julilili42/papers huggingface dataset:
Conformations and Rearrangements of Collinolactone – Experiments and Theory on a Dynamic Cyclodecatriene
2023-12-05

Abstract Collinolactone A is a microbial specialized metabolite with a unique 6‐10‐7 tricyclic bislactone skeleton which was isolated from Streptomyces bacteria. The unusual cyclodecatriene motif features dynamic interconversions of two rotamers. Given the biological profiling of collinolactone A as neuroprotective agent, semisynthetic modifications represent an invaluable strategy to enhance its efficacy. Since understanding conformations and reactions of bioactive substances is crucial for rational structure‐based design and synthesis of derivatives, we conducted computational studies on conformational behavior as well as experiments on thermal and acid induced rearrangements of the cyclodecatriene. Experimental conformer ratios of collinolactone A and its biosynthetic ketolactone precursor are well reproduced by computations at the PW6B95‐D3/def2‐QZVPP//r 2 SCAN‐3c level. Upon heating collinolactone A in anhydrous dioxane at 100 °C, three collinolactone B stereoisomers exhibiting enollactone structures form via Cope rearrangements. Our computations predict the energetic preference for a boat‐like transition state in agreement with the stereochemical outcome of the main reaction pathway. Constriction of the ten‐membered ring forms collinolactone C with four annulated rings and an exocyclic double bond. Computations and semisynthetic experiments demonstrate strong preference for an acid‐catalyzed reaction pathway over an alternative Alder‐ene route to collinolactone C with a prohibitive reaction barrier, again in line with stereochemical observations.
Contextual numismatics: a post-processual approach illustrated by application to Roman coins
2023-12-05

Abstract In this paper, ‘contextual numismatics’ is presented as the most recent and innovative research direction in the field of numismatics. In addition, its further potential for research and the limit of gaining knowledge are outlined. A historical overview of the gradual development of an archaeological-oriented approach to numismatic material serves as an introduction to the discussion. This is followed by a presentation of the distinguishing features compared to other research methods to study Roman coin finds, as well as a discussion of possible paths and goals in the further development of this approach to study these culturally significant objects.
Postural control deficits due to bilateral pyramidal tract lesions exemplified by hereditary spastic paraplegia (HSP) originate from increased feedback time delay and reduced long-term error corrections
2023-12-05

Pyramidal tract lesions determine the clinical syndrome of Hereditary Spastic Paraplegia (HSP). The clinical impairments of HSP are typically exemplified by their deficits in mobility, leading to falls and injuries. The first aim of this study was to identify the cause for postural abnormalities caused by pyramidal tract lesions in HSP. The second aim was to specify the effect of treadmill training for postural abnormalities. We examined nine HSP patients before and after treadmill training, as well as nine healthy control subjects during perturbed and unperturbed stance. We found that HSP was associated with larger sway amplitudes and velocities. Body excursions following platform tilts were larger, and upper body excursions showed a phase lead. Model-based analysis detected a greater time delay and a reduced long-term error correction of postural reactions in the center of mass. HSP patients performed significantly better in clinical assessments after treadmill training. In addition, treadmill training reduced sway amplitudes and body excursions, most likely by increasing positional and velocity error correction gain as a compensatory mechanism, while the time delay and long-term error correction gain remained largely unaffected. Moreover, the upper body’s phase lead was reduced. We conclude that HSP leads to very specific postural impairments. While postural control generally benefits from treadmill training, the effect seems to mainly rely on compensatory mechanisms, whereas the original deficits are not affected significantly.
ChemProp2 Dataset: Investigating potential biotransformations with a panel of 23 Drugs on Synthetic Community (Com20) to elucidate Drug-Microbiome-Host Dynamics
2023-12-05

