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The brain is the seat of body weight homeostasis. However, our inability to control the increasing prevalence of obesity highlights a need to look beyond canonical feeding pathways to broaden our understanding of body weight control 1 – 3 . Here we used a reverse-translational approach to identify and anatomically, molecularly and functionally characterize a neural ensemble that promotes satiation. Unbiased, task-based functional magnetic resonance imaging revealed marked differences in cerebellar responses to food in people with a genetic disorder characterized by insatiable appetite. Transcriptomic analyses in mice revealed molecularly and topographically -distinct neurons in the anterior deep cerebellar nuclei (aDCN) that are activated by feeding or nutrient infusion in the gut. Selective activation of aDCN neurons substantially decreased food intake by reducing meal size without compensatory changes to metabolic rate. We found that aDCN activity terminates food intake by increasing striatal dopamine levels and attenuating the phasic dopamine response to subsequent food consumption. Our study defines a conserved satiation centre that may represent a novel therapeutic target for the management of excessive eating, and underscores the utility of a ‘bedside-to-bench’ approach for the identification of neural circuits that influence behaviour. Activity in anterior deep cerebellar nuclei reduces food consumption in mice without reducing metabolic rate, potentially identifying a therapeutic target for disorders involving excessive eating.

The role of digital transformation in organizational innovation has received increasing attention from academia over the past decade. Although previous reviews have provided important insights, the relationship between digital transformation and innovation remains underexplored within the context of small and medium-sized enterprises (SMEs). This study aims to address this gap by examining the relationship between digital transformation and innovation in SMEs. Employing bibliometric techniques and in-depth content analysis, 115 empirical studies from 32 countries and regions were retrieved from the Scopus and Web of Science databases. The results reveal a positive correlation between digital transformation and innovation in SMEs, though the effects are often context-dependent. This study identifies two research streams, three evolutionary stages of research hotspots, and seven major thematic clusters. Building on these findings, an integrated AMMO (Antecedents–Mediators–Moderators–Outcomes)-TCM (Theory, Context and Method) framework is developed to advance the understanding of the complex and controversial relationship, along with the mediating mechanisms and boundary conditions that shape this relationship. The study offers both future research directions and practical implications for advancing SME innovation in the digital age.

Court-related fines and fees are widely levied on criminal defendants who are frequently poor and have little capacity to pay. Such financial obligations may produce a criminalization of poverty, where later court involvement results not from crime but from an inability to meet the financial burdens of the legal process. We test this hypothesis using a randomized controlled trial of court-related fee relief for misdemeanor defendants in Oklahoma County, Oklahoma. We find that relief from fees does not affect new criminal charges, convictions, or jail bookings after 12 months. However, control respondents were subject to debt collection efforts at significantly higher rates that involved new warrants, additional court debt, tax refund garnishment, and referral to a private debt collector. Despite significant efforts at debt collection among those in the control group, payments to the court totaled less than 5 percent of outstanding debt. The evidence indicates that court debt charged to indigent defendants neither caused nor deterred new crime, and the government obtained little financial benefit. Yet, fines and fees contributed to a criminalization of low-income defendants, placing them at risk of ongoing court involvement through new warrants and debt collection.

The new Golgi in the protozoan parasite Trypanosoma brucei grows near to the old and adjacent to the growing new endoplasmic reticulum exit site. Growth is now shown to be at least a two-stage process, in which a representative matrix marker (GRASP) and enzyme (GntB) are delivered to the site of assembly, followed ≈10 min later by a COPI component (ε-COP) and a trans-Golgi network (TGN) marker (GRIP70). A secretory cargo marker (signal sequence-YFP) appeared early near the new endoplasmic reticulum exit site but did not enter the Golgi until the second stage. Together these data suggest that structural and enzymatic components of the new Golgi stack are laid down first, followed by those needed to move and sort the cargo passing through it.

