bluuebunny/crossref_metadata_2025 huggingface dataset:
The DNA replication protein Orc1 from the yeast Torulaspora delbrueckii is required for heterochromatin formation but not as a silencer-binding protein
Authors: Maria Haniam , Rusche Laura N.
Published: May 2022

To understand the process by which new protein functions emerge, we examined how the yeast heterochromatin protein Sir3 arose through gene duplication from the conserved DNA replication protein Orc1. Orc1 is a subunit of the origin recognition complex (ORC), which marks origins of DNA replication. In Saccharomyces cerevisiae, Orc1 also promotes heterochromatin assembly by recruiting the structural proteins Sir1-4 to silencer DNA. In contrast, the paralog of Orc1, Sir3, is a nucleosome-binding protein that spreads across heterochromatic loci in conjunction with other Sir proteins. We previously found that a non-duplicated Orc1 from the yeast Kluyveromyces lactis behaved like ScSir3 but did not have a silencer-binding function like ScOrc1. Moreover, K. lactis lacks Sir1, the protein that interacts directly with ScOrc1. Here, we searched for the presumed intermediate state in which non-duplicated Orc1 possesses both the silencer-binding and spreading functions. In the non-duplicated species Torulaspora delbrueckii, which has an ortholog of Sir1 (TdKos3), we found that TdOrc1 spreads across heterochromatic loci independently of ORC, as ScSir3 and KlOrc1 do. This spreading is dependent on the nucleosome binding BAH domain of Orc1 and on Sir2 and Kos3. However, TdOrc1 does not have a silencer-binding function: T. delbrueckii silencers do not require ORC binding sites to function, and Orc1 and Kos3 do not appear to interact. Instead, Orc1 and Kos3 both spread across heterochromatic loci with other Sir proteins. Thus, Orc1 and Sir1/Kos3 originally had different roles in heterochromatin formation than they do now in S. cerevisiae.
Stem Cell Secretome Promotes Scarless Corneal Wound Healing and Rescues Corneal Sensory Nerves
Authors: Kumar Ajay , Li Yunshu , Mallick Shayshadri , Yang Enzhi , Dhaliwal Deepinder K. , Price Andrew , Xie Ting , Du Yiqin
Published: May 2022

Corneal scarring is a leading cause of blindness in the world. In this study, we explored the therapeutic potential of corneal stromal stem cell (CSSC)-derived secretome in a mechanical debridement mouse model of corneal scarring. CSSC secretome was able to promote scarless corneal wound healing. The mechanisms include 1) dampening inflammation with reduced CD45+, CD11b+/GR1+, and CD11b+/F4/80+ inflammatory cells in the wounded corneas; 2) reducing fibrotic extracellular matrix deposition such as collagen IV, collagen 3A1, SPARC, and α-SMA; 3) rescuing sensory nerves. The proteomic analysis shows upregulated proteins related to wound healing and cell adhesion which boost scarless wound healing. It also shows upregulated neuroprotective proteins in CSSC secretome related to axon guidance, neurogenesis, neuron projection development, and neuron differentiation. Four unique complement inhibitory proteins CD59, vitronectin, SERPING1, and C1QBP found in CSSC secretome contribute to reducing a complement cascade mediating cell death and membrane attacking complex autoantibodies after corneal injury. This study provides novel insights into mechanisms of stem cell secretome induced scarless corneal wound healing and neuroprotection and identifies regenerative proteins in the CSSC secretome.

Significance Statement

In this study, we report the therapeutic role of corneal stromal stem cell (CSSC) secretome for scarless corneal wound healing and corneal sensory nerve rescuing. We uncovered that CSSC secretome dampens inflammation, reduces fibrosis, induces sensory nerve regeneration, and rescues corneal cells by inhibiting the complement system in the wounded mouse corneas. This study provides pre-clinical evidence for the use of CSSC secretome as a biologic treatment for corneal scarring to prevent corneal blindness. We delineated a plethora of proteins in the CSSC secretome, which individually or in combination have the potential as future therapies for scarless corneal wound healing.
Phase separation of competing memories along the human hippocampal theta rhythm
Authors: Kerrén Casper , van Bree Sander , Griffiths Benjamin J. , Wimber Maria
Published: May 2022

Competition between overlapping memories is considered one of the major causes of forgetting and it is still unknown how the human brain resolves such mnemonic conflict. In the present MEG study, we empirically tested a computational model that leverages an oscillating inhibition algorithm to minimise overlap between memories. We used a proactive interference task, where a reminder word could be associated with either a single image (non-competitive condition) or two competing images, and participants were asked to always recall the most recently learned word-image association. Time-resolved pattern classifiers were trained to detect the reactivated content of target and competitor memories from MEG sensor patterns, and the timing of these neural reactivations was analysed relative to the phase of the dominant hippocampal 3Hz theta oscillation. In line with our preregistered hypotheses, target and competitor reactivations locked to different phases of the hippocampal theta rhythm after several repeated recalls. Participants who behaviourally experienced lower levels of interference also showed larger phase separation between the two overlapping memories. The findings provide evidence that the temporal segregation of memories, orchestrated by slow oscillations, plays a functional role in resolving mnemonic competition by separating and prioritising relevant memories under conditions of high interference.
Life history traits and a method for continuous mass rearing of the planthopper Pentastiridius leporinus, a vector of the causal agent of syndrome “basses richesses” in sugar beet
Authors: Pfitzer René , Varrelmann Mark , Schrameyer Klaus , Rostás Michael
Published: May 2022

BACKGROUND

The planthopper Pentastiridius leporinus (Hemiptera: Cixiidae) is the main vector of the γ-3 proteobacterium ‘Candidatus Arsenophonus phytopathogenicus’ which causes the syndrome “basses richesses” (SBR) in sugar beet. SBR is a new and fast spreading disease in Central Europe that leads to high yield losses. To date the development of management strategies is hampered by insufficient knowledge about general life history traits of the planthopper and, most importantly, the year round availability of insects reared under controlled conditions. Rearing of P. leporinus has been considered challenging and to date no protocol exists.

