A noncoding variant confers pancreatic differentiation defect and contributes to diabetes susceptibility by recruiting RXRA.

Human genetics analysis has identified many noncoding SNPs associated with diabetic traits, but whether and how these variants contribute to diabetes is largely unknown. Here, we focus on a noncoding variant, rs6048205, and report that the risk-G variant impairs the generation of PDX1+/NKX6-1+ pancreatic progenitor cells and further results in the abnormal decrease of functional β cells during pancreatic differentiation. Mechanistically, this risk-G variant greatly enhances RXRA binding and over-activates FOXA2 transcription, specifically in the pancreatic progenitor stage, which in turn represses NKX6-1 expression.

Evaluation of Bonding Behavior between Engineered Geopolymer Composites with Hybrid PE/PVA Fibers and Concrete Substrate.

Engineered geopolymer composites (EGCs) exhibit excellent tensile ductility and crack control ability, making them promising for concrete structure repair. However, their widespread use is limited by high costs of reinforcement fiber and a lack of an EGC-concrete interface bonding mechanism. This study investigated a hybrid PE/PVA fiber-reinforced EGC using domestically produced unoiled PVA fibers to replace commonly used PE fibers.

Astrocytic connexin 43 deletion ameliorates SNI-induced neuropathic pain by reducing microglia activation.

Neuropathic pain (NP) is a chronic disease caused by damage to the peripheral or central nervous system. Connexin 43 (Cx43), the primary connexin expressed by astrocytes, has been reported to be significantly increased in NP. However, the roles and mechanisms of Cx43 in the development and maintenance of NP remain largely unknown, while microglia activation has been commonly regarded as a key factor of NP.

Inducing Global Expression of Actinobacterial Biosynthetic Gene Clusters.

Bacteria produce an impressive array of bioactive specialized metabolites, with Streptomyces (and the actinobacteria more generally) being unusually diverse and prolific producers. However, the biosynthetic potential of these organisms has yet to be fully explored, as many of the biosynthetic gene clusters that direct the synthesis of these natural products are transcriptionally silent under laboratory growth conditions. Here, we describe strategies that can be employed to broadly stimulate the expression of biosynthetic gene clusters in Streptomyces and their relatives, follow the transcription of these genes, and assess the antimicrobial activity of the resulting molecules.

Interplay between Nucleoid-Associated Proteins and Transcription Factors in Controlling Specialized Metabolism in .

Lsr2 is a small nucleoid-associated protein found throughout the actinobacteria. Lsr2 functions similarly to the well-studied H-NS, in that it preferentially binds AT-rich sequences and represses gene expression. In Streptomyces venezuelae, Lsr2 represses the expression of many specialized metabolic clusters, including the chloramphenicol antibiotic biosynthetic gene cluster, and deleting leads to significant upregulation of chloramphenicol cluster expression.

MicroRNA-191 regulates differentiation and migration of mesenchymal stem cells and their paracrine effect on angiogenesis.

MicroRNAs (miRNAs) are critical regulators in organ development. Among them, miR-191 is known to be regulated in early embryogenesis and dysregulated in cancer. This role in undifferentiated tissues suggests a possible part of miR-191 also in bone marrow derived mesenchymal stem cells (BMSCs) physiology.

[Questionnaire survey and analysis of implementability of clinical practice guidelines for acupuncture-moxibustion].

The current usage and the existing problems in the implementability of clinical practice guidelines for acupuncture-moxibustion were investigated by questionnaire survey, aiming to provide reference for the development or update of clinical practice guidelines for acupuncture-moxibustion in the future. The results showed most of the acupuncture-moxibustion clinicians did not have a deep understanding of the guidelines, but they had a strong will of uniform standards and related guidelines. Although the published clinical practice guidelines for acupuncture-moxibustion achieved some success, they still had not got rid of the shackles of the previous textbook.

Streptomyces IHF uses multiple interfaces to bind DNA.

Background: Nucleoid associated proteins (NAPs) are essential for chromosome condensation in bacterial cells. Despite being a diverse group, NAPs share two common traits: they are small, oligomeric proteins and their oligomeric state is critical for DNA condensation. Streptomyces coelicolor IHF (sIHF) is an actinobacterial-specific nucleoid-associated protein that despite its name, shares neither sequence nor structural homology with the well-characterized Escherichia coli IHF.

Silencing cryptic specialized metabolism in by the nucleoid-associated protein Lsr2.

Lsr2 is a nucleoid-associated protein conserved throughout the actinobacteria, including the antibiotic-producing species encode paralogous Lsr2 proteins (Lsr2 and Lsr2-like, or LsrL), and we show here that of the two, Lsr2 has greater functional significance. We found that Lsr2 binds AT-rich sequences throughout the chromosome, and broadly represses gene expression. Strikingly, specialized metabolic clusters were over-represented amongst its targets, and the cryptic nature of many of these clusters appears to stem from Lsr2-mediated repression.

Unlocking the trove of metabolic treasures: activating silent biosynthetic gene clusters in bacteria and fungi.

