverted Feeling / Fi: Can sometimes appear analytical, personal values and sentiments, the focus on feelings of the individual and this reaction to a situation, which also involves an emotional sensitivity, prefers not to express emotion outwardly and directly. how a situation adheres or conflicts with their own values, feeling values is deprived internally.

About chapter 700+7 from a medical standpoint (spoilers, obviously)

The last time i did this was for chapter 699, about what messures could be taken to heal/regrow Naruto’s and Sasuke’s arms.
I’ll be brief now ‘cause i have to go to the hospital early and later a Radiology exam. (So yes, i have a base for saying what i’m gonna say about Genetics).

First off, about Shin and the Shins being clones…Orochimaru is right about him being exceptional. Someone who has no negative reaction to transplants or whose organism responds perfectly to it is Exceptional. Why? Because transplants in the real world are a messy subjects. What about parent/child transplants? Still messy, why? Because you don’t match your parent a 100%, heck, not even a 50% really. Why? Because when a new being is formed (the process from being two cells to multiplying them until you are an embryo) a recombination of genes hapens, meaning you don’t actually match the gene structure of your parents that way, but you can match allels (small strands of dna chains that contain your gene information).
The interesting concept that this chapter brought, was about DNA and transplants. So shin uses his own clones to transplant the exact replica of whichever organ he messed up and “live forever”? Probably? I don’t know, he’s messed up.
About the DNA test. At a first glance of that screen, i noticed that it was a 100% match. And that does mean Karin is involved, but not in the way many are thinking.
What was in her desk, is a piece of umbilical cord. This piece of flesh contains information of before the embryo was fully formed. Meaning, there are what we call Stem Cells (in my country the translation is Mother Cells, ain’t it nice for the drama this chap?). What it entails is that these particular cells can be used to produce whichever cell/tissue/organ the person is missing. In actuality, these cells are used to that purpose… Transplants.
So what does Karin have to do with this? Well, she had an umbilical cord that matched a 100% (according to the graphics) with Sarada’s DNA (that came from an epitelial sample, what Suigetsu did with the Q-tip in her mouth). If it matched Sarada in a 100% it obviously means, that cord is Sarada’s.
Remember that Sarada wasn’t born on Konoha since there are no registers or info in the Konoha Hospital. What if for whatever reason, Karin was involved in the birth? Sakura can’t help in the giving birth process if she’s the one in labour…
But why would Karin keep her DNA? Genetics ands transplants. Sarada is an Uchiha, meaning Sharingan, meaning eventual blindness, meaning she might need new eyes but there are no more uchihas… Why not grow new eyes on a lab with her Stem cells?? It can be done.
And why would Karin have her own Umbilical cord if she was your regular bullied kid when she was a child? Before Orochimaru and science was a thing in her life… Because is not her but Sarada’s. Everyone was surprised about it being a possibility, but Suigetsu wasn’t even sure that sample was Karins.
I would expand more on the topic but i gotta run right now. Maybe later today i will expand more on genetics. 'Till then, hang on people!

The Deep Lagoon : Ridges of glowing interstellar gas and dark dust clouds inhabit the turbulent, cosmic depths of the Lagoon Nebula. Also known as M8, The bright star forming region is about 5,000 light-years distant. But it still makes for a popular stop on telescopic tours of the constellation Sagittarius, toward the center of our Milky Way Galaxy. Dominated by the telltale red emission of ionized hydrogen atoms recombining with stripped electrons, this stunning, deep view of the Lagoon’s central reaches is about 40 light-years across. Near the center of the frame, the bright hourglass shape is gas ionized and sculpted by energetic radiation and extreme stellar winds from a massive young star. via NASA

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The Origin of Genetic Variation

Mutations in the nucleotide sequences are the original source of genetic variation, causing different versions of alleles to exist. Once we have these differences, alleles can then be reshuffled, like a pack of cards, in order to produce the variation that makes each individual organism have its own unique combination of characteristics.

In sexually-reproducing organisms, most variation arises from processes that happen during meiosis and fertilisation.

Independent Assortment of Chromosomes:

  • When homologous pairs (with one maternal and one paternal chromosomes) line up at the metaphase plate in meiosis I, their orientation is random—there’s a 50% chance that the daughter cell will be given the maternal or the paternal chromosome of any given homologous pair.
  • In addition, each homologous pair orients itself independent of whatever any other chromosome is doing, i.e. independent assortment.
  • The daughter cells are therefore just one of many possible combinations of maternal and paternal chromosomes. Because humans have 23 chromosomes, the number of possible combinations is 2^23, or about 8.4 million.

(Image Source)

Crossing Over:

  • Also known as recombination
  • Each individual gamete does not have only one paternal or one maternal chromosome. Rather, it actually ends up with a mix of them. This is due to recombinant chromosomes.

  • As we saw in our discussion of meiosis, in prophase I homologous pairs join up along their lengths, precisely aligning with corresponding alleles next to each other. Then, they essentially swap out alleles, exchanging them along their lengths—like swapping arms.
  • The further away alleles are from each other, the more likely they’ll be swapped. Alleles that are located close to each other are therefore more likely to be inherited together.
  • What results is a pair of homologous chromosomes that have been randomly mixed up.
  • This is incredibly important, because mutations are happening all the time. They can actually destroy the function of genes, so if no crossing over ever occurred to increase diversity, mutations would just accumulate and eventually all genes would be destroyed. Instead, crossing over helps non-mutated chromosomes to reform.

Random Fertilisation:

  • Basically, a sperm cell randomly chooses an egg cell. Because each one is already one of 8.4 million combinations, the random fusion of sperm and egg produces a zygote of 70 trillion possible combinations (2^23 x 2^23).

Body images sourced from Wikimedia Commons

Further resources: Genetic variation video