Deep-sea Ordovician lingulide brachiopods and their associated burrows suggest an early colonization of proximal turbidite systems.

Trace fossils from Ordovician deep-marine environments are typically produced by a shallow endobenthos adapted to live under conditions of food scarcity by means of specialized grazing, farming, and trapping strategies, preserved in low-energy intermediate to distal zones of turbidite systems. High-energy proximal zones have been considered essentially barren in the early Paleozoic. We report here the first trace and body fossils of lingulide brachiopods in deep-marine environments from an Upper Ordovician turbidite channel-overbank complex in Asturias, Spain. Body and trace fossils are directly associated, supporting the interpretation of a lingulide tracemaker. Ellipsoidal cross-section, cone-in-cone spreite, and spade morphologies suggest the specimens belong to Lingulichnus verticalis. The oblique orientation in both trace and body fossils is the result of tectonic deformation. The organisms were suspension feeders showing escape, dwelling, and equilibrium behaviours controlled by sedimentation rates associated with turbidite deposition. These trace fossils and their in situ producers represent the oldest evidence of widespread endobenthos colonization in high-energy, proximal areas of turbidite systems, expanding the bathymetric range of Lingulichnus and the variety of behaviours and feeding styles in early Paleozoic deep-marine environments.

Jurassic Palynology from "The Dinosaur Coast" of Asturias (Lastres Fm., Northwestern Spain): Palynostratigraphical and Palaeoecological Insights.

Abundant fossils of vertebrates (mainly footprints and bones of dinosaurs) and numerous invertebrates occur in the Upper Jurassic deposits of the Lastres Formation in the Asturias region, North of Spain. However, no palynological study has been published from this geological formation; therefore, much palaeoenvironmental and palaeoecological information is still unknown. In this study, a total of 62 morphospecies, belonging to 49 different morphogenera were identified, including pollen, spores, algae remains, fungi spores, dinoflagellates, foraminifera, and scolecodonts from four different locations on the Asturian coast. Spores are the dominant group of palynomorphs, both in diversity and abundance, contrasting with the minor diversity of pollen grains. The age of some key taxa indicates that the palynological assemblage cannot be older than the Kimmeridgian, suggesting a Kimmeridgian-Tithonian age. The botanical and environmental affinities of the pollen and spores indicate the presence of different plant assemblages, including plant communities from humid areas such as the margin of rivers and small freshwater ponds that were dominated by bryophytes and ferns, and a coastal plant community that would inhabit arid areas and would be dominated by gymnosperms and some pteridophytes. The SEM analyses of wood remains show the abundance of charcoalified remains suggesting that wildfires were usual in "The Dinosaur Coast" of Asturias during the Kimmeridgian.

Efectos protectores de las proantocianidinas a nivel intestinal frente a estrés termooxidativo por ingestión de aceite de girasol utilizado en fritura / The Origins of Enantioselective Organocatalysis and the 2021 Nobel Prize in Chemistry

Una sociedad avanzada requiere el continuo desarrollo de nuevas moléculas y materiales para su uso como fármacos, productos agroquímicos, producción y almacenaje de energía y múltiples otras aplicaciones. A su vez, este desarrollo requiere el descubrimiento y optimización de nuevos métodos de síntesis. El Premio Nobel de Química de 2021 se concedió a los profesores Benjamin List y David MacMillan “por el desarrollo de la organocatálisis asimétrica”. Se trata de una nueva herramienta en síntesis orgánica enantioselectiva que ha crecido de forma exponencial desde su introducción en 2000 por los galardonados y sirve de alternativa a los métodos tradicionales de catálisis, basados en el uso de enzimas y catalizadores metálicos. (AU)

