SUMMARY A striking neurochemical form of compartmentalization has been found in the striatum of humans and other species, dividing it into striosomes and matrix. The function of this organization has been unclear, but the anatomical connections of striosomes indicate their relation to emotion-related brain regions including the medial prefrontal cortex. We capitalized on this fact by combining pathway-specific optogenetics and electrophysiology in behaving rats to search for selective functions of striosomes. We demonstrate that a medial prefronto-striosomal circuit is selectively active in and causally necessary for cost-benefit decision-making under approach-avoidance conflict conditions known to evoke anxiety in humans. We show that this circuit has unique dynamic properties likely reflecting striatal interneuron function. These findings demonstrate that cognitive and emotion-related functions are, like sensory-motor processing, subject to encoding within compartmentally organized representations in the forebrain, and suggest that striosome-targeting corticostriatal circuits can underlie neural processing of decisions fundamental for survival.

Natural endogenously occurring peptides exhibit desirable medicinal properties, but are often limited in application by rapid proteolysis and inadequate membrane permeability. However, editing naturally occurring peptide sequences to develop peptidomimetic analogs created a promising class of therapeutics that can augment or inhibit molecular interactions. Here, we discuss a variety of chemical modifications, including L to D isomerization, cyclization, and unnatural amino acid substitution, as well as design strategies, such as attachment to cell-penetrating peptides, which are used to develop peptidomimetics. We also provide examples of approved peptidomimetics and discuss several compounds in clinical trials.

Highlights d Novel methods for isolating human M-ILFs, SM-ILFs, and GALT-free intestinal LP d Human M-ILFs and SM-ILFs are highly organized sites of adaptive immune induction d An adaptive immune roadmap of human GALT and GALTfree LP d Human ILFs contribute to regionalized adaptive immune responses

Inflammatory bowel disease (IBD) includes Crohn’s disease and ulcerative colitis. Each disease is characterized by a diverse set of potential manifestations, which determine patients’ disease phenotype. Current understanding of phenotype determinants is limited, despite increasing prevalence and healthcare costs. Diagnosis and monitoring of disease requires invasive procedures, such as endoscopy and tissue biopsy. Here we report signatures of heterogeneity between disease diagnoses and phenotypes. Using mass cytometry, we analyze leukocyte subsets, characterize their function(s), and examine gut-homing molecule expression in blood and intestinal tissue from healthy and/or IBD subjects. Some signatures persist in IBD despite remission, and many signatures are highly represented by leukocytes that express gut trafficking molecules. Moreover, distinct systemic and local immune signatures suggest patterns of cell localization in disease. Our findings highlight the importance of gut tropic leukocytes in circulation and reveal that blood-based immune signatures differentiate clinically relevant subsets of IBD.

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Despite their technological savvy, most students entering university lack the necessary computer skills to succeed in a quantitative analysis course, in which they are often expected to input, analyze, and plot results of experiments without any previous formal education in Microsoft Excel or similar programs. This lack of formal education results in increased anxiety, students spending large amounts of time using the process of "trial and error" to complete the assignments, and detracts from the students' learning of the chemistry. Microsoft Excel tutorials that were previously introduced have either been not specific to chemistry, require multiple assignments throughout the semester to acquire the necessary skills, or are designed for deprecated versions of the software. In this work, we present an argument for implementing a chemistry-specific, version-agnostic spreadsheet interactive laboratory exercise that uses basic, general chemistry concepts to have students explore and learn the computer skills that are necessary to succeed in a quantitative analysis course. Student feedback data indicate that students felt that the interactive spreadsheet lab allowed them to develop skills that they identified as necessary for success in the course as well as for their future careers.

The Southern California endemic mite Paratarsotomus macropalpis was filmed in the field on a concrete substrate and in the lab to analyze stride frequency, gait and running speed under different temperature conditions and during turning. At ground temperatures ranging from 45 to 60°C, mites ran at a mean relative speed of 192.4±2.1 body lengths (BL) s , exceeding the highest previously documented value for a land animal by 12.5%. Stride frequencies were also exceptionally high (up to 135 Hz), and increased with substrate temperature. Juveniles exhibited higher relative speeds than adults and possess proportionally longer legs, which allow for greater relative stride lengths. Although mites accelerated and decelerated rapidly during straight running (7.2±1.2 and −10.1±2.1 m s −2 , respectively), the forces involved were comparable to those found in other animals. Paratarsotomus macropalpis employs an alternating tetrapod gait during steady running. Shallow turns were accomplished by a simple asymmetry in stride length. During tight turns, mites pivoted around the tarsus of the inside third leg (L3), which thus behaved like a grappling hook. Pivot turns were characterized by a 42% decrease in turning radius and a 40% increase in angular velocity compared with non-pivot turns. The joint angle amplitudes of the inner L2 and L3 were negligible during a pivot turn. While exceptional, running speeds in P. macropalpis approximate values predicted from inter-specific scaling relationships.

Protein-protein interactions (PPIs) represent a significant portion of functionally relevant biological interactions, and therefore potential therapeutic targets. Small molecules were traditionally used to target PPIs. However, many PPI surfaces lack binding pockets due to their large and flat structures. Antibodies can also be used to modulate PPIs, but they are expensive and not cell permeable. Linear peptides are less expensive to produce than antibodies and are generally more selective than small molecules, but they are limited by decreased stability and poor permeability. Modified peptides (peptidomimetics, e.g., cyclic peptides) can overcome these obstacles. Advantages of using cyclic peptidomimetics to modulate PPIs derive from their conformational constraint, which supports target specificity, cell permeability, and metabolic stability. Methods for rational design coupled with high-throughput techniques continue to support advances in the field. Further development of cyclic peptidomimetics to modulate PPIs will improve treatment of human diseases, such as cancer, infection, neurodegeneration, and autoimmunity. Here we describe several cyclic peptidomimetics that are currently used as drugs and many potential cyclic peptides PPI inhibitors in different stages of pre-clinical and clinical development. Further development of cyclic peptidomimetics to modulate PPIs will continue to improve treatment of human diseases, such as cancer, infection, neurodegeneration, and autoimmunity.