Search

The placenta plays a crucial role in successful mammalian reproduction. Ruminant animals possess a semi-invasive placenta characterized by a highly vascularized structure formed by maternal endometrial caruncles and fetal placental cotyledons, essential for full-term fetal development. The cow placenta harbors at least two trophoblast cell populations: uninucleate (UNC) and binucleate (BNC) cells. However, the limited capacity to elucidate the transcriptomic dynamics of the placental natural environment has resulted in a poor understanding of both the molecular and cellular interactions between trophoblast cells and niches, and the molecular mechanisms governing trophoblast differentiation and functionalization. To fill this knowledge gap, we employed Stereo-seq to map spatial gene expression patterns at near single-cell resolution in the cow placenta at 90 and 130 days of gestation, attaining high-resolution, spatially resolved gene expression profiles. Based on clustering and cell marker gene expression analyses, key transcription factors, including YBX1 and NPAS2, were shown to regulate the heterogeneity of trophoblast cell subpopulations. Cell communication and trajectory analysis provided a framework for understanding cell-cell interactions and the differentiation of trophoblasts into BNCs in the placental microenvironment. Differential analysis of cell trajectories identified a set of genes involved in regulation of trophoblast differentiation. Additionally, spatial modules and co-variant genes that help shape specific tissue structures were identified. Together, these findings provide foundational insights into important biological pathways critical to the placental development and function in cows. [ABSTRACT FROM AUTHOR]

Meta‐analysis of associations between rare outcomes and binary exposures are particularly important in studies of a drug's potential side‐effects. But meta‐analysis of the resulting 2×2$$ 2\times 2 $$ contingency tables presents substantial practical difficulties, as analysts are currently forced to pick between "exact" inference—that eliminates concern over using large‐sample approximations with small cell counts—and explicitly allowing for heterogeneity of the underlying effects. A controversial example is given by the Avandia meta‐analysis (Nissen and Wolski. N Engl J Med. 2007;356(24):2457–2471) of rosiglitazone's effects on myocardial infarction and death. While the initial Avandia analysis—using simple methods—found a significant effect, its results conflict with subsequent re‐analyses that use either exact methods, or that explicitly acknowledge the plausible heterogeneity. In this article, we aim to resolve these difficulties, by providing an exact (albeit conservative) method that is valid under heterogeneity. We also provide a measure of the degree of conservatism, that indicates the approximate extent of the excess coverage. Applied to the Avandia data, we find support for Nissen and Wolski 2007's original results. Given that our method does not require strong assumptions or large cell counts, and provides intervals around the well‐known conditional maximum likelihood estimate, we anticipate that it could be an attractive default method for meta‐analysis of 2×2$$ 2\times 2 $$ tables featuring rare events. [ABSTRACT FROM AUTHOR]

In brief: The concentration of progesterone through the estrous cycle modulates uterine function to affect the luminal metabolome. This paper reports that the dynamic changes in the bovine uterine luminal metabolome during diestrus are independent of the concentration of progesterone in the previous cycle. In cattle, the concentration of sex steroids modulates uterine function, which is reflected in the composition of the luminal metabolome. Ultimately, the uterine luminal metabolome influences embryonic growth and development. Our objectives were (i) to compare the luminal metabolome 4, 7, and 14 days after estrus of cows that were exposed to greater (HP4; n = 16) vs lower (LP4; n = 24) concentrations of progesterone before displaying estrus and ovulating spontaneously and (ii) to identify changes in the luminal concentration of metabolites across these time points. Luminal epithelial cells and fluid were collected using a cytology brush, and gene expression and metabolite concentrations were assessed by RNAseq and targeted mass spectrometry, respectively. Metabolome profile was similar between treatments within each of days 4, 7, and 14 (false discovery rate (FDR): = 0.1). Concentrations of 53 metabolites changed, independent of treatment, across the diestrus. Metabolites were mostly lipids (40 out 53) and the greatest concentrations were at day 14 (FDR: = 0.1). On day 7, the concentration of putrescine and the gene expression of ODC1, PAOX, SLC3A2, and SAT1 increased (P = 0.05). On day 14, the concentration of 3 ceramides, 4 glucosylceramides, and 12 sphingomyelins and the expression of SGMS2 were increased, in addition to the concentration of choline and 20 phosphatidylcholines. Collectively, the post-estrus concentration of luminal metabolites changed dynamically, independent of the concentration of sex steroids on the previous cycle, and the greatest magnitude changes were on day 14 when lipid metabolism was the most enriched pathway. [ABSTRACT FROM AUTHOR]

