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1.
Cell ; 172(1-2): 373-386.e10, 2018 01 11.
Article in English | MEDLINE | ID: mdl-29224780

ABSTRACT

Breast cancer (BC) comprises multiple distinct subtypes that differ genetically, pathologically, and clinically. Here, we describe a robust protocol for long-term culturing of human mammary epithelial organoids. Using this protocol, >100 primary and metastatic BC organoid lines were generated, broadly recapitulating the diversity of the disease. BC organoid morphologies typically matched the histopathology, hormone receptor status, and HER2 status of the original tumor. DNA copy number variations as well as sequence changes were consistent within tumor-organoid pairs and largely retained even after extended passaging. BC organoids furthermore populated all major gene-expression-based classification groups and allowed in vitro drug screens that were consistent with in vivo xeno-transplantations and patient response. This study describes a representative collection of well-characterized BC organoids available for cancer research and drug development, as well as a strategy to assess in vitro drug response in a personalized fashion.


Subject(s)
Breast Neoplasms/pathology , Genetic Heterogeneity , Organoids/pathology , Tissue Banks , Animals , Antineoplastic Agents/pharmacology , Breast Neoplasms/genetics , Cells, Cultured , Drug Screening Assays, Antitumor/methods , Female , Humans , Mice , Mice, Nude , Organoids/drug effects , Precision Medicine/methods
2.
Cell ; 160(1-2): 324-38, 2015 Jan 15.
Article in English | MEDLINE | ID: mdl-25557080

ABSTRACT

Pancreatic cancer is one of the most lethal malignancies due to its late diagnosis and limited response to treatment. Tractable methods to identify and interrogate pathways involved in pancreatic tumorigenesis are urgently needed. We established organoid models from normal and neoplastic murine and human pancreas tissues. Pancreatic organoids can be rapidly generated from resected tumors and biopsies, survive cryopreservation, and exhibit ductal- and disease-stage-specific characteristics. Orthotopically transplanted neoplastic organoids recapitulate the full spectrum of tumor development by forming early-grade neoplasms that progress to locally invasive and metastatic carcinomas. Due to their ability to be genetically manipulated, organoids are a platform to probe genetic cooperation. Comprehensive transcriptional and proteomic analyses of murine pancreatic organoids revealed genes and pathways altered during disease progression. The confirmation of many of these protein changes in human tissues demonstrates that organoids are a facile model system to discover characteristics of this deadly malignancy.


Subject(s)
Carcinoma, Pancreatic Ductal/pathology , Models, Biological , Organ Culture Techniques , Organoids/pathology , Pancreatic Neoplasms/pathology , Animals , Humans , Mice , Mice, Inbred C57BL , Mice, Nude , Pancreas/metabolism , Pancreas/pathology
3.
Cell ; 159(1): 163-175, 2014 Sep 25.
Article in English | MEDLINE | ID: mdl-25201529

ABSTRACT

The prostate gland consists of basal and luminal cells arranged as pseudostratified epithelium. In tissue recombination models, only basal cells reconstitute a complete prostate gland, yet murine lineage-tracing experiments show that luminal cells generate basal cells. It has remained challenging to address the molecular details of these transitions and whether they apply to humans, due to the lack of culture conditions that recapitulate prostate gland architecture. Here, we describe a 3D culture system that supports long-term expansion of primary mouse and human prostate organoids, composed of fully differentiated CK5+ basal and CK8+ luminal cells. Organoids are genetically stable, reconstitute prostate glands in recombination assays, and can be experimentally manipulated. Single human luminal and basal cells give rise to organoids, yet luminal-cell-derived organoids more closely resemble prostate glands. These data support a luminal multilineage progenitor cell model for prostate tissue and establish a robust, scalable system for mechanistic studies.


