Background Forest succession is an important ecological process and has been studied for more than a century. However, changes in nitrogen (N) availability during succession remain unclear as they may lead to either N saturation or N limitation. Here, we propose a conceptual model to illustrate changes in N availability during four stages of secondary succession using the natural abundance of ¹⁵ N in plant leaves (foliar δ ¹⁵ N). We predicted that N availability would decline in the early stages of succession and then increase in late stages, coinciding with the changes in foliar δ ¹⁵ N, with the inflection point varying in different climate zones. Data on foliar δ ¹⁵ N from 16 succession sequences were synthesized to explore changes in N availability during forest succession. Results The compiled data were consistent with the proposed conceptual model. Foliar δ ¹⁵ N in boreal and temperate forests decreased significantly in the first two stages of succession (estimated to last at least 66 years in temperate forests), at a rate of 0.18‰ and 0.38‰ per decade, respectively, and decreased slightly in tropical forests in the first 23 years. Foliar δ ¹⁵ N is projected to increase in later stages in all forests, which is supported by observations in both temperate and tropical forests. The inflection points of N availability when N limitation peaked during succession were different in different climate zones, implying different ecosystem N turnovers. Conclusions Our study reconciles the controversies regarding changes in N availability during forest secondary succession. Our findings are also useful for predicting the recovery of N and carbon accumulation during succession. Nonetheless, studies on forest secondary succession using foliar δ ¹⁵ N have thus far been limited, and more research should be conducted to further verify the conceptual model proposed here.
Extracellular vesicles (EV) as drug delivery nanocarriers are under intense investigation. Although clinical-grade EVs have been produced on a large-scale, low yield and high production costs of natural EVs (nEV) limit the relevant industrial translation. Recent studies show that mechanical extrusion of cells can generate nEV-like cell-derived nanovesicles (CNV) which can also be used as drug nanocarriers. Moreover, in comparison with nEVs, CNVs have similar physicochemical properties. Nevertheless, a comprehensive comparison of cargo between nEVs and CNVs has not been investigated yet. Therefore, the aim of this study is to profile and compare CNVs to nEVs. Our results show that no significant difference was found in size, morphology, and classical markers between nEVs and CNVs derived from MDA-MB-231 cells. Protein sequencing data reveals the similarity of membrane proteins between the two groups was ∼71%, while it was ∼21% when pertaining to total protein cargo. Notably, a high similarity of membrane proteins was also found between nEVs and CNVs derived from eight additional cancer cell lines. Moreover, analysis of the top 1000 small RNAs with RNA sequencing showed a ∼65% similarity between the two groups. Altogether, we infer from the high similarity of membrane proteins and small RNA cargo that CNVs can be a good substitute for nEVs. In brief, our findings support previous studies with a notion that CNVs yield comparable performance with nEVs and could pave the way for clinical implementation of CNV-based therapeutics in the future.
In the present review, we consider technology-based methods for training and monitoring counseling skills in behavioral health (i.e., addictions, mental health, and behavioral medicine). We provide an overview of topical foci and design features, as well as review the available research. The Arksey and O'Malley framework for scoping review was used and there were two project phases. First, we reviewed and charted design features and training topics. Second, we reviewed and charted published research evaluating training outcomes. The search process yielded six commercial companies or academic research centers targeting online training of behavioral health counseling skills. These programs could be categorized by an avatar (i.e., computer-generated) or video (i.e., human actor) client interface, as well as by a completely interactive experience (i.e., virtual reality) or an experience with a pre-programmed, branch-logic interaction (i.e., computer simulation). One final company provided monitoring services only, without an explicit training component. The literature in this area is in its nascent stages, with primarily pilot scope and comparatively less progress if contrasted with fields such as general medicine. Online training and monitoring of behavioral health counseling skills is a promising emerging field with positive qualities such as scalability, resource efficiency, and standardization. Future research should emphasize (1) between-group randomized clinical trials, (2) comparisons to standard training practices, and (3) alignment with professional competency standards. Supplementary information: The online version contains supplementary material available at 10.1007/s41347-022-00252-8.
