RNF212B E3 ligase is essential for crossover designation and maturation during male and female meiosis in the mouse.

Meiosis, a reductional cell division, relies on precise initiation, maturation, and resolution of crossovers (COs) during prophase I to ensure the accurate segregation of homologous chromosomes during metaphase I. This process is regulated by the interplay of RING-E3 ligases such as RNF212 and HEI10 in mammals. In this study, we functionally characterized a recently identified RING-E3 ligase, RNF212B. RNF212B colocalizes and interacts with RNF212, forming foci along chromosomes from zygonema onward in a synapsis-dependent and DSB-independent manner. These consolidate into larger foci at maturing COs, colocalizing with HEI10, CNTD1, and MLH1 by late pachynema. Genetically, RNF212B foci formation depends on Rnf212 but not on Msh4, Hei10, and Cntd1, while the unloading of RNF212B at the end of pachynema is dependent on Hei10 and Cntd1. Mice lacking RNF212B, or expressing an inactive RNF212B protein, exhibit modest synapsis defects, a reduction in the localization of pro-CO factors (MSH4, TEX11, RPA, MZIP2) and absence of late CO-intermediates (MLH1). This loss of most COs by diakinesis results in mostly univalent chromosomes. Double mutants for Rnf212b and Rnf212 exhibit an identical phenotype to that of Rnf212b single mutants, while double heterozygous demonstrate a dosage-dependent reduction in CO number, indicating a functional interplay between paralogs. SUMOylome analysis of testes from Rnf212b mutants and pull-down analysis of Sumo- and Ubiquitin-tagged HeLa cells, suggest that RNF212B is an E3-ligase with Ubiquitin activity, serving as a crucial factor for CO maturation. Thus, RNF212 and RNF212B play vital, yet overlapping roles, in ensuring CO homeostasis through their distinct E3 ligase activities.

INTERVENTIONS TO MANAGE RESIDUAL LIMB ULCERATION DUE TO PROSTHETIC USE IN INDIVIDUALS WITH LOWER EXTREMITY AMPUTATION: A SYSTEMATIC REVIEW OF THE LITERATURE.

Patients with lower extremity amputation (LEA) experience 65% more dermatologic issues than non-amputees, and skin problems are experienced by ≈75% of LEA patients who use prostheses. Continuously referring LEA patients to a dermatologist for every stump related skin condition may be impractical. Thus, physical rehabilitation professionals should be prepared to recognize and manage common non-emergent skin conditions in this population. The purpose of this study was to determine the quantity, quality, and strength of available evidence supporting treatment methods for prosthesis-related residual limb (RL) ulcers. Systematic literature review with evidence grading and synthesis of empirical evidence statements (EES) was employed. Three EESs were formulated describing ulcer etiology, conditions in which prosthetic continuance is practical, circumstances likely requiring prosthetic discontinuance, and the consideration of additional medical or surgical interventions. Continued prosthetic use is a viable option to manage minor or early-stage ulcerated residual limbs in compliant patients lacking multiple comorbidities. Prosthetic discontinuance is also a viable method of residual limb ulcer healing and may be favored in the presence of severe acute ulcerations, chronic heavy smoking, intractable pain, rapid volume and weight change, history of chronic ulceration, systemic infections, or advanced dysvascular etiology. Surgery or other interventions may also be necessary in such cases to achieve restored prosthetic ambulation. A short bout of prosthetic discontinuance with a staged re-introduction plan is another viable option that may be warranted in patients with ulceration due to poor RL volume management. High-quality prospective research with larger samples is needed to determine the most appropriate course of treatment when a person with LEA develops an RL ulcer that is associated with prosthetic use.