Personal adornments in West‑Central Africa—the case study of a talc bead from the Kongo Kingdom (Mbanza Kongo, Angola)

A mustard-gold-colored talc bead was recovered during the 2014 excavation campaign carried out in Lumbu (Mbanza Kongo, Angola) together with the nineteenth-century glass trade beads imported from Bohemia and Venice. Results from this multianalytical and minimally invasive study suggest that this bead may have been brought to the kingdom’s capital by means of an established intra-kingdom trade network or as an offering intended for the king or a member of the nobility. However, it was undoubtedly manufactured within the Kongo kingdom using talc sources known by the local population. As such, this talc bead constitutes the first evidence of local production of personal adornment objects in the Kongo kingdom and one of the first examples of craft specialization for personal adornment purposes in central and southern Africa since pre-historic times

Two-way attack on IAPP proteotoxicity with implications for diabetes

Funding Information: This study was supported by FCT–Fundação para a Ciência e a Tecnologia (grants UIDB/04567/2020 and UIDP/ 04567/2020 to CBIOS, PTDC/BIA-MOL/31104/2017, and PhD grants PD/BD/135504/2018 to AFR and UI/BD/151421/2021 to SF. RM is funded by FCT Scientific Employment Stimulus contract with the reference number CEEC/04567/ CBIOS/2020. Authors also acknowledge COFAC/ILIND – Cooperativa De Formação e Animação Cultural CRL/Instituto Lusófono de Investigação e Desenvolvimento (grant COFAC/ILIND/CBIOS/2/2021). iNOVA4Health Research Unit (LISBOA-01-0145-FEDER-007344), which is cofunded by Fundação para a Ciência e Tecnologia (FCT) / Ministério da Ciência e do Ensino Superior, through national funds, and by FEDER under the PT2020 Partnership Agreement, is acknowledged (UIDB/04462/2020 and UIDP/04462/2020). CNS acknowledge the European Research Council (ERC) under the European Union’s Horizon 2020 Research and Innovation Programme under Grant Agreement No. 804229. JAB gratefully acknowledges FCT-Fundação para a Ciência e a Tecnologia, I.P. through MOSTMICRO-ITQB R&D Unit-UIDB/04612/2020 and LS4FUTURE Associated Laboratory-LA/P/0087/2020, and by the framework of Article 23 of Decree-Law No.57/2017 of August 29. Publisher Copyright: Copyright © 2022 Raimundo, Ferreira, Pobre, Lopes-da-Silva, Brito, dos Santos, Saraiva, dos Santos and Menezes.Introduction: Diabetes is one of the major metabolic diseases worldwide. Despite being a complex systemic pathology, the aggregation and deposition of Islet Amyloid Polypeptide (IAPP), or amylin, is a recognized histopathological marker of the disease. Although IAPP proteotoxicity represents an important trigger of β-cell dysfunction and ultimately death, its exploitation as a therapeutic tool remains underdeveloped. The bioactivity of (poly)phenols towards inhibition of pathological protein aggregation is well known, however, most of the identified molecules have limited bioavailability. Methods: Using a strategy combining in silico, cell-free and cell studies, we scrutinized a unique in-house collection of (poly)phenol metabolites predicted to appear in the human circulation after (poly)phenols ingestion. Results: We identified urolithin B as a potent inhibitor of IAPP aggregation and a powerful modulator of cell homeostasis pathways. Urolithin B was shown to affect IAPP aggregation pattern, delaying the formation of amyloid fibrils and altering their size and morphology. The molecular mechanisms underlying urolithin B-mediated protection include protein clearance pathways, mitochondrial function, and cell cycle ultimately rescuing IAPP-mediated cell dysfunction and death. Discussion: In brief, our study uncovered urolithin B as a novel small molecule targeting IAPP pathological aggregation with potential to be exploited as a therapeutic tool for mitigating cellular dysfunction in diabetes. Resulting from the colonic metabolism of dietary ellagic acid in the human body, urolithin B bioactivity has the potential to be explored in nutritional, nutraceutical, and pharmacological perspectives.publishersversionpublishe

