Examining an integrated path model of psychological and sociocultural predictors of camouflaging in autistic adults.

LAY ABSTRACT: Many autistic people use strategies known as 'camouflaging' to change how noticeable their autistic traits are in social situations. Previous research suggests that camouflaging is largely motivated by psychological and social factors. However, most studies so far have only looked at a few psychosocial factors related to camouflaging. In this study, we explored a model that included several individual psychological factors (such as fear of being negatively judged, self-esteem and autistic identity) and broader social and cultural factors (such as perceived stigma, negative life events, cultural emphasis on conformity and desire to fit in or stand out). We surveyed 225 autistic adults aged 18-77 years online. Our findings showed that several sociocultural factors were indirectly linked to camouflaging through individual psychological factors. Fear of being negatively judged emerged as a strong predictor of camouflaging. Specifically, autistic adults who perceived greater stigma, felt greater pressure to conform, had a lesser desire to stand out and a greater desire to fit in tended to experience a greater fear of being negatively judged and reported more camouflaging. In addition, those who experienced more negative life events were more likely to engage in camouflaging. Our study identifies key psychological and social factors as potential targets for social change. Our findings emphasise that our societies need to shift away from stigmatising attitudes towards accepting and including autistic people, which could reduce the pressure on autistic individuals to camouflage in social situations.

Exploring autistic adults' psychosocial experiences affecting beginnings, continuity and change in camouflaging over time: A qualitative study in Singapore.

LAY ABSTRACT: Over their lifetimes, many autistic people learn to camouflage (hide or mask) their autism-related differences to forge relationships, find work and live independently in largely non-autistic societies. Autistic adults have described camouflaging as a 'lifetime of conditioning . . . to act normal' involving 'years of effort', suggesting that camouflaging develops over an autistic person's lifetime and may start early on, in childhood or adolescence. Yet, we know very little about why and how autistic people start to camouflage, or why and how their camouflaging behaviours continue or change over time. We interviewed 11 Singaporean autistic adults (9 male, 2 female, 22-45 years old) who shared their camouflaging experiences. We found that autistic adults' earliest motivations to camouflage were largely related to the desire to fit in and connect with others. They also camouflaged to avoid difficult social experiences (such as being teased or bullied). Autistic adults shared that their camouflaging behaviours became more complex and that, for some, camouflaging became a part of their self-identity over time. Our findings suggest that society should not pathologise autistic differences, but instead accept and include autistic people, to reduce the pressure on autistic people to hide who they truly are.

Experiences of Performing Daily Activities in Middle-Aged and Older Autistic Adults: A Qualitative Study.

This is the first study to investigate instrumental activities of daily living in older autistic adults. We conducted interviews with fifteen adults (mean age = 60.1, SD = 7.4, range = 50-73) from Australia with no intellectual disability. Analysis included both deductive and inductive steps, to categorise responses using the Occupational Performance Model Australia and identify themes across participants' experiences. Strengths and challenges were unique to the individual, as were the methods they had developed to manage tasks. Challenges occurred mostly at the interaction between aspects of the environment (sensory, cognitive, social and cultural) and personal factors such as health conditions and sensory sensitivities. Enhanced person-environment fit is needed, as is a shift in wider sociocultural attitudes to enable comfort and autonomy in later life.

The use of everyday and assistive technology in the lives of older autistic adults.

LAY ABSTRACT: Technology has the potential to help people with various support needs live more autonomous lives. This includes autistic individuals. In this article, we look at how older autistic adults use technology in their daily lives. Past research examining technology use and autism has mainly focused on helping children to learn new skills. To date, very little research has been conducted looking at how to create and design technology for use by older autistic adults. This is concerning because older autistic adults will likely have supports needs that match or exceed those of similarly aged non-autistic individuals. In this article, we spoke to autistic adults over 50 years about their daily experiences and how they use technology. We identified some important ways that older autistic adults use technology in their daily lives, as well as a number of support needs and barriers to technology use. Based on the findings, we were able to provide some guidelines and recommendations for technology developers and service providers to assist with designing, creating and using technology with older autistic adults.

Multi-omics profiling of a CHO cell culture system unravels the effect of culture pH on cell growth, antibody titer, and product quality.

