Although archaea, Gram-negative bacteria, and mammalian cells constitutively secrete membrane vesicles (MVs) as a mechanism for cell-free intercellular communication, this cellular process has been ...overlooked in Gram-positive bacteria. Here, we found for the first time that Gram-positive bacteria naturally produce MVs into the extracellular milieu. Further characterizations showed that the density and size of Staphylococcus aureus-derived MVs are both similar to those of Gram-negative bacteria. With a proteomics approach, we identified with high confidence a total of 90 protein components of S. aureus-derived MVs. In the group of identified proteins, the highly enriched extracellular proteins suggested that a specific sorting mechanism for vesicular proteins exists. We also identified proteins that facilitate the transfer of proteins to other bacteria, as well to eliminate competing organisms, antibiotic resistance, pathological functions in systemic infections, and MV biogenesis. Taken together, these observations suggest that the secretion of MVs is an evolutionally conserved, universal process that occurs from simple organisms to complex multicellular organisms. This information will help us not only to elucidate the biogenesis and functions of MVs, but also to develop therapeutic tools for vaccines, diagnosis, and antibiotics effective against pathogenic strains of Gram-positive bacteria.
To evaluate the usefulness of the radiomic model in predicting early (≤2 years) and late (>2 years) recurrence after curative resection in cases involving a single hepatocellular carcinoma (HCC) 2-5 ...cm in diameter using preoperative gadoxetic acid-enhanced magnetic resonance imaging (MRI), in comparison with the clinicopathologic model.
This retrospective study included 167 patients with surgically resected and pathologically confirmed single HCC 2-5 cm in diameter (
= 167, training set:validation set = 128:39) who underwent preoperative gadoxetic acid-enhanced MRI between January 2010 and December 2015. A radiomic model, a clinicopathologic model, and a combined clinicopathologic-radiomic (CCR) model were built using a random survival forest to predict disease-free survival (DFS) in the following conditions: early DFS versus late DFS, dynamic phases, and the peritumoral area included in the segmentation.
The radiomic model showed a prognostic performance comparable with the clinicopathologic model only with 3-mm peritumoral border extension c-index difference (radiomic-clinicopathologic), -0.021,
= 0.758. The CCR model with the 3-mm border extension showed the highest c-index value but no statistically significant improvement over the clinicopathologic model CCR, 0.716 (0.627-0.799); clinicopathologic model, 0.696 (0.557-0.799).
The prognostic value of the preoperative radiomic model with 3-mm border extension showed comparable performance with that of the postoperative clinicopathologic model for predicting DFS of early recurrence of HCC using gadoxetic acid-enhanced MRI. This suggests the importance of including peritumoral changes in the radiomic analysis of HCC.
Insects are the most abundant animals on Earth, and the microbiota within their guts play important roles by engaging in beneficial and pathological interactions with these hosts. In this study, we ...comprehensively characterized insect-associated gut bacteria of 305 individuals belonging to 218 species in 21 taxonomic orders, using 454 pyrosequencing of 16S rRNA genes. In total, 174,374 sequence reads were obtained, identifying 9,301 bacterial operational taxonomic units (OTUs) at the 3% distance level from all samples, with an average of 84.3 (± 97.7) OTUs per sample. The insect gut microbiota were dominated by Proteobacteria (62.1% of the total reads, including 14.1% Wolbachia sequences) and Firmicutes (20.7%). Significant differences were found in the relative abundances of anaerobes in insects and were classified according to the criteria of host environmental habitat, diet, developmental stage, and phylogeny. Gut bacterial diversity was significantly higher in omnivorous insects than in stenophagous (carnivorous and herbivorous) insects. This insect-order-spanning investigation of the gut microbiota provides insights into the relationships between insects and their gut bacterial communities.
