AMPD2 regulates GTP synthesis and is mutated in a potentially treatable neurodegenerative brainstem disorder.

Purine biosynthesis and metabolism, conserved in all living organisms, is essential for cellular energy homeostasis and nucleic acid synthesis. The de novo synthesis of purine precursors is under tight negative feedback regulation mediated by adenosine and guanine nucleotides. We describe a distinct early-onset neurodegenerative condition resulting from mutations in the adenosine monophosphate deaminase 2 gene (AMPD2). Patients have characteristic brain imaging features of pontocerebellar hypoplasia (PCH) due to loss of brainstem and cerebellar parenchyma. We found that AMPD2 plays an evolutionary conserved role in the maintenance of cellular guanine nucleotide pools by regulating the feedback inhibition of adenosine derivatives on de novo purine synthesis. AMPD2 deficiency results in defective GTP-dependent initiation of protein translation, which can be rescued by administration of purine precursors. These data suggest AMPD2-related PCH as a potentially treatable early-onset neurodegenerative disease.

In-silico identification of putatively functional intergenic small open reading frames in the cucumber genome and their predicted response to biotic and abiotic stresses.

The availability of high-throughput sequencing technologies increased our understanding of different genomes. However, the genomes of all living organisms still have many unidentified coding sequences. The increased number of missing small open reading frames (sORFs) is due to the length threshold used in most gene identification tools, which is true in the genic and, more importantly and surprisingly, in the intergenic regions. Scanning the cucumber genome intergenic regions revealed 420 723 sORF. We excluded 3850 sORF with similarities to annotated cucumber proteins. To propose the functionality of the remaining 416 873 sORF, we calculated their codon adaptation index (CAI). We found 398 937 novel sORF (nsORF) with CAI ≥ 0.7 that were further used for downstream analysis. Searching against the Rfam database revealed 109 nsORFs similar to multiple RNA families. Using SignalP-5.0 and NLS, identified 11 592 signal peptides. Five predicted proteins interacting with Meloidogyne incognita and Powdery mildew proteins were selected using published transcriptome data of host-pathogen interactions. Gene ontology enrichment interpreted the function of those proteins, illustrating that nsORFs' expression could contribute to the cucumber's response to biotic and abiotic stresses. This research highlights the importance of previously overlooked nsORFs in the cucumber genome and provides novel insights into their potential functions.

Unveiling new thiazole-clubbed piperazine derivatives as multitarget anti-AD: Design, synthesis, and in silico studies.

New thiazole-clubbed piperazine derivatives were designed, synthesized, evaluated for their inhibitory capabilities against human acetylcholinesterase and butyrylcholinesterase (hAChE and/or hBuChE) and ß-amyloid (Aß) aggregation, and investigated for their metal chelating potential as multitarget agents for the treatment of Alzheimer's disease. Compounds 10, 19-21, and 24 showed the highest hAChE inhibitory activity at submicromolar concentrations, of which compound 10 was the most potent with a half-maximal inhibitory concentration (IC50) value of 0.151 µM. Compounds 10 and 20 showed the best hBuChE inhibitory activities (IC50 values of 0.135 and 0.103 µM, respectively), in addition to remarkable Aß1-42 aggregation inhibitory activities and metal chelating capabilities. Both compounds were further evaluated against human neuroblastoma SH-SY5Y and PC12 neuronal cells, where they proved noncytotoxic at their active concentrations against hAChE or hBuChE. They also offered a significant neuroprotective effect against Aß25-35-induced cytotoxicity in human neuroblastoma SH-SY5Y cells. Compound 10 displayed acceptable physicochemical properties and could pass the blood-brain barrier. The molecular docking study revealed the good binding interactions of compound 10 with the key amino acids of both the catalytic active site and the peripheral anionic site of hAChE, explaining its significant potency.

Evaluation of a new series of pyrazole derivatives as a potent epidermal growth factor receptor inhibitory activity: QSAR modeling using quantum-chemical descriptors.

