Miracle-dz/UniFAR-FTUs huggingface dataset:
The Evolution of Gene Therapy in the Treatment of Metabolic Liver Diseases

Monogenic metabolic disorders of hepatic origin number in the hundreds, and for many, liver transplantation remains the only cure. Liver-targeted gene therapy is an attractive treatment modality for many of these conditions, and there have been significant advances at both the preclinical and clinical stages. Viral vectors, including retroviruses, lentiviruses, adenovirus-based vectors, adeno-associated viruses and simian virus 40, have differing safety, efficacy and immunogenic profiles, and several of these have been used in clinical trials with variable success. In this review, we profile viral vectors and non-viral vectors, together with various payloads, including emerging therapies based on RNA, that are entering clinical trials. Genome editing technologies are explored, from earlier to more recent novel approaches that are more efficient, specific and safe in reaching their target sites. The various curative approaches for the multitude of monogenic hepatic metabolic disorders currently at the clinical development stage portend a favorable outlook for this class of genetic disorders.
Micromachining of Biolox Forte Ceramic Utilizing Combined Laser/Ultrasonic Processes

Micromachining has gained considerable interest across a wide range of applications. It ensures the production of microfeatures such as microchannels, micropockets, etc. Typically, the manufacturing of microchannels in bioceramics is a demanding task. The ubiquitous technologies, laser beam machining (LBM) and rotary ultrasonic machining (RUM), have tremendous potential. However, again, these machining methods do have inherent problems. LBM has issues concerning thermal damage, high surface roughness, and vulnerable dimensional accuracy. Likewise, RUM is associated with high machining costs and low material-removal rates. To overcome their limits, a synthesis of LBM and RUM processes known as laser rotary ultrasonic machining (LRUM) has been conceived. The bioceramic known as biolox forte was utilized in this investigation. The approach encompasses the exploratory study of the effects of fundamental input process parameters of LBM and RUM on the surface quality, machining time, and dimensional accuracy of the manufactured microchannels. The performance of LRUM was analyzed and the mechanism of LRUM tool wear was also investigated. The results revealed that the surface roughness, depth error, and width error is decreased by 88%, 70%, and 80% respectively in the LRUM process. Moreover, the machining time of LRUM is reduced by 85%.
Pain-CKB, A Pain-Domain-Specific Chemogenomics Knowledgebase for Target Identification and Systems Pharmacology Research

A traditional single-target analgesic, though it may be highly selective and potent, may not be sufficient to effectively mitigate pain. An alternative strategy is to seek simultaneous modulation at multiple nodes in the network of pain signalling pathways through a multi-target analgesic or drug combinations. Here, we present a comprehensive pain domain-specific chemogenomics knowledgebase (Pain-CKB) with integrated computing tools for target identification and systems pharmacology research. Pain-CKB is constructed on basis of our established chemogenomics technology with new features, including multiple-compound support, multi-cavity protein support and customizable symbol display. The determination of bioactivity is also revised to avoid the use of complex machine learning models. Our one-stop computing platform describes the chemical molecules, genes, and proteins involved in pain regulation. To date, Pain-CKB archived 272 analgesics in the market, 84 pain-related targets with 207 available 3D crystal or cryo-EM structures, and 234,662 chemical agents reported for these target proteins. Moreover, Pain-CKB is implemented with user-friendly web-interfaced computing tools and applications for the prediction and analysis of the relevant protein targets and visualization of the outputs, including HTDocking, TargetHunter, BBB predictor, NGL viewer, Spider Plot, etc. The Pain-CKB server is accessible at https://www.cbligand. org/g/pain-ckb.
An acetylcholine‐dopamine interaction in the nucleus accumbens and its involvement in ethanol's dopamine‐releasing effect

