Search

Human phosphoglycerate kinase 1(hPGK1) is a key glycolytic enzyme that regulates the balance between ADP and ATP concentrations inside the cell. Phosphorylation of hPGK1 at S203 and S256 has been associated with enzyme import from the cytosol to the mitochondria and the nucleus respectively. These changes in subcellular locations drive tumorigenesis and are likely associated with site‐specific changes in protein stability. In this work, we investigate the effects of site‐specific phosphorylation on thermal and kinetic stability and protein structural dynamics by hydrogen–deuterium exchange (HDX) and molecular dynamics (MD) simulations. We also investigate the binding of 3‐phosphoglycerate and Mg‐ADP using these approaches. We show that the phosphomimetic mutation S256D reduces hPGK1 kinetic stability by 50‐fold, with no effect of the mutation S203D. Calorimetric studies of ligand binding show a large decrease in affinity for Mg‐ADP in the S256D variant, whereas Mg‐ADP binding to the WT and S203D can be accurately investigated using protein kinetic stability and binding thermodynamic models. HDX and MD simulations confirmed the destabilization caused by the mutation S256D (with some long‐range effects on stability) and its reduced affinity for Mg‐ADP due to the strong destabilization of its binding site (particularly in the apo‐state). Our research provides evidence suggesting that modifications in protein stability could potentially enhance the translocation of hPGK1 to the nucleus in cancer. While the structural and energetic basis of its mitochondrial import remain unknown. [ABSTRACT FROM AUTHOR]

This document summarizes a study on early-onset colorectal cancer (EOCRC) and late-onset colorectal cancer (LOCRC). The study found that there are genetic differences between these two types of colorectal cancer based on the age of onset. Recurrent breakpoints and common fragile sites were identified in both cohorts, and a specific gene, CPEB1, was implicated in EOCRC. Further research is needed to confirm these findings and investigate potential treatment options for EOCRC. [Extracted from the article]

The article summarizes two international congresses that took place at the Complutense University of Madrid. The first one, titled "A Jesuit Aesthetic? Theories of the Sensible and Artistic Practices of the Society of Jesus in the Modern Age," brought together eighteen speakers from nine countries and focused on the study of art produced by and for the Society of Jesus in the Modern Age. Controversies surrounding the existence of a Jesuit aesthetic were discussed, as well as the particularities of Jesuit writings on the sensible. The second congress, called "The Papacy and the Hispanic Kingdoms in the Middle Ages," focused on the relationships between the popes and the Hispanic kingdoms during the Middle Ages, especially in the high and late medieval period. The first presentations dealt with the Hispanic-Visigothic Church and the papacy, highlighting the conception of the Hispanic prelates of the Roman pontiff as a puppet in the hands of the emperor and the strengthening of the Hispanic-Visigothic episcopal network. [Extracted from the article]

In April 2023, a Training Workshop on mixed methods in Health Education and Research was held at the University of Aveiro. In this training, a problem was posed about what plagiarism and/or self- plagiarism is, and we found very few correct answers regarding the definition of these concepts. This led us to question what is really known about this topic and where we can find concrete examples of plagiarism and self-plagiarism that have gone unnoticed in society. To carry out this study, a bibliometric and systematic review of the literature was carried out, between the years 2014 and 2022, in the International databases WOS and SCOPUS with the use of the keywords "Plagiarism", "Scientific" and "Education", using VOSViewer Software. As a result of this search, 40 documents with the greatest impact on education were selected, analyzing the content of their summaries and conclusions through CAQDAS NVivo. Among the conclusions obtained, we observe that there is a real need to make known: various recurrent instances of plagiarism and self-plagiarism that occur in academic environments of higher education and analytical models that shed light on the moments prone to these behaviours, offering concrete recommendations to prevent them. his persistence. As a limitation, since this is an exploratory study, the results obtained were not compared with other databases, such as ERIC. Finally, to obtain more significant data in the future, we intend to expand this research by conducting interviews and focus groups with different students and education professionals, to compare the information compiled with new, broader searches that include other databases. [ABSTRACT FROM AUTHOR]

We present a field-based reconstruction of the geomorphology in the Subtropical Andean mountains of the Limarí basin, semiarid central Chile (30-31° S). Fieldwork campaigns and remote-sensing analysis served for detailed geomorphological mapping at four formerly glaciated valleys in the heads of the Combarbalá and Río Hurtado sub-basins. We identify a mosaic of glacial, periglacial, and paraglacial landforms. Glacial landforms include a massive dead-ice moraine complex, with thermokarst and debris-filled fractures suggesting former ice-cored moraine degradation. This landform is superimposed by transversal and arcuate ridges suggesting active-ice processes. Periglacial landforms such as rock glaciers, gelifluction, and protalus lobes occur in cirques and U-shaped valleys, but also on moraine deposits. Paraglacial processes are indicated by talus accumulation in those formerly glaciated slopes. The geomorphological imprint is evidence for the interaction and succession between glacial, periglacial, and paraglacial dynamics from the Late Pleistocene to the present. [ABSTRACT FROM AUTHOR]

Our knowledge on the genetic diversity of the human genome is exponentially growing. However, our capacity to establish genotype–phenotype correlations on a large scale requires a combination of detailed experimental and computational work. This is a remarkable task in human proteins which are typically multifunctional and structurally complex. In addition, mutations often prevent the determination of mutant high‐resolution structures by X‐ray crystallography. We have characterized here the effects of five mutations in the active site of the disease‐associated NQO1 protein, which are found either in cancer cell lines or in massive exome sequencing analysis in human population. Using a combination of H/D exchange, rapid‐flow enzyme kinetics, binding energetics and conformational stability, we show that mutations in both sets may cause counterintuitive functional effects that are explained well by their effects on local stability regarding different functional features. Importantly, mutations predicted to be highly deleterious (even those affecting the same protein residue) may cause mild to catastrophic effects on protein function. These functional effects are not well explained by current predictive bioinformatic tools and evolutionary models that account for site conservation and physicochemical changes upon mutation. Our study also reinforces the notion that naturally occurring mutations not identified as disease‐associated can be highly deleterious. Our approach, combining protein biophysics and structural biology tools, is readily accessible to broadly increase our understanding of genotype–phenotype correlations and to improve predictive computational tools aimed at distinguishing disease‐prone against neutral missense variants in the human genome. [ABSTRACT FROM AUTHOR]

Reconstructing mid-latitude glacier variations is a prerequisite for unveiling the interhemispheric climate linkages and atmospheric-ocean forcings that triggered those changes during the last glacial cycle. Nonetheless, the timing, magnitude, and structure of glacier fluctuations in the southern mid-latitudes remain incomplete. Here, we present a new 10Be chronology of the Universidad Glacier in the Andes of central Chile (34° S, 70° W; ∼2500 m a.s.l.) based on 21 cosmogenic-exposure ages of boulders on discrete moraine ridges defining former ice margins. Our findings include the mapping and dating of three moraines, UNI I, UNI II, and UNI III, located ∼20 km, 15 km, and 10 km down-valley from the present-day glacier front, respectively. The 10Be exposure ages of the UNI I moraine range from 135.9 ± 7.1 to 51.4 ± 2.7 ka (n = 3). The UNI II moraine gave a mean age of 18.0 ± 0.9 (n = 15) and the UNI III moraine yielded a mean age of 13.9 ± 0.8 ka (n = 3). The UNI I moraine implies the largest ice extent during a pre-Last Glacial Maximum (pre-LGM) period, including the penultimate glaciation. The UNI II is a moraine complex that represents cold and humid conditions in central Chile at the end of the LGM, which we attribute to the northward-shift of the Southern Westerly Winds (SWW). The UNI III moraine represents a return to glacial conditions interrupting the Termination, evidencing both a double-step deglacial trend observed through the southern middle and high latitudes at the end of the last ice age. The Andes at this subtropical latitude record a global signal of glacial and climate change. • We constructed a new 10Be chronology of the Universidad Glacier for the last glaciation. • Universidad Glacier reached full glacial conditions during the LGM culminating by 18.0 ± 0.9 ka. • A glacier readvance occurred by 13.9 ± 0.8 ka interrupting the Termination. • The subtropical latitude of the glacier records a global signal of climate change. • Shifts of the Southern Westerly Winds ultimately forced the observed glacier fluctuations. [ABSTRACT FROM AUTHOR]