Pyrazole derivatives correspond to a family of heterocycle molecules with important pharmacological and physiological applications. At present, we perform a density functional theory (DFT) calculations and a quantitative structure-activity relationship (QSAR) evaluation on a series of 1-(4,5-dihydro-1H-pyrazol-1-yl) ethan-1-one and 4,5-dihydro-1H-pyrazole-1-carbothioamide derivatives as an epidermal growth factor receptor (EGFR) inhibitory activity. We thus propose a virtual screening protocol based on a machine-learning study. This theoretical model relates the studied compounds' biological activity to their calculated physicochemical descriptors. Moreover, the linear regression function is used to validate the model via the evaluation of Q2ext and Q2cv parameters for external and internal validations, respectively. Our QSAR model shows a good correlation between observed activities IC50 and predicted ones. Our model allows us to mitigate time-consuming problems and waste chemical and biological products in the preclinical phases.

Real-Time Human Recognition at Night via Integrated Face and Gait Recognition Technologies.

Human recognition technology is a task that determines the people existing in images with the purpose of identifying them. However, automatic human recognition at night is still a challenge because of its need to align requirements with a high accuracy rate and speed. This article aims to design a novel approach that applies integrated face and gait analyses to enhance the performance of real-time human recognition in TIR images at night under various walking conditions. Therefore, a new network is proposed to improve the YOLOv3 model by fusing face and gait classifiers to identify individuals automatically. This network optimizes the TIR images, provides more accurate features (face, gait, and body segment) of the person, and possesses it through the PDM-Net to detect the person class; then, PRM-Net classifies the images for human recognition. The proposed methodology uses accurate features to form the face and gait signatures by applying the YOLO-face algorithm and YOLO algorithm. This approach was pre-trained on three night (DHU Night, FLIR, and KAIST) databases to simulate realistic conditions during the surveillance-protecting areas. The experimental results determined that the proposed method is superior to other results-related methods in the same night databases in accuracy and detection time.

Horizontal Review on Video Surveillance for Smart Cities: Edge Devices, Applications, Datasets, and Future Trends.

The automation strategy of today's smart cities relies on large IoT (internet of Things) systems that collect big data analytics to gain insights. Although there have been recent reviews in this field, there is a remarkable gap that addresses four sides of the problem. Namely, the application of video surveillance in smart cities, algorithms, datasets, and embedded systems. In this paper, we discuss the latest datasets used, the algorithms used, and the recent advances in embedded systems to form edge vision computing are introduced. Moreover, future trends and challenges are addressed.

Relation of Serum Ferritin Level with Serum Hepcidin and Fucose Levels in Children with ß-Thalassemia Major.

The aim of this study was to assess serum ferritin, hepcidin, L-fucose, and protein binding fucose levels in ß-thalassemia major (ß-TM) patients and to correlate the serum ferritin level with hepcidin and fucose levels. A total 70 (26 males and 44 females) children with ß-TM, ages ranging from 5 to 16 years (mean age 8.3 ± 2.7 years) and 50 (25 males and 25 females) apparently healthy subjects with matching age and sex were included as a control group. An especially designed questionnaire was used to collect age, gender, body mass index (BMI), hemoglobin (Hb), serum ferritin, hepcidin-25 peptide, α-L-fucose, and protein binding fucose (PBF) levels. ß-Thalassemia major patients had significantly (p < 0.05) higher serum ferritin, fucose and PBF levels, but the serum hepcidin level was significantly (p < 0.05) lower when compared to the controls, and their levels were affected by the gender of the ß-TM patients, as it was significantly (p < 0.05) higher in female in comparison to male patients. There was no significant (p > 0.05) correlation between serum ferritin with hepcidin and fucose levels as a marker of iron overload in ß-TM. The regulation of hepcidin, and L-fucose levels in patients with ß-TM is more affected by erythropoeitic activity than by iron overload, as there was no significant correlation between serum ferritin with hepcidin and fucose levels as a marker of iron overload in ß-TM.

Mutations in EBF3 Disturb Transcriptional Profiles and Cause Intellectual Disability, Ataxia, and Facial Dysmorphism.

