Human–wildlife conflicts occur worldwide. Although many nonlethal mitigation solutions are available, they rarely use the behavioral ecology of the conflict species to derive effective and ...long-lasting solutions. Here, we use a long-term study with 106 GPS-collared free-ranging cheetahs (Acinonyx jubatus) to demonstrate how new insights into the socio-spatial organization of this species provide the key for such a solution. GPS-collared territory holders marked and defended communication hubs (CHs) in the core area of their territories. The CHs/territories were distributed in a regular pattern across the landscape such that they were not contiguous with each other but separated by a surrounding matrix. They were kept in this way by successive territory holders, thus maintaining this overdispersed distribution. The CHs were also visited by nonterritorial cheetah males and females for information exchange, thus forming hotspots of cheetah activity and presence. We hypothesized that the CHs pose an increased predation risk to young calves for cattle farmers in Namibia. In an experimental approach, farmers shifted cattle herds away from the CHs during the calving season. This drastically reduced their calf losses by cheetahs because cheetahs did not follow the herds but instead preyed on naturally occurring local wildlife prey in the CHs. This implies that in the cheetah system, there are “problem areas,” the CHs, rather than “problem individuals.” The incorporation of the behavioral ecology of conflict species opens promising areas to search for solutions in other conflict species with nonhomogenous space use.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Proliferating cell nuclear antigen (PCNA), commonly known as a nuclear protein essential for regulation of DNA replication, DNA repair, and epigenetics, has recently been associated with multiple ...cytosolic functions. Many proteins containing one of the two known PCNA-interacting motifs, the AlkB homologue 2 PCNA interacting motif (APIM) and the PCNA-interacting peptide (PIP)-box, are considered to be mainly cytosolic. APIM is found in more than 20 kinases and/or associated proteins including several direct or indirect members of the mitogen-activated protein kinase (MAPK) and PI3K/Akt pathways. Mass spectrometry analysis of PCNA-pull downs verified that many cytosolic proteins involved in the MAPK and PI3K/Akt pathways are in complex with PCNA. Furthermore, treatment of cells with a PCNA-interacting APIM-containing peptide (APIM-peptide) reduced Akt phosphorylation in human peripheral blood monocytes and a human keratinocyte cell line (HaCaT). Additionally, the APIM-peptide strongly reduced the cytokine secretion from monocytes stimulated with toll like receptor (TLR) ligands and potentiated the effects of MAPK and PI3K/Akt inhibitors. Interestingly, the protein level of the APIM-containing PKR/RIG-1 activator protein (PACT) was initially strongly reduced in HaCaT cells stimulated with APIM-peptide in combination with the TLR ligand polyinosinic–polycytidylic acid (polyIC). Our results suggest that PCNA has a platform role in cytosol affecting cellular signaling.
•Proteins involved in cellular signaling are in complex with PCNA.•Inhibiting potential PCNA–APIM-protein reduced PI3K/Akt signaling.•APIM-peptide targeting PCNA reduced cytokine secretion from TLR-stimulated cells.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPUK
Many mammalian species communicate via olfactory communication placed at particular locations. The majority of these studies focused on intraspecific communication. More recently, studies have also ...investigated interspecific communication and recorded prey animals sniffing olfactory cues left by predators and predators investigating or counter-marking cues left by other predator species. The purpose of exchanging olfactory cues within a species community is little understood. Using a comparative study design, we investigated the behaviour of a mammalian community at cheetah marking trees and paired control trees using camera traps on Namibian farmland. We tested the predictions derived from hypotheses regarding the reasons for visits to the marking trees. Cheetah marking trees and control trees were visited 1101 times by 29 mammalian species (excluding cheetahs), with more species recorded at the marking trees than control trees. Two competitively subordinate carnivore species made more visiting and sniffing events, respectively, at cheetah marking trees than control trees, possibly to assess the time since cheetahs were in the area. Two opportunistic scavenger species sniffed more frequently at the marking trees than control trees, perhaps to feed on undigested prey remains in scats. One common prey species of cheetahs had fewer visiting events at the marking trees than control trees, likely to reduce encounters with cheetahs. Further, one species that is rarely preyed by cheetahs marked cheetah marking trees at the same frequency as control trees, suggesting it uses conspicuous sites rather for intraspecific than interspecific communication. Thus, trees used by cheetahs for marking also play an important role in olfactory communication for a variety of mammalian species.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Proliferating cell nuclear antigen (PCNA) is an essential protein for DNA replication, DNA repair, cell cycle regulation, chromatin remodeling, and epigenetics. Many proteins interact with PCNA ...through the PCNA interacting peptide (PIP)-box or the newly identified AlkB homolog 2 PCNA interacting motif (APIM). The xeroderma pigmentosum group A (XPA) protein, with a central but somewhat elusive role in nucleotide excision repair (NER), contains the APIM sequence suggesting an interaction with PCNA. With an in vivo based approach, using modern techniques in live human cells, we show that APIM in XPA is a functional PCNA interacting motif and that efficient NER of UV lesions is dependent on an intact APIM sequence in XPA. We show that XPA(-/-) cells complemented with XPA containing a mutated APIM sequence have increased UV sensitivity, reduced repair of cyclobutane pyrimidine dimers and (6-4) photoproducts, and are consequently more arrested in S phase as compared to XPA(-/-) cells complemented with wild type XPA. Notably, XPA colocalizes with PCNA in replication foci and is loaded on newly synthesized DNA in undamaged cells. In addition, the TFIIH subunit XPD, as well as XPF are loaded on DNA together with XPA, and XPC and XPG colocalize with PCNA in replication foci. Altogether, our results suggest a presence of the NER complex in the vicinity of the replisome and a novel role of NER in post-replicative repair.