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International audience; The Bølling–Allerød (B-A) Interstadial (14.6–12.9 ka) was a period of intense glacier recession in the Pyrenees. All available proxies indicate that environmental conditions became substantially wetter and warmer than during the preceding post-LGM interval between 18.9 and 14.6 ka (early Last Glacial to Interglacial transition, LGIT). Most of the Pyrenean trunk glaciers vanished, being confined to the cirques and promoting the onset of paraglacial rock slope failures and the formation of rock glaciers. At lower elevations, forest expansion promoted a sharp decrease in catchment erosion rates. Braided glaciofluvial stream channels narrowed and gave way to meandering river styles. The detailed chronology of deglaciation during those 1700 years of rapid change has been documented for only a very small number of valleys, mostly relying on 10Be or 36Cl exposure ages obtained from glacially-polished bedrock steps on valley floors, with also a few results from ice-marginal boulders and/or rock glaciers. A period of glacier re-expansion occurred at the end of the B-A Interstadial in response to decreasing temperatures heralding the Younger Dryas.

International audience; The Upper Garonne Basin included the largest glacial system in the Pyrenees during the last glacial cycle. Within the long-term glacial retreat during Termination-1 (T-1), glacier fluctuations left geomorphic evidence in the area. However, the chronology of T-1 glacial oscillations on the northern slope of the Central Pyrenees is still poorly constrained. Here, we introduce new geomorphological observations and a 12-sample dataset of 10Be Cosmic-Ray Exposure (CRE) ages from the Ruda Valley. This U-shaped valley, surrounded by peaks exceeding 2800 m a.s.l., includes a sequence of moraines and polished surfaces that enabled to reconstruct the chronology of the last deglaciation. Following the maximum ice extent, warmer conditions prevailing at ~15-14 ka, during the Bølling-Allerød (B-A) Interstadial, favoured glacial retreat in the Ruda Valley. Within the B-A, glaciers experienced two phases of advance/stillstand with moraine formation at 13.5 and 13.0 ka. During the early YD, glacial retreat exposed the highest surfaces of the Saboredo Cirque (~2300-2350 m) at 12.7 ka. Small glaciers persisted only inside the highest cirques (~2470 m), such as in Sendrosa Cirque, with moraines stabilizing at 12.6 ka. The results of this work present the most complete chronology for Pyrenean glacial oscillations from the B-A to the YD.

The spatial and temporal patterns of Holocene glacial oscillations in most currently ice-free areas of Antarctica remains unknown. This work focuses on the recent deglaciation in the northern sector of the Fildes Peninsula, King George Island, northern Antarctic Peninsula. The ice cap covering ca. 90% of the island has receded since the last glacial maximum and exposed ca. 29 km2 of ice-free land. We reconstruct its glacial history based on a dataset of 12 36Cl exposure ages obtained through Cosmic-Ray Exposure (CRE) dating of moraine boulders, polished surfaces and erratic boulders surrounding the peninsula’s northern plateau. Results reveal that the deglaciation of the northern Fildes Peninsula took place during the Holocene Thermal Maximum at 7-6 ka, when warm conditions promoted a massive glacial retreat. The present arrangement of ice-free areas was in place by 6 ka. Small cirque moraines suggest the subsequent occurrence of favourable climate conditions for glacial expansion fed by intense snow deflation at 4.6 and 1 ka at the foot of the northern plateau. The deglaciation pattern of the Fildes Peninsula resulted from the combined shrinkage of different ice masses, rather than of the long-term retreat of the King George Ice Cap. No evidence of glacier expansion during more recent cold periods (i.e. the Little Ice Age) was found. These results fit well with regional deglacial histories inferred from lacustrine sediments and raised beaches and complement the existing chronological framework to help better understand the peninsula’s Holocene geoecological dynamics.

This chapter summarizes the uniqueness of the Iberian glacial landscapes and discusses the glacial evolution in the Iberian mountains from previous glaciations to the Last Glacial Cycle to the present day. Considering the results presented in the previous sections, the chapter examines the spatial and temporal patterns of glacial phases as well as the geographical and climatic factors driving glacial oscillations. In addition, we also discuss the Iberian glacial evolution in the context of the world's recent trends. At the end, we also review how some glacial morphologies have been altered by anthropic activities. This shows evidence of the need to preserve the Iberian glacial landscapes for future generations.

