222 research outputs found
A contribution to the limnology of Swartvlei: the effect of physico-chemical factors upon primary and secondary production in the pelagic zone
From ResumĂ©: The effect of physico-chemical factors on the biology of the upper reaches of Swartvlei has been investigated during 1971-1972. Physico-chemical data have shown that Swartvlei was characterized by an extremely labile ectogenic meromixis. This instability was due to three factors : (1) the inflow of freshwater, (2) the inflow of sea water, and (3) wind stress. The magnitude of the effects of these factors upon the physics, chemistry and biology of the upper reaches was dependent upon whether or not the estuary mouth was open or closed. The phytoplankton of the pelagic zone of Swartvlei was dominated by nannoplankton. Three major categories were recorded: dinoflagellates, flagellates and diatoms. The major factor regulating their productivity in the upper reaches was light. As a result of humate staining and suspended detrital matter light conditions in Swartvlei were comparable to those in extremely eutrophic northern hemisphere lakes. A maximum integral primary productivity of 39.66 mg C mâ»ÂČ hâ»Âč was recorded in November 1972. The aerobic heterotrophic bacterial population in Swartvlei was usually less than 300 col. mlâ»Âč (plate counts). The activity of the total microbial population was measured with ÂčâŽC techniques. Uptake of acetate was dominated by flagellates and one species of dinoflagellate when they were present. Glucose uptake was due to bacteria as was acetate uptake in the absence of heterotrophic phytoplankton. Glucose uptake was usually greatest in the anaerobic zone. This, and the presence of HâS, suggested that a large active photosynthetic and chemosynthetic bacterial population may have been present in the monimolimnion. The possible importance of these bacterial processes in the total productivity of the pelagic zone of Swartvlei was discussed. Daytime zooplankton population size was statistically correlated with the size of the flagellate population. The zooplankton was dominated by Acartia and Halicyclops. These two animals were found in the anaerobic bottom of Swartvlei after October 1971. This corresponded to the disappearance of the flagellate population from the water column. The dominance of these animals in the zooplankton population may have been related to their ability to live in anaerobic water where the bacterial population appeared to be considerably more abundant than in the aerobic zone. Further implications of the results are discussed in reference to phytoplankton cell size and heterotrophy indicating a possible adaptive significance of these factors in Swartvlei
Extreme Fermi surface smearing in a maximally disordered concentrated solid solution
We show that the Fermi surface can survive the presence of extreme compositional disorder in the equiatomic alloy Ni0.25Fe0.25Co0.25Cr0.25. Our high-resolution Compton scattering experiments reveal a Fermi surface which is smeared across a significant fraction of the Brillouin zone (up to 40% of 2Ï/a). The extent of this smearing and its variation on and between different sheets of the Fermi surface have been determined, and estimates of the electron mean free path and residual resistivity have been made by connecting this smearing with the coherence length of the quasiparticle states
Regulation of Liver Regeneration by Hepatocyte O-GlcNAcylation in Mice
A grant from the One-University Open Access Fund at the University of Kansas was used to defray the author's publication fees in this Open Access journal. The Open Access Fund, administered by librarians from the KU, KU Law, and KUMC libraries, is made possible by contributions from the offices of KU Provost, KU Vice Chancellor for Research & Graduate Studies, and KUMC Vice Chancellor for Research. For more information about the Open Access Fund, please see http://library.kumc.edu/authors-fund.xml.Background & Aims
The liver has a unique capacity to regenerate after injury in a highly orchestrated and regulated manner. Here, we report that O-GlcNAcylation, an intracellular post-translational modification regulated by 2 enzymes, O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), is a critical termination signal for liver regeneration following partial hepatectomy (PHX).
Methods
We studied liver regeneration after PHX on hepatocyte specific OGT and OGA knockout mice (OGT-KO and OGA-KO), which caused a significant decrease (OGT-KO) and increase (OGA-KO) in hepatic O-GlcNAcylation, respectively.
Results
OGA-KO mice had normal regeneration, but the OGT-KO mice exhibited substantial defects in termination of liver regeneration with increased liver injury, sustained cell proliferation resulting in significant hepatomegaly, hepatic dysplasia, and appearance of small nodules at 28 days after PHX. This was accompanied by a sustained increase in expression of cyclins along with significant induction in pro-inflammatory and pro-fibrotic gene expression in the OGT-KO livers. RNA-sequencing studies revealed inactivation of hepatocyte nuclear 4 alpha (HNF4α), the master regulator of hepatic differentiation and a known termination signal, in OGT-KO mice at 28 days after PHX, which was confirmed by both Western blot and immunohistochemistry analysis. Furthermore, a significant decrease in HNFα target genes was observed in OGT-KO mice, indicating a lack of hepatocyte differentiation following decreased hepatic O-GlcNAcylation. Immunoprecipitation experiments revealed HNF4α is O-GlcNAcylated in normal differentiated hepatocytes.
