The evolution of constitutively active humoral immune defenses in Drosophila populations under high parasite pressure.

Both constitutive and inducible immune mechanisms are employed by hosts for defense against infection. Constitutive immunity allows for a faster response, but it comes with an associated cost that is always present. This trade-off between speed and fitness costs leads to the theoretical prediction that constitutive immunity will be favored where parasite exposure is frequent. We selected populations of Drosophila melanogaster under high parasite pressure from the parasitoid wasp Leptopilina boulardi. With RNA sequencing, we found the evolution of resistance in these populations was associated with them developing constitutively active humoral immunity, mediated by the larval fat body. Furthermore, these evolved populations were also able to induce gene expression in response to infection to a greater level, which indicates an overall more activated humoral immune response to parasitization. The anti-parasitoid immune response also relies on the JAK/STAT signaling pathway being activated in muscles following infection, and this induced response was only seen in populations that had evolved under high parasite pressure. We found that the cytokine Upd3, which induces this JAK/STAT response, is being expressed by immature lamellocytes. Furthermore, these immune cells became constitutively present when populations evolved resistance, potentially explaining why they gained the ability to activate JAK/STAT signaling. Thus, under intense parasitism, populations evolved resistance by increasing both constitutive and induced immune defenses, and there is likely an interplay between these two forms of immunity.

Natural selection has driven the recurrent loss of an immunity gene that protects Drosophila against a major natural parasite.

Polymorphisms in immunity genes can have large effects on susceptibility to infection. To understand the origins of this variation, we have investigated the genetic basis of resistance to the parasitoid wasp Leptopilina boulardi in Drosophila melanogaster. We found that increased expression of the gene lectin-24A after infection by parasitic wasps was associated with a faster cellular immune response and greatly increased rates of killing the parasite. lectin-24A encodes a protein that is strongly up-regulated in the fat body after infection and localizes to the surface of the parasite egg. In certain susceptible lines, a deletion upstream of the lectin-24A has largely abolished expression. Other mutations predicted to abolish the function of this gene have arisen recurrently in this gene, with multiple loss-of-expression alleles and premature stop codons segregating in natural populations. The frequency of these alleles varies greatly geographically, and in some southern African populations, natural selection has driven them near to fixation. We conclude that natural selection has favored the repeated loss of an important component of the immune system, suggesting that in some populations, a pleiotropic cost to lectin-24A expression outweighs the benefits of resistance.

Trans-regulatory changes underpin the evolution of the Drosophila immune response.

When an animal is infected, the expression of a large suite of genes is changed, resulting in an immune response that can defend the host. Despite much evidence that the sequence of proteins in the immune system can evolve rapidly, the evolution of gene expression is comparatively poorly understood. We therefore investigated the transcriptional response to parasitoid wasp infection in Drosophila simulans and D. sechellia. Although these species are closely related, there has been a large scale divergence in the expression of immune-responsive genes in their two main immune tissues, the fat body and hemocytes. Many genes, including those encoding molecules that directly kill pathogens, have cis regulatory changes, frequently resulting in large differences in their expression in the two species. However, these changes in cis regulation overwhelmingly affected gene expression in immune-challenged and uninfected animals alike. Divergence in the response to infection was controlled in trans. We argue that altering trans-regulatory factors, such as signalling pathways or immune modulators, may allow natural selection to alter the expression of large numbers of immune-responsive genes in a coordinated fashion.

GIWAXS experimental methods at the NFPS-BL17B beamline at Shanghai Synchrotron Radiation Facility.

