eSignature Presentation for HR Now

First of all, getting rejected does not mean the “End of the World”.Disclaimer:The answer is going to be very long and this is my personal experience. Please read it till the end, I am sure you will get benefitted. If you want any personal suggestion, please comment on the answer and I will try to answer your query.Although I don’t want to share my personal story, let me share with you so that you might feel that you are not alone. There are others who felt almost the same.Almost 10 years back, I completed my B-Tech from Icfai University, Dehradun in Computer Science.That time, it was a big...

On the one hand: yes.On the other hand: a lot of the things that GDPR will “change” about your outbound strategy are things that 1) individual country laws already technically require, and 2) have been best practice for cold emails for a while.The big one is that now, you’ll likely need pretty explicit permission to email people.The big, glaring obvious, “no”:Bought lists. These are already, in general, bad news. Most countries already have anti-spam laws that prevent you from using bought lists. Plus, they usually lead to a lot of spam reports, and unsubscribes, and low open rates, and overall: weak returns. TheyThe usually, almost always “no”s:Third party lists: In the past, you used to see a lot of forms that looked like this: “I would like to receive updates from Company A and trusted third parties.” Then those emails would be sent off, or sold off, to “trusted third parties”—and, TaDa—you had a legally consenting list of emails to solicit. GDPR changes that. Now, all third parties have to be named. So UNLESS the disclaimer mentioned your company specifically—and it was framed in a way that was compliant with the new GDPR standards for consent-gathering—third party lists are out.Personalized, direct, targeted, signNow outs. These are the sorts of emails that seem like they should be fine. They’re the requests that seem reasonable. “Oh, this person commented on the article I shared on LinkedIn. Then they added me as a connection. I should email them about a product or service that might interest them.’This seems reasonable. But most places, it’s not allowed. Right now this comes down to other legislation on the topic, the ePrivacy Directive, which allows individual countries decide to be opt-in countries (and require a specific opt-in consent for correspondence like this) or opt-out (you can contact them, but have to give them a chance to end contact). Opt-out states have a lot of rules about what information you have to provide a data subject, if you contact them without specific consent. But all this might change, as the ePrivacy Directive is soon set to get replaced with new ePrivacy legislation. So we suspect this limited ‘window of opportunity” is set to close.The likely “yes”es.Any “info@” “marketing@” “sales@” emails, that can’t be tied back to an individual person, will likely not count as “personal data”and therefore should leave you in the clear.It’s a lot to go into here, but GDPR also allows for a legal processing basis condition called “legitimate interest.” Claiming legitimate interest can be tricky. But, precedent suggests that you have a little more wiggle room when it comes to emailing someone who’s purchased from you in the past. Granted, this isn’t a cold email—but, it does suggest that getting someone in the door on a tripwire, might be a better idea than ever.So, to sum it up: yes. GDPR will affect cold emailing. And your best bet is to start attracting some less cold addresses now, so your leads don’t run dry come May 15th.PS: We broke down the “how”s and “why”s in greater detail on a recent post on outbound email, and GDPR, here. Check it out, if you’re interested in learning more

I did my articleship from Khimji Kunverji and Co., one of the top firms in Mumbai; and it was an awesome experience. Let me shed some light on my learnings -Learn to say NO - Random seniors come and give you random work. Learn to say No. Learn to say you are busy. You are not a dustbin.Learn to say YES - You need to have a good rapport with your immediate seniors and your boss. I have filled my boss’s daughter’s BFM admission form because she needed some help. Sometimes, you have to keep your ego aside and look at the larger picture.Whether audit or tax is the one for you - You tend to spend 3 years in articleship, doing either audit or tax. It is good enough time to gauge whether you want to do this for your entire life or not. For me the answer was NO, and I switched to Finance. No point wasting time once you qualify.Domain Knowledge - In your first job interviews after becoming a CA, a lot of stress will be on what you did during these 3 years. You should be upto date with that. Get your basics right.Out time is a myth – As per my firm HR Manual, the official work time was roughly 10-30 to 6–30. Strangely, you used to be penalized for coming late, but no credit for going late. It’s the norm. Get used to it.Make Mistakes - Ask stupid questions. Make mistakes. Experiment. Because you have the license to. You are a fresher. As a CA, people expect more.Do not neglect your Social Life - Its important. Your boss will not come at 12 to your place with a cake in his hand, wishing you a happy birthday.I remember getting into a train during my 1st year articleship. I somehow started chatting with a guy standing near me. He was a CA. I told him I just cleared IPCC and started with articleship. He started laughing and said “Welcome to Hell”.With all the office and study pressure, you might feel life sucks during articleship, but it will be a great experience. You will create memories of a lifetime. Cherish it :)