Tested 23 drugs against Synthetic community (Com20) at two different timepoints (t=0, t= 2 hrs) to look for potential biotransformationsList of drugs tested:Acarbose, Clemizole, Amlodipine, Clindamycin, Amoxicillin, Clomifen, Aprepitant, Clotrimazole, Avermectin B1, Diacerein, Azithromycin, Dicumarol, Control, Dienestrol, Benzbromarone, Dienogest, Ceterizin, Doxycycline hyclate, Chlorpromazine, Duloxetin, Chlorprothixene, Erythromycin, Cilnidipine, EthinylestradiolSamples were measured (in March 18/19, 2023) using an UHPLC-Q Exactive HF Orbitrap mass spectrometer, equipped with a C18 column, following the LC-MS/MS method.
Seabirds boost coral reef resilience
2023-12-06

Global climate change threatens tropical coral reefs, yet local management can influence resilience. While increasing anthropogenic nutrients reduce coral resistance and recovery, it is unknown how the loss, or restoration, of natural nutrient flows affects reef recovery. Here, we test how natural seabird-derived nutrient subsidies, which are threatened by invasive rats, influence the mechanisms and patterns of reef recovery following an extreme marine heatwave using multiyear field experiments, repeated surveys, and Bayesian modeling. Corals transplanted from rat to seabird islands quickly assimilated seabird-derived nutrients, fully acclimating to new nutrient conditions within 3 years. Increased seabird-derived nutrients, in turn, caused a doubling of coral growth rates both within individuals and across entire reefs. Seabirds were also associated with faster recovery time of Acropora coral cover (&lt;4 years) and more dynamic recovery trajectories of entire benthic communities. We conclude that restoring seabird populations and associated nutrient pathways may foster greater coral reef resilience through enhanced growth and recovery rates of corals.
Compound Absorption in Polymer Devices Impairs the Translatability of Preclinical Safety Assessments
2023-12-06

Abstract Organotypic and microphysiological systems (MPS) that can emulate the molecular phenotype and function of human tissues, such as liver, are increasingly used in preclinical drug development. However, despite their improved predictivity, drug development success rates have remained low with most compounds failing in clinical phases despite promising preclinical data. Here, it is tested whether absorption of small molecules to polymers commonly used for MPS fabrication can impact preclinical pharmacological and toxicological assessments and contribute to the high clinical failure rates. To this end, identical devices are fabricated from eight different MPS polymers and absorption of prototypic compounds with different physicochemical properties are analyzed. It is found that overall absorption is primarily driven by compound hydrophobicity and the number of rotatable bonds. However, absorption can differ by &gt;1000‐fold between polymers with polydimethyl siloxane (PDMS) being most absorptive, whereas polytetrafluoroethylene (PTFE) and thiol‐ene epoxy (TEE) absorbed the least. Strikingly, organotypic primary human liver cultures successfully flagged hydrophobic hepatotoxins in lowly absorbing TEE devices at therapeutically relevant concentrations, whereas isogenic cultures in PDMS devices are resistant, resulting in false negative safety signals. Combined, these results can guide the selection of MPS materials and facilitate the development of preclinical assays with improved translatability.
Soil zymography: A decade of rapid development in microbial hotspot imaging
2023-12-06

This review summarizes the most important methodological developments and applications of soil zymography – the technique used to visualize enzyme activities in soil to identify and localize hotspots. After the first application of fluorogenic substrates for enzyme activity imaging in soil 10 years ago, zymography has been used in many studies. This reflects its universality, simplicity and visualization of the hidden microbial and root life in soil, which is a very heterogeneous and "dark" environment. After a short description of zymography background, we present the 10-year advances in the spectrum of enzyme activity imaging, zymography resolution, standardization and hotspot identification. A special focus is placed on combining the zymography with visualizing the localization of soil acidification, root exudation, pore distribution, nutrient and water fluxes. To date, most applications have been related to enzyme activities in the rhizosphere to visualize plant-soil-microbial interactions. Here, we go a step further and show many other important directions (i.e., biopores, detritusphere, microplastisphere) to identify the heterogeneity and localize hotspots of microbial activities and processes in soil. The past progress, current possibilities and challenges, as well as future perspectives of soil zymography are discussed. Soil zymography is widely applicable in natural and agricultural ecosystems in the field and in laboratory studies, scaling down from the whole root system (dm) to microbial communities (μm). In the decade ahead, enzyme research and specifically zymography imaging will continue to expand microbial studies and hotspot localization. This will involve intersecting with (bio)chemical, physico-chemical, microbial cell imaging and isotope applications. In summary, over the past 10 years, zymography based on fluorogenic substrates has illuminated the hidden microbial transformations of nutrients in soil hotspots. This has opened new ways to combine the localization of microbial processes with physico-chemical soil heterogeneity, and to identify the biochemical prerequisites for hotspot formation in soil.
Realizing Fluorescence Blinking in Monolayer MoSe2 with the Formation of 1D/2D Heterostructure
2023-12-06

