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Abstract Fish spawning locations are a crucial input into fisheries management and conservation plans, and many stocks are especially sensitive to the environmental conditions within these localized zones. Globally collated data on spawning locations across many species has been unavailable, hindering global stock assessments and analyses of sustainable development and global environmental change. To address this, we created a geocoded fish spawning dataset using qualitative spawning information from FishBase and Science and Conservation of Fish Aggregations (SCRFA). We cleaned and geocoded the spawning locations of 1,045 marine fish species into 2,931 regions. Each spawning region is defined by one or more polygons, and most spawning regions are associated with spawning months. The resulting dataset covers oceans globally. This dataset will be useful to scientists studying marine fish population dynamics and their interactions with the physical environment on regional to large scales.

Abstract A large stretch of the east coast of Australia experienced unprecedented rainfall and flooding over a two‐week period in early 2022. It is difficult to reliably estimate the likelihood of such a rare event from the relatively short observational record, so an alternative is to use data from an ensemble prediction system (e.g., a seasonal or decadal forecast system) to obtain a much larger sample of simulated weather events. This so‐called ‘UNSEEN’ method has been successfully applied in several scientific studies, but those studies typically rely on a single prediction system. In this study, we use data from the Decadal Climate Prediction Project to explore the model uncertainty associated with the UNSEEN method by assessing 10 different hindcast ensembles. Using the 15‐day rainfall total averaged over the river catchments impacted by the 2022 east coast event, we find that the models produce a wide range of likelihood estimates. Even after excluding a number of models that fail basic fidelity tests, estimates of the event return period ranged from 320 to 1814 years. The vast majority of models suggested the event is rarer than a standard extreme value assessment of the observational record (297 years). Such large model uncertainty suggests that multi‐model analysis should become part of the standard UNSEEN procedure.

This paper proposes that the concept of place in J.H. Prynne’s Wound Response (1974) is founded on a condition of homelessness. Prynne recognizes the complicity of a humanist idea of home with totalitarian fantasies of foundations and origins. We argue that Wound Response constitutes a homeless geography of place, which becomes an ethical alternative to the politics of exclusion that underlie the process of homemaking. Destabilizing the anchorage of home, the volume encounters both the land and the body in moments of vulnerability. Politicized and territorialized, the wounded body in Wound Response becomes a reminder of the fundamental homelessness that haunts contemporary forms of spatial being. While stressing the severe inadequacy of a concept of place marked by rootedness, security, and permanence, the poems offer transient modes of shelter consistently underlined by a sense of precarity. By analyzing the figures of shelter and ‘human’ configurations of place in Wound Response, this paper maps the alternative geography of place that emerges from an ethically charged commitment to homelessness.

Abstract Transient atmospheric vortices called monsoon low pressure systems (LPS) generate a large fraction of total rainfall over South Asia and often produce extreme precipitation. Here, we assess the influence of these storms on the occurrence of disasters, using information from the Emergency Events Database (EM-DAT) that we geocoded and then associated with LPS tracks. We show that more than half of hydro-meteorological disasters over South Asia during summer are associated with these LPS events. Weaker LPS (which are called monsoon lows) occur more frequently than stronger LPS (called monsoon depressions), but the stronger LPS produce a larger number of disasters. Furthermore, although many prior studies have shown that the peak rainfall in LPS falls southwest of the vortex centre, the disasters are concentrated on the northern edge of the LPS tracks, along the Himalayas and upper basins of the Ganga and Brahmaputra rivers. Observations show a sharp peak in rainfall on the day of disasters, confirming the physical link between LPS and these hydro-meteorological disasters. A similar peak in rainfall is found in weather forecasts made up to five days before the disaster, suggesting that short-term precipitation forecasts can be useful in disaster preparation.

In eastern Australia we expect to experience wet conditions during La Niña and dry during El Niño events. We explore how well these expectations match historical outcomes by assessing, for spring, how much rain fell during past La Niña and El Niño events. We use a tercile framing and find that for rainfall averaged across eastern Australia, La Niña approximately doubles the chance of spring rainfall being in the wet tercile whereas El Niño approximately doubles the chance of a dry spring. Also of note is that during La Niña, the dry tercile is mostly vacant and during El Niño, the wet tercile is mostly vacant, indicating that one should not expect dry conditions in La Niña or wet in El Niño for eastern Australia as a whole. At individual locations across Australia, the results vary, and in some cases, including the eastern seaboard, La Niña or El Niño events do not change the odds of wet and dry springs significantly beyond chance expectations. For example, in the Sydney region, the normal chance of experiencing a wet tercile spring is 33% and this increases only slightly in a La Niña to 38%, suggesting that La Niña is not a strong indicator for wet conditions in this region. These outcomes may help to manage our expectations for the likely rainfall outcomes during future El Niño–Southern Oscillation (ENSO) events.

