The doublesex gene regulates dimorphic sexual and aggressive behaviors in Drosophila.

Most animal species display dimorphic sexual behaviors and male-biased aggressiveness. Current models have focused on the male-specific product from the fruitless (fruM) gene, which controls male courtship and male-specific aggression patterns in fruit flies, and describe a male-specific mechanism underlying sexually dimorphic behaviors. Here we show that the doublesex (dsx) gene, which expresses male-specific DsxM and female-specific DsxF transcription factors, functions in the nervous system to control both male and female sexual and aggressive behaviors. We find that Dsx is not only required in central brain neurons for male and female sexual behaviors, but also functions in approximately eight pairs of male-specific neurons to promote male aggressiveness and approximately two pairs of female-specific neurons to inhibit female aggressiveness. DsxF knockdown females fight more frequently, even with males. Our findings reveal crucial roles of dsx, which is broadly conserved from worms to humans, in a small number of neurons in both sexes to establish dimorphic sexual and aggressive behaviors.

Versatile Cu2ZnSnS4-based synaptic memristor for multi-field-regulated neuromorphic applications.

Integrating both electrical and light-modulated multi-type neuromorphic functions in a single synaptic memristive device holds the most potential for realizing next-generation neuromorphic systems, but is still challenging yet achievable. Herein, a simple bi-terminal optoelectronic synaptic memristor is newly proposed based on kesterite Cu2ZnSnS4, exhibiting stable nonvolatile resistive switching with excellent spatial uniformity and unique optoelectronic synaptic behaviors. The device demonstrates not only low switching voltage (-0.39 ± 0.08 V), concentrated Set/Reset voltage distribution (<0.08/0.15 V), and long retention time (>104 s) but also continuously modulable conductance by both electric (different width/interval/amplitude) and light (470-808 nm with different intensity) stimulus. These advantages make the device good electrically and optically simulated synaptic functions, including excitatory and inhibitory, paired-pulsed facilitation, short-/long-term plasticity, spike-timing-dependent plasticity, and "memory-forgetting" behavior. Significantly, decimal arithmetic calculation (addition, subtraction, and commutative law) is realized based on the linear conductance regulation, and high precision pattern recognition (>88%) is well achieved with an artificial neural network constructed by 5 × 5 × 4 memristor array. Predictably, such kesterite-based optoelectronic memristors can greatly open the possibility of realizing multi-functional neuromorphic systems.

Promoting effect of lanthanum doping on photovoltaic performance of CZTSSe solar cells.

A large open-circuit voltage (VOC) deficit is the major challenge hindering the efficiency improvement of Cu2ZnSn(S,Se)4 (CZTSSe) solar cells. Cation substitution, or doping, is usually an effective strategy to achieve carrier regulation and improve efficiency. In this work, we developed a rare-earth element lanthanum (La) doped CZTSSe thin-film solar cell by directly introducing La3+ ions into the CZTS precursor solution. Such a proposed La doping approach could effectively enhance light harvesting, adjust the bandgap, and increase the electron diffusion length. Furthermore, appropriate concentrations of La doping can reduce harmful defect cluster. Benefiting from the La doping, the VOC significantly increases from 431 to 497 mV. Consequently, the power conversion efficiency is enhanced significantly from 6.54% (VOC = 431 mV, JSC = 25.50 mA/cm2, FF = 58.28%) for the reference cell to 10.21% (VOC = 497 mV, JSC = 35.20 mA/cm2, FF = 58.41%) for the optimized La-doped cell. This research provides a new direction for enhancing the performance of CZTSSe cells, offering promising prospects for the future of CZTSSe thin-film solar cells.

Kaposi's sarcoma herpesvirus is associated with osteosarcoma in Xinjiang populations.

