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The trophic dynamics of islands with low terrestrial primary productivity often depend on marine allochthonous inputs from nearby donor habitats. For instance, on Malpelo Island, Colombia (4° 00′ 05.63″ N; 81° 36′ 36.41″ W), the Nazca booby Sula granti affects the productivity and trophic dynamics of the terrestrial ecosystem by delivering nutrients, primary in the form guano, chick carcasses, and eggs. This study evaluated the trophic connectivity between the terrestrial and marine ecosystems of Malpelo Island, Colombia based on the isotopic (δ13C and δ15N) assessment of 403 samples (107 terrestrial and 296 marine) collected between 2017 and 2021. Isospaces were estimated based on δ13C and δ15N values, contribution of terrestrial sources in consumer diets (mixing model), 15 N enrichment in C3 plants, and interactions among environments (overlap). δ13C and δ15N values showed a larger terrestrial isospace (134.7‰2) than the marine isospace (117.2‰2). The mixing model indicated that detritusTerrestrial (median: 30.2%) contributed more to the food web than C3 plants (0.2%), reflecting high δ13CMarine content. The high isotopic overlap (> 60%) between terrestrial and marine isospaces suggests a significant trophic connection between environments. These results show the role of the marine ecosystem on the terrestrial ecosystem and the importance of S. granti regarding nutrient transfer between environments. The conservation of this seabird is essential to maintain the balance of this insular ecosystem. Using stable isotopes, this study was able to reveal trophic relationships between ecosystems associated with small oceanic islands that host large seabird colonies but have low primary productivity.

Changes in feeding habits during ontogeny show that organisms can present shifts in foraging behavior during their life cycle, which can alter local trophic dynamics. Therefore, describing diet across species ontogeny clarifies the ecological niche and ecosystem role of marine predators. In this study, diet tracers (stable isotope analysis) were analyzed in 16 scalloped hammerhead sharks Sphyrna lewini, using δ13C and δ15N values of collagen in vertebral cross-sections to reconstruct diet across their ontogeny. Our results suggest that S. lewini occupies a broad isotopic niche due to the consumption of prey belonging to different trophic levels (δ15N: 7.6−13.0‰) of the food chain in both coastal and oceanic zones (δ13C: −17.2 to −14.1‰) during their lifetime. Accordingly, ontogenetic changes in diet and habitat use were suggested by differences in δ13C and δ15N across age groups, indicating high consumption of coastal prey at 0−2 yr, oceanic prey at ~2−4 yr, a shift to high coastal prey at >4 yr, and a shift to high coastal prey, along with the consumption of prey from multiple trophic levels through feeding ontogeny (estimated trophic position: 2.9−6.5). This study showed migration from coastal to oceanic zones in juvenile S. lewini, and their return to coastal habitats as adults, potentially related to the use of coastal zones (i.e. mangroves) in the Eastern Tropical Pacific, both as important feeding areas for neonates and as feeding and breeding grounds for adults.

Elasmobranchs can play important roles in marine communities. But, relatively little is known about their diet, and movement. Sphyrna lewini (Griffith et Smith, 1834) consumes fishes, cephalopods, rays, and crustaceans. Carcharhinus falciformis (Müller et Henle, 1839) feed on fishes, cephalopods, crustaceans and sea turtles. To date, there are no studies available on the trophic ecology of sharks in Malpelo Island. The aim of this study was to describe the trophic ecology of S. lewini and C. falciformis, using stable isotope analysis of δ13C and δ15N, to better understand the role of both shark species in the Malpelo Island ecosystem. In January, February, and November 2013, specimens of Sphyrna lewini and Carcharhinus falciformis illegally caught at Malpelo Island were confiscated at the port of Buenaventura, Colombia. For each shark specimen, total length and sex were registered. Samples of muscle tissue were taken from the nape of all specimens. Each muscle sample was lyophilized for 24 h and analysed with lipid and urea extraction and without extraction. For each shark specimen, a subsample of ~1.0 mg was used for isotopic analysis. A total of 14 Sphyrna lewini (Griffith et Smith, 1834) and 12 Carcharhinus falciformis (Müller et Henle, 1839) were analysed. δ13C values were similar between S. lewini (-16.3 ± 0.1‰) and C. falciformis (-16.5 ± 0.1‰). Sphyrna lewini showed a wider trophic niche than C. falciformis, with low trophic overlap (5%) between the two species. The δ15N values of S. lewini (15.9 ± 0.11%o) were higher than those of C. falciformis (14.9 ± 0.09‰). In C. falciformis, δ13C values were similar in both sexes (-16.5 ± 0.1%o), while δ15N values were significantly different between males (14.6 ± 0.1‰) and females (15.0 ± 0.1‰). The trophic position of S. lewini was 5.25 ± 0.12, and that of C. falciformis, 5.48 ± 0.18, which suggests that both shark species occupy a high position in the marine food chain. Both shark species co-occur at Malpelo Island, but they do not share food resources and feeding areas, and they probably feed far from the island, using it as a resting and cleaning area. This indicates the need for more research to increase biological and ecological knowledge of both species, particularly within marine protected areas and their influence areas throughout the Colombian Pacific.

