User:Garnhami/sandbox



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https://tools.wmflabs.org/pageviews/?project=en.wikipedia.org&platform=all-access&agent=user&range=latest-20&pages=Blood_Stream_Infection

question on redirects

Hello, here I am again.. with a stupid question! I noticed that bloodstream infections (here is the page where you see the redirect: https://en.wikipedia.org/w/index.php?title=Blood_Stream_Infection&redirect=no ) is a page that "redirects" to "bacteremia. Now I do not understand this! A blood stream infection can be a bacteremia but it can also be a fungemia or a viremia or even a protozoa. So I was thinking to change this problem by requesting to remove the redirect from bloodstream infection to bacteremia and write a short page on bloodstream infections (and in that page links to the different types of bloodstream infections). However I do not really understand how to do this. I found this: https://en.wikipedia.org/wiki/Wikipedia:Redirects_for_discussion with How to list a redirect for discussion, but not sure how it works with How to list a redirect for discussion. Sorry to bother you with this , but the tutorial is not very obvious for me. Garnhami (talk) 21:14, 5 May 2017 (UTC)

Update: I actually found this:when should be delete a redirect, and here it states: Listing is not necessary if you just want to replace a redirect with an article, or change where it points

If I understand it correctly, does this mean I can edit the bloodstream page without really warning someone? (I mean, write some stuff about bloodstream infections and remove the redirect (and replace it with several links on that page to eg fungemia, bacteremia and so on..? ) Garnhami (talk) 21:19, 5 May 2017 (UTC)


 * That is a seldom-used redirect. You can view the page statistics on the wp:page history or here. There is about one or two views per week. So few if anyone will notice your edits. If you wish to take your time editing the page, you can use your sandbox (link at top right of any page while you are logged in) or an other sandbox such as user:Garnhami/Blood Stream Infection (it's a wp:redlink as the page has yet to be created). When you feel comfortable posting it, request that the page be moved. See wp:moving a page. Per CC BY-SA 3.0 license, the page history must be preserved, so they would need to be merged. I believe a fairly simple task for this case. It may take a week. Again, given the low view count, having the page incomplete is probably irrelevant. BTW: Is there another title for that subject that may already exist? Cheers Jim1138 (talk) 22:32, 5 May 2017 (UTC)


 * Ok! Thanks a lot! Now I have one more question, I have been editing some articles, one in particular, however I noticed that I am always editing small things, one by one (to keep the overview). I do wonder: could I just cope paste the whole article to my sandbox and then when I made ALL the edits (which might take some time to do) just cope paste this back into the original article? (of course, I would keep track on other, major, edits in the article and include those as well).Or is this not possible ? Garnhami (talk) 15:17, 6 May 2017 (UTC)
 * Replying on Garnhami's talk page. Jim1138 (talk) 17:37, 6 May 2017 (UTC)

When_should_we_delete_a_redirect.3F

test

editing and improving article for the future

Candida albicans, is commonly referred to as a dimorphic fungus since It grows both as yeast and filamentous cells. However it has several different morphological phenotypes that are discussed more in detail in the chapter on Morphology. It is a common member of human gut flora. It is detectable in the gastrointestinal tract and mouth in 40-60% of healthy adults. It is usually a commensal organism, but can become pathogenic in immunocompromised individuals under a variety of conditions. It is one of the few species of the Candida genus that cause the infection candidiasis in humans. Overgrowth of the fungus results in candidiasis (candidosis). Candidiasis is for example often observed in HIV-infected patients. C. albicans is responsible for 50–90% of all cases of candidiasis in humans. Together with C. tropicalis, C. parapsilosis and C. glabrata it is responsible for approximately 90% of Candida infections.

C. albicans was for a long time considered an obligate diploid organism without a haploid stage. This is however not the case. Next to a haploid stage C. albicans can also exist in a tetraploid stage. The latter is formed when diploid C. albicans cells mate when they are in the opaque form. The diploid genome size is approximately 29Mb and up to 70% of the protein coding genes have not yet been characterized. C. albicans is often found in mixed biofilms  together with Staphylococcus aureus on implanted medical devices.

Genome


The genome of C. albicans is almost 16Mb large, 8 chromosomes (28Mb for the diploid stage) and contains 6198 Open Reading Frames (ORFs). 70% of these ORFs have not yet been characterized. The whole genome has been sequenced making It one of the first fungi the be completely sequenced (next to Saccharomyces cerevisiae and Schizosaccharomyces pombe). All open reading frames (ORFs) are also available in gateway adapted vectors. Next to this ORFeome there is also the availability of a GRACE (gene replacement and conditional expression) library to study essential genes in the genome of C. albicans. The most commonly used strains to study C. albicans are the WO-1 and SC5314 strains. The WO-1 strain is known to switch between white-opaque form with higher frequency while the SC5314 strain is the strain used for gene sequence reference.

