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Lysosomes are important cellular structures for human health as centers for recycling, signaling, metabolism and stress adaptation. However, the potential role of lysosomes in stress‐related emotions has long been overlooked. Here, it is found that lysosomal morphology in astrocytes is altered in the medial prefrontal cortex (mPFC) of susceptible mice after chronic social defeat stress. A screen of lysosome‐related genes revealed that the expression of the mucolipin 1 gene (Mcoln1; protein: mucolipin TRP channel 1) is decreased in susceptible mice and depressed patients. Astrocyte‐specific knockout of mucolipin TRP channel 1 (TRPML1) induced depressive‐like behaviors by inhibiting lysosomal exocytosis‐mediated adenosine 5′‐triphosphate (ATP) release. Furthermore, this stress response of astrocytic lysosomes is mediated by the transcription factor EB (TFEB), and overexpression of TRPML1 rescued depressive‐like behaviors induced by astrocyte‐specific knockout of TFEB. Collectively, these findings reveal a lysosomal stress‐sensing signaling pathway contributing to the development of depression and identify the lysosome as a potential target organelle for antidepressants. [ABSTRACT FROM AUTHOR]

The European Food Safety Authority (EFSA) has a goal to efficiently conduct aggregate exposure assessments (AEAs) for chemicals using both exposure models and human biomonitoring (HBM) data by 2030. To achieve EFSA's vision, a roadmap for action for advancing aggregate exposure (AE) in the EU was developed. This roadmap was created by performing a series of engagement and data collection activities to map the currently available methods, data, and tools for assessing AE of chemicals, against the needs and priorities of EFSA. This allowed for the creation of a AEA framework, identification of data and knowledge gaps in our current capabilities, and identification of the challenges and blockers that would hinder efforts to fill the gaps. The roadmap identifies interdependent working areas (WAs) where additional research and development are required to achieve EFSA's goal. It also proposes future collaboration opportunities and recommends several project proposals to meet EFSA's goals. Eight proposal projects supported by SWOT analysis are presented for EFSA's consideration. The project proposals inform high‐level recommendations for multi‐annual and multi‐partner projects. Recommendations to improve stakeholder engagement and communication of EFSA's work on AEA were gathered by surveying stakeholders on specific actions to improve EFSA's communication on AE, including webinars, virtual training, social media channels, and newsletters. [ABSTRACT FROM AUTHOR]

Chronic inflammation represents a major threat to human health since long‐term systemic inflammation is known to affect distinct tissues and organs. Recently, solid evidence demonstrated that chronic inflammation affects hematopoiesis; however, how chronic inflammation affects hematopoietic stem cells (HSCs) on the mechanistic level is poorly understood. Here, we employ a mouse model of chronic multifocal osteomyelitis (CMO) to assess the effects of a spontaneously developed inflammatory condition on HSCs. We demonstrate that hematopoietic and nonhematopoietic compartments in CMO BM contribute to HSC expansion and impair their function. Remarkably, our results suggest that the typical features of murine multifocal osteomyelitis and the HSC phenotype are mechanistically decoupled. We show that the CMO environment imprints a myeloid gene signature and imposes a pro‐inflammatory profile on HSCs. We identify IL‐6 and the Jak/Stat3 signaling pathway as critical mediators. However, while IL‐6 and Stat3 blockage reduce HSC numbers in CMO mice, only inhibition of Stat3 activity significantly rescues their fitness. Our data emphasize the detrimental effects of chronic inflammation on stem cell function, opening new venues for treatment. Synopsis: Chronic inflammation induces HSC expansion and reduces HSC fitness by hyperactivating the IL‐6/Jak/Stat3 signaling pathway. These effects of chronic inflammation on HSCs are mitigated upon inhibition of Stat3. CMO mice, suffering from sterile chronic inflammation, exhibit an expansion of the HSC pool and a reduction of HSC fitness.The CMO environment imprints a myeloid gene signature and imposes a pro‐inflammatory profile in HSCs.Inactivation of the IL‐1β/MyD88 pathway in CMO mice is not sufficient to prevent defects in the HSC compartment.IL‐6 and Jak/Stat3 signaling mediate HSC alterations in CMO mice and inhibition of Stat3 activity rescues HSC function. [ABSTRACT FROM AUTHOR]

