The autophagy-lysosome pathway: a potential target in the chemical and gene therapeutic strategies for Parkinson's disease.

Parkinson's disease is a common neurodegenerative disease with movement disorders associated with the intracytoplasmic deposition of aggregate proteins such as α-synuclein in neurons. As one of the major intracellular degradation pathways, the autophagy-lysosome pathway plays an important role in eliminating these proteins. Accumulating evidence has shown that upregulation of the autophagy-lysosome pathway may contribute to the clearance of α-synuclein aggregates and protect against degeneration of dopaminergic neurons in Parkinson's disease. Moreover, multiple genes associated with the pathogenesis of Parkinson's disease are intimately linked to alterations in the autophagy-lysosome pathway. Thus, this pathway appears to be a promising therapeutic target for treatment of Parkinson's disease. In this review, we briefly introduce the machinery of autophagy. Then, we provide a description of the effects of Parkinson's disease-related genes on the autophagy-lysosome pathway. Finally, we highlight the potential chemical and genetic therapeutic strategies targeting the autophagy-lysosome pathway and their applications in Parkinson's disease.

Cryo-electron tomography reveals the packaging pattern of RuBisCOs in Synechococcus ß-carboxysome.

Carboxysomes are large self-assembled microcompartments that serve as the central machinery of a CO2-concentrating mechanism (CCM). Biogenesis of carboxysome requires the fine organization of thousands of individual proteins; however, the packaging pattern of internal RuBisCOs remains largely unknown. Here we purified the intact ß-carboxysomes from Synechococcus elongatus PCC 7942 and identified the protein components by mass spectrometry. Cryo-electron tomography combined with subtomogram averaging revealed the general organization pattern of internal RuBisCOs, in which the adjacent RuBisCOs are mainly arranged in three distinct manners: head-to-head, head-to-side, and side-by-side. The RuBisCOs in the outermost layer are regularly aligned along the shell, the majority of which directly interact with the shell. Moreover, statistical analysis enabled us to propose an ideal packaging model of RuBisCOs in the ß-carboxysome. These results provide new insights into the biogenesis of ß-carboxysomes and also advance our understanding of the efficient carbon fixation functionality of carboxysomes.

Segregation between an ornamental and a disease driver gene provides insights into pigment cell regulation.

Genetic interactions are adaptive within a species. Hybridization can disrupt such species-specific genetic interactions and creates novel interactions that alter the hybrid progeny overall fitness. Hybrid incompatibility, which refers to degenerative genetic interactions that decrease the overall hybrid survival, is one of the results from combining two diverged genomes in hybrids. The discovery of spontaneous lethal tumorigenesis and underlying genetic interactions in select hybrids between diverged Xiphophorus species showed that lethal pathological process can result from degenerative genetic interactions. Such genetic interactions leading to lethal phenotype are thought to shield gene flow between diverged species. However, hybrids between certain Xiphophorus species do not develop such tumors. Here we report the identification of a locus residing in the genome of one Xiphophorus species that represses an oncogene from a different species. Our finding provides insights into normal and pathological pigment cell development, regulation and molecular mechanism in hybrid incompatibility. Significance: The Dobzhansky-Muller model states epistatic interactions occurred between genes in diverged species underlies hybrid incompatibility. There are a few vertebrate interspecies hybrid cases that support the Dobzhansky-Muller model. This study reports a fish hybrid system where incompatible genetic interactions are involved in neuronal regulation of pigment cell biology, and also identified a novel point of regulation for pigment cells.

Distinct roles of TREM2 in central nervous system cancers and peripheral cancers.