Osteosarcoma is the most common malignant tumor of bone predominately affecting adolescents and young adults. Based on animal studies, a viral etiology of osteosarcoma was proposed more than a half-century ago, but no viral association with human osteosarcoma has been found. The Uyghur ethnic population in Xinjiang, China, has an unusually high prevalence of Kaposi's sarcoma-associated herpesvirus (KSHV) infection and elevated incidence of osteosarcoma. In the current study, we explored the possible association of KSHV infection and osteosarcoma occurrence. Our seroepidemiological study revealed that KSHV prevalence was significantly elevated in Uyghur osteosarcoma patients versus the general Uyghur population (OR, 10.23; 95%CI, 4.25, 18.89). The KSHV DNA genome and viral latent nuclear antigen LANA were detected in most osteosarcoma tumor cells. Gene expression profiling analysis showed that KSHV-positive osteosarcoma represents a distinct subtype of osteosarcomas with viral gene-activated signaling pathways important for osteosarcoma development. We conclude that KSHV infection is a risk factor for osteosarcoma, and KSHV is associated with some osteosarcomas, representing a newly identified viral-associated endemic cancer.

Optoelectronic bio-synaptic plasticity on neotype kesterite memristor with switching ratio >104.

Optoelectronic memristors hold the most potential for realizing next-generation neuromorphic computation; however, memristive devices that can integrate excellent resistive switching and both electrical-/light-induced bio-synaptic behaviors are still challenging to develop. In this study, an artificial optoelectronic synapse is proposed and realized using a kesterite-based memristor with Cu2ZnSn(S,Se)4 (CZTSSe) as the switching material and Mo/Ag as the back/top electrode. Benefiting from unique electrical features and a bi-layered structure of CZTSSe, the memristor exhibits highly stable nonvolatile resistive switching with excellent spatial uniformity, concentrated Set/Reset voltage distribution (variation <0.08/0.02 V), high On/Off ratio (>104), and long retention time (>104 s). A possible mechanism of the switching behavior in such a device is proposed. Furthermore, these memristors successfully achieve essential bio-synaptic functions under both electrical and various visible light (470-655 nm) stimulations, including electrical-induced excitatory postsynaptic current, paired pulse facilitation, long-term potentiation, long-term depression, spike-timing-dependent plasticity, as well as light-stimulated short-/long-term plasticity and learning-forgetting-relearning process. As such, the proposed neotype kesterite-based memristor demonstrates significant potential in facilitating artificial optoelectronic synapses and enabling neuromorphic computation.

Neotype kuramite optoelectronic memristor for bio-synaptic plasticity simulations.

Memristive devices with both electrically and optically induced synaptic dynamic behaviors will be crucial to the accomplishment of brain-inspired neuromorphic computing systems, in which the resistive materials and device architectures are two of the most important cornerstones, but still under challenge. Herein, kuramite Cu3SnS4 is newly introduced into poly-methacrylate as the switching medium to construct memristive devices, and the expected high-performance bio-mimicry of diverse optoelectronic synaptic plasticity is demonstrated. In addition to the excellent basic performances, such as stable bipolar resistive switching with On/Off ratio of ∼486, Set/Reset voltage of ∼-0.88/+0.96 V, and good retention feature of up to 104 s, the new designs of memristors possess not only the multi-level controllable resistive-switching memory property but also the capability of mimicking optoelectronic synaptic plasticity, including electrically and visible/near-infrared light-induced excitatory postsynaptic currents, short-/long-term memory, spike-timing-dependent plasticity, long-term plasticity/depression, short-term plasticity, paired-pulse facilitation, and "learning-forgetting-learning" behavior as well. Predictably, as a new class of switching medium material, such proposed kuramite-based artificial optoelectronic synaptic device has great potential to be applied to construct neuromorphic architectures in simulating human brain functions.

Train Axlebox Bearing Fault Diagnosis Based on MSC-SGMD.

Train axlebox bearings are subject to harsh service conditions, and the difficulty of diagnosing compound faults has brought greater challenges to the maintenance of high-quality train performance. In this paper, based on the traditional symplectic geometry mode decomposition (SGMD) algorithm, a maximum spectral coherence signal reconstruction algorithm is proposed to extract the intrinsic connection between the SGMD components with the help of the frequency domain coherence idea and reconstruct the key signal components so as to effectively improve the extraction of composite fault features of axlebox bearings under different speed conditions. Firstly, based on the traditional SGMD algorithm, the vibration signal of the axle box is decomposed to extract its symplectic geometry components (SGCs). Secondly, the spectral coherence coefficient between the SGCs is calculated, and the signal in which the maximum value is located is taken as the key component for the additive reconstruction Finally, the envelope spectrum is used to extract the reconstructed signal fault features. The inner race, outer race, and compound bearing failure vibration signal acquisition under different speed conditions were carried out on the equal scale axlebox bearing failure simulation test bench, and the effectiveness of the proposed algorithm was verified based on the axlebox vertical acceleration signal.

