Resolution Enhancement of Metabolomic J-Res NMR Spectra Using Deep Learning.

J-Resolved (J-Res) nuclear magnetic resonance (NMR) spectroscopy is pivotal in NMR-based metabolomics, but practitioners face a choice between time-consuming high-resolution (HR) experiments or shorter low-resolution (LR) experiments which exhibit significant peak overlap. Deep learning neural networks have been successfully used in many fields to enhance quality of natural images, especially with regard to resolution, and therefore offer the prospect of improving two-dimensional (2D) NMR data. Here, we introduce the J-RESRGAN, an adapted and modified generative adversarial network (GAN) for image super-resolution (SR), which we trained specifically for metabolomic J-Res spectra to enhance peak resolution. A novel symmetric loss function was introduced, exploiting the inherent vertical symmetry of J-Res NMR spectra. Model training used simulated high-resolution J-Res spectra of complex mixtures, with corresponding low-resolution spectra generated via blurring and down-sampling. Evaluation of peak pair resolvability on J-RESRGAN demonstrated remarkable improvement in resolution across a variety of samples. In simulated plasma data, 100% of peak pairs exhibited enhanced resolution in super-resolution spectra compared to their low-resolution counterparts. Similarly, enhanced resolution was observed in 80.8-100% of peak pairs in experimental plasma, 85.0-96.7% in urine, 94.4-98.9% in full fat milk, and 82.6-91.7% in orange juice. J-RESRGAN is not sample type, spectrometer or field strength dependent and improvements on previously acquired data can be seen in seconds on a standard desktop computer. We believe this demonstrates the promise of deep learning methods to enhance NMR metabolomic data, and in particular, the power of J-RESRGAN to elucidate overlapping peaks, advancing precision in a wide variety of NMR-based metabolomics studies. The model, J-RESRGAN, is openly accessible for download on GitHub at https://github.com/yanyan5420/J-RESRGAN.

Tracking DOT1L methyltransferase activity by stable isotope labelling using a selective synthetic co-factor.

Epigenetic processes influence health and disease through mechanisms which alter gene expression. In contrast to genetic changes which affect DNA sequences, epigenetic marks include DNA base modifications or post-translational modification (PTM) of proteins. Histone methylation is a prominent and versatile example of an epigenetic marker: gene expression or silencing is dependent on the location and extent of the methylation. Protein methyltransferases exhibit functional redundancy and broad preferences for multiple histone residues, which presents a challenge for the study of their individual activities. We developed an isotopically labelled analogue of co-factor S-adenosyl-L-methionine (13CD3-BrSAM), with selectivity for the histone lysine methyltransferase DOT1L, permitting tracking of methylation activity by mass spectrometry (MS). This concept could be applied to other methyltransferases, linking PTM discovery to enzymatic mediators.

A single harmonised pharmacy process to improve clinical trial set-up times.

The UK has fallen from fourth to 10th place in the global ranking for clinical trial activities in the past 6 years. Due to the limited capacity of the clinical trial pharmacy workforce and delays in providing pharmacy approvals, pharmacy has been identified as one of the constraining services that delays the set-up and delivery of clinical trials. To tackle this problem, we developed a single pharmacy review process for multicentre trials across Greater Manchester (GM) and tested its feasibility and implementation in our region. A survey completed by each GM Trust suggests that this harmonised pharmacy review process for multicentre studies would expedite trial set-up time at each pharmacy site and standardise the pharmacy review process in GM. We therefore believe that this harmonised review process could potentially reduce pharmacy set-up time and reposition the UK in the global market for clinical trials.

Transforming body composition with semaglutide in adults with obesity and type 2 diabetes mellitus.

