Neurogenesis is restricted in the adult mammalian brain; most neurons are neither exchanged during normal life nor replaced in pathological situations. We report that stroke elicits a latent ...neurogenic program in striatal astrocytes in mice. Notch1 signaling is reduced in astrocytes after stroke, and attenuated Notch1 signaling is necessary for neurogenesis by striatal astrocytes. Blocking Notch signaling triggers astrocytes in the striatum and the medial cortex to enter a neurogenic program, even in the absence of stroke, resulting in 850 ± 210 (mean ± SEM) new neurons in a mouse striatum. Thus, under Notch signaling regulation, astrocytes in the adult mouse brain parenchyma carry a latent neurogenic program that may potentially be useful for neuronal replacement strategies.
Objective
To describe the associations between autoantibodies, clinical presentation, and outcomes among patients with systemic sclerosis (SSc) in order to develop a novel SSc classification scheme ...that would incorporate both antibodies and the cutaneous disease subset as criteria.
Methods
Demographic and clinical characteristics, including cutaneous subset, time of disease and organ complication onset, and autoantibody specificities, were determined in a cohort of SSc subjects. Survival analysis was used to assess the effect of the autoantibodies on organ disease and death.
Results
The study included 1,325 subjects. Among the antibody/skin disease subsets, anticentromere antibody–positive patients with limited cutaneous SSc (lcSSc) (n = 374) had the highest 20‐year survival (65.3%), lowest incidence of clinically significant pulmonary fibrosis (PF) (8.5%) and scleroderma renal crisis (SRC) (0.3%), and lowest incidence of cardiac SSc (4.9%), whereas the frequency of pulmonary hypertension (PH) was similar to the mean value in the SSc cohort overall. The anti–Scl‐70+ groups of patients with lcSSc (n = 138) and patients with diffuse cutaneous SSc (dcSSc) (n = 149) had the highest incidence of clinically significant PF (86.1% and 84%, respectively, at 15 years). Anti‐Scl‐70+ patients with dcSSc had the lowest survival (32.4%) and the second highest incidence of cardiac SSc (12.9%) at 20 years. In contrast, in anti‐Scl‐70+ patients with lcSSc, other complications were rare, and these patients demonstrated the lowest incidence of PH (6.9%) and second highest survival (61.8%) at 20 years. Anti–RNA polymerase antibody–positive SSc patients (n = 147) had the highest incidence of SRC (28.1%) at 20 years. The anti–U3 RNP+ SSc group (n = 56) had the highest incidence of PH (33.8%) and cardiac SSc (13.2%) at 20 years. Among lcSSc patients with other autoantibodies (n = 295), the risk of SRC and cardiac SSc was low at 20 years (2.7% and 2.4%, respectively), while the frequencies of other outcomes were similar to the mean values in the full SSc cohort. Patients with dcSSc who were positive for other autoantibodies (n = 166) had a poor prognosis, demonstrating the second lowest survival (33.6%) and frequent organ complications.
Conclusion
These findings highlight the importance of autoantibodies, cutaneous subset, and disease duration when assessing morbidity and mortality in patients with SSc. Our novel classification scheme may improve disease monitoring and benefit future clinical trial designs in SSc.
The measurement of stable isotopes in ‘bulk’ animal and plant tissues (e.g., muscle or leaf) has become an important tool for studies of functional diversity from organismal to continental scales. In ...consumers, isotope values reflect their diet, trophic position, physiological state, and geographic location. However, interpretation of bulk tissue isotope values can be confounded by variation in primary producer baseline values and by overlapping values among potential food items. To resolve these issues, biologists increasingly use compound-specific isotope analysis (CSIA), in which the isotope values of monomers that constitute a macromolecule (e.g., amino acids in protein) are measured. In this review, we provide the theoretical underpinnings for CSIA, summarize its methodology and recent applications, and identify future research directions. The key principle is that some monomers are reliably routed directly from the diet into animal tissue, whereas others are biochemically transformed during assimilation. As a result, CSIA of consumer tissue simultaneously provides information about an animal’s nutrient sources (e.g., food items or contributions from gut microbes) and its physiology (e.g., nitrogen excretion mode). In combination, these data clarify many of the confounding issues in bulk analysis and enable novel precision for tracing nutrient and energy flow within and among organisms and ecosystems.
