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Letter from H.K Lewis & Co. LTD to Dr. Alfred E. Cohn
No full textLetter from H.K Lewis & Co. LTD to Dr. Alfred E. Cohn, 1934
Alfred E. Cohn (1879-1957), physician, humanist, author, and bibliophile, was one of the first cardiologists in the United States. He was born in New York City and received an MD from the College of Physicians and Surgeons at Columbia University in 1904. Between 1907 and 1909 he studied in Freiburg, Vienna, and London. When he returned to the United States, Dr. Cohn joined the staff of Mount Sinai Hospital in New York. In 1911, he moved to the Rockefeller Hospital, bringing his electrocardiograph with him. He remained at Rockefeller for the rest of his career, retiring in 1944. Dr. Cohn took a leading role in organizations such as the New York Heart Association, New York Academy of Medicine, Veterans Administration, China Medical Board, Asia Institute, Sydenham Hospital, and the Committee for Displaced Foreign Scholars and Displaced Foreign Physicians.https://digitalcommons.rockefeller.edu/objects-tell-stories/1010/thumbnail.jp
Journal Club Dinner, details
No full textJournal Club Dinner film, details
Photo by Lubosh Stepanekhttps://digitalcommons.rockefeller.edu/objects-tell-stories/1012/thumbnail.jp
Old Filing System Rolodex Used by the Library
No full textOld filing system Rolodex used by the Library, circa late 1960s
In 1964, Dr. Kreek (1937-2021) joined the lab of Vincent Dole at The Rockefeller Institute for Medical Research. Vincent Dole, along with psychiatrist Marie Nyswander, was researching the biology of addiction. Together with Kreek, the researchers determined that heroin addiction involved neurochemical alterations and that the longer-acting orally administered opioid analgesic methadone could potentially be used to help treat it.The recognition by Dr. Kreek and her colleagues that heroin addiction was a disorder of the brain that had behavioral consequences was a major shift in a world where addiction was still considered by most people to be a criminal behavior or a moral failing. Working with formerly incarcerated people in active opioid use whom they brought to Rockefeller University Hospital, the research team found that individuals with severe heroin addiction were no longer able to obtain a high (euphoria) from the drug but took it just to feel normal—a crucial distinction that remains central to how we understand addictive behavior today.https://digitalcommons.rockefeller.edu/objects-tell-stories/1029/thumbnail.jp
Integration Sites in the Persistence of Latent HIV-1
Full text linkHuman immunodeficiency virus (HIV-1), the pathogen that causes acquired immune deficiency syndrome (AIDS), remains one of the world\u27s most pressing health issues. Since the beginning of the HIV/AIDS epidemic, over 32M people have succumbed to AIDS-related illnesses. Despite remarkable advances in HIV-1 biology, neither a vaccine or cure have been achieved. While antiretroviral therapy (ART) has significantly improved disease outcomes for people with HIV-1 and reduced transmission, treatment is often accompanied by long-term side effects or stigma, or impeded by limited access to health care. Furthermore, because viral load quickly rebounds upon treatment interruption, ART is required to be a life-long medication. The major barrier to HIV cure is the persistence of long-lived latently infected CD4+ T cells. Collectively known as the latent reservoir, these cells carry integrated HIV-1 proviruses that are transcriptionally quiescent and are thus able to evade host immunity and virus-induced cell death. Cellular and molecular characterization of the latent reservoir is challenging because latently infected cells are exceedingly rare and express no known surface marker. Moreover, the infected cell pool is dominated by cells containing defective proviruses which cannot contribute to rebound viremia. The work herein elucidates the contribution of proviral integration site to HIV-1 latency and the maintenance of the replication-competent, or intact, reservoir. Using an innovative single-cell sequencing technique that provides paired proviral sequence and integration site information, as well as enables selective analysis of replication-competent HIV-1, I interrogate the integration landscape of HIV infected individuals whose reservoirs are dominated by a small number of large expanded clones. By performing viral outgrowth assays, I also show that replication-competent proviruses harbored in the expanded clones readily produce infectious virion upon stimulation. I report an integrative analysis of the clonal dynamics, inducibility, and genomic position of intact proviruses in ARTsuppressed individuals, and demonstrate that proviruses in expanded clones across patients are significant more likely to be mapped to Krüppel-associated box (KRAB) domain-containing zinc finger (ZNF) genes on chromosome 19. Transcriptional and epigenetic meta-analysis of primary CD4+ T cells reveal that these specific chromosomal locations harboring integrated provirus are associated with genes downregulated upon cellular activation. Taken together, the data indicate that selected sites in the genome, including ZNF genes, can be especially permissive for maintaining HIV-1 latency during memory CD4+ T cell clonal expansion. These findings demonstrate that gene activity at the integration site impacts the survival and persistence of intact, expanded HIV proviruses in infected cells, and provide evidence that the quality, not only the quantity, of the latent reservoir must a key consideration in HIV-1 cure strategies
Rebecca Lancefield\u27s files
No full textRebecca Lancefield\u27s files (Fischetti laboratory, Bronk Building)
When Rebecca Lancefield began studying the bacteria known as hemolytic streptococci, no one recognized that these microbes caused common—and dangerous—human diseases such as strep throat, scarlet fever, rheumatic fever, acute kidney disease, and impetigo. Beginning in 1918, and continuing over the course of six decades, Lancefield devised a system for classifying the dozens of types of streptococcal bacteria. This system, still in use today, laid the groundwork for understanding the clinical course of these diseases and how they are transmitted.
