Miracle-dz/UniFAR-FTUs huggingface dataset:
Evaluation of Tumor-Targeting Properties of an Antagonistic Bombesin Analogue RM26 Conjugated with a Non-Residualizing Radioiodine Label Comparison with a Radiometal-Labelled Counterpart

Radiolabelled antagonistic bombesin analogues are successfully used for targeting of gastrin-releasing peptide receptors (GRPR) that are overexpressed in prostate cancer. Internalization of antagonistic bombesin analogues is slow. We hypothesized that the use of a non-residualizing radioiodine label might not affect the tumour uptake but would reduce the retention in normal organs, where radiopharmaceutical would be internalized. To test this hypothesis, tyrosine was conjugated via diethylene glycol linker to N-terminus of an antagonistic bombesin analogue RM26 to form Tyr-PEG2-RM26. [111In]In-DOTA-PEG2-RM26 was used as a control with a residualizing label. Tyr-PEG2-RM26 was labelled with 125I with 95% radiochemical purity and retained binding specificity to GRPR. The IC50 values for Tyr-PEG2-RM26 and DOTA-PEG2-RM26 were 1.7 ± 0.3 nM and 3.3 ± 0.5 nM, respectively. The cellular processing of [125I]I-Tyr-PEG2-RM26 by PC-3 cells showed unusually fast internalization. Biodistribution showed that uptake in pancreas and tumour was GRPR-specific for both radioconjugates. Blood clearance of [125I]I-Tyr-PEG2-RM26 was appreciably slower and activity accumulation in all organs was significantly higher than for [111In]In-DOTA-PEG2-RM26. Tumor uptake of [111In]In-DOTA-PEG2-RM26 was significantly higher than for [125I]I-Tyr-PEG2-RM26, resulting in higher tumour-to-organ ratio for [111In]In-DOTA-PEG2-RM26 at studied time points. Incorporation of amino acids with hydrophilic side-chains next to tyrosine might overcome the problems associated with the use of tyrosine as a prosthetic group for radioiodination.
Plotting a future for Amazonian canga vegetation in a campo rupestre context

In order to establish effective conservation strategy, drivers of local and regional patterns of biodiversity need to be understood. The composition of local biodiversity is dependent on a number of factors including evolution and redistribution of lineages through dispersal and environmental heterogeneity. Brazilian canga is characterised by a ferrugineous substrate, found both in the Iron Quadrangle of Minas Gerais and in the Carajás mountains in Amazonia. Canga is one of several specialised habitat types comprising Brazilian campo rupestre, a montane vegetation found within or adjacent to several major Brazilian bioregions, including the Atlantic Forest and Amazonia, with exceptionally high levels of diversity and endemism arising from both history of dispersal and environmental variation. In order to inform biodiversity conservation for canga, and more broadly for campo rupestre, we performed floristic and phylogenetic analyses investigating affinities between 28 sites on different substrates (canga and quartzite) and geographic locations (Carajás, Pará [Amazonia]; Cadeia do Espinhaço, Minas Gerais; Chapada Diamantina, Bahia). Through analysis of 11204 occurrences of 4705 species of angiosperms, we found that Amazonian Carajás canga plant communities formed a cohesive group, distinct from species assemblages found in Eastern Brazil (Minas Gerais, Bahia), either on canga or quartzite. The phylogenetic megatree of species across all sites investigated shows associations between certain clades and Amazonian canga, with few shared species between the Amazonian Carajás and Eastern Brazil sites, while the floristic comparison shows high levels of heterogeneity between sites. The need for reserves for Amazonian Carajás canga has been recognized and addressed by the creation of a national park. However, current sampling does not provide sufficient reassurance that the canga areas now benefitting from full legal protection adequately represent the regional canga flora.
Cardiorespiratory fitness and health‐related quality of life in adolescents: A longitudinal analysis from the LabMed Physical Activity Study

The purpose of this study was to examine the longitudinal associations between cardiorespiratory fitness and health‐related quality of life (HRQoL) in a sample of adolescents, and to determine whether changes in cardiorespiratory fitness were associated with HRQoL over a 2‐year follow‐up.
Effects of Parenting Styles on Self-Regulated Learning and Academic Stress in Spanish Adolescents

