Magnetic sustentation as an adsorption characterization technique for paramagnetic metal-organic frameworks.

Nowadays, there are many reliable characterization techniques for the study of adsorption properties in gas phase. However, the techniques available for the study of adsorption processes in solution, rely on indirect characterization techniques that measure the adsorbate concentration remaining in solution. In this work, we present a sensing method based on the magnetic properties of metal-organic frameworks (MOFs) containing paramagnetic metal centres, which stands out for the rapidity, low cost and in situ direct measurement of the incorporated adsorbate within the porous material. To illustrate this sensing technique, the adsorption in solution of four MOFs have been characterized: MIL-88A(Fe), MOF-74(Cu, Co) and ZIF-67(Co). Our simple and efficient method allows the direct determination of the adsorbed mass, as well as the measurement of adsorption isotherm curves, which we hope will greatly advance the study of adsorption processes in solution, since this method is independent of the chemical nature of the adsorbate that often makes its quantification difficult.

Copper(II) invigorated EHU-30 for continuous electroreduction of CO2 into value-added chemicals.

The doping of zirconium based EHU-30 and EHU-30-NH2 metal-organic frameworks with copper(II) yielded a homogeneous distribution of the dopant with a copper/zirconium ratio of 0.04-0.05. The doping mechanism is analysed by chemical analysis, microstructural analysis and pair distribution function (PDF) analysis of synchrotron total scattering data in order to get deeper insight into the local structure. According to these data, the Cu(II) atoms are assembled within the secondary building unit by a transmetalation reaction, contrarily to UiO-66 series in which the post-synthetic metalation of the MOF takes place through chemical anchorage. The resulting materials doubled the overall performance of the parent compounds for the CO2 electroreduction, while retained stable the performance during continuous transformation reaction.

The Chemistry of Zirconium/Carboxylate Clustering Process: Acidic Conditions to Promote Carboxylate-Unsaturated Octahedral Hexamers and Pentanuclear Species.

Clustering chemistry is a key point in the design and synthesis of the secondary building units that comprise metal-organic frameworks (MOFs) based on group IV metals. In this work, the first stages of the zirconium-carboxylate clustering process in alcohol/water mixtures are studied in detail using the monocarboxylic benzoic and hydroxybenzoic acids to avoid the polymerization. Mass spectroscopy measurements performed on the reactions revealed the presence of hexa- and pentanuclear species even at low pH values and also evidenced the acid-base nature and pH dependence of the transformation between both species. The control on the chemistry governing the equilibria between these species has allowed us to isolate six new compounds in the solid state. The single-crystal X-ray diffraction analysis revealed that they are closely related to the well-known [Zr6(O)4(OH)4(OOC)12] secondary building unit found in many MOFs by removing carboxylic ligands in the case of the hexameric species ([Zr6(O)4(OH)4(OOC)8(H2O)8]4+) or by additionally removing one of the metal centers in the case of the pentameric entities ([Zr5(O)2(OH)6(OOC)4(H2O)11(alcohol)]6+). Going in detail, the unsaturated hexameric clusters exhibit different dispositions of their eight carboxylate ligands in such a way that the remaining four carboxylate-free positions are arranged according to a square planar or tetrahedral symmetry. It should be highlighted that the pentameric complexes imply an unprecedented core nuclearity in zirconium clusters and thus their isolation provides a novel building block for the design of metal-organic materials.

Secondary CoQ10 deficiency, bioenergetics unbalance in disease and aging.