Any advanced society requires new molecules and materials to be used as drugs, agrochemicals, energy production and storage and countless other applications. This, in turn, requires the development of new methods for synthesis. The 2021 Nobel Prize in Chemistry was awarded to Professors Benjamin List and David MacMillan “for the development of asymmetric organocatalysis”. This is a relatively new tool for enantioselective organic synthesis that has undergone an explosive growth since its introduction in 2000 by the awardees and serves as an alternative to the more traditional catalytic procedures based on the use of enzymes and metal-based catalysts. (AU)

Los orígenes de la organocatálisis enantioselectiva y el premio Nobel de Química de 2021 / The Origins of Enantioselective Organocatalysis and the 2021 Nobel Prize in Chemistry

Una sociedad avanzada requiere el continuo desarrollo de nuevas moléculas y materiales para su uso como fármacos, productos agroquímicos, producción y almacenaje de energía y múltiples otras aplicaciones. A su vez, este desarrollo requiere el descubrimiento y optimización de nuevos métodos de síntesis. El Premio Nobel de Química de 2021 se concedió a los profesores Benjamin List y David MacMillan “por el desarrollo de la organocatálisis asimétrica”. Se trata de una nueva herramienta en síntesis orgánica enantioselectiva que ha crecido de forma exponencial desde su introducción en 2000 por los galardonados y sirve de alternativa a los métodos tradicionales de catálisis, basados en el uso de enzimas y catalizadores metálicos. (AU)

Any advanced society requires new molecules and materials to be used as drugs, agrochemicals, energy production and storage and countless other applications. This, in turn, requires the development of new methods for synthesis. The 2021 Nobel Prize in Chemistry was awarded to Professors Benjamin List and David MacMillan “for the development of asymmetric organocatalysis”. This is a relatively new tool for enantioselective organic synthesis that has undergone an explosive growth since its introduction in 2000 by the awardees and serves as an alternative to the more traditional catalytic procedures based on the use of enzymes and metal-based catalysts. (AU)

Y a final de año llegó la esperanza / At the end of the year, hope came

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Trace fossil evidence for infaunal moulting in a Middle Devonian non-trilobite euarthropod.

Trace fossils represent the primary source of information on the evolution of animal behaviour through deep time, and provide exceptional insights into complex life strategies that would be otherwise impossible to infer from the study of body parts alone. Here, we describe unusual trace fossils found in marginal-marine, storm- and river-flood deposits from the Middle Devonian Naranco Formation of Asturias (northern Spain) that constitute the first evidence for infaunal moulting in a non-trilobite euarthropod. The trace fossils are preserved in convex hyporelief, and include two main morphological variants that reflect a behavioural continuum. Morphotype 1 consists of a structure that superficially resembles a Rusophycus with an oval outline that possesses a distinctly three lobed axis with an elevated central ridge and regularly spaced transverse furrows that convey the appearance of discrete body segments. The anterior part is the most irregular region of the structure, and it is not always recorded. Morphotype 2 displays more elongated, tubular morphology. Careful observation, however, reveals that it comprises up to three successive morphotype 1 specimens organised in a linear fashion and partially truncating each other. Trilobate morphology and effaced transverse furrows are locally evident, but the predominant morphological feature is the continuous, elevated ridge. The detailed morphology of morphotype 1 and well-preserved, discrete segments of morphotype 2 closely resemble the dorsal exoskeleton of the enigmatic late Carboniferous euarthropod Camptophyllia, suggesting the possible affinities of the producer. Comparisons with patterns of Devonian phacopid trilobite exuviation suggest that the Naranco Formation trace fossils may have been produced by the infaunal activities of an euarthropod that anchored its dorsal exoskeleton in the firm sediment during the body inversion moult procedure. Our findings expand the phylogenetic and environmental occurrence of infaunal moulting in Palaeozoic euarthropods, and suggest a defensive strategy against predation, previously only known from trilobites preserved in open-marine deposits.

Hipofosfatemia severa por hierro intravenoso en paciente intervenida de bypass gástrico / Intravenous iron induced severe hypophophatemia in a gastric bypass patient

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The largest European theropod dinosaurs: remains of a gigantic megalosaurid and giant theropod tracks from the Kimmeridgian of Asturias, Spain.