This hunger for more knowledge is good for a CA Student. It is a very good idea to know what others have learnt and re-assess oneself on the basis of same, so that you become equally competent. This is a good way of improving oneself.Part A - About the core Knowledge:(a) What your firm operates in - you can't do much beyond that.Core Knowledge = Practical Knowledge about areas your firm is operating in.See the firm you have chosen or you got into, basically will provide you with the knowledge of some of the fields in which Chartered Accountants works. You cannot gain knowledge about all fields in which Chartered Accountants work, since the scope is very wide and whether it is a Big Four or a sole proprietor Chartered Accountant, nobody can give you work experience in all fields. So basically these core areas where you get to work - you have to be satisfied with the same. All you can do is - learn from experiences of your friends who are in to different core areas. This is a rigid area, and not much can be done in this.(b) Try to get an assignment in all kinds of activities that your firms do -You can't go out of the box in which your firm operates, but atleast you can learn everything that is in your box. Many articles run away from certain things - saying it is a low category assignment or not so fascinating. It is because they all hear it from their friends about the big industry they worked in and blah blah things. But go and ask those friends, if they know, what is the procedure to obtain a PAN card and a duplicate PAN card? What is the procedure to obtain Shop Act? or atleast if they know what is Shop act?My Insights -In our office they didn't used to allow articles to do that, the administrative people like Bcom people used to do that. But I insisted on the same, to allow me to do them once. The task was easy, but it was something very basic that I learnt. Later when you start your practice or job, these are somethings that give you edge over others. If you become an entrepreneur, you can handle those things yourself. So it is beneficial always.(c) Try to get assignments in all kinds of industries that firm works in -Basically most Chartered Accountants work in some fixed industries since when you do good to one client, similar clients get attracted, so automatically, you will see that most clients are of similar category. As an article you should try to do audit of all kinds of organizations -Based on organization type like Sole proprietor, Private limited companies, Partnership firms, trusts, public limited companies etc.Based on different business forms like Retailers, Wholesalers, Chain stores, Manufacturers, Service providers, Traders, Consultants, Support Services, Maintenance services, Export oriented, etc.Based on different industries like IT, E-commerce, FMCG, Finance, Automobiles, Telecom, etc.Based on Tax benefits or special act companies like religious trusts enjoying benefits u/s 11 or 12, regulated companies like insurance, banking, etc. or may be companies in Special Economic Zones, etc.A Piece of Advice -You won't find all of the above in any one firm. Such firms giving such wide opportunities don't exist. But thing is - you need to explore every corner of your own firm, whatever it is.(d) Try to gain overall knowledge of all types of works -Don't think about specialization in Articleship, it is not that much useful, because if later in life that sector goes down, your career will get a full-stop. As a Chartered Accountant you must first learn all the basics of all types of work, when you become aware about basics, i.e. after articleship, then you should try to develop core competence when you find jobs or do practice.My Insights -If you don't get an assignment of different type - go to your principal and say that "Sir, I want to learn about that kind of work, if next time there is any work related to that xyz client, please give me a chance." I did it in my articleship, and I got those opportunities, Sir was happier indeed, that an article was ready to take up some sort of responsibility. I am pretty sure, 80% of Chartered Accountants would do the same. If you say politely, the teacher inside them will awake, and they will allow you to fly!Part B - Other things that you should learn during articleship - More important than above said things!(a) Office Ethics -You should learn about the office culture, how people dress, talk, meet and greet colleagues, seniors and clients. It is very important to observe how people form groups, how they make their juniors to work and seniors to help/guide. It is very important to notice, how others are keeping good relations with administrative staff i.e. HR, Clerks, etc. - something that is very helpful at times of problems. There are many more things - basically you have to learn how people operate in office and especially how your boss stays in office - since someday you too will be a boss.A Piece of advice -Learn good things only. Although I assume most Chartered Accountants are well cultured and natured, but exceptions may exist. But remember, may be your boss was good or bad, you have to become a good boss in future.At many times you feel that your boss did wrong, and he/she should have allowed you to do xyz thing. Remember such incidents or make a note of it. When you become a boss, you do them correctly. If you are able to do, you are a good boss, else you will realize had a wrong idea about your boss.