Angiogenesis is a multistep process that requires coordinated migration, proliferation, and junction formation of vascular endothelial cells (ECs) to form new vessel branches in response to growth ...stimuli. Major intracellular signaling pathways that regulate angiogenesis have been well elucidated, but key transcriptional regulators that mediate these signaling pathways and control EC behaviors are only beginning to be understood. Here, we show that YAP/TAZ, a transcriptional coactivator that acts as an end effector of Hippo signaling, is critical for sprouting angiogenesis and vascular barrier formation and maturation. In mice, endothelial-specific deletion of Yap/Taz led to blunted-end, aneurysm-like tip ECs with fewer and dysmorphic filopodia at the vascular front, a hyper-pruned vascular network, reduced and disarranged distributions of tight and adherens junction proteins, disrupted barrier integrity, subsequent hemorrhage in growing retina and brain vessels, and reduced pathological choroidal neovascularization. Mechanistically, YAP/TAZ activates actin cytoskeleton remodeling, an important component of filopodia formation and junction assembly. Moreover, YAP/TAZ coordinates EC proliferation and metabolic activity by upregulating MYC signaling. Overall, these results show that YAP/TAZ plays multifaceted roles for EC behaviors, proliferation, junction assembly, and metabolism in sprouting angiogenesis and barrier formation and maturation and could be a potential therapeutic target for treating neovascular diseases.
Animal locomotion is mediated by a sensory system referred to as proprioception. Defects in the proprioceptive coordination of locomotion result in uncontrolled and inefficient movements. However, ...the molecular mechanisms underlying proprioception are not fully understood. Here, we identify two transient receptor potential cation (TRPC) channels, trp-1 and trp-2, as necessary and sufficient for proprioceptive responses in C. elegans head steering locomotion. Both channels are expressed in the SMDD neurons, which are required and sufficient for head bending, and mediate coordinated head steering by sensing mechanical stretches due to the contraction of head muscle and orchestrating dorsal head muscle contractions. Moreover, the SMDD neurons play dual roles to sense muscle stretch as well as to control muscle contractions. These results demonstrate that distinct locomotion patterns require dynamic and homeostatic modulation of feedback signals between neurons and muscles.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Intelligent perception means that with the assistance of artificial intelligence (AI)‐motivated brain, flexible sensors achieve the ability of memory, learning, judgment, and reasoning about external ...information like the human brain. Due to the superiority of machine learning (ML) algorithms in data processing and intelligent recognition, intelligent perception systems possess the ability to match or even surpass human perception systems. However, the built‐in flexible sensors in these systems need to work on dynamic and irregular surfaces, inevitably affecting the precision and fidelity of the acquired data. In recent years, the strategy of introducing the developed functional materials and innovative structures into flexible sensors has made some progress toward the above challenges, and with the blessing of ML algorithms, accurate perception and reasoning in various scenarios have been achieved. Here, the most representative functional materials and innovative structures for constructing flexible sensors are comprehensively reviewed, the research progress of intelligent perception systems based on flexible sensors and ML algorithms is further summarized, and the intersection of the two is expected to unlock new opportunities for next‐stage AI development.
Developing flexible sensors with superior sensing capabilities is prominent for applications in intelligent perception systems. This article comprehensively reviews the most representative functional materials and innovative structures for constructing flexible sensors, and their potential applications in intelligent perception systems to provide an insight for next stage development of artificial intelligence.
The flat-spectrum radio quasar 1633+382 (4C 38.41) showed a significant increase of its radio flux density during the period 2012 March-2015 August, which correlates with γ-ray flaring activity. ...Multi-frequency simultaneous very long baseline interferometry (VLBI) observations were conducted as part of the interferometric monitoring of gamma-ray bright active galactic nuclei (iMOGABA) program and supplemented with additional radio monitoring observations with the OVRO 40 m telescope, the Boston University VLBI program, and the Submillimeter Array. The epochs of the maxima for the two largest γ-ray flares coincide with the ejection of two respective new VLBI components. Analysis of the spectral energy distribution indicates a higher turnover frequency after the flaring events. The evolution of the flare in the turnover frequency-turnover flux density plane probes the adiabatic losses in agreement with the shock-in-jet model. The derived synchrotron self-absorption magnetic fields, of the order of 0.1 mG, do not seem to change dramatically during the flares, and are much weaker, by a factor 104, than the estimated equipartition magnetic fields, indicating that the source of the flare may be associated with a particle-dominated emitting region.
