Substance and alcohol use disorders impose large health and economic burdens on individuals, families, communities, and society. Neither prevention nor treatment efforts are effective in all individuals. Results are often modest. Advances in neuroscience and addiction research have helped to describe the neurobiological changes that occur when a person transitions from recreational substance use to a substance use disorder or addiction. Understanding both the drivers and consequences of substance use in vulnerable populations, including those whose brains are still maturing, has revealed behavioral and biological characteristics that can increase risks of addiction. These findings are particularly timely, as law‐ and policymakers are tasked to reverse the ongoing opioid epidemic, as more states legalize marijuana, as new products including electronic cigarettes and newly designed abused substances enter the legal and illegal markets, and as “deaths of despair” from alcohol and drug misuse continue.

Cross-linking combined with mass spectrometry is an emerging approach for studying protein structure and protein-protein interactions. However, unambiguous mass spectrometric identification of cross-linked peptides derived from proteolytically digested cross-linked proteins is still challenging. Here we describe the use of a novel cross-linker, bimane bisthiopropionic acid Nsuccinimidyl ester (BiPS), that overcomes many of the challenges associated with other cross-linking reagents. BiPS is distinguished from other cross-linkers by a unique combination of properties: it is photocleavable, fluorescent, homobifunctional, amine-reactive, and isotopically coded. Numerous cellular processes involve stable or transient protein-protein interactions. Deciphering protein interaction networks and the organization of protein complexes, such as those involved in G-protein-coupled receptor and ␤-arrestin signaling, is a major focus of modern proteomics and cellular biology. An important emerging technology for the structural analysis of proteins and protein complexes involves crosslinking combined with advanced mass spectrometric techniques (1-4). This approach typically involves proteolysis of complexed proteins followed by mass spectrometric identification of the cross-linked peptides (also called "cross-links") (5).Unfortunately, experiments combining cross-linking with mass spectrometry involve many technical challenges. For example, the combinatorial nature of protein cross-links creates an intrinsic problem of identification when assayed by mass alone. Additionally insufficient fragmentation of crosslinked peptides during MS/MS sequencing often results in mass spectra that are difficult to interpret. The relatively low number of cross-links compared with non-cross-linker-containing peptides produced during proteolysis of the protein complex presents another analytical challenge.Several recent developments have resolved some of these issues. Mass spectrometers capable of determining molecular weight with high mass accuracy, such as FTICR-MS instruments, reduce the number of potential cross-links that can be assigned to a specific mass (1, 6). Also the specific mass spectrometric "signature" provided by isotopically coded cross-linkers (7) and isotope labeling of cross-links during proteolysis (8) has been a crucial development for straightforward MS detection of cross-links. We recently reported an isotopically coded, chemically cleavable crosslinker that allows discrimination between cross-link types (dead end, intrapeptide, or interpeptide) and facilitates subsequent MS/MS sequencing of the individual peptides that constitute an interpeptide cross-link (9). We have also reported a specific photocleavage of fluorescent monobromoFrom the ‡Department

Our food systems depend on complex interactions between farmers and food producers, local and federal governments, and consumers. Underlying these interactions are economic, environmental, and societal factors that can impact the types of food available, access to food, affordability, and food safety. The recent SARS‐CoV‐2 global pandemic has affected multiple aspects of our food systems, from federal governments’ decisions to limit food exports, to the ability of government agencies to inspect food and facilities to the ability of consumers to dine at restaurants. It has also provided opportunities for societies to take a close look at the vulnerabilities in our food systems and reinvent them to be more robust and resilient. For the most part, how these changes ultimately affect the safety and accessibility of food around the world remains to be seen.