International audience; The aim of this work is to study the process of transformation of debris-free mountain glaciers into debris-covered glaciers and rock glaciers, and to examine the factors driving diverging evolution in similar glacial systems. The study area is the Hofsdalur valley, in the Trollaskagi peninsula (northern Iceland), where several cirques host a great diversity of glaciers and rock glaciers as well as various glacial landforms. Four adjacent cirques have been analysed through a multidisciplinary approach: geomorphological analysis, boulder surface displacement tracking, quantification of recent glacier changes, three dimensional palaeoglacier reconstruction, equilibrium-line altitude calculations and relative and direct dating methods applied to surface boulders. Dating methods included in situ Cl-36 cosmic-ray exposure dating, Schmidt hammer weathering measurements and lichenometric dating. The results confirm that glaciers in Hofsdalur followed an evolution pattern similar to that observed in other cirques in the Trollaskagi peninsula. During the Younger Dryas (12.9-11.7 ka) many of those cirques hosted debris-free glaciers, whose retreat started in the early Holocene. Distinct retreat dynamics and cirque floor elevation conditioned the subsequent glacial evolution. In some Trollaskagi cirques, the ice completely covered the headwalls, which consequently did not supply debris onto the glacier surface, which remained debris-free. In most of these cirques, however, glacier retreat enhanced paraglacial processes and the ice-free cirque walls generated a high debris supply onto the glacier surface. As a result, the glaciers evolved towards debris-covered glaciers or rock glaciers, depending on the local topographical setting. In the lower cirques they collapsed immediately after their formation. At higher altitudes, above the lower permafrost limit, these ice-cored landforms have survived until the present day, but they have been stagnant since the Holocene Thermal Maximum, while the heads of these cirques have hosted debris-free glaciers during the Late Holocene.

International audience; The Upper Garonne Basin included the longest glacier in the Pyrenees during the Late Pleistocene. During major glacial advances, the Garonne palaeoglacier flowed northwards along similar to 80 km from peaks of the axial Pyrenees exceeding 2800-3000 m until the foreland of this mountain range at the Loures-Barousse-Barbazan basin (LBBb), at 420-440 m. Here, the palaeoglacier formed a terminal moraine complex that is examined in this work. Based on geomorphological observations and a 12-sample data set of Be-10 Cosmic-Ray Exposure (CRE) ages, the timing of the maximum glacial extent was constrained as well as the onset of the deglaciation from the end of the Last Glacial Cycle (LGC). Chronological data shows evidence that the external moraines in this basin were abandoned by the ice at the end of the Penultimate Glacial Cycle (PGC) and the onset of the Eemian Interglacial, at similar to 129 ka. No evidence of subsequent glacial advances or standstills occurred during the LGC in this basin were found, as the few existing datable boulders provided in the internal moraine showed inconsistent ages, thus probably being affected by post-glacial processes. The terminal basin was already deglaciated during the global Last Glacial Maximum at 24-21 ka, as revealed by exposure ages of polished surfaces at the confluence of the Garonne-La Pique valleys, 13 km south of the entrance of the LBBb. This study introduces the first CRE ages in the Pyrenees for the glacial advance occurred during the PGC and provides also new evidence that glaciers had already significantly shrunk during the LGM.

HL-1 cells; L-type calcium channels; Calcium regulation Células HL-1; Canales de calcio tipo L; Regulación del calcio Cel·lules HL-1; Canals de calci tipus L; Regulació del calci MicroRNAs (miRNAs) participate in atrial remodeling and atrial fibrillation (AF) promotion. We determined the circulating miRNA profile in patients with AF and heart failure with reduced ejection fraction (HFrEF), and its potential role in promoting the arrhythmia. In plasma of 98 patients with HFrEF (49 with AF and 49 in sinus rhythm, SR), differential miRNA expression was determined by high-throughput microarray analysis followed by replication of selected candidates. Validated miRNAs were determined in human atrial samples, and potential arrhythmogenic mechanisms studied in HL-1 cells. Circulating miR-199a-5p and miR-22-5p were significantly increased in HFrEF patients with AF versus those with HFrEF in SR. Both miRNAs, but particularly miR-199a-5p, were increased in atrial samples of patients with AF. Overexpression of both miRNAs in HL-1 cells resulted in decreased protein levels of L-type Ca2+ channel, NCX and connexin-40, leading to lower basal intracellular Ca2+ levels, fewer inward currents, a moderate reduction in Ca2+ buffering post-caffeine exposure, and a deficient cell-to-cell communication. In conclusion, circulating miR-199a-5p and miR-22-5p are higher in HFrEF patients with AF, with similar findings in human atrial samples of AF patients. Cells exposed to both miRNAs exhibited altered Ca2+ handling and defective cell-to-cell communication, both findings being potential arrhythmogenic mechanisms. This work was funded by the following grants, awarded to B.B.: Sociedad Española de Cardiología, Sección de Arritmias y Electrofisiología 2012; Sociedad Española de Cardiología, Sección de Insuficiencia Cardíaca 2013; Fondo Investigación Sanitaria (FIS)—Instituto Carlos III 2013 (PI13/01830); and Societat Catalana de Cardiologia 2016. Awarded to K.W.A-A. and S.R.: British Heart Foundation (BHF) Intermediate Research Fellowship. Awarded to J.M.F.F.: grant from the Spanish Ministry of Science and Innovation (RTI2018-094809-B-I00). “María de Maeztu” Programme for Units of Excellence in R&D to the Departament de Ciències Experimentals i de la Salut (MDM-2014-0370) and FEDER (Fondo Europeo de Desarrollo Regional) also contributed to this work.