Subject(s)
Organ Culture Techniques , Organoids , Prostate/cytology , Androgens/metabolism , Humans , Male , Stem Cells/cytology , Stem Cells/metabolism
4.
Proc Natl Acad Sci U S A ; 116(52): 26580-26590, 2019 Dec 26.
Article in English | MEDLINE | ID: mdl-31818951

ABSTRACT

We report the derivation of 30 patient-derived organoid lines (PDOs) from tumors arising in the pancreas and distal bile duct. PDOs recapitulate tumor histology and contain genetic alterations typical of pancreatic cancer. In vitro testing of a panel of 76 therapeutic agents revealed sensitivities currently not exploited in the clinic, and underscores the importance of personalized approaches for effective cancer treatment. The PRMT5 inhibitor EZP015556, shown to target MTAP (a gene commonly lost in pancreatic cancer)-negative tumors, was validated as such, but also appeared to constitute an effective therapy for a subset of MTAP-positive tumors. Taken together, the work presented here provides a platform to identify novel therapeutics to target pancreatic tumor cells using PDOs.

5.
Acta Clin Croat ; 61(4): 588-598, 2022 Dec.
Article in English | MEDLINE | ID: mdl-37868178

ABSTRACT

This study aimed to determine whether patients with active rheumatoid arthritis (RA) regularly take non-steroidal anti-inflammatory drugs (NSAIDs) and to clarify whether their decision to take NSAIDs depends on disease activity, intensity of pain, or functional status. The study also aimed to identify the risk factors for gastrointestinal side effects. Over 6 months, we conducted a cross-sectional single-center study of consecutively hospitalized patients with confirmed RA. Activities of daily living, pain intensity, and disease activity were evaluated by the Health Assessment Questionnaire, visual analog scale, and disease activity score, respectively, in 28 joints. Of 73 patients diagnosed with RA, 48 (66%) regularly took NSAIDs. Compared to non-users, NSAID users used glucocorticoids less frequently. The decision to use NSAIDs was independent of disease activity, pain intensity, degree of functional impairment, or presence of gastrointestinal risk factors. However, a higher degree of functional impairment was associated with a longer duration of continuous NSAID and glucocorticoid use. NSAIDs are still relevant for RA treatment. The decision to use them is not necessarily affected by disease activity or pain intensity, but their prolonged use is required in patients with a higher degree of functional disability. NSAIDs enable exclusion of glucocorticoid use, sparing patients of glucocorticoid-related side effects.


Subject(s)
Arthritis, Rheumatoid , Glucocorticoids , Humans , Activities of Daily Living , Cross-Sectional Studies , Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Arthritis, Rheumatoid/drug therapy
6.
Psychiatr Danub ; 32(Suppl 4): 547-552, 2020 Nov.
Article in English | MEDLINE | ID: mdl-33212462

ABSTRACT

BACKGROUND: Rheumatoid arthritis (RA) is a chronic and disabling disease with a great impact on the quality of life (QOL). The aim of this study was to assess QOL and health in RA patients treated with biological disease-modifying drugs (bDMARDs) as opposed to those treated with conventional synthetic DMARDs (csDMARDs). We analysed four domains of QOL: physical health (D1), mental health (D2), social relationships (D3) and one's surroundings (D4); as well as general quality of life (W1), general state of health (W2), and disease activity and physical disability. SUBJECTS AND METHODS: Seventy-seven RA patients (group A=29 on bDMARDs, group B=48 on csDMARDs) were enrolled in the study. QOL was evaluated using WHO questionnaire (WHOQOL-BREF), disease activity using Disease Activity Score 28C-reactive protein (DAS28CRP) and functional status using Health Assessment Questionnaire (HAQ). RESULTS: There was no statistically significant difference of mean values in the four domains of QOL, nor in the general QOL, between groups A and B. There was also no statistically significant difference regarding RA activity (3.51 vrs 3.54, p=0.56). However, we have found that the variable of the general state of health domain was statistically significantly higher in group B (2.66 vrs 2.89, p=0.001), while HAQ was statistically significantly higher in group A (1.19 vrs 1.07, p=0.018), as well as the duration of RA (6.25vrs 3.75 years, p=0.0006). Statistically significant correlation was found between HAQ and W2, disease duration and D3 in group A and DAS28CRP and D1, D2, W2 and HAQ and D1 and D2 in group B. CONCLUSION: These findings suggest that the inclusion of bDMARDs in the treatment regimen was overdue, with RA already advancing with developed functional disability, which prevented the achievement of the primary goals of treatment: low disease activity or remission and the improvement of patient's QOL.


