Evaluating Consistency of Snow Water Equivalent Retrievals from Passive Microwave Sensors over the North Central U. S.: SSM/I vs. SSMIS and AMSR-E vs. AMSR2

For four decades, satellite-based passive microwave sensors have provided valuable snow water equivalent (SWE) monitoring at a global scale. Before continuous long-term SWE records can be used for scientific or applied purposes, consistency of SWE measurements among different sensors is required. SWE retrievals from two passive sensors currently operating, the Special Sensor Microwave Imager Sounder (SSMIS) and the Advanced Microwave Scanning Radiometer 2 (AMSR2), have not been fully evaluated in comparison to each other and previous instruments. Here, we evaluated consistency between the Special Sensor Microwave/Imager (SSM/I) onboard the F13 Defense Meteorological Satellite Program (DMSP) and SSMIS onboard the F17 DMSP, from November 2002 to April 2011 using the Advanced Microwave Scanning Radiometer for Earth Observing System (AMSR-E) for continuity. Likewise, we evaluated consistency between AMSR-E and AMSR2 SWE retrievals from November 2007 to April 2016, using SSMIS for continuity. The analysis is conducted for 1176 watersheds in the North Central U.S. with consideration of difference among three snow classifications (Warm forest, Prairie, and Maritime). There are notable SWE differences between the SSM/I and SSMIS sensors in the Warm forest class, likely due to the different interpolation methods for brightness temperature (Tb) between the F13 SSM/I and F17 SSMIS sensors. The SWE differences between AMSR2 and AMSR-E are generally smaller than the differences between SSM/I and SSMIS SWE, based on time series comparisons and yearly mean bias. Finally, the spatial bias patterns between AMSR-E and AMSR2 versus SSMIS indicate sufficient spatial consistency to treat the AMSR-E and AMSR2 datasets as one continuous record. Our results provide useful information on systematic differences between recent satellite-based SWE retrievals and suggest subsequent studies to ensure reconciliation between different sensors in long-term SWE records

Cervical spinal cord dimensions and clinical outcomes in adults with Klippel-Feil syndrome: A comparison with matched controls.

Study Design Retrospective case–control study. Objectives To confirm the fact that spinal cord dimensions are smaller in adults with Klippel-Feil syndrome (KFS) than in pediatric patients with KFS and to compare the clinical characteristics and outcomes of neurologic complications in patients with KFS with matched controls. Methods We performed an independent 1:2 case–control retrospective radiographic and chart review of a consecutive series of adults with KFS who underwent surgical intervention. The control group consisted of consecutive non-KFS surgical patients. Patients were matched in 1:2 case–control manner. Their charts were reviewed and the clinical characteristics were compared. Axial T2-weighted magnetic resonance imaging (MRI) was used to measure the anteroposterior and mediolateral axial spinal cord and spinal canal at the operative levels and measurements were compared. Results A total of 22 patients with KFS and 44 controls were identified. The KFS group had a tendency of more myeloradiculopathy, and the control group had a tendency toward more radiculopathy. Both tendencies, however, were not significantly different. MRIs of 10 patients from the KFS group and 22 controls were available. There was no difference in the area of both spinal cord and canal at the operative levels. Conclusion Contrary to the finding in previous reports on pediatric patients, there were no differences between KFS and well-matched control groups in terms of age of onset, presentation, revision rate, complication rate, surgical outcome, and cross-sectional spinal cord and canal dimensions at the operative level

The Safety and Efficacy of Laparoscopic Surgical Staging and Debulking of Apparent Advanced Stage Ovarian, Fallopian Tube, and Primary Peritoneal Cancers

The authors contend that laparoscopy can be used for diagnosis, triage and debulking of select patients with advanced ovarian, fallopian tube or primary peritoneal cancer

CD40 promotes MHC class II expression on adipose tissue macrophages and regulates adipose tissue CD4+ T cells with obesity