A.S.T.E.R. TEAM : Georges Aumaître, Didier Bourlès et Karim Keddadouche; International audience; The objective of this work is to chronologically establish the origin of the different glacial and rock glacier complex landforms deposited by Heoinsdalsjokull glacier (65 degrees 39' N, 18 degrees 55' W), in the Heoinsdalur valley (Skagafjorour fjord, Trollaskagi peninsula, central northern Iceland). Multiple methods were applied: geomorphological analysis and mapping, glacier reconstruction and equilibrium-line altitude calculation, Cosmic-Ray Exposure dating (in situ cosmogenic Cl-36), and lichenometric dating. The results reveal that a debris-free glacier receded around 6.6 +/- 0.6 ka, during the Holocene Thermal Maximum. The retreat of the glacier exposed its headwall and accelerated paraglacial dynamics. As a result, the glacier terminus evolved into a debris-covered glacier and a rock glacier at a slightly higher elevation. The front of this rock glacier stabilized shortly after it formed, although nuclide inheritance is possible, but its sector close the valley head stabilized between 1.5 and 0.6 ka. The lowest part of the debris-covered glacier (between 600 and 820 m altitude) collapsed at ca. 2.4 ka. Since then, periods of glacial advance and retreat have alternated, particularly during the Little Ice Age. The maximum advance during this phase occurred in the 15th to 17th centuries with subsequent re-advances, namely at the beginning of the 19th and 20th centuries. After a significant retreat during the first decades of the 20th century, the glacier advanced in the 1960s to 1990s, and then retreated again, in accordance with the local climatic evolution. The internal ice of both the debris-covered and the rock glacier have survived until the present day, although enhanced subsidence provides evidence of their gradual degradation. A new rock glacier developed from an ice-cored moraine from around 1940-1950 CE. Thus, the Holocene coupling between paraglacial and climatic shifts has resulted in a complex evolution of Heoinsdalsjokull, which is conflicting with previously proposed models: a glacier, which had first evolved into a debris-covered and rock glacier, could later be transformed into a debris-free glacier, with a higher sensitivity to climatic variability.

International audience; The small ice caps distributed across the Antarctic Peninsula region have undergone large ice volume changes since the Last Glacial Cycle, in line with most of the Antarctic continent. While the surface extent of glacial shrinking is relatively well known, the timing of glacial oscillations and the magnitude of ice thinning remain little investigated. Cosmic-Ray Exposure (CRE) dating applied on ice-free vertical sequences can provide insights about the temporal framework of glacial oscillations. However, the potential occurrence of nuclide inheritance may overestimate the real timing of the last glacial retreat. This problem has been observed in many areas in Continental Antarctica, but similar studies have not yet been conducted in environments of the Maritime Antarctica, such as the South Shetland Islands (SSI). This research focuses on the Hurd Peninsula ice cap (HPIC, ca. 60 degrees 22' W, 62 degrees 40' S), located in the SW of Livingston Island, SSI. Past climate oscillations since the Last Glacial Cycle have determined the amount of ice stored in the ice cap. Today, this polythermal ice cap is surrounded by several nunataks standing out above the ice. Three of them have been selected to explore their deglaciation history and to test the potential occurrence of nuclide inheritance in deglaciated bedrocks associated with polythermal glaciers. We present a new dataset with 10 Be-10 exposure dates. Some of them were found to be anomalously old, evidencing that nuclide inheritance is present in bedrocks associated with polythermal ice caps and suggesting complex glacial exposure histories. We attribute this to limited erosion, given the gentle slope of the nunatak margins and the cold-based character of the surrounding ice. The remaining samples allowed to approach local surface-elevation changes of the HPIC. Our results suggest that ice thinning started during the Last Glacial Maximum (LGM) at similar to 22 ka but intense glacial shrinking occurred from similar to 18 to similar to 13 ka, when the nunataks became exposed, being particularly intense at the end of this period (similar to 14-13 ka) coinciding with the time of the meltwater pulse 1a (MWP-1a) and the end of the Antarctic Cold Reversal (ACR).

Pleistocene glaciers shaped the highest lands of the National Park of Sierra Nevada, South Spain. Alpine glaciers filled the western valleys of the massif with hundreds of meters of ice. Surface exposure dating shows evidence of glacial expansion during the Younger Dryas and the subsequent disappearance of glaciers of the massif during the Early Holocene. Since then, glacial records and lake sediments reveal that the massif has been ice-free for the most part of the Holocene, with the development of small glaciers during the coldest phases inside the highest northern cirques. This occurred at 2.8–2.7, 1.4–1.2 cal. ka BP and during the Little Ice Age (1300–1850 CE), when documentary sources confirm also the existence of some glaciers at the foot of the highest summits. This historical period was probably the coldest and wettest phase of the Holocene in the massif and recorded the largest glaciers of the current interglacial. Those glaciers finally melted away during the mid-20th century.

