Chemoselective Late-Stage Functionalization of Peptides via Photocatalytic C2-Alkylation of Tryptophan.

Across eukaryotic proteomes, tryptophan is the least abundant of the 20 canonical amino acids, which makes it an ideal chemical handle for the late-stage functionalization of peptide and protein scaffolds with minimal production of undesired isoforms. Herein, we report the photocatalytic C2-alkylation of tryptophan using bromodifluoroacetate/acetamide-derived radical precursors. This rapid visible-light-mediated reaction is additive-free, operationally simple, and tolerates diverse functionality. We demonstrate the late-stage modification of a variety of complex peptides, including examples of biological significance.

Procedural and declarative memory brain systems in developmental language disorder (DLD).

The aim of the current study was to examine microstructural differences in white matter relevant to procedural and declarative memory between adolescents/young adults with and without Developmental Language Disorder (DLD) using diffusion tensor imaging (DTI). The findings showed atypical age-related changes in white matter structures in the corticostriatal system, in the corticocerebellar system, and in the medial temporal region in individuals with DLD. Results highlight the importance of considering the age factor in research on DLD. Future studies are needed to examine the developmental relationship between long-term memory and individual differences in language development and learning.

Altered brain structures in the dorsal and ventral language pathways in individuals with and without developmental language disorder (DLD).

Developmental Language Disorder (DLD) is a neurodevelopmental disorder characterized by difficulty learning and using language, and this difficulty cannot be attributed to other developmental conditions. The aim of the current study was to examine structural differences in dorsal and ventral language pathways between adolescents and young adults with and without DLD (age range: 14-27 years) using anatomical magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI). Results showed age-related structural brain differences in both dorsal and ventral pathways in individuals with DLD. These findings provide evidence for neuroanatomical correlates of persistent language deficits in adolescents/young adults with DLD, and further suggest that this brain-language relationship in DLD is better characterized by taking account the dynamic course of the disorder along development.

Episodic memory retrieval in adolescents with and without developmental language disorder (DLD).

BACKGROUND: Two reasons may explain the discrepant findings regarding declarative memory in developmental language disorder (DLD) in the literature. First, standardized tests are one of the primary tools used to assess declarative memory in previous studies. It is possible they are not sensitive enough to subtle memory impairment. Second, the system underlying declarative memory is complex, and thus results may vary depending on the types of encoding and retrieval processes measured (e.g., item specific or relational) and/or task demands (e.g., recall or recognition during memory retrieval). AIMS: To adopt an experimental paradigm to examine episodic memory functioning in adolescents with and without DLD, with the focus on memory recognition of item-specific and relational information. METHODS & PROCEDURES: Two groups of adolescents, one with DLD (n = 23; mean age = 16.73 years) and the other without (n = 23; mean age = 16.75 years), participated in the study. The Relational and Item-Specific Encoding (RISE) paradigm was used to assess the effect of different encoding processes on episodic memory retrieval in DLD. The advantage of using the RISE task is that both item-specific and relational encoding/retrieval can be examined within the same learning paradigm. OUTCOMES & RESULTS: Adolescents with DLD and those with typical language development showed comparable engagement during the encoding phase. The DLD group showed significantly poorer item recognition than the comparison group. Associative recognition was not significantly different between the two groups; however, there was a non-significant trend for to be poorer in the DLD group than in the comparison group, suggesting a possible impairment in associative recognition in individuals with DLD, but to a lesser magnitude. CONCLUSIONS & IMPLICATIONS: These results indicate that adolescents with DLD have difficulty with episodic memory retrieval when stimuli are encoded and retrieved without support from contextual information. Associative recognition is relatively less affected than item recognition in adolescents with DLD.

Insensitivity to response-contingent feedback in adolescents with developmental language disorder (DLD).

The aim of the study was to investigate the efficiency of the use of response-contingent feedback in adolescents with and without developmental language disorder (DLD) by using the balloon analogue risk task (BART). The BIS/BAS scales were also used to evaluate a participant's responses to reward- or punishment-related events in everyday situations. The results showed that adolescents with DLD performed on the BART at a suboptimal level due to inefficient use of response-contingent feedback. Findings of the BIS/BAS scales also generate a possible hypothesis of reduced motivational salience for larger monetary outcomes in DLD. Given that dopamine plays an important role in modulating BART responding through the corticostriatal pathways, these behavioral findings implicate an association between dopamine and individual differences in language, including DLD. Future studies are needed to directly test whether people with DLD have reduced level of dopamine in striatal neural synapses, leading to dopamine-dependent learning difficulty.

