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Poor phonological processing has typically been considered the main cause of dyslexia. However, visuo-attentional processing abnormalities have been described as well. The goal of the present study was to determine the involvement of visual attention during fluent reading in children with dyslexia and typical readers. Here, 75 children (8-12 years old; 36 typical readers, 39 children with dyslexia) completed cognitive and reading assessments. Neuroimaging data were acquired while children performed a fluent reading task with (a) a condition where the text remained on the screen (Still) versus (b) a condition in which the letters were being deleted (Deleted). Cognitive assessment data analysis revealed that visual attention, executive functions, and phonological awareness significantly contributed to reading comprehension in both groups. A seed-to-voxel functional connectivity analysis was performed on the fluency functional magnetic resonance imaging task. Typical readers showed greater functional connectivity between the dorsal attention network and the left angular gyrus while performing the Still and Deleted reading tasks versus children with dyslexia. Higher connectivity values were associated with higher reading comprehension. The control group showed increased functional connectivity between the ventral attention network and the fronto-parietal network during the Deleted text condition (compared with the Still condition). Children with dyslexia did not display this pattern. The results suggest that the synchronized activity of executive, visual attention, and reading-related networks is a pattern of functional integration which children with dyslexia fail to achieve. The present evidence points toward a critical role of visual attention in dyslexia.

Gadolinium-based contrast agents are used across species to better visualize abnormalities during MRI and are considered generally safe in clinical practice. The aim of this study was to investigate central nervous system (CNS) gadolinium deposition in 11 dogs that had an MRI performed, received 0.22 mL/kg (0.1 mmol/kg) of gadopentetate dimeglumine, and were necropsied on the same hospital admission. The index case was a 5-year-old castrated male Australian Shepherd that presented for ataxia and following MRI developed seizure-like activity that became refractory to anticonvulsant therapy. Gadolinium concentration was quantified in CNS tissues by inductively-coupled plasma mass spectrometry and was 43-fold higher in the index case. These findings suggest the possibility of gadolinium toxicity in select patients.

The selective N-arylation of p-aminophenylalanine in polypeptides with pre-formed palladium oxidative addition complexes is described. The depressed pKa of the aniline NH2 group enables chemoselective C-N bond formation on peptides containing multiple other aliphatic amino groups at lysines or the N-terminus via Curtin-Hammett control under mild conditions. Using palladium complexes derived from electron-poor aryl halides, p-aminophenylalanine is fully arylated in aqueous buffer in as little as one hour at micromolar concentrations. A complementary protocol using the non-nucleophilic, organic base 1,5-diazabicyclo(4.3.0)non-5-ene (DBN), expands the substrate scope to tolerate electron-rich functional groups provides up to 97 % conversion. These procedures enable the chemoselective conjugation of functionally diverse small molecule pharmaceuticals to p-aminophenylalanine containing derivatives of cell-penetrating peptides.

Cisplatin is a chemotherapeutic agent highly excreted in urine and known to cause acute kidney injury (AKI). As AKI diagnosis by serum creatinine (SCr) is usually delayed, endeavors for finding early AKI biomarkers continue. This study aims to determine if urine platinum (UP) concentration 24 hours after cisplatin infusion is associated with AKI, and to evaluate the association between urine platinum and tubular damage biomarkers: neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1). Children treated with cisplatin in 12 Canadian centers (April 2013 to December 2017) were included. Urine from the morning after the first cisplatin infusion of the first or second cisplatin cycle was measured for urine platinum, NGAL, and KIM-1. SCr and serum electrolytes were used to detect AKI by either SCr elevation or urinary electrolyte wasting (potassium, magnesium, phosphate). The associations of urine platinum with AKI, NGAL, and KIM-1 were assessed. A total of 115 participants (54% boys, median age, 8.5 years; interquartile range, 4.0-13.4) were included, of which 29 (25%) and 105 (91%) developed AKI defined by SCr and electrolyte criteria, respectively. Higher urine platinum was associated with higher cisplatin dose (Spearman rho, 0.21) and with younger age (Spearman rho, -0.33). Urine platinum was not associated with postinfusion AKIor KIM-1, but was weakly associated with NGAL, particularly in participants without SCr AKI (Pearson's r, 0.22). Urine platinum may be a marker of mild tubular injury but is not likely to be a useful biomarker of clinically evident AKI.

