New Early Eocene mammalian fauna from western Patagonia, Argentina

Two new fossil mammal localities from the Paleogene of central-western Patagonia are preliminarily described as the basis for a new possible biochronological unit for the early Eocene of Patagonia, correlated as being between two conventional SALMAs, the Riochican (older) and the Vacan subage of the Casamayoran SALMA. The mammal-bearing strata belong to the Middle Chubut River Volcanic-Pyroclastic Complex (northwestern Chubut Province, Argentina), of Paleocene-Eocene age. This complex includes a variety of volcaniclastic, intrusive, pyroclastic, and extrusive rocks deposited after the K-T boundary. Geochronological data taken from nearby volcanic deposits that underlie and overlie the mammal-bearing levels indicate that both faunas are of late early Eocene age (Ypresian-Lutetian boundary). In addition to more than 50 species of mammals, including marsupials, ungulates, and xenarthrans, two lower molars are the oldest evidence of bats in South America. Paleobotanical and palynological evidence from inferred contemporary localities nearby indicate subtropical environments characterized by warm and probably moderately humid climate. Remarkably, this new fauna is tentatively correlated with Eocene mammals from the La Meseta Formation in the Antarctic Peninsula. We conclude that the two localities mentioned above are part of a possible new biochronological unit, but the formal proposal of a new SALMA awaits completion of taxonomic analysis of the materials reported upon here. If the La Meseta fauna is correlated biochronologically to western Patagonia, this also suggests a continental extension of the biogeographic Weddelian Province as far north as central-western Patagonia

Recurrence of Type 1 Diabetes After Simultaneous Pancreas-Kidney Transplantation, Despite Immunosuppression, Is Associated With Autoantibodies and Pathogenic Autoreactive CD4 T-Cells

ObjectiveTo investigate if recurrent autoimmunity explained hyperglycemia and C-peptide loss in three immunosuppressed simultaneous pancreas-kidney (SPK) transplant recipients.Research design and methodsWe monitored autoantibodies and autoreactive T-cells (using tetramers) and performed biopsy. The function of autoreactive T-cells was studied with in vitro and in vivo assays.ResultsAutoantibodies were present pretransplant and persisted on follow-up in one patient. They appeared years after transplantation but before the development of hyperglycemia in the remaining patients. Pancreas transplant biopsies were taken within approximately 1 year from hyperglycemia recurrence and revealed beta-cell loss and insulitis. We studied autoreactive T-cells from the time of biopsy and repeatedly demonstrated their presence on further follow-up, together with autoantibodies. Treatment with T-cell-directed therapies (thymoglobulin and daclizumab, all patients), alone or with the addition of B-cell-directed therapy (rituximab, two patients), nonspecifically depleted T-cells and was associated with C-peptide secretion for >1 year. Autoreactive T-cells with the same autoantigen specificity and conserved T-cell receptor later reappeared with further C-peptide loss over the next 2 years. Purified autoreactive CD4 T-cells from two patients were cotransplanted with HLA-mismatched human islets into immunodeficient mice. Grafts showed beta-cell loss in mice receiving autoreactive T-cells but not control T-cells.ConclusionsWe demonstrate the cardinal features of recurrent autoimmunity in three such patients, including the reappearance of CD4 T-cells capable of mediating beta-cell destruction. Markers of autoimmunity can help diagnose this underappreciated cause of graft loss. Immune monitoring during therapy showed that autoimmunity was not resolved by the immunosuppressive agents used

Aptamers as Diagnostic Tools in Cancer

Cancer is the second leading cause of death worldwide. Researchers have been working hard on investigating not only improved therapeutics but also on early detection methods, both critical to increasing treatment efficacy, and developing methods for disease prevention. The use of nucleic acids, or aptamers, has emerged as more specific and accurate cancer diagnostic and therapeutic tools. Aptamers are single-stranded DNA or RNA molecules that recognize specific targets based on unique three-dimensional conformations. Despite the fact aptamer development has been mainly restricted to laboratory settings, the unique attributes of these molecules suggest their high potential for clinical advances in cancer detection. Aptamers can be selected for a wide range of targets, and also linked with an extensive variety of diagnostic agents, via physical or chemical conjugation, to improve previously-established detection methods or to be used as novel biosensors for cancer diagnosis. Consequently, herein we review the principal considerations and recent updates in cancer detection and imaging through aptamer-based molecules

Growth of ultrathin epitaxial Fe/MgO spin injector on (0, 0, 1) (Ga, Mn)As

We have grown an ultrathin epitaxial Fe/MgO bilayer on (Ga, Mn)As by e-beam evaporation in UHV. The system structure has been investigated by high resolution transmission electron microscopy (TEM) experiments which show that the Fe and MgO films, covering completely the (Ga, Mn)As, grow with the epitaxial relationship Fe[100](001) [parallel] MgO[110](001) [parallel] (Ga,Mn)As[110](001). The magnetic reversal process, studied by the magneto-optical Kerr effect (MOKE) at room temperature, demonstrates that the iron is ferromagnetic and possesses a cubic anisotropy, confirming the epitaxy relationship found with TEM. Resistivity measurements across the barrier display a non-Ohmic behavior characterized by cubic conductance as a function of the applied voltage suggesting tunneling-dominated transport across the barrier

Insulin protein and proliferation in ductal cells in the transplanted pancreas of patients with type 1 diabetes and recurrence of autoimmunity

