julilili42/papers huggingface dataset:
Evidences for Mutant Huntingtin Inducing Musculoskeletal and Brain Growth Impairments via Disturbing Testosterone Biosynthesis in Male Huntington Disease Animals
2022-11-25

Body weight (BW) loss and reduced body mass index (BMI) are the most common peripheral alterations in Huntington disease (HD) and have been found in HD mutation carriers and HD animal models before the manifestation of neurological symptoms. This suggests that, at least in the early disease stage, these changes could be due to abnormal tissue growth rather than tissue atrophy. Moreover, BW and BMI are reported to be more affected in males than females in HD animal models and patients. Here, we confirmed sex-dependent growth alterations in the BACHD rat model for HD and investigated the associated contributing factors. Our results showed growth abnormalities along with decreased plasma testosterone and insulin-like growth factor 1 (IGF-1) levels only in males. Moreover, we demonstrated correlations between growth parameters, IGF-1, and testosterone. Our analyses further revealed an aberrant transcription of testosterone biosynthesis-related genes in the testes of BACHD rats with undisturbed luteinizing hormone (LH)/cAMP/PKA signaling, which plays a key role in regulating the transcription process of some of these genes. In line with the findings in BACHD rats, analyses in the R6/2 mouse model of HD showed similar results. Our findings support the view that mutant huntingtin may induce abnormal growth in males via the dysregulation of gene transcription in the testis, which in turn can affect testosterone biosynthesis.
Multimodal Assessment of Smoking cue Reactivity During a Smoking Cue Exposure Task
2022-11-25

Background. Cue-reactivity as a characteristic symptom of substance use disorders (SUD) is highly context dependent. Paradigms with high context validity need to be established for the investigation of underlying neurobiological mechanisms. While craving can be assessed by self-report as one aspect of cue-reactivity (CR), the assessment of biological measures such as the autonomous response and EEG promises a holistic perspective including CR at an automatized level. In a multimodal approach, smoking cue exposure (CE) effects on heart rate variability (HRV), EEG frequency power, and craving as well as their interrelation were assessed. This pilot study focused on the validity of CR measurements in a naturalistic CE paradigm. Methods. EEG frequency power, HRV, and craving were assessed during resting state (RS) and smoking CE in smokers (n = 14) and nonsmoking controls (n = 10) to investigate the psychophysiological and subjective reactions to CE. Results. Increased beta power was found only in smokers during CE compared to the control condition. There was an inverse correlation of beta power and maximum craving. Likewise, HRV correlated negatively with maximum smoking urges in smokers immediately after the measurements, without differentiation between CE and control condition. Conclusion. The increased beta power in smokers during CE is discussed as increased inhibitory control related to reduced craving in smokers. Furthermore, increased craving during CE seems to be associated to decreased vagal activity. The multimodal measurements during the CE showed ecological validity to be fundamental for CE assessment in clinical populations to evaluate its predictive value.
Mathematical Aspects of General Relativity
2022-11-25

General relativity is an area that naturally combines differential geometry, partial differential equations, global analysis and dynamical systems with astrophysics, cosmology, high energy physics, and numerical analysis. It is rapidly expanding and has witnessed remarkable developments in recent years.
A ‘long-forgotten’ plesiosaur provides evidence of large-bodied rhomaleosaurids in the Middle Jurassic of Germany
2022-11-25

