Overcoming thermostability challenges in mRNA-lipid nanoparticle systems with piperidine-based ionizable lipids.

Lipid nanoparticles (LNPs) have emerged as promising platforms for efficient in vivo mRNA delivery owing to advancements in ionizable lipids. However, maintaining the thermostability of mRNA/LNP systems remains challenging. While the importance of only a small amount of lipid impurities on mRNA inactivation is clear, a fundamental solution has not yet been proposed. In this study, we investigate an approach to limit the generation of aldehyde impurities that react with mRNA nucleosides through the chemical engineering of lipids. We demonstrated that piperidine-based lipids improve the long-term storage stability of mRNA/LNPs at refrigeration temperature as a liquid formulation. High-performance liquid chromatography analysis and additional lipid synthesis revealed that amine moieties of ionizable lipids play a vital role in limiting reactive aldehyde generation, mRNA-lipid adduct formation, and loss of mRNA function during mRNA/LNP storage. These findings highlight the importance of lipid design and help enhance the shelf-life of mRNA/LNP systems.

Magnetic Supramolecular Spherical Arrays: Direct Formation of Micellar Cubic Mesophase by Lanthanide Metallomesogens with 7-Coordination Geometry.

Here, an unprecedented phenomenon in which 7-coordinate lanthanide metallomesogens, which align via hydrogen bonds mediated by coordinated H2 O molecules, form micellar cubic mesophases at room temperature, creating body-centered cubic (BCC)-type supramolecular spherical arrays, is reported. The results of experiments and molecular dynamics simulations reveal that spherical assemblies of three complexes surrounded by an amorphous alkyl domain spontaneously align in an energetically stable orientation to form the BCC structure. This phenomenon differs greatly from the conventional self-assembling behavior of 6-coordinated metallomesogens, which form columnar assemblies due to strong intermolecular interactions. Since the magnetic and luminescent properties of different lanthanides vary, adding arbitrary functions to spherical arrays is possible by selecting suitable lanthanides to be used. The method developed in this study using 7-coordinate lanthanide metallomesogens as building blocks is expected to lead to the rational development of micellar cubic mesophases.

Dysmaturation of sleep state and electroencephalographic activity after hypoxia-ischaemia in preterm fetal sheep.

Antenatal hypoxia-ischaemia (HI) in preterm fetal sheep can trigger delayed evolution of severe, cystic white matter injury (WMI), in a similar timecourse to WMI in preterm infants. We therefore examined how severe hypoxia-ischaemia affects recovery of electroencephalographic (EEG) activity. Chronically instrumented preterm fetal sheep (0.7 gestation) received 25 min of complete umbilical cord occlusion (UCO, n = 9) or sham occlusion (controls, n = 9), and recovered for 21 days. HI was associated with a shift to lower frequency EEG activity for the first 5 days with persisting loss of EEG power in the delta and theta bands, and initial loss of power in the alpha and beta bands in the first 14 days of recovery. In the final 3 days of recovery, there was a marked rhythmic shift towards higher frequency EEG activity after UCO. The UCO group spent less time in high-voltage sleep, and in the early evening (7:02 pm ± 47 min) abruptly stopped cycling between sleep states, with a shift to a high frequency state for 2 h 48 min ± 40 min, with tonic electromyographic activity. These findings demonstrate persisting EEG and sleep state dysmaturation after severe hypoxia-ischaemia. Loss of fetal or neonatal sleep state cycling in the early evening may be a useful biomarker for evolving cystic WMI.

Circadian patterns of heart rate variability in fetal sheep after hypoxia-ischaemia: A biomarker of evolving brain injury.