Chemical analyses of 2,618 (1,640 new and 978 published) fluid inclusions in marine halite were used to define paleoseawater [Ca²⁺] and [SO2−4] over the past 550 million years (Myr). Three types of fluid inclusion brine chemistries were recognized based on measured [Ca²⁺] and [SO2−4]: (1) SO4-rich with [SO2−4] ≫ [Ca²⁺]; (2) Ca-rich with [Ca²⁺] ≫ [SO2−4]; and (3) Ca-SO4 crossover points with [Ca²⁺] ≈ [SO2−4]. The SO4-rich and Ca-rich fluid inclusion chemistries oscillated twice in the terminal Proterozoic and Phanerozoic. Transitions between SO4-rich and Ca-rich seas, here called “Ca2+−SO42− crossover points” occurred four times: terminal Proterozoic–Early Cambrian (544–515 Ma), Late Pennsylvanian (309–305 Ma), Triassic–Jurassic boundary (∼200 Ma), and Eocene–Oligocene (36–34 Ma). New fluid inclusion analyses using laser ablation-inductively coupled plasma-mass spectrometry better defined the [Ca²⁺] and [SO2−4] in seawater at the Late Pennsylvanian and Eocene–Oligocene crossover points and the timing of the Triassic–Jurassic crossover point. Crossover points coincide with shifts in seawater Mg²⁺/Ca²⁺ ratios, the mineralogies of marine non-skeletal carbonates and shell building organisms (aragonite vs. calcite) and potash evaporites (MgSO4 vs. KCl types). Phanerozoic and terminal Proterozoic trends in seawater [Ca²⁺] and [SO2−4] also coincide with supercontinent breakup, dispersal, and assembly cycles, greenhouse–icehouse climates, and modeled atmospheric pCO2. Paleoseawater [Ca²⁺] and [SO2−4] were calculated from the fluid inclusion data using the assumption that the [Ca²⁺] × [SO2−4] ranged from 150 to 450 mmolal², which is 0.5–1.5 times the [Ca²⁺] = 11 × [SO2−4] = 29 product in modern seawater (319 mmolal²). Two additional end-member scenarios, independent of the [Ca²⁺] × [SO2−4] = 150–450 mmolal² assumption, were tested using constraints from fluid inclusion [Ca] and [SO4]: (1) constant [SO2−4] = 29 mmolal as in modern seawater, and variable [Ca²⁺], and (2) constant [Ca²⁺] = 11 mmolal as in modern seawater and variable [SO2−4]. Mg²⁺/Ca²⁺ ratios calculated from the three scenarios were compared to independent data on the Mg²⁺/Ca²⁺ ratios from skeletal carbonates (echinoderms and corals) and mid-ocean ridge flank calcite veins. Constant [Ca²⁺] of 11 mmolal is unlikely because this relatively low concentration generated unreasonably low seawater [SO2−4] during most of the past 550 Myr and high Mg²⁺/Ca²⁺ ratios compared to independent data. Constant [SO2−4] of 29 mmolal produced unreasonably high seawater [Ca²⁺] and lower Mg²⁺/Ca²⁺ ratios than those derived from fluid inclusions, echinoderms, corals, and calcite veins. Variable [Ca²⁺] and [SO2−4] showed the best agreement with the Mg²⁺/Ca²⁺ ratios derived from fluid inclusions, echinoderms, corals, and calcite veins.
Prenatal opioid exposures lead to extensive cognitive and emotion‐regulation problems in children, persisting at least through school‐age. Methadone, an opioid typically used for the treatment of opioid use disorder, has been approved for use in pregnant women for several decades. Importantly, however, the impacts of prenatal methadone exposure (PME), particularly on offspring as they progress into adulthood, has not been extensively examined. In recent years, children and young animal models have shown cognitive deficits related to PME, including evidence of hippocampal dysfunction. The present work aims to examine the persistent nature of these deficits, as well as determine how they may differ by sex. Pregnant Sprague–Dawley rats either received subcutaneous methadone or water injections twice daily from gestational days 3–20 or were left undisturbed. Following postnatal day 70, male and female offspring were behaviourally tested for impairments in recognition memory using the Novel Object Recognition task and working spatial memory through Spontaneous Alternation. Additionally, using whole‐cell patch‐clamp electrophysiology, hippocampal dentate granule cell function was examined in adult offspring. Results indicate that methadone‐exposed females showed decreased excitability and increased inhibition of dentate granule cells compared to naïve controls, while males did not. These findings were accompanied by impairments in female working spatial memory and altered behaviour in the Object Recognition task. Overall, this work supports the continued investigation of the long‐term effects of PME on adult male and female learning and memory, as well as promotes further exploration of adult hippocampal function as a neural mechanism impacted by this exposure. Prenatal methadone exposure leads to long‐term alterations of male and female recognition and working memory, with female offspring showing more sensitivity. Female offspring also show decreased excitability and increased inhibition of hippocampal dentate granule cells.
