Detection and impact estimation of social bots in the Chilean Twitter network.

The rise of bots that mimic human behavior represents one of the most pressing threats to healthy information environments on social media. Many bots are designed to increase the visibility of low-quality content, spread misinformation, and artificially boost the reach of brands and politicians. These bots can also disrupt civic action coordination, such as by flooding a hashtag with spam and undermining political mobilization. Social media platforms have recognized these malicious bots' risks and implemented strict policies and protocols to block automated accounts. However, effective bot detection methods for Spanish are still in their early stages. Many studies and tools used for Spanish are based on English-language models and lack performance evaluations in Spanish. In response to this need, we have developed a method for detecting bots in Spanish called Botcheck. Botcheck was trained on a collection of Spanish-language accounts annotated in Twibot-20, a large-scale dataset featuring thousands of accounts annotated by humans in various languages. We evaluated Botcheck's performance on a large set of labeled accounts and found that it outperforms other competitive methods, including deep learning-based methods. As a case study, we used Botcheck to analyze the 2021 Chilean Presidential elections and discovered evidence of bot account intervention during the electoral term. In addition, we conducted an external validation of the accounts detected by Botcheck in the case study and found our method to be highly effective. We have also observed differences in behavior among the bots that are following the social media accounts of official presidential candidates.

Resin acids play key roles in shaping microbial communities during degradation of spruce bark.

The bark is the outermost defense of trees against microbial attack, largely thanks to toxicity and prevalence of extractive compounds. Nevertheless, bark decomposes in nature, though by which species and mechanisms remains unknown. Here, we have followed the development of microbial enrichments growing on spruce bark over six months, by monitoring both chemical changes in the material and performing community and metagenomic analyses. Carbohydrate metabolism was unexpectedly limited, and instead a key activity was metabolism of extractives. Resin acid degradation was principally linked to community diversification with specific bacteria revealed to dominate the process. Metagenome-guided isolation facilitated the recovery of the dominant enrichment strain in pure culture, which represents a new species (Pseudomonas abieticivorans sp. nov.), that can grow on resin acids as a sole carbon source. Our results illuminate key stages in degradation of an abundant renewable resource, and how defensive extractive compounds have major roles in shaping microbiomes.

The disease-causing mutation p.F907I reveals a novel pathogenic mechanism for POLγ-related diseases.

Mutations in the catalytic domain of mitochondrial DNA polymerase γ (POLγ) cause a broad spectrum of clinical conditions. POLγ mutations impair mitochondrial DNA replication, thereby causing deletions and/or depletion of mitochondrial DNA, which in turn impair biogenesis of the oxidative phosphorylation system. We here identify a patient with a homozygous p.F907I mutation in POLγ, manifesting a severe clinical phenotype with developmental arrest and rapid loss of skills from 18 months of age. Magnetic resonance imaging of the brain revealed extensive white matter abnormalities, Southern blot of muscle mtDNA demonstrated depletion of mtDNA and the patient deceased at 23 months of age. Interestingly, the p.F907I mutation does not affect POLγ activity on single-stranded DNA or its proofreading activity. Instead, the mutation affects unwinding of parental double-stranded DNA at the replication fork, impairing the ability of the POLγ to support leading-strand DNA synthesis with the TWINKLE helicase. Our results thus reveal a novel pathogenic mechanism for POLγ-related diseases.

Pathological variants in TOP3A cause distinct disorders of mitochondrial and nuclear genome stability.

