Miracle-dz/UniFAR-FTUs huggingface dataset:
Schrödinger’s range-shifting cat: analytic predictions for the effect of asymmetric environmental performance on climate change responses

Analytic models for how species will respond to climate change can highlight key parameter dependencies. By mapping equations for population dynamics onto corresponding well-studied problems from quantum mechanics we derive analytical results for the frequently observed case of asymmetric environmental response curves. We derive expressions in terms of parameters representing climate velocity, dispersal rate, maximum growth rate, niche width, high-frequency climate variability and environmental performance curve skew for three key responses: 1) population persistence, 2) lag between range displacement and climate displacement, 3) location of maximum population sensitivity. Surprisingly, under our model assumptions, the direction of performance curve asymmetry does not strongly contribute to either persistence or lags. Conservation measures to support range-shifting populations may have most benefit near their environmental optimum or where the environmental dependence is shallow, irrespective of whether this is the ‘leading’ or ‘trailing’ edge. A metapopulation simulation corroborates our results.
Host-specific plasmid evolution explains the variable spread of clinical antibiotic-resistance plasmids

Antibiotic resistance encoded on plasmids is a pressing global health problem. Predicting which plasmids spread/decline in the long term remains a huge challenge, even though some key parameters influencing plasmid stability have been identified, such as plasmid growth costs and horizontal transfer rates. Here, we show these parameters evolve in a strain-specific way among clinical plasmids/bacteria, and this occurs rapidly enough to alter the relative likelihoods of different bacterium-plasmid combinations spreading/declining. We used experiments with Escherichia coli and antibiotic-resistance plasmids isolated from patients, paired with a mathematical model, to show long-term plasmid stability (beyond antibiotic exposure) was better explained by evolutionary changes in plasmid-stability traits than by initial variation among bacterium-plasmid combinations. Evolutionary trajectories were specific to particular bacterium-plasmid combinations. Genome sequencing and genetic manipulation helped explain this, revealing epistatic (here, strain-dependent) effects of key genetic changes affecting horizontal plasmid transfer. Several genetic changes involved mobile elements and pathogenicity islands. Rapid strain-specific evolution can thus outweigh ancestral phenotypes as a predictor of plasmid stability. Accounting for strain-specific plasmid evolution in natural populations could improve our ability to anticipate and manage successful bacterium-plasmid combinations.
Genetic diversity in global populations of the critically endangered addax (Addax nasomaculatus) and its implications for conservation

Threatened species are frequently patchily distributed across small wild populations, ex situ populations managed with varying levels of intensity, and reintroduced populations. Best practice advocates for integrated management across in situ and ex situ populations. Wild addax (Addax nasomaculatus) now number fewer than 100 individuals, yet thousands of addax remain in ex situ populations, which can provide addax for reintroductions, as has been the case in Tunisia in the mid-1980s. However, integrated management requires genetic data to ascertain the relationships between wild and ex situ populations that have incomplete knowledge of founder origins, management histories and pedigrees. We undertook a global assessment of genetic diversity across wild, ex situ, and reintroduced populations in Tunisia to assist conservation planning for this Critically Endangered species. We show that the remnant wild populations retain more mitochondrial haplotypes which are more evolutionarily diverse than the entirety of the ex situ populations across Europe, North America and the United Arab Emirates, and the reintroduced Tunisian population. Additionally, 1704 SNPs revealed that whilst population structure within the ex situ population is minimal, each population carries unique diversity. Finally, we show that careful selection of founders and subsequent genetic management is vital to ensure genetic diversity is provided to, and minimise drift and inbreeding within, reintroductions. Our results highlight a vital need to conserve the last remaining wild addax population, and we provide a genetic foundation for determining integrated conservation strategies to prevent extinction and optimise future reintroductions.
Communication dynamics in the human connectome shape the cortex-wide propagation of direct electrical stimulation

