Decoding LINC00052 role in breast cancer by bioinformatic and experimental analyses.

LncRNA is a group of transcripts with a length exceeding 200 nucleotides that contribute to tumour development. Our research group found that LINC00052 expression was repressed during the formation of breast cancer (BC) multicellular spheroids. Intriguingly, LINC00052 precise role in BC remains uncertain. We explored LINC00052 expression in BC patients` RNA samples (TCGA) in silico, as well as in an in-house patient cohort, and inferred its cellular and molecular mechanisms. In vitro studies evaluated LINC00052 relevance in BC cells viability, cell cycle and DNA damage. Results. Bioinformatic RNAseq analysis of BC patients showed that LINC00052 is overexpressed in samples from all BC molecular subtypes. A similar LINC00052 expression pattern was observed in an in-house patient cohort. In addition, higher LINC00052 levels are related to better BC patient´s overall survival. Remarkably, MCF-7 and ZR-75-1 cells treated with estradiol showed increased LINC00052 expression compared to control, while these changes were not observed in MDA-MB-231 cells. In parallel, bioinformatic analyses indicated that LINC00052 influences DNA damage and cell cycle. MCF-7 cells with low LINC00052 levels exhibited increased cellular protection against DNA damage and diminished growth capacity. Furthermore, in cisplatin-resistant MCF-7 cells, LINC00052 expression was downregulated. Conclusion. This work shows that LINC00052 expression is associated with better BC patient survival. Remarkably, LINC00052 expression can be regulated by Estradiol. Additionally, assays suggest that LINC00052 could modulate MCF-7 cells growth and DNA damage repair. Overall, this study highlights the need for further research to unravel LINC00052 molecular mechanisms and potential clinical applications in BC.

Neuronal progenitors of the dentate gyrus express the SARS-CoV-2 cell receptor during migration in the developing human hippocampus.

The COVID-19 pandemic spread around the world is due to the enormous capacity of the SARS-CoV-2 coronavirus to be transmitted between humans, causing a threat to global public health. It has been shown that the entry of this virus into cells is highly facilitated by the presence of angiotensin-converting enzyme 2 (ACE2) in the cell membrane. Currently, we have no precise knowledge of how this receptor expresses in the brain of human fetus and, as a consequence, we do not know how susceptible the neural cells in the developing brain are to being infected through the vertical transmission of this virus, from mother to fetus. In this work, we describe the expression of ACE2 in the human brain at 20 weeks of gestation. This stage corresponds to the period of neuronal generation, migration, and differentiation in the cerebral cortex. We describe the specific expression of ACE2 in neuronal precursors and migratory neuroblasts of the dentate gyrus in the hippocampus. This finding implies that SARS-CoV-2 infection during the fetal period may affect neuronal progenitor cells and alter the normal development of the brain region where memory engrams are generated. Thus, although vertical transmission of SARS-CoV-2 infection was reported in few cases, the massive infection rate of young people in terms of the new variants leads to the possibility of increasing the ratio of congenital infections and originating cognitive alterations, as well as neuronal circuit anomalies that may represent vulnerability to mental problems throughout life.

How do engineered Yarrowia lipolytica strains secrete free fatty acids: hints from comparative transcriptomics.

Yarrowia lipolytica has been considered one of the most promising platforms for the microbial production of fatty acids and derived products. The deletion of the faa1 gene coding for an acyl-CoA synthetase leads to the accumulation and secretion of free fatty acids (FFAs) into the extracellular space. The secretion of products is beneficial for the development of microbial cell factories to avoid intracellular inhibitory effects and reduce downstream processing costs. However, the mechanism behind the secretion of fatty acids is not well known. As a starting point, we compared the transcriptome of this mutant showing FFA secretion to a wildtype-like strain not showing this phenotype. The 12 most upregulated genes were evaluated for involvement in FFA secretion by the creation of deletion and overexpression mutants, among them MCH2, YMOH, three cell wall proteins CWP3, CWP4, and CWP11, M12B, and three proteins with unknown functions YUP1, YUP2, and YUP3. None of these proteins take a clear or isolated role in FFA export. As the transcriptomic data revealed an overrepresentation of cell wall-related proteins, some of them were further examined on a theoretical and experimental way. Surprisingly, overexpression of Ygpi led to the production of FFAs in the wildtype-like genetic background. Finally, some of the evaluated genes showed involvement in resistance to FFA toxicity.