Photo by Lubosh Stepanekhttps://digitalcommons.rockefeller.edu/five-rockefeller-trailblazers/1009/thumbnail.jp
Reproductive Resilience of Aedes Aegypti Mosquitoes
Full text linkFemale Aedes aegypti mosquitoes impose a severe global public health burden as vectors of viruses that cause dengue, chikungunya, yellow fever, and Zika, and parasites that cause lymphatic filariasis. Under optimal environmental conditions, Aedes aegypti females have access to human hosts that provide blood proteins required for egg development, conspecific males that provide sperm required for fertilization, and freshwater in natural or manmade containers that serves as an egg-laying substrate suitable for offspring survival during larval and pupal stages. As global temperatures rise, Aedes aegypti females are faced with climate challenges like intense droughts and intermittent bouts of precipitation, which create unpredictable, suboptimal conditions for egg-laying. Yet, this species is highly invasive, adeptly domesticated, and continues to expand its stronghold across most continents. How do female Aedes aegypti mosquitoes successfully reproduce when freshwater availability is unpredictable? What behavioral and molecular adaptations have evolved to ensure the reproductive flexibility and resilience of this species when they are faced with intense droughts and changing climates? Here we show that the reproductive behaviors of adult Aedes aegypti females are tightly interconnected and centered on precise spatiotemporal control of egg-laying in a manner that balances intrinsic physiological needs with extrinsic environmental constraints to ensure maximal fitness. Specifically, in drought-like conditions simulated in the laboratory, females that have mated and blood fed will retain mature eggs in their ovaries for extended periods, while maintaining the viability of these eggs until they can be laid in freshwater. Using transcriptomic and proteomic profiling of Aedes aegypti ovaries, we identify two previously uncharacterized genes that we name tweedledee and tweedledum, each encoding a small, secreted protein that both show ovaryenriched, temporally-restricted expression during egg retention. These genes are mosquito-specific, linked within a syntenic locus, and rapidly evolving under positive selection, raising the possibility that they serve an adaptive function. A CRISPR-Cas9- mediated mutation that disrupts both tweedledee and tweedledum together demonstrates that they are specifically required for extended retention of viable eggs. These results highlight an elegant example of taxon-restricted genes at the heart of an important adaptation that equips Aedes aegypti females with insurance to flexibly extend their reproductive schedule without losing reproductive capacity, thus allowing this species to exploit unpredictable habitats in a changing world
Sensory and Neuromodulatory Entrainment of Foraging States in C. Elegans
Full text linkForaging animals dynamically adjust their behavioral patterns over time to optimize feeding in their environment. In the nematode Caenorhabditis. elegans, foraging animals alternate between states of locomotory arousal. I observed that animals in low activity states remain nearby food patches, whereas highly aroused animals often exit patches to explore the external environment. Using different methods of behavioral state classification reveals different aspects of foraging behavior: previously described high arousal roaming and low arousal dwelling states reflect long-term changes in locomotory patterns, whereas an Autoregressive Hidden Markov model that classifies behavior on shorter time scales effectively segments food leaving behaviors. Adaptive foraging strategies rely on animals\u27 ability to integrate internally sensed physiological needs and external sensory cues with ongoing internal state. Consistent with this, I find that animals acutely unable to eat food drastically increase high arousal behavioral states and food leaving behavior, motivated by internal sensing of the absence of food. I also find that mutants lacking sensory transduction or neuromodulatory signaling each show dysregulated behavioral states surrounding food leaving behavior. In C. elegans, animals spontaneously alternate between roaming and dwelling states in environments that contain a uniform food density. However, I find that animals encountering environments with non-uniform food distributions entrain their behavioral state transitions to locally experienced changes in food density. Experience of dwindling