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Activation of nemo-like kinase in diamond blackfan anemia suppresses early erythropoiesis by preventing mitochondrial biogenesis

Mark C Wilkes
Diamond Blackfan Anemia (DBA) is a rare macrocytic red blood cell aplasia that usually presents within the first year of life. The vast majority of patients carry a mutation in one of approximately 20 genes that results in ribosomal insufficiency with the most significant clinical manifestations being anemia and a predisposition to cancers. Nemo-like Kinase (NLK) is hyperactivated in the erythroid progenitors of DBA patients and inhibition of this kinase improves erythropoiesis, but how NLK...

ARID3A and ARID3B induce stem promoting pathways in ovarian cancer cells

Paige Dausinas
ARID3A and ARID3B are paralogs from the AT-Rich interactive Domain (ARID) family. ARID3A and ARID3B associate to regulate genes in B-cells and cancer. We were the first to demonstrate that ARID3B regulates stem cell genes and promotes the cancer stem cell phenotype. Importantly, different knockout phenotypes in mice and distinct patterns of expression in adult animals suggests that ARID3A and ARID3B may have unique functions. In addition, high levels of ARID3B but not ARID3A induce cell death....

Can Stemness and Chemoresistance Be Therapeutically Targeted via Signaling Pathways in Ovarian Cancer?

Lynn Roy
Ovarian cancer is the most lethal gynecological malignancy. Poor overall survival, particularly for patients with high grade serous (HGS) ovarian cancer, is often attributed to late stage at diagnosis and relapse following chemotherapy. HGS ovarian cancer is a heterogenous disease in that few genes are consistently mutated between patients. Additionally, HGS ovarian cancer is characterized by high genomic instability. For these reasons, personalized approaches may be necessary for effective...

Clinical evaluation of a Borrelia modified two-tiered testing (MTTT) shows increased early sensitivity for Borrelia burgdorferi but not other endemic Borrelia species in a high incidence region for Lyme disease in Wisconsin

Arick P Sabin
A modified two-tiered testing algorithm (MTTT; ZEUS Scientific) for Borrelia burgdorferi was recently FDA-cleared. We evaluated the MTTT algorithm to confirm Lyme disease and compared the findings in parallel with those obtained using standard two-tiered testing (STTT). Medical records from patients who submitted sera for laboratory confirmation of Lyme-like disease were reviewed. Three hundred twenty patient samples were run by the STTT and MTTT approaches and the results compared. Positive...

Detection of antibodies to decorin-binding protein A (DbpA) and DbpB after infection of dogs with <em>Borrelia burgdorferi</em> by tick challenge

Darby G Oldenburg
We characterized the antibody response to decorin-binding protein A (DbpA) or DbpB from immune serum samples collected from 27 dogs infected with Borrelia burgdorferi by Ixodes scapularis ticks. Immunoglobulin M (IgM) antibodies to DbpA or DbpB were rarely detected, but high levels of IgG antibodies to DbpA were detected in 16 of 27 of the immune sera collected 1 mo after infection, 20 of 25 of the sera collected after 2 mo, and each of the 23, 17, or 11 serum samples evaluated after 3, 4, or 5...

Emergence and onward transmission of a SARS-CoV-2 E484K variant among household contacts of a bamlanivimab-treated patient

Arick P Sabin
The implementation of monoclonal antibody therapeutics during the COVID-19 pandemic altered the selective pressures encountered by SARS-CoV-2, raising the possibility of selection for resistant variants. Within-host viral evolution was reported in treated immunocompromised individuals but whether this signifies a real risk of onward transmission is unclear. We used a regional SARS-CoV-2 sequencing program to monitor lineages with clinically relevant variants in identified patients, which...

Evidence of a Protein-Coding Gene Antisense to the U<sub>L</sub>5 Gene in Bovine Herpesvirus I

Victoria A Jefferson
Bovine herpesvirus type 1 (BoHV-1) is an important agricultural pathogen that infects cattle and other ruminants worldwide. Though it was first sequenced and annotated over twenty years ago, the Cooper strain, used in this study, was sequenced as recently as 2012 and is currently said to encode 72 unique proteins. However, tandem mass spectrometry has identified several peptides produced during active infection that align with the BoHV-1 genome in unannotated regions. One of these abundant...

Gemcitabine combination therapies induce apoptosis in uterine carcinosarcoma patient-derived organoids

Matías J Dahl
Uterine carcinosarcoma (UCS) is a rare but aggressive endometrial cancer. Survival outcomes for women diagnosed with UCS remain poor with lower survival than those of endometrioid or high-grade serous uterine cancers. The histopathological hallmark of carcinosarcoma is the presence of both sarcomatous and carcinomatous elements. The survival rates for UCS have not improved for over 40 years; therefore, there is a profound need to identify new treatments. To investigate novel chemotherapy...

IKKα-Mediated Noncanonical NF-κB Signaling Is Required To Support Murine Gammaherpesvirus 68 Latency <em>In Vivo</em>

Brandon Cieniewicz
Noncanonical NF-κB signaling is activated in B cells via the tumor necrosis factor (TNF) receptor superfamily members CD40, lymphotoxin β receptor (LTβR), and B-cell-activating factor receptor (BAFF-R). The noncanonical pathway is required at multiple stages of B cell maturation and differentiation, including the germinal center reaction. However, the role of this pathway in gammaherpesvirus latency is not well understood. Murine gammaherpesvirus 68 (MHV68) is a genetically tractable system used...

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