Coenzyme Q10 (CoQ10 ) deficiency is a rare disease characterized by a decreased accumulation of CoQ10 in cell membranes. Considering that CoQ10 synthesis and most of its functions are carried out in mitochondria, CoQ10 deficiency cases are usually considered a mitochondrial disease. A relevant feature of CoQ10 deficiency is that it is the only mitochondrial disease with a successful therapy available, the CoQ10 supplementation. Defects in components of the synthesis machinery caused by mutations in COQ genes generate the primary deficiency of CoQ10 . Mutations in genes that are not directly related to the synthesis machinery cause secondary deficiency. Cases of CoQ10 deficiency without genetic origin are also considered a secondary deficiency. Both types of deficiency can lead to similar clinical manifestations, but the knowledge about primary deficiency is deeper than secondary. However, secondary deficiency cases may be underestimated since many of their clinical manifestations are shared with other pathologies. This review shows the current state of secondary CoQ10 deficiency, which could be even more relevant than primary deficiency for clinical activity. The analysis covers the fundamental features of CoQ10 deficiency, which are necessary to understand the biological and clinical differences between primary and secondary CoQ10 deficiencies. Further, a more in-depth analysis of CoQ10 secondary deficiency was undertaken to consider its origins, introduce a new way of classification, and include aging as a form of secondary deficiency.

Acquired cancer cell resistance to T cell bispecific antibodies and CAR T targeting HER2 through JAK2 down-modulation.

Immunotherapy has raised high expectations in the treatment of virtually every cancer. Many current efforts are focused on ensuring the efficient delivery of active cytotoxic cells to tumors. It is assumed that, once these active cytotoxic cells are correctly engaged to cancer cells, they will unfailingly eliminate the latter, provided that inhibitory factors are in check. T cell bispecific antibodies (TCBs) and chimeric antigen receptors (CARs) offer an opportunity to test this assumption. Using TCB and CARs directed against HER2, here we show that disruption of interferon-gamma signaling confers resistance to killing by active T lymphocytes. The kinase JAK2, which transduces the signal initiated by interferon-gamma, is a component repeatedly disrupted in several independently generated resistant models. Our results unveil a seemingly widespread strategy used by cancer cells to resist clearance by redirected lymphocytes. In addition, they open the possibility that long-term inhibition of interferon-gamma signaling may impair the elimination phase of immunoediting and, thus, promote tumor progression.

Long-term monitoring of the Iberian ibex population in the Sierra Nevada of the southeast Iberian Peninsula.

This dataset provides long-term information on the presence of the Iberian ibex (Capra pyrenaica hispanica Schimper, 1848) in Sierra Nevada (SE Iberian Peninsula). Data on the abundance and demographic structure of the Iberian ibex population were compiled over the last three decades. Transects were laid out to record different variables such as the number of individuals sighted, the perpendicular distance of each group of Iberian ibex to the transect line and sex as well as age of individuals in the case of males. These data enabled the calculation of population parameters such as density, sex ratio, birth rate, and age structure. These parameters are key for Iberian ibex conservation and management, given that Sierra Nevada harbours the largest population of this species in the Iberian Peninsula. The data set we present is structured using the Darwin Core biological standard, which contains 3,091 events (582 transect walk events and 2,509 group sighting events), 5,396 occurrences, and 2,502 measurements. The occurrences include the sightings of 11,436 individuals (grouped by sex and age) from 1993 to 2018 in a total of 88 transects distributed along Sierra Nevada, of which 33 have been continuously sampled since 2008.

The Second Generation Antibody-Drug Conjugate SYD985 Overcomes Resistances to T-DM1.

Trastuzumab-emtansine (T-DM1) is an antibody-drug conjugate (ADC) approved for the treatment of HER2 (human epidermal growth factor receptor 2)-positive breast cancer. T-DM1 consists of trastuzumab covalently linked to the cytotoxic maytansinoid DM1 via a non-cleavable linker. Despite its efficacy, primary or acquired resistance frequently develops, particularly in advanced stages of the disease. Second generation ADCs targeting HER2 are meant to supersede T-DM1 by using a cleavable linker and a more potent payload with a different mechanism of action. To determine the effect of one of these novel ADCs, SYD985, on tumors resistant to T-DM1, we developed several patient-derived models of resistance to T-DM1. Characterization of these models showed that previously described mechanisms-HER2 downmodulation, impairment of lysosomal function and upregulation of drug efflux pumps-account for the resistances observed, arguing that mechanisms of resistance to T-DM1 are limited, and most of them have already been described. Importantly, SYD985 was effective in these models, showing that the resistance to first generation ADCs can be overcome with an improved design.

