bluuebunny/crossref_metadata_2025_split huggingface dataset:
Data-driven system matrix manipulation enabling fast functional imaging and intra-image nonrigid motion correction in tomography
Authors: Hu Peng , Tong Xin , Lin Li , Wang Lihong V. 
Published: January 2024

AbstractTomographic imaging modalities are described by large system matrices. Sparse sampling and tissue motion degrade system matrix and image quality. Various existing techniques improve the image quality without correcting the system matrices. Here, we compress the system matrices to improve computational efficiency (e.g., 42 times) using singular value decomposition and fast Fourier transform. Enabled by the efficiency, we propose (1) fast sparsely sampling functional imaging by incorporating a densely sampled prior image into the system matrix, which maintains the critical linearity while mitigating artifacts and (2) intra-image nonrigid motion correction by incorporating the motion as subdomain translations into the system matrix and reconstructing the translations together with the image iteratively. We demonstrate the methods in 3D photoacoustic computed tomography with significantly improved image qualities and clarify their applicability to X-ray CT and MRI or other types of imperfections due to the similarities in system matrices.
Neural precursor cells rescue symptoms of Rett syndrome by activation of the Interferon γ pathway
Authors: Frasca Angelisa , Miramondi Federica , Butti Erica , Indrigo Marzia , Arenas Maria Balbontin , Postogna Francesca M. , Piffer Arianna , Bedogni Francesco , Pizzamiglio Lara , Cambria Clara , Borello Ugo , Antonucci Flavia , Martino Gianvito , Landsberger Nicoletta 
Published: January 2024

AbstractThe beneficial effects of Neural Precursor Cell (NPC) transplantation in several neurological disorders are well established and they are generally mediated by the secretion of immunomodulatory and neurotrophic molecules. We therefore investigated whether Rett syndrome (RTT), that represents the first cause of severe intellectual disability in girls, might benefit from an NPC-based therapy.Usingin vitroco-cultures, we demonstrate that, by sensing the pathological context, NPC-secreted factors induce the recovery of morphological and synaptic defects typical ofMecp2deficient neurons.In vivo,we prove that intracerebral transplantation of NPCs in RTT mice significantly ameliorates neurological functions. To uncover the molecular mechanisms underpinning the mediated benefic effects, we analysed the transcriptional profile of the cerebellum of transplanted animals, disclosing the possible involvement of the Interferon γ (IFNγ) pathway. Accordingly, we report the capacity of IFNγ to rescue synaptic defects, as well as motor and cognitive alterations inMecp2deficient models, thereby suggesting this molecular pathway as a potential therapeutic target for RTT.
Interaction BetweenYersinia pestisAil Outer Membrane Protein and the C-Terminal Domain of Human Vitronectin
Authors: Vasseur Laurine , Barbault Florent , Monari Antonio 
Published: January 2024

ABSTRACTYersinia pestis, the causative agent of plague, is capable to evade human immune system response by recruiting the plasma circulating vitronectin proteins, which acts as a shield and avoids its lysis. Vitronectin recruitment is mediated by its interaction with the bacterial transmembrane protein Ail, protruding fromY. pestisouter membrane. By using all atom long-scale molecular dynamic simulations of Ail embedded in a realistic model of the bacterial membrane, we have shown that vitronectin forms a stable complex, mediated by interactions between the disordered moieties of the two proteins. The main amino acids driving the complexation have also been evidenced, thus favoring the possible rational design of specific peptides which, by inhibiting vitronectin recruitment, could act as original antibacterial agents.TOC ABSTRACT
Turmeric shortens lifespan in houseflies
Authors: Laurie Sophie , Ainslie Leah , Mitchell Sharon , Morimoto Juliano 
Published: January 2024

