[Changes of hemodynamic parameters in normal pregnant women and their relationship with maternal basic characteristics].

Objective: To investigate the variation of reference ranges of hemodynamic parameters in normal pregnancy and their relation to maternal basic characteristics. Methods: A total of 598 healthy pregnant women who underwent regular prenatal examination at the Third Affiliated Hospital of Guangzhou Medical University from January to December 2023 were prospectively enrolled, and noninvasive hemodynamic monitors were used to detect changes in hemodynamic parameters of the pregnant women with the week of gestation, including cardiac output (CO), stroke volume (SV), thoracic fluid content (TFC), systemic vascular resistance (SVR), mean arterial pressure (MAP), and heart rate (HR). Relationships between hemodynamic parameters and maternal basic characteristics, including age, height, and weight, were analyzed using restricted cubic spline. Results: (1) CO (r=0.155, P<0.001), TFC (r=0.338, P<0.001), MAP (r=0.204, P<0.001), and HR (r=0.352, P<0.001) were positively correlated with the week of gestation, and SV was negatively correlated with the week of gestation (r=-0.158, P<0.001). There was no significant correlation between SVR and gestational age (r=-0.051, P=0.258). (2) CO exhibited a positive correlation with maternal height and weight (all P<0.001). The taller and heavier of pregnant women, the higher their CO. A linear relationship was observed between maternal weight and SV, MAP and HR (all P<0.01). As maternal weight increased, SV, MAP and HR showed an upward trend. Furthermore, there was an inverse association between maternal age and SVR (P<0.001). (3) There was a significant nonlinear association observed between TFC and body mass index during pregnancy (P<0.05). Additionally, a nonlinear relationship was found between SVR and MAP in relation to maternal age (all P<0.05). Notably, when the age exceeded 31 years old, there was an evident upward trend observed in both SVR and MAP. Conclusions: The hemodynamic parameters of normal pregnant women are influenced by their height, body weight, and age. It is advisable to maintain a reasonable weight during pregnancy and give birth at an appropriate age.

Spatial distribution, movement, body damage, and feather condition of laying hens in a multi-tier system.

The welfare and health of laying hens in the multitier system raise concern in public. The flock distributions during feeding time at 51 and 89 wk were studied in a multitier system. Furthermore, the ultra-high frequency radio frequency identification (UHF RFID) equipment was used to identify the transition between tiers and time spent in each tier of 48 focal hens (12 hens from each tier-group of the multitier system) at 92 wk of age. The body weight, tibia size (length and width), body damage (comb and rear part), and feather condition (neck, breast, back, tail, cloaca, and wings) of focal hens from different tier-groups were further compared. The results showed that the spatial distribution in flocks changed from top to bottom with increasing age. The hens at 51 wk of age were mainly distributed in the 4th tier (19.6 ± 5.0% in 1st tier, 9.6 ± 1.1% in 2nd tier, 23.6 ± 2.9% in 3rd tier and 47.3 ± 2.6% in 4th tier), and hens at 89 wk of age were mainly distributed in the lower tiers (33.5 ± 1.5% in 1st tier, 31.9 ± 5.1% in 2nd tier, 15.7 ± 3.4% in 3rd tier and 16.6 ± 3.1% in 4th tier). The spatial distribution of hens at 89 wk of age was more even than that at 51 wk of age. At 92 wk of age, the proportion of time spent in original tier of 4 tier-groups was 91.0 ± 5.7%, 51.9 ± 5.7%, 59.0 ± 7.0% and 63.0 ± 6.7%, respectively. Focal hens preferred to stay in the original tier and spent significantly less time in other tiers (P < 0.05). There was no significant difference in body weight, body damage score, tibia width and partial feather scores (neck, breast, tail, and cloaca) of focal hens among 4 tier-groups (P > 0.05). However, focal hens from 1st tier had worse feather scores on wings and back, and shorter tibia length compared to other tiers suggesting that there were more lower ranking birds that located in lower tier to avoid competition, but had equal access to resource, which is good for their welfare and health. In summary, the overcrowding situation was improved near the end of the laying cycle in the multitier system, thereby mitigating the potential negative effects to the lower ranking hens and maintain a satisfactory level of welfare and health for laying hens near the end of the laying cycle.

