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We determine the presence and diversity of rhinoviruses in nasopharyngeal swab samples from 248 individuals who presented with influenza-like illness (ILI) at a university clinic in the Southwest United States between October 1, 2020 and March 31, 2021. We identify at least 13 rhinovirus genotypes (A11, A22, A23, A25, A67, A101, B6, B79, C1, C17, C36, and C56, as well a new genotype [AZ88**]) and 16 variants that contributed to the burden of ILI in the community. We also describe the complete capsid protein gene of a member (AZ88**) of an unassigned rhinovirus A genotype.

Pruning, the elimination of excess synapses is a phenomenon of fundamental importance for correct wiring of the central nervous system. The establishment of the cerebellar climbing fiber (CF)-to-Purkinje cell (PC) synapse provides a suitable model to study pruning and pruning-relevant processes during early postnatal development. Until now, the role of microglia in pruning remains under intense investigation. Here, we analyzed migration of microglia into the cerebellar cortex during early postnatal development and their possible contribution to the elimination of CF-to-PC synapses. Microglia enrich in the PC layer at pruning-relevant time points giving rise to the possibility that microglia are actively involved in synaptic pruning. We investigated the contribution of microglial fractalkine (CX3 CR1) signaling during postnatal development using genetic ablation of the CX3 CR1 receptor and an in-depth histological analysis of the cerebellar cortex. We found an aberrant migration of microglia into the granule and the molecular layer. By electrophysiological analysis, we show that defective fractalkine signaling and the associated migration deficits neither affect the pruning of excess CFs nor the development of functional parallel fiber and inhibitory synapses with PCs. These findings indicate that CX3 CR1 signaling is not mandatory for correct cerebellar circuit formation. MAIN POINTS: Ablation of CX3 CR1 results in a transient migration defect in cerebellar microglia. CX3 CR1 is not required for functional pruning of cerebellar climbing fibers. Functional inhibitory and parallel fiber synapse development with Purkinje cells is undisturbed in CX3 CR1-deficient mice.

Irradiation is widely used to treat brain tumors, and also to create bone marrow (BM) chimeras. BM chimeras are widely used to dissect functions and origin of microglia and blood-derived mononuclear cells under homeostatic or pathological conditions. This is facilitated by the fact that microglia survive irradiation and are thus regarded radio-resistant. In this study, we tested whether microglia are indeed radio-resistant and looked for potential mechanisms that might explain this phenomenon. We analyzed the radio-resistance of microglia independently of their physiological brain environment compared to other mononuclear cells from spleen and brain after X-irradiation with 7 Gy or 30 Gy. Furthermore, we investigated long-term effects of X-irradiation on microglia using organotypic hippocampal slice cultures (OHSCs). We found a significant higher survival rate of isolated microglia 4 hr after X-irradiation with 30 Gy accompanied by a decreased proliferation rate. Investigations of apoptosis-related genes revealed no regulation of a specific antiapoptotic pathway but ataxia telangiectasia mutated (ATM), a DNA-repair-related gene, was significantly upregulated in isolated microglia 4 hr after 30 Gy. Irradiation of OHSCs with 7 and 30 Gy revealed a highly and significantly decreased cell number, morphological changes and an increase in migration velocity of microglia. Furthermore, cell loss, increased soma size and process length of microglia was also found in BM chimeras irradiated with 9.5 Gy 5 weeks after irradiation. Here, we present new evidence implying that microglia are not a homogeneous population of radio-resistant cells and report on long-term alterations of microglia that survived irradiation.

Objective Given the paucity of data on the use of agents other than cyclosporine (CsA) in the maintenance phase of immunosuppressive therapy (IST) for severe aplastic anemia (SAA) in children, we sought to describe our experience with tacrolimus in pediatric SAA, and to compare outcomes with a preceding series of patients who received CsA. Methods Eight patients with SAA diagnosed between 2003 and 2008 for whom no human leukocyte antigen (HLA)-matched sibling donor was identified underwent tacrolimus-based IST. These children were compared with a previously described series of 13 patients who had undergone CsA-based IST at our institution between 1990 and 2003. All patients initially received equine antithymocyte globulin (ATG) and corticosteroids. Results Complete response (CR) rate was 88% for tacrolimus and 85% for CsA. Median time to CR was approximately 7 months in both groups. Median follow-up duration was 2.4 years for tacrolimus and 8.4 years for CsA. Among responders with de novo SAA, relapse rate was 25% (n = 1) at 2 years for tacrolimus and 0% at 2 years and 23% (n = 3) at 5 years for CsA; no significant difference in relapse-free survival was detected between the two groups (P = 0.07). Paroxysmal nocturnal hemoglobinuria was seen in one patient on tacrolimus who had relapsed after CsA-based IST. Tacrolimus-based IST was well-tolerated. Conclusion These data provide evidence that tacrolimus may be a suitable alternative to CsA as part of an IST regimen for SAA in children who lack an HLA-matched sibling and may have a more favorable profile of side effects than CsA. Pediatr Blood Cancer 2009;52:626–630. © 2009 Wiley-Liss, Inc.