AbstractClimate change poses a significant threat to food security and global public health with the increasing likelihood of insect pest outbreaks. Alternative ways to control insect populations, preferably using environmental-friendly compounds, are needed. Turmeric has been suggested as a natural insecticide with toxicity properties in some insect groups. However, empirical evidence of the effects turmeric – and their interaction with other ecological factors such as diet – on insect survival has been limited. Here, we tested the effects of turmeric and its interactions with diets differing in protein source in the common housefly,Musca domestica. We found that turmeric shortened lifespan independent of diet and sex. Females in turmeric diets were heavier at death, which was likely driven by a combination of relatively lower rates of body mass loss during their lifetime and a higher percentage of water content at death. Each sex responded differently to the protein source in the diet, and the magnitude of the difference in lifespan between sexes were greatest in diets in which protein source was hydrolysed yeast; individuals from both sexes lived longest in sucrose-milk diets and shortest in diets with hydrolysed yeast. There was no evidence of an interaction between turmeric and diet, suggesting that the toxicity effects are independent of protein source in the diet. Given the seemingly opposing effects of turmeric in insects and mammals being uncovered in the literature, our findings provide further evidence in support of turmeric as a potential natural insecticide.
A BODIPY-naphtholimine-BF2dyad for precision photodynamic therapy, targeting and dual imaging of endoplasmic reticulum and lipid droplets in cancer
Authors: Chauhan Nitish , Koli Mrunesh , Ghosh Rajib , Majumdar Ananda Guha , Ghosh Ayan , Ghanty Tapan Kumar , Mula Soumyaditya , Patro Birija Sankar 
Published: January 2024

ABSTRACTCurrently effective therapeutic modalities for pancreatic ductal adenocarcinoma (PDAC) is not available, leading to gloomy prognosis and ~6-months median patient survival. Recent advances showed the promise of photodynamic therapy (PDT) for PDAC patients. Next generation photosensitizers (PS) are based on “organelle-targeted-PDT” and provides new paradigm in the field of precision medicines to address the current challenge for treating PDAC. In this investigation, we have constructed a novel PS, named asNbB, for precise targeting of endoplasmic reticulum (ER) and lipid droplets (LD) in PDAC, as malignant PDAC cells are heavily relying on ER for hormone synthesis. Our live cell imaging and fluorescence recovery after photobleaching (FRAP) experiments revealed thatNbBis instantly targeted to ER and LD and show simultaneous dual fluorescence colour due to polar and non-polar milieu of ER and LD. Interestingly, the same molecule generates triplet state and singlet oxygen efficiently and cause robust ER stress and apoptosis in two different PDAC cells in the presence of light. Together, we present, for the first time, a potential next generation precision medicine for ER-LD organelle specific imaging and PDT of pancreatic cancer.
High-Resolution Molecular-Dynamics Simulations of the Pyruvate Kinase Muscle Isoform 1 and 2 (PKM1/2)
Authors: Delobelle Quentin , Inizan Théo Jaffrelot , Adjoua Olivier , Lagardère Louis , Célerse Frédéric , Maréchal Vincent , Piquemal Jean-Philip 
Published: January 2024

Glucose metabolism plays a pivotal role in physiological processes and cancer growth. The final stage of glycolysis, converting phosphoenolpyruvate (PEP) into pyruvate, is catalyzed by the pyruvate kinase (PK) enzyme. Whereas PKM1 is mainly expressed in cells with high energy requirements, PKM2 is preferentially expressed in proliferating cells, including tumor cells. Structural analysis of PKM1 and PKM2 is essential to design new molecules with antitumoral activity. To understand their structural dynamics, we performed extensive high-resolution molecular dynamics (MD) simulations using adaptive sampling techniques coupled to the polarizable AMOEBA force field. Performing more than 6 µs of simulation, we considered all oligomerization states of PKM2 and propose structural insights for PKM1 to further study the PKM2-specific allostery. We focused on key sites including the active site and the natural substrate Fructose Bi-Phosphate (FBP) fixation pocket. Additionally, we present the first MD simulation of biologically active PKM1 and uncover important similarities with its PKM2 counterpart bound to FBP. We also analysed TEPP-46’s fixation, a pharmacological activator binding a different pocket, on PKM2 and highlighted the structural differences and similarities compared to PKM2 bound to FBP. Finally, we determined potential new cryptic pockets specific to PKM2 for drug targeting.Entry for the Table of ContentsProducing more than 6µs of cumulated simulation time with the AMOEBA polarizable force field, we determined key structural properties of the PKM2 (catalytic, FBP and TEPP) and PKM1 enzymes binding sites to determine new cryptic pockets for further antiviral/antitumoral drug design.
Genetic Toolbox forPhotorhabdusandXenorhabdus: pSEVA based heterologous expression systems and CRISPR/Cpf1 based genome editing for rapid natural product profiling
Authors: Rill Alexander , Zhao Lei , Bode Helge B. 
Published: January 2024