Botulinum neurotoxin (BoNT) is a potent biological substance used to treat neuromuscular and pain disorders. Both BoNT type A and BoNT type E display high-affinity uptake into motor neurons and inhibit exocytosis through cleavage of the synaptosome-associated protein of 25 kDa (SNAP25). The therapeutic effects of BoNT/A last from 3 to 12 months, whereas the effects of BoNT/E last less than 4 weeks. Using confocal microscopy and site-specific mutagenesis, we have determined that the protease domain of BoNT/A light chain (BoNT/A-LC) localizes in a punctate manner to the plasma membrane, colocalizing with the cleaved product, SNAP25197. In contrast, the short-duration BoNT/E serotype is cytoplasmic. Mutations in the BoNT/A-LC have revealed sequences at the N terminus necessary for plasma membrane localization, and an active dileucine motif in the C terminus that is likely involved in trafficking and interaction with adaptor proteins. These data support sequence-specific signals as determinants of intracellular localization and as a basis for the different durations of action in these two BoNT serotypes.

The present study investigated the importance of psychological capabilities to support financial product salespeople in overcoming challenges and sustaining motivation and work performance during and after COVID-19 pandemic. Furthermore, this study suggests useful ways to develop the psychological capabilities. By using an interpretive phenomenological approach as the methodology, twenty financial product salespeople have been interviewed. The findings reveal that positive mindset, belief-in-oneself and not-giving-up are crucial psychological capabilities for salespeople’s sustainable work performance. These psychological capabilities match with the elements in the Psychological Capital Model. Positive mindset is associated with hope and optimism; belief-in-oneself is associated with self-efficacy, and not-giving-up is associated with resilience. The study also found approaches that help develop these psychological elements, including being proactive in seeking help and guidance, setting personal goal, and continuous learning. The findings contribute to the financial services and sales literature by providing a better understanding of how psychological capabilities help motivate financial product salespeople toward positive and sustainable work outcomes, and the ways to develop the psychological capabilities.

PurposeThis study advances network brokerage theory by examining both benefits-driven and altruistic brokerage behaviors within the mutual fund retail markets of emerging economies.Design/methodology/approachUsing a methodological combination of netnographic observations and in-depth interviews with fund investors, social influencers, sales agents and staffs from do-it-yourself (DIY) investment platforms, it uncovers the digital evolution of the mutual fund industry.FindingsOur findings illuminate a significant pivot from traditional retail channels to third-party DIY investment platforms, a change accelerated by the recent pandemic. This shift underscores a critical theoretical extension by spotlighting the altruistic actions of social influencers, or key opinion leaders (KOLs), challenging the prevalent focus on solely benefits-driven motives in network brokerage literature. Furthermore, the study reveals a diminishing significance of arbitrage network brokering amidst the industry’s digital overhaul.Originality/valueConcluding with an insightful discussion on its implications to policymakers and practitioners and acknowledging potential limitations, this research offers valuable perspectives for understanding the dynamics of network brokerage in the context of digital transformation within consumer financial markets.

