Frontiers in congenital disorders of glycosylation consortium, a cross-sectional study report at year 5 of 280 individuals in the natural history cohort.

OBJECTIVE: Our report describes clinical, genetic, and biochemical features of participants with a molecularly confirmed congenital disorder of glycosylation (CDG) enrolled in the Frontiers in Congenital Disorders of Glycosylation (FCDGC) Natural History cohort at year 5 of the study. METHODS: We enrolled individuals with a known or suspected CDG into the FCDGC Natural History Study, a multicenter prospective and retrospective natural history study of all genetic causes of CDG. We conducted a cross-sectional analysis of baseline study visit data from participants with confirmed CDG who were consented into the FCDGC Natural History Study (5U54NS115198) from October 2019 to November 2023. RESULTS: Three hundred thirty-three subjects consented to the FCDGC Natural History Study. Of these, 280 unique individuals had genetic data available that was consistent with a diagnosis of CDG. These 280 individuals were enrolled into the study between October 8, 2019 and November 29, 2023. One hundred forty-one (50.4%) were female, and 139 (49.6%) were male. Mean and median age at enrollment was 10.1 and 6.5 years, respectively, with a range of 0.22 to 71.4 years. The cohort encompassed individuals with disorders of N-linked protein glycosylation (57%), glycosylphosphatidylinositol anchor disorder (GPI anchor) (15%), disorders of Golgi homeostasis, trafficking and transport (12%), dolichol metabolism disorders (5%), disorders of multiple pathways (6%), and other (5%). The most frequent presenting symptom(s) leading to diagnosis were developmental delay/disability (77%), followed by hypotonia (56%) and feeding difficulties (42%). Mean and median time between first related symptom and diagnosis was 2.7 and 0.8 years, respectively. One hundred percent of individuals in our cohort had developmental differences/disabilities at the time of their baseline visit, followed by 97% with neurologic involvement, 91% with gastrointestinal (GI)/liver involvement, and 88% with musculoskeletal involvement. Severity of disease in individuals was scored on the Nijmegen Progression CDG Rating Scale (NPCRS) with 27% of scores categorized as mild, 44% moderate, and 29% severe. Of the individuals with N-linked protein glycosylation defects, 83% of those with data showed a type 1 pattern on carbohydrate deficient transferrin (CDT) analysis including 82/84 individuals with PMM2-CDG, 6% a type 2 pattern, 1% both type 1 and type 2 pattern and 10% a normal or nonspecific pattern. One hundred percent of individuals with Golgi homeostasis and trafficking defects with data showed a type 2 pattern on CDT analysis, while Golgi transport defect showed a type II pattern 73% of the time, a type 1 pattern for 7%, and 20% had a normal or nonspecific pattern. Most of the variants documented were classified as pathogenic or likely pathogenic using ACMG criteria. For the majority of the variants, the predicted molecular consequence was missense followed by nonsense and splice site, and the majority of the diagnoses are inherited in an autosomal recessive pattern but with disorders of all major nuclear inheritance included. DISCUSSION: The FCDGC Natural History Study serves as an important resource to build future research studies, improve clinical care, and prepare for clinical trial readiness. Herein is the first overview of CDG participants of the FCDGC Natural History Study.

A comprehensive assessment of a prototype high ratio antiscatter grid in interventional cardiology using experimental measurements and Monte Carlo simulations.

