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Mounting evidence indicates the involvement of the innate immune system in Parkinson's disease (PD). Nevertheless, the implications of peripheral monocytes have not been fully elucidated. Although alpha-synuclein (α-synuclein) has been described as a pathological hallmark of PD, the proinflammatory effect of α-synuclein on monocytes is understudied. This study aimed to comprehensively characterize peripheral monocytes in PD patients and to investigate the proinflammatory magnitude of fibrillar α-synuclein.Using flow cytometry, we explored the distribution of monocytic subpopulations. We also investigated the actions of peripheral monocytes in response to lipopolysaccharides (LPS) and to fibrillar α-synuclein stimuli by measuring inflammatory molecule levels in post-culture supernatants.Classical monocytes were enriched, in parallel with lower proportions of intermediate and nonclassical monocytes in patients with PD than in controls. Lower levels of TNF-α and IL-6 were spontaneously produced by unstimulated monocytes in patients with PD. LPS and fibrillar α-synuclein stimuli induced high levels of TNF-α, IL-1β, IL-6, and sCD163 in the PD and control groups. Strikingly, the fold induction of TNF-α and IL-6 was lower in patients with PD than that in normal controls under the same stimulation.Our results revealed a strong dysregulation of peripheral monocytes in PD patients, including subpopulation shifts and impaired response to specific stimuli, and the proinflammatory effect of α-synuclein on monocytes. Further studies are needed to clarify the specific mechanisms by which these immunological abnormalities are present in PD to open the possibility of immunoregulatory therapy.

Epilepsy is a severe neurological condition affecting 50–65 million individuals worldwide that can lead to brain damage. Nevertheless, the etiology of epilepsy remains poorly understood. Meta-analyses of genome-wide association studies involving 15,212 epilepsy cases and 29,677 controls of the ILAE Consortium cohort were used to conduct transcriptome-wide association studies (TWAS) and protein-wide association studies (PWAS). Furthermore, a protein-protein interaction (PPI) network was generated using the STRING database, and significant epilepsy-susceptible genes were verified using chip data. Chemical-related gene set enrichment analysis (CGSEA) was performed to determine novel drug targets for epilepsy. TWAS analysis identified 21,170 genes, of which 58 were significant (TWASfdr < 0.05) in ten brain regions, and 16 differentially expressed genes were verified based on mRNA expression profiles. The PWAS identified 2249 genes, of which 2 were significant (PWASfdr < 0.05). Through chemical-gene set enrichment analysis, 287 environmental chemicals associated with epilepsy were identified. We identified five significant genes (WIPF1, IQSEC1, JAM2, ICAM3, and ZNF143) that had causal relationships with epilepsy. CGSEA identified 159 chemicals that were significantly correlated with epilepsy (Pcgsea < 0.05), such as pentobarbital, ketone bodies, and polychlorinated biphenyl. In summary, we performed TWAS, PWAS (for genetic factors), and CGSEA (for environmental factors) analyses and identified several epilepsy-associated genes and chemicals. The results of this study will contribute to our understanding of genetic and environmental factors for epilepsy and may predict novel drug targets.

As an important working fluid in tight shale reservoir, supercritical CO2 has been proven to improve oil recovery efficiently. However, the high filtration caused by the low viscosity of pure supercritical CO2 hinders its development. The research objective of this investigation is to explore the filtration of supercritical CO2 with a branched siloxane (BTMT) as a CO2 thickener and filtration-reducing agent, and analyze the influence level of some parameters about rock core and chemicals on the CO2 filtration in the tight shale reservoir by using response surface method (RSM). The results demonstrate that the rising temperature causes a gradually increasing filtration, but filtration coefficient (f) decreases with increasing the pressure difference P, injection speed, and thickener concentration. The thickener concentration is the factor that causes the greatest change in filtration coefficient according to the response surface method, and the injection speed has the smallest effect on the filtration. The viscosity of fracturing fluid is the main characterization parameter leading to change of filtration coefficient, all factors that contribute to increasing the viscosity of the fracturing fluid will lead to a reduction in the filtration coefficient and an enhanced oil recovery. In addition, the adsorption and reservoir residue of BTMT on low-permeability shale were subordinated to a Langmuir monolayer theory, and a low residual of BTMT in shale can prevent thickeners and fracturing fluids from damaging shale reservoirs. The improvement of thickener and CO2 fracturing technology provided a basic reference for shale exploitation, greenhouse effect, and reservoir protection.

