A topological data analytic approach for discovering biophysical signatures in protein dynamics.

Identifying structural differences among proteins can be a non-trivial task. When contrasting ensembles of protein structures obtained from molecular dynamics simulations, biologically-relevant features can be easily overshadowed by spurious fluctuations. Here, we present SINATRA Pro, a computational pipeline designed to robustly identify topological differences between two sets of protein structures. Algorithmically, SINATRA Pro works by first taking in the 3D atomic coordinates for each protein snapshot and summarizing them according to their underlying topology. Statistically significant topological features are then projected back onto a user-selected representative protein structure, thus facilitating the visual identification of biophysical signatures of different protein ensembles. We assess the ability of SINATRA Pro to detect minute conformational changes in five independent protein systems of varying complexities. In all test cases, SINATRA Pro identifies known structural features that have been validated by previous experimental and computational studies, as well as novel features that are also likely to be biologically-relevant according to the literature. These results highlight SINATRA Pro as a promising method for facilitating the non-trivial task of pattern recognition in trajectories resulting from molecular dynamics simulations, with substantially increased resolution.

Effect of twin pregnancy chorionic properties on maternal and fetal outcomes.

OBJECTIVE: This study aimed to determine the effect of twin pregnancy chorionic properties on pregnancy complications and fetal outcomes. MATERIALS AND METHODS: A total of 559 subjects with gemellary pregnancy were included in the retrospective analysis, and clinical data, such as monitoring data during pregnancy and maternal and fetal outcomes, were recorded in detail. Based on the ultrasound results and methods of the postpartum pathologic examination of the placental membranes, the subjects were divided into the twin group with monochorionic diamnion (MCDA group, n = 198) and twin group with dichorionic diamnion (DCDA group, n = 361). The relationships of different chorionic properties and maternal and fetal outcomes were determined by comparing the maternal complications and fetal outcomes. RESULTS: The occurrence rate of gemellary pregnancy was 2.97% and that of monochorionic twin pregnancy was 34.8%. The MCDA group showed a higher incidence of pregnancy-induced hypertension, gestational diabetes mellitus, polyhydramnios, premature rupture of membranes, and abruptio placenta and a lower incidence of severe postpartum hemorrhage than the DCDA group. However, the incidence of preterm birth was significantly different (57.6% vs. 45.7%, P < 0.05). Significant differences were also detected in the incidence of fetal loss, complicated twins, neonatal asphyxia, and perinatal death between the two groups (P < 0.05). CONCLUSION: The incidence of maternal complication (such as pregnancy-induced hypertension, gestational diabetes mellitus, polyhydramnios, premature rupture of membranes, and abruptio placenta and severe postpartum hemorrhage) in the two groups was not significantly different; however, the fetal outcomes in the MCDA group were inferior to those in the DCDA group. The fetal outcomes may be improved by determining the chorionic properties in early pregnancy by using ultrasound and consequently planning for pregnancy monitoring and intervention.

A pulse programmable parahydrogen polarizer using a tunable electromagnet and dual channel NMR spectrometer.

Applications of parahydrogen induced polarization (PHIP) often warrant conversion of the chemically-synthesized singlet-state spin order into net heteronuclear magnetization. In order to obtain optimal yields from the overall hyperpolarization process, catalytic hydrogenation must be tightly synchronized to subsequent radiofrequency (RF) transformations of spin order. Commercial NMR consoles are designed to synchronize applied waves on multiple channels and consequently are well-suited as controllers for these types of hyperpolarization experiments that require tight coordination of RF and non-RF events. Described here is a PHIP instrument interfaced to a portable NMR console operating with a static field electromagnet in the milliTesla regime. In addition to providing comprehensive control over chemistry and RF events, this setup condenses the PHIP protocol into a pulse-program that in turn can be readily shared in the manner of traditional pulse sequences. In this device, a TTL multiplexer was constructed to convert spectrometer TTL outputs into 24 VDC signals. These signals then activated solenoid valves to control chemical shuttling and reactivity in PHIP experiments. Consolidating these steps in a pulse-programming environment speeded calibration and improved quality assurance by enabling the B0/B1 fields to be tuned based on the direct acquisition of thermally polarized and hyperpolarized NMR signals. Performance was tested on the parahydrogen addition product of 2-hydroxyethyl propionate-1-13C-d3, where the 13C polarization was estimated to be P13C=20±2.5% corresponding to 13C signal enhancement approximately 25 million-fold at 9.1 mT or approximately 77,000-fold 13C enhancement at 3 T with respect to thermally induced polarization at room temperature.

Expression of glucose transporter protein 1 and p63 in serous ovarian tumor.

