Explore the vast range of titles available.

\"This volume reviews the evolution of ten years' learning and discovery about water scarcity, livelihoods, and food security within the CGIAR Challenge Program on Water and Food. It draws on the experiences of over 100 projects conducted in ten river basins in the developing world. The book describes how the program's design evolved from an emphasis on water scarcity, water productivity, and water access to an emphasis on using water innovations to improve livelihoods and address development challenges in specific river basins. It shows how the research was used to foster change in stakeholder behavior, linking it to improved knowledge, attitudes, and skills, which were fostered by stakeholder participation, innovation, dialogue, and negotiation. The authors describe development challenges, their drivers and their political context, how to address them through technical, institutional, and policy innovations; and the consequences of change at different scales, time frames on equity, resilience, and ecosystem services. Overall, the work represents a major synthesis and landmark publication for all concerned with water resource management and sustainable development\"-- Provided by publisher.

In this study, the authors report that target-derived NGF signaling induces the expression of Coronin-1, which consequently gets recruited to the NGF-TrkA–carrying signaling endosome, where it regulates endosomal fusion with lysosomes, trafficking and recycling. In addition, Coronin-1 appears to be necessary for NGF-dependent signaling events such as CREB phosphorylation, Ca 2+ release and activation of calcineurin. Retrograde communication from axonal targets to neuronal cell bodies is critical for both the development and function of the nervous system. Much progress has been made in recent years linking long-distance, retrograde signaling to a signaling endosome, yet the mechanisms governing the trafficking and signaling of these endosomes remain mostly uncharacterized. Here we report that in mouse sympathetic neurons, the target-derived nerve growth factor (NGF)–tropomyosin-related kinase type 1 (TrkA, also called Ntrk1) signaling endosome, on arrival at the cell body, induces the expression and recruitment of a new effector protein known as Coronin-1 (also called Coro1a). In the absence of Coronin-1, the NGF-TrkA signaling endosome fuses to lysosomes sixfold to tenfold faster than when Coronin-1 is intact. We also define a new Coronin-1–dependent trafficking event in which signaling endosomes recycle and re-internalize on arrival at the cell body. Beyond influencing endosomal trafficking, Coronin-1 is also required for several NGF-TrkA–dependent signaling events, including calcium release, calcineurin activation and phosphorylation of cAMP responsive element binding protein (CREB). These results establish Coronin-1 as an essential component of a feedback loop that mediates NGF-TrkA endosome stability, recycling and signaling as a critical mechanism governing developmental competition for survival.

This study quantified the burdens of bipolar I disorder (BP-I) by examining patient characteristics, health-related quality of life (HRQoL), health care resource utilization (HCRU), and costs of patients with versus without BP-I. Additionally, these outcomes were assessed across BP-I severity levels. A retrospective, cross-sectional analysis of the 2020 National Health and Wellness Survey was conducted. Adults who self-reported a physician diagnosis of BP-I were assigned to the BP-I cohort, with severity-specific subgroups (mild, moderate, severe) created for analysis. A separate cohort of participants without BP-I or MDD was used for comparison. Exclusion criteria included a schizophrenia diagnosis. Bivariate analyses compared demographic and socioeconomic characteristics between cohorts. HRQoL (Short Form-36v2 Health Survey [SF36v2] mental and physical component scores, EuroQol Five-Dimension Visual Analogue Scale [EQ-5D VAS]), HCRU (health care provider visits, emergency department visits, hospitalizations), and annualized costs (direct and indirect) were evaluated for participants with versus without BP-I as well as across BP-I severity subgroups using multivariate analyses adjusted for key baseline differences. Because BP-I is often misdiagnosed as MDD, outcomes were evaluated in a subgroup of participants with MDD who according to the Mood Disorder Questionnaire screened as having probable BP-I (ie, potentially misdiagnosed BP-I) and were compared with the BP-I severity subgroups. Cohorts included 818 participants with BP-I (mild = 336, moderate = 285, severe = 197) and 53,021 participants without BP-I. Participants with BP-I reported significantly lower HRQoL scores on the SF-36v2 and EQ-5D VAS (all measures, P < 0.001), and increasing BP-I severity was predictive of declining HRQoL. Participants with BP-I had significantly greater HCRU (all measures, P < 0.05) than participants without BP-I and increasing BP-I severity was associated with greater HCRU versus the mild BP-I cohort (all measures, P < 0.05). Participants with BP-I incurred significantly greater total direct (P < 0.01) and indirect (P < 0.001) costs versus participants without BP-I. Direct costs were incrementally higher across BP-I severity, while indirect costs were high across all groups but did not differ significantly. Participants with potentially misdiagnosed BP-I (n = 302) had similar HRQoL to those with mild-to-moderate BP-I and similar HCRU and direct costs to those with mild BP-I. These results demonstrate the substantial clinical and economic burdens associated with BP-I, and these negative impacts generally increase with BP-I severity. The study also suggests that despite not having the diagnosis of BP-I, burdens of potentially misdiagnosed patients are similar to those with mild-to-moderate BP-I. Together, these results reveal substantial and diverse unmet needs among adults with BP-I.

