Comparative analysis of piRNA sequences, targets and functions in nematodes

Piwi proteins and Piwi-interacting RNAs (piRNAs) are best known for their roles in suppressing transposons and promoting fertility. Yet piRNA biogenesis and its mechanisms of action differ widely between distantly related species. To better understand the evolution of piRNAs, we characterized the piRNA pathway in C. briggsae, a sibling species of the model organism C. elegans. Our analyses define 25,883 piRNA producing-loci in C. briggsae. piRNA sequences in C. briggsae are extremely divergent from their counterparts in C. elegans, yet both species adopt similar genomic organization that drive piRNA expression. By examining production of Piwi-mediated secondary small RNAs, we identified a set of protein-coding genes that are evolutionarily conserved piRNA targets. In contrast to C. elegans, small RNAs targeting ribosomal RNAs or histone transcripts are not hyper-accumulated in C. briggsae Piwi mutants. Instead, we found that transcripts with few introns are prone to small RNA overamplification. Together our work highlights evolutionary conservation and divergence of the nematode piRNA pathway and provides insights into its role in endogenous gene regulation.</p

Mass Spectrometry and Ion Mobility Characterization of Bioactive Peptide–Synthetic Polymer Conjugates

The bioconjugate BMP2-(PEO-HA)₂, composed of a dendron with two monodisperse poly­(ethylene oxide) (PEO) branches terminated by a hydroxyapatite binding peptide (HA), and a focal point substituted with a bone growth stimulating peptide (BMP2), has been comprehensively characterized by mass spectrometry (MS) methods, encompassing matrix-assisted laser desorption ionization (MALDI), electrospray ionization (ESI), tandem mass spectrometry (MS²), and ion mobility mass spectrometry (IM-MS). MS² experiments using different ion activation techniques validated the sequences of the synthetic, bioactive peptides HA and BMP2, which contained highly basic amino acid residues either at the N-terminus (BMP2) or C-terminus (HA). Application of MALDI-MS, ESI-MS, and IM-MS to the polymer–peptide biomaterial confirmed its composition. Collision cross-section measurements and molecular modeling indicated that BMP2-(PEO-HA)₂ exists in several folded and extended conformations, depending on the degree of protonation. Protonation of all basic sites of the hybrid material nearly doubles its conformational space and accessible surface area

Comparing ROC curves for plasma NT-proBNP in all pediatric patients with sepsis, HF patients with severe sepsis, HF patients with septic shock, and all HF patients with sepsis.

<p>Comparing ROC curves for plasma NT-proBNP in all pediatric patients with sepsis, HF patients with severe sepsis, HF patients with septic shock, and all HF patients with sepsis.</p

Postelectrospinning “Click” Modification of Degradable Amino Acid-Based Poly(ester urea) Nanofibers

Amino acid-based poly­(ester urea)­s (PEU) are emerging as a new class of degradable polymers that have shown promise in regenerative medicine applications. Herein, we report the synthesis of PEUs carrying pendent “clickable” groups on modified tyrosine amino acids. The pendent species include alkyne, azide, alkene, tyrosine–phenol, and ketone groups. PEUs with <i>M</i>_w exceeding to 100K Da were obtained via interfacial polycondensation methods, and the concentration of pendent groups was varied using a copolymerization strategy. The incorporation of derivatizable functionalities is demonstrated using ¹H NMR and UV–vis spectroscopy methods. Electrospinning was used to fabricate PEU nanofibers with a diameters ranging from 350 to 500 nm. The nanofiber matricies possess mechanical strengths suitable for tissue engineering (Young’s modulus: 300 ± 45 MPa; tensile stress: 8.5 ± 1.2 MPa). A series of bioactive peptides and fluorescent molecules were conjugated to the surface of the nanofibers following electrospinning using bio-orthogonal reactions in aqueous media. The ability to derivatize PEUs with biological molecules using translationally relevant chemical methods will significantly expand their use <i>in vitro</i> and <i>in vivo</i>

The median plasma NT-proBNP levels of the sepsis HF, sepsis non-HF, and healthy control groups were 3885 ng/L, 656 ng/Land 226 ng/L, respectively; the differences among them were significant (χ² = 41.87, <i>P</i> < 0.001).

