Physical activity improves well-being and reduces the risk of heart disease, cancer and type 2 diabetes mellitus in the general population. In individuals with established type 2 diabetes, physical ...activity improves glucose and lipid levels, reduces weight and improves insulin resistance. In type 1 diabetes mellitus, however, the benefits of physical activity are less clear. There is poor evidence for a beneficial effect of physical activity on glycaemic control and microvascular complications, and significant risk of harm through hypoglycaemia. Here we review the literature relating to physical activity and health in type 1 diabetes. We examine its effect on a number of outcomes, including glycaemic control, lipids, blood pressure, diabetic complications, well-being and overall mortality. We conclude that whilst there is sufficient evidence to recommend physical activity in the management of type 1 diabetes, it is still unclear as to what form, duration and intensity should be recommended and whether there is benefit for many of the outcomes examined.
Observations of neutron-star mergers with distinct messengers, including gravitational waves and electromagnetic signals, can be used to study the behavior of matter denser than an atomic nucleus and ...to measure the expansion rate of the Universe as quantified by the Hubble constant. We performed a joint analysis of the gravitational-wave event GW170817 with its electromagnetic counterparts AT2017gfo and GRB170817A, and the gravitational-wave event GW190425, both originating from neutron-star mergers. We combined these with previous measurements of pulsars using x-ray and radio observations, and nuclear-theory computations using chiral effective field theory, to constrain the neutron-star equation of state. We found that the radius of a 1.4-solar mass neutron star is Formula: see text km at 90% confidence and the Hubble constant is Formula: see text at 1σ uncertainty.
A specific memory is thought to be encoded by a sparse population of neurons. These neurons can be tagged during learning for subsequent identification and manipulation. Moreover, their ablation or ...inactivation results in reduced memory expression, suggesting their necessity in mnemonic processes. However, the question of sufficiency remains: it is unclear whether it is possible to elicit the behavioural output of a specific memory by directly activating a population of neurons that was active during learning. Here we show in mice that optogenetic reactivation of hippocampal neurons activated during fear conditioning is sufficient to induce freezing behaviour. We labelled a population of hippocampal dentate gyrus neurons activated during fear learning with channelrhodopsin-2 (ChR2) and later optically reactivated these neurons in a different context. The mice showed increased freezing only upon light stimulation, indicating light-induced fear memory recall. This freezing was not detected in non-fear-conditioned mice expressing ChR2 in a similar proportion of cells, nor in fear-conditioned mice with cells labelled by enhanced yellow fluorescent protein instead of ChR2. Finally, activation of cells labelled in a context not associated with fear did not evoke freezing in mice that were previously fear conditioned in a different context, suggesting that light-induced fear memory recall is context specific. Together, our findings indicate that activating a sparse but specific ensemble of hippocampal neurons that contribute to a memory engram is sufficient for the recall of that memory. Moreover, our experimental approach offers a general method of mapping cellular populations bearing memory engrams.
Abstract
In the past few years, new observations of neutron stars (NSs) and NS mergers have provided a wealth of data that allow one to constrain the equation of state (EOS) of nuclear matter at ...densities above nuclear saturation density. However, most observations were based on NSs with masses of about 1.4
M
⊙
, probing densities up to ∼three to four times the nuclear saturation density. Even higher densities are probed inside massive NSs such as PSR J0740+6620. Very recently, new radio observations provided an update to the mass estimate for PSR J0740+6620, and X-ray observations by the NICER and XMM telescopes constrained its radius. Based on these new measurements, we revisit our previous nuclear physics multimessenger astrophysics constraints and derive updated constraints on the EOS describing the NS interior. By combining astrophysical observations of two radio pulsars, two NICER measurements, the two gravitational-wave detections GW170817 and GW190425, detailed modeling of the kilonova AT 2017gfo, and the gamma-ray burst GRB 170817A, we are able to estimate the radius of a typical 1.4
M
⊙
NS to be
11.94
−
0.87
+
0.76
km
at 90% confidence. Our analysis allows us to revisit the upper bound on the maximum mass of NSs and disfavors the presence of a strong first-order phase transition from nuclear matter to exotic forms of matter, such as quark matter, inside NSs.
Abstract
The observation of a compact object with a mass of 2.50–2.67
M
⊙
on 2019 August 14, by the LIGO Scientific and Virgo collaborations (LVC) has the potential to improve our understanding of ...the supranuclear equation of state. While the gravitational-wave analysis of the LVC suggests that GW190814 likely was a binary black hole system, the secondary component could also have been the heaviest neutron star observed to date. We use our previously derived nuclear-physics-multimessenger astrophysics framework to address the nature of this object. Based on our findings, we determine GW190814 to be a binary black hole merger with a probability of >99.9%. Even if we weaken previously employed constraints on the maximum mass of neutron stars, the probability of a binary black hole origin is still ∼81%. Furthermore, we study the impact that this observation has on our understanding of the nuclear equation of state by analyzing the allowed region in the mass–radius diagram of neutron stars for both a binary black hole or neutron star–black hole scenario. We find that the unlikely scenario in which the secondary object was a neutron star requires rather stiff equations of state with a maximum speed of sound
times the speed of light, while the binary black hole scenario does not offer any new insight.
