Abstract Hereditary Hemorrhagic Telangiectasia (HHT) is an autosomal dominant disorder characterized by skin and mucosal telangiectasias and visceral arteriovenous malformations (AVMs). We report a case of ischemic cholangiopathy in a 60-year-old female with HHT who initially presented with intermittent biliary colic and no significant medical history. The absence of typical HHT symptoms made imaging crucial for diagnosis. Abdominal ultrasound, CT, and MRI revealed hepatic artery dilatation, hepatic AVMs and bilomas. In this setting, the bilomas result from biliary ductal necrosis due to arterial shunting induced by AVMs. Although the patient initially presented without common HHT manifestations such as epistaxis, a subsequent reassessment during the physical exam identified mucocutaneous telangiectasias, and genetic testing later confirmed the diagnosis. This case highlights the importance of recognizing specific imaging features to diagnose and understand the implications of ischemic cholangiopathy, a rare but distinct phenotype in patients with HHT.

The quest for novel aqueous chemical strategies that allow chemo-, regio- and site-selective modifications of native biomolecules beought about major insights into basic biology and enabled the development of functional bioconjugates with unprecedented properties. The success of these bioconjugates is prominent in many applications of life science research allowing to precisely study molecular interactions relevant for the normal operation of biomolecules and uncovering their typical properties and functions within important biological processes. Besides this, chemoselective modifications made great contributions in the pharmaceutical field, opening several opportunities for the development of advanced targeted therapies. To deliver on these promises, bioconjugation strategies must allow easy access to well-defined constructs under biocompatible conditions that include low to room temperatures, mild stirring and aqueous buffered solvent at near physiological pH. Diverse Michael acceptors have been described to promote site-selective modifications on cysteine residues in peptides and native proteins giving great contributions to the design of novel advanced therapeutic and diagnostic tools. Herein, novel activated Michael acceptors have been extensively investigated for the selective modification o N-terminal cysteines either through ortho-boronic acid activation or N-Hydroxysuccinimide (NHS)-activation of acrylamides that enable a subsequent intramolecular amidation. In particular, NHS-activated acrylamides exhibited remarkable selectivity and versatility for amino-sulfhydryl stapling not only in N-terminal cysteines but also for the cross-linking of a cysteine to a nearby lysine residue under fine-tuned reaction conditions. The great control displayed by these reagents and the observed compatibility with other bioconjugation handles further allowed the dual site-selective functionalization of unprotected peptides. Finally, this approach was applied for the functionalization of bombesin peptide with a promising Ru(II) polypyridyl complex for targeted photodynamic therapy. As a targeting unit, bombesin conjugates are internalized in cells overexpressing gastrin releasing peptide receptors, that are commonly associated with diverse cancer types. The superior selectivity and high phototoxicity of the synthesized Ru(II) complex-bombesin conjugates are shown.

Este trabalho apresenta a distribuição de Trichoptera ao longo da Bacia do Rio Paranã, GO, com novos registros para gênero. Foram estabelecidas 18 estações de coleta ao longo da bacia durante as estações chuvosa (março e dezembro/2003) e seca (julho/2003 e agosto/ 2004). Foram utilizadas redes de bentos do tipo Surber e " D" , para a coleta dos organismos nos diversos ambientes.

Illegal hunting and trade threaten the high biodiversity of Guinea-Bissau (GB) in West Africa, particularly for nonhuman primates (NHP). Primate carcasses are sold at bushmeat markets and at restaurants and the primate pet trade is active. Traditional medicine practitioners also use NHP body-parts further promoting the commerce of NHP skins. A better understanding of hunting and related trade activities, including the profile of hunters and their motivations, would improve NHP conservation in GB. However, information on commercial hunting is incomplete due to a general unwillingness to describe illegal activities by the local communities. Here, we investigated aspects of hunting practice and related commercial activities targeting NHP in GB by collecting qualitative ethnographic information using semi-structured interviews. Participants were asked about hunted species, techniques and hunting locations, their motivations to hunt wild NHP, uses of carcasses, and their perceptions on the demographic trajectory of hunted species. Eight participants in the study listed species hunted in GB, which included a total of seven NHP. Hunting areas described were spread across southern GB and included locations within the limits of national protected areas and formalized ecological corridors. Participants mentioned the trade in NHP meat at bushmeat restaurants as the primary motivation for primate-targeted hunting, with the exception of western chimpanzees, which are specifically targeted for the exotic pet trade. Several strategies are used in hunting NHP, including traps, firearms, and hunting dogs. The majority of hunted NHP were perceived as having declined in population size during recent decades. Episodes when military groups hunted NHP intensively using more sophisticated weapons and methods in the 1980s were also described. This study highlights how hunting and related activities are complex and multi-dimensional and illustrates the use of ethnographic methods to improve knowledge about illegal and concealed practices impacting NHP conservation. Our results suggest an urgent need to raise awareness of local communities and subsistence hunters living within protected areas about the environmental and social impacts of hunting.