Hypoxia-ischaemia (HI) before birth is a key risk factor for stillbirth and severe neurodevelopmental disability in survivors, including cerebral palsy, although there are no reliable biomarkers to detect at risk fetuses that may have suffered a transient period of severe HI. We investigated time and frequency domain measures of fetal heart rate variability (FHRV) for 3 weeks after HI in preterm fetal sheep at 0.7 gestation (equivalent to preterm humans) until 0.8 gestation (equivalent to term humans). We have previously shown that this is associated with delayed development of severe white and grey matter injury, including cystic white matter injury (WMI) resembling that observed in human preterm infants. HI was associated with suppression of time and frequency domain measures of FHRV and reduced their circadian rhythmicity during the first 3 days of recovery. By contrast, circadian rhythms of multiple measures of FHRV were exaggerated over the final 2 weeks of recovery, mediated by a greater reduction in FHRV during the morning nadir, but no change in the evening peak. These data suggest that the time of day at which FHRV measurements are taken affects their diagnostic utility. We further propose that circadian changes in FHRV may be a low-cost, easily applied biomarker of antenatal HI and evolving brain injury. KEY POINTS: Hypoxia-ischaemia (HI) before birth is a key risk factor for stillbirth and probably for disability in survivors, although there are no reliable biomarkers for antenatal brain injury. In preterm fetal sheep, acute HI that is known to lead to delayed development of severe white and grey matter injury over 3 weeks, was associated with early suppression of multiple time and frequency domain measures of fetal heart rate variability (FHRV) and loss of their circadian rhythms during the first 3 days after HI. Over the final 2 weeks of recovery after HI, exaggerated circadian rhythms of frequency domain FHRV measures were observed. The morning nadirs were lower with no change in the evening peak of FHRV. Circadian changes in FHRV may be a low-cost, easily applied biomarker of antenatal HI and evolving brain injury.

Rapid response to a coronavirus disease 2019 (COVID-19) outbreak in a psychiatry hospital-Kanazawa City, Japan, March to April 2020.

A coronavirus disease 2019 (COVID-19) outbreak in a psychiatry hospital revealed specific challenges in its response such as difficulty in isolation, transfer, and identification of close contacts, suboptimal infection control practices, and shortage of personal protective equipment, which were overcome by support from the public health center and a neighboring university hospital.

A Retrospective Study on the Relationship Between Cognitive Function and Social Function in Patients With Schizophrenia.

Background: Social dysfunction is associated with decreased activity, employment difficulties, and poor prognosis in patients with schizophrenia. Cognitive functions, such as attention and processing speed, have been implicated in the social functions of schizophrenia patients; however, the relationship between cognitive functions and social functions remains unclear. Thus, understanding the factors that influence social functioning can aid the development of therapeutic strategies for schizophrenia. Herein, we retrospectively analyzed factors that influence social functioning in patients with schizophrenia. Methods: Patient background, intelligence quotient (IQ) scores, Japanese version of the Brief Assessment of Cognition in Schizophrenia (BACS-J) scores, the dose of antipsychotic drugs, Positive and Negative Syndrome Scale (PANSS) scores, and the factors influencing each subscale of the Japanese version of the Social Functioning Scale (SFS-J) were evaluated using univariate and multivariate analyses. The Bonferroni correction was applied to evaluate the correlation between each factor in the univariate analysis. In multivariate analysis, independent variables were selected using a stepwise method. In each model, considering the sample size, the maximum number of variables extracted using the stepwise method was set to three. We then calculated the standard partial regression coefficient (standard ß) between the SFS-J subscale scores and each factor. Results: Data from 36 patients were analyzed. The average age, illness duration, and total length of hospitalization were 57.8 years, 34.8 years, and 196.7 months, respectively. Of the seven significant correlations with the SFS-J subscale in the univariate analysis, only three were significant in the multivariate analysis model. According to the multivariable model, BACS-J verbal fluency positively correlated with SFS-J withdrawal, interpersonal communication, and employment/occupation. Moreover, BACS-J token motor and educational history were positively correlated with SFS-J recreation and SFS-J employment/occupation, respectively. PANSS scores, IQ scores, and doses of antipsychotic drugs did not show clear associations with SFS-J scores. Conclusions: In conclusion, there were significant correlations between BACS-J subscale scores for cognitive functioning and SFS-J subscale scores for social functioning in patients with schizophrenia.