Three Dimensional Shape Reconstruction via Polarization Imaging and Deep Learning.

Deep-learning-based polarization 3D imaging techniques, which train networks in a data-driven manner, are capable of estimating a target's surface normal distribution under passive lighting conditions. However, existing methods have limitations in restoring target texture details and accurately estimating surface normals. Information loss can occur in the fine-textured areas of the target during the reconstruction process, which can result in inaccurate normal estimation and reduce the overall reconstruction accuracy. The proposed method enables extraction of more comprehensive information, mitigates the loss of texture information during object reconstruction, enhances the accuracy of surface normal estimation, and facilitates more comprehensive and precise reconstruction of objects. The proposed networks optimize the polarization representation input by utilizing the Stokes-vector-based parameter, in addition to separated specular and diffuse reflection components. This approach reduces the impact of background noise, extracts more relevant polarization features of the target, and provides more accurate cues for restoration of surface normals. Experiments are performed using both the DeepSfP dataset and newly collected data. The results show that the proposed model can provide more accurate surface normal estimates. Compared to the UNet architecture-based method, the mean angular error is reduced by 19%, calculation time is reduced by 62%, and the model size is reduced by 11%.

(NH4)2S-induced improvement of interfacial wettability for high-quality heterojunctions to boost the chloride-assembled CZTSSe solar cells.

Concernin the crucial interfacial issues in multi-layered kesterite Cu2ZnSn(S,Se)4 (CZTSSe) solar cells, (NH4)2S treatment has been proven to be effective in eliminating surface secondary phases. While for the CZTSSe absorbers without impurity phases, what can the low-temperature (NH4)2S treatment do to the absorbers, thus to the device performance? Herein, the chloride-fabricated CZTSSe absorbers are surface treated with the (NH4)2S solution at room temperature, and its influence on the device performance is investigated in detail. Surprisingly, such treatment can make the absorbers' surface become nearly super-hydrophilicity, greatly decreasing the surface wetting angle from 63.1° ± 3.4° to 7.3° ± 0.6° after 50 min-treating, and thus lead to marked differences in the interfacial properties of the CdS/CZTSSe heterojunctions deposited in a chemical bath. Consequently, for the best-performing CZTSSe cells, combining the passivated interfacial defects, increased carrier concentration, reduced carrier recombination, and prolonged minority lifetime, the efficiency is improved from 6.54% to 9.88%, together with the 37 mV and 7.9% increase in VOC and FF, respectively. This study confirms the newfound results that the (NH4)2S treatment can effectively adjust the wettability of the absorbers to form high-quality heterojunctions to boost the device efficiency, which would be valuable for an in-depth understanding of the intrinsic mechanisms of interfacial processing.

Population genetic analysis of the Plasmodium falciparum erythrocyte binding antigen-175 (EBA-175) gene in Equatorial Guinea.