Adenine nucleobase directed supramolecular architectures based on ferrimagnetic heptanuclear copper(II) entities and benzenecarboxylate anions.

Two planar organic anions, benzoate and benzene-1,4-dicarboxylate (terephthalate), have been selected as potential π-stacking intercalators among ferrimagnetic [Cu7(µ-adeninato)6(µ3-OH)6(µ-H2O)6]2+ heptameric discrete entities. The resulting supramolecular architecture is highly dependent on the negative charge density distribution, mainly located in the carboxylate groups of the organic anions. In this sense, the benzoate anion, with just one carboxylate group, does not allow its intercalation between the adeninato ligands as it would imply a high steric hindrance among the heptameric entities. As a consequence, these benzoate anions are located inside the voids of the crystal structure reducing the accessible volume of compound [Cu7(µ-adeninato)6(µ3-OH)6(µ-H2O)6](benzoate)2·~17H2O (1). On the contrary, the terephthalate anion, containing two carboxylate groups at opposite sites, adopts a π-stacking sandwich arrangement between two adeninato ligands that affords the porous open structure of formula [Cu7(µ-adeninato)6(µ3-OH)6(µ-H2O)6](terephthalate)·nH2O (2a, 2b; n: 12 and 24, respectively). In addition to that, the less directional nature of the π-stacking interactions in comparison to the complementary hydrogen bonding based supramolecular metal-organic frameworks (SMOFs), suits them with a flexible architecture able to reversibly adsorb/desorb water (up to a 25-30% at 20 °C) altogether with the expansion/shrinkage of the crystal structure. The bridging adeninato and hydroxido ligands are effective magnetic exchange mediators to provide a ST = 5/2 ferrimagnetic state for the heptanuclear entity.

Dataset of occurrence and incidence of pine processionary moth in Andalusia, south Spain.

This dataset provides information about infestation caused by the pine processionary moth (Thaumetopoeapityocampa ([Denis & Schiffermüller], 1775)) in pure or mixed pine woodlands and plantations in Andalusia. It represents a long-term series (1993-2015) containing 81,908 records that describe the occurrence and incidence of this species. Data were collected within a monitoring programme known as COPLAS, developed by the Regional Ministry of Environment and Territorial Planning of the Andalusian Regional Government within the frame of the Plan de Lucha Integrada contra la Procesionaria del Pino (Plan for Integrated Control Against the Pine Processionary Moth). In particular, this dataset includes 4,386 monitoring stands which, together with the campaign year, define the dataset events in Darwin Core Archive. Events are related with occurrence data which show if the species is present or absent. In turn, the event data have a measurement associated: degree of infestation.

[Zr6O4(OH)4(benzene-1,4-dicarboxylato)6]n: a hexagonal polymorph of UiO-66.

Since its discovery in 2008, the paradigmatic UiO-66 has behaved as the germ that has prompted the chemistry of group-4 metal based metal-organic frameworks, all of them featuring outstanding thermal and chemical stability. Herein we present the first polymorph of UiO-66 and the key conditions that led to its formation.

Effects of hour of training and exercise intensity on nocturnal autonomic modulation and sleep quality of amateur ultra-endurance runners.

