On the Computational Power of DNA Annealing and Ligation

In [20] it was shown that the DNA primitives of Separate, Merge, and Amplify were not sufficiently powerful to invert functions defined by circuits in linear time. Dan Boneh et al [4] show that the addition of a ligation primitive, Append, provides the missing power. The question becomes, "How powerful is ligation? Are Separate, Merge, and Amplify necessary at all?" This paper proposes to informally explore the power of annealing and ligation for DNA computation. We conclude, in fact, that annealing and ligation alone are theoretically capable of universal computation

Do K_ATP channels open as a prominent and early feature during ischaemia in the Langendorff-perfused rat heart?

The objective was to investigate whether myocardial adenosine triphosphate-sensitive K<sup>+</sup> (K<sub>ATP</sub>) channels open during the first 10 min of regional ischaemia in Langendorff-perfused rat hearts. Changes in monophasic action potentials and arrhythmias were studied during myocardial ischaemia in both the presence and absence of pharmacological K<sub>ATP</sub> modulation. Ligation of the left main coronary artery for 10 min did not shorten the action potential duration (APD). The APD<sub>50</sub> and APD<sub>80</sub> (15.5 +/- 1.0 and 38.1 +/- 2.3 ms, respectively [mean +/- S.E., n = 15 hearts], immediately prior to ligation) increased transiently during the first 4 min of ligation (by 160 and 79% respectively, P < 0.05), before returning to pre-ligation values, but without a significant below-baseline-shortening. The cardiac electrogram showed no accompanying ventricular tachyarrhythmia (VT). These results raised the possibility that the myocardial K<sub>ATP</sub> channels had not opened during the ligation. The K<sub>ATP</sub> opener Ro 31-6930 (0.5 and 5 microM) shortened the APD50 and APD80 during coronary ligation, to significantly below both their control and pre-occlusion values (P < 0.05), and caused a concentration-dependent increase in both the incidence and duration of VT during the ligation. Ro 31-6930 at 5 microM also shortened APD50 and APD80 even before ligation (by 50 and 62% respectively, P < 0.05), and abolished the normal APD-lengthening seen during ischaemia. The K<sub>ATP</sub> blocker glibenclamide (1 μM) abolished both the APD-shortening and pro-arrhythmic effects of the K<sub>ATP</sub> opener, both before and during coronary ligation, yet when delivered on its own, at the same concentration which abolished the effects of K<sub>ATP</sub> activation, it had no significant effect on the APD changes seen during the coronary ligation alone. These results suggest that, in Langendorff-perfused rat hearts in the absence of drugs, K<sub>ATP</sub> channels do not open during early myocardial ischaemia

Safety and acceptability of tubal ligation procedures performed by trained clinical officers in rural Uganda.

OBJECTIVE: To assess safety associated with tubal ligation performed by trained clinical officers (COs) in rural Uganda. METHODS: Between March and June 2012, 518 women in 4 regions of Uganda were recruited into a prospective cohort study and followed at days 3, 7, and 45 after undergoing tubal ligation performed by a trained CO. Intraoperative and postoperative adverse events (minor, moderate, or major), and acceptability were assessed. RESULTS: Mean age was 36 years (range, 20-49 years) and mean number of living children was 6.7 (range, 0-15). The overall rate of major adverse events was 1.5%: 0.4% intraoperatively; 1.9% at day 3; and 0.2% at day 7. The majority of women who underwent tubal ligation reported a good/very good experience at the facility (range, 94%-99%) and would recommend the health services to a friend (range, 93%-98%). CONCLUSION: In the present study, task sharing of tubal ligation to trained COs in private facilities was safe. Women reported high levels of satisfaction with the procedure. Training COs could be an effective strategy for expanding family-planning services to rural Uganda

Efficient β-cell regeneration by a combination of neogenesis and replication following β-cell ablation and reversal of pancreatic duct ligation.

Achieving efficient β-cell regeneration is a major goal of diabetes research. Previously, we found that a combination of β-cell ablation and pancreatic duct ligation led to β-cell regeneration by direct conversion from α-cells. Here, we studied the effect of surgical reversal of the duct ligation, finding that there was a wave of β-cell replication following reversal. The combination of β-cell neogenesis prior to reversal of the duct ligation and β-cell replication following reversal resulted in efficient β-cell regeneration and eventual recovery of function. This provides an important proof of principle that efficient β-cell regeneration is possible, even from a starting point of profound β-cell ablation. This has important implications for efforts to promote β-cell regeneration

Lung Injury Pathways: Adenosine Receptor 2B Signaling Limits Development of Ischemic Bronchiolitis Obliterans Organizing Pneumonia