The Kimmeridgian Vega, Tereñes and Lastres formations of Asturias have yielded a rich vertebrate fauna, represented by both abundant tracks and osteological remains. However, skeletal remains of theropod dinosaurs are rare, and the diversity of theropod tracks has only partially been documented in the literature. Here we describe the only non-dental osteological theropod remain recovered so far, an isolated anterior caudal vertebra, as well as the largest theropod tracks found. The caudal vertebra can be shown to represent a megalosaurine megalosaurid and represents the largest theropod skeletal remain described from Europe so far. The tracks are also amongst the largest theropod footprints reported from any setting and can be assigned to two different morphotypes, one being characterized by its robustness and a weak mesaxony, and the other characterized by a strong mesaxony, representing a more gracile trackmaker. We discuss the recently proposed distinction between robust and gracile large to giant theropod tracks and their possible trackmakers during the Late Jurassic-Berriasian. In the absence of complete pedal skeletons of most basal tetanurans, the identity of the maker of Jurassic giant theropod tracks is difficult to establish. However, the notable robustness of megalosaurine megalosaurids fits well with the described robust morphotypes, whereas more slender large theropod tracks might have been made by a variety of basal tetanurans, including allosaurids, metriocanthosaurids or afrovenatorine megalosaurids, or even exceptionally large ceratosaurs. Concerning osteological remains of large theropods from the Late Jurassic of Europe, megalosaurids seem to be more abundant than previously recognized and occur in basically all Jurassic deposits where theropod remains have been found, whereas allosauroids seem to be represented by allosaurids in Western Europe and metriacanthosaurids in more eastern areas. Short-term fluctuations in sea level might have allowed exchange of large theropods between the islands that constituted Europe during the Late Jurassic.

Efectos de la educación comunitaria sobre factores de riesgo en adultos mayores prediabéticos / Effects of community-based education on the risk factors in prediabetic older adults

Introducción: la educación es piedra angular en la prevención, atención y tratamiento de la diabetes mellitus. Promueve efectos positivos en la salud de los enfermos y sus familiares a través del conocimiento, con la finalidad de prevenir o retardar las complicaciones de la diabetes, por lo que ningún grupo etario debe ser excluido de este beneficio. Objetivo: determinar el efecto de la educación comunitaria sobre el sedentarismo, los hábitos alimentarios y la glucemia, en adultos mayores con prediabetes. Métodos: estudio cuasi experimental en 20 adultos mayores de ambos géneros, con glucemia capilar de 100 mg/dL a 125 mg/dL, derechohabientes del Instituto Mexicano del Seguro Social, adscritos a la Unidad de Medicina Familiar No. 17 del Instituto Mexicano del Seguro Social, en Villa Juárez, Sonora, México. Resultados: el promedio de edad fue 67 ± 6 años, con predominio del género femenino (60 %) y escolaridad baja. El 72 % de la población tenía familiares directos con diabetes mellitus. Luego de la estrategia educativa, mejoraron los conocimientos sobre diabetes, y hubo cambios significativos antes-después en la evaluación global (p= 0,0001), glucemia capilar (p= 0,0001) y hemoglobina glucosilada (p= 0,003). Así mismo, mejoraron los hábitos dietéticos y de ejercicio físico. Conclusiones: la estrategia educativa tiene un efecto benéfico sobre variables metabólicas y favorece cambios en el estilo de vida(AU)

