• The 2018 Nobel Prize in Physiology or Medicine
    The Nobel Prize in Physiology or Medicine has been awarded multiple times for work related to cancer therapy. In 1966, it was awarded to Charles Huggins "for his discoveries concerning hormonal treatment of prostatic cancer." In 1988, Gertrude Elion and George Hitchings secured the prize "for their discoveries of important principles for drug treatment," which included chemotherapy. Joseph Murray and E. Donnall Thomas won the award in 1990 "for their discoveries concerning organ and cell transplantation in the treatment of human disease," which included bone marrow transplant for leukemia.1 Most recently, in 2018, it was awarded to James Allison and Tasuku Honjo "for their discovery of cancer therapy by inhibition of negative immune regulation."1
  • The 2019 Nobel Prize in Physiology or Medicine
    Oxygen is critical for supporting animal life, and animals possess adaptive mechanisms to ensure sufficient supply of oxygen to tissues. The Nobel Prize in Physiology or Medicine has been awarded multiple times for work related to this critical molecule. In 1931 it was awarded to Otto Warburg for discovering the nature and mode of action of the "respiratory enzyme," and in 1938 it was awarded to Corneille Heymans for demonstrating how blood oxygen sensing via the carotid body controls the respiratory rate through direct communication with the brain.1 More recently, the 2019 Nobel Prize in Physiology or Medicine was jointly awarded to William Kaelin, Jr, Peter Ratcliffe, and Gregg Semenza for their discoveries related to how cells sense and adapt to oxygen availability.1
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    The Rb—E2F Switch: Regulation of Cellular Quiescence
    Cell cycle progression and proliferation have been well-studied, while much less attention has been given to cellular quiescence corresponding to the G0 phase of the cell cycle. Recent studies have determined that G0 is not a single state, but a spectrum of quiescent states associated with an active transcriptional program2,4. In a new study, Yao and colleagues examined the factors that control entry into and exit from quiescence and commitment to cell cycle progression2. Being able to control this transition may be an untapped therapeutic target for cancer and other proliferative diseases2.
  • The Speed Limit of the Cell Cycle
    The growth and division of cells, a process termed the cell cycle, consists of four phases in eukaryotes. DNA replication occurs during the synthesis (S) phase whereas cell division occurs during the mitosis (M) phase. Two additional gap phases (G1 and G2) that occur before the S and M phases, respectively, identify any problems during DNA replication and chromosome segregation, and pause the cycle in order to allow for appropriate repairs1. Cell cycle arrest primarily occurs through the inhibition of cyclin-dependent kinases (CDKs), whose activity is in turn regulated by various modulators. Cyclins are necessary to activate CDKs, while Ink4 proteins and those in the Cip and Kip family (such p21, p27, and p57) exert an inhibitory effect2. Proper regulation of the cell cycle is a critical process for normal cell biology, and the loss of control (for example, through mutations that produce abnormal CDK-cyclin complexes) leads to uninhibited cell growth and cancer3.
  • The Transcriptional Effects of MED1
    Sp1 is a transcription factor that can regulate a variety of genes through direct binding to GC-rich areas of DNA and through interactions with other transcription factors including c-myc, c-Jun, and STAT11. Activation of Sp1 requires the activity of CRSP, or cofactor required for Sp1 activation, and one subunit of this protein is MED1, or mediator of RNA polymerase II transcription subunit 12. MED1 is the largest subunit in the CRSP complex and it can also be a part of the more ubiquitous Mediator complex, which activates RNA polymerase II transcription of a wide range of gene targets throughout the genome. Phosphorylation of MED1 appears to support its inclusion in the Mediator complex3. MED1 is furthermore the component of the Mediator complex that targets this complex to nuclear hormone receptors4. MED1 may be referred to by several other names including CRSP1, TRAP220, CRSP200, and PBP.
  • The VISTA of Cancer Treatment
    In a healthy host, negative checkpoint regulators (NCRs) reign in the T cell immune response, maintaining tolerance and preventing immunopathology. However, in the tumor microenvironment, NCRs can promote immune escape. Recent clinical trials have investigated the use of blocking antibodies to prevent this NCR-driven immune escape. Targeting the NCRs cytotoxic T lymphocyte-associated molecule-4 (CTLA-4) or programmed cell death 1 (PD-1) has shown clinical promise, but either results in only a 10-20% response rate when provided as monotherapy.1 However, clinical trials with combined anti-CTLA-4 and anti-PD-1 monoclonal antibody treatment have improved response rate to 40-60%.1
  • Welcome to the (B7) Family
    The adaptive immune system relies on T cells to recognize and respond to both native and foreign antigens. Appropriate T cell response is required for maintaining self-tolerance and eliminating pathogens, while aberrant T cell response can lead to autoimmune disease, rejection of transplanted organs, or cancer.
