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Reducing SARS-CoV-2 pathological protein activity with small molecules

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Journal of Pharmaceutical Analysis 2021年第4期11卷 383-397页

作者： Donata Pluskota-Karwatka Marcin hoffmann Jan Barciszewski Faculty of Chemistry Adam Mickiewicz University in Poznań61-614PoznańPoland NanoBiomedical Center of the Adam Mickiewicz University 61-614PoznańPoland Institute of Bioorganic Chemistry of the Polish Academy of Sciences 61-704 PoznańPoland

Coronaviruses are dangerous human and animal *** newly identified coronavirus SARS-CoV-2 is the causative agent of COVID-19 outbreak,which is a real threat to human health and *** world has been struggling with this epidemic for about a year,yet there are still no targeted drugs and effective treatments are very *** to the long process of developing new drugs,reposition of existing ones is one of the best ways to deal with an epidemic of emergency infectious *** the existing drugs,there are candidates potentially able to inhibit the SARS-CoV-2 replication,and thus inhibit the infection of the *** therapeutics target several proteins,and many diseases share molecular *** such cases,the use of existing pharmaceuticals for more than one purpose can reduce the time needed to design new *** aim of this review was to analyze the key targets of viral infection and potential drugs acting on them,as well as to discuss various strategies and therapeutic approaches,including the possible use of natural *** highlighted the approach based on increasing the involvement of human deaminases,particularly APOBEC deaminases in editing of SARS-CoV-2 *** can reduce the cytosine content in the viral genome,leading to the loss of its *** also indicated the nucleic acid technologies as potential approaches for COVID-19 *** numerous promising natural products,we pointed out curcumin and cannabidiol as good candidates for being antiSARS-CoV-2 agents.

关键词： SARS-CoV-2 COVID-19 Deamination APOBEC Therapeutic nucleotides Natural products Curcumin

Senescent cytotoxic T cells in acute myocardial infarction： innocent bystanders or the horsemen of apocalypse？

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Cellular & Molecular Immunology 2015年第4期12卷 510-512页

作者： Jedrzej hoffmann Ioakim Spyridopoulos Kerckhoff Heart and Thorax Center Bad Nauheim Germany Institute of Genetic Medicine Newcastle University Newcastle Upon Tyne UK Correspondence: Prof I Spyridopoulos Institute of Genetic Medicine Newcastle University Central Parkway Newcastle Upon Tyne NE1 3BZ UK.

Progressive deterioration of innate and adaptive immune functions, a status termed ＇immunosenescence＇, is associated with the higher frequency and severity of diseases in the elderly, such as chronic infections, cancer and autoimmune disorders.1 Age-related immunosenescence can be characterized by a decrease in adaptive immunity and increase in low-grade chronic inflam- mation, also referred to as ＇inflamm- aging＇.2 This dysfunctional immunity is characterized by perturbations of the T- lymphocyte compartment, largely attrib- uted to thymus involution, shrinkage of the naive T-cell repertoire and oligoclonal expansions of memory T cells, particu- larly of CD8＋ effector memory subsets.3 Age and latent viral infections, especially human cytomegalovirus （CMV）, are both considered a driving force ofCD8＋ T-cell expansion and senescence, which is char- acterized by shortened telomeres, pro- gressive loss of costimulatory receptors, CD28 and CD27, and expression of sen- escence-associated surface markers, such as KLRG1 and the glycoepitope CD57, which also reflects the proliferative his- tory of cells.

关键词： T细胞增殖急性心肌梗死衰老细胞毒性自身免疫性疾病免疫功能骑士患者

Vitamin B_(12) Deficiency in Newborns and their Mothers_Novel Approaches to Early Detection,Treatment and Prevention of a Global Health Issue

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Current Medical Science 2020年第5期40卷 801-809页

作者： Gwendolyn Gramer Georg F.hoffmann University Hospital Heidelberg Center for Pediatric and Adolescent MedicineDivision of Neuropediatrics and Metabolic MedicineDietmar Hopp Metabolic CenterIm Neuenheimer Feld 6691 Heidelberg 69120Germany