Glioblastomas (GBM) are incurable central nervous system (CNS) cancers characterized by substantial myeloid cell infiltration. Whether myeloid cell-directed therapeutic targets identified in peripheral non-CNS cancers are applicable to GBM requires further study. Here, we identify that the critical immunosuppressive target in peripheral cancers, triggering receptor expressed on myeloid cells-2 (TREM2), is immunoprotective in GBM. Genetic or pharmacological TREM2 deficiency promotes GBM progression in vivo. Single-cell and spatial sequencing reveals downregulated TREM2 in GBM-infiltrated myeloid cells. TREM2 negatively correlates with immunosuppressive myeloid and T cell exhaustion signatures in GBM. We further demonstrate that during GBM progression, CNS-enriched sphingolipids bind TREM2 on myeloid cells and elicit antitumor responses. Clinically, high TREM2 expression in myeloid cells correlates with better survival in GBM. Adeno-associated virus-mediated TREM2 overexpression impedes GBM progression and synergizes with anti-PD-1 therapy. Our results reveal distinct functions of TREM2 in CNS cancers and support organ-specific myeloid cell remodeling in cancer immunotherapy.

Profiling the interplay and coevolution of Microcystis aeruginosa and cyanosiphophage Mic1.

The cyanosiphophage Mic1 specifically infects the bloom-forming Microcystis aeruginosa FACHB 1339 from Lake Chaohu, China. Previous genomic analysis showed that its 92,627 bp double-stranded DNA genome consists of 98 putative open reading frames, 63% of which are of unknown function. Here, we investigated the transcriptome dynamics of Mic1 and its host using RNA sequencing. In the early, middle, and late phases of the 10 h lytic cycle, the Mic1 genes are sequentially expressed and could be further temporally grouped into two distinct clusters in each phase. Notably, six early genes, including gp49 that encodes a TnpB-like transposase, immediately reach the highest transcriptional level in half an hour, representing a pioneer cluster that rapidly regulates and redirects host metabolism toward the phage. An in-depth analysis of the host transcriptomic profile in response to Mic1 infection revealed significant upregulation of a polyketide synthase pathway and a type III-B CRISPR system, accompanied by moderate downregulation of the photosynthesis and key metabolism pathways. The constant increase of phage transcripts and relatively low replacement rate over the host transcripts indicated that Mic1 utilizes a unique strategy to gradually take over a small portion of host metabolism pathways after infection. In addition, genomic analysis of a less-infective Mic1 and a Mic1-resistant host strain further confirmed their dynamic interplay and coevolution via the frequent horizontal gene transfer. These findings provide insights into the mutual benefit and symbiosis of the highly polymorphic cyanobacteria M. aeruginosa and cyanophages. IMPORTANCE: The highly polymorphic Microcystis aeruginosa is one of the predominant bloom-forming cyanobacteria in eutrophic freshwater bodies and is infected by diverse and abundant cyanophages. The presence of a large number of defense systems in M. aeruginosa genome suggests a dynamic interplay and coevolution with the cyanophages. In this study, we investigated the temporal gene expression pattern of Mic1 after infection and the corresponding transcriptional responses of its host. Moreover, the identification of a less-infective Mic1 and a Mic1-resistant host strain provided the evolved genes in the phage-host coevolution during the multiple-generation cultivation in the laboratory. Our findings enrich the knowledge on the interplay and coevolution of M. aeruginosa and its cyanophages and lay the foundation for the future application of cyanophage as a potential eco-friendly and bio-safe agent in controlling the succession of harmful cyanobacterial blooms.

A novel variant of PLA2G6 gene related early-onset parkinsonism: a case report and literature review.

