Today, the number of cities implementing bike-share programs is remarkably increasing. One of the critical elements of implementing a successful bike-share program is integrating it with other transportation modes suc...
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Today, the number of cities implementing bike-share programs is remarkably increasing. One of the critical elements of implementing a successful bike-share program is integrating it with other transportation modes such as bus and metro and extending its coverage in high-density residential and employment areas to encourage more demand. In this study, we utilize a GIS-based method to visualize the spatial distribution of bike-share stations using the location-allocation problem, using the capital bike-share program in Washington D.c. metropolitan areas as a study area. We chose Washington D.c. as it was one of the first cities in the United States that launched a bike-share program and currently has one of the largest bike-share systems across the country. The location -allocation problem, including Target Market Share (TMS) and Maximize coverage and Minimize Facility (McMF), is considered to analyze the accessibility of promoting transit modes with bike-share systems across the District of columbia. Location-allocation models are investigated to determine the potential bike station loca-tions accessible to the maximum population and within a 300-m buffer around public transit stations (e.g., bus, metro). The results show that the bike-share system in Washington D.c. is more accessible for transit users as an access/egress mode. At the same time, in areas farther away from downtown D.c., docking stations are more distanced apart and offer less coverage, especially in residential-only areas. Finally, our methodology can potentially be utilized for optimal station location allocation in any other city where maximum exposure is required.
The autophagosome has two lipid bilayer membranes. The outer membrane fuses with the lysosome, while the inner membrane is degraded to release autophagiccontents for degradation. It remains unclear how the inner vesi...
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The autophagosome has two lipid bilayer membranes. The outer membrane fuses with the lysosome, while the inner membrane is degraded to release autophagiccontents for degradation. It remains unclear how the inner vesicle of the autophagosome (called the autophagic vesicle) is disintegrated after autophagosome-lysosome fusion. Here, we identified c. elegans LPLA-2/M05B5.4 as a key enzyme that degrades membranous material in lysosomes. LPLA-2 is homologous to human PLA2G15, a lysosomal phospholipase A2 family protein that catalyzes cleavage of membrane phospholipids. We found that loss of LPLA-2 causes accumulation of large membrane whor ls in enlarged lysosomes and both phenotypes are suppressed by blocking macroautophagy/autophagy. Moreover, autophagic vesicles persisted in enlarged lysosomes in PLA2G15 knockdown cells and lpla-2(lf) mutants, which suggests that the breakdown of the inner autophagosomal membrane in lysosomes is impaired. lpla-2(lf) mutants exhibit severe defects in both embryonic and larval development. Our data suggest that disintegration of the inner autophagosomal membrane by LPLA-2 promotes the release and subsequent degradation of autophagiccontents in lysosomes, which is essential for c. elegans development.
Understanding environmental influences on individuals' behaviour is challenging. Here we have investigated the housing impact of 9 weeks of enriched environment (EE) and social isolation (SI) and the impact of abr...
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Understanding environmental influences on individuals' behaviour is challenging. Here we have investigated the housing impact of 9 weeks of enriched environment (EE) and social isolation (SI) and the impact of abrupt deprivation of EE (enrichment removal: ER) on BALB/c mice. compared with the widely used c57BL/6 strain in research, BALB/c synthesises serotonin less efficiently due to a genetic variation and thus may potentially represent human populations at higher risk of stress-related disorders. We assessed the effects of EE and SI by conducting a behavioural test battery and the effects of acute ER by monitoring homecage activities and social behaviour. We found that EE and SI impact BALB/c's physiological states and behavioural performances from lower to higher cognitive processes: increased body weight, increased rectal temperature, altered performance in motor and sensory tasks, the activity level in a novel environment and altered performance in tests of anxiety-like behaviour, stress-coping strategies and learning and memory. Furthermore, acute ER triggered stress/frustration-like behaviour in BALB/c, with increased aggression, increased social distancing and disrupted daily/nightly activities. Our results demonstrate that long-lasting housing manipulation such as EE and SI, impact behaviour via multilayered processes over a wide range of functional domains, and unforeseen change to a negative environment, ER, is a major stressor that causes behavioural and psychological consequences through environment-gene interactions, a model of direct relevance to human health.
The activation of RIG-I-like receptor (RLR) signaling in cancer cells is widely recognized as a critical cancer therapy method. The expected mechanism of RLR ligand-mediated cancer therapy involves the promotion of ca...
