Genomics and Epigenomics of Gestational Diabetes Mellitus: Understanding the Molecular Pathways of the Disease Pathogenesis

One of the most common complications during pregnancy is gestational diabetes mellitus (GDM), hyperglycemia that occurs for the first time during pregnancy. The condition is multifactorial, caused by an interaction between genetic, epigenetic, and environmental factors. However, the underlying mechanisms responsible for its pathogenesis remain elusive. Moreover, in contrast to several common metabolic disorders, molecular research in GDM is lagging. It is important to recognize that GDM is still commonly diagnosed during the second trimester of pregnancy using the oral glucose tolerance test (OGGT), at a time when both a fetal and maternal pathophysiology is already present, demonstrating the increased blood glucose levels associated with exacerbated insulin resistance. Therefore, early detection of metabolic changes and associated epigenetic and genetic factors that can lead to an improved prediction of adverse pregnancy outcomes and future cardio-metabolic pathologies in GDM women and their children is imperative. Several genomic and epigenetic approaches have been used to identify the genes, genetic variants, metabolic pathways, and epigenetic modifications involved in GDM to determine its etiology. In this article, we explore these factors as well as how their functional effects may contribute to immediate and future pathologies in women with GDM and their offspring from birth to adulthood. We also discuss how these approaches contribute to the changes in different molecular pathways that contribute to the GDM pathogenesis, with a special focus on the development of insulin resistance.     

Methylmercury Causes Neurodegeneration and Downregulation of Myelin Basic Protein in the Spinal Cord of Offspring Rats after Maternal Exposure

Methylmercury (MeHg) is one of the most dangerous toxic pollutants spread throughout the earth. Chronic MeHg intoxication by contaminated food ingestion is the most common threat to human health, including impairment to the developing fetus. The present study aims at investigating the effects of maternal exposure to MeHg during gestation and lactation on the spinal cord of offspring. Pregnant rats received oral doses of MeHg (40 μg/kg/day) over a period of 42 days (21 gestation and 21 lactation). Control animals received the vehicle only. Total mercury concentration was measured in blood samples from offspring collected at the 41st postnatal day. Counting of motor neurons and immunoreactivity for myelin basic protein (MBP) were assessed in the spinal cords in both control and MeHg-intoxicated animals. Our results showed that MeHg promoted an increase in blood Hg levels. In addition, it caused a reduction in the number of spinal cord motor neurons as well as decreased MBP immunoreactivity in the cervical, thoracic and lumbar segments. Our present findings suggest that MeHg intoxication during rat pregnancy and lactation is associated with a pattern of motor neuron degeneration and downregulation of myelin basic protein in different segments of a developing spinal cord. Further studies are needed to establish the effect of MeHg intoxication in both young and adult rats.     

规划设计在房地产开发中的地位与作用

以“金山碧水”为实例,阐述规划设计在房地产业开发中的重要性。     

Implementing lean practices in manufacturing SMEs: testing ‘critical success factors’ using Necessary Condition Analysis

Lean practices are known to increase operational performance. Previous research has identified critical success factors for implementing lean practices. This research aims to examine the extent to which success factors are critical for various degrees of lean practice implementation. Using multiple-respondent self-assessments from 33 Dutch manufacturing small and medium-sized enterprises (SMEs), we conducted a Necessary Condition Analysis. Our findings indicated that the criticality of success factors is progression dependent. In the initial stages of the lean journey, SMEs could improve their lean practices in a bottom-up manner through local factors such as a learning focus, improvement training and support congruence. When lean practices are more advanced, some company-wide factors must be present: top management support, a shared improvement vision and a supplier link. Our findings question the universality of success factors such as strategic involvement and indicate the need for a more dynamic model of lean implementation.     

The high-fertility cycle: How timely pregnancies in one lactation may lead to less body condition loss,fewer health issues,greater fertility,and reduced early pregnancy losses in the next lactation

