Maxine Francesco Baculo

virtue and knowledge • leapmed ‘21 • ustmed '25

[Maxine Francesco Baculo @maxfgcbaculo]

Always do it for the people.

[Veera Rajagopal  @doctorveera]

A fascinating work is published today @Nature by Zhang & Zhang et al. on a serendipitous discovery of haemoglobin expression outside the RBC cells--in chondrocytes--and their critical role in keeping our cartilage alive under an oxygen-deprived environment.

https://t.co/DPhuZN1JGE

Our school teachers taught that haemoglobin (Hb) is an oxygen-transporting protein expressed exclusively in the red blood cells. Although there exist occasional sporadic reports of Hb expression outside the RBCs (e.g. neurons, retinal cells etc.), no one would have guessed Hb would play a critical role (required for survival) outside the RBCs.

The discovery
When studying the cartilage growth plate of neonatal mice, the authors noticed eosin-positive structures in the chondrocytes (cartilage cells) that resembled structures seen in RBCs. Out of curiosity, the researchers went on to stain and examine the chondrocytes of different cartilage tissue types both from mice and humans. They realized that no matter the source or species, the cells always displayed eosin-positive structures under the microscope.

The curious researchers were determined to find out what these structures are made of. They carefully dissected these structures out and studied the protein components using mass spectrometry and were surprised to learn the results: the top hits were Hb proteins.

Unable to believe the results, they went on to study the proteins using different methods--western blotting, immunohistochemistry--and every time they ended up with the same results: the cytoplasm of cells was loaded with organelles-like bodies made of haemoglobin proteins. Finally, they came to the realization that Hb is abundantly produced in chondrocytes. They named these cytoplasmic Hb bodies as "Hedy".

Structure of Hedy
The authors studied the structure and formation of Hb bodies floating in the cytoplasm. Are they like an organelle? Do they have a membrane? Through various experiments, the researchers found that the Hedy structures do not have a membrane. The Hb proteins condense together by phase separation to form organelle-like structures in the cytoplasm. This condensation is itself an evolved process, requiring specific sequence structures of the Hb protein.

Globin switching
We know that there are different forms of Hb each expressed during different developmental stages: embryonic, fetal and adult Hb. There exists a sophisticated molecular machinery (which was believed to be RBC-specific) that switches one Hb type to the other at appropriate times. Using gene silencing experiments, the authors were further awestruck to find that the chondrocytes too switched their Hb types from embryonic to fetal to adult stages, just like RBCs!

Regulation of chondrocyte Hb production
It is well known that hypoxia induces Hb production via upregulating hypoxia-inducible factors (HIFs), an evolutionarily conserved molecular mechanism (Nobel Prize 2019; https://t.co/Sifi8LuYIX). But it turned out that chondrocytes have evolved to increase their Hb expression not via HIF proteins, but through a different protein, the same protein that is required for fetal to adult Hb switching: KLF1 (https://t.co/Zn0X8GpYdq).

How important is Hb for chondrocytes?
Such a high Hb expression in chondrocytes with similar globin switching behaviour as RBCs would mean that this Hb is critical for chondrocytes' survival. By deleting the Hbb gene specifically in the chondrocytes, the authors found that without Hb the chondrocytes die killing the animal a few days after birth.

Conclusion
Continuous oxygen supply is a prerequisite for the survival of cells in all tissues. The only way the cells can receive oxygen is through RBCs in the blood, which requires the tissue to be highly vascularized. When demand exceeds the supply, the cells evolve to survive an oxygen-depriving environment.

Muscles evolved to produce their own globin--myoglobin which has a higher affinity to oxygen than Hb thereby withholding O2 during oxygen excess states and releasing it back during oxygen-deprived state (during exercise). Likewise, the brain has its own globin: neuroglobin (https://t.co/6v78zvHajP).

Today, we are learning that cartilage (an avascular tissue), too, has its own globin. But unlike muscle and brain, have evolved to store oxygen not by making a new type of globin but by making just the same type as the ones in RBCs, but with a higher affinity than RBC Hb.

When it comes to fundamental biology, we often assume that we have found everything and then one day a discovery like this drops, hitting us on the head to make us realize that there is a whole universe of hidden biological secrets waiting to be discovered.

Some recent posts:
1. Gene x sex interaction of PNPLA3 I148M variant (https://t.co/RFegHHRS2z)
2. Effect of consanguineous marriage on the risk of common diseases in offsprings (https://t.co/dTkPsl935K)
3. Whole genome vs. Whole exome sequencing. Which is more cost-effective for genetic association studies? (https://t.co/BCwMzw4g16)

[The Nobel Prize @NobelPrize]

BREAKING NEWS
The 2023 #NobelPrize in Physiology or Medicine has been awarded to Katalin Karikó and Drew Weissman for their discoveries concerning nucleoside base modifications that enabled the development of effective mRNA vaccines against COVID-19.

