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CatLady78

Profile Information

Gender: Female
Current location: India
Member since: Thu Jun 18, 2020, 11:40 AM
Number of posts: 445

About Me

I am an old-timer. I posted here as nam78_two for 4-5 years (2004 or 5 to 2009-10) in the Bush, Obama years.

Journal Archives

Good luck EarlG



Now don't you guys leave ;-/. Because there is no way I am joining turdbook!

Thanks Skinner

It is a bummer you are leaving but I wish you all the best in your future ventures. I wish there was a way to follow you without using one of the behemoths (google, facebook etc.) -oh well. That is why du is the only kind of social internet use I do ;-/. I do wish you all the best.

Can someone interpret this -Possible Myeloma

My mom is not doing well. We are worried it could be myeloma.

I am only looking for anecdotal stuff. We are getting medical care. But I would like to know if any of this sounds familiar to someone with a Multiple Myeloma or other cancer diagnosis.

We have to wait a hellish 3 days for test results (biopsy and serum protein electrophoresis).


My mom developed the following symptoms rapidly over the last 2 months (not sure if it is relevant but she had just stopped a diabetes medication Metformin which might have tumor suppressing properties): anemia, rapid weight loss(approx. 7 kg), fatigue, loss of appetite, back pain, nausea, edema in 1 leg. A few of these have subsided a little.

Mom's bloodwork came back yesterday with this:

Peripheral Smear:
RBC-mild hypochromia, few microcytes
WBC-Leucopenia, neutrophil predominates
platelets-thrombocytopenia

Impression: pancytopenia

Bone Marrow: particles+cellular

erythroid-normoblastic with few megaloblasts

myeloid decreased; all cells of myeloid maturation seen; plenty of atypical cells seen-possibly of lymphoid origin.

Megakaryocyte - Decreased

Impression:
Suggestive of:
(1) Lymphoproliferative disorder with plasmacytoid lymphocytes. R/o lymphoma

(2) R/o Plasma cell dyscrasias
(there was a check mark against this-possibly indicating that further investigations are required).



Some of that is about anemia...I knew a bit about lymphocytes once upon a time. But my brain is just not working. I googled most of that and it generally brings up cancer. But if you have any personal accounts I would like to hear them.

I am tense. We are very close..we are a very small family unit..just three people..mom, dad and I...

Thanks in advance for any info..

I am very worried

My mom was on the diabetes medication Metformin and she stopped taking it 2 months ago (on seeing that it was pulled for unacceptably high levels of NDMA- which is a carcinogen). This was June. However, Metformin also is suspected oddly enough of having tumor suppressing properties.

Soon after she stopped taking it, her health started deteriorating: loss of appetite, 6-8 kg weight loss in 2 months, back pain, nausea, fatigue. We kept hoping it was nothing. But the doctors did a bunch of tests and currently her blood-work has come back with comments like: myeloid decreased and scarily plasma cell dyscrasia-the worst form of which is MM.

We are waiting on biopsy and serum protein electrophoresis results. I am very worried and scared. I keep googling myeloma tensely. I am a scientist and it isn't that I have no familiarity with some of the stuff involved but somehow I cannot seem to register anything. My mom was so healthy-I still cannot wrap my head around this. We are a very small family unit-I am an only child and I am child-free. It is hard to take in the sickness of one of our trio.

I am sorry about your diagnosis Captain Queeg (Caine Mutiny fan eh?). If you caught it early I guess you will have a good prognosis. I don't know mom's status. Her Lactose Dehydrogenase Level is 258, which is in range and I saw speculation that high LDH levels could be a sign of progression. I know they say not to google diseases but I am terrified.

If it is MM I guess we will come to the acceptance stage soon..I have crossed denial and am in the intense misery stage at the moment...I can't think straight..mom and I are very close...

All the best to you....any info is very welcome. We have to wait a hellish 3 days....

Development of Sensory Organ Polarity in Zebrafish

I posted a link over a week back to studies in zebrafish showing that chemical signalling and cellular forces work together to produce polarity in this system. I made a mess of that post. I have now read the paper and written a synopsis. I want to thank NNadir for encouraging me to post in spite of blunders. I do this recreationally but it helps me think.

These are links to the original article/paper:
https://medicalxpress.com/news/2020-06-transparent-fish-reveal-subtle-cellular.html
https://www.nature.com/articles/s41567-020-0894-9

My post below is obviously not original work, a review, scientific communication or anything else. I merely made a journal club type post after reading the paper (I was bored with a chore I am stuck on and welcomed any distraction.)

