The MADS-box gene FRUITFULL (FUL) plays a critical role in Arabidopsis thaliana fruit development after fertilization, particularly in the valves. While research has uncovered a number of genes that function upstream of FUL, there is little information on how FUL is directly regulated. To address this, the FUL promoter was studied in order to isolate the cis-acting regulatory regions that are required for FUL transcription. A 3.9 kb long promoter upstream the FUL genomic sequence was demonstrated to direct the expression of the [Beta]-glucuronidase (GUS) reporter gene in a pattern that mimicked the FUL expression pattern previously reported in mRNA in situ hybridization studies and ful-1 DsE enhancer trap lines. In a "promoter-bashing" study, we identified a 682 bp long region within this 3.9 kb promoter that contained at least one cis-element required for transcriptional activation of FUL in the valves. Site-directed mutagenesis revealed that a CArG box in this aforementioned region was required for the repression of ectopic transcription in the ovules but was not required for expression in the valve cells. Further studies will precisely identify the cis-element(s) in this regulatory region that positively regulate FUL transcription in the valves. Additionally, our data showed that the 3' region of the 3.9 kb promoter was required for FUL-like expression in the inflorescence stem

As causes of death, influenza and pneumonia are typically analyzed together. We quantify influenza's contribution to the combined pneumonia and influenza mortality time series for the United States, 1959-2009. A key statistic is I/(P + I), the proportion of pneumonia and influenza mortality accounted for by influenza. Year-to-year, I/(P + I) is highly variable and shows long-term decline. Extreme values of I/(P + I) are associated with extreme P + I death rates and vice versa, but I/(P + I) is a weak predictor of P + I mortality overall. Prominence of influenza in the medical news is associated with high I/(P + I). Influenza and pneumonia should be analyzed as a combined cause.

As causes of death, influenza and pneumonia are typically analyzed together. We quantify influenza’s contribution to the combined pneumonia and influenza mortality time series for the United States, 1959–2009. A key statistic is I/(P+I), the proportion of pneumonia and influenza mortality accounted for by influenza. Year-to-year, I/(P+I) is highly variable and shows long-term decline. Extreme values of I/(P+I) are associated with extreme P+I death rates and vice-versa, but I/(P+I) is a weak predictor of P+I mortality overall. Prominence of influenza in the medical news is associated with high I/(P+I). Influenza and pneumonia should be analyzed as a combined cause.

INTRODUCTION: Mechanisms explain how implementation strategies work. Implementation research requires careful operationalisation and empirical study of the causal pathway(s) by which strategies effect change, and factors that may amplify or weaken their effects. Understanding mechanisms is critically important to replicate findings, learn from negative studies or adapt an implementation strategy developed in one setting to another. Without understanding implementation mechanisms, it is difficult to design strategies to produce expected effects across contexts, which may have disproportionate effects on settings in which priority populations receive care. This manuscript outlines the protocol for an Agency for Healthcare Research and Quality-funded initiative to: (1) establish priorities for an agenda to guide research on implementation mechanisms in health and public health, and (2) disseminate the agenda to research, policy and practice audiences. METHODS AND ANALYSIS: A network of scientific experts will convene in Deep Dive meetings across 3 years. A research agenda will be generated through analysis and synthesis of information from six sources: (1) systematic reviews, (2) network members approaches to studying mechanisms, (3) new proposals presented in implementation proposal feedback sessions, (4) working group sessions conducted in a leading implementation research training institute, (5) breakout sessions at the Society for Implementation Research Collaborations (SIRC) 2019 conference and (6) SIRC conference abstracts. Two members will extract mechanism-relevant text segments from each data source and a third member will generate statements as an input for concept mapping. Concept mapping will generate unique clusters of challenges, and the network will engage in a nominal group process to identify priorities for the research agenda. ETHICS AND DISSEMINATION: This initiative will yield an actionable research agenda to guide research to identify and test mechanisms of change for implementation strategies. The agenda will be disseminated via multiple channels to solicit feedback and promote rigorous research on implementation mechanisms.

Volume status assessment in left ventricular assist device (LVAD) patients remains challenging. Cardiac resynchronization therapy (CRT) devices are common in LVAD patients, and the impedance across the CRT leads may be associated with hemodynamics and serve as a tool for noninvasive estimation of volume status. Ninety-one sets of measurements including cardiac filling pressures and lead impedances were prospectively obtained during ramp tests from 11 LVAD patients (65.5 ± 9.7 years old; nine male) with CRT devices. Right atrial (RA), right ventricular (RV), and left ventricular (LV) lead impedances were all significantly associated with central venous pressure (CVP) (p < 0.05). We derived the following equation: estimated CVP = 47.90-(0.086 × RA lead impedance) + (0.013 × RV lead impedance)-(0.020 × LV lead impedance). The estimated CVP had a significant correlation (r = 0.795) and good agreement with the measured CVP (mean difference -0.14 ± 1.77 mmHg). Applying the above equation on the validation cohort of twenty-one patients also maintained a strong association with measured CVP (r = 0.705). In conclusion, we have derived a novel equation to estimate CVP using lead impedance measurements. This finding may allow noninvasive monitoring of volume status in LVAD patients.

Cytochrome P450c17 (P450 17A1, CYP17A1) is a critical enzyme in the synthesis of androgens and is now a target enzyme for the treatment of prostate cancer. Cytochrome P450c17 can exhibit either one or two physiological enzymatic activities differentially regulated by cytochrome b5. How this is achieved remains unknown. Here, comprehensive in silico, in vivo and in vitro analyses were undertaken. Fluorescence Resonance Energy Transfer analysis showed close interactions within living cells between cytochrome P450c17 and cytochrome b5. In silico modeling identified the sites of interaction and confirmed that E48 and E49 residues in cytochrome b5 are essential for activity. Quartz crystal microbalance studies identified specific protein-protein interactions in a lipid membrane. Voltammetric analysis revealed that the wild type cytochrome b5, but not a mutated, E48G/E49G cyt b5, altered the kinetics of electron transfer between the electrode and the P450c17. We conclude that cytochrome b5 can influence the electronic conductivity of cytochrome P450c17 via allosteric, protein-protein interactions.

Studies of material returned from Cb asteroid Ryugu have revealed considerable mineralogical and chemical heterogeneity, stemming primarily from brecciation and aqueous alteration. Isotopic anomalies could have also been affected by delivery of exogenous clasts and aqueous mobilization of soluble elements. Here, we show that isotopic anomalies for mildly soluble Cr are highly variable in Ryugu and CI chondrites, whereas those of Ti are relatively uniform. This variation in Cr isotope ratios is most likely due to physicochemical fractionation between 54Cr-rich presolar nanoparticles and Cr-bearing secondary minerals at the millimeter-scale in the bulk samples, likely due to extensive aqueous alteration in their parent bodies that occurred [Formula: see text] after Solar System birth. In contrast, Ti isotopes were marginally affected by this process. Our results show that isotopic heterogeneities in asteroids are not all nebular or accretionary in nature but can also reflect element redistribution by water.