Characterization of the novel HLA-DRB1*10:38 allele, showing an extended cytoplasmic tail.

Sequence and expression analysis of the HLA-DRB1*10:38 allele.

Rationale for combined therapies in severe-to-critical COVID-19 patients.

An unprecedented global social and economic impact as well as a significant number of fatalities have been brought on by the coronavirus disease 2019 (COVID-19), produced by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Acute SARS-CoV-2 infection can, in certain situations, cause immunological abnormalities, leading to an anomalous innate and adaptive immune response. While most patients only experience mild symptoms and recover without the need for mechanical ventilation, a substantial percentage of those who are affected develop severe respiratory illness, which can be fatal. The absence of effective therapies when disease progresses to a very severe condition coupled with the incomplete understanding of COVID-19's pathogenesis triggers the need to develop innovative therapeutic approaches for patients at high risk of mortality. As a result, we investigate the potential contribution of promising combinatorial cell therapy to prevent death in critical patients.

Computational studies of Brønsted acid-catalyzed transannular cycloadditions of cycloalkenone hydrazones.

The contribution to the energy barrier of a series of tethers in transannular cycloadditions of cycloalkenes with hydrazones has been computationally studied by using DFT. The Houk's distortion model has been employed to evaluate the influence of the tether in the cycloaddition reaction. That model has been extended to determine the contribution of each tether and, more importantly, the effect exerted between them. In addition to the distortion induced by the tethers, the entropy effects caused by them has also been studied. The analysis of the evolution of the electron localization function along the reaction revealed the highly concerted character of the reaction.

Organocatalytic Enantioselective Vinylcyclopropane-Cyclopentene (VCP-CP) Rearrangement.

We have demonstrated that the catalytic and enantioselective vinylcyclopropane-cyclopentene rearrangement can be carried out on (vinylcyclopropyl)acetaldehydes through activation via enamine intermediates. The reaction makes use of racemic starting materials that, upon ring opening facilitated by the catalytic generation of a donor-acceptor cyclopropane, deliver an acyclic iminium ion/dienolate intermediate in which all stereochemical information has been deleted. The final cyclization step forms the rearrangement product, showing that chirality transfer from the catalyst to the final compound is highly effective and leads to the stereocontrolled formation of a variety of structurally different cyclopentenes.

Identification of six novel HLA alleles, HLA-A*31:208, -B*08:306, -C*03:582, -C*04:494, -C*18:18 and -DRB1*07:133.

Characterization of six novel HLA alleles by next-generation sequencing.

Full-length characterization of the HLA-DQB1*03:25:01 allele in two Amerindian individuals.

Genomic full-length characterization of the HLA-DQB1*03:25:01 allele.

Genomic full-length confirmatory sequence of HLA-DQB1*04:59N allele in three Colombian individuals.

The extended genomic sequence of HLA-DQB1*04:59N allele.

Brønsted Acid versus Phase-Transfer Catalysis in the Enantioselective Transannular Aminohalogenation of Enesultams.

We have studied the enantioselective transannular aminohalogenation reaction of unsaturated medium-sized cyclic benzosulfonamides by using both chiral Brønsted acid and phase-transfer catalysis. Under optimized conditions, a variety of bicyclic adducts can be obtained with good yields and high enantioselectivities. The mechanism of the reaction was also studied by using computational tools; we observed that the reaction involves the participation of a conformer of the nine-membered cyclic substrate with planar chirality in which the stereochemical outcome is controlled by the relative reactivity of the two pseudorotational enantiomers when interacting with the chiral catalyst.

Long-Term Outcome of a Series of Patients With Narcolepsy Type 1 and Comorbidity With Immunopathological and Autoimmune Diseases.

Background: The aim of this study was to evaluate the long-term outcome of our series of narcolepsy type 1 (NT1) patients with comorbid autoimmune diseases (ADs) and other immunopathological diseases (IDs), focusing on the incidence of new ADs and IDs in this sample. Methods: A longitudinal observational study was conducted over 6 years (2014 - 2020) in a series of 158 Caucasians NT1 patients (96 males; mean age: 50.1 ± 19.0 years) from the previous study. All but one case (familial case) were HLA-DQB1*06:02-positive. The diagnosis of narcolepsy was made according to the International Classification of Sleep Disorders (ICSD-3). Results: Twenty-one patients have been diagnosed with a new ID, 10 of them with an AD (autoimmune thyroid disease, psoriasis, rheumatoid arthritis, transverse myelitis, granuloma annulare, primary biliary cirrhosis, alopecia areata and antiphospholipid syndrome), and 11 with other IDs (allergic rhinitis, allergic asthma, atopic dermatitis, food allergy, contact dermatitis and drug allergy). One patient was diagnosed with two new ADs. We found IDs in 46 patients (24 females and 22 males) and the overall prevalence in this series is actually 29.11%; 22 of them (13.92%) had an AD, with a percentage higher than estimated in the general population. Conclusions: The prevalence of AD/ID is high in our series, suggesting that NT1 might arise on a background of generalized susceptibility to immune-mediated processes. The occurrence of an ID can in turn influence the development of others in genetically predisposed individuals, which explains the increased associations observed in this long-term study.