From a GeneMatcher-enabled international collaboration, we identified ten individuals affected by intellectual disability, speech delay, ataxia, and facial dysmorphism and carrying a deleterious EBF3 variant detected by whole-exome sequencing. One 9-bp duplication and one splice-site, five missense, and two nonsense variants in EBF3 were found; the mutations occurred de novo in eight individuals, and the missense variant c.625C>T (p.Arg209Trp) was inherited by two affected siblings from their healthy mother, who is mosaic. EBF3 belongs to the early B cell factor family (also known as Olf, COE, or O/E) and is a transcription factor involved in neuronal differentiation and maturation. Structural assessment predicted that the five amino acid substitutions have damaging effects on DNA binding of EBF3. Transient expression of EBF3 mutant proteins in HEK293T cells revealed mislocalization of all but one mutant in the cytoplasm, as well as nuclear localization. By transactivation assays, all EBF3 mutants showed significantly reduced or no ability to activate transcription of the reporter gene CDKN1A, and in situ subcellular fractionation experiments demonstrated that EBF3 mutant proteins were less tightly associated with chromatin. Finally, in RNA-seq and ChIP-seq experiments, EBF3 acted as a transcriptional regulator, and mutant EBF3 had reduced genome-wide DNA binding and gene-regulatory activity. Our findings demonstrate that variants disrupting EBF3-mediated transcriptional regulation cause intellectual disability and developmental delay and are present in ∼0.1% of individuals with unexplained neurodevelopmental disorders.

Liver Tumor Segmentation in CT Scans Using Modified SegNet.

The main cause of death related to cancer worldwide is from hepatic cancer. Detection of hepatic cancer early using computed tomography (CT) could prevent millions of patients' death every year. However, reading hundreds or even tens of those CT scans is an enormous burden for radiologists. Therefore, there is an immediate need is to read, detect, and evaluate CT scans automatically, quickly, and accurately. However, liver segmentation and extraction from the CT scans is a bottleneck for any system, and is still a challenging problem. In this work, a deep learning-based technique that was proposed for semantic pixel-wise classification of road scenes is adopted and modified to fit liver CT segmentation and classification. The architecture of the deep convolutional encoder-decoder is named SegNet, and consists of a hierarchical correspondence of encode-decoder layers. The proposed architecture was tested on a standard dataset for liver CT scans and achieved tumor accuracy of up to 99.9% in the training phase.

Microbacterium suaedae sp. nov., isolated from Suaeda aralocaspica.

Two bacterial strains, YZYP 306T and YZGP 509, were isolated from the halophyte Suaeda aralocaspica collected from the southern edge of the Gurbantunggut desert, north-west China. Cells were Gram-stain-positive, aerobic, non-motile, short rods. Strain YZYP 306T grew at 4-40 °C, while strain YZGP 509 grew at 4-42 °C, with optimum growth at 28 °C, and they both grew at pH 6.0-12.0 and 0-15 % (w/v) NaCl. Phylogenetic analyses of the 16S rRNA gene sequences placed the two strains within the genus Microbacterium with the highest similarities to Microbacterium indicum BBH6T (97.8 %) and Microbacterium sorbitolivorans SZDIS-1-1T (97.2 %). The average nucleotide identity value between YZYP 306T and M. indicum BBH6T was 78.3 %. The genomic DNA G+C contents of strains YZYP 306T and YZGP 509 were 68.49 and 68.53 mol%, respectively. The characteristic cell-wall amino acid was ornithine. Whole-cell sugars were galactose, mannose and ribose. The acyl type of the peptidoglycan was glycolyl. The major cellular fatty acids were anteiso-C15 : 0, anteiso-C17 : 0 and iso-C16 : 0. The major menaquinones were MK-10 and MK-11. The polar lipids were diphosphatidylglycerol, phosphatidylglycerol, an unidentified phospholipid and an unidentified glycolipid. These results are consistent with the classification of the two strains into the genus Microbacterium. On the basis of the evidence presented in this study, strains YZYP 306T and YZGP 509 are representatives of a novel species in the genus Microbacterium, for which the name Microbacterium suaedae sp. nov. is proposed. The type strain is YZYP 306T (=CGMCC 1.16261T=KCTC 49101T).

Design, synthesis, and docking study of new quinoline derivatives as antitumor agents.