Communication between gray matter regions underpins all facets of brain function. To date, progress in understanding large-scale neural communication has been hampered by the inability of current neuroimaging techniques to track signaling at whole-brain, high-spatiotemporal resolution. Here, we use 2.77 million intracranial EEG recordings, acquired following 29,055 single-pulse electrical stimulations in a total of 550 individuals, to study inter-areal communication in the human brain. We found that network communication models—computed on structural connectivity inferred from diffusion MRI—can explain the propagation of direct, focal electrical stimulation through white matter, measured at millisecond time scales. Building on this finding, we show that a parsimonious statistical model comprising structural, functional and spatial factors can accurately and robustly predict cortex-wide effects of brain stimulation (out-of-sample R2=54%). Our work contributes towards the biological validation of concepts in network neuroscience and provides insight into how white matter connectivity shapes inter-areal signaling. We anticipate that our findings will have implications for research on macroscale neural information processing and the design of brain stimulation paradigms.
CHCHD2 mediates glioblastoma cell proliferation, mitochondrial metabolism, hypoxia-induced invasion and therapeutic resistance

Glioblastoma (GBM) is the most common and malignant primary brain tumor in adults and remains incurable. The mitochondrial coiled-coil-helix-coiled-coil-helix domain-containing protein 2 (CHCHD2) is demonstrated to mediate mitochondrial respiration, nuclear gene expression, and cell migration, but evidence of this in GBM is lacking. We hypothesized that CHCHD2 would serve a functional role in U87 GBM cells expressing the constitutively active epidermal growth factor receptor variant III (EGFRvIII). Amplification of the CHCHD2 gene was found to be associated with decreased patient overall survival and progression-free survival. CHCHD2 mRNA levels were increased in high-versus low-grade glioma, IDH-wt GBMs, and in tumor versus non-tumor tissue. Additionally, CHCHD2 protein expression was greatest in invasive, EGFRvIII-expressing patient-derived samples. CRISPR-Cas9-mediated knockout of CHCHD2 in EGFRvIII-expressing U87 cells resulted in altered mitochondrial respiration and glutathione status, decreased cell growth and invasion in both normoxia and hypoxia, and increased sensitivity to cytotoxic agents. CHCHD2 was distributed in both mitochondria and nuclei of U87 and U87vIII cells, and U87vIII displayed greater nuclear CHCHD2 compared to isogenic U87 cells. Incubation in hypoxia, serum starvation, and reductive unfolding of CHCHD2 induced nuclear accumulation of CHCHD2 in both cell lines. Collectively, these data indicate that CHCHD2 mediates a variety of GBM cell hallmark characteristics and highlights mitonuclear retrograde signaling as a pathway of interest in GBM cell biology. Implications These data demonstrate CHCHD2 as a mediator of a number of GBM cell functions representing disease hallmarks, as well as highlight its subcellular distribution in response to metabolic stressors. These results may inspire therapeutic strategies undermining mitochondrial biology to potentially improve GBM tumor management.
Cyclic AMP is a critical mediator of intrinsic drug resistance and fatty acid metabolism in M. tuberculosis

Cyclic AMP (cAMP) is a ubiquitous second messenger that transduces signals from cellular receptors to downstream effectors. Mycobacterium tuberculosis (Mtb), the etiological agent of tuberculosis, devotes a considerable amount of coding capacity to produce, sense, and degrade cAMP. Despite this fact, our understanding of how cAMP regulates Mtb physiology remains limited. Here, we took a genetic approach to investigate the function of the sole essential adenylate cyclase in Mtb H37Rv, Rv3645. We found that lack of rv3645 resulted in increased sensitivity to numerous antibiotics by a mechanism independent of substantial increases in envelope permeability. We made the unexpected observation that rv3645 is conditionally essential for Mtb growth only in the presence of long-chain fatty acids, a host-relevant carbon source. A suppressor screen further identified mutations in the atypical cAMP phosphodiesterase rv1339 that suppress both fatty-acid and drug sensitivity phenotypes in strains lacking rv3645. Using mass spectrometry, we found that Rv3645 is the dominant source of cAMP under standard laboratory growth conditions, that cAMP production is the essential function of Rv3645 in the presence of long-chain fatty acids, and that reduced levels of cAMP result in increased antibiotic susceptibility. Our work defines rv3645 and cAMP as central mediators of intrinsic multidrug resistance and fatty acid metabolism in Mtb and highlights the potential utility of small molecule modulators of cAMP signaling.
Flavor Classification/Categorization and Differential Toxicity of Oral Nicotine Pouches (ONPs) in Lung Epithelial Cells