This study reported a case of early-onset parkinsonism associated with a novel variant of the PLA2G6 gene. The boy first started showing symptoms at the age of 11, with gait instability and frequent falls. As the disease progressed, his gait instability worsened, and he developed difficulties with swallowing and speaking, although there was no apparent decline in cognitive function. An MRI of the head revealed significant atrophy of the cerebellum. The initial diagnosis for the boy was early-onset parkinsonism, classified as Hoehn-Yahr grade 5.Genomic sequencing of the patient indicated that he had compound heterozygous variations in the PLA2G6 gene: c.1454G>A (p.Gly485Glu) and c.991G>T (p.Asp331Tyr). Pedigree analysis revealed that his younger brother also carried the same variant, albeit with milder symptoms. The patient's unaffected mother was found to be a carrier of the c.991G>T variant. Additionally, this study reviewed 62 unrelated families with PLA2G6 gene-related early-onset parkinsonism. The analysis showed a higher proportion of female probands, with a mean age of onset of ~23.0 years. Primary symptoms were predominantly bradykinesia and psychosis, with tremors being relatively rare. Cerebellar atrophy was observed in 41 patients (66.1%). Among the reported mutations, the most common mutation was c.991G>T, presenting in 21 families (33.9%), followed by c.2222G>A in eight families (12.9%). Other mutations were less common. Notably, the c.991G>T mutation was exclusive to Chinese families and was a prevalent mutation among this population. The initial symptoms varied significantly among patients with different mutations.

The interplay of growth-regulating factor 5 and BZR1 in coregulating chlorophyll degradation in poplar.

Chlorophyll (Chl) is essential for plants to carry out photosynthesis, growth and development processes. Growth-regulating factors (GRFs) play a vital role in regulating Chl degradation in plants. However, the molecular mechanism by which GRF5 regulates Chl degradation in poplar remains unknown. Here we found that overexpression of PpnGRF5-1 increased Chl content in leaves and promoted chloroplast development in poplar. Overexpression of PpnGRF5-1 in poplar delayed Chl degradation induced by external factors, such as hormones, darkness and salt stress. PpnGRF5-1 responded to brassinosteroid (BR) signalling during BR-induced Chl degradation and reduced the expression levels of Chl degradation and senescence-related genes. PpnGRF5-1 inhibited the expression of Chl b reductases PagNYC1 and PagNOL. PpnGRF5-1 could interact with PagBZR1 in the nucleus. PagBZR1 also inhibited the expression of PagNYC1. In addition, we found that the protein-protein interaction between PagBZR1 and PpnGRF5-1 enhanced the inhibitory effect of PpnGRF5-1 on the Chl b reductases PagNYC1 and PagNOL. BZR1 and GRF5-1 were upregulated, and NOL and NYC1 were downregulated in triploid poplars compared to diploids. This study revealed a new mechanism by which PpnGRF5-1 regulates Chl degradation in poplars and lays the foundation for comprehensively analysing the molecular mechanism of Chl metabolism in triploid poplars.

Chirality tuning and reversing with resonant phase-change metasurfaces.

Dynamic control of circular dichroism in photonic structures is critically important for compact spectrometers, stereoscopic displays, and information processing exploiting multiple degrees of freedom. Metasurfaces can help miniaturize chiral devices but only produce static and limited chiral responses. While external stimuli can tune resonances, their modulations are often weak, and reversing continuously the sign of circular dichroism is extremely challenging. Here, we demonstrate the dynamically tunable chiral response of resonant metasurfaces supporting chiral bound states in the continuum combining them with phase-change materials. Phase transition between amorphous and crystalline phases allows for control of chiral response and varies chirality rapidly from -0.947 to +0.958 backward and forward via the chirality continuum. Our demonstrations underpin the rapid development of chiral photonics and its applications.

A polarization double-enhancement strategy to achieve super low energy consumption with ultra-high energy storage capacity in BCZT-based relaxor ferroelectrics.

