Miracle-dz/UniFAR-FTUs huggingface dataset:
Dynamic multi-OMICs of glioblastoma reveal sensitivity to neddylation inhibition dependent on nuclear PTEN and DNA replication pathways: Nuclear PTEN mediates MLN4924 sensitivity in GBM

The authors have withdrawn their manuscript because the reported synergy of TOP2A inhibitors plus MLN4924 proved to be untrue (not reproducible). Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author (mberens@tgen.org).
Geographic drivers of diversification in loliginid squids with an emphasis on the western Atlantic species

Aim Identifying the mechanisms driving divergence in marine organisms is challenging as opportunities for allopatric isolation are less conspicuous than in terrestrial ecosystems. Here, we aim to estimate a dated phylogeny of the squid family Loliginidae, and perform ecological niche analyses to explore biogeographic and evolutionary patterns giving rise to extant lineages in this group, with particular focus on cryptic species with population structure along the western Atlantic coast. Location World-wide. Taxon Class Cephalopoda, Family Loliginidae Methods We used three loci to infer gene trees and perform species delimitation analysis to detect putative cryptic speciation events. We then estimated a dated species tree under the Bayesian multispecies coalescent and used it to reconstruct ancestral distributions based on the currently known ranges of the species. Also, we tested the hypothesis of niche divergence in three recently diverged species subpopulations of the northwestern and southwestern Atlantic Ocean by ecological niche modeling and niche overlap measurement from occurrence data. Results The phylogenetic analyses confirmed the monophyly for the current twenty-six species of the Loliginidae family. Our ancestral area reconstruction and divergence estimation revealed the origin and geographical dispersal of loliginid lineages. Additionally, the phylogenetic analysis and the species delimitation analysis supported geographic structure within D. pleii, D. pealeii and L. brevis. The ecological niche models revealed unsuitable habitat in the immediately adjacent area of the Amazonian Orinoco Plume, yet suitable habitat characteristics beyond this area. Main conclusions Our study allowed us to confirm the monophyly of all currently recognized species within the Loliginidae family and we corroborate the biogeographical origin being the Indo-Pacific region in the Cretaceous. We found a possible new cryptic lineage and show evidence of the Amazon-Orinoco Plume as an ecological barrier, which influenced the diversification of this particular group of marine organisms.
The Isolate Caproiciproducens sp. 7D4C2 Produces n-Caproate at Mildly Acidic Conditions From Hexoses: Genome and rBOX Comparison With Related Strains and Chain-Elongating Bacteria

Background Bulk production of medium-chain carboxylates (MCCs) with 6-12 carbon atoms is of great interest to biotechnology. Open cultures (e.g., reactor microbiomes) have been utilized to generate MCCs in bioreactors. When in-line MCC extraction and prevention of product inhibition is required, the bioreactors have been operated at mildly acidic pH (5.0-5.5). However, model chain-elongating bacteria grow optimally at neutral pH values. Here, we isolated a chain-elongating bacterium (strain 7D4C2) that thrives at mildly acidic pH. We studied its metabolism and compared its whole genome and the reverse β-oxidation (rBOX) genes to other bacteria. Results Strain 7D4C2 produces lactate, acetate, n-butyrate, n-caproate, biomass, and H2/CO2 from hexoses. With only fructose as substrate (pH 5.5), the maximum n-caproate specificity (i.e., products per other carboxylates produced) was 60.9 ± 1.5%. However, this was considerably higher at 83.1 ± 0.44% when both fructose and n-butyrate (electron acceptor) were combined as a substrate. A comparison of serum bottles with fructose and n-butyrate with an increasing pH value from 4.5 to 9.0 showed a decreasing n-caproate specificity from ∼92% at mildly acidic pH (pH 4.5-5.0) to ∼24% at alkaline pH (pH 9.0). Moreover, when carboxylates were extracted from the broth (undissociated n-caproic acid was ∼0.3 mM), the n-caproate selectivity (i.e., product per substrate fed) was 42.6 ± 19.0% higher compared to serum bottles without extraction. Based on the 16S rRNA gene sequence, strain 7D4C2 is most closely related to the isolates Caproicibacter fermentans (99.5%) and Caproiciproducens galactitolivorans (94.7%), which are chain-elongating bacteria that are also capable of lactate production. Whole-genome analyses indicate that strain 7D4C2, C. fermentans, and C. galactitolivorans belong to the same genus of Caproiciproducens. Their rBOX genes are conserved and located next to each other, forming a gene cluster, which is different than for other chain-elongating bacteria such as Megasphaera spp. Conclusions Caproiciproducens spp. , comprising strain 7D4C2, C. fermentans, C. galactitolivorans, and several unclassified strains, are chain-elongating bacteria that encode a highly conserved rBOX gene cluster. Caproiciproducens sp. 7D4C2 (DSM 110548) was studied here to understand n-caproate production better at mildly acidic pH within microbiomes and has the additional potential as a pure-culture production strain to convert sugars into n-caproate.
Comparative transcriptomics identifies Botrytis cinerea induced conserved defences across different tissues of Fragaria vesca

