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Cryptococcus neoformans is a widespread fungal pathogen that can infect the human central nervous system (CNS) and cause fungal meningitis, leading to hundreds of thousands of deaths worldwide each year. Previous studies have demonstrated that many signal transduction pathways are crucial for the morphological development and virulence of C. neoformans. In this review, data from over 116 research articles have been compiled to show that many signaling pathways control various characteristics of C. neoformans, individually or in association with other pathways, and to establish strong links among them to better understand C. neoformans pathogenesis. Every characteristic of C. neoformans is closely linked to these signaling pathways, making this a rich area for further research. It is essential to thoroughly explore these pathways to address questions that remain and apply a molecular mechanistic approach to link them. Targeting these pathways is crucial for understanding the exact mechanism of infection pathogenesis and will facilitate the development of antifungal drugs as well as the diagnosis and prevention of cryptococcosis. [ABSTRACT FROM AUTHOR]

Based on one-dimensional water hammer theory and combined with an engineering example, the selection of the flow characteristics of the end control valve of gravity flow system with wide-range flow variation is numerically studied from three aspects: the influence of flow characteristics of control valve on its steady-state opening-degree, the determination of the most unfavorable flow conditions of valveclosing water hammer, and the influence of flow characteristics of contrive valve on valve-closing water hammer. And the flow characteristics of linear type, parabola type and equal percentage type are compared. The results show that: 1 The equal percentage flow characteristic is more conducive to the stable operation of the control valve under the low flow condition. Under this condition, the steady-state opening-degree of the equal percentage type control valve is larger, which can avoid cavitation and vibration caused by too small opening. 2 The most unfavorable flow condition of the valve-closing water hammer should consider the minimum initial flow condition, under which the water hammer pressure of the input point of the control valve is largest because of the largest initial pressure and the shortest closing time. 3 The equal percentage flow characteristic is more conducive to reducing the control valve-closing water hammer pressure. Under the same initial flow rate and valve closing rate, the control valve with equal percentage type flow characteristics has a larger initial opening-degree, a longer actual closing time, and a smaller change gradient of flow coefficient in the small opening-degree range, so the extreme value of the valve-closing water hammer pressure is smaller, which is more conducive to pipeline safety. [ABSTRACT FROM AUTHOR]

Cryptococcosis is a prevalent fungal infection of the central nervous system (CNS) caused by Cryptococcus neoformans, a yeast with a polysaccharide capsule in the basidiomycete group. Normally, C. neoformans infects the respiratory tract and then breaches the blood–brain barrier (BBB), leading to meningitis or meningoencephalitis, which leads to hundreds of thousands of deaths each year. Although the mechanism by which C. neoformans infiltrates the BBB to invade the brain has yet to be fully understood, research has revealed that C. neoformans can cross the BBB using transcellular penetration, paracellular traversal, and infected phagocytes (the "Trojan horse" mechanism). The secretion of multiple virulence factors by C. neoformans is crucial in facilitating the spread of infection after breaching the BBB and causing brain infections. Extensive research has shown that various virulence factors play a significant role in the dissemination of infection beyond the lungs. This review explores the mechanisms of C. neoformans entering the CNS and explains how it bypasses the BBB. Additionally, it aims to understand the interplay between the regulatory mechanisms and virulence factors of C. neoformans. [ABSTRACT FROM AUTHOR]

Although carbon dots (CDs) have been widely investigated as the fluorescence material, research on room temperature phosphorescence (RTP) CDs is still limited. In this work, diethylenetriaminepentaacetic acid (DTPA) was employed as the raw material to synthesize carbon quantum dots (denoted as CQDs-1) by a hydrothermal method. The resulting CQDs-1 inherited CO groups and N atoms from DTPA, which promoted the formation of triplet excitons under light excitation. On this basis, the CQDs-1 were dispersed in a poly-(vinyl alcohol) (PVA) matrix to prepare CQDs-1-PVA composites that exhibited an optimal emission peak at ∼466 nm and emitted the visible afterglow lasting for 8 s. Moreover, tartaric acid (TA) was combined with DTPA as the raw material to synthesize CQDs-2, which induced the formation of π–π conjugated areas in CQDs. As a result, the emission wavelength was slightly red-shifted, and the duration time of afterglow of the CQDs-2-PVA composite was increased to 9 s. Due to the ultralong-lifetime RTP properties of the CQDs-based composites, their applications in the fields of information encryption and anticounterfeiting have also been investigated. Overall, our work offered a convenient avenue for the synthesis of high-quality RTP CQDs. [ABSTRACT FROM AUTHOR]

