Category Archives: Allergy

Mikroskopische Anatomie (Bewusstseinsmodelle VII)

Was gibt es für Mechanismen für den interaktionalen Dualismus von Bewusstsein & Körper oder Leib & Seele? Etwa Quantenverschränkung und Kopenhagener Deutung?

Von Verschränkung spricht man in der Quantenphysik, wenn ein zusammengesetztes physikalisches System, z. B. ein System mit mehreren Teilchen, als Ganzes betrachtet einen wohldefinierten Zustand einnimmt, ohne dass man auch jedem der Teilsysteme einen eigenen wohldefinierten Zustand zuordnen kann. Im Bereich der klassischen Physik kann es dieses Phänomen nicht geben. Dort sind zusammengesetzte System stets separabel, d. h. jedes Teilsystem hat zu jeder Zeit einen bestimmten Zustand, der sein jeweiliges Verhalten bestimmt, wobei die Gesamtheit der Zustände der einzelnen Teilsysteme und deren Zusammenwirken das Verhalten des Gesamtsystems vollständig erklärt.

Physiker sind skeptisch, so Sean Carroll in einem Interview und Vortrag

oder auch Peter Clarke, der insbesondere die von Eccles favorisierte “open modules” an spezifischen Synapsen untersucht hat. Schwierig bleibt, das Konzept mit dem Energieerhaltungssatz der klassischen Physik zusammenzubringen. Noch schwieriger ist es, quantitativ die Vorgängen an den vielen Kontaktpunkten (etwa Ca, K, Na-Kanäle) mit Quantenverschränkung zu erklären, so Clarke 2004

Even if quantum phenomena could occasionally affect calcium flow through channels, it seems very unlikely that this could have a significant effect on synaptic transmission, because the numbers of calcium ions involved are sufficiently large to swamp any quantum effects. Smith has argued this in a detailed discussion of the possibility of quantum effects at synapses, stating that the number of ions involved is 10^18 – 10^19. The numbers going through a given channel at a single opening are much smaller, of the order of one thousand, but this would still be enough to swamp the effects of a 10 ms change in the channel due to quantum fluctuations.

Direkten Widerspruch habe ich bisher nicht dazu gefunden. Es beginnt da aber erst die Diskussion, siehe Jedlicka 2017

The recent rise of quantum biology as an emerging field at the border between quantum physics and the life sciences suggests that quantum events could play a non-trivial role also in neuronal cells.

und Pitts 2019, einer der rising stars aus Cambridge

The new general relativistic objection provides some support for realism about gravitational energy-momentum in General Relativity

Can criticial thinking been teached?

Yes, it can.

Already in 2017 there was a Lancet paper with the super-long title “Effects of the Informed Health Choices primary school intervention on the ability of children in Uganda to assess the reliability of claims about treatment effects: a cluster-randomised controlled trial”. The paper is extensively discussed at vox.com

Andy Oxman is obsessed with the study of bullshit health claims and how to prevent them from spreading.
For decades, he’s been trying to find ways to get adults to think critically about the latest diet fads, vaccine rumors, or “miracle cures.” But he realized these efforts are often in vain: Adults can be stubborn old dogs — resistant to learning new things and changing their minds.

So not only Germany but also Uganda has its own bullshit hypothesis.

Blaming genes for resistance to environmental stressors

This something that I always avoided in human research – blaming genes for resistance to environmental stressors.

Nevertheless a Californian group (https://doi.org/10.1371/journal.pgen.1008528) now tested 101 mouse strains for lung resistance with exposure to diesel exhaust particles (DEP). After sensitizing the animals with dust mite and aluminium they could also test metacholine hyperreactivity (AHR).

Strains that exhibited the highest lung resistance after control exposure were not necessarily the same as those with high lung resistance after DEP exposure. It is unclear which strain was used for the consecutive GWAS. Did they put all mice into one cage for that?

