Repurposing Synechocystis PCC6803 UirS-UirR as a UV-Violet/Green Photoreversible Transcriptional Regulatory Tool in E. coli.

We have previously engineered green/red and red/far red photoreversible E. coli phytochrome and cyanobacteriochrome (CBCR) two-component systems (TCSs) and utilized them to program tailor-made gene expression signals for gene circuit characterization. Here, we transport the UV-violet/green photoreversible CBCR TCS UirS-UirR from Synechocystis PCC6803 to E. coli. We demonstrate that the promoter of the small RNA csiR1, previously shown to be activated by inorganic carbon stress, is a UirS-UirR output. Additionally, in contrast to a recently proposed sequestration model, we show that the sensor histidine kinase UirS phosphorylates the response regulator UirR to activate PcsiR1 transcription in response to UV-violet light. Finally, we measure changes in UirS-UirR output minutes after a change in light input and exploit these rapid dynamics to program a challenging gene expression signal with high predictability. UirS-UirR is the first engineered transcriptional regulatory tool activated exclusively by UV-violet light, and the most blue shifted photoreversible transcriptional regulatory tool.

An open-hardware platform for optogenetics and photobiology.

In optogenetics, researchers use light and genetically encoded photoreceptors to control biological processes with unmatched precision. However, outside of neuroscience, the impact of optogenetics has been limited by a lack of user-friendly, flexible, accessible hardware. Here, we engineer the Light Plate Apparatus (LPA), a device that can deliver two independent 310 to 1550 nm light signals to each well of a 24-well plate with intensity control over three orders of magnitude and millisecond resolution. Signals are programmed using an intuitive web tool named Iris. All components can be purchased for under $400 and the device can be assembled and calibrated by a non-expert in one day. We use the LPA to precisely control gene expression from blue, green, and red light responsive optogenetic tools in bacteria, yeast, and mammalian cells and simplify the entrainment of cyanobacterial circadian rhythm. The LPA dramatically reduces the entry barrier to optogenetics and photobiology experiments.

The medical, functional and social challenges faced by older adults with intellectual disability.

INTRODUCTION: Little is known about the sociodemographic and clinical profile of older adults with intellectual disabilities (ID) in Singapore. We studied the sociodemographic and clinical profile of older adults with ID and investigated factors associated with caregiver availability and identity in this population. MATERIALS AND METHODS: The study population involved all adults with ID aged ≥40 years receiving services from the Movement for the Intellectually Disabled of Singapore (MINDS), the largest such provider in Singapore. Information on sociodemographic and clinical profiles, functional status, and availability of caregivers were collected via interviewer-administered questionnaires from guardians of older adults with ID. Descriptive characteristics were computed and chi-square and logistic regression identifi ed predictors of caregiver availability and identity. RESULTS: Participation was 95% (227/239). There were differences in client age, gender, and caregiver availability between recipients of residential and non-residential services (all P <0.05). Common comorbidities included hyperlipidaemia (17.6%), hypertension (15.9%), psychiatric diagnoses (16.3%) and epilepsy (10.6%). The majority were fully independent in basic activities of daily living, but only 21.1% were fully communicative. Only a small minority (9.4%) were exercising regularly. The majority (73.5%) of clients had a primary caregiver; almost equal proportions relied on either parents or siblings. Older client age was associated independently with the lack of a primary caregiver, independent of greater functional dependence and presence of medical comorbidities in the client. CONCLUSION: Older adults with ID have multiple medical, functional, and social issues. More can be done to support the care of this unique group of adults with special needs.