The BL17B beamline at the Shanghai Synchrotron Radiation Facility was first designed as a versatile high-throughput protein crystallography beamline and one of five beamlines affiliated to the National Facility for Protein Science in Shanghai. It was officially opened to users in July 2015. As a bending magnet beamline, BL17B has the advantages of high photon flux, brightness, energy resolution and continuous adjustable energy between 5 and 23 keV. The experimental station excels in crystal screening and structure determination, providing cost-effective routine experimental services to numerous users. Given the interdisciplinary and green energy research demands, BL17B beamline has undergone optimization, expanded its range of experimental methods and enhanced sample environments for a more user-friendly testing mode. These methods include single-crystal X-ray diffraction, powder crystal X-ray diffraction, wide-angle X-ray scattering, grazing-incidence wide-angle X-ray scattering (GIWAXS), and fully scattered atom pair distribution function analysis, covering structure detection from crystalline to amorphous states. This paper primarily presents the performance of the BL17B beamline and the application of the GIWAXS methodology at the beamline in the field of perovskite materials.

Crosstalk suppression in CMOS terahertz detectors by using a mushroom-like AMC structure.

The suppression of the crosstalk in a CMOS THz detector is essential for enhancing the performance of detector arrays; however, it presents several technical challenges at the chip level. In this paper, a novel structure featuring a mushroom-like artificial magnetic conductor (M-AMC) is developed to suppress the crosstalk between CMOS THz detectors with on-chip antennas. Three-dimensional simulation results show that the M-AMC structure, which is designed by metal Al and doped-Si materials in the CMOS process, not only reduces the transmission coefficient of the electromagnetic wave between adjacent pixels but also enhances the electric field of the target pixels. A 0.65 THz detector array with a M-AMC structure based on the on-chip antenna was fabricated. Experimental results present that after implanting the M-AMC structure, the noise equivalent power (NEP) at the central frequency of pixels significantly decreases by 315.5%. Moreover, the distribution of NEP becomes more uniform, as evidenced by a reduction in the standard deviation coefficient of 26.3%. This demonstrates the effectiveness of the method in suppressing crosstalk and improving the responsivity of CMOS THz detectors, which can be used for high-performance THz detector arrays.

High-security three-dimensional optical transmission mechanism utilizing time-frequency-space interleaving disruption.

In this paper, we propose a high-security three-dimensional optical transmission system utilizing time-frequency-space interleaving chaos, which simultaneously enhances the reliability and security of the system. The four-wing 3D chaos model encrypts the time-frequency space interleaved modulation domain of a orthogonal time-frequency space (OTFS) modulation signal and the modulated phase information simultaneously, improving the system's security. We also experimentally validate the proposed high-security 3D-OTFS method, utilizing the hexadecimal modulation technique. The modulated OTFS signal achieves a transmission rate of 34.1 Gb/s over a 2-km seven-core fiber link, with the OTFS signal exhibiting a maximum of 1.31 dB receiver sensitivity gain compared to orthogonal frequency division multiplexing (OFDM) signals under the forward error correction threshold of the bit error rate. The achieved keyspace is equal to 5 × 1048. The findings demonstrate that the proposed high-security three-dimensional optical transmission mechanism, based on time-frequency-space interleaved disruption, exhibits excellent anti-interference ability and confidentiality performance. Consequently, it holds promising prospects for future applications in optical communications.

Distributed State Fusion Estimation of Multi-Source Localization Nonlinear Systems.

For the state estimation problem of a multi-source localization nonlinear system with unknown and bounded noise, a distributed sequential ellipsoidal intersection fusion estimation algorithm based on the dual set-membership filtering method is proposed to ensure the reliability of the localization system. First, noise with unknown and bounded characteristics is modeled by using bounded ellipsoidal regions. At the same time, local estimators are designed at the sensor link nodes to filter out the noise interference in the localization system. The local estimator is designed using the dual set-membership filtering algorithm. It uses the dual principle to find the minimizing ellipsoid that can contain the nonlinear function by solving the optimization problem with semi-infinite constraints, and a first-order conditional gradient algorithm is used to solve the optimization problem with a low computational complexity. Meanwhile, the communication confusion among multiple sensors causes the problem of unknown correlation. The obtained estimates of local filters are fused at the fusion center by designing a distributed sequential ellipsoid intersection fusion estimation algorithm to obtain more accurate fusion localization results with lower computational cost. Finally, the stability and reliability of the proposed distributed fusion algorithm are verified by designing a simulation example of a multi-source nonlinear system.

