Synthetic GPCRs for programmable sensing and control of cell behaviour.

Synthetic receptors that mediate antigen-dependent cell responses are transforming therapeutics, drug discovery and basic research. However, established technologies such as chimeric antigen receptors can only detect immobilized antigens, have limited output scope and lack built-in drug control. Here we engineer synthetic G-protein-coupled receptors (GPCRs) that are capable of driving a wide range of native or non-native cellular processes in response to a user-defined antigen.

Electrical synapse molecular diversity revealed by proximity-based proteomic discovery.

Neuronal circuits are composed of synapses that are either chemical, where signals are transmitted via neurotransmitter release and reception, or electrical, where signals pass directly through interneuronal gap junction channels. While the molecular complexity that controls chemical synapse structure and function is well appreciated, the proteins of electrical synapses beyond the gap-junction-forming Connexins are not well defined. Yet, electrical synapses are expected to be molecularly complex beyond the gap junctions.

Directed evolution of the multicopper oxidase laccase for cell surface proximity labeling and electron microscopy.

Enzymes that oxidize aromatic substrates have shown utility in a range of cell-based technologies including live cell proximity labeling (PL) and electron microscopy (EM), but are associated with drawbacks such as the need for toxic HO. Here, we explore laccases as a novel enzyme class for PL and EM in mammalian cells. LaccID, generated via 11 rounds of directed evolution from an ancestral fungal laccase, catalyzes the one-electron oxidation of diverse aromatic substrates using O instead of toxic HO, and exhibits activity selective to the surface plasma membrane of both living and fixed cells.

Characterization of putative antimicrobial compounds produced by endolichenic exposed to light treatments.

The endolichenic (EF5), known to show induced metabolite production when exposed to red and green lights, was selected for characterization of their putative light-regulated bioactive compounds. To achieve this, fractionation was first performed for crude extracts from cultures of (EF5) incubated in green, red, white-fluorescent light and dark conditions. The extract yielded 12 (dark condition) to 15 (exposed to green, red, and white-fluorescent lights) fractions, and each of the fractions was tested for antimicrobial activities.

TBK1 and IKKε protect target cells from IFNγ-mediated T cell killing via an inflammatory apoptotic mechanism.

Cytotoxic T cells produce interferon gamma (IFNγ), which plays a critical role in anti-microbial and anti-tumor responses. However, it is not clear whether T cell-derived IFNγ directly kills infected and tumor target cells, and how this may be regulated. Here, we report that target cell expression of the kinases TBK1 and IKKε regulate IFNγ cytotoxicity by suppressing the ability of T cell-derived IFNγ to kill target cells.

Sleep Composition of Patients With Colorectal Cancer and Their Sleep-Partner Caregivers: Physical Health Correlates of Sleep Diary and Actigraphy Measurements.

Background: Disturbed sleep is frequently identified in adult patients with cancer and their caregivers, with detrimental impact on physical health. Less known is the extent to which self-reported and actigraph-measured sleep patterns are similar between patients and their sleep-partner caregivers, and how these different modes of sleep measurements are related to physical health.

Methods: Patients diagnosed with colorectal cancer and their sleep-partner caregivers (81 dyads) completed a questionnaire for physical functioning and collected saliva samples for seven consecutive days, from which cortisol slope was quantified.

The associations of spirituality and Hispanic ethnicity with neuroendocrine biomarkers among patients with colorectal cancer.

Objective: Dealing with cancer evokes not only physical and emotional distress, but may also promote resilience through spirituality. Patients with cancer are vulnerable to neuroendocrine dysregulation. This longitudinal observational study examined the degree to which spirituality was associated with neuroendocrine biomarkers and the moderating role of Hispanic ethnicity.

Molecular and cellular mechanisms of teneurin signaling in synaptic partner matching.

In developing brains, axons exhibit remarkable precision in selecting synaptic partners among many non-partner cells. Evolutionarily conserved teneurins are transmembrane proteins that instruct synaptic partner matching. However, how intracellular signaling pathways execute teneurins' functions is unclear.

Numb positively regulates Hedgehog signaling at the ciliary pocket.

Hedgehog (Hh) signaling relies on the primary cilium, a cell surface organelle that serves as a signaling hub for the cell. Using proximity labeling and quantitative proteomics, we identify Numb as a ciliary protein that positively regulates Hh signaling. Numb localizes to the ciliary pocket and acts as an endocytic adaptor to incorporate Ptch1 into clathrin-coated vesicles, thereby promoting Ptch1 exit from the cilium, a key step in Hh signaling activation.

Synthetic G protein-coupled receptors for programmable sensing and control of cell behavior.