In this introductory article for the special issue of Journal of Management Studies, entitled ‘Leading Entrepreneurial Ventures: Individual and Team‐Based Perspectives’, we leverage insights in the extant literature as well as those insights developed by the authors of the four articles published in response to our call for papers. Overall, we explore multiple nuanced questions with regards to research on entrepreneurship, research on leadership, and their intersection. Our goal is to begin to help guide research on entrepreneurship and leadership, and their intersection, for the next decade.

Capture and release of peptides is often a critical operation in the pathway to discovering materials with novel functions. However, the best methods for efficient capture impede facile release. To overcome this challenge, we report linkers based on secondary amino alcohols for the release of peptides after capture. These amino alcohols are based on serine (seramox) or isoserine (isoseramox) and can be incorporated into peptides during solid-phase peptide synthesis through reductive amination. Both linkers are quantitatively cleaved within minutes under NaIO4 treatment. Cleavage of isoseramox produced a native peptide N-terminus. This linker also showed broad substrate compatibility; incorporation into a synthetic peptide library resulted in the identification of all sequences by nanoLC-MS/MS. The linkers are cell compatible; a cell-penetrating peptide that contained this linker was efficiently captured and identified after uptake into cells. These findings suggest that such secondary amino alcohol based linkers might be suitable tools for peptide-discovery platforms., National Institutes of Health (Grants R01 GM110535, F32 GM133073), National Science Foundation (Grants 4000057398, 4000057441)

Amphipathic peptides with amino acids arranged in alternating patterns of hydrophobic and hydrophilic residues efficiently self‐assemble into β‐sheet bilayer nanoribbons. Hydrophobic side chain functionality is effectively buried in the interior of the putative bilayer of these nanoribbons. This study investigates consequences on self‐assembly of increasing the surface area of aromatic side chain groups that reside in the hydrophobic core of nanoribbons derived from Ac‐(XKXE)2‐NH2 peptides (X = hydrophobic residue). A series of Ac‐(XKXE)2‐NH2 peptides incorporating aromatic amino acids of increasing molecular volume and steric profile (X = phenylalanine [Phe], homophenylalanine [Hph], tryptophan [Trp], 1‐naphthylalanine [1‐Nal], 2‐naphthylalanine [2‐Nal], or biphenylalanine [Bip]) were assessed to determine substitution effects on self‐assembly propensity and on morphology of the resulting nanoribbon structures. Additional studies were conducted to determine the effects of incorporating amino acids of differing steric profile in the hydrophobic core (Ac‐X1KFEFKFE‐NH2 and Ac‐(X1,5KFE)‐NH2 peptides, X = Trp or Bip). Spectroscopic analysis by circular dichroism (CD) and Fourier transform infrared (FT‐IR) spectroscopy indicated β‐sheet formation for all variants. Self‐assembly rate increased with peptide hydrophobicity; increased molecular volume of the hydrophobic side chain groups did not appear to induce kinetic penalties on self‐assembly rates. Transmission electron microscopy (TEM) imaging indicated variation in fibril morphology as a function of amino acid in the X positions. This study confirms that hydrophobicity of amphipathic Ac‐(XKXE)2‐NH2 peptides correlates to self‐assembly propensity and that the hydrophobic core of the resulting nanoribbon bilayers has a significant capacity to accommodate sterically demanding functional groups. These findings provide insight that may be used to guide the exploitation of self‐assembled amphipathic peptides as functional biomaterials., Self‐assembling peptide β‐sheet nanoribbons were synthesized with varying side aromatic chain surface areas using natural and non‐natural residues. It was found that the nanoribbon bilayers can accommodate packing of very large side chain groups. The self‐assembly kinetics was accelerated as the hydrophobicity of the amino acids increased.

Space weathering processes induce changes to the physical, chemical, and optical properties of space-exposed soil grains. For the Moon, space weathering causes reddening, darkening, and diminished ...