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The emergence of SARS-CoV-2 in 2019 and its rapid spread throughout the world has caused the largest pandemic of our modern era. The zoonotic origin of this pathogen highlights the importance of the One Health concept and the need for a coordinated response to this kind of threats. Since its emergence, the virus has caused >7 million deaths worldwide. However, the animal source for human outbreaks remains unknown. The ability of the virus to jump between hosts is facilitated by the presence of the virus receptor, the highly conserved angiotensin-converting enzyme 2 (ACE2), found in various mammals. Positivity for SARS-CoV-2 has been reported in various species, including domestic animals and livestock, but their potential role in bridging viral transmission to humans is still unknown. Additionally, the virus has evolved over the pandemic, resulting in variants with different impacts on human health. Therefore, suitable animal models are crucial to evaluate the susceptibility of different mammalian species to this pathogen and the adaptability of different variants. In this work, we established a transgenic mouse model that expresses the feline ACE2 protein receptor (cACE2) under the human cytokeratin 18 (K18) gene promoter's control, enabling high expression in epithelial cells, which the virus targets. Using this model, we assessed the susceptibility, pathogenicity, and transmission of SARS-CoV-2 variants. Our results show that the sole expression of the cACE2 receptor in these mice makes them susceptible to SARS-CoV-2 variants from the initial pandemic wave but does not enhance susceptibility to omicron variants. Furthermore, we demonstrated efficient contact transmission of SARS-CoV-2 between transgenic mice that express either the feline or the human ACE2 receptor.

ackground: Allergy to kiwi fruit is being increasingly reported, but it has never been evaluated by means of a double-blind, placebo-controlled food challenge (DBPCFC) study. Objective: We sought to assess kiwi allergy on the basis of a DBPCFC and identify the patterns of allergen recognition in sensitized patients from a birch-free area. Methods: Forty-three patients with allergy symptoms who were sensitized to kiwi were evaluated by means of clinical history, skin tests, IgE determinations, and DBPCFCs. The pattern of allergen recognition was assessed by means of IgE immunoblotting. Sequence analysis of IgE-binding bands was performed by using Edman degradation. Results: DBPCFCs were performed in 33 patients; 4 patients had experienced severe anaphylaxis, and 6 patients declined informed consent. DBPCFC results were positive in 23 patients and negative in 10 patients. The most frequent clinical manifestation was oral allergy syndrome. Twenty-one percent of the patients were not allergic to pollen. Forty-six percent of patients experienced systemic symptoms, and this happened with higher frequency in patients not allergic to pollen (100%). Twenty-eight percent of the patients were sensitized to latex. The IgE-binding bands in kiwi extract more frequently recognized by patient sera were those of 30, 24, 66, and 12 kd, and they could not be associated with any pattern of kiwi-induced allergic reactions. Conclusion: The results provide evidence that kiwi allergy is not a homogeneous disorder because several clinical subgroups can be established. No definite allergen-recognition pattern was associated with the type of allergic reactions to kiwi. One of 5 patients with kiwi allergy was not allergic to pollen, and these patients had the highest risk of systemic reactions to kiwi., Depto. de Bioquímica y Biología Molecular, Fac. de Ciencias Químicas, TRUE, pub

The covalent binding of C3 (complement component C3) to antigen-antibody complexes (Ag.Ab; immune complexes (ICs)) is a key event in the uptake, transport, presentation, and elimination of Ag in the form of Ag.Ab.C3b (IC.C3b). Upon interaction of C3 with IgG.IC, C3b.C3b.IgG covalent complexes are formed that are detected on SDS-polyacrylamide gel electrophoresis by two bands corresponding to C3b.C3b (band A) and C3b.IgG (band B) covalent complexes. This allows one to evaluate the covalent binding of C3b to IgG antibodies. It has been described that C3b can attach to both the Fab (on the CH1 domain) and the Fc regions of IgG. Here the covalent interaction of C3b to the CH1 domain, a region previously described spanning residues 125-147, has been studied. This region of the CH1 domain is exposed to solvent and contains a cluster of six potential acceptor sites for ester bond formation with C3b (four Ser and two Thr). A set of 10 mutant Abs were generated with the putative acceptor residues substituted by Ala, and we studied their covalent interaction with C3b. Single (Ser-131, Ser-132, Ser-134, Thr-135, Ser-136, and Thr-139), double (positions 131-132), and multiple (positions 134-135-136, 131-132-134-135-136, and 131-132-134-135-136-139) mutants were produced. None of the mutants (single, double, or multiple) abolished completely the ability of IgG to bind C3b, indicating the presence of C3b binding regions other than in the CH1 domain. However, all mutant Abs, in which serine at position 132 was replaced by Ala, showed a significant decrease in the ability to form C3b.IgG covalent complexes, whereas the remaining mutants had normal activity. In addition we examined ICs using the F(ab')2 fragment of the mutant Abs, and only those containing Ala at position 132 (instead of Ser) failed to bind C3b. Thus Ser-132 is the binding site for C3b on the CH1 domain of the heavy chain, in the Fab region of human IgG., Depto. de Bioquímica y Biología Molecular, Fac. de Ciencias Químicas, TRUE, pub