Subject(s)
Antirheumatic Agents/therapeutic use , Arthritis, Rheumatoid/drug therapy , Arthritis, Rheumatoid/physiopathology , Patient Reported Outcome Measures , Quality of Life , Adult , Aged , Aged, 80 and over , Croatia , Female , Humans , Male , Middle Aged , Surveys and Questionnaires
7.
Acta Clin Croat ; 59(2): 312-317, 2020 Jun.
Article in English | MEDLINE | ID: mdl-33456119

ABSTRACT

The aim of this study was to investigate the association of smoking with disease activity, seropositivity, age and gender in patients with rheumatoid arthritis. We included 89 rheumatoid arthritis patients. All patients fulfilled the 2010 American College of Rheumatology/European League Against Rheumatism rheumatoid arthritis classification criteria. Activity of the disease was measured by Disease Activity Score 28-joint count C-reactive protein (DAS28CRP). The subjects were stratified into smoking and non-smoking groups and cross-sectionally analyzed. There were 24 (27%) smokers and 65 (73%) nonsmokers. The mean age of patients was 57.1±8.8 years. The mean DAS28CRP was 5.81 in the smoking group and 5.57 in the non-smoking group, without statistically significant difference between the two groups (p=0.148). Similarly, smokers did not differ significantly from non-smokers according to age (p=0.443), gender (p=0.274), rheumatoid factor positivity (p=0.231), anti-citrullinated protein antibody positivity (p=0.754) or seropositivity (p=0.163). In this study, we found no association between smoking status and disease activity, seropositivity, age or gender in rheumatoid arthritis patients. Furthermore, disease activity was not related to age, gender or seropositivity. Additional studies on the effects of smoking on rheumatoid arthritis activity are needed.


Subject(s)
Arthritis, Rheumatoid , Smoking , Aged , Arthritis, Rheumatoid/complications , Arthritis, Rheumatoid/epidemiology , C-Reactive Protein , Female , Humans , Male , Middle Aged , Rheumatoid Factor , Smoking/adverse effects , Smoking/epidemiology
8.
Int J Mol Sci ; 20(9)2019 Apr 28.
Article in English | MEDLINE | ID: mdl-31035335

ABSTRACT

The purpose of this paper was to outline the development of short peptide targeting of the human prostate specific antigen (hPSA), and to evaluate its effectiveness in staining PSA in human prostate cancer tissue. The targeting of the hPSA antigen by means of antisense peptide AVRDKVG was designed according to a three-step method involving: 1. The selection of the molecular target (hPSA epitope), 2. the modeling of an antisense peptide (paratope) based on the epitope sequence, and 3. the spectroscopic evaluation of sense-antisense peptide binding. We then modified standard hPSA immunohistochemical staining practice by using a biotinylated antisense peptide instead of the standard monoclonal antibody and compared the results of both procedures. Immunochemical testing on human tissue showed the applicability of the antisense peptide technology to human molecular targets. This methodology represents a new approach to deriving peptide ligands and potential lead compounds for the development of novel diagnostic substances, biopharmaceuticals and vaccines.


Subject(s)
Biomarkers, Tumor/immunology , Peptides/immunology , Prostate-Specific Antigen/immunology , Prostatic Neoplasms/immunology , Humans , Immunohistochemistry , Male , Nanomedicine/methods , Protein Structure, Secondary
9.
EMBO J ; 32(20): 2708-21, 2013 Oct 16.
Article in English | MEDLINE | ID: mdl-24045232

ABSTRACT

Lgr5 marks adult stem cells in multiple adult organs and is a receptor for the Wnt-agonistic R-spondins (RSPOs). Intestinal, stomach and liver Lgr5(+) stem cells grow in 3D cultures to form ever-expanding organoids, which resemble the tissues of origin. Wnt signalling is inactive and Lgr5 is not expressed under physiological conditions in the adult pancreas. However, we now report that the Wnt pathway is robustly activated upon injury by partial duct ligation (PDL), concomitant with the appearance of Lgr5 expression in regenerating pancreatic ducts. In vitro, duct fragments from mouse pancreas initiate Lgr5 expression in RSPO1-based cultures, and develop into budding cyst-like structures (organoids) that expand five-fold weekly for >40 weeks. Single isolated duct cells can also be cultured into pancreatic organoids, containing Lgr5 stem/progenitor cells that can be clonally expanded. Clonal pancreas organoids can be induced to differentiate into duct as well as endocrine cells upon transplantation, thus proving their bi-potentiality.