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142158/1/jlb1107-sup-0002.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/142158/2/jlb1107-sup-0003.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/142158/3/jlb1107.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/142158/4/jlb1107-sup-0001.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/142158/5/jlb1107-sup-0004.pd

Mcl1 haploinsufficiency protects mice from Myc-induced acute myeloid leukemia

Antiapoptotic BCL2 family members have been implicated in the pathogenesis of acute myelogenous leukemia (AML), but the functional significance and relative importance of individual proteins (e.g., BCL2, BCL-XL, and myeloid cell leukemia 1 [MCL1]) remain poorly understood. Here, we examined the expression of BCL2, BCL-XL, and MCL1 in primary human hematopoietic subsets and leukemic blasts from AML patients and found that MCL1 transcripts were consistently expressed at high levels in all samples tested. Consistent with this, Mcl1 protein was also highly expressed in myeloid leukemic blasts in a mouse Myc-induced model of AML. We used this model to test the hypothesis that Mcl1 facilitates AML development by allowing myeloid progenitor cells to evade Myc-induced cell death. Indeed, activation of Myc for 7 days in vivo substantially increased myeloid lineage cell numbers, whereas hematopoietic stem, progenitor, and B-lineage cells were depleted. Furthermore, Mcl1 haploinsufficiency abrogated AML development. In addition, deletion of a single allele of Mcl1 from fully transformed AML cells substantially prolonged the survival of transplanted mice. Conversely, the rapid lethality of disease was restored by coexpression of Bcl2 and Myc in Mcl1-haploinsufficient cells. Together, these data demonstrate a critical and dose-dependent role for Mcl1 in AML pathogenesis in mice and suggest that MCL1 may be a promising therapeutic target in patients with de novo AML

Weight Regain in Formerly Obese Mice Hastens Development of Hepatic Steatosis Due to Impaired Adipose Tissue Function

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/155467/1/oby22788-sup-0001-Supinfo.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/155467/2/oby22788_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/155467/3/oby22788.pd

Sensitivity of Mitochondrial Transcription and Resistance of RNA Polymerase II Dependent Nuclear Transcription to Antiviral Ribonucleosides

Ribonucleoside analogues have potential utility as anti-viral, -parasitic, -bacterial and -cancer agents. However, their clinical applications have been limited by off target effects. Development of antiviral ribonucleosides for treatment of hepatitis C virus (HCV) infection has been hampered by appearance of toxicity during clinical trials that evaded detection during preclinical studies. It is well established that the human mitochondrial DNA polymerase is an off target for deoxyribonucleoside reverse transcriptase inhibitors. Here we test the hypothesis that triphosphorylated metabolites of therapeutic ribonucleoside analogues are substrates for cellular RNA polymerases. We have used ribonucleoside analogues with activity against HCV as model compounds for therapeutic ribonucleosides. We have included ribonucleoside analogues containing 2′-C-methyl, 4′-methyl and 4′-azido substituents that are non-obligate chain terminators of the HCV RNA polymerase. We show that all of the anti-HCV ribonucleoside analogues are substrates for human mitochondrial RNA polymerase (POLRMT) and eukaryotic core RNA polymerase II (Pol II) in vitro. Unexpectedly, analogues containing 2′-C-methyl, 4′-methyl and 4′-azido substituents were inhibitors of POLRMT and Pol II. Importantly, the proofreading activity of TFIIS was capable of excising these analogues from Pol II transcripts. Evaluation of transcription in cells confirmed sensitivity of POLRMT to antiviral ribonucleosides, while Pol II remained predominantly refractory. We introduce a parameter termed the mitovir (mitochondrial dysfunction caused by antiviral ribonucleoside) score that can be readily obtained during preclinical studies that quantifies the mitochondrial toxicity potential of compounds. We suggest the possibility that patients exhibiting adverse effects during clinical trials may be more susceptible to damage by nucleoside analogs because of defects in mitochondrial or nuclear transcription. The paradigm reported here should facilitate development of ribonucleosides with a lower potential for toxicity