Zika virus (ZIKV) is a mosquito-borne flavivirus that was first identified in Uganda in 1947, then was essentially neglected for six decades. However, in 2007, a ZIKV outbreak emerged in the Western Pacific Ocean, and between 2013 and 2014, a larger outbreak spread in the South Pacific, reaching South America in 2015 [1]. In 2016, the World Health Organization (WHO) declared a Public Health Emergency of International Concern. Even though the virus is transmitted by mosquitoes, mainly of the genus Aedes (Stegomyia), other transmission routes have been reported: between sexual partners and from mother to fetus, as well as via the transfusion of blood and blood products [2].

West Nile virus (WNV) is a neurotropic flavivirus transmitted by the bites of infected Culex sp mosquitoes and it is widely distributed across Europe. Severe forms of West Nile disease (WND) can cause meningitis, encephalitis or even death. In 2020, WNV caused an outbreak in southwest Spain that ended up with 70 human infections and 7 deaths. There are no vaccines or specific drugs to prevent and treat the symptoms of WND in humans, so the search for novel targets for therapeutic interventions is mandatory. Lipid metabolism is gaining interest as a potential target to combat flavivirus using a host-targeted approach.

Background Viral rewiring of host bioenergetics and immunometabolism may provide novel targets for therapeu‑ tic interventions against viral infections. Here, we have explored the effect on bioenergetics during the infection with the mosquito‑borne flavivirus West Nile virus (WNV), a medically relevant neurotropic pathogen causing out‑ breaks of meningitis and encephalitis worldwide. Results A systematic literature search and meta‑analysis pointed to a misbalance of glucose homeostasis in the cen‑ tral nervous system of WNV patients. Real‑time bioenergetic analyses confirmed upregulation of aerobic glycolysis and a reduction of mitochondrial oxidative phosphorylation during viral replication in cultured cells. Transcriptom‑ ics analyses in neural tissues from experimentally infected mice unveiled a glycolytic shift including the upregula‑ tion of hexokinases 2 and 3 (Hk2 and Hk3) and pyruvate dehydrogenase kinase 4 (Pdk4). Treatment of infected mice with the Hk inhibitor, 2‑deoxy‑D‑glucose, or the Pdk4 inhibitor, dichloroacetate, alleviated WNV‑induced neuroinflammation. Conclusions These results highlight the importance of host energetic metabolism and specifically glycolysis in WNV infection in vivo. This study provides proof of concept for the druggability of the glycolytic pathway for the future development of therapies to combat WNV pathology.

West Nile virus (WNV) is a neurotropic flavivirus transmitted by the bites of infected mosquitoes. Severe forms of West Nile disease (WND) can curse with meningitis, encephalitis or acute flaccid paralysis. A better understanding of the physiopathology associated with disease progression is mandatory to find biomarkers and effective therapies. In this scenario, blood derivatives (plasma and serum) constitute the more commonly used biofluids due to its ease of collection and high value for diagnostic purposes. Therefore, the potential impact of this virus in the circulating lipidome was addressed combining the analysis of samples from experimentally infected mice and naturally WND patients. Our results unveil dynamic alterations in the lipidome that define specific metabolic fingerprints of different infection stages. Concomitant with neuroinvasion in mice, the lipid landscape was dominated by a metabolic reprograming that resulted in significant elevations of circulating sphingolipids (ceramides, dihydroceramides, and dihydrosphingomyelins), phosphatidylethanolamines and triacylglycerols. Remarkably, patients suffering from WND also displayed an elevation of ceramides, dihydroceramides, lactosylceramides, and monoacylglycerols in their sera. The dysregulation of sphingolipid metabolism by WNV may provide new therapeutic opportunities and supports the potential of certain lipids as novel peripheral biomarkers of WND progression.

