bluuebunny/crossref_metadata_2025 huggingface dataset:
Velocity-based optoretinography for clinical applications
Authors: Vienola Kari V. , Valente Denise , Zawadzki Robert J. , Jonnal Ravi S.
Published: May 2022

Optoretinography (ORG) is an emerging tool for testing neural function in the retina. Unlike existing methods, it is noninvasive, objective, and provides information about retinal structure and function at once. As such, it has great potential to transform ophthalmic care and clinical trials of novel therapeutics designed to restore or preserve visual function. Recent efforts have demonstrated the feasibility of the ORG using state-of-the-art optical coherence tomography systems. These methods measure the stimulus-evoked movement of subcellular features in the retina, using the phase of the reflected light to monitor their position. Here we present an alternative approach that monitors the velocity of these features instead. This conceptual shift has significant implications for the nascent field of optoretinography. By avoiding the need to track specific cells over time, it obviates costly and laborious aspects of the position-based approaches, such as adaptive optics, digital aberration correction, real-time tracking, and three-dimensional segmentation and registration. We used this novel velocity-based approach to measure the photoreceptor ORG responses in three healthy subjects. The resulting responses were reproducible and exhibited dependence on dose and retinal eccentricity. The position of the relevant structures was reconstructed through numerical integration of velocity.
Allelic variation in theArabidopsisTNL CHS3/CSA1 immune receptor pair reveals two functional regulatory modes
Authors: Yang Yu , Kim Nak Hyun , Cevik Volkan , Jacob Pierre , Wan Li , Furzer Oliver J. , Dangl Jeffery L.
Published: May 2022

Some plant NLR immune receptors are encoded in head-to-head pairs that function together. Alleles of the NLR pair CHS3/CSA1 form three clades. The clade 1 sensor CHS3 contains an integrated domain (ID) with homology to regulatory domains, which is lacking in clades 2 and 3. We defined two regulatory modes for CHS3/CSA1 pairs. One is likely mediated by effector binding to the clade 1 ID of CHS3 and the other relies on CHS3/CSA1 pairs from all clades detecting effector modification of an associated pattern recognition receptor. We suggest that an ancestral Arabidopsis CHS3/CSA1 pair gained a second recognition specificity and regulatory mechanism through ID acquisition, while retaining its original specificity as a ‘Guard’ against perturbation of pattern recognition receptor targeting by a pathogen effector. This likely comes with a cost, since both ID and non-ID alleles of the pair persist in diverse Arabidopsis populations through balancing selection.

We dissect a novel case where two regulatory modes emerged across three clades of the co-evolved CHS3/CSA1 plant immune receptor pairs, which features recruitment of an integrated domain (ID) into the clade 1 CHS3 alleles. Pre- and post-ID integration alleles maintain functionality; balancing selection maintains both in the Arabidopsis pan-genome.
Evaluation of operational characteristics and performance of HIV rapid diagnostic tests (RDTs): Systematic review and meta-analysis of the literature from 2012 to 2020
Authors: Kingwara Leonard , Bowen Nancy , Panpradist Nuttada , Lokamar Peter , Morangi Vera , Madada Rukia Sarah , Nyakeriga Emmanuel , Awuor Christabel , Onentia Jonah , Masyuko Sarah , Wafula Rose , Kiiru John Ndemi
Published: May 2022

Background

Most countries have rolled out HIV Rapid diagnostic tests (RDTs) due to their significant advantages over laboratory-based serological testing. These advantages are lower cost, ease of use, interpretation speed, and relatively high acceptability; the HIV diagnostic landscape has evolved fast, and newer technologies have been developed and deployed. Given the many options available, selecting an HIV rapid diagnostic test for a particular clinical program, self-test, or research setting can be daunting without the precise knowledge of their performance characteristics. This systematic review and meta-analysis aimed to compare the field diagnostic performance of available HIV rapid test kits, cost-effectiveness, ease of use, and acceptability.

Methods

PubMed and Web of Science were searched for publications on rapid HIV tests using blood specimens. We then performed a meta-analysis and systematic analysis to quantitatively and qualitatively evaluate the diagnostic performance of rapid HIV tests compared with the western blot (WB), enzyme-linked immunosorbent assay (ELISA), or an HIV diagnostic algorithm in terms of pooled sensitivity, specificity, area under the summary receiver operating characteristic (SROC) curve, and diagnostic odds ratio (DOR).

Results

The meta-analysis for the diagnostic test included 26 studies for diagnostic accuracy, while the qualitative analysis included 15 studies. On average, the RDT sensitivities were 99%; [95% CI=0.99-100%], while specificity was optimal at 100%; [95% CI=99%-100%]. The diagnostic odds ratio estimates that a single test performed better than a dual test: dual test DOR=44612.33 and single test DOR=14323.1. The impact of unobserved heterogeneity using the quantity I2 for sensitivity was 99.47%, while that for specificity was 99.96, indicating significant heterogeneity and justifying stratified analysis of the selected studies. The diagnostic test from Unigold had the best-pooled sensitivity, specificity, and diagnostic odds ratio at 99%, 99.35%, and 2896.667, respectively. Qualitative data indicate shorter time to results is preferred by both the clients and health care providers.

