A chemical genetic roadmap to improved tomato flavor Tieman, Denise; Zhu, Guangtao; Resende, Marcio F. R. ...
Science (American Association for the Advancement of Science),
01/2017, Volume:
355, Issue:
6323
Journal Article
Peer reviewed
Modern commercial tomato varieties are substantially less flavorful than heirloom varieties. To understand and ultimately correct this deficiency, we quantified flavor-associated chemicals in 398 ...modern, heirloom, and wild accessions. A subset of these accessions was evaluated in consumer panels, identifying the chemicals that made the most important contributions to flavor and consumer liking. We found that modern commercial varieties contain significantly lower amounts of many of these important flavor chemicals than older varieties. Whole-genome sequencing and a genome-wide association study permitted identification of genetic loci that affect most of the target flavor chemicals, including sugars, acids, and volatiles. Together, these results provide an understanding of the flavor deficiencies in modern commercial varieties and the information necessary for the recovery of good flavor through molecular breeding.
Peripheral artery disease is a major cardiovascular disease that affected 202 million people worldwide in 2010. In the past decade, new epidemiological data on peripheral artery disease have emerged, ...enabling us to provide updated estimates of the prevalence and risk factors for peripheral artery disease globally and regionally and, for the first time, nationally.
For this systematic review and analysis, we did a comprehensive literature search for studies reporting on the prevalence of peripheral artery disease in the general population that were published between Jan 1, 2011, and April 30, 2019, in PubMed, MEDLINE, Embase, the Global Health database, CINAHL, the Global Health Library, the Allied and Complementary Medicine Database, and ProQuest Dissertations and Theses Global. We also included the Global Peripheral Artery Disease Study of 2013 and the China Peripheral Artery Disease Study as sources. Peripheral artery disease had to be defined as an ankle–brachial index lower than or equal to 0·90. With a purpose-built data collection form, data on study characteristics, sample characteristics, prevalence, and risk factors were abstracted from all the included studies identified from the sources. Age-specific and sex-specific prevalence of peripheral artery disease was estimated in both high-income countries (HICs) and low-income and middle-income countries (LMICs). We also did random-effects meta-analyses to pool the odds ratios of 30 risk factors for peripheral artery disease in HICs and LMICs. UN population data were used to generate the number of people affected by the disease in 2015. Finally, we derived the regional and national numbers of people with peripheral artery disease on the basis of a risk factor-based model.
We included 118 articles for systematic review and analysis. The prevalence of peripheral artery disease increased consistently with age. At younger ages, prevalence was slightly higher in LMICs than HICs (4·32%, 95% CI 3·01–6·29, vs 3·54%, 1·17–10·24, at 40–44 years), but the increase with age was greater in HICs than LMICs, leading to a higher prevalence in HICs than LMICs at older ages (21·24%, 15·22–28·90, vs 12·04%, 8·67–16·60, at 80–84 years). In HICs, prevalence was slightly higher in women than in men up to age 75 years (eg, 7·81%, 3·97–14·77, vs 6·60%, 3·74–11·38, at 55–59 years), whereas in LMICs little difference was found between women and men (eg, 6·40%, 5·06–8·05, vs 6·37%, 4·74–8·49, at 55–59 years). Overall, the global prevalence of peripheral artery disease in people aged 25 years and older was 5·56%, 3·79–8·55, and the prevalence estimate was higher in HICs than that in LMICs (7·37%, 4·35–13·66, vs 5·09%, 3·64–7·24). Smoking, diabetes, hypertension, and hypercholesterolaemia were major risk factors for peripheral artery disease. Globally, a total of 236·62 million people aged 25 years and older were living with peripheral artery disease in 2015, among whom 72·91% were in LMICs. The Western Pacific Region had the most peripheral artery disease cases (74·08 million), whereas the Eastern Mediterranean Region had the least (14·67 million). More than two thirds of the global peripheral artery disease cases were concentrated in 15 individual countries in 2015.
Peripheral artery disease continues to become an increasingly serious public health problem, especially in LMICs. With the demographic trend towards ageing and projected rise in important risk factors, a larger burden of peripheral artery disease is to be expected in the foreseeable future.
None.