New quinolines substituted with various heterocycles and chalcone moieties were synthesized and evaluated as antitumor agents. All the synthesized compounds were in vitro screened against 60 human cancer cell lines. Compound 13 showed the highest cytotoxicity toward 58 cell lines, exhibiting distinct growth inhibition values (GI50 ) against the majority of them, including SR, HL-60 (TB) strains (leukemia), and MDA-MB-435 strains (melanoma), with GI50 values of 0.232, 0.260, and 0.300 µM, respectively. It exhibited great selectivity toward cancer cell lines, with less toxic effect against normal cells represented by skin fibroblast (BJ) and breast epithelial cell lines (MCF-10F). The enzyme inhibitory activity of compound 13 was evaluated against topoisomerase 1 (Topo 1), epidermal growth factor receptor and vascular endothelial growth factor receptor 2, where it displayed worthy Topo 1 inhibition activity with an IC50 value of 0.278 µM compared with camptothecin as a reference drug (IC50 0.224 µM). Docking studies were performed to investigate the recognition profile of compound 13 with the Topo 1 enzyme binding site.

MPV17-related mitochondrial DNA maintenance defect: New cases and review of clinical, biochemical, and molecular aspects.

Mitochondrial DNA (mtDNA) maintenance defects are a group of diseases caused by deficiency of proteins involved in mtDNA synthesis, mitochondrial nucleotide supply, or mitochondrial dynamics. One of the mtDNA maintenance proteins is MPV17, which is a mitochondrial inner membrane protein involved in importing deoxynucleotides into the mitochondria. In 2006, pathogenic variants in MPV17 were first reported to cause infantile-onset hepatocerebral mtDNA depletion syndrome and Navajo neurohepatopathy. To date, 75 individuals with MPV17-related mtDNA maintenance defect have been reported with 39 different MPV17 pathogenic variants. In this report, we present an additional 25 affected individuals with nine novel MPV17 pathogenic variants. We summarize the clinical features of all 100 affected individuals and review the total 48 MPV17 pathogenic variants. The vast majority of affected individuals presented with an early-onset encephalohepatopathic disease characterized by hepatic and neurological manifestations, failure to thrive, lactic acidemia, and mtDNA depletion detected mainly in liver tissue. Rarely, MPV17 deficiency can cause a late-onset neuromyopathic disease characterized by myopathy and peripheral neuropathy with no or minimal liver involvement. Approximately half of the MPV17 pathogenic variants are missense. A genotype with biallelic missense variants, in particular homozygous p.R50Q, p.P98L, and p.R41Q, can carry a relatively better prognosis.

Microbacterium halophytorum sp. nov., a novel endophytic actinobacterium isolated from halophytes.

Two actinobacterial strains, YJYP 303T and YZYP 518, were isolated from two species of halophytes collected from the southern edge of the Gurbantunggut Desert. Cells were Gram-stain-positive, aerobic, short rods and without flagella. Growth of the two strains was found to occur at 4-44 °C, pH 6.0-12.0 and in the presence of up to 15 % (w/v) NaCl. Phylogenetic analysis based on 16S rRNA gene sequences indicated that the two strains are associated with members of the genus Microbacterium. In the phylogenetic tree, the two strains shared a clade with Microbacterium halotolerans YIM 70130T (97.58 % 16S rRNA gene sequence identity) and Microbacterium populi KCTC 29152T (96.54 %). The average nucleotide identity values of strain YJYP 303T and YZYP 518 to M. halotolerans YIM 70130T were determined to be 79.97 and 80.03 %, respectively. The genomic DNA G+C contents of strains YJYP 303T and YZYP 518 were 69.72 and 70.57 %, respectively. The major fatty acids were anteiso-C15 : 0, anteiso-C17 : 0 and iso-C16 : 0. The predominant respiratory quinones was MK-11, followed by MK-10 and MK-12. The muramic acid type of peptidoglycan was N-glycolyl. The whole-cell sugars were mannose, ribose, rhamnose, glucose, galactose and two unidentified sugars. The cell-wall amino acids were glutamic acid, ornithine, glycine and alanine. The polar lipids were diphosphatidylglycerol, phosphatidylglycerol, an unidentified phospholipid and an unidentified glycolipid. On the basis of the evidence presented in this study, strains YJYP 303T and YZYP 518 are characterized as members of a novel species in the genus Microbacterium, for which the name Microbacteriumhalophytorum sp. nov. is proposed. The type strain is YJYP 303T (=CGMCC 1.16264T=KCTC 49100T).