Subject(s)
Adult Stem Cells/physiology , Cell Proliferation , Pancreas/cytology , Receptors, G-Protein-Coupled/physiology , Thrombospondins/physiology , Adult Stem Cells/cytology , Adult Stem Cells/metabolism , Animals , Cell Culture Techniques , Cells, Cultured , Embryo, Mammalian , Mice , Mice, Inbred C57BL , Mice, Nude , Mice, SCID , Mice, Transgenic , Models, Biological , Multipotent Stem Cells/cytology , Multipotent Stem Cells/metabolism , Multipotent Stem Cells/physiology , Pancreas/metabolism , Rats , Rats, Sprague-Dawley , Receptors, G-Protein-Coupled/genetics , Receptors, G-Protein-Coupled/metabolism , Signal Transduction/genetics , Thrombospondins/genetics , Thrombospondins/metabolism
10.
BMC Cancer ; 15: 545, 2015 Jul 25.
Article in English | MEDLINE | ID: mdl-26205886

ABSTRACT

BACKGROUND: Elevated basal, ligand-independent, Wnt signaling in some canine breast cancer cells is not caused by classical mutations in APC, ß-Catenin or GSK3ß but, at least partially, by enhanced LEF1 expression. We examined the expression and function of EGFR/HER-regulated pathways on the ligand-independent Wnt signaling. METHODS: Twelve canine mammary tumor cell lines with previously reported differential basal Wnt activity were used. The expression levels of genes related to EGF-signaling were analyzed by cluster analysis. Cell lines with a combined overexpression of EGF-related genes and enhanced basal Wnt activity were treated with PI3K/mTor or cSRC inhibitors or transfected with a construct expressing wild-type PTEN. Subsequently, effects were measured on Wnt activity, cell proliferation, gene expression and protein level. RESULTS: High basal Wnt/LEF1 activity was associated with overexpression of HER2/3, ID1, ID2, RAC1 and HSP90 together with low to absent cMET and PTEN mRNA expression, suggesting a connection between Wnt- and HER-signaling pathways. Inhibition of the HER-regulated PI3K/mTor pathway using the dual PI3K/mTor inhibitor BEZ235 or the mTor inhibitor Everolimus® resulted in reduced cell proliferation. In the cell line with high basal Wnt activity, however, an unexpected further increased Wnt activity was found that could be greatly reduced after inhibition of the HER-regulated cSRC activity. Inhibition of the PI3K/mTor pathway was associated with enhanced expression of ß-Catenin, Axin2, MUC1, cMET, EGFR and HER2 and a somewhat increased ß-Catenin protein content, whereas cSRC inhibition was associated with slightly enhanced HER3 and SLUG mRNA expression. A high protein expression of HER3 was found only in a cell line with high basal Wnt activity. CONCLUSIONS: High basal Wnt activity in some mammary cancer cell lines is associated with overexpression of HER-receptor related genes and HER3 protein, and the absence of PTEN. Inhibition of the PI3K/mTor pathway further stimulated, however, canonical Wnt signaling, whereas the inhibitory effect with the cSRC inhibitor Src-I1 on the Wnt activity further suggested a connection between Wnt and HER2/3-signaling.


Subject(s)
Everolimus/pharmacology , Imidazoles/pharmacology , Mammary Neoplasms, Animal/genetics , Quinolines/pharmacology , Receptor, ErbB-2/genetics , Receptor, ErbB-3/genetics , Wnt Signaling Pathway , Animals , Cell Line, Tumor , Cell Proliferation/drug effects , Dogs , Female , Gene Expression Regulation, Neoplastic , Mammary Neoplasms, Animal/metabolism , Proto-Oncogene Proteins pp60(c-src)/antagonists & inhibitors , Proto-Oncogene Proteins pp60(c-src)/genetics , Receptor, ErbB-2/metabolism , Receptor, ErbB-3/metabolism , Wnt Signaling Pathway/drug effects
11.
Reumatizam ; 62(2): 16-21, 2015.
Article in Croatian | MEDLINE | ID: mdl-26882799