A robust monoclonal antibody (mAb) bioprocess requires physiological parameters such as temperature, pH, or dissolved oxygen to be well-controlled as even small variations in them could potentially impact the final product quality. For instance, pH substantially affects N-glycosylation, protein aggregation, and charge variant profiles, as well as mAb productivity. However, relatively less is known about how pH jointly influences product quality and titer. In this study, we investigated the effect of pH on culture performance, product titer, and quality profiles by applying longitudinal multi-omics profiling, including transcriptomics, proteomics, metabolomics, and glycomics, at three different culture pH set points. The subsequent systematic analysis of multi-omics data showed that pH set points differentially regulated various intracellular pathways including intracellular vesicular trafficking, cell cycle, and apoptosis, thereby resulting in differences in specific productivity, product titer, and quality profiles. In addition, a time-dependent variation in mAb N-glycosylation profiles, independent of pH, was identified to be mainly due to the accumulation of mAb proteins in the endoplasmic reticulum disrupting cellular homeostasis over culture time. Overall, this multi-omics-based study provides an in-depth understanding of the intracellular processes in mAb-producing CHO cell line under varied pH conditions, and could serve as a baseline for enabling the quality optimization and control of mAb production.

Clarifying Self-Report Measures of Social Anxiety and Obsessive-Compulsive Disorder to Improve Reporting for Autistic Adults.

Background: Phenotypic similarities exist between autism-related experiences and anxiety (especially social anxiety and obsessive-compulsive disorder [OCD]), making it difficult for autistic people to self-report their experiences using existing measures developed for nonautistic adults. We examined whether clarifications aiming to tease out autism-related experiences from social anxiety or OCD in self-report questionnaires would influence autistic and nonautistic participants' ratings. Methods: Two autistic consultants and two experienced clinicians were consulted to develop item clarifications aiming to disentangle autistic from anxiety experiences for two questionnaires: the Social Anxiety Questionnaire (SAQ) and the Padua Inventory (PI) for OCD. Autistic adults (n = 50) and nonautistic university students with higher (n = 81) and lower autistic traits (ATs; n = 104) completed the original questionnaire followed by the clarified questionnaire items online. Results: For social anxiety, there were few significant differences between the original and clarified item and total SAQ scores. For OCD, participants reported significantly lower scores for the OCD-clarified PI items than for the original items and the autism-clarified items. Larger original-clarified PI mean item differences were noted in items describing repetitive behaviors, "obsessional" thoughts, and contamination fears. Similar patterns of differences were found in autistic and nonautistic participants with higher and lower ATs, but differences were often larger in the autistic group. Conclusion: The SAQ in its original form appears to be an appropriate measure for autistic people to self-report social anxiety. However, autistic people appeared to complete the original PI items to reflect, to some extent, their autism-related experiences, rather than the originally intended OCD symptoms. Thus, the original OCD self-report ratings were inflated using the PI. Professionals should therefore clarify the intended meanings of different items of the PI to ensure more accurate and relevant ratings of OCD symptoms in autistic people. Lay summary: Why was this study done?: Autistic people and people with higher autistic traits (ATs) often experience higher rates of anxiety. Anxiety measures developed for the general population may not be appropriate or accurate for measuring anxiety in autistic people. We investigated whether clarifying items in existing self-report questionnaires to tease out anxiety from autistic experiences would influence the way autistic adults self-report their social anxiety and obsessive-compulsive disorder (OCD) symptoms, and if so in what ways. We also wanted to know whether providing these item clarifications would affect the ratings of nonautistic individuals with varying rates of ATs to the same extent.What did the researchers do?: We initially consulted two autistic adults and two clinicians with experience working with autistic adults and co-occurring mental health difficulties. We selected two measures: the Social Anxiety Questionnaire (SAQ) for social anxiety symptoms and the Padua Inventory for OCD symptoms. The consultants identified social anxiety and OCD items that could be interpreted or experienced differently by autistic people and proposed ways to clarify them to make their meaning clearer.Next, 50 autistic people and 185 nonautistic university students participated in our online study. The nonautistic participants were grouped into those with higher or lower ATs. Participants completed the original social anxiety and OCD questionnaires first, followed by the clarified versions of the two questionnaires.What were the results of the study?: For social anxiety, we only found small differences in ratings when participants used measures with or without clarifications. This was true in both autistic and nonautistic participants. For OCD symptoms, autistic people's OCD ratings were significantly lower for many items after we provided clarifications, especially for items describing repetitive behaviors, "obsessional" thoughts, and contamination fears. This finding suggests that in the original questionnaire, autistic people may have also been rating their autism-related experiences, not just the OCD experiences or symptoms the questionnaire was trying to measure. We found similar differences between the original and clarified item ratings in nonautistic participants with higher and lower ATs. However, the differences were more common and pronounced with the autistic participants.What do these findings add to what was already known?: These findings suggest that original self-report measures of anxiety may need to be clarified so that autistic adults can better capture and rate their anxiety, rather than their autism-related experiences.What are potential weaknesses in the study?: We used only two anxiety questionnaires, so these findings may or may not be applicable to other OCD or social anxiety questionnaires available. Also, the clarifications we provided may not be representative of all autistic people's experiences, and it is possible that there are other and better ways to clarify the items. We also conducted many item comparisons in this study, so there is a possibility that some findings were due to chance.How will these findings help autistic adults now or in the future?: Our findings can help improve clinical interviews and use of anxiety questionnaires by making them more accurate. They can also help clinicians appreciate the importance of asking clarifying questions to ensure they better capture autistic adults' anxiety experiences.

