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Despite the established need for sexuality and relationship programming for autistic adults, there are extremely limited curricula for this population. This pilot study used an evidence-based sexuality and relationship education program for autistic adolescents (Tackling Teenage Training) as the basis for an adult-focused virtual psychoeducational group. Qualitative feedback, quantitative ratings of the programming, and behavioral surveys from participants were collected. Nine participants completed the program, and corresponding pre and post measures. Highly rated topics, for example gender identity and online dating, were consistent with previous research on what autistic adults want from a sexuality and relationship education program. Future programming should incorporate increased attention to themes and topics highlighted by participants, and should utilize the teaching tools (e.g., role play, peer discussions) identified as useful by the participants.

This longitudinal study assessed the impact of the COVID-19 pandemic on children with autism spectrum disorder (ASD; n = 62; Mage = 13 years) by measuring emotional and behavioral problems before and during the pandemic, and by comparing this change to a matched sample of children without ASD (n = 213; Mage = 16 years). Moreover, we examined whether indicators of parental well-being promoted resilience of children with ASD. Results showed that the mean change in problems did not differ between children with and without ASD. Importantly, some children showed an increase in problems, while others showed resilience. Parental well-being indicators were not related to resilience among children with ASD. The interindividual variability in responses, particularly among children with ASD, highlights the need for personalized support.

BackgroundThe COVID-19 pandemic is a challenge for everyone, particularly for children and adolescents with autism spectrum disorder (ASD). ASD is a developmental disorder characterised by limitations in social communication, repetitive behavioural patterns, and limited interests, and activities. It is expected that many families with children with ASD will experience more problems due to the COVID-19 pandemic and the related public health restrictions. At the same time, some may experience improved functioning, due to fewer expectations and social demands.Methods/designIn a mixed-method study to identify the impact of the COVID-19 pandemic, parents of children with ASD (ages 4–21) who were in care pre-COVID-19 at one of three large mental healthcare institutions in the region of Rotterdam participated (68 for T0, 57 for T1). The aims are (1) to investigate the impact of the COVID-19 pandemic on overall functioning and autistic symptoms of the child/adolescent with ASD, as well as parental and family functioning (QUANT-QUAL), in both the short term and longer term, and (2) to investigate risk and protective factors (in light of resilience) (QUANT-qual) and (3) to investigate care and informational needs (QUAL-quant). Pre-COVID-19 baseline data will be retrieved from clinical records. Participants will fill out two surveys (one during a COVID-19 peak—January–May 2021—and one thereafter). Survey participants were invited to participate in interviews (n=27). Surveys include measures thar were included pre-COVID-19 (ie, overall functioning and autism symptoms) as well as specific measures to identify family functioning and COVID-19 impact. The semistructured interviews focus on child, parent and family functioning and care—and informational needs.Ethics and disseminationThe Medical Ethics Committee of the Erasmus MC has approved the study. Findings will be available to families of children with ASD, their care providers, the funders, autism societies, the government and other researchers.

Bacteria proficient at producing cellulose are an attractive synthetic biology host for the emerging field of Engineered Living Materials (ELMs). Species from the Komagataeibacter genus produce high yields of pure cellulose materials in a short time with minimal resources, and pioneering work has shown that genetic engineering in these strains is possible and can be used to modify the material and its production. To accelerate synthetic biology progress in these bacteria, we introduce here the Komagataeibacter tool kit (KTK), a standardised modular cloning system based on Golden Gate DNA assembly that allows DNA parts to be combined to build complex multigene constructs expressed in bacteria from plasmids. Working in Komagataeibacter rhaeticus, we describe basic parts for this system, including promoters, fusion tags and reporter proteins, before showcasing how the assembly system enables more complex designs. Specifically, we use KTK cloning to reformat the Escherichia coli curli amyloid fibre system for functional expression in K. rhaeticus, and go on to modify it as a system for programming protein secretion from the cellulose producing bacteria. With this toolkit, we aim to accelerate modular synthetic biology in these bacteria, and enable more rapid progress in the emerging ELMs community.