Deltas and estuaries are formed through periods of marine transgression and regression, which are the continuity of a river and provide key information about its evolution. However, many of the world's deltas are increasingly exposed to the impacts of human activities. While changes affecting the subaerial parts of deltas have been intensively studied, much less is known of their subaqueous parts, the understanding of which is important in gauging overall potential delta vulnerability. This research evaluates the bathymetric changes in the submerged delta of the Turia river (Western Mediterranean, Spain) before and after the extreme flood event of 1957, after which the riverbed was diverted. Three nautical charts were processed (1878, 1988 and 2022), including georeferencing and Digital Elevation Model (DEM) generation. In order to evaluate changes before and after the event, models for 1878–1988 and 1988–2022 were compared and differences were quantified in order to assess erosion and aggradation trends. The results indicate a more aggradated submerged delta in the surroundings of the old river mouth, favored by the high sediment availability since the end of the Little Ice Age (LIA), and the presence of a smaller delta next to its current river mouth to the south of the harbor of Valencia. Bathymetric reconstructions also made it possible to map some incisions in the inner continental shelf as river channels that migrated eastwards when the sea level was lower during MIS 2. Finally, the comparison of bathymetric models also revealed the scarcity of sediments on the current shelf since 1988, which is attributed to anthropogenic action. The successive extensions of the harbor are increasingly distorting the distribution of sediments along the coast and are thus remodeling seabed sediment distribution. Knowing the sedimentation in deltaic systems means better predicting future alterations due to increased anthropization and of the climate change.

Zika virus (ZIKV) is a mosquito-borne flavivirus whose infection in pregnant women is associated with a spectrum of birth defects, which are together referred as Congenital Zika Syndrome. In addition, ZIKV can also induce Guillain–Barré syndrome, which is an autoimmune disease with neurological symptoms. The recent description of the first local infections of ZIKV in the European continent together with the expansion of one of its potential vectors, the Asian tiger mosquito (Aedes albopictus), invite us to be prepared for future outbreaks of ZIKV in this geographical region. However, the antigenic similarities of ZIKV with other flaviviruses can lead to an immune cross-reactivity with other circulating flaviviruses inducing, in some cases, flavivirus-disease exacerbation by antibody-dependent enhancement (ADE) of infection, which is a major concern for ZIKV vaccine development. Until now, West Nile virus (WNV) is the main medically relevant flavivirus circulating in the Mediterranean Basin. Therefore, anticipating the potential scenario of emergency vaccination against ZIKV in areas of Europe where WNV is endemic, in this investigation, we have evaluated the cross-reactivity between WNV and our previously developed ZIKV vaccine candidate based on modified vaccinia virus Ankara (MVA) vector expressing ZIKV structural proteins (MVA-ZIKV). To this end, mice were first immunized with MVA-ZIKV, subsequently challenged with WNV, and then, the ZIKV- and WNV-specific immune responses and protection against WNV were evaluated. Our results indicate low cross-reactivity between the MVA-ZIKV vaccine candidate and WNV and absence of ADE, supporting the safety of this ZIKV vaccine candidate in areas where the circulation of WNV is endemic.

In this paper, we conduct a palynological analysis of a high-resolution Holocene record from Cartagena Bay, southeast of the Iberian Peninsula, to establish paleoenvironmental variability of coastal areas in the western Mediterranean region at a centennial-scale over the last 7300 years. Statistical analysis of four palynozones allows reconstruction of paleotemperature and paleohumidity conditions. Pinus, steppic, xerophilous, and Mediterranean taxa persisted continuously through the record, and only during periods of increased humidity did deciduous and Mediterranean taxa expand (Zones II, subzone IIIb). Cooler and dry conditions favored the development of Cupressaceae and scrubs between 7300 and 7000 yr cal BP. The mid-Holocene (Northgrippian) mesophytic optimum took place between 6800 and 4000 yr cal BP during which time a Mediterranean climate was present and open forest developed, predominantly consisting of Mediterranean taxa and deciduous trees. The gradual rise in aridity in the Meghalayan (4000–1700 yr cal BP) led to Mediterranean forest being replaced by steppic and xerophilous vegetation, a change related mostly to a decrease in summer insolation, with superimposed centennial-scale variability in humidity. In parallel with forest degradation caused by increasing aridity, the record shows marked evidence of human influence since 4000 yr cal BP, which accelerated the progression of open landscapes from the Chalcolithic onwards, this change being especially marked during the Roman period. Significant denudation of the landscape can be attributed to the use of fire, as well as due to agriculture and grazing, with a major contributor being intense metallurgical and mining activity in the area. The Cartagena Bay record reported herein shows centennial-scale oscillations in humidity and temperature that correlate with well-known climatic events during the late Holocene in the western Mediterranean region, synchronous with variability in solar and atmospheric dyn