We present multi-frequency simultaneous VLBI radio observations of the flat spectrum radio quasar 1633+382 (4C 38.41) as part of the interferometric monitoring of γ-ray-bright active galactic nuclei ...(iMOGABA) program combined with additional observations in the radio, optical, X-rays, and γ-rays carried out during the period 2012 March-2015 August. The monitoring of this source reveals a significant long-lived increase in its activity for approximately two years in the radio bands, which correlates with a similar increase in all other bands from submillimeter to γ-rays. A significant correlation is also found between radio fluxes and simultaneous spectral indices during this period. The study of the discrete correlation function indicates time lags smaller than the uncertainties of ∼40 days among both radio bands and high-energy bands, and a time lag of ∼70 days, with γ-rays leading radio emission. We interpret this as showing that the high-energy and radio fluxes arise from different emitting regions, located at 1 13 and 40 13 pc from the central engine respectively.
The aim of the Korean Imatinib Discontinuation Study was to identify predictors for safe and successful imatinib discontinuation. A total of 90 patients with a follow-up of ≥12 months were analyzed. ...After a median follow-up of 26.6 months after imatinib discontinuation, 37 patients lost the major molecular response. The probability of sustained major molecular response at 12 months and 24 months was 62.2% and 58.5%, respectively. All 37 patients who lost major molecular response were retreated with imatinib therapy for a median of 16.9 months, and all achieved major molecular response again at a median of 3.9 months after resuming imatinib therapy. We observed newly developed or worsened musculoskeletal pain and pruritus in 27 (30%) patients after imatinib discontinuation. Imatinib withdrawal syndrome was associated with a higher probability of sustained major molecular response (P=0.003) and showed a trend for a longer time to major molecular response loss (P=0.098). Positivity (defined as ≥ 17 positive chambers) of digital polymerase chain reaction at screening and longer imatinib duration before imatinib discontinuation were associated with a higher probability of sustained major molecular response. Our data demonstrated that the occurrence of imatinib withdrawal syndrome after imatinib discontinuation and longer duration of imatinib were associated with a lower rate of molecular relapse. In addition, minimal residual leukemia measured by digital polymerase chain reaction had a trend for a higher molecular relapse. (Trial registered at ClinicalTrials.gov: NCT01564836).
Although medical requirements are urgent, no effective intervention has been proven for chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME). To facilitate the development of new therapeutics, ...we systematically reviewed the randomized controlled trials (RCTs) for CFS/ME to date.
RCTs targeting CFS/ME were surveyed using two electronic databases, PubMed and the Cochrane library, through April 2019. We included only RCTs that targeted fatigue-related symptoms, and we analyzed the data in terms of the characteristics of the participants, case definitions, primary measurements, and interventions with overall outcomes.
Among 513 potentially relevant articles, 55 RCTs met our inclusion criteria; these included 25 RCTs of 22 different pharmacological interventions, 28 RCTs of 18 non-pharmacological interventions and 2 RCTs of combined interventions. These studies accounted for a total of 6316 participants (1568 males and 4748 females, 5859 adults and 457 adolescents). CDC 1994 (Fukuda) criteria were mostly used for case definitions (42 RCTs, 76.4%), and the primary measurement tools included the Checklist Individual Strength (CIS, 36.4%) and the 36-item Short Form health survey (SF-36, 30.9%). Eight interventions showed statistical significance: 3 pharmacological (Staphypan Berna, Poly(I):poly(C
U) and CoQ
+ NADH) and 5 non-pharmacological therapies (cognitive-behavior-therapy-related treatments, graded-exercise-related therapies, rehabilitation, acupuncture and abdominal tuina). However, there was no definitely effective intervention with coherence and reproducibility.
This systematic review integrates the comprehensive features of previous RCTs for CFS/ME and reflects on their limitations and perspectives in the process of developing new interventions.
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