Serpina3n attenuates granzyme B-mediated decorin cleavage and rupture in a murine model of aortic aneurysm

Granzyme B (GZMB) is a proapoptotic serine protease that is released by cytotoxic lymphocytes. However, GZMB can also be produced by other cell types and is capable of cleaving extracellular matrix (ECM) proteins. GZMB contributes to abdominal aortic aneurysm (AAA) through an extracellular, perforin-independent mechanism involving ECM cleavage. The murine serine protease inhibitor, Serpina3n (SA3N), is an extracellular inhibitor of GZMB. In the present study, administration of SA3N was assessed using a mouse Angiotensin II-induced AAA model. Mice were injected with SA3N (0–120 μg/kg) before pump implantation. A significant dose-dependent reduction in the frequency of aortic rupture and death was observed in mice that received SA3N treatment compared with controls. Reduced degradation of the proteoglycan decorin was observed while collagen density was increased in the aortas of mice receiving SA3N treatment compared with controls. In vitro studies confirmed that decorin, which regulates collagen spacing and fibrillogenesis, is cleaved by GZMB and that its cleavage can be prevented by SA3N. In conclusion, SA3N inhibits GZMB-mediated decorin degradation leading to enhanced collagen remodelling and reinforcement of the adventitia, thereby reducing the overall rate of rupture and death in a mouse model of AAA.     

Nomogram to Assess the Risk of Central Cervical Lymph Node Metastasis in Patients With Clinical N0 Papillary Thyroid Carcinoma

ObjectiveTo develop and validate an individualized risk prediction model for the need for central cervical lymph node dissection in patients with clinical N0 papillary thyroid carcinoma (PTC) diagnosed using ultrasound.MethodsUpon retrospective review, derivation and internal validation cohorts comprised 1585 consecutive patients with PTC treated from January 2017 to December 2019 at hospital A. The external validation cohort consisted of 406 consecutive patients treated at hospital B from January 2016 to June 2020. Independent risk factors for central cervical lymph node metastasis (CLNM) were determined through univariable and multivariable logistic regression analysis. An individualized risk prediction model was constructed and illustrated as a nomogram, which was internally and externally validated.ResultsThe following risk factors of CLNM were established: a solitary primary thyroid nodule’s diameter, shape, calcification, and capsular abutment-to-lesion perimeter ratio. The areas under the receiver operating characteristic curves of the risk prediction model for the internal and external validation cohorts were 0.921 and 0.923, respectively. The calibration curve showed good agreement between the nomogram-estimated probability of CLNM and the actual CLNM rates in the 3 cohorts. The decision curve analysis confirmed the clinical usefulness of the nomogram.ConclusionThis study developed and validated a model for predicting the risk of CLNM in individual patients with clinical N0 PTC, which should be an efficient tool for guiding clinical treatment.     

Fungal endophyte diversity in tundra grasses increases by grazing

Fungal endophytes are species rich and ubiquitous, yet, apart from the genus Epichloë, their ecology is largely unknown. Here we explore how herbivores affect the diversity of fungal endophytes in tundra grasslands. We assess both hyphal morphological and taxonomic diversity in grass individuals.By microscopic examination we identified endophytes to be present in all sampled grass individuals whereas identification to taxonomic units were only achieved in a subset of the individuals using laser micro dissection pressure catapulting and culturing for endophyte isolation. Hyphal morphological diversity was significantly higher in grasses exposed to grazing, along with 45 % more taxonomic units achieved.Our results suggest that grazing is an important mediator of fungal endophyte diversity in tundra grasslands. Furthermore, we suggest laser dissection of stained endophytes as a method for further exploring the ecological role of fungal endophytes.     

Towards a general rule for estimating the stage of pregnancy in field-caught tsetse flies

Abstract. Ovarian dissections were performed on the tsetse flies Glossina morsitans morsitans Westwood and G.pallidipes Austen of known ages, maintained in the laboratory or on an island in Lake Kariba, Zimbabwe. The lengths ( l ₂ and l _u) of the second largest oocyte and of the larva in utero were found to increase approximately exponentially during pregnancy. The length ( l ₁) of the largest oocyte increased exponentially for about the first 80% of pregnancy. Linear relationships between the log values of l ₁, l ₂ and l _u in field-caught flies, of unknown chronological age, are consistent with the idea that growth patterns are similar in laboratory, island and open field situations. The egg phase takes up c. 45% of pregnancy in both species, regardless of season and the absolute duration of pregnancy. The changes in the log values of l ₁, l ₂ and l _u, over the ranges within which they change linearly, can be used to assign flies to their stage of pregnancy. When applied to field data the rule showed that G.pallidipes caught in odour-baited traps, and on a mobile electric net, exhibited major activity peaks shortly before and after parturition. Flies from the trap (but not the net) showed a smaller peak of activity near the middle of pregnancy. The egg and the three larval phases in utero take up c. 45%, 25%, 20% and 10% of pregnancy respectively.