ABSTRACTABSTRACTDescribed in 1858, Trematospondylus macrocephalus is one of the earliest established plesiosaur taxa. However, despite being historically significant, the taxon disappeared from the literature shortly after its initial description and has not been mentioned for over a century. Thus, it has never been properly assessed. The holotype comprises seven vertebrae, including a supposed sacral vertebra and caudal vertebrae. The specimens were collected from the Lochen mountain massif near Balingen in southwestern Germany and derive from the Dentalienton Formation. As such, they are most likely early Bathonian (Middle Jurassic) in age. Here, we provide a thorough redescription of the material, illustrate it, and assess its phylogenetic affinities through a parsimony analysis. Our results show that T. macrocephalus shares characters with members of the Rhomaleosauridae, including, for example, the length-height ratio of the caudal centra as well as the placement of caudal ribs and hemapophyseal facets. Rhomaleosaurid affinities of the material are likewise supported by our phylogenetic analysis. Comparisons further indicate that the taxon belonged to large-bodied members of the clade, with a body length similar to that of Rhomaleosaurus. Even though the material does not enable Trematospondylus to be properly diagnosed, thus making it a nomen dubium, it still adds to the rare Middle Jurassic record of rhomaleosaurid plesiosaurs. At the same time, it enhances our knowledge of the plesiosaur taxic diversity during the pre-Callovian Middle Jurassic, which has been very limited.View correction statement:Correction ACKNOWLEDGMENTSWe are indebted to I. Werneburg for access to the material, O. R. Regalado Fernández for discussions on taphonomy, and A. Fatz (all GPIT) for taking the photos of the elements. A. S. Smith (Nottingham Natural History Museum, U.K.), P. Vincent (Muséum national d’Histoire naturelle, France), an anonymous reviewer, and JVP Phylogenetics Editor P. L. Godoy (University of São Paulo, Brazil) provided valuable comments which helped us to improve this publication. The program TNT is made available with the sponsorship of the Willi Hennig Society.LIST OF SUPPLEMENTARY FILESSupplementary File 1: Supplemental_Data_1.rev.docx, containing supplementary figures S1 and S2Supplementary File 2: NEXUS_file.nexSupplementary File 3: TNT_file.tntCorrection StatementThis article was originally published with errors, which have now been corrected in the online version. Please see Correction (http://dx.doi.org/10.1080/02724634.2023.2221954)
The scaling of mental computation in a sorting task
2022-11-25

Many cognitive models provide valuable insights into human behavior. Yet the algorithmic complexity of candidate models can fail to capture how humanreaction times scale with increasing input complexity. In the current work,we want to understand the algorithms underlying human cognitive processes.Computer science characterizes algorithms by their time and space complexityscaling with problem size. We propose to use participants’ reaction times tostudy how human computations scale with increasing input complexity. Wetest this approach in a task where participants had to sort sequences of rectangles by their size. Our results showed that reaction times scaled linearlywith sequence length and that participants learned and actively used latentstructure whenever it was provided. This behavior was in line with a computational model that used the observed sequences to form hypotheses about the latent structures, searching through candidate hypotheses in a directed fashion. These results enrich our understanding of plausible cognitive models forefficient mental sorting and pave the way for future studies using reactiontimes to investigate the scaling of mental computations across psychologicaldomains.
RecruitNet: A global database of plant recruitment networks
2022-11-26

Abstract Plant recruitment interactions (i.e., what recruits under what) shape the composition, diversity, and structure of plant communities. Despite the huge body of knowledge on the mechanisms underlying recruitment interactions among species, we still know little about the structure of the recruitment networks emerging in ecological communities. Modeling and analyzing the community‐level structure of plant recruitment interactions as a complex network can provide relevant information on ecological and evolutionary processes acting both at the species and ecosystem levels. We report a data set containing 143 plant recruitment networks in 23 countries across five continents, including temperate and tropical ecosystems. Each network identifies the species under which another species recruits. All networks report the number of recruits (i.e., individuals) per species. The data set includes &gt;850,000 recruiting individuals involved in 118,411 paired interactions among 3318 vascular plant species across the globe. The cover of canopy species and open ground is also provided. Three sampling protocols were used: (1) The Recruitment Network (RN) protocol (106 networks) focuses on interactions among established plants (“canopy species”) and plants in their early stages of recruitment (“recruit species”). A series of plots was delimited within a locality, and all the individuals recruiting and their canopy species were identified; (2) The paired Canopy‐Open (pCO) protocol (26 networks) consists in locating a potential canopy plant and identifying recruiting individuals under the canopy and in a nearby open space of the same area; (3) The Georeferenced plot (GP) protocol (11 networks) consists in using information from georeferenced individual plants in large plots to infer canopy‐recruit interactions. Some networks incorporate data for both herbs and woody species, whereas others focus exclusively on woody species. The location of each study site, geographical coordinates, country, locality, responsible author, sampling dates, sampling method, and life habits of both canopy and recruit species are provided. This database will allow researchers to test ecological, biogeographical, and evolutionary hypotheses related to plant recruitment interactions. There are no copyright restrictions on the data set; please cite this data paper when using these data in publications.
Children anticipate past events to the left and future events to the right: Evidence from eye movements and time-space compatibility effects
2022-11-26

