Miracle-dz/UniFAR-FTUs huggingface dataset:
Polar growth protein Wag31 undergoes changes in homo-oligomeric network topology, and has distinct functions at both cell poles and the septum

Mycobacterial cell elongation occurs at the cell poles; however, it is not clear how cell wall insertion is restricted to the pole and organized. Wag31 is a pole-localized cytoplasmic protein that is essential for polar growth, but its molecular function has not been described. Wag31 homo-oligomerizes in a network at the poles, but it is not known how the structure of this network affects Wag31 function. In this study we used a protein fragment complementation assay to identify Wag31 residues involved in homo-oligomeric interactions, and found that amino acids all along the length of the protein mediate these interactions. We then used both N-terminal and C-terminal splitGFP fusions to probe Wag31 network topology at different sites in the cell, and found that Wag31 C-terminal-C-terminal interactions predominate at the septa, while C-terminal-C-terminal and C-terminal-N-terminal interactions are found equally at the poles. This suggests the Wag31 network is formed through an ordered series of associations. We then dissected Wag31’s functional roles by phenotyping a series of wag31 alanine mutants; these data show that Wag31 has separate functions in not only new and old pole elongation, but also inhibition of both septation and new pole elongation. This work establishes new functions for Wag31, and indicates that changes in Wag31 homo-oligomeric network topology may contribute to cell wall regulation in mycobacteria. Importance Many bacteria restrict cell wall elongation to their cell poles, but it is not known how polar growth is affected on the molecular level. Wag31 is a protein that is required for this polar elongation. In this work, we show that Wag31 actually has at least four distinct functions in regulating the cell wall: it promotes elongation at both poles in different ways, and it can also inhibit cell wall metabolism at the new pole and the septum. In addition, we propose a new model for how Wag31 self-associates into a protein network. This work is important because it shows that a DivIVA homolog can have distinct functions depending on cell context. And, this work clarifies that Wag31 is doing several different things in the cell, and gives us genetic tools to disentangle its functions.
Conserved cell‐type specific signature of resilience to Alzheimer’s disease nominates role for excitatory cortical neurons

Alzheimer’s disease (AD), the leading cause of dementia, affects millions of people worldwide. With no disease‐modifying medication currently available, the human toll and economic costs are rising rapidly. Under current standards, a patient is diagnosed with AD when both cognitive decline and pathology (amyloid plaques and neurofibrillary tangles) are present. Remarkably, some individuals who have AD pathology remain cognitively normal. Uncovering factors that lead to “cognitive resilience” to AD is a promising path to create new targets for therapies. However, technical challenges discovering novel human resilience factors limit testing, validation, and nomination of novel drugs for AD.
3’ RNA sequencing does not increase power or reduce costs for gene expression analysis

Background Sequencing RNA transcripts for gene expression profiling is a popular and important technique with broad utility in biological sciences. We set out to comprehensively compare the two most popular methods for generating sequencing libraries for differential gene expression analysis: 3-end sequencing, which generates libraries from the 3’ end of an RNA transcript; and traditional RNA sequencing, which generates libraries from whole RNA transcripts. We include three species in our experiment to test whether our findings replicate across genomes and genome assemblies. Results We found similar levels of precision and power to detect differentially expressed genes between the two methods. Notably, whole transcript RNA-seq performed better in the non-traditional model species included in our study. Conclusion Overall, we recommended whole transcript RNA sequencing for the added benefits of alternative splicing detection, and gene-body variant detection.
The Binding of Different Substrate Molecules at the Docking Site and the Active Site of γ-Secretase Can Trigger Toxic Events in Sporadic and Familial Alzheimer’s Disease

Significance pathogenic changes in γ-secretase activity, and its response to different drugs, can be greatly affected by changes in saturation of γ-secretase with its substrate. The molecular mechanism is unclear. Results multiscale molecular dynamics studies show that saturation of γ-secretase with its substrate can result in parallel binding of different substrate molecules at the docking site and the active site. C-terminal domain of the second substrate can bind at cytosolic end of presenilin subunit while γ-secretase is still processing its first substrate. Such interactions can disrupt dynamic presenilin structures that regulate proteolytic steps. Similar disruptions in dynamic presenilin structures can be produced by different drugs and by different disease-causing mutations. Thus, the presented two-substrate mechanism, can explain toxic inhibition of γ-secretase activity and toxic increase in production of the longer, more hydrophobic, Aβ-proteins. Toxic aggregation between N-terminal domains of the two substrates is controlled by nicastrin ectodomain. Such aggregation is more likely to happen with C99-βCTF-APP than with C83-αCTF-APP substrate, which can explain, why β-secretase path is more pathogenic than α-secretase path. The binding of C99-βCTF-APP substrate to γ-secretase can be controlled by substrate-channeling between nicastrin ectodomain and β-secretase. Conclusions The presented two-substrate mechanism can explain why different studies consistently show that increase in saturation of γ-secretase with its substrate can support pathogenic changes in different sporadic and familiar cases of the disease. Future drug-development strategies can target different physiological mechanisms that control the balance between cellular levels of γ-secretase activity and the total amyloid metabolism.
Similarity-Based Multimodal Regression