A case report of late-onset schizophrenia differentiated from a dementing disorder.

We report a case of late-onset schizophrenia that required differentiation from a dementing disorder. The patient was an 83-year-old woman who had experienced auditory hallucinations since she was 67 years old. The patient had slightly elevated total tau and slightly decreased amyloid ß1-42, cerebrospinal fluid biomarkers. This case was identified as late-onset schizophrenia. However, the results of cerebrospinal fluid biomarkers indicated that neurofibrillary tangles and neuronal death, which are characteristic of Alzheimer 's disease, may also have been present. Late-onset schizophrenia should be treated based on an appropriate differential diagnosis, including neuropathological consideration of dementing disorders.

Transient effects of forebrain ischemia on fetal heart rate variability in fetal sheep.

Fetal heart rate variability (FHRV) is a key index of antenatal and intrapartum fetal well-being. FHRV is well established to be mediated by both arms of the autonomic nervous system, but it remains unknown whether higher centers in the forebrain contribute to FHRV. We tested the hypothesis that selective forebrain ischemia would impair the generation of FHRV. Sixteen chronically instrumented near-term fetal sheep were subjected to either forebrain ischemia induced by bilateral carotid occlusion or sham-ischemia for 30 min. Time, frequency, and nonlinear measures of FHRV were assessed during and for seven days after ischemia. Ischemia was associated with profound suppression of electroencephalographic (EEG) power, which remained suppressed throughout the recovery period (P < 0.001). During the first 5 min of ischemia, multiple time and frequency domain measures were increased (all P < 0.05) before returning back to sham levels. A delayed increase in sample entropy was observed during ischemia (P < 0.05). For the first 3 h after ischemia, there was moderate suppression of two measures of FHRV (very-low frequency power and the standard deviation of RR-intervals, both P < 0.05) and increased sample entropy (P < 0.05). Thereafter, all measures of FHRV returned to control levels. In conclusion, profound forebrain ischemia sufficient to lead to severe neural injury had only transient effect on multiple measures of FHRV. These findings suggest that the forebrain makes a limited contribution to FHRV. FHRV therefore primarily originates in the hindbrain and is unlikely to provide meaningful information on forebrain neurodevelopment or metabolism.

Effects of antenatal dexamethasone and hyperglycemia on cardiovascular adaptation to asphyxia in preterm fetal sheep.

Antenatal glucocorticoids improve outcomes among premature infants but are associated with hyperglycemia, which can exacerbate hypoxic-ischemic injury. It is still unclear how antenatal glucocorticoids or hyperglycemia modulate fetal cardiovascular adaptations to severe asphyxia. In this study, preterm fetal sheep received either saline or 12 mg im maternal dexamethasone, followed 4 h later by complete umbilical cord occlusion (UCO) for 25 min. An additional cohort of fetuses received titrated glucose infusions followed 4 h later by UCO to control for the possibility that hyperglycemia contributed to the cardiovascular effects of dexamethasone. Fetuses were studied for 7 days after UCO. Maternal dexamethasone was associated with fetal hyperglycemia (P < 0.001), increased arterial pressure (P < 0.001), and reduced femoral (P < 0.005) and carotid (P < 0.05) vascular conductance before UCO. UCO was associated with bradycardia, femoral vasoconstriction, and transient hypertension. For the first 5 min of UCO, fetal blood pressure in the dexamethasone-asphyxia group was greater than saline-asphyxia (P < 0.001). However, the relative increase in arterial pressure was not different from saline-asphyxia. Fetal heart rate and femoral vascular conductance fell to similar nadirs in both saline and dexamethasone-asphyxia groups. Dexamethasone did not affect the progressive decline in femoral vascular tone or arterial pressure during continuing UCO. By contrast, there were no effects of glucose infusions on the response to UCO. In summary, maternal dexamethasone but not fetal hyperglycemia increased fetal arterial pressure before and for the first 5 min of prolonged UCO but did not augment the cardiovascular adaptations to acute asphyxia.