In this paper, the modified h-BN coating was coated on the prepreg sheets; then, the carbon fiber/epoxy composite laminates were prepared by compression molding. The through-thickness thermal conductivity, mechanical and thermomechanical properties of the laminates were studied, respectively. The results show that h-BN particles, which are flaky shape with a diameter of about 0.6 μm and thickness of about 70 nm, have been evenly incorporated into the composites, and the thermal stability, through-thickness thermal conductivity, impact strength and glass transition temperature (Tg) of the composites are improved accordingly. When the BN content is 10 m%, the initial thermal degradation temperature (Tinitial) of the prepreg is 370 ℃, which is 10 ℃ higher than that of unmodified prepreg. When the BN content is 7 m%, the thermal conductivity of the laminates reaches 0.9 and 1.0 W·m−1·K−1 at 25 and 100 ℃, respectively, which are 114% and 111% higher than that of pure laminate. When the content of BN is 5 m%, the impact strength of the laminate reaches the highest value of 225 kJ·m−2, which is 15.4% higher than that of pure laminate. BN particles form a dense heat conduction network, thus delaying the thermal degradation of the resin and improving the thermal conductivity. This study provides a facile path to fabricate composite laminates with the integrated structure and function.

Many organisms produce stunning optical displays based on structural color instead of pigmentation. This structural or photonic color is achieved through the interaction of light with intricate micro-/nano-structures, which are “grown” from strong, sustainable biological materials such as chitin, keratin, and cellulose. In contrast, current synthetic structural colored materials are usually brittle, inert, and produced via energy-intensive processes, posing significant challenges to their practical uses. Inspired by the brilliantly colored peacock feathers which selectively grow keratin-based photonic structures with different photonic bandgaps, we develop a self-growing photonic composite system in which the photonic bandgaps and hence the coloration can be easily tuned. This is achieved via the selective growth of the polymer matrix with polymerizable compounds as feeding materials in a silica nanosphere-polymer composite system, thus effectively modulating the photonic bandgaps without compromising nanostructural order. Such strategy not only allows the material system to continuously vary its colors and patterns in an on-demand manner, but also endows it with many appealing properties, including flexibility, toughness, self-healing ability, and reshaping capability. As this innovative self-growing method is simple, inexpensive, versatile, and scalable, we foresee its significant potential in meeting many emerging requirements for various applications of structural color materials.

In this study, the nonisothermal differential scanning calorimetry (DSC) was carried out to evaluate the curing reaction of fiber/epoxy laminates. The optimal curing process of the prepreg was obtained by T-β extrapolation method and nth-order reaction curing kinetic equation. The bending strength, impact strength and thermodynamic properties of the composite laminates with different ply orientations were investigated, respectively. The results show that the apparent activation energy and the reaction order of the prepregs are 82.89 kJ/mol and 0.92, respectively. The curing process of carbon fiber/epoxy resin prepreg is 130 ℃ /60min + 160 ℃/30 min. The bending strength of [0]10 laminate is 1948.3 MPa, which is 11.8 times higher than that of [+ 45/-45]5s laminate, and 96.4% higher than that of [0/90]5s laminate. The impact strength of [0]10 laminate is higher than that of [+ 45/-45]5s and [0/90]5s laminates. The glass transition temperature (Tg) of the laminates is 142 ~ 146 ℃, and the loss factor of [0]10 laminate is significantly higher than that of [+ 45/-45]5s and [0/90]5s laminates. This research provides a theoretical basis for the further application of prepregs to fiber composite materials.