Conclusion

The average of the RDT sensitivities for diagnostic accuracy were 99% (95% CI=0.99-100%), while specificity was optimal at 100%; 95% CI=99-100. The diagnostic odds ratio was DOR=44612 (95% CI=14323-138954), thus indicating better RDT test performance. The performance of single test kits in HIV diagnosis was better than those for dual tests.
Botrytis cinerea identifies host plants via the recognition of antifungal capsidiol to induce expression of a specific detoxification gene
Authors: Kuroyanagi Teruhiko , Bulasag Abriel , Fukushima Keita , Suzuki Takamasa , Tanaka Aiko , Camagna Maurizio , Sato Ikuo , Chiba Sotaro , Ojika Makoto , Takemoto Daigo
Published: May 2022

The gray mold pathogen Botrytis cinerea has a broad host range, causing disease in over 400 plant species, but it is not known how this pathogen evolved this polyxenous nature. B. cinerea can metabolize a wide range of phytoalexins, including the stilbenoid, resveratrol, and the sesquiterpenoids capsidiol in tobacco, and rishitin in potato and tomato. In this study, we analyzed the metabolism of sesquiterpenoid phytoalexins by B. cinerea. Capsidiol was dehydrogenated to capsenone which was then further oxidized, while rishitin was directly oxidized to epoxy-or hydroxy-rishitins indicating that B. cinerea has separate mechanisms to detoxify structurally similar sesquiterpenoid phytoalexins. RNAseq analysis revealed that a distinct set of genes were induced in B. cinerea when treated with capsidiol or rishitin, suggesting that B. cinerea can distinguish structurally similar phytoalexins to activate appropriate detoxification mechanisms. The gene most highly upregulated by capsidiol treatment encoded a dehydrogenase, designated Bccpdh. Heterologous expression of Bccpdh in a capsidiol-sensitive plant symbiotic fungus, Epichloë festucae, resulted in an acquired tolerance of capsidiol and the ability to metabolize capsidiol to capsenone, while B. cinerea Δbccpdh mutants became relatively sensitive to capsidiol. The Δbccpdh mutant showed reduced virulence on the capsidiol producing Nicotiana and Capsicum species but remained fully pathogenic on potato and tomato. Homologs of Bccpdh are not found in taxonomically distant Ascomycota fungi but not in related Leotiomycete species, suggesting that B. cinerea acquired the ancestral Bccpdh by horizontal gene transfer, thereby extending the pathogenic host range of this polyxenous pathogen to capsidiol-producing plant species.

Significance Statement

B. cinerea can metabolize a wide range of phytoalexins, however, the extent to which phytoalexin detoxification contributes to pathogenicity is largely unknown. In this study, we have shown that B. cinerea recognizes structurally resembling sesquiterpenoid phytoalexins, rishitin and capsidiol, to activate appropriate detoxification mechanisms. We identify Bccpdh, encoding a dehydrogenase for capsidiol detoxification, which is upregulated in B. cinerea exclusively during the infection of capsidiol producing plant species, and is required to exert full virulence. Analysis of the Bccpdh locus implicates that the gene was acquired via horizontal gene transfer. This work highlights that the polyxenous plant pathogen B. cinerea can distinguish its host plants by its anti-microbial compounds, to activate appropriate mechanisms for enhanced virulence.
RNA binding proteins Smaug and Cup induce CCR4-NOT-dependent deadenylation of the nanos mRNA in a reconstituted system
Authors: Pekovic Filip , Rammelt Christiane , Kubíková Jana , Metz Jutta , Jeske Mandy , Wahle Elmar
Published: May 2022

Posttranscriptional regulation of the maternal nanos mRNA is essential for the development of the anterior – posterior axis of the Drosophila embryo. The nanos RNA is regulated by the protein Smaug. Binding to Smaug recognition elements (SREs) in the nanos 3’-UTR, Smaug nucleates the assembly of a larger repressor complex including the eIF4E-T paralog Cup and five additional proteins. The Smaug-dependent complex represses translation of nanos and induces its deadenylation by the CCR4-NOT deadenylase. Here we report an in vitro reconstitution of the Drosophila CCR4-NOT complex and Smaug-dependent deadenylation. We find that Smaug by itself is sufficient to cause deadenylation by the Drosophila or human CCR4-NOT complexes in an SRE-dependent manner. CCR4-NOT subunits NOT10 and NOT11 are dispensable, but the NOT module, consisting of NOT2, NOT3 and the C-terminal part of NOT1, is required. Smaug interacts with the C-terminal domain of NOT3. Both catalytic subunits of CCR4-NOT contribute to Smaug-dependent deadenylation. Whereas the CCR4-NOT complex itself acts distributively, Smaug induces a processive behavior. The cytoplasmic poly(A) binding protein (PABPC) has but a minor effect on Smaug-dependent deadenylation. Among the additional constituents of the Smaug-dependent repressor complex, Cup also facilitates CCR4-NOT-dependent deadenylation, both independently and in cooperation with Smaug.
Dual control of meiotic crossover patterning
Authors: Durand Stéphanie , Lian Qichao , Jing Juli , Ernst Marcel , Grelon Mathilde , Zwicker David , Mercier Raphael
Published: May 2022