Structure modeling hints at a granular organization of the Golgi ribbon

Funding Information: This work was funded by the Medical Research Council (grants MC_UU_12018/2 and MC_UU_00012/2 to D.F.C.) and by the British Heart Foundation (grant PG/14/76/31087 to D.F.C.). Publisher Copyright: © 2022, The Author(s).Background: In vertebrate cells, the Golgi functional subunits, mini-stacks, are linked into a tri-dimensional network. How this “ribbon” architecture relates to Golgi functions remains unclear. Are all connections between mini-stacks equal? Is the local structure of the ribbon of functional importance? These are difficult questions to address, without a quantifiable readout of the output of ribbon-embedded mini-stacks. Endothelial cells produce secretory granules, the Weibel-Palade bodies (WPB), whose von Willebrand Factor (VWF) cargo is central to hemostasis. The Golgi apparatus controls WPB size at both mini-stack and ribbon levels. Mini-stack dimensions delimit the size of VWF "boluses” whilst the ribbon architecture allows their linear co-packaging, thereby generating WPBs of different lengths. This Golgi/WPB size relationship suits mathematical analysis. Results: WPB lengths were quantized as multiples of the bolus size and mathematical modeling simulated the effects of different Golgi ribbon organizations on WPB size, to be compared with the ground truth of experimental data. An initial simple model, with the Golgi as a single long ribbon composed of linearly interlinked mini-stacks, was refined to a collection of mini-ribbons and then to a mixture of mini-stack dimers plus long ribbon segments. Complementing these models with cell culture experiments led to novel findings. Firstly, one-bolus sized WPBs are secreted faster than larger secretory granules. Secondly, microtubule depolymerization unlinks the Golgi into equal proportions of mini-stack monomers and dimers. Kinetics of binding/unbinding of mini-stack monomers underpinning the presence of stable dimers was then simulated. Assuming that stable mini-stack dimers and monomers persist within the ribbon resulted in a final model that predicts a “breathing” arrangement of the Golgi, where monomer and dimer mini-stacks within longer structures undergo continuous linking/unlinking, consistent with experimentally observed WPB size distributions. Conclusions: Hypothetical Golgi organizations were validated against a quantifiable secretory output. The best-fitting Golgi model, accounting for stable mini-stack dimers, is consistent with a highly dynamic ribbon structure, capable of rapid rearrangement. Our modeling exercise therefore predicts that at the fine-grained level the Golgi ribbon is more complex than generally thought. Future experiments will confirm whether such a ribbon organization is endothelial-specific or a general feature of vertebrate cells.publishersversionpublishe

One-year mortality after hemodialysis initiation: the prognostic role of the CHA2DS2-VASc Score

© 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).Background: CKD is a significant cause of morbidity, cardiovascular and all-cause mortality. CHA2DS2-VASc is a score used in patients with atrial fibrillation to predict thromboembolic risk; it also appears to be useful to predict mortality risk. The aim of the study was to evaluate CHA2DS2-VASc scores as a tool for predicting one-year mortality after hemodialysis is started and for identifying factors associated with higher mortality. Methods: Retrospective analysis of patients who started hemodialysis between January 2014 and December 2019 in Centro Hospitalar Universitário Lisboa Norte. We evaluated mortality within one year of hemodialysis initiation. The CHA2DS2-VASc score was calculated at the start of hemodialysis. Results: Of 856 patients analyzed, their mean age was 68.3 ± 15.5 years and the majority were male (61.1%) and Caucasian (84.5%). Mortality within one-year after starting hemodialysis was 17.8% (n = 152). The CHA2DS2-VASc score was significantly higher (4.4 ± 1.7 vs. 3.5 ± 1.8, p < 0.001) in patients who died and satisfactorily predicted the one-year risk of mortality (AUC 0.646, 95% CI 0.6-0.7, p < 0.001), with a sensitivity of 71.7%, a specificity of 49.1%, a positive predictive value of 23.9% and a negative predictive value of 89.2%. In the multivariate analysis, CHA2DS2-VASc ≥3.5 (adjusted HR 2.24 95% CI (1.48-3.37), p < 0.001) and central venous catheter at dialysis initiation (adjusted HR 3.06 95% CI (1.93-4.85)) were significant predictors of one-year mortality. Conclusion: A CHA2DS2-VASc score ≥3.5 and central venous catheter at hemodialysis initiation were predictors of one-year mortality, allowing for risk stratification in hemodialysis patients.info:eu-repo/semantics/publishedVersio