BiOIO3/GO composite photocatalyst was successfully prepared by hydrothermal method and magnetic stirring method. The prepared photocatalyst was characterized by SEM, TEM, XRD, UV–Vis DRS, FT-IR and XPS. Fluorocarbon resin coating (PEVE) was modified with composite photocatalyst, the antibacterial properties of the composite coatings with different doping ratios of GO were evaluated. Among them, the composite coating BiOIO3/6 wt% GO has the highest sterilization rate, which is nearly doubled compared to the pure BiOIO3 coating. Hydroxyl radicals (⋅OH) can be demonstrated as the main active species in the photocatalytic reaction. The mechanism of improving the photocatalytic efficiency was proposed. This paper provides some new insights on the development of marine antifouling coatings, and has certain reference significance for the treatment of ship's ballast water.

Flexible manipulators are widely used in aerospace industry and precision instrument manufacturing industry. However, due to the mechanism flexibility, the system dynamics have high nonlinearity and complexity, which make controller design pretty challenging. Moreover, in real production, electromechanical systems, including flexible manipulators, usually suffer from nonlinear input dead-zones and unknown system parameters/structures. Considering the above problems, an adaptive fuzzy control method is proposed, which can make the flexible link reach a desired rotation angle within finite time and simultaneously suppress the vibration of the manipulator. In the meantime, the system uncertainties are compensated, and the effect of input dead-zones is eliminated. In addition, the stability of the equilibrium point for the single-link flexible manipulator system is proven by rigorous theoretical analysis. Finally, the effectiveness and robustness of the proposed control method are verified by numerical simulations.

Biofilm-associated infections are difficult to treat in the clinics because the bacteria embedded in biofilm are ten to thousand times more resistant to traditional antibiotics than planktonic ones. Here, a smart hydrogel comprised of aminoglycoside antibiotics, pectinase, and oxidized dextran was developed to treat local biofilm-associated infections. The primary amines on aminoglycosides and pectinase were reacted with aldehyde groups on oxidized dextran via a pH-sensitive Schiff base linkage to form the hydrogel. Upon bacterial infection, the increased acidity triggers the release of both pectinase and aminoglycoside antibiotics. The released pectinase efficiently degrades extracellular polysaccharides surrounding the bacteria in biofilm, and thus greatly sensitizes the bacteria to aminoglycosides. The smart hydrogel efficiently eradicated biofilms and killed the embedded bacteria both n tvitro and in vivo. This study provides a promising strategy for the treatment of biofilm-associated infections.

Polymer microspheres with uniform size, composition, and surface property have gained extensive researches in past decades. Conventional bottom-up approaches are using monomers or oligomers to build up desired polymer microspheres. However, directly shaping high-molecular-weight polymers into well-ordered polymer microspheres remains a great challenge. Herein, we reported a facile and efficient top-down approach to fabricate microspheres with high-molecular-weight polymer microfibers. By harnessing interfacial engineering-control during the polymer microspheres formation, uniformly sized microspheres could be produced with widely ranged diameters (from 10 µm to the capillary length of each polymer melt). The size limitation of this approach could be further extended by a controllable Plateau-Rayleigh instability phenomenon. Principally, the top-down approach allows fabrication of microspheres by various polymer melts with surface energy higher than 25 mN/m. Our work paves a way for green, cost-effective, and customizable production of a variety of functional polymer microspheres without any chemical reaction assistant.