Conclusions
These studies show that O-GlcNAcylation plays a critical role in the termination of liver regeneration via regulation of HNF4α in hepatocytes
DNA Structure Modulates the Oligomerization Properties of the AAV Initiator Protein Rep68
Rep68 is a multifunctional protein of the adeno-associated virus (AAV), a parvovirus that is mostly known for its promise as a gene therapy vector. In addition to its role as initiator in viral DNA replication, Rep68 is essential for site-specific integration of the AAV genome into human chromosome 19. Rep68 is a member of the superfamily 3 (SF3) helicases, along with the well-studied initiator proteins simian virus 40 large T antigen (SV40-LTag) and bovine papillomavirus (BPV) E1. Structurally, SF3 helicases share two domains, a DNA origin interaction domain (OID) and an AAA+ motor domain. The AAA+ motor domain is also a structural feature of cellular initiators and it functions as a platform for initiator oligomerization. Here, we studied Rep68 oligomerization in vitro in the presence of different DNA substrates using a variety of biophysical techniques and cryo-EM. We found that a dsDNA region of the AAV origin promotes the formation of a complex containing five Rep68 subunits. Interestingly, non-specific ssDNA promotes the formation of a double-ring Rep68, a known structure formed by the LTag and E1 initiator proteins. The Rep68 ring symmetry is 8-fold, thus differing from the hexameric rings formed by the other SF3 helicases. However, similiar to LTag and E1, Rep68 rings are oriented head-to-head, suggesting that DNA unwinding by the complex proceeds bidirectionally. This novel Rep68 quaternary structure requires both the DNA binding and AAA+ domains, indicating cooperativity between these regions during oligomerization in vitro. Our study clearly demonstrates that Rep68 can oligomerize through two distinct oligomerization pathways, which depend on both the DNA structure and cooperativity of Rep68 domains. These findings provide insight into the dynamics and oligomeric adaptability of Rep68 and serve as a step towards understanding the role of this multifunctional protein during AAV DNA replication and site-specific integration
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Parentsâ perspectives on their childrenâs music therapy: A synthesis of qualitative literature
There is no existing qualitative synthesis of the music therapy literature on parentsâ perspectives on their childrenâs music therapy. This study seeks to fill this gap, motivated by the first authorâs experiences as a clinician/researcher. A systematic search of health databases, hand searches of key journals and searches of doctoral theses were undertaken to identify relevant studies. Thirteen studies which met inclusion criteria, including a total of 102 participants, were identified. Relevant data were extracted from these studies for comparison and analysis, with quality of studies assessed using the CASP appraisal tool. Findings were analysed following procedures of thematic synthesis. Six descriptive themes were grouped into three analytic themes: Parents perceived positive impacts of music therapy on their children; parents experienced music therapy as a nurturing environment for themselves and their children; and some parents experienced challenges to their engagement with music therapy. Most studies (12/13) explored parentsâ perceptions of music therapy where they were included in sessions. The findings identify positive perceptions of family-centred models of music therapy for children and parents. Parentsâ perceptions of children were altered positively through experiencing them in new ways in music therapy. Parents also perceived positive outcomes for their children. These findings identify an emphasis in the qualitative literature on parentsâ perceptions on research into music therapy which includes parents in sessions. Only one study explored perceptions of a model where parents were not present during their childâs sessions. More research is needed into parentsâ perceptions of music therapy where parents are not present during sessions. Further intervention studies into family-centred models of music therapy with children are also recommended
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Physical and chemical impacts of a major storm on a temperate lake: a taste of things to come?