To better understand complex human phenotypes, large-scale studies have increasingly collected multiple data modalities across domains such as imaging, mobile health, and physical activity. The properties of each data type often differ substantially and require either separate analyses or extensive processing to obtain comparable features for a combined analysis. Multimodal data fusion enables certain analyses on matrix-valued and vector-valued data, but it generally cannot integrate modalities of different dimensions and data structures. For a single data modality, multivariate distance matrix regression provides a distance-based framework for regression accommodating a wide range of data types. However, no distancebased method exists to handle multiple complementary types of data. We propose a novel distance-based regression model, which we refer to as Similarity-based Multimodal Regression (SiMMR), that enables simultaneous regression of multiple modalities through their distance profiles. We demonstrate through simulation, imaging studies, and longitudinal mobile health analyses that our proposed method can detect associations in multimodal data of differing properties and dimensionalities, even with modest sample sizes. We perform experiments to evaluate several different test statistics and provide recommendations for applying our method across a broad range of scenarios.
Genotype-dependent responses to long-term water stress in Chenopodium quinoa Willd

Within the current climate context, freshwater resources have become scarce. Agriculture, especially in rain-fed conditions, should deal with the need for increasing yields to contribute to food security under limiting water availability. Exploring underutilized crops such as Chenopodium quinoa (quinoa) has become a unique opportunity as some of these crops possess the ability to tolerate several abiotic stresses, including drought. In line with this, this work aimed at evaluating the genotype-dependent response to drought by comparing the performance of different European-adapted cultivars (F14, F15, F16, and Titicaca). The results show that the cultivars here evaluated presented different mechanisms to cope with long-term water stress, including changes in phenology, morphology, or physiology. Among them, the cultivar F16 might be the most promising genotype to grow under water-limiting conditions as it was able to increase Water Use Efficiency (WUE), reducing the stomatal conductance and keeping CO2 assimilation rates similar to well-watered conditions, maintaining seed yield and increasing harvest index (HI) under water deficit conditions. Furthermore, based on these results, we propose a model in which differences between a tolerant and a sensitive genotype are presented. Altogether, we believe that this work will significantly contribute to broadening our understanding regarding how quinoa responds to long-term water stress highlighting genotype-related differences that will allow the selection of the best adapted genotypes for water-limiting environments. Highlight Quinoa physiological, phenological, and morphological distinct responses to long-term water stress depending on the genotype.
Integrated AlphaFold2 and DEER investigation of the conformational dynamics of a pH-dependent APC antiporter

The Amino Acid-Polyamine-Organocation transporter GadC contributes to the survival of pathogenic bacteria under extreme acid stress by exchanging extracellular glutamate for intracellular GABA. Its structure, determined exclusively in an inward-facing conformation at alkaline pH, consists of the canonical LeuT-fold of a conserved five-helix inverted repeat, thereby resembling functionally divergent transporters such as the serotonin reuptake transporter SERT and the glucose-sodium symporter transporter SGLT1. However, despite this structural similarity, it is unclear if the conformational dynamics of antiporters such as GadC follows the blueprint of these or other well-studied LeuT-fold transporters. Here, we used double electron-electron resonance (DEER) spectroscopy to monitor the conformational dynamics of GadC in lipid bilayers in response to acidification and substrate binding. To guide experimental design and facilitate the interpretation of the DEER data, we generated an ensemble of structural models in multiple conformations using a recently introduced AlphaFold2 methodology. Our experimental results reveal acid-induced conformational changes that dislodge the C-terminus from the permeation pathway coupled with rearrangement of helices that enable isomerization between both inward- and outward-facing states. The substrate glutamate, but not GABA, modulates the dynamics of an extracellular thin gate without shifting the equilibrium between inward- and outward-facing conformations. In addition to introducing an integrated methodology for probing transporter conformational dynamics, the congruence of the DEER data with patterns of structural rearrangements deduced from ensembles of AlphaFold2 models illuminate the conformational cycle of GadC underpinning transport and exposes yet another example of the divergence between the dynamics of different functional families in the LeuT-fold. SIGNIFICANCE STATEMENT The transporter GadC contributes to acid resistance in bacterial pathogens by exchanging two substrates, glutamate and GABA, using a mechanism termed alternating access. In this study, the conformational dynamics underlying alternating access was studied using a combination of spectroscopy and computational modeling. A conformationally diverse ensemble of models, generated using AlphaFold2, guided the design and interpretation of double electron-electron resonance spectroscopy experiments. We found that whereas GadC was inactive and conformationally homogeneous at neutral pH, low pH induced isomerization between two conformations. From our integrated computational/experimental investigation emerges a transport model that may be relevant to eukaryotic homologs that are involved in other cellular processes.
Prevalent Stressors Found Among Collegiate and Elite Coaches