One of the most important features of the C. albicans genome is the occurrence of numeric and structural chromosomal rearrangements as means of generating genetic diversity, named chromosome length polymorphisms (contraction/expansion of repeats), reciprocal translocations, chromosome deletions and trisomy of individual chromosomes. These karyotypic alterations lead to changes in the phenotype, which is an adaptation strategy of this fungus. These mechanisms will be better understood with the complete analysis of the C. albicans genome.

An unusual feature of the Candida genus is that in many of its species (including C. albicans and C. tropicalis, but not, for instance, C. glabrata) the CUG codon, which normally specifies leucine, specifies serine in these species. This is an unusual example of a departure from the standard genetic code, and most such departures are in start codons or, for eukaryotes, mitochondrial genetic codes. This alteration may, in some environments, help these Candida species by inducing a permanent stress response, a more generalized form of the heat shock response. However this different codon usage makes it more difficult to study C. albicans protein-protein interactions in the model organism S. cerevisiae. To overcome this problem a C. albicans specific two-hybrid system was developed.

The genome of C. albicans is highly dynamic, contributed by the different CUG translation, and this variability has been used advantageously for molecular epidemiological studies and population studies in this species. The genome sequence has allowed for identifying the presence of a parasexual cycle (no detected meiotic division) in C. albicans. This study of the evolution of sexual reproduction in six Candida species found recent losses in components of the major meiotic crossover-formation pathway, but retention of a minor pathway. The authors suggested that if Candida species undergo meiosis it is with reduced machinery, or different machinery, and indicated that unrecognized meiotic cycles may exist in many species. In another evolutionary study, introduction of partial CUG identity redefinition (from Candida species) into Saccharomyces cerevisiae clones caused a stress response that negatively affected sexual reproduction. This CUG identity redefinition, occurring in ancestors of Candida species, was thought to lock these species into a diploid or polyploid state with possible blockage of sexual reproduction.

Heterozygosity
The heterozygosity of the Candida genome exceeds that found in other genomes and is widespread among clinical isolates. Nonsynonymous single-base polymorphisms result in two proteins that differ in one or several amino acids that may confer functional differences for each protein. This situation considerably increases the number of different proteins encoded by the genome.

Morphology


Although often referred to as dimorphic, C. albicans is in fact polyphenic (often also referred to as pleomorphic). When cultured in standard yeast laboratory medium, C. albicans grows as ovoid "yeast" cells. However, mild environmental changes in temperature, CO2, nutrients and pH can result in a morphological shift to filamentous growth. Filamentous cells share many similarities with yeast cells. Both cell types seem to play a specific, distinctive role in the survival and pathogenicity of C. albicans. Yeast cells seem to be better suited for the dissemination in the bloodstream while hyphal cells have been proposed as a virulence factor. Hyphal cells are invasive and speculated to be important for tissue penetration, colonization of organs and surviving plus escaping macrophages. The transformation from yeast to hyphal cells is termed to be one of the key factors in the virulence of C. albicans, however it is not deemed necessary. When C. albicans cells are grown in a medium that mimics the physiological environment of a human host, they grow as filamentous cells (both true hyphae and pseudohyphae). Candida albicans can also form Chlamydospores, the function of which remains unknown, but it is speculated they play a role in surviving harsh environments as they are most often formed under unfavorable conditions.



Next to the dimorphism, C. albicans undergoes another process called phenotypic switching or epigenetic switching. Phenotypic switching is often used to refer to white-opaque switching, which consists of two phases: one that grows as round cells in smooth, white colonies (referred to as white form) and one that is rod-like and grows as flat, gray colonies (called opaque form). This switch from white cells to opaque cells is important for the virulence and the mating process of C. albicans as the opaque form is the mating competent form, being a million times more efficient in mating compared to the white type. This switching between white and opaque form is regulated by the WOR1 regulator (White to Opaque Regulator 1) which is controlled by the mating type locus (MTL) repressor (a1-α2) that inhibits the expression of WOR1. Besides the white and opaque phase there is also a third one: the gray phenotype. This phenotype shows the highest ability to cause cutaneous infections. The white, opaque and gray phenotypes form a tristable phenotypic switching system. Since it is often difficult to differentiate between white, opaque and gray cells phloxine B, a dye, can be added to the medium.