Galacto-oligosaccharides (GOS), which can be produced by enzymatic transgalactosylation of lactose with β-galactosidases, have attracted much attention in recent years because of their prebiotic functions and wide uses in infant formula, infant foods, livestock feed, and pet food industries. In this study, a novel β-galactosidase-producing Klebsiella oxytoca ZJUH1705, identified by its 16S rRNA sequence (GenBank accession no. MH981243), was isolated. Two β-galactosidase genes, bga 1 encoding a 2058-bp fragment (GenBank accession no. MH986613) and bga 2 encoding a 3108-bp fragment (GenBank accession no. MN182756), were cloned from K. oxytoca ZJUH1705 and expressed in E. coli. The purified β-gal 1 and β-gal 2 had the specific activity of 217.56 U mg−1 and 57.9 U mg−1, respectively, at the optimal pH of 7.0. The reaction kinetic parameters Km, Vmax, and Kcat with oNPG as the substrate at 40 °C were 5.62 mM, 167.1 μmol mg−1 min−1, and 218.1 s−1, respectively, for β-gal 1 and 3.91 mM, 14.6 μmol mg−1 min−1, and 28.9 s−1, respectively, for β-gal 2. Although β-gal 1 had a higher enzyme activity for lactose hydrolysis, only β-gal 2 had a high transgalactosylation capacity. Using β-gal 2 with the addition ratio of ~ 2.5 U g−1 lactose, a high GOS yield of 45.5 ± 2.3% (w/w−1) was obtained from lactose (40% w/w−1 or 480 g L−1) in a phosphate buffer (100 mM, pH 7.0) at 40 °C in 48 h. Thus, the β-gal 2 from K. oxytoca ZJUH1705 would be a promising biocatalyst for GOS production from lactose.

The study aimed to evaluate the safety of copper ion sterilization based on copper ion residues in zebrafish (Brachydanio rerio), as well as bacterial community structure and diversity in recirculating aquaculture systems (RASs). The copper ion content was determined using national food safety standard GB 5009.13-2017. Bacterial community structures and alpha and beta diversity indexes were examined using the 16S rRNA gene sequences produced by Illumina HiSeq sequencing. The results revealed no significant copper ion enrichment in B. rerio when the copper ion concentration was 0.15 mg/L. The relative abundances of Erythrobacter, nitrite bacteria, and Flavanobacteria were clearly higher in the treatment group than in the control and differences in bacterial species richness and diversity were obvious. In addition, there was no sharp decrease in the microflora at the outflow of the copper ion generator. In conjunction with the changes in ammonia nitrogen, nitrate, and nitrite concentrations during the experiment, the results indicated that there were no significant effects on the purification efficacy of the biological filter, but the abundances of beneficial bacteria increased significantly. This is of great relevance in order to understand the response of bacterial communities affected by changing environmental conditions, such as copper ion sterilization.

Background The giant panda (Ailuropoda melanoleuca) is an endangered mammalian species native to China. Fewer than 2500 giant pandas are known to exist, many of which are bred in captivity as a means to preserve and repopulate the species. Like other captive mammals, giant pandas acquire age-related cataracts, reducing their quality of life. Recent comparative genome-wide methylation analysis revealed 110 differentially methylated genes associated with cataract formation including six also associated with the formation of age-related cataracts in humans. Results To investigate the pathological pathway in greater detail, here we used RNA-Seq analysis to investigate the differential expression profiles of genes in three giant pandas with cataracts and three healthy controls. We identified more than 700 differentially expressed genes, 29 of which were selected for further analysis based on their low q-value. We found that many of the genes encoded regulatory and signaling proteins associated with the control of cell growth, migration, differentiation and apoptosis, supporting previous research indicating a key role for apoptosis in cataract formation. Conclusion The identification of genes involved in the formation of age-related cataracts could facilitate the development of predictive markers, preventative measures and even new therapies to improve the life of captive animals.

Single nucleotide polymorphisms (SNPs), known as the third-generation molecular markers, are becoming popular in molecular ecology studies. The rapid development of next generation sequencing technologies allow identifying large numbers of SNP markers that can be used in conservation genetics. Based on the genome resequencing dataset of Crested ibis (Nipponia nippon), we developed 31 polymorphic SNP markers using the restriction-site associated DNA (RAD) sequencing. The minor allele frequency per locus varied from 0.176 to 0.485, while the observed and expected heterozygosity varied from 0.118 to 0.794 and from 0.295 to 0.507, respectively. Three loci showed significant departures from Hardy–Weinberg equilibrium. These SNP markers could be useful in future population genetic analysis of Crested ibis.

