Persius/hicric huggingface dataset:
Transmembrane protein 254
Transmembrane protein 254 is a transmembrane protein that is encoded by the TMEM254 gene, it is predicted to have many orthologs across eukaryotes.

# Gene
TMEM254 is located on the long arm of chromosome 10, open reading frame 57 on the positive strand. It is found at position 10q22.3. It has seven known transcript variants..
File:TMEM254 cytogenetic band.png
This image shows the cytogenetic band of human chromosome 10 and the various gene locations on it. TMEM254 can be seen at the thin red band with the box around, placed at q22.3.

# mRNA
TMEM254 consists of ten total exons and is 13,911 bp in length.
Isoforms
TMEM254 has 3 isoforms produced by alternative splicing.

# Protein
TMEM254 contains:
- 147 amino acids.
- Five transmembrane domains
- Molecular weight 16.4 kilodaltons
- Isoelectric point 9.39
- domain of unknown function 4499 (DUF4499) region
The secondary structure of TMEM254 is predicted to consist of alternating pairs of alpha helices and beta sheets.

# Expression
According to a human GEO profile and human and mouse EST profiles, TMEM254 appears to be expressed at a relatively high level in most tissues.
TMEM254 is highly expressed in reproductive structures, and a wide range of cells. These include, but are not limited to, thyroid gland, pancreas, kidney, skin, breasts, and testes.

# Homology
There are no known paralogs for transmembrane protein 254, however it does have various orthologs within orthologs within eukaryotes. The following table presents some of the orthologs found using searches in BLAST. A comparison of a wide variety of known TMEM254 orthologs meant to display the diversity of species for which orthologs are found is listed in the table below:

# Predicted Post-Translational Modification
Using various tools at ExPASy the following are possible post-translational modifications for TMEM254.
- 4 possible PKC phosphorylation sites
- 3 possible PKA phosphorylation sites
Tricaine methanesulfonate
Tricaine methanesulfonate (TMS), also called as MS-222, is white powder used for anesthesia or sedation of fishes (mainly salmonids). TMS is the only anesthetic licensed in the United States for fin fish that is intended for human consumption.
TMS is a muscle relaxant that operates by preventing action potentials. By blocking action potentials, no signals can be exchanged between the brain and the extremities. There will be no sensory input or muscle contractions which would have been caused by action potential, which includes most muscles.
The optimum concentration used is 40-50 mg of TMS powder per litre of water. However, the optimium may vary with the size and species of the fish, and other variables.
It is easily soluble in water (both fresh and salt) but it drastically decreases the pH of water, increasing the acidity, which may be toxic for fish.  Baking soda or sodium bicarbonate is used to buffer the solution to a pH range of 6.5-7.5. Usually twice the amount of buffer is added to attain the neutral pH. In salt/marine/sea water, the buffer use may not be necessary because sea water itself has buffering capacity.
The solution of TMS needs to be prepared freshly each time because TMS is light-sensitive and might form toxic by-products upon exposure to light.
Trichocereus scopulicolus
Trichocereus scopulicolus is a type of cactus native to Bolivia, which contains psychedelic compounds.  Many claim this species contains mescaline, but there has never been any official studies done, so any speculation about its properties are without solid scientific support.

# Names
This cactus is synonymous with Trichocereus scopulicola, and its scientific name is Echinopsis scopulicola.

# Plant Description
This cactus grows 3-4 meters tall, and 8-10 cm in diameter, and is also noted for its unusually short spines.
Triosephosphate isomerase

# Overview
Triose-phosphate isomerase (TPI or TIM), is an enzyme (EC 5.3.1.1) that catalyzes the reversible interconversion of the triose phosphate isomers dihydroxyacetone phosphate and D-glyceraldehyde 3-phosphate.
Compound C00111 at KEGG Pathway Database.Enzyme 5.3.1.1 at KEGG Pathway Database.Compound C00118 at KEGG Pathway Database.
Triose phosphate isomerase (TPI) plays an important role in glycolysis and is essential for efficient energy production. TPI has been found in nearly every organism searched for the enzyme, including animals such as mammals and insects as well as in fungi, plants and bacteria. However, some bacteria that do not perform glycolysis, like ureaplasmas, lack TPI.
In humans, deficiencies in TPI are associated with a progressive, severe neurological disorder called Triose Phosphate Isomerase deficiency.
Triose phosphate isomerase is a massively efficient enzyme, performing the reaction billions of times faster than it would occur naturally in solution. The reaction is so efficient it is limited only by the rate the substrate can diffuse into the enzyme's active site.