A combinatorial code for CPE-mediated translational control.

Cytoplasmic polyadenylation plays a key role in the translational control of mRNAs driving biological processes such as gametogenesis, cell-cycle progression, and synaptic plasticity. What determines the distinct time of polyadenylation and extent of translational control of a given mRNA, however, is poorly understood. The polyadenylation-regulated translation is controlled by the cytoplasmic polyadenylation element (CPE) and its binding protein, CPEB, which can assemble both translational repression or activation complexes. Using a combination of mutagenesis and experimental validation of genome-wide computational predictions, we show that the number and relative position of two elements, the CPE and the Pumilio-binding element, with respect to the polyadenylation signal define a combinatorial code that determines whether an mRNA will be translationally repressed by CPEB, as well as the extent and time of cytoplasmic polyadenylation-dependent translational activation.

Effectiveness of custom-made functional foot orthoses versus flat cushioning insoles on pain in patients with systemic lupus erythematosus.

OBJECTIVE: To determine the effect of foot orthoses on pain, disability and foot functionality in patients with Systemic Lupus Erythematosus. DESIGN: Randomized clinical trial. SETTING: University Podiatric Clinical Area. SUBJECTS: Patients with systemic lupus erythematosus. INTERVENTIONS: Patients were randomly assigned to either group A, which received custom-made functional foot orthoses, or group B, which received flat cushioning insoles, for three months. MAIN MEASURES: The primary outcome was foot pain, measured by 11-point numeric pain rating scale. Foot functionality and foot-related disability were evaluated using the foot function index, the Manchester foot pain and disability, at the beginning and at days 90. RESULTS: Sixty-six participants (age 47.3 ± 11.9 years) suffering from foot pain, received either the custom-made foot orthoses (N = 33) or the flat cushioning insoles (N = 33). For the analysis of the data, only participants who had finished the follow-up period (90 days) were included. None statistically significant difference between groups were found. In group A, all variables showed statistically significant differences when comparing the initial and final measurements. Pain showed 6.8 ± 1.6 and 4.2 ± 2.9 in group A, at baseline and at 90 days, respectively, group B showed 6.5 ± 1.5 and 4.7 ± 3.0 at baseline and at 90 days, respectively. CONCLUSION: Both groups showed a reduction in foot pain. This study suggests that not only controlling the foot function, but providing cushioning to the foot, may have positive effects to manage foot pain in patients with systemic lupus erythematosus.

Methyl Jasmonate and Nanoparticles Doped with Methyl Jasmonate affect the Cell Wall Composition of Monastrell Grape Skins.

The structural composition of the cell wall of grape skins is related to the cell wall integrity and subsequent extraction of the different compounds that are contained inside vacuoles and also the cell wall breakdown products. Different reports have established that methyl jasmonate (MeJ) produces changes in the composition of the grape skin cell wall. The use of elicitors to promote the production of secondary metabolites in grapes has been studied in several reports; however, its study linked to nanotechnology is less developed. These facts led us to study the effect of methyl jasmonate (MeJ) and nanoparticles doped with MeJ (nano-MeJ) on the cell walls of Monastrell grapes during three seasons. Both treatments tended to increase cell wall material (CWM) and caused changes in different components of the skin cell walls. In 2019 and 2021, proteins were enlarged in both MeJ and nano-MeJ-treated grapes. A general decrease in total phenolic compounds was detected with both treatments, in addition to an increment in uronic acids when the grapes were well ripened. MeJ and nano-MeJ produced a diminution in the amount of cellulose in contrast to an increase in hemicellulose. It should be noted that the effects with nano-MeJ treatment occurred at a dose 10 times lower than with MeJ treatment.

Oleaginous yeasts: Time to rethink the definition?