Sleeping problems can affect physiological adaptations and the recovery process. The aim of this study was to analyse the effect of the intensity and the hour of the training session on sleep quality and cardiac autonomic activity in amateur ultra-endurance athletes. We used a comparative, randomized crossover design to test the effect of moderate (M) or vigorous (V) intensity and morning (m) or evening (e) training journey, separated by 72 h of recovery, on actigraphic and subjective sleep quality and nocturnal cardiac autonomic activity in fourteen ultra-endurance male runners. No significant differences among training sessions were found in nocturnal heart rate variability or in subjective sleep quality, but participants experienced significantly higher calm sleep after Mm than Me (p = 0.028; ES = 0.7) and more refreshed after awakening when they performed a Me than Vm (p = 0.04; ES = 0.6). Higher sleep efficiency was found when the training is performed in the morning compared to the evening sessions in both intensities, and it was also observed in Me vs Ve (p = 0.012; ES = 0.8). Significantly lower numbers of awakenings were observed when the training was performed in the morning, and actual sleep time was significantly lower when participants performed a vigorous training session compared to a moderate one (Vm vs Mm: p = 0.035; ES = 0.6; Ve vs Mm: p = 0.036; ES = 0.6). Moderate exercise performed in the morning had a higher sleep efficiency compared to other types of training and intensity training is more important than the time of the day of training on sleep quality.

Preliminary results from the use of intraoperative real-time biliary oxygen monitoring in liver transplantation.

BACKGROUND AND AIMS: Biliary anastomosis is a frequent area of complications after liver transplantation (LT) and a potential area of "microangiopathy". The concept of a "marginal bile duct" is unexplored. The main aim was to make a preliminary evaluation of the utility of an innovative real-time oxygen microtension (pO2mt) testing device for the assessment of bile duct viability during LT and to correlate these pO2mt values with microvascular tissue quality by histopathology and outcomes. PATIENTS AND METHODS: Observational prospective cohort study with 23 patients. Oxygen microtension measurements were made placing a micropO2 probe in different areas of recipient and donor's bile duct intraoperative. RESULTS: Mean pO2mt in the graft bile duct at the level of the anastomosis 103.82 (31-157) mm Hg, being 121.52 (55-174) mm Hg 1.5 cm proximal to the hilar plate (P < 0.001). Mean pO2mt in the recipient's bile duct was 117.87 (62-185) mm Hg, while a value of 137.30 (81-198) mm Hg was observed 1.5 cm distal to the anastomosis (P < 0.001). Cystic duct resection (12 cases) was also related with higher pO2mt values at anastomosis [117.8 (93-157) vs 88.54 (31-124) mm Hg] and distal to anastomosis [135.6 (111-174) vs 106.2 (55-133) mm Hg; P < 0.001]. Patients with 1-, 3-, and 12-month biliary complications had significantly lower pO2mt in the intraoperative measurements. CONCLUSION: Our preliminary results show that distal borders of donor and recipient bile ducts may be low-vascularized areas. Tissue pO2mt is significantly higher in areas close to the hilar plate and to the duodenum in donor and recipient's sides, respectively. Bile duct injury and biliary complications are associated with worse tissue pO2mt.

p95HER2-T cell bispecific antibody for breast cancer treatment.

T cell bispecific antibodies (TCBs) are engineered molecules that include, within a single entity, binding sites to the T cell receptor and to tumor-associated or tumor-specific antigens. The receptor tyrosine kinase HER2 is a tumor-associated antigen in ~25% of breast cancers. TCBs targeting HER2 may result in severe toxicities, likely due to the expression of HER2 in normal epithelia. About 40% of HER2-positive tumors express p95HER2, a carboxyl-terminal fragment of HER2. Using specific antibodies, here, we show that p95HER2 is not expressed in normal tissues. We describe the development of p95HER2-TCB and show that it has a potent antitumor effect on p95HER2-expressing breast primary cancers and brain lesions. In contrast with a TCB targeting HER2, p95HER2-TCB has no effect on nontransformed cells that do not overexpress HER2. These data pave the way for the safe treatment of a subgroup of HER2-positive tumors by targeting a tumor-specific antigen.

Heart rate variability to assess ventilatory thresholds in professional basketball players.