The metacholine AHR GWAS results are not very impressive. And there seem to be also errors, as for example the lead SNP on chr 19 (rs51547574, near IL33) is shown with different allele frequencies in text and Fig 2.  As the expression quantitative trait locus (eQTL) for Il33 is not in the lung, I think there is nothing to memorize here – IL33 is just a gatekeeper for surface integrity.

In a next step I wouldhave expected a GWAS for resistance change after DEP but FIG 3 only gives the result of Δ AHRDEP—AHRPBS data at an abitrary methacholine dose of 10mg/ml. The identifed locus could be interesting but as the LD there is rather high without any corresponding eQTL (I always wondered why there has never been a significance threshold for LD blocks, only for isolated SNPs?), the logic of the paper is broken here. Induction of lung resistance by DEP was significantly blunted in Dapp1-/- female mice? What about male Gm5105-/- Mttp-/- , and Lamtor3-/- animals?

Hopefully nobody else will now try to find diesel, ozone, NOx resistance genes in humans as this is not a a scientific but a political issue…

Dementi

Früher hätte man es nicht mitbekommen, wenn man in irgendeiner Dissertation an irgendeiner Stelle falsch zitiert wird. Heute bekommt man es von Google Alert morgens geschickt. Der letzte Fall im März 2019 war

Nora Schumacher 2019
Aus der Klinik für Dermatologie, Venerologie und Allergologie der Medizinischen Fakultät Charité –Universitätsmedizin Berlin
Direktor: Prof. Dr. med. Kamran Ghoreschi
Berichterstatterin: Prof. Dr. Margitta Worm
Da schreibt die Doktorandin

Leider ist das nun das genaue Gegenteil, von dem was ich immer gesagt habe. Who cares?

Gestern bekomme ich dann diese Dissertation

Julian Klingbeil – 2019
ORM-like protein (ORMDL) – Annäherung an die Funktion über die Interaktion
Aus der Kinderklinik und Kinderpoliklinik im Dr. von Haunerschen Kinderspital der Ludwig–Maximilians–Universität München
Direktor: Prof. Dr. med. Dr. sci. nat. C. Klein Berichterstatterin: Prof. Dr. Ania Muntau

Abgesehen von dem etwas verschraubten Titel und der Tatsache, dass ich mich mit Protein-Protein Interaktion nicht auskenne, werde ich in der Arbeit sechs Mal zitiert. Und jedesmal falsch.


Ich habe nie einen Polymorphismus in ORMDL3 untersucht. Im Gegenteil, ORMDL3 ist wohl mehr zufällig getaggt worden. Dazu habe ich habe Zweifel an der Art und Weise, wie die Nature Arbeit zustande kam.


Die Aussage bezieht sich wohl auf mein früheres Lancet Editorial 2006 – nicht auf 2013 – während wir aber durchaus einen Zusammenhang zur Asthmatherapie gefunden haben.

Sorry, nein, die Populationen waren durchweg gut charakterisiert. Linkage und GWAS Studien hatten eher keine a priori Hypothesen, es war allein die Heterogenität, die in das Nirwana führte.

Leider falsch, Denham zeigt nur eine Region, kein Gen.


Sorry nein, Dold zeigt das 5,2fache nicht dreifache Risiko (siehe Tabelle 6 im Originalartikel).


Leider kommt das Zitat im Text überhaupt nicht vor. Who cares?

Zur Geschichte der Klimaforschung

Es ist nicht einfach, hier einen Überblick zu bekommen.

Jedenfalls sollte man von Qualität der Wettervorhersagen (die für die nächsten 24 Stunden von 75% auf über 90% in den letzten 20 Jahren gestiegen ist), nicht auf die Qualität der Klimavorhersagen schliessen.

