Persius/hicric huggingface dataset:
Negative stain
Negative staining is an established method, often used in diagnostic microscopy, for contrasting a thin specimen with an optically opaque fluid.
For bright field microscopy, negative staining is typically performed using a black ink fluid such as nigrosin. The specimen, such as a wet bacterial culture spread on a glass slide, is mixed with the negative stain and allowed to dry. When viewed with the microscope the bacterial cells, and perhaps their spores, appear light against the dark surrounding background.
In the case of transmission electron microscopy, opaqueness to electrons is related to the atomic number. Some suitable negative stains include ammonium molybdate, uranyl acetate, uranyl formate, phosphotungstic acid and auroglucothionate.  These have been chosen because they scatter electrons well and also adsorb to biological matter well. The structures which can be negatively stained are much smaller than those studied with the light microscope. Here, the method is used to view viruses, bacteria, bacterial flagella, biological membrane structures and proteins or protein aggregates, which all have a low electron-scattering power.
The choice of negative stain in electron microscopy can be very important. A study of plant viruses from negatively-stained leaf dips of a diseased plant showed only spherical viruses with one stain and only rod-shaped viruses with another! The verified conclusion was that this plant suffered from a mixed infection by two separate viruses.
Negative staining should never be performed with infectious organisms unless stringent safety precautions are followed. Negative staining is a very mild preparation method and does not reduce the possibility of operator infection!
Neuromarketing
Neuromarketing is a new field of marketing that studies consumers sensorimotor, cognitive, and affective response to marketing stimuli. Researchers use technologies such as  functional Magnetic Resonance Imaging (fMRI) to measure changes in activity in parts of the brain, Electroencephalography (EEG) to measure activity in specific regional spectra of the brain response, and/or sensors to measure changes in ones physiological state (Heart Rate, Respiratory Rate, Galvanic Skin Response) to learn why consumers make the decisions they do, and what part of the brain is telling them to do it.
Marketing analysts will use neuromarketing to better measure a consumer's preference, as the verbal response given to the question "Do you like this product?" may not always be the true answer due to cognitive bias. This knowledge will help marketers create products and services designed more effectively and marketing campaigns focused more on the brain's response.
Neuromarketing will tell the marketer what the consumer reacts to, whether it was the color of the packaging, the sound the box makes when shaken, or the idea that they will have something their co-consumers do not.
The word "neuromarketing" was coined by Ale Smidts in 2002

# Priming
One of the main psychology principles behind marketing is the concept of priming.  Priming a subject with a certain topic such as "dog" sets off an electrochemical reaction in the neural frameworks that code for dogs.  Subsequent exposure to dog-related stimuli is processed faster because of the electrochemical priming.  Assimiliation is the process by which new information is assimilated or incorporated into ones' existing neural structures.  Advertising agencies know how important it is to repeat their messages so that priming and assimilation can take place.  Priming usually occurs without the conscious awareness of the individual, even though the subsequent behavior of the individual may be altered by the priming.

# Coke vs. Pepsi
In a study from the group of Read Montague, the director of the Human Neuroimaging Lab and the Center for Theoretical Neuroscience at Baylor College of Medicine, published in 2004 in Neuron, 67 people had their brains scanned while being given the "Pepsi Challenge", a blind taste test of Coca-Cola and Pepsi. Half the subjects choose Pepsi, and Pepsi tended to produce a stronger response than Coke in the brain's ventromedial prefrontal cortex, a region thought to process feelings of reward. But when the subjects were told they were drinking Coke three-fourths said that Coke tasted better. Their brain activity had also changed. The lateral prefrontal cortex, an area of the brain that scientists say governs high-level cognitive powers, and the hippocampus, an area related to memory, were now being used, indicating that the consumers were thinking about Coke and relating it to memories and other impressions.  The results demonstrated that Pepsi should have half the market share, but in reality consumers are buying Coke for reasons related less to their taste preferences and more to their experience with the Coke brand.
Neuropeptide S
Neuropeptide S (NPS) is a neuropeptide found in human and mammalian brain, mainly produced by neurons in the amygdala and between Barrington's nucleus and the locus coeruleus, although NPS-responsive neurons extend projections into many other brain areas. NPS binds specifically to a G protein-coupled receptor, NPSR. Animal studies show that NPS suppresses anxiety and appetite, induces wakefulness and hyperactivity, including hyper-sexuality, and plays a significant role in the extinction of conditioned fear. It has also been shown to significantly enhance dopamine activity in the mesolimbic pathway, and inhibits motility and increases permeability in neurocrine fashion acting through NO in the myenteric plexus in rats and humans.

