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What is positive and negative supercoiling?

What is positive and negative supercoiling?


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Is the following correct?

Positive supercoiling = the coiling of DNA helix (B-DNA) on itself during intesified coiling of the two DNA stands in right handed direction

negative supercoiling = the coiling of DNA helix(B-DNA) upon itself during uncoiling of the two DNA strands performed in left handed direction?

I'm a little confused.


According to this powerpoint from the SIU School of Medicine:

Right handed supercoiling = negative supercoiling (underwinding)

Left handed supercoiling = positive supercoiling

And from this Boston University webpage:

If DNA is in the form of a circular molecule, or if the ends are rigidly held so that it forms a loop, then overtwisting or undertwisting leads to the supercoiled state. Supercoiling occurs when the molecule relieves the helical stress by twisting around itself. Overtwisting leads to postive supercoiling, while undertwisting leads to negative supercoiling.

And finally from wikibooks:

Positive and Negative Supercoilings

  1. Positive supercoiling is the right-handed, double helical form of DNA. It is twisted tightly in a right handed direction until the helix creates knot.

  2. Negative supercoiling is the left-handed, double helical form of DNA.

Although the helix is underwound and has low twisting stress, negative supercoil's knot has high twisting stress. Prokaryotes and Eukaryotes usually have negative supercoiled DNA. Negative supercoiling is naturally prevalent because negative supercoiling prepares the molecule for processes that require separation of the DNA strands. For example, negative supercoiling would be advantageous in replication because it is easier to unwind whereas positive supercoiling is more condensed and would make separation difficult.

Topoisomerases unwind helix to do DNA transcription and DNA replication. After the proteins have been made,the DNA template supercoils by the force to make chromatin. RNA polymerase also influence DNA strand to have two different supercoiled directions. The region RNA polymerase has passed forms negative supercoil while the region RNA polymerase that have not passed forms positive supercoil. By these processes, supercoils are generated.

In the following image from web-books:

(a) Positive supercoils (the front segment of a DNA molecule cross over the back segment from left to right). (b) Negative supercoils.

This video, titled "super coil (positive and negative) formation of DNA" should help you visualize this.


Supercoiling DNA optically

Torsional stress plays a vital role in many genomic transactions, including replication and transcription, and often results in underwound (negatively supercoiled) DNA. Here, we present a single-molecule method, termed Optical DNA Supercoiling (ODS), that advances our ability to study negatively supercoiled DNA. Since ODS is based on dual-trap optical tweezers, it is compatible with a wide range of functionalities that are difficult to combine with traditional methods of DNA twist control. This includes the ability to image supercoiled DNA with fluorescence microscopy and move the supercoiled substrate rapidly between different buffer/protein solutions. We demonstrate that ODS yields unique and important insights into both the biomechanical properties of negatively supercoiled DNA and the dynamics of DNA–protein interactions on underwound DNA.


Chapter 10 Study Guide

• Most bacterial species contain a single type of chromosome, but it may be present in multiple copies.

• A typical chromosome is a few million base pairs in length.

• Several thousand different genes are interspersed throughout the chromosome. The short regions between adjacent genes are called intergenic regions.

• One origin of replication is required to initiate DNA replication.

• Eukaryotic chromosomes occur in sets. Many species are diploid, which means that somatic cells contain 2 sets of chromosomes.

• A typical chromosome is tens of millions to hundreds of millions of base pairs in length.

• Genes are interspersed throughout the chromosome. A typical chromosome contains between a few hundred and several thousand different genes.

• Each chromosome contains many origins of replication that are interspersed about every 100,000 base pairs.

• Each chromosome contains a centromere that forms a recognition site for the kinetochore proteins.

• Telomeres contain specialized sequences located at both ends of the linear chromosome.

Function: Supercoiling helps to greatly decrease the size of the bacterial chromosome.
-Negative supercoiling also affects DNA function by creating tension on DNA strands that may be released by their separation. This promotes DNA strand separation in small regions which enhances genetic activities such as replication and transcription that require the DNA strands to be separated.

Underwinding of B DNA causes a negative supercoil (or less turns) and overwinding of B DNA causes a positive supercoil (or more turns).
- The DNA conformations shown in Figure 10.4b and d are not structurally stable and do not occur in living cells.

Topoisomers- DNA conformations that differ with regard to supercoiling.
-Example: No supercoiling, negative supercoiling, and positive supercoiling.

Therefore, supercoiling helps to greatly decrease the size of the bacterial chromosome.

DNA gyrase (Topoisomerase II): double strand break relaxes positive supercoiling.

Topoisomerase I- single strand break relaxes negative supercoiling.

Telomeres- Specialized regions at the ends of chromosomes, that are important in replication and for stability.
-Protective measure (every time DNA divides/replicates they shorten and if it gets too short, it may get into a gene sequence)

Three types of repetitive sequences:
(1) Unique or non-repetitive sequences
(2) Moderately repetitive
(3) Highly repetitive

Unique or non-repetitive sequences- Found once or a few times in the genome.
- Includes structural genes as well as intergenic areas.
-In humans, make up roughly 41% of the genome (protein-encoding regions of genes [2%], introns [24%], and unique regions that are not found within genes [15%]).