•Mitochondrial dysfunction is one of the earliest pathophysiological events in amyotrophic lateral sclerosis (ALS).•ALS-associated mutant proteins accumulate in mitochondria and cause mitochondrial ...damage.•ALS-associated mitochondrial dysfunction occurs at multiple levels.•ALS affects mitochondrial respiration and ATP production, calcium handling, dynamics, and apoptotic signalling.
Mitochondria are unique organelles that are essential for a variety of cellular processes including energy metabolism, calcium homeostasis, lipid biosynthesis, and apoptosis. Mitochondrial dysfunction is a prevalent feature of many neurodegenerative diseases including motor neuron disorders such as amyotrophic lateral sclerosis (ALS). Disruption of mitochondrial structure, dynamics, bioenergetics and calcium buffering has been extensively reported in ALS patients and model systems and has been suggested to be directly involved in disease pathogenesis. Here we review the alterations in mitochondrial parameters in ALS and examine the common pathways to dysfunction.
Smith et al explore deep eutectic solvents (DESs) and their applications, focusing on the properties of DESs, metal processing applications, and synthesis applications.
The NF-κB transcription factor is the master regulator of the inflammatory response and is essential for the homeostasis of the immune system. NF-κB regulates the transcription of genes that control ...inflammation, immune cell development, cell cycle, proliferation, and cell death. The fundamental role that NF-κB plays in key physiological processes makes it an important factor in determining health and disease. The importance of NF-κB in tissue homeostasis and immunity has frustrated therapeutic approaches aimed at inhibiting NF-κB activation. However, significant research efforts have revealed the crucial contribution of NF-κB phosphorylation to controlling NF-κB directed transactivation. Importantly, NF-κB phosphorylation controls transcription in a gene-specific manner, offering new opportunities to selectively target NF-κB for therapeutic benefit. This review will focus on the phosphorylation of the NF-κB subunits and the impact on NF-κB function.
Abstract This chapter summarises the global and regional prevalence, disability (Years Lived with Disability (YLDs)) and overall burden (Disability Adjusted Life Years (DALYs)) and costs for the ...common musculoskeletal disorders including low back and neck pain, hip and knee osteoarthritis, rheumatoid arthritis, gout, and a remaining combined group of other MSK conditions. The contribution of the role of pain in disability burden is introduced. Trends over time and predictions of increasing MSK disability with demographic changes are addressed and the particular challenges facing the developing world are highlighted.
ObjectiveThe present study examines how LGBTQ‐identified adults maintain relationships with parents who reject their LGBTQ identity.
BackgroundParents often reject their children's LGBTQ identity, ...sometimes leading to relationship dissolution. But how LGBTQ adults maintain parent–child relationships despite parents' rejection is less known. We answer this question with an empirical study of how LGBTQ adults maintain relationships with parents who reject their child's LGBTQ identity, drawing on conflict management theories and the concept “family work,” or the work done to promote family functioning.
MethodQualitative in‐depth interviews with 76 LGBTQ young adults are analyzed, supplemented with data from 44 of their parents.
ResultsLGBTQ adults do extensive work to maintain their intergenerational bonds through what we theorize as “conflict work.” We define conflict work as the effort done to manage severe conflict in a way that ensures family functioning, often at the expense of personal needs. Conflict work includes conflict education work (e.g., educating parents about LGBTQ identities), conflict avoidance work (e.g., don't ask, don't tell about LGBTQ identities), conflict acceptance work (e.g., ongoing but accepted conflict about LGBTQ identities), and conflict boundary work (e.g., asserting boundaries from parents over LGBTQ‐related conflict).
ConclusionLGBTQ adults maintain the parent–child bond by managing parents' rejection of their gender or sexuality identity through “conflict work.” In doing so, LGBTQ adults reveal an important new type of family work aimed at supporting family functioning during intensive conflict, often at the expense of the conflict worker's personal needs.
