The podocytes' inflammatory responses in experimental GN are independent of canonical MYD88-dependent toll-like receptor signaling.

Podocytes form the kidney filtration barrier and continuously adjust to external stimuli to preserve their integrity even in the presence of inflammation. It was suggested that canonical toll-like receptor signaling, mediated by the adaptor protein MYD88, plays a crucial role in initiating inflammatory responses in glomerulonephritis (GN). We explored the influence of podocyte-intrinsic MYD88 by challenging wild-type (WT) and podocyte-specific Myd88 knockout (MyD88pko) mice, with a model of experimental GN (nephrotoxic nephritis, NTN). Next-generation sequencing revealed a robust upregulation of inflammatory pathways and changes in cytoskeletal and cell adhesion proteins in sorted podocytes from WT mice during disease. Unchallenged MyD88pko mice were healthy and showed no proteinuria, normal kidney function and lacked morphological changes. During NTN, MyD88pko exhibited a transient increase in proteinuria in comparison to littermates, while histological damage, podocyte ultrastructure in STED imaging and frequencies of infiltrating immune cells by flow cytometry were unchanged. MYD88-deficiency led to subtle changes in the podocyte transcriptome, without a significant impact on the overall podocyte response to inflammation, presumably through MYD88-independent signaling pathways. In conclusion, our study reveals a comprehensive analysis of podocyte adaptation to an inflammatory environment on the transcriptome level, while MYD88-deficiency had only limited impact on the course of GN suggesting additional signaling through MYD88-independent signaling.

Evaluation of non-metric variation in the crania of black and white perinates.

Reports in the literature suggest that diagnostic differences in craniofacial morphology between blacks and whites arise very early in development. These reports, however, have not been consistent regarding which traits are diagnostic and have failed to provide forensic anthropologists with a reliable method of assessment. In an effort to clarify the situation, 13 non-metric craniofacial traits were scored and analyzed statistically in a sample of 70 black and white perinatal specimens obtained from the Smithsonian's fetal osteology collection. Chi-square analysis revealed significant (p<0.05) differences in the distribution of five of the 13 non-metric traits examined. Compared with black perinates, white perinates more frequently possessed a relatively narrow supraoccipital portion of the occipital bone, a prominent anterior nasal spine, "deep" subnasal margins, an elongated vomer, and semi-circular temporal squamae. When these five traits were entered into a stepwise logistic regression, temporal squamous shape, vomer shape and subnasal margin definition were found to be predictive of race (79.1% overall correct classification). An independent sample of 39 black and white perinates was then used to validate the results; overall, 67.5% of the validation sample could be classified correctly. Reasons for the disparity in correct classification rates between the initial and follow-up sample are provided. Results of the present study may be useful for anthropologists who encounter unidentified cranial material from this age range.

Coronal suturectomy does not cause acute postoperative displacement in the cranial bases of craniosynostotic rabbits.

Approximately 300 to 500 infants per 1,000,000 have prematurely fused cranial sutures (craniosynostosis). Craniosynostosis can result in increased intracranial pressure and craniofacial deformities, which often require extensive and costly craniofacial surgery. Because the neurocranium and basicranium are developmentally interrelated, understanding their influence on one another is important for surgical planning. Although surgery has been found to have long-term effects on the cranial bases of craniosynostotic human beings and rabbits, the biological mechanisms behind these effects remain uncertain. Some researchers have suggested that the surgical release of synostosed sutures alters long-term growth patterns, resulting in cranial base differences between craniosynostotic individuals who undergo surgery and those who do not. Additionally, some investigators have proposed that an acute and surgically related displacement of basicranial elements may contribute to the observed differences. The current study examines acute postoperative changes in four lengths, three angles, and three triangles between cranial base landmarks in a sample of seven New Zealand white rabbits with familial nonsyndromic craniosynostosis. Results indicate that suturectomy caused no statistically significant (P < 0.05) acute length, angular, or shape differences in the cranial base. Thus, previous long-term cranial base differences found between rabbits that were operated on and those that were not were probably not caused by an acute displacement of skeletal elements as a result of surgery. These findings suggest that postoperative cranial base changes may be related more to chronically altered growth patterns than to acutely altered changes in intracranial pressure or dural tension.