(b) Printing, Scanning, Documenting, Letter typing, Organizing Office, Using appropriate Stationery -Your reaction - "Oh God! Really?"Consider this situation - you are in a corporate office, a high ranked employee. You tell the clerk to scan a document, but your clerk is new. He is not acquainted with the printer. What would you do, if you yourself don't know how to use a printer or scanner? In early days of your job or in many companies, you don't have clerks who do it for you, you have a printer next to you and you have to do it yourself. In case you don't know these, what a shame! A Chartered Accountant, but does know how to use a printer or how to unpin a staple! God! Dummies on earth.My Insights -One of the expert HR was sharing his experiences with interviewing Chartered Accountant, at a conference that I was listening to. He said, we tried an experiment successfully. We told every candidate entering into the interview room to arrange certain documents and properly organize them into a file. Now on the basis of how file was organized, they discovered candidates who had done dummy articleship or articleship of low grade, because those candidates never knew how to arrange a file, since they never did it in their lifetime.So basically the best thing about a good leader, boss, a senior or an entrepreneur is that he/she knows the work of all persons junior to him/her very well. That's why they can handle them well.So basically learn the following things and many more which I can't list out -How to properly document an Audit file?How to properly keep a permanent client record - both electronic & physicalHow printers, scanners, servers of your office, internet network, LAN systems, routers, biometrics, connections etc. work in your office.How to use correct stationery correctly? Like properly unpinning documents, or may be how to create sets for clients, income tax officers, registrars etc.How to draft covering letters, envelopes, request letters, etc.(c) Drafting Email Communications & Email Ethics -The most important part indeed of articleship. The fact is we never get opportunity to learn this anywhere else. This is a good ground to learn. Initially you can see how your boss writes email, how your senior does it. Then you can innovate it yourself. The thing is in business world, everything today goes on Email. Emails don't have a tone, they don't have smileys (means they are not used). Writing a good email, is an art. It is very important to learn how to write such kinds of emails.Emails asking client to provide information, with accurate requirement list.Polite Emails for making client realize the wrong they have done.Emails providing consultancy services. See email consultancy is a big time opportunity and costless service, in future a good means of earning.Writing intra-office emails.Whom to keep in CC, Never to use BCC, how should be the subject line, how should be the signature etc.When email shouldn't be used & telephonic conversations should be preferred, sending reminders, how to use meeting feature, etc.(d) Oral Communications - F2F or telephonic or over internetThis is again a great area to learn. It very necessary to learn how to interact with clients. The interaction can be face to face, or telephonic or over internet services like skype, etc. It very important to learn to learn how to deal with such situations. A conversation over telephone, has to be polite and discussing documents over telephone is also an art. Similarly communication over Skype is also an interesting thing to learn, one should know how to have business conversations over Skype and how to share documents, discuss & present over it.(e) Formatting documents - Something that stupids call stupidity!I have seen documents and emails from fellow Chartered Accountants, so pathetically formatted, that I sometimes wish to hit them with a stone, maybe their sense would come back then. But basically the idea is Chartered Accountants are professionals, and therefore, a professional behaviour is expected from them. The behaviour is expected highest in the documents and reports. Thus, it is very important to learn:Appropriate font sizes, font stylesHow to add tables in emails, how to structure an email, maximum size of emails, minimum size of emailsWhen to use and when not to use - bold, italics, underlines, shades, coloursHow to structure paragraphs, appropriate line spacingHow to convert documents into different formatsHow much margins to keep, how to make document print readyHow to make document secureHow to make documents self-explanatory by adding commentsHow to use various functions like footnotes, document review, freeze panes, grouping - sub-grouping, page numbers, author details etcCover page for report, report size, number of maximum pages, drafting executive summary, adding disclaimers, etc.Conclusion:The Part A makes you an intelligent Chartered Accountant.The Part B makes you an intelligent Human Being.And let me tell you, Part B is more important, because even if you don't become a CA, an intelligent human being can definitely live a good career!Ignoring the part B is very common amongst CA, and that's why MBAs getting an edge over CAs is also very common.Many people say 'Articleship is nothing but labour work', well it is because you think it that way, and that's why you are doing it that way. If you try, you will realize articleship period is life changing!"You will have hundreds of opportunities to learn the bigger things once you become CA, but not these small things. Once you become CA, people don't expect you to know everything, they understand it is quite impossible, but they definitely do expect that you know these basic things rightly."

