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Background and Aims: A substantial minority of autistic individuals score within typical ranges on standard language tests, suggesting that autism does not necessarily affect language acquisition. This idea is reflected in current diagnostic criteria for autism, wherein language impairment is no longer included. However, some work has suggested that probing autistic speakers' language carefully may reveal subtle differences between autistic and nonautistic people's language that cannot be captured by standardized language testing. The current study aims to test this idea, by determining whether a group of autistic and nonautistic individuals who score similarly on a standardized test show differences in the number of unconventional and erroneous language features they produce in a spontaneous language sample., Methods: Thirty-eight older children and adolescents (19 autistic; 19 nonautistic), between the ages of 10 and 18, were recruited. Both participant groups scored within normal ranges on standardized language and IQ tests. Participants engaged in a "double interview" with an experimenter, during which they were first asked questions by the experimenter about themselves, and then they switched roles, so that it was the participant's turn to ask the experimenter questions. Participants' language during the interview was transcribed and analyzed for linguistic irregularities, including both semantic anomalies and morphosyntactic errors., Results: Group membership accounted for significant variance in irregularity frequency; autistic participants produced more linguistic irregularities than nonautistic participants. Scores on a standardized language test did not improve model fit. Secondary analyses involving irregularity type (semantic vs. morphosyntactic) showed that group differences were primarily driven by relatively high numbers of semantic unconventionalities produced by the autistic group. While the autistic group made more morphosyntactic errors than the nonautistic group, differences in these numbers were only marginally significant., Conclusions and Implications: These findings suggest that a commonly used standardized language test does not adequately predict the number and perhaps type of language irregularities produced by some older autistic children and adolescents during spontaneous discourse. Results also suggest that differences in language use, especially semantic differences, may characterize autistic language, even the language produced by people who score within normal ranges on standardized language tests. It is debatable whether differences reflect underlying language impairments and/or a linguistic style adopted/preferred by autistic speakers. In this paper, we discuss both possibilities and offer suggestions to future research for teasing these possibilities apart., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

N -Acetylnorloline synthase (LolO) is one of several iron(II)- and 2-oxoglutarate-dependent (Fe/2OG) oxygenases that catalyze sequential reactions of different types in the biosynthesis of valuable natural products. LolO hydroxylates C2 of 1- exo -acetamidopyrrolizidine before coupling the C2-bonded oxygen to C7 to form the tricyclic loline core. Each reaction requires cleavage of a C-H bond by an oxoiron(IV) (ferryl) intermediate; however, different carbons are targeted, and the carbon radicals have different fates. Prior studies indicated that the substrate-cofactor disposition (SCD) controls the site of H · abstraction and can affect the reaction outcome. These indications led us to determine whether a change in SCD from the first to the second LolO reaction might contribute to the observed reactivity switch. Whereas the single ferryl complex in the C2 hydroxylation reaction was previously shown to have typical Mössbauer parameters, one of two ferryl complexes to accumulate during the oxacyclization reaction has the highest isomer shift seen to date for such a complex and abstracts H · from C7 ∼ 20 times faster than does the first ferryl complex in its previously reported off-pathway hydroxylation of C7. The detectable hydroxylation of C7 in competition with cyclization by the second ferryl complex is not enhanced in 2 H 2 O solvent, suggesting that the C2 hydroxyl is deprotonated prior to C7-H cleavage. These observations are consistent with the coordination of the C2 oxygen to the ferryl complex, which may reorient its oxo ligand, the substrate, or both to positions more favorable for C7-H cleavage and oxacyclization.

Objectives: Despite evidence for the validity of using client-led outcome measures in gender-affirming voice training (GAVT), the existing body of research on voice feminization relies heavily on acoustic-perceptual measures without additional qualitative exploration of client experience. Additionally, the authors are not aware of any existing studies prompting client input on the voice feminization methods they find most helpful in achieving their voice goals. The current study focuses on crucial client perceptions of GAVT for voice feminization and identifies the methods clients find most helpful., Methods: Using a mixed-methods approach, we gathered numeric and qualitative survey data from 21 individuals who engaged in GAVT supporting voice feminization. We conducted follow-up interviews with five survey participants to gather additional qualitative data on client experiences and perceptions of GAVT., Results: Quantitative and qualitative data reveal that clients are satisfied with GAVT supporting voice feminization, perceive their clinicians as being culturally inclusive, and identify oral/forward resonance work as one of the most helpful voice training methods. Interestingly, however, frequency of work on oral/forward resonance during training did not predict voice satisfaction post-training., Conclusions: Clients identified oral/forward resonance as one of the most helpful methods of voice feminization and found their GAVT experiences to be supportive of their voice goals. These findings emphasize the importance and value of client-led outcome measures when investigating effective approaches to GAVT., Competing Interests: Declaration of Competing Interest The first and third authors of this study declare a professional involvement in providing gender-affirming voice services to three of the study participants. This disclosure is made to ensure transparency and acknowledge our role in supporting individuals in their journey towards gender affirmation. We affirm that this potential conflict of interest has been managed appropriately throughout the research process, adhering to ethical guidelines, and maintaining the confidentiality and anonymity of the participants. Additionally, when selecting participants for the study interviews, conducted by the first author, the five participants who received services from the first and third author were excluded from consideration to minimize potential bias in interview responses stemming from this prior relationship., (Copyright © 2024 The Voice Foundation. Published by Elsevier Inc. All rights reserved.)