Objective. To assess the performance of a new antiscatter grid design in interventional cardiology for image quality improvement and dose reduction using experimental measurements and Monte Carlo (MC) simulation.Approach.Experimental measurements were performed on an angiography system, using a multi-layered tissue simulating composite phantom made from of poly(methyl methacrylate), aluminium and expanded polystyrene (2/0.2/0.7 cm). The total phantom thickness ranged from 20.3 cm to 40.6 cm. Four conditions were compared; (A) 105 cm source-image receptor distance (SID) without grid, (Bi) 105 cm SID with grid ratio (r) and strip density (N) (r15N80), (Bii) 120 cm SID without grid, and (Biii) 120 cm SID with high ratio grid (r29N80). The system efficiency (η), defined by the signal-to-noise ratio, was compared from theBconditions against caseA. These conditions were also simulated with MC techniques, allowing additional phantom compositions to be explored. Weighted image quality improvement factor (ηw(u)) was studied experimentally at a specific spatial frequency due to the SID change. Images were simulated with an anthropomorphic chest phantom for the different conditions, and the system efficiency was compared for the different anatomical regions.Main results.Good agreement was found between theηandηw(u) methods using both measured and simulated data, with average relative differences between 2%-11%. CaseBiiiprovided higherηvalues compared toA, andBifor thicknesses larger than 20.3 cm. In addition, caseBiiialso provided higherηvalues for high attenuating areas in the anthropomorphic phantom, such as behind the spine.Significance.The new antiscatter grid design provided higher system efficiency compared to the standard grid for the parameters explored in this work.

Liver disease and transplantation in telomere biology disorders: An international multicenter cohort.

BACKGROUND: Patients with telomere biology disorders (TBD) develop hepatic disease, including hepatitis, cirrhosis, and hepatopulmonary syndrome. No specific treatment exists for TBD-related liver disease, and the role of liver transplantation (LT) remains controversial. Our study objectives were to describe the clinical characteristics, management, and outcomes in patients with TBD-related liver disease, and their LT outcomes. METHODS: Data from 83 patients with TBD-associated liver disease were obtained from 17 participating centers in the Clinical Care Consortium of Telomere-Associated Ailments and by self-report for our retrospective, multicenter, international cohort study. RESULTS: Group A ("Advanced") included 40 patients with advanced liver disease. Of these, 20 underwent LT (Group AT). Group M ("Mild") included 43 patients not warranting LT evaluation, none of whom were felt to be medically unfit for liver transplantation. Supplemental oxygen requirement, pulmonary arteriovenous malformation, hepatopulmonary syndrome, and higher bilirubin and international normalized ratio values were associated with Group A. Other demographics, clinical manifestations, and laboratory findings were similar between groups. Six group A patients were declined for LT; 3 died on the waitlist. Median follow-up post-LT was 2.9 years (range 0.6-13.2 y). One-year survival post-LT was 73%. Median survival post-LT has not been reached. Group AT patients had improved survival by age compared to all nontransplant patients (log-rank test p = 0.02). Of 14 patients with pretransplant hypoxemia, 8 (57%) had improved oxygenation after transplant. CONCLUSIONS: LT recipients with TBD do not exhibit excessive posttransplant mortality, and LT improved respiratory status in 57%. A TBD diagnosis should not exclude LT consideration.

A new small-sized predatory pseudosuchian archosaur from the Middle-Late Triassic of Southern Brazil.

Before the rise of dinosaurs and pterosaurs, pseudosuchians-reptiles from the crocodilian lineage-dominated the Triassic land ecosystems. This lineage diversified into several less inclusive clades, resulting in a wide ecomorphological diversity during the Middle and Late Triassic. Some giant pseudosuchians occupied the top of the trophic webs, while others developed extensive bony armor as a defense mechanism, which later evolved as a convergence in the avemetatarsalian lineage. On the other hand, there were groups like the Gracilisuchidae, which was composed of carnivorous forms with lightweight build and less than 1 m in length. The fossil record of gracilisuchids is geographically restricted to China and Argentina, with one ambiguous record from Brazil. In the present study, the first unambiguous gracilisuchid from Brazil is described. Parvosuchus aurelioi gen. et sp. nov. comes from the Dinodontosaurus Assemblage Zone of the Santa Maria Formation, which is associated with the Ladinian-Carnian boundary. Composed of a complete cranium, vertebrae, pelvic girdle and hindlimbs, the new species nests with Gracilisuchus stipanicicorum and Maehary bonapartei in a phylogenetic analysis. Its discovery fills a taxonomic gap in Brazilian pseudosuchian fauna and reveals the smallest known member of this clade from the Dinodontosaurus Assemblage Zone, highlighting the diversity of pseudosuchians during the moment that preceded the dawn of dinosaurs.

