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The type III secretion system encoded in the Salmonella pathogenicity island-2 (SPI-2) gene cluster facilitates intracellular growth of nontyphoidal Salmonella by interfering with the maturation of Salmonella-containing vacuoles along the degradative pathway. SPI-2 gene products also protect Salmonella against the antimicrobial activity of reactive oxygen species (ROS) synthesized by the phagocyte NADPH oxidase 2 (NOX2). However, a potential relationship between inflammatory ROS and the activation of transcription of SPI-2 genes by intracellular Salmonella is unclear. Here, we show that ROS engendered in the innate host response stimulate SPI-2 gene transcription. We found that the expression of SPI-2 genes in Salmonella-sustaining oxidative stress conditions involves DksA, a protein otherwise known to regulate the stringent response of bacteria to nutritional stress. We also demonstrate that the J and zinc-2-oxidoreductase domains of DnaJ as well as the ATPase activity of the DnaK chaperone facilitate loading of DksA onto RNA polymerase complexed with SPI-2 promoters. Furthermore, the DksA-driven transcription of SPI-2 genes in Salmonella experiencing oxidative stress is contingent on upstream OmpR, PhoP, and SsrB signaling events that participate in the removal of nucleoid proteins while simultaneously recruiting RNA polymerase to SPI-2 promoter regions. Taken together, our results suggest the activation of SPI-2 gene transcription in Salmonella subjected to ROS produced by the respiratory burst of macrophages protects this intracellular pathogen against NOX2-mediated killing. We propose that Salmonella have co-opted inflammatory ROS to induce SPI-2-mediated protective responses against NOX2 host defenses. [ABSTRACT FROM AUTHOR]

In this study, the accumulation rate of plastic litter was investigated by sampling quadrats placed on the North Island of Qilianyu, and the composition was analyzed and identified to determine its source. The results showed that the annual average accumulation rate of plastic litter on North Island was 0.64 ± 0.32 pieces·m−2·month−1, with a mass accumulation rate of 11.30 ± 7.73 g·m−2·month−1. The accumulation rate of plastic litter was mainly influenced by wind speed and direction, with higher accumulation rates occurring during the southwest monsoon season and tropical cyclones. ATR-FTIR analysis indicated that polyethylene (44 %) and polypropylene (41 %) were the most abundant types of polymers. This study reveals the current status of plastic litter pollution in green turtle nesting grounds on North Island in Qilianyu, which can be used as a reference for management strategies that mitigate plastic litter pollution. • The accumulation rate of plastic litter is influenced by the monsoon winds. • Polyethylene and polypropylene were the most abundant types of polymers. • Plastic litter on North Island mainly originated from human coastal activities. [ABSTRACT FROM AUTHOR]

Insect chitin deacetylases (CDAs) catalyze the removal of acetyl groups from chitin and modify this polymer during its synthesis and reorganization. CDAs are essential for insect survival and therefore represent promising targets for insecticide development. However, the structural and biochemical characteristics of insect CDAs have remained elusive. Here, we report the crystal structures of two insect CDAs from the silk moth Bombyx mori: BmCDA1, which may function in cuticle modification, and BmCDA8, which may act in modifying peritrophic membranes in the midgut. Both enzymes belong to the carbohydrate esterase 4 (CE4) family. Comparing their overall structures at 1.98-2.4 Å resolution with those from well-studied microbial CDAs, we found that two unique loop regions in BmCDA1 and BmCDA8 contribute to the distinct architecture of their substrate-binding clefts. These comparisons revealed that both BmCDA1 and BmCDA8 possess a much longer and wider substrate-binding cleft with a very open active site in the center than the microbial CDAs, including VcCDA from Vibrio cholerae and ArCE4A from Arthrobacter species AW19M34-1. Biochemical analyses indicated that BmCDA8 is an active enzyme that requires its substrates to occupy subsites 0,+1, and +2 for catalysis. In contrast, BmCDA1 also required accessory proteins for catalysis. To the best of our knowledge, our work is the first to unveil the structural and biochemical features of insect proteins belonging to the CE4 family. [ABSTRACT FROM AUTHOR]

Due to the specific dynamics, the probes located at the halo orbits or Lissajous orbits around the Earth-Moon collinear libration point L 1 or L 2 are always studied in the synodic system to understand their trajectories. In fact, they are also orbiting the Earth in a distant Keplerian ellipse. Because of their intrinsic orbital instability, in the orbit prediction the initial errors propagate more prominently than those of the normal orbiting satellites, this requires special attention in the orbit design, maneuver, and control. Despite of all this, they are similar to the normal orbiting satellites in orbit determination and hardly require other special attentions. In this paper, the quantitative results of error propagation under the unstable dynamics, together with the theoretical analysis are presented. The results of precise orbit determination and short-arc orbit predictions are also shown, and compared with the results from the Beijing Aerospace Control Center. [ABSTRACT FROM AUTHOR]