Whole-cell biosensors hold potential in a variety of industrial, medical and environmental applications. These biosensors can be constructed through the repurposing of bacterial sensing mechanisms, including the common two-component system. Here we report on the construction of a range of novel biosensors that are sensitive to acetoacetate, a molecule that plays a number of roles in human health and biology. These biosensors are based on the AtoSC two-component system. An ordinary differential equation model to describe the action of the AtoSC two-component system was developed and sensitivity analysis of this model used to help inform biosensor design. The final collection of biosensors constructed displayed a range of switching behaviours, at physiologically relevant acetoacetate concentrations and can operate in several Escherichia coli host strains. It is envisaged that these biosensor strains will offer an alternative to currently available commercial strip tests and, in future, may be adopted for more complex in vivo or industrial monitoring applications.

Cyanobacteria are promising candidates for sustainable bioproduction of chemicals from sunlight and carbon dioxide. However, the genetics and metabolism of cyanobacteria are less well understood than those of model heterotrophic organisms, and the suite of well-characterised cyanobacterial genetic tools and parts is less mature and complete. Transcriptional terminators use specific RNA structures to halt transcription and are routinely used in both natural and recombinant contexts to achieve independent control of gene expression and to &lsquo, insulate&rsquo, genes and operons from one another. Insulating gene expression can be particularly important when heterologous or synthetic genetic constructs are inserted at genomic locations where transcriptional read-through from chromosomal promoters occurs, resulting in poor control of expression of the introduced genes. To date, few terminators have been described and characterised in cyanobacteria. In this work, nineteen heterologous, synthetic or putative native Rho-independent (intrinsic) terminators were tested in the model freshwater cyanobacterium, Synechocystis sp. PCC 6803, from which eleven strong terminators were identified. A subset of these strong terminators was then used to successfully insulate a chromosomally&ndash, integrated, rhamnose-inducible rhaBAD expression system from hypothesised &lsquo, read-through&rsquo, from a neighbouring chromosomal promoter, resulting in greatly improved inducible control. The addition of validated strong terminators to the cyanobacterial toolkit will allow improved independent control of introduced genes.

There is increasing interest in constructing artificial cells by functionalising lipid vesicles with biological and synthetic machinery. Due to their reduced complexity and lack of evolved biochemical pathways, the capabilities of artificial cells are limited in comparison to their biological counterparts. We show that encapsulating living cells in vesicles provides a means for artificial cells to leverage cellular biochemistry, with the encapsulated cells serving organelle-like functions as living modules inside a larger synthetic cell assembly. Using microfluidic technologies to construct such hybrid cellular bionic systems, we demonstrate that the vesicle host and the encapsulated cell operate in concert. The external architecture of the vesicle shields the cell from toxic surroundings, while the cell acts as a bioreactor module that processes encapsulated feedstock which is further processed by a synthetic enzymatic metabolism co-encapsulated in the vesicle.

Biosensors use biological elements to detect or quantify an analyte of interest. In bioprocessing, biosensors are employed to monitor key metabolites. There are two main types: fully biological systems or biological recognition coupled with physical/chemical detection. New developments in chemical biosensors include multiplexed detection using microfluidics. Synthetic biology can be used to engineer new biological biosensors with improved characteristics. Although there have been few biosensors developed for bioprocessing thus far, emerging trends can be applied in the future. A range of new platform technologies will enable rapid engineering of new biosensors based on transcriptional activation, riboswitches, and Förster Resonance Energy Transfer. However, translation to industry remains a challenge and more research into the robustness biosensors at scale is needed.

Whole-cell biosensors hold potential in a variety of industrial, medical and environmental applications. These biosensors can be constructed through the repurposing of bacterial sensing mechanisms, including the common two-component system. Here we report on the construction of a range of novel biosensors that are sensitive to acetoacetate, a molecule that plays a number of roles in human health and biology. These biosensors are based on the AtoSC two-component system. An ODE model to describe the action of the AtoSC two-component system was developed and sensitivity analysis of this model used to help inform biosensor design. The final collection of biosensors constructed displayed a range of switching behaviours, at physiologically relevant acetoacetate concentrations and can operate in several Escherichia coli host strains. It is envisaged that these biosensor strains will offer an alternative to currently available commercial strip tests and, in future, may be adopted for more complex in vivo or industrial monitoring applications.