Atmospheric warming and circulation reorganization at the end of the last ice age represent the most important climate change of the last 100,000 years and provide an opportunity to uncover how the southern subtropics cryosphere responded to strong changes in the global climate system. Extensive mapping and chronologic records on cryogenic landforms to better understand the association and interactions between glaciers and viscous creep of ice-rich permafrost landforms (rock glaciers) are widely missing in the region. In this paper, we reconstruct the geomorphic imprint of the Last Glacial Maximum (LGM) and the Termination I in the high Andes of the Río Limarí Basin (30–31°S) in the subtropical semiarid Andes of Chile. 74 new 10Be surface exposure dating ages constrain the timing of glaciation, deglaciation, and glacial to periglacial transition. Glacial advances occurred first by 41.2 ± 0.6 – 35.0 ± 0.5 ka during Marine Isotope Stage 3, but probably earlier also; then, a second advance occurred during the global LGM between 24.2 ± 0.4 and 18.6 ± 0.2 ka. Deglaciation by 17.6 ± 0.2 ka left extensive hummocky moraines on the main valleys. Characteristic patterns of furrows and ridges typical of rock glaciers and solifluction superimposed on the LGM hummocky moraine indicate ice-rich permafrost in glacial deposits likely between 15.5 ± 0.3 and 13.6 ± 0.3 ka. We propose that moraines deposited by LGM debris-covered glaciers served as a niche for strong seasonal frost and permafrost creep, which substantially modified the original landforms. Our results contribute to a better understanding of major transformations in an ice-rich high mountain area of the southern hemisphere where the interplay of temperature and precipitation changes drove glacial to periglacial transitions. [Display omitted] • 74 new 10Be dates constrain the age of glaciation and periglaciation in the Limarí Andes. • Glaciers expanded between 24.2 ± 0.4–18.6 ± 0.2 ka in correspondence with the LGM. • Deglaciation with steady ice retreat and thinning was completed by 17.6 ± 0.2 ka. • LGM debris-covered glaciers left a moraine niche for subsequent rock glacier development. • Ice-rich permafrost reworked LGM moraine deposits between 15.5 ± 0.3–13.6 ± 0.3 ka. [ABSTRACT FROM AUTHOR]

Phosphoglycerate kinase has been a model for the stability, folding cooperativity and catalysis of a two-domain protein. The human isoform 1 (hPGK1) is associated with cancer development and rare genetic diseases that affect several of its features. To investigate how mutations affect hPGK1 folding landscape and interaction networks, we have introduced mutations at a buried site in the N-terminal domain (F25 mutants) that either created cavities (F25L, F25V, F25A), enhanced conformational entropy (F25G) or introduced structural strain (F25W) and evaluated their effects using biophysical experimental and theoretical methods. All F25 mutants folded well, but showed reduced unfolding cooperativity, kinetic stability and altered activation energetics according to the results from thermal and chemical denaturation analyses. These alterations correlated well with the structural perturbation caused by mutations in the N-terminal domain and the destabilization caused in the interdomain interface as revealed by H/D exchange under native conditions. Importantly, experimental and theoretical analyses showed that these effects are significant even when the perturbation is mild and local. Our approach will be useful to establish the molecular basis of hPGK1 genotype–phenotype correlations due to phosphorylation events and single amino acid substitutions associated with disease. [ABSTRACT FROM AUTHOR]

The article titled "Felix Culpa: Ritual Failure and Theological Innovation in Early Christianity" is a review of a book written by Peter-Ben Smit. The book analyzes rituals in early Christianity and their relationship with the community's identity. The author argues that "failed rituals" serve as catalysts for reflecting on the ritual itself and its development. The book is based on the study of Pauline texts and the Gospel of Mark, and also includes a chapter on Philo of Alexandria. The author highlights the importance of bodily and material rituals in early Christianity. [Extracted from the article]

The crisis caused by the appearance of the COVID-19 pandemic has caused serious problems in the educational field worldwide. An unprecedented scenario has been generated for people with disabilities or disabilities, which presents major problems such as social isolation, emotional imbalance, and the widening of the digital divide. The general objective of the research has been: "Analyse the scientific production related to the use of Information and Communication Technologies as a means to improve the teaching and learning process of people with disabilities and autism spectrum disorders during the pandemic". A bibliographic, documentary and content analysis of the publications resulting from the international database, Google Scholar, which meet the eleven defined inclusion and exclusion criteria, was carried out, selecting a total of 50 articles. A table of categories was elaborated, with a double methodology: in the first place deductive, through the analysis of the existing literature on the subject analysed, selecting the fundamental categories of study. On the other hand, it is inductive, through the construction of emerging categories that arise when performing data analysis. It has been verified that most of the references are written by a single author, corresponding to doctoral theses that delve into the use of technologies to improve communication and learning of people with visual and hearing disabilities as the most relevant cases, during the period of confinement. caused by COVID-19. Likewise, it has been observed that there are still many difficulties and a great problem in access to information and communication technology resources by this group, requiring greater help from public and private institutions. The findings found show that it is necessary to provide greater access to technologies by the public administration, while physical or motor disabilities should have greater importance in the scientific literature, since they are the least treated. [ABSTRACT FROM AUTHOR]

Despite the extensive area covered by the coastal Atacama fog Desert (18–32° S), there is a lack of understanding of its most notorious characteristics, including fog water potential, frequency of fog presence, spatial fog gradients or fog effect in ecosystems, such as Tillandsia fields. Here we discuss new meteorological data for the foggiest season (July–August–September, JAS) in 2018 and 2019. Our meteorological stations lie between 750 and 1211 m a. s. l. at two sites within the Cordillera de la Costa in the hyperarid Atacama (20° S): Cerro Oyarbide and Alto Patache. The data show steep spatial gradients together with rapid changes in the low atmosphere linked to the advection of contrasting coastal (humid and cold) and continental (dry and warm) air masses. One main implication is that fog presence and fog water yields tend to be negatively related to both distance to the coast and elevation. Strong afternoon SW winds advect moisture inland, which take the form of fog in only about 6% of the JAS at 1211 m a. s. l., but 65% at 750 m a. s. l. on the coastal cliff. Although sporadic, long lasting fog events embrace well-mixed marine boundary layer conditions and thick fog cloud between 750 and 1211 m a. s. l. These fog events are thought to be the main source of water for the Tillandsia ecosystems and relate their geographic distribution to the lowest fog water yields recorded. Future climate trends may leave fog-dependent Tillandsia even less exposed to the already infrequent fog resulting in rapid vegetation decline. [ABSTRACT FROM AUTHOR]

Background: Impulse control disorders (ICDs) have an increased frequency in patients with Parkinson's disease (PD), mainly because of treatment with dopamine agonists (DA). Factors related with the country of origin (culture, economy, healthcare politics) may impact phenomenology. Objectives: To explore phenomenology of ICDs depending on the country. Methods: A systematic review following PRISMA guidelines was performed using Pubmed database. Articles published up to 2018 in which the prevalence of ICDs was analyzed were selected. Results: Thirty‐two studies from 22 countries worldwide were included. The highest prevalence of ICDs in each continent was found in UK (59%), USA (39.1%) and India (31.6%). Frequency of ICDs was higher in those studies with lower mean age, higher proportion of males, whenever a screening instrument was used and whenever prescription of DAs was more common. Prevalence of ICDs was higher in Western countries compared to Asian countries (20.8% vs. 12.8%, P < 0.001) as it was the proportion of patients treated with DAs (66% vs. 48.2%, P < 0.001). Hypersexuality was the most common ICD overall (up to 23.8%). The highest frequencies of compulsive buying and eating were found in Western countries. Gambling was less commonly diagnosed, but prevalence was relevant Japan (14%). Conclusion: We observed a tendency towards a different ICD profile in different geographical areas, which may be attributable to socio‐economical, cultural or political influences in the phenomenology of these disorders. Acknowledging these differences could help their early detection, which is critical for prognosis. [ABSTRACT FROM AUTHOR]