Diverse characteristics of El Niño Southern Oscillation (ENSO) events challenge the traditional view of tropical coupled ocean-atmosphere systems. The probability of a transition from one type of event to another is influenced by multiple factors of which many are projected to change. Here we assess the likelihood of ENSO transitions in observations and climate models, including a distinction between events that peak in the Eastern Pacific (EP) and Central Pacific (CP). We find that the initial ENSO state influences the likelihood of certain transitions and that some transitions are not physically possible or stochastically likely. For example, transitions to CP events are more likely than EP events except from a neutral state. We also find that El Niños tend to occur as singular events compared to La Niñas. While consecutive El Niño and La Niña events of EP type are possible, opposing EP events do not occur in succession. We identify several transitions likely driven by internal dynamical processes including neutral conditions to El Niño, CP El Niño to another El Niño, EP El Niño to CP La Niña, CP La Niña to CP El Niño and La Niña, and EP La Niña to neutral and CP El Niño. Projections of future transitions show an increased probability of transitions to CP El Niño events while transitions to EP La Niña events become less frequent under a high-emissions scenario. Accordingly, transitions to these events become more and less likely, respectively. We also find changes in the likelihood of specific transitions in a warming world: consecutive CP El Niño events become more likely while EP El Niño events become less likely to transition into CP La Niña events. These changes are expected to occur as early as 2050 with some changes to be accelerated by the end of the 21st century.

Mutations in the ubiquitin (Ub) chaperone Ubiquilin 2 (UBQLN2) cause X-linked forms of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) through unknown mechanisms. Here, we show that aggregation-prone, ALS-associated mutants of UBQLN2 (UBQLN2ALS) trigger heat stress-dependent neurodegeneration in Drosophila. A genetic modifier screen implicated endolysosomal and axon guidance genes, including the netrin receptor, Unc-5, as key modulators of UBQLN2 toxicity. Reduced gene dosage of Unc-5 or its coreceptor Dcc/frazzled diminished neurodegenerative phenotypes, including motor dysfunction, neuromuscular junction defects, and shortened lifespan, in flies expressing UBQLN2ALS alleles. Induced pluripotent stem cells (iPSCs) harboring UBQLN2ALS knockin mutations exhibited lysosomal defects while inducible motor neurons (iMNs) expressing UBQLN2ALS alleles exhibited cytosolic UBQLN2 inclusions, reduced neurite complexity, and growth cone defects that were partially reversed by silencing of UNC5B and DCC. The combined findings suggest that altered growth cone dynamics are a conserved pathomechanism in UBQLN2-associated ALS/FTD.

ALS and FTLD are both characterized by insoluble cytoplasmic depositions of TDP43. Here the authors show that the nucleopore protein NUP62 is mislocalized in C9orf72 and sporadic ALS/FTLD and propose that it interacts with TDP-43 to promote its insolubility.

Alice Tarbuck reviews Greg Thomas, Border Blurs: Concrete Poetry in England and Scotland (2022); Nandini Ramesh Sankar reviews Zoë Skoulding, Poetry & Listening: The Noise of Lyric (2020).

Abstract The most common genetic cause of amyotrophic lateral sclerosis (ALS) is a GGGGCC (G4C2) hexanucleotide repeat expansions in first intron of the C9orf72 gene. The accumulation of repetitive RNA sequences can mediate toxicity potentially through the formation of intranuclear RNA foci that sequester key RNA-binding proteins (RBPs), and non-ATG mediated translation into toxic dipeptide protein repeats. However, the contribution of RBP sequestration to the mechanisms underlying RNA-mediated toxicity remain unknown. Here we show that the ALS-associated RNA-binding protein, Matrin-3 (MATR3), colocalizes with G4C2 RNA foci in patient tissues as well as iPSC-derived motor neurons harboring the C9orf72 mutation. Hyperexpansion of C9 repeats perturbed subcellular distribution and levels of endogenous MATR3 in C9-ALS patient-derived motor neurons. Interestingly, we observed that ectopic expression of human MATR3 strongly mitigates G4C2-mediated neurodegeneration in vivo. MATR3-mediated suppression of C9 toxicity was dependent on the RNA-binding domain of MATR3. Importantly, we found that expression of MATR3 reduced the levels of RAN-translation products in mammalian cells in an RNA-dependent manner. Finally, we have shown that knocking down endogenous MATR3 in C9-ALS patient-derived iPSC neurons decreased the presence of G4C2 RNA foci in the nucleus. Overall, these studies suggest that MATR3 genetically modifies the neuropathological and the pathobiology of C9orf72 ALS through modulating the RNA foci and RAN translation.