Abstract The understanding and manipulating of photoluminescence blinking is essential in nano‐photonics and related device applications. The formation of mixed‐dimensional semiconductor heterostructures provides an important platform for the generation of blinking phenomena, which can be utilized to realize quantum emission properties of the heterostructures that are beyond the pure single material. Here, one‐dimensional (1D)/two‐dimensional (2D) heterostructures consisting of MoSe 2 monolayer and a single CsPbBr 3 perovskite nanowire are constructed. By studying the photoluminescence (PL) intensity time trajectory and lifetime, MoSe 2 in heterostructure exhibits fluorescent blinking behavior, which has a negative correlation relation with the PL blinking in CsPbBr 3 nanowire due to its super‐trap states. The excitation power dependent blinking and PL lifetime measurements of the heterostructure, as well as the low‐temperature PL spectroscopy, are performed to conclude that the bright state of MoSe 2 in heterostructure is due to the suppressed interfacial charge transfer. In addition, MoSe 2 /hBN/PVK heterostructure is prepared and investigated, showing no blinking phenomena due to the dominated energy transfer process. This study not only provides a deeper understanding of interfacial charge transfer process in 1D/2D heterostructure, but also offers guidance for the design of photonic device with extended functionality.
Targeting Longevity Gene SLC13A5: A Novel Approach to Prevent Age-Related Bone Fragility and Osteoporosis
2023-12-06

Reduced expression of the plasma membrane citrate transporter SLC13A5, also known as INDY, has been linked to increased longevity and mitigated age-related cardiovascular and metabolic diseases. Citrate, a vital component of the tricarboxylic acid cycle, constitutes 1–5% of bone weight, binding to mineral apatite surfaces. Our previous research highlighted osteoblasts’ specialized metabolic pathway facilitated by SLC13A5 regulating citrate uptake, production, and deposition within bones. Disrupting this pathway impairs bone mineralization in young mice. New Mendelian randomization analysis using UK Biobank data indicated that SNPs linked to reduced SLC13A5 function lowered osteoporosis risk. Comparative studies of young (10 weeks) and middle-aged (52 weeks) osteocalcin-cre-driven osteoblast-specific Slc13a5 knockout mice (Slc13a5cKO) showed a sexual dimorphism: while middle-aged females exhibited improved elasticity, middle-aged males demonstrated enhanced bone strength due to reduced SLC13A5 function. These findings suggest reduced SLC13A5 function could attenuate age-related bone fragility, advocating for SLC13A5 inhibition as a potential osteoporosis treatment.
D‐galactose might mediate some of the skeletal muscle hypertrophy‐promoting effects of milk—A nutrient to consider for sarcopenia?
2023-12-06