Due to dielectric capacitors' already-obtained fast charge-discharge speed, research has been focused on improving their Wrec. Increasing the polarization and enhancing the voltage endurance are efficient ways to reach higher Wrec, however simultaneous modification still seems a paradox. For example, in the ferroelectric-to-relaxor ferroelectric (FE-to-RFE) phase transition strategy, which has been widely used in the latest decade, electric breakdown strength (Eb) and energy storage efficiency (η) always increase, while at the same time, the maximum polarization (Pmax) inevitably decreases. The solution to this problem can be obtained from another degree of freedom, like defect engineering. By incorporating Bi(Zn2/3Ta1/3)O3 (BZT) into the Ba0.15Ca0.85Zr0.1Ti0.9O3 (BCZT) lattice to form (1 - x)Ba0.15Ca0.85Zr0.1Ti0.9O3-xBi(Zn2/3Ta1/3)O3 (BCZT-xBZT) solid-solution ceramics, in this work, ultrahigh ferroelectric polarization was achieved in BCZT-0.15BZT, which is caused by the polarization double-enhancement, comprising the contribution of interfacial and dipole polarization. In addition, due to the electron compensation, a Schottky contact formed at the interface between the electrode and the ceramic, which in the meantime, enhanced its Eb. A Wrec of 8.03 J cm-3, which is the highest among the BCZT-based ceramics reported so far, with an extremely low energy consumption, was finally achieved. BCZT-0.15BZT also has relatively good polarization fatigue after long-term use, good energy storage frequency stability and thermal stability, as well as excellent discharge properties.

Nanostructure-based orbital angular momentum encryption and multiplexing.

The orthogonality among the OAM modes provides a new degree of freedom for optical multiplexing communications. So far, traditional Dammann gratings and spatial light modulators (SLMs) have been widely used to generate OAM beams by modulating electromagnetic waves at each pixel. However, such architectures suffer from limitations in terms of having a resolution of only a few microns and the bulkiness of the entire optical system. With the rapid development of the electromagnetic theory and advanced nanofabrication methods, artificial nanostructures, especially optical metasurfaces, have been introduced which greatly shrink the size of OAM multiplexing devices while increasing the level of integration. This review focuses on the study of encryption, multiplexing and demultiplexing of OAM beams based on nanostructure platforms. After introducing the focusing characteristics of OAM beams, the interaction mechanism between OAM beams and nanostructures is discussed. The physical phenomena of helical dichroism response and spatial separation of OAM beams achieved through nanostructures, setting the stage for OAM encryption and multiplexing, are reviewed. Afterward, the further advancements and potential applications of nanophotonics-based OAM multiplexing are deliberated. Finally, the challenges of conventional design methods and dynamic tunable techniques for nanostructure-based OAM multiplexing technology are addressed.

Positive regulation of the Eucommia rubber biosynthesis-related gene EuFPS1 by EuWRKY30 in Eucommia ulmoides.

Eucommia rubber is a secondary metabolite from Eucommia ulmoides that has attracted much attention because of its unique properties and enormous potential for application. However, the transcriptional mechanism regulating its biosynthesis has not yet been determined. Farnesyl pyrophosphate synthase is a key enzyme in the Eucommia rubber biosynthesis. In this study, the promoter of EuFPS1 was used as bait, EuWRKY30 was screened from the cDNA library of EuFPS1 via a yeast one-hybrid system. EuWRKY30 belongs to the WRKY IIa subfamily and contains a WRKY domain and a C2H2 zinc finger motif, and the expressed protein is located in the nucleus. EuWRKY30 and EuFPS1 exhibited similar tissue expression patterns, and yeast one-hybrid and dual-luciferase experiments confirmed that EuWRKY30 directly binds to the W-box element in the EuFPS1 promoter and activates its expression. Moreover, the overexpression of EuWRKY30 significantly upregulated the expression level of EuFPS1, further increasing the density of the rubber particles and Eucommia rubber content. The results of this study indicated that EuWRKY30 positively regulates EuFPS1, which plays a critical role in the synthesis of Eucommia rubber, provided a basis for further analysis of the underlying transcriptional regulatory mechanisms.

Ultralow-Permittivity and Temperature-Stable Ba1-xCaxMg2Al6Si9O30 Dielectric Ceramics for C-Band Patch Antenna Applications.

