Characterization of a Murine Anti-laminin-1 Monoclonal Antibody (AK8) Produced by Immunization with Mouse-derived Laminin-1

Laminin-1 is a structural glycoprotein that forms an integral part of the scaffolding of basement membranes, and plays an important role during embryonic development. We have recently demonstrated a significant association between anti-laminin-1 antibodies (Abs) and reproductive failure, such as recurrent spontaneous abortions and infertility-associated endometriosis in both human and mouse studies. In the present study, we established an IgM (μ,κ) monoclonal anti-laminin-1 Ab (AK8) by immunizing mice with mouse Engelbreth-Holm-Swarm sarcoma (EHS)-derived laminin-α1. The AK8 monoclonal antibody (mAb) reacted with particular peptide sequences from the globular G domain of mouse laminin-α1 chain of using ELISA and Western blot techniques. The peptide tertiary structure of the epitope recognized by AK8 mAb was predicted using eight synthesized domain peptide sequences and three consensus sequences obtained by phage displayed random peptide library. Basement membranes of endometrium of pregnant mice and humans were immunostained with AK8 mAb. Thus, AK8 mAb recognized a common structure present in the G domain of the laminin-1 chain in both mice and humans. The passive immunization of mice with AK8 mAb may represent a suitable animal model for anti-laminin-1 Ab-mediated reproductive failure

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

Testing for a predicted decrease in body size in brown bears (Ursus arctos) based on a historical shift in diet

A recent study found a historical decline in the proportion of meat in the diet of brown bears (Ursus arctos (Linnaeus, 1758)) in the Hokkaido Islands, Japan. Because feeding habits are strongly correlated with the body size of animals, the shift in diet should have led to a decrease in the size of these bears. Ｔo predict the effects of this dietary shift on the skeletal size in bears, we correlated the femur length in Hokkaido brown bears with the carbon and nitrogen stable isotope values from bone samples and predicted the historical change in their body size. The variation in the femur lengths of the male and female subpopulations was positively correlated with their δ15N values, but not with their δ13C values, and the explanatory power of the constructed model was higher in males than in females. Based on the model and the δ15N values for historic and modern bears, the skeletal size of bear subpopulations in eastern Hokkaido was estimated to have decreased by 10-18% for males and 8-9% for females. Our results suggest that a historical dietary shift caused the decrease in the size of the Hokkaido brown bears.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

Factors influencing lifespan dependency on agricultural crops by brown bears

Investigating factors underlying human-wildlife conflicts in agricultural landscapes is important for both preventing crop damage and wildlife conservation. Although environments surrounding crop fields are considered causal factors, incorporating individual aspects of animals, such as demographic and physical characteristics, into the investigation may aid the prediction of how nuisance control affects wildlife population structures. Here, we assessed the relationship of corn consumption by Hokkaido brown bears (Ursus arctos) with both demographic (sex and age) and physical (body size) characteristics and environmental factors (human presence and crop accessibility). We estimated the proportion of corn in the lifespan diet for both female (n = 61) and male (n = 62) bears using carbon and nitrogen stable isotope analyses. Then, we analyzed the factors correlated with corn consumption using a generalized linear model. Female and male bears consumed corn from 1.3 to 30.9% and 1.3 to 42.0% of their lifespan diet, respectively. Corn consumption by female bears was not correlated with any explanatory variables, whereas that of male bears was positively correlated with their body size and crop accessibility but negatively correlated with human presence. Large male bears were more likely to have consumed more corn than small male bears, but the selective harvest of large bears may cause dwarfism of their overall population, impacting the local population dynamics. To reduce agricultural damage and population structure alteration of brown bears, the opportunity for them to learn to eat crops must be eliminated through border management between forests and agricultural fields and the relocation of agricultural fields when possible

Major decline in marine and terrestrial animal consumption by brown bears (Ursus arctos)