AbstractBackgroundBacteria of the genusPhotorhabdusandXenorhabdusare motile, Gram-negative bacteria that live in symbiosis with entomopathogenic nematodes. Due to their complex life cycle, they produce a large number of specialized metabolites (natural products) encoded in biosynthetic gene clusters (BGC). Genetic tools for this genus have been rare and applicable to only a few strains. In the past, several tools have been developed for the activation of BGCs and the deletion of individual genes. However, these often have limited efficiency or are time consuming. Among the limitations, it is essential to have versatile expression systems and genome editing tools that could facilitate the practical work.ResultsIn the present study, we developed several expression vectors and a CRISPR-Cpf1 genome editing vector for genetic manipulations inPhotorhabdusandXenorhabdususing SEVA plasmids. The SEVA collection is based on modular vectors that allow exchangeability of different elements (e.g. origin of replication and antibiotic selection markers with the ability to insert desired sequences for different end applications. Initially, we tested different SEVA vectors containing the broad host range origins and three different resistance genes for kanamycin, gentamycin and chloramphenicol, respectively. We demonstrated that these vectors are replicative not only in well-known representatives, e.g.Photorhabdus laumondiiTTO1, but also in other rarely described strains likeXenorhabdussp. TS4. For our CRISPR/Cpf1-based system, we used the pSEVA231 backbone to delete not only small genes but also large parts of BGCs. Furthermore, we were able to activate and refactor BGCs to obtain high production titers of high value compounds such as safracin B, a semisynthetic precursor for the anti-cancer drug ET-743.ConclusionsThe results of this study provide new inducible expression vectors and a CRISPR/CPf1 encoding vector all based on the SEVA (Standard European Vector Architecture) collection, which can improve genetic manipulation and genome editing processes inPhotorhabdusandXenorhabdus.
Interactions between saccades and smooth pursuit eye movements in marmosets
Authors: Pattadkal Jagruti J. , Barr Carrie , Priebe Nicholas J. 
Published: January 2024

ABSTRACTAnimals use a combination of eye movements to track moving objects. These different eye movements need to be coordinated for successful tracking, requiring interactions between the systems involved. Here, we study the interaction between the saccadic and smooth pursuit eye movement systems in marmosets. Using a single target pursuit task, we show that saccades cause an enhancement in pursuit following a saccade. Using a two-target pursuit task, we show that this enhancement in pursuit is selective towards the motion of the target selected by the saccade, irrespective of any biases in pursuit prior to the saccade. These experiments highlight the similarities in the functioning of saccadic and smooth pursuit eye movement systems across primates.SIGNIFICANCE STATEMENTWe study the coordination between the smooth-pursuit and saccadic eye movement systems in marmosets using single and multiple object motions. We find that saccade to a target increases pursuit velocity towards the target. If multiple objects are visible, saccade choice makes pursuit more selective towards the saccade target. Our results show that coordination between different eye movement systems to successfully track moving objects is similar between marmosets and primates.
MUM, a maternal unknown message, inhibits early establishment of the medio-lateral axis in the embryo of the kelpSaccharina latissima
Authors: Boscq Samuel , Billoud Bernard , Theodorou Ioannis , Joemmanbaks Tanweer , Charrier Bénédicte 
Published: January 2024