Pathogenic variants in Lysyl-tRNA synthetase 1 (KARS1) have increasingly been recognized as a cause of early-onset complex neurological phenotypes. To advance the timely diagnosis of KARS1-related disorders, we sought to delineate its phenotype and generate a disease model to understand its function in vivo. Through international collaboration, we identified 22 affected individuals from 16 unrelated families harboring biallelic likely pathogenic or pathogenic in KARS1 variants. Sequencing approaches ranged from disease-specific panels to genome sequencing. We generated loss-of-function alleles in zebrafish. We identify ten new and four known biallelic missense variants in KARS1 presenting with a moderate-to-severe developmental delay, progressive neurological and neurosensory abnormalities, and variable white matter involvement. We describe novel KARS1-associated signs such as autism, hyperactive behavior, pontine hypoplasia, and cerebellar atrophy with prevalent vermian involvement. Loss of kars1 leads to upregulation of p53, tissue-specific apoptosis, and downregulation of neurodevelopmental related genes, recapitulating key tissue-specific disease phenotypes of patients. Inhibition of p53 rescued several defects of kars1−/− knockouts. Our work delineates the clinical spectrum associated with KARS1 defects and provides a novel animal model for KARS1-related human diseases revealing p53 signaling components as potential therapeutic targets.

Alveolar echinococcosis (AE) is a severe zoonotic disease caused by the metacestode stage of the fox tapeworm Echinococcus multilocularis. We recently showed that E. multilocularis metacestode vesicles scavenge large amounts of L-threonine from the culture medium that were neither stored nor overused for protein synthesis. This motivated us to study the effect of L-threonine on the parasite and how it is metabolized. We established a novel metacestode vesicle growth assay with an automated readout, which showed that L-threonine treatment led to significantly increased parasite growth. In addition, L-threonine increased the formation of novel metacestode vesicles from primary parasite cell cultures in contrast to the non-proteinogenic threonine analog 3-hydroxynorvaline. Tracing of [U-13C]-L-threonine and metabolites in metacestode vesicles and culture medium resulted in the detection of [U-13C]-labeling in aminoacetone and glycine, indicating that L-threonine was metabolized by threonine dehydrogenase (TDH). In addition, the detection of [13C2]-glutathione, suggested that E. multilocularis metacestode vesicles synthesize glutathione via L-threonine-derived glycine. EmTDH-mediated threonine metabolism in the E. multilocularis metacestode stage was further confirmed by quantitative real-time PCR, which demonstrated high expression of emtdh in in vitro cultured metacestode vesicles and also in metacestode samples obtained from infected animals. EmTDH was enzymatically active in metacestode vesicle extracts. Thus, the drugs disulfiram, myricetin, quercetin, sanguinarine and seven quinazoline carboxamides were assessed for inhibition of recombinantly expressed EmTDH, and the most potent inhibitors disulfiram, myricetin and sanguinarine were further tested for activity against E. multilocularis metacestode vesicles and primary parasite cells. Sanguinarine exhibited significant in vitro activity and IC50-values for metacestode vesicles, primary parasite cells, as well as mammalian cells were determined. Our results suggest that sanguinarine treatment should be further assessed in vivo employing suitable AE mouse models. Furthermore, the EmTDH assay could serve as high-throughput target-based discovery platform for novel anti-echinococcal compounds.