The coupled hydrology and mechanics of soft porous materials (such as clays, hydrogels, membranes, and biofilms) is an important research area in several fields, including water and energy technologies as well as biomedical engineering. Well‐established models based on poromechanics theory exist for describing these coupled properties, but these models are not adapted to describe systems with more than one characteristic length scale, that is, systems that contain both macropores and micropores. In this paper, we expand upon the well‐known Darcy‐Brinkman formulation of fluid flow in two‐scale porous media to develop a "Darcy‐Brinkman‐Biot" formulation: a general coupled system of equations that approximates the Navier‐Stokes equations in fluid‐filled macropores and resembles the equations for poroelasticity in microporous regions. We parameterized and validated our model for systems that contain either plastic (swelling clay) or elastic microporous regions. In particular, we used our model to predict the permeability of an idealized siliciclastic sedimentary rock as a function of pore water salinity and clay content. Predicted permeability values are well described by a single parametric relation between permeability and clay volume fraction that agrees with existing experimental data sets. Our novel formulation captures the coupled hydro‐chemo‐mechanical properties of sedimentary rocks and other deformable porous media in a manner that can be readily implemented within the framework of Digital Rock Physics. Plain Language Summary: Knowledge of how fluids flow through porous materials has significant implications for the design and operation of batteries, aquifers, oil rigs, and biomedical devices. Even though scientists have been successful in creating computer models that capture fluid flow through rigid porous media, it has been very challenging to create models that can model flow through deformable porous media. In this paper, we describe a new model that can predict flow through and around deformable porous media. We derived this model by superimposing separate conventional fluid‐flow and solid‐deformation models into a single simulation through a technique called volume averaging. We then connected the two models using Newton's Third Law, meaning that when fluids flow through a porous solid they "push" the solid, and whenever a solid resists fluid movement or deforms, it "pushes" the fluid in turn. The resulting model can capture complex multiscale, multiphysics phenomena such as the impact of clay swelling (think of an expanding sponge absorbing water) on the ability of fluids to flow through soils or sedimentary rock formations. Given the model's generality and its successful verification presented in this paper, we believe that it can help understand important phenomena in the fields of water and energy resources. Key Points: We developed a novel approach to model coupled fluid flow and solid mechanics in porous media with two characteristic length scalesThe model was validated against data on flow and chemically driven deformation in viscoplastic and elastic solidsSedimentary rock permeability is predicted to have an error function dependence on the volume fraction occupied by microporous clay [ABSTRACT FROM AUTHOR]

Abstract: Using topography‐corrected reflectance maps of the Moon, we present a new methodology for quantifying the spectral distribution of craters in the 750 nm reflectance and 950 nm/750 nm reflectance ratio space (R‐C space) and investigate how the spectral trend changes as the crater matures and degrades. Considering more than 3,495 craters across the Moon, we calculate three parameters to describe spectral trends of the pixels in each crater: 95th‐percentile length, clockwise rotation angle from the horizontal line, and statistical skewness along the principal axis of the distribution, as well as median values of the reflectance and the reflectance ratio. We find that the shape of the spectral trend of a crater in R‐C space becomes shorter, steeper, and more skewed toward the upper left as it optically matures and topographically degrades. Skewness shows a similar relationship to topographical degradation in both mare and highland craters. The skewness is useful in age estimation because it can be calculated easily from reflectance data and is applicable to craters of large size or in low‐iron‐content regions where a topographic model is currently not available. Using these three parameters, one can define the representative trends of a group of craters. We show representative trends of craters with various iron contents at different latitudes. The trends are parallel to one another, with offset controlled by latitude and radial rotation controlled by local iron content; these observations integrate the results of previous studies that reported the two behaviors individually. [ABSTRACT FROM AUTHOR]