Bacteria and fungi are prolific producers of secondary metabolites, yet they house a multitude of silent biosynthetic gene clusters that are poorly expressed and whose products are unknown or 'cryptic'. Stimulating the expression of these clusters and accessing their associated molecules is a major priority, as they are expected to have a veritable cornucopia of bioactivites. Here, we highlight three strategies that have been the focus of recent developments.

Synthesis and Evaluation of a Chitosan Oligosaccharide-Streptomycin Conjugate against Biofilms.

Microbial biofilms are considerably more resistant to antibiotics than planktonic cells. It has been reported that chitosan coupling with the aminoglycoside antibiotic streptomycin dramatically disrupted biofilms of several Gram-positive bacteria. This finding suggested the application of the covalent conjugate of antimicrobial natural polysaccharides and antibiotics on anti-infection therapy.

New Kid on the Block: LmbU Expands the Repertoire of Specialized Metabolic Regulators in Streptomyces.

has an extensive natural product repertoire, including most of the naturally derived antibiotics. Understanding the control of natural product biosynthesis is central to antibiotic discovery and production optimization. Here, Hou et al.

A selective and label-free strategy for rapid screening of telomere-binding Ligands via fluorescence regulation of DNA/silver nanocluster.

Herein, the conformational switch of G-rich oligonucleotide (GDNA) demonstrated the obvious functional switch of GDNA which was found to significantly affect the fluorescence of the in-situ synthesized DNA/silver nanocluster (DNA-AgNC) in homogeneous solution. We envisioned that the allosteric interaction between GDNA and DNA-AgNC would be possible to be used for screening telomere-binding ligands. A unimolecular probe (12C5TG) is ingeniously designed consisting of three contiguous DNA elements: G-rich telomeric DNA (GDNA) as molecular recognition sequence, T-rich DNA as linker and C-rich DNA as template of DNA-AgNC.

Sensitive detection of intracellular RNA of human telomerase by using graphene oxide as a carrier to deliver the assembly element of hybridization chain reaction.

Since the level of human telomerase RNA (hTR) in tumor cells is higher than that in normal somatic cells, the quantitative assay of hTR is of significant importance in tumor diagnosis. Herein, graphene oxide (GO) was simultaneously exploited as a fluorescence quencher and a carrier of nucleic acid to successfully deliver two hairpin DNA probes of hybridization chain reaction (HCR) into the cancer cell for detecting telomerase RNA based on DNA nanoassembly of HCR. The sticky end of HCR probes could tightly absorb on the surface of GO, resulting in fluorescence quenching of the dye which was tagged at the sticky end of two hairpin probes.

A PCR-free fluorescence strategy for detecting telomerase activity via double amplification strategy.

As a universal tumor biomarker, research on the activity and inhibition of telomerase is of great importance for cancer diagnosis and therapy. Although the telomeric repeat amplification protocol (TRAP) has served as a powerful assay for detecting telomerase activity, its application has been significantly limited by amplification related errors and time-consuming procedure. To address the limitations of PCR-based protocol, a dual amplification fluorescence assay was developed for PCR-free detecting telomerase activity.

A label-free cyclic assembly of G-quadruplex nanowires for cascade amplification detection of T4 polynucleotide kinase activity and inhibition.

Several fluorescence methods have been developed for sensitive detection of PNK activity based on signal amplification techniques, but they need fluorescently labeled DNA probes and superabundant assistant enzymes. We have addressed these limitations and report here a label-free and enzyme-free amplification strategy for sensitively and specifically studying PNK activity and inhibition via hybridization chain reaction (HCR). First, the phosphorylation of hairpin DNA H1 by T4 PNK makes it be specifically digested by lambda exonuclease (λ exo) from 5' to 3' direction to generate a single-stranded initiator which can successively open hairpins H2 and H3 to trigger an autonomous assembly of long DNA nanowires.

Label-free and sensitive detection of T4 polynucleotide kinase activity via coupling DNA strand displacement reaction with enzymatic-aided amplification.

Several fluorescence signal amplification strategies have been developed for sensitive detection of T4 polynucleotide kinase (T4 PNK) activity, but they need fluorescence dye labeled DNA probe. We have addressed the limitation and report here a label-free strategy for sensitive detection of PNK activity by coupling DNA strand displacement reaction with enzymatic-aided amplification. A hairpin oligonucleotide (hpDNA) with blunt ends was used as the substrate for T4 PNK phosphorylation.

[Effectiveness of preoperative autologous plateletpheresis combined with intraoperative autotransfusion on the blood coagulation in orthopaedic patients].

Objective: To investigate the effectiveness of preoperative plateletpheresis combined with intraoperative autotransfusion on the blood coagulation of orthopaedic patients.

Methods: Sixty patients (ASA I-II) undergoing selective orthopaedic surgery were randomized into three groups (n = 20), that is, preoperative plateletpheresis combined with intraoperative autotransfusion for group I, intraoperative autotransfusion for group II, and group III without any managements of blood conservation. Coagulation parameters (prothrombin time, partial thromboplastin time, fibrinogen), hemoglobin and hematocrit values, platelet counts and aggregability were evaluated before the anaesthesia, 10 minutes after plateletpheresis, 10 minutes before the infusion of platelet rich plasma or autologous blood, 10 minutes after infusion, 24 and 48 hours postoperation.