Abstract Background Amyotrophic lateral sclerosis (ALS) is an adult-onset, fatal neurodegenerative disease characterized by progressive loss of upper and lower motor neurons. While pathogenic mutations in the DNA/RNA-binding protein Matrin-3 (MATR3) are linked to ALS and distal myopathy, the molecular mechanisms underlying MATR3-mediated neuromuscular degeneration remain unclear. Methods We generated Drosophila lines with transgenic insertion of human MATR3 wildtype, disease-associated variants F115C and S85C, and deletion variants in functional domains, ΔRRM1, ΔRRM2, ΔZNF1 and ΔZNF2. We utilized genetic, behavioral and biochemical tools for comprehensive characterization of our models in vivo and in vitro. Additionally, we employed in silico approaches to find transcriptomic targets of MATR3 and hnRNPM from publicly available eCLIP datasets. Results We found that targeted expression of MATR3 in Drosophila muscles or motor neurons shorten lifespan and produces progressive motor defects, muscle degeneration and atrophy. Strikingly, deletion of its RNA-recognition motif (RRM2) mitigates MATR3 toxicity. We identified rump, the Drosophila homolog of human RNA-binding protein hnRNPM, as a modifier of mutant MATR3 toxicity in vivo. Interestingly, hnRNPM physically and functionally interacts with MATR3 in an RNA-dependent manner in mammalian cells. Furthermore, common RNA targets of MATR3 and hnRNPM converge in biological processes important for neuronal health and survival. Conclusions We propose a model of MATR3-mediated neuromuscular degeneration governed by its RNA-binding domains and modulated by interaction with splicing factor hnRNPM.

The record-shattering hot day in the Pacific Northwest in June 2021 is used to motivate a study of record-shattering temperature extremes in a very large hindcast ensemble. The hottest days in the Pacific Northwest in the large ensemble have similar large scale and synoptic patterns to those associated with the observed event. From the perspective of a fixed location, the hottest ensemble days are acutely sensitive to the chance sequencing of a dry period with a precisely positioned weather pattern. These days are thus rare and require very large samples (tens of thousands of years) to capture. The enduring nature of record-shattering heat records can be understood through this lens of weather ‘noise’ and sampling. When a record-shattering event occurs due to chance alignment of weather systems in the optimal configuration, any small sample of years subsequent to the (very unlikely) record event has an extremely low chance of finding yet another chance extreme. While warming of the baseline climate can narrow the gap between more regular extremes and record-shattering extremes, this can take many decades depending on the pace of climate change. Climate models are unlikely to capture record-shattering extremes at fixed locations given by observations unless the model samples are large enough to provide enough weather outcomes to include the optimal weather alignments. This underscores the need to account for sampling in assessing models and changes in weather-sensitive extremes. In particular, climate models are not necessarily deficient in representing extremes if that assessment is based on their absence in undersize samples.

The exact molecular mechanisms driving FUS-mediated toxicity remain unclear. Here, the authors demonstrate that muscleblind (Mbl) is a novel modifier of FUS-associated ALS, with knockdown of endogenous Mbl suppressing neuromuscular junction defects and motor dysfunctions associated with FUS expression in Drosophila, as well as restoring reduced SMN protein levels in mammalian neuronal and human iPSC-derived motor neurons.