Moderately repetitive-Found a few hundred to several thousand times. In a few cases, moderately repetitive sequences are multiple copies of the same gene.
-Includes genes for rRNA and histones, sequences that regulate gene expression and translation, and transposable elements.


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Evolution, Adaptation, and Supercoiling ▿

Geometrical and, to some extent, physical and informational properties of covalently closed DNA molecules (or molecules that can be ideally viewed as closed) are determined by their connectivity, i.e., the number of times one strand of DNA is topologically linked to another. Any link that cannot be removed by merely sliding one strand over another but can be removed only by breaking a strand or two is a topological link. All living forms evolved to maintain the numbers of links, per unit of DNA length, most suited for their respective environments and growth conditions. The study by Champion and Higgins (4) offers a tantalizing insight into how two very closely related bacterial species control the topological states of their DNA.

Over the years, the properties of closed circular DNA have been systematically investigated and successfully modeled (5), and some relevant features of such molecules are descriptively presented below. Incision of covalently closed double-stranded DNA will produce a relaxed molecule in which, under standard conditions, one strand will wind around another with a frequency of about one turn per 10.5 base pairs. The length of the molecule (in base pairs) divided by the number of base pairs per turn yields the expected linking number of topologically relaxed DNA. Resealing such incised DNA results in the formation of a discrete distribution of molecules with different linking numbers, centered around the relaxed form (Fig. ​ (Fig.1). 1 ). The molecules with linking numbers greater than that of the relaxed form are known as overwound, and those with linking numbers smaller than that of the relaxed form are known as underwound. In such a distribution, which can be approximated by a bell curve, the probability of occurrence of molecules with increasing degrees of under- and overwinding drops exponentially. The shapes of both types of molecules can be described in three dimensions only by a characteristic coiling of the axis of the double helix (Fig. ​ (Fig.1). 1 ). Since the axis of the double helix of a relaxed, covalently closed double-stranded DNA molecule has the shape of a coil, sufficiently represented in two dimensions, further coiling of that coil is referred to as supercoiling. The greater the difference between the linking number of a given topological species of DNA molecules and that of its respective relaxed form, the more supercoiled the species is. Interestingly, covalently closed circular double-stranded DNA molecules isolated as plasmid or viral DNAs from almost all studied organisms are supercoiled more than their respective relaxed and resealed forms (see, for example, reference 1). In other words, the distributions of linking numbers in populations of plasmids isolated from living cells are different from the corresponding distributions for relaxed DNA molecules. Given this observation, supercoiling is considered to be a ubiquitous property of covalently closed double-stranded DNA molecules in vivo.

Cartoon depiction of conformational states of covalently closed circular DNA. Resealing a break in circular DNA (a) will result in a distribution of DNA molecules with different topological properties (b): overwound (top), relaxed (center), and underwound (bottom). The double helices of overwound and underwound DNA species conform to an intertwined superhelical state (c). One strand of the double helix is shown as a contour line of a planar oval (gray) and another as a wavy curve topologically linked to the contour line (black).

The supercoiling difference is at least twofold. First, the average linking number in a population of DNA molecules isolated from living cells is usually smaller than that in a population of DNAs prepared by breaking/resealing them in vitro, suggesting that DNA in vivo is underwound, or negatively supercoiled. Second, the distributions of linking numbers in populations of isolated DNAs are usually wider than expected based on the statistical properties of a distribution of relaxed DNAs, sometimes with heavy tails or even two modes. These properties have been widely used by many researchers to deduce the state of DNA supercoiling inside the cell and impute some information about the factors contributing to supercoiling maintenance and dynamics. The study presented in this issue (4) exemplifies a continued interest in this subject, but with a twist. Control and regulation of supercoiling in organisms as close as Escherichia coli and Salmonella enterica serovar Typhimurium are expected to be very similar, if not identical. Indeed, both species have the entire complement of genes implicated in establishing steady-state supercoiling and/or in buffering the consequences of fluctuations in supercoiling levels (2, 14). Moreover, all of the pairs of orthologs are very similar, with seqA genes being the most distant, at 87.9% identity, and fis being absolutely conserved gyrA, rnhA, mukB, topB, hns, parC, topA, gyrB, parE, mukF, hupA, hupB, infB, infA, and mukE are between seqA and fis and listed here in ascending order of percent identity. However, as it happens, the expectation is not fulfilled. It has been known for some time that loss of function of topA (the gene coding for a topoisomerase activity that reduces negative supercoiling [23]) is tolerated by S. enterica serovar Typhimurium better than by E. coli (20). Specifically, topA knockouts in Salmonella can be constructed in one step and propagated for multiple generations without any compensatory mutations. Whereas it has been reported that topA knockouts in E. coli either cannot be constructed and/or propagated without compensatory mutations (19) or can be generated only in multiple steps (21). The genetic and biochemical natures of some compensatory mutations (6, 9, 18) indicate that the main mechanism of adaptation to the loss of topA function involves reduction of gyrase activity (gyrase is encoded by gyrA and gyrB genes and converts relaxed closed circular DNA into negatively supercoiled DNA by using energy from ATP [8]).