India’s forest-dependent communities constitute one of the most marginalized sections of the country’s population. Despite legal recognition of the rights of forest dwellers over community forest resources through the enactment of Scheduled Tribes and Other Traditional Forest Dwellers (Recognition of Forest Rights) Act in 2006, the communities still struggle in adequately exercising their rights, in fact, in most cases exercising rights is highly unlikely unless the communties are capable of asserting their rights and resisting deprivation from resources they are legally entitled to. This has led to a protracted struggle by forest dependent communities as they demand resettlement of their claims to rights over forest resources. In that context, we draw on evidence from a case study of a village in Maharashtra. Using this case study, we exemplify that statutory recognition of the rights of forest dwellers over community forest resources, when combined with sustained mobilization, allows the community to fully exercise their rights. This can then eventually lead to rewarding outcomes for local communities in the resettlement of their claims to rights over community forest resources in cases of acquisition of forest lands.
Breast cancer is the most common cancer in women worldwide with increasing incidence. Significant therapeutics advances in the field of breast cancer have resulted in a growing number of treatment options, whereas de novo or acquired resistance is still a persistent clinical challenge. Drug resistance involves a variety of mechanisms, and hypoxia is one of the many causes. Hypoxia-inducible Factor-1 Alpha (HIF-1α) is a key transcription factor which can regulate the response of cells to hypoxia. HIF-1α can trigger anaerobic glycolysis of tumor cells, induce angiogenesis, promote the proliferation, invasion, and migration of tumor cells, and lead to multidrug resistance. This review mainly discusses the role of HIF-1α in the drug-resistant breast cancer and highlighted the potential of HIF-1α -targeted therapy.
A firm’s publicly available information reflects ex ante committed information releases and ex post discretionary disclosures. In a setting wherein a firm’s CEO is concerned with stock market valuation and confrontations with the employee union, this paper endogenizes when the CEO retains ex post disclosure discretion and when the CEO curtails discretion, opting instead to ex ante commit to not gathering information or publicly disclosing information. The underlying economic forces entail a trade-off between the time-inconsistency problem (the CEO’s ex post preferences can diverge from the CEO’s ex ante goals) and how silence (absence of information) under the ex ante and ex post paths is valued differentially by the union. In effect, silence under different systems “speaks” differently, and this influences both the labor union’s incentives to engage in bargaining with the firm and the stock market’s pricing of the firm’s equity. This paper was accepted by Ranjani Krishnan, accounting.
Bacterial biofilms are often defined as communities of surface-attached bacteria and are typically depicted with a classic mushroom-shaped structure characteristic of Pseudomonas aeruginosa. However, it has become evident that this is not how all biofilms develop, especially in vivo, in clinical and industrial settings, and in the environment, where biofilms often are observed as non-surface-attached aggregates. In this Review, we describe the origin of the current five-step biofilm development model and why it fails to capture many aspects of bacterial biofilm physiology. We aim to present a simplistic developmental model for biofilm formation that is flexible enough to include all the diverse scenarios and microenvironments where biofilms are formed. With this new expanded, inclusive model, we hereby introduce a common platform for developing an understanding of biofilms and anti-biofilm strategies that can be tailored to the microenvironment under investigation. In this Review, Bjarnsholt and colleagues propose a revised conceptual model of the biofilm life cycle that encompasses the three major steps of biofilm formation — aggregation, growth and disaggregation — independently of surfaces, and initiation from single-cell planktonic bacteria, and thus represents a broader range of biofilm systems.
Background and Objectives Falls are a leading cause of injuries and injury deaths for older adults. The Centers for Disease Control and Prevention’s Stopping Elderly Accidents Deaths and Injuries (STEADI) initiative, a multifactorial approach to fall prevention, was adapted for implementation within the primary care setting of a health system in upstate New York. The purpose of this paper is to: (a) report process evaluation results for this implementation using the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework and (b) examine the utility of RE-AIM for assessing barriers and facilitators. Research Design and Methods This evaluation used mixed methods. Qualitative evaluation involved semi-structured interviews with key stakeholders and intercept interviews with healthcare providers and clinic staff. Quantitative methods utilized surveys with clinic staff. Process evaluation tools were developed based on the AIM dimensions of the RE-AIM framework. The study was conducted over a 2-month period approximately 18 months post-implementation and complements previously published results of the program’s reach and effectiveness. Results Primary barriers by RE-AIM construct included competing organizational priorities (Adoption); competing patient care demands (Implementation); and staff turnover (Maintenance). Primary facilitators included having a physician champion (Adoption); preparing and training staff (Implementation); and communicating about STEADI and recognizing accomplishments (Maintenance). Discussion and Implications Results revealed a high degree of concordance between qualitative and quantitative analyses. The framework supported assessments of various stakeholders, multiple organizational levels, and the sequence of practice change activities. Mixed methods yielded rich data to inform future implementations of STEADI-based fall prevention.