Four previous papers reported the isolation and structural determination of 10 polycyclic polyprenylated acylphloroglucinols (PPAPs), uraliones F, G, K, and O, attenuatumiones E and F, and scabrumiones A-D, from Hypericum species. Their structures were identified as type B PPAPs that featured not only the characteristic acyl group at C-3 of the bicyclo[3.3.1]nonane core but also a partly reduced furan ring fused to the C-1-C-2-O-2 atoms of the core. However, the 1D and 2D NMR data of these compounds were more consistent with type A PPAPs that featured not only the acyl group at C-1 but also a partially reduced furan ring fused to the C-3-C-2-O-2 atoms of the core. Now we revise these 10 previously proposed structures to the corresponding type A PPAPs via NMR analysis. Additionally, we propose a rule that uses NMR data to determine whether a particular PPAP that is fused to a partly reduced furan ring at C-3-C-2-O-2 or C-1-C-2-O-2 is type A or type B, respectively. We also propose a rule to assign the relative configurations of corresponding type A PPAPs at C-18 and revise the configurations of sampsonione N, hypericumoxides A-C, and hyperscabin G.

Diamine ligands are effective structural scaffolds for tuning the reactivity of transition-metal complexes for catalytic, materials, and phosphorescent applications and have been leveraged for biological use. In this work, we report the synthesis and characterization of a novel class of cyclometalated [C^N] Au(III) complexes bearing secondary diamines including a norbornane backbone, (2 R ,3 S )- N 2 , N 3 -dibenzylbicyclo[2.2.1]heptane-2,3-diamine, or a cyclohexane backbone, (1 R ,2 R )- N 1 , N 2 -dibenzylcyclohexane-1,2-diamine. X-ray crystallography confirms the square-planar geometry and chirality at nitrogen. The electronic character of the conformationally restricted norbornane backbone influences the electrochemical behavior with redox potentials of -0.8 to -1.1 V, atypical for Au(III) complexes. These compounds demonstrate promising anticancer activity, particularly, complex 1 , which bears a benzylpyridine organogold framework, and supported by the bicyclic conformationally restricted diaminonorbornane, shows good potency in A2780 cells. We further show that a cellular response to 1 evokes reactive oxygen species (ROS) production and does not induce mitochondrial dysfunction. This class of complexes provides significant stability and reactivity for different applications in protein modification, catalysis, and therapeutics.

Purpose: Stories told by autistic narrators often contain relatively frequent use of ambiguous references. However, it remains unclear whether this ambiguity is driven by ambiguous character establishment (e.g., "Once upon a time, she/the girl…") and/or ambiguous cohesion (e.g., "Two girls lived in a castle. She/The girl…"). In this study, we directly compared rates of each type of ambiguity within and between narratives told by autistic and non-autistic children, to determine which type of ambiguity is relatively more common in narratives told by autistic children., Method: Thirty-three 10- to 17-year-old autistic participants ( n = 17) and non-autistic peers ( n = 16), who were not statistically different in age, standardized language scores, and IQ scores ( p > .8 for all), watched two short animated videos alone and then described the videos' events to two listeners who were openly unfamiliar with the videos. We transcribed video recordings of narratives and coded all referential noun phrases (NPs) as either clear or ambiguous. We further categorized ambiguous NPs as either ineffective introduction or ineffective cohesion., Results: Autistic children produced significantly higher rates of ambiguous establishment than non-autistic peers, whereas between-group comparisons' rates of ambiguous cohesion were not statistically significant., Conclusions: Older children on the autism spectrum show differences in the way they introduce characters, selecting NP types that are only appropriate when their listener is already familiar with the referent. In contrast, once they have introduced characters, they show cohesive skills that are comparable to those of non-autistic peers. Findings support theories arguing that autistic children show differences in their application of social pragmatic principles (listener/context-specific pragmatic rules), whereas their use of linguistic pragmatics (context-independent rules) is similar to that of non-autistic peers.

Garcinielliptone FC (GFC) was assigned to be a type A polycyclic polyprenylated acylphloroglucinol (PPAP) and was found to exhibit diverse biological activities. Now we revise the structure of GFC to xanthochymol, a type B PPAP, via NMR and total synthesis methods. The total syntheses of (±)-xanthochymol and (±)-cycloxanthochymol were accomplished in 12 and 13 steps, respectively.