Exploiting the Disialyl Galactose Activity of α2,6-Sialyltransferase from Photobacterium damselae To Generate a Highly Sialylated Recombinant α-1-Antitrypsin.

Sialic acids are sugars present in many animal glycoproteins and are of particular interest in biopharmaceuticals, where a lack of sialylation can reduce bioactivity. Here, we describe how α-2,6-sialyltransferase from Photobacterium damselae can be used to markedly increase the level of sialylation of CHO-produced α-1-antitrypsin. Detailed analysis of the sialylation products showed that in addition to the expected α-2,6-sialylation of galactose, a second disialyl galactose motif Neu5Ac-α2,3(Neu5Ac-α2,6)Gal was produced, which, to our knowledge, had never been detected on a mammalian glycoprotein. We exploited this disialyl galactose activity of the P. damselae in a multienzyme reaction to produce a highly sialylated α-1-antitrypsin. The influence of this unique disialylation on the in vitro activity of α-1-antitrypsin was studied, and a toolkit of mass spectrometry methods for identifying this new disialyl galactose motif in complex mixtures was developed.

Comparative phenotypic analysis of CHO clones and culture media for lactate shift.

We explored the effects of media and clonal variation on the lactate shift which can be considered as one of the desirable features in CHO cell culture. Various culture profiles with the specific growth and antibody production rates under three different media conditions in two CHO producing clones were evaluated by resorting to multivariate statistical analysis. In most cases, glutamine depletion coincided with lactate consumption, suggesting that glutaminolysis rather than glycolysis was the preferred pathway for the pyruvate supply toward lactate production. With respect to the lactate shift, high performing medium showed higher glutamate uptake, higher aspartate secretion and lower serine uptake compared to other media conditions. In addition, clone itself exhibited the desired lactate consumption more consistently accompanying with distinguishing phenotype. The clone exhibiting lactate shift produced lesser lactate in exponential phase but two-fold higher non-toxic alanine, thus leading to better culture environment. Thus, we understand the balanced selection of clone and media composition enables cells to utilize the metabolic pathways for the desired lactate shift.

Application of maltose as energy source in protein-free CHO-K1 culture to improve the production of recombinant monoclonal antibody.

Oligosaccharides are generally considered to be un-utilized for growth of mammalian cells because their permeability across the cell membrane is low. However, in our previous study, we discovered that CHO and HEK293 cells consume maltose in culture media without serum and glucose. This is interesting because the transporter for maltose in mammalian cells has not been discovered to-date, and the only animal disaccharide transporter that is recently discovered is a sucrose transporter. The application of oligosaccharides in mammalian cell-based biopharmaceutical manufacturing can be beneficial, because it can theoretically increase carbohydrate content of the culture medium and decrease lactate production. Here, we first determined that specific maltose consumption rate in CHO cells was similar to galactose and fructose at 0.257 ng/cell/day. We then demonstrated that CHO cells can be cultivated with reasonable cell growth using higher maltose concentrations. After which, we evaluated the use of maltose supplementation in the production of a recombinant monoclonal antibody in batch and fed-batch cultures, demonstrating improvements in recombinant monoclonal antibody titer of 15% and 23% respectively. Finally, glycosylation profiles of the antibodies were analyzed.

Evaluation and use of disaccharides as energy source in protein-free mammalian cell cultures.

Mammalian cells are generally considered to be unable to utilize polysaccharides for cell growth because the phospholipid bilayer in the cell membrane has very low permeability to sugars. With the recent discovery of the only known animal disaccharide transporter, a sucrose transporter, we considered the potential use of polysaccharides as energy source, because that can impact biopharmaceutical manufacturing by potentially increasing carbohydrate loading in the culture medium and decreasing lactate accumulation. In this study, we found that mammalian cells can utilize maltose for growth in the absence of glucose and successfully adapted CHO-K1, CHO-DG44 and HEK293 cells to grow in glucose-free, maltose-containing serum-free protein-free media. We then cultivated a non-adapted CHO-K1 producer cell line in media containing both glucose and maltose to show that the cells can utilize maltose in a biphasic manner, that maltose enters the cells, and that maltose utilization only took place in the presence of the cells. This is the first report of a protein-free mammalian cell culture using a disaccharide as energy source.