Die Geschichte der Klimaforschung kann jedenfalls in vier Beiträgen lückenlos nachgelesen werden:

Wenn der Wind weht

Wenn der Wind weht” mit diesem Film (und seiner Titelmelodie von David Bowie) sind wir Mitte der 80er Jahre sozialisiert worden. Der drohenden Atomkrieg, das wardie reale und unmittelbare Gefahr dass eine der Pershing II in die Luft geflogen wäre.

Roland Emmerichs Katastrophenfilm The Day after Tomorrow 2004 konnte das nur schwer toppen. Experten sind aber der Meinung, dass die Spiefilme einen falschen Eindruck der Kimakrise vermittelt haben: zu sehr Katastrophen-orientiert, bekommt man allenfalls das Gefühl der Ohnmacht. Auch kommt neben der erfundenen Darstellung einer allumfassenden Katastrophe in dem Spielfilm die reale Erderwärmung vergleichsweise harmlos daher.

Oder doch nicht, wenn man sich “chasing ice” auf Youtube ansieht?

Urs Bruderer hat diese Frage in einem wunderbaren Essay über “Die große Überforderung” thematisiert

Ich habe die Klimakatastrophe viele Jahre kaum beachtet. Und hielt das für die klügste Entscheidung.
Seit Menschen denken können, warnen sie vor ihrem Ende.

Ob der Atomkrieg, das Waldsterben oder das Auslaufen des Maya-Kalenders im Dezember 2012, ob im Cern produzierte schwarze Löcher, Milleniumsbug oder Vogelgrippe – im Rückblick bewies jedes Weltuntergangsszenario nur, dass wir eine Lust an der Angst vor dem Ende haben.

Der Weltklimarat hat inzwischen unzählige Berichte und Sonderberichte veröentlicht. Die Warnungen wurden immer genauer und bedrohlicher. Und ich wurde immer besser darin, sie zu überhören.

Einen Artikel, den man vollständig gelesen haben muss.

A 498 references paper on climate change and allergy

This is certainly the most comprehensive paper that examines the association of air pollution, climate change and allergen exposure: “Air Pollution and Climate Change Effects on Allergies in the Anthropocene: Abundance, Interaction, and Modification of Allergens and Adjuvants

Air pollution and climate change are potential drivers for the increasing burden of allergic diseases. The molecular mechanisms by which air pollutants and climate parameters may influence allergic diseases, however, are complex and elusive.

There is no causal effect of allergens on human allergy, as allergens have been always abundant even without allergy. Nevertheless allergens are drivers aggravating symptoms in allergy-prone patients by basically four factors

  1. Stability effects; influencing the accumulation and degradation of allergenic proteins, the duration of exposure times to cellular receptors, and the process of antigen presentation via major histocompatibility complex (MHC) class II
  2. Epitope effects, i.e., generation of new epitopes or modification of existing epitopes, changing the binding properties of antibodies and receptors, by direct chemical modification or as a result of conformational changes
  3. Adjuvant effects, i.e., generation of new adjuvant functions or modification of existing adjuvant functions such as lipid-binding capacities due to modified ligand binding sites
  4. Agglomeration effects, i.e., multiplication or shielding of epitopes or adjuvant functions by cross-linking (oligomerization) of allergenic proteins, which may enhance the cross-linking

I would add 5. that the absolute number of pollens increased in some areas as a stress response of dying trees.

Harmed by the hygiene hypothesis

A new paper by a British-Kazakhstan-Armenian group nicely summarizes why we need good hypothesis papers.
As a deterring example they use the hygiene hypothesis

the hygiene hypothesis that was originally proposed by David Strachan in 1989. David Strachan studied the epidemiology of hay fever in a cohort of 17,414 British children and concluded that declining family size and improved personal hygiene had reduced the chances of cross infections in families, resulting in epidemics of atopic disease in post-industrial Britain. Over the past four decades, several related hypotheses have been proposed to expand the potential role of symbiotic microorganisms and parasites in the development of human physiological immune responses early in life and protection from allergic and autoimmune diseases later on.