Alcohol use disorder is a chronic, relapsing brain disorder causing substantial morbidity and mortality. Cholinergic interneurons (CIN) within the nucleus accumbens (nAc) have been suggested to exert a regulatory impact on dopamine (DA) neurotransmission locally, and defects in CIN have been implied in several psychiatric disorders. The aim of this study was to investigate the role of CIN in regulation of basal extracellular levels of DA and in modulation of nAc DA release following ethanol administration locally within the nAc of male Wistar rats. Using reversed in vivo microdialysis, the acetylcholinesterase inhibitor physostigmine was administered locally in the nAc followed by addition of either the muscarinic acetylcholine (ACh) receptor antagonist scopolamine or the nicotinic ACh receptor antagonist mecamylamine. Further, ethanol was locally perfused in the nAc following pretreatment with scopolamine and/or mecamylamine. Lastly, ethanol was administered locally into the nAc of animals with accumbal CIN‐ablation induced by anticholine acetyl transferase‐saporin. Physostigmine increased accumbal DA levels via activation of muscarinic ACh receptors. Neither scopolamine and/or mecamylamine nor CIN‐ablation altered basal DA levels, suggesting that extracellular DA levels are not tonically controlled by ACh in the nAc. In contrast, ethanol‐induced DA elevation was prevented following coadministration of scopolamine and mecamylamine and blunted in CIN‐ablated animals, suggesting involvement of CIN‐ACh in ethanol‐mediated DA signaling. The data presented in this study suggest that basal extracellular levels of DA within the nAc are not sustained by ACh, whereas accumbal CIN‐ACh is involved in mediating ethanol‐induced DA release.
Can serum periostin, YKL‐40, and osteopontin levels in pre‐school children with recurrent wheezing predict later development of asthma?

Currently, there are no reliable clinical tools available for predicting asthma in pre–school‐aged children with recurrent wheezing. The aim of this study was to evaluate the usefulness of serum periostin, YKL‐40, and osteopontin biomarkers in wheezy pre–school‐aged children for predicting the development of asthma in school ages.
The Response of Red Clover (Trifolium pratense L.) to Separate and Mixed Inoculations with Rhizobium leguminosarum and Azospirillum brasilense in Presence of Polycyclic Aromatic Hydrocarbons

This study aimed to evaluate the impact of co-inoculation Rhizobium sp. and Azospirillum sp. on plant (Trifolium pratense L.) growth in the presence of polycyclic aromatic hydrocarbon (PAH) contamination (anthracene, phenanthrene, and pyrene). Eight strains from the genus Rhizobium leguminosarum bv. trifolii were selected for biotest analysis. Two methods of inoculation were used in the chamber experiment: (1) R. leguminosarum alone and (2) a combined inoculant (R. leguminosarum and Azospirillum brasilense). For comparison, non-contaminated controls were also used. The results demonstrated that co-inoculation of plants with Rhizobium and Azospirillum resulted in more root and shoot biomass than in plants inoculated with R. leguminosarum alone. The results indicated that application of a co-inoculation of bacteria from Rhizobium and Azospirillum species had a positive effect on clover nodulation and growth under the condition of PAH contamination.
Novel insights into the function of CD24: A driving force in cancer

CD24 is a highly glycosylated protein with a small protein core that is linked to the plasma membrane via a glycosyl‐phosphatidylinositol anchor. CD24 is primarily expressed by immune cells but is often overexpressed in human tumors. In cancer, CD24 is a regulator of cell migration, invasion and proliferation. Its expression is associated with poor prognosis and it is used as cancer stemness marker. Recently, CD24 on tumor cells was identified as a phagocytic inhibitor (“do not eat me” signal) having a suppressive role in tumor immunity via binding to Siglec‐10 on macrophages. This finding is reminiscent of the demonstration that soluble CD24‐Fc can dampen the immune system in autoimmune disease. In the present review, we summarize recent progress on the role of the CD24‐Siglec‐10 binding axis at the interface between tumor cells and the immune system, and the role of CD24 genetic polymorphisms in cancer. We describe the specific function of cytoplasmic CD24 and discuss the presence of CD24 on tumor‐released extracellular vesicles. Finally, we evaluate the potential of CD24‐based immunotherapy.
Two novel PDE6C gene mutations in Chinese family with achromatopsia