Abstract Sarcopenia is a process of progressive aging‐associated loss of skeletal muscle mass (SMM) recognized as a serious global health issue contributing to frailty and increased all‐cause mortality. Exercise and nutritional interventions (particularly intake of dairy products and milk) demonstrate good efficacy, safety, and broad applicability. Here, we propose that at least some of the well‐documented favorable effects of milk and milk‐derived protein supplements on SMM might be mediated by D‐galactose, a monosaccharide present in large quantities in milk in the form of disaccharide lactose (milk sugar). We suggest that ingestion of dairy products results in exposure to D‐galactose in concentrations metabolized primarily via the Leloir pathway with the potential to (i) promote anabolic signaling via maintenance of growth factor (e.g., insulin‐like growth factor 1 [IGF‐1]) receptor mature glycosylation patterns; and (ii) provide extracellular (liver glycogen) and intracellular substrates for short (muscle glycolysis) and long‐term (muscle glycogen, intramyocellular lipids) energy availability. Additionally, D‐galactose might optimize the metabolic function of skeletal muscles by increasing mitochondrial content and stimulating glucose and fatty acid utilization. The proposed potential of D‐galactose to promote the accretion of SMM is discussed in the context of its therapeutic potential in sarcopenia.
Female Hyperplastic PSA-Positive Prostate Tissue in the Bladder Neck
2023-12-06

&lt;b&gt;&lt;i&gt;Introduction:&lt;/i&gt;&lt;/b&gt; We report a rare case of Skene’s gland hyperplasia where the serum prostate-specific antigen (PSA) level was measurable. &lt;b&gt;&lt;i&gt;Case Presentation:&lt;/i&gt;&lt;/b&gt; The patient was a 91-year-old woman with a suspected bladder mass at the bladder trigone. Cystoscopy revealed a suspected lesion and an obstructed anterior bladder neck with a large mass located from a “7 o’clock” to “11 o’clock” area. The photodynamic diagnosis was negative. Transurethral subtotal resection of the mass was performed. The serum PSA level at the third postoperative day was 0.08 ng/mL. Postoperative cystography showed no contrast media extravasation. Thus, histopathology revealed massive adenomyomatous hyperplasia of the Skene’s gland, as well as nondysplastic urothelium and glandular and squamous epithelium. Immunohistochemistry showed strong PSA and NKX3.1 positivity, confirming the diagnosis of “female prostate.” FISH analysis showed only green signals that confirm an XX karyotype. In follow-up to 17 months, there was no disease recurrence or need for a urinary catheter. &lt;b&gt;&lt;i&gt;Conclusion:&lt;/i&gt;&lt;/b&gt; Effective therapeutic strategies for these lesions are unknown due to the absence of reported cases. Given the patient’s age, we assumed that bladder neck resection by transurethral resection with a controlled level of serum PSA would be a suitable therapeutic approach.
Biases in the spectral amplitude distribution of a natural scene modulate horizontal size perception
2023-12-06

Introduction Visual perception is a complex process that involves the analysis of different spatial and temporal features of the visual environment. One critical aspect of this process is adaptation, which allows the visual system to adjust its sensitivity to specific features based on the context of the environment. Numerous theories highlight the significance of the visual scene and its spectral properties in perceptual and adaptation mechanisms. For example, size perception is known to be influenced by the spatial frequency content of the visual scene. Nonetheless, several inquiries still exist, including how specific spectral properties of the scene play a role in size perception and adaptation mechanisms. Methods In this study, we explore aftereffects on size perception following adaptation to a natural scene with a biased spectral amplitude distribution. Twenty participants had to manually estimate the horizontal size of a projected rectangle after adaptation to three visually biased conditions: vertical-biased, non-biased, and horizontal-biased. Size adaptation aftereffects were quantified by comparing the perceptual responses from the non-biased condition with the vertical- and horizontal-biased conditions. Results We found size perception shifts which were contingent upon the specific orientation and spatial frequency distribution inherent in the amplitude spectra of the adaptation stimuli. Particularly, adaptation to vertical-biased produced a horizontal enlargement, while adaptation to horizontal-biased generated a decrease in the horizontal size perception of the rectangle. On average, size perception was modulated by 5–6%. Discussion These findings provide supporting evidence for the hypothesis that the neural mechanisms responsible for processing spatial frequency channels are involved in the encoding and perception of size information. The implications for neural mechanisms underlying spatial frequency and size information encoding are discussed.
Is it possible to generate an additional pleasant and pain‐relieving muscle stimulation when using a low‐frequency spinal cord stimulation (SCS) for the treatment of lower back pain? Pilot study: A new technique: “MuscleSCS”
2023-12-06