It has also been established that in the absence of the topA gene, the distribution of linking numbers in a population of some plasmid DNA molecules becomes heavily skewed toward extremely underwound, hyper-negatively supercoiled species (e.g., reference 17). Thus, the connection between the observable steady-state supercoiling and the opposing effects of TopA and gyrase has been established. The intolerance to the topA loss in E. coli is generally attributed to excessive underwinding of the DNA template attained in the presence of fully active gyrase, whose activity is unbalanced in topA-deficient mutants. Since in the mutants of both species the topA gene is missing, Champion and Higgins reasoned that the difference must be in the gyrase side of the equation. (Of course, the tolerance is an organismal-scale phenomenon and may be explained by some yet poorly understood differences in how two species deal with the consequences of excessive DNA underwinding.) In the study, the authors focused on the GyrB subunit of gyrase as a follow-up to an earlier work from the same group. Salmonella GyrB is 96.6% identical to its E. coli homolog however, their results demonstrated that Salmonella GyrB, as well as a catalytically defective single-residue mutant which can be reasonably well tolerated by Salmonella, compromised the ability of E. coli to grow. The most straightforward explanation of this observation is that E. coli is sensitive to the levels of supercoiling activity of gyrase and that when the activity drops below a certain threshold, efficient growth cannot be sustained. This is presumably because DNA becomes insufficiently negatively supercoiled. But what is insufficient for E. coli may be well within the acceptable range for Salmonella after all, the evolutionary paths of the bugs diverged many millions of years ago. Indeed, plasmids isolated from Salmonella are less underwound than those isolated from E. coli (4, 20), suggesting that the balance between relaxation and supercoiling in Salmonella is shifted, relative to that in E. coli, to a somewhat more relaxed state.

Qualitatively, the existence of the species-specific balance states can be rationalized as resulting from E. coli having either lower relaxation or higher supercoiling activity than Salmonella. Although the nonviability of E. coli carrying a supercoiling-deficient mutant allele of gyrB argues in favor of E. coli sensitivity to the supercoiling activity per se, the issue of balancing can be addressed only by a reciprocal swapping of orthologs between the species.

Steady-state supercoiling of plasmid DNA, which is commonly analyzed by the band-counting method with a gel following electrophoresis in the presence of a DNA intercalator in one (10) or two (12) dimensions, is observed in vitro after removal of all proteins. In vivo, however, the supercoils of underwound DNA can be bound by proteins which wrap DNA around themselves, effectively constraining the loops of supercoiled DNA just like histones in eukaryotes, or supercoils can be unconstrained by proteins, freely participating in various DNA transactions and stress-induced reactions. One such reaction is a transition from the right-handed B form of double helix to the left-handed Z form of DNA in sequences containing GC tracks. The transition occurs at some threshold level of torsional stress in underwound DNA with a certain linking number deficit all DNA molecules with equal or greater degrees of underwinding will extrude the track into the Z form (15). Such extrusion, in turn, will consume some free supercoils, effectively shifting the distribution of linking numbers toward less underwound DNA species. When gyrase acts upon this “relaxed” substrate, it will introduce additional negative supercoils whose presence can be visualized on a two-dimensional gel along with the break in distribution associated with the B-to-Z transition. This is in comparison to the distribution of linking numbers in the population of the same plasmid without the GC segment. Champion and Higgins found that the surplus of negative supercoils, pumped into the GC-containing DNA by gyrase, was significantly less in Salmonella than in E. coli, so much that the Salmonella distribution did not seem to have DNA species that were sufficiently stressed to undergo the conformational transition. Thus, not only is the level of steady-state supercoiling in Salmonella less than that in E. coli, but the extent of unconstrained, free supercoiling is also less: free supercoiling seems to account for more than half of the apparent supercoiling in E. coli and for less than half of that in Salmonella. It follows that the majority of negative supercoils in Salmonella, unlike that in E. coli, are constrained by proteins, and it might be expected that dispensing with the proteins which do that will have a more adverse effect on Salmonella than on E. coli. The results of the study and other evidence are consistent with this hypothesis. Salmonella was much more sensitive than E. coli to the presence of MukB and H-NS, which are known to constrain underwound DNA in vivo and in vitro (16, 22). At the same time, the lack of SeqA, which can sequester also positive supercoils (11), among other things, had no discernible effect on Salmonella growth.