We describe two new methods for the 1,2-diamination of alkenes. First, either an azidium ion (ArN═N + ═NAr) undergoes 1,3-dipolar cycloaddition with an alkene to give a 1,2,3-triazolinium ion directly, or an intramolecular azide-alkene cycloaddition followed by N-benzylation provides the same. Second, hydrogenation of the 1,2,3-triazolinium ion over Raney Ni excises the central N atom and gives the 1,2-diamine. The stereochemistry of the alkene is usually, but not always, preserved in the 1,2-diamine.

Many type B polycyclic polyprenylated acylphloroglucinols (PPAPs) bear a lavandulyl-derived substituent, and the configurational assignment of this side chain can be difficult and sometimes leads to erroneous conclusions. In this study, 21 PPAPs, including the new xanthochymusones A-I ( 1 - 9 ), have been isolated from the fruits of Garcinia xanthochymus and structurally characterized. The relative configuration of the C-30 stereocenter was assigned by a combination of chemical transformations, 1 H- 1 H coupling constants, conformational analysis, and NOE experiments. The configurational assignment of compound 7 indicates that the relative configuration at C-30 of PPAPs is not always the same. The absolute configurations of the new compounds were assigned by ECD and X-ray diffraction data, as well as by biosynthetic considerations. Analysis of NMR data enabled the configurational revision of garcicowins C and D. All the isolated PPAPs were tested for antiproliferative activity against three human hepatocellular carcinoma cell lines, including Huh-7, Hep 3B, and HepG2. Compounds 5 and 6 , 7- epi -isogarcinol ( 16 ), and coccinone C ( 17 ) exhibited moderate antiproliferative activity. Compounds 6 and 16 induced apoptosis and inhibited cell migration in Huh-7 cells, probably through downregulating the STAT3 signaling pathway. This study provides effective methods for configurational assignments of type B PPAPs.

Background & Aims: Discourse markers, such as well or like , serve a variety of functions to support conversational reciprocity: filling pauses, aiding word-finding, and modulating turn-taking by holding the conversational floor. Previous research shows that autistic individuals use discourse markers less frequently than non-autistic (NonAu) peers; however, the discourse marker like has not been included in that research, despite its ubiquitous use by NonAu individuals, and despite the fact that like serves important pragmatic functions that are not encoded by any other discourse marker. Specifically, like signals to the listener that the content of upcoming speech is 1) Important/new; 2) Loose/approximate; 3) Reformulative; or 4) Quotative. The current study addresses this gap in the literature by comparing the frequency of discourse marker like use between older autistic and non-autistic children as well as exploring patterns of usage between the four like functions., Methods: Twenty-one 10-to-17-year-old children on the autism spectrum and 20 NonAu peers-statistically matched on age, sex, IQ and language scores-engaged in a semi-structured interview with a researcher. Uses of discourse-marker like were identified from written transcripts of interviews and each use was categorized into one of the four functions., Results: There were no significant differences in like frequencies between groups, nor were there differences in relative proportions of functions used by each group., Conclusions: Research consistently indicates that autistic individuals use discourse markers significantly less often than their NonAu counterparts, but the findings from our study suggest that this pattern does not persist to all such markers. This group of older autistic children use like as often as their peers and use it to signify similar information about upcoming speech to their listener., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2022.)

LolO, a 2-oxoglutarate-dependent nonheme Fe oxygenase, catalyzes both the hydroxylation of 1-exo-acetamidopyrrolizidine (AcAP), a pathway intermediate in the biosynthesis of the loline alkaloids, and the cycloetherification of the resulting alcohol. We have prepared fluorinated AcAP analogues to aid in continued mechanistic investigation of the remarkable LolO-catalyzed cycloetherification step. LolO was able to hydroxylate 6,6-difluoro-AcAP (prepared from N,O-protected 4-oxoproline) and then cycloetherify the resulting alcohol, forming a difluorinated analogue of N-acetylnorloline and providing evidence for a cycloetherification mechanism involving a C(7) radical as opposed to a C(7) carbocation. By contrast, LolO was able to hydroxylate 7,7-difluoro-AcAP (prepared from 3-oxoproline) but failed to cycloetherify it, forming (1R,2R,8S)-7,7-difluoro-2-hydroxy-AcAP as the sole product. The divergent LolO-catalyzed reactions of the difluorinated AcAP analogues provide insight into the LolO cycloetherification mechanism and indicate that the 7,7-difluorinated compound, in particular, may be a useful tool to accumulate and characterize the iron intermediate that initiates the cycloetherification reaction., (© 2022 Wiley-VCH GmbH.)