Chronic opiate use induces opiate dependence, which is characterized by extremely unpleasant physical and emotional feelings after drug use is terminated. Both the rewarding effects of a drug and the ...desire to avoid withdrawal symptoms motivate continued drug use, and the nucleus accumbens is important for orchestrating both processes. While multiple inputs to the nucleus accumbens regulate reward, little is known about the nucleus accumbens circuitry underlying withdrawal. Here we identify the paraventricular nucleus of the thalamus as a prominent input to the nucleus accumbens mediating the expression of opiate-withdrawal-induced physical signs and aversive memory. Activity in the paraventricular nucleus of the thalamus to nucleus accumbens pathway is necessary and sufficient to mediate behavioural aversion. Selectively silencing this pathway abolishes aversive symptoms in two different mouse models of opiate withdrawal. Chronic morphine exposure selectively potentiates excitatory transmission between the paraventricular nucleus of the thalamus and D2-receptor-expressing medium spiny neurons via synaptic insertion of GluA2-lacking AMPA receptors. Notably, in vivo optogenetic depotentiation restores normal transmission at these synapses and robustly suppresses morphine withdrawal symptoms. This links morphine-evoked pathway- and cell-type-specific plasticity in the paraventricular nucleus of the thalamus to nucleus accumbens circuit to opiate dependence, and suggests that reprogramming this circuit holds promise for treating opiate addiction.
Aim
Gastroparesis is a common non‐motor system symptom of Parkinson's disease (PD). However, the mechanism responsible for the gastric motor abnormality is not clear. We previously reported on the ...impaired gastric motility in 6‐hydroxydopamine (6‐OHDA) rats, which were treated with a bilateral microinjection of 6‐OHDA in the substantia nigra (SN). We hypothesize that the enhanced dopamine system and reduced acetylcholine (Ach) in gastric tissues might contribute to the delayed gastric emptying observed in PD.
Methods
A strain gauge force transducer, digital X‐ray imaging system, Western blot, immunofluorescence and Radio Immunoassay were used in this study.
Results
Dopaminergic neurones in the SN were greatly reduced following the bilateral microinjection of 6‐OHDA. 6‐OHDA rats exhibited impaired gastric motility and delayed gastric emptying, accompanied by increased dopamine content and the overexpression of D2 receptors in the stomach. The administration of the D2 receptor antagonist domperidone relieved gastric dysmotility in 6‐OHDA rats, but the D1 receptor antagonist SCH23390 failed to do so. Subdiaphragmatic vagotomy prevented the increase in the gastric dopamine content and D2 receptor expression and improved gastric dysmotility in 6‐OHDA rats.
Conclusion
Dopaminergic deficiency in the SN results in impaired gastric motility, possibly as a result of the enhanced activity of dopamine system and reduced Ach in gastric tissue. The vagus nerve plays an important role in peripheral gastric motility disorder.
We report the experimental generation of highly energetic carbon ions up to 48 MeV per nucleon by shooting double-layer targets composed of well-controlled slightly underdense plasma and ultrathin ...foils with ultraintense femtosecond laser pulses. Particle-in-cell simulations reveal that carbon ions are ejected from the ultrathin foils due to radiation pressure and then accelerated in an enhanced sheath field established by the superponderomotive electron flow. Such a cascaded acceleration is especially suited for heavy ion acceleration with femtosecond laser pulses. The breakthrough of heavy ion energy up to many tens of MeV/u at a high repetition rate would be able to trigger significant advances in nuclear physics, high energy density physics, and medical physics.
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This study evaluated maintenance treatment with niraparib, a potent inhibitor of poly(ADP-ribose) polymerase 1/2, in patients with platinum-sensitive recurrent ovarian cancer.
In this phase III, ...double-blind, placebo-controlled study conducted at 30 centers in China, adults with platinum-sensitive recurrent ovarian cancer who had responded to their most recent platinum-containing chemotherapy were randomized 2 : 1 to receive oral niraparib (300 mg/day) or matched placebo until disease progression or unacceptable toxicity (NCT03705156). Following a protocol amendment, patients with a bodyweight <77 kg or a platelet count <150 × 103/μl received 200 mg/day, and all other patients 300 mg/day, as an individualized starting dose (ISD). Randomization was carried out by an interactive web response system and stratified by BRCA mutation, time to recurrence following penultimate chemotherapy, and response to most recent chemotherapy. The primary endpoint was progression-free survival (PFS) assessed by blinded independent central review.