Many road accidents happen due to the misjudgments and miscalculations of human drivers when overtaking their lead vehicles. Using unaided sight, the human drivers cannot calculate the accurate velocity of lead vehicles that traveling in similar and opposite directions with respect to their vehicles and can work only by approximation. This incapability of human drivers ends in miscalculation of Time-to-Collision (TTC) and causes accidents between ego and lead vehicles, which kill people in road accidents. A novel Intelligent Overtaking Advice System (IOAS) is proposed in this paper to provide advice to human drivers during attempts to overtake. IOAS is developed to predict both accurate velocity of lead vehicles and accurate TTC. The IOAS is powered by a Velocity Network (VNet) and a Time-to-Collision-Network (TTC-Net). The proposed VNet and TTC-Net are well trained with a huge volume of ground truth datasets to provide better accuracy, robustness, and quick response time. The performance of the proposed IOAS is analyzed and it is observed that the proposed VNet and TTC-Net provide 97% and 98% accuracy, respectively. The proposed IOAS can be integrated into real vehicles as an add-on to the Advanced Driver Assistance System (ADAS) to prevent accidents during the overtaking process.
Failure of infection therapy in the presence of antibiotics has become a major problem which has been mostly attributed to the ability of bacterial persister cell formation. Bacteria use various mechanisms to form persister cells in different phases, among which is the toxin–antitoxin (TA) systems. This study aimed at investigating the expression of type II TA system genes under the stress of ciprofloxacin and colistin antibiotics in the exponential and stationary phases. To determine the effects of ciprofloxacin and colistin on persister cell formation in the exponential and stationary phases of Pseudomonas aeruginosa strains, colony counting was performed at different time intervals in the presence of fivefold MIC of ciprofloxacin and colistin. In addition, the expression of relBE, Xre-COG5654, vapBC, and Xre-GNAT genes in P. aeruginosa isolates was assessed 3.5 h after antibiotic treatment in the exponential and stationary phases using qRT-PCR. Our results indicated the presence of persister phenotype of P. aeruginosa strains in the presence of fivefold MIC of ciprofloxacin and colistin compared to the control after 3.5 h of incubation in the exponential and stationary phases. Also, the number of persister cells in the stationary phase was higher than that of the exponential phase. According to the results of qRT-PCR, ciprofloxacin and colistin may induce persister cells by increasing the expression of type II TA systems in stationary and exponential phases. Ciprofloxacin and colistin may increase the formation of persister cells by affecting the expression of type II TA systems.
Leadership as a social influence process has always involved a complex set of phenomena that demands an interdisciplinary lens. Leadership scholarship has now entered into a digital era. In a digital era, the overall phenomenon is changing, as are the tools through which we study it, demanding a new “lens” through which we view leadership. Yet, this raises the question, to what extent is leadership different in a digital era? In acknowledgement of this trend, a special issue was commissioned at The Leadership Quarterly that sought to stimulate the imagination of leadership scholars and practitioners. In the current work, we begin with a brief review of who, what, when, where and why of digital leadership. We cover leadership in informal contexts (e.g., social media), generalization from face-to-face to virtual contexts, computational modeling, the leveraging of technology (e.g., machine learning; Big Data), as well methodological how-to guides. We then plot a path forward for leadership scholars in the dawn of the digital era.
Research using the Recognition Without Identification paradigm (Cleary & Greene, 2000, Journal of Experimental Psychology: Learning, Memory, and Cognition, 26, 1063-1069; Peynircioǧlu, 1990, Journal of Memory and Language, 29, 493-500) has found that participants can discriminate between old and new stimuli even when the stimuli are obscured to a degree that they are unidentifiable. This methodology has been adapted in the past by using heavily obscured threatening and nonthreatening images and asking participants to try to identify each image followed by a familiarity rating of the image. Past results showed that threatening images that were not able to be identified were rated as more familiar than nonthreatening images that were not able to be identified (Cleary et al., 2013, Memory & Cognition, 41, 989-999). The current study used a similar methodology to explore the possibility that a sense of familiarity can serve to guide our attention toward potential threats in the environment. However, contrary to earlier results, we found that positive images were rated as more familiar than negative images. This pattern was found with both identified and unidentified images and was replicated across five experiments. The current findings are consistent with the view that feelings of positivity and familiarity are closely linked (e.g., de Vries et al., 2010, Psychological Science, 21, 321-328; Garcia-Marques et al., 2004, Personality and Social Psychology Bulletin, 30, 585-593; Monin, 2003, Journal of Personality and Social Psychology, 85, 1035-1048).