Examining Procedural Learning and Corticostriatal Pathways for Individual Differences in Language: Testing Endophenotypes of DRD2/ANKK1.

The aim of the study was to explore whether genetic variation in the dopaminergic system is associated with procedural learning and the corticostriatal pathways in individuals with developmental language impairment (DLI). We viewed these two systems as endophenotypes and hypothesized that they would be more sensitive indicators of genetic effects than the language phenotype itself. Thus, we genotyped two SNPs in the DRD2/ANKK1 gene complex, and tested for their associations to the phenotype of DLI and the two endophenotypes. Results showed that individuals with DLI revealed poor procedural learning abilities and abnormal structures of the basal ganglia. Genetic variation in DRD2/ANKK1 was associated with procedural learning abilities and with microstructural differences of the caudate nucleus. The association of the language phenotype with these DRD2/ANKK1 polymorphisms was not significant, but the phenotype was significantly associated with the two endophenotypes. We suggest that procedural learning and the corticostriatal pathways could be used as effective endophenotypes to aid molecular genetic studies searching for genes predisposing to DLI.

Procedural Learning and Individual Differences in Language.

The aim of the current study was to examine different aspects of procedural memory in young adults who varied with regard to their language abilities. We selected a sample of procedural memory tasks, each of which represented a unique type of procedural learning, and has been linked, at least partially, to the functionality of the corticostriatal system. The findings showed that variance in language abilities is associated with performance on different domains of procedural memory, including the motor domain (as shown in the pursuit rotor task), the cognitive domain (as shown in the weather prediction task), and the linguistic domain (as shown in the nonword repetition priming task). These results implicate the corticostriatal system in individual differences in language.

Abnormal subcortical components of the corticostriatal system in young adults with DLI: a combined structural MRI and DTI study.

Developmental Language Impairment (DLI) is a neurodevelopmental disorder affecting 12% to 14% of the school-age children in the United States. While substantial studies have shown a wide range of linguistic and non-linguistic difficulty in individuals with DLI, very little is known about the neuroanatomical mechanisms underlying this disorder. In the current study, we examined the subcortical components of the corticostriatal system in young adults with DLI, including the caudate nucleus, the putamen, the nucleus accumbens, the globus pallidus, and the thalamus. Additionally, the four cerebral lobes and the hippocampus were also comprised for an exploratory analysis. We used conventional magnetic resonance imaging (MRI) to measure regional brain volumes, as well as diffusion tensor imaging (DTI) to assess water diffusion anisotropy as quantified by fractional anisotropy (FA). Two groups of participants, one with DLI (n=12) and the other without (n=12), were recruited from a prior behavioral study, and all were matched on age, gender, and handedness. Volumetric analyses revealed region-specific abnormalities in individuals with DLI, showing pathological enlargement bilaterally in the putamen and the nucleus accumbens, and unilaterally in the right globus pallidus after the intracranial volumes were controlled. Regarding the DTI findings, the DLI group showed decreased FA values in the globus pallidus and the thalamus but these significant differences disappeared after controlling for the whole-brain FA value, indicating that microstructural abnormality is diffuse and affects other regions of the brain. Taken together, these results suggest region-specific corticostriatal abnormalities in DLI at the macrostructural level, but corticostriatal abnormalities at the microstructural level may be a part of a diffuse pattern of brain development. Future work is suggested to investigate the relationship between corticostriatal connectivity and individual differences in language development.

Reinforcement learning in young adults with developmental language impairment.

The aim of the study was to examine reinforcement learning (RL) in young adults with developmental language impairment (DLI) within the context of a neurocomputational model of the basal ganglia-dopamine system (Frank, Seeberger, & O'Reilly, 2004). Two groups of young adults, one with DLI and the other without, were recruited. A probabilistic selection task was used to assess how participants implicitly extracted reinforcement history from the environment based on probabilistic positive/negative feedback. The findings showed impaired RL in individuals with DLI, indicating an altered gating function of the striatum in testing. However, they exploited similar learning strategies as comparison participants at the beginning of training, reflecting relatively intact functions of the prefrontal cortex to rapidly update reinforcement information. Within the context of Frank's model, these results can be interpreted as evidence for alterations in the basal ganglia of individuals with DLI.