Information

Does blood typing still provide a use for ancient tissue analysis?


Modern techniques.

In recent years, DNA sequencing has become extremely cheap. This, compounded by the ability to PCR miniscule samples to viable samples for analysis, means that aDNA can be extracted and analysed from ancient tissue samples that 20 years ago would have been impossible to sequence.

Pre sequencing techniques.

However ancient biochemical analysis was around before the human genome project revolutionised sequencing technology.

Although blood typing was fiddly, grossly time consuming, and expensive, people were able to define historical lineages.

Question.

How does the "old-school" approach of blood-typing compare in terms of cost, accuracy, sample required, and speed against the modern aDNA analysis? Do those sort of experiments still have a place in a modern ancient tissue lab?


Micro-Computed Tomography

Abstract

Microcomputed tomography (micro-CT) has demonstrated its unique value in developmental toxicology. This chapter starts with a brief introduction to X-ray imaging and micro-CT volumetric imaging technologies in developmental toxicology, with modern micro-CT systems. Various applications for nondestructive volumetric visualization and analyses of fetal skeletons of mouse, rat, and rabbit are concisely overviewed. Examples presented include micro-CT volumetric visualization and analysis of unstained, and single-/double-stained fetuses for evaluation of skeletal malformation high-resolution volumetric imaging and analysis of embryonic bone microarchitecture micro-CT volumetric imaging–based whole body soft-tissue/organ visualization and in vivo micro-CT imaging of rat fetuses in utero. Other volumetric imaging technologies such as magnetic resonance imaging, positron emission tomography, single photon emission computed tomography, optical projection tomography, and ultrasound imaging for developmental toxicology are also very briefly discussed. Finally, the future directions of preclinical volumetric imaging in developmental toxicology are provided from the perspectives of methodology, technology, and applications.


The Different Blood Types

There are eight different blood types:

A positive: This is one of the most common blood types (35.7% of the U.S. population has it). Someone with this type can give blood only to people who are A positive or AB positive.

A negative: Someone with this rare type (6.3% of the U.S. population) can give blood to anyone with A or AB blood type.

B positive: Someone with this rare type (8.5%) can give blood only to people who are B positive or AB positive.

B negative: Someone with this very rare type (1.5%) can give blood to anyone with B or AB blood type.

AB positive: People with this rare blood type (3.4%) can receive blood or plasma of any type. They’re known as universal recipients.

AB negative: This is the rarest blood type -- only 0.6% of the U.S. population has it. Someone with this blood type is known as a “universal plasma donor,” because anyone can receive this type of plasma.

O positive: This is one of the most common blood types (37.4%). Someone with this can give blood to anyone with a positive blood type.

O negative: Someone with this rare blood type (6.6%) can give blood to anyone with any blood type.

Continued

The four major blood groups are based on whether or not you have two specific antigens -- A and B. Doctors call this the ABO Blood Group System.

Group A has the A antigen and B antibody.

Group B has the B antigen and the A antibody.

Group AB has A and B antigens but neither A nor B antibodies.

Group O doesn’t have A or B antigens but has both A and B antibodies.

The third kind of antigen is called the Rh factor. You either have this antigen (meaning your blood type is “Rh+” or “positive”), or you don’t (meaning your blood type is “Rh-” or “negative”).


Live Blood Analysis: The Modern Auguries

I saw a patient last week who was self referred. He had been seeing a DC/ND for a variety of symptoms that turned out to be asthma. Not that the DC/ND made that diagnosis. His DC/ND diagnosed him with an infection, based on live blood analysis, and offered the patient a colonic detox as a cure. My patient thought he should get a second opinion before he submitted to a cleansing enema, always a good policy

Live blood analysis to diagnose an infection. I had never heard of the technique, but thanks to the google and the interwebs, I was soon immersed in the field.

In live blood analysis, the “physician” takes a drop of the patients blood and examines it under a high power phase contrast or a darkfield microscope. Changes in the constituents of the blood are noted and linked to a variety of ills.

