Charge Detection Mass Spectrometry: What's the "Big" Deal?

In 2002, the first fully humanized mAb was approved by the U.S. Food and Drug Administration (FDA) (3). [...]the biopharmaceutical industry is still in its infancy and new, more complex products are in development and will ikely dominant the market in the future. [...]the most common forms of LC-MS have limitations when characterizing large macromolecules (4). [...]in this column, we discuss the potential for charge detection MS (CDMS) as an analytical tool for characterizing large, complex, and heterogenous biopharmaceuticals. [...]in October 2021 at the American Association for Mass Spectrometry (ASMS) annua meeting in Philadelphia, TrueMass presented the first commercial CDMS (6,7). The cylinder is often inside an electrostatic linear ion trap (ELIT) instrument, where ions oscillate back and forth. [...]the oscillation frequency gives the m/z and the charge is determined by the magnitude.

Network-based Approach to Identify Pathways and Macromolecule Interactions that Mediate Influences of COVID-19 on the Progression of Respiratory System Diseases

COVID-19 is an infectious illness concerning coronavirus that is transmitted through droplets propagated by an infected person exhales, coughs, or sneezes. People affected by coronavirus have a risk to occur respiratory diseases (RDs). The longevity of COVID-19 may appear a vital risk of manifesting RDs. To address these issues, we explored transcriptomic data to identify the genetic effects of COVID-19 on the development of RDs such as Bronchitis (BC), Asthma (AT), Lung cancer (LC), and Pulmonary Edema (PE). We explored GEO datasets from NCBI for COVID-19, BC, AT, LC, PE case, and control subjects. We identified COVID-19 is associated with RDs by sharing 16, 19, 27, and 59 commonly DEGs accordingly. By using these genes we performed some bioinformatics analysis and constructed diseasome networks, identified functional and ontological pathways. We formed PPIs networks and PDIs network. On the basis of PPIs and PDIs, we have identified hub proteins and constructed hub proteins network. We have successfully developed a quantitative model to identify the genetic effects of COVID-19 on the progression of RDs. We also validated our investigations through gold-benchmark datasets. Our results are an effective resource to mark out the most important influences on the development of RDs for COVID-19. © 2022 IEEE.

Connecting aging biology and inflammation in the omics era

Aging is characterized by the accumulation of damage to macromolecules and cell architecture that triggers a proinflammatory state in blood and solid tissues, termed inflammaging. Inflammaging has been implicated in the pathogenesis of many age-associated chronic diseases as well as loss of physical and cognitive function. The search for mechanisms that underlie inflammaging focused initially on the hallmarks of aging, but it is rapidly expanding in multiple directions. Here, we discuss the threads connecting cellular senescence and mitochondrial dysfunction to impaired mitophagy and DNA damage, which may act as a hub for inflammaging. We explore the emerging multi-omics efforts that aspire to define the complexity of inflammaging - and identify molecular signatures and novel targets for interventions aimed at counteracting excessive inflammation and its deleterious consequences while preserving the physiological immune response. Finally, we review the emerging evidence that inflammation is involved in brain aging and neurodegenerative diseases. Our goal is to broaden the research agenda for inflammaging with an eye on new therapeutic opportunities.

Exosomal and Non-Exosomal MicroRNAs: New Kids on the Block for Cancer Therapy

MicroRNAs have been projected as promising tools for diagnostic and prognostic purposes in cancer. More recently, they have been highlighted as RNA therapeutic targets for cancer therapy. Though miRs perform a generic function of post-transcriptional gene regulation, their utility in RNA therapeutics mostly relies on their biochemical nature and their assembly with other macromolecules. Release of extracellular miRs is broadly categorized into two different compositions, namely exosomal (extracellular vesicles) and non-exosomal. This nature of miRs not only affects the uptake into target cells but also poses a challenge and opportunity for RNA therapeutics in cancer. By virtue of their ability to act as mediators of intercellular communication in the tumor microenvironment, extracellular miRs perform both, depending upon the target cell and target landscape, pro- and anti-tumor functions. Tumor-derived miRs mostly perform pro-tumor functions, whereas host cell- or stroma-derived miRs are involved in anti-tumor activities. This review deals with the recent understanding of exosomal and non-exosomal miRs in the tumor microenvironment, as a tool for pro- and anti-tumor activity and prospective exploit options for cancer therapy.

Macromolecular Viral Entry Inhibitors as Broad-Spectrum First-Line Antivirals with Activity against SARS-CoV-2.