# Structure
Triose phosphate isomerase is a dimer of identical subunits, each of which is made up of about 250 amino acid residues. The three-dimensional structure of a subunit contains eight -helices (blue and red) on the outside and eight parallel -strands on the inside (violet and yellow). This structural motif is called an -barrel, or a TIM-barrel, and is by far the most commonly observed protein fold. The active site of this enzyme is in the center of the barrel. A glutamic acid residue is involved in the catalytic mechanism.  The sequence around the active site residue is conserved in all known triose phosphate isomerases.
Tubuloglomerular feedback
In the physiology of the kidney, tubuloglomerular feedback (TGF) is one of several mechanisms the kidney uses to regulate glomerular filtration rate (GFR). Changes in GFR are detected by the renal tubule, which sends feedback signals to the glomerulus, initiating a cascade of events that ultimately brings GFR to an appropriate level.

# Background
Normal renal function requires that the flow through the nephron is kept within a narrow range. When tubular flow (that is, GFR) lies outside this range, the ability of the nephron to maintain solute and water balance is compromised. Additionally, changes in GFR may result from changes in renal blood flow (RBF), which itself must be maintained within narrow limits. Elevated RBF may damage the glomerulus, while diminished RBF may deprive the kidney of oxygen. Tubuloglomerular feedback provides a mechanism by which changes in GFR can be detected and rapidly corrected for on a minute-to-minute basis as well as over sustained periods.
Regulation of GFR requires both a mechanism of detecting an inappropriate GFR as well as an effector mechanism that corrects it. The macula densa serves as the detector, while the glomerulus acts as the effector. When the macula densa detects an elevated GFR, it releases several molecules that cause the glomerulus to rapidly decrease its filtration rate. (Technically, the macula densa detects a SNGFR, single nephron GFR, but GFR is used here for simplicity.)

# Mechanism
The macula densa is a collection of densely packed epithelial cells in the distal convoluted tubule. As the loop of Henle ascends through the renal cortex, it encounters its own glomerulus, bringing the macula densa to rest at the angle between the afferent and efferent arterioles. This places the macula densa in a unique position to rapidly alter glomerular resistance in response to changes in the flow rate through the distal nephron.
The distal renal tubule uses the composition of the tubular fluid as an indicator of GFR. A large amount of sodium chloride is indicative of an elevated GFR, while low sodium chloride indicates a depressed GFR. Sodium chloride is sensed by the macula densa by an apical Na-K-2Cl cotransporter (NKCC2). Detection of elevated sodium chloride levels triggers the release of signaling molecules from the macula densa, causing a drop in GFR. This drop is thought to be mediated largely by constriction of the afferent arteriole.
Precisely how the macula densa's detection of elevated sodium chloride leads to a decrease in GFR remains unknown. One proposed mechanism is that delivery of sodium chloride to the macula densa enhances the conversion of ATP to adenosine. Adenosine may then bind to adenosine A1 receptors on extraglomerular mesangial cells, triggering a rise in intracellular calcium levels. This calcium signal may be propagated via gap junctions to adjacent cells, including granular cells of the juxtaglomerular apparatus and vascular smooth muscle cells of the afferent arteriole, resulting in afferent arteriole vasoconstriction and a decrease in renin release.
U box gene transcriptions
"The U box is a domain of 70 amino acids that is present in proteins from yeast to humans."
"The prototype U box protein, yeast Ufd2, was identified as a ubiquitin chain assembly factor that cooperates with a ubiquitin-activating enzyme (E1), a ubiquitin-conjugating enzyme (E2), and a ubiquitin-protein ligase (E3) to catalyze ubiquitin chain formation on artificial substrates."
"The UFD2 protein and its homologs in other eukaryotes share a conserved domain designated the U box."
"The U box mediates the interaction of UFD2 with ubiquitin conjugated proteins  the U box is a derived version of the RING-finger domain that lacks the hallmark metal-chelating residues of the latter  but is likely to function similarly to the RING-finger in mediating ubiquitin-conjugation of protein substrates."