# Synthetic ligands
The non-peptide NPS receptor antagonist SHA-68 blocks the effects of NPS in animals and is anxiogenic. Several peptide derived NPS agonists and antagonists have also been developed.

# Peptide sequence
Below are the sequences of mature neuropeptide S in several representative species in which it is expressed:
Neurophysin II
Neurophysin II is a carrier protein with a size of 19,687.3 Da and is made up of a dimer of two virtually identical chains of amino acids. Neurophysin II is a cleavage product (formed by splitting of a compound molecule into a simpler one) of the prepro-vasopressin. It is a neurohypophysial hormone that is transported in vesicles with vasopressin, the other cleavage product, along axons, from magnocellular neurons of the hypothalamus to the posterior lobe of the pituitary. Although it is stored in neurosecretory granules with vasopressin and released with vasopressin into the bloodstream, its biological action is unclear. Neurophysin II is also known as a stimulator of prolactin secretion.

# Function
Neurophysin II is a carrier protein for vasopressin (ADH). It is produced in the cell bodies of the paraventricular and supraoptic nuclei and transported to its site of release in the axon terminals of the posterior pituitary. Oxytocin, a hormone similar in structure to vasopressin, is analogously bound and transported by Neurophysin I. Both hormones are nine residues long, and only differ by the amino acids at positions three and eight. Oxytocin possesses Ile-3 whereas vasopressin possesses Phe-3. Both Ile and Phe are hydrophobic amino acids and undergo analogous binding to neurophysins.

# Structure
Neurophysin II is a dimer with each monomer consisting of two anti-parallel -sheets. Each chain is identical with the exception of a single amino acid substitution (Chain 1 contains Lys-18, whereas chain 2 contains Ala-18). Each chain is 95 amino acids in length and binds a single oxytocin molecule.
The amino acid sequence of Neurophysin II is:
NH2 - Ala - Met - Ser - Asp - Leu - Glu - Leu - Arg - Gln - Cys - Leu - Pro - Cys - Gly - Pro - Gly - Gly - Lys - Gly - Arg - Cys - Phe - Gly - Pro - Ser - Ile - Cys - Cys - Ala - Asp - Glu - Leu - Gly - Cys - Phe - Val - Gly - Thr - Ala - Glu - Ala - Leu - Arg - Cys - Gln - Glu - Glu - Asn - Tyr - Leu - Pro - Ser - Pro - Cys - Gln - Ser - Gly - Gln - Lys - Ala - Cys - Gly - Ser - Gly - Gly - Arg - Cys - Ala - Ala - Phe - Gly - Val - Cys - Cys - Asn - Asp - Glu - Ser - Cys - Val - Thr - Glu - Pro - Glu - Cys - Arg - Glu - Gly - Phe - His - Arg - Arg - Ala - OH
(Disulfide - bridge: - 10-54; - 13-27; - 21-44; - 28-34; - 61-73; - 67-85; - 74-79)

# Clinical significance
Point mutations in the genes that encode arginine vasopressin and or its carrier protein neurophysin II underlie most cases of the familial, autosomal dominant disorder neurohypophyseal diabetes insipidus. (also called hereditary hypothalamic diabetes insipidus). This condition results from insufficient ADH release into systemic circulation.
Neuroscientist

# Overview
A neuroscientist is an individual who studies the scientific field of neuroscience or any of its related sub-fields. Neuroscience as a distinct discipline separate from anatomy, neurology, physiology, psychology, or psychiatry is fairly recent, aided in large part by the advent of newer, faster computing methods and neuroimaging techniques. Neuroscientist is sometimes used synonymously with neurobiologist.
These scientists generally work as researchers within a college, university, government agency, or private industry setting.