The timing, structure, and landscape change during the Patagonian Ice Sheet deglaciation remains unresolved. In this article, we provide a geomorphic, stratigraphic, and geochronological deglacial record of Río Cisnes Glacier at 44°S and also from the nearby Río Ñirehuao and Río El Toqui valleys (45°S) in Chilean Patagonia. Our 14C, 10Be, and optically stimulated luminescence data indicate that after the last glacial maximum, Río Cisnes Glacier experienced ~100 km deglaciation between >19.0 and 12.3 ka, accompanied by the formation of large glacial paleolakes. Deglaciation was interrupted by several ice readvances, and by 16.9±0.3 ka, Río Cisnes Glacier extended only ~40% of its full glacial extent. The deglaciation of Río Cisnes Glacier and other sensitive Patagonian glaciers occurred at least 1 ka earlier than the ca. 17.8 ka normally assumed for the local termination, coincident with West Antarctic isotope records. This early deglaciation can be linked to an orbital forcing–driven decline of Southern Ocean sea ice associated with a distinct atmospheric warming that is apparent for West Antarctica through Patagonia. [ABSTRACT FROM AUTHOR]

The article is a review of the book "The Theology of the Early Christians (1st to 5th centuries)" written by Emanuela Prinzivali and Manlio Simonetti. The book, translated from Italian to Spanish, offers an updated and documented view of ancient Christian theology. The book is divided into two main parts: reflection on God and Christ, and reflection on man. The authors explore the theological and anthropological issues of the first five centuries of Christianity, highlighting the importance of understanding the origins and development of Christian thought. [Extracted from the article]

The timing, structure and termination of the last southern mountain glaciation and its forcing remains unclear. Most studies have focused on the global Last Glacial Maximum (LGM; 26.5–19 ka) time period, which is just part of the extensive time-frame within the last glacial period, including Marine Isotope Stages 3 and 4. Understanding the glacial fluctuations throughout the glacial period is a prerequisite for uncovering the cause and climate mechanism driving southern glaciation and the interhemispheric linkages of climate change. Here, we present an extensive (n = 65) cosmogenic 10 Be glacier chronology derived from moraine belts marking the pre-global LGM extent of the former Patagonian Ice Sheet in southernmost South America. Our results show the mountain ice sheet reached its maximum extent at 48.0 ± 1.8 ka during the local LGM, but attained just half this extent at 21.5 ± 1.8 ka during the global LGM. This finding, supported by nearby glacier chronologies, indicates that at orbital time scales, the southern mid-latitude glaciers fluctuated out-of-phase with northern hemisphere ice sheets. At millennial time-scales, our data suggest that Patagonian and New Zealand glaciers advanced in unison with cold Antarctic stadials and reductions in Southern Ocean sea surface temperatures. This implies a southern middle latitudes-wide millennial rhythm of climate change throughout the last glacial period linked to the north Atlantic by the bipolar seesaw. We suggest that winter insolation, acting alongside other drivers such as the strength and/or position of the southern westerlies, controlled the extents of major southern mountain glaciers such as those in southernmost South America. [ABSTRACT FROM AUTHOR]

The reconstruction of glacier fluctuations during the latest Holocene (<1000 years) is necessary for understanding the climate context preceding the warmer conditions of the 20th and 21st centuries. The glacier records in the Andes of central Chile are suitably located to track former latitudinal changes of the Southern Westerly Winds (SSW), which are mostly unknown at this middle latitude region. Here, we present a reconstruction of the glacial fluctuations using Terrestrial Cosmogenic Nuclides (10Be) dating of boulders resting on moraines and other glacial landforms that make up the moraine complex in the forefield of the Universidad Glacier (34° S). This massive and chaotic-looking moraine was built during the latest Holocene ice advances and subsequent decay of the Universidad Glacier to its present position. Geomorphological mapping and 10Be surface exposure ages (n = 20) show that the Universidad Glacier advanced at least twice to nearly the same maximum extent, first by the 13th to 16th centuries and then by the early to the mid-19th century. Since then, eight moraine ridges denote a rather active and gradual ice demise. We interpret the glacier advances as a response to an equatorward shift of the SWW linked to a long-term negative phase of the Southern Annular Mode (SAM), which embraced net humid and cold atmospheric conditions in central Chile between the 13th century and the mid-19th century. Our glacier chronology is comparable to others from Patagonia and New Zealand, altogether exposing the culmination of the latest Holocene glacial maximum by the mid-19th century, before overall ice decay in a global warming world, with accelerated ice loss since the mid-20th century. • The fluctuations of the Universidad Glacier are 10Be reconstructed for the last millennium. • Glacier advances culminated by the 13th-16th centuries and early-to-mid 19th century. • A northward shift of the Southern Westerly Winds (SWW) triggered the glacier advances. • Glacier advances are linked to a negative phase of the Southern Annular Mode (SAM). • Southern glacier expansions seem to be near-synchronous in the last millennium. [ABSTRACT FROM AUTHOR]

Objective: To analyze changes in body mass index (BMI) in a group of obese patients after a nurse-based intervention to promote changes in their lifestyle through low- calorie diet, exercise and behavioral therapy. Method: quasi-experimental study with a non-probabilistic sample of 32 patients whose inclusion criteria were healthy patients, with autonomy for activities of daily living without dementia. The intervention was based on a nurse-based intervention to promote changes in their lifestyle and was subsequently evaluated by the decrease in BMI. Results: The mean value of the BMR was 34, 2 at the beginning of the study. After the nursing intervention there is a progressive decrease in BMI which was statistically significant after 6 months of treatment, which resulted in an mean value of 32,7. That is, a reduction in BMI of around 4%. Conclusions: personalized nursing intervention and intensive follow-up favor good acceptance or accession to the program and allow us to observe changes in the lifestyle of patients which is essential for controlling obesity. [ABSTRACT FROM AUTHOR]

Post-Tridentine decrees and manuals on the ministry of preaching intensified the visuality of discourse in order to combat Reformation iconoclasm. As a result, correlations between rhetoric and imagery were not limited to speculation among theologians, but had real consequences for the public who listened to sermons and/or contemplated religious images. Just as sacred subject matter conferred upon preaching a status superior to profane oratory, Paleotti or Pacheco, amongst others, defended the nobility of visual arts because of the subjects they represented, notably those with religious themes. In Spain, a particular consequence of the querelle between the intrinsic quality of an artwork, bound to its mimetic capacity, and an artwork's persuasive efficacy, was the necessity to sort out the comparison (paragone) between painting and polychrome sculpture. This latter art form was circumscribed by the jurisdiction of a mature corpus of ecclesiastical theory on the image, which attempted to prevent idolatrous abuses and immoderate iconic veneration. On the one hand, Counter-Reformation theology sought to reduce the work's impact on irrational sensibility; on the other hand, it urged 'image-makers' to move the spirit and elevate piety, whilst simultaneously avoiding the undesirable secondary effects of awkward or lascivious images. By inter-acting with altarpieces and individual sculptures to make the sermon almost visible, Spanish preachers would reconcile delectare with docere and movere, while shaking up their audiences with the aid of visual imagery. [ABSTRACT FROM AUTHOR]

In Golden Age Spain, religious art functioned within the boundaries of a time-honoured corpus of ecclesiastical and rhetorical theory on the image, which attempted to prevent immoderate iconic veneration aided by metaphors taken from the well-known world of portraiture, the most imitative of pictorial genres. Counter-Reformation theologians and preachers also sought to reduce the artwork's impact on irrational sensibility by urging artists to avoid the undesirable effects of awkward or lascivious images. This article will explore how the laws of decorum equipped Post-Tridentine Spanish imagery with aesthetic values meant to reconcile delectare with docere and moveré, and how this finally resulted in a dispute between high culture and popular taste, between an art favored by royal collectors (painting) and another much more generalized as a result of ecclesiastical patronage (sculpture). [ABSTRACT FROM AUTHOR]