HEX-P is a probe-class mission concept that will combine high spatial resolution X-ray imaging (<10" FWHM) and broad spectral coverage (0.2-80 keV) with an effective area far superior to current facilities' (including XMM-Newton and NuSTAR). These capabilities will enable revolutionary new insights into a variety of important astrophysical problems. We present scientific objectives and simulations of HEX-P observations of the Galactic Center (GC) and Bulge. We demonstrate the unique and powerful capabilities of the HEX-P observatory for studying both X-ray point sources and diffuse X-ray emission. HEX-P will be uniquely equipped to explore a variety of major topics in Galactic astrophysics, allowing us to 1) investigate broad-band properties of X-ray flares emitted from the supermassive black hole (BH) at Sgr A* and probe the associated particle acceleration and emission mechanisms; 2) identify hard X-ray sources detected by NuSTAR and determine X-ray point source populations in different regions and luminosity ranges; 3) determine the distribution of compact object binaries in the nuclear star cluster and the composition of the Galactic Ridge X-ray emission; 4) identify X-ray transients and measure fundamental parameters such as black hole spin; 5) find hidden pulsars in the Galactic Center; 6) search for BH-OB binaries and hard X-ray flares from young stellar objects in young massive clusters; 7) measure white dwarf (WD) masses of magnetic CVs to deepen our understanding of CV evolution and the origin of white dwarf magnetic fields; 8) explore primary particle accelerators in the GC in synergy with future TeV and neutrino observatories; 9) map out cosmic-ray distributions by observing nonthermal X-ray filaments; 10) explore past X-ray outbursts from Sgr A* through X-ray reflection components from giant molecular clouds. [ABSTRACT FROM AUTHOR]

This article discusses the importance of motion reconstruction in studying fossilized invertebrates. While most paleontological studies focus on static anatomical features, understanding the dynamic motion of extinct species is crucial for linking form and function. Recent advancements in 3D digital technologies have provided paleontologists with the opportunity to non-destructively investigate the motion characteristics of extinct species. The article presents a step-by-step approach for achieving motion reconstruction in fossil invertebrates, using the example of the Cretaceous hell ants Dhagnathos. The results of motion reconstruction can provide valuable insights into the evolutionary traces and ecological landscapes of extinct species. However, there are challenges in accurately reconstructing the motion of tiny invertebrates and in replicating their structures in robotic models. Overall, motion reconstruction offers a holistic approach to understanding invertebrate paleontology and encourages interdisciplinary collaboration. [Extracted from the article]

In order to explore the potential influence of new mobile payment services on the Ephesus model developed by Kao and Hwang (2008), we investigated the relative performance of 19 Taiwanese banks from 2018 to 2021. The network efficiency was divided into two parts: management efficiency and profitability efficiency. Only one bank achieved total efficiency from 2019 to 2021. The stage efficiencies showed increments during the first three years (2018–2020), but they declined in 2021. Most banks had low efficiency in the management stage and high efficiency in the profitability stage, suggesting that there are weaknesses in the management of physical resources but high awareness that mobile payment services can be exploited to achieve high profitability. Our results prove that mobile payment is a potential and profitable new service that Taiwanese banks should take advantage of. Comparing the results between the CCR model and the NDEA model, we observed that the NDEA model has more explanatory power, as it provides insight into the internal structure of the working process of Taiwanese banks. [ABSTRACT FROM AUTHOR]

Graphene quantum dots (GQDs) are promising for bioimaging applications due to their unique optical properties and good biocompatibility. However, the facile synthesis of GQDs with long-wavelength emission and high quantum yield (QY) under long-wavelength excitation is still a challenge. Herein, dual-emissive GQDs were synthesized via a facile one-pot solvothermal method using 2,7-dihydroxynaphthalene (2,7-DHN) and piperazine anhydrous (PA) as the raw materials. The obtained GQDs exhibited a green-emission band (core state emission) and a red-emission band (surface state emission), which originated from the inner π-conjugated structure and various surface functional groups, respectively. The π-conjugated structure mainly comes from the aromatic rings in 2,7-DHN, and the N–H of PA acts as the main nitrogen source, which is beneficial for the QY. The obtained GQDs showed obvious concentration-dependent optical properties. Importantly, they are able to generate red emission with a high absolute QY of 54.9% in ethanol and 24.9% in water, among the best values of reported GQDs. In addition, the prepared GQDs have good water-solubility, low cytotoxicity, and superior stability against photobleaching. Based on the above advantages, the as-prepared GQDs were successfully applied for labeling HeLa cells in vitro. Therefore, our prepared GQDs demonstrated that they can be an efficient biomarker for fluorescent bioimaging. [ABSTRACT FROM AUTHOR]

Fungal pathogens often undergo morphological switches, including cell size changes, to adapt to the host environment and cause disease. The pathogenic yeast Cryptococcus neoformans forms so-called 'titan cells' during infection. Titan cells are large, polyploid, display alterations in cell wall and capsule, and are more resistant to phagocytosis and various types of stress. Titan cell formation is regulated by the cAMP/PKA signal pathway, which is stimulated by the protein Gpa1. Here, we show that Gpa1 is activated through phosphorylation by a CDK-related kinase (Crk1), which is targeted for degradation by an E3 ubiquitin ligase (Fbp1). Strains overexpressing CRK1 or an allele lacking a PEST domain exhibit increased production of titan cells similarly to the fbp1∆ mutant. Conversely, CRK1 deletion results in reduced titan cell production, indicating that Crk1 stimulates titan cell formation. Crk1 phosphorylates Gpa1, which then localizes to the plasma membrane and activates the cAMP/PKA signal pathway to induce cell enlargement. Furthermore, titan cell-overproducing strains trigger increased Th1 and Th17 cytokine production in CD4+ T cells and show attenuated virulence in a mouse model of systemic cryptococcosis. Overall, our study provides insights into the regulation of titan cell formation and fungal virulence. The pathogenic yeast Cryptococcus neoformans forms large, so-called 'titan cells' during infection. Here, Cao et al. show that a ubiquitin ligase inhibits this process by targeting for degradation a CDK-related kinase that stimulates titan cell formation. [ABSTRACT FROM AUTHOR]