Body condition loss during early lactation varies among cows in the herd and is associated with future health and reproductive outcomes. The objective of this study was to gain a greater understanding of the relationship between previous calving interval and body condition change during the first 30 d in milk (DIM) and their relationship to subsequent fertility and health variables and sex ratio at birth. Dry cows and heifers (n = 851) from a single farm entered the study approximately 25 d before the due date. They were evaluated and given a body condition score on a 1-to-5 scale with 0.1-point increments weekly until parturition. Body condition score was assessed within 1 wk of parturition and then again 27 to 33 DIM. Previous calving interval, gestation length, periparturient health events (giving birth to twins, dystocia, retained placentas, ketosis, metritis, and displaced abomasum), sire net merit ($), and milk data were used for each cow as recorded in PCDART (Dairy Records Management Systems, Raleigh, NC) by the herd managers. Longer previous calving intervals were related to greater body condition at parturition and body condition loss during the first 30 DIM. A 75% greater proportion of cows with a calving-to-pregnancy interval shorter than 130 d maintained or gained body condition during the first 30 DIM compared with cows with calving-to-pregnancy intervals longer than 130 d. Multiparous cows that maintained or gained body condition (n = 144) had greater pregnancies per AI following first service compared with cows that lost body condition (n = 577) during the first 30 DIM when health events were considered or removed. When cows with health events were considered, multiparous cows that maintained or gained body condition had a greater percentage pregnant by 130 DIM compared with cows that lost body condition (67 vs. 55%; n = 522). Cows that lost body condition during the first 30 DIM regardless of health events experienced greater pregnancy loss (n = 224) between 35 and 60 d after first AI (0.0 vs. 6.7%) compared with cows that maintained or gained body condition (n = 69) during that period. Based on data in this study from a single herd, maintaining a cycle of pregnancy before 130 DIM may reduce the amount of body condition lost after the next parturition, enhance subsequent pregnancies per AI, and reduce the possibility of early pregnancy loss. We refer to this phenomenon as the high-fertility cycle.     

Quantifying the effects of mastitis on the reproductive performance of dairy cows: A meta-analysis

The objective of this study was to conduct a meta-analysis to quantitatively characterize the effects of mastitis on the reproductive performance of dairy cows as well as to identify factors that interact with this relationship. A total of 29 publications were identified that contributed 24, 41, 27, 38, and 13 trial results to the meta-analysis of how mastitis is related to time to first service (TFS), days open (DO), services per conception (SPC), pregnancies per insemination at first service (FSP/AI) and pregnancy loss (PL), respectively. The meta-analyses were conducted using multilevel linear mixed-effects models. Overall, high levels of heterogeneity were present and meta-regression models only explained a small amount of heterogeneity. Results suggest that cows with mastitis pre-first insemination experience, on average, an additional 13.29 d to first service [95% confidence interval (CI): 6.64, 19.95] when compared with cows with no mastitis in the same time period. Moreover, in relation to cows with no mastitis in the same time period, 22.34 additional DO (95% CI: 12.89, 31.79) were estimated, on average, for cows with clinical mastitis at pre-insemination leading to conception. Additionally, 32.41 added DO (95% CI: 20.58, 44.25) were estimated, on average, for cows with clinical mastitis at pre- or post-insemination leading to conception compared with cows with no mastitis in the same time period. Finally, 20.03 additional DO (95% CI: 3.11, 36.95) were estimated, on average, for cows with subclinical mastitis pre- or post-insemination leading to conception compared with cows with no mastitis in the same time period. Effect size estimates from the meta-regression models for SPC, in relation to cows with no mastitis in the same time period, suggest that, on average, SPC increases by 0.46 inseminations (95% CI: 0.30, 0.62) for a cow experiencing mastitis pre-insemination leading to conception. When mastitis occurs either pre- or post-insemination leading to conception, SPC is expected to increase, on average, by 0.72 inseminations (95% CI: 0.48, 0.95) compared with cows with no mastitis in the same time period. The estimated effect sizes for FSP/AI suggest a risk ratio of conceiving at first insemination of 0.90 (95% CI: 0.82, 0.99) for cows with mastitis diagnosed pre-first insemination with respect to cows with no mastitis in the same time period, and a risk ratio of 0.79 (95% CI: 0.72, 0.86) for cows diagnosed with mastitis either pre- or post-first insemination with respect to cows with no mastitis in the same time period. Publication bias was identified in 4 of the meta-analysis models (TFS, DO, SPC, and FSCR), but no influential trials were identified in any models; the reliability of the meta-analysis results should be interpreted carefully keeping these limitations in mind. Further meta-regression analysis would be valuable as additional studies are published that report other potential sources of heterogeneity.     

Resolving Apparent Contradictions Concerning the Relationships Among Fear or Anxiety and Aggression During Lactation: Theoretical Comment on D'Anna, Stevenson, and Gammie (2005).

Pregnancy and lactation involve dramatic changes in behavior and physiology necessary for the successful production and sustenance of offspring. This requires numerous processes to emerge and be coordinated in a finely tuned manner. Reduced corticotropin releasing factor (CRF) receptor activity and hypothalamic-pituitary-adrenal function are thought to be involved in numerous functions during lactation, such as reducing fear and anxiety, which in turn, is proposed to disinhibit aggressive behaviors. K. L. D'Anna, S. A. Stevenson, and S. C. Gammie (2005) reported that central infusion of urocortin 1 and 3, anxiogenic peptides that bind to CRF receptors, reduce maternal aggression in lactating mice and alter neural c-fos expression. However, the relationship between stress hormones and where they act, emotional state, and aggression during lactation is complicated, and our understanding of how these factors influence each other might benefit from a comprehensive reevaluation of these literatures. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Characterizing nicotine withdrawal in pregnant cigarette smokers.