# Training and education
Many colleges and universities now have a neuroscience program, existing either as its own distinct department or as an institute within another, larger department. Often the neuroscience program exists within the psychology, molecular and cell biology, or other biology department. There are now many schools that offer Ph.D.s in neuroscience and/or neurobiology.
Nevus anemicus

# Overview
Nevus anemicus is a congenital disorder characterized by hypopigmented macules of varying size and shape.

# Pathophysiology
The hypopigmentation is due to increased sensitivity of the blood vessels within the area to the bodys normal vasoconstricting chemicals, such as catecholamines. The involved area is lighter than the normal skin, not because of a loss of pigment occurs, but because blood vessels are constricted, producing a permanent blanching of the area. This blanching is a functional rather than a structual abnormality, presumed to be caused by local increased sensitivity to catecholamines.  Although the cutaneous vasculature appears normal histologically, the blood vessels within the nevus do not respond to injection of vasodilators.

# Differential Diagnosis
- Nevus anemicus must be differentiated from vitiligo and other diseases causing hypopigmentation.
- Rubbing the area causes the skin around the lesion to become red while the lesion itself does not change in color.
- Diascopy is used to differentiate nevus anemicus from other hypopigmented skin lesions, such as vitiligo.
- Results of a skin biopsy are often interpreted as normal unlike other conditions.
- Physiological testing can exacerbate the appearance of the nevus in contrast to normal skin. Normally, when the skin is stroked, normal skin would react with a characteristic erythematous response.  In nevus anemicus, stroking the patch elicits no red flare.
- Examination under a Wood lamp can also distinguish the patch form vitiligo. 

# Natural History, Prognosis, and Complications
- The patch appears on the skin at birth or in early childhood and the lesion is benign.

# Physical Examination
- In most people, the patches are under 10 cm in size.
- Often the patches are difficult to see against the background color of the patients skin, but if sunburn develops, then the white area stands out prominently.

# Treatment
Since the histopathology of nevus anemicus is normal, nevus anemicus is a pharmacologic nevus and not an anatomic one. In most people a nevus anemicus is on a covered area and so light in appearance that no treatment is needed.

# Gallery
Image obtained from Dermatology Atlas
Pseudarthrosis
Synonyms and keywords: Nonunion

# Overview
Pseudarthrosis (or "nonunions") is the movement of a bone at the location of a fracture resulting from inadequate healing of the fracture.
Pseudarthrosis can also result from a developmental failure.

# Etymology
The Latin root "pseud" means false and "arthrosis" means joint.  "Pseudarthrosis", then, is a false joint.  In the case of a 'non-union' , a fracture that does not heal, this is often evidenced by the obliteration of the medullary cavity of a long bone at the site of the non union.  This non union is not a true joint, and has no ligamentous support, but often has motion, and remodels into a rounded end that looks like a true joint.

# Treatment
The point of movement can be treated with electrical stimulations that hopefuly will trigger the bone cells to form the hydroxyapatite structure that keeps bones from bending too much. More recently, non-unions are treated by bone grafting, internal fixation, and external fixation, including a technique pioneered by Ilizarov, used to compress the bones at the site of the fracture.
More recently, non-unions are treated by bone grafting, internal fixation, and external fixation, including a technique pioneered by Ilizarov, used to compress the bones at the site of the fracture. Ilizarov originally used Bicycle spokes.
Grafting
This is using donor bone or autologous bone (harvested from the same person undergoing the surgery) as a stimulus to bone healing. The presence of the bone is thought to cause stem cells in the circulation and marrow to form cartilage, which then turns to bone, instead of a fibrous scar that forms to heal all other tissues of the body. Bone is the only tissue that can heal without a fibrous scar.
Fixation
The use of metal plates, pins, screws, and rods, that are screw or driven into a bone, to stabilize the broken bone fragments.
Nuclear matrix
In biology, the nuclear matrix is the network of fibres found throughout the inside of a cell nucleus and is analogous to the cell cytoskeleton.  The exact function of this matrix is still disputed, and it's very existence has recently been called into question.  There is evidence that the nuclear matrix is involved in regulation of gene expression in Arabidopsis thaliana. 

