Movements and site fidelity of killer whales (Orcinus orca) relative to seasonal and long-term shifts in herring (Clupea harengus) distribution

Predators specialising on migratory prey that frequently change migration route face the challenge of finding prey with an unpredictable distribution. Here, we used photo-identification data to investigate whether killer whales observed in herring overwintering and spawning grounds off Iceland follow herring year-round, as previously proposed, and have the ability to adapt to long-term changes in herring distribution. Of 327 identified whales seen more than once, 45% were seen in both grounds, and were thus presumed herring-specialists, likely following herring year-round, while others were only seen on one of the grounds, possibly following herring to unsampled grounds or moving to other locations and exploiting different prey. High seasonal site fidelity to herring grounds, long-term site fidelity to herring spawning grounds, and matches of individual whales between past and recently occupied herring overwintering grounds showed an ability to adapt to long-term changes in prey distribution as well as diversity of movement patterns which are maintained over time, likely as socially-learnt traditions. Such population structuring shows that the movement patterns and foraging ecology of herring-eating killer whales are more complex than previously assumed and must be taken into account in future population assessments. Identifying the factors driving these differences in movements and resource use will be relevant towards our understanding of how prey predictability may drive specialization in this and other top predator species

Neuropeptide kyotorphin (tyrosyl-arginine) has decreased levels in the cerebro-spinal fluid of Alzheimer’s disease patients: potential diagnostic and pharmacological implications

In Alzheimer’s disease (AD), besides the characteristic deterioration of memory, studies also point to a higher pain tolerance in spite of sensibility preservation. A change in the normal tau protein phosphorylation is also characteristic of AD, which contributes to the pathogenesis of the disease and is useful in early diagnosis. Kyotorphin (KTP) is an endoge-nous analgesic dipeptide (Tyr-Arg) for which there is evidence of eventual neuroprotective and neuromodulatory properties. The objective of this work was to study the possible cor-relation between KTP and phosphorylated tau protein (p-tau) levels in cerebro-spinal fluid (CSF) samples of AD patients. CSF samples were collected from 25 AD patients and 13 age-matched controls (N), where p-tau and KTP levels were measured.We found a statis-tically significant difference between p-tau/KTP values in AD and N groups with an inverse correlation between p-tau and KTP values in AD samples. These results suggest that in the future KTP may be a candidate biomarker for neurodegeneration and may be a lead compound to be used pharmacologically for neuroprotection.Fundação para a Ciência e Tecnologia (FCT, Portugal) is acknowledged for fellowship SFRH/BPD/79542/2011 to Sónia Sá Santos and Grant PTDC/QUI-BIQ/112929/2009. MarieCurie International Research Staff Exchange Scheme (IRSES) is also acknowledged forfunding (FP7-PEOPLE-2009-IRSES, project MEMPEPACROSS)

A multilevel society of herring-eating killer whales indicates adaptation to prey characteristics

This work was supported by the Fundação para a Ciência e a Tecnologia (grant numbers SFSFRH/BD/30303/2006 and SFRH/BD/84714/2012); Icelandic Research Fund (i. Rannsóknasjóđur, grant number 120248402); National Geographic Society Science and Exploration Europe (grant number GEFNE65-12); Office of Naval Research (grant number N00014-08-10984); and a Russell Trust Award from the University of St. Andrews.Non-social factors can influence animal social structure. In killer whales (Orcinus orca), fish- versus mammal-eating ecological differences are regarded as key ecological drivers of their multilevel society, including group size, but the potential importance of specific target prey remains unclear. Here, we investigate the social structure of herring-eating killer whales in Iceland and compare it to the described social structures of primarily salmon- and seal-eating populations in the Northeast Pacific, which form stable coherent basic units nested within a hierarchical multilevel society. Using 29023 photographs collected over 6 years, we examined the association patterns of 198 individuals combining clustering, social network structure, and temporal patterns of association analysis. The Icelandic population had largely weak but non-random associations, which were not completely assorted by known ranging patterns. A fission–fusion dynamic of constant and temporary associations was observed but this was not due to permanent units joining. The population-level society was significantly structured but not in a clear hierarchical tier system. Social clusters were highly diverse in complexity and there were indications of subsclusters. There was no indication of dispersal nor strong sex differences in associations. These results indicate that the Icelandic herring-eating killer whale population has a multilevel social structure without clear hierarchical tiers or nested coherent social units, different from other populations of killer whales. We suggest that local ecological context, such as the characteristics of the specific target prey (e.g., predictability, biomass, and density) and subsequent foraging strategies may strongly influence killer whale social association patterns.PostprintPeer reviewe