food resources over several minutes triggers increased locomotion speed and stimulates roaming behavior, whereas entry into denser food patches suppresses speed and causes animals to dwell. In mutants with deficient chemosensory transduction, this sensory entrainment is lost. I also find that animals lacking a functional PDF receptor (PDFR-1) show both reduced roaming and attenuated sensory coupling of locomotory behavior. Restoring pdfr-1 expression in interneurons stimulates roaming but fails to rescue sensory coupling, suggesting that other sites of pdfr-1 expression may drive this. I conclude that internal states integrate sensory stimuli and physiological needs to facilitate effective foraging strategies on both short and long time scales
The Effect of Early Dietary Intervention on Alzheimer\u27s Disease-Related Pathology and Cognitive Function in Mice
Full text linkAlzheimer\u27s disease (AD) is a fatal cognitive disorder with proteinaceous brain deposits, neuroinflammation, cerebrovascular dysfunction, and extensive neuronal loss. AD is a multifactorial disease, and lifestyle factors, including diet, are likely associated with the development of AD pathology. Since obesity and diabetes are recognized as risk factors for AD, it might be predicted that a high fat diet (HFD) would worsen AD pathology. However, modeling HFD-induced obesity in animal models of AD has yielded inconclusive results. Some studies report a deleterious effect of HFD on Aβ accumulation, neuroinflammation, and cognitive function, while others report that HFD worsens memory without affecting AD brain pathology. Moreover, several studies report no major effect of HFD on AD-related phenotypes in mice, while other studies show that HFD might, in fact, be protective. The lack of a clear association between HFD consumption and AD-related pathology and cognitive function in AD mouse models might be explained by experimental variations, including AD mouse model, sex of the animals, composition of the HFD, and timeline of HFD consumption. Our study examined the effect of varying the timeline of HFD or control diet (CON) consumption on AD-related pathology and cognitive function in transgenic Tg6799 AD mice. HFD consumption that started at or before 3 months-of-age, prior to severe AD pathology, had protective effects in AD mice. Specifically, it reduced extracellular beta-amyloid (Aβ) deposition, decreased fibrinogen extravasation from blood vessels into the brain parenchyma, and improved cognitive function. RNAseq analysis revealed that HFD affected the expression of genes in the AD mouse cortex related to the stress response, protein folding, endoplasmic reticulum stress, chaperone-mediated protein folding, and the immune system process in AD mice. However, delaying HFD consumption until 6 months-ofage, when AD pathology is ubiquitous, did not provide neuroprotection in AD mice, as there was no change in cortical Aβ deposition in 11-month-old mice. Surprisingly, despite the delayed onset of HFD consumption, HFD still reduced the extravasation of fibrinogen into the brain. Overall, we demonstrate that the timeline of HFD consumption plays an important role in how dietary fats affect AD-related pathology and cognitive function in a transgenic mouse model of AD
Vintage Safety Goggles
No full textVintage safety goggles with green glass, circa 1940s
Courtesy of Laboratory Safety Departmenthttps://digitalcommons.rockefeller.edu/objects-tell-stories/1016/thumbnail.jp
Anthony Campo
No full textAnthony Campo, 1963
Through the early twenties, almost 75% of the institute’s laboratory glassware, equipment, microscopes, chemicals, and dyes were imported from Europe. Anthony Campo (1902-1982) and his colleagues in Purchasing handled the importing and customs clearance and arranged for delivery to the Institute. He came to RIMR in 1917 as a stock clerk and was appointed superintendent of Purchase and Supply and pharmacist in 1957, a post he held until his retirement in 1970. Anthony Campo recalled some of the odd items his department has been asked to procure: horse dander sweat and saliva; dwarf coconut seeds from South America; eggs of wild eagles and guinea hens; butterfly pupae in the diapause stage; and pregnant salamanders. One of the most exotic items requested was 40,000 firefly tails. He contacted the appropriate officials on the island of Jamaica who turned him down because this request might extinguish the winking summer lights and hurt the tourist trade.https://digitalcommons.rockefeller.edu/objects-tell-stories/1014/thumbnail.jp