Background: Glucagon-like peptide-1 receptor-agonists (GLP-1ra), such as semaglutide, have emerged as promising treatments, demonstrating sustained weight reduction and metabolic benefits. This study aims to assess the impact of oral and subcutaneous semaglutide on body composition and metabolic parameters in patients with T2DM and obesity. Methods: A 24-week quasi-experimental retrospective study including adults with T2DM and obesity (BMI ≥ 30 kg/m²) who were treated with either daily-oral or weekly-subcutaneous semaglutide. Body composition was measured using bioelectrical impedance analysis, evaluating fat mass, fat-free mass, total body water, skeletal muscle mass, and whole-body phase angle. Analytical parameters included lipid profile and glycaemic control. Statistical analyses were performed using SPSS v.26. Results: Participants (n=88) experienced significant weight loss after treatment with semaglutide (9.5% in subcutaneous, 9.4% in oral, P<0.001). Weight reduction primarily resulted from fat mass reduction without substantial lean mass compromise. Visceral fat area decreased, whiles phase-angle remained stable. Improvements in lipid profiles and glycaemic control were observed, with a decrease in both HbA1c and insulin requirements. Multivariate analysis demonstrated comparable impacts of oral and subcutaneous semaglutide on body composition. Conclusion: Semaglutide, administered orally or subcutaneously, demonstrated positive effects on body composition, metabolic and glycaemic control in patients with T2DM and obesity. This real-world study highlights the potential of bioelectrical impedance analysis in assessing antidiabetic drugs' impact on body composition, providing valuable insights for future research and clinical applications.

Burden of Disease Study of Patients with Neovascular Age-Related Macular Degeneration in Spain.

INTRODUCTION: Neovascular age-related macular degeneration (nAMD) is a progressive retinal disease that causes severe and irreversible vision loss. The disease can therefore have a significant impact on the life of patients' and their families. The aim of this study was to evaluate the socio-economic burden of nAMD in Spain. METHODS: The annual cost per patient with nAMD was estimated for the first, second, and third year (or beyond) of treatment since diagnosis. Several cost categories were considered including direct healthcare costs (DHC), direct non-healthcare costs (DNHC), labor productivity losses (LPL), and intangible costs (IC) related to loss of quality of life. The average annual cost per patient was estimated by assigning a unit price or financial proxy to the resources consumed per patient. Reference year of costs was 2021. RESULTS: The mean annual cost of nAMD was estimated at €17,265, €15,403, and €14,465 per patient in the first, second, and third year of treatment after diagnosis. There was an additional one-off cost of €744 associated with the diagnosis of nAMD. DHC accounted for most of the total annual cost per patient independent of the year of treatment since diagnosis (48% in year 1; 42% in year 2; 39% in year 3). Similarly, DNHC had an important contribution to the total costs (32% in year 1; 35% in year 2; 37% in year 3), followed by IC (20% in year 1; 23% in year 2; 24% in year 3), while the contribution of patients' LPL was minimal. CONCLUSION: This study estimated a high economic burden associated with nAMD for patients and their families, the healthcare system, and society at large. There is a need to improve the management of these patients to reduce the impact of nAMD disease progression.

Burden of Disease Study of Patients with Diabetic Macular Oedema in Spain.

INTRODUCTION: Diabetic macular oedema (DMO) is a complication of diabetic retinopathy that can result in vision loss. The disease can impact different spheres of a patient's life, including physical and psychological health, work, and activities of daily living, entailing an important use of healthcare and non-healthcare resources. This study aimed to estimate the socio-economic burden of DMO in Spain. METHODS: The burden of DMO was estimated from a societal perspective, per patient, year of treatment since diagnosis, and type of treatment. Four categories were considered: direct healthcare costs (DHC), direct non-healthcare costs (DNHC), labour productivity losses (LPL), and intangible costs (IC) associated with loss of quality of life. Average annual costs were calculated by multiplying the resources used per patient by their corresponding unit price (or financial proxy). For a more accurate estimation, differences in resource use between treatments (intravitreal anti-vascular endothelial growth factor injections of ranibizumab or aflibercept, and intravitreal dexamethasone implants) and year since diagnosis (first, second, and third year or beyond) were considered and presented separately. The reference year for costs was 2021. RESULTS: The average annual costs of DMO in the first year of treatment after diagnosis was estimated at €18,774, €17,512, and €16,188 per patient treated with ranibizumab, aflibercept, and dexamethasone, respectively. This burden would be reduced to €15,783, €15,701, and €12,233 in the second year, and to €15,119, €15,043, and €12,790 in the third year, respectively. Diagnosis of DMO entails an additional one-off cost of €485. DHC accounted for the greatest proportion of total annual costs per patient, independent of the year, with LPL also making an important contribution to total costs. CONCLUSIONS: The socio-economic impact of DMO on patients, the healthcare system, and society at large is substantial. The constant increase in its prevalence accentuates the need for planning and implementation of healthcare strategies to prevent vision loss and reduce the socio-economic burden of the disease.