Amidated and ibuprofen-conjugated kyotorphins promote neuronal rescue and memory recovery in cerebral hypoperfusion dementia model

Copyright © 2016 Sá Santos, Santos, Pinto, Ramu, Heras, Bardaji, Tavares and Castanho. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.Chronic brain ischemia is a prominent risk factor for neurological dysfunction and progression for dementias, including Alzheimer's disease (AD). In rats, permanent bilateral common carotid artery occlusion (2VO) causes a progressive neurodegeneration in the hippocampus, learning deficits and memory loss as it occurs in AD. Kyotorphin (KTP) is an endogenous antinociceptive dipeptide whose role as neuromodulator/neuroprotector has been suggested. Recently, we designed two analgesic KTP-derivatives, KTP-amide (KTP-NH2) and KTP-NH2 linked to ibuprofen (IbKTP-NH2) to improve KTP brain targeting. This study investigated the effects of KTP-derivatives on cognitive/behavioral functions (motor/spatial memory/nociception) and hippocampal pathology of female rats in chronic cerebral hypoperfusion (2VO-rat model). 2VO-animals were treated with KTP-NH2 or IbKTP-NH2 for 7 days at weeks 2 and 5 post-surgery. After behavioral testing (week 6), coronal sections of hippocampus were H&E-stained or immunolabeled for the cellular markers GFAP (astrocytes) and NFL (neurons). Our findings show that KTP-derivatives, mainly IbKTP-NH2, enhanced cognitive impairment of 2VO-animals and prevented neuronal damage in hippocampal CA1 subfield, suggesting their potential usefulness for the treatment of dementia.Funding was provided by the Portuguese Agency Fundação para a Ciência e a Tecnologia SFRH/BPD/79542/2011 fellowship)info:eu-repo/semantics/publishedVersio

Biallelic BUB1 mutations cause microcephaly, developmental delay, and variable effects on cohesion and chromosome segregation

Budding uninhibited by benzimidazoles (BUB1) contributes to multiple mitotic processes. Here, we describe the first two patients with biallelic BUB1 germline mutations, who both display microcephaly, intellectual disability, and several patient-specific features. The identified mutations cause variable degrees of reduced total protein level and kinase activity, leading to distinct mitotic defects. Both patients' cells show prolonged mitosis duration, chromosome segregation errors, and an overall functional spindle assembly checkpoint. However, while BUB1 levels mostly affect BUBR1 kinetochore recruitment, impaired kinase activity prohibits centromeric recruitment of Aurora B, SGO1, and TOP2A, correlating with anaphase bridges, aneuploidy, and defective sister chromatid cohesion. We do not observe accelerated cohesion fatigue. We hypothesize that unresolved DNA catenanes increase cohesion strength, with concomitant increase in anaphase bridges. In conclusion, BUB1 mutations cause a neurodevelopmental disorder, with clinical and cellular phenotypes that partially resemble previously described syndromes, including autosomal recessive primary microcephaly, mosaic variegated aneuploidy, and cohesinopathies.info:eu-repo/semantics/publishedVersio

Rabbit derived VL single-domains as promising scaffolds to generate antibody–drug conjugates