The prevalence of flavored tobacco product usage amongst youth in the United States is partly due to the emergence of non-combustible nicotine-containing products (NCNPs), including oral nicotine pouches (ONPs) and smokeless tobacco products. ONPs are available in various different flavors (mint, fruity, tobacco, dessert, citrus, coffee, wintergreen, and berry) and may use either Tobacco-Derived Nicotine (TDN) or Tobacco-Free Nicotine (TFN). Currently, several brands of ONPs are sold in the U.S and comprise a significant portion of NCNP sales in the U.S. There is a growing concern that flavored ONPs may not only induce oral health effects, but may also induce systemic toxic effects due to nicotine and other ONP byproducts being absorbed into systemic circulation through the oral mucosa. These byproducts can act locally on other tissues and may potentially cause redox dysregulation and heightened inflammatory responses systemically in the respiratory, cardiovascular, and/or renal systems. Hence, we determined the effects of flavored ONPs from four of the most widely sold brands in the U.S in inducing toxicological effects on the respiratory epithelium. Prior to analyzing the effects ONPs, we first classified ONPs sold in the US based on their flavor and the flavor category to which they belong to using a wheel diagram. Subsequently, using human bronchial epithelial cells (16-HBE and BEAS-2B) exposed to extracts of flavored ONPs, we assessed the levels of ONP-induced inflammatory cytokine release (IL-6 and IL-8), cellular Reactive Oxygen Species (ROS) production, and cytotoxicity in the airway epithelium. Our data showed that cells exposed to the lowest concentration treatments showed increased cytotoxicity, differential cellular ROS production, and proinflammatory cytokine release. The most striking response was observed among cells treated with the spearmint ONP, whereas ONPs containing original tobacco and fruity flavors showed varied levels of ROS release in 16-HBE cells. Our data suggest that flavored ONPs are unsafe and likely to cause systemic and local toxicological responses during chronic usage. Our study is a part of ongoing efforts to use in vitro, ex-vivo, and in vivo systems to understand how the usage of various flavored ONPs may cause both oral and pulmonary toxicity, and impact human periodontal health.
On the automaticity of visual statistical learning

Humans can extract regularities from their environment, enabling them to recognize and predict sequences of events. The process of regularity extraction is called ‘statistical learning’ and is generally thought to occur rapidly and automatically; that is, regularities are extracted from repeated stimulus presentations, without intent or awareness, as long as the stimuli are attended. We hypothesized that visual statistical learning is not entirely automatic, even when stimuli are attended, and that the learning depends on the extent to which viewers process the relationships between stimuli. To test this, we measured statistical learning performance across seven conditions in which participants (N=774) viewed image sequences. As task instructions across conditions increasingly required participants to attend to relationships between stimuli, their learning performance increased from chance to robust levels. We conclude that the learning observed in visual statistical learning paradigms is, for the most part, not automatic and requires more than passively attending to stimuli.
Common Neural Mechanisms Control Attention and Working Memory

