Mary E.

Abstract. Bone marrow vascular endothelial cells (BM ECs) regulate multiple myeloma (MM) pathogenesis. Identification of the mechanisms underlying this interaction could lead to the development of improved strategies for treating MM. Here, we performed a transcriptomic analysis of human ECs with high capacity to promote MM growth, revealing overexpression of the receptor tyrosine kinases, EPHB1 and EPHB4, in MM – supportive ECs. Expression of ephrin B2 (EFNB2), the binding partner for EPHB1 and EPHB4, was significantly increased in MM cells. Silencing EPHB1 or EPHB4 in ECs suppressed MM growth in co-culture. Similarly, loss of EFNB2 in MM cells blocked MM proliferation and survival in vitro, abrogated MM engraftment in immune-deficient mice, and increased MM sensitivity to chemotherapy. Administration of an EFNB2-targeted single chain variable fragment also suppressed MM growth in vivo. In contrast, overexpression of EFNB2 in MM cells increased STAT5 activation, increased MM cell survival and proliferation, and decreased MM sensitivity to chemotherapy. Conversely, expression of mutant EFNB2 lacking reverse signaling capacity in MM cells increased MM cell death and sensitivity to chemotherapy and abolished MM growth in vivo. Complementary analysis of MM patient data revealed that increased EFNB2 expression is associated with adverse-risk disease and decreased survival. This study suggests that EFNB2 reverse signaling controls MM pathogenesis and can be therapeutically targeted to improve MM outcomes.

Limited attention is given to the efficacy of protocols for the estimation of infant intake of milk components when investigating their impact on infant outcomes. We compared the actual measured intake of human milk components with estimations derived from 15 protocols to determine the most reliable approach for estimating intake of HM leptin, adiponectin, insulin, glucose, and total lipid. Twenty mothers who were 3–5 months postpartum completed a 24 h milk profile study with pre-/post-feed milk samples collection. The true infant intake (control group) based on 24 h milk intake (MI) was compared to estimated infant intakes using concentrations from five sampling protocols that were multiplied by one of true infant MI, considered mean MI (800 mL), or global mean MI (766 mL). The mean measured concentrations of six samples (three sets of pre- and post-feed samples, from morning (06:00–09:00), afternoon (13:00–16:00), and evening (19:00–22:00)) multiplied by the true infant MI, mean considered MI, and global mean MI produced the most accurate estimates of infant intake of these components. Therefore, in the absence of 24 h measurements and sampling, a sampling protocol comprising three sets of pre-/post-feed samples provides the most reliable infant intake estimates of HM leptin, adiponectin, insulin, glucose, and total lipid.

The purpose of this study was to evaluate the biodistribution of a platelet-derived exosome product (PEP), previously shown to promote regeneration in the setting of wound healing, in a porcine model delivered through various approaches. Exosomes were labeled with DiR far-red lipophilic dye to track and quantify exosomes in tissue, following delivery via intravenous, pulmonary artery balloon catheter, or nebulization in sus scrofa domestic pigs. Following euthanasia, far-red dye was detected by Xenogen IVUS imaging, while exosomal protein CD63 was detected by Western blot and immunohistochemistry. Nebulization and intravenous delivery both resulted in global uptake of exosomes within the lung parenchyma. However, nebulization resulted in the greatest degree of exosome uptake. Pulmonary artery balloon catheter-guided delivery provided the further ability to localize pulmonary delivery. No off-target absorption was noted in the heart, spleen, or kidney. However, the liver demonstrated uptake primarily in nebulization-treated animals. Nebulization also resulted in uptake in the trachea, without significant absorption in the esophagus. Overall, this study demonstrated the feasibility of pulmonary delivery of exosomes using nebulization or intravenous infusion to accomplish global delivery or pulmonary artery balloon catheter-guided delivery for localized delivery.

In the original publication [...]

Abstract Background Invasive bacterial infections (IBIs) in febrile infants are rare but potentially devastating.

Typesetting math: 100% University of Mississippi Medical Center, Department of Biomedical Materials Science, Jackson, MS 39216, USA

Abstract Partial heart transplantation (PHT) is a novel surgical approach that involves transplantation of only the part of the heart containing a valve.

Abstract The Anopheles gambiae 1000 Genomes (Ag1000G) Consortium previously utilized deep sequencing methods to catalogue genetic diversity across African An. gambiae populations.

This review seeks to address major gaps and delays between our rapidly evolving body of knowledge on type 2 diabetes and its translation into real-world practice. Through updated and improved best practices informed by recent evidence and described herein, we stand to better attain A1c targets, help preserve beta cell integrity and moderate glycemic variability, minimize treatment-emergent hypoglycemia, circumvent prescribing to “treatment failure,” and prevent long-term complications. The first topic addressed in this review concerns updates in the 2023 and 2024 diabetes treatment guidelines for which further elaboration can help facilitate integration into routine care. The second concerns advances in diabetes research that have not yet found their way into guidelines, though they are endorsed by strong evidence and are ready for real-world use in appropriate patients. The final theme addresses lingering misconceptions about the underpinnings of type 2 diabetes—fundamental fallacies that continue to be asserted in the textbooks and continuing medical education upon which physicians build their approaches. A corrected and up-to-date understanding of the disease state is essential for practitioners to both conceptually and translationally manage initial onset through late-stage type 2 diabetes.

The International Mouse Phenotyping Consortium (IMPC) systematically produces and phenotypes mouse lines with presumptive null mutations to provide insight into gene function. The IMPC now uses the programmable RNA-guided nuclease Cas9 for its increased capacity and flexibility to efficiently generate null alleles in the C57BL/6N strain. In addition to being a valuable novel and accessible research resource, the production of 3313 knockout mouse lines using comparable protocols provides a rich dataset to analyze experimental and biological variables affecting in vivo gene engineering with Cas9. Mouse line production has two critical steps – generation of founders with the desired allele and germline transmission (GLT) of that allele from founders to offspring. A systematic evaluation of the variables impacting success rates identified gene essentiality as the primary factor influencing successful production of null alleles. Collectively, our findings provide best practice recommendations for using Cas9 to generate alleles in mouse essential genes, many of which are orthologs of genes linked to human disease.