The room temperature liquid metal (LM) is recently emerging as a new class of versatile materials with fascinating characteristics mostly originated from its simultaneous metallic and liquid natures. The melting point is a typical parameter to describe the peculiarity of LM, and a pivotal factor to consider concerning its practical applications such as phase change materials (PCMs) and advanced thermal management. Therefore, the theoretical exploration into the melting point of LM is an essential issue, which can be of special value for the design of new LM materials with desired properties. So far, some available strategies such as molecular dynamics (MD) simulation and classical thermodynamic theory have been applied to perform correlative analysis. This paper is primarily dedicated to performing a comprehensive overview regarding typical theoretical strategies on analyzing the melting points. It, then, presents evaluations on several factors like components, pressure, size and supercooling that may be critical for melting processes of liquid metal. After that, it discusses applications associated with the characteristic of low melting points of LM. It is expected that a great many fundamental and practical works are to be conducted in the coming future.

Unexpected intercalation-dominated process is observed during K+ insertion in WS2 in a voltage range of 0.01–3.0 V. This is different from the previously reported two-dimensional (2D) transition metal dichalcogenides that undergo a conversion reaction in a low voltage range when used as anodes in potassium-ion batteries. Charge/discharge processes in the K and Na cells are studied in parallel to demonstrate the different ion storage mechanisms. The Na+ storage proceeds through intercalation and conversion reactions while the K+ storage is governed by an intercalation reaction. Owing to the reversible K+ intercalation in the van der Waals gaps, the WS2 anode exhibits a low decay rate of 0.07% per cycle, delivering a capacity of 103 mAh·g-1 after 100 cycles at 100 mA·g-1. It maintains 57% capacity at 800 mA·g-1 and shows stable cyclability up to 400 cycles at 500 mA·g-1. Kinetics study proves the facilitation of K+ transport is derived from the intercalation-dominated mechanism. Furthermore, the mechanism is verified by the density functional theory (DFT) calculations, showing that the progressive expansion of the interlayer space can account for the observed results.

With the development of machine learning and data mining, rapid design, rapid verification and rapid manufacturing have become the mainstream in the machinery industry. In this paper, the mapping function between the mechanical properties of the hood and its 11 dimensional parameters was mined using machine learning algorithms. By combining XGBoost and LightGBM algorithms with the bagging method, we proposed a hybrid model with hyperparameters optimized by the grey wolf algorithm. Subsequently, several machine learning models were trained and tested on a dataset of 6959 simulation samples, and the proposed hybrid model was found to have excellent predictive performance for the torsional stiffness ( $$R^{2}$$ of 0.9969 and root-mean-square error of 1.32185) and first-order modal frequency (0.9977 and 0.00989) of the hood. Moreover, the SHAP method (Shapley additive explanations) was used as a machine learning interpretation method to explain the predictive process of the mechanical performance. The results show that SHAP has great potential in model interpretation. This paper aims to develop a mathematical model of the mechanical properties of the hood, which can quickly predict the mechanical properties based on each key dimensional parameter. Therefore, engineers and designers can apply this approximate model in their design space exploration algorithms directly without training extra low-dimensional surrogate models.

Cataracts are a common cause of visual impairment and blindness in mammals. They are usually associated with aging, but approximately one third of cases have a significant genetic component. Cataracts are increasingly prevalent among aging populations of captive giant pandas (Ailuropoda melanoleuca) and it is therefore important to identify genetic determinants that influence the likelihood of cataract development in order to distinguish between congenital and age-related disease. Here we screened for cataract-related genetic effects using a functional candidate gene approach combined with bioinformatics to identify the underlying genetic defect in a giant panda with congenital cataracts. We identified a missense mutation in exon 10 of the HSF4 gene encoding heat shock transcription factor 4. The mutation causes the amino acid substitution R377W in a highly conserved segment of the protein between the isoform-specific and downstream hydrophobic regions. Predictive modeling revealed that the substitution is likely to increase the hydrophobicity of the protein and disrupt interactions with spatially adjacent amino acid side chains. The mutation was not found in 13 unaffected unrelated animals but was found in an unrelated animal also diagnosed with senile congenital cataract. The novel missense mutation in the HSF4 gene therefore provides a potential new genetic determinant that could help to predict the risk of cataracts in giant pandas.