The processes affecting paleoclimate variability and Pleistocene glacial landscape development in the southern mid-latitudes remain poorly understood, in part because of the scarcity of comprehensive, well-studied records. Glacial landforms are invaluable for reconstructing past ice-sheet, climate, and associated environmental changes along the southern Andes, but there are significant spatial and temporal gaps in existing data. In this paper, we present new geomorphic and sedimentologic analyses, including surficial maps, for the Torres del Paine region (51°S, 73°W), southern South America. Our findings provide a new framework for understanding changes in the regional glacier history and Pleistocene landscape development. Glacial extent during the local last glacial maximum (LGM) remains unknown but new chronological data supported by geomorphic evidence afford evidence for a larger ice sheet at Torres del Paine than previously assumed. Deglaciation from the local LGM was underway by 17,400±200(1σ)cal.yr. BP. As opposed to previous suggestions, we have found that most of the moraines fringing the lakes in the Torres del Paine national park were deposited during a late-glacial expansion that occurred between 14,100 and 12,500cal.yr. BP. Late-glacial advances also have been documented recently for the Última Esperanza and Lago Argentino basins to the south and north of Torres del Paine, respectively, suggesting an overall regional ice response to a climate signal. The Tehuelche paleolake accompanied each of the ice-sheet fluctuations in Torres del Paine. New data document at least three main phases of this paleolake, which drained eastward to the Atlantic Ocean, while the Andes gaps were blocked with ice. During the late phase of glacial lake formation, when water levels reached 125–155m a.s.l., the lake likely merged with paleolake Consuelo in the Última Esperanza area at the end of the last glaciation. Lake Tehuelche in Torres del Paine had drained into the Pacific Ocean by the late-glacial period, suggesting that ice southwest of Torres del Paine may have retreated back into the mountains by this time. [ABSTRACT FROM AUTHOR]

This essay analyzes several issues relating to Philip V's art collections, beginning with the influence of his grandfather Louis XIV. Together with dynastic tradition, the awareness of the academic doctrines of Félibien and Le Brun, the closeness to the quietism of Madame Guyon and the familiarity with amateurs such as Piles or Fénelon unquestionably furnished his cultural makeup. Another aspect that I will deal with is the presumed process of españolización of Philip d'Anjou's manners and portraits and the corresponding afrancesamiento of the royal court and its artists. Finally, I will look at the role of Antiquity in the definition of King Philip's collecting preferences. [ABSTRACT FROM AUTHOR]

Reconstructing latest Holocene (<1000 years) glacial landscape development in the Central Andes of Chile (30–35° S) is key for understanding the response of the cryosphere during periods of negative glacier mass balance, such as the current one. The excellently preserved glacial landscape produced during the latest ice advance and retreat cycle is of particular interest for examining the detailed response of glaciers to deglaciation. To establish a conceptual model of glacier behavior under warm and dry climatic conditions, we reconstructed and dated the recent glacial history of the Universidad Glacier (34° S) through detailed geomorphological mapping and 10Be cosmogenic surface exposure dating. Our mapping describes a landsystem that spans from the current ice front to ~3 km down-valley, where a mosaic of glacial landforms includes mounded relief; sinkholes; debris-filled stripes; moraine belts; flutings; and a prominent basal till plain. Our 10Be ages suggest that the Universidad Glacier has fluctuated in its forefield since the 13th – 15th centuries CE. We propose that the glacier evolved from a clean glacier to a debris-covered glacier, to an ice-cored moraine, and finally, to a massive dead-ice topography. This deglacial evolution intermittent and potentially reset by multiple standstills and/or re-advances during the overall retreat. The implication is that phases of active ice were followed by stagnation associated with progressive melting of dead ice under the supraglacial debris layer. Similar geomorphic features and processes are recorded in the present-day Universidad Glacier ablation zone, denoting a recurrent reconditioning over time analogous to the glacier's evolution during the latest Holocene. • We present a deglaciation model for Universidad Glacier in the Central Andes of Chile. • The glacier front progresses to an ice-cored moraine and then to hummocky terrain. • De-icing was interrupted by eight standstills/re-advances of the ice front. • The landsytem includes juxtaposed active and stagnant glacier-derived landforms. • The supraglacial debris layer affects ice dynamics in warm and dry periods. [ABSTRACT FROM AUTHOR]

Climatic and vegetation features of the mid-latitudes of the Southern Hemisphere before the global Last Glacial Maximum (gLGM) are still a matter of discussion. The signatures of Marine Isotope Stage (MIS) 3 show strong variability at the poles that has not yet been resolved at lower latitudes. This work discusses one of the first terrestrial records that reflects the vegetation, glacier, and climate conditions in southern South America during this period. The stratigraphic, palynological, and geomorphological features of the Punta Pihuío, Río Huicha, Punta Pirquén and Punta Detico sites (41–42° S) on the Isla Grande de Chiloé (southern Chile) are described and discussed. Glacially sourced sediment intercalated with peat soils constrained by single-grain feldspar (SGIR50) luminescence and radiocarbon (14C) dating show that the Late MIS 5 and the MIS 3 were periods of high environmental variability at these locations. Pollen records from peat layers indicate an open forest with conifers, Nothofagus and thermophilic elements, such as Myrtaceae, representing interstadial conditions that were abruptly interrupted by glacial expansions during stadials. High variability between arboreal and herbaceous taxa is also interpreted as environmental instability. Moreover, we show that the Patagonian Ice Sheet (PIS) reached full glacial extent during Early to Middle MIS 3, as is also observed in other Southern Hemisphere glacier records on both sides of the Pacific Ocean. Our data support that millennial-to multi-millennial-scale climate changes characterized the pre-gLGM not only at the poles, but also at the southern mid-latitudes. • Interstadial and stadial events are well preserved in terrestrial sediments of Chiloé Island. • The pollen record allows for reconstruction of Late MIS 5 and MIS 3 paleoclimate for southern South America. • We record an early to middle MIS 3 local LGM. • High pre-gLGM environmental variability is recorded at mid-latitudes of South America. [ABSTRACT FROM AUTHOR]

The functional and pathological implications of the enormous genetic diversity of the human genome are mostly unknown, primarily due to our unability to predict pathogenicity in a high-throughput manner. In this work, we characterized the phenotypic consequences of eight naturally-occurring missense variants on the multifunctional and disease-associated NQO1 protein using biophysical and structural analyses on several protein traits. Mutations found in both exome-sequencing initiatives and in cancer cell lines cause mild to catastrophic effects on NQO1 stability and function. Importantly, some mutations perturb functional features located structurally far from the mutated site. These effects are well rationalized by considering the nature of the mutation, its location in protein structure and the local stability of its environment. Using a set of 22 experimentally characterized mutations in NQO1, we generated experimental scores for pathogenicity that correlate reasonably well with bioinformatic scores derived from a set of commonly used algorithms, although the latter fail to semiquantitatively predict the phenotypic alterations caused by a significant fraction of mutations individually. These results provide insight into the propagation of mutational effects on multifunctional proteins, the implementation of in silico approaches for establishing genotype-phenotype correlations and the molecular determinants underlying loss-of-function in genetic diseases. [ABSTRACT FROM AUTHOR]