ABSTRACT Background: Achromatopsia (ACHM) is an inherited retinal disease affecting the cone cell function. To date, six pathogenic genes of ACHM have been identified. However, the diagnostic and therapeutic methods of this disorder remain limited. Herein, to characterize the clinical features and genetic causes of three affected siblings in a Chinese family with ACHM, we used target next-generation sequencing (NGS) and found new pathogenic factors associated with ACHM in this family. Materials and methods: Three patients with ACHM and three healthy family members were included in this study. All participants received comprehensive ophthalmic tests. NGS approach was performed on the patients to determine the causative mutation for this family. The silico analysis was also applied to predict the pathogenesis of identified mutations. Results: Genetic assessments revealed compound heterozygous mutations of the PDE6C gene (c.1413 + 1 G > C, c.305 G > A), carried by all three patients. Both mutations were novel and predicted to be deleterious by six types of online predictive software. The heterozygous PDE6C missense mutation (c.305 G > A) was found from the mother and the heterozygous PDE6C splice site mutation (c.1413 + 1 G > C) was found in the father and all the children. All patients in the family showed typical signs and symptoms of ACHM. Conclusions: We report novel compound heterozygous PDE6C mutations in causing ACHM and further confirm the clinical diagnosis. Our study extends the genotypic spectrums for PDE6C-ACHM and better illustrates its genotype–phenotype correlations, which would help the ACHM patients with better genetic diagnosis, prognosis, and gene treatment.
Diagnostic testing for ocular myasthenia gravis

Single-fiber EMG (SFEMG) is a highly sensitive test for ocular myasthenia gravis (OMG) that provides quantitative measurement of neuromuscular transmission.1,2 It plays a pivotal role in diagnosing patients with OMG because serologic testing is positive in <50% of patients with OMG. Repetitive nerve stimulation (RNS) is even less sensitive than antibody testing, with abnormal findings in only one-third of patients with OMG.3 In contrast, SFEMG is rarely needed for generalized myasthenia gravis because testing for muscle-specific kinase antibodies and lipoprotein receptor-related protein 4 antibodies in addition to acetylcholine receptor (AChR) antibodies allows easy and rapid confirmation of the diagnosis for >90% of patients.4 SFEMG, however, is not a perfect test. Whereas serologic testing is highly specific, abnormal jitter on SFEMG is nonspecific and can be seen in other neurogenic and myopathic disorders. SFEMG can be lengthy, may not be tolerated by all patients, and is available only at specialized centers.
Analysis of melatonin regulation of germination and antioxidant metabolism in different wheat cultivars under polyethylene glycol stress

Melatonin is effective in enhancing various abiotic stress resistances of plants. However, its underlying mechanisms in drought-resistance in winter wheat (Triticum aestivum L.) is not clear. The goal of this work was to investigate the effect of melatonin on seed germination and to evaluate leaf antioxidant physiology for two wheat varieties. Experiments included 20% PEG, melatonin plus 20% PEG and a control using two contrasting wheat varieties (JM22– drought sensitive and HG35– drought resistant). Melatonin levels were 0, 1, 10, 100 and 300 μmol L-1. Results revealed that 300 μmol L-1 of melatonin alleviated the negative effect of water stress on germination and increased radicle length, radicle number, and plumule length of the germinated seeds. Principal component analysis showed a significant change in amino acid content during germination and this change was dependent on melatonin concentration and the variety. Lysine (Lys) content in wheat seeds under the PEG plus 300 μmol L-1 melatonin treatment increased compared with that of the seeds under PEG alone. There was a significant and positive correlation between Lys content and morphological index of germination. During seedling growth, soluble protein was involved in osmotic adjustment and superoxide dismutase (SOD) activity was increased to mitigate the damage in the cytomembrane of JM 22 leaf under 300 μmol L-1 melatonin plus PEG treatment. The effect of melatonin was dependent on SOD activity increasing significantly for HG35—a drought resistant variety. The results of this work lays a foundation for further studies to determine if melatonin can be economically used to mitigate the impact of dry planting conditions on wheat productivity in North China Plain.
Dynamics of Staphylococcus aureus Cas9 in DNA target Association and Dissociation

