Immunohistochemical Analysis of GATA2 Expression in Endometrium and its Relationship with Hormone Receptor Expression in Benign and Premalignant Endometrial Disorders.

The GATA gene family encodes highly conserved zinc-finger transcription factors that facilitate the development and function of multiple organ systems including the uterus. In the endometrium, GATA2 functions in a positive autoregulatory loop with the progesterone receptor (PGR) and colocalizes with PGR on chromatin to promote PGR transcriptional programs. GATA2 also has PGR-independent functions that maintain endometrial cell identity, and GATA2 transcripts reportedly are down-regulated in endometrial disorders including endometriosis.

Thermodynamic assessment of evaporation during molten steel testing onboard the International Space Station.

Evaporation control is a critical facility resource during solidification experiments that limits processing time and must be tracked to ensure facility health. A thermodynamic analysis was performed on a ternary FeCrNi sample processed onboard the International Space Station (ISS) using ESA Electromagnetic Levitation (EML) facility in a microgravity environment. A non-ideal solution-based mathematical model was applied for the overall sample mass loss prediction during this study.

Linking GATA2 to myeloid dysplasia and complex cytogenetics in adult myelodysplastic neoplasm and acute myeloid leukemia.

GATA binding protein 2 (GATA2) is a conserved zinc finger transcription factor that regulates the emergence and maintenance of complex genetic programs driving development and function of hematopoietic stem and progenitor cells (HSPCs). Patients born with monoallelic GATA2 mutations develop myelodysplastic neoplasm (MDS) and acute myeloid leukemia (AML), whereas acquired GATA2 mutations are reported in 3% to 5% of sporadic AML cases. The mechanisms by which aberrant GATA2 activity promotes MDS and AML are incompletely understood.

A gain-of-function p53 mutant synergizes with oncogenic NRAS to promote acute myeloid leukemia in mice.

We previously demonstrated that a subset of acute myeloid leukemia (AML) patients with concurrent RAS pathway and TP53 mutations have an extremely poor prognosis and that most of these TP53 mutations are missense mutations. Here, we report that, in contrast to the mixed AML and T cell malignancy that developed in NrasG12D/+ p53-/- (NP-/-) mice, NrasG12D/+ p53R172H/+ (NPmut) mice rapidly developed inflammation-associated AML. Under the inflammatory conditions, NPmut hematopoietic stem and progenitor cells (HSPCs) displayed imbalanced myelopoiesis and lymphopoiesis and mostly normal cell proliferation despite MEK/ERK hyperactivation.

Diffuse Large B-Cell Lymphoma, Not Otherwise Specified (DLBCL NOS) Presenting as Multiple Subcutaneous Nodules: An Unusual Cutaneous Presentation of Systemic Disease.

Diffuse large B-cell lymphoma, not otherwise specified (DLBCL NOS) is the most common lymphoid malignancy in the Western world and classically presents as a rapidly enlarging nodal or extranodal mass. Cutaneous involvement by systemic DLBCL NOS is an infrequent clinical presentation, encountered in only 1.5-3.

Spatial transcriptomics of a giant pilomatricoma.

Pilomatricomas (PMs) are common benign adnexal tumors that show a predilection for the head and neck region and are characterized at the molecular level by activating mutations in the beta-catenin (CTNNB1) gene. Giant PMs are a rare histopathological variant, according to the World Health Organization, which are defined by a size greater than 4 cm and are reported to show upregulation of yes-associated protein compared to PMs of typical 1-3 cm size. We describe the case of a 67-year-old man with an 8 cm giant PM involving his temporal scalp, whose PM we characterized by 10X spatial gene expression analysis.

Electromagnetic levitation containerless processing of metallic materials in microgravity: rapid solidification.

Space levitation processing allows researchers to conduct benchmark tests in an effort to understand the physical phenomena involved in rapid solidification processing, including alloy thermodynamics, nucleation and growth, heat and mass transfer, solid/liquid interface dynamics, macro- and microstructural evolution, and defect formation. Supported by ground-based investigations, a major thrust is to develop and refine robust computational tools based on theoretical and applied approaches. This work is accomplished in conjunction with experiments designed for precise model validation with application to a broad range of industrial processes.

Needle in a haystack or elephant in the room? Identifying germline predisposition syndromes in the setting of a new myeloid malignancy diagnosis.

Myeloid malignancies associated with germline predisposition syndromes account for up to 10% of myeloid neoplasms. They are classified into three categories by the proposed 5 Edition of the World Health Organization Classification of Hematolymphoid Tumors: (1) neoplasms with germline predisposition without a pre-existing platelet disorder or organ dysfunction, (2) neoplasms with germline predisposition and pre-existing platelet disorder, or (3) neoplasms with germline predisposition and potential organ dysfunction. Recognizing these entities is critical because patients and affected family members benefit from interfacing with hematologists who specialize in these disorders and can facilitate tailored treatment strategies.

Uncertainty analysis and performance evaluation of thermophysical property measurement of liquid Au in microgravity.

A new method for quantifying facility performance has been discussed in this study that encompasses uncertainties associated with thermophysical property measurement. Four key thermophysical properties: density, volumetric thermal expansion coefficient, surface tension, and viscosity of liquid Au have been measured in microgravity environment using two different levitation facilities. Levitation experiments were conducted using the Electrostatic Levitation Furnace (ELF) onboard the ISS in Argon and air, and the TEMPUS Electromagnetic Levitation (EML) facility on a Novespace Zero-G aircraft parabolic flight in Argon.