Oleaginous yeasts are typically defined as those able to accumulate more than 20% of their cell dry weight as lipids or triacylglycerides. Research on these yeasts has increased lately fuelled by an interest to use biotechnology to produce lipids and oleochemicals that can substitute those coming from fossil fuels or offer sustainable alternatives to traditional extractions (e.g., palm oil). Some oleaginous yeasts are attracting attention both in research and industry, with Yarrowia lipolytica one of the best-known and studied ones. Oleaginous yeasts can be found across several clades and different metabolic adaptations have been found, affecting not only fatty acid and neutral lipid synthesis, but also lipid particle stability and degradation. Recently, many novel oleaginous yeasts are being discovered, including oleaginous strains of the traditionally considered non-oleaginous Saccharomyces cerevisiae. In the face of this boom, a closer analysis of the definition of "oleaginous yeast" reveals that this term has instrumental value for biotechnology, while it does not give information about distinct types of yeasts. Having this perspective in mind, we propose to expand the term "oleaginous yeast" to those able to produce either intracellular or extracellular lipids, not limited to triacylglycerides, in at least one growth condition (including ex novo lipid synthesis). Finally, a critical look at Y. lipolytica as a model for oleaginous yeasts shows that the term "oleaginous" should be reserved only for strains and not species and that in the case of Y. lipolytica, it is necessary to distinguish clearly between the lipophilic and oleaginous phenotype.

The oleaginous yeast Starmerella bombicola reveals limitations of Saccharomyces cerevisiae as a model for fatty acid transport studies.

Saccharomyces cerevisiae is the model organism to most yeast researchers, and information obtained from its physiology is generally extrapolated to other yeasts. Studies on fatty acid transport in S. cerevisiae are based on the expression of both native fatty acid export genes as well as heterologous proteins. Starmerella bombicola, on the other hand, is an oleaginous yeast of industrial relevance but its fatty acid transport mechanisms are unknown. In this study, we attempt to use existing knowledge from S. cerevisiae to study fatty acid transport in S. bombicola, but the obtained results differ from those observed in S. cerevisiae. First, we observed that deletion of SbPRY1 in S. bombicola leads to higher fatty acid export, the opposite effect to the one previously observed for the Pry homologues in S. cerevisiae. Second, following reports that human FATP1 could export fatty acids and alcohols in S. cerevisiae, we expressed FATP1 in a fatty acid-accumulating S. bombicola strain. However, FATP1 reduced fatty acid export in S. bombicola, most likely due to its acyl-CoA synthetase activity. These results not only advance knowledge on fatty acid physiology of S. bombicola, but also improve our understanding of S. cerevisiae and its limitations as a model organism.

Error Reduction in Vision-Based Multirotor Landing System.

New applications are continuously appearing with drones as protagonists, but all of them share an essential critical maneuver-landing. New application requirements have led the study of novel landing strategies, in which vision systems have played and continue to play a key role. Generally, the new applications use the control and navigation systems embedded in the aircraft. However, the internal dynamics of these systems, initially focused on other tasks such as the smoothing trajectories between different waypoints, can trigger undesired behaviors. In this paper, we propose a landing system based on monocular vision and navigation information to estimate the helipad global position. In addition, the global estimation system includes a position error correction module by cylinder space transformation and a filtering system with a sliding window. To conclude, the landing system is evaluated with three quality metrics, showing how the proposed correction system together with stationary filtering improves the raw landing system.

Cellular and Molecular Alterations Underlying Abnormal Bone Growth in X-Linked Hypophosphatemia.

X-linked hypophosphatemia (XLH), the most common form of hereditary hypophosphatemic rickets, is caused by inactivating mutations of the phosphate-regulating endopeptidase gene (PHEX). XLH is mainly characterized by short stature, bone deformities and rickets, while in hypophosphatemia, normal or low vitamin D levels and low renal phosphate reabsorption are the principal biochemical aspects. The cause of growth impairment in patients with XLH is not completely understood yet, thus making the study of the growth plate (GP) alterations necessary. New treatment strategies targeting FGF23 have shown promising results in normalizing the growth velocity and improving the skeletal effects of XLH patients. However, further studies are necessary to evaluate how this treatment affects the GP as well as its long-term effects and the impact on adult height.