# Problems with nuclear matrix hypothesis
While a matrix structure may be viewed once the nucleus has been isolated, it has been suggested that the process of isolation itself induces fibre-like artifacts. Furthermore, it has been noted that experimental observations of the movement of RNA within the nucleus corresponds well to that expected from a purely diffusive process.
Finally, one may argue that a nuclear matrix is not necessary for nuclear function, and thus Occam's Razor sides with the simpler explanation

# Notes
-  See . Evidence for such a structure was recognised as long ago as 1948 (Zbarskii and Debov), and consequently many proteins associated with the matrix have been discovered. The presence of intra-cellular proteins is largely indisputable, and it is well recognized that proteins such as the Scaffold, or Matrix Associated Proteins (SAR or MAR) have some role in the organisation of chromatins.
-  See, for example  .
de:Kernmatrix
hu:Nuklearis matrix
Nuclear run-on
A nuclear run-on assay is conducted to identify the genes that are being transcribed at a certain point in time. Cell nuclei are isolated rapidly, and incubated with labelled nucleotides and the results are hybridized to a slot blot, which is then exposed to film. It was originally developed by Gariglio et al. (1981) and Brown et al. (1984) (see discussion).
Adding actinomycin-D to the reaction buffer is sufficient to stop transcription, while other toxins, such as -amanitin, show different effects, making it a good way to assay the effects of these compounds.
This method allows changes in transcription rates to be seen, which often differ from steady-state mRNA levels used in microarrays. This method is obsolete and is not popular due to its "trickiness", the radiolabel and the number of cells needed. Several attempts recently have been made to make this method microarray compatible, but other methods are much more favourable. To have a publication quality blot about 107 nuclei are needed, but 106 nuclei are sufficient to give results: these quantities of cells are higher than for most protocols.
It is often cited that this method is has been surpassed by microarrays, even though it should be noted that this method compares transcription rates and not total transcript expression levels, which differ.
It is incompatible with microarray experiments due to the fact eukaryotic polymerases are more intolerant towards fluorescently labelled or aminoallyl nucleotides, so UTP with phosphorus-32 on the alpha phosphate group is normally used. Cheadle et al (2005) used spotted nylon blots to obtain a high-throughput analysis of T-cell activation.
Alternative microarray methods have recently been developed, mainly PolII RIP-chip: RNA immunoprecipitation of RNA polymerase II with phosphorylated C-terminal domain directed antibodies and hybridization on a microarray slide or chip (the word chip in the name stems from "ChIP-chip" where a special affymetrix genechip was required). No research has been publishing comparing the results obtained with the methods, but each method has its disadvantages and advantages. The main issue on the validity of run on assay results is the presence of artifacts due to the isolation step: some transcripts may stop prematurely others might start out of place.
Another point to add is about the nuclei: There are various methods that require nuclear isolation. The problem is that the nuclear membrane is contiguous with the ER which is rich in protein and cytoplasmic mRNA; some methods require pure nuclear lysate while others, like a nuclear run-on, require "dirty" nuclei with an intact nuclear membrane even if the ER is attached. Some types of cell are notoriously difficult to isolate this way such as lymphocytes, which require a sucrose gradient purification.
Nucleobindin 1
Nucleobindin-1 (NUCB1), also known as calnuc, is a protein that in humans is encoded by the NUCB1 gene.