Of course, neither histones nor any other proteins capable of constraining negative supercoils can change the topological characteristics of DNA on their own, as measured by shifts in distributions of linking numbers. These proteins can wrap DNA only in such a way that generates positive torsional stress in a protein-free portion of covalently closed DNA, equivalent to overwinding. When the stress is removed by the topoisomerases, which can react on positively supercoiled DNA, DNA becomes relaxed while bound by the proteins, and when the proteins are removed, DNA assumes its underwound conformation. Since the potentials to remove positive supercoils are indistinguishable between E. coli and Salmonella (17), it is quite plausible that the variations in the sequence of the Salmonella gyrase affect only its supercoiling activity, not its ability to relax overwound, positively supercoiled DNA.

It is also plausible, albeit not as easily falsifiable, that Salmonella reliance on constrained supercoiling represents an evolutionary choice consistent with the Salmonella environment. The principal ecological difference between the intracellular pathogen Salmonella and the commensal bacterium E. coli is that Salmonella has to survive in macrophage phagolysosomes (3), where it is subject to extensive oxidative stress (7). It has been demonstrated that wrapping DNA in nucleosomes protects DNA from oxidative damage (13). It remains to be seen whether the method(s) of supercoil constraint “practiced” by Salmonella has a similarly protective effect.


Positive And Negative Contrast Media Types Biology

After one twelvemonth the X ray were discovered, divine air became the first recognized contrast agent in radiographic scrutinies of the thorax. The first contrast surveies were carried out the upper GI piece of land utilizing Bi salts on a animate being.

Barium sulfate and bismuth solutions were being used in concurrence with the roentgenoscope, Ba sulfate holding been used different additives of all time since for imagination of GI piece of land. First I based contrast used was a derivative of chemical ring pyridine, to which the individual I atom could be bound in order to render it radio opaque.

Iodine based contrast media have been used of all time since.Radiographic contrast has been used for over a century to heighten the contrast of radiographic images.

Contrast media ( besides known as contrast agents ) are substances used to foreground countries of the organic structure in radiographic contrast to their encompassing tissue. Contrast media enhance the wireless opacity and optical denseness of the country under probe so that the tissue or construction soaking up derived functions are sufficient to bring forth equal contrast with next construction.

Its enhances the information contained to produced image by the medical diagnostic equipment like traditional and digital radiology, atomic medical specialty, ultrasounds, magnetic resonance. When used for imaging intents contrast media can be administered by injection, interpolation or consumption.

The contrast media is divided into positive and negative. The negative types is which have less soaking up and it will be shown up dark or Grey. Negative contrast media are radiolucent and it low atomic figure. Gass are normally used to bring forth negative contrast on radiographic images For illustrations air or C dioxide.

Air is the introduced by the patient during radiographic scrutiny, illustration when the patient take breath during the chest x-ray. Carbon dioxide is introduced into the GI piece of land in concurrence with the Ba sulfate to visualise the mucosal form, illustration dual contrast Ba repast.The general positive contrast media are which have an increased soaking up of X ray and it will demo up the white or Grey. These are wireless opaque and are of a high atomic figure.

Barium and iodine based solutions are used in medical imagination to bring forth positive contrast. Both positive and negative contrast can be employed together in dual contrast to bring forth radiographic image. For illustrations is iodinates compounds.Barium sulfate solutions used in GI imagination.

Features of Ba solutions make them suited for imagination of the gastrointestinal ( GI ) piece of land, the features such as high atomic figure bring forthing good radiographic contract, stable, indissoluble, first-class surfacing belongingss of the GI mucous membrane and besides comparatively cheap. Barium suspension composed from the pure Ba sulfate assorted additivies and with the scattering agents, it held in suspension in H2O.If want to fixing the Ba solutions, the of import is to look into the termination day of the months and guarantee the packaging is integral. The solutions should be administered at organic structure temperature to better patient tolerability and its besides cut down the cramp of the colon.

Barium sulphate solutions are contraindicated with the pathologies, suspected fistulous withers or look into inosculation site, toxic megacolon, paralytic intestinal obstruction, suspected partial or complete stricture, prior to sugery or endoscopy.Iodine based contrast media used in medical imagination. The many of utilizing imaging contrast media at the imagination section are H2O soluble organic readyings in which molecules I are the opaque egent. Its contain, I atoms, edge to a bearer molecule.

It id for holds the I in stable the compound and besides to carries it to organ when making the scrutiny. Iodine based compounds its divided into four types and its depend their molecular construction, the group are ionic monomers, ionic dimmers, non-ionic monomers and non-ionic dimmers.Contrast media is needed in radiology scrutiny is because, the figure of probe at the radiology will necessitate disposal of the contrast into the patient organic structure through the vena or the arteria. A illustration is alike the endovenous urogram ( IVU ) .

At the contrast media have a two types of the I, there are ionic or non aa‚ ” ionic its respects to chemical construction. Basically, merely the castanetss and the air can see at the movie X ray. If need to define the transition piss or the blood flow at the vass, contrast media that have contained the I is use to increase the denseness of piss or the blood. The consequences is, the flow of urine or blood will look white on the movie X ray, its merely like the bone on movie X ray.