This is height of hypocracy and believing themselves to be above law .What is the difference between ShriShri Ravishankar from the so called DABANGS of Bihar and UP who flout law openly and brazenly.Please do not start with comparison proving difference between the two.He is a renowned man with million of followers this hypocracy and behaviour puts him in a wrong colour and picture.If people like him are so brazen in not sticking to their commitments what kind of message does his act convey in general masses and his followers in particular.This is the difference between as real sadhu and teacher and a pseudo sadhu and teacher.The real teacher leads by example and put a very correct picture of himself to his followers.he is not a teacher and there is no difference between the people who indulge in crime but brazen it out and he who with his WCF raped the flood plains of Yamuna, promised to pay the nominal fine imposed by NGT on the eve of the festival and got approval on condition that the fine will be paid after the festival but has since refused to stick to his commitment.He is trying to be a states man by writing to ISIS and they joked about his naivety by sending him a picture of beheaded man.There are some question which should be asked :A. How does he know ISIS.B. Why did he corrosponded with them.C. Who or whose behalf did he write this letter.D. Did  GOI appointed him as  incoluter with ISIS .E. What is his standing among Arabs and supporters of ISIS .F. Is he looking for a active political role with GOI.G. Should not NIA question him on his relationships inside ISIS high command?H. On relationship with person to whom the letter was addressed?.I . If he wrote directly to Bagdadi and Bagdadi replied to him then it really becomes a case for thorough investigation by intelligence agencies across the globe because there is no intelligence available on Bagdai, his movements, and his place of stay and his permanent postal address.I. He should voluntarily cooperate with intelligence agencies and share details of Bagdadi it may help in eliminating Bagdadi.

In the context of the Jallikattu battle, of all the external forces representing mercenary elements and the interests of multinationals in India the biggest is Ingrid E Newkirk, the founder of PETA USA and host of PETA branches across the world, including “People for the Ethical Treatment of Animals” (PETA) in India. It was based on the writ petition filed by PETA India that the Supreme Court went on to hold the Tamilnadu Regulation of Jallikattu Act as illegal and void.This article aims to expose the egregious instance of a foreign citizen trying to further her personal and professional in...

We are far from understanding function of fungi in the human microbiome. Our understanding is at the 1st rung, the most primitive stage, where we continue to examine mammalian-microbial interactions through the biased lens of pathogenesis, as in 'eeks! Microbes are bad, cause diseases'. For the picture to become clearer, this bias needs to go the way of the dodo and that'll take a few years yet.Fungal communities of the human body: the Human MycobiomeI've organized this answer into 4 sections:I. To identify and enumerate the human mycobiome (human body fungal communities) is no easy task. Why?II. Mycobiome-human relationship in health and disease.III. Location-wise human mycobiome in health and disease (skin-scalp, gut-oral cavity, lung, plasma, vagina).IV. Saccharaomyces boulardii, example of probiotic fungus.I. To identify and enumerate the human mycobiome is no easy task. Why?Need to identify to understand function. However, human microbiota fungi are so rare as to make identification a challenge.From 1 Traditionally, fungi were identified by culture. Human mycobiome inhabitants are likely novel and we don't  yet know how to grow them in culture, at least many of them.Taking a leaf out of bacterial studies, where efforts center on the bacterial 18S rRNA locus, now PCR (Polymerase Chain Reaction)-based methods focus on the fungal genetic locus encompassing 18S, 5.8S and 28S rDNA genes, and the internal transcribed spacer regions (ITS1 and ITS2) that encode nonfunctional RNA transcribed during rRNA synthesis.  