Southern Hemisphere Holocene glacier chronologies are important for unraveling past climate change, mid-to-high latitude teleconnections, and regional to global climate forcing. At present, a significant number of glacier chronologies for Patagonia are based on 14C dating, which may afford only maximum- or minimum-limiting dates. Here, we combine geomorphology and stratigraphy with radiocarbon (14C) and beryllium-10 (10Be) surface exposure-age dating at three outlet glaciers, Zapata, Tyndall, and Pingo. These glaciers drain the southernmost tip of the Southern Patagonian Ice Field at Torres del Paine National Park, Chile (51°S). After an expansion that we date at 3200 yr. B.P., the Torres del Paine glaciers expanded to their last major Late Holocene maxima at 600 and 340 yr. B.P., with the final dated readvance after 190 yr. B.P. We use these data, together with other Patagonian glacier records, to define the early, mid and final glacial stages of the last millennium. These cold events were separated by warm conditions that allowed the Nothofagus forest to colonize deglaciated land. The presence of near-concurrent glacier fluctuations in Patagonia and Antarctic Peninsula indicates widespread cooling punctuated the Late Holocene, including the last millennium, across much of the extratropical Southern Hemisphere. We link this cooling to cold oceanographic-atmospheric conditions forced by a northern shift or intensification of the Southern Westerly Winds. Such scenario increased northward advection of cold Antarctic circumpolar water along western Patagonia and favored decreased upwelling of warm circumpolar deep water together with expanded sea ice around the Antarctic Peninsula. • We present a 10Be and 14C chronology spanning the Late Holocene of glaciers draining the Southern Patagonian Ice Sheet. • The Zapata, Pingo and Tyndall Glaciers in Torres del Paine advanced by 3,200, 600, 340 and 190 yr B.P. • Patagonian glaciers uncover centennial-scale climate oscillations during the last millennium. • In sync glaciers of Patagonia and Antarctic Peninsula followed the change of the SWW through its link to the Southern Ocean. [ABSTRACT FROM AUTHOR]

Andean glaciers are losing mass rapidly but a centennial‐scale context to those rates is lacking. Here we show the extent of >5,500 glaciers during the Little Ice Age chronozone (LIA; c. 1,400 to c. 1,850) and compute an overall area change of −25% from then to year 2000 at an average rate of −36.5 km2 yr−1 or −0.11% yr−1. Glaciers in the Tropical Andes (Peru, Bolivia) have depleted the most; median −56% of LIA area, and the fastest; median −0.16% yr−1. Up to 10 × acceleration in glacier area loss has occurred in Tropical mountain sub‐regions comparing LIA to 2,000 rates to post‐2000 rates. Regional climate controls inter‐regional variability, whereas local factors affect intra‐region glacier response time. Analyzing glacier area change by river basins and by protected areas leads us to suggest that conservation and environmental management strategies should be re‐visited as proglacial areas expand. Plain Language Summary: Andean glaciers are melting fast but how that rate compares in a longer‐term context is unknown. In this study we mapped the extent of >5,500 glaciers during the Little Ice Age, which was the last major glacial advance culminating about c. 150 years ago. We analyzed the change in glacier size and computed overall area change of −25% from the LIA to year 2000 at a rate of −36.5 km2 per year or −0.11% per year. Glaciers within Peru and Bolivia have shrunk the most by median −56% of LIA area, and the fastest by median −0.16% per year. We discuss that these glaciers are depleting and retreating due to climate change but that response is compounded by glacier size, shape and terminus environment effects. As glaciers melt they reveal proglacial landscapes that tend to be highly unstable, impacting water resources, natural hazards and terrestrial and aquatic ecology. Key Points: Little Ice Age (LIA) chronozone extent of >5,500 glaciers mapped from geomorphological evidenceOverall glacier area change of −25% to year 2000 at a rate of −36.5 km2 yr−1 or −0.11% yr−1Up to 10 × acceleration in glacier area loss for Tropical sub‐regions comparing LIA to 2,000 with post‐2000 rates [ABSTRACT FROM AUTHOR]

Reconstructing the evolution of the glacial landscape of the semi-arid Andes (32°–34° S) during phases of Holocene deglaciation is key to understand the responses of the cryosphere during warmer periods such as the current one. Despite having geomorphological records with good degrees of preservation, few studies have addressed the changes of the Andes during the glacial-paraglacial transition. In this paper, we investigate and compare geomorphological mappings of four glacial sub-basins of the central Andes of Chile: Juncal Norte (32° S, glacier terminus at ~ 3000 m asl.), Loma Larga (33° S, terminus at ~ 3000 m asl.), Nieves Negras (33° S, terminus at ~ 3000 m asl.), and Universidad (34° S, terminus at ~ 2500 m asl.). The ablation zones of Loma Larga and Nieves Negras glaciers have a mantle of debris, which suggests a process of ablation in situ rather than retreat of the glacier tongue. Both glaciers have a morphology of internal collapse in their debris-covered section. On the other hand, Juncal Norte and Universidad glaciers both have lateral moraines with ice cores, where the differential ablation has triggered backwasting and downwasting processes. The presence of ice-cored lateral moraines indicates greater activity of processes in the lateral sections. The Universidad glacier is characterized by two branches feeding the glacier tongue which shows a prominent medial moraine.For the first time in this part of the Andes, we used 36Cl terrestrial cosmogenic nuclides (TCN) for dating deglaciation geomorphology. We complement our 36Cl data with 14C ages that suggest that glaciers advanced before ~2500 and then before ~850/1000 years BP.The combination of the geomorphology and the geochronology in the different proglacial areas allows the analysis of the deglaciation history and related processes. Identifying how ablation occurs in semi-arid mountain environments is important to assess the behaviour of ice under changing climatic conditions and its preservation under a cover of debris. One of the characteristics and challenges of the deglaciation in the semi-arid Andes is the high production of debris in the ablation zones. [ABSTRACT FROM AUTHOR]

Background: Alemtuzumab is a high-efficacy treatment approved for relapsing-remitting multiple sclerosis (RRMS). Although clinical trials and observational studies are consistent in showing its efficacy and manageable safety profile, further studies under clinical practice conditions are needed to further support its clinical use. Objective: The aim of this observational retrospective study was to evaluate the effectiveness and safety of alemtuzumab to add to the current real-world evidence on the drug. Methods: A cohort of 115 adult patients with RRMS treated with alemtuzumab between 2014 and 2020 was retrospectively followed up in five centers in Spain. Analysis included annualized relapse rate (ARR), 6-month confirmed disability worsening (CDW), 6-month confirmed disability improvement (CDI), radiological activity, no evidence of disease activity (NEDA-3), and safety signals. Given the different follow-up periods among participants, ARR was calculated using the person-years method. CDI was defined as a ≥ 1.0-point decrease in Expanded Disability Status Scale (EDSS) score assessed in patients with a baseline EDSS score ≥ 2.0 confirmed 6 months apart. CDW was defined as a ≥ 1.0-point increase in EDSS score assessed in patients with a baseline EDSS score ≥ 1.0 (≥ 1.5 if baseline EDSS = 0), confirmed 6 months apart. Results: ARR decreased from 1.9 (95% confidence interval 1.60–2.33) in the year prior to alemtuzumab initiation to 0.28 (0.17–0.37) after 1 year of treatment (87% reduction), and to 0.22 (0.13–0.35) after the second year. Over the entire follow-up period, ARR was 0.24 (0.18–0.30). At year 1, 75% of patients showed no signs of magnetic resonance imaging (MRI) activity and 70% at year 5. One percent of patients experienced 6-month CDW at year 1, 2.6% at year 2, 7.4% at year 3, and no patients over years 4 and 5. A total of 7.7% of patients achieved 6-month CDI in year 1, 3.6% in year 2, and maintained it at years 3 and 4. Most patients achieved annual NEDA-3: year 1, 72%; year 2, 79%; year 3, 80%; year 4, 89%; year 5, 75%. Infusion-related reactions were observed in 95% of patients and infections in 74%. Thyroid disorders occurred in 30% of patients, and only three patients developed immune thrombocytopenia. No cases of progressive multifocal leukoencephalopathy were reported. Conclusions: This study shows that alemtuzumab reduced the relapse rate and disability worsening in real-world clinical practice, with many patients achieving and sustaining NEDA-3 over time. The safety profile of alemtuzumab was consistent with previous findings, and no new or unexpected safety signals were observed. As this was an observational and retrospective study, the main limitation of not having all variables comprehensively available for all patients should be considered when interpreting results. [ABSTRACT FROM AUTHOR]

