SummaryThe motivation to seek social contact may arise from either positive or negative emotional states, as social interaction can be rewarding and social isolation can be aversive. While ventral tegmental area (VTA) dopamine (DA) neurons may mediate social reward, a cellular substrate for the negative affective state of loneliness has remained elusive. Here, we identify a functional role for DA neurons in the dorsal raphe nucleus (DRN), in which we observe synaptic changes following acute social isolation. DRN DA neurons show increased activity upon social contact following isolation, revealed by in vivo calcium imaging. Optogenetic activation of DRN DA neurons increases social preference but causes place avoidance. Furthermore, these neurons are necessary for promoting rebound sociability following an acute period of isolation. Finally, the degree to which these neurons modulate behavior is predicted by social rank, together supporting a role for DRN dopamine neurons in mediating a loneliness-like state.PaperClip

Recent advances in immuno-oncology have generated renewed optimism for therapeutic antitumor vaccination, and peptide vaccines in particular are being extensively employed in clinical studies. However, peptide vaccines generally suffer from poor immunogenicity. Here, we pharmacokinetically tune vaccine responses via fusion of peptide epitopes to carrier proteins to optimize vaccine potency. Antigen-carrier fusions enable three factors to be simultaneously *

Tuberculosis (TB) infections in India account for one-third of the global burden, making it important to develop speedy, cost-effective diagnostic tools. This study evaluated recombinant RD1-encoded antigens of Mycobacterium tuberculosis as tools for serodiagnosis by determining the immunological reactivity of these proteins against sera from healthy, bacille Calmette-Guérin (BCG)-vaccinated and TB-infected individuals from Kolkata. Rv3872, Rv3875 (ESAT-6) and Rv3878 were able to discriminate healthy BCG-vaccinated controls from TB patients. Rv3872 showed the highest level of antibody response in comparison with other antigens, and also showed statistically significant differences between pulmonary (p <0.0001) or extra-pulmonary (p <0.001) TB patients and healthy BCG-vaccinated individuals. The levels of antibody were measured using 20-mer overlapping peptides spanning the entire Rv3872 sequence. The immunological reactivity against a mixture of two peptides (P8 and P9) encompassing amino-acids 57-84 correlated well with that obtained using full-length Rv3872. This result was explained by the fact that two of the predicted regions of high antigenicity lie within amino-acid residues 57-85 of Rv3872. The high sensitivity and specificity of Rv3872, as well as the mixture of two synthetic overlapping peptides derived from Rv3872, highlight their potential and argue in favour of their use in serodiagnosis of both pulmonary and extra-pulmonary TB.

Programa de Estudio y Control de Enfermedades Tropicales (PECET) is a multidisciplinary tropical medicine research group based at the University of Antioquia, Colombia. PECET is currently conducting clinical trials in the treatment of Cutaneous Leishmaniosis (CL) in rural Colombia, using the OpenMRS database (an open source health record). Like many research groups in the developing world, PECET has encountered challenges recruiting and retaining study patients. This paper investigates the potential use of mobile digital tools to assist PECET with recruitment and retention of patients in clinical trials. We will explore how a 'prescreening' digital tool and 'patient messaging' tool might generate value for patients, community health workers, and PECET staff to improve patient recruitment and retention and ultimately result in more efficient and effective clinical trials. This paper is a preliminary study, and the recommendations therein will provide the foundation for further investigation, development, and iteration of these digital tools in the future.

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