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"Javier Rivera"
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AutoScan3D: A low-cost, portable photogrammetry system for automated 3D digitization of anatomical specimens
This study presents the development and preliminary validation of AutoScan3D, a portable and low-cost device for three-dimensional surface digitization of skulls using photogrammetry. The growing demand for accessible digitalization methods has encouraged the use of photogrammetry as a practical complement to high-end imaging technologies such as micro-computed tomography (micro-CT), which, although capable of visualizing internal structures with superior resolution, remains expensive and requires specialized facilities. AutoScan3D automates photographic capture through a smartphone camera, stepper motors, and an Arduino UNO controller. The system integrates a camera positioning module and an object rotation module to standardize image acquisition at fixed intervals. Its performance was evaluated by comparing the resulting 3D models with reference models derived from micro-CT scans to verify geometric accuracy and surface reconstruction fidelity. The results indicate that AutoScan3D reliably reproduces external morphology with realistic photographic textures and compact file sizes that facilitate subsequent manipulation in modeling software. Although its spatial resolution is lower than that of micro-CT, the device’s total hardware cost (≈USD 90) and ease of operation make it suitable for educational, demonstrative, and museographic contexts where external morphology is the main focus. Planned improvements include enhanced lighting control, compatibility with higher-resolution cameras, and a dedicated user interface. AutoScan3D thus provides a reproducible and affordable framework for surface-based three-dimensional digitization, expanding access to digital morphology tools in resource-limited settings.
Journal Article
Spatiotemporally controlled generation of NTPs for single-molecule studies
Many essential processes in the cell depend on proteins that use nucleoside triphosphates (NTPs). Methods that directly monitor the often-complex dynamics of these proteins at the single-molecule level have helped to uncover their mechanisms of action. However, the measurement throughput is typically limited for NTP-utilizing reactions, and the quantitative dissection of complex dynamics over multiple sequential turnovers remains challenging. Here we present a method for controlling NTP-driven reactions in single-molecule experiments via the local generation of NTPs (LAGOON) that markedly increases the measurement throughput and enables single-turnover observations. We demonstrate the effectiveness of LAGOON in single-molecule fluorescence and force spectroscopy assays by monitoring DNA unwinding, nucleosome sliding and RNA polymerase elongation. LAGOON can be readily integrated with many single-molecule techniques, and we anticipate that it will facilitate studies of a wide range of crucial NTP-driven processes.A new method for controlling NTP-driven reactions in single-molecule experiments via the local generation of NTPs (LAGOON) markedly increases the measurement throughput and enables single-turnover observations.
Journal Article
The phenotypic spectrum associated with loss-of-function variants in monogenic epilepsy genes in the general population
Variants in monogenic epilepsy genes can cause phenotypes of varying severity. For example, pathogenic variants in the SCN1A gene can cause the severe, sporadic, and drug-resistant Dravet syndrome or the milder familiar GEFS + syndrome. We hypothesized that coding variants in epilepsy-associated genes could lead to other disease-related phenotypes in the general population. We selected 127 established monogenic epilepsy genes and explored rare loss-of-function (LoF) variant associations with 3700 phenotypes across 281,850 individuals from the UK Biobank with whole-exome sequencing data. For 5.5% of epilepsy genes, we found significant associations of LoF variants with non-epilepsy phenotypes, mostly related to mental health. These findings suggest that LoF variants in epilepsy genes are associated with neurological or psychiatric phenotypes in the general population. The evidence provided may warrant further research and genetic screening of patients with atypical presentation and inform clinical care of comorbid disorders in individuals with monogenic epilepsy forms.
Journal Article
Angiogenesis in adipose tissue and obesity
While most tissues exhibit their greatest growth during development, adipose tissue is capable of additional massive expansion in adults. Adipose tissue expandability is advantageous when temporarily storing fuel for use during fasting, but becomes pathological upon continuous food intake, leading to obesity and its many comorbidities. The dense vasculature of adipose tissue provides necessary oxygen and nutrients, and supports delivery of fuel to and from adipocytes under fed or fasting conditions. Moreover, the vasculature of adipose tissue comprises a major niche for multipotent progenitor cells, which give rise to new adipocytes and are necessary for tissue repair. Given the multiple, pivotal roles of the adipose tissue vasculature, impairments in angiogenic capacity may underlie obesity-associated diseases such as diabetes and cardiometabolic disease. Exciting new studies on the single-cell and single-nuclei composition of adipose tissues in mouse and humans are providing new insights into mechanisms of adipose tissue angiogenesis. Moreover, new modes of intercellular communication involving micro vesicle and exosome transfer of proteins, nucleic acids and organelles are also being recognized to play key roles. This review focuses on new insights on the cellular and signaling mechanisms underlying adipose tissue angiogenesis, and on their impact on obesity and its pathophysiological consequences.
Journal Article
CRISPR-enhanced human adipocyte browning as cell therapy for metabolic disease
Obesity and type 2 diabetes are associated with disturbances in insulin-regulated glucose and lipid fluxes and severe comorbidities including cardiovascular disease and steatohepatitis. Whole body metabolism is regulated by lipid-storing white adipocytes as well as “brown” and “brite/beige” adipocytes that express thermogenic uncoupling protein 1 (UCP1) and secrete factors favorable to metabolic health. Implantation of brown fat into obese mice improves glucose tolerance, but translation to humans has been stymied by low abundance of primary human beige adipocytes. Here we apply methods to greatly expand human adipocyte progenitors from small samples of human subcutaneous adipose tissue and then disrupt the thermogenic suppressor gene
NRIP1
by CRISPR. Ribonucleoprotein consisting of Cas9 and sgRNA delivered ex vivo are fully degraded by the human cells following high efficiency NRIP1 depletion without detectable off-target editing. Implantation of such CRISPR-enhanced human or mouse brown-like adipocytes into high fat diet fed mice decreases adiposity and liver triglycerides while enhancing glucose tolerance compared to implantation with unmodified adipocytes. These findings advance a therapeutic strategy to improve metabolic homeostasis through CRISPR-based genetic enhancement of human adipocytes without exposing the recipient to immunogenic Cas9 or delivery vectors.