# Tomato U boxes
"The promoter region of the identified 62 tomato U-box E3 genes was analyzed using PlantCARE database50 for the presence of the cis-regulatory elements . The cis-regulatory elements, the binding sites for transcription factors, carry information to regulate the gene expression in certain environmental responses or biological pathways. The occurrence frequency of the elements was represented as a word cloud image . We found jasmonic acid-responsive elements (TGACG, CGTCA), MYB binding site involved in drought induction (TAACTG), gibberellin responsive elements (CCTTTTG,AAACAGA), endosperm expression (TGTGTCA), abscisic acid-responsive elements (CACGTG), ethylene responsive elements (ATTTCAAA), heat-responsive elements (AAAAAATTTC), defense and stress-responsive elements (ATTTTCTTCA), circadian control elements (CAANNNNATC) abundantly in U-box E3 family. The presence of these elements predicts the notable participation of U-box E3 gene family members in hormonal pathways and stress responses. We have noticed jasmonic acid, drought inductive, endosperm expression, defense, stress-responsive and abscisic acid-responsive elements with the highest frequency compared to other elements in the U-box E3 gene family. It suggests the critical requirement of the U-box E3 ubiquitin ligase in various cellular pathways. However, we could not observe any definite pattern of cis-element appearance with the four classes of the U-box E3 gene family. A few genes were also noticed with the shoot (GATAatGATG) and root (TGACGTCA) specific elements, cell cycle regulation (CCCAACGGT), seed-specific element (CATGCATG) and alpha-amylase conserved elements (TATCCATCCATCC)."
Upper motor neuron lesion

# Overview
An upper motor neuron lesion is a lesion of the neural pathway above the anterior horn cell or motor nuclei of the cranial nerves. This is in contrast to a lower motor neuron lesion, which affects nerve fibers traveling from the anterior horn of the spinal cord to the relevant muscle(s).

# Causes

## Life Threatening Causes
- Cerebral palsy
- Cerebrovascular accident
- Cervical myelopathy
- Multiple sclerosis
- Spinal cord injury
- Stroke
- Traumatic brain injury

## Common Causes
- Cerebral palsy,
- Cerebrovascular accident,
- Cervical myelopathy,
- Cervical spondylosis,
- Friedreich ataxia,
- Juvenile primary lateral sclerosis,
- Konzo,
- Motor neuron disease,
- Multiple sclerosis,
- Pseudobulbar palsy,
- Spastic paralysis,
- Spina bifida,
- Spinal cord injury,
- Subacute combined degeneration of the cord,
- Syringomyelia,
- Traumatic brain injury,
- Weber syndrome,
- X-linked sideroblastic ataxia,

## Causes by Organ System

## Causes in Alphabetical Order
- Adult polyglucosan body disease
- Cerebral palsy
- Cerebrovascular accident
- Cervical myelopathy
- Cervical spondylosis
- Friedreich ataxia
- Juvenile primary lateral sclerosis
- Konzo
- Lathyrus poisoning
- Leukoencephalopathy
- Motor neuron disease
- Multiple sclerosis
- Pellagra
- Pernicious anemia
- Progressive multifocal leucoencephalopathy
- Pseudobulbar palsy
- Quaternary syphilis
- Spastic paralysis
- Spina bifida
- Spinal cord injury
- Stroke
- Subacute combined degeneration of the cord
- Syringomyelia
- Traumatic brain injury
- Vitamin b12 deficiency
- Weber syndrome
- X-linked sideroblastic ataxia

# Symptoms
- Spastic increase in tone in the extensor muscles (lower limbs) or flexor muscles (upper limbs)
- Clasp-knife response where initial resistance to movement is followed by relaxation
- Weakness in the flexors (lower limbs) or extensors (upper limbs), but no muscle wasting
- Brisk tendon jerk reflexes
- Babinski sign positive, where the big toe is raised rather than curled downwards on stimulation of the sole of the foot

# Corticospinal/pyramidal tract
These are the neural tracts which descend in the spinal cord, in the lateral columns, carrying signals for voluntary movement of skeletal muscle.   These nerve fibres usually originate  in the cerebral cortex, then gather in the internal capsule before crossing over to the opposite side (decussation) in the medulla oblongata and proceeding down the spinal cord to meet lower motor neurons in the anterior horn.
Valacyclovir how supplied

# How Supplied
VALTREX Caplets (blue, filmcoated, capsuleshaped tablets) containing valacyclovir hydrochloride equivalent to 500 mg valacyclovir and printed with "VALTREX 500 mg."
Bottle of 30 (NDC 0173-0933-08).
Bottle of 90 (NDC 0173-0933-10).
Unit dose pack of 100 (NDC 0173-0933-56).
VALTREX Caplets (blue, filmcoated, capsuleshaped tablets, with a partial scorebar on both sides) containing valacyclovir hydrochloride equivalent to 1 gram valacyclovir and printed with "VALTREX 1 gram."
Bottle of 30 (NDC 0173-0565-04).
Bottle of 90 (NDC 0173-0565-10).