Topoisomerase 3α (TOP3A) is an enzyme that removes torsional strain and interlinks between DNA molecules. TOP3A localises to both the nucleus and mitochondria, with the two isoforms playing specialised roles in DNA recombination and replication respectively. Pathogenic variants in TOP3A can cause a disorder similar to Bloom syndrome, which results from bi-allelic pathogenic variants in BLM, encoding a nuclear-binding partner of TOP3A. In this work, we describe 11 individuals from 9 families with an adult-onset mitochondrial disease resulting from bi-allelic TOP3A gene variants. The majority of patients have a consistent clinical phenotype characterised by bilateral ptosis, ophthalmoplegia, myopathy and axonal sensory-motor neuropathy. We present a comprehensive characterisation of the effect of TOP3A variants, from individuals with mitochondrial disease and Bloom-like syndrome, upon mtDNA maintenance and different aspects of enzyme function. Based on these results, we suggest a model whereby the overall severity of the TOP3A catalytic defect determines the clinical outcome, with milder variants causing adult-onset mitochondrial disease and more severe variants causing a Bloom-like syndrome with mitochondrial dysfunction in childhood.

Non-coding 7S RNA inhibits transcription via mitochondrial RNA polymerase dimerization.

The mitochondrial genome encodes 13 components of the oxidative phosphorylation system, and altered mitochondrial transcription drives various human pathologies. A polyadenylated, non-coding RNA molecule known as 7S RNA is transcribed from a region immediately downstream of the light strand promoter in mammalian cells, and its levels change rapidly in response to physiological conditions. Here, we report that 7S RNA has a regulatory function, as it controls levels of mitochondrial transcription both in vitro and in cultured human cells. Using cryo-EM, we show that POLRMT dimerization is induced by interactions with 7S RNA. The resulting POLRMT dimer interface sequesters domains necessary for promoter recognition and unwinding, thereby preventing transcription initiation. We propose that the non-coding 7S RNA molecule is a component of a negative feedback loop that regulates mitochondrial transcription in mammalian cells.

Morbimortality assessment in abdominal surgery: are we predicting or overreacting?

BACKGROUND: High-risk surgical procedures represent a fundamental part of general surgery practice due to its significant rates of morbidity and mortality. Different predictive tools have been created in order to quantify perioperative morbidity and mortality risk. POSSUM (Physiological and Operative Severity Score for the enumeration of Mortality and morbidity) is one of the most widely validated predictive scores considering physiological and operative variables to precisely define morbimortality risk. Nevertheless, seeking greater accuracy in predictions P-POSSUM was proposed. We aimed to compare POSSUM and P-POSSUM for patients undergoing abdominal surgery. METHODS: A retrospective observational study with a prospective database was conducted. Patients over 18 years old who complied with inclusion criteria between 2015 and 2016 were included. Variables included in the POSSUM and P-POSSUM Scores were analyzed. Descriptive statistics of all study parameters were provided. The analysis included socio-demographic data, laboratory values ​​, and imaging. Bivariate analysis was performed. RESULTS: 350 Patients were included in the analysis, 55.1% were female. The mean age was 55.9 ± 20.4 years old. POSSUM revealed a moderated index score in 61.7% of the patients, mean score of 12.85 points ± 5.61. 89.1% of patients had no neoplastic diagnosis associated. Overall morbidity and mortality rate was 14.2% and 7.1%. P-POSSUM could predict more precisely mortality (p < 0.00). CONCLUSIONS: The POSSUM score is likely to overestimate the risk of morbidity and mortality in patients with high/moderate risk, while the P-POSSUM score seems to be a more accurate predictor of mortality risk. Further studies are needed to confirm our results.

The copper chaperone CCS facilitates copper binding to MEK1/2 to promote kinase activation.