RESULTS

Here we describe a method for mass rearing P. leporinus on sugar beet from egg to adult, which has produced five generations and >20,000 individuals between June 2020 and March 2022. An alternative host such as wheat is not necessary for completing the life cycle. No-choice experiments showed that P. leporinus lays 139.1 ± 132.9 eggs on sugar beet, whereas no oviposition was observed on its nymphal host wheat. Head capsule width was identified as a trait that unequivocally distinguished the five nymphal instars. Developmental time from first instar to adult was 193.6 ± 35.8 days for males and 193.5 ± 59.2 days for females. Infection rates of adults were tested with nested polymerase chain reaction (PCR). The results demonstrated that 70-80% of reared planthoppers across all generations carried the SBR proteobacterium.

CONCLUSION

The mass rearing protocol and life history data will help overcome an important bottleneck in SBR research and enhance efforts in developing integrated pest management tools.
Preconfigured dynamics in the hippocampus are guided by embryonic birthdate and rate of neurogenesis
Authors: Huszár Roman , Zhang Yunchang , Blockus Heike , Buzsáki György
Published: May 2022

The incorporation of novel information into the hippocampal network is likely be constrained by its innate architecture and internally generated activity patterns. However, the origin, organization, and consequences of such patterns remain poorly understood. Here, we show that hippocampal network dynamics are affected by sequential neurogenesis. We birthdated CA1 pyramidal neurons with in-utero electroporation over 4 embryonic days encompassing the peak of hippocampal neurogenesis, and compared their functional features in freely moving, adult mice. Neurons of the same birthdate displayed distinct connectivity, coactivity across brain states, and assembly dynamics. Same birthdate hippocampal neurons were topographically organized, in that anatomically clustered (<500µm) neurons exhibited overlapping spatial representations. Overall, the wiring and functional features of CA1 pyramidal neurons reflected a combination of birthdate and the rate of neurogenesis. These observations demonstrate that sequential neurogenesis in embryonic development shapes the preconfigured forms of adult network dynamics.
Opposing associations of Internet Use Disorder symptom domains with structural and functional organization of the striatum: a dimensional neuroimaging approach
Authors: Yu Fangwen , Li Jialin , Xu Lei , Zheng Xiaoxiao , Fu Meina , Li Keshuang , Yao Shuxia , Kendrick Keith M , Montag Christian , Becker Benjamin
Published: May 2022

Background

Accumulating evidence suggests brain structural and functional alterations in Internet Use Disorder (IUD). However, conclusions are strongly limited due to the retrospective case-control design of the studies, small samples, and the focus on general rather than symptom-specific approaches.

Methods

We here employed a dimensional multi-methodical MRI-neuroimaging design in a final sample of n = 203 subjects to examine associations between levels of IUD and its symptom-dimensions (loss of control/time management, craving/social problems) with brain structure, resting state and task-based (pain empathy, affective go/no-go) brain function.

Results

Although the present sample covered the entire range of IUD, including normal, problematic as well as pathological levels, general IUD symptom load was not associated with brain structural or functional alterations. However, the symptom-dimensions exhibited opposing associations with the intrinsic and structural organization of the brain, such that loss of control/time management exhibited negative associations with intrinsic striatal networks and hippocampal volume, while craving/social problems exhibited a positive association with intrinsic striatal networks and caudate volume.

Conclusions

Our findings provided the first evidence for IUD symptom-domain specific associations with progressive alterations in the intrinsic structural and functional organization of the brain, particularly of striatal systems involved in reward, habitual and cognitive control processes.
Cryo-EM structure of gas vesicles for buoyancy-controlled motility
Authors: Huber Stefan T. , Terwiel Dion , Evers Wiel H. , Maresca David , Jakobi Arjen J.
Published: May 2022

Gas vesicles allow a diverse group of bacteria and archaea to move in the water column by controlling their buoyancy (1). These gas-filled cellular nanocompartments are formed by up to micrometers long protein shells that are permeable only to gas. The molecular basis of their unique properties and mechanism of assembly remains unknown. Here, we solve the 3.2 Å cryo-EM structure of the B.megaterium gas vesicle shell made from the structural protein GvpA that self-assembles into hollow helical cylinders closed off by cone-shaped tips. Remarkably, the unique fold adopted by GvpA generates a corrugated cylinder surface typically found in force-bearing thin-walled structures. We identified pores in the vesicle wall that enable gas molecules to freely diffuse in and out of the GV shell, while the exceptionally hydrophobic interior surface effectively repels water. Our results show that gas vesicles consist of two helical half-shells connected through a unique arrangement of GvpA monomers, suggesting a mechanism of gas vesicle biogenesis. Comparative structural analysis confirms the evolutionary conservation of gas vesicle assemblies and reveals molecular details of how the secondary structural protein GvpC reinforces the GvpA shell. Our findings provide a structural framework that will further research into the biology of gas vesicles, and enable rational molecular engineering to harness their unique properties for acoustic imaging (2, 3).
Capacitation promotes a shift in the energy metabolism in murine sperm
Authors: Tourmente Maximiliano , Sansegundo Ester , Rial Eduardo , Roldan Eduardo R. S.
Published: May 2022