Most meiotic crossovers (COs), called class I crossovers, are produced by a conserved pathway catalyzed by the ZMM proteins; COs are limited in number, typically to 1–3 per chromosome, and are prevented from occurring close to one other by crossover interference1-3. In many species, CO number is subject to dimorphism between males and females, and a lower CO number is associated with shorter chromosome axes and stronger interference4. How the patterning of COs is imposed, however, remains poorly understood. Here, we show that overexpression of the ZMM protein HEI10 increases COs and reduces crossover interference but maintains sexual dimorphism; shorter axes length in female meiosis is still associated with fewer COs and stronger interference than in male meiocytes. Disrupting the synaptonemal complex (SC) by mutating ZYP1 also leads to an increase in class I COs but, in contrast, abolishes interference and disrupts the link between chromosome axis length and COs, with female and male meiocytes having the same CO frequency despite different axis lengths. Combining HEI10 overexpression and zyp1 mutation leads to a massive increase in class I COs and absence of interference, while axes lengths are still unaffected. These observations support, and can be effectively predicted by, a recently proposed coarsening model5,6 in which HEI10 diffusion is funneled by the central element of the SC before coarsening into large, well-spaced CO-promoting droplets. Given the conservation of the components, this model may account for CO patterning in many eukaryotes.
An in vivo and in silico evaluation of the magical hepatoprotective potentialities of Gynura procumbens: a promising agent for combating hepatotoxicity
Authors: Tithi Tanzia Islam , Tahsin Md. Rafat , Zaman Tasnuva Sharmin , Anjum Juhaer , Bahar Nasiba Binte , Sen Priyanka , Tasnim Sabiha , Sultana Arifa , Koly Fahima Jannat , Jahan Ishrat , Aktar Fahima , Chowdhury Jakir Ahmed , Kabir Shaila , Chowdhury Abu Asad , Amran Md. Shah
Published: May 2022

Introduction

Liver being the most important metabolic organ of the body performs a wide variety of vital functions. Hepatic cell injury occurs by the activation of reactive oxygen species (ROS) by CCl4, xenobiotics and other toxic substances generated through cytochrome P450 dependent step resulting from covalent bond formation with lipoproteins and nucleic acids. Observing the alarming state of hepatotoxic patients worldwide, different medicinal plants and their properties can be explored to combat against such free radical degermation of liver. This paper evaluates the antioxidant property ofGynura procumbensin both in silico and in an in vivo assay, and its hepatoprotective activity in CCl4induced hepatotoxicity.

Materials and Methods

Gynura procumbensleaves were collected and extracted using 50% ethanol. Required chemicals (CCl4), standard drug (Silymarin) and blood serum analyzing kits were stocked. The in vivo tests were performed in 140 healthy Wister albino male rats under well controlled parameters dividing into 14 groups, strictly maintaining IEAC protocols. In silico molecular docking and ADMET studies were performed and the results were analyzed statistically.

Results and discussion

The body weight increased significantly in CCl4induced,G. procumbensadministered hepatotoxic rats. The increase in SGPT, SGOT, ALP, creatinine, LFH, triglycerides, LDL, SOD, MDA, total cholesterol, DNA fragmentation ranges, γGT levels of CCl4treated group was decreased by both standard drug Silymarin andG. procumbensleaf extract. On the other hand,G. procumbensincreased HDL levels and displayed contrasting results in CAT level tests. Some results contradicted with the negative controlled group displaying varying efficacy between leaf extract and Silymarin. In the molecular docking analysis,G. procumbensphytoconstituents performed poorly against TGF-β1 compared to the control drug Galunisertib while 26 phytoconstituents scored better than the control, bezafibrate against PPAR-α. Flavonoids and phenolic compounds performed better than other constituents in providing hepatoprotective activity.
MEAHNE: MiRNA-disease association prediction based on semantic information in heterogeneous networks
Authors: Huang Chen , Cen Keliang , Zhang Yang , Liu Bo , Wang Yadong , Li Junyi
Published: May 2022

Prior studies have suggested close associations between miRNAs and diseases. Correct prediction of potential miRNA-disease pairs by computational methods is able to greatly accelerate the experimental process in biomedical research. However, many methods cannot effectively learn the complex information in the multi-source data, and limits the performance of the prediction model. A heterogeneous network prediction model MEAHNE is proposed to make full use of the complex information in multi-source data. We first constructed a heterogeneous network using miRNA-disease associations, miRNA-gene associations, disease-gene associations, and gene-gene associations. Because the rich semantic information in the heterogeneous network contains a lot of relational information of the network. To mine the relational information in heterogeneous network, we use neural networks to extract semantic information in metapath instances. We encode the obtained semantic information into weights using the attention mechanism, and use the weights to aggregate nodes in the network. At the same time, we also aggregate the semantic information in the metapath instances into the nodes associated with the instances, which can make the node embedding have excellent ability to represent the network. MEAHNE optimizes parameters through end-to-end training. MEAHNE is compared with other state-of-the-art heterogeneous graph neural network methods. The values of area under precision-recall curve and receiver operating characteristic curve show the superiority of MEAHNE. Additionally, MEAHNE predicted 50 miRNAs for lung cancer and esophageal cancer each and verified 49 miRNAs associated with lung cancer and 44 miRNAs associated with esophageal cancer by consulting relevant databases. MEAHNE has good performance and interpretability by experimental verification.
A phospho-switch provided by LRR receptor-like kinase, ALK1/QSK1/KIN7, prioritizes ABCG36/PEN3/PDR8 transport toward defense
Authors: Aryal Bibek , Xia Jian , Hu Zehan , Tsering Tashi , Liu Jie , Huynh John , Fukao Yoichiro , Glöckner Nina , Huang Hsin-Yao , Sáncho-Andrés Gloria , Pakula Konrad , Gorzolka Karin , Zwiewka Marta , Nodzynski Tomasz , Harter Klaus , Sánchez-Rodríguez Clara , Jasiński Michał , Rosahl Sabine , Geisler Markus
Published: May 2022

Based on its proposed substrate preferences, the ABC transporter, ABCG36/PDR8/PEN3, from the model plant Arabidopsis stands at the cross-road between growth and defence. Recently, ABCG36 was shown to export a few indolic compounds, including the auxin precursor, indole-3-butyric acid (IBA), and to be implicated in the export of the major phytoalexin of Arabidopsis, camalexin, although clear-cut proof of camalexin transport activity is still lacking.