Staphylococcus aureus Cas9 (SaCas9) is an RNA‐guided endonuclease that targets complementary DNA adjacent to a protospacer adjacent motif (PAM) for cleavage. Its small size facilitates in vivo delivery for genome editing in various organisms. Herein, using single‐molecule and ensemble approaches, we systemically study the mechanism of SaCas9 underlying its interplay with DNA. We find that the DNA binding and cleavage of SaCas9 require complementarities of 6‐ and 18‐bp of PAM‐proximal DNA with guide RNA, respectively. These activities are mediated by two steady interactions among the ternary complex, one of which is located approximately 6 bp from the PAM and beyond the apparent footprint of SaCas9 on DNA. Notably, the other interaction within the protospacer is significantly strong and thus poses DNA‐bound SaCas9 a persistent block to DNA‐tracking motors. Intriguingly, after cleavage, SaCas9 autonomously releases the PAM‐distal DNA while retaining binding to the PAM. This partial DNA release immediately abolishes its strong interaction with the protospacer DNA and consequently promotes its subsequent dissociation from the PAM. Overall, these data provide a dynamic understanding of SaCas9 and instruct its effective applications.
Patterns of Expansion and Expression Divergence of the Polygalacturonase Gene Family in Brassica oleracea

Plant polygalacturonases (PGs) are closely related to cell-separation events during plant growth and development by degrading pectin. Identifying and investigating their diversification of evolution and expression could shed light on research on their function. We conducted sequence, molecular evolution, and gene expression analyses of PG genes in Brassica oleracea. Ninety-nine B. oleracea PGs (BoPGs) were identified and divided into seven clades through phylogenetic analysis. The exon/intron structures and motifs were conserved within, but divergent between, clades. The second conserved domain (GDDC) may be more closely related to the identification of PGs. There were at least 79 common ancestor PGs between Arabidopsis thaliana and B. oleracea. The event of whole genome triplication and tandem duplication played important roles in the rapid expansion of the BoPG gene family, and gene loss may be an important mechanism in the generation of the diversity of BoPGs. By evaluating the expression in five tissues, we found that most of the expressed BoPGs in clades A, B, and E showed ubiquitous expression characteristics, and the expressed BoPGs in clades C, D, and F were mainly responsible for reproduction development. Most of the paralogous gene pairs (76.2%) exhibited divergent expression patterns, indicating that they may have experienced neofunctionalization or subfunctionalization. The cis-elements analysis showed that up to 96 BoPGs contained the hormone response elements in their promoters. In conclusion, our comparative analysis may provide a valuable data foundation for the further functional analysis of BoPGs during the development of B. oleracea.
The Behaviour of Honeybee Foragers when their Colonies are Fed Sugar Syrup

SUMMARYThe increased pollen collection by colonies fed sugar syrup is mostly due to changes in the behaviour of individual foragers. When sugar syrup is provided inside the hive, most of the bees that collect it have not foraged before; they are at that stage of their lives when they would normally receive nectar loads from foragers, and their absence from the entrance area probably discourages the foragers from collecting nectar.
Early life stress facilitates synapse premature unsilencing to enhance AMPA receptor function in the developing hippocampus.

Chronic early life stress (ELS) increases vulnerability to psychopathologies and cognitive deficits in adulthood by disrupting the function of related neural circuits. However, whether this disruption emerges early in the developing brain remains largely unexplored. In the current study, using an established limited-bedding and nesting model of ELS in P2-10 mice, we provide direct evidence that ELS caused early modification of hippocampal glutamatergic synapses in the developing brain. We demonstrated that ELS induced rapid enhancement of AMPA receptor function in hippocampal CA1 pyramidal neurons through a postsynaptic mechanism, and importantly, this was associated with premature unsilencing of NMDA receptor-only silent hippocampal synapses. These results suggest that potentiation of AMPAR function may represent an early mediator of ELS-induced alterations of neural networks in the developing brain and may potentially contribute to subsequent cognitive impairments later in life.
Restocking Natural Beds with Remote-Set Disease-Resistant Oysters in Connecticut: A Field Trial