Extracellular vesicles (EVs) are membrane-bound vesicles released by cells and act as media for transfer of proteins, small RNAs and mRNAs to distant sites. They can be isolated by different methods. ...However, the biological activities of the purified EVs have seldom been studied. In this study, we compared the use of ultracentrifugation (UC), ultra-filtration (UF), polymer-based precipitation (PBP), and PBP with size-based purification (PBP+SP) for isolation of EVs from human endometrial cells and mouse uterine luminal fluid (ULF). Electron microscopy revealed that the diameters of the isolated EVs were similar among the tested methods. UF recovered the highest number of EVs followed by PBP, while UC and PBP+SP were significantly less efficient (P<0.05). Based on the number of EVs-to-protein ratios, PBP had the least protein contamination, significantly better than the other methods (P<0.05). All the isolated EVs expressed exosome-enriched proteins CD63, TSG101 and HSP70. Incubation of the trophoblast JEG-3 cells with an equal amount of the fluorescence-labelled EVs isolated by the studied methods showed that many of the PBP-EVs treated cells were fluorescence positive but only a few cells were labelled in the UC- and UF-EVs treated groups. Moreover, the PBP-EVs could transfer significantly more miRNA to the recipient cells than the other 3 methods (P<0.05). The PBP method could isolate EVs from mouse ULF; the diameter of the isolated EVs was 62±19 nm and expressed CD63, TSG101 and HSP70 proteins. In conclusion, PBP could best preserve the activities of the isolated EVs among the 4 methods studied and was able to isolate EVs from a small volume of sample. The simple setup and low equipment demands makes PBP the most suitable method for rapid EV assessment and isolation of EVs in clinical and basic research settings.
Recent research has built a strong, compelling and persuasive case for continued support and commitment for efforts to improve women's and children's health. Apart from the main international ...priorities in women's and children's health, and multiple global initiatives to support them, the relevance and importance of science for the future of global women's health should also be emphasised, as knowledge is the foundation of future progress. In this regard, several key research priorities are worth mentioning. First, more needs to be done to promote the inclusion of women and minorities in health research to strengthen further the knowledge base in women's health.
In mammals, the sperm deliver mRNA of unknown function into the oocytes during fertilization. The role of sperm microRNAs (miRNAs) in preimplantation development is unknown. miRNA profiling ...identified six miRNAs expressed in the sperm and the zygotes but not in the oocytes or preimplantation embryos. Sperm contained both the precursor and the mature form of one of these miRNAs, miR-34c. The absence of an increased level of miR-34c in zygotes derived from α-amanitin—treated oocytes and in parthenogenetic oocytes supported a sperm origin of zygotic miR-34c. Injection of miR-34c inhibitor into zygotes inhibited DNA synthesis and significantly suppressed first cleavage division. A 3′ UTR luciferase assay and Western blotting demonstrated that miR-34c regulates B-cell leukemia/lymphoma 2 (Bcl-2) expression in the zygotes. Coinjection of anti—Bcl-2 antibody in zygotes partially reversed but injection of Bcl-2 protein mimicked the effect of miR-34c inhibition. Oocyte activation is essential for the miR-34c action in zygotes, as demonstrated by a decrease in 3′ UTR luciferase reporter activity and Bcl-2 expression after injection of precursor miR-34c into parthenogenetic oocytes. Our findings provide evidence that sperm-borne miR-34c is important for the first cell division via modulation of Bcl-2 expression.
20(R)-ginsenoside Rh2 (Rh2) is one of the most active components of red ginseng, possessing the beneficial effects in cancer prevention and metabolic diseases. However, the detailed mechanisms that ...contribute to Rh2-mediated bone formation remain largely unknown. In this study, we assessed the expression of 17 long non-coding RNAs (lncRNAs) in cultured MC3T3-E1 cells under Rh2 treatments. We found that lncRNA H19 was significantly increased in Rh2-treated MC3T3-E1 cells. Expression of lncRNA H19 was promoted in a dose- and time-dependent manner after Rh2 treatments. Increased expression of lncRNA H19 resulted in osteopontin (OPN) overexpression in Rh2-treated MC3T3-E1 cells. Furthermore, knockdown of lncRNA H19 by specific siRNAs significantly abolished the Rh2-mediated cell proliferation effects. Knockdown of lncRNA H19 also decreased both mRNA and protein levels of OPN in the Rh2-treated cells, which was accomplished by inhibiting histones H3 and H4 acetylation of OPN promoter. Importantly, OPN knockdown fully blocked Rh2 induced MC3T3-E1 cell proliferation. Our results suggest that lncRNA H19 is an important contributor to Rh2-mediated MC3T3-E1 proliferation by regulation of OPN.
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