This paper analyses changes in the surface morphology of rock and debris-covered glaciers in the Holadalsjokull and Fremri-Grjotardalur cirques near Holar village in the Trollaskagi peninsula (northern Iceland) (65°43′55″N; 19°06′49″W, 160 m), to understand the dynamics and climatic significance of these landforms. The study includes an analysis of historical aerial photographs from 1946 to 2000. The aim was to evaluate surface changes in these landforms and obtain the horizontal displacement and elevation changes of large boulders and linear features (ridges and furrows) at each date. In addition, the surface elevation differences between 1980 and 1994 were obtained from digital elevation models. The horizontal displacement results obtain a mean velocity of 0.33 m yr−1 and an average elevation difference of −0.72 m for the boulders, with the linear features advancing 14.84 m during the period 1946–2000. Except for this slow mobility, no changes occurred in the surface morphology of these landforms during the 54 years. The low displacement rates of boulders and linear features, together with the surface lowering processes observed in these landforms, indicate that widespread melting is the most important activity in the debris-covered and rock glaciers in Trollaskagi. This is confirmed by the recent formation of collapse depressions.

The Greenland Ice Sheet (GrIS) plays a key role in the global climate system. Its response to recent warming concerns the scientific community due to its potential contribution to the global sea-level rise, oceanographic changes and the related heat distribution in the atmosphere. Therefore, a better understanding of the GrIS response to past glacial oscillations can provide insights into its sensitivity to rapidly changing climates. Past natural GrIS dynamics are still poorly constrained, and there are important knowledge gaps in the spatio-temporal pattern of its past fluctuations, especially on the NE margins, in response to climate variability. Here, we present new records of past GRIS extents and a detailed space-time reconstruction of the deglaciation process in the Zackenberg Valley (74ºN, 20ºE), NE Greenland, based on geomorphological mapping combined with a new dataset of 39 10Be cosmic-ray exposure (CRE) ages of moraine boulders, polished surfaces, and erratic boulders. Our dataset records glacial oscillations from the Last Glacial Cycle to the Early Holocene. Geomorphic evidence at the summit surfaces reveal that glaciers were significantly thicker (>800 m) at ca. 80 ka, when valleys and fjords were ice-covered and only the highest peaks remained ice-free. The Zackenberg outlet glacier must have been slightly smaller during the Last Glacial Maximum, although no glacial records of this period were found. Samples from moraine boulders indicate rapid and massive deglaciation of the Zackenberg Valley slopes by ca. 14 ka, during the Bølling-Allerød interstadial. Ice thinning exposed the upper and intermediate slopes surrounding the valley floor, while stabilization phases within the long-term glacial retreat favoured the development of several moraine ridges. At the end of the Younger Dryas, by ca. 12 ka, a glacier readvance favoured the development of the lowest moraine ridges of the slopes, connected with the outermost moraine system on the valley floor. Within the limits of this moraine, a debris-covered glacier formed due to the intense paraglacial readjustment of rock slopes and moraines triggered by glacier thinning. This process favoured the degradation of the moraine ridges on the slopes, supplying large amounts of debris to the shrinking glacier. By ~10.5 ka, the last remnants of glacial ice disappeared from the Zackenberg Valley floor, exposing polished bedrock outcrops and leaving scattered erratic boulders. Higher temperatures also favoured the irregular collapse of the debris-covered glacier, transforming this area into a hummocky terrain. This deglaciation chronology shows a particularly intense recession during the Bølling-Allerød and Early Holocene, a path that is broadly similar to that observed in other sites across NE Greenland.