Ca-substituted Ba1-xCaxMg2Al6Si9O30 ceramics were prepared to explore the relationships among their crystal structural parameters, phase compositions, dielectric properties, and coefficients of thermal expansion and applications in C-band antenna. The maximum solubility of Ba1-xCaxMg2Al6Si9O30 was located at x = 0.25, and Ba1-xCaxMg2Al6Si9O30 ceramics (0 ≤ x ≤ 0.25) crystallized in the space group P6/mcc. In Ba1-xCaxMg2Al6Si9O30 single-phase ceramics, εr was dominated by ionic polarizability and "rattling effects" of Ba2+ and Al(2)3+; Q × f was controlled by the roundness of [Si4Al2O18] inner rings and total lattice energy; and τf was affected by the bond valence of Si/Al(1)-O(1). Notably, the low average coefficients of thermal expansion (2.668 ppm/°C) at -150 °C ≤ T ≤ 850 °C and near-zero coefficients of thermal expansion (1.254 ppm/°C) at -150 °C ≤ T ≤ 260 °C were achieved for the Ba1-xCaxMg2Al6Si9O30 (x = 0.1) ceramic. Optimum microwave and terahertz dielectric properties were obtained for the Ba1-xCaxMg2Al6Si9O30 (x = 0.1) ceramic with εr = 5.80, Q × f = 31,174 at 13.99 GHz, τf = -7.10 ppm/°C, and εr = 5.71-5.85 at 0.2 THz ≤ f ≤ 1.0 THz. Also, the Ba1-xCaxMg2Al6Si9O30 (x = 0.1) ceramic substrate had been designed as a C-band patch antenna with a high simulated radiation efficiency (87.76%) and gain (6.30 dBi) at 7.70 GHz (|S11| = -38.41 dB).

Development of highly sensitive dual-enhanced fluorescence quenching immunochromatographic test strips based on Pt nanoprobes.

The fluorescence-quenching method is crucial in vitro analysis, particularly for immunochromatographic test strips (ICTs) using noble metal nanoparticles as probes. However, ICTs still fall short in meeting the requirements for the detection of traces biomarkers due to the noble metal nanoparticles can only quench fluorescence of the dyes within a confined distance. Interestingly, noble metal nanoparticles, such as Pt NPs cannot only perform fluorescence-quenching ability based on the Förster resonance energy transfer (FRET), but also show perfect oxidase-like catalytic performance on many kinds of substrates, such as 3,3',5,5' -tetramethylbenzidine (TMB). We observed that the oxTMB (the oxidation products of TMB) exhibited notable effectiveness in quenching Cy5 fluorescence by the strong inner filter effect (IFE), which obviously improved the fluorescence-quenching efficiency with extremely low background signal. Through the dual-enhanced fluorescence quenching mechanism, the fluorescence quenching constant (Kn) was 661.24-fold that of only Pt NPs on the NC membrane. To validate the feasibility of this technique, we employed two types of biomarkers, namely microRNA (miR-15a-5p) and the signature protein (PSA). The sensitivity of miR-15a-5p was 9.286 × 10-18 mol/L and 17.5-fold more than that based on Pt NPs. As for the PSA, the LOD (0.6265 pg/mL) was 15.5-fold enhancement more sensitive after catalysis. Overall, the dual-enhanced fluorescence quenching rFICTs could act as a practical detection for biomarker in real samples.

The effect of reflux ratio on sulfur disproportionation tendency in anaerobic baffled reactor with the heterotrophic combining sulfur autotrophic processes under high concentration perchlorate stress.