I agree with the description although David never claimed to be the first author writing about the hygiene hypothesis. When I spoke to him the last time London he wasn’t even happy with this popularity.

The chain certainly started also much earlier than 1989 with “continuing activity of an immune system made redundant by man’s cleanliness” (Godfrey, 1975) continued with Gerrard 1976, Frick 1986, Busse, 1989 until David Barker argued in 1985 that there is a “decreased incidence of infection among children, especially in wealthier families, that changed their pattern of immunity”.

The harm inducted by the hygiene hypothesis is described as

The misunderstanding of the hygiene hypothesis that primarily aimed to shed light on the role of the microbiome in allergic and autoimmune diseases resulted in decline of public confidence in hygiene with dire societal implications, forcing some experts to abandon the original idea. Although that hypothesis is unrelated to the issue of vaccinations, the public misunderstanding has resulted in decline of vaccinations at a time of upsurge of old and new infections.

I fear the authors are right – some people may have been harmed by the hygiene hypothesis leading them back in the pre-Semmelweis era.

Useful reveal.js plugins

The list is somewhat hidden but here is the link https://github.com/hakimel/reveal.js/wiki/Plugins,-Tools-and-Hardware
My preference is

dependencies: [
{ src: 'library/reveal.js/lib/js/classList.js', condition: function() { return !document.body.classList; } },
{ src: 'library/reveal.js/plugin/highlight/highlight.js', async: true, callback: function() { hljs.initHighlightingOnLoad(); } },
{ src: 'library/reveal.js/plugin/zoom-js/zoom.js', async: true },
{ src: "library/speech.js",
callback: function() {
RevealSpeech.configure({
nextKeyword: 'nextslide', 
prevKeyword: 'previousslide',
lastKeyword: 'lastslide',
firstKeyword: 'firstslide',
debug: true,
lang: 'en-GB' // default de-DE
});
}

plus zenpen in an iframe.

The slide builders at the plugin page are quite useless except for slides.com which is, however, too expensive.
I therefore design everything in Keynote, export as jpg and loop over all jpgs to write the section tags.

The best option would certainly be if Apple would directly support reveal.js and not some fancy own HTML formats

slide/assets/7D643FA7-9A1F-45A5-A30F-7828735F3C35/7D643FA7-9A1F-45A5-A30F-7828735F3C35.json

Or is anyone willing to write a converter?

A new research route for fighting allergy?

Sci Immunol today shows an incomplete genetic reconstitution of B cell pools after measles infection.

Using B cell receptor (BCR) sequencing of human peripheral blood lymphocytes before and after MeV infection, we identified two immunological con- sequences from measles underlying immunosuppression: (i) incomplete reconstitution of the naïve B cell pool leading to immunological immaturity and (ii) compromised immune memory to previously encountered pathogens due to depletion of previously expanded B memory clones.

This “immune amnesia” is noteworthy as sensitivity to D pter was observed less frequent in children with a history of measles than in those without.

City-Country-River

In1989, we compared the City of Munich and Upper Bavaria in a big study. Although we did not find so many differences, there is an increased interest now in city – urban differences. Another two papers appeared yesterday, one in ScienceVulnerability of the industrialized microbiota” and one in Environment InternationalUrban-associated diseases: Candidate diseases, environmental risk factors, and a path forward“. The latter study finds
Continue reading City-Country-River

VDR variants are associated with asthma

It is always nice to see an own study 15 years later appearing in a meta-analysis. A new paper in the Annals of Allergy, Asthma and Immunology now shows the results of 17 case–control studies.

Pooled odds ratio (OR) and 95% confidence interval of individual studies and pooled data for the association between TaqI polymorphism and asthma risk in overall populations and B for tt vs. TTof the TaqI variant.

We are in line #1…

Another nice paper on a genetic interaction is Vimaleswaran et al.

https://www.ncbi.nlm.nih.gov/pubmed/22686937