Metal-oxygen batteries, especially Li-oxygen batteries (LOBs), have attracted tremendous research attentions in the past decades. It is necessary to design novel cost-effective catalysts in the development of high performance rechargeable LOBs. Herein, we prepare the atom-layered two-dimensional (2D) β -Co(OH) 2 nanosheets (AL- β -Co(OH) 2 ) via phase transition of layered α- Co(OH) 2 nanosheets ( α- Co(OH) 2 ) in a mild wet chemical process. The thickness of AL- β- Co(OH) 2 is less than 1.5 nm. It is the first time of using atom-layered β -Co(OH) 2 in the system of LOBs and this material shows outstanding catalytic performance. The AL- β -Co(OH) 2 nanosheets as electrocatalysts in LOBs can better reduce the over-potential, enhance the specific capacity and improve cycling capability. It demonstrates a high initial capacity 11841 mAh g −1 at a current density of 100 mA g −1 . It displays long cycle stability more than 70 cycles with a capacity restriction of 1000 mAh g −1 . These results suggest that this strategy for designing oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) catalysts via exfoliation of materials to atom-layered level could be a promising way to improve the performance of LOBs. [ABSTRACT FROM AUTHOR]

Newborn neurons undergo inside-out migration to their final destinations during neocortical development. Reelin-induced tyrosine phosphorylation of disabled 1 (Dab1) is a critical mechanism controlling cortical neuron migration. However, the roles of Reelin-independent phosphorylation of Dab1 remain unclear. Here, we report that deleted in colorectal carcinoma (DCC) interacts with Dab1 via its P3 domain. Netrin 1, a DCC ligand, induces Dab1 phosphorylation at Y220 and Y232. Interestingly, knockdown of DCC or truncation of its P3 domain dramatically delays neuronal migration and impairs the multipolar-to-bipolar transition of migrating neurons. Notably, the migration delay and morphological transition defects are rescued by the expression of a phospho-mimetic Dab1 or a constitutively active form of Fyn proto-oncogene (Fyn), a member of the Src-family tyrosine kinases that effectively induces Dab1 phosphorylation. Collectively, these findings illustrate a DCC-Dab1 interaction that ensures proper neuronal migration during neocortical development. [ABSTRACT FROM AUTHOR]

In this study, thiolated magnetic iron oxide nanoparticles (Fe 3 O 4 -SH) were prepared and characterized in detail, which exhibited benign superparamagnetism and magnetic recoverability. And the adsorption and desorption processes for various heavy metals, including Pb 2+ , Ni 2+ , Zn 2+ and Cu 2+ , had been investigated comprehensively both in single and mixed systems using the Fe 3 O 4 -SH nanoparticles as adsorbents. The results showed that heavy metal ions could be removed rapidly depending on the complexation with the SH-groups on the Fe 3 O 4 -SH surface. Besides, the adsorption was all sensitive to pH and ionic strength while the nano-adsorbents had the highest adsorption capacity and rate for Ni 2+ according to the adsorption kinetics and thermodynamics. In addition, the corresponding competitive adsorption processes and desorption experiments reflected that Fe 3 O 4 -SH had the strongest affinity and adsorption selectivity for Pb 2+ , followed by Ni 2+ and finally by Cu 2+ and Zn 2+ . Generally, the present study might provide a serviceable direction for the future efforts towards the application of Fe 3 O 4 -SH nano-adsorbents in industrial wastewater treatments involving multiple heavy metal contaminants. [ABSTRACT FROM AUTHOR]