Propionicimonas ferrireducens sp. nov., isolated from dissimilatory iron(III)-reducing microbial enrichment obtained from paddy soil.

A novel strain, designated Y1A-10 4-9-1T, with Gram-stain-positive and rod-shaped cells, was isolated from paddy soil in Yingtan, Jiangxi, China. Cells were 0.15-0.2 µm wide and 1.5-3.3 µm long. The optimal growth temperature was 30 °C and the optimal pH was 7.0. Phylogenetic analysis based on 16S rRNA gene sequences indicated that the novel strain is closely related to Propionicimonas paludicola JCM 11933T (98.57 %). The genomic DNA G+C content was 63.9 mol%. The predominant menaquinone was MK-9(H4) and meso-diaminopimelic acid was present in the cell-wall peptidoglycan layer. The major polar lipids were diphosphatidylglycerol, one unidentified phospholipid and two unidentified lipids. The dominant cellular fatty acids detected were anteiso-C15 : 0 and iso-C16 : 0. The phylogenetic and phenotypic results supported that strain Y1A-10 4-9-1T is a novel species of the genus Propionicimonas, for which the name Propionicimonas ferrireducens sp. nov. is proposed. The type strain is Y1A-10 4-9-1T (=CCTCC AB 2016249T=KCTC 15566T=LMG 29810T).

Saccharopolyspora deserti sp. nov., a novel halotolerant actinobacterium isolated from a desert.

Strain SYSU D8010T was isolated from a desert sand sample collected in Saudi Arabia. The taxonomic position of the isolate was investigated by the polyphasic taxonomic approach. The isolate was found to be Gram-positive and aerobic. The strain was able to grow at 14-40 °C, pH 5.0-9.0 and in the presence of up to 22 % (w/v) NaCl. Strain SYSU D8010T contained meso-diaminopimelic acid as cell-wall diamino acid, and arabinose, fucose, galactose, glucose and rhamnose as the whole-cell sugars. The primary polar lipids were diphosphatidylglycerol, phosphatidylcholine, phosphatidylglycerol, phosphatidylinositol and phosphatidylinositolmannosides. Menaquinone MK-9(H4) was detected as the respiratory quinone; and anteiso-C17 : 0, iso-C16 : 0, iso-C15 : 0 and iso-C17 : 0 as the predominant fatty acids. Pairwise comparison of the 16S rRNA gene sequences indicated that strain SYSU D8010T had a sequence similarity of 97.8 % to Saccharopolyspora halophila YIM 90500T. The genomic DNA G+C content of strain SYSU D8010T was determined to be 69.9 mol%. Based on the analyses of the phenotypic, genotypic and phylogenetic characteristics, strain SYSU D8010T was determined to represent a novel species of the genus Saccharopolyspora, for which the name Saccharopolyspora deserti sp. nov. is proposed. The type strain of the species is SYSU D8010T (=KCTC 39989T=CPCC 204620T).

Molecular and clinical spectra of FBXL4 deficiency.

F-box and leucine-rich repeat protein 4 (FBXL4) is a mitochondrial protein whose exact function is not yet known. However, cellular studies have suggested that it plays significant roles in mitochondrial bioenergetics, mitochondrial DNA (mtDNA) maintenance, and mitochondrial dynamics. Biallelic pathogenic variants in FBXL4 are associated with an encephalopathic mtDNA maintenance defect syndrome that is a multisystem disease characterized by lactic acidemia, developmental delay, and hypotonia. Other features are feeding difficulties, growth failure, microcephaly, hyperammonemia, seizures, hypertrophic cardiomyopathy, elevated liver transaminases, recurrent infections, variable distinctive facial features, white matter abnormalities and cerebral atrophy found in neuroimaging, combined deficiencies of multiple electron transport complexes, and mtDNA depletion. Since its initial description in 2013, 36 different pathogenic variants in FBXL4 were reported in 50 affected individuals. In this report, we present 37 additional affected individuals and 11 previously unreported pathogenic variants. We summarize the clinical features of all 87 individuals with FBXL4-related mtDNA maintenance defect, review FBXL4 structure and function, map the 47 pathogenic variants onto the gene structure to assess the variants distribution, and investigate the genotype-phenotype correlation. Finally, we provide future directions to understand the disease mechanism and identify treatment strategies.