Although previous studies point to qualitative similarities between working memory (WM) and attention, the degree to which these two constructs rely on shared neural mechanisms remains unknown. Focusing on one such potentially shared mechanism, we tested the hypothesis that selecting an item within WM utilizes similar neural mechanisms as selecting a visible item via a shift of attention. We used fMRI and machine learning to decode both the selection among items visually available and the selection among items stored in WM in human subjects (both sexes). Patterns of activity in visual, parietal, and to a lesser extent frontal cortex predicted the locations of the selected items. Critically, these patterns were strikingly interchangeable; classifiers trained on data during attentional selection predicted selection from WM, and classifiers trained on data during selection from memory predicted attentional selection. Using models of voxel receptive fields, we visualized topographic population activity that revealed gain enhancements at the locations of the externally and internally selected items. Our results suggest that selecting among perceived items and selecting among items in WM share a common mechanism. This common mechanism, analogous to a shift of spatial attention, controls the relative gains of neural populations that encode behaviorally relevant information. SIGNIFICANCE STATEMENT How we allocate our attention to external stimuli that we see and to internal representations of stimuli stored in memory might rely on a common mechanism. Supporting this hypothesis, we demonstrated that not only could patterns of human brain activity predict which items were selected during perception and memory, but that these patterns were interchangeable during external and internal selection. Additionally, this generalized selection mechanism operates by changes in the gains of the neural populations both encoding attended sensory representations and storing relevant memory representations.
Characterizing the Dependence on Non-timber Forest Products Among Communities Living Around Forest Conservation Areas in Marrupa-Mecula Corridor, Niassa Special Reserve, Niassa Province of Mozambique

The role of forests across the world has been recognized as key natural assets that offer several goods and services, especially to communities adjacent to them. Given this role, there have been minimal efforts to determine the factors characterizing this dependence of communities on non-timber forest products (NTFPs), especially in developing nations. This study surveyed and assessed different factors influencing household dependence on NTFPs in the Marrupa-Mecula Corridor, Niassa Special Reserve, Niassa Province of Mozambique. In total, 377 household members from eight villages attended the interview while employing proportional random sampling. Data analysis was done using descriptive statistics and binary logistic regression. The study revealed that 90.9% of the households participate in collecting, producing, and selling NTFPs. Three factors, namely, social, economic, and physical, with twenty sub-factors or characteristics were found to have a significant association with dependence on forest resources. They include the availability of NTFPs, taking a collection of NTFPs as a family job, strong cultural attachment to forests, seasonal engagement in collection, nearby forests being home for community leaders, distance to the nearby forest, the housing needs of forests, forests being a major source of medicine, forests being a resource for educational institutions, forests being a major source of household food security, forests being a ready income for households, forests being a tourist attraction in the area, and affordability of distance to markets. The binary logistic regression revealed that gender, age, education, family size, and time spent in the area are significantly associated with dependence on NTFPs. Additionally, strong cultural attachment to forests, seasonal engagement in collection, nearby forests being homes for community leaders, distance to the nearby forest, housing needs, a major source of medicine, education, household food security, ready income, tourist attraction, and affordability of distance to markets were found to have a significant influence. On the contrary, scary dangerous wild animals, restriction of cultivation in non-gazetted forests, restriction of hunting in non-gazetted forests, and forest fires negatively affected the dependence on NTFPs/resources. As a way of achieving sustainable utilization of NTFPs, management plans and strategies need to incorporate these factors characterizing the dependence on NTFPs.
Pathogen Filtration: An Untapped Ecosystem Service

Marine pathogens present serious challenges to aquaculture, fisheries productivity, and marine conservation requiring novel solutions to identify, control, and mitigate their effects. Several ecological habitats, such as mangroves and wetlands can recycle waste and serve as aquatic filtration systems. While nutrient cycling and other ecosystem services of these habitats have been well-studied, their potential to remove pathogens and mechanisms of filtration remain largely unstudied. Here, we review how mangroves, shellfish beds, seagrasses, and constructed wetlands can reduce pathogen pressure in coastal ecosystems. Mangroves may inhibit bacterial growth through phytochemicals in their leaves and remove viruses through desalination in their roots. Some bivalves remove pathogens by excreting pathogens through their pseudofeces and others concentrate pathogens within their tissues. Seagrasses slow flow rates, increase sedimentation rates and may reduce pathogens through allelopathy. Constructed wetlands decrease pathogens through a combination of mechanical, biological, and chemical filtration mechanisms. Protecting and restoring coastal ecosystems is key to maintaining pathogen filtration capacity, benefiting conservation efforts of threatened host populations, and mitigating large disease outbreaks.
Prefrontal Dopaminergic Regulation of Cue-Guided Risky Decision-Making Performance in Rats