In a laboratory scale, an anaerobic baffled reactor (ABR) consisting of eight compartments, the heterotrophic combining sulfur autotrophic processes under different reflux ratios were constructed to achieve effective perchlorate removal and alleviate sulfur disproportionation reaction. Perchlorate was efficiently removed with effluent perchlorate concentration below 0.5 µg/L when the influent perchlorate concentration was 1030 mg/L during stages I ~ V, indicating that heterotrophic combining sulfur autotrophic perchlorate reduction processes can effectively achieve high concentration perchlorate removal. Furthermore, the 100% reflux ratio could reduce the contact time between sulfur particles and water; thus, the sulfur disproportionation reaction was inhibited. However, the inhibition effect of reflux on sulfur disproportionation was attenuated due to dilute perchlorate concentration when a reflux ratio of 150% and 200% was implemented. Meanwhile, the content of extracellular polymeric substances (EPS) in the heterotrophic unit (36.79 ~ 45.71 mg/g VSS) was higher than that in the sulfur autotrophic unit (22.19 ~ 25.77 mg/g VSS), indicating that high concentration perchlorate stress in the heterotrophic unit promoted EPS secretion. Thereinto, the PN content of sulfur autotrophic unit decreased in stage III and stage V due to decreasing perchlorate concentration in the autotrophic unit. Meanwhile, the PS content increased with increasing reflux in the autotrophic unit, which was conducive to the formation of biofilm. Furthermore, the high-throughput sequencing result showed that Proteobacteria, Chloroflexi, Firmicutes, and Bacteroidetes were the dominant phyla and Longilinea, Diaphorobacter, Acinetobacter, and Nitrobacter were the dominant genus in ABR, which were associated with heterotrophic or autotrophic perchlorate reduction and beneficial for effective perchlorate removal. The study indicated that reflux was a reasonable strategy for alleviating sulfur disproportionation in heterotrophic combining sulfur autotrophic perchlorate removal processes.

Structure of the intact tail machine of Anabaena myophage A-1(L).

The Myoviridae cyanophage A-1(L) specifically infects the model cyanobacteria Anabaena sp. PCC 7120. Following our recent report on the capsid structure of A-1(L), here we present the high-resolution cryo-EM structure of its intact tail machine including the neck, tail and attached fibers. Besides the dodecameric portal, the neck contains a canonical hexamer connected to a unique pentadecamer that anchors five extended bead-chain-like neck fibers. The 1045-Å-long contractile tail is composed of a helical bundle of tape measure proteins surrounded by a layer of tube proteins and a layer of sheath proteins, ended with a five-component baseplate. The six long and six short tail fibers are folded back pairwise, each with one end anchoring to the baseplate and the distal end pointing to the capsid. Structural analysis combined with biochemical assays further enable us to identify the dual hydrolytic activities of the baseplate hub, in addition to two host receptor binding domains in the tail fibers. Moreover, the structure of the intact A-1(L) also helps us to reannotate its genome. These findings will facilitate the application of A-1(L) as a chassis cyanophage in synthetic biology.

A hybrid variable selection method combining Fisher's linear discriminant combined population analysis and an improved binary cuckoo search algorithm.

In this paper, a novel hybrid variable selection method for model building by near-infrared (NIR) spectroscopy is proposed for composition measurement in industrial processes. A double-layer structure is designed for variable selection by combining Fisher's linear discriminant combined population analysis (FCPA) and an improved binary cuckoo search algorithm (IBCS). The Fisher classifier combined with model population analysis is used to select the variable interval wherein the useful variables are roughly located even when strong multicollinearity exists among spectral variables. Opposition-based learning (OBL) and jumping genes (JG) are introduced to improve the binary cuckoo search algorithm for the fine selection of key variables, thus avoiding the loss of excellent solutions due to randomness and the local optimum. Different variable selection methods were used to select variables for beer, corn, and diesel fuel datasets, and the partial least squares (PLS) algorithms were used to build calibration models to predict the original extract concentration of beer, the protein and starch content of corn, and the boiling point of diesel fuel, respectively. The results showed that the proposed PLS modeling method based on FCPA-IBCS has higher fitting accuracy and smaller prediction errors.

MYC2 regulates stomatal density and water use efficiency via targeting EPF2/EPFL4/EPFL9 in poplar.