Vitamin B 12 deficiency,mostly of maternal origin in newborns,is a well treatable condition but can cause severe neurologic *** women of childbearing age and pregnant women worldwide vitamin B12 deficiency has been reported with frequencies of 10%-50%.Children with vitam in B I2 deficiency are asym ptom atic at birth but may develop severe multisystemic symptoms,including irreversible developmental impairment in the second halfyear of *** detection of vitamin B12 deficiency allows for presymptomatic *** article provides an overview over the function of vitamin B12 and discusses causes and frequency of vitamin B12 deficiency in newborns,infants,and women of childbearing *** describes novel successful approaches to newborn screening(NBS)for vitamin B,2 deficiency and results of a pilot study which performed systematic NBS for vitamin B12 deficiency using so-called second-tier strategies by measuring homocysteine and methylmalonic acid in dried blood *** for diagnostics in mothers of children with vitamin B12 deficiency are described as well as results of systematic work-up in mothers and treatment and follow-up of children with vitamin B12 deficiency detected by *** options of vitamin B12 deficiency are presented including a newly developed standardized supplementation scheme with exclusively oral vitamin BI2 *** for preventive approaches to vitamin Bl2 deficiency for children and mothers are *** children worldwide could benefit from systematic inclusion of vitamin B12 deficiency into NBS *** addition,preventive approaches to maternal vitamin B12 deficiency should be implemented systematically during maternal care.

关键词： vitamin B_(12)deficiency prevention treatment mother and child health newborn screening maternal

Mitochondrial DNA suggests a single maternal origin for the widespread triploid parthenogenetic pest species, Paratanytarsus grimmii, but microsatellite variation shows local endemism

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Insect Science 2013年第3期20卷 345-357页

作者： Melissa Carew Bryant Gagliardi Ary A. hoffmann Victorian Centre of Aquatic Pollution Identification and Management Bio21 Institute The Department of Zoology The University ofMelbourne Parkville Victoria 3010 Austrafia

Parthenogenesis is common among invasive pest species, with many partheno- genetic species also showing polyploidy. Parthenogenetic polyploid species often have multiple hybrid origins and the potential to rapidly spread over vast geographical ar- eas. In this study, we examine patterns of mitochondrial and microsatellite variation in a widespread triploid parthenogenetic chironomid pest species, Paratanytarsus grimmii. Based on samples from five countries, including Australia, England, Germany, Japan, and Canada, we found extremely low mitochondrial diversity （〈0.14%）, with most individuals sharing a common and widespread haplotype. In contrast, microsatellite diversity revealed 41 clonal variants, which were regionally endemic. These findings suggest a single invasive maternal lineage ofP grimmii is likely to have recently spread over a broad geographical range. High levels of genotypic endemism suggest P grimmii populations have remained relatively isolated after an initial spread, with little ongoing migration. This, in part, can be attributed to rapid genetic differentiation via mutations of common clonal genotypes after P. grimmii spread, but multiple polyploidization and subsequent founder events are also likely to be contributing factors.

关键词： invasive microsatellites mitochondrial Paratanytarsus grimmii parthenogenesis triploid

Signals from the interface:protein nanoclusters stabilize biomolecular condensates

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Signal Transduction and Targeted Therapy 2022年第2期7卷 341-342页

作者： Christian hoffmann Branislava Rankovic Dragomir Milovanovic Laboratory of Molecular Neuroscience German Center for Neurodegenerative Diseases(DZNE)10117 BerlinGermany

In a recent study,Folkmann and colleagues1 show that protein nanoclusters at the surface of biomolecular condensates act as Pickering agents stabilizing these emulsions in *** accumulating evidence suggests that cytosol represents a complex emulsion where multiple membrane-bound organelles and biomolecular condensates co-exist together.2 Each of these condensates is a crucible that can enrich for numerous proteins,RNAs,and even the entire membrane-bound organelles,such as the cluster of synaptic vesicles or the Golgi *** molecules in these condensates remain highly mobile,readily exchange with the surrounding environment and grow/coarsening over time(by coalescence or Ostwald ripening),often towards the round structures to minimize the surface tension.

关键词： clusters molecular readily

Omicron:Master of immune evasion maintains robust ACE2 binding

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Signal Transduction and Targeted Therapy 2022年第5期7卷 1360-1362页

作者： Markus hoffmann Lu Zhang Stefan Pohlmann Infection Biology Unit German Primate Center—Leibniz Institute for Primate ResearchGöttingenGermany Georg-August-University Göttingen GöttingenGermany

The spike(S)protein of the SARS-CoV-2 Omicron variant is highly mutated but the impact of these mutations on viral entry into cells and its inhibition by antibodies has been unclear.A recent study published in Science by Mannar et *** shows that these mutations are compatible with robust ACE2 binding and allow for efficient evasion of neutralizing *** emergence of SARS-CoV-2 variants has become a hallmark of the COVID-19 *** of concern(VOC)harbor mutations in the viral S protein that can increase transmissibility,potentially by promoting S protein binding to the cellular receptor ACE2.