# Structure
The human calnuc protein contains 461 amino acids and has a pI of 4.9.
The protein contains the following regions and domains:
- Signal peptide
- Leucine-zipper The leucine-zipper of calnuc may be responsible for its dimerization.
- aa 347-389  Nuclear localization signal
- 2 zinc binding sites with high affinity (Kd = 20 nM)
- carboxypeptidase-like motifs : HFREXnH (aa 66) and HFTEXnH (aa 146)
- 2 EF-hands
- Potential anchor region 15-aa hydrophobic region at its COOH terminus that may be sufficient for membrane anchoring
Nucleoporin 62
Nucleoporin p62 (p62) is a protein complex associated with the nuclear envelope. The p62 protein remains associated with the nuclear pore complex-lamina fraction. p62 is synthesized as a soluble cytoplasmic precursor of 61 kDa followed by modification that involve addition of N-acetylglucosamine residues, followed by association with other complex proteins.
The nuclear pore complex is a massive structure that extends across the nuclear envelope, forming a gateway that regulates the flow of macromolecules between the nucleus and the cytoplasm. Nucleoporins are the main components of the nuclear pore complex in eukaryotic cells. The protein encoded by this gene is a member of the FG-repeat containing nucleoporins and is localized to the nuclear pore central plug. This protein associates with the importin alpha/beta complex which is involved in the import of proteins containing nuclear localization signals. Multiple transcript variants of this gene encode a single protein isoform.

# Structure
P62 is a serine/threonine rich protein of ~520 amino acids, with tetrapeptide repeats on the amino terminus and a series of alpha-helical regions with hydrophobic heptad repeats forming beta-propeller domain. P62 assembles into a complex containing 3 addition proteins, p60, p54 and p45  forming the p62 complex of ~235 kDa. Glycosylation appears to be involved in the assembly and disassembly of p62 into higher order complexes, and a serine/threonine rich linker region between Ser270 to Thr294 appear to be regulatory. The p62 complex is localized to both the nucleoplasmic and cytoplasmic sides of the pore complex and the relative diameter of p62 complex relative to the nuclear pore complex suggests it interacts in pore gating.

# Function
P62 appears to interact with mRNA during transport out of the nucleus. P62 also interacts with a nuclear transport factor (NTF2) protein that is involved in trafficking proteins between cytoplasm and nucleus. Another protein, importin (beta) binds to the helical rod section of p62, which also
binds NTF2 suggesting the formation of a higher order gating complex. Karyopherin beta2 (transportin), a riboprotein transporter also interacts with p62. P62 also interacts with Nup93, and when Nup98 is depleted p62 fails to assemble with nuclear pore complexes. Mutant pores could not dock/transport proteins with nuclear localization signals or M9 import signals.

# Pathology
Antibodies to p62 complex are involved in one or more autoimmune diseases. P62 glycosylation is increased in diabetes and may influence its association with other diseases. p62 is also more frequent in Stage IV primary biliary cirrhosis and is prognostic for severe disease.

# Interactions
Nucleoporin 62 has been shown to interact with:
- HSF2,
- KPNB1,
- NUTF2,
- TRAF3,  and
- XPO1,
- Nup93.
Nucleoporin 85
Nucleoporin 85 (Nup85) is a protein that in humans is encoded by the NUP85 gene.

# Function
Bidirectional transport of macromolecules between the cytoplasm and nucleus occurs through nuclear pore complexes (NPCs) embedded in the nuclear envelope. NPCs are composed of subcomplexes, and NUP85 is part of one such subcomplex, Nup107-160.

# Model organisms
Model organisms have been used in the study of NUP85 function. A conditional knockout mouse line called Nup85tm1a(KOMP)Wtsi was generated at the Wellcome Trust Sanger Institute. Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. Additional screens performed:  - In-depth immunological phenotyping
Obturator sign

# Overview
The obturator sign is an indicator of irritation to the obturator internus muscle.

# Technique
The technique is carried out on each leg in succession. First the patient lies on his back with the right hip flexed at 90 degrees. The examiner then holds the patient's right ankle in his right hand. With his left hand, the examiner rotates the hip by pulling the right knee to and away from the patient's body.

# Positive Obturator Sign
In the clinical context, it is performed when acute appendicitis is suspected. In this condition, the appendix becomes inflamed and enlarged. The appendix may come into physical contact with the obturator internus muscle, which will be stretched by this physical examination maneuver. This causes pain and is an evidence in support of an inflamed appendix.
The principles of the obturator sign in the diagnosis of appendicitis are similar to that of the psoas sign.

# Video

# Related Chapters
- Abdominal exam
- Appendicitis
- Psoas sign
- Rovsing's sign
- Obturator internus muscle