Although a wide range of literature has investigated the network-level highway maintenance plans and policies, few of them focused on the maintenance scheduling problem. This study proposes a methodology framework to model and compare two different maintenance scheduling strategies for highway networks, i.e., minimal makespan strategy (MMS) and minimal increased travel delay strategy (MITDS). We formulate MMS as a mixed integer linear programming model subject to the constraints of the quantity of manpower and the worst-first maintenance sequence. A bi-level programming model is proposed to quantify and optimize MITDS. The upper level model determines the optimal scheduling to minimize the increased traffic delays during the maintenance makespan. In the lower level, a modified day-to-day traffic assignment model is put forward to reflect the traffic evolution dynamics by simulating travelers' route choice behaviors. A simulated annealing algorithm and augmented Lagrange algorithm are employed to solve the two proposed models, respectively. Finally, a numerical example using a highway network is developed. The two proposed strategies are tested considering different traffic demands, numbers of engineering teams, and travelers' sensitivities to traffic congestion. The experiment results reveal that compared with MMS, MITDS extends makespan by 2 days though, it reduces the total increased travel delays by 4% and both MMS and MITDS can obtain the minimum total increased travel delays when the number of engineering teams is 6. The sensitivity analysis indicates that both the two strategies have the maximum and minimum total increased travel delays when the weight of prediction in travelers' perception is 0.3 and 0.7, respectively. The proposed framework has the potential to provide reference in implementing highway maintenance activities reasonably. [ABSTRACT FROM AUTHOR]

Cryptococcus neoformans is an opportunistic yeast-like pathogen that mainly infects immunocompromised individuals and causes fatal meningitis. Sexual reproduction can promote the exchange of genetic material between different strains of C. neoformans , which is one of the reasons leading to the emergence of highly pathogenic and drug-resistant strains of C. neoformans. Although much research has been done on the regulation mechanism of Cryptococcus sexual reproduction, there are few studies on the sexual reproduction regulation of Cryptococcus by the ubiquitin-proteasome system. This study identified an F-box protein, Cdc4, which contains a putative F-box domain and eight WD40 domains. The expression pattern analysis showed that the CDC4 gene was expressed in various developmental stages of C. neoformans , and the Cdc4 protein was localized in the nucleus of cryptococcal cells. In vitro stress responses assays showed that the CDC4 overexpression strains are sensitive to SDS and MMS but not Congo red, implying that Cdc4 may regulate the cell membrane integrity and repair of DNA damage of C. neoformans. Fungal virulence assay showed that although the cdc4 Δ mutant grows normally and can produce typical virulence factors such as capsule and melanin, the cdc4 Δ mutant completely loses its pathogenicity in a mouse systemic-infection model. Fungal mating assays showed that Cdc4 is also essential for fungal sexual reproduction in C. neoformans. Although normal mating hyphae were observed during mating, the basidiospores' production was blocked in bilateral mating between cdc4 Δ mutants. Fungal nuclei development assay showed that the nuclei failed to undergo meiosis after fusion inside the basidia during the bilateral mating of cdc4 Δ mutants, indicating that Cdc4 is critical to regulating meiosis during cryptococcal mating. In summary, our study revealed that the F-box protein Cdc4 is critical for fungal virulence and sexual reproduction in C. neoformans. [ABSTRACT FROM AUTHOR]

The optimal delivery route problem for truck–drone delivery is defined as a traveling salesman problem with drone (TSP-D), which has been studied in a wide range of previous literature. However, most of the existing studies ignore truck waiting time at rendezvous points. To fill this gap, this paper builds a mixed integer nonlinear programming model subject to time constraints and route constraints, aiming to minimize the total delivery time. Since the TSP-D is non-deterministic polynomial-time hard (NP-hard), the proposed model is solved by the variable neighborhood tabu search algorithm, where the neighborhood structure is changed by point exchange and link exchange to expand the tabu search range. A delivery network with 1 warehouse and 23 customer points are employed as a case study to verify the effectiveness of the model and algorithm. The 23 customer points are visited by three truck–drones. The results indicate that truck–drone delivery can effectively reduce the total delivery time by 20.1% compared with traditional pure-truck delivery. Sensitivity analysis of different parameters shows that increasing the number of truck–drones can effectively save the total delivery time, but gradually reduce the marginal benefits. Only increasing either the truck speed or drone speed can reduce the total delivery time, but not to the greatest extent. Bilateral increase of truck speed and drone speed can minimize the delivery time. It can clearly be seen that the proposed method can effectively optimize the truck–drone delivery route and improve the delivery efficiency. [ABSTRACT FROM AUTHOR]