ABSTRACT

INTRODUCTION: Patients with systemic lupus erythematosus (SLE) are at an increased risk of developing low bone mass (LBM) or osteoporosis, either because of the disease itself or due to its treatment. Osteoporosis and osteoporotic fractures significantly contribute to morbidity and mortality. We aimed to determine the associations of bone mineral density (BMD) changes with the duration of SLE, age, gender, and glucocorticoid treatment in SLE patients treated at our Department. PATIENTS AND METHODS: BMD measurements of the lumbar spine and total hip were performed by dual-energy X-ray absorptiometry (DXA). Osteoporosis and LBM were determined according to the 1994 World Health Organization definition. In the statistical analysis, the independent Mann-Whitney U test and Tukey post-hoc testing were used. RESULTS: The study included 48 SLE patients (44 female and 4 male), with a mean age of 45.8 years and an average SLE duration of 9.8 years. Osteoporosis was diagnosed in 21%, and LBM in 15% of the patients. The mean ages of the subgroups with normal BMD, LBM, and osteoporosis were 41.1, 47.6, and 59.0 years, respectively. Variant analysis showed a statistically significant correlation between age and BMD (p < 0.05). The duration of SLE was significantly shorter in patients with normal BMD (7.3 years), compared to patients with LBM (16.1 years) and osteoporosis (12.9 years) (p < 0.05). Nearly all patients (47 of 48) were on long-term treatment with glucocorticoids. One third (33.3 %) of patients did not take vitamin D3, and 56.3 % did not take calcium supplements. CONCLUSION: The etiopathogenesis of decreased BMD in SLE patients is multifactorial and includes both traditional and SLE-related risk factors. In our group of SLE patients age and glucocorticoid treatment were the major risk factors for LBM. Timely prevention and treatment of LBM and osteoporosis in SLE patients, according to current knowledge, are essential for reducing morbidity and mortality.


Subject(s)
Bone Density , Lupus Erythematosus, Systemic/complications , Osteoporosis/complications , Adult , Female , Glucocorticoids/therapeutic use , Humans , Male , Middle Aged , Osteoporosis/drug therapy , Osteoporotic Fractures/complications , Risk Factors
12.
Lijec Vjesn ; 136(1-2): 22-4, 2014.
Article in Croatian | MEDLINE | ID: mdl-24720151

ABSTRACT

Visceral leishmaniasis or kala-azar is a systemic infectious vector-borne disease caused by protozoa Leishmania donovani and Leishmania infantum that are transmitted to mammalian hosts by sand flies. It occurrs sporadically in endemic areas, including Mediterranean basin. Southern coastal territories of Croatia have been recognized as the foci of the disease. Dogs are the main reservoir of human infection. Clinical features include prolonged fever, malaise, hepatosplenomegaly, pancytopenia and inversion of albumin-globulin ratio. If left untreated, the disease causes death in majority of cases. We report a 47-year-old Croatian patient who was admitted to hospital with 2-month history of fever of unknown origin. Based on bone marrow aspirate findings and positive serological tests, the diagnosis of visceral leishmaniasis was established. We also considered secondary hemophagocytic lymphohystiocytosis in the differential diagnosis. After a 4-week treatment with sodium-stibogluconate clinical remission was achieved as well as complete recovery of hematopoesis. The aim of our case-report is to stress the importance of considering visceral leishmaniasis in patients with longstanding fever in endemic areas.


Subject(s)
Fever of Unknown Origin/parasitology , Leishmaniasis, Visceral/diagnosis , Animals , Antiprotozoal Agents/therapeutic use , Bone Marrow/parasitology , Croatia , Diagnosis, Differential , Dogs , Humans , Leishmania infantum/isolation & purification , Leishmaniasis, Visceral/drug therapy , Male , Middle Aged , Treatment Outcome
13.
Coll Antropol ; 37(1): 131-3, 2013 Mar.
Article in English | MEDLINE | ID: mdl-23697262