Enhanced Li+ Diffusion and Lattice oxygen Stability by the High Entropy Effect in Disordered-Rocksalt Cathodes.

Cation-disordered Rocksalt oxides (DRXs) are a promising new class of cathode materials for Li-ion batteries due to their natural abundance, low cost and great electrochemical performance. High entropy strategy in Mn-based DRXs appears to be an effective strategy for improving the rate capability, but it suffers from challenges including capacity degradation. The present paper reports a new group of high entropy DRXs (HE DRX) based on Ni2+ -Nb5+ pair; the structural and chemical evolution upon cycling of DRXs with an increasing transition metal (TM) species are systematically investigated. An explanation is proposed for how the crystal field stability energy determines that HE DRX could exist in single Rocksalt solid solution structures. We further reveal that the charge compensation mechanism in HE DRX is the result of various TM synergistic effect. More importantly, through various in situ and ex situ techniques and theoretical calculation, the effective integration of more TM cation species within the HE DRX framework promotes better Li+ diffusion and improves lattice oxygen stability, consequently increasing capacity upon cycling.

Directional Transformation of Heterometallic Oxo Clusters: A New Approach to Prepare Wide-Bandgap Cathode Interlayers for Perovskite Solar Cells.

Typical wide-band gap cathode interlayer materials are difficulty in reducing interface recombination without limiting charge transport in perovskite solar cells (PSCs). Here, a lead-doped titanium-oxo cluster protected by S-containing ligands is introduced at the interface of perovskite and SnO2 . By in situ heating, the cluster is transformed into PbSO4 -PbTi3 O7 heterostructure. The oxygen atoms from sulfate ion in heterostructure connect with iodine from perovskite to boost interfacial electron extraction and reduce charge recombination. While the yielded metallic interface between PbSO4 and PbTi3 O7 promotes the electron transport across the interface. Finally, an efficiency as high as 24.2 % for the modified PSC is obtained. The heterostructure well-stabilize the interface of perovskite and SnO2 , to greatly improve the device stability. This work provides a novel strategy to prepare wide-band gap cathode interlayer by directional transformation of heterometallic oxo clusters.

Distributed Ellipsoidal Intersection Fusion Estimation for Multi-Sensor Complex Systems.

This paper investigates the problem of distributed ellipsoidal intersection (DEI) fusion estimation for linear time-varying multi-sensor complex systems with unknown input disturbances and measurement data transmission delays. For the problem with external unknown input disturbance signals, a non-informative prior distribution is used to model the problem. A set of independent random variables obeying Bernoulli distribution is also used to describe the situation of measurement data transmission delay caused by network channel congestion, and appropriate buffer areas are added at the link nodes to retrieve the delayed transmission data values. For multi-sensor systems with complex situations, a minimum mean square error (MMSE) local estimator is designed in a Bayesian framework based on the maximum a posteriori (MAP) estimation criterion. In order to deal with the unknown correlations among the local estimators and to select the fusion estimator with lower computational complexity, the fusion estimator is designed using ellipsoidal intersection (EI) fusion technique, and the consistency of the estimator is demonstrated. In this paper, the difference between DEI fusion and distributed covariance intersection (DCI) fusion and centralized fusion estimation is analyzed by a numerical example, and the superiority of the DEI fusion method is demonstrated.

Structural insights into thebaine synthase 2 catalysis.