Traumatic brain injury (TBI) is a predisposing factor for many neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), Alzheimer’s disease (AD), Parkinson’s disease (PD), and chronic traumatic encephalopathy (CTE). Although defects in nucleocytoplasmic transport (NCT) is reported ALS and other neurodegenerative diseases, whether defects in NCT occur in TBI remains unknown. We performed proteomic analysis on Drosophila exposed to repeated TBI and identified resultant alterations in several novel molecular pathways. TBI upregulated nuclear pore complex (NPC) and nucleocytoplasmic transport (NCT) proteins as well as alter nucleoporin stability. Traumatic injury disrupted RanGAP1 and NPC protein distribution in flies and a rat model and led to coaggregation of NPC components and TDP-43. In addition, trauma-mediated NCT defects and lethality are rescued by nuclear export inhibitors. Importantly, genetic upregulation of nucleoporins in vivo and in vitro triggered TDP-43 cytoplasmic mislocalization, aggregation, and altered solubility and reduced motor function and lifespan of animals. We also found NUP62 pathology and elevated NUP62 concentrations in postmortem brain tissues of patients with mild or severe CTE as well as co-localization of NUP62 and TDP-43 in CTE. These findings indicate that TBI leads to NCT defects, which potentially mediate the TDP-43 pathology in CTE.

TDP-43 is a predominantly nuclear DNA/RNA binding protein that is often mislocalized into insoluble cytoplasmic inclusions in post-mortem patient tissue in a variety of neurodegenerative disorders including Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal dementia (FTD). The underlying causes of TDP-43 proteinopathies remain unclear, but recent studies indicate the formation of these protein assemblies is driven by aberrant phase transitions of RNA deficient TDP-43. Technical limitations have prevented our ability to understand how TDP-43 proteinopathy relates to disease pathogenesis. Current animal models of TDP-43 proteinopathy often rely on overexpression of wild-type TDP-43 to non-physiological levels that may initiate neurotoxicity through nuclear gain of function mechanisms, or by the expression of disease-causing mutations found in only a fraction of ALS patients. New technologies allowing for light-responsive control of subcellular protein crowding provide a promising approach to drive intracellular protein aggregation, as we have previously demonstrated in vitro. Here we present a model for the optogenetic induction of TDP-43 proteinopathy in Drosophila that recapitulates key features of patient pathology, including detergent insoluble cytoplamsic inclusions and progressive motor dysfunction.

Amyotrophic Lateral Sclerosis (ALS), a late-onset neurodegenerative disorder characterized by the loss of motor neurons in the central nervous system, has no known cure to-date. Disease causing mutations in human Fused in Sarcoma (FUS) leads to aggressive and juvenile onset of ALS. FUS is a well-conserved protein across different species, which plays a crucial role in regulating different aspects of RNA metabolism. Targeted misexpression of FUS in Drosophila model recapitulates several interesting phenotypes relevant to ALS including cytoplasmic mislocalization, defects at the neuromuscular junction and motor dysfunction. We screened for the genetic modifiers of human FUS-mediated neurodegenerative phenotype using molecularly defined deficiencies. We identified hippo (hpo), a component of the evolutionarily conserved Hippo growth regulatory pathway, as a genetic modifier of FUS mediated neurodegeneration. Gain-of-function of hpo triggers cell death whereas its loss-of-function promotes cell proliferation. Downregulation of the Hippo signaling pathway, using mutants of Hippo signaling, exhibit rescue of FUS-mediated neurodegeneration in the Drosophila eye, as evident from reduction in the number of TUNEL positive nuclei as well as rescue of axonal targeting from the retina to the brain. The Hippo pathway activates c-Jun amino-terminal (NH2) Kinase (JNK) mediated cell death. We found that downregulation of JNK signaling is sufficient to rescue FUS-mediated neurodegeneration in the Drosophila eye. Our study elucidates that Hippo signaling and JNK signaling are activated in response to FUS accumulation to induce neurodegeneration. These studies will shed light on the genetic mechanism involved in neurodegeneration observed in ALS and other associated disorders.

Elevated carbon dioxide (EC) can increase the growth and development of different C3 fruit crops, which may further increase the nutrient demand by the accumulated biomass. In this context, the current investigation was conceptualized to evaluate the growth performance and nutrient uptake by tomato plants under elevated CO2 (EC700 and EC550 ppm) and temperature (+2 °C) in comparison to ambient conditions. Significant improvement in the growth indicating parameters like leaf area, leaf area index, leaf area duration and crop growth rate were measured at EC700 and EC550 at different stages of crop growth. Further, broader and thicker leaves of plants under EC700 and EC550 have intercepted higher radiation by almost 11% more than open field plants. Conversely, elevated temperature (+2 °C) had negative influence on crop growth and intercepted almost 7% lower radiation over plants under ambient conditions. Interestingly, earliness of phenophases viz., branch initiation (3.0 days), flower initiation (4.14 days), fruit initiation (4.07 days) and fruit maturation (7.60 days) were observed at EC700 + 2 °C, but it was statistically on par with EC700 and EC550 + 2 °C. Irrespective of the plant parts and growth stages, plants under EC700 and EC550 have showed significantly higher nutrient uptake due to higher root biomass. At EC700, the tune of increase in total nitrogen, phosphorus and potassium uptake was almost 134%, 126% and 135%, respectively compared to open field crop. This indicates higher nutrient demand by the crop under elevated CO2 levels because of higher dry matter accumulation and radiation interception. Thus, nutrient application is needed to be monitored at different growth stages as per the crop needs.