Recent studies have explored the stress that individuals experience in the coaching profession. Stress can have negative effects on an individual physically, mentally, and emotionally. The impact that stress has on a coach can directly influence the anxiety and performance of their athletes. The purpose of this study was to identify and prioritize stressors found in the literature. The prevalence of these stressors was then used to recommend coping techniques to help coaches reduce the impact that coaches experience. A total of 10 studies were analyzed for this synthesis. Results found seven prevalent stressors. The seven prevalent stressors found in the literature were performance, resources, many roles and responsibilities, athletes, assistant coaches, and self-imposed demands. Based on the stressors identified, four different types of coping techniques were recommended for coaches to use. The recommended coping techniques for these stressors were mindfulness training, self-talk, goal setting, and dyadic coping.
from ready-to-drink tea Bioavailability of catechins from ready-to-drink tea. Identification of flavan-3-ols and their metabolites in urine.

24 Objective: As consumption of teas may be associated with potential health benefits due to its 25 content in polyphenols and as in Western countries the consumption of tea is equally divided 26 between the hot and the ready-to-drink (RTD) cold version of this typical beverage, aim of this 27 work is studying absorption and metabolism of flavan-3-ols in human volunteers after the ingestion 28 of a commercial RTD tea. 29 Research Methods & Procedures: A feeding study was carried out on 20 healthy human 30 volunteers and urine samples were collected for 24 hours after tea ingestion. Flavan-3-ols derived 31 molecules were identified and quantified in urine samples by HPLC with tandem mass 32 spectrometric detection. 33 Results: Eight relevant metabolites were identified in urine, all modified flavan-3-ols with the 34 exception of unmetabolised gallic acid. The urinary excretion of flavan-3-ols was equal to the 7.2% 35 of the intake with tea. Gallic acid, which was abundant in the RTD tea used in this study, reached a 36 4.5% of the drunk amount. 37 Conclusions: The bioavailability values observed are in agreement with previous reports even 38 though the dosage of polyphenols ingested in this study is remarkably lower. Moreover, the use of a 39 group of twenty volunteers, more than the average number of subjects used for usual human acute 40 feeding studies involving polyphenols, gives additional credibility to the results. After drinking the 41 ready-to-drink ice tea used in this study, the internal compartments are exposed to non-marginal 42 doses of flavanols and flavanol metabolites up to 24 hours. 43 44 This paper reports on absorption and metabolism of flavan-3-ols in 20 healthy human volunteers after the ingestion of 500 mL of a commercial RTD tea. The work was performed by analysing flavan-3-ols and their metabolites in urine samples collected over 4 periods in 24 h after 86 intake. Catechin metabolites were identified by HPLC-MS/MS and subsequently quantified using HPLC with MS in the selective ion recording (SIR) mode.
Energy-Efficient System Design for Future Wireless Communications

The exponential growth of wireless data traffic has caused a significant increase in the power consumption of wireless communications systems due to the higher complexity of the transceiver structures required to establish the communication links. For this reason, in this Thesis we propose and characterize technologies for improving the energy efficiency of multiple-antenna wireless communications. This Thesis firstly focuses on energy-efficient transmission schemes and commences by introducing a scheme for alleviating the power loss experienced by the Tomlinson-Harashima precoder, by aligning the interference of a number of users with the symbols to transmit. Subsequently, a strategy for improving the performance of space shift keying transmission via symbol pre-scaling is presented. This scheme re-formulates complex optimization problems via semidefinite relaxation to yield problem formulations that can be efficiently solved. In a similar line, this Thesis designs a signal detection scheme based on compressive sensing to improve the energy efficiency of spatial modulation systems in multiple access channels. The proposed technique relies on exploiting the particular structure and sparsity that spatial modulation systems inherently possess to enhance performance. This Thesis also presents research carried out with the aim of reducing the hardware complexity and associated power consumption of large scale multiple-antenna base stations. In this context, the employment of incomplete channel state information is proposed to achieve the above-mentioned objective in correlated communication channels. The candidate’s work developed in Bell Labs is also presented, where the feasibility of simplified hardware architectures for massive antenna systems is assessed with real channel measurements. Moreover, a strategy for reducing the hardware complexity of antenna selection schemes by simplifying the design of the switching procedure is also analyzed. Overall, extensive theoretical and simulation results support the improved energy efficiency and complexity of the proposed schemes, towards green wireless communications systems.
Impact of tie strength on knowledge sharing: Focusing on the moderating effect of environmental uncertainty