Soft-tissue fossilization illuminates the stepwise evolution of the ray-finned fish brain.

A complex brain is central to the success of backboned animals. However, direct evidence bearing on vertebrate brain evolution comes almost exclusively from extant species, leaving substantial knowledge gaps. Although rare, soft-tissue preservation in fossils can yield unique insights on patterns of neuroanatomical evolution. Paleontological evidence from an exceptionally preserved Pennsylvanian (∼318 Ma) actinopterygian, Coccocephalus, calls into question prior interpretations of ancestral actinopterygian brain conditions. However, the ordering and timing of major evolutionary innovations, such as an everted telencephalon, modified meningeal tissues, and hypothalamic inferior lobes, remain unclear. Here, we report two distinct actinopterygian morphotypes from the latest Carboniferous-earliest Permian (∼299 Ma) of Brazil that show extensive soft-tissue preservation of brains, cranial nerves, eyes, and potential cardiovascular tissues. These fossils corroborate inferences drawn from ✝Coccocephalus, while adding new information about neuroanatomical evolution. Skeletal features indicate that one of these Brazilian morphotypes is more closely related to living actinopterygians than the other, which is also reflected in soft-tissue features. Significantly, the more crownward morphotype shows a key neuroanatomical feature of extant actinopterygians-an everted telencephalon-that is absent in the other morphotype and ✝Coccocephalus. All preserved Paleozoic actinopterygian brains show broad similarities, including an invaginated cerebellum, hypothalamus inferior lobes, and a small forebrain. In each case, preserved brains are substantially smaller than the enclosing cranial chamber. The neuroanatomical similarities shared by this grade of Permo-Carboniferous actinopterygians reflect probable primitive conditions for actinopterygians, providing a revised model for interpreting brain evolution in a major branch of the vertebrate tree of life.

Monoclonal gammopathy-associated peripheral neuropathies: Uncovering pearls and challenges.

Monoclonal gammopathy-related peripheral neuropathies encompass a spectrum of clinical presentations in which the monoclonal protein directly damages the tissues, including the peripheral nervous system. Given the prevalence of both peripheral neuropathy and monoclonal gammopathy in the general population, these conditions may overlap in clinical practice, posing a challenge for clinicians in determining causality. Therefore, a comprehensive understanding of primary clinical syndromes and their neurophysiological patterns is of great importance for accurate differential diagnoses and effective treatment strategies. In this article, we examine the main forms of monoclonal gammopathies that affect the peripheral nerve. We explore the clinical and electrophysiological aspects and their correlation with each syndrome's corresponding monoclonal protein type. This knowledge is essential for healthcare professionals to diagnose better and manage patients presenting with monoclonal gammopathy-related peripheral nervous system involvement.

RecQ helicase expression in patients with telomeropathies.

BACKGROUND: Telomeropathies are a group of inherited disorders caused by germline pathogenic variants in genes involved in telomere maintenance, resulting in excessive telomere attrition that affects several tissues, including hematopoiesis. RecQ and RTEL1 helicases contribute to telomere maintenance by unwinding telomeric structures such as G-quadruplexes (G4), preventing replication defects. Germline RTEL1 variants also are etiologic in telomeropathies. METHODS AND RESULTS: Here we investigated the expression of RecQ (RECQL1, BLM, WRN, RECQL4, and RECQL5) and RTEL1 helicase genes in peripheral blood mononuclear cells (PBMCs) from human telomeropathy patients. The mRNA expression levels of all RecQ helicases, but not RTEL1, were significantly downregulated in patients' primary cells. Reduced RecQ expression was not attributable to cell proliferative exhaustion, as RecQ helicases were not attenuated in T cells exhausted in vitro. An additional fifteen genes involved in DNA damage repair and RecQ functional partners also were downregulated in the telomeropathy cells. CONCLUSION: These findings indicate that the expression of RecQ helicases and functional partners involved in DNA repair is downregulated in PBMCs of telomeropathy patients.

Factors associated with referrals for directly observed treatment and unsuccessful treatment.