  • When DNA Repair Goes Wrong
    Within the genome there exist short, repeating segments of DNA - motifs of, typically, one through six base pairs that repeat five to 50 times1. These segments of DNA are known as microsatellites and comprise approximately 3% of the human genome, in both coding and noncoding regions of the genome2,3. Microsatellites are particularly susceptible to accumulating mutations during DNA replication. This phenomenon is known as microsatellite instability, or MSI. Microsatellites have a mutation rate of 10-100-fold higher than the average DNA segment4. These mutations are hypothesized to be caused by slipped strand mispairing5, where the DNA polymerase disengages from the DNA and reassociates at a nearby but different location.
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    "B" Is For Bursa
    The B lymphocyte lineage of cells is responsible for antibody production. Most of us assume that B lymphocytes, or B cells, got their name because they mature in the bone marrow: "B" for bone marrow. However, this is not really the case. The "B" in B cells comes from the Bursa of Fabricius in birds.
  • HERC2, Don’t It Make My Brown Eyes Blue
    Does Crystal Gayle have blue or brown eyes?

    A Google search on this subject tells us that she is reported to have brown or hazel eyes (isn't it great to have such critical information at our fingertips, thanks Google).

    But as the song says, when her man has found someone new, don't it make her brown eyes blue? But what really does make someone's eyes blue?
  • Navigating the Sea of Blots
    The terms Western blot, Southern blot, and Northern blot are so widely known, accepted, and used that we refer to them simply as Westerns, Southerns, and Northerns. Ever wonder how they got their names?
  • Self-Renewal
    No bars on your cell phone, no connection for mail, just warm sand on your soles, a salty breeze on your skin, and a frosty coconut concoction cooling you from the inside out. Then the sun sets west pulling down its heat, leaving only cool stars on the ocean that break apart at the shore. And under the tone of fizz and breaking waves, Mr. Marley is in the distance, telling you in a most lovely and melodic manner…"turn your lights down low". The day is done and all that will be left is the relaxing energy that will become your self-renewal.
  • The Big BRD Wolf
    In recent years antibodies specifically targeting proteins that contain regions known as bromodomains have become popular among researchers. The bromodomain targets BRD proteins to other proteins known as histones. Histones bind to DNA, acting as a gatekeeper that can allow or prevent other proteins from interacting with DNA. Using their bromodomains, the BRD proteins can activate histone proteins allowing other proteins, such as RNA polymerase, to interact with DNA. Once RNA polymerase interacts and binds to DNA it can perform its function of transcribing RNA.
  • UBA6: An E1 enzyme critical for hippocampal and amygdalar development
    Protein turnover and degradation is an essential component for the proper functioning of all eukaryotic cells. Proteins are tagged for degradation by the addition of ubiquitin, a process which requires three distinct enzyme classes. The classes are E1, the ubiquitin-activating enzyme; E2, the ubiquitin-conjugating enzymes; and E3, the ubiquitin-protein ligases. Although many E2 and E3 enzymes exist, the canonical ubiquitination pathway has only one ubiquitin-activating E1 enzyme, termed UBE1. However, within the last decade, researchers have identified a second ubiquitin-activating E1 enzyme, termed UBA1, 2, 3. UBA6 has both distinct and overlapping traits with UBE1. For example, these enzymes are able to activate ubiquitin but UBA6 is also able to activate the ubiquitin-like modifier, FAT10. Both E1 enzymes can interact with a population of E2 enzymes but only UBA6 interacts with the E2 enzyme USE14.
  • You are what (and when) you eat
    Humans and animals typically consume nutrients in a feeding-fasting cycle. For example, in the typical breakfast-lunch-dinner daily eating pattern, consumption of a meal is usually followed by at least several hours of fasting. This feeding-fasting cycle means that organisms must be able to cope with large shifts in concentrations of nutrients such as glucose, amino acids, and lipids within the blood. The blood levels of these nutrients reach a peak shortly after a meal, and may become very low during fasting. Maintenance of homeostasis during the feeding-fasting cycle requires careful coordination of gene regulation to optimize metabolic efficiency. If gene regulation is disturbed or timed incorrectly, the resulting metabolic dysfunction can lead to development of diseases such as obesity and diabetes.1 Thus, it seems as though not only what an organism eats, but also when that organism eats, is important for maintaining metabolic health.