Browse Articles

The role of dietary inflammation in the risk of osteoporosis in Iranian postmenopausal women: a case-control study

Out-of-distribution generalization via composition: A lens through induction heads in Transformers

Large language models (LLMs) such as GPT-4 sometimes appear to be creative, solving novel tasks often with a few demonstrations in the prompt. These tasks require the models to generalize on distributions different from those from training data—which is known as out-of-distribution (OOD) generalization. Despite the tremendous success of LLMs, how they approach OOD generalization remains an open and underexplored question. We examine OOD generalization in settings where instances are generated according to hidden rules, including in-context learning with symbolic reasoning. Models are required to infer the hidden rules behind input prompts without any fine-tuning. We empirically examined the training dynamics of Transformers on a synthetic example and conducted extensive experiments on a variety of pretrained LLMs, focusing on a type of component known as induction heads. We found that OOD generalization and composition are tied together—models can learn rules by composing two self-attention layers, thereby achieving OOD generalization. Furthermore, a shared latent subspace in the embedding (or feature) space acts as a bridge for composition by aligning early layers and later layers, which we refer to as the common bridge representation hypothesis.

Cluster analysis of physical activity and physical fitness and their associations with components of school skills in children aged 8–9 years

The genomic and epigenomic landscapes of hemizygous genes across crops with contrasting reproductive systems

Hemizygous genes, which are present on only one of the two homologous chromosomes of diploid organisms, have been mainly studied in the context of sex chromosomes and sex-linked genes. However, these genes can also occur on the autosomes of diploid plants due to structural variants (SVs), such as a deletion/insertion of one allele, and this phenomenon largely unexplored in plants. Here, we investigated the genomic and epigenomic landscapes of hemizygous genes across 22 genomes with varying propagation histories: eleven clonal lineages, seven outcrossed samples, and four inbred and putatively homozygous genomes. We identified SVs leading to genic hemizygosity. As expected, very few genes (0.01 to 1.2%) were hemizygous in the homozygous genomes, representing negative controls. Hemizygosity was appreciable among outcrossed lineages, averaging 8.7% of genes, but consistently elevated for the clonal samples at 13.8% genes, likely reflecting heterozygous SV accumulation during clonal propagation. Compared to diploid genes, hemizygous genes were more often situated in centromeric than telomeric regions and experienced weaker purifying selection. They also had reduced levels of expression, averaging ~20% of the expression levels of diploid genes, violating the evolutionary model of dosage compensation. We also detected higher DNA methylation levels in hemizygous genes and transposable elements, which may contribute to their reduced expression. Finally, expression profiles showed that hemizygous genes were more specifically expressed in contexts related to fruit development, organ differentiation, and stress responses. Overall, hemizygous genes accumulate in clonally propagated lineages and display distinct genetic and epigenetic features compared to diploid genes, shedding unique insights into genetic studies and breeding programs of clonal crops.

Investigating brain activity at rest in patients with persistent genital arousal disorder (PGAD) using functional magnetic resonance imaging

Abstract Persistent genital arousal disorder (PGAD) is a rare disease causing high emotional distress eminently impacting the individual’s quality of life. Experts in this field assume that the disease is caused by a multifaceted interplay of different etiologies which may share a common neurobiological basis. However, only one functional neuroimaging investigation exist, and a more in-depth comprehension of the neurobiological foundation is required. Therefore, this study aims to provide new insights into how the functional integration of brain regions may relate to PGAD. By using the functional magnetic resonance imaging (fMRI) technique, functional connectivity at rest (rs-FC) was compared between patients suffering PGAD (n = 26) and healthy controls (n = 26). Patients with PGAD showed different pattern in connectivity within brain structures putatively associated with the psychological and somatic dimensions of the disease including the right amygdala, left anterior cingulate cortex, right insula cortex, thalamic nuclei and prefrontal regions as seeds. The majority of these showed differences in brain connectivity pattern to the precuneus and prefrontal regions. The study offers preliminary insights into the characteristics and relevant neural mechanisms of PGAD. Nevertheless, since this study did not identify any peripheral correlates that would corroborate the interpretation of these findings, they were interpreted from a more theoretical perspective, thereby offering potential areas of focus for future research.

Contextual neural dynamics during time perception in the primate ventral premotor cortex

Understanding how time perception adapts to cognitive demands remains a significant challenge. In some contexts, the brain encodes time categorically (as “long” or “short”), while in others, it encodes precise time intervals on a continuous scale. Although the ventral premotor cortex (VPC) is known for its role in complex temporal processes, such as speech, its specific involvement in time estimation remains underexplored. In this study, we investigated how the VPC processes temporal information during a time interval comparison task (TICT) and a time interval categorization task (TCT) in primates. We found a notable heterogeneity in neuronal responses associated with time perception across both tasks. While most neurons responded during time interval presentation, a smaller subset retained this information during the working memory periods. Population-level analysis revealed distinct dynamics between tasks: In the TICT, population activity exhibited a linear and parametric relationship with interval duration, whereas in the TCT, neuronal activity diverged into two distinct dynamics corresponding to the interval categories. During delay periods, these categorical or parametric representations remained consistent within each task context. This contextual shift underscores the VPC’s adaptive role in interval estimation and highlights how temporal representations are modulated by cognitive demands.

