Project description:Incremental increases in a driver variable, such as nutrients or detritus, can trigger abrupt shifts in aquatic ecosystems that may exhibit hysteretic dynamics and a slow return to the initial state. A model system for understanding these dynamics is the microbial assemblage that inhabits the cup-shaped leaves of the pitcher plant Sarracenia purpurea. With enrichment of organic matter, this system flips within three days from an oxygen-rich state to an oxygen-poor state. In a replicated greenhouse experiment, we enriched pitcher-plant leaves at different rates with bovine serum albumin (BSA), a molecular substitute for detritus. Changes in dissolved oxygen (DO) and undigested BSA concentration were monitored during enrichment and recovery phases. With increasing enrichment rates, the dynamics ranged from clockwise hysteresis (low), to environmental tracking (medium), to novel counter-clockwise hysteresis (high). These experiments demonstrate that detrital enrichment rate can modulate a diversity of hysteretic responses within a single aquatic ecosystem, and suggest different management strategies may be needed to mitigate the effects of high vs. low rates of detrital enrichment.
Project description:The bacterial flagellar motor is a reversible rotary machine that rotates a left-handed helical filament, allowing bacteria to swim toward a more favorable environment. The direction of rotation reverses from counterclockwise (CCW) to clockwise (CW), and vice versa, in response to input from the chemotaxis signaling circuit. CW rotation is normally caused by binding of the phosphorylated response regulator CheY (CheY-P), and strains lacking CheY are typically locked in CCW rotation. The detailed mechanism of switching remains unresolved because it is technically difficult to regulate the level of CheY-P within the concentration range that produces flagellar reversals. Here, we demonstrate that high hydrostatic pressure can induce CW rotation even in the absence of CheY-P. The rotation of single flagellar motors in Escherichia coli cells with the cheY gene deleted was monitored at various pressures and temperatures. Application of >120 MPa pressure induced a reversal from CCW to CW at 20°C, although at that temperature, no motor rotated CW at ambient pressure (0.1 MPa). At lower temperatures, pressure-induced changes in direction were observed at pressures of <120 MPa. CW rotation increased with pressure in a sigmoidal fashion, as it does in response to increasing concentrations of CheY-P. Application of pressure generally promotes the formation of clusters of ordered water molecules on the surfaces of proteins. It is possible that hydration of the switch complex at high pressure induces structural changes similar to those caused by the binding of CheY-P.
Project description:Clinical electrophysiology has made the traditional classification of rapid atrial rhythms into flutter and tachycardia of little clinical use. Electrophysiological studies have defined multiple mechanisms of tachycardia, both re-entrant and focal, with varying ECG morphologies and rates, authenticated by the results of catheter ablation of the focal triggers or critical isthmuses of re-entry circuits. In patients without a history of heart disease, cardiac surgery or catheter ablation, typical flutter ECG remains predictive of a right atrial re-entry circuit dependent on the inferior vena cava-tricuspid isthmus that can be very effectively treated by ablation, although late incidence of atrial fibrillation remains a problem. Secondary prevention, based on the treatment of associated atrial fibrillation risk factors, is emerging as a therapeutic option. In patients subjected to cardiac surgery or catheter ablation for the treatment of atrial fibrillation or showing atypical ECG patterns, macro-re-entrant and focal tachycardia mechanisms can be very complex and electrophysiological studies are necessary to guide ablation treatment in poorly tolerated cases.
Project description:A few studies have recently reported clockwise and counterclockwise rotations of QRS transition zone as predictors of mortality. However, their prospective correlates and associations with individual cardiovascular disease (CVD) outcomes are yet to be investigated. Among 13 567 ARIC (Atherosclerosis Risk in Communities) study participants aged 45 to 64 years, we studied key correlates of changes in the status of clockwise and counterclockwise rotation over time as well as the association of rotation status with incidence of coronary heart disease (2408 events), heart failure (2196 events), stroke (991 events), composite CVD (4124 events), 898 CVD deaths, and 3469 non-CVD deaths over 23 years of follow-up. At baseline, counterclockwise rotation was most prevalent (52.9%), followed by no (40.5%) and clockwise (6.6%) rotation. Of patients with no rotation, 57.9% experienced counterclockwise or clockwise rotation during follow-up, with diabetes mellitus and black race significantly predicting clockwise and counterclockwise conversion, respectively. Clockwise rotation was significantly associated with higher risk of heart failure (hazard ratio, 1.20; 95% confidence interval [CI], 1.02-1.41) and non-CVD death (hazard ratio, 1.28; 95% CI, 1.12-1.46) after adjusting for potential confounders including other ECG parameters. On the contrary, counterclockwise rotation was significantly related to lower risk of composite CVD (hazard ratio, 0.93; 95% CI, 0.87-0.99]), CVD mortality (hazard ratio, 0.76; 95% CI, 0.65-0.88), and non-CVD deaths (hazard ratio, 0.92; 95% CI, 0.85-0.99 [borderline significance with heart failure]). Counterclockwise rotation, the most prevalent QRS transition zone pattern, demonstrated the lowest risk of CVD and mortality, whereas clockwise rotation was associated with the highest risk of heart failure and non-CVD mortality. These results have implications on how to interpret QRS transition zone rotation when ECG was recorded.