Overuse of antimicrobials has greatly contributed to the increase in the emergence of multidrug-resistant bacteria, a situation that hinders the control and treatment of infectious diseases. This is the case with urinary tract infections (UTIs), which represent a substantial percentage of worldwide public health problems, thus the need to look for alternatives for their control and treatment. Previous studies have shown the usefulness of autologous bacterial lysates as an alternative for the treatment and control of UTIs. However, a limitation is the high cost of producing individual immunogens. At the same time, an important aspect of vaccines is their immunogenic amplitude, which is the reason why they must be constituted of diverse antigenic components. In the case of UTIs, the etiology of the disease is associated with different bacteria, and even Escherichia coli, the main causal agent of the disease, is made up of several antigenic variants. In this work, we present results on the study of a bacterial lysate composed of 10 serotypes of Escherichia coli and by Klebsiella pneumoniae, Klebsiella aerogenes, Enterococcus faecalis, Proteus mirabilis, Citrobacter freundii, and Staphylococcus haemolyticus. The safety of the compound was tested on cells in culture and in an animal model, and its immunogenic capacity by analysing in vitro human and murine macrophages (cell line J774 A1). The results show that the polyvalent lysate did not cause damage to the cells in culture or alterations in the animal model used. The immunostimulatory activity assay showed that it activates the secretion of TNF-α and IL-6 in human macrophages and TNF-α in murine cells. The obtained results suggest that the polyvalent lysate evaluated can be an alternative for the treatment and control of chronic urinary tract infections, which will reduce the use of antimicrobials.

Idiopathic achalasia is a relatively infrequent esophageal motor disorder for which major histocompatibility complex (MHC) genes are well-identified risk factors. However, no information about HLA-achalasia susceptibility in Mexicans has previously been reported. We studied a group of 91 patients diagnosed with achalasia and 234 healthy controls with Mexican admixed ancestry. HLA alleles and conserved extended haplotypes were analyzed using high-resolution HLA typing based on Sanger and next-generation sequencing technologies. Admixture estimates were determined using HLA-B and short tandem repeats. Results were analyzed by non-parametric statistical analysis and Bonferroni correction. P-values < 0.05 were considered significant. Patients with achalasia had 56.7% Native American genes, 24.7% European genes, 16.5% African genes and 2.0% Asian genes, which was comparable with the estimates in the controls. Significant increases in the frequencies of alleles DRB1*14:54 and DQB1*05:03 and the extended haplotypes DRB1*14:54-DQB1*05:03 and DRB1*11:01-DQB1*03:01, even after Bonferroni correction (pC<0.05), were found in the achalasia group compared to those in the controls. Concluding, the HLA class II alleles HLA-DRB1*14:54:01 and DQB1*05:03:01 and the extended haplotype are risk factors for achalasia in mixed-ancestry Mexican individuals. These results also suggest that the HLA-DRB1*14:54-DQB1*05:03 haplotype was introduced by admixture with European and/or Asian populations.