Thebaine synthase 2 (THS2) that can transform (7S)-salutaridinol 7-O-acetate to thebaine catalyzes the final step of thebaine biosynthesis in Papaver somniferum. Here, the crystal structures of THS2 and its complex with thebaine are reported, revealing the interaction network in the substrate-binding pocket. Subsequent docking and QM/MM studies was performed to further explore the catalytic mechanism of THS2. Our results suggest that T105 may abstract the proton of C4-OH from the substrate under the assistance of H89. The resulting C4-O- phenolate anion then attacks the nearby C5, and triggers intramolecular SN2' syn displacement with the elimination of O-acetyl group. Moreover, the latter SN2' reaction is the rate-determining step of the whole enzymatic reaction with an overall energy barrier of 18.8 kcal/mol. These findings are of pivotal importance to understand the mechanism of action of thebaine biosynthesis, and would guide enzyme engineering to enhance the production of opiate alkaloids via metabolic engineering.

Structure basis of non-structural protein pA151R from African Swine Fever Virus.

African Swine Fever Virus (ASFV) is an enveloped double-stranded DNA icosahedral virus that causes the devastating hemorrhagic fever of pigs. ASFV infections severely impact swine production and cause an enormous economic loss, but no effective vaccine and therapeutic regimen is available. pA151R is a non-structural protein of ASFV, which is expressed at both early and late stages of viral infection. Significantly, pA151R may play a key role in ASFV replication and virus assembly as suppressing pA151R expression can reduce virus replication. However, little is known about the functional and structural mechanisms of pA151R because it shares a very low sequence identity to known structures. It was proposed that pA151R might participate in the redox pathway owing to the presence of a thioredoxin active site feature, the WCTKC motif. In this study, we determined the crystal structure of pA151R. Based on the crystal structure, we found that pA151R comprises of a central five-stranded ß-sheet packing against two helices on one side and an incompact C-terminal region containing the WCTKC motif on the other side. Notably, two cysteines in the WCTKC motif, an additional cysteine C116 from the ß7-ß8 loop together with ND1 of H109 coordinate a Zn2+ ion to form a Zn-binding motif. These findings suggest that the structure of pA151R is significantly different from that of typical thioredoxins. Our structure should provide molecular insights into the understanding of functional and structural mechanisms of pA151R from ASFV and shall benefit the development of prophylactic and therapeutic anti-ASFV agents.

Structure of a gut microbial diltiazem-metabolizing enzyme suggests possible substrate binding mode.

When administrated orally, the vasodilating drug diltiazem can be metabolized into diacetyl diltiazem in the presence of Bacteroides thetaiotaomicron, a human gut microbe. The removal of acetyl group from the parent drug is carried out by the GDSL/SGNH-family hydrolase BT4096. Here the crystal structure of the enzyme was solved by mercury soaking and single-wavelength anomalous diffraction. The protein folds into two parts. The N-terminal part comprises the catalytic domain which is similar to other GDSL/SGNH hydrolases. The flanking C-terminal part is made up of a ß-barrel subdomain and an α-helical subdomain. Structural comparison shows that the catalytic domain is most akin to acetyl-xylooligosaccharide esterase and allows a plausible binding mode of diltiazem to be proposed. The ß-barrel subdomain is similar in topology to the immunoglobulin-like domains, including some carbohydrate-binding modules, of various bacterial glycoside hydrolases. Consequently, BT4096 might originally function as an oligosaccharide deacetylase with additional subdomains that could enhance substrate binding, and it acts on diltiazem just by accident.

Design of double-slot antennas for terahertz array detectors in flip chip packaging.

In flip chip packaging, the performance of terahertz (THz) array detectors is directly influenced by the flip chip. In addition, predicting this effect is difficult because the readout circuits in the flip chip are very complex. In this study, to reduce the influence of the flip chip, we design a new type of double-slot antennas for THz array detectors. For comparison, we designed and analyzed dipole antennas with the same period. Numerical simulations showed that the coupling efficiency of the double-slot array antennas at approximately 0.6255 THz does not degrade, if the flip chip structure is changed. However, in the case of dipole array antennas with the same period of 250 µm, coupling efficiency was severely affected by the flip chip structure. These results revealed that double-slot antennas are more applicable to THz array detectors compared with dipole antennas, as they can more effectively reduce the influence of the flip chip. Furthermore, we integrated the double-slot antennas into Nb5N6 THz array detectors using the micro-fabrication technology. Measurement results indicated that double-slot antennas possess the advantages of facile preparation and large-scale integration, which provide great potential for THz array detectors in flip chip packaging.

