Placenta has a wide range of functions. Some are supported by novel genes that have evolved following gene duplication events while others require acquisition of gene expression by the trophoblast. ...Although not expressed in the placenta, high-affinity fetal hemoglobins play a key role in placental gas exchange. They evolved following duplications within the beta-globin gene family with convergent evolution occurring in ruminants and primates. In primates there was also an interesting rearrangement of a cassette of genes in relation to an upstream locus control region. Substrate transfer from mother to fetus is maintained by expression of classic sugar and amino acid transporters at the trophoblast microvillous and basal membranes. In contrast, placental peptide hormones have arisen largely by gene duplication, yielding for example chorionic gonadotropins from the luteinizing hormone gene and placental lactogens from the growth hormone and prolactin genes. There has been a remarkable degree of convergent evolution with placental lactogens emerging separately in the ruminant, rodent, and primate lineages and chorionic gonadotropins evolving separately in equids and higher primates. Finally, coevolution in the primate lineage of killer immunoglobulin-like receptors and human leukocyte antigens can be linked to the deep invasion of the uterus by trophoblast that is a characteristic feature of human placentation.
Legumes are able to access atmospheric di-nitrogen (N2) through a symbiotic relationship with rhizobia that reside within root nodules. In soybean, following N2 fixation by the bacteroids, ammonia is ...finally reduced in uninfected cells to allantoin and allantoic acid 1. These ureides present the primary long-distance transport forms of nitrogen (N), and are exported from nodules via the xylem for shoot N supply. Transport of allantoin and allantoic acid out of nodules requires the function of ureide permeases (UPS1) located in cells adjacent to the vasculature 2, 3. We expressed a common bean UPS1 transporter in cortex and endodermis cells of soybean nodules and found that delivery of N from nodules to shoot, as well as seed set, was significantly increased. In addition, the number of transgenic nodules was increased and symbiotic N2 fixation per nodule was elevated, indicating that transporter function in nodule N export is a limiting step in bacterial N acquisition. Further, the transgenic nodules showed considerable increases in nodule N assimilation, ureide synthesis, and metabolite levels. This suggests complex adjustments of nodule N metabolism and partitioning processes in support of symbiotic N2 fixation. We propose that the transgenic UPS1 plants display metabolic and allocation plasticity to overcome N2 fixation and seed yield limitations. Overall, it is demonstrated that transporter function in N export from nodules is a key step for enhancing atmospheric N2 fixation and nodule function and for improving shoot N nutrition and seed development in legumes.
•Increasing nodule ureide export improves nitrogen fixation and shoot nutrition•UPS1 function is coupled with nodule metabolic and transport pathways•Nitrogen partitioning processes and nodulation are linked•Organic nitrogen transporters can be used in plant breeding and seed production
Legumes access atmospheric nitrogen (N) in a symbiotic relationship with bacteria that reside in root nodules. Carter and Tegeder demonstrate that enhancing N export from nodules leads to improved N fixation, shoot nutrition, and seed yield. They show that N transport out of nodules is tightly linked to nodule metabolic and partitioning pathways.
Genetic robustness, or the ability of an organism to maintain fitness in the presence of harmful mutations, can be achieved via protein feedback loops. Previous work has suggested that organisms may ...also respond to mutations by transcriptional adaptation, a process by which related gene(s) are upregulated independently of protein feedback loops. However, the prevalence of transcriptional adaptation and its underlying molecular mechanisms are unknown. Here, by analysing several models of transcriptional adaptation in zebrafish and mouse, we uncover a requirement for mutant mRNA degradation. Alleles that fail to transcribe the mutated gene do not exhibit transcriptional adaptation, and these alleles give rise to more severe phenotypes than alleles displaying mutant mRNA decay. Transcriptome analysis in alleles displaying mutant mRNA decay reveals the upregulation of a substantial proportion of the genes that exhibit sequence similarity with the mutated gene's mRNA, suggesting a sequence-dependent mechanism. These findings have implications for our understanding of disease-causing mutations, and will help in the design of mutant alleles with minimal transcriptional adaptation-derived compensation.
Unique Aspects of Human Placentation Carter, Anthony M.
International journal of molecular sciences,
07/2021, Letnik:
22, Številka:
15
Journal Article
Recenzirano
Odprti dostop
Human placentation differs from that of other mammals. A suite of characteristics is shared with haplorrhine primates, including early development of the embryonic membranes and placental hormones ...such as chorionic gonadotrophin and placental lactogen. A comparable architecture of the intervillous space is found only in Old World monkeys and apes. The routes of trophoblast invasion and the precise role of extravillous trophoblast in uterine artery transformation is similar in chimpanzee and gorilla. Extended parental care is shared with the great apes, and though human babies are rather helpless at birth, they are well developed (precocial) in other respects. Primates and rodents last shared a common ancestor in the Cretaceous period, and their placentation has evolved independently for some 80 million years. This is reflected in many aspects of their placentation. Some apparent resemblances such as interstitial implantation and placental lactogens are the result of convergent evolution. For rodent models such as the mouse, the differences are compounded by short gestations leading to the delivery of poorly developed (altricial) young.