The role of temperature profile during the pyrolysis of end-of-life-tyres in an industrially relevant conditions auger plant.

Pyrolysis is a chemical recycling process of interest as a means to achieve a sustainable circular economy for end-of-life tyres (ELTs). In the pyrolysis process, ELTs are converted into tyre pyrolysis gas (TPG), tyre pyrolysis oil (TPO) and raw recovered carbon black (RRCB). This work investigates for the first time the effect of different temperature profiles by using a single-auger pyrolysis reactor in an industrially relevant scale (TRL-5). Since the development of this process at this representative scale is quite limited and the temperature profile has not been previously studied, the results achieved in this work can provide a useful database for the development of this process at industrial scale. For this purpose, two different sources of ELTs, commercial truck tyres (CTTs) and passenger car tyres (PCTs), were used. Accordingly, the experimental campaign was conducted using two different incremental temperature profiles (425-550-775 °C and 600-700-800 °C) based on those that can be replicated in an industrial-scale auger pyrolysis plant. For the sake of comparison, two isothermal heating conditions (500-500-500 °C and 600-600-600 °C) were also tested. The results confirmed the remarkable influence of temperature profile on both the distribution and properties of products. The 425-550-775 °C temperature profile was found to enhance limonene production, which is associated with the minimisation of secondary reactions in the first heating zone of the reactor. Additionally, there were very low carbonaceous deposits found in the RRCB because of the high severity of devolatilisation conditions in the third heating zone of the reactor. On the other hand, when the temperature profile was raised, the production of single-ring aromatics, particularly benzene, toluene, ethylbenzene and xylenes (BTEX) significantly increased in the TPO at the expense of limonene. Thus, from this strategy, it is possible to tune the properties of the products depending on the requirements of the application in a single step, getting closer for circular economy in the ELT recycling domain.

Effects of Methyl Jasmonate and Nano-Methyl Jasmonate Treatments on Monastrell Wine Volatile Composition.

The application of methyl jasmonate (MeJ) as an elicitor to enhance secondary metabolites in grapes and wines has been studied, but there is little information about its use in conjunction with nanotechnology and no information about its effects on wine volatile compounds. This led us to study the impact of nanoparticles doped with MeJ (Nano-MeJ, 1mM MeJ) on the volatile composition of Monastrell wines over three seasons, compared with the application of MeJ in a conventional way (10 mM MeJ). The results showed how both treatments enhanced fruity esters in wines regardless of the vintage year, although the increase was more evident when grapes were less ripe. These treatments also achieved these results in 2019 in the cases of 1-propanol, ß-phenyl-ethanol, and methionol, in 2020 in the cases of hexanol and methionol, and in 2021, but only in the case of hexanol. On the other hand, MeJ treatment also increased the terpene fraction, whereas Nano-MeJ, at the applied concentration, did not increase it in any of the seasons. In summary, although not all families of volatile compounds were increased by Nano-MeJ, the Nano-MeJ treatment generally increased the volatile composition to an extent similar to that obtained with MeJ used in a conventional way, but at a 10 times lower dose. Therefore, the use of nanotechnology could be a good option for improving the quality of wines from an aromatic point of view, while reducing the necessary dosage of agrochemicals, in line with more sustainable agricultural practices.

Adsorptive Capacity, Inhibitory Activity and Processing Techniques for a Copper-MOF Based on the 3,4-Dihydroxybenzoate Ligand.

Due to the fast, emerging development of antibiotic-resistant bacteria, the need for novel, efficient routes to battle these pathogens is crucial; in this scenario, metal-organic frameworks (MOFs) are promising materials for combating them effectively. Herein, a novel Cu-MOF-namely 1-that displays the formula [Cu3L2(DMF)2]n (DMF = N,N-dimethylformamide) is described, synthesized by the combination of copper(II) and 3,4-dihydroxybenzoic acid (H3L)-both having well-known antibacterial properties. The resulting three-dimensional structure motivated us to study the antibacterial activity, adsorptive capacity and processability of the MOF in the form of pellets and membranes as a proof-of-concept to evaluate its future application in devices.