Introduction: education is the milestone in the prevention, care and treatment of diabetes mellitus. It promotes positive effects for the patient's and the relatives' health through acquisition of knowledge for the purpose of preventing or delaying the diabetes complications, so any age group should be excluded from this benefit. Objective: to determine the effect of community-based education on sedentary and feeding habits and glycemia in pre-diabetic older adults. Methods: quasi-experimental study of 20 older adults of both sexes with capillary glycemia of 100 mg/dL a 125 mg/dL, rightful owners of the Instituto Mexicano del Seguro Social and ascribed to the family medicine unit no. 17 of Instituto Mexicano del Seguro Social in Villa Juarez, Sonora, Mexico. Results: the average age was 67 ± 6 years, females (60 percent) and low schooling prevailed. Seventy two percent of the population had first-line relatives with diabetes. After the educational strategy implementation, knowledge on diabetes improved and significant changes occurred when comparing before and after this intervention in terms of global assessment (p= 0.0001), capillary glycemia (p= 0.0001), and glycosylate hemoglobin (p= 0.003). Feeding habits and physical exercising showed some improvement. Conclusions: educational strategy has beneficial effects on the metabolic parameters and encourages lifestyle changes(AU)

Coordinated involvement of mast cells and T cells in allergic mucosal inflammation: critical role of the CC chemokine ligand 1:CCR8 axis.

CCL1 is the predominant chemokine secreted from IgE-activated human and mouse mast cells in vitro, colocalizes to mast cells in lung biopsies, and is elevated in asthmatic airways. CCR8, the receptor for CCL1, is expressed by approximately 70% of CD4(+) T lymphocytes recruited to the asthmatic airways, and the number of CCR8-expressing cells is increased 3-fold in the airways of asthmatic subjects compared with normal volunteers. In vivo, CCL1 expression in the lung is reduced in mast cell-deficient mice after aeroallergen provocation. Neutralization of CCL1 or CCR8 deficiency results in reduced mucosal lung inflammation, airway hyperresponsiveness, and mucus hypersecretion to a similar degree as detected in mast cell-deficient mice. Adenoviral delivery of CCL1 to the lungs of mast cell-deficient mice restores airway hyperresponsiveness, lung inflammation, and mucus hypersecretion to the degree observed in wild-type mice. The consequences of CCR8 deficiency, including a marked reduction in Th2 cytokine levels, are comparable with those observed by depletion of CD4(+) T lymphocytes. Thus, mast cell-derived CCL1- and CCR8-expressing CD4(+) effector T lymphocytes play an essential role in orchestrating lung mucosal inflammatory responses.

Tumor necrosis factor-alpha triggers mucus production in airway epithelium through an IkappaB kinase beta-dependent mechanism.

Excessive mucus production by airway epithelium is a major characteristic of a number of respiratory diseases, including asthma, chronic bronchitis, and cystic fibrosis. However, the signal transduction pathways leading to mucus production are poorly understood. Here we examined the potential role of IkappaB kinase beta (IKKbeta) in mucus synthesis in vitro and in vivo. Tumor necrosis factor-alpha (TNF-alpha) or transforming growth factor-alpha stimulation of human epithelial cells resulted in mucus secretion as measured by MUC5AC mRNA and protein. TNF-alpha stimulation induced IKKbeta-dependent p65 nuclear translocation, mucus synthesis, and production of cytokines from epithelial cells. TNF-alpha, but not transforming growth factor-alpha, induced mucus production dependent on IKKbeta-mediated NF-kappaB activation. In vivo, TNF-alpha induced NF-kappaB as determined by whole mouse body bioluminescence. This activation was localized to the epithelium as revealed by LacZ staining in NF-kappaB-LacZ transgenic mice. TNF-alpha-induced mucus production in vivo could also be inhibited by administration into the epithelium of an IKKbeta dominant negative adenovirus. Taken together, our results demonstrated the important role of IKKbeta in TNF-alpha-mediated mucus production in airway epithelium in vitro and in vivo.

Major reduction of atherosclerosis in fractalkine (CX3CL1)-deficient mice is at the brachiocephalic artery, not the aortic root.

