Promiscuity of Exiguobacterium sp. AT1b o-succinylbenzoate synthase illustrates evolutionary transitions in the OSBS family.

Catalytic promiscuity, which is the ability to catalyze more than one reaction in the same active site, is thought to facilitate the evolution of new protein functions. Although many enzymes are catalytically promiscuous, there is little direct evidence to show how promiscuous activities evolved into biological functions. We are seeking evidence for this model by studying the o-succinylbenzoate synthase (OSBS) family. Most enzymes within this family only catalyze OSBS, which is a step in menaquinone synthesis. However, several characterized enzymes in one branch of the family (called the NSAR/OSBS subfamily) efficiently catalyze both OSBS and N-succinylamino acid racemization (NSAR). Based on genome context, NSAR appears to be the only biological function of some characterized NSAR/OSBS enzymes, while both activities are biologically relevant in others. The promiscuity model predicts that these enzymes evolved from an ancestral OSBS which promiscuously catalyzed NSAR as a side reaction that was not biologically relevant. If so, the model predicts that some extant OSBS enzymes would have low levels of promiscuous NSAR activity. This manuscript describes such an enzyme from Exiguobacterium sp. AT1b (ExiOSBS). We show that ExiOSBS efficiently catalyzes OSBS (kcat/KM=2.6×10(6) M(-1) s(-1)), but its efficiency for the NSAR reaction is only 41 M(-1) s(-1). Moreover, genome context indicates that OSBS is the only biologically relevant activity. ExiOSBS diverged from the NSAR/OSBS subfamily before NSAR emerged as a biologically relevant activity. These results provide evidence that NSAR activity originated as a promiscuous activity in an ancestor of the NSAR/OSBS subfamily.

CD5+ Diffuse Large B-Cell Lymphoma With Leukemic Transformation: A Rare Case With Central Nervous System Involvement, Treated With R-CHOP and Intrathecal Methotrexate/Cytarabine.

Diffuse large B-cell lymphoma (DLBCL) is one of several subtypes of non-Hodgkin's lymphoma, and one that can present in a myriad of ways. One unique and particularly aggressive presentation is leukemic transformation with CD5 positivity, which leads to systemic symptoms, a relatively high peripheral tumor load, and higher rates of CNS involvement. The prevalence of leukemic transformation has not been determined, as published literature is limited to case reports and small case series. CD5 positivity appears to be even rarer and is only found in a small fraction of DLBCL with leukemic transformation. Treatment regimens for this presentation have not been well-established due to the rarity of the disease and paucity of literature on the subject. Our patient, a 76-year-old female with a history of previously treated stage IIIB follicular lymphoma, was found to have CD5+ DLBCL with leukemic transformation. She was treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) along with intrathecal methotrexate (IT MTX)/cytarabine after CNS involvement was diagnosed. The patient tolerated therapy well, with an objective reduction in leukocytosis and blast count. To our knowledge, this is the first such case of CD5+ DLBCL with leukemic transformation treated with dose-reduced R-CHOP and IT MTX/cytarabine. Her response to therapy indicates that this regimen could be a viable option for the treatment of this exceedingly rare disease presentation.

Case of HER2neu+ Invasive Pleomorphic Lobular Carcinoma With Response to Conventional Neoadjuvant Chemotherapy: A Viable Option for an Exceedingly Rare Breast Cancer Type.

Invasive pleomorphic lobular carcinoma (IPLC) is an extremely rare form of breast cancer that accounts for less than 1% of all breast cancer cases. Due to this rarity, currently, there is a lack of an established standard of care for patients diagnosed with this form of breast cancer. In this case report, we present a 57-year-old female with a complex oncologic history diagnosed with clinical prognostic Stage IIA (ER 5%, PR 0%, HER2neu 3+) invasive pleomorphic lobular carcinoma of the left breast treated with neoadjuvant docetaxel, carboplatin, trastuzumab, and pertuzumab-based therapy (TCHP) followed by surgery. Surgical pathology revealed treatment-related changes with a definite response to neoadjuvant therapy. We report this case to highlight the response of this rare pathological entity to a standard neoadjuvant regimen such as docetaxel, carboplatin, trastuzumab, and pertuzumab.

Complete Genome Sequence of Bacillus megaterium Siphophage Stahl.

Stahl is a siphophage active against Bacillus megaterium, a Gram-positive bacterium often used as a model system in research and as a protein production strain in industrial applications. Here, we present the complete annotated genome of phage Stahl and describe its major features.