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In this paper, we examine the Federal Reserve’s newest policy tool, known as the overnight reverse repo (ONRRP) facility, to understand its effects on the repo market. Using exogenous variation in the parameters of the ONRRP, we show that private repo activity is crowded out when money funds invest in the ONRRP. Additionally, we find that the ONRRP increases lenders’ bargaining power, thereby raising borrower funding costs. Lastly, we show that repo borrowers reallocate to repo backed by riskier collateral and borrow more from ONRRP-ineligible asset managers, both of which could increase financial vulnerability due to instability in dealer funding.

Bacterial cell surface glycoconjugates are critical for cell survival and for interactions between bacteria and their hosts. Consequently, the pathways responsible for their biosynthesis have untapped potential as therapeutic targets. The localization of many glycoconjugate biosynthesis enzymes to the membrane represents a significant challenge for expressing, purifying, and characterizing these enzymes. Here, we leverage cutting-edge detergent-free methods to stabilize, purify, and structurally characterize WbaP, a phosphoglycosyl transferase (PGT) from the Salmonella enterica (LT2) O-antigen biosynthesis. From a functional perspective, these studies establish WbaP as a homodimer, reveal the structural elements responsible for dimerization, shed light on the regulatory role of a domain of unknown function embedded within WbaP, and identify conserved structural motifs between PGTs and functionally unrelated UDP-sugar dehydratases. From a technological perspective, the strategy developed here is generalizable and provides a toolkit for studying other classes of small membrane proteins embedded in liponanoparticles beyond PGTs.

This article demonstrates that easily processed texts affect investor trading behavior even in the absence of any informational content. We examine the trading symbols of US firms and find that stocks with clever tickers (those that are actual words in the English language) are more liquid, as measured by higher turnover and trading volume, as well as lower spreads. Furthermore, clever ticker stocks are traded more by uninformed investors and have larger market reactions on earnings announcement days. These results suggest that ticker fluency facilitates trading by improving the firm's visibility among retail investors through attention grabbing and memorization.

We used an integrative-taxonomy approach to help resolve taxonomic issues within the genus Micropsectra (Diptera:Chironomidae). We used partial cytochrome c oxidase subunit I (COI) and nuclear carbamylphosphate synthetase (CAD) sequences and morphological data to provide a framework for better understanding of North American species in this group of nonbiting midges. As part of our results, we describe 3 new species: Micropsectra neoappendica, n. sp., Micropsectra penicillata, n. sp., and Micropsectra subletteorum, n. sp., and 1 species new to the north-central USA, Micropsectra xantha (Roback). Two of the species, M. neoappendica n. sp. and M. subletteorum n. sp., initially appeared to be morphologically identical to species known from the Palearctic. However, molecular data indicated that they were genetically distinct, and reexamination of adult and pupal morphology revealed slight but consistent diagnostic differences. The implications of using species-level identifications for cryptic-species complexes in biological monitoring and conservation management are briefly discussed with reference to our findings. Our results emphasize the importance of using molecular tools in conjunction with traditional morphological techniques when studying Chironomidae diversity, especially when relying on diagnoses from other geographic regions.

Multiple sclerosis (MS) is a chronic autoimmune, demyelinating, and neurodegenerative disease that results in motor, visual, and cognitive deficits. While existing treatments can slow disease progression, they rarely restore lost neurological function or significantly enhance quality of life. Estrogen receptor β (ERβ) has emerged as a promising therapeutic target due to its ability to activate non-classical signaling pathways involved in neuroprotection, immune modulation, and remyelination. In this study, two chloroindazole-based ERβ-selective ligands, K102 and K110, were identified for their favorable pharmacokinetic profiles and performance in preclinical absorption, distribution, metabolism, and elimination (ADME) screening. These compounds demonstrated biological activity by promoting oligodendrocyte (OL) differentiation in both primary mouse and human OL cultures. In vivo, they enhanced axonal remyelination and improved functional electrophysiological outcomes in two mouse models of MS: experimental autoimmune encephalomyelitis (EAE) and cuprizone diet-induced demyelination. Additionally, K102 and K110 modulated immune responses, supporting OL survival and contributing to motor and visual recovery in EAE mice. These findings provide compelling preclinical evidence for advancing K102 and K110 to clinical development. By simultaneously addressing neurodegeneration and inflammation through ERβ-mediated signaling, these compounds offer a novel and potentially transformative approach to MS therapy.