Grey mould is one of the most devastating plant diseases that causes huge losses to the agricultural sector worldwide. Botrytis cinerea, the causal pathogen of grey mould, is a generalist necrotrophic fungus with the ability to infect over 1000 species and influence a broad array of host’s physiological responses. B. cinerea is capable of infecting a wide variety of tissues such as leaves, stem, flowers and fruits that adds to the already complex problem in controlling its spread. Understanding the pathogen induced transcriptional reprogramming in different tissues is important to identify key genes for targeted gene modifications. Identifying the genes that are common between different tissue infections will reveal similarities and differences between these pathogen-tissue pairs. In this study, the transcriptomic datasets of Botrytis infected white berries of Fragaria vesca (WhiteBc) and Botrytis infected red berries of F. vesca (RedBc) were (re)mapped to the latest F. vesca transcriptome to enable direct comparisons with the Botrytis infected F. vesca leaves (LeafBc). The genes involved in MAP kinase signalling, pathogenesis-related, allergens, cell-wall defences, detoxification and secondary metabolites were Common Responsive and Upregulated (CoReUp) between LeafBc, WhiteBc and RedBc, suggesting their important roles against B. cinerea infection in all three tissues. These insights maybe helpful for generating B. cinerea resistant varieties of strawberry.
CAMSAP3 is required for mTORC1-dependent ependymal cell growth and lateral ventricle shaping in mouse brains

ABSTRACT Microtubules (MTs) regulate numerous cellular processes, but their roles in brain morphogenesis are not well known. Here, we show that CAMSAP3, a non-centrosomal microtubule regulator, is important for shaping the lateral ventricles. In differentiating ependymal cells, CAMSAP3 became concentrated at the apical domains, serving to generate MT networks at these sites. Camsap3-mutated mice showed abnormally narrow lateral ventricles, in which excessive stenosis or fusion was induced, leading to a decrease of neural stem cells at the ventricular and subventricular zones. This defect was ascribed at least in part to a failure of neocortical ependymal cells to broaden their apical domain, a process necessary for expanding the ventricular cavities. mTORC1 was required for ependymal cell growth but its activity was downregulated in mutant cells. Lysosomes, which mediate mTORC1 activation, tended to be reduced at the apical regions of the mutant cells, along with disorganized apical MT networks at the corresponding sites. These findings suggest that CAMSAP3 supports mTORC1 signaling required for ependymal cell growth via MT network regulation, and, in turn, shaping of the lateral ventricles. Highlighted Article: CAMSAP3, which mediates non-centrosomal microtubule assembly, is required for mTORC1-dependent maturation of ependymal cells at the neocortex of developing mouse brains. Loss of CAMSAP3 causes deformation of the lateral ventricles.
Ether lipid and sphingolipid expression patterns are G-protein coupled estrogen receptor 1-dependently altered in breast cancer cells