An intriguing question in the field of stress is what makes an individual more likely to be susceptible or resilient to stress‐induced depression. Predisposition to stress susceptibility is believed to be influenced by genetic factors and early adversity. However, beyond genetics and life experiences, recent evidence has highlighted social rank as a key determinant of susceptibility to stress, underscoring dominant individuals as the vulnerable ones. This evidence is in conflict with epidemiological, clinical, and animal work pointing at a link between social subordination and depression. Here, we review and analyze rodent protocols addressing the relevance of social rank to predict vulnerability to chronic social stress. We also discuss whether a specific social status (i.e., dominance or subordination) is the appropriate predictor of vulnerability to develop stress‐induced depression or rather, the loss of social rank and resources. [ABSTRACT FROM AUTHOR]

The amygdala is a key brain area regulating responses to stress and emotional stimuli, so improving our understanding of how it is regulated could offer novel strategies for treating disturbances in emotion regulation. As we review here, a growing body of evidence indicates that the gut microbiota may contribute to a range of amygdala-dependent brain functions from pain sensitivity to social behavior, emotion regulation, and therefore, psychiatric health. In addition, it appears that the microbiota is necessary for normal development of the amygdala at both the structural and functional levels. While further investigations are needed to elucidate the exact mechanisms of microbiota-to-amygdala communication, ultimately, this work raises the intriguing possibility that the gut microbiota may become a viable treatment target in disorders associated with amygdala dysregulation, including visceral pain, post-traumatic stress disorder, and beyond. Also see the video abstract here: [ABSTRACT FROM AUTHOR]

This study explored personality and motivational traits related to teleworker performance and satisfaction, including sociability, need for achievement and autonomy, diligence and organisation. Situational factors were also compared between teleworkers and non-teleworkers, such as number of children, job autonomy and job complexity. Implications for research and practice are discussed. [ABSTRACT FROM AUTHOR]

We examined the relation between cancer mortality and time-dependent cumulative exposure to 2,3,7,8-tetrachlorodibenzo- p-dioxin (TCDD) estimated from a concentration- and age-dependent kinetic model of elimination, and we estimated incremental cancer risks at age 75. Data from the National Institute for Occupational Safety and Health study of 3,538 workers with occupational exposure to TCDD were analyzed using standardized mortality ratios and Cox regression procedures. Analyses adjusted for potential confounding by age, year of birth, and race and considered exposure lag periods of 0, 10, or 15 years. Other potential confounders including smoking and other occupational exposures were evaluated indirectly. To explore the influence of extreme values of cumulative TCDD ppt-years, we restricted the analysis to observations with exposure below the 95th percentile or used logarithmic (ln) transformed exposure values. We applied penalized smoothing splines to examine variation in the exposure-response relation across the exposure range. TCDD was not statistically significantly associated with cancer mortality using the full data set, regardless of the lag period. When we restricted the analysis to observations with exposure below the 95th percentile, TCDD was associated positively with cancer mortality, particularly when a 15-year lag was applied (untransformed exposure data: regression coefficient , standard error (s.e.) = 1.4 × 10−6, p < 0.05; ln-transformed exposure data: , s.e. = 2.9 × 10−2, p < 0.05). The estimated incremental lifetime risk of mortality at age 75 from all cancers was about 6 to more than 10 times lower than previous estimates derived from this cohort using exposure models that did not consider the age and concentration dependence of TCDD elimination. [ABSTRACT FROM AUTHOR]

This paper reports the empirical findings of several surveys conducted among enterprises in Portugal in order to identify and summarise relevant enablers and constraints that may influence the implementation of telework in the Portuguese business environment. It also provided some common characteristics that will help us draw the profile of a Portuguese potential teleworker. [ABSTRACT FROM AUTHOR]