Maternal smoking is a leading preventable cause of poor pregnancy outcomes and infant morbidity and mortality. Whereas pregnancy has been thought of as a "window of opportunity" when women are more motivated to change health behaviors such as smoking, only 20% of pregnant women quit smoking upon learning they are pregnant and remain abstinent at the end of the pregnancy. Greater understanding of possible obstacles to smoking during pregnancy, such as nicotine withdrawal, is needed. The symptoms of nicotine withdrawal have been well characterized in nonpregnant smokers, but there has been only 1 report conducted during pregnancy, and that was a retrospective study. The aim of the present study was to characterize nicotine withdrawal and craving in pregnant cigarette smokers. These data were collected as part of prospective clinical trials assessing the efficacy of voucher-based incentives to promote abstinence from cigarette smoking during pregnancy and postpartum. The authors examined results from the Minnesota Nicotine Withdrawal Scale (J. R. Hughes & D. K. Hatsukami, 1998) in 27 abstainers (reported no or very low levels of smoking, which was confirmed biochemically) and 21 smokers (smoked at >80% of their baseline smoking level) during the first 5 days of a cessation attempt. Abstainers reported more impatience, anger, and difficulty concentrating than did smokers. The results also suggest that pregnant smokers generally may have elevated baseline levels of withdrawal, which need to be considered in the design and analysis of future studies. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

"Snatching defeat from the jaws of victory: Self-esteem differences in the experience and anticipation of success": Correction to Wood et al (2005).

Reports an error in "Snatching Defeat From the Jaws of Victory: Self-Esteem Differences in the Experience and Anticipation of Success" by Joanne V. Wood, Sara A. Heimpel, Ian R. Newby-Clark and Michael Ross (Journal of Personality and Social Psychology, 2005[Nov], Vol 89[5], 764-780). There are typographical errors in Table 2 (certain values should not have been in bold face). The corrected table is provided in the erratum. (The following abstract of the original article appeared in record 2005-15658-009.) Successes--defined broadly as meeting important standards or receiving positive evaluations--are widely assumed to be enjoyed equally by people with high self-esteem (HSEs) and low self-esteem (LSEs). Three studies examined the contradictory hypothesis that HSEs react more favorably to success than do LSEs and that success brings about certain unfavorable consequences for LSEs. Undergraduate participants reacted to a laboratory-manipulated success (Studies 1 and 2) or imagined highly positive events in the future (Study 3). Self-esteem differences emerged in anxiety, thoughts about the self, and (in Study 3) thoughts about non-self-related aspects of the event. LSEs were more anxious than HSEs after succeeding, success improved HSEs' self-relevant thoughts but not LSEs', and LSEs focused more on success's negative aspects. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Overview of Human HtrA Family Proteases and Their Distinctive Physiological Roles and Unique Involvement in Diseases,Especially Cancer and Pregnancy Complications

The mammalian high temperature requirement A (HtrA) proteins are a family of evolutionarily conserved serine proteases, consisting of four homologs (HtrA1-4) that are involved in many cellular processes such as growth, unfolded protein stress response and programmed cell death. In humans, while HtrA1, 2 and 3 are widely expressed in multiple tissues with variable levels, HtrA4 expression is largely restricted to the placenta with the protein released into maternal circulation during pregnancy. This limited expression sets HtrA4 apart from the rest of the family. All four HtrAs are active proteases, and their specific cellular and physiological roles depend on tissue type. The dysregulation of HtrAs has been implicated in many human diseases such as cancer, arthritis, neurogenerative ailments and reproductive disorders. This review first discusses HtrAs broadly and then focuses on the current knowledge of key molecular characteristics of individual human HtrAs, their similarities and differences and their reported physiological functions. HtrAs in other species are also briefly mentioned in the context of understanding the human HtrAs. It then reviews the distinctive involvement of each HtrA in various human diseases, especially cancer and pregnancy complications. It is noteworthy that HtrA4 expression has not yet been reported in any primary tumour samples, suggesting an unlikely involvement of this HtrA in cancer. Collectively, we accentuate that a better understanding of tissue-specific regulation and distinctive physiological and pathological roles of each HtrA will improve our knowledge of many processes that are critical for human health.