© The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.Antibody-drug conjugates (ADCs) are among the fastest-growing classes of therapeutics in oncology. Although ADCs are in the spotlight, they still present significant engineering challenges. Therefore, there is an urgent need to develop more stable and effective ADCs. Most rabbit light chains have an extra disulfide bridge, that links the variable and constant domains, between Cys80 and Cys171, which is not found in the human or mouse. Thus, to develop a new generation of ADCs, we explored the potential of rabbit-derived VL-single-domain antibody scaffolds (sdAbs) to selectively conjugate a payload to Cys80. Hence, a rabbit sdAb library directed towards canine non-Hodgkin lymphoma (cNHL) was subjected to in vitro and in vivo phage display. This allowed the identification of several highly specific VL-sdAbs, including C5, which specifically target cNHL cells in vitro and present promising in vivo tumor uptake. C5 was selected for SN-38 site-selective payload conjugation through its exposed free Cys80 to generate a stable and homogenous C5-DAB-SN-38. C5-DAB-SN-38 exhibited potent cytotoxicity activity against cNHL cells while inhibiting DNA-TopoI activity. Overall, our strategy validates a platform to develop a novel class of ADCs that combines the benefits of rabbit VL-sdAb scaffolds and the canine lymphoma model as a powerful framework for clinically translation of novel therapeutics for cancer.This work was supported by the Portuguese Funding Agency, Fundação para a Ciência e Tecnologia, FCT IP (SAICT/2017/32085, PTDC/QUI-OUT/3989/2021 and Ph.D. fellowship SFRH/BD/131468/2017 to ASA and SFRH/BD/90514/2012 to JD). CIISA has provided support through Project UIDB/00276/2020, funded by FCT and LA/P/0059/2020-AL4AnimalS. Research Institute for Medicines (iMed.ULisboa) acknowledges the financial support of Fundação para a Ciência e Tecnologia (Projects: PTDC/QUI-OUT/3989/2021; UIDB/04138/2020 and UIDP/04138/2020). The NMR spectrometers are part of the National NMR Network (PTNMR) and are partially supported by Infrastructure Project Nº 022161 (co-financed by FEDER through COMPETE 2020, POCI and PORL and FCT through PIDDAC).info:eu-repo/semantics/publishedVersio

Mutation of the surface layer protein SlpB has pleiotropic effects in the probiotic propionibacterium freudenreichii CIRM-BIA 129

Propionibacterium freudenreichii is a beneficial Gram-positive bacterium, traditionally used as a cheese-ripening starter, and currently considered as an emerging probiotic. As an example, the P. freudenreichii CIRM-BIA 129 strain recently revealed promising immunomodulatory properties. Its consumption accordingly exerts healing effects in different animal models of colitis, suggesting a potent role in the context of inflammatory bowel diseases. This anti-inflammatory effect depends on surface layer proteins (SLPs). SLPs may be involved in key functions in probiotics, such as persistence within the gut, adhesion to host cells and mucus, or immunomodulation. Several SLPs coexist in P. freudenreichii CIRM-BIA 129 and mediate immunomodulation and adhesion. A mutant P. freudenreichii CIRM-BIA 129ΔslpB (CB129ΔslpB) strain was shown to exhibit decreased adhesion to intestinal epithelial cells. In the present study, we thoroughly analyzed the impact of this mutation on cellular properties. Firstly, we investigated alterations of surface properties in CB129ΔslpB. Surface extractable proteins, surface charges (ζ-potential) and surface hydrophobicity were affected by the mutation. Whole-cell proteomics, using high definition mass spectrometry, identified 1,288 quantifiable proteins in the wild-type strain, i.e., 53% of the theoretical proteome predicted according to P. freudenreichii CIRM-BIA 129 genome sequence. In the mutant strain, we detected 1,252 proteins, including 1,227 proteins in common with the wild-type strain. Comparative quantitative analysis revealed 97 proteins with significant differences between wild-type and mutant strains. These proteins are involved in various cellular process like signaling, metabolism, and DNA repair and replication. Finally, in silico analysis predicted that slpB gene is not part of an operon, thus not affecting the downstream genes after gene knockout. This study, in accordance with the various roles attributed in the literature to SLPs, revealed a pleiotropic effect of a single slpB mutation, in the probiotic P. freudenreichii. This suggests that SlpB may be at a central node of cellular processes and confirms that both nature and amount of SLPs, which are highly variable within the P. freudenreichii species, determine the probiotic abilities of strains.Fil: do Carmo, Fillipe L. R.. Institut National de la Recherche Agronomique; Francia. Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas; BrasilFil: Marques Da Silva, Wanderson. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Biotecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Tavares, Guilherme C.. Universidade Federal de Minas Gerais; BrasilFil: Ibraim, Izabela C.. Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas; BrasilFil: Cordeiro, Barbara F.. Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas; BrasilFil: Oliveira, Emiliano R.. Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas; BrasilFil: Rabah, Houem. Institut National de la Recherche Agronomique; FranciaFil: Cauty, Chantal. Institut National de la Recherche Agronomique; FranciaFil: da Silva, Sara H.. Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas; BrasilFil: Canário Viana, Marcus V.. Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas; BrasilFil: Caetano, Ana C. B.. Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas; BrasilFil: dos Santos, Roselane G.. Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas; BrasilFil: de Oliveira Carvalho, Rodrigo D.. Instituto de Ciencias Da Saúde; BrasilFil: Jardin, Julien. Institut National de la Recherche Agronomique; FranciaFil: Pereira, Felipe L.. Universidade Federal de Minas Gerais; BrasilFil: Folador, Edson L.. Universidade Estadual da Paraiba; BrasilFil: Le Loir, Yves. Institut National de la Recherche Agronomique; FranciaFil: Figueiredo, Henrique C. P.. Universidade Federal de Minas Gerais; BrasilFil: Jan, Gwénaël. Institut National de la Recherche Agronomique; FranciaFil: Azevedo, Vasco. Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas; Brasi