In mammals, sperm acquire fertilization ability after a series of physiological and biochemical changes, collectively known as capacitation, that occur inside the female reproductive tract. In addition to other requirements, sperm bioenergetic metabolism has been identified as fundamental component in the acquisition of the capacitated status. Mammalian sperm produce ATP by means of two main metabolic processes, oxidative phosphorylation (OXPHOS) and aerobic glycolysis, that are localized in two different flagellar compartments, midpiece and principal piece, respectively. In mouse sperm, the occurrence of many events associated to capacitation depends on the activity of these two energy-producing pathways, leading to the hypothesis that some of these events may impose changes in sperm energetic demands. In the present study, we used extracellular flux analysis to evaluate the changes in the glycolytic and respiratory parameters of murine sperm that occur as a consequence of capacitation. Furthermore, we examined whether these variations affect sperm ATP sustainability. Our results show that capacitation promotes a shift in the usage ratio of the two main metabolic pathways, from oxidative to glycolytic. However, this metabolic rewiring does not seem to affect the rate at which the sperm consume ATP. We conclude that the probable function of the metabolic switch is to increase the ATP supply in the distal flagellar regions, thus sustaining the energetic demands that arise from capacitation.
Integrated Analysis of Tissue-specific Gene Expression in Diabetes by Tensor Decomposition Can Identify Possible Associated Diseases
Authors: Taguchi Y-H. , Turki Turki
Published: May 2022

In the field of gene expression analysis, methods of integrating multiple gene expression profiles are still being developed and the existing methods have scope for improvement. The previously proposed tensor decomposition-based unsupervised feature extraction method was improved by introducing standard deviation optimization. The improved method was applied to perform an integrated analysis of three tissue-specific gene expression profiles (namely, adipose, muscle, and liver) for diabetes mellitus, and the results showed that it can detect diseases that are associated with diabetes (e.g., neurodegenerative diseases) but that cannot be predicted by individual tissue expression analyses using state-of-the-art methods. Although the selected genes differed from those identified by the individual tissue analyses, the selected genes are known to be expressed in all three tissues. Thus, compared with individual tissue analyses, an integrated analysis can provide more in-depth data and identify additional factors, namely, the association with other diseases.
Characteristics and Impact of the rNST GABA Network on Neural and Behavioral Taste Responses
Authors: Travers Susan P. , Kalyanasundar B. , Breza Joseph , Houser Grace , Klimovich Charlotte , Travers Joseph
Published: May 2022

The rostral nucleus of the solitary tract (rNST), the initial CNS site for processing gustatory information, is comprised of two major cell types, glutamatergic excitatory and GABAergic inhibitory neurons. Many investigators have described taste responses of rNST neurons, but the phenotypes of these cells were unknown. The current investigation used mice expressing ChR2 under the control of GAD65, a synthetic enzyme for GABA. In vivo single-unit recording of rNST cells during optogenetic stimulation allowed us to address two important questions: (1) what are the gustatory response characteristics of “optotagged”, putative GABAergic (G+TASTE) neurons? and (2) how does optogenetic activation of the rNST GABA network impact taste responses in non-GABAergic (G-TASTE) neurons? We observed that chemosensitive profiles of G+TASTE neurons were similar to non-GABA taste neurons but had much lower response rates. We further observed that there was a population of GABA cells unresponsive to taste stimulation (G+UNR) and located more ventrally in the nucleus. Activating rNST inhibitory circuitry suppressed gustatory responses of G-TASTE neurons across all qualities and types of chemosensitive neurons. Tuning curves were modestly sharpened but the overall shape of response profiles and the ensemble pattern remained highly stable. These neurophysiological effects were consistent with the behavioral consequences of activating GAD65-expressing inhibitory neurons using DREADDs. In a brief-access licking task, concentration-response curves to both palatable (sucrose, maltrin) and unpalatable (quinine) stimuli were shifted to the right when GABA neurons were activated. Thus, the rNST GABAergic network is poised to modulate taste intensity across the qualitative and hedonic spectrum.

SIGNIFICANCE STATEMENT

The rNST, the CNS gateway for taste, is rich in GABAergic neurons and synapses. Our in vivo recordings from GAD65/ChR2 mice reveal that gustatory response profiles of optotagged GABAergic neurons resemble non-GABAergic neurons, but with much reduced amplitudes. A novel population of GABA neurons were unresponsive to oral stimulation suggesting they are targets for centrifugal influences. Activating rNST inhibitory circuitry modestly sharpened gustatory tuning but preserved the ensemble pattern for taste quality despite markedly suppressed responses. In behaving mice, activating rNST GAD65-expressing neurons with DREADDs shifted response-concentration curves for palatable and unpalatable stimuli, but preserved appropriate behaviors. These observations unveil previously unknown features of rNST GABA cells and demonstrate substantial inhibitory modulation at the first central taste relay.
Closed-loop and automatic tuning of pulse amplitude and width in EMG-guided controllable transcranial magnetic stimulation (cTMS)⋆
Authors: Alavi S. M. Mahdi , Vila-Rodriguez Fidel , Mahdi Adam , Goetz Stefan M.
Published: May 2022