Inhibitors of viral cell entry based on poly(styrene sulfonate) and its core-shell nanoformulations based on gold nanoparticles are investigated against a panel of viruses, including clinical isolates of SARS-CoV-2. Macromolecular inhibitors are shown to exhibit the highly sought-after broad-spectrum antiviral activity, which covers most analyzed enveloped viruses and all of the variants of concern for SARS-CoV-2 tested. The inhibitory activity is quantified in vitro in appropriate cell culture models and for respiratory viral pathogens (respiratory syncytial virus and SARS-CoV-2) in mice. Results of this study comprise a significant step along the translational path of macromolecular inhibitors of virus cell entry, specifically against enveloped respiratory viruses.

Biosensors Based on Bivalent and Multivalent Recognition by Nucleic Acid Scaffolds

Several biological macromolecules adopt bivalent or multivalent interactions to perform various cellular processes. In this regard, the development of molecular constructs presenting multiple ligands in a specific manner is becoming crucial for the understanding of multivalent interactions and for the detection of target macromolecules. Nucleic acids are attractive molecules to achieve this goal because they are capable of forming various, structurally well-defined 2D or 3D nanostructures and can bear multiple ligands on their structures with precisely controlled ligand–ligand distances. Thanks to the features of nucleic acids, researchers have proposed a wide range of bivalent and multivalent binding agents that strongly bind to target biomolecules;consequently, these findings have uncovered new biosensing strategies for biomolecule detection. To date, various bivalent and multivalent interactions of nucleic acid architectures have been applied to the design of biosensors with enhanced sensitivity and target accuracy. In this review, we describe not only basic biosensor designs but also recently designed biosensors operating through the bivalent and multivalent recognition of nucleic acid scaffolds. Based on these designs, strategies to transduce bi- or multivalent interaction signals into readable signals are discussed in detail, and the future prospects and challenges of the field of multivalence-based biosensors are explored.

Histidine-enhanced gene delivery systems: The state of the art.

Gene therapy has emerged as a promising tool for treating different intractable diseases, particularly cancer or even viral diseases such as COVID-19 (coronavirus disease 2019). In this context, various non-viral gene carriers are being explored to transfer DNA or RNA sequences into target cells. Here, we review the applications of the naturally occurring amino acid histidine in the delivery of nucleic acids into cells. The biocompatibility of histidine-enhanced gene delivery systems has encouraged their wider use in gene therapy. Histidine-based gene carriers can involve the modification of peptides, dendrimers, lipids or nanocomposites. Several linear polymers, such as polyethylenimine, poly-l-lysine (synthetic) or dextran and chitosan (natural), have been conjugated with histidine residues to form complexes with nucleic acids for intracellular delivery. The challenges, opportunities and future research trends of histidine-based gene deliveries are investigated.