Runs of homozygosity in killer whale genomes provide a global record of demographic histories

Runs of homozygosity (ROH) occur when offspring inherit haplotypes that are identical by descent from each parent. Length distributions of ROH are informative about population history; specifically, the probability of inbreeding mediated by mating system and/or population demography. Here, we investigated whether variation in killer whale (Orcinus orca) demographic history is reflected in genome-wide heterozygosity and ROH length distributions, using a global data set of 26 genomes representative of geographic and ecotypic variation in this species, and two F1 admixed individuals with Pacific-Atlantic parentage. We first reconstructed demographic history for each population as changes in effective population size through time using the pairwise sequential Markovian coalescent (PSMC) method. We found a subset of populations declined in effective population size during the Late Pleistocene, while others had more stable demography. Genomes inferred to have undergone ancestral declines in effective population size, were autozygous at hundreds of short ROH (1.5 Mb) were found in low latitude populations, and populations of known conservation concern. These include a Scottish killer whale, for which 37.8% of the autosomes were comprised of ROH >1.5 Mb in length. The fate of this population, in which only two adult males have been sighted in the past five years, and zero fecundity over the last two decades, may be inextricably linked to its demographic history and consequential inbreeding depression

Quality of life, psychological morbidity and family stress in elderly residing in the community

Este estudo procurou investigar as relações existentes entre morbilidade psicológica, stress familiar e qualidade de vida (QV) da pessoa idosa. A amostra foi constituída por 126 idosos. Os instrumentos utilizados foram: The Lawton Instrumental Activities of Daily Living (IADL), Quality of Life (WHOQOL-Bref), Geriatric Anxiety Inventory (GSI), Geriatric Depression Scale (GDS); e Index of Family Relations (IFR). Os resultados revelaram a importância da idade, estado civil, escolaridade e número de patologias assim como o género na capacidade funcional, morbilidade, stress familiar e QV. Ao nível dos preditores, a depressão foi a variável que mais contribuiu para a QV. Não foram encontradas variáveis moderadoras no modelo. A discussão e implicações dos resultados são abordadas bem como a intervenção psicológica nesta população.This study sought to understand the relationships among psychological morbidity, family stress and quality of life (QL) of elderly. The sample consisted of 126 elderly. The following instruments were used: the Lawton Instrumental Activities of Daily Living (IADL); Quality of Life (WHOQOL-Bref), Geriatric Anxiety Inventory (GSI), Geriatric Depression Scale (GDS), and the Index of Family Relations (IFR). Results revealed the importance of age, marital status, education and number of pathologies as well as gender on functional capacity, morbidity, family stress and QV. In terms of predictors, depression was the variable that contributed the most to QL. There were no moderating variables in the model. Discussion and implications of results are addressed as well as psychological interventions.(undefined