Dear Editor, Although dexamethasone is approved for the hyperinflammation treatment of hospitalised COVID-19 patients, non-hospitalised patients do not benefit from this therapy.1 A potential drug for treating COVID-19 patients is polymerised type I collagen (PTIC). A downregulator of pro-inflammatory cytokines, adhesion molecules (ELAM-1, VCAM-1, and ICAM-1), cyclooxygenase (Cox)-1 enzyme and the collagenases expression through the modulation of transcription of factor NF-kB.2–6 The intramuscular or subcutaneous administration of PTIC to patients with active RA (Phase II studies) improved the count of swollen joints and morning stiffness; 57% of patients achieved an ACR score of 50, and 30% had disease remission with this therapeutic combination. PTIC was safe and well-tolerated in long-term treatment, without adverse effects.7–9 A double-blind, randomised, placebo-controlled clinical trial evaluated the PTIC intramuscular administration's safety and efficacy on hyperinflammation, oxygen saturation and symptom improvement in adult symptomatic COVID-19 outpatients (https://www.medrxiv.org/content/10.1101/2021.05.12.21257133v1). TABLE 1 Baseline demographic and clinical characteristics of the trial population Characteristic All subjects (N = 89) PTCI (N = 45) Placebo (N = 44) p Value Comparability of randomised groups Age (years), mean ± SD Median Range 48.5 ± 14.1 48.0 19.0–78.0 48.4 ± 14.4 47.0 19.0–77.0 48.6 ± 13.9 48.0 22.0–78.0 .9917 18–39 years, n (%) 24 (27.0) 13 (28.9) 11 (25.0) .7585 40–64 years, n (%) 52 (58.4) 25 (55.6) 27 (61.4) 65+ years, n (%) 13 (14.6) 7 (16.3) 6 (13.6) Male sex, n (%) 37 (41.6) 18 (40.0) 19 (44.2) .9008 BMI (kg/m2), mean ±SD Median Range 28.0 ± 4.5 27.9 18.6–40.8 27.8 ± 4.5 27.9 18.6–40.3 28.2 ± 4.5 27.7 20.1–40.8 .7934 Overweight, n (%) 39 (43.8) 21 (46.7) 18 (40.1) .3847 Obesity, n (%) 25 (28.1) 11 (25.0) 14 (32.5) .4758 Baseline Guangzhou Severity Index, mean ± SD Median Range 87.6 ± 25.9 90.1 29.4–137.5 87.9 ± 30.2 92.0 29.4–135.1 87.3 ± 20.8 88.7 35.5–137.5 .4362 Baseline Chest CT Score <20% ≥20% 20–50% >50% 53 (59.6) 20 (22.5) 27 (60.0) 8 (17.8) 5 (11.1) 3 (6.7) 26 (59.1) 12 (27.3) 12 (27.3) 0 (0.0) .3353 Days from symptom onset to onset of treatment (Median, IQR) 7.0 (4.0) 7.0 (4.0) 7.0 (4.0) .7257 Oxygen Saturation pSO2 ≤ 92% (%) 28 (31.5) 13 (28.5) 16 (36.4) .325 pSO2; mean ± SD Median IQR 92 ± 2.5 92.0 –91 to 94 93 ± 2.0 93 –91 to 95 92 ± 2.9 92 –91 to 93 .252 Laboratory variables Complete blood count Leukocyte count (×103/μl), mean ± SD Median Range 5.87 ± 2.08 5.30 2.80–12.50 6.03 ± 2.04 5.60 2.80–12.40 5.70 ± 2.13 5.00 3.00–12.50 .240b Haemoglobin (g/dl), mean ± SD Median Range 15.48 ± 1.72 15.30 10.50–20.10 15.50 ± 1.80 15.40 11.90–20.10 15.45 ± 1.66 15.15 10.50–18.70 .743a Platelets (K/μl), mean ± SD Median Range 273.80 ± 116.16 249 73–910 283.18 ± 130.35 249 148–910 264.20 ± 100.21 250 73–568 .625b Lymphocyte count (%), mean ± SD Median Range 30.13 ± 10.79 30.80 8–57 30.15 ± 10.99 31.40 8.1–57 30.13 ± 10.72 30.45 8–54 0.866a Neutrophil count (%), mean ± SD Median Range 60.05 ± 11.23 58.70 31–82 59.89 ± 11.82 58.70 31–81 60.22 ± 10.73 58.85 39–82 .835a Neutrophil-lymphocyte ratio (NLR), mean ± SD Median Range 2.58 ± 1.91 1.88 0.54–10.25 2.62 ± 2.05 1.81 