Guar, the most popular vegetable, is tolerant of drought and is a valuable industrial crop enormously grown across India, Pakistan, USA, and South Africa for pharmaceutically and cosmetically usable galactomannan (gum) content present in seed endosperm. Guar genotypes with productive traits which could perform better in differential environmental conditions are of utmost priority for genotype selection. This could be achieved by employing multivariate trait analysis. In this context, Multi-Trait Stability Index (MTSI) and Multi-Trait Genotype-Ideotype Distance Index (MGIDI) were employed for identifying high-performing genotypes exhibiting multiple traits. In the current investigation, 85 guar accessions growing in different seasons were assessed for 15 morphological traits. The results obtained by MTSI and MGIDI indexes revealed that, out of 85, only 13 genotypes performed better across and within the seasons, and, based on the coincidence index, only three genotypes (IC-415106, IC-420320, and IC-402301) were found stable with high seed production in multi-environmental conditions. View on strengths and weakness as described by the MGIDI reveals that breeders concentrated on developing genotype with desired traits, such as quality of the gum and seed yield. The strength of the ideal genotypes in the present work is mainly focused on high gum content, short crop cycle, and high seed yield possessing good biochemical traits. Thus, MTSI and MGIDI serve as a novel tool for desired genotype selection process simultaneously in plant breeding programs across multi-environments due to uniqueness and ease in interpreting data with minimal multicollinearity issues.

Monsoon fluctuation due to El Niño Southern Oscillation (ENSO) has a reflective influence on rice production, which is the major food grain crop in India. The impact of ENSO on the spatial variability of summer monsoon rainfall was analyzed from 1950 to 2018 and that on Kharif rice production for the period of 1998–2016. It was clear from the analysis that ENSO had varied influences on rainfall and rice production over different rice-growing districts of Karnataka. During El Niño (strong, moderate, and weak) years, southwest (S-W) monsoon rainfall was below normal in all the districts of Karnataka, wherein the highest negative deviation from normal was recorded in the Mysore district (−21.43%). In contrast, the rice production was higher in 15 districts out of 25, and the deviation from normal ranged from −39.73% in Bidar to 42.11% in Gulbarga district. During the La Niña (strong, moderate, and weak) years, S-W monsoon rainfall was above normal in 12 districts in which Bidar and Bengaluru urban districts have shown the highest positive deviation (19.93 and 19.82%, respectively). However, except for Udupi, Dakshina Kannada, Bidar, Davanagere, and Hassan districts, all the other major rice-growing districts have shown a positive deviation in rice production with the highest deviation of 62.39% in Tumkur district. Additionally, correlation coefficient values indicated the influence of southwest monsoon rainfall on Kharif rice production during El Niño years with a major contribution from September month rainfall. This kind of ENSO impact analysis on spatial rice production could be useful for formulating the farm-level site-specific management, planning, and policy decisions during ENSO periods in advance.