In the Antarctic Peninsula (AP), the small ice caps distributed across its periphery and surrounding islands have recorded important ice volume changes since the end of the Last Glacial Cycle. These volume changes have occurred in the form of surface extent shrinking and ice thinning. The latter has been investigated only at a reduced number of locations. In this context, nunataks constitute key spots to assess the environmental evolution of deglaciated areas as they offer the opportunity to track the deglaciation history and reconstruct past ice losses by using Cosmic-Ray Exposure (CRE) dating. Indeed, nunataks are supposed to have played a prominent role in the vegetal and animal colonization of Antarctica.The South Shetland Islands archipelago is one of the AP areas where past ice thinning has been least investigated, with only one study conducted in King George Island. In order to shed some light on the last deglaciation and its associated ice thinning, we apply 10Be CRE dating to vertical sequences of glacially polished outcrops on two palaeonunataks and one nunatak distributed across the ice-cap covering part of the Hurd Peninsula (SW of Livingston Island): Reina Sofía Peak (62°40'8" S, 60°22'51" W, 273 m a.s.l.), Moores Peak (62°41'21" S, 60°20'42" W, 407 m a.s.l.) and Napier Peak (62°40'18"S, 60°19'31" W, 382 m a.s.l.).Most of the resulting exposure ages provided a logical chronological sequence and allowed reconstructing past vertical changes of the ice surface. The uppermost surfaces of the Moores and Reina Sofía peaks became deglaciated during the Last Glacial Maximum (LGM), between ~24 ka and ~20 ka. Following the LGM, between ~20 and ~14 ka (Termination-1), a massive deglaciation occurred. This trend was especially exacerbated at around ~14 ka, triggering the onset of the deglaciation at other nunataks, such as the Napier Peak, in good agreement with the coetaneous global melt-water pulse 1a. From our results, we infer that ice shrinking during the Holocene must have been very limited compared to the post-LGM period.Nevertheless, some of the exposure ages were either anomalously old or inconsistent, such as those found at the summits of the Reina Sofía and Moores peaks or at the base of the Napier nunatak. These artifacts suggest the occurrence of nuclide inheritance and are indicative of the conservation of previously exposed surfaces. These ages allow to qualitatively infer cold-based regimes characterized by basal ice frozen to bed, with slow mobility and inefficient subglacial erosion due to the gentle slope gradient, not capable of removing inherited nuclides accumulated during former exposure periods. But, as a whole, the dataset adds valuable knowledge on the polythermal character of the Hurd Peninsula Ice cap. This paper was supported by the project NUNANTAR (02/SAICT/2017 – 32002; Fundação para a Ciência e a Tecnologia, Portugal) and the College on Polar and Extreme Environments (University of Lisbon).

The CACNA1A gene encodes the pore-forming α1A subunit of the voltage-gated CaV2.1 Ca2+ channel, essential in neurotransmission, especially in Purkinje cells. Mutations in CACNA1A result in great clinical heterogeneity with progressive symptoms, paroxysmal events or both. During infancy, clinical and neuroimaging findings may be unspecific, and no dysmorphic features have been reported. We present the clinical, radiological and evolutionary features of three patients with congenital ataxia, one of them carrying a new variant. We report the structural localization of variants and their expected functional consequences. There was an improvement in cerebellar syndrome over time despite a cerebellar atrophy progression, inconsistent response to acetazolamide and positive response to methylphenidate. The patients shared distinctive facial gestalt: oval face, prominent forehead, hypertelorism, downslanting palpebral fissures and narrow nasal bridge. The two α1A affected residues are fully conserved throughout evolution and among the whole human CaV channel family. They contribute to the channel pore and the voltage sensor segment. According to structural data analysis and available functional characterization, they are expected to exert gain- (F1394L) and loss-of-function (R1664Q/R1669Q) effect, respectively. Among the CACNA1A-related phenotypes, our results suggest that non-progressive congenital ataxia is associated with developmental delay and dysmorphic features, constituting a recognizable syndromic neurodevelopmental disorder. This work was funded by the Spanish Ministry of Health, Consumer Affairs and Social Welfare, the Spanish Ministry of Science and Innovation, the State Research Agency (AEI, Agencia Estatal de Investigación), and FEDER Funds (Fondo Europeo de Desarrollo Regional): Grants RTI2018-094809-B-I00 to J.M.F.F. and CEX2018-000792-M through the “María de Maeztu” Programme for Units of Excellence in R&D to “Departament de Ciències Experimentals i de la Salut”. M.S. is supported by the Generalitat de Catalunya (PERIS SLT008/18/00194) and National Grant PI17/00101 from the National R&D&I Plan, cofinanced by the Instituto de Salud Carlos III (Subdirectorate-General for Evaluation and Promotion of Health Research) and FEDER (European Regional Development Fund).

Mitochondria play key roles in ATP supply, calcium homeostasis, redox balance control and apoptosis, which in neurons are fundamental for neurotransmission and to allow synaptic plasticity. Their functional integrity is maintained by mitostasis, a process that involves mitochondrial transport, anchoring, fusion and fission processes regulated by different signaling pathways but mainly by the peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α). PGC-1α also favors Ca2+ homeostasis, reduces oxidative stress, modulates inflammatory processes and mobilizes mitochondria to where they are needed. To achieve their functions, mitochondria are tightly connected to the endoplasmic reticulum (ER) through specialized structures of the ER termed mitochondria-associated membranes (MAMs), which facilitate the communication between these two organelles mainly to aim Ca2+ buffering. Alterations in mitochondrial activity enhance reactive oxygen species (ROS) production, disturbing the physiological metabolism and causing cell damage. Furthermore, cytosolic Ca2+ overload results in an increase in mitochondrial Ca2+, resulting in mitochondrial dysfunction and the induction of mitochondrial permeability transition pore (mPTP) opening, leading to mitochondrial swelling and cell death through apoptosis as demonstrated in several neuropathologies. In summary, mitochondrial homeostasis is critical to maintain neuronal function; in fact, their regulation aims to improve neuronal viability and to protect against aging and neurodegenerative diseases. This work was supported by the Spanish Ministry of Science and Innovation and FEDER Funds through grants SAF2017-83372-R (FJM); RTI2018-094809-B-I00 (JMFF); PID2019-106755RB-I00 (RV); and through the “María de Maeztu” Programme for Units of Excellence in R&D (award CEX2018-000792-M).