## Storage
Store at 15 to 25C (59 to 77F). Dispense in a well-closed container as defined in the USP.
Valacyclovir microbiology

# Microbiology
Antiviral Activities: The quantitative relationship between the cell culture susceptibility of herpesviruses to antivirals and the clinical response to therapy has not been established in humans, and virus sensitivity testing has not been standardized. Sensitivity testing results, expressed as the concentration of drug required to inhibit by 50% the growth of virus in cell culture (EC50), vary greatly depending upon a number of factors. Using plaque-reduction assays, the EC50 values against herpes simplex virus isolates range from 0.09 to 60 M (0.02 to 13.5 mcg/mL) for HSV1 and from 0.04 to 44 M (0.01 to 9.9 mcg/mL) for HSV2. The EC50 values for acyclovir against most laboratory strains and clinical isolates of VZV range from 0.53 to 48 M (0.12 to 10.8 mcg/mL). Acyclovir also demonstrates activity against the Oka vaccine strain of VZV with a mean EC50 of 6 M (1.35 mcg/mL).
Resistance: Resistance of HSV and VZV to acyclovir can result from qualitative and quantitative changes in the viral TK and/or DNA polymerase. Clinical isolates of VZV with reduced susceptibility to acyclovir have been recovered from patients with AIDS. In these cases, TK-deficient mutants of VZV have been recovered.
Resistance of HSV and VZV to acyclovir occurs by the same mechanisms. While most of the acyclovirresistant mutants isolated thus far from immunocompromised patients have been found to be TKdeficient mutants, other mutants involving the viral TK gene (TK partial and TK altered) and DNA polymerase have also been isolated. TKnegative mutants may cause severe disease in immunocompromised patients. The possibility of viral resistance to valacyclovir (and therefore, to acyclovir) should be considered in patients who show poor clinical response during therapy.
Velopharyngeal inadequacy

# Overview
Velopharyngeal inadequacy (VPI) is a malfunction of a velopharyngeal mechanism.
The velopharyngeal mechanism is responsible for directing the transmission of sound energy and air pressure in both the oral cavity and the nasal cavity. When this mechanism is impaired in some way, the valve does not fully close, and a condition known as 'velopharyngeal inadequacy' can develop. VPI can either be congenital or acquired later in life.

# Terminology
Different terms can be used to describe this phenomenon in addition to velopharyngeal inadequacy. These terms and definitions are as follows:
- Velopharyngeal insufficiency: The mobility of the velopharyngeal sphincter to sufficiently separate the nasal cavity from the oral cavity during speech.
- Velopharyngeal incompetency: When the velum and the lateral/posterior pharyngeal walls fail to separate the oral cavity from the nasal cavity during speech.
Although the definitions are similar, the etiologies correlated with each term differ slightly; however, in the field of medical professionals these terms are typically used interchangeably. Velopharyngeal inadequacy is the generic term most often used to describe the functionality of the velopharyngeal valve.

# Relationship to cleft palate
A cleft palate is one of the most common causes of VPI. Cleft palate is an anatomical abnormality that occurs in utero and is present at birth. This malformation can affect the lip, the lip and palate, or the palate only. A cleft palate can affect the mobility of the velopharyngeal valve, thereby resulting in VPI.

# Classification
The most frequent types of cleft palates are overt, submucous, and occult submucous.

# Causes
While cleft is the most common cause of VPI, other significant etiologies exist. These other causes are outlined in the chart below:
Vhr1p gene transcriptions
"Transcription of the Saccharomyces cerevisiae vitamin H transporter gene VHT1 is enhanced by low extracellular biotin."
"Vhr1p  a transcriptional regulator of VHT1 (VHR1 (YIL056w)".
"Deletion and linker scanning analyses of the VHT1 promoter revealed the palindromic 18-nucleotide sequence AATCA-N8-TGAYT as the vitamin H-responsive element."

# Human genes

# Gene expressions
Vhr1p upstream activator sequence (UAS) occurs in the promoters of VHT1, BIO5 Saccharomyces cerevisiae genes. Its inducer is biotin where it responds to low biotin concentrations.

# Interactions

# Consensus sequences
AATCA-N8-TGA(C/T)T is the UAS sequence for the transcription factor Vhr1p.

# Binding site for

# Hypotheses
- A1BG has no regulatory elements in either promoter.
- A1BG is not transcribed by a regulatory element.
- No regulatory element participates in the transcription of A1BG.