Design and fabrication of an ultra small quadband diplexer integrated with a diplexed power amplifier for mid band 5G applications

tRNA selectivity during ribosome-associated quality control regulates the critical sterility-inducing temperature in two-line hybrid rice

The two-line hybrid rice system, a cutting-edge hybrid rice breeding technology, has greatly boosted global food security. In thermo-sensitive genic male sterile (TGMS) lines, the critical sterility-inducing temperature (CSIT; the temperature at which TGMS lines change from male fertile to complete male sterile) acts as a key threshold. We recently uncovered that thermo-sensitive genic male sterility 5 ( tms5 ), a sterile locus presenting in over 95% of TGMS lines, leads to the overaccumulation of 2′,3′-cyclic phosphate (cP)-ΔCCA-tRNAs and a deficiency of mature tRNAs, which underlies the molecular mechanism of tms5 -mediated TGMS. However, there are a few reports on the regulatory mechanism controlling CSIT. Here, we identified a suppressor of tms5 , an amino acid substitution (T552I) in the rice Rqc2 (ribosome-associated quality control 2), increases the CSIT in tms5 lines through its C-terminal alanine and threonine modification (CATylation) activity. This substitution alters tRNA selectivity, leading to the recruitment of different tRNAs to the A-site of ribosome and CATylation rate by OsRqc2 during ribosome-associated quality control (RQC), a process that rescues stalled ribosomes and degrades abnormal nascent chains during translational elongation. Further, the mutation restores the levels of mature tRNA-Ser/Ile to increase the CSIT of tms5 lines. Our findings reveal the origin of overaccumulated cP-ΔCCA-tRNAs in tms5 lines, further deepening our understanding of the regulatory network in governing CSIT of TGMS lines containing tms5.

Health risk assessment via Monte Carlo simulation and sensitivity analysis for fluoride and nitrate content in bottled waters consumed in Kermanshah city, Iran

Abstract Bottled water consumption has increased in recent decade due to many reasons, especially significant decline in water quality and quantity. The concentration of fluoride and nitrate in bottled waters may vary based on brands and locations. This study was carried out to determine the levels of fluoride and nitrate in bottled waters consumed in Kermanshah city and assess the related non -carcinogenic risks. Totally, 22 brands of bottled water were collected from markets. Fluoride and nitrate measurement was conducted via a UV-visible spectrophotometer (DR-5000). From the results, Fluoride and nitrate levels in the studied bottled waters were 0.32 ± 0.18 mg/L and 2.3 ± 1.41 mg/L, respectively. The risk of non-carcinogenic in term of HQ for fluoride exposure, for only 2 brands of bottled water were > 1 for infants group. HQ was less than 1 for nitrate in all the brands for all the age groups revealed non-carcinogen risks. Hazard index (HI) calculation showed that only in 2 brands of bottled water HI was > 1 for infants group. The HI were as infants (0.64) > children (0.36) > teenagers (0.27) > adults (0.24). From Monte Carlo simulation, 95th Percentile for nitrate and fluoride was less than 1 for all the groups. This result indicated non-carcinogenic risks of nitrate and fluoride for 95% of the studied groups. Moreover, sensitivity analysis showered that concentration for both nitrate and fluoride had the highest effect on HQ for all the groups. From this work, although fluoride and nitrate content in the bottled waters were at standard range, but infants were proportionally at higher risk.

Trajectories of quality of life during hematopoietic stem cell transplantation: longitudinal cohort study

Dynamic response and damage mechanism of reinforced concrete beam bridges under rockfall impacts

Microwave resonance detection method for hidden crack depth in rock and cementitious mortar

Top-performing girls are more impactful peer role models than boys, teachers say

We examine teachers’ perceptions toward top-performing students and their role model influence on others in an online survey-based experiment. We randomly expose teachers to profiles of top-performing students and inquire whether they consider the profiled top performers to be influential role models. These profiles varied by gender and field of study (STEM or Non-STEM). Our findings show that teachers perceive top-performing girls as more influential peer role models compared to top-performing boys ( β ̂ = 0.289 ; P < 0.001 ). We also investigate the qualities teachers perceive top performers who are successful role models to have. We show that teachers associate a greater sense of learning autonomy and sense of being an example with top-performing girls compared to top-performing boys. Estimated effects are more pronounced among teachers with children and teachers in urban areas. Administrative data from a representative sample show limited observed differences between top-performing boys’ and girls’ educational outcomes that could justify the differences in teachers’ gender perceptions. These findings carry significant implications for education, as teachers play a crucial role in the cultivation of positive externalities between students.