Resumo O manejo inadequado da irrigação e a drenagem deficiente dos solos são considerados as principais causas de salinização das áreas irrigadas no Nordeste brasileiro. O presente estudo objetivou avaliar o efeito de duas fontes de água (poço raso e Rio Jaguaribe) e três lâminas de irrigação (W) correspondentes a 0,75, 1,00 e 1,25 da necessidade hídrica da cultura, sobre a evolução da salinidade no solo e o desenvolvimento e a nutrição mineral da bananeira cv. Pacovan. O experimento foi conduzido durante dois ciclos da cultura, em solo Neossolo Flúvico Eutrófico, em blocos casualizados, em arranjo fatorial 3 x 2, com quatro repetições e 24 unidades experimentais em uma área de 3600 m2. As diferentes lâminas de água aplicadas não influenciaram o desenvolvimento da bananeira cv. Pacovan nem se observou qualquer interação entre lâmina de irrigação e qualidade da água sobre as variáveis avaliadas. A maior salinidade da água do poço não afetou as variáveis de crescimento vegetativo avaliadas, nem a nutrição mineral das plantas, porém reduziu, significativamente, o número de pencas por cacho e o peso médio dos cachos, no 2º ciclo da cultura.

The understanding of acclimation strategies to low temperature and water availability is decisive to ensure coffee crop sustainability, since these environmental conditions determine the suitability of cultivation areas. In this context, the impacts of single and combined exposure to drought and cold were evaluated in three genotypes of the two major cropped species, Coffea arabica cv. Icatu, Coffea canephora cv. Apoatã, and the hybrid Obatã. Crucial traits of plant resilience to environmental stresses have been examined: photosynthesis, lipoperoxidation and the antioxidant response. Drought and/or cold promoted leaf dehydration, which was accompanied by stomatal and mesophyll limitations that impaired leaf C-assimilation in all genotypes. However, Icatu showed a lower impact upon stress exposure and a faster and complete photosynthetic recovery. Although lipoperoxidation was increased by drought (Icatu) and cold (all genotypes), it was greatly reduced by stress interaction, especially in Icatu. In fact, although the antioxidative system was reinforced under single drought and cold exposure (e.g., activity of enzymes as Cu,Zn-superoxide dismutase, ascorbate peroxidase, APX, glutathione reductase and catalase, CAT), the stronger increases were observed upon the simultaneous exposure to both stresses, which was accompanied with a transcriptional response of some genes, namely related to APX. Complementary, non-enzyme antioxidant molecules were promoted mostly by cold and the stress interaction, including α-tocopherol (in C. arabica plants), ascorbate (ASC), zeaxanthin, and phenolic compounds (all genotypes). In general, drought promoted antioxidant enzymes activity, whereas cold enhanced the synthesis of both enzyme and non-enzyme antioxidants, the latter likely related to a higher need of antioxidative capability when enzyme reactions were probably quite repressed by low temperature. Icatu showed the wider antioxidative capability, with the triggering of all studied antioxidative molecules by drought (except CAT), cold, and, particularly, stress interaction (except ASC), revealing a clear stress cross-tolerance. This justified the lower impacts on membrane lipoperoxidation and photosynthetic capacity under stress interaction conditions, related to a better ROS control. These findings are also relevant to coffee water management, showing that watering in the cold season should be largely avoided