Which region of this fungal locus to amplify is still debated, and different studies make different choices. With as many as 6 choices, studies run the gamut in target choice. Problem? Yes, makes it difficult to generalize datasets across studies.Debate also rages on which is better choice, 18S rDNA or ITS, 28S rDNA having been side-lined recently.From 2As expected from a rapidly growing field, much chaos, redundancy and mis-interpretation reigns.While the Fungal Genome Initiative (FGI; Fungal Genomics | Broad Institute of MIT and Harvard) aims to establish genomes throughout the fungal kingdom, such databases prioritize human disease-associated fungi with as yet little or no information on human mycobiome, i.e. commensal, inhabitants.From 3.Fungal databases are puny and growing slowly compared to those for bacteria. For example, a major database on fungal ITS regions maintained by Henrik Nillsson at the University of Gothenburg, Sweden, was last updated in 2012 Page on emerencia.org.Genome sequences of over a hundred fungal species are publicly available (3) but few of them are human-associated.From 3.Among Next-Generation Sequencing (NGS) technologies, RNA deep sequencing or RNA-seq offers several advantages for human mycobiome analysis: not hybridization-based; provide insight into transcriptional mechanisms (boundaries, links between exons). RNA-seq studies that pyrosequence (Pyrosequencing) fungal ITS and rDNA genes to study the human mycobiome started appearing in the past 4 or 5 years.Different studies use hugely varying approaches, ranging from different DNA isolation kits, analysis of different genes, different qPCR primer pairs and reactions ranging from 25 to even 45 cycles. Let's remember PCR is not only exquisitely sensitive but also exponential so a 20 cycle difference runs the gamut from entirely missing low abundance species to detecting many artifacts.Molecular techniques such as qPCR are also so sensitive that environmental contaminants turn up frequently in the datasets. Lacking prior knowledge of what to look for, it's difficult to exclude them.Not only do such differences make meta-analyses near-impossible, they make it difficult to distinguish clinically relevant datasets from experimental artifacts, unwittingly generated by sub-optimal experimental design and decisions.Problem with molecular analyses in a field of sparse databases is that in each study, data that doesn't align to database sequences is discarded. Is such discarded data truly irrelevant or is it the missed iceberg?Fungal nomenclature is a major problem. Synonyms and different names for different sexual stages of the same species abound. For example, a recent study re-annotated 'set of marker reference sequences that represent each currently accepted order of Fungi' (4). Careful and methodical curation required? Certainly!From 5.II. Mycobiome-human relationship in health and diseaseCommensal and environmental fungi constantly interact with the human body. How do they cause disease? Typically, underlying body perturbations such as immuodeficiencies and dysregulated immune function promote opportunistic fungal growth.For e.g., environmental Aspergillus spores that normally get killed could instead develop hyphae and invade tissue.From 6or commensal Candida could switch from yeast to biofilms, which in turn provide rich nutritious milieu for variety of pathogenic bacteria as well as an effective barrier against antibiotics.III. Human mycobiome health-versus-disease comparison by locationHuman Skin MycobiomeMalassezia, a common human skin mycobiome inhabitantLipid-dependent fungus Malassezia are the most abundant fungi living on human skin (7, 8)Lack fatty acid synthase, and express lipases and hydrolases, helping them adapt to human skin (3).Almost all epidermal skin cells express aryl-hydrocarbon receptor (AhR) (9) and Malassezia synthesizes powerful AhR ligands, indirubin and indolo [3,2-b] carbazole (ICZ) (10). Thus, Malassezia influences skin metabolism and function by exploiting the AhR-AhR ligand pathway.Requiring lipids for its growth, Malassezia preferentially colonizes face, scalp and upper trunk rather than limbs , i.e. the sebaceous gland-rich areas of skin.Malassezia is dimorphic, i.e. has yeast and mycelial (hyphal) phases.Its lipid dependence makes it challenging to isolate and grow in culture. For example, Sabouraud's dextrose agar is a commonly used fungal culture medium. Yet it does not support growth of many Malassezia species (11). Rather all Malassezia yeasts identified thus far grow in the nutritionally complex (containing Ox bile and Tween 60, a fatty acid) and unconventional Leeming and Notham agar (LNA). Even so, such approaches can miss M. restricta. Slower-growing than others in such cultures, it's easily