Diffusion of oligomeric species in polymer solutions

Self-diffusion coefficients (D(s)) for analogs of polystyrene (PS) oligomers were measured using pulsed field gradient (PFG) H-1 NMR as a function of the weight fraction (w(p)) of high molecular weight PS (125000-250000) in solution over the range 0 less-than-or-equal-to w(p) less-than-or-equal-to 0.6. The studies were performed at 25-degrees-C using benzene as solvent. Model compounds used were benzene, 1,3-diphenyl-1-butanol, and a commercially-available, monodisperse sample of PS (so-called M5) of a peak-average molecular weight of M(p) = 580 as determined by gel permeation chromatography (GPC). GPC data and PFG NMR data were used to determine a new average molecular weight for M5 of 500. The scaling law dependence of the D(s) values on the molecular weight of the model compounds was determined and a simple scaling dependence was observed with the scaling law changing linearly with w(p) over the range studied. This is discussed in light of current models. D(s) data are also presented for the diffusion of toluene in toluene/PS solutions over the range 0 less-than-or-equal-to w(p) less-than-or-equal-to 0.7 and are 20%-30% smaller than identical experiments reported by Pickup and Blum (see ref 13)

SLITRK2 variants associated with neurodevelopmental disorders impair excitatory synaptic function and cognition in mice

SLITRK2 is a single-pass transmembrane protein expressed at postsynaptic neurons that regulates neurite outgrowth and excitatory synapse maintenance. In the present study, we report on rare variants (one nonsense and six missense variants) in SLITRK2 on the X chromosome identified by exome sequencing in individuals with neurodevelopmental disorders. Functional studies showed that some variants displayed impaired membrane transport and impaired excitatory synapse-promoting effects. Strikingly, these variations abolished the ability of SLITRK2 wild-type to reduce the levels of the receptor tyrosine kinase TrkB in neurons. Moreover, Slitrk2 conditional knockout mice exhibited impaired long-term memory and abnormal gait, recapitulating a subset of clinical features of patients with SLITRK2 variants. Furthermore, impaired excitatory synapse maintenance induced by hippocampal CA1-specific cKO of Slitrk2 caused abnormalities in spatial reference memory. Collectively, these data suggest that SLITRK2 is involved in X-linked neurodevelopmental disorders that are caused by perturbation of diverse facets of SLITRK2 function.The protein SLITRK2 plays an important role in synaptic communication. This study identifies X-linked SLITRK2 variants that underlie neurodevelopmental disorders by impairing excitatory synapses

Real-world EGFR testing practices for non-small-cell lung cancer by thoracic pathology laboratories across Europe

Background: Testing for epidermal growth factor receptor (EGFR) mutations is an essential recommendation in guidelines for metastatic non-squamous non-small-cell lung cancer, and is considered mandatory in European countries. However, in practice, challenges are often faced when carrying out routine biomarker testing, including access to testing, inadequate tissue samples and long turnaround times (TATs). Materials and methods: To evaluate the real-world EGFR testing practices of European pathology laboratories, an online survey was set up and validated by the Pulmonary Pathology Working Group of the European Society of Pathology and distributed to 64 expert testing laboratories. The retrospective survey focussed on laboratory organisation and daily EGFR testing practice of pathologists and molecular biologists between 2018 and 2021. Results: TATs varied greatly both between and within countries. These discrepancies may be partly due to reflex testing practices, as 20.8% of laboratories carried out EGFR testing only at the request of the clinician. Many laboratories across Europe still favour single-test sequencing as a primary method of EGFR mutation identification; 32.7% indicated that they only used targeted techniques and 45.1% used single-gene testing followed by next-generation sequencing (NGS), depending on the case. Reported testing rates were consistent over time with no significant decrease in the number of EGFR tests carried out in 2020, despite the increased pressure faced by testing facilities during the COVID-19 pandemic. ISO 15189 accreditation was reported by 42.0% of molecular biology laboratories for single-test sequencing, and by 42.3% for NGS. 92.5% of laboratories indicated they regularly participate in an external quality assessment scheme. Conclusions: These results highlight the strong heterogeneity of EGFR testing that still occurs within thoracic pathology and molecular biology laboratories across Europe. Even among expert testing facilities there is variability in testing capabilities, TAT, reflex testing practice and laboratory accreditation, stressing the need to harmonise reimbursement technologies and decision-making algorithms in Europe