Latest preprints

Enhancing cryogenic electron microscopy (cryo-EM) 3D density maps at intermediate resolution (4-8 Å) is crucial in protein structure determination. Recent advances in deep learning have led to the development of automated approaches for enhancing experimental cryo-EM density maps. Yet, these methods are not optimized for intermediate-resolution maps and rely on map density features alone. To address this, we propose CryoSAMU, a novel method designed to enhance 3D cryo-EM density maps of protein structures using structure-aware multimodal U-Nets and trained on curated intermediate-resolution density maps. We comprehensively evaluate CryoSAMU across various metrics and demonstrate its competitive performance compared to state-of-the-art methods. Notably, CryoSAMU achieves significantly faster processing speed, showing promise for future practical applications. Our code is available at https://github.com/chenwei-zhang/CryoSAMU.

Seminal frameworks of predictive coding propose a hierarchy of generative modules, each attempting to infer the neural representation of the module one level below; the predictions are carried by top-down feedback projections, while the predictive error is propagated by reciprocal forward pathways. Such symmetric feedback connections support visual processing of noisy stimuli in computational models. However, neurophysiological studies have yielded evidence of asymmetric cortical feedback connections. We investigated the contribution of neural feedback during sensorimotor processes, in particular visual processing during grasp planning, by utilizing convolutional neural network models that had been augmented with predictive feedback and were trained to compute grasp positions for real-world objects. After establishing an ameliorative effect of symmetric feedback on grasp detection performance when evaluated on noisy stimuli, we characterized the performance effects of asymmetric feedback, similar to that observed in the cortex. Specifically, we tested model variants extended with short-, medium- and long-range feedback connections (i) originating at the same source layer or (ii) terminating at the same target layer. We found that the performance-enhancing effect of predictive coding under adverse conditions was optimal for medium-range asymmetric feedback. Moreover, this effect was most prominent when medium-range feedback originated at a level of representational abstraction that was proximal to the input layer, in contrast to more distal layers. To conclude, our simulations show that introducing biologically realistic asymmetric predictive feedback improves model robustness to noisy visual stimuli in a neural network model optimized for grasp detection.Significance statement: It is commonly held that the brain predicts the causes of its sensorium via top-down neural pathways. While canonical models of predictive coding assume reciprocal feedforward and feedback connections, functional evidence highlights the importance of non-reciprocal ‘asymmetric’ feedback, whose role remains poorly understood, particularly in sensorimotor functions. Using neural network models of grasp planning, we characterized optimal pathlengths and source regions for asymmetric feedback facilitating visuomotor processing of noisy sensory inputs. Our findings show that medium-range feedback from early layers marks a sweet spot, incorporating optimal distance between the neural representations of source/target layers and representational abstraction of the feedback source. This intimates an uncharted role of intermediate brain areas along the visuomotor stream as a source of predictive signals.

Genetics has been the cornerstone for understanding life for over a century, how it reproduces and evolves, and how human health is sustained. Johannsen’s 1911 genotype conception, that ‘genes are the units of heredity,’ replaced the phenotype conception upon which Galton’s successful 1897 law of ancestral heredity was based[1]. However, the case is far from being closed.In 1992, radiation-induced genomic instability and the bystander effect challenged the genotype conception[2]. Further, in 2009, genetic variance could not explain the fitness trajectory of the E. coli bacteria in the Long-Term Evolution Experiment (LTEE)[3]. In 2013, it was clear that evolution in the LTEE was thermodynamically, not genetically, driven[4].This paper briefly outlines the history of heredity from 1880 and Mendelism from 1900 and reviews recent empirical evidence that fundamentally challenges those two domains. Although in the past century genetics has moved on to encompass such disciplines as epigenetic inheritance, genetic regulatory networks, system biology, etc., 20th century gene-centric concepts of heredity remain foundational.

Complete and partial sex role reversals, where males are selective and females compete, are common in species in which males contribute more than just sperm to reproduction. In the Lepidoptera order, and particularly in the pink bollworm moth, both sexes invest significantly in reproduction. Therefore, we hypothesized that both females and males would exhibit some degree of mate selectiveness. Our study found that males delayed mating with smaller, less fecund females when larger, more fecund females were present in their surroundings. In contrast, males raised without exposure to females mated indiscriminately with both large and small females. Additionally, larger, more fecund females were more selective than their smaller, less reproductive counterparts. Even though large females exhibited greater selectiveness than small females, their selectiveness appears to be an indirect form of mate choice, as they did not choose based on the males’ size but rather rejected a higher number of males overall.