It is an impressive and expensive system: microscopes and various support equipment start at around $5000 (3). However, live blood analysis has the opportunity to be lucrative in the right hands as the patient often gets weekly analysis to see how the interventions (usually supplements sold by the blood analyst) are working. Evidently in the hands of a skilled snake oil salesman, an income of $100,000 a year to more can be generated (8).

Live blood analysis is one of these alternative methodologies that has a hint of legitimacy that is extrapolated far out of proportion to its validity.

Phase contrast and darkfield microscopes are used in medicine, in my world primarily to look for syphilis. As a rule, most pathologic changes in the blood are best seen when various stains are applied to the blood sample. Most commonly a Wright”s stain is used on blood cells, because many diagnostic features are invisible on phase contrast. There are many different stains used in the pathology laboratory to help identify what you are observing under the microscope. Using different stains on microbial specimens can help categorize organisms before they can grow. It is not either-or, both phase contrast and other modalities are used in clinical medicine. More practical clinical information is derived from light microscopy on stained specimens.

An evaluation of the cells of the blood can give hints to the presence or cause of many diseases, from vitamin deficiencies to infection to leukemia. The CBC (complete blood count) with or without a differential (the types of cells seen) is part of any initial evaluation of ill patients.

With live blood analysis, practitioners take the seed of truth that the evaluation of the blood constituents can give valuable information and grow a forest of fantasy and magic. It is something to behold.

Besides live blood, some practitioners also practice dry blood analysis, where they examine clot to look for patterns that are allegedly indicative of diseases.

Let’s evaluate each diagnosis made on live blood analysis. Note the key feature of each alleged diagnosis. The problem lies in diet, and supplements are the solution to the problem, which, it just so happens, are sold by the live blood analyst. Curious that while I am alleged to be a shill of big pharma, I do not get dime one from any supplements or other products sold in my office because I don’t sell stuff to my patients. Any alternative provider who makes part of their living from selling supplements has far more conflict of interest than most physicians.

Someone may argue that I am an Infectious Disease doctor, what do I know about blood analysis. I also showed these photographs to a hematopathologist and a hematologist. It was refreshing how they laughed and laughed and laughed at the descriptions I showed them of live blood analysis.

Live blood analysis evidently began with Gunther Enderlein at the turn of the last century. He was in the Bechamp school of disease etiology and his concepts are unintelligible in the context of modern biology and physiology. Enderlein placed blood under a darkflield microscope and interpreted the artifacts he saw as quasi-life forms, which he called protits, symbionts or endobionts, that could transform into pathogens (11). Only Live Blood analysts can see these forms. As one site says “Enderlein’s “Endobiont” only had meanings to dark field microscopists following his teaching (10).” There is large inter-operator variability in analyzing live blood and no two live blood analysts see the same pathologic changes on the same slide (7). Live blood analysis is the N-Ray of microscopy.

Overtime live blood analysis expanded to include multiple diet related diagnosis, and is sometimes called nutritional blood analysis, the better, I suppose, to sell expensive supplements.

Here is where I apologize.

It appears that copyright laws prevent me from showing specific examples to blood analysis, so I add the link instead. Lots of clicking back and forth, I know, but I do respect intellectual property, although to apply the word “intellectual” to live blood analysis is akin to calling a naturopath a doctor. Lets say I respect their property. These photographs are widely reproduced on the net, but I am uncertain as to who, if anyone, owns the copyright, so I will be careful. There is evidently one lawyer for every 265 Americans.

In real medicine rouleau is an anomaly seen with paraproteinemias such as multiple myeloma. The extra proteins in the blood alter the charge on red cells, causing them to stack like coins.

In the world of live blood analysis, the are more causes:

“Often poor protein digestion. The pancreas may be off. Excess dietary protein, poor assimilation. Eating too much animal protein. Blood too toxic (altered blood pH) from stress, coffee, cigarettes, meat, etc. Dehydration, not drinking enough water (2).” None of these issues is known to cause rouleau formation. However, it you have multiple myeloma and you see a live blood analyst, the chance of having a serious and important diagnosis misdiagnosed and incorrectly treated is high.

