Bergmann's rule near the equator: latitudinal clines in body size of an Andean passerine bird

Critical correlative support for Bergmann's ecogeographic rule is provided by symmetrical patterns of size variation in Diglossa carbonaria, a tropical passerine bird whose geographic range in the Andes Mountains of South America straddles the equator. Body size is positively correlated with latitude both north and south of the equator. Moreover, parapatric taxa that exhibit either partial (north-western Bolivia) or complete (northern Peru) reproductive isolation converge in body size. Relative uniformity in the length of the highly modified flower-piercing bill among populations of D. carbonaria that differ significantly in body size suggests that character displacement or interspecific competition is not responsible for these patterns. These findings support the hypothesis that climate, particularly temperature seasonality, is an important environmental determinant of geographic size variation in homeotherms. In addition they demonstrate that clinal variation correlated with subtle climatic gradients can occur in tropical environments.     

Development of a new metastatic human breast carcinoma xenograft line.

Xenografts originated from human tumours offer the most appropriate research material for in vivo experimental research. However, primary human breast carcinomas are difficult to grow when transplanted in athymic mice: tumour take is less than 15%. Recently, we have achieved 60% tumour take by injecting tumour cell suspensions mixed with Matrigel. Human breast xenografts originated from primary breast carcinoma also frequently show the potential to metastasize spontaneously. In the present study, we generated a human breast carcinoma xenograft line (UISO-BCA-NMT-18) that shows 100% tumorigenicity and 80-100% lung metastasis when transplanted s.c. in athymic mice. We have studied in detail the characteristics of the xenograft and the patient''s tumour from which the xenograft line originated. Both the xenograft and the patient''s tumour showed intense staining for mutant p53 nuclear protein, and high expression of U-PA, PAI and u-PAR. In vivo growth of the xenograft is stimulated by exogenous supplementation of oestrogen. This xenograft is continuously growing in mice and has shown 80-100% metastasis for the last three successive in vivo passages. This well-characterized, oestrogen-responsive, metastatic breast carcinoma xenograft line will provide excellent research material for metastasis-related research.     

Malignancy‐induced autoimmunity to MUC1: initial antibody characterization

Abstract: Numerous reports document the existence of autoantibodies to MUC1 in the circulation of individuals with breast and other solid malignancies, with the majority of researchers utilizing MUC1 peptides in their detection. This report documents the purification, using peptide and whole molecule, and characterization of such autoantibodies from an individual with an unusual, highly MUC1‐positive, myosarcoma. Purification of autoantibodies from serum was performed using affinity chromatography against either MUC1 peptide or whole molecule MUC1 [derived both from the patient (Pt‐MUC1) and from a pool of sera from patients with advanced breast cancer (ABC‐MUC1)]. Enzyme‐linked immunosorbent assays (ELISAs) were used to compare specificity of purified autoantibodies. Peptide epitopes were determined by Ptifcan system against 7‐mer peptides covering the 20 amino acid repeat of the MUC1 extracellular domain. Substantially higher amounts of autoantibodies were isolated when purifying against Pt‐MUC1 rather than either ABC‐MUC1 or peptide. Whole molecule purified autoantibodies demonstrated an increased specificity for tumour‐derived MUC1. Pt‐MUC1 autoantibodies were of both the immunoglobulin (Ig)G and IgM class, whilst autoantibodies purified against ABC‐MUC1 and MUC1 peptide were IgG only. A greater range of peptide epitopes was defined by those autoantibodies purified against whole molecule. This report presents data indicating the presence of autoantibodies to MUC1 in an individual diagnosed with a MUC1 over‐expressing myosarcoma. Confirmation of these autoantibodies as being specific for tumour‐associated MUC1 is given. Further, it suggests that, although autoantibodies are present that recognize core protein determinants, the initial, and dominant, immunizing epitope is not purely pretentious in nature.     