Typically, people in cultures with a left-to-right reading direction mentally link past-related stimuli with the left space and future-related stimuli with the right space ("mental timeline”; MTL). Hence, enhanced reading experience might play a fundamental role in the development of the MTL. To test this, we implemented a child-friendly time-space compatibility design. Children from different grades of elementary school saw a picture (e.g., a half-peeled orange) together with the word “earlier” or the word “later”. This design allowed us to assess whether the MTL biases anticipatory eye movements in response to word processing. Thereafter, two horizontally arranged pictures appeared either compatible with the MTL (e.g., an unpeeled orange on the left side and a completely peeled orange on the right side) or in a reversed, i.e. incompatible mapping. Participants responded with their right or left hand to indicate which picture matched the previously heard auditory prompt. In Study 1, we tested children (first to fourth grade) and adults. Anticipatory looks elicited by auditory prompts and response times reflected MTL effects with no differences between age groups. In Study 2, we contrasted two larger groups of first and fourth graders. We replicated MTL effects for anticipatory looks, but not for response times. Anticipatory looks were stronger biased by the MTL in fourth compared to first graders. We conclude that studying MTL effects in children is restricted by task difficulty. If MTL effects appear, they are not strongly modulated by formal education. Thus, basic MTL effects might be acquired before elementary school.
Design, synthesis, and structure–activity relationships of diindolylmethane derivatives as cannabinoid CB2 receptor agonists
2022-11-27

Abstract 3,3′‐Diindolylmethane (DIM), a natural product‐derived compound formed upon ingestion of cruciferous vegetables, was recently described to act as a partial agonist of the anti‐inflammatory cannabinoid (CB) receptor subtype CB 2 . In the present study, we synthesized and evaluated a series of DIM derivatives and determined their affinities for human CB receptor subtypes in radioligand binding studies. Potent compounds were additionally evaluated in functional cAMP accumulation and β‐arrestin recruitment assays. Small substituents in the 4‐position of both indole rings of DIM were beneficial for high CB 2 receptor affinity and efficacy. Di‐(4‐cyano‐1 H ‐indol‐3‐yl)methane ( 46 , PSB‐19837, EC 50 : cAMP, 0.0144 μM, 95% efficacy compared to the full standard agonist CP55,940; β‐arrestin, 0.0149 μM, 67% efficacy) was the most potent CB 2 receptor agonist of the present series. Di‐(4‐bromo‐1 H ‐indol‐3‐yl)methane ( 44 , PSB‐19571) showed higher potency in β‐arrestin (EC 50 0.0450 μM, 61% efficacy) than in cAMP accumulation assays (EC 50 0.509 μM, 85% efficacy) while 3‐((1 H ‐indol‐3‐yl)methyl)−4‐methyl‐1 H ‐indole ( 149 , PSB‐18691) displayed a 19‐fold bias for the G protein pathway (EC 50 : cAMP, 0.0652 μM; β‐arrestin, 1.08 μM). DIM and its analogs act as allosteric CB 2 receptor agonists. These potent CB 2 receptor agonists have potential as novel drugs for the treatment of inflammatory diseases.
The near-miss to cross-modal commutativity
2022-11-27

This paper is a follow-up on Ellermeier, Kattner &amp;amp; Raum (2021, Attention, Perception, &amp;amp; Psychophysics, 83 , 2955 2967), and provides a reanalysis of their data on cross modal commutativity, which is based on Bayesian tests as well as a theory-based analysis grounded on a recently suggested extension of a global psychophysical approach to cross-modal judgments (Heller, 2021, Psychological Review, 128, 509-524). This theory assumes that stimuli are judged against respondent-generated internal references which are modality-specific and potentially role-dependent (i.e., sensitive to whether they pertain to the standard or the variable stimulus in the performed cross-modal magnitude production task). While the Bayesian tests turn out to be inconclusive, the theory-based analysis reveals a massive and systematic role dependence of internal references. This leads to predicting small, but systematic deviations from cross modal commutativity which are in line with the observed data. In analogy to a term coined in the context of Weber’s law this phenomenon is referred to as a near miss to cross-modal commutativity.
Testing spin-dependent dark matter interactions with lithium aluminate targets in CRESST-III
2022-11-28