Forecasting Nonlinear Systems with LSTM: Analysis and Comparison with EKF.

Certain difficulties in path forecasting and filtering problems are based in the initial hypothesis of estimation and filtering techniques. Common hypotheses include that the system can be modeled as linear, Markovian, Gaussian, or all at one time. Although, in many cases, there are strategies to tackle problems with approaches that show very good results, the associated engineering process can become highly complex, requiring a great deal of time or even becoming unapproachable. To have tools to tackle complex problems without starting from a previous hypothesis but to continue to solve classic challenges and sharpen the implementation of estimation and filtering systems is of high scientific interest. This paper addresses the forecast-filter problem from deep learning paradigms with a neural network architecture inspired by natural language processing techniques and data structure. Unlike Kalman, this proposal performs the process of prediction and filtering in the same phase, while Kalman requires two phases. We propose three different study cases of incremental conceptual difficulty. The experimentation is divided into five parts: the standardization effect in raw data, proposal validation, filtering, loss of measurements (forecasting), and, finally, robustness. The results are compared with a Kalman filter, showing that the proposal is comparable in terms of the error within the linear case, with improved performance when facing non-linear systems.

Use of Plantar Pressure Sensors to Take Weight-Bearing Foot Casts.

Techniques of taking casts mainly rely not on the objectivity of the procedure, but on the experience and skill of the technician. The aim of this study was to demonstrate the efficiency of a technique of taking standing foot casts controlled via pressure sensors. In this way, we mean to objectivize the degree of correction. The study was carried out through 150 procedures on 50 feet of 29 patients. The value of the "Heel Symmetry Index" was calculated on three casts in three different situations of the same foot: A first cast in which the subject did not control the position of his/her foot; a second cast where manipulations corrected the foot's pronator position; and a third cast with pressure sensors placed in the subject's heel. This enabled the control and quantification of the pressure during the manipulation when taking the cast. The comparison of the "Heel Symmetry Index" in the different groups showed significant p-values of 0.05. Conclusion: The technique of taking casts controlled by pressure sensors achieved more equilibrated casts with a better symmetry index of the heel's outline.

Study of the Distortion of the Indirect Angular Measurements of the Calcaneus Due to Perspective: In Vitro Testing.

The study of the foot is relevant in kinematic analyses of gait. Images captured through a lens can be subjected to various aberrations or distortions that affect the measurements. An in vitro study was performed with a rearfoot simulator to compare the apparent degrees (photographed) with the real ones (placed in the simulator) in the plane of the rearfoot's orientation, according to variations in the capture angle in other planes of space (the sagittal plane and transverse plane-the latter determined by the foot progression angle). The following regression formula was calculated to correct the distortion of the image: real frontal plane = 0.045 + (1.014 × apparent frontal plane) - (0.018 × sagittal plane × foot progression angle). Considering the results of this study, and already knowing its angle in the transverse and sagittal planes, it is possible to determine the angle of a simulated calcaneus with respect to the ground in the frontal plane, in spite of distortions caused by perspective and the lack of perpendicularity, by applying the above regression formula. The results show that the angular measurements of a body segment made on frames can produce erroneous data due to the variation in the perspective from which the image is taken. This distortion must be considered when determining the real values of the measurements.

The Formation of the Epiphyseal Bone Plate Occurs via Combined Endochondral and Intramembranous-Like Ossification.

The formation of the epiphyseal bone plate, the flat bony structure that provides strength and firmness to the growth plate cartilage, was studied in the present study by using light, confocal, and scanning electron microscopy. Results obtained evidenced that this bone tissue is generated by the replacement of the lower portion of the epiphyseal cartilage. However, this process differs considerably from the usual bone tissue formation through endochondral ossification. Osteoblasts deposit bone matrix on remnants of mineralized cartilage matrix that serve as a scaffold, but also on non-mineralized cartilage surfaces and as well as within the perivascular space. These processes occur simultaneously at sites located close to each other, so that, a core of the sheet of bone is established very quickly. Subsequently, thickening and reshaping occurs by appositional growth to generate a dense parallel-fibered bone structurally intermediate between woven and lamellar bone. All these processes occur in close relationship with a cartilage but most of the bone tissue is generated in a manner that may be considered as intramembranous-like. Overall, the findings here reported provide for the first time an accurate description of the tissues and events involved in the formation of the epiphyseal bone plate and gives insight into the complex cellular events underlying bone formation at different sites on the skeleton.