If want to utilize the contrast media, the patient have to follow some readying to make the process. Normally, the patient will be asked to fasting, its mean the patient can non take any nutrient or imbibe about 4 until 6 hours prior the scrutiny start. But have some status that patient can non follow the readying, the patient must necessitate to take the particular safeguards and must to mind of somewhat hazards.The some status that patient can non follow the readying because patient have definite history of allergic reaction, old reaction to the contrast media, old reaction to drug, asthma, bosom conditions is non normal, terrible diabetes and the contrast media besides non promote to the old people about 65 old ages above and besides for the kids about below 6 month.

The of import for the patient have diabetic andon Glucophage, the patient must to halt the medicine 48 hours prior to make the scrutiny necessitating endovenous or to acquire the contrast media injection.The radiographer besides must to fix n cognizant some status before making the scrutiny, the radiographer must associate the anatomy, physiology and besides pathology. Besides right pick and disposal of any equipment to used. Must cognize the standards for taking the vena and cognize the possible jobs if it will be happen.

From the contrast media besides, the patient still can acquire the some hazard, but the reaction of hazard are highly low. At the first, the physician must state the patient about the benefits of contrast media and besides the hazard. The contrast media is like the drug that the all people know and familiar with. But, the new of I that incorporating contrast media are really safe.

Event though, the contrast like the all drug its besides including acetaminophen, there still have the possible hazard reaction to the contrast media. Its classified into three types, which is mild, moderate and besides severe. If the contrast media is non aa‚ ” Attic, the reactions is will be reduced.The reactions most are no intervention will necessitate, mild, and transient, it bulk will be occur within first 20 proceedingss after the injection.

Mild reaction merely necessitate careful observation of the patient. The symptoms of a mild reaction is nausea, a warm feeling that may be associated with hot flushing, lividness, a metallic gustatory sensation in oral cavity, sneezing, rhinorrhoea, rubing and sudating. Treatment of mild reactions normally merely involves observation of the patient and reassurance. At the moderate, this is a more terrible reaction in which medical intervention is necessary.

The include symptoms is pruritis, chest hurting, erythema, abdominal hurting, vasogal faint, abdominal hurting. The intervention of moderate reaction may change. Compression and tight vesture should be released and the patient reassured. Severe reaction is need to happen the medical advice instantly.


What is positive and negative supercoiling? - Biology

DNA supercoiling is important for DNA packaging within all cells. Because the length of DNA can be thousands of times that of a cell, packaging this genetic material into the cell or nucleus (in eukaryotes) is a difficult feat. Supercoiling of DNA reduces the space and allows for much more DNA to be packaged. In prokaryotes, plectonemic supercoils are predominant, because of the circular chromosome and relatively small amount of genetic material. In eukaryotes, DNA supercoiling exists on many levels of both plectonemic and solenoidal supercoils, with the solenoidal supercoiling proving most effective in compacting the DNA. Solenoidal supercoiling is achieved with histones to form a 10 nm fiber. This fiber is further coiled into a 30 nm fiber, and further coiled upon itself numerous times more.

DNA packaging is greatly increased during nuclear division events such as mitosis or meiosis, where DNA must be compacted and segregated to daughter cells. Condensins and cohesins are Structural Maintenance of Chromosome proteins that aid in the condensation of sister chromatids and the linkage of the centromere in sister chromatids. These SMC proteins induce positive supercoils.

Supercoiling is also required for DNA/RNA synthesis. Because DNA must be unwound for DNA/RNA polymerase action, supercoils will result. The region ahead of the polymerase complex will be unwound this stress is compensated with positive supercoils ahead of the complex. Behind the complex, DNA is rewound and there will be compensatory negative supercoils. It is important to note that topoisomerases such as DNA gyrase (Type II Topoisomerase) play a role in relieving some of the stress during DNA/RNA synthesis.


Resistance to Topoisomerase-Targeting Agents

John L. Nitiss , Karin C. Nitiss , in Encyclopedia of Cancer (Second Edition) , 2002

I Introduction

DNA topoisomerases are the principal targets for many clinically important antitumor agents. There are two major families of topoisomerases: type I enzymes that introduce transient single strand cuts in DNA and type II enzymes, which in eukaryotes are dimeric enzymes that make double strand cuts in DNA. Both type I and type II enzymes are the targets of important anticancer agents. The principal drugs acting against type I topoisomerases are the camptothecins, including topotecan and irinotecan. A wider range of agents act against eukaryotic topoisomerase II, including the anthracyclines doxorubicin and daunomycin, the epipodophyllotoxins etoposide and teniposide, and other agents, including amsacrine and mitoxantrone. The strong intercalating agent dactinomycin has shown activity against both topoisomerase I and topoisomerase II, as have other experimental agents that have yet to be introduced into the clinic.