Parasympathetic activity is the key regulator of heart rate variability between decelerations during brief repeated umbilical cord occlusions in fetal sheep.

Fetal heart rate variability (FHRV) is a widely used index of intrapartum well being. Both arms of the autonomic system regulate FHRV under normoxic conditions in the antenatal period. However, autonomic control of FHRV during labor when the fetus is exposed to repeated, brief hypoxemia during uterine contractions is poorly understood. We have previously shown that the sympathetic nervous system (SNS) does not regulate FHRV during labor-like hypoxia. We therefore investigated the hypothesis that the parasympathetic system is the main mediator of intrapartum FHRV. Twenty-six chronically instrumented fetal sheep at 0.85 of gestation received either bilateral cervical vagotomy (n = 7), atropine sulfate (n = 7), or sham treatment (control, n = 12), followed by three 1-min complete umbilical cord occlusions (UCOs) separated by 4-min reperfusion periods. Parasympathetic blockade reduced three measures of FHRV before UCOs (all P < 0.01). Between UCOs, atropine and vagotomy were associated with marked tachycardia (both P < 0.005), suppressed measures of FHRV (all P < 0.01), and abolished FHRV on visual inspection compared with the control group. Tachycardia in the atropine and vagotomy groups resolved over the first 10 min after the final UCO, in association with evidence that the SNS contribution to FHRV progressively returned during this time. Our findings support that SNS control of FHRV is acutely suppressed for at least 4 min after a deep intrapartum deceleration and takes 5-10 min to recover. The parasympathetic system is therefore likely to be the key mediator of FHRV once frequent FHR decelerations are established during labor.

Peripheral chemoreflex control of fetal heart rate decelerations overwhelms the baroreflex during brief umbilical cord occlusions in fetal sheep.

KEY POINTS: The majority of intrapartum decelerations are widely believed to be mediated by the baroreflex secondary to brief umbilical cord occlusions (UCOs) but this remains unproven. We examined the responses to brief-UCOs in fetal sheep and compared these to a phenylephrine-stimulated baroreflex in a separate cohort. A further cohort was instrumented with near-infrared spectroscopy to measure cerebral oxygenation during UCO. The first 3-4 s of the brief-UCOs were consistent with a baroreflex, and associated with a minor fall in fetal heart rate (FHR). Thereafter, the remainder of the FHR decelerations were highly consistent with the peripheral chemoreflex. The baroreflex is not sufficient to produce deep, rapid decelerations characteristic of variable decelerations and it is therefore likely to be a minor contributor to intrapartum decelerations. ABSTRACT: Fetal heart rate (FHR) monitoring is widely used to assess fetal wellbeing during labour, yet the physiology underlying FHR patterns remains incompletely understood. The baroreflex is widely believed to mediate brief intrapartum decelerations, but evidence supporting this theory is lacking. We therefore investigated the physiological changes in near-term fetal sheep during brief repeated umbilical cord occlusions (brief-UCOs, n = 15). We compared this to separate cohorts that underwent a phenylephrine challenge to stimulate the baroreflex (n = 9) or were instrumented with near-infrared spectroscopy and underwent prolonged 15-min complete UCO (prolonged-UCO, n = 9). The first 3-4 s of brief-UCOs were associated with hypertension (P = 0.000), a fall in FHR by 9.7-16.9 bpm (P = 0.002). The FHR/MAP relationship during this time was consistent with that observed during a phenylephrine-induced baroreflex. At 4-5 s, the FHR/MAP relationship began to deviate from the phenylephrine baroreflex curve as FHR fell independently of MAP until its nadir in association with intense peripheral vasoconstriction (P = 0.000). During prolonged-UCO, cerebral oxygenation remained steady until 4 s after the start of prolonged-UCO, and then began to fall (P = 0.000). FHR and cerebral oxygenation then fell in parallel until the FHR nadir. In conclusion, the baroreflex has a minor role in mediating the first 3-4 s of FHR decelerations during complete UCO, but thereafter the peripheral chemoreflex is the dominant mediator. Overall, the baroreflex is neither necessary nor sufficient to produce deep, rapid decelerations characteristic of variable decelerations; it is therefore likely to be a minor contributor to intrapartum decelerations.

