Inhibition of growth by p205: a nuclear protein and putative tumor suppressor expressed during myeloid cell differentiation

p205 belongs to a family of interferon-inducible proteins called the IFI-200 family, which have been implicated in the regulation of cell growth and differentiation. While p205 is induced in hematopoietic stem cells during myeloid cell differentiation, its function is not known. Therefore, the aim of this study was to determine the role of p205 in regulating proliferation in hematopoietic progenitor cells and in nonhematopoietic cell lines. We found that p205 localizes to the nucleus in hematopoietic and nonhematopoietic cell lines. Transient expression of p205 in murine IL-3-dependent BaF3 and 32D-C123 progenitor cell lines inhibited IL-3-induced growth and proliferation. The closely related IFI-200 family members, p204 and p202, similarly inhibited IL-3-dependent progenitor cell proliferation. p205 also inhibited the proliferation and growth of normal hematopoietic progenitor cells. In nonhematopoietic cell lines, p205 and p204 expression inhibited NIH3T3 cell colony formation in vitro, and microinjection of p205 expression vectors into NIH3T3 fibroblasts inhibited serum-induced proliferation. We have determined the functional domains of p205 necessary for activity, which were identified as the N-terminal domain in apoptosis and interferon response (DAPIN)/PYRIN domain, and the C-terminal retinoblastoma protein (Rb)-binding motif. In addition, we have demonstrated that a putative ataxia telangiectasia, mutated (ATM) kinase phosphorylation site specifically regulates the activity of p205. Taken together, these data suggest that p205 is a potent cell growth regulator whose activity is mediated by its protein-binding domains. We propose that during myelomonocytic cell differentiation, induction of p205 expression contributes to cell growth arrest, thus allowing progenitor cells to differentiate.     

A Pilot Study Comparing the Effects of Consuming 100% Orange Juice or Sucrose-Sweetened Beverage on Risk Factors for Cardiometabolic Disease in Women

Overconsumption of sugar-sweetened beverages increases risk factors associated with cardiometabolic disease, in part due to hepatic fructose overload. However, it is not clear whether consumption of beverages containing fructose as naturally occurring sugar produces equivalent metabolic dysregulation as beverages containing added sugars. We compared the effects of consuming naturally-sweetened orange juice (OJ) or sucrose-sweetened beverages (sucrose-SB) for two weeks on risk factors for cardiometabolic disease. Healthy, overweight women (n = 20) were assigned to consume either 3 servings of 100% orange juice or sucrose-SB/day. We conducted 16-hour serial blood collections and 3-h oral glucose tolerance tests during a 30-h inpatient visit at baseline and after the 2-week diet intervention. The 16-h area under the curve (AUC) for uric acid increased in subjects consuming sucrose-SB compared with subjects consuming OJ. Unlike sucrose-SB, OJ did not significantly increase fasting or postprandial lipoproteins. Consumption of both beverages resulted in reductions in the Matsuda insulin sensitivity index (OJ: −0.40 ± 0.18, p = 0.04 within group; sucrose-SB: −1.0 ± 0.38, p = 0.006 within group; p = 0.53 between groups). Findings from this pilot study suggest that consumption of OJ at levels above the current dietary guidelines for sugar intake does not increase plasma uric acid concentrations compared with sucrose-SB, but appears to lead to comparable decreases of insulin sensitivity.     

Epidemiology of emergency department-treated traumatic brain injury in Minnesota

A number of population-based studies have been published on mortality and hospitalizations associated with traumatic brain injury (TBI). However, very little has been published on treatment of TBI in the emergency department (ED), despite the fact that most cases are seen in such settings. Minnesota is 1 of 2 states funded by the Centers for Disease Control and Prevention since 2001 to conduct surveillance of TBIs treated in EDs. A sample of medical records from 2002 and 2003 was reviewed to better understand the epidemiology of ED-treated TBI and identify risk factors for and interventions to prevent them. We found males, infants, adolescents and young adults, blacks, and residents of the 7-county Twin Cities metropolitan area were most likely to be seen in the ED for TBI. Sports and recreational activities were the leading causes of these injuries, followed by falls and motor vehicle crashes.     

Eastern equine encephalomyelitis virus infection in a horse from California

A yearling quarter horse, which was raised in southern California, received routine vaccinations for prevention of infection by Eastern equine encephalomyelitis virus (EEEV). One week later, severe neurologic signs developed, and the horse was humanely destroyed. A vaccine-related encephalomyelitis was later suspected. A final diagnosis of EEEV infection was established on the basis of acute onset of the neurologic signs, histopathologic and serologic testing, and isolation and molecular characterization of EEEV from brain tissue. The vaccine was extensively tested for viral inactivation. Nucleotide sequences from the vaccine and the virus isolated in the affected horse were also compared. In California, arboviral encephalomyelitides are rarely reported, and EEEV infection has not previously been documented. This report describes the occurrence of EEEV infection in the horse and the investigation to determine the source of infection, which was not definitively identified.     

Registration accuracy enhancement of a surgical navigation system for anterior cruciate ligament reconstruction: A phantom and cadaveric study

Background

Recently, surgical navigation systems have been widely used to improve the results of various orthopaedic surgeries. However, surgical navigation has not been successful in anterior cruciate ligament reconstruction, owing to its inaccuracy and inconvenience. This study investigated the registration of preoperative and intraoperative data, which are the key components in improving accuracy of the navigation system.

Proceedings of the 2022 NHLBI and OASH state of the science in transfusion medicine symposium

Background

State of the Science (SoS) meetings are used to define and highlight important unanswered scientific questions. The National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health, and the Office of the Assistant Secretary for Health (OASH), Department of Health and Human Services held a virtual SoS in transfusion medicine (TM) symposium.

Study Design and Methods

In advance of the symposium, six multidisciplinary working groups (WG) convened to define research priorities in the areas of: blood donors and the supply, optimizing transfusion outcomes for recipients, emerging infections, mechanistic aspects of components and transfusion, new computational methods in transfusion science, and impact of health disparities on donors and recipients. The overall objective was to identify key basic, translational, and clinical research questions that will help to increase and diversify the volunteer donor pool, ensure safe and effective transfusion strategies for recipients, and identify which blood products from which donors best meet the clinical needs of specific recipient populations.

Results

On August 29–30, 2022, over 400 researchers, clinicians, industry experts, government officials, community members, and patient advocates discussed the research priorities presented by each WG. Dialogue focused on the five highest priority research areas identified by each WG and included the rationale, proposed methodological approaches, feasibility, and barriers for success.

Discussion

This report summarizes the key ideas and research priorities identified during the NHLBI/OASH SoS in TM symposium. The report highlights major gaps in our current knowledge and provides a road map for TM research.