International audience; Eighteen samples for 36Cl Cosmic-Ray Exposure (CRE) dating were taken from glacially polished bedrocks, mo- raine boulders, fossil/active rock glaciers and debris-covered glaciers in Fremri-Grjótárdalur and Hóladalur cirques in the Víðinesdalur, Hofsdalur and Héðinsdalur valleys, close to Hólar village, in the Tröllaskagi peninsula, northern Iceland. Boulder sampling was preceded by a study of the boulder stability with the twofold aim of: en- suring that the surfaces to be sampled were stable enough for the reliable application of CRE dating, and to better understand the relation between the glacier dynamics and exposition history. The results show that the glaciers which occupy the valleys in Tröllaskagi began their retreat around 16 ka. Later, the glaciers advanced again around 11 ka within the cirques, and small moraines were formed. Thereafter, these small glaciers retreated and evolved into rock glaciers as debris from paraglacial processes accumulated on the glacier surface. The fronts of these rock glaciers stabilized definitively shortly after their formation and became eventually fossil after the melting of their internal ice. New rock glaciers and debris-covered glaciers formed afterwards, which still have internal ice at present, although their current dynamics are mostly related to subsidence. The stabilization of these rock glaciers and debris-covered glaciers is dated to the period between 7 and 3 ka, although they may have been reactivated during cold neoglacial periods. This research demonstrates the potential interest in apply- ing CRE dating methods to debris-covered glaciers and rock glaciers to determine their origin, evolution and phase of cessation of internal movement until they finally lost their internal ice and became fossil.

[EN] Three-dimensional cartographic resources are an important tool in the teaching of Physical Geography and other Earth Sciences. They are also able to help the students to reach a better understanding of the natural landscape. The objective of this work is to design appropriate 3D didactic resources to facilitate the teaching of the landforms in the Higher Education context. These didactic materials have been prepared by using Geographic Information Technologies (GIT). These graphical materials have been created with specific GIT tools, but they can be used by teachers and students with standardized sotfware (Google Earth, Adobe Acrobat Reader or image viewers). Specifically, files with topographical and geological information have been prepared to work with Google Earth. The digital elevation models (DEM) can be viewed in three-dimensional files in 3D PDF format. This work also proposes the creation of photo-realistic images with thematic information draped with the DEM in isometric perspective. Finally, 3D models have been made from the application of photogrammetric techniques so that can be seen in stereoscopic mode as an alternative to the traditional techniques. In conclusion, all these 3D didactic materials proposed in this work showed a great potential as complementary resources in the teaching and learning of Physical Geography and other Earth Sciences., This work is part of the GeoFieldTIG project (nº 87), founded by the Complutense University of Madrid.

The timing of neoglacial advances in the Antarctic Peninsula (AP) is not yet well constrained. Accurate temporal reconstruction of Neoglaciation in the AP is needed to better understand past glacial responses and regional and global teleconnections during the Holocene. Here, we examine all available information about neoglacial advances in the South Shetland Islands (SSI) as well as in the broader geographical context of the AP region and Antarctic continent. In order to shed light on the contrasting chronologies existing for neoglacial advances in these regions, we focused on a case study where a detailed picture of the Holocene deglaciation was already available. Lake sediments revealed that Byers Peninsula, west of Livingston Island (SSI), was fully deglaciated during the Holocene Thermal Maximum. To complement this approach, we identified glacially polished bedrock surfaces, erratic boulders and a moraine ridge near the present front of the glacier in the SE corner. We applied cosmogenic ray exposure (CRE) dating using in situ Cl-36 for basalt rocks and Be-10 for granitic rocks in: (i) 8 samples from glacial erratic and ice-rafted boulders, (ii) 2 samples from moraine boulders, (iii) 2 samples from polished bedrock surfaces, and (iv) 1 sample from an erratic boulder deposited on one of these surfaces. The CRE dates indicate that the onset of deglaciation started around 9.9 +/- 1.2 ka, with two phases of glacier expansion during the Mid-Late Holocene forming moraines at similar to 4.1 +/- 0.5 and similar to 1.0 +/- 0.2 ka, respectively. The main neoglacial advances in the AP and the SSI were mostly synchronous and coincided with cold periods, as shown by other records (e.g. glacio-isostatic marine terraces, marine and lake sediments). In addition, these periods of glacial expansion show a similar timing to those recorded in the Arctic. These results suggest that Neoglaciation was driven by global climate forcing in both polar areas despite temporal variations at regional and local scale.