Resistive switching memory performance in oxide hetero-nanocrystals with well-controlled interfaces.

For realization of new informative systems, the memristor working like synapse has drawn much attention. We developed isolated high-density Fe3O4 nanocrystals on Ge nuclei/Si with uniform and high resistive switching performance using low-temperature growth. The Fe3O4 nanocrystals on Ge nuclei had a well-controlled interface (Fe3O4/GeOx/Ge) composed of high-crystallinity Fe3O4 and high-quality GeOx layers. The nanocrystals showed uniform resistive switching characteristics (high switching probability of ~90%) and relatively high Off/On resistance ratio (~58). The high-quality interface enables electric field application to Fe3O4 and GeOx near the interface, which leads to effective positively charged oxygen vacancy movement, resulting in high-performance resistive switching. Furthermore, we successfully observed memory effect in nanocrystals with well-controlled interface. The experimental confirmation of the memory effect existence even in ultrasmall nanocrystals is significant for realizing non-volatile nanocrystal memory leading to neuromorphic devices.

Early sinusoidal heart rate patterns and heart rate variability to assess hypoxia-ischaemia in near-term fetal sheep.

KEY POINTS: •Therapeutic hypothermia needs to be started as early as possible in the first 6 h after acute injury caused by hypoxia-ischaemia (HI), but the severity and timing of HI are often unclear. In this study we evaluated whether measures of heart rate variability (HRV) might provide early biomarkers of HI. •The duration but not magnitude of suppression of HRV power and conversely increased sample entropy of the heart rate were associated with severity of HI, such that changes in the first 3 h did not discriminate between groups. •Relative changes in HRV power bands showed different patterns between groups and therefore may have the potential to evaluate the severity of HI. •Aberrant fetal heart rate patterns and increased arginine vasopressin levels in the first hour after moderate and severe HI were correlated with loss of EEG power after 3 days' recovery, suggesting potential utility as early biomarkers of outcome. ABSTRACT: Therapeutic hypothermia is partially neuroprotective after acute injury caused by hypoxia-ischaemia (HI), likely because the timing and severity of HI are often unclear, making timely recruitment for treatment challenging. We evaluated the utility of changes in heart rate variability (HRV) after HI as biomarkers of the timing and severity of acute HI. Chronically instrumented fetal sheep at 0.85 gestational age were exposed to different durations of umbilical cord occlusion to produce mild (n = 6), moderate (n = 8) or severe HI (n = 8) or to sham occlusion (n = 5). Heart rate (HR) and HRV indices were assessed until 72 h after HI. All HI groups showed suppressed very low frequency HRV power and elevated sample entropy for the first 3 h; more prolonged changes were associated with greater severity of HI. Analysis of relative changes in spectral power showed that the moderate and severe groups showed a shift towards higher HRV frequencies, which was most marked after severe HI. This shift was associated with abnormal rhythmic HR patterns including sinusoidal patterns in the first hour after HI, and with elevated plasma levels of arginine vasopressin, which were correlated with subsequent loss of EEG power by day 3. In conclusion, absolute changes in HRV power in the first 3 h after acute HI were not significantly related to the severity of HI. The intriguing relative shift in spectral power towards higher frequencies likely reflects greater autonomic dysfunction after severe HI. However, sinusoidal HR patterns and elevated vasopressin levels may have utility as biomarkers of severe HI.