Regulation of TSC2 lysosome translocation and mitochondrial turnover by TSC2 acetylation status.

Sirtuin1 (SIRT1) activity decreases the tuberous sclerosis complex 2 (TSC2) lysine acetylation status, inhibiting the mechanistic target of rapamycin complex 1 (mTORC1) signalling and concomitantly, activating autophagy. This study analyzes the role of TSC2 acetylation levels in its translocation to the lysosome and the mitochondrial turnover in both mouse embryonic fibroblast (MEF) and in mouse insulinoma cells (MIN6) as a model of pancreatic ß cells. Resveratrol (RESV), an activator of SIRT1 activity, promotes TSC2 deacetylation and its translocation to the lysosome, inhibiting mTORC1 activity. An improvement in mitochondrial turnover was also observed in cells treated with RESV, associated with an increase in the fissioned mitochondria, positive autophagic and mitophagic fluxes and an enhancement of mitochondrial biogenesis. This study proves that TSC2 in its deacetylated form is essential for regulating mTORC1 signalling and the maintenance of the mitochondrial quality control, which is involved in the homeostasis of pancreatic beta cells and prevents from several metabolic disorders such as Type 2 Diabetes Mellitus.

Predictors for liver fibrosis in non-alcoholic patients with psoriatic diseases: A multicenter cross sectional-study.

Psoriasis has been related to metabolic dysfunction-associated fatty liver disease and, liver fibrosis. This study aimed to evaluate the prevalence of liver fibrosis in psoriasis and identify predictors for fibrosis. This is a cross-sectional study conducted from December 2012 to June 2016 assessing psoriasis and psoriatic arthritis patients attended at four centers in Mexico City. Data regarding history of the skin disease, previous and current medication, and previously diagnosed liver disease was collected. Liver fibrosis was assessed with four different non-invasive methods (FIB4, APRI, NAFLD score and elastography). We compared data based on the presence of fibrosis. Adjusted-logistic regression models were performed to estimate OR and 95% CI. A total of 160 patients were included. The prevalence of significant fibrosis using elastography was 25% (n = 40), and 7.5% (n = 12) for advanced fibrosis. Patients with fibrosis had higher prevalence of obesity (60% vs 30.8%, P = 0.04), type 2 diabetes (40% vs 27.5%, P = 0.003), gamma-glutamyl transpeptidase levels (70.8±84.4 vs. 40.1±39.2, P = 0.002), and lower platelets (210.7±58.9 vs. 242.8±49.7, P = 0.0009). Multivariate analysis showed that body mass index (OR1.11, 95%CI 1.02-1.21), type 2 diabetes (OR 3.44, 95%CI 1.2-9.88), and gamma-glutamyl transpeptidase (OR 1.01, 95%CI1-1.02) were associated with the presence of fibrosis. The use of methotrexate was not associated. Patients with psoriasis are at higher risk of fibrosis. Metabolic dysfunction, rather than solely the use of hepatotoxic drugs, likely plays a major role; it may be beneficial to consider elastography regardless of the treatment used. Metabolic factors should be assessed, and lifestyle modification should be encouraged.