Variation and trends in reasons for knee replacement revision: a multi-registry study of revision burden

Background and purpose — Studies describing time-related change in reasons for knee replacement revision have been limited to single regions or institutions, commonly analyze only 1st revisions, and may not reflect true caseloads or findings from other areas. We used revision procedure data from 3 arthroplasty registries to determine trends and differences in knee replacement revision diagnoses.Patients and methods — We obtained aggregated data for 78,151 revision knee replacement procedures recorded by the Swedish Knee Arthroplasty Register (SKAR), the Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR), and the Kaiser Permanente Joint Replacement Registry (KPJRR) for the period 2003–2017. Equivalent diagnosis groups were created. We calculated the annual proportions of the most common reasons for revision.Results — Infection, loosening, and instability were among the 5 most common reasons for revision but magnitude and ranking varied between registries. Over time there were increases in proportions of revisions for infection and decreases in revisions for wear. There were inconsistent proportions and trends for the other reasons for revision. The incidence of revision for infection showed a uniform increase.Interpretation — Despite some differences in terminology, comparison of registry-recorded revision diagnoses is possible, but defining a single reason for revision is not always clear-cut. There were common increases in revision for infection and decreases in revision for wear, but variable changes in other categories. This may reflect regional practice differences and therefore generalizability of studies regarding reasons for revision is unwise.

Although the survivorship of knee arthroplasty has improved over the last 15 years, the increased volume of primary knee replacement has led to growing numbers of revision procedures (Kumar et al. 2015, Patel et al. 2015). A prior study we undertook outlined changes in the volume and incidence of revision rates in Sweden, Australia, and the Kaiser Permanente registry from the USA (Lewis et al. 2020b).Factors influencing revision change with time. Patient factors may affect the rate of primary procedures, such as rising patient and surgeon acceptance of knee replacement (Hamilton et al. 2015), increasing rates of osteoarthritis (Hunter and Bierma-Zeinstra 2019), growing use in younger patients (Leyland et al. 2016, Karas et al. 2019), and also survivorship, such as longer life expectancy, increasing obesity, and higher physical activity of those receiving a replacement (Hamilton et al. 2015). In addition, prosthesis designs change to improve perceived shortcomings such as wear, instability, and patellofemoral pain and tracking (Lewis et al. 2020a). Methods to improve surgical precision, such as computer navigation (Jones and Jerabek 2018), image-derived instrumentation (Kizaki et al. 2019), and robotic assistance (Jacofsky et al. 2016) may decrease revision requirements (Price et al. 2018)These changing factors alter the reasons for revision. Previous studies observed a decrease in revisions for wear and loosening (Sharkey et al. 2014, Thiele et al. 2015), and related this to improved prosthesis design and materials. Other studies note infection is now the most common reason for revision (Koh et al. 2017, Postler et al. 2018). Studies of changing knee replacement failure modes are limited by being derived from single institutions or regions and may not accurately reflect what is occurring elsewhere (Sharkey et al. 2014, Thiele et al. 2015, Dyrhovden et al. 2017, Koh et al. 2017, Lum et al. 2018, Postler et al. 2018). Additionally, these studies do not show the true revision burden as they are restricted to 1st revision procedures, or only revisions of previous total knee replacements (TKR), and do not include revisions of partial knee replacement procedures.Combining registry data can be difficult due to inconsistency in the definition of revision (Liebs et al. 2015), and lack of consensus in defining modes of failure, with different terminologies used (Niinimaki 2015, Siqueira et al. 2015). Some have attempted to overcome this by defining equivalent diagnoses (Havelin et al. 2011, Paxton et al. 2011, Rasmussen et al. 2016).We determined variations and trends in reasons for knee replacement revision using data on all knee arthroplasty revision procedures from the national registries of Sweden and Australia and the institutional registry of Kaiser Permanente in the USA by using equivalent diagnosis groups (Table 1, see Supplementary data).     