This paper proposes a tool for automatic and optimal tuning of pulse amplitude and width for sequential parameter estimation (SPE) of the membrane time constant and input–output curve in closed-loop electromyography-guided (EMG-guided) controllable transcranial magnetic stimulation (cTMS). A normalized depolarization factor is defined which separates the optimization of the pulse amplitude and width. Then, the pulse amplitude is chosen by the maximization of the Fisher information matrix (FIM), while the pulse width is chosen by the maximization of the normalized depolarization factor. The simulation results confirm satisfactory estimation. The results show that the normalized depolarization factor maximization can identify the critical pulse width, which is an important parameter in the identifiability analysis, without any prior neurophysiological or anatomical knowledge of the neural membrane.
Two complete genomes of male-killing Wolbachia infecting Ostrinia moth species illuminate their evolutionary dynamics and association with hosts
Authors: Muro Tomohiro , Hikida Hiroyuki , Fujii Takeshi , Kiuchi Takashi , Katsuma Susumu
Published: May 2022

Wolbachia is an extremely widespread endocellular symbiont which causes reproductive manipulation on various arthropod hosts. Male progenies are killed in Wolbachia-infected lineages of the Japanese Ostrinia moth population. While the mechanism of male killing and the evolutionary interaction between host and symbiont are significant concerns for this system, the absence of Wolbachia genomic information has limited approaches to these issues. We determined the complete genome sequences of wFur and wSca, the male-killing Wolbachia of O. furnacalis and O. scapulalis. The two genomes shared an extremely high degree of homology, with over 95% of the predicted protein sequences being identical. A comparison of these two genomes revealed nearly minimal genome evolution, with a strong emphasis on the frequent genome rearrangements and the rapid evolution of ankyrin repeat-containing proteins. Additionally, we determined the mitochondrial genomes of both species’ infected lineages and performed phylogenetic analyses to deduce the evolutionary dynamics of Wolbachia infection in the Ostrinia clade. According to the inferred phylogenetic relationship, Wolbachia infection was established in the Ostrinia clade prior to the speciation of related species such as O. furnacalis and O. scapulalis. Simultaneously, the relatively high homology of mitochondrial genomes suggested recent Wolbachia introgression between infected Ostrinia species. The findings of this study collectively shed light on the host-symbiont interaction from an evolutionary standpoint.

Significance

Despite the growing number of publicly available Wolbachia genome sequences, only a few high-quality male-killer genomes exist, particularly those found in lepidopteran hosts. The complete genomes of two male-killing Wolbachia of Ostrinia moth hosts were determined in this study. The genomic data obtained here will be used to elucidate the mechanism of reproductive manipulation and the origins of this endosymbiont’s extraordinary diversity. Additionally, phylogenetic analysis of mitochondria and Wolbachia revealed the evolutionary history of Ostrinia hosts and Wolbachia. The inferred dynamic pattern of infection adds to our understanding of evolution and ecology of Wolbachia endosymbiont, a promising agent for biological pest control.
Reproducibility ofin vivoelectrophysiological measurements in mice
Authors:   International Brain Laboratory, Banga Kush , Benson Julius , Bhagat Jai , Biderman Dan , Birman Daniel , Bonacchi Niccolò , Bruijns Sebastian A , Buchanan Kelly , Campbell Robert AA , Carandini Matteo , Chapuis Gaëlle A , Churchland Anne K , Davatolhagh M Felicia , Lee Hyun Dong , Faulkner Mayo , Gerçek Berk , Hu Fei , Huntenburg Julia , Hurwitz Cole , Khanal Anup , Krasniak Christopher , Langfield Christopher , Meijer Guido T , Miska Nathaniel J , Mohammadi Zeinab , Noel Jean-Paul , Paninski Liam , Pan-Vazquez Alejandro , Roth Noam , Schartner Michael , Socha Karolina , Steinmetz Nicholas A , Svoboda Karel , Taheri Marsa , Urai Anne E , Wells Miles , West Steven J , Whiteway Matthew R , Winter Olivier , Witten Ilana B
Published: May 2022

Understanding brain function relies on the collective work of many labs generating reproducible results. However, reproducibility has not been systematically assessed within the context of electrophysiological recordings during cognitive behaviors. To address this, we formed a multi-lab collaboration using a shared, open-source behavioral task and experimental apparatus. Experimenters in ten laboratories repeatedly targeted Neuropixels probes to the same location (spanning secondary visual areas, hippocampus, and thalamus) in mice making decisions; this generated a total of 121 experimental replicates, a unique dataset for evaluating reproducibility of electrophysiology experiments. Despite standardizing both behavioral and electrophysiological procedures, some experimental outcomes were highly variable. A closer analysis uncovered that variability in electrode targeting hindered reproducibility, as did the limited statistical power of some routinely used electrophysiological analyses, such as single-neuron tests of modulation by task parameters. Reproducibility was enhanced by histological and electrophysiological quality-control criteria. Our observations suggest that data from systems neuroscience is vulnerable to a lack of reproducibility, but that across-lab standardization, including metrics we propose, can serve to mitigate this.
Deformable Mirror based Optimal PSF Engineering for 3D Super-resolution Imaging
Authors: Fu Shuang , Li Mengfan , Zhou Lulu , He Yingchuan , Liu Xin , Hao Xiang , Li Yiming
Published: May 2022

