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British Columbia (BC), Canada, is home to 34 Indigenous languages, all of them classified as endangered. Considerable work is underway by First Nation communities to revitalize their languages. Linguists classify many of the languages of BC as polysynthetic, meaning that words are composed of many morphemes, or units of meaning. While strong fluent speakers and linguists who work with these languages have knowledge and appreciation of these units of meaning, those understandings are often not reflected in the approaches for teaching and learning BC languages. Drawing on examples from Kwak'wala, a language of coastal BC, we discuss how an Indigenized approach to language revitalization can recognize and respect the highly regarded ancestral origins and messages about identity that are reflected within the language. In developing understanding of the morphemes of the language, learners can grasp literal meanings and metaphors embedded in Kwak'wala words, leading to deeper understandings of Kwakwaka'wakw worldview and appreciation of the beauty of the language. In addition, learners can be supported to use morphemes as building blocks in their language learning. Rather than memorizing words and phrases, learners can be encouraged to listen for and use the morphemes they know to understand and produce new words and phrases.

The series of C2-symmetric biaryl core-based non-racemic bisphosphines possessing substituents of different electronic properties: both EDG and EWG were obtained in a short sequence of good yielding transformations, started from commercial 1,3-dimethyl-2-nitrobenzene. Several different approaches leading to the desirable ligands were practically evaluated. Notably, the synthesis of the entire series of ligands could be performed with the utilization of a single early-stage precursor DIDAB (6,6′-diiodo-2,2′,4,4′-tetramethylbiphenyl-3,3′-diamine), which could be easily obtained in enantiomerically pure form. The obtained compounds at concentrations of 50 and 200 µM showed various biological activity against normal human dermal fibroblast, ranging from inactivity through time-dependent action and ending up with high toxicity.

Background: Due to resistance to conventional therapy, a blood–brain barrier that results in poor drug delivery, and a high potential for metastasis, glioblastoma (GBM) presents a great medical challenge. Since the repertoire of the possible therapies is very limited, novel therapeutic strategies require new drugs as well as new approaches. The multiple roles played by L-tryptophan (Trp) in tumorigenesis of GBM and the previously found antiproliferative properties of Trp-bearing dendrimers against this malignancy prompted us to design novel polyfunctional peptide-based dendrimers covalently attached to N1-alkyl tryptophan (Trp) residues. Their antiproliferative properties against GBM and normal human astrocytes (NHA) and their antioxidant potential were tested. Methods: Two groups of amphiphilic peptide dendrimers terminated with N1-butyl and N1-aminopentane tryptophan were designed. The influence of dendrimers on viability of NHA and human GBM cell lines, displaying different genetic backgrounds and tumorigenic potentials, was determined by the MTT test. The influence of compounds on the clonogenic potential of GBM cells was assessed by colony-formation assay. Dendrimers were tested for radical scavenging potency as well as redox capability (DPPH, ABTS, and FRAP models). Results: Several peptide dendrimers functionalized with N1-alkyl-tryptophan at 5 µM concentration exhibited high selectivity towards GBM cells retaining 85–95% viable NHA cells while killing cancer cells. In both the MTT and colony-formation assays, compounds 21 (functionalized with N1-butyl-Trp and (+)8 charged) and 25 (functionalized with N1-aminopentane-Trp and (+)12 charged) showed the most promise for their development into anticancer drugs. According to ABTS, DPPH, and FRAP antioxidant tests, dendrimers functionalized with N1-alkylated Trp expressed higher ROS-scavenging capacity (ABTS and DPPH) than those with unsubstituted Trp. Conclusions: Peptide dendrimers functionalized with N1-alkyl-tryptophan showed varying toxicity to NHA, while all were toxic to GBM cells. Based on their activity towards inhibition of GBM viability and relatively mild effect on NHA cells the most advantageous were derivatives 21 and 25 with the respective di-dodecyl and dodecyl residue located at the C-terminus. As expected, peptide dendrimers functionalized with N1-alkyl-tryptophan expressed higher scavenging potency against ROS than dendrimers with unsubstituted tryptophan.