BACKGROUND: Plasmodium falciparum erythrocyte binding antigen-175 (PfEBA-175) is a candidate antigen for a blood-stage malaria vaccine, while various polymorphisms and dimorphism have prevented to development of effective vaccines based on this gene. This study aimed to investigate the dimorphism of PfEBA-175 on both the Bioko Island and continent of Equatorial Guinea, as well as the genetic polymorphism and natural selection of global PfEBA-175. METHODS: The allelic dimorphism of PfEBA-175 region II of 297 bloods samples from Equatorial Guinea in 2018 and 2019 were investigated by nested polymerase chain reaction and sequencing. Polymorphic characteristics and the effect of natural selection were analyzed using MEGA 7.0, DnaSP 6.0 and PopART programs. Protein function prediction of new amino acid mutation sites was performed using PolyPhen-2 and Foldx program. RESULTS: Both Bioko Island and Bata district populations, the frequency of the F-fragment was higher than that of the C-fragment of PfEBA-175 gene. The PfEBA-175 of Bioko Island and Bata district isolates showed a high degree of genetic variability and heterogeneity, with π values of 0.00407 & 0.00411 and Hd values of 0.958 & 0.976 for nucleotide diversity, respectively. The values of Tajima's D of PfEBA-175 on Bata district and Bioko Island were 0.56395 and - 0.27018, respectively. Globally, PfEBA-175 isolates from Asia were more diverse than those from Africa and South America, and genetic differentiation quantified by the fixation index between Asian and South American countries populations was significant (FST > 0.15, P < 0.05). A total of 310 global isolates clustered in 92 haplotypes, and only one cluster contained isolates from three continents. The mutations A34T, K109E, D278Y, K301N, L305V and D329N were predicted as probably damaging. CONCLUSIONS: This study demonstrated that the dimorphism of F-fragment PfEBA-175 was remarkably predominant in the study area. The distribution patterns and genetic diversity of PfEBA-175 in Equatorial Guinea isolates were similar another region isolates. And the levels of recombination events suggested that natural selection and intragenic recombination might be the main drivers of genetic diversity in global PfEBA-175. These results have important reference value for the development of blood-stage malaria vaccine based on this antigen.

Genetic diversity and natural selection on the thrombospondin-related adhesive protein (TRAP) gene of Plasmodium falciparum on Bioko Island, Equatorial Guinea and global comparative analysis.

BACKGROUND: Thrombospondin-related adhesive protein (TRAP) is a transmembrane protein that plays a crucial role during the invasion of Plasmodium falciparum into liver cells. As a potential malaria vaccine candidate, the genetic diversity and natural selection of PfTRAP was assessed and the global PfTRAP polymorphism pattern was described. METHODS: 153 blood spot samples from Bioko malaria patients were collected during 2016-2018 and the target TRAP gene was amplified. Together with the sequences from database, nucleotide diversity and natural selection analysis, and the structural prediction were preformed using bioinformatical tools. RESULTS: A total of 119 Bioko PfTRAP sequences were amplified successfully. On Bioko Island, PfTRAP shows its high degree of genetic diversity and heterogeneity, with π value for 0.01046 and Hd for 0.99. The value of dN-dS (6.2231, p < 0.05) hinted at natural selection of PfTRAP on Bioko Island. Globally, the African PfTRAPs showed more diverse than the Asian ones, and significant genetic differentiation was discovered by the fixation index between African and Asian countries (Fst > 0.15, p < 0.05). 667 Asian isolates clustered in 136 haplotypes and 739 African isolates clustered in 528 haplotypes by network analysis. The mutations I116T, L221I, Y128F, G228V and P299S were predicted as probably damaging by PolyPhen online service, while mutations L49V, R285G, R285S, P299S and K421N would lead to a significant increase of free energy difference (ΔΔG > 1) indicated a destabilization of protein structure. CONCLUSIONS: Evidences in the present investigation supported that PfTRAP gene from Bioko Island and other malaria endemic countries is highly polymorphic (especially at T cell epitopes), which provided the genetic information background for developing an PfTRAP-based universal effective vaccine. Moreover, some mutations have been shown to be detrimental to the protein structure or function and deserve further study and continuous monitoring.

Long noncoding RNA plasmacytoma variant translocation gene 1 promotes epithelial-mesenchymal transition in osteosarcoma.

OBJECTIVE: Long noncoding RNAs (lncRNAs) are involved in the proliferation, migration, and invasion of tumors. In the current study, our aim was to explore the role of lncRNA plasmacytoma variant translocation gene 1 (PVT1) in osteosarcoma. METHODS: Quantitative real-time reverse transcription-polymerase chain reaction was used to detect the expression of lncRNA PVT1 in osteosarcoma tissues and cells. The relationship between lncRNA PVT1 expression status and the prognosis of patients with osteosarcoma was analyzed. The effect of lncRNA PVT1 on the malignant biological behavior of osteosarcoma cells in vitro was also analyzed. RESULTS: LncRNA PVT1 was upregulated in osteosarcoma. High lncRNA PVT1 expression indicated poor prognosis in patients with osteosarcoma. In vitro knockdown of lncRNA PVT1 inhibited the proliferation, migration, and invasion ability of osteosarcoma cells. In addition, we confirmed that lncRNA PVT1 affected the epithelial-mesenchymal transition of osteosarcoma cells. CONCLUSION: LncRNA PVT1 is a potential therapeutic target for osteosarcoma.