Project description:BackgroundGnosis is a modality-specific ability to access semantic knowledge of an object or stimulus in the presence of normal perception. Failure of this is agnosia or disorder of recognition. It can be highly selective within a mode. self-images are different from others as none has seen one's own image except in reflection. Failure to recognize this image can be labeled as mirror image agnosia or Prosopagnosia for reflected self-image. Whereas mirror agnosia is a well-recognized situation where the person while looking at reflected images of other objects in the mirror he imagines that the objects are in fact inside the mirror and not outside.Material and methodsFive patients, four females, and one male presented with failure to recognize reflected self-image, resulting in patients conversing with the image as a friend, fighting because the person in mirror is wearing her nose stud, suspecting the reflected self-image to be an intruder; but did not have prosopagnosia for others faces, non living objects on self and also apraxias except dressing apraxia in one patient. This phenomena is new to our knowledge.ResultsMirror image agnosia is an unique phenomena which is seen in patients with parietal lobe atrophy without specificity to a category of dementing illness and seems to disappear as disease advances.DiscussionReflected self-images probably have a specific neural substrate that gets affected very early in posterior dementias specially the ones which predominantly affect the right side. At that phase most patients are mistaken as suffering from psychiatric disorder as cognition is moderately preserved. As disease becomes more widespread this symptom becomes masked. A high degree of suspicion and proper assessment might help physicians to recognize the organic cause of the symptom so that early therapeutic interventions can be initiated. Further assessment of the symptom with FMRI and PET scan is likely to solve the mystery of how brain handles reflected self-images.ConclusionA new observation involving failure to recognize reflected self-images is reported.
Project description:DNA amplification circuits that rely on thermodynamically-driven hybridization events triggered by a target nucleic acid are becoming increasingly utilized due to their relative simplicity. A drawback of these circuits is that non-specific amplification, or circuit leakage, must be estimated using a separate "no-target" control reaction to eliminate false positives. Aside from requiring an additional reaction, the problem with this approach is the difficulty of creating a no-target control for biological specimens. To overcome this limitation, we propose a strategy that combines both reactions into the same tube using naturally-occurring right-handed D-DNA circuit elements for the target detection reaction and identical synthetic mirror-image left-handed L-DNA circuit elements for the no-target control reaction. We illustrate this approach using catalyzed hairpin assembly (CHA), one of the most studied DNA amplification circuits. In a dual-chirality CHA design, the right-handed circuit signal is produced by target-specific amplification and circuit leakage, whereas the left-handed circuit signal is produced only by circuit leakage. The target-specific amplification is calculated as the difference between the two signals. The limit of detection of this dual-chirality CHA reaction was found to be similar to that of traditional CHA (81 vs 92 pM, respectively). Furthermore, the left-handed no-target signal matched the right-handed leakage across a wide range of sample conditions including background DNA, increased salt concentration, increased temperature, and urine. These results demonstrate the robustness of a dual-chirality design and the potential utility of left-handed DNA in the development of new DNA amplification circuits better-suited for target detection applications in biological samples.