Every single chemical formula of modern models of glycolysis violates the scientific rules formulated by Newton (Physics) and Lavoisier (Chemistry). Yet, the formulae of the pioneers who investigated metabolism did not violate the laws of nature. Recently, the well-established models of metabolism have collapsed by re-introducing hydrogen (Chemistry, Physics) as the energy entity driving the Krebs-cycle (Biochemistry). This review builds on a scientific concept of metabolism by introducing that glycolytically generated energy is either transformed into ATP or drives a biological process. The dynamic production and utilization of lactate (lactate flow non-equilibrium) is introduced as a central ATP-driven process and the first step of biosynthesis. A metabolism model based on non-equilibrium thermodynamics replaces the current understanding that one end product of glycolysis is consumed by mitochondria with two intermediates of the two-cell model of metabolism that are consumed by mitochondria. The pyruvate dehydrogenase complex, consuming pyruvic acid, saves one redox unit (2H) for storage as lipid or glycogen, whereas mitochondrial consumption of lactic acid enhances ATP recovery. An uncounted number of signalling pathways temporarily regulate the distribution of this single redox unit. Glycogenolysis massively impacts the flow non-equilibrium, an event permanently memorized by cells. The two-cell model of metabolism starts to functionally unite fields such as memory formation, obesity, exercise, schizophrenia, cancer, and inflammation by the common denominator: metabolism.

Awassi sheep are well-adapted to arid climates, showcasing the potential of sheep farming in diverse and challenging environments. However, productivity remains a concern, necessitating selective breeding and improved management practices. This study, conducted at the Al-Fjaj Station in Jordan, analyzed 2,263 weight records of Awassi sheep raised under a semi-intensive system. The objective was to evaluate the environmental and genetic factors influencing lamb weight and to estimate heritability and breeding values.Analysis of variance revealed that birth type, sex, parity, and the age of the ewe at lambing significantly affected lamb weight at all developmental stages. Single-born lambs were heavier at birth, males outweighed females, and younger ewes produced lighter lambs that exhibited compensatory growth over time. Strong positive correlations were found among weaning, six-month, and yearling weights, while birth weight had a relatively weaker influence on later weight development.The results also indicated that individual rams had the most substantial effect on lamb weights, while heritability showed a moderate contribution. Strong genetic correlations among traits suggest that selection for one weight trait can lead to improvements in others. Breeding values tended to decline with age due to environmental influences, supporting the use of index selection to enhance desirable traits. Moreover, the strong correlations between breeding values and actual weights indicate that selecting individuals with high breeding values can enhance genetic potential and predict future performance.Improving weight gain in future generations hinges on the selection of rams with superior breeding values. Average weight measures serve as critical indicators for both genetic progress and economic viability. This study identifies birth type, sex, parity, and ewe age as key determinants of lamb growth, highlighting the advantages of single births and male lambs. An index selection strategy that integrates both genetic and environmental factors is recommended to support sustainable lamb production in arid regions.

The emergence of SARS-CoV-2 in late 2019 triggered a global pandemic (COVID-19) that has claimed millions of lives and continues to impact public health systems worldwide. This review examines current scientific evidence regarding the virus's origins, focusing on two primary hypotheses: zoonotic spillover and laboratory-related emergence. A comprehensive analysis of peer-reviewed literature primarily published between December 2023 and January 2025 was conducted, identifying relevant studies through searches of the PubMed and Scopus databases. Key earlier publications are also included to provide essential background and context. The analysis revealed strong phylogenetic evidence supporting a natural zoonotic origin, with several studies indicating close genetic relationships to bat coronaviruses. Environmental sampling data from the Huanan Seafood Market detected SARS-CoV-2 RNA in a high number of environmental samples from animal stalls. While the preponderance of evidence supports natural zoonotic spillover, the absence of a definitively identified intermediate host maintains some uncertainty. This review concludes with evidence-based recommendations for enhanced viral surveillance, implementation of One Health approaches, and strengthened international collaboration frameworks to prevent future coronavirus pandemics.

The protozoan parasite Toxoplasma gondii can alter behavior by heightening the boldness of multiple taxa to increase predation by their definitive host—Felids. We screened northern raccoons (Procyon lotor) for Toxoplasma-infection and monitored American crocodile (Crocodylus acutus) nests with camera traps in the Florida Keys, USA. On four occasions, we documented raccoons investigating a monitored active nest until the female crocodile chased them off. We quantified the elapsed reaction time (ERT) as the number of seconds between raccoon retreat and crocodile surfacing into the photo frame, with longer times representing faster responses of retreat prior to the crocodile attack. Three of the incidents resulted in ERTs of 4-8 seconds (mean = 6 seconds) before the crocodile surfaced. Yet, the radio-collared raccoon from our study had a 0 second ERT and narrowly escaped, which may be the result of chronic seropositive (titer = 1:200) and mind-altering effects of Toxoplasma beyond ordinary raccoon boldness. That individual successfully depredated a crocodile nest the following season. We hypothesize that Toxoplasma-infection is a Simpson’s paradox wherein short-term net benefits appear positive (e.g., successful nestpredation due to boldness), but overall they may result in lower fitness (e.g., lower survivorship due to boldness). Camera traps can elucidate behavioral changes in species interactions by explicitly quantifying reaction times.