“The loss of the negative surface charge this is a more disorganizing symptom where plasma acids act as molecular glue, causing RBCs to stick together (0).”

The “Live Blood Analysis Diploma Course (1)” says it is due to “ingestion of high fat meals, high blood cholesterol levels, and blood fat chemistry imbalances.”

No. That is not the cause of red cell aggregation outside of Dr. Young, the acid maven. There are no plasma acids that act as a molecular glue. Diet does not make red cells stick together, unless you dine on Elmer’s.

“Over acidity and blood pH imbalance. The diet is high in strong acids from proteins and carbohydrates. (0)” Perhaps “digestive insufficiency, excess protein consumption, imbalanced electrolytes, and inability to assimilate lipids or toxicity (1). ” A pathologic finding due to an excess and an insufficiency.

This is a made up nonsense. Blood pH is constant at 7.4 and varies not at all except under severe metabolic derangements like diabetic ketoacidosis and sepsis.

“Ingestion of an excessive amount of over acidic food and drinks which causes a deficiency of sodium bicarbonate in the alkalophile glands (4).”

Macrocytes are most often due to B12 or folate deficiency, although there are other causes like AZT and hypothyroidism. Microcytes are most often due to iron deficiency and can be a marker of bowel cancer. Microcytes and macrocytes on a smear can represent serious underlying diseases, but are not due to “a deficiency of sodium bicarbonate in the alkalophile glands. ” Missing the real cause of these abnormalities could prove fatal, which, with their erroneous understanding of blood cell morphology, live blood analysts would be prone to do.

“Latent tissue acidosis in the extra cellular fluid and the body’s inability to remove acid waste build up in the blood causing the cells to break down (0).”

No, latent tissue acidosis is not the cause of echinocytes. These are pathologic and a marker of liver disease.

“Indicates a nationalization of bacteria, yeast/fungus, mold, and their acid wastes and acid crystals lying in a dormant/inactive state (0).” Sounds worrisome. Biomedx says “The presence of large numbers of protoplast structures in peripheral blood is an unfavorable sign. Some authors propose they are a collection of progenitor cryptocides (Livingston-Wheeler). Progenitor meaning existing across millennia at the beginning, cryptocides meaning cellular killer. Protoplasts are thought to be related with infectious disease or neoplastic activity and or L-form bacteria. They are thought to be viral in origin (5).” Try as I might, I cannot understand what any of this means.

When you look at the photograph, what is seen is artifact of the slide, not a constituent of blood. Schmutz. Slides are not pristine and stray bits of cloth, cells and environmental dirt is common on the cells. A skilled microscopist understands the difference between artifact and real pathology. The patient, however, does not, and if I were not knowledgeable about cellular morphology I would be most impressed to see a large fibrous thallus in my blood. The explanation of fibrous thallus is nonsensical pseudoscientific gibberish.

“Involved in clotting to prevent internal bleeding. There is usually an increase during detoxification with the complete program and effective diet because the body is pulling acids stored in the connective tissues back into bloodstream for elimination (1).”

Glass is good at causing fibrin to precipitate out of blood, so occasionally you will see clot on the slide. Some of the photos in the net are artifact, some are fibrin, and all are the normal response to blood on glass. Again, the explanation is nonsense.

“Yeast overgrowth, collection of yeast, bacterial, fungus, mold. very toxic. Indicated in advanced stages of latent tissue acidosis. Highly disruptive to normal blood circulation (0).”

You never see mould in the blood in people who are not in the ICU dying of sepsis and profound immunocompromise.

These are not mold, they are artifacts on the slide.

“Fermenting RBCs White spots or white yeast forms inside RBCs Indicates the diet is too high in carbohydrates/simple sugars sugar intolerance and/or imbalance endocrine system/ pancreas stress (0).”