Here we provide strong evidence that ABCG36 catalyses the direct, ATP-dependent export of camalexin over the plasma membrane, however, most likely in functional interplay with non-camalexin transporting ABCG isoforms. We identify the leucin-rich repeat receptor-like kinase, Auxin-induced LRR Kinase1 (ALK1/KIN7/QSK1), as a functional kinase to physically interact with and phosphorylate ABCG36. ABCG36 phosphorylation by ALK1 represses unilaterally IBA but not camalexin export leading to a prioritization of ABCG transport toward defense. As a consequence, phospho-dead mutants of ABCG36, likealk1andabcg36alleles, are hypersensitive toward infection with the root pathogen,F. oxysporum, caused by elevated fungal progression.

Our findings indicate a novel, direct regulatory circuit between a receptor kinase and an ABC transporter determining transporter substrate specificity. It appears that growth and defense balance decisions in plants are performed on the transporter level by means of a reversible phospho-switch.
In situ identification of secondary structures in unpurifiedBombyx morisilk fibrils using polarized two-dimensional infrared spectroscopy
Authors: Giubertoni Giulia , Caporaletti Federico , Roeters Steven , Chatterley Adam S. , Weidner Tobias , Laity Peter , Holland Chris , Woutersen Sander
Published: May 2022

The mechanical properties of biomaterials are dictated by the interactions and conformations of their building blocks, typically proteins. Although the macroscopic behaviour of biomaterials is widely studied, our understanding of the underlying molecular properties is generally limited. Among the non-invasive and label-free methods to investigate molecular structures, infrared spectroscopy is one of the most commonly used tools, because the absorption bands of the amide groups strongly depend on protein secondary structure. However, spectral congestion usually complicates the analysis of the amide spectrum. Here, we apply polarized two-dimensional (2D) infrared spectroscopy (IR) to directly identify the protein secondary structures in native silk filks cast fromBombyx morisilk feedstock. Without any additional analysis, such as peak fitting, we find that the initial effect of hydration is an increase of the random-coil content at the expense of theα-helix content, while theβ-sheet content is unchanged, and only increases at a later stage. This paper demonstrates that 2D-IR can be a valuable tool for characterizing biomaterials.
Methodological comparison of different approaches to cultivate postnatal organotypic hippocampal cultures
Authors: Czapla Vivien , Reiterer Pia , Funke Klaus
Published: May 2022

To study molecular and cellular processes of the brainin vitro, the cultivation of postnatal organotypic hippocampal slices should be established. The methodological approach had to be optimized several times because the result of the cultivation was not optimal. Initially, cultivation was performed by roller tube culture, which is the first developed cultivation method for these cultures. As the cultures detached or even dissolved, further cultivation was carried out using inserts, which represent a modification of the roller tube cultures. In the further course it came also to the use of different preparation methods and to the exchange of the medium and the incubator, in order to obtain a result of the organ cultivation corresponding to the expectations. The results show that cultivation on semi-permeable membranes has an advantage over roller tube cultures. On the one hand, there is no detachment and dissolution of hippocampal slices due to the mechanical influence and on the other hand, the tissue shows an improvement in general condition compared to roller tube cultures. Furthermore, it was found that an acceleration of the preparation time has positive effects on the neurons. In addition, it could be shown by the recorded time series that a cultivation over a longer period of time stabilizes the tissue. If the hippocampi remain connected to the entorhinal cortex, wallerian degeneration does not occur, resulting in longer survival of the cells in the postnatal cultures and thus strengthening the tissue.
The length of the thalamo-cortical white matter fibers brings insight into sex differences in sleep spindle frequency
Authors: Gaudreault Pierre-Olivier , Lina Jean-Marc , Descoteaux Maxime , Gosselin Nadia , Doyon Julien , Deslauriers-Gauthier Samuel , Carrier Julie
Published: May 2022

Sleep spindles (SS) are crucial to brain functions like memory and learning. SS characteristics result from the propagation of nerve impulses along white matter (WM) projections underlying an intricate loop between the thalamus and the cortex. SS amplitude and density have been associated with WM diffusion microarchitecture but physiological mechanisms underlying individual and sex-related variations in SS frequency are unknown. Here, we tested a model of traveling signals along the thalamo-cortico-thalamic projections to explain individual differences in spindle frequency. We predicted the presence of a relationship between the length of the thalamo-cortical WM bundles and a specific characteristic of this functional network, SS frequency.

Thirty young participants underwent a polysomnographic recording and a 3T MRI including a diffusion sequence. The length of WM fiber bundles between the thalamus and the frontal cortex was derived from probabilistic tractography computed through constrained spherical deconvolution.