[Leni Robredo @lenirobredo]

Muli, nagpapasalamat ako sa sipag, pagkamalikhain, at pusong dinala ng ating hanay sa kampanya. Dahil sa inyo, nasilip natin ang uri ng lipunang kaya nating maabot.

Alam kong pinoproseso pa ninyo ang mga pangyayari kahapon.

[JC Gotinga @JCGotinga]

OUTTAKES: VP Leni Robredo

Reporters stake out to capture fleeting moments with a VIP. You end up with successive shots, hoping for one good take.

Early in her term @lenirobredo tended to avoid the media. She now says she regrets it because it left room for fake news to spread.

[I Keep It Taco 𓆏 @IKeepItTaco]

My girlfriend rly picked valentine's day to argue that she's better than me at league so we 1v1'd LMFAO

[🌻🌾 Mango Bango 🌾🌻 @yellowestmango]

Sett using his E to pull all of his friends into a hug is the cutest damn thing I've ever seen, I feel so blessed, you're so precious Sett league of legends 😭💖❣️💕♥

[Maxine Francesco Baculo @maxfgcbaculo]

(Me, a med student, explaining to my mother the benefits of using sunscreen and other skin-related products)

Mama: Anak, pwede ka nang maging...

Me: Dermatologist?

Mama: Hindi. Yung nagbebenta sa mall.

Baka iba talaga calling ko 😅

[Maxine Francesco Baculo @maxfgcbaculo]

@kimatendido Thank you Bobie! 🥰

[Maxine Francesco Baculo @maxfgcbaculo]

Made this article during one of my breaks while studying for our final exams. Check it out at Philippine Daily Inquirer's Young Blood! 🌱

[Inquirer Opinion @Inq_Opinion]

From puzzles to purpose https://t.co/eRFGNwvqnm

[philbertdy.bsky.social @philbertdy]

Oh hey, Bambanti's going on Netflix. It's one of those small grant-funded Filipino films that just kind of got forgotten about. It's a solid little picture.

[FILMIFINO @filmifino]

the beauty of philippine cinema

[SINAG @sinagtulong]

‼️ CALL FOR HELP ‼️
We are SINAG— an independent, non-profit youth organization by UST LEAPMed students who aim to help our fellow Filipinos affected by Typhoon Ulysses in Region 2 through the project, “Kapit-Bisig Para sa Cagayan.”

(1/2)

#TyphoonUlysses
#SinagPagAsa
#ReliefPH

[Maxine Francesco Baculo @maxfgcbaculo]

@andrei_np At maglalaro ng wild rift 🥳

[Dr. Glaucomflecken @DGlaucomflecken]

Happy Halloween

[The Good Drive 2023 | @thegooddrive23]

Hello, everyone! We are reviving this drive for the benefit of our brother, Mulbert Dominguez, who suffered subarachnoid hemorrhage last September 16, 2020. Once again, we are humbly asking for your support and donations.
#ParaKayMulbert

[DayonTuon @dayontuon_ph]

Let's support education through pledging/donating to help our 1st school beneficiary:

𝗣. 𝗞𝗜𝗡𝗗𝗔𝗧 𝗘𝗟𝗘𝗠𝗘𝗡𝗧𝗔𝗥𝗬 𝗦𝗖𝗛𝗢𝗢𝗟.

Check our donation link for full instructions at https://t.co/GnVqHi6j73.

RTs are appreciated! Every effort counts! #PadayonSaPagtuon

[Ronnie E. Baticulon @ronibats]

Today, I was invited to talk about being a doctor-writer in the Lit class of @UST1611official LEAPMed. What an honor to meet the pioneer batch! As I said, reading is important, so here’s the list of short stories I recommend to Filipino med students! https://t.co/ZEExOBrK2W

[Maxine Francesco Baculo @maxfgcbaculo]

@_cabrerafrances Waah! Miss you doktora! Stay safe 🥰

[Maxine Francesco Baculo @maxfgcbaculo]

During a kwentuhan session with my mom...

Me: Ma, ano sa tingin niyo yung specialty na bagay sa akin?
Mama: Yung sisig.
Me: Ha? Sisig? Saan galing 'yan?
Mama: Favorite mo 'yon 'di ba?
Me: Hala Ma. I meant, like, surgery or pediatrics. HAHAHAHA

[Earl Louis Sempio @earlouismd]

2 months ago sinabihan ka na bawal lumangoy dahil mataas alon.
Tapos ngayon mataas pa rin alon pinayagan ka.

Di ka pa rin marunong lumangoy at walang salbabida.