Red cells do not ferment and yeast do not live in red cells. This is fiction.

“Born out of RBCs due to blood pH Imbalance from latent tissue acidosis diet too high in protein, carbohydrates/ sugars may be caused by excess antibiotic use, hormonal therapy, steroid use fungal outfection (0)”

This is artifact, not yeasts. Yeasts can only been seen in people dying of overwhelming sepsis from profound neutropenia. Yeasts are not “born out of RBC’s.” More nonsense.

“High counts are due to latent tissue acidosis and excess acids in the bloodstream not being eliminated through the urinary tract causing RBCs to biologically transform giving birth to “filthy, dirty, platelets.”

Red blood cells do not biologically transform into platelets, much less filthy dirty ones.

“Bacterial forms born out of RBCs and found in the blood when there is latent tissue acidosis which alters the blood pH due to acidic diet, emotional or physical stress, low nascent oxygen (O1) waste products of bacteria and yeast/ fungus (0). ”

Bacteria are not born out of red blood cells. More fiction and fantasy. The rod forms, like the L forms seen in some slides, are artifacts. The rods are many times larger than any known bacteria.

“Indicates recent consumption of excess sugars/ carbohydrates or proteins WBCs are paralyzed by the acids (acetyl aldehyde, ethanol alcohol, lactic, nitric, uric, sulfuric, and phosphoric) for up to 5 hours (0).”

White cells cannot be anesthetized, although I can be when reading these sites. The photo to me and others appears to be a normal cell. Of course, if you can diagnosis a normal cell as paralyzed by a dietary lack, then everyone can benefit from supplements.

“Perceived to be related to allergies and/or sensitivities to foods or the environment exotoxic and mycotoxic reactions histaminea. Alergic reactions to dairy (0).”

The only way you can diagnose a basophile is by staining it.

“Crystals are observed when there is excess acidity. It is the body’s preservation mechanism to buffer acidity and create a solid form which is less toxic than the liquid acids. Crystal are perceived to be he signature of the microzyma fermenting sugar, protein or fat (0).”

Making more stuff up. I feel like there should be a midget shouting “Boss, Boss, Da live blood, the live blood” as they only place such physiology exists is on fantasy island.

The crystals on every live blood site are artifact not of blood, but of schmutz on the slide. One practitioner noted some of the crystals looked like glass, but were in cholesterol. No, it was glass, a by-product of making the slides from glass. Microzyma are not the small empress of Oz, but the imaginary micro organisms of Bechamp and are artifacts of darkfield microscopy.

More schmutz/artifact on the slide.

“Tobacco, marijuana chemical, recreational and prescription drugs. Brown is also associate with the fermentation of protein (0).”

I can imagine some gullible person losing a job because of drug use found on live blood analysis. If companies will use handwriting analysis or, in Japan, blood type as a basis for hiring and firing, live blood analysis will be next.

More schmutz on the slide. You cannot see cholesterol on a blood smear.

“Usually indicates high blood pressure, arterial sclerosis, high cholesterol. Diet is too high in animal source proteins. Dehydration, acidosis (0).”

Taking the blood pressure usually indicates high blood pressure. It is a simple enough diagnostic procedure and more reliable than looking at live blood. Similarly, a fasting lipid panel may be the more accurate way to diagnosis hypercholesterolemia.

In summary, virtually every diagnosis in live blood analysis is nonsense and much of the alleged pathology is either normal or artifact on the slide. The alleged pathophysiology is also nonsense they just make this stuff up.

Live blood analysts tend to make up words and processes that sound scientific and cromulous (6): several sites refer to seeing orimbryonic bacteria, but the google cannot find a definition. This pseudoscientific jargon and imaginary physiology combined with the a microscope and a view of their own blood, which most people have never seen, gives the live blood analysis proponents the trappings of real science. A nickel says they wear white coats.