Between 26 September 2017 and 2 February 2019, 265 patients were randomized to receive niraparib (n = 177) or placebo (n = 88); 249 patients received an ISD (300 mg, n = 14; 200 mg, n = 235) as per protocol. In the intention-to-treat population, median PFS was significantly longer for patients receiving niraparib versus placebo: 18.3 95% confidence interval (CI), 10.9-not evaluable versus 5.4 (95% CI, 3.7-5.7) months hazard ratio (HR) = 0.32; 95% CI, 0.23-0.45; P < 0.0001, and a similar PFS benefit was observed in patients receiving an ISD, regardless of BRCA mutation status. Grade ≥3 treatment-emergent adverse events occurred in 50.8% and 19.3% of patients who received niraparib and placebo, respectively; the most common events were neutrophil count decreased (20.3% versus 8.0%) and anemia (14.7% versus 2.3%).
Niraparib maintenance treatment reduced the risk of disease progression or death by 68% and prolonged PFS compared to placebo in patients with platinum-sensitive recurrent ovarian cancer. Individualized niraparib dosing is effective and safe and should be considered standard practice in this setting.
•Chinese patients with platinum-sensitive recurrent ovarian cancer received maintenance niraparib (n = 177) or placebo (n = 88).•Median PFS was longer for niraparib versus placebo: 18.3 versus 5.4 months (HR = 0.32; 95% CI, 0.23-0.45; P < 0.0001).•Niraparib had a similar PFS benefit for 249 patients receiving individualized dosing based on bodyweight and platelet count.•Grade ≥3 treatment-emergent adverse events occurred in 50.8% and 19.3% of patients who received niraparib and placebo, respectively.•In the niraparib group, Grade ≥3 platelet count decreased/thrombocytopenia occurred in 11.3% of patients.
Estimation of the epidemiological burden of carotid atherosclerosis can serve as a basis for prevention and management of cardiovascular disease. We aimed to provide the first estimation on the ...prevalence, number of cases, and risk factors for carotid atherosclerosis in the general population globally and regionally.
In this systematic review, meta-analysis, and modelling study, we searched PubMed, MEDLINE, Embase, Global Health, and China National Knowledge Infrastructure for articles published from database inception until May 7, 2019, with no language restrictions, for population-based studies that quantified prevalence of carotid atherosclerosis by means of increased carotid intima-media thickness, carotid plaque, and carotid stenosis. Studies were eligible if they included bilaterally scanned carotid arteries using ultrasonography and defined increased carotid intima-media thickness as a thickness of 1·0 mm or more, carotid plaque as a focal carotid intima-media thickness of 1·5 mm or more encroaching into the lumen or at least 0·5 mm or 50% compared with the surrounding carotid intima-media thickness values, and carotid stenosis as 50% or more stenosis. Studies were excluded if the sample was not representative of the general population. We also included studies identified in our previous systematic review and meta-analysis of the prevalence of carotid atherosclerosis in China. We estimated age-specific and sex-specific prevalences of increased carotid intima-media thickness, carotid plaque, and carotid stenosis. We used UN population data to generate the number of people affected in 2000, 2015, and 2020. We did random-effects meta-analyses to assess the effects of risk factors for increased carotid intima-media thickness and carotid plaque. We derived regional numbers of people living with increased carotid intima-media thickness and carotid plaque in 2015 using a risk factors-based model by WHO region. All analyses were done in populations aged 30–79 years due to availability of data. This systematic review and meta-analysis is registered online on PROSPERO, CRD42019134709.