Biomimetic Mineralization Promotes Viability and Differentiation of Human Mesenchymal Stem Cells in a Perfusion Bioreactor.

In bone tissue engineering, the design of 3D systems capable of recreating composition, architecture and micromechanical environment of the native extracellular matrix (ECM) is still a challenge. While perfusion bioreactors have been proposed as potential tool to apply biomechanical stimuli, its use has been limited to a low number of biomaterials. In this work, we propose the culture of human mesenchymal stem cells (hMSC) in biomimetic mineralized recombinant collagen scaffolds with a perfusion bioreactor to simultaneously provide biochemical and biophysical cues guiding stem cell fate. The scaffolds were fabricated by mineralization of recombinant collagen in the presence of magnesium (RCP.MgAp). The organic matrix was homogeneously mineralized with apatite nanocrystals, similar in composition to those found in bone. X-Ray microtomography images revealed isotropic porous structure with optimum porosity for cell ingrowth. In fact, an optimal cell repopulation through the entire scaffolds was obtained after 1 day of dynamic seeding in the bioreactor. Remarkably, RCP.MgAp scaffolds exhibited higher cell viability and a clear trend of up-regulation of osteogenic genes than control (non-mineralized) scaffolds. Results demonstrate the potential of the combination of biomimetic mineralization of recombinant collagen in presence of magnesium and dynamic culture of hMSC as a promising strategy to closely mimic bone ECM.

Depression and Cognitive Impairment in Institutionalized Older Adults.

BACKGROUND: In the last three decades, the relationship between depression and cognition in geriatric patients has been a popular topic among researchers and clinicians. Clinical and epidemiological research has focused on the identification of risk factors that could be modified in pre-dementia syndromes, at a preclinical and early clinical stage of dementia disorders, with specific attention to the role of depression. The objective of this work was to determine the relationship between depressive disorder and cognitive deterioration in institutionalized older adults. METHODS: In this descriptive, correlational study, data were gathered from two nursing homes in the province of Jaen (Spain), from a random sample of 140 older adults (70 nondependent and 70 dependent). The variables were measured using comprehensive geriatric assessment, the Cambridge Cognitive Test (CAMCOG), and the Geriatric Depression Scale (GDS). RESULTS: Depression was correlated with cognitive level in the nondependent older adult sample (r = -0.471, p = 0.004). Age was inversely associated with the score obtained in the CAMCOG of the nondependent older adult sample (r = -0.352, p = 0.038). The functional capacity in several activities of daily living was correlated with the score obtained in the CAMCOG in each of the two groups. Depression was more prevalent in the dependent than in the nondependent older adults (82.85 vs. 57.14%). No association was observed between institutionalization time and the score obtained on the cognitive and affective scales (GDS and CAMCOG) in both groups (GDS-nondependent, r = -0.209, p = 0.234; CAMCOG-nondependent, r = 0.007, p = 0.967; GDS-dependent, r = 0.251, p = 0.152; CAMCOG-dependent, r = -0.021, p = 0.907). CONCLUSION: Depressive symptomatology is associated with cognitive deterioration. Depression is prevalent in institutions that care for older, more dependent adults.

Growth plate alterations in chronic kidney disease.

Growth retardation is a major feature of chronic kidney disease (CKD) of onset in infants or children and is associated with increased morbidity and mortality. Several factors have been shown to play a causal role in the growth impairment of CKD. All these factors interfere with growth by disturbing the normal physiology of the growth plate of long bones. To facilitate the understanding of the pathogenesis of growth impairment in CKD, this review discusses cellular and molecular alterations of the growth plate during uremia, including structural and dynamic changes of chondrocytes, alterations in their process of maturation and hypertrophy, and disturbances in the growth hormone signaling pathway.