Genetic polymorphism of Plasmodium falciparum circumsporozoite protein on Bioko Island, Equatorial Guinea and global comparative analysis.

BACKGROUND: Plasmodium falciparum circumsporozoite protein (PfCSP) is a potential malaria vaccine candidate, but various polymorphisms of the pfcsp gene among global P. falciparum population become the major barrier to the effectiveness of vaccines. This study aimed to investigate the genetic polymorphisms and natural selection of pfcsp in Bioko and the comparison among global P. falciparum population. METHODS: From January 2011 to December 2018, 148 blood samples were collected from P. falciparum infected Bioko patients and 96 monoclonal sequences of them were successfully acquired and analysed with 2200 global pfcsp sequences mined from MalariaGEN Pf3k Database and NCBI. RESULTS: In Bioko, the N-terminus of pfcsp showed limited genetic variations and the numbers of repetitive sequences (NANP/NVDP) were mainly found as 40 (35%) and 41 (34%) in central region. Most polymorphic characters were found in Th2R/Th3R region, where natural selection (p > 0.05) and recombination occurred. The overall pattern of Bioko pfcsp gene had no obvious deviation from African mainland pfcsp (Fst = 0.00878, p < 0.05). The comparative analysis of Bioko and global pfcsp displayed the various mutation patterns and obvious geographic differentiation among populations from four continents (p < 0.05). The global pfcsp C-terminal sequences were clustered into 138 different haplotypes (H_1 to H_138). Only 3.35% of sequences matched 3D7 strain haplotype (H_1). CONCLUSIONS: The genetic polymorphism phenomena of pfcsp were found universal in Bioko and global isolates and the majority mutations located at T cell epitopes. Global genetic polymorphism and geographical characteristics were recommended to be considered for future improvement of malaria vaccine design.

Ti3C2 (MXene) based field electron emitters.

As a novel class of two-dimensional materials, MXene has provoked tremendous progress for various applications in functional devices. Here, we pioneer a preliminary understanding on the field emission behavior of MXene for the first time. Ti3C2 paper is fabricated by using facile filtration method, and multiple vertical sheets appear on the surface of MXene paper with high electrical conductivity (2.93 × 105 S m-1) and low work function (3.77 eV). The field electron emission performance and electric field distribution on MXene emitters are measured and simulated under planar and standing conditions. Both emitter conditions exhibit stable, uniform electron emission pattern, and the standing emitter achieves high emission current density of 59 mA cm-2 under 7.5 V µm-1. This work demonstrates the feasibility of MXene as cold electron source, establishing a preliminary foundation for its applications in field emission-based devices.

Customized 2D Barcode Sensing for Anti-Counterfeiting Application in Smart IoT with Fast Encoding and Information Hiding.

With the development of commodity economy, the emergence of fake and shoddy products has seriously harmed the interests of consumers and enterprises. To tackle this challenge, customized 2D barcode is proposed to satisfy the requirements of the enterprise anti-counterfeiting certification. Based on information hiding technology, the proposed approach can solve these challenging problems and provide a low-cost, difficult to forge, and easy to identify solution, while achieving the function of conventional 2D barcodes. By weighting between the perceptual quality and decoding robustness in sensing recognition, the customized 2D barcode can maintain a better aesthetic appearance for anti-counterfeiting and achieve fast encoding. A new picture-embedding scheme was designed to consider 2D barcode, within a unit image block as a basic encoding unit, where the 2D barcode finder patterns were embedded after encoding. Experimental results demonstrated that the proposed customized barcode could provide better encoding characteristics, while maintaining better decoding robustness than several state-of-the-art methods. Additionally, as a closed source 2D barcode that could be visually anti-counterfeit, the customized 2D barcode could effectively prevent counterfeiting that replicate physical labels. Benefitting from the high-security, high information capacity, and low-cost, the proposed customized 2D barcode with sensing recognition scheme provide a highly practical, valuable in terms of marketing, and anti-counterfeiting traceable solution for future smart IoT applications.