2021 Acknowledgment of mSphere Ad Hoc Reviewers

Yet, we accomplished it, in no small part due to years of fundamental research on how the immune system recognizes and responds to pathogens, how mRNAs are synthesized and translated, and how to effectively deliver macromolecules into cells. Much of this progress was anchored in the microbial sciences: studies of viral immunology, landmark work on mRNA metabolism in bacteria and virally infected cells, understanding how pathogens bind to and enter cells, development of techniques that were originally used to introduce viral oncogenes into mammalian cells in culture, and the use of viral vectors for gene therapy all set the stage for the COVID-19 vaccines. [...]we list below the many individuals who served as ad hoc reviewers in 2021. Kjersti Aagaard Mohamed M. H. Abdelbary Sabrina Absalon Michael C. Abt Mark D. Adams Josephine Azikuru Afema Kayode Olayinka Afolabi Surya D. Aggarwal Hector Aguilar-Carreno Christian Paul Ahearn Brian M. M. Ahmer Mustafa Akkoyunlu Md. Tauqeer Alam Ashraf Al Ashhab M. John Albert Anoop Alex Caroline Alfieri Holly M. Scott Algood Jonathan Allen Emma Allen-Vercoe Juan C. Alonso Francis Alonzo Christopher Alteri John Alverdy Christopher S. Anderson Matthew Zack Anderson David R. Andes Laura Maria Andrade De Oliveira Marco Andreolli Diego O. Andrey Alberto Antonelli Yoshiteru Aoi Cristian Apetrei Chelsie Elizabeth Armbruster Sandra K. Armstrong Jennifer M. Auchtung Tatjana Avšič-Županc Domenico Azarnia Tehran Sophie Bachellier-Bassi Michael A. Bachman Steffen Backert Matthew Baideme Camden R. Bair Jonathon L. Baker Katherine H. Baker Scott Baliban Jimmy D. Ballard Guilia Bandini Fernando Baquero Noa Barak-Gavish Joseph T. Barbieri Brianne Barker Jason C. Bartz Martine Bassilana Christine Marie Bassis Tilman Baumstark Marco Becherelli Sara Beier Daniel P. Beiting Georgios N. Belibasakis Aeriel D. Belk Samantha L. Bell Jessica A. Belser Jorge L. Benach Jose A. Bengoechea Peter Bergholz Teresa M. Bergholz Tanja Berić David Bernstein Stefan Bertilsson Ralph Bertram Sanchita Bhadra Dipankar Bhattacharyya Bijit Bhowmik Fadil A. Bidmos Claire H. Birkenheuer Jacob P. Bitoun Daniel Blanco-Melo Jon S. Blevins Joseph M. Bliss Patricia Pringle Bloom Antje Blumenthal Kasun H. Bodawatta Pierre Bogaerts Gregory Bonito Sébastien Bontemps-Gallo Angela Bordin Jens Bosse Anna Both Travis Bourret Kate Bowerman Eric Boyd Ethna Fidelma Boyd Todd Bradley Rita Branco Kyndall Braumuller Linda Breeden Mathieu Brochet Nichole A. Broderick Christopher B. Brooke Grayson Brown Jeremy S. Brown Kevin M. Brown Michael G. Brown Harry Brumer Donald A. Bryant Alison Buchan Lori L. Burrows Karen Bush Andrea Cabibbe Laty A. Cahoon Yi Cai Eloiza Helena Campana Edgar I. Campos-Madueno Eric Caragata Alessandra Carattoli Franck Gael Carbonero Miguel Carda Diéguez Jeffrey Carey Ryan B. Carnegie Jaime Carrasco Vern B. Carruthers Leslie S. Casey Irene Castano Santiago Castillo-Ramírez Clayton C. Caswell Rodrigo Cayô Daniel Cazares Brandi N. Celia Nuno Cerca Miguel Angel Cevallos Dipshikha Chakravortty Douglas L. Chalker Thomas M. Chambers Josephine R. Chandler Michael Chandler Robert L. Charlebois Sujata S. Chaudhari Neeraj Chauhan Damien Chaussabel Michael S. Chaussee Francisco P. Chavez Liang Chen Chiuping Cheng Rachel A. Cheng Laurent Roberto Chiarelli Alex W. H. Chin Michaelle Chojnacki Stephen A. Clark Erika C. Claud David W. Cleary Sara Clohisey Shira Milo Cochavi Darrell Cockburn Ashley Cohen Sean Conlan Laura Cook Gretchen Cooley Brendan Cormack Pierre Cornelis Caitlin Cossaboom Siobhan C. Cowley Robert A. Cramer Max Cravener Alison K. Criss Karissa L. Cross Robert W. Cross Liwang Cui Paul J. Cullen Natacha Cuoto Cameron R. Currie Todd Andrew Cutts Dennis G. Cvitkovitch F. Heath Damron Ajai A. Dandekar Stephen Daniels Biswadip Das Bryan W. Davies Charles R. Dean Jean-Winoc Decousser Elizabeth N. De