Physicochemical Properties and Microbiome of Vineyard Soils from DOP Ribeiro (NW Spain) Are Influenced by Agricultural Management.

Agricultural management influences the soil ecosystem by affecting its physicochemical properties, residues of pesticides and microbiome. As vineyards grow crops with the highest incidence of pesticides, the aim of this study was to evaluate the impact of conventional and sustainable management systems of vineyards from DOP Ribeiro on the soil's condition. Samples from soils under three different management systems were collected, and the main soil physicochemical properties were evaluated. A selection of 50 pesticides were investigated by liquid chromatography with tandem mass spectrometry. The bacterial and fungal microbiomes were characterized through amplicon sequencing. The results show that organic agriculture positively influences soil pH and the concentration of some nutrients compared to conventional management. Our microbiome analysis demonstrated that transitioning from conventional to organic management significantly improves several BeCrop® indexes related to key microbial metabolism and soil bio-sustainability. Such a transition does not affect soil alpha diversity, but leads to a higher interconnected microbial network structure. Moreover, differential core genera and species for each management system are observed. In addition, the correlation of the microbiome with geographical distance is evidence of the existence of different microbial terroirs within DOP Ribeiro. Indeed, sustainable management leads to higher nutrient availability and enhances soil health in the short term, while lowering pesticide usage.

Short impact on soil microbiome of a Bacillus amyloliquefaciens QST713 based product that correlates with higher potato yield across USA.

Potato (Solanum tuberosum L.) is considered one of the most widely consumed crops worldwide, due to its high yield and nutritional profile, climate change-related environmental threats and increasing food demand. This scenario highlights the need of sustainable agricultural practices to enhance potato productivity, while preserving and maintaining soil health. Plant growth-promoting bacteria (PGPB) stimulate crop production through biofertilization mechanisms with low environmental impact. For instance, PGPB promote biological nitrogen fixation, phosphate solubilization, production of phytohormones, and biocontrol processes. Hence, these microbes provide a promising solution for more productive and sustainable agriculture. In this study, the effects of Bacillus amyloliquefaciens QST713 based-product (MINUET™, Bayer) were assessed in terms of yield, soil microbiome, potato peel and petiole nutrient profile as a promising PGPB in a wide range of potato cultivars across the United States of America. Depending on the location, potato yield and boron petiole content increased after biostimulant inoculation to maximum of 24% and 14%, respectively. Similarly, nutrient profile in potato peel was greatly improved depending on the location with a maximum of 73%, 62% and 36% for manganese, zinc and phosphorus. Notably, fungal composition was shifted in the treated group. Yield showed strong associations with specific microbial taxa, such as Pseudoarthrobacter, Ammoniphilus, Ideonella, Candidatus Berkiella, Dongia. Moreover, local networks strongly associated with yield, highlighting the important role of the native soil microbiome structure in indirectly maintaining soil health. Our results showed that treatment with B. amyloliquefaciens based product correlated with enhanced yield, with minor impacts on the soil microbiome diversity. Further studies are suggested to disentangle the underlying mechanisms of identified patterns and associations.

RET Fusion Testing in Patients With NSCLC: The RETING Study.