There is no validity behind almost all of the claims made by the practitioners. The one study that looked at the ability for blinded live blood analyzers to make the same diagnosis demonstrated that no two viewers saw the same thing (7). The one diagnostic trial of live blood analysis demonstrated that practitioners were unable to accurately diagnose patients with known metastatic cancer (9).

Many of the web sites show before and after slides to demonstrate the benefits of the detox or supplements or diet have had on the blood. It all depends on what microscopic field on a given slide you choose to present. If you were to show the front of my scalp as the before and the back as the after, you would conclude that something made my hair grow in the interim.

Live blood analysis is a remarkable the combination of artifacts being diagnosed as pathology combined with an imaginary pathophysiology that is completely divorced from reality. It is microscopic paradolia, with the practitioners seeing their own imagining in the structures on the slides. When I was a child, before I learned to cursive writing, I would make squiggles on paper occasionally crossing a ‘t’ and dotting an ‘i’. It was gibberish but I called it real writing. I didn’t realize I was in training to be a live blood analyst.

Live blood analysis does not resemble most alternative medicine modalities, but is more akin to high tech reading of tea leaves or the entrails of pig to divine the future. It is the cargo cult of quackery, with the trappings of science but none of the substance.

4) “alkalophile glands” appears to be an invention of Dr. Young, a major shill for acids as the cause of every diseases. As he says “alkalophile glands that need these quick bases in order to build up their strong sodium bicarbonate secretions. These glands and organs are the stomach, pancreas, Brunner”s glands (between the pylorus and the junctions of the bile and pancreatic ducts) Lieberkuhn”s glands in the liver and its bile with its strong acid binding capabilities which it has to produce.” http://articlesofhealth.blogspot.com/2008/10/get-off-your-fat-acid.html

7) Altern Ther Health Med. 2006 Jul-Aug12(4):36-41. Reliability of Enderlein’s darkfield analysis of live blood.

CONTEXT: In 1925, the German zoologist Günther Enderlein, PhD, published a concept of microbial life cycles. His observations of live blood using darkfield microscopy revealed structures and phenomena that had not yet been described. Although very little research has been conducted to explain the phenomena Dr. Enderlein observed, the diagnostic test is still used in complementary and alternative medicine.

OBJECTIVE: To test the interobserver reliability and test-retest reliability of 2 experienced darkfield specialists who had undergone comparable training in Enderlein blood analysis.

SETTING: Inpatient clinic for internal medicine and geriatrics.

METHODS: Both observers assessed 48 capillary blood samples from 24 patients with diabetes. The observers were mutually blind and assessed their findings according to a specific item randomization list that allowed observers to specify whether Enderlein structures were visible or not.

RESULTS: The interobserver reliability for the visibility of various structures was kappa = .35 (95% CI: .27-.43), the test-retest reliability was kappa = .44 (95% CI: .36-.53).

CONCLUSIONS: This pilot study indicates that Enderlein darkfield analysis is very difficult to standardize and that the reliability of the diagnostic test is low.

(9) Forsch Komplementarmed Klass Naturheilkd. 2005 Jun12(3):148-51. Epub 2005 Jun 23. [Does dark field microscopy according to Enderlein allow for cancer diagnosis? A prospective study]

BACKGROUND: Dark field microscopy according to Enderlin claims to be able to detect forthcoming or beginning cancer at an early stage through minute abnormalities in the blood. In Germany and the USA, this method is used by an increasing number of physicians and health practitioners (non-medically qualified complementary practitioners), because this easy test seems to give important information about patients’ health status.

OBJECTIVE: Can dark field microscopy reliably detect cancer?

MATERIALS AND METHODS: In the course of a prospective study on iridology, blood samples were drawn for dark field microscopy in 110 patients. A health practitioner with several years of training in the field carried out the examination without prior information about the patients. RESULTS: Out of 12 patients with present tumor metastasis as confirmed by radiological methods (CT, MRI or ultra-sound) 3 were correctly identified. Analysis of sensitivity (0.25), specificity (0.64), positive (0.09) and negative (0.85) predictive values revealed unsatisfactory results.

