Publication

Pleasurable touch is paramount during social behavior, including sexual encounters. However, the identity and precise role of sensory neurons that transduce sexual touch remain unknown. A population of sensory neurons labeled by developmental expression of the G protein-coupled receptor Mrgprb4 detects mechanical stimulation in mice. Here, we study the social relevance of Mrgprb4-lineage neurons and reveal that these neurons are required for sexual receptivity and sufficient to induce dopamine release in the brain.

Mass cytometry (cytometry by time-of-flight detection [CyTOF]) is a bioanalytical technique that enables the identification and quantification of diverse features of cellular systems with single-cell resolution. In suspension mass cytometry, cells are stained with stable heavy-atom isotope-tagged reagents, and then the cells are nebulized into an inductively coupled plasma time-of-flight mass spectrometry (ICP-TOF-MS) instrument. In imaging mass cytometry, a pulsed laser is used to ablate ca. 1 μm2 spots of a tissue section.

Affinity-optimized T cell receptors can enhance the potency of adoptive T cell therapy. Afamitresgene autoleucel (afami-cel) is a human leukocyte antigen-restricted autologous T cell therapy targeting melanoma-associated antigen A4 (MAGE-A4), a cancer/testis antigen expressed at varying levels in multiple solid tumors. We conducted a multicenter, dose-escalation, phase 1 trial in patients with relapsed/refractory metastatic solid tumors expressing MAGE-A4, including synovial sarcoma (SS), ovarian cancer and head and neck cancer ( NCT03132922 ).

In a neuropathological series of 20 COVID-19 cases, we analyzed six cases (three biopsies and three autopsies) with multiple foci predominantly affecting the white matter as shown by MRI. The cases presented with microhemorrhages evocative of small artery diseases. This COVID-19 associated cerebral microangiopathy (CCM) was characterized by perivascular changes: arterioles were surrounded by vacuolized tissue, clustered macrophages, large axonal swellings and a crown arrangement of aquaporin-4 immunoreactivity. There was evidence of blood-brain-barrier leakage.

The accurate localization of transgene expression after viral vector delivery is essential to the interpretation of experiments based on genetic-based approaches, such as chemo- or optogenetics. Postmortem histological analysis can be used to examine the injection target, the extent of the virus transduction, the types of cells expressing the transgene, and the subcellular localization of the protein. In this chapter, we will provide a general description of methods to identify transgene expression, immunocytochemistry protocols, and examples of specific protocols.

The development of new genetic tools has revolutionized our ability to study the functional role of specific neuronal populations and circuits generating behavior. Although this revolution has already taken place in small animal models such as mice, adoption of these techniques has been relatively slow for animals more closely related to humans, such as nonhuman primates. Current challenges include effective delivery to much larger structural targets in the primate brain, cell-type specific transduction, and immunological responses.

Recombinant adeno-associated viruses can be coupled with short regulatory elements to restrict viral expression to specific cellular populations. These viral vectors can be used as tools for basic research to dissect many aspects of the biology of specific cellular subtypes in health and disease, and across species. A handful of enhancers have already been described in the nervous system, and recent studies suggest that transcriptomic and epigenetic data can be leveraged to systematize the discovery of novel elements to restrict viral expression to any cell type.

The intestine is critical for not only processing and resorbing nutrients but also protecting the organism from the environment. These functions are mainly carried out by the epithelium, which is constantly being self-renewed. Many genes and pathways can influence intestinal epithelial cell proliferation. Among them is mTORC1, whose activation increases cell proliferation. Here, we report the first intestinal epithelial cell-specific knockout ( ΔIEC ) of an amino acid transporter capable of activating mTORC1.

We use cookies to make sure that our website works properly, as well as some ‘optional’ cookies to personalise content and advertising, provide social media features and analyse how people use our site. By accepting some or all optional cookies you give consent to the processing of your personal data, including transfer to third parties, some in countries outside of the European Economic Area that do not offer the same data protection standards as the country where you live.

Nucleic acid pharmaceutical (NAP) agents are a relatively recent class of therapeutics that are uniquely capable of inhibiting protein translation through direct interaction with RNA. These classes of pharmaceuticals have demonstrated clinical benefit for diseases previously considered untreatable by small molecules and biologics by their theoretical ability to target any cellular RNA associated with disease.