Longer WM fiber bundles between the thalamus and specific regions of the frontal cortex (rostral middle frontal gyrus and anterior and middle part of the superior frontal gyrus) were associated with slower SS frequency. Moreover, the length of these WM fiber bundles statistically mediated the sex-related differences in SS frequency.

By providing a neuroanatomical marker of individual and sex-related differences in SS frequency, this study is the first to highlight the association between the anatomy of a specific brain network and a specific functional characteristic of this network, the frequency of oscillations produced during sleep.
Eudicot primary cell wall glucomannan is related in synthesis, structure and function to xyloglucani
Authors: Yu Li , Yoshimi Yoshihisa , Cresswell Rosalie , Wightman Raymond , Lyczakowski Jan J. , Wilson Louis F.L. , Ishida Konan , Stott Katherine , Yu Xiaolan , Charalambous Stephan , Wurman-Rodrich Joel , Dupree Ray , Terrett Oliver M. , Brown Steven P. , Temple Henry , Krogh Kristian B.R.M. , Dupree Paul
Published: May 2022

The functional differences between plant cell wall hemicelluloses such as glucomannan, xylan and xyloglucan (XyG) remain unclear. These polysaccharides influence assembly and properties of the wall, perhaps by interacting with cellulose to affect the deposition and bundling of the fibrils. As the most abundant hemicellulose, XyG is considered important in eudicot primary cell walls (PCWs), but plants devoid of XyG show relatively mild phenotypes. We report here that a patterned β-galactoglucomannan (β-GGM) is widespread in PCW of eudicots and shows remarkable similarities to XyG. The sugar linkages forming the backbone and side chains of β-GGM are analogous to those that make up XyG, and moreover, these linkages are formed by glycosyltransferases from the same CAZy families. Solid-state NMR indicated that β-GGM shows low mobility in the cell wall, consistent with interaction with cellulose. Although Arabidopsis β-GGM synthesis mutants show no obvious growth defects, genetic crosses between β-GGM and XyG mutants produce exacerbated phenotypes compared to XyG mutants. These findings demonstrate a related role of these two similar but distinct classes of hemicelluloses in PCWs. This work will provide new avenues to study the roles of both β-GGM and XyG in PCWs.

One sentence summary

Patterned β-GGM resembles xyloglucan in structure, biosynthesis and function.
Infestation and growth ofTribolium confusum(Coleoptera: Tenebrionidae) on two varieties of local durum wheat: nutritional value and varietal susceptibility
Authors: Faouzia Haffari , Malika Boualem , Saida Bergheul , Aicha Merzoug
Published: May 2022

Tribolium confusumis a pest of stored produce on many cereals. This study was planned to see quantitative losses and feelings of the equipped grains owed to the infestation by the red genus Tribolium on 2 forms of native durum in Algeria. Selection Puts tire chains S am cultivated within the region of Adrar, underneath associate arid climate; and also the existent selection Vitron of a production of the region of Ain Témounchent underneath a dry Mediterranean climate. Study was accomplished during two months to determine the weight loss of grains, damage caused byT. confusumand the influence of two varieties of hard wheat on growth and reproduction of this vandal. Damage of the couples (5, 10, 15, 20) on grains showed significant difference. A similar tendency was noted for the weight loss of grains Put snow chains S; while Vitron noticed not significant losses. Also, an increase in the consumption of proteins, lipids and starch of grains was noticed with the increase of the length of stocking. The appearance of generations was variable according to the level of density and the variety; nevertheless, it was generally highest on Vitron and low on Chain S. The results show that the quantitative and qualitative losses of stored grains are linked to the storage time, the chemical composition of the grains and the susceptibility to insects of the stored products. These results can be integrated into food safety management to ensure the quality of stored wheat and their stored food derivatives.
Effects of temperature on mating behaviour and mating success: a meta-analysis
Authors: Pilakouta Natalie , Baillet Anaїs
Published: May 2022

In light of global climate change, there is a pressing need to understand how populations will respond to rising temperatures. Understanding the effects of temperature changes on mating behaviour is particularly important, given its implications for population viability.

To this end, we performed a meta-analysis of 53 studies to examine how temperature changes influence mating latency, choosiness, and mating success. We hypothesized that if higher temperatures make mate searching and mate assessment more costly due to an elevated metabolism, this may lead to a reduction in mating latency and choosiness, thereby increasing overall mating success.

We found no evidence for a global effect of temperature on mating latency, choosiness, or mating success. There was an increase in mating success when animals were exposed to higher temperatures during mating, but not when they were exposed before mating.

Interestingly, in a subset of studies that measured both mating latency and mating success, there was a strong negative relationship between the effect sizes for these traits. This suggests that a decrease in mating latency at higher temperatures was associated with an increase in mating success and vice versa.