In a celebrated 1996 article, Schervish showed that, for testing interval null hypotheses, tests typically viewed as optimal can be logically incoherent. Specifically, one may fail to reject a specific interval null, but nevertheless—testing at the same level with the same data—reject a larger null, in which the original one is nested. This result has been used to argue against the widespread practice of viewing p-values as measures of evidence. In the current work we approach tests of interval nulls using simple Bayesian decision theory, and establish straightforward conditions that ensure coherence in Schervish's sense. From these, we go on to establish novel frequentist criteria—different to Type I error rate—that, when controlled at fixed levels, give tests that are coherent in Schervish's sense. The results suggest that exploring frequentist properties beyond the familiar Neyman–Pearson framework may ameliorate some of statistical testing's well-known problems. [ABSTRACT FROM AUTHOR]

Non-human primates (NHPs) are precious resources for cutting-edge neuroscientific research, including large-scale viral vector-based experimentation such as optogenetics. We propose to improve surgical outcomes by enhancing the surgical preparation practices of convection-enhanced delivery (CED), which is an efficient viral vector infusion technique for large brains such as NHPs'. Here, we present both real-time and next-day MRI data of CED in the brains of ten NHPs, and we present a quantitative, inexpensive, and practical bench-side model of the in vivo CED data. Our bench-side model is composed of food coloring infused into a transparent agar phantom, and the spread of infusion is optically monitored over time. Our proposed method approximates CED infusions into the cortex, thalamus, medial temporal lobe, and caudate nucleus of NHPs, confirmed by MRI data acquired with either gadolinium-based or manganese-based contrast agents co-infused with optogenetic viral vectors. These methods and data serve to guide researchers and surgical team members in key surgical preparations for intracranial viral delivery using CED in NHPs, and thus improve expression targeting and efficacy and, as a result, reduce surgical risks. [ABSTRACT FROM AUTHOR]

Meta‐analysis of proportions is conceptually simple: Faced with a binary outcome in multiple studies, we seek inference on some overall proportion of successes/failures. Under common effect models, exact inference has long been available, but is not when we more realistically allow for heterogeneity of the proportions. Instead a wide range of nonexact fixed‐effects methods are used, the interpretation of some of which is challenging. In this paper, we present methods for exact statistical tests and confidence intervals for fixed‐effects meta‐analysis of proportions. These methods retain the interpretability of the underlying parameter of interest, and can be implemented in straightforward software. We also show how our inference on the overall proportion is compatible with exact inference on heterogeneity of proportions. An illustrative example from a recent kidney disease study shows how the method's performance can be assessed in practice. [ABSTRACT FROM AUTHOR]

Inappropriate corpus luteum (CL) regression can produce pregnancy loss. An experimental model was utilized to investigate regression of accessory CL during pregnancy in dairy cows. Cows were bred (day 0) and treated with gonadotrophin-releasing hormone 6 days later to form accessory CL. Transrectal ultrasound (every other days) and blood samples for progesterone (P4; daily) were performed until day 56 of pregnancy. On day 28, 13 cows were confirmed pregnant, and accessory CL were found contralateral (n = 9) or ipsilateral (n = 4) to previous ovulation. On day 18, CL biopsy was performed to analyze mRNA expression for interferonstimulated genes (ISGs). Luteolysis occurred more frequently in cows that had contralateral accessory CL (88.9% (8/9)) than in cows with ipsilateral accessory CL (0% (0/4)). Luteolysis of contralateral accessory CL occurred either earlier (days 19-23; 2/8) or later (days 48-53; 6/8) in pregnancy and occurred rapidly (24 h), based on daily P4. After onset of earlier or later accessory CL regression, circulating P4 decreased by 41.2%. There was no difference in luteal tissue mRNA expression for ISGs on day 18 between accessory and original CL and between CL that subsequently regressed or did not regress. On day 56, an oxytocin challenge dramatically increased prostaglandin F2a metabolite (PGFM) in all cows but produced no pregnancy losses, although cows with previous accessory CL regression had greater PGFM. In summary, ipsilateral accessory CL did not regress during pregnancy, whereas most contralateral CL regressed by 63 days of pregnancy, providing evidence for local mechanisms in regression of accessory CL and protection of CL during pregnancy. [ABSTRACT FROM AUTHOR]