Sedimentological, paleobiological, mineralogical, and geochemical analyses of a sediment core retrieved on the seafront of Cartagena Bay were performed after high-resolution sampling. A wide series of dates obtained through radiocarbon and amino acid racemization proved that the Holocene record on the analyzed core began at ca. 7300 yr cal BP. Reinterpretation of the marine seismic profiles indicated that the beginning of this transgression was channeled along erosive paleochannels excavated on a coastal plain of, at least, MIS5c age. The Holocene paleoenvironmental evolution consisted of a first period marked by marine conditions with strong inputs from a fan delta linked to the reorganized fluvial network that occurred after the sudden rise of the base level, which caused a growing sedimentary prism. Later, the full marine environment was reflected in the development of a Posidonia-Cymodocea meadow hosting a rich biodiversity of marine species (mollusks, foraminifera, ostracoda). Around 3800 yr cal BP, the area underwent a profound change and a silting process started to alter the conditions, turning the area into a paucispecific brackish marsh environment in which mud deposition was dominant. Since Carthaginian times, arrangement works locally affected the record, allowing the arrival of some marine species due to port work (dredging) undertaken to gain depth and showing anthropic influence.

We reconstructed the palaeoenvironmental conditions of Cartagena Bay during the Holocene after a multidisciplinary study to identify natural variations and the anthropic processes of this coastal area. A total of 119 samples were recovered for amino acid racemization dating, 3 for radiocarbon dating (14C), and four sets of 80 samples for sedimentological and palaeontological determination, mineralogical content, biomarker and trace elements quantification. Two natural scenarios were identified from the variations of n-alkane indices and palaeobiological content. The first period (6650-5750 yr cal BP) was marked by the development of euhaline marine conditions with strong inputs from aquatic macrophytes and high biodiversity. After a hiatus, the area underwent a profound change, becoming a paucispecific brackish marsh environment with increasing inputs from land plants, with possible episodes of emersion with a greater presence from terrestrial gastropods (3600-300 cal yr BP). By combining trace element abundance and stanol distributions, our study also provides a novel approach to identify the predominant influence of anthropogenic factors in the last three millennia in the coastal record of Cartagena Bay. Findings confirmed that Pb mining and metallurgy began during the Bronze Age, with considerable inputs of this heavy metal into the atmosphere during Phoenician, Punic and particularly Roman times compared to the Middle Ages. Pollution by Cu and Zn was also observed during Punic and Roman times, and was first documented in the Middle Ages. In addition, faecal stanols, such as coprostanol, derived mainly from humans, and 24-ethylcoprostanol from herbivores were present, thereby indicating for the first time a continuous presence of human populations and significant pollution input since 3600 yr cal BP, this being greater in the late Bronze Age and Phoenician, Punic and Roman times than during Late Antiquity and the Middle Ages, when the city was in decline.

Zika virus (ZIKV) is a mosquito-borne flavivirus whose infection in pregnant women is associated with a spectrum of birth defects, which are together referred as Congenital Zika Syndrome. In addition, ZIKV can also induce Guillain-Barré syndrome, which is an autoimmune disease with neurological symptoms. The recent description of the first local infections of ZIKV in the European continent together with the expansion of one of its potential vectors, the Asian tiger mosquito (Aedes albopictus), invite us to be prepared for future outbreaks of ZIKV in this geographical region. However, the antigenic similarities of ZIKV with other flaviviruses can lead to an immune cross-reactivity with other circulating flaviviruses inducing, in some cases, flavivirus-disease exacerbation by antibody-dependent enhancement (ADE) of infection, which is a major concern for ZIKV vaccine development. Until now, West Nile virus (WNV) is the main medically relevant flavivirus circulating in the Mediterranean Basin. Therefore, anticipating the potential scenario of emergency vaccination against ZIKV in areas of Europe where WNV is endemic, in this investigation, we have evaluated the cross-reactivity between WNV and our previously developed ZIKV vaccine candidate based on modified vaccinia virus Ankara (MVA) vector expressing ZIKV structural proteins (MVA-ZIKV). To this end, mice were first immunized with MVA-ZIKV, subsequently challenged with WNV, and then, the ZIKV- and WNV-specific immune responses and protection against WNV were evaluated. Our results indicate low cross-reactivity between the MVA-ZIKV vaccine candidate and WNV and absence of ADE, supporting the safety of this ZIKV vaccine candidate in areas where the circulation of WNV is endemic.