Reef‐building corals are mixotrophic organisms that can obtain nutrition from endosymbiotic microalgae (autotrophy) and particle capture (heterotrophy). Heterotrophic nutrition is highly beneficial ...to many corals, particularly in times of stress. Yet, the extent to which different coral species rely on heterotrophic nutrition remains largely unknown because it is challenging to quantify.
We developed a quantitative approach to investigate coral nutrition using carbon isotope (δ13C) analysis of six essential amino acids (AAESS) in a common Indo‐Pacific coral (Pocillopora meandrina) from the fore reef habitat of Palmyra Atoll. We sampled particulate organic matter (POM) and zooplankton as the dominant heterotrophic food sources in addition to the coral host and endosymbionts. We also measured bulk tissue carbon (δ13C) and nitrogen (δ15N) isotope values of each sample type.
Patterns among δ13C values of individual AAESS provided complete separation between the autotrophic (endosymbionts) and heterotrophic nutritional sources. In contrast, bulk tissue δ13C and δ15N values were highly variable across the putative food sources and among the coral and endosymbiont fractions, preventing accurate estimates of coral nutrition on Palmyra.
We used linear discriminant analysis to quantify differences among patterns of AAESS δ13C values, or ‘fingerprints’, of the food resources available to corals. This allowed for the development of a quantitative continuum of coral nutrition that can identify the relative contribution of autotrophic and heterotopic nutrition to individual colonies. Our approach revealed exceptional variation in conspecific colonies at scales of metres to kilometres. On average, 41% of AAESS in P. meandrina on Palmyra are acquired via heterotrophy, but some colonies appear capable of obtaining the majority of AAESS from one source or the other.
The use of AAESS δ13C fingerprinting analysis offers a significant improvement on the current methods for quantitatively assessing coral trophic ecology. We anticipate that this approach will facilitate studies of coral nutrition in the field, which are essential for comparing coral trophic ecology across taxa and multiple spatial scales. Such information will be critical for understanding the role of heterotrophic nutrition in coral resistance and/or resilience to ongoing environmental change.
A free Plain Language Summary can be found within the Supporting Information of this article.
A free Plain Language Summary can be found within the Supporting Information of this article.
The widespread importance of variable types of primary production, or energy channels, to consumer communities has become increasingly apparent. However, the mechanisms underlying this “multichannel” ...feeding remain poorly understood, especially for aquatic ecosystems that pose unique logistical constraints given the diversity of potential energy channels. Here, we use bulk tissue isotopic analysis along with carbon isotope (δ13C) analysis of individual amino acids to characterize the relative contribution of pelagic and benthic energy sources to a kelp forest consumer community in northern Chile. We measured bulk tissue δ13C and δ15N for >120 samples; of these we analyzed δ13C values of six essential amino acids (EAA) from nine primary producer groups (n = 41) and 11 representative nearshore consumer taxa (n = 56). Using EAA δ13C data, we employed linear discriminant analysis (LDA) to assess how distinct EAA δ13C values were between local pelagic (phytoplankton/particulate organic matter), and benthic (kelps, red algae, and green algae) endmembers. With this model, we were able to correctly classify nearly 90% of producer samples to their original groupings, a significant improvement on traditional bulk isotopic analysis. With this EAA isotopic library, we then generated probability distributions for the most important sources of production for each individual consumer and species using a bootstrap-resampling LDA approach. We found evidence for multichannel feeding within the community at the species level. Invertebrates tended to focus on either pelagic or benthic energy, deriving 13–67% of their EAA from pelagic sources. In contrast, mobile (fish) taxa at higher trophic levels used more equal proportions of each channel, ranging from 19% to 47% pelagically derived energy. Within a taxon, multichannel feeding was a result of specialization among individuals in energy channel usage, with 37 of 56 individual consumers estimated to derive >80% of their EAA from a single channel. Our study reveals how a cutting-edge isotopic technique can characterize the dynamics of energy flow in coastal food webs, a topic that has historically been difficult to address. More broadly, our work provides a mechanism as to how multichannel feeding may occur in nearshore communities, and we suggest this pattern be investigated in additional ecosystems.
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