A large conformational heterogeneity of human NAD(P)H:quinone oxidoreductase 1 (NQO1), a flavoprotein associated with various human diseases, has been observed to occur in the catalytic site of the enzyme. Here, we report the X‐ray structure of NQO1 with phenylmethylsulfonyl fluoride (PMSF) at 1.6 Å resolution. Activity assays confirmed that, despite being covalently bound to the Tyr128 residue at the catalytic site, PMSF did not abolish NQO1 activity. This may indicate that the PMSF molecule does not reduce the high flexibility of Tyr128, thus allowing NADH and DCPIP substrates to bind to the enzyme. Our results show that targeting Tyr128, a key residue in NQO1 function, with small covalently bound molecules could possibly not be a good drug discovery strategy to inhibit this enzyme. [ABSTRACT FROM AUTHOR]

The long-term climate dynamics of the central Andes are part of an ongoing international research effort to reconstruct past climatic variations and sensitivity to different regional and global drivers during the last 50,000 years. The large number of diverse records, however, makes it difficult to compare results without an integrated spatial analysis that considers the nature of the record and whether they are integrating environmental conditions across a large basin (i.e., a lake record) or at a very local scale (such as a rodent midden). We compiled 92 records from the southern sector of the central Andes (SCA, 18°-35°S). Recalibrated records were further compared by converting the original author's interpretation into a scale of relative moisture anomalies (compared to the present) that ranges from −2 (very dry) to very wet (+2). Moisture anomaly maps were generated for intervals at 4, 6, 9.5, 14, 17, 21 and 32 ka BP (103 calibrated 14C years before present) using records within a 5% age uncertainty. Our compilations show a surprising degree of agreement in the extent and magnitude of past climate changes during late Pleistocene, but less spatial agreement during the Holocene. The TRACE21 transient climate model shows similar results, with better agreement during the Pleistocene compared to the Holocene. Our analyses not only reveal discrepancies between proxy record interpretations at sites from the same region but show which regions in the SCA require more study. • We compiled 92 paleorecords from the South-Central Andes and produced paleoclimate maps from 32 to 4 ky. • The wettest period in our maps occurs at 17 ky BP during Heinrich Event 1. • Holocene maps show much less spatial agreement than reconstructions for the Pleistocene. • Proxy-model comparisons using TRACE21 show better agreement in Late Pleistocene maps than for Holocene maps. • The most arid period recorded occurred in the map of 6 ky BP (Northgrippian). [ABSTRACT FROM AUTHOR]

Raised shorelines and associated lacustrine sediments in the central Estrecho de Magallanes (Strait of Magellan) have been interpreted as products of cordilleran glaciers impounding a large proglacial lake and preventing drainage to the South Pacific and Southern Ocean during the Late glacial between c. 15.0 and 12.0 cal ka BP. However, a growing body of glacial geological evidence points towards an earlier retreat of the Magellan cordilleran ice dome, insufficient to dam lakes at that time. We critically re-evaluate the extant evidence for the c. 15.0–12.0 cal ka BP lake, here named 'Lago Kawésqar', and provide further sedimentological and chronological evidence for its existence. We also provide new cosmogenic surface nuclide dating of erratic and bedrock samples collected from extensive field campaigns that confirm the rapid and widespread retreat of the Magellan ice fields to the inner fjords of the Fuegian archipelago by c. 16.0 ka. To resolve the apparent paradox between these two lines of evidence we propose that glacial isostatic adjustment led to a topographic barrier to lake drainage rather than an ice dam. We use Glacial Isostatic Adjustment modelling to demonstrate that rapid isostatic recovery following the early deglaciation after c. 17.0 cal ka BP likely led to elevation of the present shallow south-western coastal margin of the Fuegian archipelago. Final drainage of Lago Kawésqar was probably caused by neotectonic subsidence of the same margin along the boundary of the South American – Scotia tectonic plates at c. 12.0 cal ka BP. • Evidence for a large Late glacial lake in the Strait of Magellan is confirmed. • New ages for deglaciation of the Magellan ice dome after the LGM are presented. • An alternative theory for the damming of the Late glacial Magellan lake is discussed. • Glacial isostatic adjustment modelling supports bedrock uplift damming the lake. • A neotectonic event likely led to final drainage of the Magellan lake. [ABSTRACT FROM AUTHOR]

HIF-1α is a master regulator of oxygen homeostasis involved in different stages of cancer development. Thus, HIF-1α inhibition represents an interesting target for anti-cancer therapy. It was recently shown that the HIF-1α interaction with NQO1 inhibits proteasomal degradation of the former, thus suggesting that targeting the stability and/or function of NQO1 could lead to the destabilization of HIF-1α as a therapeutic approach. Since the molecular interactions of NQO1 with HIF-1α are beginning to be unraveled, in this review we discuss: (1) Structure–function relationships of HIF-1α; (2) our current knowledge on the intracellular functions and stability of NQO1; (3) the pharmacological modulation of NQO1 by small ligands regarding function and stability; (4) the potential effects of genetic variability of NQO1 in HIF-1α levels and function; (5) the molecular determinants of NQO1 as a chaperone of many different proteins including cancer-associated factors such as HIF-1α, p53 and p73α. This knowledge is then further discussed in the context of potentially targeting the intracellular stability of HIF-1α by acting on its chaperone, NQO1. This could result in novel anti-cancer therapies, always considering that the substantial genetic variability in NQO1 would likely result in different phenotypic responses among individuals. [ABSTRACT FROM AUTHOR]

The different types of cyber-attacks on information and telecommunications systems are becoming increasingly sophisticated and complex, with several defined phases (attack pattern). Therefore, it is necessary to research and develop new infrastructures to understand and detect them. This work addresses the design and implementation of a system capable of detecting, analyzing, modeling and visualizing attack patterns in real time to build a dataset with labeled events attacks. The system consists of the three subsystems, detection of attack events subsystem; attack events analysis subsystem to model active patterns based on Common Attack Pattern Enumeration and Classification (CAPEC) definitions; and the attack pattern visualization subsystem. The results obtained from the attacks carried out over a period of six months under a series of assumptions are shown. These results have allowed the construction of a dataset with attack events labelled according to the possible attack patterns to which they belong. The developed system can provide an organization with a very real situational awareness of the cybersecurity situation. [ABSTRACT FROM AUTHOR]

Using the multiband imager MapCam on board the OSIRIS-REx (Origins, Spectral Interpretation, Resource Identification, and Security–Regolith Explorer) spacecraft, we identified 77 instances of proposed exogenic materials distributed globally on the surface of the B-type asteroid (101955) Bennu. We identified materials as exogenic on the basis of an absorption near 1  |$\mu$| m that is indicative of anhydrous silicates. The exogenic materials are spatially resolved by the telescopic camera PolyCam. All such materials are brighter than their surroundings, and they are expressed in a variety of morphologies: homogeneous, breccia-like, inclusion-like, and others. Inclusion-like features are the most common. Visible spectrophotometry was obtained for 46 of the 77 locations from MapCam images. Principal component analysis indicates at least two trends: (i) mixing of Bennu's average spectrum with a strong 1- |$\mu$| m band absorption, possibly from pyroxene-rich material, and (ii) mixing with a weak 1- |$\mu$| m band absorption. The end member with a strong 1- |$\mu$| m feature is consistent with Howardite-Eucrite-Diogenite (HED) meteorites, whereas the one showing a weak 1- |$\mu$| m feature may be consistent with HEDs, ordinary chondrites, or carbonaceous chondrites. The variation in the few available near-infrared reflectance spectra strongly suggests varying compositions among the exogenic materials. Thus, Bennu might record the remnants of multiple impacts with different compositions to its parent body, which could have happened in the very early history of the Solar system. Moreover, at least one of the exogenic objects is compositionally different from the exogenic materials found on the similar asteroid (162173) Ryugu, and they suggest different impact tracks. [ABSTRACT FROM AUTHOR]