Besides the the well studied white-to opaque switching several other switching systems have been described. During this switching different cellular morphologies (phenotypes) are generated spontaneously by an epigenetic process influenced by environmental conditions such as the level of CO2, anaerobic conditions, medium used and temperature. The strain 3153A produces at least seven different colony morphologies. In many strains the different phases convert spontaneously to the other(s) at a low frequency. The switching is reversible, and colony type can be inherited from one generation to another. While several genes that are expressed differently in different colony morphologies have been identified, some recent efforts focus on what might control these changes. Further, whether a potential molecular link between dimorphism and phenotypic switching occurs is a tantalizing question. Being able to switch through so many different (morphological) phenotypes makes C. albicans able to grow in different environments and this both as a commensal as a pathogen.

In the 3153A strain, a gene called SIR2 (for silent information regulator), which seems to be important for phenotypic switching, has been found. SIR2 was originally found in Saccharomyces cerevisiae (brewer's yeast), where it is involved in chromosomal silencing—a form of transcriptional regulation, in which regions of the genome are reversibly inactivated by changes in chromatin structure (chromatin is the complex of DNA and proteins that make chromosomes). In yeast, genes involved in the control of mating type are found in these silent regions, and SIR2 represses their expression by maintaining a silent-competent chromatin structure in this region. The discovery of a C. albicans SIR2 implicated in phenotypic switching suggests it, too, has silent regions controlled by SIR2, in which the phenotype-specific genes may reside. How SIR2 itself is regulated in S. cerevisiae may yet provide more clues as to the switching mechanisms of C. albicans.

Another potential regulatory molecule is Efg1p, a transcription factor found in the WO-1 strain that regulates dimorphism, and more recently has been suggested to help regulate phenotypic switching. Efg1p is expressed only in the white and not in the gray cell-type, and overexpression of Efg1p in the gray form causes a rapid conversion to the white form.

C. albicans as a pathogen
Candida is found worldwide but most commonly compromises immunocompromised individuals diagnosed with serious diseases such as HIV and cancer. Candida are ranked as one of the most common groups of organisms that cause nosocomial infections. Especially high risk individuals are patients that have recently undergone surgery, a transplant or are in the Intensive Care Units (ICU), Candida albicans infections is the top source of fungal infections in critically ill or otherwise immuncompromised patients. These patients predominantly develop oropharyngeal or thrush candidiasis, which can lead to malnutrition and interfere with the absorption of medication. Methods of transmission include mother to infant through childbirth, people-to-people acquired infections that most commonly occur in hospital settings where immunocompromised patients acquire the yeast from healthcare workers and has a 40% incident rate. Men can become infected after having sex with a woman that has an existing vaginal yeast infection. Parts of the body that are commonly infected include the skin, genitals, throat, mouth, and blood. Some distinguishing features also include, discharge, dry and, red appearance of vaginal mucosa or skin. Candida continues to be the fourth most commonly isolated organism in bloodstream infections.

Superficial and local infections
It commonly occurs, as a superficial infection, on mucous membranes in the mouth or vagina. Once in their life around 75% of women will suffer from vulvovaginal candidiasis (VVC) and about 90% of these infections are caused by C. albicans. It however may also affect a number of other regions. For example, higher prevalence of colonization of C. albicans was reported in young individuals with tongue piercing, in comparison to unpierced matched individuals. To infect host tissue, the usual unicellular yeast-like form of C. albicans reacts to environmental cues and switches into an invasive, multicellular filamentous form, a phenomenon called dimorphism. In addition, an overgrowth infection is considered superinfection, usually applied when an infection become opportunistic and very resistant to antifungals. It then becomes suppressed by antibiotics. The infection is prolonged when the original sensitive strain is replaced by the antibiotic-resistant strain.

Candidiasis is known to cause GI symptoms particularly in immunocompromised patients or those receiving steroids or antibiotics. Recently, there is emerging literature that an overgrowth of fungus in the small intestine of non-immunocompromised subjects may cause unexplained GI symptoms. Small intestinal fungal overgrowth (SIFO) is characterized by the presence of excessive number of fungal organisms in the small intestine associated with gastrointestinal (GI) symptoms. The most common symptoms observed in these patients were belching, bloating, indigestion, nausea, diarrhea, and gas. The underlying mechanism(s) that predisposes to SIFO is unclear. Further studies are needed; both to confirm these observations and to examine the clinical relevance of fungal overgrowth.