The ubiquitin-proteasome system (UPS) is the major protein turnover mechanism that plays an important role in regulating various cellular functions. F-box proteins are the key proteins of the UPS, responsible for the specific recognition and ubiquitination of downstream targets. Our previous studies showed that the F-box protein Fbp1 plays an essential role in the virulence of C. neoformans. However, the molecular mechanism of Fbp1 regulating the virulence of C. neoformans is still unclear. In this study, we analyzed the potential Fbp1 substrates using an iTRAQ-based proteomic approach and identified the zinc-binding protein Zbp1 as a substrate of Fbp1. Protein interaction and stability assays showed that Zbp1 interacts with Fbp1 and is a downstream target of Fbp1. Ubiquitination analysis in vivo showed that the ubiquitination of Zbp1 is dependent on Fbp1 in C. neoformans. Subcellular localization analysis revealed that the Zbp1 protein was localized in the nucleus of C. neoformans cells. In addition, both deletion and overexpression of the ZBP1 gene led to the reduced capsule size, while overexpression has a more significant impact on capsule size reduction. Fungal virulence assays showed that although the zbp1 Δ mutants are virulent, virulence was significantly attenuated in the ZBP1 overexpression strains. Fungal load assay showed that the fungal burdens recovered from the mouse lungs decreased gradually after infection, while no yeast cells were recovered from the brains and spleens of the mice infected by ZBP1 overexpression strains. Thus, our results revealed a new determinant of fungal virulence involving the post-translational regulation of a zinc-binding protein. [ABSTRACT FROM AUTHOR]

Cryptococcus neoformans is an encapsulated yeast pathogen that infects immunocompromised patients to cause fungal meningitis, resulting in hundreds of thousands of deaths each year. F-box protein Fbp1, the key component of the E3 ubiquitin ligase, plays a critical role in fungal development and virulence in fungal pathogens. In this study, we identified a potential substrate of Fbp1, the vacuolar morphogenesis protein Vam6-like protein Vlp1, and evaluated its role in virulence in C. neoformans. Deletion or overexpression of the VLP1 gene results in abnormal capsule formation and melanin production of C. neoformans. Stress tolerance assay showed that the vlp1∆ mutant was sensitive to SDS and NaCl but not to CFW or Congo red, indicating that Vlp1 might regulate the cell membrane integrity in C. neoformans. Fungal virulence assay showed that Vlp1 was essential for the pathogenicity of C. neoformans, as vlp1∆ mutants are avirulent in the mouse systematic infection model of cryptococcosis. The progression of fungal infection revealed that the vlp1∆ mutants were gradually eliminated from the lungs of the mice after infection. Moreover, the vlp1∆ mutants showed a proliferation defect inside macrophages and a viability defect in the host complement system, which likely contributes to the virulence attenuation of the vlp1∆ mutants. In summary, our results revealed that the vacuolar morphogenesis protein Vam6-like protein Vlp1 is essential for the pathogenicity of C. neoformans. [ABSTRACT FROM AUTHOR]

Objective: During the COVID-19 epidemic, the hand hygiene of nursing workers in a third-grade a traditional Chinese medicine hospital was investigated to find out existing problems and put forward management countermeasures. Methods: A cross-sectional questionnaire survey was conducted to investigate the hand hygiene cognitive status and influencing factors of 78 nurses in the hospital. Results: Through the early training, the nursing workers had a good grasp of the hand hygiene signs and related knowledge. Among the factors affecting hand hygiene, there are some problems in facilities and management factors. The cognitive factors of different categories of nursing workers have different influences on hand hygiene, especially the influence of length of service on hand hygiene is significantly different (P < 0.05); Nursing workers should be trained on how to use hand washing. Conclusion: Hand hygiene of nursing workers is of great significance for the prevention and control of hospital infection. Medical institutions at all levels and of various types should, in light of their own actual conditions, formulate operational and feasible hand hygiene management systems for various groups of people in hospitals, strengthen training and supervision, and improve compliance with hand hygiene, so as to prevent hospital infections and fight the battle against COVID-19. [ABSTRACT FROM AUTHOR]

Insect pollination of flowering plants (angiosperms) is responsible for the majority of the world’s flowering plant diversity and is key to the Cretaceous radiation of angiosperms. Although both insects and angiosperms were common by the mid-Cretaceous, direct fossil evidence of insect pollination is lacking. Direct evidence of Cretaceous insect pollination is associated with insect-gymnosperm pollination. Here, we report a specialized beetle-angiosperm pollination mode from mid-Cretaceous Burmese amber (99 mega-annum [Ma]) in which a tumbling flower beetle (Mordellidae), Angimordella burmitina gen. et sp. nov., has many tricolpate pollen grains attached. A. burmitina exhibits several specialized body structures for flower-visiting behavior including its body shape and pollen-feeding mouthparts revealed by X-ray microcomputed tomography (micro-CT). The tricolpate pollen in the amber belongs to the eudicots that comprise the majority of extant angiosperm species. These pollen grains exhibit zoophilous pollination attributes including their ornamentation, size, and clumping characteristics. Tricolpate pollen grains attached to the beetle’s hairs are revealed by confocal laser scanning microscopy, which is a powerful tool for investigating pollen in amber. Our findings provide direct evidence of insect pollination of Cretaceous angiosperms, extending the range insect-angiosperm pollination association by at least 50 million years. Our results support the hypothesis that specialized insect pollination modes were present in eudicots 99 million years ago. [ABSTRACT FROM AUTHOR]