The hyperarid Atacama Desert coast receives scarce moisture inputs mainly from the Pacific Ocean in the form of marine advective fog. The collected moisture supports highly specialized ecosystems, where the bromeliad Tillandsia landbeckii is the dominant species. The fog and low clouds (FLCs) on which these ecosystems depend are affected in their interannual variability and spatial distribution by global phenomena, such as ENSO. Yet, there is a lack of understanding of how ENSO influences recent FLCs spatial changes and their interconnections and how these variations can affect existing Tillandsia stands. In this study, we analyze FLCs occurrence, its trends and the influence of ENSO on the interannual variations of FLCs presence by processing GOES satellite images (1995–2017). Our results show that ENSO exerts a significant influence over FLCs interannual variability in the Atacama at ~ 20°S. Linear regression analyses reveal a relation between ENSO3.4 anomalies and FLCs with opposite seasonal effects depending on the ENSO phase. During summer (winter), the ENSO warm phase is associated with an increase (decrease) of the FLCs occurrence, whereas the opposite occurs during ENSO cool phases. In addition, the ONI Index explains up to ~ 50 and ~ 60% variance of the interannual FLCs presence in the T. landbeckii site during summer and winter, respectively. Finally, weak negative (positive) trends of FLCs presence are observed above (below) 1000 m a. s. l. These results have direct implications for understanding the present and past distribution of Tillandsia ecosystems under the extreme conditions characterizing our study area. [ABSTRACT FROM AUTHOR]

The interplay between plants and soil drives the structure and function of soil microbial communities. In water-limited environments where vascular plants are often absent and only specialized groups of rootless plants grow, this interaction could be mainly asymmetric, with plants supporting nutrients and resources via litter deposition. In this study, we use observational approaches to evaluate the impact of local distribution of Tillandsia landbeckii across elevation on soil bacterial community structure and composition in the Atacama Fog Desert. Tillandsia landbeckii is a plant without functional roots that develops on meter-scale sand dunes and depends mainly on marine fog that transports resources (water and nutrients) from the Pacific Ocean. Our data show that soil bacterial abundance, richness, and diversity were significantly higher beneath T. landbeckii plants relative to bare soils. However, these differences were not significant across T. landbeckii located at different elevations and with different input of marine fog. On the other hand, bacterial community composition was significantly different with T. landbeckii plants across elevations. Further, samples beneath T. landbeckii and bare soils showed significant differences in bacterial community composition. Around 99% of all operational taxonomic units (OTUs) were recorded exclusively beneath T. landbeckii, and only 1% of OTUs were observed in bare soils. These findings suggest that the presence of T. landbeckii promotes significant increases in bacterial abundance and diversity compared with bare soils, although we fail to demonstrate that local-scale changes in elevation can affect patterns of soil bacterial diversity and abundance beneath T. landbeckii. [ABSTRACT FROM AUTHOR]

We map the glacial geomorphology of the former Patagonian Ice Sheet between 44°S and 46°S. Building on previous work, our map covers a ~50,000 km² region of west-central Patagonia. The study area includes the eastward-flowing Río Pico, Río Caceres, Río Cisnes, Lago Plata-Fontana, El Toqui, Lago Coyt/Río Ñirehuao, Simpson/Paso Coyhaique, and Balmaceda palaeo-outlet glaciers, adjacent valleys, and the Andean Cordillera. The inventory contains >70,000 individual landforms mapped from remotely-sensed imagery and field surveys. Mapping was classified into ice-marginal (e.g. moraine ridges, trimlines), subglacial (e.g. glacial lineations, flutes), glaciolacustrine (e.g. palaeolake shorelines, perched deltas), glaciofluvial (e.g. proglacial outwash plains, meltwater channels), and non-glacial (e.g. palaeochannels, landslides or slumps) landform groups. The new map will inform future interpretations of regional glacier dynamics, and the development of robust geochronological datasets that test the timing of glaciation and deglaciation. [ABSTRACT FROM AUTHOR]

Background: Turner syndrome is a genetic disorder that affects women. It is caused by an absent or incomplete X chromosome, which can be presented in mosaicism or not. There are 12 cases of Turner syndrome patients who present structural alterations in autosomal chromosomes. Case presentation: The present case report describes a patient with a reciprocal, maternally inherited translocation between chromosomes 2 and 12 with a mosaicism of X monosomy 45,X,t(2;12)(p13;q24)[95]/46,XX,t(2;12)(p13;q24)[5]. Through genetic mapping arrays, altered genes in the patient were determined within the 23 chromosome pairs. These genes were associated with the patient's clinical features using a bioinformatics tool. Conclusion: To our knowledge, this is the first case in which a translocation (2;12) is reported in a patient with Turner syndrome and confirmed by conventional cytogenetics, FISH and molecular genetics. Clinical features of our patient are closely related with the loss of one X chromosome, however mild intellectual disability can be likely explained by autosomal genes. The presence of familial translocations was a common finding, thus emphasizing the need for familiar testing for further genetic counselling. [ABSTRACT FROM AUTHOR]

The northern Chilean Atacama Desert is among those regions on Earth where life exists at its dry limits. There is almost zero rainfall in its core zone, and the only source of water is a spatio-temporally complex fog system along the Pacific coast, which is reaching far into the hyperarid mainland. Hardly any vascular plants grow in these areas, and, thus, it is intriguing to be faced with a vegetation-type build-up by one single and highly specialized bromeliad species, Tillandsia landbeckii Phil., forming regular linear structures in a sloped landscape. We studied the genetic make-up of a population system extending an area of approximately 1500 km2 and demonstrated a fine-scale correlation of genetic diversity with spatial population structure and following an elevational gradient of approximately 150 m. Increase in genetic diversity is correlated with increased fitness as measured by flowering frequency, and evidence is provided that outbreeding is linked with a large-distance flying pollinator feeding occasionally as generalist on its flowers, but not using the plant as source for larvae feeding. Our data demonstrate that establishment of linear vegetation structure is in principle a process driven by clonal growth and propagation of ramets over short distances. However, optimal conditions (slope, elevation, fog occurrence) for linear growth pattern formation also increase sexual plant reproductive fitness, thus providing the reservoir for newly combined genetic variation and counteracting genetic uniformity. Our study highlights the Tillandsia vegetation, also called Tillandsia lomas, as unique and genetically diverse system, which is highly threatened by global climate change and disturbance of the coastal fog system. [ABSTRACT FROM AUTHOR]

The northern Chilean Atacama Desert is among those regions on Earth where life exists at its dry limits. There is almost zero rainfall in its core zone, and the only source of water is a spatio-temporally complex fog system along the Pacific coast, which is reaching far into the hyperarid mainland. Hardly any vascular plants grow in these areas, and, thus, it is intriguing to be faced with a vegetation-type build-up by one single and highly specialized bromeliad species, Tillandsia landbeckii Phil., forming regular linear structures in a sloped landscape. We studied the genetic make-up of a population system extending an area of approximately 1500 km2 and demonstrated a fine-scale correlation of genetic diversity with spatial population structure and following an elevational gradient of approximately 150 m. Increase in genetic diversity is correlated with increased fitness as measured by flowering frequency, and evidence is provided that outbreeding is linked with a large-distance flying pollinator feeding occasionally as generalist on its flowers, but not using the plant as source for larvae feeding. Our data demonstrate that establishment of linear vegetation structure is in principle a process driven by clonal growth and propagation of ramets over short distances. However, optimal conditions (slope, elevation, fog occurrence) for linear growth pattern formation also increase sexual plant reproductive fitness, thus providing the reservoir for newly combined genetic variation and counteracting genetic uniformity. Our study highlights the Tillandsia vegetation, also called Tillandsia lomas, as unique and genetically diverse system, which is highly threatened by global climate change and disturbance of the coastal fog system. [ABSTRACT FROM AUTHOR]