Electromagnetic levitation containerless processing of metallic materials in microgravity: thermophysical properties.

Transitions from the liquid to the solid state of matter are omnipresent. They form a crucial step in the industrial solidification of metallic alloy melts and are greatly influenced by the thermophysical properties of the melt. Knowledge of the thermophysical properties of liquid metallic alloys is necessary in order to gain a tight control over the solidification pathway, and over the obtained material structure of the solid.

Aurora A phosphorylates Ndel1 to reduce the levels of Mad1 and NuMA at spindle poles.

Dynein inactivates the spindle assembly checkpoint (SAC) by transporting checkpoint proteins away from kinetochores toward spindle poles in a process known as "stripping." We find that inhibition of Aurora A kinase, which is localized to spindle poles, enables the accumulation of the spindle checkpoint activator Mad1 at poles where it is normally absent. Aurora kinases phosphorylate the dynein activator NudE neurodevelopment protein 1 like 1 (Ndel1) on Ser285 and Mad1 accumulates at poles when Ndel1 is replaced by a nonphosphorylatable mutant in human cells.

Impact of local mask mandates upon COVID-19 case rates in Oklahoma.

Use of face coverings has been shown to reduce transmission of SARS-CoV-2. Despite encouragements from the CDC and other public health entities, resistance to usage of masks remains, forcing government entities to create mandates to compel use. The state of Oklahoma did not create a state-wide mask mandate, but numerous municipalities within the state did.

HMGA1 chromatin regulators induce transcriptional networks involved in GATA2 and proliferation during MPN progression.

Myeloproliferative neoplasms (MPNs) transform to myelofibrosis (MF) and highly lethal acute myeloid leukemia (AML), although the actionable mechanisms driving progression remain elusive. Here, we elucidate the role of the high mobility group A1 (HMGA1) chromatin regulator as a novel driver of MPN progression. HMGA1 is upregulated in MPN, with highest levels after transformation to MF or AML.

Conditionally pathogenic genetic variants of a hematopoietic disease-suppressing enhancer.

Human genetic variants are classified on the basis of potential pathogenicity to guide clinical decisions. However, mechanistic uncertainties often preclude definitive categorization. Germline coding and enhancer variants within the hematopoietic regulator create a bone marrow failure and leukemia predisposition.

Impact of convection on the damping of an oscillating droplet during viscosity measurement using the ISS-EML facility.

Oscillating droplet experiments are conducted using the Electromagnetic Levitation (EML) facility under microgravity conditions. The droplet of molten metal is internally stirred concurrently with the pulse excitation initiating shape oscillations, allowing viscosity measurement of the liquid melts based on the damping rate of the oscillating droplet. We experimentally investigate the impact of convection on the droplet's damping behavior.

A "Null" Pattern of p16 Immunostaining in Endometrial Serous Carcinoma: An Under-recognized and Important Aberrant Staining Pattern.

The ability to distinguish endometrial serous carcinoma (SC) from high-grade endometrioid adenocarcinoma is of great importance given their differences in prognosis and management. In practice, this distinction typically relies upon the use of a focused immunohistochemical panel including p53, p16, and mismatch repair proteins. The expression of p16 is characteristically strong and diffuse in SCs, and weak and/or patchy in many high-grade endometrioid adenocarcinomas.

SARS-CoV-2 B.1.617.2 (Delta) Variant COVID-19 Outbreak Associated with a Gymnastics Facility - Oklahoma, April-May 2021.

The B.1.617.

RNA-regulatory exosome complex confers cellular survival to promote erythropoiesis.

Cellular differentiation requires vast remodeling of transcriptomes, and therefore machinery mediating remodeling controls differentiation. Relative to transcriptional mechanisms governing differentiation, post-transcriptional processes are less well understood. As an important post-transcriptional determinant of transcriptomes, the RNA exosome complex (EC) mediates processing and/or degradation of select RNAs.

Selective Requirement of MYB for Oncogenic Hyperactivation of a Translocated Enhancer in Leukemia.

In acute myeloid leukemia (AML) with inv(3)(q21;q26) or t(3;3)(q21;q26), a translocated enhancer drives oncogenic expression of . We generated an EVI1-GFP AML model and applied an unbiased CRISPR/Cas9 enhancer scan to uncover sequence motifs essential for transcription. Using this approach, we pinpointed a single regulatory element in the translocated enhancer that is critically required for aberrant expression.

Concurrent Central Diabetes Insipidus and Acute Myeloid Leukemia.

Central diabetes insipidus (CDI) is a rare reported complication of acute myeloid leukemia (AML). The onset of AML-associated CDI often precedes the diagnosis of AML by weeks or months and is considered an adverse prognostic indicator in this setting. The mechanism of AML-associated CDI is not known; however, it is often reported in the setting of cytogenetic events resulting in MDS1 and EVI1 complex locus protein (MECOM) gene overexpression.

High nuclear TPX2 expression correlates with TP53 mutation and poor clinical behavior in a large breast cancer cohort, but is not an independent predictor of chromosomal instability.

Background: Targeting Protein for Xenopus Kinesin Like Protein 2 (TPX2) is a microtubule associated protein that functions in mitotic spindle assembly. TPX2 also localizes to the nucleus where it functions in DNA damage repair during S-phase. We and others have previously shown that TPX2 RNA levels are strongly associated with chromosomal instability (CIN) in breast and other cancers, and TPX2 RNA levels have been demonstrated to correlate with aggressive behavior and poor clinical outcome across a range of solid malignancies, including breast cancer.