Point spread function (PSF) engineering is an important technique to encode the properties (e.g., 3D positions, color, and orientation) of single molecule in the shape of the PSF, often with the help of a programmable phase modulator. Deformable mirror (DM) is currently the most widely used phase modulator for fluorescence detection as it shows negligible photon loss. However, it relies on careful calibration for precise wavefront control. Therefore, design of an optimal PSF not only relies on the theoretical calculation of maximum information content, but also the physical behavior of the phase modulator, which is often ignored during the optimization process. Here, we developed a framework of PSF engineering which could generate a device specific optimal PSF for 3D super-resolution imaging using DM. We used our method to generate two types of PSFs with depths of field comparable to the widely used astigmatism and Tetrapod PSFs, respectively. We demonstrated the superior performance of the DM specific optimal PSF over the conventional astigmatism and Tetrapod PSF both theoretically and experimentally.
Sequence-based pH-dependent prediction of protein solubility using CamSol
Authors: Oeller Marc , Kang Ryan , Sormanni Pietro , Vendruscolo Michele
Published: May 2022

Solubility is a property of central importance for the use of proteins in research and in applications in biotechnology and medicine. Since experimental methods for measuring protein solubility are resource-intensive and time-consuming, computational methods have recently emerged to enable the rapid and inexpensive screening of large libraries of proteins, as it is routinely required in development pipelines. Here, we describe the extension of one of such methods, CamSol, to include in the predictions the effect of the pH of the solubility. We illustrate the accuracy of the pH-dependent predictions on a variety of antibodies and other proteins.
Distinct cortical networks subserve spatio-temporal sampling in vision through different oscillatory rhythms
Authors: Ronconi Luca , Balestrieri Elio , Baldauf Daniel , Melcher David
Published: May 2022

Although visual input arrives continuously, sensory information is segmented into discrete events. Here, the neural correlates of spatiotemporal binding in male/female human subjects were investigated with MEG using two tasks where separate flashes were presented on each trial but were perceived, in a bi-stable way, as either a single, or two separate, events. The first task (two-flash fusion: TFF) involved judging one versus two flashes while in the second task (apparent motion: AM) participants judged coherent motion versus two stationary flashes. Results indicate two different functional networks underlying two unique aspects of visual temporal binding. In the TFF task, involving an integration window of ≈50 ms, evoked responses differed as a function of perceptual interpretation by ≈25 ms after stimuli presentation. Multivariate decoding of subjective perception based on prestimulus oscillatory phase was significant for alpha-band activity in the right medial temporal (MT) area, with the strength of pre-stimulus connectivity between early visual areas and MT being predictive of performance. In contrast, the longer integration window (≈130 ms) for AM showed evoked field differences only ≈250 ms after stimuli onset. Phase decoding of the perceptual outcome in the AM task was strongest for theta-band activity, localized to a right intra-parietal sulcus (IPS) source. Pre-stimulus connectivity between MT and IPS seeds in the theta band best predicted perceptual outcome. Overall, these results show a strong relationship between specific spatiotemporal binding windows and specific oscillations, linked to the information flow between different areas of the “where” and “when” visual processing pathways.

Significance Statement

Multiple neural rhythms seem relevant for sampling visual information across space and time, but the cortical networks underlying these fundamental computational principles of the visual system remain unexplored. We filled this gap by employing source-level multivariate decoding and connectivity analyses of magnetoencephalographic data recorded during an integration/segregation task of temporal and spatio-temporal events. We identified a first and faster network involving early visual areas (V2 to MT/V5) that determines the basic temporal resolution of visual perception at the speed of the alpha rhythm, and a second slower network involving parietal regions (IPS) that had a key role in the integration of more complex spatiotemporal events at a theta speed. These findings elucidate the neural mechanisms that transfer sensory information into temporal sequences.
Rapid evolution of ecological sexual dimorphism driven by resource competition
Authors: De Lisle Stephen P.
Published: May 2022

Sex differences in ecologically-important traits are common in animals and plants, and prompted Darwin to first propose an ecological cause of sexual dimorphism. Despite theoretical plausibility and Darwin’s original notion, a role for ecological resource competition in the evolution of sexual dimorphism has never been directly demonstrated and remains controversial. I used experimental evolution in Drosophila melanogaster to test the hypothesis that resource competition can drive the evolution of sex differences in diet. Following just three generations of adaptation, offspring from flies evolved in low-resource, high-competition environments show elevated sexual dimorphism in diet preference compared to both the ancestor and populations evolved on high resource availability. These results provide the first real-time direct evidence for evolution of sexual dimorphism driven by an ecological cause.