I drew some graphs that are heavily derived from the original paper because it is hard to describe the work without pictures or equations. It is a homage to their work and so I hope this doesn't cross over into plagiarism or piracy. I don't think it should cross any lines. It isn't even work I work on or am interested in except as cool work from another lab. If it does, I will take it down. And please let me know if there are any errors (signs, eqns or biology) - I was a little rusty on some of the mechanics (torque, right-hand rule, dipoles etc.). Though overall it is a fairly accessible paper if you have some exposure to mechanics at the undergraduate level.


This Nature Physics paper illustrates how biological pattern formation occurs in zebrafish as a result of
chemical signaling working in concert with cellular forces. An important concept here is planar cell
polarity (PCP), which is the property by which self-organization results in in-plane polarity (as opposed
to apical-basal, i.e. top-bottom polarity) in biological tissues. The zebrafish in this treatment has an axis
of planar cell polarity along “x” – i.e. it is oriented head-to-tail along the x-axis, which is therefore the PCP axis of
interest.
The specific organ under consideration is the neuromast, a sensory organ, several of which are
distributed along the lateral line of the zebrafish. The neuromast senses movements resulting from fluid
flow using hair-cells arranged in a specific pattern along its mid-line. Hair-cells have polarized hair￾bundles which are directionally sensitive (Panel 1).



Half of the hair cells found in the Neuromast are
sensitive to tail-ward (caudad) flows-such as those resulting from the movement of water while
swimming. The other half are sensitive to head-ward (rostrad) flows-such as those resulting from say
predator movement.

The authors of this paper studied hair-cell development and regeneration in the larval neuromasts of
zebrafish. They demonstrated that the Notch signaling pathway in combination with cellular surface
tension regulation, leads to the precise arrangement of hair-cells seen in these organs. The neuromasts
of zebrafish invariably sport hair-cells in a specific pattern as seen below:



The deep green (+) cells are rostrad motion sensors, while the caudad motion sensors are in light green
(-). Hair-cell pairs always develop so as to have have opposing polarities in wild type (WT) i.e. typical
animals.
The authors liken this to an electric dipole, which always has a specific orientation in an external electric
field. (They emphasize that this is distinct from an actual electric dipole in an electric field-it is merely a
simile.)
With respect to the PCP axis, hair-cell pairs that have a (-+) orientation are considered positive dipoles
while hair-cell pairs with a (+-) orientation are called negative dipoles (Panel 2). And in WT animals, hair￾cell pairs in neuromasts are always found in the positive dipole configuration.

Chemical Signaling
First the authors looked at how chemical signaling results in hair-cells with reversed polarities. Previous
work by the same last author (Current Biology, 2019) has demonstrated that Notch signaling
downregulates a protein called Emx2. And that sibling cells develop opposing polarities with one
expressing Emx2 and the other expressing Notch. The Notch expressing cells develop rostrad sensitivity
while the Emx2 expressing cells develop caudad sensitivity. The authors postulated a rate equation (eqn
1) which is indicative of a bi-stable system as shown. I inferred that the system must behave roughly as
sketched out there (Panel 3). If that is inaccurate, please let me know.


Prior to the development of the final polarities, both possible dipole states are equally energetically
favorable. However, in WT animals, matured hair-cell pairs are found exclusively in the positive dipole
orientation.
The authors found from imaging studies that roughly half the dipoles initially formed are in the negative
dipole configuration. However, prior to maturation, they undergo a dipole transition and realign
themselves with the PCP axis in the positive dipole orientation (Panel 4).




The authors found in summary that the WT neuromast hair-cells undergo specific patterns of
maturation. Two daughter cells are generated by a precursor cell. Mitosis usually occurs in alignment
with the PCP axis. But whatever the specific geometry (i.e. whether mitosis occurs out of alignment with the PCP axis, whether positive or negative dipoles result), prior to hair-cell maturation, all the cell-pairs get oriented such that they are in the positive dipole configuration (Panel 5). As they differentiate and mature, actin-filled, lamellipodial protrusions common in motile cells form at the opposite poles of the cells. In WT animals, the centroid of the cell-pair does not change much, however the daughter cells translate away from each other.
Intercalating cells fill the space between them.
In contrast, in a Notch mutant with disrupted Notch signaling, all cell-pairs are in the (--) configuration
and translate together without increasing their separation. These cells translate more than the WT cells
but the inter-cell separation does not change much. Incidentally, a mutation in Vangl2 -where PCP
signaling is disrupted altogether, results in hair-cell pairs oriented in all sorts of directions in the x-y
plane. Vangl2 is a core PCP protein required to orient the cells along the anteroposterior axis.