ABSTRACT

The etiology and epidemiology of obstructive jaundice in Continental Croatia has been studied in 174 patients. The objective of this research was also to explore the importance and efficiency of endoscopic retrograde cholangiopancreatography (ERCP) as a non-surgical method of treatment of obstructive jaundice in the population of Continental Croatia. Obstructive jaundice is the illness of elderly population which is also confirmed by the information on the average age of our patients. The frequency of illness is higher among female population, and the most frequent cause of obstructive jaundice are gallstones (54.1% of patients). In 29.8% of patients the primary or secondary malignant disease was the cause of blockage in gall flow and subsequent jaundice, and the most frequent malignant cause of obstructive jaundice is pancreas cancer in 11.5% of patients. The mean value of serum concentrations of total bilirubin, alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase and gamma glutamiltransferase 24 hours before the biliary decompression by ERCP has been significantly above the upper referential value, and 24 hours after the ERCP it has dropped to normal with their statistically significant difference (p < 0.0001). The normal values of markers for synthetic liver function (total proteins and prothrombin time) have been noticed as well as elevated values of inflammatory markers in obstructive jaundice independently of etiology. Out of the total number of patients, 37.7% required the surgical treatment while 60.3% of patients were treated by ERCP, i.e. either the stone extraction or the implantation of endobiliary stent was performed.


Subject(s)
Cholangiopancreatography, Endoscopic Retrograde/methods , Jaundice, Obstructive/epidemiology , Jaundice, Obstructive/etiology , Adult , Aged , Aged, 80 and over , Alanine Transaminase/metabolism , Alkaline Phosphatase/metabolism , Aspartate Aminotransferases/metabolism , Bilirubin/metabolism , Croatia/epidemiology , Female , Humans , Inflammation , Liver/pathology , Male , Middle Aged , Young Adult , gamma-Glutamyltransferase/metabolism
14.
Reumatizam ; 60(2): 35-8, 2013.
Article in Croatian | MEDLINE | ID: mdl-24979994

ABSTRACT

Large vessel vasculitis includes Giant cell arteritis and Takayasu arteritis. Giant cell arteritis is the most common form of vasculitis affect patients aged 50 years or over. The diagnosis should be considered in older patients who present with new onset of headache, visual disturbance, polymyalgia rheumatica and/or fever unknown cause. Glucocorticoides remain the cornerstone of therapy. Takayasu arteritis is a chronic panarteritis of the aorta ant its major branches presenting commonly in young ages. Although all large arteries can be affected, the aorta, subclavian and carotid arteries are most commonly involved. The most common symptoms included upper extremity claudication, hypertension, pain over the carotid arteries (carotidynia), dizziness and visual disturbances. Early diagnosis and treatment has improved the outcome in patients with TA.


Subject(s)
Giant Cell Arteritis/diagnosis , Takayasu Arteritis/diagnosis , Age Factors , Giant Cell Arteritis/complications , Giant Cell Arteritis/therapy , Humans , Takayasu Arteritis/complications , Takayasu Arteritis/therapy
15.
Reumatizam ; 60(1): 32-6, 2013.
Article in Croatian | MEDLINE | ID: mdl-24003682

ABSTRACT

Gluten-sensitive enteropathy or celiac disease is a chronic small intestinal immune-mediated enteropathy precipitated by exposure to dietary gluten in genetically predisposed individuals. Although the disease may manifest itself at any age, it occurs mostly in either early childhood or in the third or fourth decade of life. Malabsorption syndrome as a typical clinical feature is commonly absent. Patients may exhibit minor gastrointestinal complaints, as well as numerous extraintestinal manifestations. We report a 43-year-old female patient with mi gratory arthralgias as the leading symptom, fatigue, sideropenic anemia and mild intermittent diarrhoea, who was diagnosed with gluten-sensitive enteropathy. Four months after introduction of gluten-free diet the patient reported no arthralgias, and complete clinical response was achieved. The aim of our case-report was to show that migratory arthralgias can be an extraintestinal manifestation of gluten-sensitive enteropathy. Unexplained articular complaints should raise clinical suspicion of celiac disease.