Background The mammalian major histocompatibility complex (MHC) harbours clusters of genes associated with the immunological defence of animals against infectious pathogens. At present, no complete MHC physical map is available for any of the wild ruminant species in the world. Results The high-density physical map is composed of two contigs of 47 overlapping bacterial artificial chromosome (BAC) clones, with an average of 115 Kb for each BAC, covering the entire addax MHC genome. The first contig has 40 overlapping BAC clones covering an approximately 2.9 Mb region of MHC class I, class III, and class IIa, and the second contig has 7 BAC clones covering an approximately 500 Kb genomic region that harbours MHC class IIb. The relative position of each BAC corresponding to the MHC sequence was determined by comparative mapping using PCR screening of the BAC library of 192,000 clones, and the order of BACs was determined by DNA fingerprinting. The overlaps of neighboring BACs were cross-verified by both BAC-end sequencing and co-amplification of identical PCR fragments within the overlapped region, with their identities further confirmed by DNA sequencing. Conclusions We report here the successful construction of a high-quality physical map for the addax MHC region using BACs and comparative mapping. The addax MHC physical map we constructed showed one gap of approximately 18 Mb formed by an ancient autosomal inversion that divided the MHC class II into IIa and IIb. The autosomal inversion provides compelling evidence that the MHC organizations in all of the ruminant species are relatively conserved. Electronic supplementary material The online version of this article (10.1186/s12864-019-5790-2) contains supplementary material, which is available to authorized users.

Background In the assisted reproduction, the infertile molecules of spermatozoa from normozoospermic men who underwent the unexplained failure of in vitro fertilization (IVF) due to the lack of sperm binding to the normal zona pellucida, and then achieved pregnancy with the rescue intracytoplasmic sperm injection (R-ICSI) remain unclear. More works are still necessary to explore this male infertile mechanism. Methods Normozoospermicmen with the IVF pregnancy and normozoospermic men with the R-ICSI pregnancy after the conventional IVF failure were collected. iTRAQ-based proteomic approach were performed to reveal the new infertile causes between the IVF pregnancy men and the R-ICSI pregnancy men. To validate the confidence of proteome data, the individual samples were analyzed by western blot and immunofluorescence. Further, the spontaneous acrosome reactions were measured to evaluate the sperm quality. Results Compared with IVF pregnancy group, 56 sperm proteins were differentially expressed in the R-ICSI pregnancy group. Bioinformatic analyses (PANTHER, DAVID, PubMed and STRING) indicated these altered sperm proteins were involved in various molecular functions: reproduction, chromosome organization, and sperm-oocyte interaction. Moreover, the confidence of proteome data was confirmed by western blot and immunofluorescence using the individual samples, which were consistent with our proteomic data. Additionally, an increased rate of the spontaneous acrosome reaction rate was found in the R-ICSI pregnancy group. Conclusions The sealtered sperm proteins and the increased spontaneous acrosome reaction rate might account for this unexplained male infertility in the R-ICSI pregnancy patients. The present proteomic results will throw light on the better understanding of the unexplained infertile mechanisms underlying these normozoospermic man who achieved R-ICSI pregnancy after IVF failure. Electronic supplementary material The online version of this article (10.1186/s12014-018-9203-3) contains supplementary material, which is available to authorized users.

A method was presented, which allowed for Zero-valent copper (Cu0) nanoparticles fabricated in/on polyacrylonitrile (PAN) nanofibers by two-step including the preparation of the copper(II)/polyacrylonitrile (Cu2+/PAN) nanofibers by electrospinning, and the preparation of the Cu0/PAN nanofibers by high-pressure hydrogenation reduction. The Cu0/PAN nanofibers were characterized by scanning electron microscope (SEM), transmission electron microscope (TEM), Fourier transform infrared (FT-IR), and X-ray photoelectron spectroscopy (XPS). The results showed that the copper nanoparticles were successfully synthesized in the composite fibers. Furthermore, antibacterial tests indicated that the Cu0/PAN nanofibers have good bactericidal effects.