In the past decades, numerous experiments have emerged to unveil the nature of dark matter, one of the most discussed open questions in modern particle physics. Among them, the Cryogenic Rare Event Search with Superconducting Thermometers (CRESST) experiment, located at the Laboratori Nazionali del Gran Sasso, operates scintillating crystals as cryogenic phonon detectors. In this work, we present first results from the operation of two detector modules which both have 10.46 g LiAlO2 targets in CRESST-III. The lithium contents in the crystal are Li6, with an odd number of protons and neutrons, and Li7, with an odd number of protons. By considering both isotopes of lithium and Al27, we set the currently strongest cross section upper limits on spin-dependent interaction of dark matter with protons and neutrons for the mass region between 0.25 and 1.5 GeV/c2.
Comprehensive Online Reversed-Phase × Chiral Two-Dimensional Liquid Chromatography-Mass Spectrometry with Data-Independent Sequential Window Acquisition of All Theoretical Fragment-Ion Spectra-Acquisition for Untargeted Enantioselective Amino Acid Analysis
2022-11-28

This work presents an advanced analytical platform for untargeted enantioselective amino acid analysis (eAAA) by comprehensive achiral × chiral 2D-LC hyphenated to ESI-QTOF-MS/MS utilizing data-independent SWATH (sequential window acquisition of all theoretical fragment-ion spectra) technology. The methodology involves <i>N</i>-terminal pre-column derivatization with 6-aminoquinolyl-<i>N</i>-hydroxysuccinimidyl carbamate (AQC; AccQ) as retention, selectivity, and MS tag, supporting retention and UV detection in RPLC (<sup>1</sup>D), chiral recognition, and thus enantioselectivity by the core-shell tandem column composed of a quinine carbamate weak anion exchanger (QN-AX) and a zwitterionic chiral ion-exchanger (ZWIX(+)) (<sup>2</sup>D) as well as the ionization efficiency during positive electrospray ionization due to a high proton affinity of the AQC label. Furthermore, the urea-type MS tag gives rise to the generation of AQC-tag characteristic signature fragments in MS<sup>2</sup>. The latter allows the chemoselective mass spectrometric filtering of targeted and untargeted <i>N</i>-derivatized amino acids or related labeled species. The chiral core-shell tandem column provides a complete enantioselective amino acid profile of all proteinogenic amino acids within 1 min, with full baseline separation of all enantiomers, but without resolution of isomeric Ile/<i>allo</i>-Ile (aIle)/Leu, which can be resolved by RPLC. The entire LC × LC separation occurs within a total run time of 60 min (<sup>1</sup>D), with the chiral <sup>2</sup>D operated in gradient elution mode and a cycle time of 60 s. A strategy to mine the 2D-LC-SWATH data is presented and demonstrated for the qualitative eAAA of two peptide hydrolysate samples of therapeutic peptides containing common and uncommon as well as primary and secondary amino acids. Absolute configuration assignment of amino acids using template matching for all proteinogenic amino acids was made feasible due to method robustness and the inclusion of an isotopically labeled L-[U-<sup>13</sup>C<sup>15</sup>N]-AA standard. The quantification performance of this LC × LC-MS/MS assay was also evaluated. Accuracies were acceptable for the majority of AAs enabling AA composition determination in peptide hydrolysates simultaneously with configuration assignment, as exemplified by oxytocin. This methodology represents a step toward truly untargeted 2D enantioselective amino acid analysis and metabolomics.
Impact of RNA Signatures on pCR and Survival after 12-Week Neoadjuvant Pertuzumab plus Trastuzumab with or without Paclitaxel in the WSG-ADAPT HER2+/HR− Trial
2022-11-28