Rapidly Tuning the PID Controller Based on the Regional Surrogate Model Technique in the UAV Formation.

The leader-follower structure is widely used in unmanned aerial vehicle formation. This paper adopts the proportional-integral-derivative (PID) and the linear quadratic regulator controllers to construct the leader-follower formation. Tuning the PID controllers is generally empirical; hence, various surrogate models have been introduced to identify more refined parameters with relatively lower cost. However, the construction of surrogate models faces the problem that the singular points may affect the accuracy, such that the global surrogate models may be invalid. Thus, to tune controllers quickly and accurately, the regional surrogate model technique (RSMT), based on analyzing the regional information entropy, is proposed. The proposed RSMT cooperates only with the successful samples to mitigate the effect of singular points along with a classifier screening failed samples. Implementing the RSMT with various kinds of surrogate models, this study evaluates the Pareto fronts of the original simulation model and the RSMT to compare their effectiveness. The results show that the RSMT can accurately reconstruct the simulation model. Compared with the global surrogate models, the RSMT reduces the run time of tuning PID controllers by one order of magnitude, and it improves the accuracy of surrogate models by dozens of orders of magnitude.

ZNF281 Regulates Cell Proliferation, Migration and Invasion in Colorectal Cancer through Wnt/ß-Catenin Signaling.

BACKGROUND/AIMS: Zinc Finger Protein 281 (ZNF281) was recently identified as a novel oncogene in several human carcinomas. However, the clinical significance of ZNF281 in colorectal cancer (CRC) and the molecular mechanisms by which ZNF281 promotes the growth and metastasis of CRC remain unknown. METHODS: ZNF281 expression in CRC tissues was assessed, and the outcomes were analyzed to determine the clinical importance of ZNF281 expression. Cell Transwell assays and a wound healing assay were performed to assess the effects of ZNF281 on CRC cell migration and invasion in vitro. Western blotting was applied to analyze the potential mechanisms. RESULTS: ZNF281 mRNA and protein levels were significantly increased in CRC tissues compared with normal colon tissues, and high ZNF281 expression was associated with advanced T stage, N stage, TNM stage and differentiation. Therefore, ZNF281 expression might be an independent prognostic indicator in CRC patients. Moreover, knockdown of ZNF281 expression suppressed cell proliferation, migration and invasion by inhibiting the Wnt/ß-catenin pathway. CONCLUSION: Our study indicates that ZNF281 plays a critical role in the progression and metastasis of CRC and could represent a potential therapeutic target for CRC.

High prevalence of Pfdhfr-Pfdhps quadruple mutations associated with sulfadoxine-pyrimethamine resistance in Plasmodium falciparum isolates from Bioko Island, Equatorial Guinea.

BACKGROUND: Sulfadoxine-pyrimethamine (SP) is recommended for intermittent preventive treatment of malaria in Africa. However, increasing SP resistance (SPR) affects the therapeutic efficacy of the SP. As molecular markers, Pfdhfr (dihydrofolate reductase) and Pfdhps (dihydropteroate synthase) genes are widely used for SPR surveillance. This study aimed to assess the prevalence of Pfdhfr and Pfdhps genes mutations and haplotypes in Plasmodium falciparum isolates collected from Bioko Island, Equatorial Guinea (EG). METHODS: In total, 180 samples were collected in 2013-2014. The single nucleotide polymorphisms (SNPs) of the Pfdhfr and Pfdhps genes were identified with nested PCR and Sanger sequencing. The genotypes and linkage disequilibrium (LD) tests were also analysed. RESULTS: Sequences of Pfdhfr and Pfdhps genes were obtained from 92.78% (167/180) and 87.78% (158/180) of the samples, respectively. For Pfdhfr, 97.60% (163/167), 87.43% (146/167) and 97.01% (162/167) of the samples carried N51I, C59R and S108N mutant alleles, respectively. The prevalence of the Pfdhps S436A, A437G, K540E, A581G, and A613S mutations were observed in 20.25% (32/158), 90.51% (143/158), 5.06% (8/158), 0.63% (1/158), and 3.16% (5/158) of the samples, respectively. In total, 3 unique haplotypes at the Pfdhfr locus and 8 haplotypes at the Pfdhps locus were identified. A triple mutation (CIRNI) in Pfdhfr was the most prevalent haplotype (86.83%), and a single mutant haplotype (SGKAA; 62.66%) was predominant in Pfdhps. A total of 130 isolates with 12 unique haplotypes were found in the Pfdhfr and Pfdhps combined haplotypes, 65.38% (85/130) of them carried quadruple allele combinations (CIRNI-SGKAA), whereas only one isolate (0.77%, 1/130) was found to carry the wild-type (CNCSI-SAKAA). For LD analysis, the Pfdhfr N51I was significantly associated with the Pfdhps A437G (P < 0.05). CONCLUSION: Bioko Island possesses a high prevalence of the Pfdhfr triple mutation (CIRNI) and Pfdhps single mutation (SGKAA), which will undermine the pharmaceutical effect of SP for malaria treatment strategies. To avoid an increase in SPR, continuous molecular monitoring and additional control efforts are urgently needed in Bioko Island, Equatorial Guinea.