PURPOSE: The aim of this study was to determine if heart rate variability (HRV) during incremental test could be used to estimate ventilatory threshold (VT) in professional basketball players, with sufficient precision to be used in their training. Furthermore, the second aim was to analyse the association between HRV and 3 methods of VT determination by gas analysis. METHODS: Twenty-four professional basketball players (age: 23.4 ± 4.9 years; height: 195.4 ± 9.8 cm; body mass: 92.2 ± 11.9 kg) performed an incremental running test to exhaustion. First ventilatory threshold (VT1) was determined by ventilatory equivalent (VE) and HRV and second ventilatory threshold (VT2) was determined by 3 methods of gases analysis (V-slope, VE and gas exchange ratio (R), and HRV). Pearson's coefficient (r) was used to detect differences between data and the strength of each relationship. The mean of absolute differences and Bland-Altman analysis were used to evaluate whether there was agreement. RESULTS: The results showed no significant differences in HR and oxygen consumption (VO2) at VT1 between the 2 methods. Furthermore, no significant differences among the methods of gases analysis and HRV were observed in speed, HR, and VO2 at VT2. Moreover, VTs estimated using HRV and gas methods were significantly correlated. Correlation in HR values was higher between R and HRV (r = 0.96) and VE and HRV (r = 0.96) than V-slope and HRV (r = 0.90). CONCLUSION: These findings provide a practical, inexpensive approach for evaluating specific training loads when determining VT2 in basketball players. Therefore, HRV is an alternative method to determine VT2 without the application of expensive technology that limits its use to laboratories.

Spontaneous liver rupture as first sign of polyarteritis nodosa.

Polyarteritis nodosa (PAN) is one of the systemic vasculitis that affects the media wall of arteries of small and medium diameter. Diagnosis proves difficult due to the unspecific symptoms that dominate the clinical profile. Liver involvement is very diverse, ranging from the development of cirrhotic liver disease to acute abdomen presentation that requires surgery because of liver rupture. The management of these patients requires an expert multidisciplinary team. There are several cases in the literature that describe a sudden liver rupture as the first manifestation of a PAN. In this paper we present the case of a 75 years old patient without any previous disease, who is subjected to major hepatic resection for spontaneous liver rupture.

3D Magnetically Ordered Open Supramolecular Architectures Based on Ferrimagnetic Cu/Adenine/Hydroxide Heptameric Wheels.

The present work provides two new examples of supramolecular metal-organic frameworks consisting of three-dimensional extended noncovalent assemblies of wheel-shaped heptanuclear [Cu7(µ-H2O)6(µ3-OH)6(µ-adeninato-κN3:κN9)6](2+) entities. The heptanuclear entity consists of a central [Cu(OH)6](4-) core connected to six additional copper(II) metal centers in a radial and planar arrangement through the hydroxides. It generates a wheel-shaped entity in which water molecules and µ-κN3:κN9 adeninato ligands bridge the peripheral copper atoms. The magnetic characterization indicates the central copper(II) center is anti-ferromagnetically coupled to external copper(II) centers, which are ferromagnetically coupled among them leading to an S = 5/2 ground state. The packing of these entities is sustained by π-π stacking interactions between the adenine nucleobases and by hydrogen bonds established among the hydroxide ligands, sulfate anions, and adenine nucleobases. The sum of both types of supramolecular interactions creates a rigid synthon that in combination with the rigidity of the heptameric entity generates an open supramolecular structure (40-50% of available space) in which additional sulfate and triethylammonium ions are located altogether with solvent molecules. These compounds represent an interesting example of materials combining both porosity and magnetic relevant features.

Dataset of Passerine bird communities in a Mediterranean high mountain (Sierra Nevada, Spain).