An oil‐air lubrication system is driven by high‐speed air. Oil is transported to the contact portion in the form of fine oil droplets to form a lubrication film, thereby improving lubrication performance among matching pairs. A test for point contact sliding friction and wear was conducted under oil‐air lubrication conditions. Oil‐phase and pressure distributions near the contact zone were investigated through numerical simulation. This study aims to explore the effect of air velocity on sliding wear characteristics of a point contact. Results show that point contact sliding wear is considerably affected by air supply speed. The lubrication performance between friction pairs is optimal under appropriate air supply speed, which can enable the oil‐air pressure and oil‐phase volume fraction near the point contact area to obtain appropriate values that are useful to the spread of fine oil droplets. This process ensures that the sliding friction coefficient and specific wear rate can be reduced. The friction coefficient decreases to approximately 0.027, and the specific wear rate is 1.06 × 10−5 mm3/N·m. Under oil‐air lubrication, microfurrows appear on the worn surfaces of materials with the change in air supply speed. The shape of debris is mainly a flake or block with a few long strip abrasives. The wear mechanism is abrasive. [ABSTRACT FROM AUTHOR]

Hybrid improper ferroelectric Ca3Ti2O7 (CTO) ceramics were synthesized by a solid‐state reaction method. Their polarization switching currents, dynamic processes of polarization‐switching, and leakage current properties were investigated. It was found that the dynamic polarization curves of CTO ceramics exhibit obvious dependence on the frequency of the driving electric fields. Moreover, CTO ceramics show a switchable diode effect. The underlying mechanism for the observed effects were proposed based on the interplaying between mobile charged defects and bound charges. The charged defects also lead to a decrease in the band gap of the CTO ceramic, as revealed by absorption spectrum analysis. [ABSTRACT FROM AUTHOR]

Soil bacteria play a key role in the ecological and evolutionary responses of agricultural ecosystems. Domestic herbivore grazing is known to influence soil bacterial community. However, the effects of grazing and its major driving factors on soil bacterial community remain unknown for different plant community compositions under increasing grazing intensity. Thus, to investigate soil bacterial community diversity under five plant community compositions (Grass; Leymus chinensis; Forb; L. chinensis & Forb; and Legume), we performed a four-year field experiment with different grazing intensity treatments (no grazing; light grazing, 4 sheep·ha−1; and heavy grazing, 6 sheep·ha−1) in a grassland in China. Total DNA was obtained from soil samples collected from the plots in August, and polymerase chain reaction (PCR) analysis and denaturing gradient gel electrophoresis (DGGE) fingerprinting were used to investigate soil bacterial community. The results showed that light grazing significantly increased indices of soil bacterial community diversity for the Forb and Legume groups but not the Grass and L. chinensis groups. Heavy grazing significantly reduced these soil bacterial diversity indices, except for the Pielou evenness index in the Legume group. Further analyses revealed that the soil N/P ratio, electrical conductivity (EC), total nitrogen (TN) and pH were the major environmental factors affecting the soil bacterial community. Our study suggests that the soil bacterial community diversity was influenced by grazing intensity and plant community composition in a meadow steppe. The present study provides a baseline assessment of the soil bacterial community diversity in a temperate meadow steppe. [ABSTRACT FROM AUTHOR]

Although observational studies have assessed the relationship between parity and thyroid cancer risk, the findings are inconsistent. To quantitatively assess the association, we conducted a systematic review and meta-analysis. PubMed and Embase were searched up to January 2015. Prospective or case-control studies that evaluated the association between parity and thyroid cancer risk were included. We used the fixed-effects model to pool risk estimates. After literature search, 10 prospective studies, 12 case-control studies and 1 pooled analysis of 14 case-control studies including 8860 patients were identified. The studies had fair methodological quality. Pooled analysis suggested that there was a significant association between parity and risk of thyroid cancer (RR for parous versus nulliparous: 1.09, 95% CI 1.03-1.15; I2=33.4%). The positive association persisted in almost all strata of subgroup analyses based on study design, location, study quality, type of controls, and confounder adjustment, although in some strata statistical significance was not detected. By evaluating the number of parity, we identified that both parity number of 2 versus nulliparous and parity number of 3 versus nulliparous demonstrated significant positive associations (RR=1.11, 95% CI 1.01-1.22; I2=31.1% and RR=1.16, 95% CI 1.01-1.33; I2=19.6% respectively). The dose-response analysis suggested neither a non-linear nor linear relationship between the number of parity and thyroid cancer risk. In conclusion, this meta-analysis suggests a potential association between parity and risk of thyroid cancer in females. However, the lack of detection of a dose-response relationship suggests that further studies are needed to better understand the relationship. [ABSTRACT FROM AUTHOR]