Verbal Instruction Can Induce Extinction of Fear of Movement-Related Pain.

The fear avoidance model of chronic musculoskeletal pain highlights the importance of pain-related fear in chronification of pain. Although several interventions have been developed on the basis of this model, the following issues remain unresolved: first, whether movement conditioned to pain can evoke fear responses particularly sympathetic activation, and second, whether verbal instructions can attenuate conditioned fear of movement-related pain as with direct experience. To investigate these issues, we induced proprioceptive conditioning (learning the relationship between proprioceptive sensations and an aversive event) and extinction learning in healthy volunteers, and we compared psychophysiological and subjective indices of fear between an instructed and a normal extinction group. Using paired presentation of painful heat stimuli as an unconditioned stimulus and flexion of the wrist as a conditioned stimulus, all participants acquired the conditioned fear response (skin potential response) to the conditioned stimulus. The instructed extinction group was then told that the movement was no longer followed by painful stimulus at the beginning of the extinction phase, and only this group showed significant decreases on both indices of fear. This finding indicates that verbal instruction can attenuate conditioned fear of movement-related pain, supporting the clinical importance of providing information regarding the relationship between movement and pain. PERSPECTIVE: This article presents evidence that, in a laboratory setting, verbal instructions rapidly decrease conditioned fear of movement-related pain on psychophysiological as well as subjective indices. This result indicates that it is important for chronic musculoskeletal pain patients to precisely understand the relationship between movement and pain in clinical situations.

Development of one-shot aspheric measurement system with a Shack-Hartmann sensor.

We present a measurement system for a rotationally symmetric aspheric surface that is designed for accurate and high-volume measurements. The system uses the Shack-Hartmann sensor and is capable of measuring aspheres with a maximum diameter of 90 mm in one shot. In our system, a reference surface, made with the same aspheric parameter as the test surface, is prepared. The test surface is recovered as the deviation from the reference surface using a figure-error reconstruction algorithm with a ray coordinate and angle variant table. In addition, we developed a method to calibrate the rotationally symmetric system error. These techniques produce stable measurements and high accuracy. For high-throughput measurements, a single measurement scheme and auto alignment are implemented; they produce a 4.5 min measurement time, including calibration and alignment. In this paper, we introduce the principle and calibration method of our system. We also demonstrate that our system achieved an accuracy better than 5.8 nm RMS and a repeatability of 0.75 nm RMS by comparing our system's aspheric measurement results with those of a probe measurement machine.

(Near-Infrared) Fluorescence-Guided Surgery Under Ambient Light Conditions: A Next Step to Embedment of the Technology in Clinical Routine.

BACKGROUND AND PURPOSE: In open surgery procedures, after temporarily dimming the lights in the operation theatre, the Photo Dynamic Eye (PDE) fluorescence camera has, amongst others, been used for fluorescence-guided sentinel node (SN) biopsy procedures. To improve the clinical utility and logistics of fluorescence-guided surgery, we developed and evaluated a prototype modified PDE (m-PDE) fluorescence camera system. METHODS: The m-PDE works under ambient light conditions and includes a white light mode and a pseudo-green-colored fluorescence mode (including a gray-scaled anatomical background). Twenty-seven patients scheduled for SN biopsy for (head and neck) melanoma (n = 16), oral cavity (n = 6), or penile (n = 5) cancer were included. The number and location of SNs were determined following an indocyanine green-(99m)Tc-nanocolloid injection and preoperative imaging. Intraoperatively, fluorescence guidance was used to visualize the SNs. The m-PDE and conventional PDE were compared head-to-head in a phantom study, and in seven patients. In the remaining 20 patients, only the m-PDE was evaluated. RESULTS: Phantom study: The m-PDE was superior over the conventional PDE, with a detection sensitivity of 1.20 × 10(-11) M (vs. 3.08 × 10(-9) M) ICG in human serum albumin. In the head-to-head clinical comparison (n = 7), the m-PDE was also superior: (i) SN visualization: 100 versus 81.4 %; (ii) transcutaneous SN visualization: 40.7 versus 22.2 %; and (iii) lymphatic duct visualization: 7.4 versus 0 %. Findings were further underlined in the 20 additionally included patients. CONCLUSION: The m-PDE enhanced fluorescence imaging properties compared with its predecessor, and provides a next step towards routine integration of real-time fluorescence guidance in open surgery.