To describe the characteristics of people indicated for directly observed treatment (DOT) in Spain, and the factors associated with unsuccessful treatment.This was a multicentre observational study based on a prospective follow-up of patients over 18 years old diagnosed with TB between 2006 and 2019 from the registry of the Programa Integrado de Investigación en Tuberculosis (PII-TB). Sociodemographic and clinical variables were collected. Adjusted odds ratios (aORs) were calculated for the indication of DOT and for having an unsuccessful treatment.A total of 7,883 patients were included. The indication of DOT was associated with being homeless (aOR 5.93, 95% CI 3.03-11.59), inactivity status (aOR 2.55, 95% CI 2.02-3.23), alcohol consumption (aOR 1.94, 95% CI 1.51-2.48), parenteral drug use (aOR 1.77, 95% CI 1.06-2.95) and HIV diagnosis (aOR 1.96, 95% CI 1.16-3.29). Unsuccessful treatment was associated with having an HIV diagnosis (aPR 2.31, 95% CI 1.31-4.08), having a worse clinical and radiological evolution (clinical progression: APR 15.59, 95% CI 8.21-29.60; radiological progression: aPR 12.84, 95% CI 6.46-25.52), need for hospitalisation (aPR 1.73, 95% CI 1.10-2.73), unsatisfactory tolerability (aPR 2.82, 95% CI 1.49-5.29), the existence of difficulties in understanding the prescribed treatment (aPR 1.92, 95% CI 1.21-3.06), as well as worse treatment satisfaction (aPR 7.27, 95% CI 4.32-12.24).The prioritisation of vulnerable populations is a key aspect to carry out the new Global Plan to End TB 2023-2030. In these groups DOT indication should be increased to ensure adherence and patient follow-up and outcomes..

Design, simulation, and testing of a tunable MEMS multi-threshold inertial switch.

This paper presents a tunable multi-threshold micro-electromechanical inertial switch with adjustable threshold capability. The demonstrated device combines the advantages of accelerometers in providing quantitative acceleration measurements and g-threshold switches in saving power when in the inactive state upon experiencing acceleration below the thresholds. The designed proof-of-concept device with two thresholds consists of a cantilever microbeam and two stationary electrodes placed at different positions in the sensing direction. The adjustable threshold capability and the effect of the shock duration on the threshold acceleration are analytically investigated using a nonlinear beam model. Results are shown for the relationships among the applied bias voltage, the duration of shock impact, and the tunable threshold. The fabricated prototypes are tested using a shock-table system. The analytical results agree with the experimental results. The designed device concept is very promising for the classification of the shock and impact loads in transportation and healthcare applications.

Distribution of Badhamiopsis and Badhamia (Physaraceae, Myxomycetes) in brazilian Biomes.

The family Physaraceae (Physarales, Myxomycetes) is represented in Brazil by eight genera and 75 species. Based on data obtained from the GBIF, SpeciesLink, Flora and Funga do Brasil platforms, collections from the IPA and URM Herbaria and material collected since 1960 deposited in the UFP Herbarium, the microhabitats and distribution of Badhamiopsis (1sp.) and Badhamia (10 spp.) in Brazilian biomes are commented. An identification key for the species and the first report of B. melanospora from the state of Paraíba, B. panicea from the state of Paraná and B. ovispora from Brazil are presented.

Expression of the locus of enterocyte effacement genes during the invasion process of the atypical enteropathogenic Escherichia coli 1711-4 strain of serotype O51:H40.