Introduction: RET inhibitors with impressive overall response rates are now available for patients with NSCLC, yet the identification of RET fusions remains a difficult challenge. Most guidelines encourage the upfront use of next-generation sequencing (NGS), or alternatively, fluorescence in situ hybridization (FISH) or reverse transcriptase-polymerase chain reaction (RT-PCR) when NGS is not possible or available. Taken together, the suboptimal performance of single-analyte assays to detect RET fusions, although consistent with the notion of encouraging universal NGS, is currently widening some of the clinical practice gaps in the implementation of predictive biomarkers in patients with advanced NSCLC. Methods: This situation prompted us to evaluate several RET assays in a large multicenter cohort of RET fusion-positive NSCLC (n = 38) to obtain real-world data. In addition to RNA-based NGS (the criterion standard method), all positive specimens underwent break-apart RET FISH with two different assays and were also tested by an RT-PCR assay. Results: The most common RET partners were KIF5B (78.9%), followed by CCDC6 (15.8%). The two RET NGS-positive but FISH-negative samples contained a KIF5B(15)-RET(12) fusion. The three RET fusions not identified with RT-PCR were AKAP13(35)-RET(12), KIF5B(24)-RET(9) and KIF5B(24)-RET(11). All three false-negative RT-PCR cases were FISH-positive, exhibited a typical break-apart pattern, and contained a very high number of positive tumor cells with both FISH assays. Signet ring cells, psammoma bodies, and pleomorphic features were frequently observed (in 34.2%, 39.5%, and 39.5% of tumors, respectively). Conclusions: In-depth knowledge of the advantages and disadvantages of the different RET testing methodologies could help clinical and molecular tumor boards implement and maintain sensible algorithms for the rapid and effective detection of RET fusions in patients with NSCLC. The likelihood of RET false-negative results with both FISH and RT-PCR reinforces the need for upfront NGS in patients with NSCLC.

Rhizoctonia solani disease suppression: addition of keratin-rich soil amendment leads to functional shifts in soil microbial communities.

Promoting soil suppressiveness against soil borne pathogens could be a promising strategy to manage crop diseases. One way to increase the suppression potential in agricultural soils is via the addition of organic amendments. This microbe-mediated phenomenon, although not fully understood, prompted our study to explore the microbial taxa and functional properties associated with Rhizoctonia solani disease suppression in sugar beet seedlings after amending soil with a keratin-rich waste stream. Soil samples were analyzed using shotgun metagenomics sequencing. Results showed that both amended soils were enriched in bacterial families found in disease suppressive soils before, indicating that the amendment of keratin-rich material can support the transformation into a suppressive soil. On a functional level, genes encoding keratinolytic enzymes were found to be abundant in the keratin-amended samples. Proteins enriched in amended soils were those potentially involved in the production of secondary metabolites/antibiotics, motility, keratin-degradation, and contractile secretion system proteins. We hypothesize these taxa contribute to the amendment-induced suppression effect due to their genomic potential to produce antibiotics, secrete effectors via the contractile secretion system, and degrade oxalate-a potential virulence factor of R. solani-while simultaneously possessing the ability to metabolize keratin.

Impact of Flash Glucose Monitoring on the Fear of Hypoglycemia Phenomenon in Adults with Type 1 Diabetes.

Objective: To assess the clinical impact of flash glucose monitoring (FGM) systems on fear of hypoglycemia (FoH) and quality of life in adults with type 1 diabetes mellitus (T1DM). Methods: Prospective quasi-experimental study with a 12-month follow-up. People with T1DM (18-80 years old) and self-monitoring by blood capillary glycemia controls were included. The FH15 questionnaire, a survey validated in Spanish in a comparable study population, was used to diagnose FoH with a cutoff point of 28 points. Results: A total of 181 participants were included, with a FoH prevalence of 69% (n = 123). A mean reduction in FH15 score of -4 points (95% confidence interval [-5.5 to -3]; P < 0.001) was observed, along with an improvement in quality of life (EsDQOL-test (Diabetes Quality of Life, Spanish version), -7 points [-10; -4], P < 0.001) and satisfaction with treatment (Diabetes Treatment Satisfaction questionnaire, self-reported version [DTSQ-s] test, +4.5 points [4; 5.5], P < 0.001). At the end of the follow-up, 64.2% of the participants saw an improved FoH intensity, compared to 35.8% who scored the same or higher. This improvement in FoH status was associated with a higher time-in-range at the end of the follow-up (P = 0.003), as well as a lower time spent in hyperglycemia (P = 0.005). In addition, it was linked to participants with a high baseline FoH levels (P < 0.001) and those who were university degree holders (P = 0.07). Conclusions: FGM is associated with an overall reduction of FoH in adults with T1DM and with an increase in their quality of life. Nevertheless, a significant percentage of patients may experience an increase of this phenomenon leading to clinical repercussions and a profound impact on quality of life.