关键词： ACE2 maintain

Fusing MEMS technology with lab-on-chip: nanoliter-scale silicon microcavity arrays for digital DNA quantification and multiplex testing

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Microsystems & Nanoengineering 2020年第1期6卷 345-356页

作者： Daniel Podbiel Franz Laermer Roland Zengerle Jochen hoffmann Robert Bosch GmbH Corporate Sector ResearchMicrosystems and NanotechnologiesRobert-Bosch-Campus 171272 RenningenGermany IMTEK-Department of Microsystems Engineering University of Freiburg Georges-Koehler-Allee 10379110 FreiburgGermany

We report on the development of a microfluidic multiplexing technology for highly parallelized sample analysis via quantitative polymerase chain reaction(PCR)in an array of 96 nanoliter-scale microcavities made from *** PCR array technology features fully automatable aliquoting microfluidics,a robust sample compartmentalization up to temperatures of 95°C,and an application-specific prestorage of reagents within the 25nl *** here presented hybrid silicon–polymer microfluidic chip allows both a rapid thermal cycling of the liquid compartments and a real-time fluorescence read-out for a tracking of the individual amplification reactions taking place inside the *** demonstrate that the technology provides very low reagent carryover of prestored reagents<6×10^(−2) and a cross talk rate<1×10^(−3) per PCR cycle,which facilitate a multi-targeted sample analysis via geometric ***,we apply this PCR array technology to introduce a novel digital PCR-based DNA quantification method:by taking the assay-specific amplification characteristics like the limit of detection into account,the method allows for an absolute gene target quantification by means of a statistical analysis of the amplification results.

关键词： liter testing apply

Comparative studies of critical physiological limits and vulnerability to environmental extremes in small ectotherms:How much environmental control is needed?

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Integrative Zoology 2018年第4期13卷 355-371页

作者： Ary A.hoffmann Carla M.SGRÒ School of BioSciences Bio21 InstituteThe University of MelbourneMelbourneAustralia School of Biological Sciences Monash UniversityMelbourneAustralia

Researchers and practitioners are increasingly using comparative assessments of critical thermal and physiological limits to assess the relative vulnerability of ectothermic species to extreme thermal and aridity conditions occurring under climate *** most assessments of vulnerability,critical limits are compared across taxa exposed to different environmental and developmental ***,many aspects of vulnerability should ideally be compared when species are exposed to the same environmental conditions,allowing a partitioning of sources of variation such as used in quantitative *** is particularly important when assessing the importance of different types of plasticity to critical limits,using phylogenetic analyses to test for evolutionary constraints,isolating genetic variants that contribute to limits,characterizing evolutionary interactions among traits limiting adaptive responses,and when assessing the role of cross generation ***,vulnerability assessments based on critical thermal/physiological limits also need to take place within a context that is relevant to field conditions,which is not easily provided under controlled environmental conditions where behavior,microhabitat,stress exposure rates and other factors will differ from field *** are ways of reconciling these requirements,such as by taking organisms from controlled environments and then testing their performance under field conditions(or vice versa).While comparisons under controlled environments are challenging for many taxa,assessments of critical thermal limits and vulnerability will always be incomplete unless environmental effects within and across generations are considered,and where the ecological relevance of assays measuring critical limits can be established.

关键词： comparative studies common garden critical limits ectotherms environmental control thermal limits stress resistance

Traceable long range scanning tunneling microscopy

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Optoelectronics Letters 2008年第1期4卷 49-50页

作者： A. Weckenmann J. hoffmann Chair Quality Management and Manufacturing Metrology University of Erlangen-Nuremberg

Dimensionally correct and directly traceable measurement is not feasible with conventional scanning tunneling microscopy (STMs) due to severe hysteresis and non-linearity of the commonly applied piezo tube scanners and the very short range. By integrating a custom made probing system based on tunneling current measurement into a commercially available and laser-interferometrically position controlled positioning system, an STM with a principal measuring

关键词：远程扫描隧道显微镜显微镜技术干涉测量激光定位控制