AIM/HYPOTHESIS: To investigate if beta cell neoformation occurs in the transplanted pancreas in patients with type 1 diabetes who received a simultaneous pancreas-kidney (SPK) transplant and later developed recurrence of autoimmunity. METHODS: We examined pancreas transplant biopsies from 9 SPK patients with/without recurrent autoimmunity/recurrent diabetes and 16 non-diabetic organ donors. Tissues were analyzed by immunohistochemistry and immunofluorescence. RESULTS: Numerous CK-19(+) pancreatic ductal cells expressed insulin in 6 SPK recipients with recurrent autoimmunity, of whom 5 developed recurrence of diabetes requiring insulin therapy. These cells expressed the pancreatic-duodenal homeobox-1 transcription factor (PDX-1), implicated in pancreatic development and beta cell differentiation. The number of insulin(+) ductal cells varied, being highest in the patient with the most severe beta cell loss and lowest in the normoglycemic patient. We detected insulin(+)CK-19(+)PDX-1(+) cells expressing Ki-67 in the patient with the most severe beta cell loss, indicating proliferation. We could not detect Ki-67(+) beta cells within the islets in any SPK patient. Some insulin(+)CK-19(−) ductal cells expressed chromogranin A, suggesting further endocrine differentiation. Insulin(+) cells were rarely noted in the pancreas transplant ducts in 3 SPK patients without islet autoimmunity and in 6/16 non-diabetic organ donors; these insulin(+) cells never expressed CK-19. CONCLUSIONS/INTERPRETATION: Insulin-expressing pancreatic ductal cells, some apparently proliferating, were found in the transplanted pancreas with recurrent islet autoimmunity/diabetes. Replicating beta cells were not detected within islets. The observed changes may represent attempts at tissue remodelling and beta cell regeneration involving ductal cells in the human transplanted pancreas, possibly stimulated by hyperglycaemia and chronic inflammation

Activity budgets for the sedentary Argentine sea bass Acanthistius patachonicus inferred from accelerometer data loggers

The amount of energy an animal uses to move may constitute a significant fraction of its energy budget, so detailed descriptions of wild animal activity budgets can help to understand the ecology of a species, both at the individual and at the population levels. The rocky‐reef fishes inhabiting the northern Patagonian gulfs of Argentina are important economic and recreational resources for which no activity or energy budgets are available. This fish assemblage may reach high aggregated biomasses (exceeding several hundreds of kilogrammes of fish distributed along a few hundred metres of linear reef ledges) and is not clear how such biomasses can be supported by the low productivity of the Patagonian coastal waters. We used animal‐attached accelerometers to characterise the behaviours and activity budgets for the most abundant and ubiquitous species of this assemblage, the Argentine sea bass or ‘Mero’ Acanthistius patachonicus (Jenyns, 1840; Osteichthyes: Serranidae). Sixteen individuals were tagged (two in captivity and 14 free‐living) and an ethogram was generated from acceleration recordings in varying environmental conditions. Two algorithms were used to classify the behaviours of wild fish. Both showed generally similar results during the cold‐water season (8–10°C), but differed slightly in the warm‐water season (16–18°C). Overall, sea bass were more active during warm season (mean time spent engaged in active behaviours; 46%, range; 24–60%). In contrast, during cold season fish only spent a mean of 29% of their time in active behaviours (range; 15–49%). No clear response to tidal state or ambient light was found, but some fish were more active during the night in the cold water season. Here, we provide the first activity budgets for the conspicuous Argentine sea bass, which contribute to our understanding of rocky‐reef fish behaviour in Patagonia.Fil: Beltramino, Lucas Esteban. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico. Centro para el Estudio de Sistemas Marinos; ArgentinaFil: Venerus, Leonardo Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico. Centro para el Estudio de Sistemas Marinos; ArgentinaFil: Trobbiani, Gastón Andres. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico. Centro para el Estudio de Sistemas Marinos; ArgentinaFil: Wilson, Rory P.. Swansea University; Reino UnidoFil: Ciancio Blanc, Javier Ernesto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico. Centro para el Estudio de Sistemas Marinos; Argentin

A Pilot Single-Blinded, Randomized, Controlled Trial Comparing BNT162b2 vs. JNJ-78436735 Vaccine as the Third Dose After Two Doses of BNT162b2 Vaccine in Solid Organ Transplant Recipients

Solid Organ Transplant (SOT) recipients are at significant higher risk for COVID-19 and due to immunosuppressive medication, the immunogenicity after vaccination is suboptimal. In the previous studies, booster method showed significant benefit in this population. In the current study, we compared using a mix-and-match method vs. same vaccine as a third dose in SOT recipients. This was a patient-blinded, single center, randomized controlled trial comparing BNT162b2 vs. JNJ-78436735 vaccine as the third dose after two doses of BNT162b2 vaccine. We included adult SOT recipients with functional graft who had received two doses of BNT162b2 vaccine. Participants were randomly assigned to receive either BNT162b2 or JNJ-78436735 in one-to-one ratio. Primary outcome was SARS-CoV-2 IgG positivity at 1 month after the third dose. Sixty SOT recipients, including 36 kidney, 12 liver, 2 lung, 3 heart, and 5 combined transplants, were enrolled, and 57 recipients were analyzed per protocol. There were no statistically significant differences between the two vaccine protocols for IgG positivity (83.3% vs. 85.2% for BNT162b2 and JNJ-78436735, respectively,p= 0.85, Odds Ratio 0.95, 95% Confidence Interval 0.23–4.00). Comparison of the geometric mean titer demonstrated a higher trend with BNT162b2 (p= 0.09). In this pilot randomized controlled trial comparing mix and match method vs. uniform vaccination in SOT recipients, both vaccines were safely used. Since this was a small sample sized study, there was no statistically significant difference in immunogenicity; though, the mix and match method showed relatively lower geometric mean titer, as compared to uniform vaccine. Further studies need to be conducted to determine duration of this immunogenicity.Clinical Trial Registration:https://clinicaltrials.gov/ct2/show/NCT05047640?term=20210641&draw=2&rank=1, identifier 20210641