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The activation of RIG-I-like receptor (RLR) signaling in cancer cells is widely recognized as a critical cancer therapy method. The expected mechanism of RLR ligand-mediated cancer therapy involves the promotion of cancer cell death and strong induction of interferon (IFN)-beta that affects the tumor microenvironment. We have recently shown that activation of RLR signaling in triple-negative breast cancer cells (TNBc) attenuates transforming growth factor-beta (TGF-beta) signaling, which partly contributes to the promotion of cancer cell pyroptosis. However, the consequences of suppression of TGF-beta signaling by RLR ligands with respect to IFN-beta-mediated tumor suppression are not well characterized. This study showed that transfection of a typical RLR ligand polyI:c in cancer cells produces significant levels of IFN-beta, which inhibits the growth of the surrounding cancer cells. In addition, IFN-beta-induced cell cycle arrest in surrounding cancer cells was inhibited by the expression of constitutively active Smad3. constitutively active Smad3 suppresses IFN-beta expression through the alleviation of IFN regulatory factor 3 binding to the canonical target genes, as suggested by chIP sequencing analysis. Based on these findings, a new facet of the protumorigenic function of TGF-beta that suppresses IFN-beta expression is suggested when RLR-mediated cancer treatment is used in TNBc.
Background Toll-like receptor (TLR) agonist polyinosinic-polycytidylic acid (poly I:c) exerts neuroprotective effects against cerebral ischemia (cI), but concrete evidence supporting its exact mechanism of action is u...
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Background Toll-like receptor (TLR) agonist polyinosinic-polycytidylic acid (poly I:c) exerts neuroprotective effects against cerebral ischemia (cI), but concrete evidence supporting its exact mechanism of action is unclear. Methods We evaluated the neuroprotective role of poly I:c by assessing cI indicators such as brain infarct volume (BIV), neurological deficit score (N.S.), and signaling pathway proteins. Moreover, we performed a narrative review to illustrate the mechanism of action of TLRs and their role in cI. Our search identified 164 articles and 10 met the inclusion criterion. Results Poly I:c reduces BIV and N.S. (p = 0.00 and p = 0.03). Interestingly, both pre- and post-conditioning decrease BIV (prec p = 0.04 and postc p = 0.00) and N.S. (prec p = 0.03 and postc p = 0.00). Furthermore, poly I:c upregulates TLR3 [SMD = 0.64;cIs (0.56, 0.72);p = 0.00], downregulates nuclear factor-kappa B (NF-kappa B) [SMD = -1.78;cIs (-2.67, -0.88);p = 0.0)], and tumor necrosis factor alpha (TNF-alpha) [SMD = -16.83;cIs (-22.63, -11.02);p = 0.00]. conclusion We showed that poly I:c is neuroprotective and acts via the TLR3/NF-kappa B/TNF-alpha pathway. Our review indicated that suppressing TLR 2/4 may illicit neuroprotection against cI. Further research on simultaneous activation of TLR3 with poly I:c and suppression of TLR 2/4 might open new vistas for the development of therapeutics against cI.
While conceiving with hard real time systems, determinism is the main requirement that must be satisfied in order to properly predict their behaviour as required by their definition. For achieving this purpose an avai...
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While conceiving with hard real time systems, determinism is the main requirement that must be satisfied in order to properly predict their behaviour as required by their definition. For achieving this purpose an available solution is restricting Ada language tasking features to the Ada Ravenscar profile subset. This paper presents a solution to apply the Ravenscar profile concepts in systems where the tasking management is based on RTEMS real-time operating system, and c and Ada languages are used together. Moreover, a SW tool to automatically check the compliance with Ravenscar is proposed and the outcomes of some experimental activities proving the effectiveness of the SW tool are discussed.
Germ granules harbor processes that maintain germline integrity and germline stem cell capacity. Depleting core germ granule components in c. elegans leads to the reprogramming of germ cells, causing them to express m...