One sentence summary

Sex differences in fly diet evolved rapidly under elevated competition, demonstrating ecological cause of sex differences.
Persistence of Cajal-Retzius cells in the postnatal hippocampus is required for development of dendritic spines of CA1 pyramidal cells
Authors: Glærum Ingvild Lynneberg , Dunville Keagan , Montaldo Nicola Pietro , Kirikae Hinako , Nigro Maximiliano Jose , Sætrom Pål , van Loon Barbara , Quattrocolo Giulia
Published: May 2022

Cajal-Retzius (CR) cells are a transient type of neuron that populate the postnatal hippocampus. The role of transient cell types and circuits have been vastly addressed in neocortical regions, but poorly studied in the hippocampus. To understand how CR cells’ persistence influences the maturation of hippocampal circuits, we specifically ablated CR cells from the postnatal hippocampus. Our results highlighted layer-specific effects on dendritic spines and synaptic-related genes and revealed a critical role of CR cells in the establishment of the hippocampal network.
Quantification of astrocytic synaptic pruning in hippocampus in response to in vitro Aβ oligomer incubation via colocalization analysis with C1q
Authors: Pradhan Arpit Kumar , Shi Qinfang , Tartler Katharina Johanna , Rammes Gerhard
Published: May 2022

Quantification of synaptic engulfment is an indirect measurement of synaptic pruning. Here, we provide a detailed protocol for the volumetric rendering of individual high-resolution astrocytes in the CA1 region of hippocampus in an in vitro slice model of Amyloid-beta (Aβ) treatment. This includes free floating slice preparation, treatment with Aβ oligomers, immunofluorescence, confocal imaging and analysis of individual astrocytes. We also provide a comprehensive analysis for 3D rendering of astrocytes and assessment of synaptic engulfment via “eat-me tag” C1q protein and synaptic marker PSD95.

Highlights

Measurement of synaptic engulfment in response to treatment with Aβ peptide

Volumetric reconstruction of high resolution individual astrocyte

Colocalization analysis of astrocyte and complementary “eat-me” protein C1q

Graphical abstract
The Role of Conjunctive Representations in Prioritizing and Selecting Planned Actions
Authors: Kikumoto Atsushi , Mayr Ulrich , Badre David
Published: May 2022

For flexible goal-directed behavior, prioritizing and selecting a specific action among multiple candidates is often important. Working memory has long been assumed to play a role in prioritization and planning, while bridging cross-temporal contingencies during action selection. However, studies of working memory have mostly focused on memory for single components of an action plan, such as a rule or a stimulus, rather than management of all of these elements during planning. Therefore, it is not known how post-encoding prioritization and selection operate on the entire profile of representations for prospective actions. Here, we assessed how such control processes unfold over action representations, highlighting the role of conjunctive representations that nonlinearly integrate task-relevant features during maintenance and prioritization of action plans. For each trial, participants prepared two independent rule-based actions simultaneously, then they were retro-cued to select one as their response. Prior to the start of the trial, one rule-based action was randomly assigned to be high priority by cueing that it was more likely to be tested. We found that both full action plans were maintained as conjunctive representations during action preparation, regardless of priority. However, during output selection, the conjunctive representation of the high priority action plan was more enhanced and readily selected as an output. Further, the strength of conjunctive representation was related to behavioral interference when the low priority action was tested. Thus, multiple integrated representations were maintained for upcoming actions and served as the target of post-encoding attentional selection mechanisms to prioritize and select an action from those in working memory.
A general mechanism of air-borne hearing in Recent and early non-tympanate tetrapods
Authors: Christensen-Dalsgaard Jakob , Lauridsen Tanya Bojesen , Capshaw Grace , Carr Catherine E.
Published: May 2022

Tetrapod tympanic hearing probably emerged in the Triassic with independent origins in each of the major groups, more than 120 Myr after the water-land transition. During this long period, any auditory sensitivity must have been based on non-tympanic, bone conduction mechanisms. However, ‘bone conduction’ is a non-specific term describing several different modes of vibration that can stimulate the inner ear.

To understand hearing in a non-tympanic ear, we focus on the simplest model: that sound translates the head, i.e., that the head is pushed and pulled by the sound wave, and that this vibration is transduced by the inner ear. Simple translation is the mode of human low-frequency bone conduction sensitivity and translation by underwater sound is also the mode of auditory stimulation for most fishes. It is therefore a straightforward assumption that this may have been the mechanism of hearing in the early tetrapods. According to acoustic theory, the efficiency of translation of an object by sound is determined by its density and ka, the product of the acoustic wavenumber (k) and the radius (a) of the head. Simple finite-element models of translation by sound show that vibration velocities only depend on ka and density (for objects of the same shape and composition) and are almost constant (between 4 and 5 µm/s/Pa depending on shape) for objects with ka<1. We compare sensitivity to sound and to vibrations of the skull in animals lacking tympanic middle ears (snakes, salamanders, earless frogs, and lungfish) and show that the low-frequency air-borne sound sensitivity in these species is largely consistent with a translation mechanism. How translation of the head or body can stimulate the inner ear is most evident in an inertial system like the otolithic/otoconial ears of fish and early tetrapods, but fluid inertia in the inner ear may also generate hydrodynamic waves that can stimulate hair cells in the tetrapod inner ear, providing a mechanism for this simple mode of sound reception to confer hearing in earless animals.
The Drosophila ZAD zinc finger protein Kipferl guides Rhino to piRNA clusters
Authors: Baumgartner Lisa , Handler Dominik , Platzer Sebastian , Duchek Peter , Brennecke Julius
Published: May 2022