This paper discusses the potential implications of a risk society on identities due to alterations in work practices. The promise of ‘flexibility’ via at-home telework entails a renegotiation of the home–work boundary. This brings into play the gendered identities and roles attached to these different spheres of life. After deconstructing promises made on behalf of telework, we construct an alternative research agenda engaging with writings on changing work identities in the risk society where traditional sureties are called into question. [ABSTRACT FROM AUTHOR]

Although Finland is one of the most advanced and competitive economies in the world, with a sophisticated technological infrastructure, only four per cent of Finnish wage earners regard themselves as doing telework, and a further four per cent had tried telework. Empirical evidence of telework is presented in this paper. [ABSTRACT FROM AUTHOR]

Examines the effects of teleworking on individuals as perceived by professionals and managers in Great Britain. Perceptions on the nature of the work of teleworkers compared to office based employment; Advantages and disadvantages of teleworking; Effect of teleworking on employee productivity and satisfaction.

Examines trends in the labor market in Great Britain. Increased incidence of people working from home using information technology; Emergence of freelance employees; Creation of dynamic networks based on temporary contractual ties.

Bisphosphonates are used clinically to inhibit bone resorption but they may also cause renal damage. For the profiling of new, potent bisphosphonates, their adverse renal effects were investigated in 2 rat models. In the first model, bisphosphonate was repeatedly injected (1 mg/kg, subcutaneously) over 2 weeks and the urinary excretion of malate dehydrogenase was monitored to assess nephrotoxic potential. Of the 6 new compounds tested, 3 markedly elevated malate dehydrogenase whereas 3 others caused only minor changes similar to those observed with 6 reference bisphosphonates that are already used clinically. On the basis of a therapeutic index (inhibition of bone resorption versus renal effects) 7-180 fold greater than that of other analogues, the compound CGP 42446 was further profiled. In the second model, CGP 42446 or pamidronate was infused (1.5-50 mg/kg, intravenously) into anaesthetized rats and the serum urea concentration was monitored as an indicator of renal dysfunction. Both compounds elevated serum urea in a time-and dose-dependent manner, but the ED100 value for CGP 42446 was 3.8-fold higher than that of pamidronate. It is concluded that CGP 42446 (zoledronate) has a low nephrotoxic potential and can be further developed as a new, potent inhibitor of bone resorption. [ABSTRACT FROM AUTHOR]

Conventional bioassays for environmental assessment frequently rely on nonindigenous single species. We employed an assay in which whole environmental samples were distinguished by the ability of the nativeheterotrophic microbial communities to oxidize 95 different sole carbon sources generating a community-level physiological profile (CLPP). The average metabolic response (AMR) to the 95 variables defining the CLPP was used in laboratory bioassay studies with copper to construct dose-response curves over several different periods of exposure: 1 h (acute), 1 d, 2 d, and 4 d. The acute dose-response of Snake River bacterioplankton communities measured by AMR was compared to the dose-response of Photobacterium phosphoreum (used in the Microtox test)and a proprietary mixed consortia (used in the Polytox test). In laboratory bioassay studies, CLPP AMR exhibited acute dose-response behavior over a greater range in copper concentrations and with less variability (per dose) than Microtox and Polytox. The acute sensitivity of CLPP AMR to copper was roughly equal to Microtox and much greater than Polytox. After a longer exposure (1 d) to copper, Snake River communities became more sensitive to copper but no additional effect wasobserved when the exposure was increased to 2 and 4 d. Snake River communities pre-exposed to copper (1 mg/L) for 4 d prior to acute dose-response experiments showed no difference in AMR with respect to doses up to 10 mg/L, indicating the ability of the assay to detect adaptation. Several metal-contaminated streams in Idaho were used to fieldvalidate the CLPP approach for detecting impacts of metals in the environment. The response profiles of the bacterioplankton from two downstream sites receiving metal laden mine drainage were compared to those from reference sites upstream and further downstream of the location receiving the mine drainage. The AMR of the communities at the stream reference sites were greater than sites just below the mines. Weascr [ABSTRACT FROM AUTHOR]