Prospective evaluation of whole-body cancer screening with multiple modalities including [18F]fluorodeoxyglucose positron emission tomography in a healthy population: a preliminary report.

PURPOSE: To prospectively evaluate the utility of whole-body cancer screening with multiple modalities including [(18)F]fluorodeoxyglucose positron emission tomography (FDG-PET) in a healthy population. This report summarizes the results of the first three annual screenings. PARTICIPANTS AND METHODS: A total of 1,197 healthy volunteers > or = 35 years old were enrolled between August 2003 and July 2004 and offered annual cancer screening for 5 years with subsequent long-term follow-up. Screening modalities included were whole-body FDG-PET, chest and abdominal computed tomography (CT), brain and pelvic magnetic resonance imaging, several tumor markers, and fecal occult blood testing. RESULTS: As of the end of 2006, 22 primary cancers were pathologically confirmed. Nineteen of 22 were detected by the screening; 18 in the initial, one in the second, and none in the third. Three were diagnosed after development of symptoms. Of the 18 detected in the initial screening (six thyroid, four lung, three prostate, three breast, one endometrial, and one thymic), 12 were at stage I and 11 were PET positive. PET-negative cancers were detected by CT or the prostate-specific antigen (PSA) test. Sensitivity and specificity were 50.0% (11 of 22) and 93.2% (1,095 of 1,175), respectively, for FDG-PET alone and 81.8% (18 of 22) and 82.0% (963 of 1,175), respectively, for the combination of imaging modalities and PSA. CONCLUSION: While FDG-PET alone is insufficient, whole-body cancer screening with selected modalities including FDG-PET has initial performance supporting possible utility by detecting a wide variety of early-stage cancers with reasonable sensitivity. However, the detection of many indolent cancers and false positives necessitate continuing study for appropriate evaluation.

Synthesis of peptide ribonucleic acid (PRNA)-DNA chimera and interaction with DNA and RNA.

Recently, we have demonstrated that effective control of the recognition behavior of peptide ribonucleic acid (PRNA) with complementary DNA is possible through the anti-to-synorientational change of pyrimidine nucleobase induced by borate ester formation. In this study, DNA-PRNA chimera was prepared by the solidphase synthesis. In the DNA-PRNA chimeras, both PRNA and DNA domains work as recognition sites for the complementary DNA/RNAs to form stable complex, while DNA-RNA hybrids formed in the DNA domains of DNA-PRNA chimera should be substrates to the hydrolysis by RNase H and PRNA moieties work as recognition control/switching devices and as inhibitor for the hydrolysis by exonucleases. Interaction of the DNA-PRNA chimera with DNA and RNA has been discussed.

RNA recognition and recognition control of alpha-peptide ribonucleic acids containing arginine residue by external factors.

A novel nucleic acid model using alpha-peptide ribonucleic acid (alpha-PRNA) possessing alternative alpha-PRNA/lysine and alpha-PRNA/arginine sequences, where the lysine or arginine residue are expected to stabilize the complex not only by the conventional hydrogen-bonding interactions between the complementary nucleobase pairs but also through the electrostatic interactions between basic amino acid side-chain groups and DNA's phosphate anions on the backbone. These alpha-PRNAs form stable sequence-specific complex with the complementary DNA.