Enhancing Intelligent HVAC optimization with graph attention networks and stacking ensemble learning, a recommender system approach in Shenzhen Qianhai Smart Community

Facile fabrication of novel magnetic chitosan@Ag-MWCN nanocomposite for the adsorptive removal of ciprofloxacin from aqueous solutions

Author Correction: Lignan enriched fraction (LRF) of Phyllanthus amarus promotes apoptotic cell death in human cervical cancer cells in vitro

The ER–PM interaction is essential for cytokinesis and recruits the actin cytoskeleton through the SCAR/WAVE complex

Plant cytokinesis requires coordination between the actin cytoskeleton, microtubules, and membranes to guide division plane formation and cell plate expansion; how these regulatory factors are coordinated remains unknown. The actin cytoskeleton assembly is controlled by several actin nucleation factors, such as the SCAR/WAVE complex, which regulates actin nucleation and branching through the activation of the ARP2/3 complex. The activity of these actin regulatory proteins is likely influenced by interactions with specific membranes; however, the molecular basis and the biological relevance of SCAR–membrane interactions are also unclear. In this study, we demonstrate that the ER–PM tethering protein VAP27-1 directly interacts with SCAR2 at the ER membrane and that they colocalize to guide cell plate orientation during cell division. In the root meristem, both VAP27-1 and SCAR2 exhibit polarized localization at the cell plates, where the interaction between ER and PM is abundant. VAP27-1 recruits SCAR2 to the cell division plane, where there is a high concentration of actin filaments. In the vap27-1346 mutant, the densities of cortical ER, SCAR2, and consequently actin filaments are significantly reduced at the cell division plane, affecting cell plate orientation, cell division, and root development. A similar phenomenon is also observed in the scar1234 mutant, suggesting that VAP27 and SCAR proteins regulate cell division through a similar pathway. In conclusion, our data reveal a plant-specific function of VAP27-regulated ER–PM interaction and advance our understanding of plant ER–PM contact site and its role in cell division.

Combining plant extracts and hot water treatments for the management of postharvest mango anthracnose (Colletotrichum gloeosporioides)

The structure of full-length AFPK supports the ACP linker in a role that regulates iterative polyketide and fatty acid assembly

The polyketide synthases (PKSs) in microbes and the cytoplasmic fatty acid synthases in humans (FASs) are related enzymes that have been well studied. As a result, there is a paradigm explaining in general terms how FASs repeatedly use a set of enzymatic domains to produce simple fats, while PKSs use the domains in a much more complex manner to produce pharmaceuticals and other elaborate molecules. However, most animals also have PKSs that do not conform to the rules described in microbes, including a large family of enzymes that bridge fatty acid and polyketide metabolism, the animal FAS-like PKSs (AFPKs). Here, we present the cryoelectron microscopy structures of two AFPKs from sea slugs. While the AFPK resemble mammalian FASs, their chemical products mimic those of PKSs in complexity. How then does the architecture of AFPKs facilitate this structural complexity? Unexpectedly, chemical complexity is controlled not solely by the enzymatic domains but is aided by the dynamics of the acyl carrier protein (ACP), a shuttle that moves intermediates between these domains. We observed interactions between enzyme domains and the linker-ACP domain, which, when manipulated, altered the kinetic properties of the enzyme to change the resulting chemical products. This unveils elaborate mechanisms and enzyme motions underlying lipid and polyketide biochemistry across the domains of life.

Effect of pH and buffer on substrate binding and catalysis by cis-aconitate decarboxylase

Abstract cis-Aconitate decarboxylase (ACOD1, CAD, IRG1) catalyses the synthesis of itaconic acid in activated myeloid cells such as macrophages. Several histidine residues in the active site bind the substrate and enable the decarboxylation reaction. The in vitro activity of ACOD1 enzymes is commonly determined by incubation with substrate, followed by HPLC measurement of itaconic acid production. Phosphate buffers have often been used for this assay. However, the influence of buffer type on enzyme activity has not been investigated. Here, the effect of buffer and pH on enzyme kinetics of human and mouse ACOD1 and Aspergillus terreus CAD was investigated. It was found that high concentrations of phosphate inhibit the three enzymes. An alternative buffer was selected and the assay was adapted to the 96-well microtitre plate format for increased throughput. Enzyme kinetics were determined in the pH range of 5.5–8.25. A strong increase of K M values was observed between the physiologically relevant pH values 7.5 and 8.25. The data indicate that more than one histidine residue needs to be protonated in the active site for binding the substrate.