Background Cryptococcus neoformans is the most common cause of fungal meningitis among individuals with HIV/AIDS, which is uniformly fatal without proper treatment. The underlying mechanism of disease development in the brain that leads to cryptococcal meningoencephalitis remains incompletely understood. We have previously demonstrated that inositol transporters (ITR) are required for Cryptococcus virulence. The itr1aΔ itr3cΔ double mutant of C. neoformans was attenuated for virulence in a murine model of intracerebral infection; demonstrating that Itr1a and Itr3c are required for full virulence during brain infection, despite a similar growth rate between the mutant and wild type strains in the infected brain. Results To understand the immune pathology associated with infection by the itr1aΔ itr3cΔ double mutant, we investigated the molecular correlates of host immune response during mouse brain infection. We used genome-wide transcriptome shotgun sequencing (RNA-Seq) and quantitative real-time PCR (qRT-PCR) methods to examine the host gene expression profile in the infected brain. Our results show that compared to the wild type, infection of mouse brains by the mutant leads to significant activation of cellular networks/pathways associated with host protective immunity. Most of the significantly differentially expressed genes (SDEG) are part of immune cell networks such as tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ) regulon, indicating that infection by the mutant mounts a stronger host immune response compared to the wild type. Interestingly, a significant reduction in glucuronoxylomannan (GXM) secretion was observed in the itr1aΔ itr3cΔ mutant cells, indicating that inositol utilization pathways play a role in capsule production. Conclusions Since capsule has been shown to impact the host response during Cryptococcus-host interactions, our results suggest that the reduced GXM production may contribute to the increased immune activation in the mutant-infected animals. [ABSTRACT FROM AUTHOR]

The use of the dipole force on atoms is a new technology that is used to build nanostructures. In this way, a high quality standard nano-grating can be obtained. Based on the semi-classical model, the motion equation is investigated and the trajectories of atoms in double half Gaussian standing wave field are simulated. Compared with the Gaussian standing wave field, the double half Gaussian standing wave can well focus the Cr atoms. In order to obtain this kind of beam, a prism is designed and the experimental result shows that the beam is well generated. [ABSTRACT FROM AUTHOR]

Cryptococcus is a major fungal pathogen that frequently causes systemic infection in patients with compromised immunity. Glucose, an important signal molecule and the preferred carbon source for Cryptococcus, plays a critical role in fungal development and virulence. Cryptococcus contains more than 50 genes sharing high sequence homology with hexose transporters in Saccharomyces cerevisiae. However, there is no report on their function in glucose sensing or transport. In this study, we investigated two hexose transporter-like proteins (Hxs1 and Hxs2) in Cryptococcus that share the highest sequence identity with the glucose sensors Snf3 and Rgt2 in S. cerevisiae. The expression of HXS1 is repressed by high glucose, while the HXS2 expression is not regulated by glucose. Functional studies showed that Hxs1 is required for fungal resistance to oxidative stress and fungal virulence. The hxs1Δ mutant exhibited a significant reduction in glucose uptake activity, indicating that Hxs1 is required for glucose uptake. Heterologous expression of Cryptococcus HXS1 rendered the S. cerevisiae mutant lacking all 20 hexose transporters a high glucose uptake activity, demonstrating that Hxs1 functions as a glucose transporter. Heterologous expression of HXS1 in the snf3Δ rgt2Δ double mutant did not complement its growth in YPD medium containing the respiration inhibitor antimycin A, suggesting that Hxs1 may not function as a glucose sensor. Taken together, our results demonstrate that Hxs1 is a high-affinity glucose transporter and required for fungal virulence. [ABSTRACT FROM AUTHOR]

Cryptococcus neoformans is the most common cause of fungal meningitis, with high mortality and morbidity. The reason for the frequent occurrence of Cryptococcus infection in the central nervous system (CNS) is poorly understood. The facts that human and animal brains contain abundant inositol and that Cryptococcus has a sophisticated system for the acquisition of inositol from the environment suggests that host inositol utilization may contribute to the development of cryptococcal meningitis. In this study, we found that inositol plays an important role in Cryptococcus traversal across the blood-brain barrier (BBB) both in an in vitro human BBB model and in in vivo animal models. The capacity of inositol to stimulate BBB crossing was dependent upon fungal inositol transporters, indicated by a 70% reduction in transmigration efficiency in mutant strains lacking two major inositol transporters, Itr1a and Itr3c. Upregulation of genes involved in the inositol catabolic pathway was evident in a microarray analysis following inositol treatment. In addition, inositol increased the production of hyaluronic acid in Cryptococcus cells, which is a ligand known to binding host CD44 receptor for their invasion. These studies suggest an inositol-dependent Cryptococcus traversal of the BBB, and support our hypothesis that utilization of host-derived inositol by Cryptococcus contributes to CNS infection. [ABSTRACT FROM AUTHOR]

Direct-write atom lithography, one of the potential nanofabrication techniques, is restricted by some difficulties in producing optical masks for the deposition of complex structures. In order to make further progress, a structured mirror array is developed to transversely collimate the chromium atomic beam in two dimensions. The best collimation is obtained when the laser red detunes by natural line-width of transition 7S3 → 7P40 of the chromium atom. The collimation ratio is 0.45 vertically (in x axis), and it is 0.55 horizontally (in y axis). The theoretical model is also simulated, and success of our structured mirror array is achieved. [ABSTRACT FROM AUTHOR]