Synthetic receptors that mediate antigen-dependent cell responses are transforming therapeutics, drug discovery, and basic research. However, established technologies such as chimeric antigen receptors (CARs) can only detect immobilized antigens, have limited output scope, and lack built-in drug control. Here, we engineer synthetic G protein-coupled receptors (GPCRs) capable of driving a wide range of native or nonnative cellular processes in response to user-defined antigen.

Microbial degradation of low-density polyethylene, polyethylene terephthalate, and polystyrene by novel isolates from plastic-polluted environment.

Biodegradation is an eco-friendly measure to address plastic pollution. This study screened four bacterial isolates that were capable of degrading recalcitrant polymers, i.e.

Directed evolution of genetically encoded LYTACs for cell-mediated delivery.

Lysosome-targeting chimeras (LYTACs) are a promising therapeutic modality to drive the degradation of extracellular proteins. However, early versions of LYTAC contain synthetic glycopeptides that cannot be genetically encoded. Here, we present our designs for a fully genetically encodable LYTAC (GELYTAC), making our tool compatible with integration into therapeutic cells for targeted delivery at diseased sites.

Pathogenicity of monokaryotic and dikaryotic mycelia of Ganoderma boninense revealed via LC-MS-based metabolomics.

This study compared the pathogenicity of monokaryotic (monokaryon) and dikaryotic (dikaryon) mycelia of the oil palm pathogen Ganoderma boninense via metabolomics approach. Ethyl acetate crude extracts of monokaryon and dikaryon were analysed by liquid chromatography quadrupole/time-of-flight-mass spectrometry (LC-Q/TOF-MS) coupled with multivariate data analysis using MetaboAnalyst. The mummichog algorithm was also used to identify the functional activities of monokaryon and dikaryon without a priori identification of all their secondary metabolites.

Dyadic Investigation of Posttraumatic Stress Symptoms and Daily Sleep Health in Patients With Cancer and Their Caregivers.

Objective: Cancer can be a traumatic experience affecting multidimensional aspects of sleep among patients and caregivers. This study examined the differential associations of cancer-related posttraumatic stress symptoms (PTSS) with various sleep markers in this population.

Methods: Patients newly diagnosed with colorectal cancer ( n = 138, mean age = 56.

Effects of Electronic Cigarette Vaping on Cardiac and Vascular Function, and Post-myocardial Infarction Remodeling in Rats.

The effect of electronic cigarette (E-cig) vaping on cardiac and vascular function during the healing phase of myocardial infarction (MI), and post-MI remodeling was investigated. Sprague Dawley rats were subjected to left coronary artery ligation to induce MI. One week later, rats were randomized to receive either 12 weeks of exposure to purified air (n = 37) or E-cig vapor (15 mg/ml of nicotine) (n = 32).

Influence of coloured lights on growth and enzyme production of beneficial endophytic fungi.

The influence of light regulation on fungal growth and enzyme production was tested on endophytic isolates of Fusarium proliferatum (CCH), Colletotrichum boninense (PL1, PL9, OL2), Colletotrichum gloeosporiodes (OL3) and Colletotrichum siamense (PL3). The isolates were treated with blue, red, green, and yellow light, while white fluorescent light (12 h light/12 h dark photoperiod) and 24 h dark conditions were applied as control. Results revealed that coloured light treatments induced formation of circadian rings, while exposure to white light and dark conditions showed less pronounced circadian rings.

Risk of Streptococcus pneumoniae-associated haemolytic uraemic syndrome in industrialised nations: a systematic review of the literature.

Background And Aim: Haemolytic uraemic syndrome (HUS) is a triad of haemolytic anaemia, thrombocytopaenia, and acute kidney injury. It is a leading cause of acute kidney injury in children and has a high rate of long-term sequelae. Streptococcus pneumoniae-associated HUS (SpHUS) is a rare complication from pneumococcal disease.

Healthcare resource utilization, costs and treatment associated with myasthenia gravis exacerbations among patients with myasthenia gravis in the USA: a retrospective analysis of claims data.

There are limited data on the clinical and economic burden of exacerbations in patients with myasthenia gravis (MG). We assessed patient clinical characteristics, treatments and healthcare resource utilization (HCRU) associated with MG exacerbation. This was a retrospective analysis of adult patients with MG identified by commercial, Medicare or Medicaid insurance claims from the IBM MarketScan database.

Directed Evolution of Genetically Encoded LYTACs for Cell-Mediated Delivery.

Lysosome-targeting chimeras (LYTACs) are a promising therapeutic modality to drive the degradation of extracellular proteins. However, early versions of LYTAC contain synthetic glycopeptides that cannot be genetically encoded. Here we present our designs for a fully genetically encodable LYTAC (GELYTAC), making our tool compatible with integration into therapeutic cells for targeted delivery at diseased sites.