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Multiple myeloma is a hematological cancer that is considered incurable despite advances in treatment strategy during the last decade. Therapies targeting single pathways are unlikely to succeed due ...to the heterogeneous nature of the malignancy. Proliferating cell nuclear antigen (PCNA) is a multifunctional protein essential for DNA replication and repair that is often overexpressed in cancer cells. Many proteins involved in the cellular stress response interact with PCNA through the five amino acid sequence AlkB homologue 2 PCNA-interacting motif (APIM). Thus inhibiting PCNA's protein interactions may be a good strategy to target multiple pathways simultaneously. We initially found that overexpression of peptides containing the APIM sequence increases the sensitivity of cancer cells to contemporary therapeutics. Here we have designed a cell-penetrating APIM-containing peptide, ATX-101, that targets PCNA and show that it has anti-myeloma activity. We found that ATX-101 induced apoptosis in multiple myeloma cell lines and primary cancer cells, while bone marrow stromal cells and primary healthy lymphocytes were much less sensitive. ATX-101-induced apoptosis was caspase-dependent and cell cycle phase-independent. ATX-101 also increased multiple myeloma cells' sensitivity against melphalan, a DNA damaging agent commonly used for treatment of multiple myeloma. In a xenograft mouse model, ATX-101 was well tolerated and increased the anti-tumor activity of melphalan. Therefore, targeting PCNA by ATX-101 may be a novel strategy in multiple myeloma treatment.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
COVID-19 lockdowns in early 2020 reduced human mobility, providing an opportunity to disentangle its effects on animals from those of landscape modifications. Using GPS data, we compared movements ...and road avoidance of 2300 terrestrial mammals (43 species) during the lockdowns to the same period in 2019. Individual responses were variable with no change in average movements or road avoidance behavior, likely due to variable lockdown conditions. However, under strict lockdowns 10-day 95th percentile displacements increased by 73%, suggesting increased landscape permeability. Animals' 1-hour 95th percentile displacements declined by 12% and animals were 36% closer to roads in areas of high human footprint, indicating reduced avoidance during lockdowns. Overall, lockdowns rapidly altered some spatial behaviors, highlighting variable but substantial impacts of human mobility on wildlife worldwide.
Numerous proteins, many essential for the DNA replication machinery, interact with proliferating cell nuclear antigen (PCNA) through the PCNA-interacting peptide (PIP) sequence called the PIP box. We ...have previously shown that the oxidative demethylase human AlkB homologue 2 (hABH2) colocalizes with PCNA in replication foci. In this study, we show that hABH2 interacts with a posttranslationally modified PCNA via a novel PCNA-interacting motif, which we term AlkB homologue 2 PCNA-interacting motif (APIM). We identify APIM in >200 other proteins involved in DNA maintenance, transcription, and cell cycle regulation, and verify a functional APIM in five of these. Expression of an APIM peptide increases the cellular sensitivity to several cytostatic agents not accounted for by perturbing only the hABH2-PCNA interaction. Thus, APIM is likely to mediate PCNA binding in many proteins involved in DNA repair and cell cycle control during genotoxic stress.
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Proliferating cell nuclear antigen (PCNA) is essential for the organization of DNA replication and the bypass of DNA lesions via translesion synthesis (TLS). TLS is mediated by specialized DNA ...polymerases, which all interact, directly or indirectly, with PCNA. How interactions between the TLS polymerases and PCNA affects TLS specificity and/or coordination is not fully understood. Here we show that the catalytic subunit of the essential mammalian TLS polymerase POLζ, REV3L, contains a functional AlkB homolog 2 PCNA interacting motif, APIM. APIM from REV3L fused to YFP, and full-length REV3L-YFP colocalizes with PCNA in replication foci. Colocalization of REV3L-YFP with PCNA is strongly reduced when an APIM-CFP construct is overexpressed. We also found that overexpression of full-length REV3L with mutated APIM leads to significantly altered mutation frequencies and mutation spectra, when compared to overexpression of full-length REV3L wild-type (WT) protein in multiple cell lines. Altogether, these data suggest that APIM is a functional PCNA-interacting motif in REV3L, and that the APIM-mediated PCNA interaction is important for the function and specificity of POLζ in TLS. Finally, a PCNA-targeting cell-penetrating peptide, containing APIM, reduced the mutation frequencies and changed the mutation spectra in several cell lines, suggesting that efficient TLS requires coordination mediated by interactions with PCNA.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
In times of economic crisis, many employers in liberal labor markets reduce their employees’ working hours, which leads to an increase in the incidence of involuntary part-time work. We analyze the ...effectiveness of working time regulation in preventing such an increase during downswings. For this we look at the case of Germany, where hours adjustments are highly restricted by law. Using a state-level panel regression approach, we find that the incidence of involuntary part-time work is positively associated with the unemployment rate but that the association is much weaker than in the US and in the UK. Transition probabilities between employment states over the cycle suggest two particular underlying mechanisms: First, already employed workers are more likely to want a full-time position in economic downturns (“added hours effect”). Second, job seekers make concessions with regards to their desired hours when labor market conditions are bad (“reservation hours effect”). We are the first to document these margins of cyclical hours adjustments which are fundamentally different from those in less regulated labor markets, where the cyclicality of involuntary part-time work is predominantly driven by hours changes at the same employer.
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