Longitudinal vitamin D status in pregnancy and the risk of pre-eclampsia.

OBJECTIVE: Whether vitamin D deficiency in pregnancy is a cause of pre-eclampsia remains controversial. Most previous studies to date have assessed exposure at only one time-point in pregnancy. We assessed longitudinal vitamin D status during pregnancy and the risk of pre-eclampsia. DESIGN: Prospective cohort study. SETTING: Seventeen urban obstetric hospitals, Canada. POPULATION: Pregnant women who were participants in a trial of vitamin C and E supplementation for the prevention of pre-eclampsia. Canadian participants who consented to participate in a biobank with plasma specimens available at the baseline visit were included (n = 697). METHODS: Maternal plasma 25-hydroxyvitamin D (25(OH)D) concentrations were measured at 12-18 and 24-26 weeks of gestation using chemiluminescence immunoassay. MAIN OUTCOME MEASURES: Pre-eclampsia. RESULTS: Of the women, 39% were vitamin D deficient (25(OH)D <50 nmol/l). A strong positive correlation was observed in maternal 25(OH)D concentrations between the two gestational age windows (r = 0.69, P < 0.0001). Mean maternal 25(OH)D concentrations at 24-26 weeks of gestation were significantly lower in women who subsequently developed pre-eclampsia compared with those who did not (mean ± SD: 48.9 ± 16.8 versus 57.0 ± 19.1 nmol/l, P = 0.03). Women with 25(OH)D < 50 nmol/l at 24-26 weeks gestation experienced an increased risk of pre-eclampsia (adjusted odds ratio 3.24, 95% confidence interval 1.37-7.69), whereas the association was not statistically significant for maternal 25(OH)D level at 12-18 weeks of gestation. CONCLUSIONS: Lower maternal 25(OH)D levels at late mid-trimester were associated with an increased risk of pre-eclampsia.

Diabetes in pregnancy may differentially affect neonatal outcomes for twins and singletons.

AIM: We tested the hypothesis that diabetes in pregnancy may differentially affect neonatal outcomes in twin vs. singleton pregnancies. METHODS: In a retrospective cohort analysis of twins (n = 422 068) and singletons (n = 14 298 367) born in the USA from 1998 to 2001, we evaluated the adjusted odds ratios of adverse neonatal outcomes comparing diabetic vs. non-diabetic pregnancies, controlling for maternal characteristics. Primary outcomes include macrosomia (birthweight for gestational age > 90th percentile), congenital anomalies, low 5-min Apgar score (< 4) and neonatal death. RESULTS: Diabetes in pregnancy was associated with a similarly increased risk of congenital anomalies (adjusted odds ratios 1.52 vs. 1.59) and smaller increased risks of preterm birth (adjusted odds ratios 1.27 vs. 1.49) and macrosomia (adjusted odds ratios 1.38 vs. 2.03) in twins vs. singletons, but reduced risks of low 5-min Apgar score (adjusted odds ratio 0.74) and neonatal death (adjusted odds ratio 0.76) in twins but not singletons. CONCLUSIONS: Diabetes in pregnancy may differentially affect neonatal outcomes in twins and singletons, indicating a need for further studies to differentiate the effects by clinical subtypes of diabetes in pregnancy, and to consider/evaluate differential clinical management protocols of diabetes in multiple vs. singleton pregnancies.

Temperature effect of the local structure in liquid Sb studied with x-ray absorption spectroscopy.

The temperature dependence of the local structure of liquid Sb has been studied by x-ray absorption spectroscopy. It is shown that about 10% of the atoms with coordination of 3 and weak Peierls distortion exist in liquid Sb just above its melting point. The Peierls distortion weakens gradually with increasing temperature and vanishes at about 750 degrees C. This structural variation in liquid Sb is different from the normal liquid-liquid phase transition. This work reveals the relationship between the variation in the local structure and the change in the physical properties, such as the electrical resisitvity of liquid Sb, with temperature. The complete agreement between the measured electrical resistivity values during heating and cooling processes suggests that the structural units with the features of a rhombohedron appear above the melting point of Sb during solidification.