Human activities have had the strongest impacts on natural ecosystems since the last glacial period, including the alteration of interspecific relationships such as food webs. In this paper, we present a historical record of major alterations of trophic structure by revealing millennium-scale dietary shifts of brown bears (Ursus arctos) on the Hokkaido islands, Japan, using carbon, nitrogen, and sulfur stable isotope analysis. Dietary analysis of brown bears revealed that salmon consumption by bears in the eastern region of Hokkaido significantly decreased from 19% to 8%. In addition, consumption of terrestrial animals decreased from 56% to 5% in western region, and 64% to 8% in eastern region. These dietary shifts are likely to have occurred in the last approximately 100-200 years, which coincides with the beginning of modernisation in this region. Our results suggest that human activities have caused an alteration in the trophic structure of brown bears in the Hokkaido islands. This alteration includes a major decline in the marine-terrestrial linkage in eastern region, and a loss of indirect-interactions between bears and wolves, because the interactions potentially enhanced deer predation by brown bears

Major decline in marine and terrestrial animal consumption by brown bears (Ursus arctos).

北海道のヒグマ、肉食から草食傾向へ。明治以降の開発が影響か？ －考古試料の安定同位体分析から－ 京都大学プレスリリース. 2015-03-27.Human activities have had the strongest impacts on natural ecosystems since the last glacial period, including the alteration of interspecific relationships such as food webs. In this paper, we present a historical record of major alterations of trophic structure by revealing millennium-scale dietary shifts of brown bears (Ursus arctos) on the Hokkaido islands, Japan, using carbon, nitrogen, and sulfur stable isotope analysis. Dietary analysis of brown bears revealed that salmon consumption by bears in the eastern region of Hokkaido significantly decreased from 19% to 8%. In addition, consumption of terrestrial animals decreased from 56% to 5% in western region, and 64% to 8% in eastern region. These dietary shifts are likely to have occurred in the last approximately 100-200 years, which coincides with the beginning of modernisation in this region. Our results suggest that human activities have caused an alteration in the trophic structure of brown bears in the Hokkaido islands. This alteration includes a major decline in the marine-terrestrial linkage in eastern region, and a loss of indirect-interactions between bears and wolves, because the interactions potentially enhanced deer predation by brown bears

Data from: Incremental analysis of vertebral centra can reconstruct the stable isotope chronology of teleost fishes

1. Isotope analysis has high potential for understanding fish ecology and food-web structure in aquatic ecosystems. The utility of isotope analysis will be greatly improved if we can reconstruct the chronology of several isotopes at multiple growth stages of individual fish. However, no practical methods exist for reconstructing the chronology of light-element isotopes (e.g. δ13C, δ15N, δ34S, and Δ14C) in teleost fishes. Here, we present and test a new analytical approach for reconstructing the isotopic ratios of light isotopes at multiple life-stages in teleost fishes. 2. We sampled an anadromous salmon species, masu salmon Oncorhynchus masou (n = 3), along with water from its natal stream and from the ocean. We subdivided the vertebral centra of the salmon equally into 10 sections and extracted bone collagen from each sample. We then measured the stable sulfur isotope ratios of each vertebral section and compared them with δ34S values of the river water and sea water. We also measured the 87Sr/86Sr ratios of otoliths as a reference indicator of salmon migration between fresh water and the ocean. 3. In all samples, the bone section closest to the centre of the centrum had the lowest δ34S values, which were similar to those of fresh water. The δ34S values gradually increased from the centre to marginal sections, finally reaching constant values similar to those of seawater. The 87Sr/86Sr ratios of sagittal otolith sections had significant inter-individual differences and were consistent with the patterns of variation of the δ34S values of the vertebral sections. 4. Our results show that the vertebral centra of teleost fishes record isotopic information from juvenile to adult life-stages. We suggest that our method can provide reproducible isotopic chronology, even in teleost fishes smaller than 50 cm. This method can be used in isoscape studies and in studies of the ecology of marine teleost fishes

Sulfur stable isotope data

Sulfur stable isotope ratios of water and vertebral sections of masu salmon. Each vertebral centrum was subdivided equally into 10 sections numbered from the center (01) to the margin (10). Fish and water samples were collected in the Churui River, Hokkaido Islands, japan. All fish samples analyzed consisted of bone collagen

Strontium stable isotope data

Results of elemental and 87Sr/86Sr analyses of fish otolith sections from masu salmon (identified as OM-01, OM-02 and OM-03) collected from the Churui River, water from the Churui River, and sea water collected approximately 10 km south of the mouth of the Churui River