Targeted social media campaigns in Nigeria helped to disseminate accurate information about the disease—and to correct hoax messages, Meg Carter reports
Extraintestinal manifestations are more common in Crohn's colitis and ileocolitis than in exclusively small bowel disease. 8.6 Osteoporosis 147- 151 Osteoporosis is common in patients with IBD (see ...BSG Guidelines for osteoporosis in coeliac disease and inflammatory bowel disease), although the absolute fracture risk, contribution of steroids and role of prophylaxis remain a subject for debate. 8.7 The role of the IBD nurse specialist 151 The IBD clinical nurse specialist represents a new role for the management of patients with IBD. The role of the IBD specialist nurse needs defining, but may encompass: liaising with all members of the MDT, patients, primary care, and other agencies; support of patients and carers both in hospital and the community in all aspects of care of IBD; establishment of nurse-led services, including clinics, telephone helplines, and follow up, rapid access for patients, and referral to other professionals; development of systems to enable audit and participation in research projects promoting the care of IBD patients; developing and leading teaching plans for patients and other healthcare professionals involved in IBD management. 8.8 Sources of patient information Many sources of information are available to complement explanations or advice given by clinical staff.
Transvaginal mesh (TVM) surgeries emerged as an innovative treatment for stress urine incontinency and/or pelvic organ prolapse in 1996. Years after rapid adoption of these surgeries into practice, ...they are a key example of worldwide failure of healthcare quality and patient safety. The prevalence of TVM-associated harms eventually prompted action globally, including an Australian Commonwealth Government Senate Inquiry in 2017.
We analysed 425 submissions made by women (n = 417) and their advocates (n = 8) to the Australian Senate Inquiry, and documents from 5 public hearings, using deductive and inductive coding, categorisation and thematic analysis informed by three 'linked dilemmas' from healthcare quality and safety theory. We focused on women's accounts of: a) how harms arose from TVM procedures, and b) micro, meso and macro factors that contributed to their experience. Our aim was to explain, from a patient perspective, how these harms persisted in Australian healthcare, and to identify mechanisms at micro, meso and macro levels explaining quality and safety system failure.
Our findings suggest three mechanisms explaining quality and safety failure: 1. Individual clinicians could ignore cases of TVM injury or define them as 'non-preventable'; 2. Women could not go beyond their treating clinicians to participate in defining and governing quality and safety; and. 3. Health services set thresholds for concern based on proportion of cases harmed, not absolute number or severity of harms.
We argue that privileging clinical perspectives over patient perspectives in evaluating TVM outcomes allowed micro-level actors to dismiss women's lived experience, such that women's accounts of harms had insufficient or no weight at meso and macro levels. Establishing system-wide expectations regarding responsiveness to patients, and communication of patient reported outcomes in evaluation of healthcare delivery, may help prevent similar failures.
Abstract This review examines the strengths and weaknesses of animal models of human placentation and pays particular attention to the mouse and non-human primates. Analogies can be drawn between ...mouse and human in placental cell types and genes controlling placental development. There are, however, substantive differences, including a different mode of implantation, a prominent yolk sac placenta, and fewer placental hormones in the mouse. Crucially, trophoblast invasion is very limited in the mouse and transformation of uterine arteries depends on maternal factors. The mouse also has a short gestation and delivers poorly developed young. Guinea pig is a good alternative rodent model and among the few species known to develop pregnancy toxaemia. The sheep is well established as a model in fetal physiology but is of limited value for placental research. The ovine placenta is epitheliochorial, there is no trophoblast invasion of uterine vessels, and the immunology of pregnancy may be quite different. We conclude that continued research on non-human primates is needed to clarify embryonic–endometrial interactions. The interstitial implantation of human is unusual, but the initial interaction between trophoblast and endometrium is similar in macaques and baboons, as is the subsequent lacunar stage. The absence of interstitial trophoblast cells in the monkey is an important difference from human placentation. However, there is a strong resemblance in the way spiral arteries are invaded and transformed in the macaque, baboon and human. Non-human primates are therefore important models for understanding the dysfunction that has been linked to pre-eclampsia and fetal growth restriction. Models that are likely to be established in the wake of comparative genomics include the marmoset, tree shrew, hedgehog tenrec and nine-banded armadillo.
The repair outcomes at site-specific DNA double-strand breaks (DSBs) generated by the RNA-guided DNA endonuclease Cas9 determine how gene function is altered. Despite the widespread adoption ...of CRISPR-Cas9 technology to induce DSBs for genome engineering, the resulting repair products have not been examined in depth. Here, the DNA repair profiles of 223 sites in the human genome demonstrate that the pattern of DNA repair following Cas9 cutting at each site is nonrandom and consistent across experimental replicates, cell lines, and reagent delivery methods. Furthermore, the repair outcomes are determined by the protospacer sequence rather than genomic context, indicating that DNA repair profiling in cell lines can be used to anticipate repair outcomes in primary cells. Chemical inhibition of DNA-PK enabled dissection of the DNA repair profiles into contributions from c-NHEJ and MMEJ. Finally, this work elucidates a strategy for using “error-prone” DNA-repair machinery to generate precise edits.
Display omitted
•DNA repair profiles of 223 sites in the human genome reveal nonrandom outcomes•The protospacer sequence, not genomic context, determines Cas9 DSB repair outcomes•Each DNA repair profile is composed of specific contributions from c-NHEJ and MMEJ•DNA repair profiling can be used to anticipate repair outcomes in primary cells
van Overbeek, Capurso et al. demonstrate that repair outcomes are nonrandom at S. pyogenes Cas9-mediated DSBs and are determined by the protospacer sequence rather than genomic context. DNA repair profiling reveals specific contributions of c-NHEJ and MMEJ at each site and an approach to generate precise edits without exogenous template.
PDF