Purpose/Aim of the Study: Adenosine signaling was studied in bronchiolitis obliterans organizing pneumonia (BOOP) resulting from unilateral lung ischemia. Materials and Methods: Ischemia was achieved by either left main pulmonary artery or complete hilar ligation. Sprague–Dawley (SD) rats, Dahl salt sensitive (SS) rats and SS mutant rat strains containing a mutation in the A2B adenosine receptor gene (Adora2b) were studied. Adenosine concentrations were measured in bronchoalveolar lavage (BAL) by HPLC. A2A (A2AAR) and A2B adenosine receptor (A2BAR) mRNA and protein were quantified. Results: Twenty-four hours after unilateral PA ligation, BAL adenosine concentrations from ischemic lungs were increased relative to contralateral lungs in SD rats. A2BAR mRNA and protein concentrations were increased after PA ligation while miR27a, a negatively regulating microRNA, was decreased in ischemic lungs. A2AAR mRNA and protein concentrations remained unchanged following ischemia. A2BAR protein was increased in PA ligated lungs of SS rats after 7 days, and 4 h after complete hilar ligation in SD rats. SS-Adora2b mutants showed a greater extent of BOOP relative to SS rats, and greater inflammatory changes. Conclusion: Increased A2BAR and adenosine following unilateral lung ischemia as well as more BOOP in A2BAR mutant rats implicate a protective role for A2BAR signaling in countering ischemic lung injury

Molecular biology on a microfluidic chip

We have developed microfluidic chips for automating molecular biology processes such as gene ligation and gene transformation from nanolitre sample volumes with parallel architecture. Unlike conventional tube methods with cumbersome pipetting procedures, all processes, including metering of samples, ligation and transformation, were carried out in the microfluidic chips through pneumatic control of the nanofluid. The microfluidic devices presented here offer an illustration of some of the basic physics that arises when trying to miniaturize and automate biological techniques

Hepatic artery pseudoaneurysm ligation after orthotopic liver transplantation-a report of 7 cases

Pseudoaneurysm (PA) is a rare but life-threatening complication of liver transplantation. The authors present their experience on 7 patients treated by ligation of a post-OLT PA. Hepatic artery ligation or embolization was performed from 10 to 70 days after liver transplantation. Of the seven patients, four survived, one developed a biliary stricture, treated by percutaneous ballon dilatation, two died of a complication not related to treatment, and one died of multiple organ failure. © 1992 by Williams & Wilkins

Temporal profile and mechanisms of the prompt sympathoexcitation following coronary ligation in Wistar rats

Our aim was to assess the timing and mechanisms of the sympathoexcitation that occurs immediately after coronary ligation. We recorded thoracic sympathetic (tSNA) and phrenic activities, heart rate (HR) and perfusion pressure in Wistar rats subjected to either ligation of the left anterior descending coronary artery (LAD) or Sham operated in the working heart-brainstem preparation. Thirty minutes after LAD ligation, tSNA had increased (basal: 2.5±0.2 µV, 30 min: 3.5±0.3 µV), being even higher at 60 min (5.2±0.5 µV, P<0.01); while no change was observed in Sham animals. HR increased significantly 45 min after LAD (P<0.01). Sixty minutes after LAD ligation, there was: (i) an augmented peripheral chemoreflex - greater sympathoexcitatory response (50, 45 and 27% of increase to 25, 50 and 75 µL injections of NaCN 0.03%, respectively, when compared to Sham, P<0.01); (ii) an elevated pressor response (32±1 versus 23±1 mmHg in Sham, P<0.01) and a reduced baroreflex sympathetic gain (1.3±0.1 versus Sham 2.0±0.1%.mmHg-1, P<0.01) to phenylephrine injection; (iii) an elevated cardiac sympathetic tone (ΔHR after atenolol: -108±8 versus -82±7 bpm in Sham, P<0.05). In contrast, no changes were observed in cardiac vagal tone and bradycardic response to both baroreflex and chemoreflex between LAD and Sham groups. The immediate sympathoexcitatory response in LAD rats was dependent on an excitatory spinal sympathetic cardiocardiac reflex, whereas at 3 h an angiotensin II type 1 receptor mechanism was essential since Losartan curbed the response by 34% relative to LAD rats administered saline (P<0.05). A spinal reflex appears key to the immediate sympathoexcitatory response after coronary ligation. Therefore, the sympathoexcitatory response seems to be maintained by an angiotensinergic mechanism and concomitant augmentation of sympathoexcitatory reflexes

Sturdier DNA nanotubes via ligation

DNA nanotubes are crystalline self-assemblies of DNA tiles ~10 nm in diameter that readily grow tens of micrometers in length. Easy assembly, programmability, and stiffness make them interesting for many applications, but DNA nanotubes begin to melt at temperatures below 40 °C, break open when deposited on mica or scanned by AFM, and disintegrate in deionized water. These weaknesses can be traced to the presence of discontinuities in the phosphate backbone, called nicks. The nanotubes studied here have five nicks, one in the core of a tile and one at each corner. We report the successful ligation of all four corner nicks by T4 DNA ligase. Although ligation does not change the nanotubes’ stiffness, ligated nanotubes withstand temperatures over 70 °C, resist breaking during AFM, and are stable in pure water for over a month. Ligated DNA nanotubes are thus physically and chemically sturdy enough to withstand the manipulations necessary for many technological applications