Research has repeatedly highlighted the important influence of parental socialization styles on children’s psychosocial adjustment. However, previous studies about their effects on school adjustment have traditionally addressed a limited set of indicators, such as academic achievement or self-concept, which should be broadened in order to increase our level of knowledge about this topic. Thus, the aim of the present study was to analyze the relationships between parenting styles and other relevant school adjustment criteria (self-regulated learning and academic stress) in adolescence. The study participants were 437 Spanish adolescents (44.7% men) from 12 to 18 years old (M = 14.55, SD = 1.80) who were enrolled in high school. A multivariate factorial design (parenting × sex × educational level) was used for each set of criteria. The results are consistent with previous research, showing that the indulgent style was related to better school adjustment during adolescence, evaluated through self-regulated learning and academic stress, thus increasing the available evidence about the influence of parenting styles in this setting. Additionally, this relationship remains invariant with regard to sex and the educational level of the participants in the study. Therefore, this study highlights the importance of parenting practices related to high acceptance/involvement for the adequate school adjustment of Spanish adolescents.
Bridging crystal engineering and drug discovery by utilizing intermolecular interactions and molecular shapes in crystals.

Most structure-based drug discovery protocols utilize crystal structures of receptor proteins. Crystal engineering, on the other hand, utilizes the wealth of chemical information inherent in small-molecule crystal structures in the Cambridge Structural Database (CSD). Here we show that interaction surfaces and shapes of molecules in experimentally determined small-molecule crystal structures can serve as effective tools in drug discovery. Our description of the shape and interaction propensities of molecules in their crystal structures can be used to screen them for specific binding compatibility with protein targets - as demonstrated through a high-throughput profiling of around 138,000 small molecule structures in the CSD, and a series of drug-protein crystal structures. Electron density-based intermolecular boundary surfaces in small-molecule crystal structures and in target protein pockets are utilized to identify potential ligand molecules from the CSD - based on 3D shape and intermolecular interaction matching. Bridging small-molecule crystallography and protein crystallography results in the identification of ligand molecules from the CSD with remarkable chemical diversity, promising receptor-binding indicators and suitable drug-likeness parameters.
Structure-based design of selective histone deacetylase 6 zinc binding groups

Abstract The binding site of the second catalytic domain of human histone deacetylase 6 (HDAC6 CDII) has structural features that differ from the other human orthologues, being also mainly responsible for the overall enzymatic activity of this isoform. Aiming to identify new fragments as a possible novel selective zinc binding group (ZBG) for HDAC6 CDII, two fragment libraries were designed: one library consisting of known chelators and a second one using the fragments of the ZINC15 database. The most promising fragments identified in a structure-based virtual screening of designed libraries were further evaluated through molecular docking and molecular dynamics simulations. An interesting benzimidazole fragment was selected from the in silico studies and presented as potential zing binding group for the development of novel HDAC6 selective inhibitors. Communicated by Ramaswamy H. Sarma Graphical Abstract
AtERF#111/ABR1 is a transcriptional activator involved in the wounding response.

AtERF#111/ABR1 belongs to the group X of the ERF/AP2 transcription factor family (GXERFs) and is shoot specifically induced under submergence and hypoxia. It was described to be an ABA-response repressor, but our data reveal a completely different function. Surprisingly, AtERF#111 expression is strongly responsive to wounding stress. Expression profiling of ERF#111-overexpressing (OE) plants, which show morphological phenotypes like increased root hair length and number, strengthens the hypothesis of AtERF#111 being involved in the wounding response, thereby acting as a transcriptional activator of gene expression. Consistent with a potential function outside of oxygen signaling, we could not assign AtERF#111 as a target of the PRT6 N-degron pathway, even though it starts with a highly conserved N-terminal Met-Cys (MC) motif. However, the protein is unstable as it is degraded in an ubiquitin-dependent manner. Finally, direct target genes of AtERF#111 were identified by microarray analyses and subsequently confirmed by protoplast transactivation assays. The special roles of diverse members of the plant-specific GXERFs in coordinating stress signaling and wound repair mechanisms have been recently hypothesized, and our data suggest that AtERF#111 is indeed involved in these processes. This article is protected by copyright. All rights reserved.
Phenolic, flavonoid content and radical scavenging activity of Smilax china with its inhibitory potential against clinically important enzymes