CONCLUSION: Dark field microscopy does not seem to reliably detect the presence of cancer. Clinical use of the method can therefore not be recommended until future studies are conducted.


DIRECT FRACTURE HEALING

Direct healing does not commonly occur in the natural process of fracture healing. This since it requires a correct anatomical reduction of the fracture ends, without any gap formation, and a stable fixation. However, this type of healing is often the primary goal to achieve after open reduction and internal fixation surgery. When these requirements are achieved, direct bone healing can occur by direct remodeling of lamellar bone, the Haversian canals and blood vessels. Depending on the species, it usually takes from a few months to a few years, before complete healing is achieved. 37

Contact Healing

Primary healing of fractures can either occur through contact healing or gap healing. Both processes involve an attempt to directly re-establish an anatomically correct and biomechanically competent lamellar bone structure. Direct bone healing can only occur when an anatomic restoration of the fracture fragments is achieved and rigid fixation is provided resulting in a substantial decrease in interfragmentary strain. Bone on one side of the cortex must unite with bone on the other side of the cortex to re-establish mechanical continuity. If the gap between bone ends is less than 0.01 mm and interfragmentary strain is less than 2%, the fracture unite by so-called contact healing. 41 Under these conditions, cutting cones are formed at the ends of the osteons closest to the fracture site. 22 The tips of the cutting cones consist of osteoclasts which cross the fracture line, generating longitudinal cavities at a rate of 50� μm/day. These cavities are later filled by bone produced by osteoblasts residing at the rear of the cutting cone. This results in the simultaneous generation of a bony union and the restoration of Haversian systems formed in an axial direction. 23, 37 The re-established Haversian systems allow for penetration of blood vessels carrying osteoblastic precursors. 15, 21 The bridging osteons later mature by direct remodelling into lamellar bone resulting in fracture healing without the formation of periosteal callus.

Gap Healing

Gap healing differs from contact healing in that bony union and Haversian remodelling do not occur simultaneously. It occurs if stable conditions and an anatomical reduction are achieved, although the gap must be less than 800 μm to 1 mm. 23 In this process the fracture site is primarily filled by lamellar bone oriented perpendicular to the long axis, requiring a secondary osteonal reconstruction unlike the process of contact healing. 39 The primary bone structure is then gradually replaced by longitudinal revascularized osteons carrying osteoprogenitor cells which differentiate into osteoblasts and produce lamellar bone on each surface of the gap. 41 This lamellar bone, however, is laid down perpendicular to the long axis and is mechanically weak. This initial process takes approximately 3 and 8 weeks, after which a secondary remodelling resembling the contact healing cascade with cutting cones takes place. Although not as extensive as endochondral remodelling, this phase is necessary in order to fully restore the anatomical and biomechanical properties of the bone. 41


Where does your blood actually come from?

Scientists at Lund University in Sweden have developed a new understanding of how the first blood cells form during human development as they transition from endothelial cells to form blood cells of different types.

Using a laboratory model of human stem cell development and by looking at the expression of blood cell and endothelial cell genes in each individual cell, they found a progression from an endothelial state, to a mixed endothelial/blood state, to a blood-only state. This is the first study showing the molecular processes of this transition in the human developmental context.

"Understanding how the first human blood cells develop will provide missing clues for us to generate blood stem cells in the laboratory for use in the treatment of blood disorders and malignancies," says Niels-Bjarne Woods, in charge of the study.

The blood running through our veins is composed of billions of specialized cells, responsible for many important functions required for life, including providing oxygen to all tissues in our body and providing immune responses against viruses, bacteria, and even cancer cells. During a narrow window of time in embryonic development, the first blood stem cells form. These give rise to all the blood cells you will produce in your lifetime. The birth of these blood stem cells is a transition from another cell type into blood cells -- a process known as endothelial to hematopoietic transition.