In this preliminary report, two optimization approaches, gradient descent with automatic differentiation and particle swarm optimization, are presented, applied, and compared in an effort to leverage dynamic information collected during contrast-enhanced medical imaging of tumors to estimate four blood flow parameters: perfusion, permeability surface area product, volume of the plasma, and volume of the interstitial space. Using Fick's law on a simple two-compartment model, the resulting PDEs are numerically integrated using a collocation method for a set of boundary and initial conditions and known values of the parameters, and the resulting tracer concentrations were spatially integrated to generate truth data of signal intensity as a function of time only. After using physical constraints on the boundaries to recover reasonable estimates for two of the parameters, the two optimization approaches are used in an attempt to recover estimates for the remaining two parameters. The resulting efficacy and efficiency of the two optimization approaches are compared. [ABSTRACT FROM AUTHOR]

This experiment evaluated the effects of subnutrition during early gestation on hematology in cows (Bos Taurus) and on hematological, metabolic, endocrine, and vitality parameters in their calves. Parda de Montaña and Pirenaica dams were inseminated and assigned to either a control (CONTROL, 100% requirements) or a nutrient‐restricted group (SUBNUT, 65%) during the first third of gestation. Dam blood samples were collected on days 20 and 253 of gestation, and calf samples were obtained during the first days of life. Pirenaica dams presented higher red series parameters than Parda de Montaña dams, both in the first and the last months of gestation. During early pregnancy, granulocyte numbers and mean corpuscular hemoglobin were lower in Pirenaica‐SUBNUT than in Pirenaica‐CONTROL cows. Calves from the SUBNUT cows did not show a physiological reduction in red series values in early life, suggesting later maturation of the hematopoietic system. Poor maternal nutrition affected calf endocrine parameters. Newborns from dystocic parturitions showed lower NEFA concentrations and weaker vitality responses. In conclusion, maternal nutrition had short‐term effects on cow hematology, Pirenaica cows showing a higher susceptibility to undernutrition; and a long‐term effect on their offspring endocrinology, SUBNUT newborns showing lower levels of IGF‐1 and higher levels of cortisol. [ABSTRACT FROM AUTHOR]

Contents: Embryo mortality is a major contributor to poor reproductive efficiency and profitability in cattle production systems. While conception is achieved (i.e., the oocyte is fertilized) in the vast majority of cases if insemination is carried out correctly, a significant proportion of the resulting embryos fail to develop to term. Appropriate communication between the developing conceptus and the maternal endometrium is essential for the establishment and maintenance of pregnancy in all mammals. Up to the blastocyst stage, around Days 7–9, contact worth the female reproductive system is not required. However, the process of conceptus elongation after hatching and prior to implantation is entirely maternally driven and is essential to ensure that sufficient quantities of interferon‐tau (IFNT) are secreted by the developing conceptus to abrogate the mechanisms that bring about luteolysis. While the importance of conceptus‐derived IFNT in maternal recognition of pregnancy and prevention of luteolysis in cattle is unequivocal, many questions, such as the threshold level of IFNT required for pregnancy maintenance, remain unanswered. Furthermore, the precise role of IFNT‐independent mechanisms in pregnancy establishment remains to be elucidated. Irrespective of this, failure of the conceptus to elongate undoubtedly results in embryonic loss and is thus believed to contribute greatly to reproductive failure in cattle. This review will address some of these answered questions and try to shed some light on those gaps in knowledge that could potentially contribute to improved embryo survival and reproductive efficiency. [ABSTRACT FROM AUTHOR]