Normal physiology relies on the precise coordination of intracellular signaling pathways that respond to nutrient availability to balance cell growth and cell death. The canonical mitogen-activated protein kinase pathway consists of the RAF-MEK-ERK signaling cascade and represents one of the most well-defined axes within eukaryotic cells to promote cell proliferation, which underscores its frequent mutational activation in human cancers. Our recent studies illuminated a function for the redox-active micronutrient copper (Cu) as an intracellular mediator of signaling by connecting Cu to the amplitude of mitogen-activated protein kinase signaling via a direct interaction between Cu and the kinases MEK1 and MEK2. Given the large quantities of molecules such as glutathione and metallothionein that limit cellular toxicity from free Cu ions, evolutionarily conserved Cu chaperones facilitate efficient delivery of Cu to cuproenzymes. Thus, a dedicated cellular delivery mechanism of Cu to MEK1/2 likely exists. Using surface plasmon resonance and proximity-dependent biotin ligase studies, we report here that the Cu chaperone for superoxide dismutase (CCS) selectively bound to and facilitated Cu transfer to MEK1. Mutants of CCS that disrupt Cu(I) acquisition and exchange or a CCS small-molecule inhibitor were used and resulted in reduced Cu-stimulated MEK1 kinase activity. Our findings indicate that the Cu chaperone CCS provides fidelity within a complex biological system to achieve appropriate installation of Cu within the MEK1 kinase active site that in turn modulates kinase activity and supports the development of novel MEK1/2 inhibitors that target the Cu structural interface or blunt dedicated Cu delivery mechanisms via CCS.

DNA polymerase gamma mutations that impair holoenzyme stability cause catalytic subunit depletion.

Mutations in POLG, encoding POLγA, the catalytic subunit of the mitochondrial DNA polymerase, cause a spectrum of disorders characterized by mtDNA instability. However, the molecular pathogenesis of POLG-related diseases is poorly understood and efficient treatments are missing. Here, we generate the PolgA449T/A449T mouse model, which reproduces the A467T change, the most common human recessive mutation of POLG. We show that the mouse A449T mutation impairs DNA binding and mtDNA synthesis activities of POLγ, leading to a stalling phenotype. Most importantly, the A449T mutation also strongly impairs interactions with POLγB, the accessory subunit of the POLγ holoenzyme. This allows the free POLγA to become a substrate for LONP1 protease degradation, leading to dramatically reduced levels of POLγA in A449T mouse tissues. Therefore, in addition to its role as a processivity factor, POLγB acts to stabilize POLγA and to prevent LONP1-dependent degradation. Notably, we validated this mechanism for other disease-associated mutations affecting the interaction between the two POLγ subunits. We suggest that targeting POLγA turnover can be exploited as a target for the development of future therapies.

The Type IV Secretion System of ICEAfe1: Formation of a Conjugative Pilus in Acidithiobacillus ferrooxidans.

The dispersal of mobile genetic elements and their gene cargo relies on type IV secretion systems (T4SS). In this work the ICEAfe1 Tra-type T4SS nanomachine, encoded in the publicly available genome of Acidithiobacillus ferrooxidans ATCC 23270TY, was characterized in terms of its organization, conservation, expression and mating bridge formation. Twenty-one conjugative genes grouped in four genetic clusters encode the ICEAfe1 T4SS, containing all the indispensable functions for the formation and stabilization of the pili and for DNA processing. The clusters' organization resembles that of other mobile genetic elements (such as plasmids and integrative and conjugative elements-ICEs). Sequence conservation, genetic organization and distribution of the tra system in the genomes of other sequenced Acidithiobacillus spp. suggests that the ICEAfe1 T4SS could mediate the lateral gene transfer between related bacteria. All ICEAfe1 T4SS genes are transcriptionally active and expressed from four independent operons. The transcriptional levels of selected marker genes increase in response to Mitomycin C treatment, a DNA damage elicitor that has acknowledged stimulatory effects on excision rates and gene expression of other ICEs, including ICEAfe1. Using a tailor-made pilin-antiserum against ICEAfe1 T4SS TraA pilin and epifluorescence microscopy, the presence of the conjugative pili on the cell surface of A. ferrooxidans could be demonstrated. Additionally, immunodetection assays, by immunogold, allowed the identification of pili-like extracellular structures. Together, the results obtained in this work demonstrate that the ICEAfe1 T4SS is phylogenetically conserved within the taxon, is expressed at mRNA and protein levels in vivo in the A. ferrooxidans type strain, and produces a pili-like structure of extracellular and intercellular localization in this model acidophile, supporting its functionality. Additional efforts will be required to prove conjugation of the ICEAfe1 or parts of this element through the cognate T4SS.