To rationally identify targets for enhancing adenosine production, transcription level of genes involved in adenosine synthesis of Bacillus subtilis XGL was detected during the fermentation process, complemented with metabolite pool analysis.PurR-regulated genes (pur operon and purA) and prs were down-regulated and 5-phosphoribosyl 1-pyrophosphate (PRPP) decreased considerably after 24 h when adenosine significantly accumulated. Since PRPP could strongly antagonize the binding of PurR to its targets, it was inferred that down-regulation of pur operon and purA might be due to a low PRPP pool, which was confirmed by metabolite analysis. So desensitized prs responsible for PRPP synthesis was overexpressed, resulting in increased PRPP concentration and pur operon transcription. To further enhance the adenosine production, desensitized purF and prs were co-overexpressed with integrating additional copy of purA to B. subtilis XGL genome, resulting in 24.3 % (1.29 g/g DCW) higher adenosine production than that by B. subtilis XG.Overexpression of prs, purF and purA under the guidance of transcriptional and metabolite pool analysis significantly increased adenosine production. Strategies used in this study have potential applications for rational modification of industrial microorganisms.

We investigated long-wavelength nematic fluctuations in an Fe-based superconductor LiFeAs near q = (0.05, 0, 0) by measuring temperature-dependent renormalization of acoustic phonons through inelastic neutron scattering. We found that the phonons have a conventional behavior, as would be expected in the absence of electronic nematic fluctuations. This observation implies that either electron-phonon coupling is too weak to see any effect or that nematic fluctuations are not present.

Colobines are a unique group of Old World monkeys that principally eat leaves and seeds rather than fruits and insects. We report the sequencing at 146× coverage, de novo assembly and analyses of the genome of a male golden snub-nosed monkey (Rhinopithecus roxellana) and resequencing at 30× coverage of three related species (Rhinopithecus bieti, Rhinopithecus brelichi and Rhinopithecus strykeri). Comparative analyses showed that Asian colobines have an enhanced ability to derive energy from fatty acids and to degrade xenobiotics. We found evidence for functional evolution in the colobine RNASE1 gene, encoding a key secretory RNase that digests the high concentrations of bacterial RNA derived from symbiotic microflora. Demographic reconstructions indicated that the profile of ancient effective population sizes for R. roxellana more closely resembles that of giant panda rather than its congeners. These findings offer new insights into the dietary adaptations and evolutionary history of colobine primates.

Cytidine is a nucleoside molecule that is widely used as a precursor for antiviral drugs. In this study, a cytidine-producing strain Cyt18 was developed from Escherichia coli K-12 through 3-step genetic manipulation strategies. Cytidine deaminase gene (cdd) was firstly deleted from the E. coli K-12 strain to develop Cyt10. Furthermore, homoserine dehydrogenase gene (thrA) was inactivated from the Cyt10 strain to develop Cyt12, in which the intracellular aspartate concentration was expected to be increased. The recombinant plasmid pMG1105 containing an pyrB-pyrA operon from Bacillus amyloliquefaciens CYTI was constructed and was introduced into Cyt12 to obtain the Cyt18 strain. Compared to the Cyt12 strain, the cytidine production by the recombinant strain Cyt18 was increased by ~3-fold (722.9 mg/l vs. 249.3 mg/l).