Abstract Smilax china (SC) is a medicinal plant that has been traditionally used for a number of pathological disorders. In current study, its various fractions were assessed for radical scavenging, phenolic, flavonoid content and enzyme inhibition. The methanolic extract (MSC) of SC was subjected to fractionation using different solvents including n-hexane, benzene, chloroform, ethyl acetate and n-butanol. Results revealed that ethyl acetate fraction showed maximum phenolic (101.81 ± 0.13 mg GAE/g) and flavonoid (96.80 ± 0.39 mg QE/g) content with maximum radical scavenging potential (82.51 ± 0.18%, IC50=104.45 µg/ml) as well as urease (82.63 ± 0.79%), tyrosinase (81.30 ± 0.41%) and Butyrylcholinesterase (BChE) (62.47 ± 0.76%) inhibition at 0.5 mg/ml. Whereas, maximum α-Glucosidase (87.56 ± 0.13%) and Acetylcholinesterase (AChE) inhibition (82.34 ± 0.64%) was exhibited by n-hexane and benzene fractions, respectively. Present study has revealed the promising radical scavenging, phenolic, flavonoid and enzyme inhibitory potential of various fractions of SC extract. Thus, the study is a step forward towards evidence-based phyto-medicine. Graphical Abstract
Multi-omics Analyses Reveal Synergistic Carbohydrate Metabolism in Streptococcus mutans-Candida albicans Mixed-Species Biofilms

Candida albicans, a major opportunistic fungal pathogen, is frequently found together with Streptococcus mutans in dental biofilms associated with severe childhood caries (tooth decay), a prevalent pediatric oral disease. However, the impact of this cross-kingdom relationship on C. albicans remains largely uncharacterized. Here, we employed a novel quantitative proteomics approach in conjunction with transcriptomic profiling to unravel molecular pathways of C. albicans when cocultured with S. mutans in mixed biofilms. ABSTRACT Candida albicans, a major opportunistic fungal pathogen, is frequently found together with Streptococcus mutans in dental biofilms associated with severe childhood caries (tooth decay), a prevalent pediatric oral disease. However, the impact of this cross-kingdom relationship on C. albicans remains largely uncharacterized. Here, we employed a novel quantitative proteomics approach in conjunction with transcriptomic profiling to unravel molecular pathways of C. albicans when cocultured with S. mutans in mixed biofilms. RNA sequencing and iTRAQ (isobaric tags for relative and absolute quantitation)-based quantitative proteomics revealed that C. albicans genes and proteins associated with carbohydrate metabolism were significantly enhanced, including sugar transport, aerobic respiration, pyruvate breakdown, and the glyoxylate cycle. Other C. albicans genes and proteins directly and indirectly related to cell morphogenesis and cell wall components such as mannan and glucan were also upregulated, indicating enhanced fungal activity in mixed-species biofilm. Further analyses revealed that S. mutans-derived exoenzyme glucosyltransferase B (GtfB), which binds to the fungal cell surface to promote coadhesion, can break down sucrose into glucose and fructose that can be readily metabolized by C. albicans, enhancing growth and acid production. Altogether, we identified key pathways used by C. albicans in the mixed biofilm, indicating an active fungal role in the sugar metabolism and environmental acidification (key virulence traits associated with caries onset) when interacting with S. mutans, and a new cross-feeding mechanism mediated by GtfB that enhances C. albicans carbohydrate utilization. In addition, we demonstrate that comprehensive transcriptomics and quantitative proteomics can be powerful tools to study microbial contributions which remain underexplored in cross-kingdom biofilms.
Impact of Beef and Beef Product Intake on Cognition in Children and Young Adults: A Systematic Review