Risky decision-making is the decision made by individuals when they know the probability of each outcome. In order to survive in unpredictable environments, it is necessary for individuals to assess the probability of events occurring to an make appropriate decisions. There are few studies on the neural basis of risky decision-making behavior guided by external cues, which is related to the relative paucity of animal behavioral paradigms. Previous studies have shown that the prefrontal cortex (PFC) plays a key role in risk-based decision-making. The PFC receives projections from the dopamine (DA) system from the ventral tegmental area of the midbrain. The mesocorticolimbic DA system regulates the judgments of reward and value in decision-making. However, the specific receptor mechanism for prefrontal DA regulation of cue-guided risky decision-making behavior remains unclear. Here we established a cue-guided risky decision-making behavioral paradigm (RDM task) to detect the behavior of rats making decisions between a small certain reward and a large uncertain reward in a self-paced manner. The D1 receptor antagonist SCH-23390 (5 mM) or agonist SKF-82958 (5 mM), and the D2 receptor antagonist thioridazine hydrochloride (5 mM) or agonist MLS-1547 (5 mM) was injected into the mPFC, respectively, to investigate how the behavior in the RDM task was changed. The results showed that: (1) rats were able to master the operation of the cue-guided RDM task in a self-paced way; (2) a majority of rats were inclined to choose risk rather than a safe option when the reward expectations were equal; and (3) risk selection was reduced upon inhibition of D1 receptors or stimulation of D2 receptors, but increased upon stimulation of D1 receptors or inhibition of D2 receptors, suggesting that the RDM performance is regulated by D1 and D2 receptors in the mPFC. The present results suggest that DA receptors in the mPFC of rats are involved in regulating cue-guided RDM behavior, with differential involvement of D1 and D2 receptors in the regulation.
Nitrogen Leaching From Agricultural Soils Under Imposed Freeze-Thaw Cycles: A Column Study With and Without Fertilizer Amendment

Cold regions are warming faster than the rest of the planet, with the greatest warming occurring during the winter and shoulder seasons. Warmer winters are further predicted to result in more frequent soil freezing and thawing events. Freeze-thaw cycles affect biogeochemical soil processes and alter carbon and nutrient export from soils, hence impacting receiving ground and surface waters. Cold region agricultural management should therefore consider the possible effects on water quality of changing soil freeze-thaw dynamics under future climate conditions. In this study, soil column experiments were conducted to assess the leaching of fertilizer nitrogen (N) from an agricultural soil during the non-growing season. Identical time series temperature and precipitation were imposed to four parallel soil columns, two of which had received fertilizer amendments, the two others not. A 15-30-15 N-P-K fertilizer (5.8% ammonium and 9.2% urea) was used for fertilizer amendments. Leachates from the soil columns were collected and analyzed for major cations and anions. The results show that thawing following freezing caused significant export of chloride (Cl−), sulfate (SO4 2−) and nitrate (NO3 −) from the fertilizer-amended soils. Simple plug flow reactor model calculations indicated that the high NO3 − concentrations produced during the fertilized soil thawing events were due to nitrification of fertilizer N in the upper oxidized portion of the soil. The very low concentrations of NO3 − and ammonium in the non-fertilized soils leachates implied that the freeze-thaw cycles had little impact on the mineralization of soil organic N. The findings, while preliminary, indicate that unwanted N enrichment of aquifers and rivers in agricultural areas caused by fall application of N fertilizers may be exacerbated by changing freeze-thaw activity.