Abstract Purpose: To identify associations of biological signatures and stromal tumor-infiltrating lymphocytes (sTIL) with pathological complete response (pCR; ypT0 ypN0) and survival in the Phase II WSG-ADAPT HER2+/HR− trial (NCT01817452). Experimental Design: Patients with cT1-cT4c, cN0–3 HER2+/HR− early breast cancer (EBC) were randomized to pertuzumab+trastuzumab (P+T, n = 92) or P+T+paclitaxel (n = 42). Gene expression signatures were analyzed in baseline biopsies using NanoString Breast Cancer 360 panel (n = 117); baseline and on-treatment (week 3) sTIL levels were available in 119 and 76 patients, respectively. Impacts of standardized gene expression signatures on pCR and invasive disease-free survival (iDFS) were estimated by logistic and Cox regression. Results: In all patients, ERBB2 [OR, 1.70; 95% confidence interval (CI), 1.08–2.67] and estrogen receptor (ER) signaling (OR, 1.72; 95% CI, 1.13–2.61) were favorable, whereas PTEN (OR, 0.57; 95% CI, 0.38–0.87) was unfavorable for pCR. After 60 months median follow-up, 13 invasive events occurred (P+T: n = 11, P+T+paclitaxel: n = 2), none following pCR. Gene signatures related to immune response (IR) and ER signaling were favorable for iDFS, all with similar HR about 0.43–0.55. These patterns were even more prominent in the neoadjuvant chemotherapy-free group, where additionally BRCAness signature was unfavorable (HR, 2.00; 95% CI, 1.04–3.84). IR signatures were strongly intercorrelated. sTILs (baseline/week 3/change) were not associated with pCR or iDFS, though baseline sTILs correlated positively with IR signatures. Conclusions: Distinct gene signatures were associated with pCR versus iDFS in HER2+/HR− EBC. The potential role of IR in preventing recurrence suggests that patients with upregulated IR signatures could be candidates for de-escalation concepts in HER2+ EBC.
Exogenous and endogenous spatial attention in crows
2022-11-28

Attention describes the ability to selectively process a particular aspect of the environment at the expense of others. Despite the significance of selective processing, the types and scopes of attentional mechanisms in nonprimate species remain underexplored. We trained four carrion crows in Posner spatial cueing tasks using two separate protocols where the attention-capturing cues are shown at different times before target onset at either the same or a different location as the impending target. To probe automatic bottom-up, or exogenous, attention, two naïve crows were tested with a cue that had no predictive value concerning the location of the subsequent target. To examine volitional top-down, or endogenous, attention, the other two crows were tested with the previously learned cues that predicted the impending target location. Comparing the performance for valid (cue and target at same location) and invalid (cue and target at opposing locations) cues in the nonpredictive cue condition showed a transient, mild reaction time advantage signifying exogenous attention. In contrast, there was a strong and long-lasting performance advantage for the valid conditions with predictive cues indicating endogenous attention. Together, these results demonstrate that crows possess two different attention mechanisms (exogenous and endogenous). These findings signify that crows possess a substantial attentional capacity and robust cognitive control over attention allocation.
70 years later – New research at Holley Shelter, a Middle and Later Stone Age site in KwaZulu-Natal, South Africa
2022-11-28

In 1952, Gordon Cramb published the first report on his excavations at Holley Shelter, in KwaZulu-Natal, South Africa. Although Cramb’s work implied organic preservation associated with a unique stone tool assemblage from a Middle Stone Age (MSA) context, Holley Shelter disappeared from the archaeological landscape until 2015, when we provided a reinvestigation of the lithic assemblages from the 1950s. Our study indicated a tentative chronological framework around Marine Isotope Stage 3 (MIS3) for the human occupation of the site. However, Cramb’s excavations did not produce reliable chronometric ages and the botanical and zoological finds from Holley Shelter remain for the most part unstudied. This is problematic as the site constitutes one of the few inland MSA rock shelters of KwaZulu-Natal featuring organic preservation. In 2022, 70 years after Cramb’s first report, we started a new research project focusing on renewed excavations to obtain archaeological remains from a controlled stratigraphy, absolute chronometric ages and reliable data on the palaeoenvironment at the border between the coastal belt and the midlands of KwaZulu-Natal. Here, we provide initial results from the first field campaign in 2022 on the stratigraphic sequence and archaeological finds and discuss their implications for future multidisciplinary research. Significance: Environmental change can have a strong impact on hunter-gatherer behaviour, migration and technological choices. It is thus crucial to contextualise archaeological material with a strong palaeoenvironmental record. The inland of KwaZulu-Natal, South Africa, represents an understudied region in terms of Stone Age archaeological sites and palaeoenvironmental record. Holley Shelter is one of the few sites in South Africa with excellent organic preservation and a deep stratigraphic record, which provide a great opportunity to investigate human-landscape interaction and technological change throughout the Middle and Later Stone Age.