The design of vesicle microsystems as artificial cells (bottom-up synthetic biology) has traditionally relied on the incorporation of molecular components to impart functionality. These cell mimics have reduced capabilities compared with their engineered biological counterparts (top-down synthetic biology), as they lack the powerful metabolic and regulatory pathways associated with living systems. There is increasing scope for using whole intact cellular components as functional modules within artificial cells, as a route to increase the capabilities of artificial cells. In this feasibility study, we design and embed genetically engineered microbes ( Escherichia coli ) in a vesicle-based cell mimic and use them as biosensing modules for real-time monitoring of lactate in the external environment. Using this conceptual framework, the functionality of other microbial devices can be conferred into vesicle microsystems in the future, bridging the gap between bottom-up and top-down synthetic biology.

Acidithiobacillus ferrooxidans is an acidophile that thrives in metal-contaminated environments and tolerates high levels of uranium. To gain a better understanding of the processes involved in U(VI) resistance, comparative proteomics was used. The proteome of A. ferrooxidans was grown in the presence and absence of 0.5 mM U(VI); expression of 17 proteins was upregulated and one was downregulated. Most proteins with increased expression are part of the general stress response or are involved in reactive oxygen species detoxification. Four novel proteins showed increased expression in the presence of U(VI) and may contribute to U(VI) resistance via thiol homoeostasis and U(VI) binding.

One of the issues facing the nuclear power industry is how to store spent nuclear fuel which is contaminated with radionuclides produced during nuclear fission, including caesium ((134)Cs(+), (135)Cs(+) and (137)Cs(+)) and cobalt ((60)Co(2+)). In this study, we have isolated Co(2+)- and Cs(+)-resistant bacteria from water collected from a nuclear fuel storage pond. The most resistant Cs(+) and Co(2+) isolates grew in the presence of 500 mM CsCl and 3 mM CoCl2. Strain Cs67-2 is resistant to fourfold more Cs(+) than Cupriavidus metallidurans str. CH34 making it the most Cs(+)-resistant strain identified to date. The Cs(+)-resistant isolates were closely related to bacteria in the Serratia and Yersinia genera, while the Co(2+)-resistant isolates were closely related to the Curvibacter and Tardiphaga genera. These new isolates could be used for bioremediation.

Resistance to lysostaphin, a staphylolytic glycylglycine endopeptidase, is due to a FemABX-like immunity protein that inserts serines in place of some glycines in peptidoglycan cross bridges. These modifications inhibit both binding of the recombinant cell wall targeting domain and catalysis by the recombinant catalytic domain of lysostaphin.

Whether temporary antiretroviral treatment during primary HIV infection (PHI) lowers the viral set point or affects the subsequent CD4 count decline remains unclear. The objectives of this study were to analyze the clinical, viral, and immunological effects of temporary early HAART during PHI. This is a cohort study of patients with laboratory evidence of PHI. Independent predictors of early HAART and the viral set point were analyzed using multiple regression analysis. Plasma HIV-1 RNA (pVL) and CD4 trajectories were analyzed using linear mixed models. A total of 332 patients were included in the analysis. Sixty-four patients started HAART within 180 days of seroconversion. A higher baseline pVL was independently predictive of the start of early HAART (OR: 2.69/log10pVL, p = 0.001). Thirty-two patients who interrupted early HAART were compared with 250 patients who remained untreated for more than 180 days after seroconversion. Temporary early HAART was not significantly associated with a longer AIDS-free survival but did result in an initial, but transient lowering of the viral set point. The viral set point was initially 0.6 log copies/ml lower after interruption of early HAART (p < 0.001) and remained lower during 83 weeks of follow-up. No significant difference in the slopes of CD4 decline was detected between the groups. Temporary HAART in PHI is started more frequently in patients with a higher pVL and can transiently lower the viral set point compared to never treated patients.