Richter’s Transformation (RT) is a poorly understood and fatal progression of chronic lymphocytic leukemia (CLL) manifesting histologically as diffuse large B-cell lymphoma. Protein arginine methyltransferase 5 (PRMT5) is implicated in lymphomagenesis, but its role in CLL or RT progression is unknown. We demonstrate herein that tumors uniformly overexpress PRMT5 in patients with progression to RT. Furthermore, mice with B-specific overexpression of hPRMT5 develop a B-lymphoid expansion with increased risk of death, and Eµ-PRMT5/TCL1 double transgenic mice develop a highly aggressive disease with transformation that histologically resembles RT; where large-scale transcriptional profiling identifies oncogenic pathways mediating PRMT5-driven disease progression. Lastly, we report the development of a SAM-competitive PRMT5 inhibitor, PRT382, with exclusive selectivity and optimal in vitro and in vivo activity compared to available PRMT5 inhibitors. Taken together, the discovery that PRMT5 drives oncogenic pathways promoting RT provides a compelling rationale for clinical investigation of PRMT5 inhibitors such as PRT382 in aggressive CLL/RT cases. Richter’s Transformation is a treatment-resistant and fatal progression from Chronic Lymphocytic Leukemia (CLL) to an aggressive lymphoma. Here, the authors show that PRMT5 is upregulated months prior to and after transformation, PRMT5 overexpression in a CLL mouse model leads to increased risk of transformation, and that targeted PRMT5 inhibition prolongs survival and delays disease development.

Retrograde communication from axonal targets to neuronal cell bodies is critical for both development and function of the nervous system. Much progress has been made in recent years linking long-distance, retrograde signaling to a signaling endosome, yet the mechanisms governing the trafficking and signaling of these endosomes remain mainly uncharacterized. Here we report that in mouse sympathetic neurons the target-derived NGF-TrkA signaling endosome, upon arrival at the cell body, induces the expression and recruitment of a novel effector protein known as Coronin-1. In the absence of Coronin-1, the NGF-TrkA signaling endosome fuses to lysosomes 6–10 fold faster than when Coronin-1 is intact. We also define a novel Coronin-1-dependent trafficking event where signaling endosomes recycle and re-internalize upon arrival at the cell body. Beyond influencing endosomal trafficking, Coronin-1 is also required for several NGF-TrkA dependent-signaling events including calcium release, calcineurin activation, and CREB phosphorylation. These results establish Coronin-1 as an essential component of a novel feedback loop mediating NGF-TrkA endosome stability, recycling, and signaling as a critical mechanism governing developmental competition for survival.

We give an overview and describe the rationale, methods, and first results from NIRCam images of the JWST \"Prime Extragalactic Areas for Reionization and Lensing Science\" (\"PEARLS\") project. PEARLS uses up to eight NIRCam filters to survey several prime extragalactic survey areas: two fields at the North Ecliptic Pole (NEP); seven gravitationally lensing clusters; two high redshift proto-clusters; and the iconic backlit VV 191 galaxy system to map its dust attenuation. PEARLS also includes NIRISS spectra for one of the NEP fields and NIRSpec spectra of two high-redshift quasars. The main goal of PEARLS is to study the epoch of galaxy assembly, AGN growth, and First Light. Five fields, the JWST NEP Time-Domain Field (TDF), IRAC Dark Field (IDF), and three lensing clusters, will be observed in up to four epochs over a year. The cadence and sensitivity of the imaging data are ideally suited to find faint variable objects such as weak AGN, high-redshift supernovae, and cluster caustic transits. Both NEP fields have sightlines through our Galaxy, providing significant numbers of very faint brown dwarfs whose proper motions can be studied. Observations from the first spoke in the NEP TDF are public. This paper presents our first PEARLS observations, their NIRCam data reduction and analysis, our first object catalogs, the 0.9-4.5 \\(\\)m galaxy counts and Integrated Galaxy Light. We assess the JWST sky brightness in 13 NIRCam filters, yielding our first constraints to diffuse light at 0.9-4.5 m. PEARLS is designed to be of lasting benefit to the community.

We search for an infrared signature of the transiting extrasolar planet HD 209458b during secondary eclipse. Our method, which we call `occultation spectroscopy,' searches for the disappearance and reappearance of weak spectral features due to the exoplanet as it passes behind the star and later reappears. We argue that at the longest infrared wavelengths, this technique becomes preferable to conventional `transit spectroscopy'. We observed the system in the wing of the strong nu-3 band of methane near 3.6 microns during two secondary eclipses, using the VLT/ISAAC spectrometer at a spectral resolution of 3300. Our analysis, which utilizes a model template spectrum, achieves sufficient precision to expect detection of the spectral structure predicted by an irradiated, low-opacity (cloudless), low-albedo, thermochemical equilibrium model for the exoplanet atmosphere. However, our observations show no evidence for the presence of this spectrum from the exoplanet, with the statistical significance of the non-detection depending on the timing of the secondary eclipse, which depends on the assumed value for the orbital eccentricity. Our results reject certain specific models of the atmosphere of HD 209458b as inconsistent with our observations at the 3-sigma level, given assumptions about the stellar and planetary parameters.