Cruise Report PASSAGE23

[EN]Cruise PASSAGE23 started on the 17th of November from Cádiz Port (Spain) and ended on the 23rd of November at Cádiz Port. The cruise took place aboard the R/V Ramón Margalef. During the cruise, two mooring lines were deployed on the southwestern Portuguese margin (Fig. 1). Each mooring line was equipped with two sediment traps and three different types of hydrographic sensors to measure turbidity, current speed, temperature, and salinity. The mooring lines were deployed at 2625 and 1515 meters water depth (mwd) using train wheels as anchors. CTD profiles and seawater samples were collected at 21 stations along the southwestern Iberian margin with a 12-bottle rosette. Sea water was filtered with a filtration ramp at selected water depths on cellulose filters for ecological studies and on glass fiber filters for carbon cycle studies. Surface sediment samples were collected whenever possible by two types of corers: a brand-new monocorer from Unidad de Tecnología Marina (UTM-CSIC) that descends attached to the rosette and a small box-corer loaned by the Instituto Español de Oceanografía (IEO). Monocorer and boxcorer tubes were sampled aboard at 1-cm intervals using a handcrafted core extruder

Thermolytic CpG-containing DNA oligonucleotides as potential immunotherapeutic prodrugs

A CpG-containing DNA oligonucleotide functionalized with the 2-(N-formyl-N-methyl)aminoethyl thiophosphate protecting group (CpG ODN fma1555) was prepared from phosphoramidites 1a–d using solid-phase techniques. The oligonucleotide behaved as a prodrug by virtue of its conversion to the well-studied immunomodulatory CpG ODN 1555 through thermolytic cleavage of the 2-(N-formyl-N-methyl)aminoethyl thiophosphate protecting group. Such a conversion occurred at 37°C with a half-time of 73 h. The immunostimulatory properties of CpG ODN fma1555 were evaluated in two in vivo assays, one of which consisted of mice challenged in the ear with live Leishmania major metacyclic promastigotes. Local intradermal administration of CpG ODN fma1555 was as effective as that of CpG ODN 1555 in reducing the size of Leishmania lesions over time. In a different infectious model, CpG ODN 1555 prevented the death of Tacaribe-infected mice (43% survival) when administered between day 0 and 3 post infection. Administration of CpG ODN fma1555 three days before infection resulted in improved immunoprotection (60–70% survival). Moreover, co-administration of CpG ODN fma1555 and CpG ODN 1555 in this model increased the window for therapeutic treatment against Tacaribe virus infection, and thus supports the use of thermolytic oligonucleotides as prodrugs in the effective treatment of infectious diseases

Radiocarbon Age Offsets Between Two Surface Dwelling Planktonic Foraminifera Species During Abrupt Climate Events in the SW Iberian Margin

[EN]This study identifies temporal biases in the radiocarbon ages of the planktonic foraminifera species Globigerina bulloides and Globigerinoides ruber (white) in a sediment core from the SW Iberian margin (so‐called Shackleton site). Leaching of the outer shell and measurement of the radiocarbon content of both the leachate and leached sample enabled us to identify surface contamination of the tests and its impact on their 14C ages. Incorporation of younger radiocarbon on the outer shell affected both species and had a larger impact downcore. Interspecies comparison of the 14C ages of the leached samples reveal systematic offsets with 14C ages for G. ruber being younger than G. bulloides ages during the last deglaciation and part of the Early and mid‐Holocene. The greatest offsets (up to 1,030 years) were found during Heinrich Stadial 1, the Younger Dryas, and part of the Holocene. The potential factors differentially affecting these two planktonic species were assessed by complementary 14C, oxygen and carbon isotopes, and species abundance determinations. The coupled effect of bioturbation with changes in the abundance of G. ruber is invoked to account for the large age offsets. Our results highlight that 14C ages of planktonic foraminifera might be largely compromised even in settings characterized by high sediment accumulation rates. Thus, a careful assessment of potential temporal biases must be performed prior to using 14C ages for paleoclimate investigations or radiocarbon calibrations (e.g., marine calibration curve Marine13, Reimer et al., 201

Digestibilidad y respuesta ovárica de conejas reproductoras alimentadas con dietas suplementadas con ácidos grasos poliinsaturados n-3

Aumentar el número de gazapos destetados por coneja y parto es un objetivo importante para incrementar la rentabilidad del sector cunícola industrial con efectos directos. La mejora genética de la prolificidad en las líneas de madres ha demostrado ser una estrategia eficaz para alcanzar este objetivo; sin embargo otras vías, como la influencia de diferentes fuentes de grasa en las dietas de conejas reproductoras, han sido muy poco estudiadas. Los ácidos grasos (AG) n-3 interfieren en la fisiología reproductiva porque pueden modular las enzimas involucradas en el metabolismo de las prostaglandinas y del colesterol que es el precursor de los esteroides como la progesterona (revisado en Gulliver et al., 2012). El objetivo de este trabajo es estudiar si la suplementación con AG poliinsaturados (PUFA) n-3 de las dietas de conejas durante la recría puede afectar a la tasa de ovulación y a la síntesis esteroidogénica ovárica determinada mediante las concentraciones de progesterona plasmática

Estudio inicial de la estructura genética del conejo ibicenco a aprtir de información genealógica.

