Cellular & Molecular Imaging

to be described

to be described

to be described

The source image data for the manuscript: 'BMP-9 mediates fibroproliferation in fibrodysplasia ossificans progressiva through TGF-β signaling'.

The neglected tropical disease schistosomiasis impacts over 700 million people globally. Schistosoma mansoni, the trematode parasite that causes the most common type of schistosomiasis, requires planorbid pond snails of the genus Biomphalaria to support its larval development and transformation to the cercarial form that can infect humans. A greater understanding of neural signaling systems that are specific to the Biomphalaria intermediate host could lead to novel strategies for parasite or snail control. This study examined a Biomphalaria glabrata neural channel that is gated by the neuropeptide FMRF-NH2. The Biomphalaria glabrata FMRF-NH2 gated sodium channel (Bgl-FaNaC) amino acid sequence was highly conserved with FaNaCs found in related gastropods, especially the planorbid Planorbella trivolvis (91% sequence identity). In common with the P. trivolvis FaNaC, the B. glabrata channel exhibited a low affinity (EC50: 3 x 10-4 M) and high specificity for the FMRF-NH2 agonist. Its expression in the central nervous system, detected with immunohistochemistry and in situ hybridization, was widespread, with the protein localized mainly to neuronal fibers and the mRNA confined to cell bodies. Colocalization of the Bgl-FaNaC message with its FMRF-NH2 agonist precursor occurred in some neurons associated with male mating behavior. At the mRNA level, Bgl-FaNaC expression was decreased at 20 and 35 days post infection (dpi) by S. mansoni. Increased expression of the transcript encoding the FMRF-NH2 agonist at 35 dpi was proposed to reflect a compensatory response to decreased receptor levels. Altered FMRF-NH2 signaling could be vital for parasite proliferation in its intermediate host and may therefore present innovative opportunities for snail control.

TGFβ drives fibroblast activation in cancer and is a resistance biomarker to PD-1/PD-L1 blockade. Focusing on the tumor stroma, we characterized the impact of neoadjuvant treatment with bintrafusp-alfa (BA), a dual PD-L1 and TGFβ inhibitor, in a window-of-opportunity study with six head and neck squamous cell carcinoma (HNSCC) patients. Tumor biopsies pre-treatment and 3-weeks post-therapy were analyzed using single-cell RNA sequencing, imaging and spatial transcriptomics. After treatment, we observed significant decreased levels of activated LRRC15+ cancer-associated fibroblasts (CAF); remodeled stromal architecture with reduced collagen I and XII content; and increased CD8+ T-cell infiltration in immune-excluded tumors. These changes were independently confirmed in an additional neoadjuvant BA-treated cohort of six HNSCC patients. The drastic CAF and stromal compartment reduction observed indicated a fibroblast depletion rather than a fibroblast polarization shift. While our final clinical cohort does not allow to assess the treatment clinical effect, this study demonstrated that targeting TGFβ in patients can disrupt the tumor stroma within a short timeframe. Further trials and novel biomarkers are now needed to select patients who could benefit.

Sample videos acquired with the InVision device. Videos are of schistosome miracidia swimming in a custom arena and can be used to develop and optimize tracking pipelines.

Skeletal muscle wasting results from numerous conditions, such as sarcopenia, glucocorticoid therapy or intensive care. It prevents independent living in the elderly, predisposes to secondary diseases, and ultimately reduces lifespan. There is no approved drug therapy and the major causative mechanisms are not fully understood. Dual specificity phosphatase 22 (DUSP22) is a pleiotropic signaling molecule that plays important roles in immunity and cancer. However, the role of DUSP22 in skeletal muscle wasting is unknown. In this study, DUSP22 was found to be upregulated in sarcopenia patients and models of skeletal muscle wasting. DUSP22 knockdown or pharmacological inhibition with BML-260 prevented multiple forms of muscle wasting. Mechanistically, targeting DUSP22 suppressed FOXO3a, a master regulator of skeletal muscle wasting, via downregulation of the stress-activated kinase JNK, which occurred independently of aberrant Akt activation. DUSP22 targeting was also effective in human skeletal muscle cells undergoing atrophy. In conclusion, phosphatase DUSP22 is a novel target for preventing skeletal muscle wasting and BML-260 is a therapeutically effective small molecule inhibitor. The DUSP22-JNK-FOXO3a axis could be exploited to treat sarcopenia or related aging disorders

The Darwin Tree of Life project has the goal to sequence the genomes of 70,000 species of eukaryotic organisms in Britain and Ireland. This is a collection of photographs of the samples included in the study, provided by the National History Museum (NHM).

The images are tissue-based screens for autoantibodies in the cerebrospinal fluid of individuals with schizophrenia spectrum disorders (N=28 of 32) and healthy controls (N=27 of 32). For screening, sagittal adult mouse brain sections were incubated with cerebrospinal fluid at a 1:4 dilution and counterstained with anti-human IgG (488 channel). Blue = DAPI. Though all 32 subjects were screened by tissue-based assay, 4 and 5 schizophrenia spectrum and control files, respectively, were lost due to a hardware failure after the images had been evaluated as negative. Photobleaching of slides prevented faithful reacquisition of the images.