Copyright of Indialogs, Spanish Journal of India Studies is the property of Universitat Autonoma de Barcelona and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

This review focuses on the paracrine and endocrine actions of interferon tau (IFNT) during pregnancy recognition and establishment in ruminants. Pregnancy recognition involves the suppression of the endometrial luteolytic mechanism by the conceptus to maintain progesterone production by the corpus luteum (CL). The paracrine antiluteolytic effects of conceptus-derived IFNT inhibit upregulation of oxytocin receptors in the endometrial epithelia of the uterus, thereby preventing the production of luteolytic prostaglandin F2 alpha (PGF2α) pulses. In the endometrium, IFNT induces or upregulates a large number of classical IFN-stimulated genes (ISGs) and regulates expression of many other genes in a cell-specific manner that are likely important for conceptus elongation, implantation and establishment of pregnancy. Further, IFNT has endocrine effects on extrauterine cells and tissues. In sheep, IFNT induces luteal resistance to PGF2α, thereby ensuring survival of the CL for maintenance of pregnancy. The ISGs induced in circulating peripheral blood mononuclear cells by IFNT may also be useful as an indicator of pregnancy status in cattle. An increased knowledge of IFNT and ISGs is important to improve the reproductive efficiency in ruminants. [ABSTRACT FROM AUTHOR]

Thirty years ago, a novel type I interferon (IFN) was identified by molecular cloning of cDNA libraries constructed from RNA extracted from ovine and bovine pre-implantation embryos. This protein was eventually designated as IFN-tau (IFNT) to highlight its trophoblast-dependent expression. IFNT function is not immune related. Instead, it interacts with the maternal system to initiate the establishment and maintenance of pregnancy. This activity is indispensable for the continuation of pregnancy. Our review will describe how IFNT evolved from other type I IFNs to function in this new capacity. IFNT genes have only been identified in pecoran ruminants within the Artiodactyla order (e.g. cattle, sheep, goats, deer, antelope, giraffe). The ancestral IFNT gene emerged approximately 36 million years ago most likely from rearrangement and/or insertion events that combined an ancestral IFN-omega (IFNW) gene with a trophoblast-specifying promoter/enhancer. Since then, IFNT genes have duplicated, likely through conversion events, and mutations have allowed them to adapt to their new function in concert with the emergence of different species. Multiple IFNT polymorphisms have been identified in cattle, sheep and goats. These genes and gene alleles encode proteins that do not display identical antiviral, antiproliferative and antiluteolytic activities. The need for multiple IFNT genes, numerous alleles and distinct activities remains debatable, but the consensus is that this complexity in IFNT expression and biological activity must be needed to provide the best opportunity for pregnancy to be recognized by the maternal system so that gestation may continue. [ABSTRACT FROM AUTHOR]

Purpose. To illustrate the conceptualization and development of a research institution from the comprehensive perspective based on the integrative model of functioning provided by the World Health Organization's (WHO) International Classification of Functioning, Disability and Health (ICF). The newly founded research institution Swiss Paraplegic Research which focuses on the comprehensive study of spinal cord injury (SCI) serves as an example. Method. Description of organizational development and structure. Results. The creation of specialized research institutions which develop their core competence from the comprehensive perspective poses unique challenges. It is depicted how these challenges can be met through several approaches. These encompass the identification and specification of a common mission and research goals, the organization of research along distinct scientific fields, the set-up of a respective core competence, and the design of research structures suited to conduct studies of high methodological and organizational complexity. Finally, they comprise the development of a transdisciplinary workforce and the integration into a research landscape which is organized along scientific disciplines and not along interdisciplinary themes. Conclusion. The ideas and approaches described in this paper may serve as an example for creating integrative research institutions dedicated to human functioning and rehabilitation research from the comprehensive perspective. [ABSTRACT FROM AUTHOR]

The article lists conference programs related to agricultural economics in 2007 which include "Environmental Policy Issues for Sustainable Economic Development in China," and "Which Italian Family Farms Will Have a Successor?" and "An Economic Analysis of Bushfire Management Programs."