Adult stem cells are rare, undifferentiated cells found in all tissues of the body. Although normally kept in a quiescent, nondividing state, these cells can proliferate and differentiate to replace naturally dying cells within their tissue and to repair its wounds in response to injury. Due to their proliferative nature and ability to regenerate tissue, adult stem cells have the potential to treat a variety of degenerative diseases as well as aging. In addition, since stem cells are often thought to be the source of malignant tumors, understanding the mechanisms that keep their proliferative abilities in check can pave the way for new cancer therapies. While adult stem cells have had limited practical and clinical applications to date, several clinical trials of stem cell–based therapies are underway. This report details recent research presented at the New York Academy of Sciences on March 14, 2019 on understanding the factors that regulate stem cell activity and differentiation, with the hope of translating these findings into the clinic.

Cancer immunotherapy has dramatically changed the approach to cancer treatment. The aim of targeting the immune system to recognize and destroy cancer cells has afforded many patients the prospect of achieving deep, long‐term remission and potential cures. However, many challenges remain for achieving the goal of effective immunotherapy for all cancer patients. Checkpoint inhibitors have been able to achieve long‐term responses in a minority of patients, yet improving response rates with combination therapies increases the possibility of toxicity. Chimeric antigen receptor T cells have demonstrated high response rates in hematological cancers, although most patients experience relapse. In addition, some cancers are notoriously immunologically “cold” and typically are not effective targets for immunotherapy. Overcoming these obstacles will require new strategies to improve upon the efficacy of current agents, identify biomarkers to select appropriate therapies, and discover new modalities to expand the accessibility of immunotherapy to additional tumor types and patient populations.

Focal adhesion kinase (FAK), a key regulator of cell adhesion and migration, is overexpressed in many types of cancer. The C-terminal focal adhesion targeting (FAT) domain of FAK is necessary for proper localization of FAK to focal adhesions and subsequent activation. Phosphorylation of Y926 in the FAT domain by the tyrosine kinase Src has been shown to promote metastasis and invasion in vivo by linking the FAT domain to the MAPK pathway via its interaction with Grb2. Several groups have reported that inherent conformational dynamics in the FAT domain likely regulate phosphorylation of Y926; however, what regulates these dynamics is unknown. In this paper, we demonstrate that there are two sites of in vitro Src-mediated phosphorylation in the FAT domain: Y926, which has been shown to affect FAK function in vivo, and Y1008, which has no known biological role. The phosphorylation of these two tyrosine residues is pH dependent, but this does not reflect the pH dependence of Src kinase activity. CD and NMR data indicate that the stability and conformational dynamics of the FAT domain are sensitive to changes in pH over a physiological pH range. In particular, regions of the FAT domain previously shown to regulate phosphorylation of Y926 as well as regions near Y1008 show pH-dependent dynamics on the μs-ms time scale.

reversible nonstoichiometric, membraneless assemblies. These assemblies, referred to as biomolecular condensates, help with the spatial organization and compartmentalization of cellular matter. Each biomolecular condensate is defined by a distinct macromolecular composition. Distinct condensates have distinct preferential locations within cells, and they are associated with distinct biological functions, including DNA replication, RNA metabolism, signal transduction, synaptic transmission, and stress response. Several proteins found in biomolecular condensates have also been implicated in disease, including Huntington's disease, amyotrophic lateral sclerosis, and several types of cancer. Disease-associated mutations in these proteins have been found to affect the material properties of condensates as well as the driving forces for phase separation. Understanding the intrinsic and extrinsic forces driving the formation and dissolution of biomolecular condensates via spontaneous and driven phase separation is an important step in understanding the processes associated with biological regulation in health and disease.

Vaccines have been incredibly successful at stemming the morbidity and mortality of infectious diseases worldwide. However, there are still no effective vaccines for many serious and potentially preventable infectious diseases. Advances in vaccine technology, including new delivery methods and adjuvants, as well as progress in systems biology and an increased understanding of the human immune system, hold the potential to address these issues. In addition, maternal immunization has opened an avenue to address infectious diseases in neonates and very young infants. This report summarizes the presentations from a 1‐day symposium at the New York Academy of Sciences entitled “Innovative Vaccines against Resistant Infectious Diseases and Emerging Threats,” held on May 20, 2019.