Lactate dehydrogenase (LDH) catalyzes the interconversion of pyruvate and lactate, which are critical fuel metabolites of skeletal muscle particularly during exercise. However, the physiological relevance of LDH remains poorly understood. Here we show that Ldhb expression is induced by exercise inhumanmuscle and negatively correlated with changes in intramuscular pH levels, a marker of lactate production, during isometric exercise. We found that the expression of Ldhb is regulated by exerciseinduced peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α). Ldhb gene promoter reporter studies demonstrated that PGC-1α activates Ldhb gene expression through multiple conserved estrogen-related receptor (ERR) and myocyte enhancer factor 2 (MEF2) binding sites. Transgenic mice overexpressing Ldhb in muscle (muscle creatine kinase (MCK)- Ldhb) exhibited increased exercise performance and enhanced oxygen consumption during exercise. MCK-Ldhb muscle was shown to have enhanced mitochondrial enzyme activity and increased mitochondrial gene expression, suggesting an adaptive oxidative muscle transformation. In addition, mitochondrial respiration capacity was increased and lactate production decreased inMCK-Ldhbskeletal myotubes in culture. Together, these results identified a previously unrecognized Ldhb-driven alteration in muscle mitochondrial function and suggested a mechanism for the adaptive metabolic response induced by exercise training. [ABSTRACT FROM AUTHOR]

• Definition of new type 18 operator to enhance the model ability of GO methodology for MC(k,n) system. • Optimization of BN structure corresponding to large-scale MC(k,n) system. • Mapping procedure transforming GO model of MC(k,n) system to corresponding BN. • Fault diagnosis and improvement guidance of MC(k,n) system based on extended GO model and BN. As a success-oriented system reliability and safety analysis technique, GO methodology is widely used in the modeling and analysis scenarios of critical safety engineering systems with signal flow, such as nuclear, chemical industry, electric power transportation, wireless network and microwave communication network. Consecutive- k -out-of- n systems are also widely applied in these fields, but due to their relatively complex logic, there are no corresponding graphical modeling and calculation methods. In this paper, the basic GO methodology is extended to support the modeling and analysis of multi-state linear and circular consecutive- k -out-of- n : F system (MLC(k,n) &MCC(k,n)) models. Two new operators are defined in graphical modeling to represent the two types of complex system logic. The multi-state logic semantics of the new operators and mapping rules to Bayesian networks (BN) are given. And the programmable process is presented to transform the extended GO model into BN, and the reliability of the MLC(k,n)/MCC(k,n) is calculated. Finally, three cases are used to verify i) the correctness of the method supporting multi-state model, ii) the efficiency and ability of the algorithm, and iii) the forward calculation and reverse diagnosis of the MLC(k,n) and MCC(k,n) systems with external shared components. [ABSTRACT FROM AUTHOR]

7-Hydroxymethyl chlorophyll a reductase (HCAR) catalyzes the second half-reaction in chlorophyll b to chlorophyll a conversion. HCAR is required for the degradation of light-harvesting complexes and is necessary for efficient photosynthesis by balancing the chlorophyll a/b ratio. Reduction of the hydroxymethyl group uses redox cofactors [4Fe-4S] cluster and FAD to transfer electrons and is difficult because of the strong carbonoxygen bond. Here, we report the crystal structure of Arabidopsis HCAR at 2.7-Å resolution and reveal that two [4Fe-4S] clusters and one FAD within a very short distance form a consecutive electron pathway to the substrate pocket. In vitro kinetic analysis confirms the ferredoxin-dependent electron transport chain, thus supporting a proton-activated electron transfer mechanism. HCAR resembles a partial reconstruction of an archaeal F420-reducing [NiFe] hydrogenase, which suggests a common mode of efficient proton-coupled electron transfer through conserved cofactor arrangements. Furthermore, the trimeric form ofHCARprovides a biological clue of its interaction with light-harvesting complex II. [ABSTRACT FROM AUTHOR]

MoS 2 have been regarded as promising catalysts for the hydrogen evolution reaction (HER). However, its poor catalytic performance in neutral and alkaline solution would be problematic for the practical application. Combining semiconductors with metals as Mott-Schottky heterojunctions (MSH) has been regarded as an effective way to improve catalytic activity. Herein, a pH-universal adaptability Mo-MoS 2 MSH has been constructed via an in-situ lithiation method. The constructed MSH structure can effectively optimize the sulfur sites' electronic structure with interfacial electron redistribution and enhance the proton adsorption property under all pH conditions. To achieve the current density of 10 mA cm−2, it only needs overpotentials of 91, 138 and 128 mV in 0.5 M H 2 SO 4 , 1.0 M KOH and 1.0 M PBS, respectively, which has been one of the best values of current noble-metal-free electrocatalyst. This work can pave a valuable approach for the design high activity HER electrocatalysts for pH-universal with Pt-like activity. [Display omitted] • Mo-MoS 2 Mott-Schottky heterojunctions have been successfully constructed by means of in-situ lithiation tailoring methods. • The performance of Mo-MoS 2 Mott-Schottky heterojunctions is superior to Pt/C at high current density in a wide pH range. • The Mo-MoS 2 Mott–Schottky heterostructure can induce the interfacial electron redistribution. • Mo-MoS 2 Mott-Schottky heterojunctions is demonstrated to own excellent proton adsorption and ultralow overpotential for HER. [ABSTRACT FROM AUTHOR]