overgrown by related species.Mis-identification is another common problem with purely phenotypic approaches.Careful characterization of microbial species requires isolation in culture, freeze-down and subculture of frozen aliquots. Even this routine task is difficult in the case of Malassezia which, poorly viable in culture, only maintains viability when stored at -80oC, and not at 4 to 12oC, the norm for yeasts (12).Culture-independent, molecular approaches are thus more suitable. Tape or swab is used to take the skin sample, fungal DNA extracted and subjected to PCR. DNA extraction method, and sensitivity and specificity of the particular PCR method used greatly influence the outcome. The specific approach taken to accurately identify Malassezia needs to keep in mind that human skin is after all host to multitude of bacteria as well as other fungi such as Candida.Malassezia in human skinPresumed to colonize immediately post-birth (13).Found in skin swabs from 78 out of 245 British neonates (<28 days of age) on LNA culture, with 41 out of 42 still positive at follow-up (14).M. furfur and globosa found in 60.5% and 7.2%, respectively, cultures of 195 Iranian neonates (15). Melassezia species colonizing human skin are thus neither random nor inter-changeable.M. dermatis found in skin of 19 healthy Koreans aged 17 to 55 years by both culture-dependent and -independent (ITS-1 and 26 rDNA) (16). Geographic difference?Why do we have Malassezia in our skin? Are its lipid dependence and its human skin colonization pattern related to age-related human sebaceous gland activity? Data suggest so.Minimal in children, sebaceous gland activity increases during the teens in response to androgens, and then stabilizes from late teens until old age (17).Sebum, product of sebaceous glands, consists of ceramides, fatty acids, cholesterol, squalene (cholesterol precursor and also popular vaccine adjuvant but that's another story!), triglycerides and wax esters. Sebum fatty acid composition changes markedly with puberty (18).Healthy human skin from 245 Canadians ranked by age (0–3, 4–14, 15–25, 26–40, 41–60, and >60-years old), swabbed on LNA cultures, showed marked increase in Malassezia-positive cultures starting from age 15, with no noticeable difference in positivity between genders (19).DNA analysis of 770 healthy Japanese aged 0 to 82 years also showed marked increase in early teens but had major gender differences, being much more abundant in males. M. restricta predominated in males of all ages, while doing so only in females >23 years, with M. globosa dominating at 1o to 18 years (20). From 20.Similar dominance of M. restricta followed by M. globosa was also found by 5.8S/ ITS2 rDNA analysis in a small Brazilian study of scalp and forehead skin from healthy and seborrheic dermatitis subjects (21).Sampling trunk, arms, plantar heel, toenail and toeweb fungal communities using ITS 1 and 18S rDNA gene in 10 healthy adults, Findley et al found Malassezia dominance at all sites with much greater species diversity in the foot sites (22).Clearly Malassezia colonization of human skin closely mirrors sebaceous gland distribution and activity and sebum fatty acid composition. Malassezia-human skin interactions (adapted from 23) range all the way from Healthy commensalismMild, non-clinical altered skin melanocyte pigmentation and plaques that mildly alter epidermal barrier function (Pityriasis Versicolor)Inflammation without adaptive immune function involvement (Seborrheic dermatitis; SD and dandruff)Inflammation with adaptive immune function involvement (Atopic dermatitis; AD)Hair follicle invasion and inflammation (Malassezia folliculitis). Much less is known about Malassezia's role in psoriasis (20).- Geographic differences in Malassezia distribution: Rare elsewhere, M. dermatis and M. japonica are more frequently found in East Asia, (20, 24, 25), and in India (26).Malassezia and PsoriasisPsoriasis is a chronic skin inflammation marked by hyperproliferation and hyperkeratinization of the epidermis. Malassezia's role in this disease is as yet undetermined. Data are all over the place.While an Indian study that examined ITS 2 in addition to 28S rDNA gene found no difference in Malassezia prevalence in skin from psoriatic and healthy subjects (n=50 each) (26), a Japanese analysis of 28S rDNA gene sequences from skin samples from healthy (n=12) and psoriasis (n=12) subjects found psoriatic skin contained more diverse fungi compared to healthy skin though Malassezia