AbstractBrown algae are multicellular photosynthetic organisms that have evolved independently of plants and other algae. Apart from studies on the polarisation of theFucuszygote in the 1990s, little is known about the mechanisms controlling the embryogenesis of these organisms. Here, we studied the determinism of embryogenesis in the kelpSaccharina latissima,focusing on the formation of its body axes. This alga initially develops an oblong embryo formed of a cell monolayer, which subsequently thickens; growth axes are then established in temporally distinct stages, starting with the formation of a dominant apico-basal axis. Our experiments focused on the role of the stalk, an empty cell that retains the embryo attached to the maternal tissue, in the development of the growth axes in mature embryos. In response to the removal of the stalk, the embryos developed as a monolayered disc rather than an elongated blade, demonstrating that attachment to the stalk inhibits the formation of the medio-lateral axis at the onset of embryogenesis. In addition, compared with embryos attached to the stalk, the cells of detached embryos were smaller and displayed an altered shape. The topology of the tissue was also disrupted, as cells had a higher number of cell neighbours. Observation of cell division patterns just after removal of the stalk showed that the stalk represses longitudinal cell divisions, thereby reinforcing the establishment of the main apico-basal axis. This unique quantitative study of brown algal embryogenesis revealed that, in kelps, a signal from maternal tissue (MUM for maternal unknown message) is necessary for the establishment of growth axes at the onset of embryogenesis and of the organisation of growing embryonic tissues. In addition, we discovered that, although the stalk persists for several weeks until the embryo reaches at least 500 cells, MUM is emitted in the first 4 days after fertilisation only, before the embryo reaches the 8-cell stage. Finally, transplantation experiments indicated that MUM does not diffuse in seawater, but requires contact between the embryo and the stalk. The potential chemical or mechanical nature of MUM is discussed.
Structural dynamics of the methyl-coenzyme M reductase active site are influenced by coenzyme F430modifications
Authors: Polêto Marcelo D. , Allen Kylie D. , Lemkul Justin A. 
Published: January 2024

AbstractMethyl-coenzyme M reductase (MCR) is a central player in methane biogeochemistry, governing methanogenesis and the anaerobic oxidation of methane (AOM) in methanogens and anaerobic methanotrophs (ANME), respectively. The prosthetic group of MCR is coenzyme F430, a nickel-containing tetrapyrrole derivative. Additionally, a few modified versions of F430have been discovered, including the 172-methylthio-F430(mt-F430) that functions with ANME-1 MCR. This study employs molecular dynamics (MD) simulations to unravel the intricacies of the active-site dynamics of MCR fromMethanosarcina acetivoransand ANME-1 when bound to the canonical F430compared to 172-thioether coenzyme F430variants and substrates for methane formation. Overall, our simulations indicate that each MCR active site is optimized for a given version of F430and support the importance of the Gln to Val substitution in accommodating the 172methylthio modification. Notably, modifications in the 172position disrupt the canonical coordination among cofactors inM. acetivoransMCR, implicating structural perturbations, but evidence of active site reorganization to maintain substrate positions suggest that the modified F430s could be accommodated in a methanogenic MCR. We additionally report the first quantitative estimate of MCR intrinsic electric fields pivotal in driving methane formation. Our results suggest that the electric field aligned along the CH3-S-CoM thioether bond facilitates homolytic bond cleavage, coinciding with the proposed catalytic mechanism. Structural perturbations, however, weaken and misalign these electric fields, emphasizing the significance of the active site structure in maintaining their integrity. In conclusion, our results deepen the understanding of MCR active-site dynamics, the enzyme’s organizational role in intrinsic electric fields for catalysis, and the interplay between active site structure and electrostatics. This work not only advances our comprehension of MCR functionality but also provides a foundation for future investigations employing sophisticated models to capture the complex electronic properties of MCR active sites quantitatively.
Self-organized emergence of modularity, hierarchy, and mirror reversals from competitive synaptic growth in a developmental model of the visual pathway
Authors: Chandra Sarthak , Khona Mikail , Konkle Talia , Fiete Ila R. 
Published: January 2024

AbstractA hallmark of the primate visual system is itsarchitectural organizationconsisting of multiple distinct (modular) areas that connect hierarchically. These areas exhibit specificspatial organizationon the cortical sheet, with primary visual cortex at the center and subsequent regions in the hierarchy encircling the earlier one, and detailedtopological organization, with retinotopy in each area but striking mirror reversals across area boundaries. The developmental rules that drive the simultaneous formation of these architectural, spatial, and topographic aspects of organization are unknown. Here we demonstrate that a simple synaptic growth rule driven by spontaneous activity and heterosynaptic competition generates a detailed connectome of the visual pathway, with emergence of all three types of organization. We identify a theoretical principle — local greedy wiring minimization via spontaneous drive (GWM-S) — implemented by the mechanism, and use this insight to propose biologically distinct growth rules that predict similar endpoints but testably distinguishable developmental trajectories. The same rules predict how input geometry and cortical geometry together drive emergence of hierarchical, convolution-like, spatially and topographically organized sensory processing pathways for different modalities and species, providing a possible explanation for the observed pluripotency of cortical structure formation. We find that the few parameters governing structure emergence in the growth rule constitute simple knobs for rich control, that could (potentially genetically) encode a projection neuron-like connectivity patterns and interneuron-like ones. In all, the presented rules provide a parsimonious mechanistic model for the organization of sensory cortical hierarchies even without detailed genetic cues for features like map reversal, and provide numerous predictions for experiment during normal and perturbed development.
Diverse bacteriohemerythrin genes ofMethylomonas denitrificansFJG1 provide insight into the survival and activity of proteobacterial methanotrophs under hypoxia
Authors: Weiblen Cerrise , Sauvageau Dominic , Stein Lisa Y. 
Published: January 2024