Systemic infections
Systemic fungal infections (fungemias) including those by C. albicans have emerged as important causes of morbidity and mortality in immunocompromised patients (e.g., AIDS, cancer chemotherapy, organ or bone marrow transplantation). Especially once candida cells are introduced in the bloodstream a high mortality can occur. C. albicans biofilms may form on the surface of implantable medical devices. In addition, hospital-acquired infections by C. albicans have become a cause of major health concerns.

Although Candida albicans is the most common cause of candidemia, there has been a decrease in the incidence and an increases isolation of non-albicans species of Candida in recent years. Preventive measures include keeping a healthy lifestyle including good nutrition, proper nutrition, and careful antibiotic use.

Hwp1
Hwp1 stands for Hyphal wall protein 1. Hwp1 is a mannoprotein located on the surface of the hyphae in the hyphal form of Candida albicans. Hwp1 is a mammalian transglutaminase substrate. This host enzyme allows Candida albicans to attach stably to host epithelial cells. Adhesion of Candida albicans to host cells is an essential first step in the infection process for colonization and subsequent induction of mucosal infection.

Slr1
RNA-binding protein Slr1 was recently discovered to play a role in instigating the hyphal formation and virulence in C. albicans.

Candidalysin
Candidalysin is a cytolytic 31-amino acid α-helical peptide toxin that is released during hyphal formation. It contributes to virulence during mucosal infections.

Tools
Due to his nature as an important human pathogen and the alternative codon usage (CUG translated into serine rather than leucine), several specific projects and tools have been created to study C. albicans.

Full sequence genome
The full genome of C. albicans has been sequenced and made publicly available in a candida database. The heterozygous diploid strain used for this full genome sequence project is the laboratory strain SC5314. The sequencing was done using a whole-genome shotgun approach.

ORFeome project
Every predicted ORF has been created in a gateway adapted vector (pDONR207) and made publicly available. The vectors (plasmids) can be propagated in E.coli and grown on LB+gentamicin medium. This way every ORF is readily available in an easy to use vector. Using the gatewaysystem it is possible to transfer the ORF of interest to any other gateway adapted vector for further studies of the specific ORF.

Candida two-hybrid (C2H) system
Due to the aberrant codon usage of C. albicans it is less feasible to use the common host organism (Saccharomyces cerevisiae) for two-hybrid studies. To overcome this problem a Candida albicans two-hybrid (C2H) system was created. The strain SN152 that is auxotrophic for leucine, arginine and histidine was used to create this C2H system. It was adapted by integrating a HIS1 reporter gene preceded by five LexAOp sequences. In the C2H system the bait plasmid (pC2HB) contains the staphylococcus aureus LexA BD, while the prey plasmid (pC2HP) harbors the viral AD VP16. The reporter gene used in the system is the HIS1 gene. When proteins interact, the cells will be able to grow on medium lacking histidine due to the activation of the HIS1 reporter gene.

CIp10 integrative plasmid
Contrary to the yeast S. cerevisiae episomal plasmids do not stay stable in C. ablicans. In order to work with plasmids in C. albicans an integrative approach (plasmid integration into the genome) thus has to be used. A second problem is that most plasmid transformations are rather inefficient in C. albicans, however the CIp10 plasmid overcomes these problems and can be used with ease to transform C. ablicans in a very efficient way. The plasmid integrates inside the RP10 locus as disruption of one RP10 allele does not seem to affect the viability and growth of C. albicans. Several adaptations of this plasmid have been made after the original became available.

Microarrays
Both DNA and protein microarrays were designed to study DNA expression profiles and antibody production in patients against C. albicans cell wall proteins.

GRACE library
Using a tetracycline-regulatable promoter system a gene replacement and conditional expression (GRACE) library was created for 1152 genes. By using the regulatable promoter and having deleted 1 of the alleles of the specific gene it was possible to discriminate between non-essential and essential genes. Of the tested 1152 genes 567 showed to be essential. The knowledge on essential genes can be used to discover novel antifungals. .

Application in engineering
Candida albicans has been used in combination with carbon nanotubes (CNT) to produce stable electrically conductive bio-nano-composite tissue materials that have been used as temperature sensing elements

Treatment
Treatment commonly includes:
 * amphotericin B, echinocandin, or fluconazole for systemic infections
 * Nystatin for oral and esophageal infections
 * Clotrimazole for skin and genital yeast infections

Important to note is that similar to antibiotic resistance, resistance to many anti-fungals is becoming a big problem. New anti-fungals have to be developed to cope with this problem since only a limited number of anti-fungals are available.