Distinct Contributions of Enzymic Functional Groups to the 2',3'-Cyclic Phosphodiesterase, 3'-Phosphate Guanylylation, and 3'-ppG/5'-OH Ligation Steps of the Escherichia coli RtcB Nucleic Acid Splicing Pathway.

Unlabelled: Escherichia coli RtcB is a founding member of a family of manganese-dependent RNA repair enzymes that join RNA 2′,3′-cyclic phosphate (RNA>p) or RNA 3′-phosphate (RNAp) ends to 5′-OH RNA (HORNA) ends in a multistep pathway whereby RtcB (i) hydrolyzes RNA>p to RNAp, (ii) transfers GMP from GTP to RNAp to form to RNAppG, and (iii) directs the attack of 5′-OH on RNAppG to form a 3′-5′ phosphodiester splice junction. The crystal structure of the homologous archaeal RtcB enzyme revealed an active site with two closely spaced manganese ions, Mn1 and Mn2, that interact with the GTP phosphates. By studying the reactions of wild-type E.

Characterization of 3'-Phosphate RNA Ligase Paralogs RtcB1, RtcB2, and RtcB3 from Myxococcus xanthus Highlights DNA and RNA 5'-Phosphate Capping Activity of RtcB3.

Unlabelled: Escherichia coli RtcB exemplifies a family of GTP-dependent RNA repair/splicing enzymes that join 3'-PO4 ends to 5'-OH ends via stable RtcB-(histidinyl-N)-GMP and transient RNA3'pp5'G intermediates. E. coli RtcB also transfers GMP to a DNA 3'-PO4 end to form a stable "capped" product, DNA3'pp5'G.

Right ventricular dysfunction in systemic sclerosis-associated pulmonary arterial hypertension.

Background: Systemic sclerosis–associated pulmonary artery hypertension (SScPAH) has a worse prognosis compared with idiopathic pulmonary arterial hypertension (IPAH), with a median survival of 3 years after diagnosis often caused by right ventricular (RV) failure. We tested whether SScPAH or systemic sclerosis–related pulmonary hypertension with interstitial lung disease imposes a greater pulmonary vascular load than IPAH and leads to worse RV contractile function.

Methods And Results: We analyzed pulmonary artery pressures and mean flow in 282 patients with pulmonary hypertension (166 SScPAH, 49 systemic sclerosis–related pulmonary hypertension with interstitial lung disease, and 67 IPAH).

Intact p53-dependent responses in miR-34-deficient mice.

MicroRNAs belonging to the miR-34 family have been proposed as critical modulators of the p53 pathway and potential tumor suppressors in human cancers. To formally test these hypotheses, we have generated mice carrying targeted deletion of all three members of this microRNA family. We show that complete inactivation of miR-34 function is compatible with normal development in mice.

Finger photoplethysmography during the Valsalva maneuver reflects left ventricular filling pressure.

It is often challenging to assess cardiac filling pressure clinically. An improved system for detecting or ruling out elevated cardiac filling pressure may help reduce hospitalizations for heart failure. The blood pressure response to the Valsalva maneuver reflects left heart filling pressure, but its underuse clinically may be due in part to lack of continuous blood pressure recording along with lack of standardization of expiratory effort.