ABSTRACT Oyster production in Connecticut historically has had large fluctuations due to two major factors: disease epizootics caused by a protozoan parasite multinucleate sphere X (Haplosporidium nelsoni), and long periods without successful natural sets. A field trial was performed to investigate whether the remote set of oysters can be used to restock natural beds during mortalities caused by disease epizootics and lack of recruitment due to periods without sets. Disease-resistant oysters were remote set in a hatchery and placed either in or without biodegradable nets on a natural bed. Aged, clean cultch was used as the control, and the growth, mortality, predation, fouling, and prevalence of disease were monitored for two growing seasons. The oysters grew to market size (3 inches, 76.2 mm) in 15 mo. Predation, due mainly to Atlantic oyster drills Urosalpinx cinerea, and overgrowth of oysters caused a mortality of 72% in the oyster seed during the first growing season. More abundant wild oysters set but fewer fouling organisms landed on the remote-set shells than on the clean cultch. To evaluate the effect of siltation on mortality, the oysters were left on the natural bed instead of being transplanted to growing areas, as is standardly done in commercial shellfishing operations. During the second growing period, siltation caused additional mortality until only 1.5% of the oysters deployed were alive. The method of restocking natural beds in Connecticut with remote-set oyster seed for use by the oyster industry looks promising due to the fast growth of the oyster seed. This experiment also demonstrates the challenges presented by nonharvest oyster restoration activities due to significant siltation-associated mortality.
Correlation of apolipoprocein A5 SNP3 gene single nucleotide polymorphism with coronary artery disease in Chinese

Objective To study the variation of apolipoprotein(Apo) A5 influence un-related Shandong han patients with coronary artery disease(CAD) and lipid disorder.Methods The study was investigated by case-control method. Polymorphism of ApoA5 SNP3 was identified by polymerase chain reaction-restriction fragment length polymorphism(PCRRFLP) and DNA sequence.Results The frequency of the ApoA5 SNP3 TC in CAD patients was significantly higher than that of the control group,and this difference existed after adjustment for age,gender,levels of lipid.In CAD patients,the levels of triglyceride(TG) were significantly elevated in ApoA5 SNP3 TC compared to two other genotype.Conclusions ApoA5 SNP3 maybe a genetic marker for CAD;the variation of ApoA5 SNP3 influence plasma TG.
Perennial Ryegrass Transformed with the Adversity-Resistant Transcription Factor DREB1B Gene

Driven with the adversity-inducible promoter rd29B,two expression vectors carrying the adversity-resistant transcription factor DREB1B gene,pBAC123 and pBAC128,and one selection marker,bar gene were constructed.By means of PDS1000/He,the expression vectors were separately transformed into the calluses of mature embryos of Topgun,a perennial ryegrass variety(Lolium perenne). Sixty two transgenic plantlets were obtained from the callused by bialaphos resistance selection and regeneration culture.PCR and Dot-blotting tests showed that DREB1B gene has been transformed into the genomes in some of the transgenic plants.after the leaves of the ryegrass plants were smeared with bialaphos at five different concentrations,the non-transgenic plants appeared not resistant and the transgenic plants appeared resistant to bialaphos at the concentration as high as 135～200 mg/L.Proline determination showed that treated with 15% PEG8000,the transgenic plants had a proline content in their leaves that was about one times higher than that in the leaves of the non-transgenic plants.Under drought in growth chamber for 25 days,there were five transgenic plants left alive of which,three returned to their normal growth after they were watered.It was shown that the enhanced expression of exogenous DREB1B gene was capable of improving the drought resistance of ryegrass.
Identification and characterization of resistance gene analogs (RGA) from castor (Ricinus communis L.) for Fusarium wilt

"“Identification and characterization of resistance gene analogs (RGA) from castor (Ricinus communis L.) for Fusarium wilt. ” Name of student Major Advisor Mr. KAPADIA CHINTAN VIKRAM Dr . M. K.MAHATMA Department of Biotechnology N.M College of Agriculture Navsari Agricultural University Navsari396 450.