Climate changes with global warming associated with rising atmospheric [CO2] can strongly impact crop performance, including coffee, which is one of the most world’s traded agricultural commodities. Therefore, it is of utmost importance to understand the mechanisms of heat tolerance and the potential role of elevated air CO2 (eCO2) in the coffee plant response, particularly regarding the antioxidant and other protective mechanisms, which are crucial for coffee plant acclimation. For that, plants of Coffea arabica cv. Geisha 3, cv. Marsellesa and their hybrid (Geisha 3 Marsellesa) were grown for 2 years at 25/20 C (day/night), under 400 (ambient CO2, aCO2) or 700 L (elevated CO2, eCO2) CO2 L-1, and then gradually submitted to a temperature increase up to 42/30 C, followed by recovery periods of 4 (Rec4) and 14 days (Rec14). Heat (37/28 C and/or 42/30 C) was the major driver of the response of the studied protective molecules and associated genes in all genotypes. That was the case for carotenoids (mostly neoxanthin and lutein), but the maximal (a + b) carotenes pool was found at 37/28 C only in Marsellesa. All genes (except VDE) encoding for antioxidative enzymes (catalase, CAT; superoxide dismutases, CuSODs; ascorbate peroxidases, APX) or other protective proteins (HSP70, ELIP, Chape20, Chape60) were strongly upregulated at 37/28 C, and, especially, at 42/30 C, in all genotypes, but with maximal transcription in Hybrid plants. Accordingly, heat greatly stimulated the activity of APX and CAT (all genotypes) and glutathione reductase (Geisha3, Hybrid) but not of SOD. Notably, CAT activity increased even at 42/30 C, concomitantly with a strongly declined APX activity. Therefore, increased thermotolerance might arise through the reinforcement of some ROS-scavenging enzymes and other protective molecules (HSP70, ELIP, Chape20, Chape60). Plants showed low responsiveness to single eCO2 under unstressed conditions, while heat promoted changes in aCO2 plants. Only eCO2 Marsellesa plants showed greater contents of lutein, the pool of the xanthophyll cycle components (V + A + Z), and b-carotene, compared to aCO2 plants at 42/30 C. This, together with a lower CAT activity, suggests a lower presence of H2O2, likely also associated with the higher photochemical use of energy under eCO2. An incomplete heat stress recovery seemed evident, especially in aCO2 plants, as judged by the maintenance of the greater expression of all genes in all genotypes and increased levels of zeaxanthin (Marsellesa and Hybrid) relative to their initial controls. Altogether, heat was the main response driver of the addressed protective molecules and genes, whereas eCO2 usually attenuated the heat response and promoted a better recovery. Hybrid plants showed stronger gene expression responses, especially at the highest temperature, when compared to their parental genotypes, but altogether, Marsellesa showed a greater acclimation potential. The reinforcement of antioxidative and other protective molecules are, therefore, useful biomarkers to be included in breeding and selection programs to obtain coffee genotypes to thrive under global warming conditions, thus contributing to improved crop sustainability

The application of the Comet assay in environmental monitoring remains challenging in face of the complexity of environmental stressors, e.g., when dealing with estuarine sediments, that hampers the drawing of cause-effect relationships. Although the in vitro Comet assay may circumvent confounding factors, its application in environmental risk assessment (ERA) still needs validation. As such, the present work aims at integrating genotoxicity and oxidative DNA damage induced by sediment-bound toxicants in HepG2 cells with oxidative stress-related effects observed in three species collected from an impacted estuary. Distinct patterns were observed in cells exposed to crude mixtures of sediment contaminants from the urban/industrial area comparatively to the ones from the rural/riverine area of the estuary, with respect to oxidative DNA damage and oxidative DNA damage. The extracts obtained with the most polar solvent and the crude extracts caused the most significant oxidative DNA damage in HepG2 cells, as measured by the formamidopyrimidine-DNA glycosylase (FPG)-modified Comet assay. This observation suggests that metals and unknown toxicants more hydrophilic than polycyclic aromatic hydrocarbons may be important causative agents, especially in samples from the rural part of the estuary, where oxidative DNA damage was the most significant. Clams, sole, and cuttlefish responded differentially to environmental agents triggering oxidative stress, albeit yielding results accordant with the oxidative DNA damage observed in HepG2 cells. Overall, the integration of in vivo biomarker responses and Comet assay data in HepG2 cells yielded a comparable pattern, indicating that the in vitro FPG-modified Comet assay may be an effective and complementary line-of-evidence in ERA even in particularly challenging, natural, scenarios such as estuarine environments.