Natural selection and genetic diversity of domain I of Plasmodium falciparum apical membrane antigen-1 on Bioko Island.

BACKGROUND: Plasmodium falciparum apical membrane antigen-1 (PfAMA-1) is a promising candidate antigen for a blood-stage malaria vaccine. However, antigenic variation and diversity of PfAMA-1 are still major problems to design a universal malaria vaccine based on this antigen, especially against domain I (DI). Detail understanding of the PfAMA-1 gene polymorphism can provide useful information on this potential vaccine component. Here, general characteristics of genetic structure and the effect of natural selection of DIs among Bioko P. falciparum isolates were analysed. METHODS: 214 blood samples were collected from Bioko Island patients with P. falciparum malaria between 2011 and 2017. A fragment spanning DI of PfAMA-1 was amplified by nested polymerase chain reaction and sequenced. Polymorphic characteristics and the effect of natural selection were analysed using MEGA 5.0, DnaSP 6.0 and Popart programs. Genetic diversity in 576 global PfAMA-1 DIs were also analysed. Protein function prediction of new amino acid mutation sites was performed using PolyPhen-2 program. RESULTS: 131 different haplotypes of PfAMA-1 were identified in 214 Bioko Island P. falciparum isolates. Most amino acid changes identified on Bioko Island were found in C1L. 32 amino acid changes identified in PfAMA-1 sequences from Bioko Island were found in predicted RBC-binding sites, B cell epitopes or IUR regions. Overall patterns of amino acid changes of Bioko PfAMA-1 DIs were similar to those in global PfAMA-1 isolates. Differential amino acid substitution frequencies were observed for samples from different geographical regions. Eight new amino acid changes of Bioko island isolates were also identified and their three-dimensional protein structural consequences were predicted. Evidence for natural selection and recombination event were observed in global isolates. CONCLUSIONS: Patterns of nucleotide diversity and amino acid polymorphisms of Bioko Island isolates were similar to those of global PfAMA-1 DIs. Balancing natural selection across DIs might play a major role in generating genetic diversity in global isolates. Most amino acid changes in DIs occurred in predicted B-cell epitopes. Novel sites mapped on a three dimensional structure of PfAMA-1 showed that these regions were located at the corner. These results may provide significant value in the design of a malaria vaccine based on this antigen.

[The underlying mechanism for the connection between visual long-term memory and visual working memory].

Visual memory, mainly composed of visual long-term memory (VLTM) and visual working memory (VWM), is an important mechanism of human information storage. Since Baddeley proposed the multicomponent working memory model, the idea that VWM is independent of the VLTM system has been widely accepted. However, the new theoretical evidence suggested a close connection between VLTM and VWM. For instance, the three embedded components model describes the VLTM and VWM in the same framework, which suggests that VWM is only a distinct state of VLTM. On the one hand, the operating function of VWM is supported by the persistence of VLTM. On the other hand, the evidence from neuroimaging studies shows that VWM and VLTM tasks activate some same brain areas. In addition, the whole visual memory system shows a trend of processing from early visual cortex to prefrontal cortex. The present article not only reviews the current studies about the relationship between VLTM and VWM but also gives some forecasts for future studies.