DNA topoisomerases participate in a wide variety of cellular functions. The discovery of DNA topoisomerases was motivated by the problem of separating DNA strands following semiconservative DNA replication, and it is clear that topoisomerases play critical roles during this process. Subsequent work has indicated that topoisomerases also play key roles in transcription, chromosome structure, and recombination. The central role of topoisomerases in DNA metabolism, particularly in proliferating cells, might suggest that these enzymes would be potential targets for anticancer agents. While some agents have been identified that act mainly by inhibiting the catalytic activity of topoisomerases, the main action of topoisomerase-targeting drugs in clinical use is to convert the enzyme into a unique form of DNA damage. This unique mechanism of action of topoisomerase-targeting agents dictates many of the potential resistance mechanisms.


Contents

Paul Rozin and Edward Royzman proposed four elements of the negativity bias in order to explain its manifestation: negative potency, steeper negative gradients, negativity dominance, and negative differentiation. [4]

Negative potency refers to the notion that, while possibly of equal magnitude or emotionality, negative and positive items/events/etc. are not equally salient. Rozin and Royzman note that this characteristic of the negativity bias is only empirically demonstrable in situations with inherent measurability, such as comparing how positively or negatively a change in temperature is interpreted.

With respect to positive and negative gradients, it appears to be the case that negative events are thought to be perceived as increasingly more negative than positive events are increasingly positive the closer one gets (spatially or temporally) to the affective event itself. In other words, there is a steeper negative gradient than positive gradient. For example, the negative experience of an impending dental surgery is perceived as increasingly more negative the closer one gets to the date of surgery than the positive experience of an impending party is perceived as increasingly more positive the closer one gets to the date of celebration (assuming for the sake of this example that these events are equally positive and negative). Rozin and Royzman argue that this characteristic is distinct from that of negative potency because there appears to be evidence of steeper negative slopes relative to positive slopes even when potency itself is low.

Negativity dominance describes the tendency for the combination of positive and negative items/events/etc. to skew towards an overall more negative interpretation than would be suggested by the summation of the individual positive and negative components. Phrasing in more Gestalt-friendly terms, the whole is more negative than the sum of its parts.

Negative differentiation is consistent with evidence suggesting that the conceptualization of negativity is more elaborate and complex than that of positivity. For instance, research indicates that negative vocabulary is more richly descriptive of the affective experience than that of positive vocabulary. [5] Furthermore, there appear to be more terms employed to indicate negative emotions than positive emotions. [6] [7] The notion of negative differentiation is consistent with the mobilization-minimization hypothesis, [8] which posits that negative events, as a consequence of this complexity, require a greater mobilization of cognitive resources to deal with the affective experience and a greater effort to minimize the consequences.

Social judgments and impression formation Edit

Most of the early evidence suggesting a negativity bias stems from research on social judgments and impression formation, in which it became clear that negative information was typically more heavily weighted when participants were tasked with forming comprehensive evaluations and impressions of other target individuals. [9] [10] Generally speaking, when people are presented with a range of trait information about a target individual, the traits are neither "averaged" nor "summed" to reach a final impression. [11] When these traits differ in terms of their positivity and negativity, negative traits disproportionately impact the final impression. [12] [13] [14] [15] [16] This is specifically in line with the notion of negativity dominance [4] (see "Explanations" above).

As an example, a famous study by Leon Festinger and colleagues investigated critical factors in predicting friendship formation the researchers concluded that whether or not people became friends was most strongly predicted by their proximity to one another. [17] Ebbesen, Kjos, and Konecni, however, demonstrated that proximity itself does not predict friendship formation rather, proximity serves to amplify the information that is relevant to the decision of either forming or not forming a friendship. [18] Negative information is just as amplified as positive information by proximity. As negative information tends to outweigh positive information, proximity may predict a failure to form friendships even more so than successful friendship formation. [2]

One explanation that has been put forth as to why such a negativity bias is demonstrated in social judgments is that people may generally consider negative information to be more diagnostic of an individual's character than positive information, that it is more useful than positive information in forming an overall impression. [19] This is supported by indications of higher confidence in the accuracy of one's formed impression when it was formed more on the basis of negative traits than positive traits. [2] [14] People consider negative information to be more important to impression formation and, when it is available to them, they are subsequently more confident.

An oft-cited paradox, [20] [21] a dishonest person can sometimes act honestly while still being considered to be predominantly dishonest on the other hand, an honest person who sometimes does dishonest things will likely be reclassified as a dishonest person. It is expected that a dishonest person will occasionally be honest, but this honesty will not counteract the prior demonstrations of dishonesty. Honesty is considered more easily tarnished by acts of dishonesty. Honesty itself would then be not diagnostic of an honest nature, only the absence of dishonesty.

The presumption that negative information has greater diagnostic accuracy is also evident in voting patterns. Voting behaviors have been shown to be more affected or motivated by negative information than positive: people tend to be more motivated to vote against a candidate because of negative information than they are to vote for a candidate because of positive information. [22] [23] As noted by researcher Jill Klein, "character weaknesses were more important than strengths in determining. the ultimate vote". [23]

This diagnostic preference for negative traits over positive traits is thought to be a consequence of behavioral expectations: there is a general expectation that, owing to social requirements and regulations, people will generally behave positively and exhibit positive traits. Contrastingly, negative behaviors/traits are more unexpected and, thus, more salient when they are exhibited. [1] [2] [10] [19] [24] The relatively greater salience of negative events or information means they ultimately play a greater role in the judgment process.