Modelingstudieshavepredictedthatcoffeecropwillbeendangeredbyfutureglobalwarming,butrecentreportshighlightedthathigh[CO2]canmitigateheatimpactsoncoffee.ThisworkaimedatidentifyingheatprotectivemechanismspromotedbyCO2inCoffeaarabica(cv.IcatuandIPR108)andCoffeacanephoracv.ConilonCL153.Plantsweregrownat25/20◦C(day/night),under380or700μLCO−2L1,andthengraduallysubmittedto31/25,37/30,and42/34◦C.Relevantheattoleranceupto37/30◦Cforboth[CO2]andallcoffeegenotypeswasobserved,likelysupportedbythemaintenanceorincreaseofthepoolsofseveralprotectivemolecules(neoxanthin,lutein,carotenes,a-tocopherol,HSP70,raffinose),activitiesofantioxidantenzymes,suchassuperoxidedismutase(SOD),ascorbateperoxidase(APX),glutathionereductase(GR),catalase(CAT),andtheupregulatedexpressionofsomegenes(ELIP,Chaperonin20).However,at42/34◦Catolerancethresholdwasreached,mostlyinthe380-plantsandIcatu.Adjustmentsinraffinose,lutein,b-carotene,a-tocopherolandHSP70pools,andtheupregulatedexpressionofgenesrelatedtoprotective(ELIPS,HSP70,Chape20,and60)andantioxidant(CAT,CuSOD2,APXCyt,APXChl)proteinswerelargelydrivenbytemperature.However,enhanced[CO2]maintainedhigheractivitiesofGR(Icatu)andCAT(IcatuandIPR108),kept(orevenincreased)theCu,Zn-SOD,APX,andCATactivities,andpromotedagreaterupregulationofthoseenzymegenes,aswellasthoserelatedtoHSP70,ELIPs,ChaperoninsinCL153,andIcatu.Thesechangeslikelyfavoredthemaintenanceofreactiveoxygenspecies(ROS)atcontrolledlevelsandcontributedtomitigateofphotosystemIIphotoinhibitionatthehighesttemperature.Overall,ourresultshighlightedtheimportantroleofenhanced[CO2]onthecoffeecropacclimationandsustainabilityunderpredictedfutureglobalwarmingscenarios

Under the influence of multiple anthropogenic pressures, from industrial to agricultural activities, estuaries have long been regarded as particularly sensitive ecosystems to contamination. The present study aimed at investigating the genotoxic potential of a contaminated sediment sample from an urban and industrial area of the Sado Estuary, by combining the analysis of multiple endpoints in the LacZ plasmid-based transgenic mouse model exposed for 28 days to contaminated estuarine sediment extracts through drinking water. The DNA and chromosome damaging effects were monitored in peripheral blood at 7-day intervals using the standard and enzyme-modified Comet assay, as well as the micronucleus assays in peripheral blood cells. After euthanasia, DNA damage was analyzed in several mouse tissues, and LacZ mutant frequencies were determined in the liver. Livers were also surveyed for histopathological analysis. A time-dependent increase in micronuclei frequency was seen at all tested doses, in spite of no induction of DNA damage in any organ or mutation induction in the liver of exposed mice. The liver from mice exposed to sediment extracts did not reveal major alterations besides evidence of inflammation. Overall, the integration of the endpoints analyzed in the mice is suggestive of potential chronic, rather than acute, adverse effects in vivo, and points to the need for further research in the resident human population in the area. This experimental design can be used to assess the genotoxicity of complex environmental mixtures, understand how they work, and reduce costs and resources while speeding up data collection and interpretation.