Phenylobacterium deserti sp. nov., isolated from desert soil.

A novel bacterial strain, designated YIM 73061T, was isolated from the Cholistan desert in Punjab, Pakistan, and characterized by using a polyphasic taxonomic approach. 16S rRNA gene sequence analysis revealed the highest levels of sequence similarity with respect to Phenylobacterium conjunctum FWC21T (97.6 %), Phenylobacterium lituiforme FaiI3T (97.4 %), Phenylobacteriumcomposti 4T-6T (97.0 %) and Phenylobacterium aquaticum W2-3-4T (96.8 %). Cells were Gram-stain-negative, aerobic and motile rods that formed orange colonies. The strain was oxidase- and catalase-positive. Growth occurred at 20-40 °C (optimum, 30-37 °C) at pH 5.0-8.0 (optimum, pH 7.0) and with 0-1 % (w/v) NaCl (optimum, 0-0.5 %). The major cellular fatty acids (>10 %) were summed feature 8 (comprising C18 : 1ω7c and/or C18 : 1ω6c) and C16 : 0. The polar lipid profile consisted of phosphatidylglycerol and four unidentified glycolipids. The major isoprenoid quinone was ubiquinone-10 (Q-10). The G+C content of the genomic DNA was 66.8 mol%. Strain YIM 73061T showed low levels of DNA-DNA relatedness to P. conjunctum FWC21T (27.2±2.6 %), P. lituiforme FaiI3T (24.6±1.1 %) and P.composti 4T-6T (18.4±3.1 %). On the basis of phylogenetic inference, chemotaxonomic characteristics and phenotypic data, strain YIM 73061T should be classified as representing a novel species, for which the name Phenylobacterium deserti sp. nov. is proposed. The type strain is YIM 73061T (=DSM 103871T=CCTCC AB 2016297T).

Termination of a long RP supraventricular tachycardia by carotid sinus massage.

Carotid sinus massage is a useful diagnostic and therapeutic maneuver in patients with supraventricular tachycardia. Abrupt tachycardia termination with carotid sinus massage typically indicates a mechanism dependent on the atrioventricular node. Here, we present the case of a 79-year-old patient presenting with a long-RP supraventricular tachycardia terminated with carotid sinus massage that was proven invasively to be due to a focal atrial tachycardia. We discuss mechanistic explanations for this unusual phenomenon and review the literature.

Frigoribacterium endophyticum sp. nov., an endophytic actinobacterium isolated from the root of Anabasis elatior (C. A. Mey.) Schischk.

A novel endophytic actinobacterium, designated EGI 6500707(T), was isolated from the surface-sterilized root of a halophyte Anabasis elatior (C. A. Mey.) Schischk collected from Urumqi, Xinjiang province, north-west China, and characterized using a polyphasic approach. Cells were Gram-stain-positive, non-motile, short rods and produced white colonies. Growth occurred at 10-45 °C (optimum 25-30 °C), at pH 5-10 (optimum pH 8) and in presence of 0-4% (w/v) NaCl (optimum 0-3%). The predominant menaquinone was MK-9. The diagnostic phospholipids were diphosphatidylglycerol and phosphatidylglycerol. The major fatty acids were anteiso-C(15 : 0), anteiso-C(17 : 0) and iso-C(16 : 0). The DNA G+C content of strain EGI 6500707(T) was 69.1 mol%. Phylogenetic analyses based on 16S rRNA gene sequences showed that strain EGI 6500707(T) should be placed in the genus Frigoribacterium (family Microbacteriaceae , phylum Actinobacteria ), and that the novel strain exhibited the highest 16S rRNA gene sequence similarity to Frigoribacterium faeni JCM 11265(T) (99.1%) and Frigoribacterium mesophilum MSL-08(T) (96.5%). DNA-DNA relatedness between strain EGI 6500707(T) and F. faeni JCM 11265(T) was 47.2%. On the basis of phenotypic and chemotaxonomic characteristics, phylogenetic analysis and DNA-DNA relatedness data, strain EGI 6500707(T) represents a novel species of the genus Frigoribacterium , for which the name Frigoribacterium endophyticum sp. nov. is proposed. The type strain is EGI 6500707(T) ( = JCM 30093(T) = KCTC 29493(T)).