Subject(s)
Arthralgia/etiology , Celiac Disease/diagnosis , Adult , Celiac Disease/complications , Celiac Disease/diet therapy , Diarrhea/etiology , Fatigue/etiology , Female , Humans
16.
Sci Rep ; 13(1): 480, 2023 01 10.
Article in English | MEDLINE | ID: mdl-36627361

ABSTRACT

The impacts of a changing climate threaten species, populations and ecosystems. Despite these significant and large-scale impacts on threatened species, many remain understudied and have little to no genetic information available. The greater glider, Petauroides volans, is an endangered species highly sensitive to the predicted changes in temperature under a changing climate and was recently severely impacted by a megafire natural disaster (85% estimated population loss). Baseline genetic data is essential for conservation management and for detecting detrimental changes in fire-effected populations. We collected genetic samples within 2 years post the 2019-2020 catastrophic Australian bushfires to examine adaptive potential, baseline genetic diversity and population structure, across their southern range in the state of New South Wales. Population genomic analyses were conducted using 8493 genome-wide SNPs for 86 greater glider individuals across 14 geographic locations. Substantial genetic structure was detected across locations, with low genetic diversity and effective population sizes observed in isolated areas. Additionally, we found signals of putative adaptation in response to temperature in greater gliders using a genotype-environment association analysis. These findings have important implications for the management of greater glider populations by identifying at-risk populations and identifying adaptive potential. We demonstrate the importance of baseline genetic information for endangered species as a practical approach to conservation. This is particularly important given the threat that changes in temperatures and megafire events, as predicted under a changing climate, poses for this species.


Subject(s)
Ecosystem , Trees , Humans , Animals , Australia , Genomics , Endangered Species , Mammals , Conservation of Natural Resources , Genetic Variation
17.
Genes (Basel) ; 14(2)2023 01 29.
Article in English | MEDLINE | ID: mdl-36833276

ABSTRACT

Habitat loss and fragmentation contribute significantly to the decline of arboreal mammal populations. As populations become fragmented and isolated, a reduction in gene flow can result in a loss of genetic diversity and have an overall impact upon long-term persistence. Creating wildlife corridors can mitigate such effects by increasing the movement and dispersal of animals, thus acting to reduce population isolation. To evaluate the success of a corridor, a before-after experimental research framework can be used. Here, we report the genetic diversity and structure of sugar glider (Petaurus breviceps) sampling locations within a fragmented landscape prior to the implementation of a wildlife corridor. This study used 5999 genome-wide SNPs from 94 sugar gliders caught from 8 locations in a fragmented landscape in south-eastern New South Wales, Australia. Overall genetic structure was limited, and gene flow was detected across the landscape. Our findings indicate that the study area contains one large population. A major highway dissecting the landscape did not act as a significant barrier to dispersal, though this may be because of its relatively new presence in the landscape (completed in 2018). Future studies may yet indicate its long-term impact as a barrier to gene flow. Future work should aim to repeat the methods of this study to examine the medium-to-long-term impacts of the wildlife corridor on sugar gliders, as well as examine the genetic structure of other native, specialist species in the landscape.


Subject(s)
Animals, Wild , Marsupialia , Animals , Marsupialia/genetics , Trees , Genetics, Population , Mammals , Sugars
18.
J Nephrol ; 36(2): 441-449, 2023 03.
Article in English | MEDLINE | ID: mdl-36447124

ABSTRACT

INTRODUCTION: Several histologic classifications are used in the evaluation of IgA vasculitis nephritis (IgAVN), however, to date, no studies have determined which one has the strongest association with the severity of IgAVN and, as a consequence, its outcomes. MATERIALS AND METHODS: Patients included in the study were diagnosed with IgAV and IgAVN in seven tertiary university medical centers in Croatia, Italy and Israel. The International Study of Kidney Disease in Children (ISKDC), Haas, Oxford, and Semiquantitative classification (SQC) classifications were used in the analysis and description of renal biopsy. Time from biopsy to outcome evaluation was a statistically significant factor in outcome prediction that was used to define the base model, and was a covariate in all the tested models. RESULTS: Sixty-seven patients were included in this study. The SQC classification proved to be the best one in outcome prediction, followed by the Oxford classification. The ISKDC and Haas classifications could not predict renal outcome. The Oxford parameters for mesangial hypercellularity and tubular atrophy, as well as the SQC parameters for cellular crescents showed an independent statistically significant contribution to outcome prediction. High level of twenty-four hour protein excretion was associated with a higher grade in the Oxford, SQC and ISKDC classifications. Endocapillary proliferation was positively associated with the Pediatric Vasculitis Activity Score (PVAS) at diagnosis, while tubular atrophy was negatively associated. CONCLUSION: The SQC, followed by the Oxford classification were found to provide the best classifications of renal biopsy analysis in patients to predict the outcome in patients with IgAVN. Cellular crescents, mesangial hypercellularity and tubular atrophy showed significant contributions, indicating that active and chronic variables should be included in the estimation.