Identifying co-expression of lipid species is challenging, but indispensable to identify novel therapeutic targets for breast cancer treatment. Lipid metabolism is often dysregulated in cancer cells, and changes in lipid metabolism affect cellular processes such as proliferation, autophagy, and tumor development. In addition to mRNA analysis of sphingolipid metabolizing enzymes, we performed liquid chromatography time-of-flight mass spectrometry analysis in three breast cancer cell lines. These breast cancer cell lines differ in estrogen receptor and G-protein coupled estrogen receptor 1 status. Our data show that sphingolipids and non-sphingolipids are strongly increased in SKBr3 cells. SKBr3 cells are estrogen receptor negative and G-protein coupled estrogen receptor 1 positive. Treatment with G15, a G-protein coupled estrogen receptor 1 antagonist, abolishes the effect of increased sphingolipid and non-sphingolipid levels in SKBr3 cells. In particular, ether lipids are expressed at much higher levels in cancer compared to normal cells and are strongly increased in SKBr3 cells. Our analysis reveals that this is accompanied by increased sphingolipid levels such as ceramide, sphingadiene-ceramide and sphingomyelin. This shows the importance of focusing on more than one lipid class when investigating molecular mechanisms in breast cancer cells. Our analysis allows unbiased screening for different lipid classes leading to identification of co-expression patterns of lipids in the context of breast cancer. Co-expression of different lipid classes could influence tumorigenic potential of breast cancer cells. Identification of co-regulated lipid species is important to achieve improved breast cancer treatment outcome. Highlights LC-HRMS analysis allows identification of co-expression between lipid classes Putative co-expression of sphingolipid and non-sphingolipid classes Ether lipids are strongly upregulated in SKBr3 cells (ER negative, GPER1 positive)
Effect of secondary associations on meiosis, pollen fertility and pollen size in cape gooseberry (Physalis peruviana L.)

This study deals with the detailed analysis on various meiotic abnormalities in the tetraploid cytotype (2n=4x=48) of Physalis peruviana L. The meiotic abnormalities include secondary associations of bivalents, stickiness of chromosomes, multivalents and univalents, and unoriented bivalents during metaphase-I, non-synchronization in the separation of some bivalents, laggards, chromatin bridges and cytomixis at various meiotic stages besides aberrant microsporogenesis. In spite of all these abnormalities, distribution of chromosomes at anaphases found to be normal. Microsporogenesis includes monads, dyads and tetrads with micronuclei besides normal tetrads, consequently reducing the pollen fertility (76%).
Conflict Processing in Schizophrenia: Dissociable neural mechanisms revealed by the N2 and frontal midline theta

Deficits in executive control have long been regarded as one of the hallmark cognitive characteristics in people with schizophrenia (SZ), and current neurocognitive models of SZ generally regard the dysfunctional anterior cingulate cortex (ACC) as the possible neural mechanism. This however, contrasts with recent studies showing that conflict processing, a key component of executive functions that relies on ACC, remains relatively intact in SZ. The current study aimed to investigate this issue through two well-known electrophysiological signatures of conflict processing that have been suggested to origin from ACC, i.e., the N2 component of event-related potentials (ERPs) and frontal midline theta (FMθ) oscillations. We recorded 64-channel scalp electroencephalography from 29 SZ (17 women; mean age: 30.4 years) and 31 healthy control subjects (HC; 17 women; mean age: 29.1 years) performing a modified flanker task. Behavioral data revealed no significant differences in flanker conflict effects (lower accuracy and longer reaction time in incongruent trials than in congruent trials) between HC and SZ. Trial-averaged ERP and spectral analysis suggested that both N2 and FMθ were significantly impaired in SZ relative to HC. Furthermore, by sorting incongruent trials according to their reaction times within individual subjects, we found that the trial-by-trial modulation of N2 (larger amplitude and longer latency in slower trials) which was observed and localized in ACC in HC was totally absent in SZ. By contrast, the trial-by-trial modulation of FMθ (larger power in slower trials) was observed and localized in ACC in both groups, despite a relatively smaller magnitude in SZ. Notably, such trial-by-trial FMθ modulation was only present in incongruent trials that demanded conflict processing. Taken together, our results not only support the idea that FMθ, not N2, serves as the neural substrate of conflict processing in SZ, but also provide novel insights into the functional roles of ACC during executive control, enriching the current neurocognitive models of SZ.
Evidence for a system in the auditory periphery that may contribute to linking sounds and images in space