Aumentar el número de gazapos destetados por coneja y parto es un objetivo importante para incrementar la rentabilidad del sector cunícola industrial con efectos directos. La mejora genética de la prolificidad en las líneas de madres ha demostrado ser una estrategia eficaz para alcanzar este objetivo; sin embargo otras vías, como la influencia de diferentes fuentes de grasa en las dietas de conejas reproductoras, han sido muy poco estudiadas. Los ácidos grasos (AG) n-3 interfieren en la fisiología reproductiva porque pueden modular las enzimas involucradas en el metabolismo de las prostaglandinas y del colesterol que es el precursor de los esteroides como la progesterona (revisado en Gulliver et al., 2012). El objetivo de este trabajo es estudiar si la suplementación con AG poliinsaturados (PUFA) n-3 de las dietas de conejas durante la recría puede afectar a la tasa de ovulación y a la síntesis esteroidogénica ovárica determinada mediante las concentraciones de progesterona plasmática

Levels and variables associated with psychological distress during confinement due to the coronavirus pandemic in a community sample of Spanish adults

Due to the COVID-19 pandemic's consequences and the state of alarm, literature has shown that people worldwide have experienced severe stressors that have been associated with increased prevalence of emotional distress. In this study, we explored psychological distress (depression, anxiety, and somatization symptoms) using an online survey platform in a sample of 1,781 Spanish adults during the confinement due to COVID-19, relationships between distress and sleep problems, affect, pain, sleep, emotional regulation, gender, type of housing, history of psychopathology, and living alone during the confinement, and differences depending on demographic and psychological variables. Results showed that between 25% and 39% of the sample referred to clinically significant levels of distress. In addition, women showed higher levels of distress, negative affect, perception of pain, and cognitive reappraisal and lower levels of emotional suppression and sleep quality than men. A history of psychopathology, being younger, living alone or in a flat was associated with higher distress. Finally, the variables most strongly related to distress were negative and positive affect, levels of pain, sleep quality, and emotional suppression. Our results highlight the important role of emotional suppression, cognitive reappraisal, and loneliness and the impact of being a woman and younger in Spain during the COVID-19 pandemic. Therefore, it would be necessary to provide assessments of distress levels in these population groups and focus psychological preventive and therapeutic online interventions on expressing emotions and preventing loneliness

Use of thermolytic protective groups to prevent G-tetrad formation in CpG ODN type D: structural studies and immunomodulatory activity in primates

CpG oligodeoxynucleotides (ODN) show promise as immunoprotective agents and vaccine adjuvants. CpG ODN type D were shown to improve clinical outcome in rhesus macaques challenged with Leishmania major. These ODN have a self-complementary core sequence and a 3′ end poly(G) track that favors G-tetrad formation leading to multimerization. Although multimerization appears necessary for localization to early endosomes and signaling via Toll-like receptor 9 (TLR-9), it can result in product polymorphisms, aggregation and precipitation, thereby hampering their clinical applications. This study shows that functionalizing the poly(G) track of D ODN with thermolytic 2-(N-formyl-N-methyl)aminoethyl (fma) phosphate/thiophosphate protecting groups (pro-D ODN) reduces G-tetrad formation in solution, while allowing tetrad formation inside the cell where the potassium concentration is higher. Temperature-dependent cleavage of the fma groups over time further promoted formation of stable G-tetrads. Peripheral blood cells internalized pro-D ODN efficiently, inducing high levels of IFNα, IL-6, IFNγ and IP-10 and triggering dendritic cell maturation. Administration of pro-D35 to macaques challenged with L.major significantly increased the number of antigen-specific IFNγ-secreting PBMC and reduced the severity of the skin lesions demonstrating immunoprotective activity of pro-D ODN in vivo. This technology fosters the development of more efficient immunotherapeutic oligonucleotide formulations for the treatment of allergies, cancer and infectious diseases

The MentDis_ICF65+ study protocol: prevalence, 1-year incidence and symptom severity of mental disorders in the elderly and their relationship to impairment, functioning (ICF) and service utilisation.