Structural basis of DNA bridging by barrier-to-autointegration factor.

Barrier-to-autointegration factor (BAF) is a host cell protein that plays a crucial role in retroviral integration. Preintegration complexes (PICs) stripped of BAF lose their normal integration activity, which can be restored by incubation with purified BAF. BAF bridges double-stranded DNA both intra- and intermolecularly in a non-sequence-specific manner, leading to the formation of a nucleoprotein network. BAF also binds to the nuclear protein lamina-associated polypeptide 2 (LAP2), and is localized with chromatin during interphase and mitosis. The crystal structure of homodimeric human BAF has been determined to 1.9 A resolution. The fold of the BAF monomer resembles that of the second domain of RuvA. This comparison revealed the presence of the helix-hairpin-helix (HhH) nonspecific DNA binding motif within BAF. A novel feature of BAF's HhH motif is the occupation of the metal binding site by the epsilon-amino group of Lys 6, providing an alternative means of sequestering positive charge. Mutational analysis corroborates the HhH motif's prominent role in DNA binding and argues against a previously proposed helix-turn-helix (HTH) binding site located in another region of the monomer. A model of BAF bridging DNA via the HhH motif is proposed.

Multiple integrase functions are required to form the native structure of the human immunodeficiency virus type I intasome.

Mu-mediated polymerase chain reaction footprinting was used to investigate the protein-DNA structure of human immunodeficiency virus type I (HIV-I) preintegration complexes. Preintegration complexes were partially purified from cells after using an established coculture infection technique as well as a novel technique using cell-free supernatant from transfected cells as the source of virus. Footprinting revealed that bound proteins protected the terminal 200-250 base pairs of each viral end from nuclease attack. Bound proteins also caused strong transpositional enhancements near each end of HIV-I. In contrast, regions of viral DNA internal to the ends did not show evidence of strong protein binding. The end regions of preintegrative HIV-I apparently form a unique nucleoprotein structure, which we term the intasome to distinguish it from the greater preintegration complex. Our novel system also allowed us to analyze the structure and function of preintegration complexes isolated from cells infected with integrase mutant viruses. Complexes were derived from viruses defective for either integrase catalysis, integrase binding to the viral DNA substrate, or an unknown function in the carboxyl-terminal domain of the integrase protein. None of these mutant complexes supported detectable integration activity. Despite the presence of the mutant integrase proteins in purified samples, none of these nucleoprotein complexes displayed the native intasome structure detected in wild-type preintegration complexes. We conclude that multiple integrase functions are required to form the native structure of the HIV-I intasome in infected cells.

Solution structure of the cellular factor BAF responsible for protecting retroviral DNA from autointegration.

The solution structure of the human barrier-to-autointegration factor, BAF, a 21,000 Mr dimer, has been solved by NMR, including extensive use of dipolar couplings which provide a priori long range structural information. BAF is a highly evolutionarily conserved DNA binding protein that is responsible for inhibiting autointegration of retroviral DNA, thereby promoting integration of retroviral DNA into the host chromosome. BAF is largely helical, and each subunit is composed of five helices. The dimer is elongated in shape and the dimer interface comprises principally hydrophobic contacts supplemented by a single salt bridge. Despite the absence of any sequence similarity to any other known protein family, the topology of helices 3-5 is similar to that of a number of DNA binding proteins, with helices 4 and 5 constituting a helix-turn-helix motif. A model for the interaction of BAF with DNA that is consistent with structural and mutagenesis data is proposed.

Footprints on the viral DNA ends in moloney murine leukemia virus preintegration complexes reflect a specific association with integrase.

Retroviral DNA integration is mediated by the preintegration complex, a large nucleoprotein complex derived from the core of the infecting virion. We previously have used Mu-mediated PCR to probe the nucleoprotein organization of Moloney murine leukemia virus preintegration complexes. A region of protection spans several hundred base pairs at each end of the viral DNA, and strong enhancements are present near the termini. Here, we show that these footprints reflect a specific association between integrase and the viral DNA ends in functional preintegration complexes. Barrier-to-autointegration factor, a cellular protein that blocks autointegration of Moloney murine leukemia virus DNA, also plays an indirect role in generating the footprints at the ends of the viral DNA. We have exploited Mu-mediated PCR to examine the effect of mutations at the viral DNA termini on complex formation. We find that a replication competent mutant with a deletion at one end of the viral DNA still exhibits a strong enhancement about 20 bp from the terminus of the mutant DNA end. The site of the enhancement therefore appears to be at a fixed distance from the ends of the viral DNA. We also find that a mutation at one end of the viral DNA, which renders the virus incompetent for replication, abolishes the enhancements and protection at both the U3 and U5 ends. A pair of functional viral DNA ends therefore are required to interact before the chemical step of 3' end processing.