Short DNA sequences and bacterial DNA induce esophageal,gastric, and colorectal cancer cell invasion

Toll‐like receptor 9 (TLR9) recognizes both bacterial and self‐DNA and it is abundantly expressed in the gastrointestinal tract. In this study, we investigated the influences of both bacterial DNA and specific short DNA sequences on TLR9‐mediated gastrointestinal cancer cell invasion. We assessed the effect of various DNA ligands on cellular invasion and on TLR9 and matrix metalloproteinase expression of three gastrointestinal cancer cell lines. DNA‐ligands described in this study include CpG‐ODN M362, 9‐mer (hairpin), human telomeric sequence h‐Tel22 G‐quadruplex, and bacterial DNAs from Escherichia coli and Helicobacter pylori. All of the DNAs studied were demonstrated to induce invasion in the studied cells. The DNA‐induced invasion was inhibited with a broad‐spectrum MMP inhibitor and partly also with chloroquine suggesting that it could be mediated via MMP activation, endosomal signaling, and TLR9. Interestingly, H. pylori DNA was shown to induce a more pronounced invasion in a gastric cancer cell line than in the other cell lines. Our results suggest that bacterial DNA as well as deoxynucleotides having stable secondary structures (i.e. hairpins or G‐quadruplex structures) may serve as endogenous, invasion‐inducing TLR9‐ligands and promote local progression and metastasis of cancers in the alimentary tract.     

Measures of initiation and progression to increased smoking among current menthol compared to non-menthol cigarette smokers based on data from four U.S. government surveys

There are no large-scale, carefully designed cohort studies that provide evidence on whether menthol cigarette use is associated with a differential risk of initiating and/or progressing to increased smoking. However, questions of whether current menthol cigarette smokers initiated smoking at a younger age or are more likely to have transitioned from non-daily to daily cigarette use compared to non-menthol smokers can be addressed using cross-sectional data from U.S. government surveys. Analyses of nationally representative samples of adult and youth smokers indicate that current menthol cigarette use is not associated with an earlier age of having initiated smoking or greater likelihood of being a daily versus non-daily smoker. Some surveys likewise provide information on cigarette type preference (menthol versus non-menthol) among youth at different stages or trajectories of smoking, based on number of days smoked during the past month and/or cigarettes smoked per day. Prevalence of menthol cigarette use does not appear to differ among new, less experienced youth smokers compared to established youth smokers. While there are limitations with regard to inferences that can be drawn from cross-sectional analyses, these data do not suggest any adverse effects for menthol cigarettes on measures of initiation and progression to increased smoking.     

Dual views of SRF: a genomic exposure

Esnault and colleagues (pp. 943–958) take a genomics approach to investigate the role of SRF (serum response factor) in the serum response of fibroblasts. The well-established dual role of SRF with alternative cofactors and responsiveness to two signaling pathways is illustrated at the genome-wide level, yet new insight comes from this global picture.     

Kidney retransplantation in children following rejection and recurrent disease

Retransplantation accounts for approximately 15 % of the annual transplants performed in the USA, and in the recent International Collaborative Transplant Study report on pediatric patients 15.2 % of the 9209 patients included in the report were retransplant recipients. Although the significant advances in clinical management and newer immunosuppressive agents have had a significant impact on improving short-term allograft function, it is apparent that long-term allograft function remains suboptimal. Therefore, it is likely that the majority of pediatric renal allograft recipients will require one or more retransplants during their lifetime. Unfortunately, a second or subsequent graft in pediatric recipients has inferior long-term graft survival rates compared to initial grafts, with decreasing rates with each subsequent graft. Multiple issues influence the outcome of retransplantation, with the most significant being the cause of the prior transplant failure. Non-adherence-associated graft loss poses unresolved ethical issues that may impact access to retransplantation. Graft nephrectomy prior to retransplantation may benefit selected patients, but the impact of an in situ failed graft on the development of panel-reactive antibodies remains to be definitively determined. It is important that these and other factors discussed in this review be taken into consideration during the counseling of families on the optimal approach for their child who requires a retransplant.