Different features have been associated with low susceptibility to HIV type 1 (HIV-1) infection in exposed seronegative individuals. These include genetic make-up such as homozygosity for the CCR5-Δ32 allele and the presence of HIV-specific CTLs. We studied immune activation and immune responsiveness in relation to HIV-1 susceptibility in 42 high-risk seronegative (HRSN) participants of the Amsterdam Cohort Studies and 54 men from the same cohort who were seronegative at the moment of analysis but later became HIV seropositive. HRSN had higher naive (CD45RO CD27) CD4 and CD8 T cell numbers and lower percentages of activated (HLADR CD38, CD70) CD4 and proliferating (Ki67) CD4 and CD8 T cells, irrespective of previous episodes of sexually transmittable infections. Furthermore, whole blood cultures from HRSN showed lower lymphoproliferative responses than healthy laboratory controls. These data suggest that low levels of immune activation and low T cell responsiveness may contribute to low HIV susceptibility.

Because of the increasing resistance of bacteria to antibiotics there is considerable interest in light-activated antimicrobial agents (LAAAs) as alternatives to antibiotics for treating localized infections. In this paper we report that covalently coupling the LAAA tin-chlorin e6 to a gold nanoparticleviaglutathione results in a potent antimicrobial agent when activated by white light. On a molar basis, the tin chlorin e6–nanogold conjugate was a hundred times more effective at killing Staphylococcus aureus than free tin chlorin e6. The conjugate also displayed antibacterial activity against methicillin-resistant S. aureus and Streptococcus pyogenes. This potent new LAAA may be useful for the treatment of topical infections or could be incorporated into coatings that could be used to reduce the microbial load in sensitive environments such as hospitals and food processing facilities.

Iron oxide nanoparticles were made in the presence of three carboxylic acid functionalised organic ligands (tiopronin, oxamic acid and succinic acid) using a co-precipitation method. The iron oxide was a mixture of magnetite and maghemite with an average crystallite size less than 10 nm. The samples were all dialysed prior to analysis to ensure high purity. Without the presence of a carboxylic acid, the dialysis purification stage invoked complete precipitation and the sample was completely intractable. The carboxylic acid stabilised particles could be dissolved in water to form a stable solution. The samples prepared with tiopronin and succinic acid were close to neutral pH and were suitable for magnetic fluid hyperthermia testing on Staphyloccocus aureus. Iron oxide produced with tiopronin was able to achieve a 107-fold reduction in the viable count of the organism using a 2 × 2 minute exposure to an AC magnetic field and this bactericidal effect could still be achieved using the same batch of particles one week later. Oxidation of the samples did occur with aging or sonication and made the heating response less effective after one month. The tiopronin stabilised nanoparticles were able to achieve substantial kills of bacteria at concentrations between 6.25–50 mg/ml. This is, to our knowledge, the first time magnetic hyperthermia has been used to kill bacteria. The heating rates obtained from using an external magnetic alternating field on the iron oxide nanoparticle solutions were four times greater than the best commercially available material. This novel method of killing bacteria could form the basis of a new approach to the treatment of a variety of infectious diseases.

Covalently coupling toluidine blue O–tiopronin to a gold nanoparticle forms an enhanced, exceptionally potent antimicrobial agent when activated by white light or 632 nm laser light. Aqueous solutions of tiopronin–gold nanoparticles had no antimicrobial effect and, when added to solutions of toluidine blue O, did not enhance the antimicrobial effect of the latter. The minimum bactericidal concentration of the covalently coupled toluidine blue O–tiopronin gold conjugate for Staphylococcus aureus was at least four times lower than that of free toluidine blue O.

Macaca irus, reared without physical contact with other monkeys for 6 of 12 months after birth, were deficient in dominance-submissiveness behaviors. A relatively short period of group experience at age 2.5 years resulted in the development of dominance-submissiveness behavior. Therefore, social experience later in development appears to be effective in reversing some of the consequences of early social deprivation.