Atypical enteropathogenic Escherichia coli (aEPEC) is a significant cause of diarrhea in developing countries. Some aEPEC strains, including the Brazilian representative strain of serotype O51:H40 called aEPEC 1711-4, can use flagella to attach to, invade, and persist in T84 and Caco-2 intestinal cells. They can even translocate from the gut to extraintestinal sites in a rat model. Although various aspects of the virulence of this strain were studied and the requirement of the T3SS for the efficiency of the invasion process was demonstrated, the expression of the LEE genes during the invasion and intracellular persistence remains unclear. To address this, the expression of flagella and the different LEE operons was evaluated during kinetic experiments of the interaction of aEPEC 1711-4 with enterocytes in vitro. The genome of the strain was also sequenced. The results showed that flagella expression remained unchanged, but the expression of eae and escJ increased during the early interaction and invasion of aEPEC 1711-4 into Caco-2 cells, and there was no change 24 hours post-infection during the persistence period. The number of pedestal-like structures formed on HeLa cells also increased during the 24-hour analysis. No known gene related to the invasion process was identified in the genome of aEPEC 1711-4, which was shown to belong to the global EPEC lineage 10. These findings suggest that LEE components and the intimate adherence promoted by intimin are necessary for the invasion and persistence of aEPEC 1711-4, but the detailed mechanism needs further study.

Obesity contributes to telomere shortening in polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is a multifactorial disorder and obesity occurs in 38% to 88% of these women. Although hyperandrogenism may contribute to telomere lengthening, increased body mass index (BMI) is associated with telomere erosion. We sought to compare leukocyte telomere length (LTL) in PCOS women with normal, overweight, and obese BMI. We evaluated the relationship between LTL and clinical variables of PCOS and inflammatory biomarkers independent of BMI. A total of 348 women (243 PCOS and 105 non-PCOS) were evaluated for anthropometric measures, total testosterone, androstenedione, estradiol (E2), follicle-stimulating hormone (FSH), luteinizing hormone (LH), sex hormone-binding globulin (SHBG), free androgen index (FAI), fasting insulin and glycemia, lipid profile, homocysteine, C-reactive protein (CRP) and homeostatic model of insulin resistance (HOMA-IR). LTL was measured by qPCR. The PCOS group presented higher weight, waist circumference, BMI, testosterone, LH, fasting insulin, FAI, and HOMA-IR, and lower E2, SHBG, and fasting glycemia measures compared with the non-PCOS. When stratified by BMI, LTL was increased in all subgroups in PCOS compared to non-PCOS. However, in the PCOS group, LTL was lower in overweight (P = 0.0187) and obese (P = 0.0018) compared to normal-weight women. The generalized linear model showed that BMI, androstenedione, homocysteine, and CRP were associated with telomere biology. Women with PCOS had longer LTL, however, overweight or obesity progressively contributes to telomere shortening and may affect reproductive outcomes of PCOS, while androstenedione may increase LTL.

The recombinant L-lysine α-oxidase from the fungus Trichoderma harzianum promotes apoptosis and necrosis of leukemia CD34 + hematopoietic cells.

BACKGROUND: In hematologic cancers, including leukemia, cells depend on amino acids for rapid growth. Anti-metabolites that prevent their synthesis or promote their degradation are considered potential cancer treatment agents. Amino acid deprivation triggers proliferation inhibition, autophagy, and programmed cell death. L-lysine, an essential amino acid, is required for tumor growth and has been investigated for its potential as a target for cancer treatment. L-lysine α-oxidase, a flavoenzyme that degrades L-lysine, has been studied for its ability to induce apoptosis and prevent cancer cell proliferation. In this study, we describe the use of L-lysine α-oxidase (LO) from the filamentous fungus Trichoderma harzianum for cancer treatment. RESULTS: The study identified and characterized a novel LO from T. harzianum and demonstrated that the recombinant protein (rLO) has potent and selective cytotoxic effects on leukemic cells by triggering the apoptotic cascade through mitochondrial dysfunction. CONCLUSIONS: The results support future translational studies using the recombinant LO as a potential drug for the treatment of leukemia.

Disturbances in the IgG Antibody Profile in HIV-Exposed Uninfected Infants Associated with Maternal Factors.