Structure modeling hints at a granular organization of the Golgi ribbon

Background In vertebrate cells, the Golgi functional subunits, mini-stacks, are linked into a tri-dimensional network. How this “ribbon” architecture relates to Golgi functions remains unclear. Are all connections between mini-stacks equal? Is the local structure of the ribbon of functional importance? These are difficult questions to address, without a quantifiable readout of the output of ribbon-embedded mini-stacks. Endothelial cells produce secretory granules, the Weibel-Palade bodies (WPB), whose von Willebrand Factor (VWF) cargo is central to hemostasis. The Golgi apparatus controls WPB size at both mini-stack and ribbon levels. Mini-stack dimensions delimit the size of VWF "boluses” whilst the ribbon architecture allows their linear co-packaging, thereby generating WPBs of different lengths. This Golgi/WPB size relationship suits mathematical analysis. Results WPB lengths were quantized as multiples of the bolus size and mathematical modeling simulated the effects of different Golgi ribbon organizations on WPB size, to be compared with the ground truth of experimental data. An initial simple model, with the Golgi as a single long ribbon composed of linearly interlinked mini-stacks, was refined to a collection of mini-ribbons and then to a mixture of mini-stack dimers plus long ribbon segments. Complementing these models with cell culture experiments led to novel findings. Firstly, one-bolus sized WPBs are secreted faster than larger secretory granules. Secondly, microtubule depolymerization unlinks the Golgi into equal proportions of mini-stack monomers and dimers. Kinetics of binding/unbinding of mini-stack monomers underpinning the presence of stable dimers was then simulated. Assuming that stable mini-stack dimers and monomers persist within the ribbon resulted in a final model that predicts a “breathing” arrangement of the Golgi, where monomer and dimer mini-stacks within longer structures undergo continuous linking/unlinking, consistent with experimentally observed WPB size distributions. Conclusions Hypothetical Golgi organizations were validated against a quantifiable secretory output. The best-fitting Golgi model, accounting for stable mini-stack dimers, is consistent with a highly dynamic ribbon structure, capable of rapid rearrangement. Our modeling exercise therefore predicts that at the fine-grained level the Golgi ribbon is more complex than generally thought. Future experiments will confirm whether such a ribbon organization is endothelial-specific or a general feature of vertebrate cells

A História da Alimentação: balizas historiográficas

Os M. pretenderam traçar um quadro da História da Alimentação, não como um novo ramo epistemológico da disciplina, mas como um campo em desenvolvimento de práticas e atividades especializadas, incluindo pesquisa, formação, publicações, associações, encontros acadêmicos, etc. Um breve relato das condições em que tal campo se assentou faz-se preceder de um panorama dos estudos de alimentação e temas correia tos, em geral, segundo cinco abardagens Ia biológica, a econômica, a social, a cultural e a filosófica!, assim como da identificação das contribuições mais relevantes da Antropologia, Arqueologia, Sociologia e Geografia. A fim de comentar a multiforme e volumosa bibliografia histórica, foi ela organizada segundo critérios morfológicos. A seguir, alguns tópicos importantes mereceram tratamento à parte: a fome, o alimento e o domínio religioso, as descobertas européias e a difusão mundial de alimentos, gosto e gastronomia. O artigo se encerra com um rápido balanço crítico da historiografia brasileira sobre o tema

Dissecting the molecular interaction between hepatocytes and Plasmodium liver parasites

Dissertation presented to obtain the Ph.D degree in BiologyMalaria is one of the world´s leading causes of death, responsible for over 700,000 deaths per year, the majority of which are African children under 5 years of age. Malaria disease is caused by the transmission of an Apicomplexa parasite, Plasmodium, through the bit of a female Anopheles mosquito, and transmitted parasites quickly reach the mammalian host liver, where the first round of replication begins. Plasmodium sporozoites, once inside the liver, must invade and survive within hepatocytes until the first replicative stage within the mammalian host is accomplished. Upon migration through various cells, sporozoites are able to actively enter hepatocytes, forming a Parasitophorous Vacuole Membrane (PVM) around itself. Once this intracellular niche is established, parasite replication and growth is initiated. Dramatic morphological as well as gene expression modifications occur at this stage, and the parasite achieves one of the highest replication rates known within eukaryotic species (Sinnis and Sim, 1997). Although the Plasmodium life-cycle has been extensively characterized, relatively little is known about sporozoite interaction with host organelles, vesicles and proteins. To address this issue, Plasmodium interactions with the host cell endomembranes was analyzed at various stages of liver infection using indirect immunofluorescence. Plasmodium parasites were seen closely associated with host endoplasmic reticulum (ER) and the Golgi apparatus. Surprisingly, late endosomes/lysosomes, observed with the membrane markers Rab7a, CD63 and LAMP1, aggregated around the parasite. No interaction with host peroxisomes, early and recycling endosomes was observed.(...)Financial support was provided by Fundação para a Ciência e Tecnologia. Portugal, through the Ph.D. fellowship grant SFRH/BD/27705/2006