Copper Chaperone Atox1 Interacts with Cell Cycle Proteins.

The anaphase-promoting complex (APC) is involved in several processes in the cell cycle, most prominently it facilitates the separation of the sister chromatids during mitosis, before cell division. Because of the key role in the cell cycle, APC is suggested as a putative target for anticancer agents. We here show that the copper chaperone Atox1, known for shuttling copper in the cytoplasm from Ctr1 to ATP7A/B in the secretory pathway, interacts with several APC subunits. Atox1 interactions with APC subunits were discovered by mass spectrometry of co-immunoprecipitated samples and further confirmed using proximity ligation assays in HEK293T cells. Upon comparing wild-type cells with those in which the Atox1 gene had been knocked out, we found that in the absence of Atox1 protein, cells have prolonged G2/M phases and a slower proliferation rate. Thus, in addition to copper transport for loading of copper-dependent enzymes, Atox1 may modulate the cell cycle by interacting with APC subunits.

Micronucleated erythrocytes in newborns rats exposed to three different types of ultraviolet-A (UVA) lamps from commonly uses devices.

Exposure to ultraviolet-A (UVA) light can accidentally cause adverse effects in the skin and eyes. UVA induces DNA damage directly by creating pyrimidine dimers or by the formation of reactive oxygen species that can indirectly affect DNA integrity. UVA radiation is emitted by lamps from everyday devices. In adult rats, micronucleated erythrocytes (MNE) are removed from the circulation by the spleen. However, in newborn rats, MNE have been observed in peripheral blood erythrocytes. The objective of this study was to use micronucleus tests to evaluate the DNA damage caused in newborn rats exposed to UVA light from three different types of UVA lamps obtained from commonly used devices: counterfeit detectors, insecticide devices, and equipment used to harden resins for artificial nails. Rat neonates were exposed to UVA lamps for 20min daily for 6days. The neonates were sampled every third day, and the numbers of MNE and micronucleated polychromatic erythrocytes (MNPCE) in the peripheral blood were determined. The rat neonates exposed to the three types of UVA lamps showed increased numbers of MNE and MNPCE from 48h to 144h (P<0.05 and P<0.001 respectively). However, no relationship was observed between the number of MNE and the wattage of the lamps. In conclusion, under these conditions, UVA light exposure induced an increase in MNE without causing any apparent damage to the skin.

Targeting antisense mitochondrial ncRNAs inhibits murine melanoma tumor growth and metastasis through reduction in survival and invasion factors.

We reported that knockdown of the antisense noncoding mitochondrial RNAs (ASncmtRNAs) induces apoptotic death of several human tumor cell lines, but not normal cells, suggesting this approach for selective therapy against different types of cancer. In order to translate these results to a preclinical scenario, we characterized the murine noncoding mitochondrial RNAs (ncmtRNAs) and performed in vivo knockdown in syngeneic murine melanoma models. Mouse ncmtRNAs display structures similar to the human counterparts, including long double-stranded regions arising from the presence of inverted repeats. Knockdown of ASncmtRNAs with specific antisense oligonucleotides (ASO) reduces murine melanoma B16F10 cell proliferation and induces apoptosis in vitro through downregulation of pro-survival and metastasis markers, particularly survivin. For in vivo studies, subcutaneous B16F10 melanoma tumors in C57BL/6 mice were treated systemically with specific and control antisense oligonucleotides (ASO). For metastasis studies, tumors were resected, followed by systemic administration of ASOs and the presence of metastatic nodules in lungs and liver was assessed. Treatment with specific ASO inhibited tumor growth and metastasis after primary tumor resection. In a metastasis-only assay, mice inoculated intravenously with cells and treated with the same ASO displayed reduced number and size of melanoma nodules in the lungs, compared to controls. Our results suggest that ASncmtRNAs could be potent targets for melanoma therapy. To our knowledge, the ASncmtRNAs are the first potential non-nuclear targets for melanoma therapy.