Human mutations in the CACNA1A gene that encodes the pore-forming α1A subunit of the voltage-gated CaV2.1 (P/Q-type) Ca2+ channel cause multiple neurological disorders including sporadic and familial hemiplegic migraine, as well as cerebellar pathologies such as episodic ataxia, progressive ataxia, and early-onset cerebellar syndrome consistent with the definition of congenital ataxia (CA), with presentation before the age of 2 years. Such a pathological role is in accordance with the physiological relevance of CaV2.1 in neuronal tissue, especially in the cerebellum. This review deals with the report of the main clinical features defining CA, along with the presentation of an increasing number of CACNA1A genetic variants linked to this severe cerebellar disorder in the context of Ca2+ homeostasis alteration. Moreover, the review describes each pathological mutation according to structural location and known molecular and cellular functional effects in both heterologous expression systems and animal models. In view of this information in correlation with the clinical phenotype, we take into consideration different pathomechanisms underlying the observed motor dysfunction in CA patients carrying CACNA1A mutations. Present therapeutic management in CA and options for the development of future personalized treatment based on CaV2.1 dysfunction are also discussed. This work was funded by the Spanish Ministry of Science and Innovation, the State Research Agency (AEI, Agencia Estatal de Investigación), and FEDER Funds (Fondo Europeo de Desarrollo Regional): Grants RTI2018-094809-B-I00 to J.M.F.F. and CEX2018-000792-M through the “María de Maeztu” Programme for Units of Excellence in R&D to “Departament de Ciències Experimentals i de la Salut”. M.S. is supported by the Generalitat de Catalunya (PERIS SLT008/18/00194) and National Grant PI17/00101 from the National R&D&I Plan, cofinanced by the Instituto de Salud Carlos III (Subdirectorate-General for Evaluation and Promotion of Health Research) and European Regional Development Fund. M.I.-S. holds a “Juan de la Cierva-Incorporación” Fellowship funded by the Spanish Ministry of Science and Innovation.

Through a detailed geomorphological study, including thourough mapping of the geomorphic features as well as Be-10 Cosmic-Ray Exposure (CRE) dating, the geomorphological evolution of the Mulhacen cirque since the maximum ice extent of the last glacial cycle until nowadays was determined. This glacial cirque is shaped on the northern face of the Mulhacen peak (3479 m a.s.l. 37 degrees 03'12 ' N/3 degrees 18'41 ' W), Sierra Nevada, southern Spain. It includes several depositional and erosional glacial landforms that allowed reconstructing its environmental evolution since the last glacial cycle. Furthermore, the sequence of glacial oscillations from this site was compared to that of other cirques of the massif, evidencing that: (i) new glaciers formed in these cirques during the Younger Dryas (YD), and (ii) disappeared at 11.7 +/- 1.0 ka. Depending on the altitude, orientation and height of the cirque walls, the final deglaciation of the cirques generated a diversity of landscapes, including a wide range of glacial and periglacial landforms, such as polished surfaces, sequences of moraines, proto-rock glaciers or large rock glacier systems. No glaciers existed in the Sierra Nevada during the Middle Holocene. Only the cirques whose summits exceed 3300 m, are north-exposed and whose walls exceed 300 m high (i.e. Mulhacen and Veleta) hosted glaciers during Neoglacial phases, including the Little Ice Age (LIA) (approx.1300-1850 CE). During these periods, climate oscillations favoured the formation of small glaciers in these cirques, which generated large moraine systems with either one polygenic ridge or a sequence of spaced frontal arcs. The existence of glaciers impeded the formation of permafrost-related landforms, such as rock glaciers and protalus lobes until the end of the LIA, when they started to form. These results are compared with the deglacial evolution in 55 cirques from Iberian mountains as well as from glacial cirques from other mid-latitude mountains and subpolar regions. The chronology of their deglaciation as well as the landforms generated during glacial retreat followed similar patterns, with no significant differences at regional scale. For each mountain range, the geomorphological diversity existing in each cirque depends on the local topographic characteristics although they formed during the same climatic phases.