RNA interference systems depend on the synthesis of small RNA precursors whose sequences define the target spectrum of these silencing pathways. The Drosophila Heterochromatin Protein 1 (HP1) variant Rhino permits transcription of PIWI-interacting RNA (piRNA) precursors within transposon-rich heterochromatic loci in germline cells. Current models propose that Rhino’s specific chromatin occupancy at piRNA source loci is determined by histone marks and maternally inherited piRNAs, but also imply the existence of other, undiscovered specificity cues. Here, we identify a member of the diverse family of zinc finger associated domain (ZAD)-C2H2 proteins, Kipferl, as critical Rhino cofactor in ovaries. By binding to guanosine-rich DNA motifs and interacting with the Rhino chromodomain, Kipferl recruits Rhino to specific loci and stabilizes it on chromatin. In kipferl mutant flies, Rhino is lost from most of its target chromatin loci and instead accumulates on pericentromeric satellite arrays, resulting in decreased levels of transposon targeting piRNAs and impaired fertility. Our findings reveal that DNA sequence, in addition to the H3K9me3 mark, determines the identity of piRNA source loci and provide insight into how Rhino might be caught in the crossfire of genetic conflicts.
Adenovirus-Vectored SARS-CoV-2 Vaccine Expressing S1-N Fusion Protein
Authors: Khan Muhammad S. , Kim Eun , McPherson Alex , Weisel Florian J. , Huang Shaohua , Kenniston Thomas W. , Percivalle Elena , Cassaniti Irene , Baldanti Fausto , Meisel Marlies , Gambotto Andrea
Published: May 2022

Additional COVID-19 vaccines that are safe, easy to manufacture, and immunogenic are needed for global vaccine equity. Here, we developed a recombinant type 5 adenovirus vector encoding for the SARS-CoV-2-S1 subunit antigen and nucleocapsid as a fusion protein (Ad5.SARS-CoV-2-S1N) delivered to BALB/c mice through multiple vaccine administration routes. A single subcutaneous (S.C.) immunization with Ad5.SARS-CoV-2-S1N induced a similar humoral response, along with a significantly higher S1-specific cellular response, as a recombinant type 5 adenovirus vector encoding for S1 alone (Ad5.SARS-CoV-2-S1). Immunogenicity was improved by homologous prime boost strategies, using either S.C. or intranasal (I.N.) delivery of Ad5.SARS-CoV-2-S1N, and further improved through heterologous prime boost, with traditional intramuscular (I.M.) injection, using subunit recombinant S1 protein. Priming with low dose (1×1010 v.p.) of Ad5.SARS-CoV-2-S1N and boosting with either wildtype recombinant rS1 or B.1.351 recombinant rS1 induced a robust neutralizing response, that was sustained against immune evasive Beta and Gamma SARS-CoV-2 variants, along with a long-lived plasma cell response in the bone marrow 29 weeks post vaccination. This novel Ad5-vectored SARS-CoV-2 vaccine candidate showed promising immunogenicity in mice and supports the further development of COVID-19 based vaccines incorporating the nucleoprotein as a target antigen.
Identification of Banana heat responsive long non-coding RNAs and their gene expression analysis
Authors: Murthy Vidya Srinivasa , Murthy Swarupa Venkatesa , Ramesh Pooja , Niranjan Vidya , Kumar Vasanth , Bharthi H Vidya , Bhatt Ravindra M. , Hunashikatti Laxman R. , Ravishankar Kundapura Venkataramana
Published: May 2022

Identification and characterization of long non-coding RNAs (lncRNAs) in the last decade has attained great attention because of their importance in gene regulatory functions in response to various plant stresses. Rising temperature is a potential threat to the agriculture world. Banana being an important economic crop, identification and characterization of genes and RNAs that regulate high temperature stress is imperative. As the prediction of lncRNAs in response to heat stress in banana is largely unknown, the present study was focused to identify the heat stress responsive lncRNA in banana (DH Pahang). Perl script was written to identify the novel transcripts, using the work flow. StringTie and CPC softwares were used and a total of 363 novel HS-lncRNA were identified in banana. Further, lncRNA were classified as 288 lincRNAs, 71 antisense LncRNA, 5 sense lncRNAs. The functional classification was done and transcripts were broadly classified into molecular function, cellular components and biological processes. Differential expression of lncRNA showed the varied patterns at different stages of heat stress. Finally, qPCR results confirmed DGE expression pattern of lncRNAs. Further, the Cytoscape analysis was performed which showed protein coding genes involved in membrane integrity and other signal transduction pathways. Taken together, these findings expand our understanding of lncRNAs as ubiquitous regulators under heat stress conditions in banana.
Structure of maize BZR1-type β-amylase BAM8 provides new insights into its noncatalytic adaptation
Authors: Sun Fuai , Palayam Malathy , Shabek Nitzan
Published: May 2022

Plant β-Amylase (BAM) proteins play an essential role in growth, development, stress response, and hormone regulation. Despite their typical (β/α)8 barrel structure as active catalysts in starch breakdown, catalytically inactive BAMs are implicated in diverse yet elusive functions in plants. The noncatalytic BAM7/8 contain N-terminal BZR1 domains and were shown to be involved in the regulation of brassinosteroid signaling and possibly serve as sensors of yet an uncharacterized metabolic signal. While the structures of several catalytically active BAMs have been reported, structural characterization of the catalytically inactive BZR1-type BAMs remain unknown. Here, we determine the crystal structure of Zea mays BZR1-type BAM8 and provide comprehensive insights into its noncatalytic adaptation. Using structural-guided comparison combined with biochemical analysis and molecular dynamics simulations, we revealed conformational changes in multiple distinct highly conserved regions resulting in rearrangement of the binding pocket. Altogether, this study adds a new layer of understanding to starch breakdown mechanism and elucidates the acquired adjustments of noncatalytic BZR1-type BAMs as putative regulatory domains and/or metabolic sensors in plants.
A histone deacetylase network regulates epigenetic reprogramming and viral silencing in HIV infected cells
Authors: Peterson Jackson J , Lewis Catherine A , Burgos Samuel D , Manickam Ashokkumar , Xu Yinyan , Rowley Allison A , Clutton Genevieve , Richardson Brian , Zou Fei , Simon Jeremy M , Margolis David M , Goonetilleke Nilu , Browne Edward P
Published: May 2022