Attribution of Intentions Edit

Studies reported in a paper in the Journal of Experimental Psychology: General by Carey Morewedge (2009) found that people exhibit a negativity bias in attribution of external agency, such that they are more likely to attribute negative outcomes to the intentions of another person than similar neutral and positive outcomes. [25] In laboratory experiments, Morewedge found that participants were more likely to believe that a partner had influenced the outcome of a gamble in when the participants lost money than won money, even when the probability of winning and losing money was held even. This bias is not limited to adults. Children also appear to be more likely to attribute negative events to intentional causes than similarly positive events. [26]

Cognition Edit

As addressed by negative differentiation, [4] negative information seems to require greater information processing resources and activity than does positive information people tend to think and reason more about negative events than positive events. [8] [27] Neurological differences also point to greater processing of negative information: participants exhibit greater event-related potentials when reading about, or viewing photographs of, people performing negative acts that were incongruent with their traits than when reading about incongruent positive acts. [28] [29] [30] This additional processing leads to differences between positive and negative information in attention, learning, and memory.

Attention Edit

A number of studies have suggested that negativity is essentially an attention magnet. For example, when tasked with forming an impression of presented target individuals, participants spent longer looking at negative photographs than they did looking at positive photographs. [10] Similarly, participants registered more eye blinks when studying negative words than positive words [31] (blinking rate has been positively linked to cognitive activity [32] [33] ). Also, people were found to show greater orienting responses following negative than positive outcomes, including larger increases in pupil diameter, heart rate, and peripheral arterial tone [34] [35]

Importantly, this preferential attendance to negative information is evident even when the affective nature of the stimuli is irrelevant to the task itself. The automatic vigilance hypothesis has been investigated using a modified Stroop task. [36] Participants were presented with a series of positive and negative personality traits in several different colors as each trait appeared on the screen, participants were to name the color as quickly as possible. Even though the positive and negative elements of the words were immaterial to the color-naming task, participants were slower to name the color of negative traits than they were positive traits. This difference in response latencies indicates that greater attention was devoted to processing the trait itself when it was negative.

Aside from studies of eye blinks and color naming, Baumeister and colleagues noted in their review of bad events versus good events [2] that there is also easily accessible, real-world evidence for this attentional bias: bad news sells more papers and the bulk of successful novels are full of negative events and turmoil. When taken in conjunction with the laboratory-based experiments, there is strong support for the notion that negative information generally has a stronger pull on attention than does positive information.

Learning and memory Edit

Learning and memory are direct consequences of attentional processing: the more attention is directed or devoted toward something, the more likely it is that it will be later learned and remembered. Research concerning the effects of punishment and reward on learning suggests that punishment for incorrect responses is more effective in enhancing learning than are rewards for correct responses—learning occurs more quickly following bad events than good events. [37] [38]

Drs. Pratto and John addressed the effects of affective information on incidental memory as well as attention using their modified Stroop paradigm (see section concerning "Attention"). Not only were participants slower to name the colors of negative traits, they also exhibited better incidental memory for the presented negative traits than they did for the positive traits, regardless of the proportion of negative to positive traits in the stimuli set. [36]

Intentional memory is also impacted by the stimuli's negative or positive quality. When studying both positive and negative behaviors, participants tend to recall more negative behaviors during a later memory test than they do positive behaviors, even after controlling for serial position effects. [39] [40] There is also evidence that people exhibit better recognition memory and source memory for negative information. [31] [41]

When asked to recall a recent emotional event, people tend to report negative events more often than they report positive events, [42] and this is thought to be because these negative memories are more salient than are the positive memories. People also tend to underestimate how frequently they experience positive affect, in that they more often forget the positively emotional experiences than they forget negatively emotional experiences. [43]

Decision-making Edit

Studies of the negativity bias have also been related to research within the domain of decision-making, specifically as it relates to risk aversion or loss aversion. When presented with a situation in which a person stands to either gain something or lose something depending on the outcome, potential costs were argued to be more heavily considered than potential gains. [44] [1] [37] [45] The greater consideration of losses (i.e. negative outcomes) is in line with the principle of negative potency as proposed by Rozin and Royzman. [4] This issue of negativity and loss aversion as it relates to decision-making is most notably addressed by Drs. Daniel Kahneman's and Amos Tversky's prospect theory.