Project description:Background: New-onset atrial fibrillation (AF) after ablation of typical atrial flutter (AFL) is not rare. This study aimed to investigate the predictive value of electrocardiographic parameters on new-onset AF post-typical AFL ablation. Methods: A total of 158 consecutive patients (79.1% males, mean age 57.8 ± 14.3 years) with typical AFL were enrolled between January 2012 and August 2017 in this single-center study. Patients with a history of AF before ablation were excluded. ECGs during sinus rhythm (SR) and AFL were collected. The duration of the negative component of flutter wave in lead II (DFNII), proportion of the DFNII of the total circle length of AFL (DFNII%), amplitude of the negative component of flutter wave in lead II (AFNII), duration (DPNV1), and amplitude (APNV1) of negative component of the P wave in lead V1, and P wave duration in lead II (DPII) during sinus rhythm were measured. Results: During a median follow-up of 26.9 ± 11.8 months, 22 cases (13.9%) developed new-onset AF. DFNII was significantly longer in patients with new-onset AF compared to patients without AF (114.7 ± 29.6 ms vs. 82.7 ± 12.8 ms, p < 0.0001). AFNII was significantly lower (0.118 ± 0.034 mV vs. 0.168 ± 0.051 mV, p < 0.0001), DPII (144.21 ± 23.77 ms vs. 111.46 ± 14.19 ms, p < 0.0001), and DPNV1 was significantly longer (81.07 ± 16.87 ms vs. 59.86 ± 14.42 ms, p < 0.0001) in patients with new-onset AF. In the multivariate analysis, DFNII [odds ratio (OR), 1.428; 95% CI, 1.039-1.962; p = 0.028] and DPII (OR, 1.429; 95% CI, 1.046-1.953; p = 0.025) were found to be independently associated with new-onset AF after typical AFL ablation. Conclusion: Parameters representing left atrial activation time under both the SR and AFL were independently associated with new-onset AF post-typical AFL ablation and may be useful in risk prediction, which needs to be confirmed by further prospective studies.
Project description:The construction of mirror-image biological systems may open the next frontier for biomedical technology development and discovery. Here we have designed and chemically synthesized a mutant version of the thermostable Sulfolobus solfataricus P2 DNA polymerase IV (Dpo4) consisting of d-amino acids. With a total peptide length of 358 amino acid residues, it is the largest chemically synthesized d-amino acid protein reported to date. We show that the d-polymerase is able to amplify a 120-bp l-DNA sequence coding for the Escherichia coli 5S ribosomal RNA gene rrfB by mirror-image polymerase chain reaction, and that both the natural and mirror-image systems operate with strict chiral specificity. The development of efficient miPCR systems may lead to many practical applications, such as mirror-image systematic evolution of ligands by exponential enrichment for the selection of therapeutically promising nuclease-resistant l-nucleic acid aptamers.
Project description:After realizing mirror-image genetic replication, transcription, and reverse transcription, the biggest challenge in establishing a mirror-image version of the central dogma is to build a mirror-image ribosome-based translation machine. Here, we chemically synthesized the natural and mirror-image versions of three ribosomal proteins (L5, L18, and L25) in the large subunit of the Escherichia coli ribosome with post-translational modifications. We show that the synthetic mirror-image proteins can fold in vitro despite limited efficiency and assemble with enzymatically transcribed mirror-image 5S ribosomal RNA into ribonucleoprotein complexes. In addition, the RNA-protein interactions are chiral-specific in that the mirror-image ribosomal proteins do not bind with natural 5S ribosomal RNA and vice versa. The synthesis and assembly of mirror-image 5S ribonucleoprotein complexes are important steps towards building a functional mirror-image ribosome.
Project description:The development of mirror-image biology systems and related applications is hindered by the lack of effective methods to sequence mirror-image (D-) proteins. Although natural-chirality (L-) proteins can be sequenced by bottom–up liquid chromatography–tandem mass spectrometry (LC–MS/MS), the sequencing of long D-peptides and D-proteins with the same strategy requires digestion by a site-specific D-protease before mass analysis. Here we apply solid-phase peptide synthesis and native chemical ligation to chemically synthesize a mirror-image version of trypsin, a widely used protease for site-specific protein digestion. Using mirror-image trypsin digestion and LC–MS/MS, we sequence a mirror-image large subunit ribosomal protein (L25) and a mirror-image Sulfolobus solfataricus P2 DNA polymerase IV (Dpo4), and distinguish between different mutants of D-Dpo4. We also perform writing and reading of digital information in a long D-peptide of 50 amino acids. Thus, mirror-image trypsin digestion in conjunction with LC–MS/MS may facilitate practical applications of D-peptides and D-proteins as potential therapeutic and informational tools.