Inaccurate sex and gender narratives have saturated the political landscape, resulting in legal restrictions for people with queer genders. Biology educators can correct these false narratives by teaching scientifically accurate and queer gender and intersex inclusive sex and gender curriculum. Here, we interviewed four undergraduate biology instructors who were working to reform their sex and gender curriculum.
View Article and Find Full Text PDFIntratumoral injections have the potential for enhanced cancer treatment efficacy while reducing costs and systemic exposure. However, intratumoral drug injections can result in substantial off-target leakage and are invisible under standard imaging modalities like ultrasound (US) and x-ray. A thermosensitive poloxamer-based gel for drug delivery was developed that is visible using x-ray imaging (computed tomography (CT), cone beam CT, fluoroscopy), as well as using US by means of integrating perfluorobutane-filled microbubbles (MBs).
View Article and Find Full Text PDFLiver cancer ranks as the fifth leading cause of cancer-related death globally. Direct intratumoral injections of anti-cancer therapeutics may improve therapeutic efficacy and mitigate adverse effects compared to intravenous injections. Some challenges of intratumoral injections are that the liquid drug formulation may not remain localized and have unpredictable volumetric distribution.
View Article and Find Full Text PDFBroad size distributions and poor long-term colloidal stability of microRNA-carrying nanoparticles, especially those formed by polyelectrolyte complexation, represent major hurdles in realizing their clinical translation. Herein, peptide design is used alongside optimized flash nanocomplexation (FNC) to produce uniform peptide-based miRNA particles of exceptional stability that display anticancer activity against mesothelioma in vitro and in vivo. Modulating the content and display of lysine-based charge from small intrinsically disordered peptides used to complex miRNA proves essential in achieving stable colloids.
View Article and Find Full Text PDFLiver cancer ranks as the fifth leading cause of cancer-related death globally. Direct intratumoral injections of anti-cancer therapeutics may improve therapeutic efficacy and mitigate adverse effects compared to intravenous injections. Some challenges of intratumoral injections are that the liquid drug formulation may not remain localized and have unpredictable volumetric distribution.
View Article and Find Full Text PDFPatterns of Strengths and Weaknesses (PSW) methods are widely used for identifying specific learning disabilities (SLDs). Several researchers, however, have reported that the diagnostic accuracy of PSW methods is unacceptably low when strict thresholds were used to identify students with SLDs. We believe these findings give a misleading impression of the magnitude of the diagnostic errors that are likely to arise in PSW assessments.
View Article and Find Full Text PDFBromodomain and extra-terminal domain (BET) proteins and histone deacetylases (HDACs) are prime targets in cancer therapy. Recent research has particularly focused on the development of dual BET/HDAC inhibitors for hard-to-treat tumors, such as pancreatic cancer. Here, we developed a new series of potent dual BET/HDAC inhibitors by choosing starting scaffolds that enabled us to optimally merge the two functionalities into a single compound.
View Article and Find Full Text PDFHerein, peptide nucleic acids (PNAs) are employed in the design of a participatory duplex PNA-peptide crosslinking agent. Biophysical and mechanical studies show that crosslinkers present during peptide assembly leading to hydrogelation participate in the formation of fibrils while simultaneously installing crosslinks into the higher-order network that constitutes the peptide gel. The addition of 2 mol % crosslinker into the assembling system results in a ~100 % increase in mechanical stiffness without affecting the rate of peptide assembly or the local morphology of fibrils within the gel network.
View Article and Find Full Text PDFAllogeneic Hematopoietic Cell Transplantation (HCT) is a curative therapy for hematologic disorders and often requires human leukocyte antigen (HLA)-matched donors. Donor registries have recruited donors utilizing evolving technologies of HLA genotyping methods. This necessitates in-silico ambiguity resolution and statistical imputation based on haplotype frequencies estimated from donor data stratified by self-identified race and ethnicity (SIRE).
View Article and Find Full Text PDFThe nomenclatures used to describe HLA and killer-cell immunoglobulin-like receptor (KIR) alleles distinguish unique nucleotide and peptide sequences, and patterns of expression, but are insufficient for describing genotyping results, as description of ambiguities and relations across loci require terminology beyond allele names. The genotype list (GL) String grammar describes genotyping results for genetic systems with defined nomenclatures, like HLA and KIR, documenting what is known and unknown about a given genotyping result. However, the accuracy of a GL String is dependent on the reference database version under which it was generated.
View Article and Find Full Text PDFThe Genotype List (GL) String grammar for reporting HLA and Killer-cell Immunoglobulin-like Receptor (KIR) genotypes in a text string was described in 2013. Since this initial description, GL Strings have been used to describe HLA and KIR genotypes for more than 40 million subjects, allowing these data to be recorded, stored and transmitted in an easily parsed, text-based format. After a decade of working with HLA and KIR data in GL String format, with advances in HLA and KIR genotyping technologies that have fostered the generation of full-gene sequence data, the need for an extension of the GL String system has become clear.
View Article and Find Full Text PDFPeptide sequence periodicity is a simple design tool that can be used to generate functional peptide-based surface coatings. De novo-designed peptide N-PEG-VK16 is characterized by a hydrophobic periodicity of two that avidly binds to native polystyrene priming its surface for subsequent targeted functionalization via chemical ligation. The peptidic portion of N-PEG-VK16 is responsible for surface binding, converting polystyrene's hydrophobic surface into a wettable and electrostatically charged environment that facilitates cell attachment.