AbstractProteobacterial methanotrophic bacteria are dependent on the oxidation of methane and methanol for the assimilation of carbon. Interestingly, these types of methanotrophs can thrive in oxygen-depleted zones of lakes and other aquatic ecosystems despite the fact they are considered obligate aerobes. Bacteriohemerythrin (Bhr), a homologue of eukaryotic hemerythrin, is a protein associated with oxygen binding. The model gammaproteobacterial methanotrophic strain,Methylomonas denitrificansFJG1, oxidizes methane at the expense of nitrate reduction under extreme hypoxia and upregulatesbhrgenes, yet this strain encodes 10 homologues ofbhrin its genome. UsingM. denitrificansFJG1 as a model, this study examined the prevalence and phylogeny of each of its 10bhrhomologues in other methanotroph and general bacterial genomes. One gene copy denoted as “bhr-00” was found to be methanotroph-specific, was upregulated under hypoxia inM. denitrificansFJG1, and was predicted to have a structure nearly identical to the crystalized, oxygen-scavenging, Bhr-Bath protein from,Methylococcus capsulatusBath. Other upregulatedbhrgenes from hypoxic cultures of nitrate-grownM. denitrificansFJG1 included those with gene neighborhoods related to oxygen sensing, denitrification and chemotaxis. Together, this study uncovered multifunctional roles of bacteriohemerythrin proteins encoded and expressed by methanotrophs that likely enable their survival in hypoxic ecosystems.ImportanceAerobic gammaproteobacterial methanotrophs encoding bacteriohemerythrin (bhr) genes are reported to have an enhanced ability to survive and grow in oxygen-limited environments. The methanotrophic bacterium,Methylomonas denitrificansFJG1, encodes 10 copies ofbhrgenes, of which 7 are expressed under oxygen depleted and denitrifying conditions. Comparing these 10bhrgene homologues fromM. denitrificansFJG1 with those from other prokaryotic genomes revealed that copy “bhr-00” is nearly exclusive to methanotrophs. Gene neighbourhoods surrounding conservedbhrgene sequences in methanotroph genomes suggest a range of potential functions including oxygen sensing and delivery, chemotaxis, and nitrate reduction. The results from this study illuminate a previously undescribed diversity of the structure and function ofbhrgenes inM. denitrificansFJG1 and related methanotrophic bacteria and pinpoints roles of Bhr that likely promote survival of methanotrophs in hypoxic ecosystems.
The concept of the gain curve
Authors: Burd Martin 
Published: January 2024

AbstractGain curves were introduced to explain how hermaphrodites could displace a dioecious population, and to account for sexual allocation in hermaphrodites. Terms for gamete production employed for the first purpose were transformed for the second into male and female gain curves that ostensibly defined fitness outcomes. These gain curves pose a conceptual challenge if they are specified separately because fitness at the population level cannot occur through one sex function independently of success through the other. If gain curves truly represent fitness outcomes, anomalies can arise, such as inequality of total male and female fitness in a population. Gain curves were originally used in a mathematical framework that treated the ostensible gain functions as inputs of male and female actors to a mating arena rather than as mating outcomes from that arena. I present a model of sex allocation that incorporates power functions to describe both gamete production and fitness gain in a manner that explicitly separates these two roles. In this formulation, the gamete production functions have the identical effect on optimal sex allocation originally attributed to gain curves while the true fitness gain curves lose nearly all effect on the optimum. Thus, despite the label, gain curves were implicitly describing inputs rather than outcomes. Because gain curves have been a staple of evolutionary ecology for decades, the implication is that much of our understanding of sexual allocation in hermaphrodites needs to be revisited. I outline some directions such an effort might take.