Genetically Encoded Photo-cross-linkers Map the Binding Site of an Allosteric Drug on a G Protein-Coupled Receptor

G protein-coupled receptors (GPCRs) are dynamic membrane proteins that bind extracellular molecules to transduce signals. Although GPCRs represent the largest class of therapeutic targets, only a small percentage of their ligand-binding sites are precisely defined. Here we describe the novel application of targeted photo-cross-linking using unnatural amino acids to obtain structural information about the allosteric binding site of a small molecule drug, the CCR5-targeted HIV-1 co-receptor blocker maraviroc

Baryonic Regge trajectories with analyticity constraints

A model for baryonic Regge trajectories compatible with the threshold behavior required by unitarity and asymptotic behavior in agreement with analyticity constraints is given in explicit form. Widths and masses of the baryonic resonances on the N and $\Delta$ trajectories are reproduced. The MacDowell symmetry is exploited and an application is given.Comment: 12 pages, 6 figure

What Makes a Family: How an Empowerment-Based Health Care Delivery Model Employs Family Planning to Positively Impact Families in Rural Maharashtra: A Study in Jamkhed, Ahmadneger

The paper examines how an empowerment-based health care delivery model employs family planning services to positively impact families in rural Maharashtra. Family planning services provide those with the ability to become pregnant the option to control their own reproductive lives, whether they choose in favor of or against having children. Contraceptive use advances people’s human rights to choose whether they want to bear children and how many children they want, and people should have the choice of their preferred contraceptive method. The paper examines this issue within the framework of the Comprehensive Rural Health Project’s Jamkhed Model. Through the Jamkhed Model, Village Health Workers (VHWs), the Mobile Health Team (MHT), and Comprehensive Rural Health Project (CRHP) leadership work together to provide necessary primary health care in underserved village populations. The paper approaches analysis through a mix of literature review and interviews with relevant stakeholders. Around the world, healthcare has become a topic of business rather than a topic of how healthcare providers can best serve their patient populations – I hope that this paper will bring to attention the need we have as healthcare providers to help our patients feel comfortable, empowered, and supported in their healthcare experience

The Aesthetics of May Stevens’ Big Daddy Series: How an Artist’s Stylistic Choice Influences Political Symbolism

Political art and aesthetics are undoubtedly intertwined. An artist\u27s stylistic choices will affect the final outcome of the artwork, and in turn how its political symbolism is perceived. May Stevens, an activist, feminist, and artist was conscious of the aesthetics of her intensely political artwork. This is especially evident in her Big Daddy series, which is anchored by a grotesque male figure that Stevens treats as a vessel representing the blasé American attitude towards culture and politics. The series was completed between 1967 to 1976 and follows major political events, including the Vietnam War. Initial inspiration, however, was found in her father’s own mindset towards culture and politics. Throughout the series, we see the development of both symbolism and stylistic choice, which presents itself in the form of changing medium, technique, and exaggerated political imagery. Despite this temporal development, the collection of paintings remains identifiable and unified. Her lesser-known painting titled Living Room (1967) also features the “Big Daddy” male figure, but it differs in symbolism and stylistic choice. Here, the male figure is uncharacteristically accompanied by a female figure and features a less stylized and more traditional impasto painting technique. My research probes the relationship between the Big Daddy series and Living Room (1967). It explores how political art is intertwined with aesthetics. My examination of May Stevens’ Living Room (1967) and its relationship to the Big Daddy series addresses the way in which the political symbolism of painting can be animated by an artist’s stylistic choices.https://orb.binghamton.edu/research_days_posters_2022/1072/thumbnail.jp

Har Gobind Khorana (1922–2011): Pioneering Spirit

Thomas Sakmar remembers one of the founding fathers of chemical biology

Globalization and Trade Initiatives in the Arab World: Historical Context, Progress to Date, and Prospects for the Future

This Article discusses whether external trade intervention, such as the MEFTA Initiative proposed, will lead to greater economic integration of the Arab world into the multilateral trading regime, and whether MEFTA can serve as the catalyst to enhance intra-regional trade and investment

Use of G-Protein-Coupled and -Uncoupled CCR5 Receptors by CCR5 Inhibitor-Resistant and -Sensitive Human Immunodeficiency Virus Type 1 Variants

Small-molecule CCR5 inhibitors such as vicriviroc (VVC) and maraviroc (MVC) are allosteric modulators that impair HIV-1 entry by stabilizing a CCR5 conformation that the virus recognizes inefficiently. Viruses resistant to these compounds are able to bind the inhibitor-CCR5 complex while also interacting with the free coreceptor. CCR5 also interacts intracellularly with G proteins, as part of its signal transduction functions, and this process alters its conformation. Here we investigated whether the action of VVC against inhibitor-sensitive and -resistant viruses is affected by whether or not CCR5 is coupled to G proteins such as Gαi. Treating CD4^(+)T cells with pertussis toxin to uncouple the Gαi subunit from CCR5 increased the potency of VVC against the sensitive viruses and revealed that VVC-resistant viruses use the inhibitor-bound form of Gα_(i)-coupled CCR5 more efficiently than they use uncoupled CCR5. Supportive evidence was obtained by expressing a signaling-deficient CCR5 mutant with an impaired ability to bind to G proteins, as well as two constitutively active mutants that activate G proteins in the absence of external stimuli. The implication of these various studies is that the association of intracellular domains of CCR5 with the signaling machinery affects the conformation of the external and transmembrane domains and how they interact with small-molecule inhibitors of HIV-1 entry