In this data paper, a dataset of passerine bird communities is described in Sierra Nevada, a Mediterranean high mountain located in southern Spain. The dataset includes occurrence data from bird surveys conducted in four representative ecosystem types of Sierra Nevada from 2008 to 2015. For each visit, bird species numbers as well as distance to the transect line were recorded. A total of 27847 occurrence records were compiled with accompanying measurements on distance to the transect and animal counts. All records are of species in the order Passeriformes. Records of 16 different families and 44 genera were collected. Some of the taxa in the dataset are included in the European Red List. This dataset belongs to the Sierra Nevada Global-Change Observatory (OBSNEV), a long-term research project designed to compile socio-ecological information on the major ecosystem types in order to identify the impacts of global change in this area.

Aerogels of 1D Coordination Polymers: From a Non-Porous Metal-Organic Crystal Structure to a Highly Porous Material.

The processing of an originally non-porous 1D coordination polymer as monolithic gel, xerogel and aerogel is reported as an alternative method to obtain novel metal-organic porous materials, conceptually different to conventional crystalline porous coordination polymer (PCPs) or metal-organic frameworks (MOFs). Although the work herein reported is focused upon a particular kind of coordination polymer ([M(µ-ox)(4-apy)2]n, M: Co(II), Ni(II)), the results are of interest in the field of porous materials and of MOFs, as the employed synthetic approach implies that any coordination polymer could be processable as a mesoporous material. The polymerization conditions were fixed to obtain stiff gels at the synthesis stage. Gels were dried at ambient pressure and at supercritical conditions to render well shaped monolithic xerogels and aerogels, respectively. The monolithic shape of the synthesis product is another remarkable result, as it does not require a post-processing or the use of additives or binders. The aerogels of the 1D coordination polymers are featured by exhibiting high pore volumes and diameters ranging in the mesoporous/macroporous regions which endow to these materials the ability to deal with large-sized molecules. The aerogel monoliths present markedly low densities (0.082⁻0.311 g·cm-3), an aspect of interest for applications that persecute light materials.

Dataset of MIGRAME Project (Global Change, Altitudinal Range Shift and Colonization of Degraded Habitats in Mediterranean Mountains).

In this data paper, we describe the dataset of the Global Change, Altitudinal Range Shift and Colonization of Degraded Habitats in Mediterranean Mountains (MIGRAME) project, which aims to assess the capacity of altitudinal migration and colonization of marginal habitats by Quercus pyrenaica Willd. forests in Sierra Nevada (southern Spain) considering two global-change drivers: temperature increase and land-use changes. The dataset includes information of the forest structure (diameter size, tree height, and abundance) of the Quercus pyrenaica ecosystem in Sierra Nevada obtained from 199 transects sampled at the treeline ecotone, mature forest, and marginal habitats (abandoned cropland and pine plantations). A total of 3839 occurrence records were collected and 5751 measurements recorded. The dataset is included in the Sierra Nevada Global-Change Observatory (OBSNEV), a long-term research project designed to compile socio-ecological information on the major ecosystem types in order to identify the impacts of global change in this mountain range.

Dataset of Phenology of Mediterranean high-mountain meadows flora (Sierra Nevada, Spain).

Sierra Nevada mountain range (southern Spain) hosts a high number of endemic plant species, being one of the most important biodiversity hotspots in the Mediterranean basin. The high-mountain meadow ecosystems (borreguiles) harbour a large number of endemic and threatened plant species. In this data paper, we describe a dataset of the flora inhabiting this threatened ecosystem in this Mediterranean mountain. The dataset includes occurrence data for flora collected in those ecosystems in two periods: 1988-1990 and 2009-2013. A total of 11002 records of occurrences belonging to 19 orders, 28 families 52 genera were collected. 73 taxa were recorded with 29 threatened taxa. We also included data of cover-abundance and phenology attributes for the records. The dataset is included in the Sierra Nevada Global-Change Observatory (OBSNEV), a long-term research project designed to compile socio-ecological information on the major ecosystem types in order to identify the impacts of global change in this area.