Most follicles in the mammalian ovary undergo atresia. Granulosa cell apoptosis is a hallmark of follicle atresia. Our previous study using a microRNA (miRNA) microarray showed that the let-7 microRNA family was differentially expressed during follicular atresia. However, whether the let- 7 miRNA family members are related to porcine (Sus scrofa) ovary follicular apoptosis is unclear. In the current study, real-time quantitative polymerase chain reaction showed that the expression levels of let-7 family members in follicles and granulosa cells were similar to our microarray data, in which miRNAs let-7a, let-7b, let-7c, and let-7i were significantly decreased in early atretic and progressively atretic porcine ovary follicles compared with healthy follicles, while let-7g was highly expressed during follicle atresia. Furthermore, flow cytometric analysis and Hoechst33342 staining demonstrated that let-7g increased the apoptotic rate of cultured granulosa cells. In addition, let-7 target genes were predicted and annotated by TargetScan, PicTar, gene ontology and Kyoto encyclopedia of genes and genomes pathways. Our data provide new insight into the association between the let-7 miRNA family in granulosa cell programmed death. [ABSTRACT FROM AUTHOR]

Studies have found lower risk of childhood cancer among Asian children. We aim to characterize the recent incidence and incidence-trend of childhood cancer in Taiwan after the National Health Insurance program was launched in March 1995. Data were extracted from the Taiwan Cancer Registry, a population-based database established in 1979. Cases diagnosed at age 0-14 from 1996 to 2010 were analyzed and categorized according to the International Classification of Childhood Cancer, Third Edition (ICCC-3). In total, 8032 childhood cancer cases were included, with a microscopic verification rate of 93.9%. The overall age-standardized rate (ASR) of incidence adjusted to the 2000 World Standard Population is 125.0 cases/million, with a male-to-female ratio of 1.3. The top five cancer types (ICCC-3 subgroup[s]; ASR per million) are acute lymphoblastic leukemia (Ia, 30.3), acute myeloid leukemia (Ib; 9.4), non-Hodgkin lymphoma (IIb,c,e, 9.0), extracranial germ cell tumor (Xb,c; 8.3), and neuroblastoma (IVa; 7.8). The median age of diagnosis was 6 years for both genders. During the study period, the ASR of childhood cancer has been increasing at a rate of 1.2% per year (95% confidence interval, 0.6-1.7%). In contrast to Western countries, China, Japan, and Taiwan have lower incidence of childhood cancer; however, Taiwan's incidence rates of childhood germ cell tumors and hepatic tumors are higher. In conclusion, this population-based study reveals that the incidence rate of childhood cancer in Taiwan is rising consistently. The high incidence of germ cell tumors warrants further investigation. [ABSTRACT FROM AUTHOR]

Introduction: In this study, we aimed to evaluate the adenoidal nasopharyngeal ratio (ANR) on lateral cephalograms by assessing upper airway volumes using cone-beam computed tomography (CBCT) images as the validation method. Methods: Fifty-five patients were included in the study, and it was essential that the lateral cephalograms and CBCT images taken at their examinations were not more than 1 week apart. There were 32 subjects in group A (age ≤15 years) and 23 subjects in group B (age >15 years). The ANR was measured on the lateral cephalograms. The area and volumetric measurements of the nasopharynx and the total upper airway were obtained from CBCT images. Repeated measurements of the ANR and airway volume were performed on 10 subjects by 2 observers. Results: Group A had a higher correlation (r = -0.78) between the ANR and the nasopharynx volume than did group B (r = -0.57). The ANR had a weak correlation with the total upper airway volume (group A, r = -0.48; group B, r = -0.32). Both measurements made on lateral cephalograms and CBCT were highly reproducible in terms of intraobserver and interobserver agreement. Conclusions: Based on our results, the measurement of the ANR on lateral cephalograms can be used as an initial screening method to estimate the nasopharynx volumes of younger patients (age ≤15 years). [ABSTRACT FROM AUTHOR]