This study aims to investigate how tie strength in business networks affects successful knowledge sharing, as well as the impact of environmental uncertainty on the relationship between knowledge sharing and tie strength. We gathered data through a questionnaire-based survey of 310 employees affiliated with a high-technology industry in Korea. The results highlighted the positive influence of strong ties on tacit knowledge sharing and weak ties on explicit knowledge sharing. Additionally, in this study, we determine that strong ties are strengthened to share tacit knowledge with exchange parties when environmental uncertainty is high, whereas weak ties may remain unaffected by environmental uncertainty. This study contributes to the literature on tie strength and knowledge sharing by applying social capital theory to a high-technology industry. The findings suggest that firms must take advantage of strong and weak ties to facilitate knowledge sharing to enhance competency, create novel knowledge, and obtain a competitive advantage.
UvA-DARE The new Dutch timetable: The OR revolution

which was constructed in 1970, were not an option; additional growth would require signiﬁcant investments in the rail infrastructure.Constructingarailway timetable from scratch for about 5,500 daily trains was a complex problem. To support this process, we generated several timetables using sophisticated operations research techniques. Furthermore, because rolling-stock and crew costs are principal components of the costs of a passenger railway operator, we used innovative operations research tools to devise efﬁcient schedules for these two resources. The new resource schedules and the increased number of passengers resulted in an additional annual proﬁt of E 40 million ($60 million); the additional revenues generated approximately E 10 million of this proﬁt. We expect this proﬁt to increase to E 70 million ($105 million) annually in the coming years. However, the beneﬁts of the new timetable for the Dutch society as a whole are much greater: more trains are transporting more passengers on the same railway infrastructure, and these trains are arriving and departing on schedule more than they ever have in the past. In addition, the rail transport system will be able to handle future transportation demand growth and thus allow cities to remain accessible to more people. Therefore, we expect that many will switch from car transport to rail transport, thus reducing the emission of greenhouse gases.
Molecular Dynamics Simulation and Cryo-Electron Microscopy Investigation of AOT Surfactant Structure at the Hydrated Mica Surface

Structural properties of the anionic surfactant dioctyl sodium sulfosuccinate (AOT or Aerosol-OT) adsorbed on the mica surface were investigated by molecular dynamics simulation, including the effect of surface loading in the presence of monovalent and divalent cations. The simulations confirmed recent neutron reflectivity experiments that revealed the binding of anionic surfactant to the negatively charged surface via adsorbed cations. At low loading, cylindrical micelles formed on the surface, with sulfate head groups bound to the surface by water molecules or adsorbed cations. Cation bridging was observed in the presence of weakly hydrating monovalent cations, while sulfate groups interacted with strongly hydrating divalent cations through water bridges. The adsorbed micelle structure was confirmed experimentally with cryogenic electronic microscopy, which revealed micelles approximately 2 nm in diameter at the basal surface. At higher AOT loading, the simulations reveal adsorbed bilayers with similar surface binding mechanisms. Adsorbed micelles were slightly thicker (2.2–3.0 nm) than the corresponding bilayers (2.0–2.4 nm). Upon heating the low loading systems from 300 K to 350 K, the adsorbed micelles transformed to a more planar configuration resembling bilayers. The driving force for this transition is an increase in the number of sulfate head groups interacting directly with adsorbed cations.
EDUCATION OF RURAL SOCIETY INFLUENCES GREEN BEHAVIOR IN DISPOSING FOOD PACKAGING

Green consumer behavior avoids using the products that have a negative impact on human health and the environment. The study aimed to analyze the consumer’s attitudes, choice, and disposal behaviour of the food packaging. These analysis compared the society based on their education, both on rural and urban societies. Data were collected from Desa Sidodadi (rural) at Ngantang Subdistrict and Kelurahan Tunggulwulung (urban) at Lowokwaru Subdistrict, both places are parts of Malang Regency, East Java, Indonesia. The Mann-Whitney test was used to compare all indicators between higher and lower education. The results showed that the three indicators (attitude, packaging choice and disposal behavior) were significantly different between higher and lower education on rural society. Meanwhile, they were not significantly different on the urban society. The majority of people in rural and urban areas show a good response in protecting the environment. Such condition represented that the consumption activities have considered the environmental sustainability. Therefore, the business activities also should comprihend green consumers. Food producers have to developt green food products and the green packaging, while government should developt society to become more environmentally friendly and minimize waste.