was less abundant (27).Itraconazole, ketoconazole, and posaconazole are the most effective drugs for treating Malassezia infections (28, 29).Malassezia and DandruffIn a French study of 49 volunteers examining fungal ITS 1-5.8S-ITS2 and part of the 28S rDNA genes, Malassezia restricta was found more frequently associated with dandruff (30).Similar dominance of M. restricta (and globosa) in dandruff scalps also seen in comparison of 62 and 57 dandruff and healthy scalp in Japanese volunteers (31).Human Gut MycobiomeHuman Gut Mycobiome is influenced by dietYeasts in human stool were first reported in 1917 (32) so human gut-fungal association is not a novel finding.Geotrichum candidum and Saccharomyces cerevisiae were found in gut mycobiome of people who ate cheese and drank sake among French and Japanese, respectively (33, 34).Reduced gut fungal diversity in US urban/suburban residents (Boulder, CO and Philadelphia, PA) eating typical western diets compared to rural Malawi residents eating diets 'rich in maize, legumes and other plants' (35) revives the old question of the hygiene hypothesis, namely, whether loss of our co-evolved microbial diversity triggered the greater autoimmune prevalence in Western populations. Differences between these 2 populations include diet, hygiene and contact with animals to mention just a few of the more obvious ones.ITS 1 pyrosequencing found fungal genome signals in every one of 96 stool samples from healthy American volunteers (36). Proportionally Saccharomyces (89%), Candida (57%) and Cladosporium (42%). Candida correlated positively with carbohydrates and negatively with total saturated fatty acids, while Aspergillus correlated negatively with SCFA (Short-chain fatty acids). Saccharomyces showed no particular dietary trend.The Wayampi people are an indigenous Amerindian tribe living in French Guiana and Brazil in South America. Fungal ITS1-ITS4 and NL1-NL4 PCR and pyrosequencing of stool samples from 151 healthy volunteers on two different occasions, 2006 and 2010, showed not Candida albicans but Candida krusei and Saccharomyces cerevisiae were the most abundant gut fungal species. In other words a very different gut mycobiome in an isolated rural human population from the one observed in humans living in industrialized environments.From 37Human Gut Mycobiome in health and diseaseA 2005 stool culture study of 80 pediatric bone marrow transplant or cancer patients and 61 healthy controls on Sabouraud's Dextrose agar found Candida albicans in 41.2% and 40.5%, respectively, and non-albicans Candida in 50% and 40.5%, respectively (38). In other words, similar Candida proportion in stool.Anti-Saccharomyces cerevisiae antibodies are found more frequently in Crohn's disease (CD) patients compared to Ulcerative colits patients and healthy controls (39, 40). No consensus yet on what this signifies.18S rDNA pyrosequencing of distal colon (rectal/sigmoid) biopsies from 25 children with IBD (Inflammatory Bowel Disease) compared to 12 age-matched controls, and 2 adults each either normal or with Ulcerative Colitis (UC) showed that Ascomycota and Basidiomycota were the dominant phyla. Fungal DNA was only found in few, not all, subjects (41). Antibiotics or immunosuppression weren't responsible for these differences since these newly diagnosed IBD patients hadn't been administered them yet. Why such poor recovery? Could it be site (colon biopsy versus stool) or choice of fungal gene (18S rDNA versus ITS 1 in other studies)?A Chinese ileal biopsy and stool sample study of 19 CD patients and 7 healthy volunteers (42) found CD patients had increased Candida prevalence and different gut mucosa- and stool-associated fungi species compared to controls. Red: CD; Green: Controls.From 42Human Oral MycobiomeIn a study of 20 healthy volunteers, ITS 1 pyrosequencing found Candida (75%), Cladosporium (65%), Aureobasidium and Saccharomycetales (50% each), Aspergillus (35%), Fusarium (30%) and Cryptococcus (20%) but no Malassezia (43).But a more recent ITS 1 pyrosequencing found Malassezia in saliva of 6 out of 6 healthy adult volunteers, identifying it for the 1st time as a commensal fungal inhabitant of the human oral cavity (44). This raises the question how previous studies missed such a basic finding? Malassezia culture is difficult, requiring specialized culture media, nomenclature is muddled, fungal databases are incomplete and confusing, Malassezia is dimorphic, all possible reasons.Summary of Human Gut-Oral Mycobiome