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The last 5 y have seen the development and widespread adoption of high-plex spatial transcriptomic technology. This technique detects and quantifies mRNA transcripts in situ, meaning that transcriptomic signatures can be sampled from specific cells, structures, lesions, or anatomical regions while conserving the physical relationships that exist within complex tissues. These methods now frequently implement next-generation sequencing, enabling the simultaneous measurement of many targets, up to and including the whole mRNA transcriptome. To date, spatial transcriptomics has been foremost used in the fields of neuroscience and oncology, but there is potential for its use in transplantation sciences. Transplantation has a clear dependence on biopsies for diagnosis, monitoring, and research. Transplant patients represent a unique cohort with multiple organs of interest, clinical courses, demographics, and immunosuppressive regimens. Obtaining high complexity data on the disease processes underlying rejection, tolerance, infection, malignancy, and injury could identify new opportunities for therapeutic intervention and biomarker identification. In this review, we discuss currently available spatial transcriptomic technologies and how they can be applied to transplantation.

Autosomal dominant hyper-IgE syndrome (AD-HIES) is typically caused by dominant-negative (DN) STAT3 mutations. Patients suffer from cold staphylococcal lesions and mucocutaneous candidiasis, severe allergy, and skeletal abnormalities. We report 12 patients from 8 unrelated kindreds with AD-HIES due to DN IL6ST mutations. We identified seven different truncating mutations, one of which was recurrent. The mutant alleles encode GP130 receptors bearing the transmembrane domain but lacking both the recycling motif and all four STAT3-recruiting tyrosine residues. Upon overexpression, the mutant proteins accumulate at the cell surface and are loss of function and DN for cellular responses to IL-6, IL-11, LIF, and OSM. Moreover, the patients’ heterozygous leukocytes and fibroblasts respond poorly to IL-6 and IL-11. Consistently, patients with STAT3 and IL6ST mutations display infectious and allergic manifestations of IL-6R deficiency, and some of the skeletal abnormalities of IL-11R deficiency. DN STAT3 and IL6ST mutations thus appear to underlie clinical phenocopies through impairment of the IL-6 and IL-11 response pathways.

The authors regret that in the original version of Table S1, the column for patient 12 was mistakenly duplicated in the column for patient 8. The online Table S1 PDF has been corrected. The error appears only in PDFs downloaded before June 4, 2020.

In physics, the term ‘solid’ is frequently associated with crystals, despite the fact that there is a vast number of solid structures that are not crystalline, such as amorphous or glassy solids. Due to their periodic structures and long-range order, even complex crystalline structures can be studied with the help of mathematical tools such as Bloch states, Brillouin zones, k-space, etc. Glassy solids, on the other hand, do not offer any mitigating circumstances with respect to their theoretical treatment due to their lack of long-range order and low predictability of internal structure. Nevertheless, glassy materials can be studied experimentally, theoretically, and by using computer simulations. In this thesis, we firstly study the properties of glasses close to the yielding transition. The yielding transition occurs as the amorphous solid is irreversibly deformed beyond its elastic limit. Though extensively studied, this transition is still not well understood. We take a look at this elusive phenomenon at a micro-mechanical level and develop an approach that has embedded within it the very carriers of plasticity that are responsible for it. Secondly, we explore the free energy in the hard sphere model and its experimental equivalent-colloidal glass. Specifically, we aim to establish local-particle level-free energy as a bridge between micro-structure and glassy dynamics.

The palatal shelf epithelium of the Mongolian gerbil was examined for succinic dehydrogenase activity prior to, during and the after palatal fusion (days 18-20 post coitus). Enzyme activity was present during all stages examined, and was noted even in the epithelial pearls of fused palates. The presence of SDH activity in these epithelial pearls lends support to the theory 'epithelial stretching', and questions the theory of 'programmed cell death' in relation to the loss of the epithelium along the plane of fusion.

Nell'abstract, sintesi dell'intervento al convegno internazionale organizzato dall'Institute of Education di Londra, sono illustrate alcune tappe e problemi della scuola elementare in guerra nella città di Bologna, tra emergenza e progetto.