The formation of a SEI layer and its growth cause internal resistance increase and capacity loss, leading to performance degradation of lithium-ion batteries. In order to comprehensively investigate the effects of SEI growth on battery performance, a one-dimensional thermal-electrochemical model was developed. This model is equipped with a growth mechanism of the SEI layer coupled with thermal evolution, based on the diffusional process of the solvent through the SEI layer and the kinetic process at the interface between the solid and liquid phases. The model is able to reveal the effects of diffusivity, reaction kinetics and temperature on SEI layer growth and cell capacity fade. We show that depending on the SEI thickness, the growth can be kinetics-limited or diffusion-limited. With the layer becoming thicker, its growth rate slows down gradually due to increased diffusion resistance. The SEI layer grows faster during charge than discharge due to the difference in the electron flux through the SEI layer and the temperature change during cycling. Temperature rise due to reaction and joule heating accelerates the SEI layer growth, leading to more capacity loss. Our model can provide insights on position-dependent SEI growth rate and be used to guide the strategic monitoring location. [ABSTRACT FROM AUTHOR]

This study evaluated microplastic pollution in beaches that have served as historical nesting grounds for green turtles in Hainan Island, China and explored the sources of microplastic pollutants to conduct habitat restoration for sea turtles. The average abundance of the microplastics in the beach surface sediments was 2567.38 ± 2937.37 pieces·m−2 or 641.85 ± 734.34 thousand pieces·m−3, foam and plastic block were the main microplastics identified. Microplastic size was predominantly within the 0.05–1 mm category (small microplastic particles), and most microplastic particles were white. Polystyrene and polyethylene were the dominant plastic compositions. The type and compositions of microplastics indicate that most microplastics in this study were broken from large plastic blocks and foam. To reduce the threat of microplastic pollution to marine life, including sea turtles, we suggested removing plastic litter, especially small plastic on beaches, and replacing and recovering the foam used in aquaculture before it ages and fragments. • Microplastic were found in all beaches that served as historical nesting grounds for green turtles in Hainan Island, China. • Polystyrene and polyethylene were the dominant compositions of microplastic in this study. • Microplastic size was mostly in 0.05–1 mm (small microplastic particles), and the color of microplastic was mostly white. • Removing small plastic litter and replacing and recovering the foam maybe can reduce microplastic pollution. [ABSTRACT FROM AUTHOR]

Mutations that cause loss of function of GlcNAc-1- phosphotransferase (PTase) lead to the lysosomal storage disorder mucolipidosis II. PTase is the key enzyme of the mannose 6-phosphate (M6P) targeting system that is responsible for tagging lysosomal hydrolases with the M6P moiety for their delivery to the lysosome. We had previously generated a truncated hyperactive form of PTase termed S1S3 which was shown to notably increase the phosphorylation level of secreted lysosomal enzymes and enhance their uptake by cells. Here, we report the 3.4 Å cryo-EM structure of soluble S1S3 lacking both transmembrane domains and cytosolic tails. The structure reveals a high degree of conservation of the catalytic core to fulllength PTase. In this dimeric structure, the EF-hand of one protomer is observed interacting with the conserved region four of the other. In addition, we present a high-quality EM 3D map of the UDP-GlcNAc bound form of the full-length soluble protein showing the key molecular interactions between the nucleotide sugar donor and side chain amino acids of the protein. Finally, although the domain organization of S1S3 is very similar to that of the Drosophila melanogaster (fruit fly) PTase homolog, we establish that the latter does not act on lysosomal hydrolases. [ABSTRACT FROM AUTHOR]

Atlantic salmon heads (ASH) and bighead carp heads (BHCH) were used to prepare fish head soups. The migration of nutrients and the formation and structure of micro/nano-sized particles (MNP) in the cooking process were studied. With the optimal cooking conditions including a ratio of fish head to water of 1:8 (w/w) and oil-fried 40 s before cooking, nutrients including total lipids, water-soluble proteins, total sugars, total minerals, solids and vitamins in the fish head tissue migrated continuously into the soup. At 150 min, the total lipids, total sugars, and tocopherol in the soup were maximized. After 150 min, the water-soluble proteins, total minerals and solids continued to increase, but there were no significant differences (P ≥ 0.05) between 150 and 180 min. The migration of nutrients from ASH was greater than that from BHCH. An inverted optical microscopy was used to study the formation and changes of the MNP in the fish head soups. From 30 min, the nutrients in the soup had already interacted and self-assembled to form MNP. At 150 min, the most stable bilayer of MNP were formed, and at 180 min, the MNP combined to form larger aggregates. The microscopic structure of the MNP was studied using laser scanning confocal microscopy. Triglycerides self-assembled to form spherical particles, while proteins, phospholipids and glycosylated molecules were distributed on the periphery of the triglyceride globules. [ABSTRACT FROM AUTHOR]