TRPP3 (also called PKD2L1) is a nonselective, cation-permeable channel activated by multiple stimuli, including extracellular pH changes. TRPP3 had been considered a candidate for sour sensor in humans, due to its high expression in a subset of tongue receptor cells detecting sour, along with its membership to the TRP channel family known to function as sensory receptors. Here, we describe the functional consequences of two non-synonymous genetic variants (R278Q and R378W) found to be under strong positive selection in an Ethiopian population, the Gumuz. Electrophysiological studies and 3D modelling reveal TRPP3 loss-of-functions produced by both substitutions. R278Q impairs TRPP3 activation after alkalinisation by mislocation of H binding residues at the extracellular polycystin mucolipin domain. R378W dramatically reduces channel activity by altering conformation of the voltage sensor domain and hampering channel transition from closed to open state. Sour sensitivity tests in R278Q/R378W carriers argue against both any involvement of TRPP3 in sour detection and the role of such physiological process in the reported evolutionary positive selection past event., Tis work was funded by the Spanish Ministry of Science and Innovation, the State Research Agency (AEI, Agencia Estatal de Investigación) and FEDER Funds (Fondo Europeo de Desarrollo Regional): Grants BFU2016-77961-P to J.B. and E.B., RTI2018-094809-B-I00 to J.M.F.F., PID2019-110933GB-I00/AEI/10.13039/501100011033 to E.B. and J.B., and CEX2018-000792-M through the “María de Maeztu” Programme for Units of Excellence in R&D to “Departament de Ciències Experimentals i de la Salut”. With the support of Secretaria d’Universitats i Recerca del Departament d’Economia i Coneixement de la Generalitat de Catalunya (GRC 2017 SGR 702). S.W. has had a F.P.I. grant (BES-2014-068994) and M.I.-S. a “Juan de la Cierva-Incorporación” Fellowship funded by the Spanish Ministry of Science and Innovation.

Actin polymerization and assembly into stress fibers (SFs) is central to many cellular processes. However, how SFs form in response to the mechanical interaction of cells with their environment is not fully understood. Here we have identified Piezo2 mechanosensitive cationic channel as a transducer of environmental physical cues into mechanobiological responses. Piezo2 is needed by brain metastatic cells from breast cancer (MDA-MB-231-BrM2) to probe their physical environment as they anchor and pull on their surroundings or when confronted with confined migration through narrow pores. Piezo2-mediated Ca2+ influx activates RhoA to control the formation and orientation of SFs and focal adhesions (FAs). A possible mechanism for the Piezo2-mediated activation of RhoA involves the recruitment of the Fyn kinase to the cell leading edge as well as calpain activation. Knockdown of Piezo2 in BrM2 cells alters SFs, FAs, and nuclear translocation of YAP; a phenotype rescued by overexpression of dominant-positive RhoA or its downstream effector, mDia1. Consequently, hallmarks of cancer invasion and metastasis related to RhoA, actin cytoskeleton, and/or force transmission, such as migration, extracellular matrix degradation, and Serpin B2 secretion, were reduced in cells lacking Piezo2.

Arachidonic acid (AA) is a fatty acid involved in the modulation of several ion channels. Previously, we reported that AA activates the high conductance Ca2+- and voltage-dependent K+ channel (BK) in vascular smooth muscle depending on the expression of the auxiliary β1 subunit. Here, using the patch-clamp technique on BK channel co-expressed with β1 subunit in a heterologous cell expression system, we analyzed whether AA modifies the three functional modules involved in the channel gating: the voltage sensor domain (VSD), the pore domain (PD), and the intracellular calcium sensor domain (CSD). We present evidence that AA activates BK channel in a direct way, inducing VSD stabilization on its active configuration observed as a significant left shift in the Q-V curve obtained from gating currents recordings. Moreover, AA facilitates the channel opening transitions when VSD are at rest, and the CSD are unoccupied. Furthermore, the activation was independent of the intracellular Ca2+ concentration and reduced when the BK channel was co-expressed with the Y74A mutant of the β1 subunit. These results allow us to present new insigths in the mechanism by which AA modulates BK channels co-expressed with its auxiliary β1 subunit. This work was partly supported by UNLP 11X/690 (V.M) and ANPCyT PICT 2014-0603 (P.M.), 2018-2435 (P.M.), Argentina; FONDECYT no. 1180999 (K.C.) and 1180464 (CG) and, the Spanish Ministry of Science and Innovation, the State Research Agency (AEI, Agencia Estatal de Investigación), and FEDER Funds (Fondo Europeo de Desarrollo Regional) (Grants RTI2018-094809-B-I00 to J.M.F-F., and CEX2018-000792-M through the “María de Maeztu” Programme for Units of Excellence in R&D to “Departament de Ciències Experimentals i de la Salut”. Martín P and Milesi V are members of the Carrera del Investigador, CONICET. Moncada M is member of the Carrera del Personal de Apoyo a la Investigación y Desarrollo, CONICET. The Centro Interdisciplinario de Neurociencia de Valparaíso (CINV) is a Millennium Institute supported by the Millennium Scientific Initiative of the Ministerio de Economía, Fomento y Turismo, ICM-MINECOM P09-022-F.