Climate change has increasing effects on horticultural crops. To investigate the impact of CO2 and temperature at elevated levels on tomato production and quality of fruits an experiment was conducted by growing plants in open top chambers. The tomato plants were raised at EC550 (elevated CO2 at 550 ppm) and EC700 (elevated CO2 at 700 ppm) alone and in combination with elevated temperature (ET) + 2 °C in the open top chambers. These elevate CO2 and temperature treatment effects were compared with plants grown under ambient conditions. Outcome of the experiment indicated that growth parameters namely plant stature in terms of height (152.20 cm), leaf number (158.67), canopy spread (6127.70 cm2), leaf area (9110.68 cm2) and total dry matter (223.0 g/plant) were found to be high at EC700 compared to plants grown at ambient conditions in open field. The plants grown at EC700 also exhibited significantly higher number of flowers (273.80) and fruits (261.13), more fruit weight (90.46 g) and yield (5.09 kg plant−1) compared to plants grown at ambient conditions in open field. The percent increase in fruit yield due to EC varied from 18.37 (EC550) to 21.41 (EC700) percent respectively compared to open field and the ET by 2 °C has reduced the fruit yield by 20.01 percent. Quality traits like Total Soluble Solids (3.67 °Brix), reducing sugars (2.48%), total sugars (4.41%) and ascorbic acid (18.18 mg/100 g) were found maximum in EC700 treated tomato than other elevated conditions. Keeping quality was also improved in tomato cultivated under EC700 (25.60 days) than the open field (17.80 days). These findings reveal that CO2 at 700 ppm would be a better option to improve both quantitative as well as qualitative traits in tomato. Among the combinations, EC550 + 2 °C proved better than EC700 + 2 °C with respect to yield as well as for the quality traits. The tomato grown under ET (+2 °C) alone recorded lowest growth and yield attributes compared to open field conditions and rest of the treatments. The positive influence of EC700 is negated to an extent of 14.35 % when the EC700 combined with elevated temperature of + 2 °C. The present study clearly demonstrates that the climate change in terms of increased temperature and CO2 will have a positive effect on tomato by way of increase in production and quality of fruits. Meanwhile the increase in EC beyond 700 ppm along with ET may reduce the positive effects on yield and quality of tomato.

Sorghum is an important dual-purpose crop of India grown for food and fodder. Prevailing weather conditions during the crop growth period determine the yield of sorghum. Hence, the crop yield forecasting models based on weather parameters will be an appropriate option for policymakers and researchers to develop sustainable cropping strategies. In the present study, six multivariate weather-based models viz., least absolute shrinkage and selection operator (LASSO), elastic net (ENET), principal component analysis (PCA) in combination with stepwise multiple linear regression (SMLR), artificial neural network (ANN) alone and in combination with PCA and ridge regression model are examined by fixing 90% of the data for calibration and remaining dataset for validation to forecast rabi sorghum yield for different districts of Karnataka. The R2 and root mean square error (RMSE) during calibration ranged between 0.42 to 0.98 and 30.48 to 304.17 kg ha−1, respectively, without actual evapotranspiration (AET) whereas, these evaluation parameters varied from 0.38 to 0.99 and 19.84 to 308.79 kg ha−1, respectively with AET inclusion. During validation, the RMSE and nRMSE (normalized root mean square error) varied between 88.99 to 1265.03 kg ha−1 and 4.49 to 96.84%, respectively without AET and including AET as one of the weather variable RMSE and nRMSE were 63.48 to 1172.01 kg ha−1 and 4.16 to 92.56%, respectively. The performance of six multivariate models revealed that LASSO was the best model followed by ENET compared to PCA_SMLR, ANN, PCA_ANN and ridge regression models because of reduced overfitting through penalisation of regression coefficient. Thus, it can be concluded that LASSO and ENET weather-based models can be effectively utilized for the district level forecast of sorghum yield.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder that results from the loss of upper and lower motor neurons. One of the key pathological hallmarks in diseased neurons is the mislocalization of disease-associated proteins and the formation of cytoplasmic aggregates of these proteins and their interactors due to defective protein quality control. This apparent imbalance in the cellular protein homeostasis could be a crucial factor in causing motor neuron death in the later stages of the disease in patients. Autophagy is a major protein degradation pathway that is involved in the clearance of protein aggregates and damaged organelles. Abnormalities in autophagy have been observed in numerous neurodegenerative disorders, including ALS. In this review, we discuss the contribution of autophagy dysfunction in various in vitro and in vivo models of ALS. Furthermore, we examine the crosstalk between autophagy and other cellular stresses implicated in ALS pathogenesis and the therapeutic implications of regulating autophagy in ALS.

This article examines Mark Z. Danielewski's House of Leaves (2000), a gothic novel that augments its postmodernist credentials by preemptively imagining and representing the theoretical gaze that would otherwise have been directed on itself. The article suggests that despite the novel's intense performance of self-reflexivity, it demonstrates a traumatic suppression of its own immediate historical conditions, particularly its temporal proximity to the events of the First Gulf War. This article thus reads the text's telling silences and its thematization of uncanny spatial violations as indexing a minimally acknowledged guilt over the war in Iraq. The novel's slippages in self-awareness not only point to an avoidance of its own scotomized history but also foreground the shifting boundaries and dispersed locations of textual self-consciousness. [ABSTRACT FROM AUTHOR]