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Invited for the cover of this issue is the group of Evamarie Hey-Hawkins at the University of Leipzig and colleagues at the University of Stuttgart and University of Regensburg. The image depicts the reported complexes as three similar flowers growing from one common branch representing the ligand. Read the full text of the article at 10.1002/chem.202000226. © 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.BACKGROUND Progressive multifocal leukoencephalopathy (PML) is a rare demyelinating disease of the central nervous system caused by JC virus (JCV). The disease occurs in the setting of significant immunocompromise and has now been reported in many different settings, although only very rarely after lung transplantation. The mortality rate is high and therapeutic options are limited. CASE PRESENTATION We report a case of a 66-year-old man who presented with non-specific memory disturbance at 19 months after lung transplantation for chronic hypersensitivity pneumonitis. He had required methylprednisolone for acute allograft rejection but achieved good graft function. Physical examination was unremarkable. CT revealed hypodensity in the left frontal lobe. MR demonstrated significant hyperintense white-matter abnormalities on T2-weighted and fluid-attenuated inversion recovery (FLAIR) sequences, mainly focused on the periventricular region adjacent the frontal horn of the left lateral ventricle. Brain biopsy confirmed PML. The patient had his immunosuppression reduced but then developed antibody-mediated rejection four months later. Despite re-escalation of immunosuppression, he remains neurologically stable on mirtazapine at eight months post-diagnosis. CONCLUSIONS This very rare case highlights the challenges presented by PML, especially in the lung transplant population. It reveals the difficult balance between reducing immunosuppression to protect the brain versus prevention of lung allograft rejection. It clearly highlights the need for improved therapeutic modalities. © 2020 Wiley Periodicals LLC.OBJECTIVE Sexual and gender minorities are at elevated risk for suicide, yet few studies have examined differences in risk within many sexual and gender minority subgroups. The purpose of this study was to examine differences in prevalence for suicide risk factors among a wide range of sexual orientations and gender identities. METHOD Forty-one thousand four hundred and twelve college students (62% cis-female, 37% cis-male, 1% transgender/genderqueer) completed a wellness screen that included four suicide risk factors (depression, heavy alcohol use, suicide ideation, suicide attempt). RESULTS Gender minority students (i.e., transgender, genderqueer/non-binary) had significantly higher rates of depression, suicide ideation, and suicide attempts relative to cisgender peers, although there were no within-group differences among gender minority students. Adjusted odds ratios for endorsing two or more (2+) suicide risk factors were substantially higher for all sexual minority subgroups relative to heterosexuals. Among sexual minorities, those identifying as pansexual, bisexual, queer, or mostly gay/lesbian had greater odds of endorsing 2+ suicide risk factors relative to students identifying as mostly heterosexual, gay/lesbian, asexual, or 'other sexual minority'. Pansexual students had 33% greater odds of endorsing 2+ suicide risk factors relative to bisexual students. CONCLUSIONS These findings highlight significant variation in suicide risk among sexual minority subgroups and the need for targeted interventions for subgroups at highest risk. © 2020 The American Association of Suicidology.BACKGROUND Multiple system atrophy (MSA) is a rare, untreatable neurodegenerative disorder characterized by accumulation of α-synuclein in oligodendroglial inclusions. As such, MSA is a synucleinopathy along with Parkinson's disease (PD) and dementia with Lewy bodies. Activation of the abelson tyrosine kinase c-Abl leads to phosphorylation of α-synuclein at tyrosine 39, thereby promoting its aggregation and subsequent neurodegeneration. The c-Abl inhibitor nilotinib used for the treatment of chronic myeloid leukemia based on data collected in preclinical models of PD might interfere with pathogenic mechanisms that are relevant to PD and dementia with Lewy bodies, which motivated its assessment in an open-label clinical trial in PD and dementia with Lewy bodies patients. The objective of this study was to assess the preclinical efficacy of nilotinib in the specific context of MSA. METHODS Mice expressing human wild-type α-synuclein in oligodendrocytes received daily injection of nilotinib (1 or 10 mg/kg) over 12 weeks. Postmortem analysis included the assessment of c-Abl activation, α-synuclein burden, and dopaminergic neurodegeneration. RESULTS α-Synuclein phosphorylated at tyrosine 39 was detected in glial cytoplasmic inclusions in MSA patients. Increased activation of c-Abl and α-synuclein phosphorylation at tyrosine 39 were found in transgenic mice. see more Despite significant inhibition of c-Abl and associated reduction of α-synuclein phosphorylation at tyrosine 39 by 40%, nilotinib failed to reduce α-synuclein aggregate burden (including phosphorylation at serine 129) in the striatum and cortex or to lessen neurodegeneration in the substantia nigra. CONCLUSIONS This preclinical study suggests that partial inhibition of c-Abl and reduction of α-synuclein phosphorylation at tyrosine 39 may not be a relevant target for MSA. © 2020 International Parkinson and Movement Disorder Society. © 2020 International Parkinson and Movement Disorder Society.Haouamines A, B, and their derivatives were synthesized via Suzuki-Miyaura coupling and three key cyclization reactions as follows the newly developed palladium(0)-catalyzed arylative cyclization of phenylalanine-derived alkyne-aldehydes with 2-bromoarylboronic acid (an 'anti-Wacker'-type cyclization); BF3·OEt2-promoted Friedel-Crafts-type cyclization of symmetrical electron-rich aromatic rings adjacent to a tertiary allylic alcohol leading to the indeno-tetrahydropyridine skeleton; and (cyanomethyl)trimethylphosphonium iodide-mediated macrocyclization of amino alcohols to afford aza-paracyclophane precursors. The palladium-catalyzed reduction of mono- and di-triflate intermediates in the later stages enabled the alteration of both the position and number of hydroxyl groups on the C-ring. The instability of haouamine B was dramatically improved by salt formation with formic acid. An unambiguous evaluation of the cytotoxicity of the prepared haouamine derivative formates with and without hydroxyl groups at different positions on the C-ring indicated that the catechol structure in haouamine B produced weak cytotoxicity.