Cellular Mechanics



To explain the cellular mechanics underlying these behaviors the authors used imaging with deep￾learning to probe two specific parameters: 1) the angle 2*alpha between dividing cells and 2) the
deviation in cell shape relative to an ideal sphere of radius R0 (corresponding to uniform surface
tension).
The basic model the authors have come up with is one where the angle alpha is specified by eqn 2.
Alpha starts off at pi/2 and drops off rapidly close to cytokinesis/cell-separation (as seen in the graph).
This behavior is well fit by a model involving changes in one parameter-the cellular surface tension￾gamma-s-which is the surface tension between the dividing cells and intercalating cells. They explain this
as follows-as the cells start to differentiate, an increase in heterophilic adhesion, drives gamma-s down.
Two factors drive the dynamics observed: 1) gamma-s drops and 2) importantly, a gradient in surface
tension along the PCP axis across the cell. This gradient is determined by the signaling state of the cell.
Therefore, the cell-pairs have oppositely oriented surface tension gradients for both positive and
negative dipoles. In positive dipoles the drop in surface tension across the cell is positive-i.e. the surface
tension decreases on going out from the cell-cell interface. This facilitates the lowering of the surface
energy (eqn 3) to the point where protrusions can form at opposite poles of the cells, enabling them to
move away from each other. In negative dipoles however, surface tension increases across the cell.

I confess I was a little hazy on the next part. While I understood the general drift of their argument, I had
difficulty visualizing the geometry as they explained it. But the rough gist is this: a negative dipole is in
an energetically unstable state because of PCP signaling; therefore, minor fluctuations in the x-y plane.
cause it to rotate around till it is in alignment with the PCP axis. So the hair-cell dipole mimics an electric
dipole in how it rotates around to its stable position in an external electric field. The angular velocity/the
torque on the dipole are maximum for psi=pi/2. The angular velocities they measured from their
imaging studies roughly agreed with this.


Finally, they obtained further proof of their model from imaging the shape of the cell-pairs both late and
early in the maturation process. Negative and positive dipoles had distinctly different shapes early on.
However, they had acquired similar profiles late in the maturation process (post dipole transition for
negative dipoles). They compared it to a model they derived for shape change as a function of the angle
theta (Panel 8, eqn.(5)) and surface tension drop, delta(gamma-s). Values of delta(gamma-s) obtained by
fitting imaging data to eqn.(5) validated their predictions that dipole transitions would be accompanied
by a change in sign for delta(gamma-s) –there was some scatter in their data but the trend indicated the
predicted sign change. And delta(gamma-s) increased over time in the positive direction for both types
of dipoles.


The figure shows how positive and negative dipoles result in different shapes/shape changes. Their
fluorescent micrographs show these differences.
Future directions will probably focus on identifying the precise mechanisms by which PCP signaling
causes these changes in surface tension. Because, if I read this right, while they correlate cell polarity
and surface tension generally, the exact sub-mechanisms by which PCP signaling affects gamma-s are
not yet spelt out. Other recent work has looked at how acto-myosin tension and Notch signaling are
generally coupled though:
https://bmcbiol.biomedcentral.com/articles/10.1186/s12915-019-0625-9

That is the gist. Please let me know if there is anything inaccurate in there. I wrote it myself and so I hope there is no plagiarism. But in case I have unconsciously recycled their language, I am attributing that as appropriate to them.

It is no demon reproduction biology. I don't think recent issues of Nature have covered that. Nature is orthodox that way . But interesting work regardless....

Thank you for posting this

I love that chart. It is the funniest thing I have seen in a while.
Also, they misspelled "dissident voices"...


Help with imgur (RESOLVED)

Edit: Issue resolved thanks to CurtEastPoint.

I have checked out CurtEastPoint's thread and others but am still having trouble with imgur.

In brief:

DUer BumDaRush show had said:
I did a right-click on that pic (I use Firefox) to get a drop-down menu that offered a choice to "View image". Selecting that gave me the image full screen and I just copied the URL of that page and pasted here!

I am not even offered that "view image" option. But if I copy the permalink and open it in a browser like firefox, I get an ugly sort of link like this:

https://i.imgur.com/ucztuyf_d.webp?maxwidth=640&shape=thumb&fidelity=medium

As I have seen others recommend, I trimmed out everything past the dot and added jpg. Now I can see the image but its resolution is much lower.

See:



This is the original link:
http://imgur.com/a/k6o11dC

I made a post for the science forum with some pics but am stuck with this issue :-/.

I have to go work but thanks in advance for any help. It is truly appreciated...

Horrible

We are a pretty awful species....