Planar double-slot antenna integrated into a Nb5N6 microbolometer THz detector.

In this Letter, we propose and demonstrate a new type of planar double-slot antenna for a Nb5N6 microbolometer terahertz (THz) detector. The calculated results show that the planar antenna possessed high coupling efficiency, and the THz signals were obviously focused on the antenna center place. The new planar antenna was integrated with Nb5N6 microbolometer THz detectors using micro-fabrication technology. The measured results showed that the maximum optical voltage responsivity (Ro) of the detectors reached up to 113 V/W at 0.643 THz, and the corresponding noise equivalent power was 44pW/√Hz. In addition, the performance of double-slot antennas applied into array detectors in a tunable Fabry-Perot cavity was investigated. The measured results of the Nb5N6 THz detector remained almost unchanged when the distance between the chip substrate and the copper plate was altered. This indicated that this planar double-slot antenna, which possessed the advantages of high coupling efficiency and easy integration, has great application prospects in a THz detector.

Lead-Doped Titanium-Oxo Clusters as Molecular Models of Perovskite-Type PbTiO3 and Electron-Transport Material in Solar Cells.

In this work we have successfully prepared two lead-doped titanium-oxo clusters with core structures that resemble isolated perovskite PbTiO3 species. In the obtained highly symmetric Pb8 Ti7 -oxo cluster, the central TiO6 octahedra are orthogonally extended to adjacent octahedra through corner-sharing and the eight dopant lead ions form a cubic arrangement, making it the first molecular model of perovskite PbTiO3 . Moreover, the clusters readily dissolved in chloroform and showed high solution stability, as confirmed by MALDI-TOF MS measurements. Based on such solution processability, they can be easily spin-coated to form homogeneous films, which were employed as electron-transport materials in perovskite solar cells to give an average power conversion efficiency of around 15 % and improved device stability. This newly developed bottom-up cluster assembly method provides an efficient approach to the construction of atomically precise models of perovskite metal oxides as well as potential molecular tools to extend their applications.

Complex structures of MoeN5 with substrate analogues suggest sequential catalytic mechanism.

The antibiotic moenomycin A is a phosphoglycerate derivative with a C25-moenocinyl chain and a branched oligosaccharide. Formation of the C25-chain is catalyzed by the enzyme MoeN5 with geranyl pyrophosphate (GPP) and the sugar-linked 2-Z,E-farnesyl-3-phosphoglycerate (FPG) as its substrates. Previous complex crystal structures with GPP and long-chain alkyl glycosides suggested that GPP binds to the S1 site in a similar way as in most other α-helical prenyltransferases (PTs), and FPG is likely to assume a bent conformation in the S2 site. However, two FPG derivatives synthesized in the current study were found in the S1 site rather than S2 in their complex crystal structures with MoeN5. Apparently S1 is the preferred site for prenyl-containing ligand, and S2 binding may proceed only after S1 is occupied. Thus, like most trans-type PTs, MoeN5 may employ a sequential ionization-condensation-elimination mechanism that involves a carbocation intermediate.

Streptomyces castaneus sp. nov., a novel actinomycete isolated from the rhizosphere of Peucedanum praeruptorum Dunn.