Although polyploid plants have lower stomatal density than their diploid counterparts, the molecular mechanisms underlying this difference remain elusive. Here, we constructed a network based on the triploid poplar transcriptome data and triple-gene mutual interaction algorithm and found that PpnMYC2 was related to stomatal development-related genes PpnEPF2, PpnEPFL4, and PpnEPFL9. The interactions between PpnMYC2 and PagJAZs were experimentally validated. PpnMYC2-overexpressing poplar and Arabidopsis thaliana had reduced stomatal density. Poplar overexpressing PpnMYC2 had higher water use efficiency and drought resistance. RNA-sequencing data of poplars overexpressing PpnMYC2 showed that PpnMYC2 promotes the expression of stomatal density inhibitors PagEPF2 and PagEPFL4 and inhibits the expression of the stomatal density-positive regulator PagEPFL9. Yeast one-hybrid system, electrophoretic mobility shift assay, ChIP-qPCR, and dual-luciferase assay were employed to substantiate that PpnMYC2 directly regulated PagEPF2, PagEPFL4, and PagEPFL9. PpnMYC2, PpnEPF2, and PpnEPFL4 were significantly upregulated, whereas PpnEPFL9 was downregulated during stomatal formation in triploid poplar. Our results are of great significance for revealing the regulation mechanism of plant stomatal occurrence and polyploid stomatal density, as well as reducing stomatal density and improving plant water use efficiency by overexpressing MYC2.

Phylogenomics analyses of all species of Swordtails (Genus Xiphophorus ) highlights hybridization precedes speciation.

Hybridization has been recognized as an important driving force for evolution, however studies of the genetic consequence and its cause are still lagging behind in vertebrates due to the lack of appropriate experimental systems. Fish of the central American genus Xiphophorus were proposed to have evolved with multiple ancient and ongoing hybridization events, and served as a valuable research model in evolutionary biology and in biomedical research on human disease for more than a century. Here, we provide the complete genome resource and its annotation of all 26 Xiphophorus species. On this dataset we resolved the so far conflicting phylogeny. Through comparative genomic analyses we investigated the molecular evolution of genes related to melanoma, for a main sexually selected trait and for the genetic control of puberty timing, which are predicted to be involved in pre-and postzygotic isolation and thus to influence the probability of interspecific hybridization in Xiphophorus . We demonstrate dramatic size-variation of some gene families across species, despite the reticulate evolution and short divergence time. Finally, we clarify the hybridization history in the genus Xiphophorus genus, settle the long dispute on the hybridization origin of two Southern swordtails, highlight hybridizations precedes speciation, and reveal the distribution of hybridization ancestry remaining in the fused genome.

Structural and biochemical insights into the mechanism of the Gabija bacterial immunity system.

The Gabija system is a newly discovered bacterial immune system that consists of GajA and GajB. Here we report the cryo-EM structure of the Gabija complex from Bacillus cereus VD045 at 3.6 Å, which provides the direct evidence of interactions between GajA and GajB. The Gabija complex is an octameric ring structure with four GajA and four GajB. GajA is an OLD nucleases family protein, while GajB belongs to the SF1 helicases. The Gabija complex has sequence-specific DNA nuclease activity and prefers circular rather than linear DNA as substrate, its activity is more sensitive to concentrations change of nucleotides compared to GajA alone. Our data suggest a mechanism of Gabija immunity: the nuclease activity of Gabija complex is inhibited under physiological conditions, while it is activated by depletion of NTP and dNTP upon the replication and transcription of invading phages and cleave the circular DNA to prevent phage DNA replication.

Novel mutations in FLVCR1 cause tremors, sensory neuropathy with retinitis pigmentosa.

The mutations of the feline leukemia virus subgroup C receptor-related protein 1 (FLVCR1) cause ataxia with retinitis pigmentosa. Recent studies indicated a large variation in the phenotype of FLVCR1-associated diseases. In this report, we describe an adult male who manifested first with tremors in his third decade, followed by retinitis pigmentosa, sensory ataxia, and sensory neuropathy in his fourth decade. While retinitis pigmentosa and sensory ataxia are well-recognized features of FLVCR1-associated disease, tremor is rarely described. Whole-exome sequencing revealed novel compound heterozygous pathogenic FLVCR1 variants: c.498 G > A; p.(Trp166*) and c.369 T > G; p.(Phe123Leu). In addition, we have highlighted the ultrastructural abnormalities of the sural biopsy in this patient.