Heart disease can be caused by a myriad of factors, including age, diet, and genetic markers. Viral infections can activate the immune system against self-antigens including cardiac myosin. In these cases, cardiac myopathy can be autoimmune in nature. Female NOD mice carrying the human Major Histocompatibility Complex protein HLA.DQ8 demonstrate spontaneous myocarditis with enlarged hearts, autoreactive T-cells, and antibodies to cardiac specific myosin. To determine the cellular effectors of this pathology, I depleted T-cells (CD4+ and CD8+) using monoclonal antibodies in the NOD.DQ8 background to attempt to rescue the disease phenotype. I also investigated the sex-bias by hormone treating both male and female mice (at various ages) to determine whether the increased susceptibility to heart disease is driven by hormonal differences.
Like us, all mammals can die of a broken heart. Funny thing is that broken hearts are bigger than average, bigger than the healthy muscle that pumps our life through our bodies, bigger than the right fist held over the left breast that we learn in 7th grade health.
This is my own work. These lab mice died of swollen, broken hearts. They were humanized, given molecules from a human body to mimic our defense system. What did these molecules do but eat the heart alive.
I slice open their skin and crack open their rib cage and discard their blood, matted in their fur, as it’s of no use to me. I take only their heart, sometimes still beating, so large, and I lie it on a perfectly clean – sterile – plastic dish. But I don’t stop there. I cut out spleen and liver and lymph nodes to steal the cells, half man half mouse, that did the breaking.
Every time my heart has been broken, I have felt it grow too large. It never shrinks. I feel every laborious beating of the muscle. Every time my heart has been broken, how I’ve longed to cut it out, to slice open my skin and crack open my rib cage. To discard my blood, now of no use to me. To place my heart, broken, swollen, sometimes still beating, in a sterile white dish to determine its mass. To collect the cells of my heart and the cells of my body to learn how this happened, how this could have happened. To learn who broke this heart, and why, so that it can never happen again.
Taneja V, Behrens M, Cooper LT, et al. Spontaneous Myocarditis mimicking human disease occurs in the presence of an appropriate MHC and non-MHC background in transgenic mice. Journal of molecular and cellular cardiology. 2007;42(6):1054-1064.)
I worked on a related project as a research student at the Mayo Clinic in 2003.
Life is mostly composed of the elements carbon, hydrogen, nitrogen, oxygen, sulfur, and phosphorus. Although these six elements make up nucleic acids, proteins, and lipids and thus the bulk of living matter, it is theoretically possible that some other elements in the periodic table could serve the same functions. Here, we describe a bacterium, strain GFAJ-1 of the Halomonadaceae, isolated from Mono Lake, California, that is able to substitute arsenic for phosphorus to sustain its growth. Our data show evidence for arsenate in macromolecules that normally contain phosphate, most notably nucleic acids and proteins. Exchange of one of the major bio-elements may have profound evolutionary and geochemical importance.
I’ve never been wrong. Not ever. Not once. If I say something, it’s true. If I say something, only I can unsay it. But I won’t have been wrong. Nope, not me. You see, life looks like this. Some of this and a little of that. This is what makes up life. There are differences between life and not-life. Carbon is life. Gold is not-life. I’ve never, not once, been wrong. Oxygen is life. Water, so delicious; air, so precious as it fills up my lungs. Water, air, what would we do without you? Caesium, Arsenic, Palladium. Not-life, not-life, not-life. Maybe on some other planet, maybe in some other life. But not this life. Not here. There will never be a bug or a mouse or a man made of anything but this: carbon and oxygen and nitrogen, breathed in and breathed out from the air. You can’t build a man from poison, from arsenic. I’ve never been wrong. Not even a cockroach. Not ever. Not even a bacterium. Not once.
Wolfe-Simon F1, Switzer Blum J, Kulp TR, Gordon GW, Hoeft SE, Pett-Ridge J, Stolz JF, Webb SM, Weber PK, Davies PC, Anbar AD, Oremland RS. A bacterium that can grow by using arsenic instead of phosphorus. Science 03 Jun 2011: aVol. 332, Issue 6034, pp. 1163-1166.
The protein clathrin mediates one of the major pathways of endocytosis from the extracellular milieu and plasma membrane. In single-cell eukaryotes, such as Saccharomyces cerevisiae, the gene encoding clathrin is not an essential gene, raising the question of whether clathrin conveys specific advantages for multicellularity. Furthermore, in contrast to mammalian cells, endocytosis in S. cerevisiae is not dependent on either clathrin or adaptor protein 2 (AP2), an endocytic adaptor molecule. In this study, we investigated the requirement for components of clathrin-mediated endocytosis (CME) in another unicellular organism, the amoeba Dictyostelium. We identified a heterotetrameric AP2 complex in Dictyostelium that is similar to that which is found in higher eukaryotes. By simultaneously imaging fluorescently tagged clathrin and AP2, we found that, similar to higher eukaryotes, these proteins colocalized to membrane puncta that move into the cell together. In addition, the contractile vacuole marker protein, dajumin-green fluorescent protein (GFP), is trafficked via the cell membrane and internalized by CME in a clathrin-dependent, AP2-independent mechanism. This pathway is distinct from other endocytic mechanisms in Dictyostelium. Our finding that CME is required for the internalization of contractile vacuole proteins from the cell membrane explains the contractile vacuole biogenesis defect in Dictyostelium cells lacking clathrin. Our results also suggest that the machinery for CME and its role in organelle maintenance appeared early during eukaryotic evolution. We hypothesize that dependence of endocytosis on specific components of the CME pathway evolved later, as demonstrated by internalization independent of AP2 function.
What makes us live
[ Necessity – for one
– financial and otherwise. ]
A body of one of our bodies. A body of
both of our bodies. Our bodies bound by
the same walls, the same membrane, now
holding inside from out.
A home for each of us
and for both.
A front door we both share.
We’d never have become friends if we
We were thrown together, roommates,
your door next to mine for five years.
It stung because I knew it was true.
You, hard working but outside of that more funny than political, wanting always to travel and drink and laugh. Me, always, my nose in a book and trying to change the world, but maybe never opening my eyes to it.
Making dinner one after the other. Making
dinner together sometimes.
We have so little in common except that we care for each other. We took care of each other through all the false starts and failure and bad days not just in a life but in what it took us to become our own type of doctor.
All this came slow.
Together, we grew strong.
All that that took years.
Together, we grow strong.
Our doors no longer three feet apart. When we shared a home, you studied a little amoeba that could grow alone sometimes and sometimes that comes together into a single stalk, a single organism.
Our world, now much larger,
now no longer bound by the same walls.
Now even without coming home to
the same front door, some windows, one
kitchen, two sinks. You in an office, me
in a lab. Our world larger but now a single
stalk, a single city, which we still share.
Laura Macro, Jyoti K. Jaiswal* and Sanford M. Simon. Dynamics of clathrin-mediated endocytosis and its requirement for organelle biogenesis in Dictyostelium. Journal of cell science 125, 5721–5732.