Fractalkine (CX3CL1) is of particular interest in atherogenesis because it can serve as an adhesion molecule and a chemokine. Fractalkine and its receptor CX3CR1 are expressed in atherosclerotic lesions of humans and mice. However, the effect of fractalkine deficiency on atherosclerosis susceptibility is unknown. Fractalkine-deficient mice on the C57BL/6 (B6) background were bred to the atherosclerosis-sensitizing B6.ApoE(-/-) and B6.LDLR(-/-) backgrounds. Compared with controls, aortic-root lesion area was unchanged in fractalkine-deficient male and female B6.ApoE(-/-) mice at 16 weeks of age and males at 12 weeks of age, but it was mildly reduced (30%, P = 0.005) in females at 12 weeks of age. In contrast, lesion area at the brachiocephalic artery (BCA) was reduced dramatically by approximately 85% in fractalkine-deficient females [42,251 +/- 26,136 microm(2) (n = 15) vs. 6,538 +/- 11,320 microm(2);(n = 24), P < 0.0001] and males [36,911 +/- 32,504 microm(2) (n = 24) vs. 6,768 +/- 8,595 microm(2) (n = 14); P = 0.001] at 16 weeks of age. Fractalkine-deficient B6.ApoE(-/-) mice were comparable with controls in body weight, plasma cholesterol, plasma high-density lipoprotein cholesterol and white blood cell counts. On the B6.LDLR(-/-) background, lesion areas were reduced by 35% at the aortic root (P < 0.01) and by 50% at the BCA (P < 0.05) in fractalkine-deficient females at 16 weeks of age. Lesions in fractalkine-deficient mice on the B6.ApoE(-/-) and B6.LDLR(-/-) backgrounds were less complex and contained significantly fewer macrophages than controls. In conclusion, the major reduction of atherosclerosis in fractalkine-deficient mice appears to be at the BCA rather than the aortic root.

Intranasal exposure of mice to house dust mite elicits allergic airway inflammation via a GM-CSF-mediated mechanism.

It is now well established that passive exposure to inhaled OVA leads to a state of immunological tolerance. Therefore, to elicit allergic sensitization, researchers have been compelled to devise alternative strategies, such as the systemic delivery of OVA in the context of powerful adjuvants, which are alien to the way humans are exposed and sensitized to allergens. The objectives of these studies were to investigate immune-inflammatory responses to intranasal delivery of a purified house dust mite (HDM) extract and to evaluate the role of GM-CSF in this process. HDM was delivered to BALB/c mice daily for 10 days. After the last exposure, mice were killed, bronchoalveolar lavage was performed, and samples were obtained. Expression/production of Th2-associated molecules in the lymph nodes, lung, and spleen were evaluated by real-time quantitative PCR and ELISA, respectively. Using this exposure protocol, exposure to HDM alone generated Th2 sensitization based on the expression/production of Th2 effector molecules and airway eosinophilic inflammation. Flow cytometric analysis demonstrated expansion and activation of APCs in the lung and an influx of activated Th2 effector cells. Moreover, this inflammation was accompanied by airways hyper-responsiveness and a robust memory-driven immune response. Finally, administration of anti-GM-CSF-neutralizing Abs markedly reduced immune-inflammatory responses in both lung and spleen. Thus, intranasal delivery of HDM results in Th2 sensitization and airway eosinophilic inflammation that appear to be mediated, at least in part, by endogenous GM-CSF production.

Effect of inducible costimulator blockade on the pathological and protective immune responses induced by the gastrointestinal helminth Trichinella spiralis.