The cells undergoing the transition to blood in the embryo start as endothelial cells that make up the walls of the developing arteries. During a short temporal window in development, a small number of tightly packed spindle shaped endothelial cells round up forming nascent blood, detach, and are released into the circulation. In this process, the endothelial cells undergoing the transition to blood show dramatic changes in their size and shape (from spindle shaped to the round cells of the blood).

However, what happens inside the cell during this time, as it changes shape and identity, had until now never been described at a molecular level. Thanks to single-cell molecular analysis, the scientists in Lund have now analyzed individual cells from an in vitro model of human blood development, known to comprise endothelial cells that transition to blood. The analysis revealed new populations of endothelial cells undergoing transition. These new cell populations showed differences in the repertoire of blood cell types that could be produced. which is a critically important finding in the understanding of origins of blood. Niels-Bjarne Woods explains:

"Most cell types are believed to result from a linear sequence of undifferentiated stages, progressively restricting their potential until they are restricted to the mature state. Cells arising from a transitioning process may not need to follow this rule, giving wider flexibility to which blood cell types can be produced."

This is a significant step towards understanding how the first blood cells are formed and how numbers and types of blood cells is regulated in development.

"It would also be interesting to find out if there are any endothelial cells in the adult that can still be "triggered" to produce new blood stem cells," says Niels-Bjarne Woods.


Introduction

Techniques for spatial transcriptomics have advanced to a state where the entire transcriptome now can be spatially resolved however, methods providing an exhaustive portrait of the expression with deep coverage do not yet guarantee resolution at the single-cell level 1,2,3 . Thus, transcripts captured at a given position may stem from a heterogeneous set of cells, not all necessarily of the same type. Hence, the observed expression profile at any location can be considered a mixture of transcripts originating from multiple distinct sources. Implicitly the presence of such composite profiles means that even though the transcriptional landscape can be thoroughly charted, the biological identity and spatial distribution of the cells generating this remains largely unknown.

As mentioned, spatial transcriptomics techniques face a dilemma of knowing the location of transcripts but not which cell that produced them. Conversely, single-cell RNA-sequencing experiments associate each transcript to an individual cell, but information regarding the positions of these transcripts within the tissue is lost. Given this set of complementary strengths and weaknesses, the notion of combining data from the two techniques to delineate the spatial topography of cell type populations is compelling.

Methods to deconvolve (bulk) RNA-seq data, informed by single-cell data, have existed for some time and could theoretically be applied to spatial data 4,5,6 . More recently, similar methods designed specifically for cell type deconvolution in spatial data have emerged and offered new biological insights. For example, the molecular characteristics of pancreatic ductal adenocarcinoma was thoroughly explored by such integration, testifying to the value of this approach 7 . However, these methods tend to exhibit certain limitations such as: only select cell types can be assessed, manual curation of data is required to form representative cell type “signatures”, dependence on marker genes, or the results—usually some form of normalized score—lack a clear biological interpretation.

Here we first present a new alternative model-based method to integrate single-cell RNA-seq and spatial transcriptomics data, which utilize complete expression profiles rather than a select set of marker genes. Next, we use this method to spatially map cell types present in single-cell data originating from mouse brain and developmental heart onto corresponding tissue sections. Finally, we show how our approach outperforms others (designed for bulk RNA-seq deconvolution) when presented with synthetic data.


Necrosis

Necrosis is the name given to unprogrammed death of cells and living tissue.

It is less orderly than apoptosis, which are part of programmed cell death.

In contrast with apoptosis, cleanup of cell debris by phagocytes of the immune system is generally more difficult, as the disorderly death generally does not send cell signals which tell nearby phagocytes to engulf the dying cell.

This lack of signalling makes it harder for the immune system to locate and recycle dead cells which have died through necrosis than if the cell had undergone apoptosis.

The release of intracellular content after cellular membrane damage is the cause of inflammation in necrosis.

There are many causes of necrosis including injury, infection, cancer, infarction, toxins and inflammation.