Over the last 20 years, the incidence of vertical HIV transmission has decreased from 25%-42% to less than 1%. Although there are no signs of infection, the health of HIV-exposed uninfected (HEU) infants is notoriously affected during the first months of life, with opportunistic infections being the most common disease. Some studies have reported effects on the vertical transfer of antibodies, but little is known about the subclass distribution of these antibodies. We proposed to evaluate the total IgG concentration and its subclasses in HIV+ mothers and HEU pairs and to determine which maternal factors condition their levels. In this study, plasma from 69 HEU newborns, their mothers, and 71 control pairs was quantified via immunoassays for each IgG isotype. Furthermore, we followed the antibody profile of HEUs throughout the first year of life. We showed that mothers present an antibody profile characterized by high concentrations of IgG1 and IgG3 but reduced IgG2, and HEU infants are born with an IgG subclass profile similar to that of their maternal pair. Interestingly, this passively transferred profile could remain influenced even during their own antibody production in HEU infants, depending on maternal conditions such as CD4+ T-cell counts and maternal antiretroviral treatment. Our findings indicate that HEU infants exhibit an altered IgG subclass profile influenced by maternal factors, potentially contributing to their increased susceptibility to infections.

A combined analytical and Monte Carlo method for detailed simulations of antiscatter grids in x-ray medical imaging: implementing scatter within the grid.

Objective. To implement a hybrid method, which combines analytical tracking and interaction simulation using Monte Carlo (MC) techniques, in order to model photon transport inside antiscatter grids (ASG) for x-ray imaging.Approach. A new tally was developed for PENELOPE (v.2018) and penEasy (v. 2020) MC code to simulate photon transmission through ASGs. Two established analytical algorithms from the literature were implemented in this tally. In addition, a new hybrid method was introduced by extending one of the analytical algorithms to include photon-interactions inside the grid, while preserving the imaged grid structure. Calculations of primary(TP),scatter(TS),and total(TT)grid transmissions in addition to theQfactor (Q=TP2/TT) were performed. The new tally was validated for a quadric geometry ASG, and experimental measurements with a PMMA phantom of several thicknesses. In addition, the contribution of the scatter inside the grid was studied for three interspace materials, and a high resolution image of the grid was simulated.Main results. An excellent agreement was found between the two analytical models compared with the quadric grid without scatter, and the hybrid method with the geometrical grid with scatter. Average deviations of 0.2% and 1.4% were found betweenTPandTSfor the hybrid method and quadric grid, while for the hybrid method and experimental measurements these values were 1% and 20%. Antiscatter grids with aluminium as interspace material had the highest amount of scatter from inside the grid to the final image, followed up by paper fibre and air. The high resolution image of the grid was equivalent using the quadric geometry or the hybrid mode.Significance. The hybrid method provides a means of studying scattered radiation from the antiscatter grid with the advantage of higher performance, with results that are consistent with a full quadric geometry simulation of the ASG.

Activity and safety of eltrombopag in combination with cyclosporin A as first­line treatment of adults with severe aplastic anaemia (SOAR): a phase 2, single-arm study.

BACKGROUND: Antithymocyte globulin (ATG)-based immunosuppression is standard in front-line treatment for people with severe aplastic anaemia without a histocompatible donor or who are 40 years or older. However, ATG requires in-hospital administration, is associated with infusion-related toxicities and has limited availability worldwide. In this study, we investigated the activity and safety of an ATG-free regimen of eltrombopag with cyclosporin A as a potential treatment for patients with severe aplastic anaemia who might not have access to or cannot tolerate horse-ATG. METHODS: SOAR was a multicentre, single-arm phase 2 trial investigating eltrombopag and cyclosporin in adult (≥18 years) patients with severe aplastic anaemia who were treatment-naive and had an Eastern Cooperative Oncology Group performance status of less than 2. Participants were recruited from 20 hospitals in ten countries. Eltrombopag was initiated at 150 mg (100 mg in patients of Asian ethnicity) and cyclosporin at 10 mg/kg per day (adjusted to a trough of 200-400 µg/L) orally from day 1 to 6 months. The primary outcome was an overall haematological response rate by 6 months in the intention-to-treat population. This is the final report of the primary analysis period. The trial was registered with ClinicalTrials.gov, NCT02998645, and has been completed. FINDINGS: 54 patients were enrolled between May 11, 2017, and March 23, 2020. 34 (63%) patients were male and 20 (37%) were female. 22 (41%) were Asian, 22 (41%) were White, one (2%) was Native American or Alaska Native, one (2%) was Black or African American, and eight (15%) were other race or ethnicity. 35 patients (65%) completed 6 months of treatment with eltrombopag and cyclosporin and six (11%) completed the cyclosporin tapering period up to month 24. Overall haematological response rate by month 6 of treatment was 46% (25 of 54; 95% CI 33-60). The most reported adverse events were increased serum bilirubin (in 22 patients [41%]), nausea (16 [30%]), increased alanine aminotransferase concentration (12 [22%]), and diarrhoea (12 [22%]). Eight patients died on-treatment, but no deaths were considered related to the treatment. INTERPRETATION: Eltrombopag and cyclosporin was active as front-line treatment of severe aplastic anaemia, with no unexpected safety concerns. This approach might be beneficial where horse-ATG is not available or not tolerated. FUNDING: Novartis Pharmaceuticals.