Worldwide pandemics of obesity and diabetes prompt an urgent need for new approaches to their prevention and cure. Here the authors present a CRISPR-based strategy that enhances the therapeutic potential of human adipocytes when implanted in obese mice.
Journal Article
Real-time measurements of aminoglycoside effects on protein synthesis in live cells
The spread of antibiotic resistance is turning many of the currently used antibiotics less effective against common infections. To address this public health challenge, it is critical to enhance our understanding of the mechanisms of action of these compounds. Aminoglycoside drugs bind the bacterial ribosome, and decades of results from in vitro biochemical and structural approaches suggest that these drugs disrupt protein synthesis by inhibiting the ribosome’s translocation on the messenger RNA, as well as by inducing miscoding errors. So far, however, we have sparse information about the dynamic effects of these compounds on protein synthesis inside the cell. In the present study, we measured the effect of the aminoglycosides apramycin, gentamicin, and paromomycin on ongoing protein synthesis directly in live Escherichia coli cells by tracking the binding of dye-labeled transfer RNAs to ribosomes. Our results suggest that the drugs slow down translation elongation two- to fourfold in general, and the number of elongation cycles per initiation event seems to decrease to the same extent. Hence, our results imply that none of the drugs used in this study cause severe inhibition of translocation.
Journal Article
A Guide to Understanding and Combatting Digital Capitalism
This article offers a general description of digital capitalism, understood as a system in which social and economic dynamics revolve around digital corporations and their infrastructures. The aim of this analysis is to help develop strategies to counteract capitalism. It takes an historical perspective, considering capitalism as an evolving system driven by a continuous flight from the law of diminishing returns. Fixed Capital and General Intellect are addressed as key analytical concepts for understanding the role of technology in capitalism, particularly in the digital era. Subjectivity formation is also a key element, as capitalism needs to progressively improve its strategies of ideological manipulation in order to survive. In the conclusion, I present five strategic principles to counteract digital capitalism. These strategies were developed in the Grupo de Estudios Críticos de Madrid (GEC-Madrid), an interdisciplinary group created in 2018 by the National Museum Reina Sofia (Spain) in order to coordinate the cycle “Six Contradictions and the End of the Present”, a series of lectures and workshops with internationally recognized scholars, followed by research seminars to discuss their ideas.
Journal Article
tRNA tracking for direct measurements of protein synthesis kinetics in live cells
Our ability to directly relate results from test-tube biochemical experiments to the kinetics in living cells is very limited. Here we present experimental and analytical tools to directly study the kinetics of fast biochemical reactions in live cells. Dye-labeled molecules are electroporated into bacterial cells and tracked using super-resolved single-molecule microscopy. Trajectories are analyzed by machine-learning algorithms to directly monitor transitions between bound and free states. In particular, we measure the dwell time of tRNAs on ribosomes, and hence achieve direct measurements of translation rates inside living cells at codon resolution. We find elongation rates with tRNAPhe that are in perfect agreement with previous indirect estimates, and once fMet-tRNAfMet has bound to the 30S ribosomal subunit, initiation of translation is surprisingly fast and does not limit the overall rate of protein synthesis. The experimental and analytical tools for direct kinetics measurements in live cells have applications far beyond bacterial protein synthesis.
Journal Article
A novel gene from the acidophilic bacterium Leptospirillum sp. CF-1 and its role in oxidative stress and chromate tolerance
Background
Acidophilic microorganisms like
Leptospirillum
sp. CF-1 thrive in environments with extremely low pH and high concentrations of dissolved heavy metals that can induce the generation of reactive oxygen species (ROS). Several hypothetical genes and proteins from
Leptospirillum
sp. CF-1 are known to be up-regulated under oxidative stress conditions.
Results
In the present work, the function of hypothetical gene ABH19_09590 from
Leptospirillum
sp. CF-1 was studied. Heterologous expression of this gene in
Escherichia coli
led to an increase in the ability to grow under oxidant conditions with 5 mM K
2
CrO
4
or 5 mM H
2
O
2
. Similarly, a significant reduction in ROS production in
E. coli
transformed with a plasmid carrying ABH19_09590 was observed after exposure to these oxidative stress elicitors for 30 min, compared to a strain complemented with the empty vector. A co-transcriptional study using RT-PCR showed that ABH19_09590 is contained in an operon, here named the “
och
” operon, that also contains ABH19_09585, ABH19_09595 and ABH19_09600 genes. The expression of the
och
operon was significantly up-regulated in
Leptospirillum
sp. CF-1 exposed to 5 mM K
2
CrO
4
for 15 and 30 min. Genes of this operon potentially encode a NADH:ubiquinone oxidoreductase, a CXXC motif-containing protein likely involved in thiol/disulfide exchange, a hypothetical protein, and a di-hydroxy-acid dehydratase. A comparative genomic analysis revealed that the
och
operon is a characteristic genetic determinant of the
Leptospirillum
genus that is not present in other acidophiles.
Conclusions
Altogether, these results suggest that the
och
operon plays a protective role against chromate and hydrogen peroxide and is an important mechanism required to face polyextremophilic conditions in acid environments.
Journal Article