In sum, our meta-analysis provides new insights into the effects of temperature on mating patterns. The absence of a consistent directional effect of temperature on mating behaviours and mating success suggests it may be difficult to predict changes in the strength of sexual selection in natural populations in a warming world. Nevertheless, there is some evidence that (i) higher temperatures during mating may lead to an increase in mating success and that (ii) an increase in mating success is associated with a decrease in mating latency.
Translation of the ERM-1 membrane-binding domain directserm-1mRNA localization to the plasma membrane in theC. elegansembryo
Authors: Winkenbach Lindsay P. , Parker Dylan M. , Williams Robert T. P. , Nishimura Erin Osborne
Published: May 2022

mRNA localization and transport are integral in regulating gene expression. InCaenorhabditis elegansembryos, the maternally inherited mRNAerm-1 (Ezrin/Radixin/Moesin)concentrates in anterior blastomeres.erm-1mRNA localizes within those blastomeres to the plasma membrane where the essential ERM-1 protein, a membrane-actin linker, is also found. We demonstrate that the localization oferm-1mRNA to the plasma membrane is translation-dependent and requires its encoded N-terminal membrane-binding (FERM) domain. By perturbing translation through multiple methods, we founderm-1mRNA localization at the plasma membrane was maintained only if the nascent peptide remained in complex with the translating mRNA. Indeed, recoding theerm-1mRNA coding sequence while preserving the encoded amino acid sequence did not disrupterm-1mRNA localization, corroborating that the information directing mRNA localization resides within its membrane-binding protein domain. A smiFISH screen of 17 genes encoding similar membrane-binding domains identified three plasma membrane localized mRNAs in the early embryo. Nine additional transcripts showed apparent membrane localization later in development. These findings point to a translation-dependent pathway for localization of mRNAs encoding membrane-associated proteins.

SUMMARY STATEMENT

InC. elegans, erm-1mRNA localization to plasma membranes requires translation of the ERM-1 membrane-binding domain
Efficient neural codes naturally emerge through gradient descent learning
Authors: Benjamin Ari S. , Zhang Ling-Qi , Qiu Cheng , Stocker Alan , Kording Konrad P.
Published: May 2022

Animal sensory systems are more sensitive to common features in the environment than uncommon features. For example, small deviations from the more frequently encountered horizontal orientations can be more easily detected than small deviations from the less frequent diagonal ones. Here we find that artificial neural networks trained to recognize objects also have patterns of sensitivity that match the statistics of features in images. To interpret these findings, we show mathematically that learning with gradient descent in deep neural networks preferentially creates representations that are more sensitive to common features, a hallmark of efficient coding. This result suggests that efficient coding naturally emerges from gradient-like learning on natural stimuli.
Microinjection inC. elegansby direct penetration of elastomeric membranes
Authors: Lockery Shawn R. , Pop Stelian , Jussila Ben
Published: May 2022

The nematode wormC. elegansis widely used in basic and translational research. The creation of transgenic strains by injecting DNA constructs into the worm’s gonad is an essential step in manyC. elegansresearch projects. This paper describes the fabrication and use of a minimalist microfluidic chip for performing microinjections. The worm is immobilized in a tight-fitting microchannel one sidewall of which is a thin elastomeric membrane which the injection pipette penetrates to reach the worm. The pipette is neither broken nor clogged by passing through the membrane, and the membrane reseals when the pipette is withdrawn. Rates of survival and transgenesis are similar to those in the conventional method. Novice users found injections using the device easier to learn than the conventional method. The principle of direct penetration of elastomeric membranes is readily adaptable to microinjections in a wide range of organisms including cells, embryos, and other small animal models. It could therefore lead to a new generation of microinjection systems for basic, translational, and industrial applications.
Deep Learning on Multimodal Chemical and Whole Slide Imaging Data for Predicting Prostate Cancer Directly from Tissue Images
Authors: Haque Md Inzamam Ul , Mukherjee Debangshu , Stopka Sylwia A. , Agar Nathalie Y.R. , Hinkle Jacob , Ovchinnikova Olga S.
Published: May 2022

Prostate cancer is one of the most common cancers globally and is the second most common cancer in the male population in the US. Here we develop a study based on correlating the H&E-stained biopsy data with MALDI mass-spectrometric imaging of the corresponding tissue to determine the cancerous regions and their unique chemical signatures, and variation of the predicted regions with original pathological annotations. We spatially register features obtained through deep learning from high-resolution optical micrographs of whole slide H&E stained data with MSI data to correlate the chemical signature with the tissue anatomy of the data, and then use the learned correlation to predict prostate cancer from observed H&E images using trained co-registered MSI data. We found that this system is more robust than predicting from a single imaging modality and can predict cancerous regions with ∼80% accuracy. Two chemical biomarkers were also found to be predicting the ground truth cancerous regions. This will improve on generating patient treatment trajectories by more accurately predicting prostate cancer directly from H&E-stained biopsy images.
Racial differences in vaccine acceptance in a rural southern US state
Authors: Amick Benjamin C. , Allen Jaimi L. , Brown Clare C. , Goudie Anthony , Tilford Mick , Williams Mark
Published: May 2022

Introduction

To assess vaccine acceptance among adults living in a largely rural Southern state.

Methods

Data were collected between October 3 and October 17, 2020 using random digit dialing. Participants included residents aged 18+, able to understand English or Spanish, and provide informed consent. The primary outcome was a multi-dimensional COVID-19 vaccine acceptance measure. Scores varied between -3 to +3.

Results

The sample (n=1,164) was weighted to be representative of the state’s population. Black participants had the lowest overall vaccine acceptance (0.5) compared to White participants (1.2). Hispanic participants had the highest scores (1.4). In adjusted models, Black participants had 0.81 points lower acceptance than White participants, and Hispanic participants had 0.35 points higher acceptance. Hispanic participants had the highest scores for all five vaccine acceptance dimensions, relatively equivalent to White participants. Black participants had consistently lower scores, especially perceived vaccine safety (mean -0.2, SD 0.1).