Neuromolecular Imaging (NMI) with novel biosensors enables the selective detection of neurotransmitters in vivo within seconds, on line and in real time. Biosensors remain in place for continuing studies over a period of months. This biotechnological advance is based on conventional electrochemistry; the biosensors detect neurotransmitters by electron transfer. Simply stated, biosensors adsorb electrons from each neurotransmitter at specific oxidation potentials; the current derived from electron transfer is proportional to neurotransmitter concentration. Selective electron transfer properties of these biosensors permit the imaging of neurotransmitters, metabolites and precursors. The novel BRODERICK PROBE® biosensors we have developed, differ in formulation and detection capabilities from biosensors/electrodes used in conventional electrochemistry/ voltammetry. In these studies, NMI, specifically, the BRODERICK PROBE® laurate biosensor images neurotransmitter signals within mesolimbic neuronal terminals, nucleus accumbens (NAc); dopamine (DA), serotonin (5-HT), homovanillic acid (HVA) and Ltryptophan (L-TP) are selectively imaged. Simultaneously, we use infrared photobeams to monitor open-field movement behaviors on line with NMI in the same animal subjects. The goals are to investigate integrated neurochemical and behavioral effects of cocaine and caffeine alone and co-administered and further, to use ketanserin to decipher receptor profiles for these psychostimulants, alone and co-administered. The rationale for selecting this medication is: ketanserin (a) is an antihypertensive and cocaine and caffeine produce hypertension and (b) acts at 5-HT2A/2C receptors, prevalent in NAc and implicated in hypertension and cocaine addiction. Key findings are: (a) the moderate dose of caffeine simultaneously potentiates cocaine's neurochemical and behavioral responses. (b) ketanserin simultaneously inhibits cocaine-increased DA and 5-HT release in NAc and open-field behaviors and (c) ketanserin inhibits 5-HT release in NAc and open-field behaviors produced by caffeine, but, surprisingly, acts to increase DA release in NAc. Importantly, the latter effect may be a possible adverse effect of the moderate dose of caffeine in hypertensive patients. Thus, an antihypertensive medication is shown here to play a role in inhibiting brain reward possibly via antihypertensive mechanisms at DA and 5-HT receptor subtypes within DA motor neurons. An explanatory note for the results obtained, is the role likely played by the G Protein Receptor Complex (GPRC) family of proteins. Empirical evidence shows that GPRC dimers, heteromers and heterotrimers may cause cross-talk between distinct signalling cascade pathways in the actions of cocaine and caffeine. Ligand-directed functional selectivity, particularly for ketanserin, in addition to GPRCs, may also cause differential responses. The results promise new therapeutic strategies for drug addiction, brain reward and cardiovascular medicine.

This dissertation explores topics in labor economics and topics in the economics of the criminal legal system. In the first chapter, I study how worker voice can lead to worse outcomes for workers and employers when employers cannot adopt workers' suggestions. I develop and empirically test a model where voice changes a worker's reference point for working conditions, creating the risk of reference-dependent ``loss'' and lowered productivity. I test the disappointment hypothesis in an online experiment with real-effort tasks. I find that when a worker receives their less preferred working condition, asking about preferences beforehand lowers willingness-to-work by about 9 percent. I find similar patterns in observational analyses of nationally representative surveys in the US and UK. Furthermore, I find patterns of employer voice-seeking that are consistent with a counter-intuitive prediction of my model---for low-ability employers, being more able to adopt workers' preferences can lead to less voice-seeking. My findings caution that voice-seeking without follow through is worse for labor productivity than not asking at all. The second chapter explores the consequences of violating compulsory government procedures. Millions of Americans must navigate complex government procedures under the threat of punishment. Violating these requirements can lead to poverty traps or deepening legal system involvement. We use a field experiment to estimate the effect of failing to appear for court on subsequent legal contact. The treatments reduce failure to appear by 39 percent. Using treatment assignment to identify the causal impact of minor procedural violations, we find no effect on arrests. However, for lower-level cases, violations increase fines and fees paid by 60 percent or \\$80, equivalent to a high-interest loan, showing that minor procedural violations can be costly. The third chapter studies how criminal legal system fines and fees criminalizes poverty. This chapter and the following abstract are reproduced from (Pager et al., 2022). Court-related fines and fees are widely levied on criminal defendants who are frequently poor and have little capacity to pay. Such financial obligations may produce a criminalization of poverty, where later court involvement results not from crime but from an inability to meet the financial burdens of the legal process. We test this hypothesis using a randomized controlled trial of court-related fee relief for misdemeanor defendants in Oklahoma County, Oklahoma. We find that relief from fees does not affect new criminal charges, convictions, or jail bookings after 12 months. However, control respondents were subject to debt collection efforts at significantly higher rates that involved new warrants, additional court debt, tax refund garnishment, and referral to a private debt collector. Despite significant efforts at debt collection among those in the control group, payments to the court totaled less than 5 percent of outstanding debt. Court debt charged to indigent defendants thus neither caused nor deterred new crime, and the government obtained little financial benefit. Yet, fines and fees contributed to a criminalization of low-income defendants, placing them at risk of ongoing court involvement through new warrants and debt collection.