0.54–9.93 2.53 ± 1.78 1.91 0.72–10.25 .931b Liver function test (LFT) Total bilirubin (mg/dl), mean ± SD Median Range 0.62 ± 0.28 0.56 0.18–1.87 0.62 ± 0.24 0.54 0.26–1.34 0.62 ± 0.33 0.57 0.18–1.87 .709b Direct bilirubin (mg/dl), mean ± SD Median Range 0.13 ± 0.07 0.11 0.03–0.44 0.13 ± 0.06 0.11 0.04–0.33 0.14 ± 0.08 0.12 0.03–0.44 .372b Indirect bilirubin (mg/dl), mean ± SD Median Range 0.49 ± 0.22 0.45 0.15–1.56 0.49 ± 0.19 0.45 0.22–1.11 0.49 ± 0.26 0.46 0.15–1.56 .617b Aminotransferase, serum aspartate (AST) (U/L), mean ± SD Median Range 31.09 ± 20.82 26 9–158 28.39 ± 15.60 22 11–83 33.87 ± 24.97 27.50 9 –1 58 .150b Aminotransferase, serum alanine (ALT) (U/L), mean ± SD Median Range 37.42 ± 28.14 29.80 7–129.80 35.64 ±29.90 23 9–129.80 39.24 ± 26.43 31.50 7–120 .176b Albumin (g/dl), mean ± SD Median Range 4.35 ± 0.44 4.34 2.55–5.71 4.40 ± 0.50 4.43 2.55–5.71 4.32 ± 0.38 4.30 3.52–5.45 .189b Fasting glucose (mg/dl) Mean ± SD Median Range 116.75 ± 61.85 98 66–386 119.31 ± 64.32 102 66–386 114.14 ± 59.86 96.50 72–354 .380b Lactate dehydrogenase (LDH) (U/L) Mean ± SD Median Range 166.70 ± 50.59 155 97–325 165.09 ± 60.76 150 97–325 168.34 ± 38.15 160 99–311 .500b C-reactive protein (high sensitivity) (mg/dl) Mean ± SD Median Range 1.63 ± 2.58 0.73 0.02–16.47 1.32 ± 2.67 0.50 0.05–16.47 1.95 ± 2.49 0.97 0.02–11.49 .650b Ferritin (ng/ml) Mean ± SD Median Range 243.46 ± 285.20 161.70 4–1614.40 235.14 ± 293.70 161.70 4–1614.40 251.96 ± 279.39 161.45 5.60–1277 .599b D-dimer (ng/dl) Mean ± SD Median Range 1106.74 ± 3537.99 456 185–29948 1732.33 ± 4916.88 491 185–29948 466.93 ± 225.22 417 210–1264 .226b Summary of comorbidities None, n (%) 9 (10.1) 6 (13.3) 3 (6.8) .3645 One, n (%) 17 (19.1) 7 (15.5) 10 (22.7) 2 or More, n (%) 63 (70.8) 32 (71.1) 31 (70.5) Clinical Comorbidities History or current tobacco use, n (%) 15 (16.9) 7 (15.5) 8 (18.1) .7762 Overweight, n (%) 39 (43.8) 21 (46.6) 18 (40.1) .3847 Obesity, n (%) 25 (28.1) 11 (24.4) 14 (31.8) .4758 Hypertension, n (%) 18 (20.2) 11 (24.4) 7 (15.9) .2640 Diabetes, n (%) 15 (16.9) 8 (17.7) 7 (15.9) .7393 Dyslipidaemia, n (%) 15 (16.9) 11 (24.4) 4 (9.1) .0418 Hypertriglyceridemia, n (%) 43 (48.3) 22 (48.8) 21 (47.7) .7486 Coronary artery disease, n (%) 0 (0.0) 0 (0.0) 0 (0.0) – Congestive heart failure, n (%) 1 (1.1) 0 (0.0) 1 (2.3) .3201 Chronic respiratory disease (emphysema), n (%) 2 (2.3) 1 (2.3) 1 (2.3) .9869 Asthma, n (%) 4 (4.5) 0 (0.0) 4 (9.1) .0429 Chronic liver disease (chronic hepatitis, cirrhosis), n (%) 0 (0.0) 0 (0.0) 0 (0.0) – Chronic kidney disease, n (%) 0 (0.0) 0 (0.0) 0 (0.0) – Cancer, n (%) 0 (0.0) 0 (0.0) 0 (0.0) – Immune deficiency (acquired or innate), n (%) 0 (0.0) 0 (0.0) 0 (0.0) – Symptoms Dyspnoea, n (%) 33 (37.1) 18 (40) 15 (34.1) .564 Cough, n (%) 67 (75.2) 34 (75.6) 33 (75.0) .952 Chest pain, n (%) 35 (39.3) 19 (42.2) 16 (36.4) .572 Rhinorrhoea, n (%) 39 (43.8) 19 (42.2) 20 (45.5) .759 Headache, n (%) 46 (51.7) 22 (48.9) 24 (54.5) .593 Sore throat, n (%) 41 (46.1) 20 (44.4) 21 (47.7) .756 Malaise, n (%) 54 (60.7) 27 (60.0) 27 (61.4) .895 Arthralgia, n (%) 44 (49.4) 18 (40.0) 26 (59.1) .072 Myalgia, n (%) 48 (53.9) 23 (51.1) 25 (56.8) .589 Brain fog, n (%) 43 (48.3) 25 (55.6) 18 (40.9) .167 Ageusia, n (%) 50 (56.2) 28 (62.2) 