The role of gastrointestinal endoscopy in Kaposi sarcoma / El papel de la endoscopia gastrointestinal en el sarcoma de Kaposi

We are writing to make endoscopists aware of the paramount of a prompt diagnosis of gastrointestinal Kaposi sarcoma (GI-KS). Patients with GI involvement have a two to five times higher risk of death and will benefit from chemotherapy to improve their survival. However, current evidence found that one out of three patients might have a false negative result even with HHV-8 since other entities such as gastrointestinal stromal tumors, angiosarcoma, and lymphoma shared macroscopic and histopathological characteristics. These cause a delay in treatment and significantly worsen the prognosis. We observed a trend for a positive diagnosis from ulcers and nodules. To our knowledge, this is the largest cohort of patients with GI-KS in the world. Our study suggests that in cases where a complete immunochemistry panel for KS is not available, HHV-8 remains as a bare minimum. However, other gastrointestinal lesions shared histopathological characteristics. Therefore, we suggest taking biopsies from nodular and ulcer-type lesions to increase the probability to establish a histopathological diagnosis.(AU)

Brief report: High incidence of peridiagnosis thromboembolic events in patients with BRAF-mutant lung cancer.

INTRODUCTION: We aimed to determine if advanced BRAF-mutant NSCLC has a higher thromboembolic events (TEE) rate than the expected. METHODS: Between 2008 and 2021, 182 patients with BRAF-mutant advanced NSCLC (BRAF V600E, n = 70; BRAF non-V600E, n = 112) were retrospectively identified from 18 centers in Spain. Patients received chemotherapy (n = 147), immunotherapy (n = 69), targeted therapy (n = 42), and immunotherapy + chemotherapy (n = 26). RESULTS: Incidence rate of TEE was 26.4 % (95%CI: 19.9 %-32.9 %). A total of 72 TEE were documented among 48 patients, as 18 patients (37.5 %) developed more than one event. Median time to TEE onset was 2 months, 69 % of TEE occurred in the peridiagnostic period (+/- 90 days from cancer diagnosis), and in 16 pts. (33 %) TEE was the form of lung cancer presentation. Although most TEE were only venous (82 %; PE, n = 33; DVT, n = 16), arterial events were reported in 31 % and occurred earlier, or TEE presented in atypical locations (13.9 %). TEE were related to high hospitalization rate (59 %), recurrence (23 %), and mortality (10.4 %) despite appropriate anticoagulant/antiaggregant treatment. Median OS in patients without-TEE was 19.4 months (95%CI: 4.6-34.1), and significantly shorter in patients with arterial-TEE vs venous-TEE vs both of them: 9.9 months (95%CI: 0-23.5) vs 41.7 months (95%CI: 11.3-72.2 m) vs 2.7 months (95%CI: 2.1-3.3), p = 0.001. Neither clinical or molecular features (BRAF V600E/non-V600E), nor cancer treatment was associated to TEE occurrence. Khorana score underperformed to predict thrombosis at cancer diagnosis, as only 19.2 % of patients were classified as high-risk. CONCLUSIONS: Thrombotic events represent a new clinical feature of BRAF-mutant lung cancer. Patients with almost a 30 % incidence of TEE should be offered systematic anticoagulation.

Polyploidy-associated autophagy promotes larval tracheal histolysis at Drosophila metamorphosis.