The disease cryptococcosis, caused by the fungus Cryptococcus neoformans, is acquired directly from environmental exposure rather than transmitted person-to-person. One explanation for the pathogenicity of this species is that interactions with environmental predators select for virulence. However, co-incubation of C. neoformans with amoeba can cause a "switch" from the normal yeast morphology to a pseudohyphal form, enabling fungi to survive exposure to amoeba, yet conversely reducing virulence in mammalian models of cryptococcosis. Like other human pathogenic fungi, C. neoformans is capable of microevolutionary changes that influence the biology of the organism and outcome of the host-pathogen interaction. A yeast-pseudohyphal phenotypic switch also happens under in vitro conditions. Here, we demonstrate that this morphological switch, rather than being under epigenetic control, is controlled by DNA mutation since all pseudohyphal strains bear mutations within genes encoding components of the RAM pathway. High rates of isolation of pseudohyphal strains can be explained by the physical size of RAM pathway genes and a hypermutator phenotype of the strain used in phenotypic switching studies. Reversion to wild type yeast morphology in vitro or within a mammalian host can occur through different mechanisms, with one being counter-acting mutations. Infection of mice with RAM mutants reveals several outcomes: clearance of the infection, asymptomatic maintenance of the strains, or reversion to wild type forms and progression of disease. These findings demonstrate a key role of mutation events in microevolution to modulate the ability of a fungal pathogen to cause disease. [ABSTRACT FROM AUTHOR]

Fungal meningitis is a serious disease caused by a fungal infection of the central nervous system (CNS) mostly in individuals with immune system deficiencies. Fungal meningitis is often fatal without proper treatment, and the mortality rate remains unacceptably high even with antifungal drug interventions. Currently, cryptococcal meningitis is the most common fungal meningitis in HIV-1/AIDS, and its disease mechanism has been extensively studied. The key steps for fungi to infect brain and cause meningitis after establishment of local infection are the dissemination of fungal cells to the bloodstream and invasion through the blood brain barrier to reach the CNS. In this review, we use cryptococcal CNS infection as an example to describe the current molecular understanding of fungal meningitis, including the establishment of the infection, dissemination, and brain invasion. Host and microbial factors that contribute to these infection steps are also discussed. [ABSTRACT FROM AUTHOR]

The ubiquitin-proteasome system is one of the major protein turnover mechanisms that plays important roles in the regulation of a variety of cellular functions. It is composed of E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3 ubiquitin ligases that transfer ubiquitin to the substrates that are subjected to degradation in the 26S proteasome. The Skp1, Cullin, F-box protein (SCF) E3 ligases are the largest E3 gene family, in which the F-box protein is the key component to determine substrate specificity. Although the SCF E3 ligase and its F-box proteins have been extensively studied in the model yeast Saccharomyces cerevisiae, only limited studies have been reported on the role of F-box proteins in other fungi. Recently, a number of studies revealed that F-box proteins are required for fungal pathogenicity. In this communication, we review the current understanding of F-box proteins in pathogenic fungi. [ABSTRACT FROM AUTHOR]

This study was designed to examine whether exogenous Ca2+ would improve nitrogen nutrition, water status and growth of high temperature (HT)-stressed wheat ( Triticum aestivum) seedlings. Wheat plants were exposed to 35/30 and 25/20°C as temperature control. Some of HT-stressed plants were simultaneously treated with 4 mM Ca2+. External Ca2+ could obviously improve growth of HT-exposed wheat seedlings indicated by the biomass. Compared with Ca2+-untreated plants, total nitrogen content showed a significant increase in Ca2+-treated plants under HT stress, this primarily resulted from enhanced nitrate reductase activity and depressed loss of ammonium through photorespiration. External Ca2+ application could also increase leaf relative water content and alleviate osmotic stress via increased K+ ion and water-soluble carbohydrates in HT-stressed plants. Whereas free proline content showed remarkable decline in Ca2+-treated plants at HT stress. [ABSTRACT FROM AUTHOR]

Fasciclin family proteins have been identified as cell adhesion molecules in various organisms. In this study, a novel Magnaporthe oryzae fasciclin-like protein encoding gene, named MoFLP1, was isolated from a subtractive suppressive cDNA library and functionally analyzed. Sequence analysis showed that the MoFLP1 gene contains an open reading frame (ORF) of 1050 nucleotides encoding 349 amino acids with a calculated molecular weight of 35.85 kDa and a pI of 7.76. The deduced MoFLP1 protein contains a 17-amino acid secretion signal sequence and an 18-amino acid sequence with the characteristics of a glycosylphosphotidylinositol (GPI) anchor additional signal at its N- and C-terminuses, respectively. Potential N-glycosylation sites and domains involving cell adhesion were also identified in MoFLP1. Sequence analysis and subcellular localization by the expression of MoFLP1-GFP fusion construct in M. oryzae indicated that the MoFLP1 protein is probably localized on the vacuole membrane. Two MoFLP1 null mutants generated by targeted gene disruption exhibited marked reduction of conidiation, conidial adhesion, appressorium turgor, and pathogenicity. Our results indicate that fasciclin proteins play important roles in fungal development and pathogenicity in M. oryzae. [ABSTRACT FROM AUTHOR]