On a skeletally immature individual of Unaysaurus tolentinoi (Dinosauria: Sauropodomorpha) from the upper Triassic of southern Brazil.

The lineage of sauropodomorph dinosaurs raised some of the most impressive animals that ever walked on Earth. However, the massive titans of the Mesozoic Era originated from far smaller dinosaurs. The Triassic beds from Brazil yielded the earliest part of this evolutionary history. Despite the diverse fossil record of early sauropodomorphs, juvenile specimens, as well as certain species are poorly sampled. This is the case for Unaysaurus tolentinoi, an unaysaurid sauropodomorph from Caturrita Formation (ca. 225 Ma; early Norian, Late Triassic). The holotype and only specimen of U. tolentinoi was excavated from the Água Negra Locality (São Martinho da Serra, Rio Grande do Sul, Brazil) in 1998. More than two decades later, no other fossil vertebrates have been reported from the same fossiliferous site. Here we describe a skeletally immature specimen which was found in association with the holotype of U. tolentinoi. The specimen was discovered after a first-hand examination of the holotype and comprises some isolated vertebrae and elements from the posterior autopodium. According to linear regressions, its metatarsal I is approximately 41.7 mm in length, compared to approximately 75.9 mm in the holotype. The repeated elements and reduced size indicates that it does not belong to the elements originally used to erect U. tolentinoi. Rather, the specimen is assigned to U. tolentinoi by topotypy and shared morphology. In addition to the reduced size, distinct lines of evidence (e.g., neurocentral sutures; bone texture) support its assignment to a skeletally immature individual. In sum, the new material expands the record of U. tolentinoi, and represents an additional juvenile dinosaur from the Caturrita Formation.

The origin of an invasive air sac system in sauropodomorph dinosaurs.

One of the most remarkable features in sauropod dinosaurs relates to their pneumatized skeletons permeated by a bird-like air sac system. Many studies described the late evolution and diversification of this trait in mid to late Mesozoic forms but few focused on the origin of the invasive respiratory diverticula in sauropodomorphs. Fortunately, it is possible to solve this thanks to the boom of new species described in the last decade as well as the broad accessibility of new technologies. Here we analyze the unaysaurid sauropodomorph Macrocollum itaquii from the Late Triassic (early Norian) of southern Brazil using micro-computed tomography. We describe the chronologically oldest and phylogenetically earliest unambiguous evidence of an invasive air sac system in a dinosaur. Surprisingly, this species presented a unique pattern of pneumatization in non-sauropod sauropodomorphs, with pneumatic foramina in posterior cervical and anterior dorsal vertebrae. This suggests that patterns of pneumatization were not cladistically consistent prior to the arrival of Jurassic eusauropods. Additionally, we describe the protocamerae tissue, a new type of pneumatic tissue with properties of both camellae and camerae. This reverts the previous hypothesis which stated that the skeletal pneumatization first evolved into camarae, and derived into delicate trabecular arrangements. This tissue is evidence of thin camellate-like tissue developing into larger chambers. Finally, Macrocollum is an example of the gradual evolution of skeletal tissues responding to the fastly specializing Respiratory System of saurischian dinosaurs.