Subject(s)
IgA Vasculitis , Kidney Diseases , Nephritis , Humans , Child , Kidney/pathology , Kidney Diseases/pathology , IgA Vasculitis/complications , Atrophy/pathology , Retrospective Studies
19.
Animals (Basel) ; 12(7)2022 Apr 02.
Article in English | MEDLINE | ID: mdl-35405900

ABSTRACT

The use of camera traps to track individual mammals to estimate home range and movement patterns, has not been previously applied to small mammal species. Our aim was to evaluate the use of camera trapping, using the selfie trap method, to record movements of small mammals within and between fragments of habitat. In a fragmented landscape, 164 cameras were set up across four survey areas, with cameras left to record continuously for 28 nights. Live trapping was performed prior to ear mark animals to facilitate individual identification on camera. Four small mammal species (sugar glider; Petaurus breviceps; brown antechinus; Antechinus stuartii, bush rat; Rattus fuscipes, and brown rat; Rattus norvigecus) were recorded on camera (N = 284 individuals). The maximum distance travelled by an individual sugar glider was 14.66 km, antechinus 4.24 km; bush rat 1.90 km and brown rat 1.28 km. Movements of both female and male sugar gliders in linear fragments were recorded at much higher rates than in larger patches of forest sampled in grids. Short term core homes ranges (50% KDE) of 34 sugar gliders ranged from 0.3 ha to 4.2 ha. Sugar glider core home ranges were on average 1.2 ha (±0.17) for females and 2.4 ha (±0.28) for males. The selfie trap is an efficient camera trapping method for estimating home ranges and movements due to its ability to obtain high recapture rates for multiple species and individuals. In our study landscape, linear strips of habitat were readily utilised by all small mammals, highlighting their importance as wildlife corridors in a fragmented landscape.

20.
Mamm Res ; 67(4): 467-482, 2022.
Article in English | MEDLINE | ID: mdl-35891629

ABSTRACT

Camera trapping to study wildlife allows for data collection, without the need to capture animals. Traditionally, camera traps have been used to target larger terrestrial mammal species, though recently novel methods and adjustments in procedures have meant camera traps can be used to study small mammals. The selfie trap (a camera trapping method) may present robust sampling and ecological study of small mammals. This study aimed to evaluate the selfie trap method in terms of its ability to detect species and estimate population density. To address this aim, standard small mammal live trapping was undertaken, immediately followed by camera trapping using the selfie trap. Both methods were set to target the arboreal sugar glider (Petaurus breviceps) and semi-arboreal brown antechinus (Antechinus stuartii). The more ground-dwelling bush rat (Rattus fuscipes) was also live trapped and recorded on camera. Across four survey areas, the probability of detection for each of the three species was higher for selfie traps than for live trapping. Spatially explicit capture-recapture models showed that selfie traps were superior at estimating density for brown antechinus and sugar gliders, when compared to simulated live trapping data. Hit rates (number of videos per various time intervals) were correlated with abundance. When correlating various hit rate intervals with abundance, the use of 10-min hit rate was best for predicting sugar glider abundance (R2 = 0.94). The abundance of brown antechinus was estimated from selfie traps using a 24-h hit rate as a predictor (R2 = 0.85). For sugar gliders, the selfie trap can replace live trapping as individuals can be identified through their unique facial stripes and natural ear scars, and thus used in capture-recapture analysis. This method may be useful for monitoring the abundance of other small mammal species that can also be individually recognized from photographs. Supplementary Information: The online version contains supplementary material available at 10.1007/s13364-022-00643-5.

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