<p>The median plasma NT-proBNP levels of the sepsis HF, sepsis non-HF, and healthy control groups were 3885 ng/L, 656 ng/Land 226 ng/L, respectively; the differences among them were significant (χ² = 41.87, <i>P</i> < 0.001).</p

Image_3_Alterations in vaginal microbiota in uterine fibroids patients with ultrasound-guided high-intensity focused ultrasound ablation.TIF

IntroductionVaginal microbiota dysbiosis is closely related to diseases of the vagina and uterus. Uterine fibroids (UF) are the most common benign neoplasms of the uterus, and increased diversity in vaginal microbial of UF patients. High-intensity focused ultrasound (HIFU) is effective invasive treatment for fibroids in women who are not good surgical candidates. Whether HIFU of uterine fibroids will cause the change in vaginal microbiota has not been reported. We aimed to investigate the vaginal microbiota of UF patients with/without HIFU treatment using 16S rRNA gene sequencing.MethodsVaginal secretions were collected from 77 UF patients (pre-operative and post-operative) and were used for comparative composition, diversity, and richness analyses of microbial communities.ResultsThe microbial α-diversity was significantly lower in the vaginal of UF patients with HIFU treatment. The relative abundance of some pathogenic bacteria of UF patients with HIFU treatment were significantly decreased in the bacterial phylum and genus level. Proteobacteria were found to be significantly upregulated as a biomarker in the HIFU treatment group in our study.ConclusionThese findings might confirm the effectiveness of HIFU treatment from the point of view of microbiota.</p

Image_2_Alterations in vaginal microbiota in uterine fibroids patients with ultrasound-guided high-intensity focused ultrasound ablation.TIF

IntroductionVaginal microbiota dysbiosis is closely related to diseases of the vagina and uterus. Uterine fibroids (UF) are the most common benign neoplasms of the uterus, and increased diversity in vaginal microbial of UF patients. High-intensity focused ultrasound (HIFU) is effective invasive treatment for fibroids in women who are not good surgical candidates. Whether HIFU of uterine fibroids will cause the change in vaginal microbiota has not been reported. We aimed to investigate the vaginal microbiota of UF patients with/without HIFU treatment using 16S rRNA gene sequencing.MethodsVaginal secretions were collected from 77 UF patients (pre-operative and post-operative) and were used for comparative composition, diversity, and richness analyses of microbial communities.ResultsThe microbial α-diversity was significantly lower in the vaginal of UF patients with HIFU treatment. The relative abundance of some pathogenic bacteria of UF patients with HIFU treatment were significantly decreased in the bacterial phylum and genus level. Proteobacteria were found to be significantly upregulated as a biomarker in the HIFU treatment group in our study.ConclusionThese findings might confirm the effectiveness of HIFU treatment from the point of view of microbiota.</p

Image_1_Alterations in vaginal microbiota in uterine fibroids patients with ultrasound-guided high-intensity focused ultrasound ablation.TIF

IntroductionVaginal microbiota dysbiosis is closely related to diseases of the vagina and uterus. Uterine fibroids (UF) are the most common benign neoplasms of the uterus, and increased diversity in vaginal microbial of UF patients. High-intensity focused ultrasound (HIFU) is effective invasive treatment for fibroids in women who are not good surgical candidates. Whether HIFU of uterine fibroids will cause the change in vaginal microbiota has not been reported. We aimed to investigate the vaginal microbiota of UF patients with/without HIFU treatment using 16S rRNA gene sequencing.MethodsVaginal secretions were collected from 77 UF patients (pre-operative and post-operative) and were used for comparative composition, diversity, and richness analyses of microbial communities.ResultsThe microbial α-diversity was significantly lower in the vaginal of UF patients with HIFU treatment. The relative abundance of some pathogenic bacteria of UF patients with HIFU treatment were significantly decreased in the bacterial phylum and genus level. Proteobacteria were found to be significantly upregulated as a biomarker in the HIFU treatment group in our study.ConclusionThese findings might confirm the effectiveness of HIFU treatment from the point of view of microbiota.</p

In the heart Doppler examination, the ejection fractions in HF and non-HF patients with sepsis were 25% ± 10.4% and 65% ± 7.5%, respectively, a significant difference (<i>P</i> < 0.001); the E peak/A peak of the 2 groups were normal and not significantly different (1.4 ± 0.2 cf. 1.6 ± 0.2).

<p>The results suggested a left ventricle systolic dysfunction in all heart failure patients with sepsis.</p

Valency-Dependent Affinity of Bioactive Hydroxyapatite-Binding Dendrons

Hydroxyapatite (HA)-coated surfaces are used widely as stationary phase for protein and enzyme purification, coatings for dental and orthopedic implants, and composite materials for tissue engineering substrates. More advanced applications are envisioned, but progress has been slowed by the limited ability to controllably functionalize the surface of HA with biomolecules in a translationally relevant manner. Herein we report the synthesis and characterization of a series of multivalent, HA-binding peptide bioconjugates with variable valency and tether length which afford the ability to precisely tune the desired binding behavior. The respective binding affinities of the multivalent constructs to HA surface were characterized by quartz crystal microbalance with dissipation monitoring (QCM-D) techniques, and the relationship between dendron structure and binding affinity was revealed. Tetravalent constructs of HA-binding peptides show a 100-fold enhancement in binding affinity compared to HA-binding peptide sequences reported previously. Both biotin and bone morphogenic protein-2 (BMP-2) derivative peptide were successfully linked to the focal point as initial demonstrations