# VHR samplings
Copying a responsive elements consensus sequence AATCA-N8-TGA(C/T)T and putting the sequence in "F" finds none between ZNF497 and A1BG or none between ZSCAN22 and A1BG as can be found by the computer programs.
For the Basic programs testing consensus sequence AATCA-N8-TGA(C/T)T (starting with SuccessablesVHR.bas) written to compare nucleotide sequences with the sequences on either the template strand (-), or coding strand (+), of the DNA, in the negative direction (-), or the positive direction (+), the programs are, are looking for, and found:
- negative strand, negative direction, looking for AATCANNNNNNNNTGA(C/T)T, 0.
- positive strand, negative direction, looking for AATCANNNNNNNNTGA(C/T)T, 0.
- positive strand, positive direction, looking for AATCANNNNNNNNTGA(C/T)T, 0.
- negative strand, positive direction, looking for AATCANNNNNNNNTGA(C/T)T, 0.
- complement, negative strand, negative direction, looking for TTAGTNNNNNNNNACT(A/G)A, 0.
- complement, positive strand, negative direction, looking for TTAGTNNNNNNNNACT(A/G)A, 0.
- complement, positive strand, positive direction, looking for TTAGTNNNNNNNNACT(A/G)A, 0.
- complement, negative strand, positive direction, looking for TTAGTNNNNNNNNACT(A/G)A, 0.
- inverse complement, negative strand, negative direction, looking for A(A/G)TCANNNNNNNNTGATT, 0.
- inverse complement, positive strand, negative direction, looking for A(A/G)TCANNNNNNNNTGATT, 0.
- inverse complement, positive strand, positive direction, looking for A(A/G)TCANNNNNNNNTGATT, 0.
- inverse complement, negative strand, positive direction, looking for A(A/G)TCANNNNNNNNTGATT, 0.
- inverse negative strand, negative direction, looking for T(C/T)AGTNNNNNNNNACTAA, 0.
- inverse positive strand, negative direction, looking for T(C/T)AGTNNNNNNNNACTAA, 0.
- inverse positive strand, positive direction, looking for T(C/T)AGTNNNNNNNNACTAA, 0.
- inverse negative strand, positive direction, looking for T(C/T)AGTNNNNNNNNACTAA, 0.

# Acknowledgements
The content on this page was first contributed by: Henry A. Hoff.
Voltage-gated ion channel

# Overview
Voltage-gated ion channels are a class of transmembrane ion channels that are activated by changes in electrical potential difference near the channel; these types of ion channels are especially critical in neurons, but are common in many types of cells.  All voltage gates contain repeating sequences of arginine that are responsible for the charged portion of the domain.
They have a crucial role in excitable neuronal and muscle tissues, allowing a rapid and coordinated depolarization in response to triggering voltage change. Found along the axon and at the synapse, voltage-gated ion channels directionally propagate electrical signals.

# Structure
They generally are composed of several subunits arranged in such a way that there is a central pore through which ions can travel down their electrochemical gradients. The channels tend to be quite ion-specific, although similarly sized and charged ions may also travel through them to some extent.

# Examples
Examples include:
- the sodium and potassium voltage-gated channels of nerve and muscle.
- the voltage-gated calcium channels that play a role in neurotransmitter release in pre-synaptic nerve endings.

# Mechanism
From crystallographic structural studies of a potassium channel, assuming that this structure remains intact in the corresponding plasma membrane, it is possible to surmise that when a potential difference is introduced over the membrane, the associated electromagnetic field induces a conformational change in the potassium channel. The conformational change distorts the shape of the channel proteins sufficiently such that the cavity, or channel, opens to admit ion influx or efflux to occur across the membrane, down its electrochemical gradient. This subsequently generates an electrical current sufficient to depolarise the cell membrane.
Voltage-gated sodium channels and calcium channels are made up of a single polypeptide with four homologous domains. Each domain contains 6 membrane spanning alpha helices. One of these helices, S4, is the voltage sensing helix. It has many positive charges such that a high positive charge outside the cell repels the helix - inducing a conformational change such that ions may flow through the channel. Potassium channels function in a similar way, with the exception that they are composed of four separate polypeptide chains, each comprising one domain.
The voltage-sensitive protein domain of these channels (the "voltage sensor") generally contains a region composed of S3b and S4 helices, known as the "paddle" due to its shape, which appears to be a conserved sequence, interchangable across a wide variety of cells and species. Genetic engineering of the paddle region from a species of volcano-dwelling archaebacteria into rat brain potassium channels results in a fully functional ion channel, as long as the whole intact paddle is replaced. This "modularity" allows use of simple and inexpensive model systems to study the function of this region, its role in disease, and pharmaceutical control of its behavior rather than being limited to poorly characterized, expensive, and/or difficult to study preparations.