Phytoremediation is a promising tool in removing pollutants from the environment or in rendering them harmless. The objective of this research was to determine the effect of iron-deficiency on the uptake of cadmium by Solanum nigrum L. Results showed that iron-deficiency induced cadmium uptake, biomass decrease and changes in pH and Eh in hydroponic culture. Under iron-deficiency status, the decrease in pH and the increase in Eh might result in higher cadmium availability. Bioconcentration and translocation factors indicated that iron-deficiency status affected cadmium accumulation and translocation in Solanum nigrum L. [ABSTRACT FROM AUTHOR]

Appressorium formation is an important event in establishing a successful interaction between the rice blast fungus, Magnaporthe oryzae, and its host plant, rice. An understanding of molecular events occurring in appressorium differentiation will give new strategies to control rice blast. A quick and reliable method to extract total RNA from appressorium is essential for studying gene expression during appressorium formation and its mechanism. We found that duplicate film is an efficient substratum for appressorium formation, even when inoculated with high density conidia. When inoculated with conidia at 1×106 ml−1, the percentages of conidium germination and appressorium formation were (97.98±0.67)% and (97.88±0.45)%, respectively. We applied Trizol before appressorium collection for total RNA isolation, and as much as 113.6 μg total RNA was isolated from the mature appressoria at 24 h after inoculation. Functional analysis of two genes, MNH6 and MgATG1, isolated from the cDNA subtractive library, revealed that the quantity of RNA was good enough to construct a cDNA (complementary DNA) library or a cDNA subtractive library. This method may be also applicable for the appressorium RNA isolation of other pathogenic fungi in which conidia differentiate into appressoria in the early stages of host infection. [ABSTRACT FROM AUTHOR]

The promoter of NAR gene in Magnaporthe grisea was isolated and sequenced. The promoter sequences contained the “TATA” box, the “CAAT” box, and binding sites for fungal regulatory proteins. Programs that predict promoter sequences indicated that promoter sequence lies between locations 430 and 857 of the NAR promoter fragment. GFP expression under the NAR promoter and NAR transcript analysis revealed that this promoter is activated primarily at the mycelial stage in the rice blast fungus and could be used to express native or extrinsic genes in the mycelia of the rice blast fungus. [ABSTRACT FROM AUTHOR]

Abstract: We have constructed a fungal subtractive suppressive library enriched in genes expressed during appressorium maturation in Magnaporthe grisea. Sequencing of 250 clones from the subtracted appressorium cDNA library revealed 142 unique genes, represented by 155 non-redundant ESTs (expressed sequence tags). Of these ESTs, 72 have not been previously isolated in M. grisea. RT-PCR analysis of 105 of the genes discovered found transcripts corresponding to 71 of the ESTs only in mature appressoria while transcripts corresponding to a further 34 of the isolated ESTs were expressed both in appressoria and conidia/mycelia. Genes specifically expressed in appressorium identified by SSH included a number that have been previously implicated in appressorium formation or function including GAS1, GAS3, and PTH11. [Copyright &y& Elsevier]

A numerical simulation is performed to study the influence on the heat transfer rate of the heated wall in the channel with an oscillating cylinder. An arbitrary Lagrangian-Eulerian kinematic description method is adopted to describe the flow and thermal fields. A penalty consistent finite-element formulation is applied to solve the governing equations. The effects of Reynolds number, oscillating amplitude, oscillating frequency, eccentric ratio, and blockage on the heat transfer characteristics of the heated wall are examined. The results show that not only the region relating to heat transfer is enlarged substantially, but also that the heat transfer rate of this region is enhanced remarkably. [ABSTRACT FROM AUTHOR]

Silverleaf whitefly (SLW), Bemisia argentifolii Bellows and Perring, is one of the most noxious pests of numerous field and vegetable crops, causing billions of dollars worth of damage throughout the world. SLW is a phloem feeder whose feeding is likely to interfere with phloem transport. The aim of this study was to test the hypothesis that SLW infestation impairs carbohydrate export from source leaves, and consequently increases their carbohydrate content. The youngest fully expanded leaves of cotton (Gossypium hirsutum L., cv. Siv'on), grown under SLW-infested and noninfested conditions, were characterized for their diurnal changes in carbohydrate content and photoassimilate export. SLW infestation induced a considerable reduction in net photosynthetic rate (Pn), coupled with increased sucrose, glucose and fructose and decreased starch concentrations. Export rate was determined after 14CO2, pulse-labeling both by in situ monitoring of leaf radioactivity and by analyzing the content and radioactivity of the major carbon metabolites. Radioactive counting indicated a lower rate of 14C efflux for the infested plants. A similar trend was found for the specific activities of sucrose and the three soluble sugars combined (sucrose, glucose and fructose). A single exponential decay function with asymptote was fitted to the above efflux curves. All the calculated exponential coefficients demonstrated lower export rates after SLW injury. These results indicate that SLW impairs photoassimilate export, suggesting possible down-regulation of Pn due to increased foliar soluble sugar contents. [ABSTRACT FROM AUTHOR]