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Germ granules harbor processes that maintain germline integrity and germline stem cell capacity. Depleting core germ granule components in c. elegans leads to the reprogramming of germ cells, causing them to express markers of somatic differentiation in day-two adults. Somatic reprogramming is associated with complete sterility at this stage. The resulting germ cell atrophy and other pleiotropic defects complicate our understanding of the initiation of reprogramming and how processes within germ granules safeguard the totipotency and immortal potential of germline stem cells. To better understand the initial events of somatic reprogramming, we examined total mRNA (transcriptome) and polysome-associated mRNA (translatome) changes in a precision full-length deletion of glh-1, which encodes a homolog of the germline-specific Vasa/DDX4 DEAD-box RNA helicase. Fertile animals at a permissive temperature were analyzed as young adults, a stage that precedes by 24 h the previously determined onset of somatic reporter-gene expression in the germline. Two significant changes are observed at this early stage. First, the majority of neuropeptide-encoding transcripts increase in both the total and polysomal mRNA fractions, suggesting that GLH-1 or its effectors suppress this expression. Second, there is a significant decrease in Major Sperm Protein (MSP)-domain mRNAs when glh-1 is deleted. We find that the presence of GLH-1 helps repress spermatogenic expression during oogenesis, but boosts MSP expression to drive spermiogenesis and sperm motility. These insights define an early role for GLH-1 in repressing somatic reprogramming to maintain germline integrity.
A rapid and efficient one-pot three-component synthesis of 2-amino-3-cyano-4-aryl-7-methyl-5-oxo-4,5-dihydro-pyrano-[3,2-c]pyran and 2-amino-3-cyano-4-aryl-6-methyl5,6-dihydro-5-oxo-4H-pyrano-[3,2-c]quinoline derivati...
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A rapid and efficient one-pot three-component synthesis of 2-amino-3-cyano-4-aryl-7-methyl-5-oxo-4,5-dihydro-pyrano-[3,2-c]pyran and 2-amino-3-cyano-4-aryl-6-methyl5,6-dihydro-5-oxo-4H-pyrano-[3,2-c]quinoline derivatives catalyzed by copper nanoparticles grafted on carbon microspheres is developed. The use of heterogeneous catalyst, mild reaction conditions, and excellent yield of the corresponding products are the key features of the present protocol.
Background Body size is a fundamental organismal trait. However, as body size and ecological contexts change across developmental time, evolutionary divergence may cause unexpected patterns of body size diversity amon...
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Background Body size is a fundamental organismal trait. However, as body size and ecological contexts change across developmental time, evolutionary divergence may cause unexpected patterns of body size diversity among developmental stages. This may be particularly evident in polyphenic developmental stages specialized for dispersal. The dauer larva is such a stage in nematodes, and caenorhabditis species disperse by traveling on invertebrate carriers. Here, we describe the morphology of a stress-resistant, dauer-like larval stage of the nematode caenorhabditis inopinata, whose adults can grow to be nearly twice as long as its close relative, the model organism c. elegans. Results We find that a dauer-like, stress-resistant larval stage in two isolates of c. inopinata is on average 13% shorter and 30% wider than the dauer larvae of c. elegans, despite its much longer adult stage. Additionally, many c. inopinata dauer-like larvae were ensheathed, a possible novelty in this lineage reminiscent of the infective juveniles of parasitic nematodes. Variation in dauer-like larva formation frequency among twenty-four wild isolates of c. inopinata was also observed, although frequencies were low across all isolates (< 2%), with many isolates unable to produce dauer-like larvae under conventional laboratory conditions. conclusion Most caenorhabditis species thrive on rotting plants and disperse on snails, slugs, or isopods (among others) whereas c. inopinata is ecologically divergent and thrives in fresh Ficus septica figs and disperses on their pollinating wasps. While there is some unknown factor of the fig environment that promotes elongated body size in c. inopinata adults, the small size or unique life history of its fig wasp carrier may be driving the divergent morphology of its stress-resistant larval stages. Further characterization of the behavior, development, and morphology of this stage will refine connections to homologous developmental stages in other species and
Physiological stress triggers aversive learning that profoundly alters animal behavior. Systemic mitochondrial disruption induces avoidance of c. elegans to non-pathogenic food bacteria. Mutations in cat-2 and dat-1, ...
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Physiological stress triggers aversive learning that profoundly alters animal behavior. Systemic mitochondrial disruption induces avoidance of c. elegans to non-pathogenic food bacteria. Mutations in cat-2 and dat-1, which control dopamine synthesis and reuptake, respectively, impair this learned bacterial avoidance, suggesting that dopaminergic modulation is essential. cell-specific rescue experiments indicate that dopamine likely acts from the cEP and ADE neurons to regulate learned bacterial avoidance. We find that mutations in multiple dopamine receptor genes, including dop-1, dop-2 and dop-3, reduced learned bacterial avoidance. Our work reveals a role for dopamine signaling in c. elegans learned avoidance behavior induced by mitochondrial stress.
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