Background The US federal regulations allow pharmacy administration and dispensing of methadone for opioid use disorder (PADMOUD) to increase the capability of opioid treatment programs (OTPs) in providing methadone maintenance treatment (MMT) for opioid use disorder (OUD) as part of a medication unit. However, there is a lack of research data from both pharmacy and OTP staff to inform the implementation of PADMOUD. Methods Staff of a pharmacy (n = 8) and an OTP (n = 9) that participated in the first completed US trial on PADMOUD through electronic prescribing for methadone (parent study) were recruited to participate in this qualitative interview study to explore implementation-related factors for PADMOUD. Each interview was recorded and transcribed verbatim. NVivo was used to help identify themes of qualitative interview data. The Promoting Action on Research Implementation in Health Services (PARIHS) framework was used to guide the coding and interpretation of data. Results Six pharmacy staff and eight OTP staff (n = 14) completed the interview. Results based on PARIHS domains were summarized, including evidence, context, and facilitation domains. Participants perceived benefits of PADMOUD for patients, pharmacies, OTPs, and payers. PADMOUD was considered to increase access for stable patients, provide additional patient service opportunities and revenues for pharmacies/pharmacists, enhance the capability of OTPs to treat more new patients, and reduce patients’ cost when receiving medication at a pharmacy relative to an OTP. Both pharmacy and OTP staff were perceived to be supportive of the implementation of PADMOUD. Pharmacy staff/pharmacists were perceived to need proper training on addiction and methadone as well as a protocol of PADMOUD to conduct PADMOUD. Facilitators include having thought leaders to guide the operation, a certification program to ensure proper training of pharmacy staff/pharmacist, having updated pharmacy service software or technology to streamline the workflow of delivering PADMOUD and inventory management, and reimbursement for pharmacists. Conclusion This study presents the first findings on perspectives of PADMOUD from both staff of a community pharmacy and an OTP in the US. Finding on barriers and facilitators are useful data to guide the development of strategies to implement PADMOUD to help address the US opioid crisis.

Background Pharmacy administration and dispensing of methadone treatment for opioid use disorder (PADMOUD) may address inadequate capability of opioid treatment programs (OTPs) in the US by expanding access to methadone at community pharmacies nationally. PADMOUD is vastly underutilized in the US. There is no published US study on OUD patients’ perspectives on PADMOUD. Data are timely and needed to inform the implementation of PADMOUD in the US to address its serious opioid overdose crisis. Methods Patient participants of the first completed US trial on PADMOUD through electronic prescribing for methadone (parent study) were interviewed to explore implementation-related factors for PADMOUD. All 20 participants of the parent study were invited to participate in this interview study. Each interview was recorded and transcribed verbatim. Thematic analysis was conducted to identify emergent themes. Results Seventeen participants completed the interview. Patients’ perspectives on PADMOUD were grouped into five areas. Participants reported feasibility of taking the tablet formulation of methadone at the pharmacy and identified benefits from PADMOUD (e.g., better access, efficiency, convenience) compared with usual care at the OTP. Participants perceived support for PADMOUD from their family/friends, OTP staff, and pharmacy staff. PADMOUD was perceived to be a great option for stable patients with take-home doses and those with transportation barriers. The distance (convenience), office hours, and the cost were considered factors most influencing their decision to receive methadone from a pharmacy. Nonjudgmental communication, pharmacists’ training on methadone treatment, selection of patients (stable status), workflow of PADMOUD, and protection of privacy were considered key factors for improving operations of PADMOUD. Conclusion This study presents the first findings on patient perspectives on PADMOUD. Participants considered pharmacies more accessible than OTPs, which could encourage more people to receive methadone treatment earlier and help transition stable patients from an OTP into a local pharmacy. The findings have timely implications for informing implementation strategies of PADMOUD that consider patients’ views and needs.

Disturbances caused by rainfall are common in streams with the impact on stream inhabitants determined by the frequency, intensity, and predictability of the event. Here, we examine the response of winter-emerging Chironomidae (Diptera) to extreme flooding disturbance. In August of 2007, a severe flood impacted southeastern Minnesota, imparting stress on aquatic communities. Chironomid pupal exuviae collections were obtained biweekly from 18 southeast Minnesota streams during the following winter to assess resistance and resilience of winter-active chironomids to flooding. Streams examined were divided into moderate (2.5–10 cm), heavy (10–20 cm), or extreme (20+ cm) rainfall categories with rainfall amounts in each category representing total precipitation during the 3-day storm. Post-flood samples were compared to samples obtained from the same localities during prior winters. Our findings contradict studies of responses by Chironomidae to flooding during warmer-water conditions and show that winter-emerging Chironomidae are resistant to stress imposed by summer spates. Significantly more taxa emerged during winter after flooding as compared to historic collections, and the number of species emerging in winter was positively correlated with rainfall severity, indicating that 15 species responded opportunistically to disturbance. This indicates that winter-active Chironomidae may be resistant to increased severity of summer spates associated with climate change predictions.

We used an integrative-taxonomy approach to help resolve taxonomic issues within the genusMicropsectra(Diptera:Chironomidae). We used partial cytochromecoxidase subunit I (COI) and nuclear carbamylphosphate synthetase (CAD) sequences and morphological data to provide a framework for better understanding of North American species in this group of nonbiting midges. As part of our results, we describe 3 new species:Micropsectra neoappendica, n. sp.,Micropsectra penicillata, n. sp., andMicropsectra subletteorum, n. sp., and 1 species new to the north-central USA,Micropsectra xantha(Roback). Two of the species,M. neoappendican. sp. andM. subletteorumn. sp., initially appeared to be morphologically identical to species known from the Palearctic. However, molecular data indicated that they were genetically distinct, and reexamination of adult and pupal morphology revealed slight but consistent diagnostic differences. The implications of using species-level identifications for cryptic-species complexes in biological monitoring and conservation management are briefly discussed with reference to our findings. Our results emphasize the importance of using molecular tools in conjunction with traditional morphological techniques when studying Chironomidae diversity, especially when relying on diagnoses from other geographic regions.