ANALISIS KUALITAS PELAYANAN PEMBAYARAN GAJI PEGAWAI DI TIMOR LESTE

Service is the main task of the essence of the figure as a servant of the state apparatus and public servant. The scope of services and public services aspects of community life that is very broad. Service starts since someone is still in the womb until death. Broad scope of services and public services tend to be highly dependent on ideology and economic system of a country. Since the break-away Republic of Indonesia (NKRI) in September of 1999, Timor-Leste began to establish them and begin to build his government to catch up with other countries. One tangible manifestation of that done is to build financial institutions to turn the wheels of the economy in East Timor. With UNTAET Regulation No. 01 of 2000 concerning the establishment of the Central Fiscal Authority (CFA) and UNTAET Regulation No. 08 of 2000 concerning the establishment of the Central Payments Office (CPO), which aims to record the employees working in government and implement the payment of salaries in question. From year to year, the second function of this agency began developing in 2001 the Central Payments Office was renamed the Banking and Payments Authority (BPA), but the service system of payment of salaries of East Timor has not experienced a change to the present. The purpose of this research is to understand the situation that actually happened and to get a view of various problems that arise in the implementation of payroll services and to identify factors that affect the quality of payroll services in East Timor. Type of research is a descriptive qualitative research, because qualitative methods as research procedures which produce descriptive data in the form of words written or spoken of the people or the observed behavior. The analysis in this study carried out by processing the data whether it is primary data and secondary data to then be processed and interpreted descriptively. From the results of research conducted on BPA Timor-Leste can be concluded that service quality is still not good, this result is based on the indicators used by the authors to measure the quality that exists. Quality of service provided to service users do not meet the desires and expectations of service users which means the satisfaction of service users has not been achieved. In addition, coupled with the supporting factors such as technology tools those have not been fully utilized in accordance with its existence due to lack of expertise available human resources. Thus the authors suggest Banking and Payments Authority of East Timor to pay more attention to the functions and responsibilities as the Central Bank of East Timor, which began putting owned facilities and infrastructure in accordance with their respective authorities

Deacidification of endolysosomes by neuronal aging drives synapse loss

Funding Information: The authors thank the lab members for technical assistance, helpful discussions and for the critical reading of the manuscript. The authors thank Dr. S. Miserey‐Lenkei (Institute Curie), Dr. D. Barral, Dr. O. Vieira and Dr. S. Tenreiro (NOVA Medical School), for the gift of antibodies and reagents. The authors thank Dr. A. Marques, Dr. C. Escrevente, Dr. C. Perdigão and Dr. L. Lopes for helpful discussions. The authors thank L. Almeida for excel macros. The authors thank Dr. D. Barral (NOVA Medical School) and Dr. O. Vieira (NOVA Medical School) for the critical reading of the manuscript. The authors thank Dr. A. Farinho (NOVA Medical School Histology Facility), Dr. S. Marques (NOVA Medical School Animal Facility), Dr. T. Pereira (NOVA Medical School Microscopy Platform) and the Electron Microscopy Facility (Instituto Gulbenkian de Ciência). This project has received funding from the Marie Curie Integration Grant (PCIG‐GA‐2012‐334366‐trafficinAD; Marie Curie Actions, EC); iNOVA4Health—UID/Multi/04462/2019, a program financially supported by Fundação para a Ciência e Tecnologia (FCT)/Ministério da Educação e Ciência, through national funds and cofunded by FEDER under the PT2020 Partnership Agreement; Maratona da Saúde 2016; Investigator FCT (IF/00998/2012, FCT); CEECIND/00410/2017 financed by FCT; ALZ AARG‐19‐618007 Alzheimer's Association; from the research infrastructure PPBI‐POCI‐01‐0145‐FEDER‐022122, co‐financed by FCT (Portugal) and Lisboa2020, under the PORTUGAL2020 agreement (European Regional Development Fund); the European Union's Horizon 2020 Research and Innovation Program under Grant agreement no. 811087 (Lysocil). TB has been the recipient of an FCT doctoral fellowship (SFRH/BD/131513/2017). MLS was funded by FCT‐CEECIND/01536/2018. Publisher Copyright: © 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.Previously, we found that age-dependent accumulation of beta-amyloid is not sufficient to cause synaptic decline. Late-endocytic organelles (LEOs) may be driving synaptic decline as lysosomes (Lys) are a target of cellular aging and relevant for synapses. We found that LAMP1-positive LEOs increased in size and number and accumulated near synapses in aged neurons and brains. LEOs' distal accumulation might relate to the increased anterograde movement in aged neurons. Dissecting the LEOs, we found that late-endosomes accumulated while there are fewer terminal Lys in aged neurites, but not in the cell body. The most abundant LEOs were degradative Lys or endolysosomes (ELys), especially in neurites. ELys activity was reduced because of acidification defects, supported by the reduction in v-ATPase subunit V0a1 with aging. Increasing the acidification of aged ELys recovered degradation and reverted synaptic decline, while alkalinization or v-ATPase inhibition, mimicked age-dependent Lys and synapse dysfunction. We identify ELys deacidification as a neuronal mechanism of age-dependent synapse loss. Our findings suggest that future therapeutic strategies to address endolysosomal defects might be able to delay age-related synaptic decline.publishersversionpublishe