A large nucleoprotein assembly at the ends of the viral DNA mediates retroviral DNA integration.

We have probed the nucleoprotein organization of Moloney murine leukemia virus (MLV) pre-integration complexes using a novel footprinting technique that utilizes a simplified in vitro phage Mu transposition system. We find that several hundred base pairs at each end of the viral DNA are organized in a large nucleoprotein complex, which we call the intasome. This structure is not formed when pre-integration complexes are made by infecting cells with integrase-minus virus, demonstrating a requirement for integrase. In contrast, footprinting of internal regions of the viral DNA did not reveal significant differences between pre-integration complexes with and without integrase. Treatment with high salt disrupts the intasome in parallel with loss of intermolecular integration activity. We show that a cellular factor is required for reconstitution of the intasome. Finally, we demonstrate that DNA-protein interactions involving extensive regions at the ends of the viral DNA are functionally important for retroviral DNA integration activity. Current in vitro integration systems utilizing purified integrase lack the full fidelity of the in vivo reaction. Our results indicate that both host factors and long viral DNA substrates may be required to reconstitute an in vitro system with all the hallmarks of DNA integration in vivo.

A new suppressor of a lamB signal sequence mutation, prlZ1, maps to 69 minutes on the Escherichia coli chromosome.

Reversion analysis has been employed to isolate suppressors that restore export of a unique LamB signal sequence mutant. The mutation results in a substitution of Arg for Met at position 19, which prevents LamB export to the outer membrane and leads to a Dex- phenotype. Unlike other LamB signal sequence mutants utilized for reversion analysis, LamB19R becomes stably associated with the inner membrane in an export-specific manner. In this study, Dex+ revertants were selected and various suppressors were isolated. One of the extragenic suppressors, designated prlZ1, was chosen for further study. prlZ1 maps to 69 min on the Escherichia coli chromosome. The suppressor is dominant and SecB dependent. In addition to its effect on lamB19R, prlZ1 suppresses the export defect of signal sequence point mutations at positions 12, 15, and 16, as well as several point mutations in the maltose-binding protein signal sequence. prlZ1 does not suppress deletion mutations in either signal sequence. This pattern of suppression can be explained by interaction of a helical LamB signal sequence with the suppressor.

Two distinct regions of the LamB signal sequence function in different steps in export.

The hydrophobic core of the Escherichia coli LamB signal sequence contains two structurally distinct regions. One region forms a helix in nonpolar environments, and the other is less structured. These regions seem to be of special importance for export, as judged by the magnitude of the defect caused by their mutational inactivation. To gain insight into the mechanistic importance of these two regions, we examined the ability of precursors to pass partially through the export pathway when each region is mutated. The results demonstrate that mutations in the helical and unstructured regions of the signal sequence block different steps in the export pathway.

Different methods for wound management of radiation-burn injury in rats.

Different methods of burn wound management were used in rats with severe radiation-burn injury. The 30-day survival rate and the functional recovery of thymocytes and splenocytes were significantly higher in the group with early escharectomy and skin grafting than in the group without operational intervention and in the group with skin grafting in the recovery stage. In the group with early escharectomy and skin grafting on the 1st day after injury, all the autografts survived and the survival of the homografts was also markedly prolonged. Escharectomy and skin grafting performed in the late stage aggravated the wound condition, and infection and hemorrhage were the main factors hastening the death of the skin grafts as well as the animals. The findings indicate that escharectomy and skin grafting in the early stage after injury are conducive to the recovery of immune function and consequently to the recovery of the whole organism because infections are minimized after escharectomy and closure of the wound surfaces by skin grafting.