During an investigation of microbial diversity in medicinal herbs, a novel actinomycete, strain NEAU-QHHV11T was isolated from the rhizosphere of Peucedanum praeruptorum Dunn collected from Xianglu Mountain in Heilongjiang Province, northeast China and characterized using a polyphasic approach. The organism was found to have typical characteristics of the genus Streptomyces. Phylogenetic analysis based on 16S rRNA gene sequence also indicated that strain NEAU-QHHV11T belongs to the genus Streptomyces and was most closely related to Streptomyces graminilatus NBRC 108882T (98.7 % sequence similarity) and Streptomyces turgidiscabies NBRC 16080T (98.7 % sequence similarity). The results of DNA-DNA hybridization and some phenotypic characteristics indicated that strain NEAU-QHHV11T could be distinguished from its close phylogenetic relatives. Thus, strain NEAU-QHHV11T represents a novel species of the genus Streptomyces, for which the name Streptomyces castaneus sp. nov. is proposed. The type strain is NEAU-QHHV11T (=CGMCC 4.7235T = DSM 100520T).

The Relationship between Neutrophil-to-Lymphocyte Ratio and Aortic Arch Calcification in Ischemic Stroke Patients.

BACKGROUND: Inflammation plays a central role in atherogenesis and artery calcification. Although neutrophil-to-lymphocyte ratio (NLR) has been introduced as an inflammatory marker for atherosclerosis, the relationship between NLR and aortic arch calcification (AAC) has not been studied. This study aimed to determine the association between NLR and AAC. METHODS: A total of 749 participants were enrolled. Demographic and clinical data were collected. Degree of AAC in each enrolled patient was determined with Agatston method based on a neck computed tomography angiography. NLR was divided into 4 groups according to quartile values. Generalized linear model (ordinal probit) was performed to assess the association between NLR quartiles and severity of AAC. RESULTS: There were 151 (20.2%), 153 (20.4%), and 445 (59.4%) patients classified as without AAC, with mild AAC, and with severe AAC, respectively. Patients with severe AAC had the highest NLR values (2.37[1.79-3.42] versus 2.29[1.55-2.96] versus 2.17[1.64-2.91], P = .025) compared to patients without AAC and with mild AAC. In age- and sex-adjusted models, patients with the highest NLR (quartile 4) were correlated with severer AAC (ß = .348 ± .128, P = .006) compared to those with the lowest levels (quartile 1). The correlation between NLR quartile 4 and severer AAC still existed (ß = .335 ± .129, P = .009) in multivariable-adjusted model. CONCLUSIONS: This study suggested that NLR may reflect the severity of AAC. NLR may be considered as a valuable predictor of the degree of artery calcification.

CDKN2B methylation is associated with carotid artery calcification in ischemic stroke patients.

BACKGROUND: Cyclin-dependent kinase inhibitor 2A/2B (CDKN2A/2B) near chromosome 9p21 have been associated with both atherosclerosis and artery calcification, but the underlying mechanisms remained largely unknown. Considering that CDKN2A/2B is a frequently reported site for DNA methylation, this study aimed to evaluate whether carotid artery calcification (CarAC) is related to methylation levels of CDKN2A/2B in patients with ischemic stroke. METHODS: DNA methylation levels of CDKN2A/2B were measured in 322 ischemic stroke patients using peripheral blood leukocytes. Methylation levels of 36 CpG sites around promoter regions of CDKN2A/2B were examined with BiSulfite Amplicon Sequencing. CarAC was quantified with Agatston score based on results of computed tomography angiography. Generalized liner model was performed to explore the association between methylation levels and CarAC. RESULTS: Of the 322 analyzed patients, 187 (58.1%) were classified as with and 135 (41.9%) without evident CarAC. The average methylation levels of CDKN2B were higher in patents with CarAC than those without (5.7 vs 5.4, p = 0.001). After adjustment for potential confounders, methylation levels of CDKN2B were positively correlated with cube root transformed calcification scores (ß = 0.591 ± 0.172, p = 0.001) in generalized liner model. A positive correlation was also detected between average methylation levels of CDKN2B and cube root transformed calcium volumes (ß = 0.533 ± 0.160, p = 0.001). CONCLUSIONS: DNA methylation of CDKN2B may play a potential role in artery calcification.