studiesThe table to the right is my original summation of the differences between the major human gut and oral mycobiome studies published thus far.Differences include different diseases, tissue samples and methods, and absence of controls.Boy, are the methods different!Any generalizable observations? Yes, fungal diversity increases in GI tract-associated diseases such as CD, HBV (Hepatitis B). From 45.Human Lung Mycobiome changes with lung disease: cause or effect? Not clear- Mouthwash/gargle (oropharyngeal wash, OW) and BAL (bronchoalveolar lavage) ITS PCR and pyrosequencing comparison of lung transplant patients and controls indicated fungi had colonized deeper lung tissues in lung transplant patients.From 46Same group showed clinically relevant fungi like Candida and Aspergillus were enriched in BAL of HIV-infected and lung transplant patients, and more frequently present, i.e. more samples positive compared to healthy controls (47).Comparison of mouthwash, induced sputum and BAL (bronchoalveolar lavage) of HIV-infected, COPD (Chronic Obstructive Pulmonary Disease) and normal people (48) using 18S rDNA and ITS PCR and pyrosequencing. Showed two things, one, the three sites had overlapping as well as distinct fungi with Candida dominating in mouthwash and sputum, two, Pneumocystis jirovecii was enriched in HIV-infected and COPD samples.Common theme emerging as in human lung mycobiome changes with diseases as it does in gut. Cause-effect distinction not yet clear.Human Lung Mycobiome SummaryFrom 49.Human Plasma and Vagina MycobiomeReports of mycobiome in human plasma, milk, vagina are currently restricted to only one or few peer-reviewed studies.One human plasma study found a surprise. Ascomycota, in particular the order Hypocreales, was dominant fungal signature in 5 of 6 subjects (50). Could source be gut since Ascomycota are prevalent there?A large study of 494 pre-menopausal Estonian women examined fungal mycobiome using ITS1 and 2 pyrosequencing in vaginal fornix and cervix brush samples. They found great diversity consisting of 196 OTUs including 16 for Candida alone (51). As with other mycobiome studies, results were plagued with the issue of air-borne contamination.IV. Saccharaomyces boulardii, example of probiotic fungusEffective against diarrhea in human clinical trial (52) in a study of 35 children each given either S. boulardii (250mg orally twice a day) or not. Children given S. boulardii recovered faster from both diarrhea (3.4 versus 5.5 days) and vomiting (2.5 versus 3.3 days) (statistically signNow).Could such differences be biologically relevant? Absolutely and this table explains why.From 53.Other S. boulardii studies: 11 randomised clinical trials for acute infectious diarrhea (AID), 9 for antibiotic-associated diarrhea (ADD), 4 each for Helicobater pylori infection, and Crohn's disease (CD), 1 for Ulcerative colitis (UC), 5 newborn studies, and 3 for IBS (Irritable Bowel Syndrome).S. boulardii is very effective in disease treatment either alone (for AID and ADD) or as an adjunct (for H. pylori, CD, UC).Extensive and larger trials of S. boulardii for CD, UC and IBS are very much warranted.A good place to learn more about S. boulardii, especially its history is here: Saccharomyces boulardiiHow does S.boulardii work against so many diseases? Many hypotheses (adapted from 53): Secretes polyaminesRestores normal levels of colonic Short-chain fatty acids (SCFA)Stabilizes gut epithelium barrier function Restores fluid transport pathwaysInduces enhanced gut mucosal secretory IgA productionNeutralizes bacterial toxins, specifically those of Clostridium difficileIts metabolic functions, such as polyamines, accelerate re-establishment of normal gut microbiotaMycobiome BibliographyHuffnagle, Gary B., and Mairi C. Noverr. "The emerging world of the fungal microbiome." Trends in microbiology 21.7 (2013): 334-341. Page on europepmc.orgCui, Lijia, Alison Morris, and Elodie Ghedin. "The human mycobiome in health and disease." Genome Med 5 (2013): 63. Page on biomedcentral.comSharma, Krishna Kant. "Fungal genome sequencing: basic biology to biotechnology." Critical reviews in biotechnology 0 (2015): 1-17.Schoch, Conrad L., et al. "Finding needles in haystacks: linking scientific names, reference specimens and molecular data for Fungi." 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Expert opinion on biological therapy 14.11 (2014): 1593-1609.Thanks for the A2A, Matt Chanoff.

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