Functional comparison of blood-stage Plasmodium falciparum malaria vaccine candidate antigens

The malaria genome encodes over 5,000 proteins and many of these have also been proposed to be potential vaccine candidates, although few of these have been tested clinically. RH5 is one of the leading blood-stage Plasmodium falciparum malaria vaccine antigens and Phase I/II clinical trials of vaccines containing this antigen are currently underway. Its likely mechanism of action is to elicit antibodies that can neutralize merozoites by blocking their invasion of red blood cells (RBC). However, many other antigens could also elicit neutralizing antibodies against the merozoite, and most of these have never been compared directly to RH5. The objective of this study was to compare a range of blood-stage antigens to RH5, to identify any antigens that outperform or synergize with anti-RH5 antibodies. We selected 55 gene products, covering 15 candidate antigens that have been described in the literature and 40 genes selected on the basis of bioinformatics functional prediction. We were able to make 20 protein-in-adjuvant vaccines from the original selection. Of these, S-antigen and CyRPA robustly elicited antibodies with neutralizing properties. Anti-CyRPA IgG generally showed additive GIA with anti-RH5 IgG, although high levels of anti-CyRPA-specific rabbit polyclonal IgG were required to achieve 50% GIA. Our data suggest that further vaccine antigen screening efforts are required to identify a second merozoite target with similar antibody-susceptibility to RH5

Cardiac autonomic dysfunction is associated with high-risk albumin-to-creatinine ratio in young adolescents with type 1 diabetes in AdDIT (adolescent type 1 diabetes cardio-renal interventional trial).

OBJECTIVE: This study examined the association between cardiac autonomic dysfunction and high albumin-to-creatinine ratio (ACR) in adolescents with type 1 diabetes. RESEARCH DESIGN AND METHODS: Adolescents recruited as part of a multicenter screening study (n = 445, 49% female, aged 10-17 years, mean duration 6.9 years; mean HbA1c 8.4%, 68 mmol/mol) underwent a 10-min continuous electrocardiogram recording for heart rate variability analysis. Time-domain heart rate variability measures included baseline heart rate, SD of the R-R interval (SDNN), and root mean squared difference of successive R-R intervals (RMSSD). Spectral analysis included sympathetic (low-frequency) and parasympathetic (high-frequency) components. Standardized ACR were calculated from six early morning urine collections using an established algorithm, reflecting age, sex, and duration, and stratified into ACR tertiles, where the upper tertile reflects higher nephropathy risk. RESULTS: The upper-tertile ACR group had a faster heart rate (76 vs. 73 bpm; P < 0.01) and less heart rate variability (SDNN 68 vs. 76 ms, P = 0.02; RMSSD 63 vs. 71 ms, P = 0.04). HbA1c was 8.5% (69 mmol/mmol) in the upper tertile vs. 8.3% (67 mmol/mol) in the lower tertiles (P = 0.07). In multivariable analysis, upper-tertile ACR was associated with faster heart rate (β = 2.5, 95% CI 0.2-4.8, P = 0.03) and lower RMSSD (β = -9.5, 95% CI -18.2 to -0.8, P = 0.03), independent of age and HbA1c. CONCLUSIONS: Adolescents at potentially higher risk for nephropathy show an adverse cardiac autonomic profile, indicating sympathetic overdrive, compared with the lower-risk group. Longitudinal follow-up of this cohort will further characterize the relationship between autonomic and renal dysfunction and the effect of interventions in this population.National Health and Medical Research Council, Australia (NHMRC) 632521, Australasian Paediatric Endocrine Group (APEG), Juvenile Diabetes Research Foundation, British Heart Foundation, Diabetes UK.This is the accepted manuscript. The final version is available at http://care.diabetesjournals.org/content/early/2015/01/01/dc14-1848