(1) Background: Undernutrition and micronutrient deficiency have been consistently linked to cognitive impairment among children and young adults. As a primary source of dietary animal protein, beef consumption holds the potential to improve diet quality and positively influence cognitive function. This study systematically reviewed evidence linking beef intake to cognition among children and young adults. (2) Methods: A literature search was conducted in seven electronic bibliographic databases for studies assessing the impact of beef consumption on cognition. (3) Results: We identified eight studies reporting results from five unique interventions. Two interventions were conducted in Kenya, two in the U.S. and one in four countries including Guatemala, Pakistan, Democratic Republic of the Congo and Zambia. Only one intervention employed a non-feeding control arm and found beef consumption to improve cognitive abilities compared to the control. However, the other interventions comparing beef consumption to other food types found no consistent result. (4) Conclusions: Evidence pertaining to the impact of beef consumption on cognition remains limited due to the small and heterogeneous set of studies. Future research should adopt a population representative sample and longer follow-up period, employ a non-feeding control arm and comprehensively measure nutrient intakes among study participants.
Identification of a noncanonical RNA binding domain in the U2 snRNP protein SF3A1

During splicing of pre-mRNA, 5′ and 3′ splice sites are brought within proximity by interactions between the pre-mRNA bound U1 and U2 snRNPs, followed by recruitment of the tri-snRNP for assembly of the mature spliceosome. Previously, we identified an interaction between the U2 snRNP-specific protein SF3A1 and the stem–loop 4 (SL4) of the U1 snRNA that occurs during the early steps of spliceosome assembly. Although harboring many annotated domains, SF3A1 lacks a canonical RNA binding domain. To identify the U1-SL4 binding region in SF3A1, we expressed amino- and carboxy-terminal deletion constructs using a HeLa cell-based cell free expression system. UV-crosslinking of the truncated proteins with 32P-U1-SL4 RNA identified the carboxy-terminal ubiquitin-like (UBL) domain of SF3A1 as the RNA binding region. Characterization of the interaction between SF3A1-UBL and U1-SL4 by electrophoretic mobility shift assay and surface plasmon resonance determined high binding affinity (KD = ∼97 nM), and revealed the double-stranded G-C rich stem of U1-SL4 as an important feature for binding to the UBL domain. Further, mutations of two conserved tyrosine residues, Y772 and Y773, were found to cause a two- and fivefold decrease in the binding affinity for U1-SL4, respectively. Finally, we found that SF3A1-UBL can specifically pull down the U1 snRNP from HeLa nuclear extract, demonstrating its capacity to bind U1-SL4 in the context of the intact snRNP. Thus, the data show that the UBL domain of SF3A1 can function as an RNA binding domain and that mutations in this region may interfere with U1-SL4 binding.
Absorption of 1,3-dioleyl-2-palmitoylglycerol and intestinal flora profiles changes in mice

Abstract The purpose of this study was to investigate the digestion and absorption of 1,3-dioleyl-2-palmitoylglycerol (OPO) and its effects on mineral absorption and intestinal flora in vivo. Fatty acids and mineral faeces were measured using gas chromatography-mass spectrometry and inductively coupled plasma mass spectrometry, respectively. The intestinal flora composition was assessed using high-throughput 16S rRNA sequencing. After 4-week feeding experiment, the apparent absorption rate of calcium in O group (mice fed with OPO) was 48.54 ± 0.21%, which was significantly higher than that in Z group (mice fed with mixed vegetable oil), the percentage of palmitic acid in serum of the O group mice was significantly higher. Compared with Z group, the mean relative abundance of Bifidobacteriaceae and Lactobacillaceae in the O group mice was higher. These results show that OPO can promote the absorption of fat and calcium, promote the growth of beneficial bacteria.
Normative data for the oldest old: Trail Making Test A, Symbol Digit Modalities Test, Victoria Stroop Test and Parallel Serial Mental Operations