Infections with gastrointestinal helminths elicit potent Th2 responses, which ultimately result in their expulsion. However, during expulsion of Trichinella spiralis this Th2 response also induces a severe enteropathy characterized by villus atrophy and crypt hyperplasia. Inducible costimulator (ICOS), a homologue of CD28, interacts with B7-related protein 1, and has been shown to be important in T-B cell interactions and antibody class switching. Significantly, ICOS appears to be involved in the induction of both Th1 and Th2 responses, but may be of heightened importance in Th2 responses. Here we employed a blocking antibody against ICOS to investigate the contribution of ICOS costimulation to the development of the protective and pathological immune responses induced during infection with T. spiralis. We show that, although blocking ICOS resulted in a decrease in TNF-alpha and the Th2 cytokines IL-4 and IL-5 and serum levels of total IgE, it did not affect the expulsion of the adult parasites. Surprisingly, levels of IL-9, IL-13 and IL-10 were elevated and protection against the larval muscle stage of the parasite was enhanced. Importantly, these findings may relate to the fact that ICOS blockade significantly ameliorated the enteropathy that usually accompanies expulsion of the adult parasite.

ICOS-mediated signaling regulates cytokine production by human T cells and provides a unique signal to selectively control the clonal expansion of Th2 helper cells.

The CD28 homologue inducible costimulator (ICOS) has been demonstrated to regulate a number of T cell-dependent immune responses in vivo. However, the expression and functional importance of ICOS during APC-Th cell interaction in the human is not fully understood. Here, we demonstrate that ICOS-mediated signaling plays an important role in the production of selective cytokines during both primary and subsequent Th cell responses upon allospecific or superantigen activation. In contrast, ICOS does not play a role in the differentiation of naive cells into Th1 or Th2 effector cells, nor does it determine the type of effector function of memory cells upon subsequent allogeneic challenge. In addition, our data demonstrate that ICOS provides a novel and unique role in regulating DC-mediated Th2, but not Th1 cell clonal expansion. These data suggest that ICOS-mediated signaling plays a discrete role in the regulation of human T helper cell responses.

The role of ICOS and other costimulatory molecules in allergy and asthma.

Activation and differentiation of T cells play a critical role in the pathogenesis of allergies and asthma. Upon encounter with specific antigen, naïve T helper precursor (ThP) cells become activated, an event that is regulated not only by engagement of the T cell receptor (TCR) with peptide presented in the context of MHC class II molecules, but also by a number of costimulatory signals. CD28 engagement by B7-1 and B7-2 on resting ThP cells provides a critical signal for initial cell cycle progression, interleukin-2 production and clonal expansion. However, in recent years, other related members of the immunoglobulin (Ig) family, such as inducible costimulatory molecules (ICOS) and the TNF receptor family members which include OX40, have also been demonstrated to play an important role in providing unique and complementary signals that regulate the outcome of immune responses. These positive costimulatory signals are counterbalanced by signals that dampen down immune responses and include CTLA-4, PD-1 and the recently described Ig superfamily members BTLA and TIM-3. This review discusses the role of these costimulatory signals and their potential involvement in the pathogenesis of asthma and allergic responses.

Blocking inducible co-stimulator in the absence of CD28 impairs Th1 and CD25+ regulatory T cells in murine colitis.

Several autoimmune disease models depend on an imbalance in the activation of aggressor T(h)1 and CD4(+)CD25(+) regulatory T (T(reg)) cells. Here we compare the requirement for signals through the co-stimulatory molecules CD28 and inducible co-stimulator (ICOS) in chronic murine colitis, a model for inflammatory bowel disease. We used a colitis model in which disease-causing CD45RB(hi) T cells alone or in combination with CD4(+)CD25(+) T cells from either CD28-deficient or wild-type donors were transferred into T cell-deficient animals, half of which were treated with ICOS-blocking reagents. Blocking ICOS on the surface of CD28-deficient T(h)1 cells abrogated development of colitis, whereas blocking CD28 or ICOS alone had little to no effect on disease induction. In contrast to T(h)1 cells, regulatory T cell functioning depended mostly on CD28 signaling with only a minor contribution for ICOS. We conclude that CD28 and ICOS collaborate to development of murine colitis by aggressor T(h)1 cells, and that CD28 is required for T(reg) cells, which should caution against the use of CD28-blocking reagents in inflammatory bowel disease.