We identified 8632 articles through our database search, of which 515 were eligible for full-text review, including 37 articles from our previous study, and 59 articles were eligible for inclusion in our systematic review and meta-analysis. Overall, in people aged 30–79 years in 2020, the global prevalence of increased carotid intima-media thickness is estimated to be 27·6% (95% CI 16·9–41·3), equivalent to 1066·70 million affected people and a percentage change of 57·46% from 2000; of carotid plaque is estimated to be 21·1% (13·2–31·5), equivalent to 815·76 million affected people and a percentage change of 58·97% from 2000; and carotid stenosis is estimated to be 1·5% (1·1–2·1), equivalent to 57·79 million affected people and a percentage change of 59·13% from 2000. The prevalence of increased carotid intima-media thickness, carotid plaque, and carotid stenosis increased consistently with age and was higher in men than in women. Current smoking, diabetes, and hypertension were common risk factors for increased carotid intima-media thickness and carotid plaque. In 2015, the Western Pacific region had the largest share of global cases of increased carotid intima-media thickness (317·62 million 33·36% of 952·13 million affected people) and carotid plaque (240·77 million 33·20% of 725·25 million), whereas the African region had the smallest share of cases of increased carotid intima-media thickness (59·08 million 6·21%) and the Eastern Mediterranean region had the smallest share of carotid plaque cases (44·59 million 6·15%).
A substantial global burden of carotid atherosclerosis exists. Effective strategies are needed for primary prevention and management of carotid atherosclerosis. High-quality epidemiological investigations on carotid atherosclerosis are needed to better address the global burden of carotid atherosclerosis at finer levels.
None.
Abstract
We first review the significance of resolution and contrast in electron microscopy and the effect of the electron optics on these two quantities. We then outline the physics of the ...generation of secondary electrons (SEs) and their transport and emission from the surface of a specimen. Contrast and resolution are discussed for different kinds of SE imaging in scanning electron microscope (SEM) and scanning-transmission microscope instruments, with some emphasis on the observation of individual atoms and atomic columns in a thin specimen. The possibility of achieving atomic resolution from a bulk specimen at SEM energies is also considered.
Clinical outcomes after primary graft failure (PGF) remain poor. Here we present a large retrospective analysis (n=23,272) which investigates means to prevent PGF and early detection of patients at ...high risk. In patients with hematologic malignancies, who underwent their first myeloablative allogeneic hematopoietic cell transplantation, PGF was reported in 1278 (5.5%), and there was a marked difference in PGFs using peripheral blood stem cell compared with bone marrow grafts (2.5 vs 7.3%; P<0.001). A fourfold increase of PGF was observed in myeloproliferative disorders compared with acute leukemia (P<0.001). Other risk factors for PGF included recipient age <30, HLA mismatch, male recipients of female donor grafts, ABO incompatibility, busulfan/cyclophosphamide conditioning and cryopreservation. In bone marrow transplants, total nucleated cell doses ⩽2.4 × 10(8) per kg were associated with PGF (odds ratio 1.39; P<0.001). The use of tacrolimus-based immunosuppression and granulocyte colony-stimulating factor were associated with decreased PGF risk. These data, allow clinicians to do more informed choices with respect to graft source, donor selection, conditioning and immunosuppressive regimens to reduce the risk of PGF. Moreover, a novel risk score determined on day 21 post transplant may provide the rationale for an early request for additional hematopoietic stem cells.
We present the apparent stellar angular momentum over the optical extent of 300 galaxies across the Hubble sequence using integral-field spectroscopic (IFS) data from the CALIFA survey. Adopting the ...same λR parameter previously used to distinguish between slow and fast rotating early-type (elliptical and lenticular) galaxies, we show that spiral galaxies are almost all fast rotators, as expected. Given the extent of our data, we provide relations for λR measured in different apertures (e.g. fractions of the effective radius: 0.5 Re, Re, 2 Re), including conversions to long-slit 1D apertures. Our sample displays a wide range of λRe values, consistent with previous IFS studies. The fastest rotators are dominated by relatively massive and highly star-forming Sb galaxies, which preferentially reside in the main star-forming sequence. These galaxies reach λRe values of ∼0.85, and they are the largest galaxies at a given mass, while also displaying some of the strongest stellar population gradients. Compared to the population of S0 galaxies, our findings suggest that fading may not be the dominant mechanism transforming spirals into lenticulars. Interestingly, we find that λRe decreases for late-type Sc and Sd spiral galaxies, with values that occasionally set them in the slow-rotator regime. While for some of them this can be explained by their irregular morphologies and/or face-on configurations, others are edge-on systems with no signs of significant dust obscuration. The latter are typically at the low-mass end, but this does not explain their location in the classical (V/σ, ε) and (λRe, ε) diagrams. Our initial investigations, based on dynamical models, suggest that these are dynamically hot disks, probably influenced by the observed important fraction of dark matter within Re.
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