L-isoleucine is synthesized from 2-ketobutyrate and pyruvate in Corynebacterium glutamicum, and the supplies of these two precursors are important for L-isoleucine synthesis. C. glutamicum YILWΔalaT with alaT gene deletion (encoding alanine aminotransferase, a principal enzyme for L-alanine synthesis) was constructed to increase intracellular pyruvate availability, and the thrABC genes from Escherichia coli (encoding bifunctional aspartate kinase I-homoserine dehydrogenase I, homoserine kinase, and threonine synthetase) were overexpressed in C. glutamicum YILW and YILWΔalaT to increase the supply of intracellular 2-ketobutyrate. In the fed-batch fermentation, YILWpXMJ19thrABC, YILWΔalaT, and YILWΔalaTpXMJ19thrABC exhibited 5.3, 17.6, and 8.4 % higher L-isoleucine production than the original strain, respectively. Both YILWpXMJ19thrABC and YILWΔalaT excreted lower concentrations of L-lysine, L-alanine, and L-valine. YILWΔalaTpXMJ19thrABC exhibited a cumulative reduction of these by-products excretion, which indicated that thrABC overexpression combined with alaT deletion resulted in the metabolic flux redistribution from 2-ketobutyrate and pyruvate to L-isoleucine synthesis, and decreased the fluxes to by-products synthesis accordingly.

Histidine biosynthesis in Corynebacterium glutamicum is regulated not only by feedback inhibition by the first enzyme in the pathway, but also by repression control of the synthesis of the histidine enzymes. C. glutamicum histidine genes are located and transcribed in two unlinked loci, hisEG and hisDCB-orf1-orf2-hisHA-impA-hisFI. We constructed plasmid pK18hisDPtac to replace the native hisD promoter with the tac promoter, and overexpressed phosphoribosyl-ATP-pyrophosphohydrolase, encoded by hisE, and ATP-phosphoribosyltransferase, encoded by hisG. The L-histidine titer at 0.85 g l(-1) was 80 % greater in the transformed bacterium and production of byproducts, L-alanine and L-tryptophan, was significantly decreased. However, accumulation of glutamic acid increased by 58 % (2.8 g l(-1)). This study represents the first attempt to substitute the histidine biosynthesis pathway promoter in the chromosome with a stronger promoter to increase histidine production.

About 336-444 bp mitochondrial D-loop region and tRNA gene were sequenced for 40 individuals of the giant panda which were collected from Mabian, Meigu, Yuexi, Baoxing, Pingwu, Qingchuan, Nanping and Baishuijiang, respectively. 9 haplotypes were found in 21 founders. The results showed that the giant panda has low genetic variations, and that there is no notable genetic isolation among geographical populations. The ancestor of the living giant panda population perhaps appeared in the late Pleistocene, and unfortunately, might have suffered bottleneck attacks. Afterwards, its genetic diversity seemed to recover to some extent.

Crocodilians are a group of reptiles that are closely related to birds and are thought to possess a strong immune system. Here we report that the IgH locus in the Siamese crocodile and the Chinese alligator contains multiple μ genes, in contrast to other tetrapods. Both the μ2 and μ3 genes are expressed through class-switch recombination involving the switch region and germline transcription. Both IgM1 and IgM2 are present in the serum as polymers, which implies that IgM class switching may have significant roles in humoural immunity. The crocodilian α genes are the first IgA-encoding genes identified in reptiles, and these genes show an inverted transcriptional orientation similar to that of birds. The identification of both α and δ genes in crocodilians suggests that the IgH loci of modern living mammals, reptiles and birds share a common ancestral organization. Different mechanisms for generating antibody diversity have evolved since the emergence of immunoglobulin genes in jawed vertebrates. By sequencing the crocodilian immunoglobulin heavy-chain locus, Chenget al. uncover new insights into the evolutionary origins of adaptive immunity.

We report inelastic neutron scattering experiments on single crystals of superconducting Ba(0.67)K(0.33)Fe(2)As(2) (T(c) = 38 K). In addition to confirming the resonance previously found in powder samples, we find that spin excitations in the normal state form longitudinally elongated ellipses along the Q(AFM) direction in momentum space, consistent with density functional theory predictions. On cooling below T(c), while the resonance preserves its momentum anisotropy as expected, spin excitations at energies below the resonance become essentially isotropic in the in-plane momentum space and dramatically increase their correlation length. These results suggest that the superconducting gap structures in Ba(0.67)Ka(0.33)Fe(2)As(2) are more complicated than those suggested from angle resolved photoemission experiments.