Background: Since 1969, 49 cases have been presented on ring chromosome 4. All of these cases have been characterized for the loss of genetic material. The genes located in these chromosomal regions are related to the phenotype. Case presentation: A 10-year-old Ecuadorian Mestizo girl with ring chromosome 4 was clinically, cytogenetically and molecularly analysed. Clinical examination revealed congenital anomalies, including microcephaly, prominent nose, micrognathia, low set ears, bilateral clinodactyly of the fifth finger, small sacrococcygeal dimple, short stature and mental retardation. Cytogenetic studies showed a mosaic karyotype, mos 46,XX,r(4)(p16.3q35.2)/46,XX, with a ring chromosome 4 from 75 to 79% in three studies conducted over ten years. These results were confirmed by fluorescence in situ hybridization (FISH). Loss of 1.7 Mb and gain of 342 kb in 4p16.3 and loss of 3 Mb in 4q35.2 were identified by high-resolution mapping array. Conclusion: Most cases with ring chromosome 4 have deletion of genetic material in terminal regions; however, our case has inv dup del rearrangement in the ring chromosome formation. Heterogeneous clinical features in all cases reviewed are related to the amount of genetic material lost or gained. The application of several techniques can increase our knowledge of ring chromosome 4 and its deviations from typical "ring syndrome." [ABSTRACT FROM AUTHOR]

Abstract Over a quarter million of protein phosphorylation sites have been identified so far, although the effects of site-specific phosphorylation on protein function and stability, as well as their possible impact in the phenotypic manifestation in genetic diseases are vastly unknown. We investigated here the effects of phosphorylating S82 in human NADP(H):quinone oxidoreductase 1, a representative example of disease-associated flavoprotein in which protein stability is coupled to the intracellular flavin levels. Additionally, the cancer-associated P187S polymorphism causes inactivation and destabilization of the enzyme. By using extensive in vitro and in silico characterization of phosphomimetic S82D mutations, we showed that S82D locally affected the flavin binding site of the wild-type (WT) and P187S proteins thus altering flavin binding affinity, conformational stability and aggregation propensity. Consequently, the phosphomimetic S82D may destabilize the WT protein intracellularly by promoting the formation of the degradation-prone apo-protein. Noteworthy, WT and P187S proteins respond differently to the phosphomimetic mutation in terms of intracellular stability, further supporting differences in molecular recognition of these two variants by the proteasomal degradation pathway. We propose that phosphorylation could have critical consequences on stability and function of human flavoproteins, important for our understanding of genotype-phenotype relationships in their related genetic diseases. Highlights • Flavoproteins are often phosphorylated but their consequences are not known well. • We investigated phosphorylation in NQO1 using a phosphomimetic S82D mutant. • S82D affects protein structure and dynamics of the FAD binding site. • S82D increases the population of the apo-state and may destabilize NQO1 in cells. • Phosphorylation can be critical for the stability/function of the flavoproteome. [ABSTRACT FROM AUTHOR]

The first satellite-derived inventory of glaciers and rock glaciers in Chile, created from Landsat TM/ETM+ images spanning between 2000 and 2003 using a semi-automated procedure, is presented in a single standardized format. Large glacierized areas in the Altiplano, Palena Province and the periphery of the Patagonian icefields are inventoried. The Chilean glacierized area is 23 708 ± 1185 km2, including ~3200 km2 of both debris-covered glaciers and rock glaciers. Glacier distribution varies as a result of climatic gradients with latitude and elevation, with 0.8% occurring in the Desert Andes (17°30′–32° S); 3.6% in the Central Andes (32–36° S), 6.2% in the Lakes District and Palena Province (36–46° S), and 89.3% in Patagonia and Tierra del Fuego (46–56° S). Glacier outlines, across all glacierized regions and size classes, updated to 2015 using Landsat 8 images for 98 complexes indicate a decline in areal extent affecting mostly clean-ice glaciers (−92.3 ± 4.6 km2), whereas debris-covered glaciers and rock glaciers in the Desert and Central Andes appear nearly unchanged in their extent. Glacier attributes estimated from this new inventory provide valuable insights into spatial patterns of glacier shrinkage for assessing future glacier changes in response to climate change. [ABSTRACT FROM AUTHOR]

Unique fog ecosystems that occur inland along the Chilean coastal desert are dominated by Tillandsia landbeckii. The average annual precipitation in this hyperarid area lies below 1 mm per year. Tillandsia are specialized in the foliar uptake of fog as a main source of water. The detailed mapping of the distribution of Tillandsia is lacking, making it difficult to understand their geo-ecological niche and to determine the impacts that climate change may have on this species. The objective of this study is to create a detailed spatial distribution of Tillandsia in the Atacama Desert in northern Chile based on remote sensing semi-automatic detection process. For this purpose, high-resolution WorldView-3 optical satellite data has been acquired. The extraction of Tillandsia was done with ENVI Deep Learning tools. As a result, a map of Tillandsia has been created. Several fields were found between Cerro Huantajaya in the north and Cerro Soronal in the south in the study area between 800 and 1300 m a.s.l. For validation purposes ground truth data has been used. The overall accuracy of this classification is 92.02%. The results can be used as a basis for geo-ecological niche modeling, further monitoring and for the development of conservation strategies. • High resolution map of Tillandsia distribution in the Atacama Desert was created. • A remote sensing-based approach has been developed, using WorldView-3 satellite data. • The overall accuracy of the classification is 92.02%, based on deep learning approach. • The developed workflow can be used for monitoring of Tillandsia for other regions. • Results can be used as a basis for geo-ecological niche modeling of fog ecosystems. [ABSTRACT FROM AUTHOR]

Background: MicroRNAs are known to inhibit gene expression by binding to the 3'UTR of the target transcript. Downregulation of miR-223 has been recently reported to have prognostic significance in CLL. However, there is no evidence of the pathogenetic mechanism of this miRNA in CLL patients. Methods: By applying next-generation sequencing techniques we have detected a common polymorphism (rs2307842), in 24% of CLL patients, which disrupts the binding site for miR-223 in HSP90B1 3'UTR. We investigated whether miR-223 directly targets HSP90B1 through luciferase assays and ectopic expression of miR-223. Quantitative real-time polymerase chain reaction and western blot were used to determine HSP90B1 expression in CLL patients. The relationship between rs2307842 status, HSP90B1 expression and clinico-biological data were assessed. Results: HSP90B1 is a direct target for miR-223 by interaction with the putative miR-223 binding site. The analysis in paired samples (CD19+ fraction cell and non-CD19+ fraction cell) showed that the presence of rs2307842 and IGHV unmutated genes determined HSP90B1 overexpression in B lymphocytes from CLL patients. These results were confirmed at the protein level by western blot. Of note, HSP90B1 overexpression was independently predictive of shorter time to the first therapy in CLL patients. By contrast, the presence of rs2307842 was not related to the outcome. Conclusions: HSP90B1 is a direct target gene of miR-223. Our results provide a plausible explanation of why CLL patients harboring miR-223 downregulation are associated with a poor outcome, pointing out HSP90B1 as a new pathogenic mechanism in CLL and a promising therapeutic target. [ABSTRACT FROM AUTHOR]

To assess the presence of genetic imbalances in patients with myeloproliferative neoplasms (MPNs), 38 patients with chronic eosinophilia were studied by array comparative genomic hybridization ( aCGH): seven had chronic myelogenous leukaemia (CML), BCR-ABL1 positive, nine patients had myeloproliferative neoplasia Ph− (MPN-Ph−), three had a myeloid neoplasm associated with a PDGFRA rearrangement, and the remaining two cases were Lymphoproliferative T neoplasms associated with eosinophilia. In addition, 17 patients had a secondary eosinophilia and were used as controls. Eosinophilic enrichment was carried out in all cases. Genomic imbalances were found in 76% of all MPN patients. Losses on 20q were the most frequent genetic abnormality in MPNs (32%), affected the three types of MPN studied. This study also found losses at 11q13.3 in 26% of patients with MPN-Ph− and in 19p13.11 in two of the three patients with an MPN associated with a PDGFRA rearrangement. In addition, 29% of patients with CML had losses on 8q24. In summary, aCGH revealed clonality in eosinophils in most MPNs, suggesting that it could be a useful technique for defining clonality in these diseases. The presence of genetic losses in new regions could provide new insights into the knowledge of these MPN associated with eosinophilia. [ABSTRACT FROM AUTHOR]