High-calorie diets increase the risk of developing obesity, cardiovascular disease, type-two diabetes (T2D), and other comorbidities. These “overnutrition” diets also promote the accumulation of a variety of harmful lipids in the heart and other peripheral organs, known as lipotoxicity. However, the mechanisms underlying lipotoxicity and its influence on pathophysiology remain unknown. Our study uses genetics to identify the role of ether lipids, a class of potential lipotoxins, in a Drosophila model of overnutrition. A high-sugar diet (HSD) increases ether lipids and produces T2D-like pathophysiology phenotypes, including obesity, insulin resistance, and cardiac failure. Therefore, we targeted ether lipid biosynthesis through the enzyme dihydroxyacetonephosphate acyltransferase (encoded by the gene DHAPAT). We found that reducing DHAPAT in the fat body improved TAG and glucose homeostasis, cardiac function, respiration, and insulin signaling in flies fed a HSD. The reduction of DHAPAT may cause a switch in molecular signaling from lipogenesis to fatty acid oxidation via activation of a PPARα-like receptor, as bezafibrate produced similar improvements in HS-fed flies. Taken together, our findings suggest that ether lipids may be lipotoxins that reduce fitness during overnutrition.
Traditional antibody-drug conjugate (ADC) technology has employed tumor-targeting antibodies to selectively deliver ultrapotent cytotoxins to tumor tissue. While this technology has been highly successful, resulting in the FDA approval of over 10 ADCs, the field continues to struggle with modest efficacy and significant off-target toxicity. Concurrent with the struggles of the ADC field, a new generation of immune-activating therapeutics has arisen, most clearly exemplified by the PD-1/PD-L1 inhibitors that are now part of standard-of-care treatment regimens for a variety of cancers. The success of these immuno-oncology therapeutic agents has prompted the investigation of a variety of new immuno-stimulant approaches, including toll-like receptor (TLR) activators. Herein, we describe the optimization of ADC technology for the selective delivery of a potent series of TLR7 agonists. A series of imidazole[4,5-c]quinoline agonists (as exemplified by compound 1) were shown to selectively agonize the human and mouse TLR7 receptor at low nanomolar concentrations, resulting in the release of IFNα from human peripheral blood mononuclear cells (hPBMCs) and the upregulation of CD86 on antigen-presenting cells. Compound 1 was attached to a deglycosylated (Fc-γ null) HER2-targeting antibody via a cleavable linker, resulting in an ADC (anti-HER2_vc-1) that potently and selectively activated the TLR7 pathway in tumor-associated macrophages via a "bystander" mechanism. We demonstrated that this ADC rapidly released the TLR7 agonist into the media when incubated with HER2+ cells. This release was not observed upon incubation with an isotype control ADC and furthermore was suppressed by co-administration of the naked antibody. In co-culture experiments with HER2+ HCC1954 cells, this ADC induced the activation of the NFκB pathway in mouse macrophages and the release of IFNα from hPBMCs, while a corresponding isotype control ADC did not. Finally, we demonstrated that IP administration of anti-HER2_vc-1 induced complete tumor regression in an HCC1954 xenograft study in SCID beige mice. Unlike related ADC technology that has been reported recently, our technology relies on the passive diffusion of the TLR7 agonist into tumor-associated macrophages rather than Fc-γ-mediated uptake. Based on these observations, we believe that this ADC technology holds significant potential for both oncology and infectious disease applications.
Course-based undergraduate research experiences (CUREs) represent an innovative educational strategy to engage more science, technology, engineering, and math undergraduates in authentic research experiences. Research shows that student participation in CUREs results in positive student outcomes similar to those for traditional research experiences.
The design of repulsive electrostatic actuators having enlarged travel range is achieved by combining the boundary element approach and a genetic algorithm. The boundary element method enables calculating the electrostatic forces without time consuming finite element simulations. Once a static equation that uses a model of effective lumped mass solves the travel ranges, the GA maximizes travel ranges by optimizing the dimensional parameters. The effectiveness of the scheme is demonstrated with extensive experimental results showing the travel ranges of a micro out-of-plane actuator are increased by up to 190%. The developed platform can improve the signal-to-noise ratios and the performance of general multi-electrode systems. Index Terms-electrostatic MEMS, out-of-plane actuator, optimization, boundary element approach, genetic algorithm
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