[Giant Meckel's diverticulum in an adult]. / Divertículo de Meckel gigante en un adulto.

Meckel's diverticulum results from a partial persistence of the omphalomesenteric duct and is the most common congenital anomaly of the gastrointestinal tract, affecting about 2% of the general population. Its presentation as a giant Meckel's diverticulum (>5 cm) is rare and is associated with major complications. We report a case of a 53 year-old woman with constipation for at least ten years. A colonoscopy from eight years ago suggested megacolon. The patient consults in the last month for abdominal pain associated with anorexia. The computed tomography scan image suggested an ileal megadiverticulum. An exploratory laparotomy revealed a saccular dilatation of the distal ileum of 6 x 15.5 cm, located 20 cm away from the ileocecal valve. We resected the involved segment of distal ileum and performed a manual ileo-ascendo anastomosis. The biopsy showed a saccular dilatation of the wall, lined by small intestinal mucosa with areas of gastric metaplasia, supporting the diagnosis of giant Meckel's diverticulum.

El divertículo de Meckel corresponde a la persistencia parcial del conducto onfalomesentérico, representa la anomalía congénita más frecuente del tracto gastrointestinal y afecta alrededor del 2% de la población general. La presentación como divertículo de Meckel gigante (>5 cm) es infrecuente y está asociada a una mayor tasa de complicaciones. Se presenta el caso de una mujer de 53 años que refiere constipación de al menos diez años; una colonoscopía de hace ocho años sugiere un megacolon y en el último mes la paciente ha presentado dolor abdominal asociado a anorexia. Se realiza una tomografía computarizada con imagen que sugiere la presencia de megadivertículo ileal, por lo que se decide realizar una laparotomía exploradora que evidencia una dilatación sacular del íleon distal a 20 cm de la válvula ileocecal de 15,5 x 6 cm aproximadamente. Se reseca el segmento comprometido del íleon distal, que queda cerrado a nivel de la válvula ileocecal, y se realiza una íleo-ascendo anastomosis manual. La biopsia informa dilatación sacular de la pared, revestida por mucosa de intestino delgado con áreas de metaplasia gástrica, hallazgos compatibles con un divertículo de Meckel gigante.

Genomic evidence for the emergence and evolution of pathogenicity and niche preferences in the genus Campylobacter.

The genus Campylobacter includes some of the most relevant pathogens for human and animal health; the continuous effort in their characterization has also revealed new species putatively involved in different kind of infections. Nowadays, the available genomic data for the genus comprise a wide variety of species with different pathogenic potential and niche preferences. In this work, we contribute to enlarge this available information presenting the first genome for the species Campylobacter sputorum bv. sputorum and use this and the already sequenced organisms to analyze the emergence and evolution of pathogenicity and niche preferences among Campylobacter species. We found that campylobacters can be unequivocally distinguished in established and putative pathogens depending on their repertory of virulence genes, which have been horizontally acquired from other bacteria because the nonpathogenic Campylobacter ancestor emerged, and posteriorly interchanged between some members of the genus. Additionally, we demonstrated the role of both horizontal gene transfers and diversifying evolution in niche preferences, being able to distinguish genetic features associated to the tropism for oral, genital, and gastrointestinal tissues. In particular, we highlight the role of nonsynonymous evolution of disulphide bond proteins, the invasion antigen B (CiaB), and other secreted proteins in the determination of niche preferences. Our results arise from assessing the previously unmet goal of considering the whole available Campylobacter diversity for genome comparisons, unveiling notorious genetic features that could explain particular phenotypes and set the basis for future research in Campylobacter biology.