22 (50.0) .8041 Anosmia, n (%) 47 (52.8) 27 (60.0) 20 (45.5) .7651 Diarrhoea, n (%) 19 (21.3) 11 (24.4) 8 (18.2) .471 Abdominal pain, n (%) 22 (24.7) 8 (17.8) 14 (31.8) .125 Jaundice, n (%) 4 (4.5) 3 (6.7) 1 (2.3) .317 Vomiting and nausea, n (%) 5 (5.6) 2 (4.4) 3 (6.8) .627 Conjunctivitis, n (%) 20 (22.5) 9 (20.0) 11 (25.0) .572 Cyanosis, n (%) 0 (0.0) 0 (0.0) 0 (0.0) – aT-Student; bMann-Whitney BMI: body mass index; IQR: interquartile range; PTCI: polymerised type I collagen; pSO2: oxygen saturation; SD: standard deviation.

Trachoma, caused by Chlamydia trachomatis , is the most common infectious blindness in the world and is present in indigenous Mayan from Chiapas (Mexico). Inflammatory genes are activated when suffering from trachoma, thus some polymorphisms could increase the susceptibility to develop irreversible blindness. This study aimed to evaluate the genetic risk of developing late-stage trachoma in Mayan ethnic groups. In a case–control study ( n  = 51 vs n  = 102, respectively), the following single-nucleotide polymorphisms (SNPs) in genes related to inflammation were analysed: HSD11B1 (rs11807619), HSD11B1 (rs932335), ABCG2 (rs2231142), SLCO1B1 (rs4149056), IL-10 (rs1800890), TNF (rs1800629), MMP2 (rs243865) and ACE . Three SNPs were associated with late-stage trachoma risk: (i) the T allele of rs11807619, (ii) the C allele of rs932335, which are linked to the HSD11B1 gene (OR = 22.5–27.3), particularly in men when adjusts for gender (OR = 16–16.7); and (iii) D allele of rs4340 in the ACE gene (OR = 5.2–5.3). In fact, significant linkage disequilibrium demonstrated association between ACE gene and HSD11B1 SNPs (r = 0.17–0.179; P  = 0.0048–0.0073). Two SNPs HSD11B1 gene ( P  = 0.013 vs 0.0039) and HSD11B1 – ACE haplotypes showed association with late-stage trachoma in Mayan ethnic groups.

Historical records and genetic analyses indicate that Latin Americans trace their ancestry mainly to the intermixing (admixture) of Native Americans, Europeans and Sub-Saharan Africans. Using novel haplotype-based methods, here we infer sub-continental ancestry in over 6,500 Latin Americans and evaluate the impact of regional ancestry variation on physical appearance. We find that Native American ancestry components in Latin Americans correspond geographically to the present-day genetic structure of Native groups, and that sources of non-Native ancestry, and admixture timings, match documented migratory flows. We also detect South/East Mediterranean ancestry across Latin America, probably stemming mostly from the clandestine colonial migration of Christian converts of non-European origin (Conversos). Furthermore, we find that ancestry related to highland (Central Andean) versus lowland (Mapuche) Natives is associated with variation in facial features, particularly nose morphology, and detect significant differences in allele frequencies between these groups at loci previously associated with nose morphology in this sample. Latin Americans trace their ancestry to the admixture of Native Americans, Europeans and Sub-Saharan Africans. Here, the authors develop a novel haplotype-based approach and analyse over 6,500 Latin Americans to infer the geographically-detailed genetic structure of this population.