Conclusions

The lowest vaccine acceptance rates were among Black participants particularly on perceived vaccine safety. While Black participants had the lowest acceptance scores, Hispanic participants had the highest. This variability shows the value of a multi-dimensional vaccine acceptance measure to inform COVID-19 vaccination campaign strategies.
Increased uptake of tuberculosis preventive therapy (TPT) among people living with HIV following the 100-days accelerated campaign: A retrospective review of routinely collected data at six urban public health facilities in Uganda
Authors: Musaazi Joseph , Sekaggya-Wiltshire Christine , Okoboi Stephen , Zawedde-Muyanja Stella , Senkoro Mbazi , Kalema Nelson , Kavuma Paul , Namuwenge Proscovia M. , Manabe Yukari C , Castelnuovo Barbara , Kiragga Agnes
Published: May 2022

Introduction

Tuberculosis preventive therapy (TPT) effectively decreases rates of tuberculosis reactivation in people living with HIV (PLHIV) who are at increased risk. The Uganda Ministry of Health launched a 100-day campaign to scale-up TPT in PLHIV in July 2019. We sought to examine the effect of the campaign on trends of TPT uptake and characteristics associated with TPT uptake and TPT completion among persons in HIV care. We retrospectively reviewed routinely collected data from 2016 to 2019 at six urban public health facilities in Uganda.

Methods

A cross-sectional review of the HIV care database and paper-based TPT registers at six public health facilities in Kampala, Uganda. Estimated trends of prevalence of TPT (given as Isoniazid preventive therapy [IPT]) uptake and treatment completion across the 4 years, among PLHIV aged 15 years and above, and factors associated, were examined using Poisson regression model with robust standard errors using generalized estimating equation (GEE) models.

Results

On average a total of 43,215 patients aged 15 years and above were eligible for TPT each calendar year at the six health facilities. More than 70% were females and median age was 34 years (inter-quartile range 28 to 41 years on overall). There was consistently low TPT uptake from 2016 to 2018, but as expected, the uptake significantly increased by about 25% (relative increase) from 2.5% of eligible PLHIV in 2018 to 64.8% in 2019 (prevalence of TPT uptake 4.5% (1,746/38,704), 4.4% (1,743/39,630), 2.5% (1,018/40,390), and 64.8% (26,478/40,867) during 2016, 2017, 2018 and 2019 respectively). TPT uptake in 2019 was 26.0 times higher compared to that in 2018 (adjusted prevalence ratio [aPR] = 26.0 [95%CI 24.5, 27.7], P-value<0.001). Also, TPT completion was consistently high at about 80% between years 2016 – 2018 but dramatically increased by 17% (relative increase) in 2019 compared to that in 2018 (prevalence of TPT completion was 81.2%, 76.3%, 82.6% and 96.5% in year 2016, 2017, 2018 and 2019 respectively). The increase in TPT completion prevalence from 2018 to 2019 remained significant even after adjusting for patients’ baseline characteristics (aPR [95%CI] = 1.12 [1.04, 1.21], P value=0.003). Not on ART or newly started on ART compared ART experienced were associated with poor TPT completion, whereas older age (≥25 years versus 15-24 years) was associated with higher TPT completion.

Conclusion

The targeted 100-day campaign dramatically increased TPT uptake and completion among PLHIV suggesting a viable catch up strategy to meet WHO guidelines.
Reversal of lactate and PD-1-mediated macrophage immunosuppression controls growth of PTEN/p53-deficient prostate cancer
Authors: Chaudagar Kiranj , Hieromnimon Hanna M. , Khurana Rimpi , Labadie Brian , Hirz Taghreed , Mei Shenglin , Hasan Raisa , Shafran Jordan , Kelley Anne , Apostolov Eva , Al-Eryani Ghamdan , Harvey Kate , Rameshbabu Srikrishnan , Loyd Mayme , Bynoe Kaela , Drovetsky Catherine , Solanki Ani , Markiewicz Erica , Zamora Marta , Fan Xiaobing , Schürer Stephan , Swarbrick Alex , Sykes David B. , Patnaik Akash
Published: May 2022

PTEN loss-of-function occurs in approximately 50% of mCRPC patients, and is associated with a poor prognosis, therapeutic outcomes and resistance to immune-checkpoint inhibitors. Recent clinical studies demonstrated that dual PI3K/AKT pathway inhibition and androgen axis blockade led to a modest improvement in progression-free survival of PTEN-deficient mCRPC patients, but the mechanistic basis for this limited efficacy is unknown. To elucidate potential resistance mechanism(s), we performed co-clinical trials in a prostate-specific PTEN/p53-deficient genetically-engineered mouse model, and discovered that the recruitment of PD-1-expressing tumor-associated macrophages (TAM) thwarts the phagocytosis-mediated anti-tumor efficacy of androgen deprivation therapy (ADT)/PI3K inhibitor (PI3Ki) combination. Strikingly, we observed a TAM-dependent ∼3-fold enhancement in the overall response rate with the addition of PD-1 antibody (aPD-1) to ADT/PI3Ki combination therapy. Mechanistically, decreased lactate production from PI3Ki-treated tumor cells suppressed histone lactylation (H3K18lac) within TAM, resulting in their phagocytic activation, which was augmented by concurrent ADT/aPD-1 treatment. Consistent with our murine observations, single cell RNA-sequencing analysis of human metastatic PC samples revealed a direct correlation between high glycolytic activity and phagocytosis suppression. Critically, feedback activation of Wnt/β-catenin signaling observed in non-responder mice following ADT/PI3Ki/aPD-1 combination treatment, restored lactate-mediated H3K18lac and suppressed phagocytosis within macrophages. Altogether, these data suggest that reversal of lactate and PD-1-mediated TAM immunosuppression by PI3Ki and aPD-1, respectively, controls tumor growth in combination with ADT, and warrants further clinical investigation in PTEN/p53-deficient mCRPC patients.