Experiencia de prevención en salud mental pediátrica: psicoprofilaxis quirúrgica en pacientes sometidos a cirugía de escoliosis / Prevention experience in pediatric mental health: surgical pychoprophylaxis in patients undergoing scoliosis surgery

El presente artículo presenta un proyecto piloto de Psicoprofilaxis Quirúrgica en el Departamento de Traumatología, Unidad de Escoliosis, Hospital de niños Dr. Luis Calvo Mackenna. La Psicoprofilaxis Quirúrgica, enmarcada dentro de la psicología de la salud, tiene por objetivo apoyar al paciente que será sometido a cirugía, en el manejo de emociones, actitudes y comportamientos que se derivan de la situación quirúrgica, a través de una intervención psicoterapéutica preventiva, breve y focalizada. Se planteó una intervención psicológica para pacientes que debían ser sometidos a cirugía correctiva de escoliosis. Esta constó de 3 instancias: (a) entrevista inicial y evaluación de ansiedad, (b) intervención intrahospitalaria y (c) control postquirúrgico. En todas ellas se midió Nivel Anímico, Nivel de Actividad, Calidad del Sueño y Calidad de la Alimentación. Los resultados sugieren que si los pacientes tienen un adecuado conocimiento del proceso al cual se enfrentarán, aumentaría su sensación de control de la situación y por ende, disminuiría su ansiedad pre-quirúrgica. No obstante, no basta informar, sino que además es necesario adecuarse a las características de cada paciente al hacer entrega de la información, siendo este factor el que permitiría el cambio en los niveles de ansiedad pre-quirúrgica.

This article presents a trial scheme of surgical psychoprophylaxis in the Scoliosis Unit of the Traumatology department at “Doctor Luis Calvo Mackenna childrens” Hospital. This project arises from The surgical psychoprophylaxis is to an area within Health Psychology that aims to support the patient that will undergo surgery, by performing a brief preventive psychotherapeutic intervention that helps him/her to handle possible emotions, attitudes and behaviors that may appear as a result of the surgical experience. The intervention had three stages: (a) Initial interview and anxiety assessment (b) intra- hospital intervention (c) post surgical control. In each stage mood level was measured as well as activity level, sleep quality and feeding behavior quality. The results suggest that, if patients have adequate knowledge of the process they are going to face their feeling of control over the situation would increase and thus reduce preoperative anxiety. Nevertheless, informing is not enough but it is also necessary to adapt the delivery of information to each patient’s characteristics, for this would be the main factor that would allow changes in preoperative anxiety levels.

Being immersed in social networking environment: Facebook groups, uses and gratifications, and social outcomes.

A Web survey of 1,715 college students was conducted to examine Facebook Groups users' gratifications and the relationship between users' gratifications and their political and civic participation offline. A factor analysis revealed four primary needs for participating in groups within Facebook: socializing, entertainment, self-status seeking, and information. These gratifications vary depending on user demographics such as gender, hometown, and year in school. The analysis of the relationship between users' needs and civic and political participation indicated that, as predicted, informational uses were more correlated to civic and political action than to recreational uses.

A vaccine against the salmonid pathogen Piscirickettsia salmonis based on recombinant proteins.

We report here the protective effect against piscirickettsiosis elicited in fish by a mixture of recombinant proteins. A comparative genomics strategy was used on a genomic library of Piscirickettsia salmonis in order to select optimal candidates for a recombinant subunit vaccine to protect fish from rickettsial septicaemia (SRS). Based on this information, 15 P. salmonis ORFs encoding heat shock proteins, virulence factors, membrane bound and other surface exposed antigens, were isolated and expressed. Seven of the most promising antigens were formulated in three mixtures (V1-V3) containing two or three recombinant proteins each and injected into salmon to test their protective efficacy. Two of the three formulations (V1, V2) elicited a strong protective response in a challenge against the pathogen, which was coincident with the humoral response against the corresponding recombinant proteins present in each formulation. V1, formulated with recombinant chaperonines Hsp60, Hsp70 and flagellar protein FlgG of P. salmonis achieved the highest level of protection with a relative percent survival (RPS) of 95%.