Eye movements alter the relationship between the visual and auditory spatial scenes. Signals related to eye movements affect the brain’s auditory pathways from the ear through auditory cortex and beyond, but how these signals might contribute to computing the locations of sounds with respect to the visual scene is poorly understood. Here, we evaluated the information contained in the signals observed at the earliest processing stage, eye movement-related eardrum oscillations (EMREOs). We report that human EMREOs carry information about both horizontal and vertical eye displacement as well as initial/final eye position. We conclude that all of the information necessary to contribute to a suitable coordinate transformation of auditory spatial cues into a common reference frame with visual information is present in this signal. We hypothesize that the underlying mechanism causing EMREOs could impose a transfer function on any incoming sound signal, which could permit subsequent processing stages to compute the positions of sounds in relation to the visual scene.
Increased processing of SINE B2 non coding RNAs unveils a novel type of transcriptome de-regulation underlying amyloid beta neuro-pathology

More than 97% of the mammalian genome is non-protein coding, and repetitive elements account for more than 50% of noncoding space. However, the functional importance of many non-coding RNAs generated by these elements and their connection with pathologic processes remains elusive. We have previously shown that B2 RNAs, a class of non-coding RNAs that belong to the B2 family of SINE repeats, mediate the transcriptional activation of stress response genes (SRGs) upon application of a stimulus. Notably, B2 RNAs bind RNA Polymerase II (RNA Pol II) and suppress SRG transcription during pro-stimulation state. Upon application of a stimulus, B2 RNAs are processed into fragments and degraded, which in turn releases RNA Pol II from suppression and upregulates SRGs. Here, we demonstrate a novel role for B2 RNAs in transcriptome response to amyloid beta toxicity and pathology in the mouse hippocampus. In healthy hippocampi, activation of SRGs is followed by a transient upregulation of pro-apoptotic factors, such as p53 and miRNA-34c, which target SRGs creating a negative feedback loop that facilitates transition to the pro-stimulation state. Using an integrative RNA genomics approach, we show that in mouse hippocampi of an amyloid precursor protein knock-in mouse model and in an in vitro cell culture model of amyloid beta toxicity, this regulatory loop is dysfunctional due to increased levels of B2 RNA processing, constitutively elevated SRG expression and high p53 levels. Evidence indicates that Hsf1, a master regulator of stress response, mediates B2 RNA processing in cells, and is upregulated during amyloid toxicity accelerating the processing of SINE RNAs and SRG hyper-activation. Our study reveals that in mouse, SINE RNAs constitute a novel pathway deregulated in amyloid beta pathology, with potential implications for similar cases in the human brain, such as Alzheimer’s disease (AD). This data attributes a role to SINE RNA processing in a pathological process as well as a new function to Hsf1 that is independent of its transcription factor activity.
The Effect of Refractive Blur in the Vividness of Mental Imagery

Background Visual mental imagery or “seeing with the mind’s eye” is an everyday phenomenon. Visual mental imagery and visual perception share common neural-networks. Hence deficits that affect the visual perception may also affect visual mental imagery. Aim We aimed to study the effect of refractive blur on the vividness of mental imagery. Methods Subjects were recruited from volunteers and divided into two groups; individuals with refractive errors–Ametropes(AM), and individuals without refractive errors – Emmetropes(EM). After filling in the Verbalizer-Visualizer-Questionnaire (VVQ), the subjects were asked to perform a mental imagery task with and without refractive blur. The participants were asked to generate a mental image of a specific object initially with eyes closed, eyes open and then with refractive blur in random order, and then judge the vividness of the mental image on a Likert scale ranging from 1 (low vividness) to 5 (good vividness). The EM participants had to wear a + 2D spectacles to produce refractive blur. Results A total of 162 participants were recruited to the study. Of these 73 were EM and 89 were AM. Of the AM, 30 had additional astigmatism. The mean VVQ score was 64.9(11.2). The mean refractive error was 1.8(1.3)D. Following the mental imagery task, at baseline with eyes closed, 138 (85.5%)subjects had vivid mental imagery close to visual perception(Likert scale:5). With the opening of the eyes, the vividness dropped by at least 1 point in the Likert scale in 139(85.8%). With the introduction of refractive blur, 153(94.4%) subjects had a drop in the vividness of the image by at least 1 point and 22(13.6%) subjects by at least 2 points. Conclusion Introduction of refractory blur results in the reduction of the vividness of mental imagery.
Morphological evolution in the ant reproductive caste