Recent Advances in the Prins Reaction.

The Prins reaction is a very convenient synthetic platform for the preparation of oxygen-containing heterocyclic compounds, especially tetrahydropyrans and tetrahydrofurans. While this reaction has been extensively used by synthetic chemists since its discovery, the last years have witnessed impressive improvements in its performance and scope and especially in the development of new catalytic and enantioselective versions. This mini-review presents these recent advances through selected representative examples.

Sequencing of two novel HLA class I null alleles, A*32:160N and B*14:113N, produced by single-nucleotide mutations.

Characterization of two novel HLA class I null alleles.

Transannular Approach to 2,3-Dihydropyrrolo[1,2-b]isoquinolin-5(1H)-ones through Brønsted Acid-Catalyzed Amidohalogenation.

A transannular approach has been developed for the construction of pyrrolo[1,2-b]isoquinolinones starting from benzo-fused nine-membered enelactams. This process takes place in the presence of a halogenating agent and under Brønsted acid catalysis and proceeds via a transannular amidohalogenation, followed by elimination. The reaction has been found to be wide in scope, enabling the formation of a variety of tricyclic products in good overall yield, regardless of the substitution pattern in the initial lactam substrate. The reaction has also been applied to the total synthesis of a reported topoisomerase I inhibitor and to the formal synthesis of rosettacin. Further extension of this methodology allows the preparation of 10-iodopyrrolo[1,2-b]isoquinolinones by using an excess of halogenating agent and these compounds can be further manipulated through standard Suzuki coupling chemistry into a variety of 10-aryl-substituted pyrrolo[1,2-b]isoquinolinones.

Sequencing of a novel HLA-DQB1 allele, DQB1*04:02:01:16Q, with a mutation in the intron 3 donor splicing site.

The novel HLA-DQB1*04:02:01:16Q allele showing a point mutation in the intron 3.

Identification of the novel HLA-C*08:243 allele in a Spanish bone marrow donor.

HLA-C*08:243 differs from C*08:51 by a single nucleotide substitution in codon 156 (G > T).

Ultrafast CO2 photodissociation in the energy region of the lowest Rydberg series.

We present a detailed theoretical survey of the electronic structure of excited states of the CO2 molecule, with the aim of providing a well-defined theoretical framework for the quantum dynamical studies at energies beyond 12 eV from the ground state. One of the major goals of our work is to emphasize the need for dealing with the presence of both molecular valence and Rydberg states. Although a CASSCF/MRCI approach can be used to appropriately describe the lowest-lying valence states, it becomes incapable of describing the upper electronic states due to the exceedingly large number of electronic excitations required. To circumvent this we employ instead the EOM-CCSD monoconfigurational method to describe the manifold of both valence and Rydberg states in the Franck-Condon region and then a matching procedure to connect these EOM-CCSD eigensolutions with those obtained from CASSCF/MRCI in the outer region, thus ensuring the correct asymptotic behavior. Within this hybrid level of theory, we then analyze the role of valence and Rydberg states in the dynamical mechanism of the photodissociation of quasi-linear CO2 into CO + O fragments, by considering a simple but effective 1D multistate non-adiabatic model for the ultrafast C-O bond break up. We show evidence that the metastability of the Rydberg states must be accounted for in the ultrafast dynamics since they produce changes in the photodissociation yields within the first tens of fs.

Enantioselective transannular reactions by palladium-catalysed conjugate addition of aryl boronic acids.

A palladium-catalyzed asymmeric conjugate addition of aryl boronic acids to medium-sized cycloalkenones followed by intramolecular aldol trapping is reported. The use of in situ formed [Pd/(QuinoxP*)] as the catalyst enables the synthesis of arylbicyclic scaffolds in good yields and with excellent stereocontrol (up to 7 : 1 dr, up to 99% ee). The reaction is applicable to a range of medium size ketoenone substrates and funcionalized aryl boronic acids, including heterocyclic compounds.

The novel HLA-C*07:1000 allele was likely generated by an intragenic recombination event.

Characterization of the novel HLA-C allele, HLA-C*07:1000.