However, it is worth noting that Rozin and Royzman were never able to find loss aversion in decision making. [4] They wrote, "in particular, strict gain and loss of money does not reliably demonstrate loss aversion". This is consistent with the findings of a recent review of more than 40 studies of loss aversion focusing on decision problems with equal sized gains and losses. [46] In their review, Yechiam and Hochman (2013) did find a positive effect of losses on performance, autonomic arousal, and response time in decision tasks, which they suggested is due to the effect of losses on attention. This was labeled by them as loss attention. [46]

Politics Edit

Research points to a correlation between political affiliation and negativity bias, [47] [48] where conservatives are more sensitive to negative stimuli and therefore tend to lean towards right-leaning ideology which considers threat reduction and social-order to be its main focus. [49] Individuals with lower negativity bias tend to lean towards liberal political policies such as pluralism and are accepting of diverse social groups which by proxy could threaten social structure and cause greater risk of unrest. [50]

Infancy Edit

Although most of the research concerning the negativity bias has been conducted with adults (particularly undergraduate students), there have been a small number of infant studies also suggesting negativity biases.

Infants are thought to interpret ambiguous situations on the basis of how others around them react. When an adult (e.g. experimenter, mother) displays reactions of happiness, fear, or neutrality towards target toys, infants tend to approach the toy associated with the negative reaction significantly less than the neutral and positive toys. [51] [52] [53] [54] Furthermore, there was greater evidence of neural activity when the infants were shown pictures of the "negative" toy than when shown the "positive" and "neutral" toys. [55] Although recent work with 3-month-olds suggests a negativity bias in social evaluations, as well, [56] there is also work suggesting a potential positivity bias in attention to emotional expressions in infants younger than 7 months. [57] [58] [59] A review of the literature conducted by Drs. Amrisha Vaish, Tobias Grossman, and Amanda Woodward suggests the negativity bias may emerge during the second half of an infant's first year, although the authors also note that research on the negativity bias and affective information has been woefully neglected within the developmental literature. [54]

Aging and older adults Edit

Some research indicates that older adults may display, at least in certain situations, a positivity bias or positivity effect. [60] [61] [62] Proposed by Dr. Laura Carstensen and colleagues, the socioemotional selectivity theory outlines a shift in goals and emotion regulation tendencies with advancing age, resulting in a preference for positive information over negative information. Aside from the evidence in favor of a positivity bias, though, there have still been many documented cases of older adults displaying a negativity bias. [63] [64]


What is positive and negative supercoiling? - Biology

Some scientists (particularly scientists involved in biological sciences) talk of “positive controls” (other scientists may call these a “reference” or a “standard”) and “negative controls”. The terms don’t make a lot of sense, until you understand what they mean and then it’s quite easy.

Examples from everyday life.

Positive controls. Have you ever bought a new car? Did you have a test drive first to get an idea of how the car performs? The test drive tells you the standard that you can expect. When you get your new car, it might not be the actual car you took on a test drive, but it should be the same model and so perform similarly. Now suppose you take delivery of your new car, and it doesn’t match up to the car you took on a test drive. Maybe it doesn’t accelerate as well, or some accessories are missing. You could reasonably go back to the showroom, point out the deficiencies and get your new car repaired, replaced or maybe even ask for your money back.

The test drive was your “positive control” – it set the standard, it showed you what should happen. If you hadn’t taken the test drive, you might not have realised that your new car was defective. That’s why positive controls are so useful – they tell you what to expect if things go well.

Negative controls. A negative control is the opposite of a positive control. It tells you what should happen if your experimental intervention does nothing. Suppose you have heard that adding grated beetroot to chocolate cake mix makes it tastes even better. So you head to the kitchen and bake a chocolate cake with beetroot in it and it tastes great! But, wait! How do you know it’s any better than your normal chocolate cake? The only way to test this is to bake a chocolate cake using your normal recipe – instead of adding beetroot you just use the regular ingredients. This is your “negative control” – it sets the standard if you do nothing to alter the recipe. So now you can compare the beetroot-enhanced cake with the normal one and see whether there really is a difference.

Scientific examples.

For scientists, positive controls are very helpful because it allows us to be sure that our experimental set-up is working properly. For example, suppose we want to test how well a new drug works and we have designed a laboratory test to do this. We test the drug and it works, but has it worked as well as well as it should? The only way to be sure is to compare it to another drug (the positive control) which we know works well. The positive control drug is also useful because it tells us our experimental equipment is working properly. If the new drug doesn’t work, we can rule out a problem with our equipment by showing that the positive control drug works.

The “negative-control” sets what we sometimes call the “baseline”. Suppose we are testing a new drug to kill bacteria (an antibiotic) and to do this we are going to count the number of bacteria that are still alive in a test tube after we add the drug. We could set up an experiment with three tubes.

  1. One tube could contain the drug we want to test.
  2. The second tube would contain our positive control (a different drug which we know will kill the bacteria)
  3. The last tube is our negative control – it contains a drug which we know has no effect on the bacteria. This tells us how many bacteria would be alive if we didn’t kill any of them.

If the new drug is working, there should be fewer cells left alive in the first tube compared to the last tube and ideally then number of cells still alive (if any) should be the same in the first and second tube.

So “controls” are important to scientists because it helps us validate the performance of our experimental set-up and tells us what effects we can reasonably expect to observe.

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