View Article and Find Full Text PDFFor over a century, the structure of intelligence has been dominated by factor analytic methods that presume tests are indicators of latent entities (e.g., general intelligence or ).
View Article and Find Full Text PDFDuchenne muscular dystrophy (DMD) is a progressive muscle wasting disease caused by the absence of dystrophin, a membrane-stabilizing protein encoded by the gene. Although mouse models of DMD provide insight into the potential of a corrective therapy, data from genetically homologous large animals, such as the dystrophin-deficient golden retriever muscular dystrophy (GRMD) model, may more readily translate to humans. To evaluate the clinical translatability of an adeno-associated virus serotype 9 vector (AAV9)-microdystrophin (μDys5) construct, we performed a blinded, placebo-controlled study in which 12 GRMD dogs were divided among four dose groups [control, 1 × 10 vector genomes per kilogram (vg/kg), 1 × 10 vg/kg, and 2 × 10 vg/kg; = 3 each], treated intravenously at 3 months of age with a canine codon-optimized microdystrophin construct, rAAV9-CK8e-c-μDys5, and followed for 90 days after dosing.
View Article and Find Full Text PDFWe report a new positively charged azidoamino acid for strain-promoted azide-alkyne cycloaddition (SPAAC) applications that overcomes possible solubility limitations of commonly used azidolysine, especially in systems with numerous ligation sites. The residue is easily synthesized, is compatible with Fmoc-based solid-phase peptide synthesis employing a range of coupling conditions, and offers efficient second-order rate constants in SPAAC ligations employing DBCO (0.34 M s) and BCN (0.
View Article and Find Full Text PDFThe electrodeposition of low surface area lithium is critical to successful adoption of lithium metal batteries. Here, we discover the dependence of lithium metal morphology on electrical resistance of substrates, enabling us to design an alternative strategy for controlling lithium morphology and improving electrochemical performance. By modifying the current collector with atomic layer deposited conductive (ZnO, SnO) and resistive (AlO) nanofilms, we show that conductive films promote the formation of high surface area lithium deposits, whereas highly resistive films promote the formation of lithium clusters of low surface area.
View Article and Find Full Text PDFObjectives: The aim of this study was to identify the post-percutaneous coronary intervention (PCI) target value of instantaneous wave-free ratio (iFR) that would best discriminate clinical events at 1 year in the DEFINE PCI (Physiologic Assessment of Coronary Stenosis Following PCI) study.
Background: The impact of residual ischemia detected by iFR post-PCI on clinical and symptom-related outcomes is unknown.
Methods: Blinded iFR pull back was performed after successful stent implantation in 500 patients.
Achieving facile nucleation of noble metal films through atomic layer deposition (ALD) is extremely challenging. To this end, η -2,3-dimethylbutadiene ruthenium tricarbonyl (Ru(DMBD)(CO) ), a zero-valent complex, has recently been reported to achieve good nucleation by ALD at relatively low temperatures and mild reaction conditions. The authors study the growth mechanism of this precursor by in situ quartz-crystal microbalance and quadrupole mass spectrometry during Ru ALD, complemented by ex situ film characterization and kinetic modeling.
View Article and Find Full Text PDFIntegrase strand transfer inhibitors (INSTIs) are a class of antiretroviral compounds that prevent the insertion of a DNA copy of the viral genome into the host genome by targeting the viral enzyme integrase (IN). Dolutegravir (DTG) is a leading INSTI that is given, usually in combination with nucleoside reverse transcriptase inhibitors (NRTIs), to treat HIV-1 infections. The emergence of resistance to DTG and other leading INSTIs is rare.
View Article and Find Full Text PDFBackground: Acellular nerve allograft (ANA) occupies an increasingly prominent role in the treatment of peripheral nerve reconstruction. There is demonstrable efficacy; however, some grafts fail to support axonal regrowth and the reasons for this are unclear. This study examines the ANA experience in a specialized peripheral nerve surgery department to discuss the clinical and histological findings in failed cases.
View Article and Find Full Text PDFThe development of devices for the precise and controlled delivery of therapeutics has grown rapidly over the last few decades. Drug delivery materials must provide a depot with delivery profiles that satisfy pharmacodynamic and pharmacokinetic requirements resulting in clinical benefit. Therapeutic efficacy can be limited due to short half-life and poor stability.
View Article and Find Full Text PDFTumours growing in a sheet-like manner on the surface of organs and tissues with complex topologies represent a difficult-to-treat clinical scenario. Their complete surgical resection is difficult due to the complicated anatomy of the diseased tissue. Residual cancer often responds poorly to systemic therapy and locoregional treatment is hindered by the limited accessibility to microscopic tumour foci.
View Article and Find Full Text PDFAlthough the adhesive and cohesive nature of mussel byssal proteins have long served to inspire the design of materials embodying these properties, their characteristic amino acid compositions suggest that they might also serve to inspire an unrelated material function not yet associated with this class of protein. Herein, it is demonstrated that a peptide derived from mussel foot protein-5, a key protein in mussel adhesion, displays antibacterial properties, a yet unreported activity. This cryptic function serves as inspiration for the design of a new class of peptide-based antibacterial adhesive hydrogels prepared via self-assembly, which are active against drug-resistant Gram-positive bacteria.
View Article and Find Full Text PDFCurr Opin Chem Biol
October 2021
For over 20 years, peptide materials in their hydrogel or soluble fibril form have been used for biomedical applications such as drug delivery, cell culture, vaccines, and tissue regeneration. To facilitate the translation of these materials, key areas of research still need to be addressed. Their structural characterization lags compared to amyloid proteins.
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