Severe damage to one essential system in the cell leads to secondary damage to other systems, a so-called "cascade of effects".

Necrosis can arise from lack of proper care to a wound site.

Necrosis is accompanied by the release of special enzymes, that are stored by lysosomes, which are capable of digesting cell components or the entire cell itself.

The injuries received by the cell may compromise the lysosome membrane, or may initiate an unorganized chain reaction which causes the release in enzymes.

Unlike in apoptosis, cells that die by necrosis may release harmful chemicals that damage other cells.


8. CRISPR-Cas9 Has Been a Game-Changer in Human Biology Research

CRISPR or Clustered Regularly Interspaced Short Palindromic Repeats, were first discovered in Archaea, and later bacteria, by Fransiciso Mojica from the University of Alicante in Spain, in 2007. Experimental observations allowed him to note that these pieces of genetic materials formed an integral part of the parent cells defense mechanisms to fend of invading viruses.

CRISPR are pieces of genetic code that are interrupted by 'spacer' sequences that act like the immuno-memory of the cell from previous 'infections'. Archaea and bacteria use CRISPR's to detect and fight off invaders in a process called bacteriophage in the future.

CRISPR was catapulted into the public domain when in 2013 Zhang Lab was able to demonstrate the first edit of a genome in mammals using CRISPR-Cas9 (CRISPR-associated protein 9).

This successful experiment showed that CRISPR could be used to target specific parts of an animal's genetic code and edit the DNA in situ.

CRISPR could be incredibly important for the future of human biology through permanently modifying genes in living cells to correct future potential mutations and treat the causes of disease.

This is impressive enough but CRISPR technology is constantly undergoing refinement and improvement.

Many industry experts believe CRISPR-Cas9 has a bright future. It will likely become a vital diagnostic and corrective tool in the field of human biology and could be used as a treatment for cancer and rare diseases like cystic fibrosis.


Hematopoiesis

the process by which blood cells form, develop, and mature in animals and man.

The blood&rsquos formed elements are highly specialized cells with a short life cycle: about 120 days for human erythrocytes, about five days for leukocytes, from several days to several months for lymphocytes, and about four days for thrombocytes. Despite the continuous destruction of blood cells, the number of cells re-mains more or less constant throughout the life of the organism, since the dying cells are replaced by new ones. In invertebrates, hematopoiesis takes place mainly in the perivisceral fluids and in the blood itself. In adult mammals and man, it takes place in the hematopoietic organs: the erythrocytes, granular leukocytes, and thrombocytes in the bone marrow lymphocytes in the lymph nodes, spleen, thymus, and bone marrow and monocytes and macrophages, in the bone marrow. All mature blood cells, regardless of their differences, apparently originate from a single type of parental hematopoietic (stem) cell. The strain of these parental cells is maintained in the body for life, thus ensuring the continuity of hematopoiesis. Upon maturing (differentiating), the hematopoietic cells undergo complex changes and divide several times more. Therefore, a great many specialized formed elements develop from a small number of parental cells.

Hematopoiesis is controlled in a complex manner by changes in the quantity and quality of the blood cells according to the needs of the body (for example, when the amount of oxygen in the air changes). Cells are replenished when blood is lost. This regulation is accomplished by a number of hormones, vitamins (for example, cyanocobalamin, or B12 and folic acid, or Bc), and special substances, called erythropoietins, to which various stages of the hematopoietic process are sensitive. The mechanisms regulating the rate of reproduction and maturation of the individual categories of hematopoietic cells are still largely un-known.

In the embryos of all mammals, including man, hematopoiesis starts in the yolk sac, where the hematopoietic cells originate from mesenchymal cells. Foci of hematopoietic tissue form in the embryonic mesenchyma and, later, in the liver (where red and white blood cells are formed) and thymus (where lymphocytes are formed). Still later, hematopoiesis shifts to the bone marrow, and lymphocytes begin to develop in the thymus, spleen, and lymph nodes.