Background: The EU currently lacks reliable data on the prevalence and incidence of mental disorders in older people. Despite the availability of several national and international epidemiological studies, the size and burden of mental disorders in the elderly remain unclear due to various reasons. Therefore, the aims of the MentDis_ICF65+ study are (1) to adapt existing assessment instruments, and (2) to collect data on the prevalence, the incidence, and the natural course and prognosis of mental disorders in the elderly. Method/design: Using a cross-sectional and prospective longitudinal design, this multi-centre study from six European countries and associated states (Germany, Great Britain, Israel, Italy, Spain, and Switzerland) is based on age-stratified, random samples of elderly people living in the community. The study program consists of three phases: (1) a methodological phase devoted primarily to the adaptation of age- and gender-specific assessment tools for older people (e.g., the Composite International Diagnostic Interview, CIDI) as well as psychometric evaluations including translation, back translation; (2) a baseline community study in all participating countries to assess the lifetime, 12 month and 1 month prevalence and comorbidity of mental disorders, including prior course, quality of life, health care utilization and helpseeking, impairments and participation and, (3) a 12 month follow-up of all baseline participants to monitor course and outcome as well as examine predictors. Discussion: The study is an essential step forward towards the further development and improvement of harmonised instruments for the assessment of mental disorders as well as the evaluation of activity impairment and participation in older adults. This study will also facilitate the comparison of cross-cultural results. These results will have bearing on mental health care in the EU and will offer a starting point for necessary structural changes to be initiated for mental health care policy at the level of mental health care politics

Abrupt intrinsic and extrinsic responses of southwestern Iberian vegetation to millennial-scale variability over the past 28 ka

ABSTRACT: We present new high‐resolution pollen records combined with palaeoceanographic proxies from the same samples in deep‐sea cores SHAK06‐5K and MD01‐2444 on the southwestern Iberian Margin, documenting regional vegetation responses to orbital and millennial‐scale climate changes over the last 28 ka. The chronology of these records is based on high‐resolution radiocarbon dates of monospecific samples of the planktonic foraminifera Globigerina bulloides, measured from SHAK06‐5K and MD01‐2444 and aligned using an automated stratigraphical alignment method. Changes in temperate and steppe vegetation during Marine Isotope Stage 2 are closely coupled with sea surface temperature (SST) and global ice‐volume changes. The peak expansion of thermophilous woodland between ~10.1 and 8.4 cal ka bp lags behind the boreal summer insolation maximum by ~2 ka, possibly arising from residual high‐latitude ice‐sheets into the Holocene. Rapid changes in pollen percentages are coeval with abrupt transitions in SSTs, precipitation and winter temperature at the onset and end of Heinrich Stadial 2, the ice‐rafted debris event and end of Heinrich Stadial 1, and the onset of the Younger Dryas, suggesting extrinsically forced southwestern Iberian ecosystem changes by abrupt North Atlantic climate events. In contrast, the abrupt decline in thermophilous elements at ~7.8 cal ka bp indicates an intrinsically mediated abrupt vegetation response to the gradually declining boreal insolation, potentially resulting from the crossing of a seasonality of precipitation threshold

Permanent or reversible conjugation of 2′-O- or 5′-O-aminooxymethylated nucleosides with functional groups as a convenient and efficient approach to the modification of RNA and DNA sequences

2′-O-Aminooxymethyl ribonucleosides are prepared from their 3′,5′-disilylated 2′-O-phthalimidooxymethyl derivatives by treatment with NH4F in MeOH. The reaction of these novel ribonucleosides with 1-pyrenecarboxaldehyde results in the efficient formation of stable and yet reversible ribonucleoside 2′-conjugates in yields of 69–82%. Indeed, exposure of these conjugates to 0.5 M tetra-n-butylammonium fluoride (TBAF) in THF results in the cleavage of their iminoether functions to give the native ribonucleosides along with the innocuous nitrile side product. Conversely, the reaction of 5-cholesten-3-one or dansyl chloride with 2′-O-aminooxymethyl uridine provides permanent uridine 2′-conjugates, which are left essentially intact upon treatment with TBAF. Alternatively, 5′-O-aminooxymethyl thymidine is prepared by hydrazinolysis of its 3′-O-levulinyl-5′-O-phthalimidooxymethyl precursor. Pyrenylation of 5′-O-aminooxymethyl thymidine and the sensitivity of the 5′-conjugate to TBAF further exemplify the usefulness of this nucleoside for modifying DNA sequences either permanently or reversibly. Although the versatility and uniqueness of 2′-O-aminooxymethyl ribonucleosides in the preparation of modified RNA sequences is demonstrated by the single or double incorporation of a reversible pyrenylated uridine 2′-conjugate into an RNA sequence, the conjugation of 2′-O-aminooxymethyl ribonucleosides with aldehydes, including those generated from their acetals, provides reversible 2′-O-protected ribonucleosides for potential applications in the solid-phase synthesis of native RNA sequences. The synthesis of a chimeric polyuridylic acid is presented as an exemplary model