The oxygen evolution reaction (OER) process involves the magnetic reversal of oxygen-containing intermediates, and the influence of defect structures on the magnetic behavior of catalysts might play a crucial role in this process. There is scarce research on the intrinsic relationship among defects, magnetism and catalysis. Herein, cation vacancy β -Ni(OH) 2 nanosheets were successfully prepared through alkaline selective etching. To further analyze their spin-magnetic behavior, we found that the presence of defects caused the transformation of Ni(OH) 2 from antiferromagnetic to ferromagnetic. Furthermore, to further elucidate their intrinsic spin-magnetic effects, it was observed that the initially antiferromagnetic β -Ni(OH) 2 exhibited almost no spin-magnetic response upon the introduction of a magnetic field, with the overpotential almost unchanged. Conversely, introducing defect structures showed a noticeable spin-magnetic effect, reducing the overpotential by 20 mV at 20 mA cm−2. The combination of defects and magnetic fields provides new principles for developing high-performance catalysts and understanding catalytic mechanisms at the spin-electronic level. • Ni 1-x Vac x (OH) 2 was prepared to investigate the spin-magnetic behavior of defect. • The defects of Ni(OH) 2 led to transformation from antiferromagnetic to ferromagnetic. • The spin-magnetic effect can reduce the overpotential by 20 mV at 20 mA cm−2. [ABSTRACT FROM AUTHOR]

Achieving improved energy efficiency, a green economy and degradation of environmental pollutants are important challenges to achieving sustainable development strategies. Herein, we have designed and synthesized a series of LaFe 1-x O 3 (LaFeO 3 , LaFe 0.95 O 3 , and LaFe 0.9 O 3) crystals with Fe vacancies for photo-assisted electrocatalysis (PAEC). These catalysts are used for both the anodic and cathodic reactions, where the anode efficiently removes persistent organic pollutants such as methylene blue (MB), and the cathode converts water into hydrogen gas. We observed that the presence of Fe vacancies leads to rearranging the electronic structure on the surface, enhancing the photo-assisted electrocatalytic activity. The rate constant for the photo-assisted electrocatalytic LaFe 0.90 O 3 was measured to be 0.996 min−1, which is 2.37 times and 2.74 times higher than that of the electrocatalytic (0.420 min−1) and photocatalytic (0.363 min−1) processes, respectively. The hydrogen production efficiency reached 1.42 μmol min−1. This study provides the first evidence of the photo-assisted electrocatalytic mechanism and potential applications of LaFeO 3 -based catalysts in enhancing the electro-oxidation of pollutants. It offers additional insights for the rational design and construction of more efficient PAEC catalysts for effective wastewater purification and energy recovery. [Display omitted] • The photo-assisted electrocatalysis for LaFe 1-x O 3 has been demonstrated. • The LaFe 0.90 O 3 owned outstanding electrocatalytic and photocatalytic performance. • The presence of Fe vacancies can enhance photo-assisted electrocatalytic activity. [ABSTRACT FROM AUTHOR]

Mammalian Asn-linked glycans are extensively processed as they transit the secretory pathway to generate diverse glycans on cell surface and secreted glycoproteins. Additional modification of the glycan core by a-1,6-fucose addition to the innermost GlcNAc residue (core fucosylation) is catalyzed by an a-1,6-fucosyltransferase (FUT8). The importance of core fucosylation can be seen in the complex pathological phenotypes of FUT8 null mice, which display defects in cellular signaling, development, and subsequent neonatal lethality. Elevated core fucosylation has also been identified in several human cancers. However, the structural basis for FUT8 substrate specificity remains unknown. Here, using various crystal structures of FUT8 in complex with a donor substrate analog, and with four distinct glycan acceptors, we identify the molecular basis for FUT8 specificity and activity. The ordering of three active site loops corresponds to an increased occupancy for bound GDP, suggesting an induced-fit folding of the donor-binding subsite. Structures of the various acceptor complexes were compared with kinetic data on FUT8 active site mutants and with specificity data from a library of glycan acceptors to reveal how binding site complementarity and steric hindrance can tune substrate affinity. The FUT8 structure was also compared with other known fucosyltransferases to identify conserved and divergent structural features for donor and acceptor recognition and catalysis. These data provide insights into the evolution of modular templates for donor and acceptor recognition among GT-B fold glycosyltransferases in the synthesis of diverse glycan structures in biological systems. [ABSTRACT FROM AUTHOR]