Gaspari Miranda De Graaf Kirk W. Deitsch Harry P. De Koning Frank R. DeLeo Thomas G. Denes David W. Denning Rajendar Deora Cynthia Ann Derdeyn Steven C. Derrick Jigar V. Desai Lalitagauri Deshpande Sanjay Kumar Dey Vijaykrishn Dhanasekaran Rishu Dheer Robert P. Dickson Diego G. Diel Beatriz Diez Moreno Stephen P. Diggle Joseph P. Dillard Siyuan Ding Marc S. Dionne Alan Angelo Dispirito Dirk P. Dittmer Eunsoo Do Carlota Dobaño Lazaro Yohei Doi Janet Donaldson Caihong Dong Matthew J. Dorman Laurent Dortet Benoît Doublet Charles M. Dozois Jan Felix Drexler Yuchun Du Elves Duarte Edward G. Dudley Breck A. Duerkop Anne K. Dunn Sanjucta Dutta Kathryn Eaton Leo Eberl Kathryn M. Edenborough Tom Edlind Elizabeth A. Edwards Maren Eggers Sabine Ehrt Patrick Eichenberger Waldir P. Elias Jeremy R. Ellermeier Roland Elling Najib M. El-Sayed Mostafa S. Elshahed Joanne B. Emerson Virve Irene Enne Eeva Liisa Eronen-Rasimus Alice L. Erwin Javier Antonio Escobar-Perez Matthe J. Evans Franziska Faber Robert Fagan Christina S. Faherty Linda Falgenhauer Séamus Fanning Mauricio J. Farfan Matthew L. Faron Amy K. Feehan Mario F. Feldman Jinrong Feng J. Christopher Fenno David J. Ferguson Isabel Fernández Escapa Astrid Ferrer Richard L. Ferrero Kenneth A. Fields Joshua Fierer Sergio R. Filipe Maria F. Fillat Scott G. Filler Douglas K. Fischer Carlos Flores Stephanie Flowers Fabrizio Foieni Steven L. Foley Laura Ford Jarrod R. Fortwendel Michael T. France Kristi L. Frank Natalia Freund Georg Fritz Inga Fröding Takasuke Fukuhara Marta M. Gaglia Hannah Gaimster Raj Gaji James E. Galen Markus Ganter Michael G. Ganzle Erin C. Garcia Sarahi L. Garcia Amy Shirley Gargis Kathleen Gärtner Caroline Attardo Genco Noel Gerald Carmen Gherasim Lorenzo Giacani Heather L. Glasgow Oleg Glebov Erin S. Gloag Marek Gniadkowski Richard V. Goering Gustavo H. Goldman Jonathan Louis Golob Benjamin Golomb Laura Gómez-Consarnau Angela Gomez-Simmonds Yanhai Gong Jesus Gonzalo-Asensio Steven D. Goodman Tobias Goris Morgan Gorris Ria Goswami Matthias Gotte Revathi Govind Manish Goyal Andreas Grabrucker Lisa Gralinski Luke R. Green Alexander L. Greninger Finn Grey Elizabeth Grice Dennis Grogan Elisabeth Grohmann Trudy H. Grossman Cassandra Guarino Marc-Jan Gubbels Eric Guédon Pascale S. Guiton Arda Gulay Ravindra Kumar Gupta Gabriel Gutkind David Hackstadt Andrea Hahn Anders P. Hakansson Riley Hale Vanessa L. Hale Robert Hall Roy A. Hall Ruth M. Hall Brian K. Hammer Tobin Hammer Abdul N. Hamood Axel Georg Hamprecht Ken-Ichi Hanaki Lynn E. Hancock Blake M. Hanson Mingju Hao Md. Manjurul Haque Sohei Harada Clare Harding Lee H. Harrison Oliver Harschnitz Erica M. Hartmann Eric T. Harvill Asma Hatoum-Aslan Ben M. Hause Margo G. Haygood Cynthia Y. He Susu He Aoife T. Heaslip Nicholas S. Heaton Nagendra R. Hegde Christine Heilmann Henry S. Heine David E. Heinrichs Peera Hemarajata Tory A. Hendry Cristina Herencias Ana Hernandez Cordero Robert L. Hettich Andrés Hidalgo Steven Higgins Penelope Higgs Takahiro Hiono Itaru Hirai Theresa D. Ho Thomas Hoenen Nicole A. Hoff Deborah A. Hogan Peiying Hong Lauren Michelle Hook Thomas Hooven Alexander M. Horspool Paul A. Hoskisson Daniel K. Howe Gongzheng Hu Ke Hu Linden T. Hu Stephen S. H. Huang Eili Huhtamo Lewis Hun Jason F. Huntley Jillian H. Hurst Bonnie L. Hurwitz Wilhelmina Huston Justin Hutchison Albina Ibrayeva Melissa Ingala Thomas J. Inzana William W. Ja Mary Ann Jabra-Rizk Cody B. Jackson Anna C. Jacobs William R. Jacobs Guilhem Janbon Ingmar Janse Michael A. Jarvis Vicki Jeffers Niuniu Ji Dong-Yan Jin William Johnson Susan Joseph Lok R. Joshi Yuan Jun Barbara C. Kahl Maria Kalamvoki Suzanne R. Kalb Jeremy Phillip Kamil Manabu Kanno Fathi Karouia Anbu Kumar Karuppannan Fatah Kashanchi Joseph Keane Daniel B. Kearns Scott P. Keely Eliisa Kekäläinen Brendan Kelly Volkhard A. J. Kempf Arnaud Kengmo Tchoupa Nemat O. Keyhani Shabaana A. Khader Arifa