Publication

The Role of Sodium Glucose Co-Transporter 1 in Hyperglycemia Ischemia Reperfusion Injury

Introduction: Hyperglycemia is a common finding in ACS patients in both diabetic and non-diabetic, it is considered a powerful predictor of prognosis and mortality. The role of hyperglycemia in ischemia-reperfusion injury is not fully understood, whether the Sodium Glucose Co-Transporter 1(SGLT1) plays a role in increase injury, before and/or after reperfusion, remains to be elucidated.

Evidence for Clonal Proliferation of Smooth Muscle Cells in Unstable Human Atherosclerotic Lesions

Background: Studies using techniques that relied on expression of an X-linked gene suggested predominant clones of smooth muscle cells (SMC) may exist in human atherosclerosis. These studies were limited by spatial resolution and nature of plaque types studied. We investigated whether clones of SMCs exist in unstable human atheroma. Methods and Results: We used a 25 nucleotide deletion in the 3’ UTR of the BGN gene, highly expressed by SMC and prevalent in 30% of females, to study clonal proliferation.

Cortical wiring by synapse type-specific control of local protein synthesis

Neurons use local protein synthesis to support their morphological complexity, which requires independent control across multiple subcellular compartments up to the level of individual synapses. We identify a signaling pathway that regulates the local synthesis of proteins required to form excitatory synapses on parvalbumin-expressing (PV+) interneurons in the mouse cerebral cortex.

Mechanoreceptor signal convergence and transformation in the dorsal horn flexibly shape a diversity of outputs to the brain

The encoding of touch in the spinal cord dorsal horn (DH) and its influence on tactile representations in the brain are poorly understood. Using a range of mechanical stimuli applied to the skin, large-scale in vivo electrophysiological recordings, and genetic manipulations, here we show that neurons in the mouse spinal cord DH receive convergent inputs from both low- and high-threshold mechanoreceptor subtypes and exhibit one of six functionally distinct mechanical response profiles.

Polony gels enable amplifiable DNA stamping and spatial transcriptomics of chronic pain

Methods for acquiring spatially resolved omics data from complex tissues use barcoded DNA arrays of low- to sub-micrometer features to achieve single-cell resolution. However, fabricating such arrays (randomly assembled beads, DNA nanoballs, or clusters) requires sequencing barcodes in each array, limiting cost-effectiveness and throughput. Here, we describe a vastly scalable stamping method to fabricate polony gels, arrays of ∼1-micrometer clonal DNA clusters bearing unique barcodes.

Metastatic recurrence in colorectal cancer arises from residual EMP1 cells

Around 30-40% of patients with colorectal cancer (CRC) undergoing curative resection of the primary tumour will develop metastases in the subsequent years<sup>1</sup>. Therapies to prevent disease relapse remain an unmet medical need. Here we uncover the identity and features of the residual tumour cells responsible for CRC relapse. An analysis of single-cell transcriptomes of samples from patients with CRC revealed that the majority of genes associated with a poor prognosis are expressed by a unique tumour cell population that we named high-relapse cells (HRCs).

The neurons that restore walking after paralysis

A spinal cord injury interrupts pathways from the brain and brainstem that project to the lumbar spinal cord, leading to paralysis. Here we show that spatiotemporal epidural electrical stimulation (EES) of the lumbar spinal cord<sup>1-3</sup> applied during neurorehabilitation<sup>4,5</sup> (EES<sup>REHAB</sup>) restored walking in nine individuals with chronic spinal cord injury. This recovery involved a reduction in neuronal activity in the lumbar spinal cord of humans during walking.

Effect of the intratumoral microbiota on spatial and cellular heterogeneity in cancer

The tumour-associated microbiota is an intrinsic component of the tumour microenvironment across human cancer types1,2. Intratumoral host-microbiota studies have so far largely relied on bulk tissue analysis1-3, which obscures the spatial distribution and localized effect of the microbiota within tumours. Here, by applying in situ spatial-profiling technologies4 and single-cell RNA sequencing5 to oral squamous cell carcinoma and colorectal cancer, we reveal spatial, cellular and molecular host-microbe interactions.

Safety De-risking Approaches for Advanced Modalities

Artificial intelligence (AI) is now a powerful tool which can be applied to significantly improve the safety de-risking process early in discovery, with AI-driven  pipelines of biotechs expanding at a very fast rate. Data from screening studies with DNA-encoded libraries together with high throughput in silico data are screened through AI-enabled computational platforms.

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