The genus Salmonella is responsible for many illnesses in humans and other vertebrate animals. We report here that Salmonella enterica serovar Typhimurium harbors three transketolases that support the non-oxidative branch of the pentose phosphate pathway. BLAST analysis identified two genes, STM14_2885 and STM14_2886, that together encode a putative transketolase (TktC) with 46-47% similarity to the known TktA and TktB isoforms. Assessing themRNAand protein expression for each of the three transketolases, we determined that all are expressed in WT cells and regulated to varying extents by the alternative sigma factor RpoS. Enzyme assays with lysates from WTand transketolase-knockout strains established that TktA is responsible for >88% of the transketolase activity in WT cells. We purified recombinant forms of each isoenzyme to assess the kinetics for canonical transketolase reactions. TktA and TktB had comparable values for Vmax (539-1362 µM NADH consumed/s), Km (80-739 µM), and catalytic efficiency (1.02 x 108-1.06 x 109 M-1/s) for each substrate tested. The recombinant form of TktC had lower Km values (23-120 µM), whereas the Vmax (7.8-16 µM NADH consumed/s) and catalytic efficiency (5.58 x 106 to 6.07 x 108 M-1/s) were 10-100-fold lower. Using a murine model of Salmonella infection, we showed that a strain lacking all three transketolases is avirulent in C57BL/6 mice. These data provide evidence that S. Typhimurium possesses three transketolases that contribute to pathogenesis. [ABSTRACT FROM AUTHOR]

Considerable research has been conducted on evaluating the effectiveness of land consolidation (LC). However, most of the previous studies dealt with such evaluation in the areas where LC has taken place, whereas few focused on the potential evaluation before LC is implemented. Furthermore, land fragmentation has critical effects on the effectiveness evaluation of LC, but is not appropriately measured by currently used landscape metrics in the potential evaluation since project zones of LC cannot be delimited before LC implementation. To fill these gaps, this study demonstrates a potential evaluation model for LC, in which land fragmentation is taken into account by buffering land parcels and then quantifying their contiguity with a proper method. This model was tested in a case study area – Yangshan County of Guangdong, China, and the results showed that the new model is more robust than the traditional approach that evaluates the potential of land parcels in LC in terms of their locations, quality, terrains, and distances to infrastructural facilities. Moreover, the model revealed that land fragmentation plays an important role in LC potential evaluation. These findings imply that the proposed method can provide more appropriate guidelines for land decision-makers. [ABSTRACT FROM AUTHOR]

Members of glycosyltransferase family 75 (GT75) not only reversibly catalyze the autoglycosylation of a conserved arginine residue with specific NDP-sugars but also exhibit NDPpyranose mutase activity that reversibly converts specific NDP-pyranose to NDP-furanose. The latter activity provides valuable NDP-furanosyl donors for glycosyltransferases and requires a divalent cation as a cofactor instead of FAD used by UDP-D-galactopyranose mutase. However, details of the mechanism for NDP-pyranose mutase activity are not clear. Here we report the first crystal structures of GT75 family NDPpyranose mutases. The novel structures of GT75 member MtdL in complex with Mn2+ and GDP, GDP-D-glucopyranose, GDPL-fucopyranose, GDP-L-fucofuranose, respectively, combined with site-directed mutagenesis studies, reveal key residues involved in Mn2+ coordination, substrate binding, and catalytic reactions. We also provide a possible catalytic mechanism for this unique type of NDP-pyranose mutase. Taken together, our results highlight key elements of an enzyme family important for furanose biosynthesis. [ABSTRACT FROM AUTHOR]

Fewer than 250 Asian elephants remain in China, occupying fragmented habitats of Yunnan Province. One such fragmented population of 18–23 individuals occupies the Nangunhe Nature Reserve Area in Lincang City, Yunnan Province, China. The greatest threat to the survival of this population is the loss and fragmentation of habitat. In this study, we applied an ecological niche factor analysis (ENFA) model to evaluate the habitat suitability of Lincang City for Asian elephants based on geographical factors, vegetation type, and human disturbance. Optimal, relatively suitable, and marginal habitat accounted for 0.16% (38.45 km 2 ), 0.61% (150.00 km 2 ), and 3.34% (817.26 km 2 ) of the total study area, whereas non-suitable habitat accounted for 95.89% (23,463.29 km 2 ) of this area. The marginality of Asian elephant habitat in Lincang was 1.954, indicating nonrandom selection of various eco-geographical variables in the environment. The primary factor affecting Asian elephant habitat quality was vegetation type, followed by geographical factors and human disturbance. A habitat quality map for the total distribution of Asian elephants remaining in China (i.e., Yunnan Province: Xishuangbanna, Lincang, and Pu'er) based on our current and previous study showed that just 1400.57 km 2 and 2689.62 km 2 relatively suitable and optimal habitat is available, owing to significant deforestation. In addition to reintroduction programs, conservation strategies should focus on improving the quality of marginal habitats for elephants, in parallel to placing ecological corridors through non-suitable habitat to connect all suitable habitats for this and other extremely small elephant populations in China to reduce genetic isolation and secure long-term survival for the species. [ABSTRACT FROM AUTHOR]