The evolution of eusociality led to severe changes in the general hymenopteran body plan. In particular, the evolution of reproductive division of labour caused the worker caste to be largely freed from the demands involved in reproduction. As a consequence, workers were able to evolve highly specialized morphologies for foraging and colony maintenance, whereas the reproductive caste became specialized for reproduction. Despite these important changes, little is known about general patterns of morphological evolution within the ant reproductive caste. Our goals were to characterize morphological variation in the ant reproductive caste and to test whether different sexes display variation in their evolutionary rates. We obtained measurements of 897 specimens from a total of 678 ant species. The shapes of the size distributions were similar between sexes, with queens being larger than males in all traits except for eye length. Contrary to the expectation based on Rensch’s rule, although queens were larger, the degree of dimorphism increased with body size. Finally, there is strong evidence for an accelerated tempo of morphological evolution in queens in relation to males. These results represent the first comprehensive treatment of morphological variation in the ant reproductive caste and provide important new insights into their evolution.
Plexin-B1 mutation drives prostate cancer metastasis

Prostate cancer mortality is associated with the metastatic spread of tumour cells. A better understanding of the mechanisms which allow a locally advanced tumour to disseminate around the body will identify new therapeutic targets to block this process. One of set of genes implicated in metastasis are plexins, which can promote or suppress tumour progression depending on cancer type and cellular context. We have taken a mouse genetics approach to gain insight into the role of Plexin-B1 in prostate cancer progression in vivo. We show here that genetic deletion of Plexin-B1 in PbCre+Ptenfl/flKrasG12V and PbCre+Ptenfl/flp53fl/fl mouse prostate cancer models significantly decreased metastasis. High levels of prostate epithelial cell-specific expression of wild-type Plexin-B1 in knock-in mice with a PbCre+Ptenfl/flKrasG12V background also significantly decreased metastasis. In contrast, expression of a Plexin-B1 mutant (P1597L; identified from metastatic deposits in prostate cancer patients) in prostate epithelial cells in PbCre+Ptenfl/flKrasG12V and PbCre+Ptenfl/flp53fl/fl mice significantly increased metastasis, in particular metastasis to distant sites. In line with these findings, both deletion and overexpression of wild-type Plexin-B1 reduced invasion of tumour cells into the prostate stroma, while overexpression of mutant Plexin-B1 significantly increased invasion, suggesting that Plexin-B1 has a role in the initial stages of metastasis. Invasion and metastasis also correlated with phosphorylation of myosin light chain, suggesting that Plexin-B1 signals via the Rho/ROCK pathway to promote metastasis. Our results demonstrate that mutant Plexin-B1 promotes metastasis in prostate cancer and represents a new therapeutic target to suppress tumour spread.
Clerodendrum Chinensis Extracts; AeC and EeC Exerts Rapid Antihypertensive Effects in L-NAME Hypertensive Experimental Models

Background The rise in occurrence of hypertension, a non-communicable disease and a major factor for chronic renal failure, cardiovascular disease, and stroke, which most times lead to sudden death is worrisome. Resistant hypertension is more common and may have no symptoms at all for months or years, but then can cause heart attack, stroke, and vision and kidney damage. Prevention and quick management of hypertension are therefore essential in reducing the risk of these debilitating ailments. Aqueous and ethanolic extracts of the leaves of Clerodendrum chinensis (AeC and EeC) are used by local communities of West Africa as medicine for rapid antihypertensive actions. We aim to discover the scientific basis for the use of the herb as medicine. Methods This work investigates the antihypertensive effects of AeC and EeC in L-Arginine Methyl Ester Hydrochloride (L-NAME)-induced hypertensive rats Acetylcholine, L-Arginine and Sodium Nitroprusside were used as standards. All results were expressed as means ± standard error of mean. Differences were considered significant at p <0.05. Results Intravenous administration of the extracts caused a significant decrease in the Mean Arterial Blood Pressure (MABP) in a dose-dependent manner. AeC at 100mg/kg caused a significant decline in blood pressure in a dose-related manner. Likewise at 100mg/kg, EeC reduced MABP steadily from 103.9± 2.55 to 34.1± 0.95mmHg. The two extracts; possess significant antihypertensive properties. Conclusions Both extracts show significant antihypertensive effects and at high doses could lead to hypotension and so should be used with care. Further research is necessary to determine safe dosage forms.