Abstract Ischemia impacts multiple organ systems and is the major cause of morbidity and mortality in the developed world. Ischemia disrupts tissue homeostasis, driving cell death, and damages tissue structure integrity. Strategies to heal organs, like the infarcted heart, or to replace cells, as done in pancreatic islet β‐cell transplantations, are often hindered by ischemic conditions. Here, it is discovered that the basement membrane glycoprotein nidogen‐1 attenuates the apoptotic effect of hypoxia in cardiomyocytes and pancreatic β‐cells via the αvβ3 integrin and beneficially modulates immune responses in vitro. It is shown that nidogen‐1 significantly increases heart function and angiogenesis, while reducing fibrosis, in a mouse postmyocardial infarction model. These results demonstrate the protective and regenerative potential of nidogen‐1 in ischemic conditions.

Introduction: Acute carotid-related stroke (CRS), with its large thrombo-embolic load and large volume of affected brain tissue, poses significant management challenges. First generation (single-layer) carotid stents fail to insulate the athero-thrombotic material; thus they are often non-optimized (increasing thrombosis risk), yet their use is associated with a significant (20-30%) risk of new cerebral embolism. Aim: To evaluate, in a multi-center multi-specialty investigator-initiated study, outcomes of the MicroNET-covered (cell area ≈ 0.02-0.03 mm² ) carotid stent (CGuard, InspireMD) in consecutive CRS patients eligible for emergency recanalization. Treatment, other than study device use, was according to center/operator routine. Material and methods: Seventy-five patients (age 40-89 years, 26.7% women) were enrolled in 7 interventional stroke centers. Results: The median Alberta Stroke Program Early CT Score (ASPECTS) was 9 (6-10). Study stent use was 100% (no other stent types implanted); retrograde strategy predominated (69.2%) in tandem lesions. Technical success was 100%. Post-dilatation balloon diameter was 4.0 to 8.0 mm. 89% of patients achieved final modified Thrombolysis in Cerebral Infarction (mTICI) 2b-c/3. Glycoprotein IIb/IIIa inhibitor use as intraarterial (IA) bolus + intravenous (IV) infusion was an independent predictor of symptomatic intracranial hemorrhage (OR = 13.9, 95% CI: 5.1-84.5, p < 0.001). The mortality rate was 9.4% in-hospital and 12.2% at 90 days. Ninety-day mRS0-2 was 74.3%, mRS3-5 13.5%; stent patency was 93.2%. Heparin-limited-to-flush predicted patency loss on univariate (OR = 14.3, 95% CI: 1.5-53.1, p < 0.007) but not on multivariate analysis. Small-diameter balloon/absent post-dilatation was an independent predictor of stent patency loss (OR = 15.2, 95% CI: 5.7-73.2, p < 0.001). Conclusions: This largest to-date study of the MicroNET-covered stent in consecutive CRS patients demonstrated a high acute angiographic success rate, high 90-day patency and favorable clinical outcomes despite variability in procedural strategies and pharmacotherapy (SAFEGUARD-STROKE NCT05195658). [ABSTRACT FROM AUTHOR]

In magnetic confinement fusion devices, the plasma particle and energy transport depend on the turbulence transport. Ion cyclotron range of frequency (ICRF) wave heating can interact with the turbulence in the plasma edge and change the turbulence transport. To understand their interaction/correlation, the radial modification of turbulence by ICRF in the scrape-off layer (SOL) was investigated using midplane reciprocating Langmuir probe, reflectometry, Doppler reflectometry, and Divertor probes on the EAST tokamak. We showed a first demonstration that this interaction occurs at all radii and affects the turbulence across the whole SOL. It was observed that ICRF attenuates the large-scale turbulence structures (usually in the form of blobs) by breaking them into smaller ones, leading to a suppression of low-frequency turbulence in the whole SOL. Moreover, this turbulence reduction is accompanied by an increase in the high-frequency turbulence fluctuations and an increase in the poloidal velocity in the SOL. This poloidal velocity is generated by the radial electric field during ICRF. Following this, BOUT++ simulations were conducted, and the simulations results are in line with the experimental results. They show that the RF-sheath induced radial electric field can explain the increase in high-frequency fluctuations and suppression of turbulence in the SOL. [ABSTRACT FROM AUTHOR]