Abstract Objective The combined use of spinal cord stimulation (SCS) and muscle stimulation, in the treatment of chronic pain, using the same probe, could improve the clinical results. However, this technique has not been established as yet. It was our hypothesis that it is possible to generate muscle stimulation by using low frequencies with SCS electrodes and use it to additionally treat chronic back pain. Methods We generated muscle stimulation in patients with previously implanted SCS electrodes, for the treatment of lower back pain, by using low frequencies (2, 4, 6, and 8 Hz) and different contact combinations of the electrodes. The results were evaluated by using visual inspection (videos), haptic control, surface electromyography (EMG), and sonographic recordings. Results This pilot study (17 patients, seven females, age 36–87 years, 11 percutaneous paddle leads, and 6 octrodes) was performed at the Neurosurgical Department of the University of Tuebingen. The most preferred frequencies were 6 Hz (45.5% of percutaneous paddle leads) and 8 Hz (50% of octrodes) at contacts 3&amp;4 or 5&amp;6. The preference of frequencies differed significantly among genders ( p = 0.023). Simultaneous EMG and ultrasonic recordings demonstrated the generation of muscle potentials and the stimulation of deeper muscle groups. Conclusion In this study, it has been shown that with low‐frequency SCS stimulation, pleasant and pain‐relieving muscle contractions of the lower and upper back can also be generated. This combined method has been coined by us as “MuscleSCS” technique. Clinical trials are necessary to establish the value of this combined technique and its subtypes.
Simulating Vision Impairment in Virtual Reality -- A Comparison of Visual Task Performance with Real and Simulated Tunnel Vision
2023-12-06

Purpose: In this work, we explore the potential and limitations of simulating gaze-contingent tunnel vision conditions using Virtual Reality (VR) with built-in eye tracking technology. This approach promises an easy and accessible way of expanding study populations and test groups for visual training, visual aids, or accessibility evaluations. However, it is crucial to assess the validity and reliability of simulating these types of visual impairments and evaluate the extend to which participants with simulated tunnel vision can represent real patients. Methods: Two age-matched participant groups were acquired: The first group (n=8 aged 20-60, average 49.1, sd 13.2) consisted of patients diagnosed with Retinitis pigmentosa (RP). The second group (n=8, aged 27-59, average 46.5, sd 10.8) consisted of visually healthy participants with simulated tunnel vision. Both groups carried out different visual tasks in a virtual environment for 30 minutes per day over the course of four weeks. Task performances as well as gaze characteristics were evaluated in both groups over the course of the study. Results: Using the "two one-sided tests for equivalence" method, the two groups were found to perform similar in all three visual tasks. Significant differences between groups were found in different aspects of their gaze behavior, though most of these aspects seem to converge over time. Conclusion: Our study evaluates the potential and limitations of using Virtual Reality technology to simulate the effects of tunnel vision within controlled virtual environments. We find that the simulation accurately represents performance of RP patients in the context of group averages, but fails to fully replicate effects on gaze behavior.
From Valuable Merchandise to Violent Rebels
2023-12-06

From the moment the Dutch West Indian Company formally entered the slave trade in 1637, the Dutch periodical press consistently carried reports on slavery and the transatlantic slave trade. This article offers a long-term analysis of this coverage in the Dutch Republic, showing for the first time how the representation of slavery developed over the seventeenth and eighteenth centuries. It demonstrates, first, that through the periodical press, knowledge of slavery was more widely spread in the Dutch Republic in the seventeenth century than is often assumed. The consistent, if intermittent, newspaper coverage meant that – well before the debates on abolition emerged – Dutch readers would be familiar with stereotypes of enslaved Africans as valuable merchandise or violent rebels. Second, this article argues that, in the second half of the eighteenth century, the periodical press offered its readers an ambiguous and contradictory image of slavery, contributing, on the one hand, to a public discourse underpinning slavery by depicting enslaved Africans as violent rebels, while at the same time covering political debates on the abolition of slavery.