Extreme weather can have a substantial influence on lakes and is expected to become more frequent with climate change. We explored the influence of one particular extreme event, Storm Ophelia, on the physical and chemical environment of England's largest lake, Windermere. We found that the substantial influence of Ophelia on meteorological conditions at Windermere, in particular wind speed, resulted in a 25-fold increase (relative to the study-period average) in the wind energy flux at the lake-air interface. Following Ophelia, there was a short-lived mixing event in which the Schmidt stability decreased by over 100 Jm-2 and the thermocline deepened by over 10 m during a 12-hour period. As a result of changes to the strength of stratification, Ophelia also changed the internal seiche regime of Windermere with the dominant seiche period increasing from ~17 h pre-storm to ~21 h post-storm. Following Ophelia, there was an upwelling of cold and low-oxygenated waters at the southern-end of the lake. This had a substantial influence on the main outflow of Windermere, the River Leven, where dissolved oxygen concentrations decreased by ~48 %, from 9.3 mg L-1 to 4.8 mg L-1, while at the mid-lake monitoring station in Windermere, it decreased by only ~3%. This study illustrates that the response of a lake to extreme weather can cause important effects downstream, the influence of which may not be evident at the lake surface. To understand the impact of future extreme events fully, the whole lake and downstream-river system need to be studied together
Perioperative fluid and volume management: physiological basis, tools and strategies
Fluid and volume therapy is an important cornerstone of treating critically ill patients in the intensive care unit and in the operating room. New findings concerning the vascular barrier, its physiological functions, and its role regarding vascular leakage have lead to a new view of fluid and volume administration. Avoiding hypervolemia, as well as hypovolemia, plays a pivotal role when treating patients both perioperatively and in the intensive care unit. The various studies comparing restrictive vs. liberal fluid and volume management are not directly comparable, do not differ (in most instances) between colloid and crystalloid administration, and mostly do not refer to the vascular barrier's physiologic basis. In addition, very few studies have analyzed the use of advanced hemodynamic monitoring for volume management
Exchange of functional domains between a bacterial conjugative relaxase and the integrase of the human adeno-associated virus
Endonucleases of the HUH family are specialized in processing single-stranded DNA in a variety of evolutionarily highly conserved biological processes related to mobile genetic elements. They share a structurally defined catalytic domain for site-specific nicking and strand-transfer reactions, which is often linked to the activities of additional functional domains, contributing to their overall versatility. To assess if these HUH domains could be interchanged, we created a chimeric protein from two distantly related HUH endonucleases, containing the N-terminal HUH domain of the bacterial conjugative relaxase TrwC and the C-terminal DNA helicase domain of the human adeno-associated virus (AAV) replicase and site-specific integrase. The purified chimeric protein retained oligomerization properties and DNA helicase activities similar to Rep68, while its DNA binding specificity and cleaving-joining activity at oriT was similar to TrwC. Interestingly, the chimeric protein could catalyse site-specific integration in bacteria with an efficiency comparable to that of TrwC, while the HUH domain of TrwC alone was unable to catalyze this reaction, implying that the Rep68 C-terminal helicase domain is complementing the TrwC HUH domain to achieve site-specific integration into TrwC targets in bacteria. Our results illustrate how HUH domains could have acquired through evolution other domains in order to attain new roles, contributing to the functional flexibility observed in this protein superfamily.This work was supported by the Medical Research Council (MRC) grant MR/N022890/1 to EH and grant 1001764 to RML; National Institutes of Health (NIH) grant RO1-GM09285 to CRE; Spanish Ministry of Economy and competitiveness (MINECO) grant BIO2013-46414-P to ML and AFM is supported by a Doc.Mobility fellowship from the Swiss National Science Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
Members of the public in the USA, UK, Canada and Australia expressing genetic exceptionalism say they are more willing to donate genomic data
Funder: State Government of Victoria (Victorian Government); doi: https://doi.org/10.13039/501100004752Funder: Victorian State GovernmentAbstract: Public acceptance is critical for sharing of genomic data at scale. This paper examines how acceptance of data sharing pertains to the perceived similarities and differences between DNA and other forms of personal data. It explores the perceptions of representative publics from the USA, Canada, the UK and Australia (n = 8967) towards the donation of DNA and health data. Fifty-two percent of this public held âexceptionalistâ views about genetics (i.e., believed DNA is different or âspecialâ compared to other types of medical information). This group was more likely to be familiar with or have had personal experience with genomics and to perceive DNA information as having personal as well as clinical and scientific value. Those with personal experience with genetics and genetic exceptionalist views were nearly six times more likely to be willing to donate their anonymous DNA and medical information for research than other respondents. Perceived harms from re-identification did not appear to dissuade publics from being willing to participate in research. The interplay between exceptionalist views about genetics and the personal, scientific and clinical value attributed to data would be a valuable focus for future research
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