One Sentence Summary

Inhibition of tumor-cell intrinsic lactate production suppresses PTEN/p53-deficient prostate cancer growth via macrophage activation/phagocytosis
Contrasting patterns of genetic admixture explain the phylogeographic history of Iberian high mountain populations of midwife toads
Authors: Lucati Federica , Miró Alexandre , Bosch Jaime , Caner Jenny , Jowers Michael Joseph , Rivera Xavier , Donaire-Barroso David , Rebelo Rui , Ventura Marc
Published: May 2022

Multiple Quaternary glacial refugia in the Iberian Peninsula, commonly known as “refugia within refugia”, allowed diverging populations to come into contact and admix, potentially boosting substantial mito-nuclear discordances. In this study, we employ a comprehensive set of mitochondrial and nuclear markers to shed light onto the drivers of geographical differentiation in Iberian high mountain populations of the midwife toadsAlytes obstetricansandA. almogavariifrom the Pyrenees, Picos de Europa and Guadarrama Mountains. In the three analysed mountain regions, we detected evidence of extensive mito-nuclear discordances and/or admixture between taxa. Clustering analyses identified three major divergent lineages in the Pyrenees (corresponding to the eastern, central and central-western Pyrenees), which possibly recurrently expanded and admixed during the succession of glacial- interglacial periods that characterised the Late Pleistocene, and that currently follow a ring-shaped diversification pattern. On the other hand, populations from the Picos de Europa mountains (NW Iberian Peninsula) showed a mitochondrial affinity to central-western Pyrenean populations and a nuclear affinity to populations from the central Iberian Peninsula, suggesting a likely admixed origin for Picos de Europa populations. Finally, populations from the Guadarrama Mountain Range (central Iberian Peninsula) were depleted of genetic diversity, possibly as a consequence of a recent epidemic of chytridiomycosis. This work highlights the complex evolutionary history that shaped the current genetic composition of high mountain populations, and underscores the importance of using a multilocus approach to better infer the dynamics of population divergence.
Increased structural connectivity in high schizotypy
Authors: Messaritaki Eirini , Foley Sonya , Barawi Kali , Ettinger Ulrich , Jones Derek K
Published: May 2022

The link between brain structural connectivity and schizotypy was explored in two healthy-participant cohorts, collected at two different neuroimaging centres, comprising 140 and 115 participants respectively. The participants completed the Schizotypal Personality Questionnaire (SPQ), through which their schizotypy scores were calculated. Diffusion-MRI data were used to perform tractography and to generate the structural brain networks of the participants. The edges of the networks were weighted with the inverse radial diffusivity. Graph theoretical metrics of the default-mode, sensorimotor, visual and auditory subnetworks were derived and their correlation coefficients with the schizotypy scores were calculated. To the best of our knowledge, this is the first time that graph theoretical measures of structural brain networks are investigated in relation to schizotypy.

A positive correlation was found between the schizotypy score and the mean node degree and mean clustering coefficient of the sensorimotor and the default-mode subnetworks. The nodes driving these correlations were the right postcentral gyrus, the left paracentral lobule, the right superior frontal gyrus, the left parahippocampal gyrus and the bilateral precuneus, i.e., nodes that exhibit compromised functional connectivity in schizophrenia. Implications for schizophrenia and schizotypy are discussed.
Strongly truncated Dnaaf4 plays a conserved role in Drosophila ciliary dynein assembly as part of an R2TP-like co-chaperone complex with Dnaaf6
Authors: Lennon Jennifer , Lage Petra zur , Kriegsheim Alex von , Jarman Andrew P.
Published: May 2022

Axonemal dynein motors are large multi-subunit complexes that drive ciliary movement. Cytoplasmic assembly of these motor complexes involves several co-chaperones, some of which are related to the R2TP co-chaperone complex. Mutations of these genes in humans cause the motile ciliopathy, Primary Ciliary Dyskinesia (PCD), but their different roles are not completely known. Two such dynein (axonemal) assembly factors (DNAAFs) that are thought to function together in an R2TP-like complex are DNAAF4 (DYX1C1) and DNAAF6 (PIH1D3). Here we investigate the Drosophila homologues, CG14921/Dnaaf4 and CG5048/Dnaaf6. Surprisingly, Drosophila Dnaaf4 is truncated such that it completely lacks a TPR domain, which in human DNAAF4 is likely required to recruit HSP90. Despite this, we provide evidence that Drosophila Dnaaf4 and Dnaaf6 proteins can associate in an R2TP-like complex that has a conserved role in dynein assembly. Both are specifically expressed and required during the development of the two Drosophila cell types with motile cilia: mechanosensory chordotonal neurons and sperm. Flies that lack either gene are viable but with impaired chordotonal neuron function and lack motile sperm. We provide molecular evidence that Dnaaf4 and Dnaaf6 are required for assembly of outer dynein arms (ODAs) and a subset of inner dynein arms (IDAs).