ABSTRACT Normative data for evaluating cognitive function in the oldest old, aged 85 years and above, are currently sparse. The normative values used in clinical practice are often derived from younger old persons, from small sample sizes or from broad age spans (e.g. >75 years) resulting in a risk of misjudgment in assessments of cognitive decline. This longitudinal study presents normative values for the Trail Making Test A (TMT-A), the Symbol Digit Modalities Test (SDMT), the Victoria Stroop Test (VST) and the Parallel Serial Mental Operations (PaSMO) from cognitively intact Swedes aged 85 years and above. 207 participants, born in 1922, were tested at 85, 90 (n = 68) and 93 (n = 35) years of age with a cognitive screening test battery. The participants were originally recruited for participation in the Elderly in Linköping Screening Assessment. Normative values are presented as mean values and standard deviations, with and without adjustment for education. There were no clinically important differences between genders, but education had a significant effect on test results for the 85-year-olds. Age effects emerged in analyses of those participants who completed the entire study and were evident for TMT-A, SDMT, VST1 and PaSMO. When comparisons can be made, our results are in accordance with previous data for TMT-A, SDMT and VST, and we present new normative values for PaSMO.
Low latency CDMA-based protocol to support IoT traffic in 5g

OF THE THESIS Low Latency CDMA-Based Protocol to Support IoT Traffic in 5G by Siddarth Mathur Thesis Director: Prof. Dipankar Raychaudhuri The upcoming 5th generation mobile network architecture is envisioned to deploy massive Internet-of-Things (IoTs) devices with a variety of traffic patterns. These devices will often transmit short sporadic messages, which are not well suited to the connection-oriented modes associated with legacy 3GPP networks resulting in high service latency and excessive control overhead. This thesis presents the design of a low latency MAC (Medium Access Layer) / PHY (Physical Layer) protocol for emerging Internet of Things (IoT) devices that require low access delay. The goal is to operate in the same band as current LTE, thus not requiring any separate channel allocation, while maintaining backward compatibility with the current LTE system. The physical layer access is achieved using an underlay CDMA-based low power transmission scheme, which operates in the same frequency range as the LTE’s uplink/downlink frequencies. The MAC layer is designed for low access latency by transmitting small sized data in a random access mode as it becomes available, eliminating the need to setup a connection. A proof of concept prototype was developed to demonstrate the feasibility of the proposed design and the performance of the CDMA system and in presence of LTE. The CDMA based transmission was prototyped using the Software Defined Radio (SDR)
How do women with social risk factors experience United Kingdom maternity care? A realist synthesis

Abstract Background Echoing international trends, the most recent United Kingdom reports of infant and maternal mortality found that pregnancies to women with social risk factors are over 50% more likely to end in stillbirth or neonatal death and carry an increased risk of premature birth and maternal death. The aim of this realist synthesis was to uncover the mechanisms that affect women's experiences of maternity care. Methods Using realist methodology, 22 papers exploring how women with a wide range of social risk factors experience maternity care in the United Kingdom were included. The data extraction process identified contexts (C), mechanisms (M), and outcomes (0). Results Three themes, Resources, Relationships, and Candidacy, overarched eight CMO configurations. Access to services, appropriate education, interpreters, practical support, and continuity of care were particularly relevant for women who are unfamiliar with the United Kingdom system and those living chaotic lives. For women with experience of trauma, or those who lack a sense of control, a trusting relationship with a health care professional was key to regaining trust. Many women who have social care involvement during their pregnancy perceive health care services as a system of surveillance rather than support, impacting on their engagement. This, as well as experiences of paternalistic care and discrimination, could be mitigated through the ability to develop trusting relationships. Conclusions The findings provide underlying theory and practical guidance on how to develop safe services that aim to reduce inequalities in women's experiences and birth outcomes.
2004 Special issue Early lexical development in a self-organizing neural network

In this paper we present a self-organizing neural network model of early lexical development called DevLex. The network consists of two self-organizing maps (a growing semantic map and a growing phonological map) that are connected via associative links trained by Hebbian learning. The model captures a number of important phenomena that occur in early lexical acquisition by children, as it allows for the representation of a dynamically changing linguistic environment in language learning. In our simulations, DevLex develops topographically organized representations for linguistic categories over time, models lexical confusion as a function of word density and semantic similarity, and shows age-of-acquisition effects in the course of learning a growing lexicon. These results match up with patterns from empirical research on lexical development, and have significant implications for models of language acquisition based on self-organizing neural networks.