Homeo, 5G and Covid-19 (via Retraction Watch)

Two papers have been retracted: one for advocating homeo in the treatment of infection by COVID-19 and the other for blaming COVID-19 on 5G.


https://retractionwatch.com/2020/07/27/blaming-overflow-of-manuscripts-and-obviously-biased-reviewers-journal-will-retract-homeopathy-covid-19-paper/

Excerpts below:

Blaming “overflow of manuscripts” and “obviously biased” reviewers, journal will retract homeopathy-COVID-19 paper.

A public health journal will be retracting a paper that argued for the adoption of homeopathy in the fight against the coronavirus pandemic, according to the editor in chief.


We reported on Saturday that the Journal of Public Health: From Theory to Practice, a Springer Nature title also known by its German name, Zeitschrift für Gesundheitswissenschaften, had published “Homeopathy combat against coronavirus disease (Covid-19)” on June 5.

At the time, we had not yet heard from Joachim Kugler, the journal’s editor, about how this might have happened. Today, Kugler told Retraction Watch:

You are tipping the finger in an open wound. Over the last weeks, we experienced an overflow of manuscripts, esp. with regard to COVID-19. The paper was reviewed by two reviewers who were obviously biased. Unfortunately, our quality control was not properly working, so the manuscript got accepted. We are now discussing with the publishers to retract this article soon.

In any case, I will write an editorial note.


https://retractionwatch.com/2020/07/26/paper-blaming-covid-19-on-5g-technology-withdrawn/

Paper blaming COVID-19 on 5G technology withdrawn
A paper which argued that 5G cellphone technology could lead to infection with the novel coronavirus has been retracted, but not before scientific sleuth Elisabeth Bik wondered whether it was the “worst paper of 2020.”

The article, “5G Technology and induction of coronavirus in skin cells,” came from a group from Italy, the United States and Russia, and appeared in the Journal of Biological Regulators and Homeostatic Agents. The journal is published by Biolife, which asserts that it’s peer reviewed but has not responded to a request for comment.

The abstract is now marked “WITHDRAWN” on PubMed and the paper has disappeared from the journal’s website. The abstract has been preserved here. According to the authors:

In this research, we show that 5G millimeter waves could be absorbed by dermatologic cells acting like antennas, transferred to other cells and play the main role in producing Coronaviruses in biological cells.

The authors of the paper clearly have a problem with 5G — but also with math.



The rest is at those links.

Researchers use Electric Fields to Direct Cell Movement

This is the first I have heard of this. I was familiar with chemotaxis where cells engage in directed migration in response to chemical gradients. I have even heard of magnetotaxis where some bacteria align themselves in response to magnetic fields. But this I have not really come across before...

https://www.princeton.edu/news/2020/06/24/researchers-use-electric-fields-herd-cells-flocks-sheep

Excerpts below:


Princeton researchers created a device that uses electrical fields to herd cells like sheep. This time-lapse movie shows a 90-degree turn in a layer of cells viewed under a microscope for eight hours. Video courtesy of the researchers; GIF by Neil Adelantar


This time-lapse movie shows a programmed circle maneuver in a layer of cells over eight hours. At left, a microscope image of the cells; center, their trajectories; right, changes in the electrical field’s direction.
Video courtesy of the researchers; GIF by Neil Adelantar





Researchers use electric fields to herd cells like flocks of sheep
Molly Sharlach, Office of Engineering Communications

Scientists have long known that naturally occurring electrochemical signals within the body can influence the migration, growth and development of cells — a phenomenon known as electrotaxis. These behaviors are not nearly as well understood as chemotaxis, in which cells respond to chemical concentration differences. One barrier has been a lack of accessible tools to rigorously examine cells’ responses to electric fields.

The new system, assembled from inexpensive and readily available parts, enables researchers to manipulate and measure cultured cells’ movements in a reliable and repeatable way. In a paper published June 24 in Cell Systems, the Princeton team described the assembly and preliminary studies using the device, which they call SCHEEPDOG, for Spatiotemporal Cellular HErding with Electrochemical Potentials to Dynamically Orient Galvanotaxis.

The SCHEEPDOG device contains two pairs of electrodes that are used to generate electric fields along horizontal and vertical axes, as well as recording probes to measure voltage and integrated materials to separate the cells from chemical byproducts of the electrodes. The voltage level is similar to that of an AA battery concentrated over the centimeter-wide chamber containing the cells.

“What the cells perceive is sort of a virtual angle, and that allows us to program any complex maneuver, like a full circle,” said Cohen. “That’s really surprising — that’s an amazing level of control that we wouldn’t have expected to be possible, especially with thousands of neighboring cells executing these maneuvers on command.”

The study “adds to the growing appreciation of cells’ responses to bioelectric aspects of their environment,” said Michael Levin, who directs the Center for Regenerative and Developmental Biology at Tufts University and was not involved in the research.


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