The Golgi enzyme UDP-GlcNAc:lysosomal enzymeN-acetylglucosamine- 1-phosphotransferase (GlcNAc-1-phosphotransferase), an α2β2γ2 hexamer, mediates the initial step in the addition of the mannose 6-phosphate targeting signal on newly synthesized lysosomal enzymes. This tag serves to direct the lysosomal enzymes to lysosomes. A key property of GlcNAc-1-phosphotransferase is its unique ability to distinguish the 60 or so lysosomal enzymes from the numerous nonlysosomal glycoproteins with identical Asn-linked glycans. In this study, we demonstrate that the two Notch repeat modules and the DNA methyltransferase-associated protein interaction domain of the αsubunit are key components of this recognition process. Importantly, different combinations of these domains are involved in binding to individual lysosomal enzymes. This study also identifies the γ-binding site on the α subunit and demonstrates that in the majority of instances the mannose 6-phosphate receptor homology domain of the γ subunit is required for optimal phosphorylation. These findings serve to explain how GlcNAc-1-phosphotransferase recognizes a large number of proteins that lack a common structural motif. [ABSTRACT FROM AUTHOR]

Aflatoxins are a series of highly toxic and carcinogenic secondary metabolites that are synthesized by Aspergillus species. The degradation of aflatoxin enzymes is an important regulatory mechanism which modulates mycotoxin producing. The retromer complex is responsible for the retrograde transport of specific biomolecules and the vacuolar fusion in the intracellular transport. Late endosomal-associated GTPase (Rab7) has been shown to be a downstream effector protein of the retromer complex. A deficiency in the retromer complex or Rab7 results in several cellular trafficking problems in yeast and humans, like protein abnormal accumulation. However, whether retromer dysfunction is involved in aflatoxin synthesis remains unclear. Here, we report that the core retromer complex, which comprises three vacuolar protein sortingassociated proteins (AflVps26-AflVps29-AflVps35), is essential for the development of dormant and resistant fungal forms such as conidia (asexual reproductive spore) and sclerotia (hardened fungal mycelium), as well as aflatoxin production and pathogenicity, in Aspergillus flavus. In particular, we show the AflVps26-AflVps29-AflVps35 complex is negatively correlated with aflatoxin exportation. Structural simulation, sitespecific mutagenesis, and coimmunoprecipitation experiments showed that interactions among AflVps26, AflVps29, and AflVps35 played crucial roles in the retromer complex executing its core functions. We further found an intrinsic connection between AflRab7 and the retromer involved in vesicle-vacuole fusion, which in turn affected the accumulation of aflatoxin synthesis-associated enzymes, suggesting that they work together to regulate the production of toxins. Overall, these results provide mechanistic insights that contribute to our understanding of the regulatory role of the core retromer complex in aflatoxin metabolism. [ABSTRACT FROM AUTHOR]

Novel architectured porous Cu@Cu 2 O hybrid microspheres were successfully designed and synthesized using silk sericin (SS) as structure-director to firstly form the hierarchical Cu 2 O/SS microspheres by self-assembly, followed by a calcination process. A possible mechanism has been proposed based on the results of FESEM, TEM and XRD analysis. The photocatalytic performance of obtained porous Cu@Cu 2 O hybrid microspheres was investigated, and the synergistic effect of Cu and Cu 2 O phases contributed to improving the light absorption ability, electron-hole separation and transfer compared with pure Cu 2 O. Importantly, the photo-degradation ratio of Cu@Cu 2 O hybrid microspheres for methyl orange (MO) reached up to 99.9% after 110 min visible light irradiation, which is almost 1.3 times than that of pure Cu 2 O. Furthermore, Cu@Cu 2 O hybrid microspheres also exhibited outstanding reusability and stability because that its degradation efficiency for MO still maintained at 93.5% after five cycles. [ABSTRACT FROM AUTHOR]