Polyploidy is an extended phenomenon in biology. However, its physiological significance and whether it defines specific cell behaviors is not well understood. Here we study its connection to macroautophagy/autophagy, using the larval respiratory system of Drosophila as a model. This system comprises cells with the same function yet with notably different ploidy status, namely diploid progenitors and their polyploid larval counterparts, the latter destined to die during metamorphosis. We identified an association between polyploidy and autophagy and found that higher endoreplication status correlates with elevated autophagy. Finally, we report that tissue histolysis in the trachea during Drosophila metamorphosis is mediated by autophagy, which triggers the apoptosis of polyploid cells.Abbreviations: APF: after pupa formation; Atg: autophagy related; btl: breathless; CycE: Cyclin E; DT: dorsal trunk; fzr: fizzy-related; L3: larval stage 3; PBS: phosphate-buffered saline; RI: RNAi; Tr: tracheal metamere; yki: yorkie.

Genetic Mapping of the Root Mycobiota in Rice and its Role in Drought Tolerance.

BACKGROUND: Rice is the second most produced crop worldwide, but is highly susceptible to drought. Micro-organisms can potentially alleviate the effects of drought. The aim of the present study was to unravel the genetic factors involved in the rice-microbe interaction, and whether genetics play a role in rice drought tolerance. For this purpose, the composition of the root mycobiota was characterized in 296 rice accessions (Oryza sativa L. subsp. indica) under control and drought conditions. Genome wide association mapping (GWAS) resulted in the identification of ten significant (LOD > 4) single nucleotide polymorphisms (SNPs) associated with six root-associated fungi: Ceratosphaeria spp., Cladosporium spp., Boudiera spp., Chaetomium spp., and with a few fungi from the Rhizophydiales order. Four SNPs associated with fungi-mediated drought tolerance were also found. Genes located around those SNPs, such as a DEFENSIN-LIKE (DEFL) protein, EXOCYST TETHERING COMPLEX (EXO70), RAPID ALKALINIZATION FACTOR-LIKE (RALFL) protein, peroxidase and xylosyltransferase, have been shown to be involved in pathogen defense, abiotic stress responses and cell wall remodeling processes. Our study shows that rice genetics affects the recruitment of fungi, and that some fungi affect yield under drought. We identified candidate target genes for breeding to improve rice-fungal interactions and hence drought tolerance.

Testing the stress gradient hypothesis in soil bacterial communities associated with vegetation belts in the Andean Atacama Desert.

BACKGROUND: Soil microorganisms are in constant interaction with plants, and these interactions shape the composition of soil bacterial communities by modifying their environment. However, little is known about the relationship between microorganisms and native plants present in extreme environments that are not affected by human intervention. Using high-throughput sequencing in combination with random forest and co-occurrence network analyses, we compared soil bacterial communities inhabiting the rhizosphere surrounding soil (RSS) and the corresponding bulk soil (BS) of 21 native plant species organized into three vegetation belts along the altitudinal gradient (2400-4500 m a.s.l.) of the Talabre-Lejía transect (TLT) in the slopes of the Andes in the Atacama Desert. We assessed how each plant community influenced the taxa, potential functions, and ecological interactions of the soil bacterial communities in this extreme natural ecosystem. We tested the ability of the stress gradient hypothesis, which predicts that positive species interactions become increasingly important as stressful conditions increase, to explain the interactions among members of TLT soil microbial communities. RESULTS: Our comparison of RSS and BS compartments along the TLT provided evidence of plant-specific microbial community composition in the RSS and showed that bacterial communities modify their ecological interactions, in particular, their positive:negative connection ratios in the presence of plant roots at each vegetation belt. We also identified the taxa driving the transition of the BS to the RSS, which appear to be indicators of key host-microbial relationships in the rhizosphere of plants in response to different abiotic conditions. Finally, the potential functions of the bacterial communities also diverge between the BS and the RSS compartments, particularly in the extreme and harshest belts of the TLT. CONCLUSIONS: In this study, we identified taxa of bacterial communities that establish species-specific relationships with native plants and showed that over a gradient of changing abiotic conditions, these relationships may also be plant community specific. These findings also reveal that the interactions among members of the soil microbial communities do not support the stress gradient hypothesis. However, through the RSS compartment, each plant community appears to moderate the abiotic stress gradient and increase the efficiency of the soil microbial community, suggesting that positive interactions may be context dependent.