AIM: It has been shown that glycolytic metabolism is increased in malignant cells. Cancer cell growth is an energy-related process supported by an increased glucose metabolism. In addition, p63, a known homolog of p53, is expressed predominantly in basal cell and squamous cell carcinomas. The purpose of this study was to evaluate the expression of glucose transporter protein 1 (GLUT1) and p63 in patients with serous ovarian tumor (benign, borderline and malignant) and study their close relationship with the malignant transformation of serous ovarian tumors. METHODS: Two hundred formalin-fixed, paraffin-embedded sections were immunostained with rabbit anti-GLUT1 polyclonal antibody and mouse anti-p63 monoclonal antibody using the streptavidin-biotin method. The samples were as follows: 40 normal ovarian tissues, 40 serous cystadenomas, 40 borderline serous cystadenomas and 80 serous cystadenocarcinomas were stained. RESULT: Normal ovarian tissues showed completely negative staining for GLUT1 and p63. However, from benign serious cystadenomas, borderline cystadenomas to cystadenocarcinomas, the expression of GLUT1 and p63 grew stronger (P < 0.05). Moreover, the intensity staining of GLUT1 maintained a significant association with the expression of p63 (P < 0.05). In χ²-test analysis, expression of borderline cystadenomas and cystadenocarcinomas, intraperitoneal implants, ascites, lymph node status and International Federation of Gynecology and Obstetrics (FIGO) stage and GLUT1 expression levels have an appalling significance (P < 0.05), while FIGO stage, intraperitoneal implants and lymph node status except patient age and ascites have a statistical significance with the expression of p63 levels (P < 0.05). CONCLUSION: Our findings show a progressive increase in the expression of GLUT1 and p63 from the benign serous cystadenomas, borderline cystadenomas to cystadenocarcinomas. Overexpression of GLUT1 and p63 are associated with the histology FIGO stage and metastasis of the tumors. These data suggested that the expression of GLUT1 and p63 may be closely related to the malignant transformation of serous ovarian tumors. However, the relative importance of GLUT1 and p63 in ovarian serous tumor development and tumorigenesis remains mostly unclear and awaits further investigation.

Investigation on delivery analgesia effect of combined spinal epidural anesthesia plus Doula and safety of mother and baby.

OBJECTIVE: To explore the effect of patient-controlled lumbar epidural combined anesthesia with Doula for labor analgesia with ropivacaine and sufentanil, and its influence on the progress of labor, and outcomes of mother and infant. MATERIALS AND METHODS: Two hundred parturients that requested labor analgesia were randomly selected by patient-controlled lumbar epidural combined anesthesia with Doula as the observation group, meanwhile another 200 parturients were selected as the control group without any analgesic measurements. Labor pain score, labor duration, blood gas analysis results, the incidence of cesarean section, neonatal asphyxia, and postpartum hemorrhage were compared between the two groups. RESULTS: Compared with the control group, labor analgesic effect was remarkable, the cesarean section rate was significantly reduced in observation group, and the difference was statistically significant (p < 0.05), but with respect to the duration of labor, maternal, postpartum hemorrhage, and neonatal asphyxia, there was no statistical significance between the two groups (p > 0.5). In the observation group regarding maternal and neonatal blood gas analysis results, PO2 was higher and PCO2 was lower than those in the control group. The differences were statistically significant (p < 0.05). CONCLUSION: Labor analgesia by patient-controlled lumbar epidural combined anesthesia accompanied with Doula with ropivacaine and sufentanil is effective, safe, reliable, has no adverse effects, and reduces cesarean section rate.

A pulsed injection parahydrogen generator and techniques for quantifying enrichment.

A device is presented for efficiently enriching parahydrogen by pulsed injection of ambient hydrogen gas. Hydrogen input to the generator is pulsed at high pressure to a catalyst chamber making thermal contact with the cold head of a closed-cycle cryocooler maintained between 15 and 20K. The system enables fast production (0.9 standard liters per minute) and allows for a wide range of production targets. Production rates can be systematically adjusted by varying the actuation sequence of high-pressure solenoid valves, which are controlled via an open source microcontroller to sample all combinations between fast and thorough enrichment by varying duration of hydrogen contact in the catalyst chamber. The entire enrichment cycle from optimization to quantification and storage kinetics are also described. Conversion of the para spin-isomer to orthohydrogen in borosilicate tubes was measured at 8 min intervals over a period of 64 h with a 12 T NMR spectrometer. These relaxation curves were then used to extract initial enrichment by exploiting the known equilibrium (relaxed) distribution of spin isomers with linear least squares fitting to a single exponential decay curve with an estimated error less than or equal to 1%. This procedure is time-consuming, but requires only one sample pressurized to atmosphere. Given that tedious matching to external references are unnecessary with this procedure, we find it to be useful for periodic inspection of generator performance. The equipment and procedures offer a variation in generator design that eliminate the need to meter flow while enabling access to increased rates of production. These tools for enriching and quantifying parahydrogen have been in steady use for 3 years and should be helpful as a template or as reference material for building and operating a parahydrogen production facility.