STAT3 gain-of-function mutations connect leukemia with autoimmune disease by pathological NKG2Dhi CD8+T cell dysregulation and accumulation

The association between cancer and autoimmune disease is unexplained, exemplified by T cell large granular lymphocytic leukemia (T-LGL) where gain-of-function (GOF) somatic STAT3 mutations correlate with co -exist-ing autoimmunity. To investigate whether these mutations are the cause or consequence of CD8+ T cell clonal expansions and autoimmunity, we analyzed patients and mice with germline STAT3 GOF mutations. STAT3 GOF mutations drove the accumulation of effector CD8+ T cell clones highly expressing NKG2D, the receptor for stress-induced MHC-class-I-related molecules. This subset also expressed genes for granzymes, perforin, interferon-y, and Ccl5/Rantes and required NKG2D and the IL-15/IL-2 receptor IL2RB for maximal accumula-tion. Leukocyte-restricted STAT3 GOF was sufficient and CD8+ T cells were essential for lethal pathology in mice. These results demonstrate that STAT3 GOF mutations cause effector CD8+ T cell oligoclonal accumu-lation and that these rogue cells contribute to autoimmune pathology, supporting the hypothesis that somatic mutations in leukemia/lymphoma driver genes contribute to autoimmune disease.Peer reviewe

Discovery of a recent, natural whale fall on the continental slope off Anvers Island, western Antarctic Peninsula

Whale falls provide a substantial, nutrient-rich resource for opportunistic species in areas of the ocean that may otherwise be largely devoid of food. We report the discovery of a natural whale fall at 1430 m depth in the cold waters of the continental slope off the western Antarctic Peninsula. This is the highest latitude whale fall reported to date. The section of the carcass we observed—the tail fluke—was more complete than any previously reported natural whale fall from the deep sea and in the early stages of decomposition. We estimate the entire cetacean to measure 5 to 8 m in length. The flesh remained almost intact on the carcass but the skin had been removed from the entire section except for the end of the fluke, clearly exposing blubber and soft tissue. The absence of skin indicates rapid and homogenous removal by scavengers. The dominant macrofauna present were crustaceans, including most prominently the lithodid crab Paralomis birsteini, and zoarcid fish typical of the ‘mobile-scavenger’ successional stage. The density of mobile macrofauna was greatest on the carcass and declined to background levels within 100 m, indicating that they were attracted to the whale fall. This whale fall offers an important opportunity to examine the decomposition of a carcass under deep-sea conditions at polar latitudes

Poly(anhydride-esters) Comprised Exclusively of Naturally Occurring Antimicrobials and EDTA: Antioxidant and Antibacterial Activities

[Image: see text] Carvacrol, thymol, and eugenol are naturally occurring phenolic compounds known to possess antimicrobial activity against a range of bacteria, as well as antioxidant activity. Biodegradable poly(anhydride-esters) composed of an ethylenediaminetetraacetic acid (EDTA) backbone and antimicrobial pendant groups (i.e., carvacrol, thymol, or eugenol) were synthesized via solution polymerization. The resulting polymers were characterized to confirm their chemical composition and understand their thermal properties and molecular weight. In vitro release studies demonstrated that polymer hydrolytic degradation was complete after 16 days, resulting in the release of free antimicrobials and EDTA. Antioxidant and antibacterial assays determined that polymer release media exhibited bioactivity similar to that of free compound, demonstrating that polymer incorporation and subsequent release had no effect on activity. These polymers completely degrade into components that are biologically relevant and have the capability to promote preservation of consumer products in the food and personal care industries via antimicrobial and antioxidant pathways