Approximately 70% of the HIV-1 latent reservoir originates from infections of CD4 T cells that occur in the months near the time of ART initiation, raising the possibility that interventions during this period might prevent reservoir seeding and reduce reservoir size. We identify class 1 histone deacetylase inhibitors (HDACi) as potent agents of latency prevention. Inhibiting HDACs in productively infected cells caused extended maintenance of HIV expression and this activity was associated with persistently elevated H3K9 acetylation and reduced H3K9 methylation at the viral LTR promoter region. HDAC inhibition in HIV-infected CD4 T cells during effector-to-memory transition led to striking changes in the memory phenotype of infected cells. Proviral silencing is accomplished through distinct activities of HDAC1/2 and HDAC3. Thus HDACs regulate a critical gateway process for HIV latency establishment and are required for the development of CD4 T-cell memory subsets that preferentially harbor long-lived, latent provirus.
COVID-19 mRNA third dose induces a unique hybrid immunity-like antibody response
Authors: Andreano Emanuele , Paciello Ida , Pierleoni Giulio , Piccini Giulia , Abbiento Valentina , Antonelli Giada , Pileri Piero , Manganaro Noemi , Pantano Elisa , Maccari Giuseppe , Marchese Silvia , Donnici Lorena , Benincasa Linda , Giglioli Ginevra , Leonardi Margherita , De Santi Concetta , Fabbiani Massimiliano , Rancan Ilaria , Tumbarello Mario , Montagnani Francesca , Sala Claudia , Medini Duccio , De Francesco Raffaele , Montomoli Emanuele , Rappuoli Rino
Published: May 2022

The continuous evolution of SARS-CoV-2 generated highly mutated variants, like omicron BA.1 and BA.2, able to escape natural and vaccine-induced primary immunity1,2. The administration of a third dose of mRNA vaccines induces a secondary response with increased protection. We investigated, at single-cell level, the longitudinal evolution of the neutralizing antibody response in four donors after three mRNA doses3. A total of 4,100 spike protein specific memory B cells were single cell sorted and 350 neutralizing antibodies were identified. The third dose increased the antibody neutralization potency and breadth against all SARS-CoV-2 variants of concern as previously observed with hybrid immunity3. However, the B cell repertoire that stands behind the response is dramatically different. The increased neutralizing response was largely due to the expansion of B cell germlines poorly represented after two doses, and the reduction of germlines predominant after primary immunization such as IGHV3-53;IGHJ6-1 and IGHV3-66;IGHJ4-1. Divergently to hybrid immunity, cross-protection after a third dose was mainly guided by Class 1/2 antibodies encoded by IGHV1-58;IGHJ3-1 and IGHV1-69;IGHJ4-1 germlines. The IGHV2-5;IGHJ3-1 germline, which induced broadly cross-reactive Class 3 antibodies after infection or viral vector vaccination, was not induced by a third mRNA dose. Our data show that while neutralizing breadth and potency can be improved by different immunization regimens, each of them has a unique molecular signature which should be considered while designing novel vaccines and immunization strategies.
A novel ALDH1A1 inhibitor blocks platinum-induced senescence and stemness in ovarian cancer
Authors: Muralikrishnan Vaishnavi , Fang Fang , Given Tyler C. , Podicheti Ram , Chchterbinine Mikhail , Sriramkumar Shruthi , O’Hagan Heather M. , Hurley Thomas D. , Nephew Kenneth P.
Published: May 2022

Ovarian cancer is a deadly disease attributed to late-stage detection as well as recurrence and development of chemoresistance. Ovarian cancer stem cells (OCSCs) are hypothesized to be largely responsible for emergence of chemoresistant tumors. Although chemotherapy may initially succeed at decreasing the size and number of tumors, it leaves behind residual malignant OCSCs. In this study, we demonstrate that Aldehyde dehydrogenase 1A1 (ALDH1A1) is essential for the survival of OCSCs. We identified a first in class ALDH1A1 inhibitor, compound 974, and used 974 as a tool to decipher the mechanism of stemness regulation by ALDH1A1. Treatment of OCSCs with 974 significantly inhibited ALDH activity, expression of stemness genes, spheroid, and colony formation. In vivo limiting dilution assay demonstrated that 974 significantly inhibited CSC frequency. Transcriptomic sequencing of cells treated with 974 revealed significant downregulation of genes related to stemness and chemoresistance as well as senescence and senescence associated secretory phenotype (SASP). We confirmed that 974 inhibited senescence and stemness induced by platinum-based chemotherapy in functional assays. Overall, these data establish that ALDH1A1 is essential for OCSCs survival and ALDH1A1 inhibition suppresses chemotherapy induced senescence and stemness. Targeting ALDH1A1 using small molecule inhibitors in combination with chemotherapy therefore presents a promising strategy to prevent ovarian cancer recurrence and has potential for clinical translation.