bluuebunny/crossref_metadata_2025 huggingface dataset:
Somatosensory Stimulation Therapy in Patients with Somatosensory Tinnitus: A Pilot Study
Authors: Hong Guowei
Published: April 2023

Objective

To explore the efficacy and safety of EMS (Exercise to improve muscle strength, Motion of joints, and Stretch training) in somatosensory tinnitus symptoms.

Study Design

A randomized delayed-start controlled trial.

Setting

At the Department of Otorhinolaryngology, Eye and Ear, Nose, and Throat Hospital between February 2019 and May 2019.

Patients

Patients with somatosensory tinnitus.

Intervention(s)

In the immediate-start group, the participants received EMS somatosensory stimulation therapy for 3 weeks and were followed up for 3 weeks. In the delayed-start group, the participants first waited for 3 weeks and were treated with EMS somatosensory stimulation therapy for 3 weeks.

Main Outcome Measure(s)

The primary endpoint was the changes in Tinnitus Handicap Inventory (THI) and the visual analog scale (VAS) scores after 3 weeks of treatment. The secondary endpoint was the proportion of patients achieving improvements in VAS and THI scores. THI and VAS were collected at baseline and at 3, 6, 9, and 12 weeks.

Results

Sixty-four patients were randomized to the immediate-start group and delayed-start treatment with each 32. After the 3-week treatment, the immediate-start group showed significant lower in VAS (25.7 ± 3.3 versus 38.9 ± 5.8, p < 0.001) and THI (29.1 ± 5.1 versus 42.8 ± 6.6, p < 0.001). There were no differences in VAS and THI between the two groups after treatment (i.e., at weeks 6, 9, and 12). All patients were followed up for 6, 9, and 12 weeks, and the therapeutic effect was stable.

Conclusion

The EMS somatosensory stimulation therapy might be an effective and safe treatment for improving symptoms, and the therapeutic effect was still stable in 3, 6, 9, and 12 weeks.

Clinical trial registration number

ChiCTR1900020746.
Craniomaxillofacial Trauma: The Past, Present and the Future
Authors: Salinas Cristina A. , Morris Jonathan M. , Sharaf Basel A.
Published: April 2023

Reconstruction of facial trauma has seen a significant evolutionary leap in the last 100 years. The current surgical management of facial fractures was made possible by the efforts and creativity of pioneer surgeons, advances in anatomic understanding, and the continued development of biomaterials and imaging technologies. Virtual surgical planning (VSP) and 3-dimensional printing (3DP) are being incorporated into the management of acute facial trauma. The integration of this technology at the point of care is rapidly expanding globally. This article reviews the history of the management of craniomaxillofacial trauma, current practices, and future directions. The use of VSP and 3DP in facial trauma care is highlighted with a description of EPPOCRATIS, a rapid point-of-care process incorporating VSP and 3DP at the trauma center.
Genetic correlation between aggressive signals and fighting
Authors: Baxter Carling M. , Shams Ieta , Dworkin Ian , Dukas Reuven
Published: April 2023

Theoretical analyses indicate that aggressive signals should positively correlate with the signallers' willingness and abilities to fight. Few experimental studies, however, have tested this prediction. In two experiments employing distinct, ecologically realistic protocols, we quantified the association between aggressive signals and fighting in fruit fly genotypes and found high positive genetic correlations between threat and fighting (
r
G
= 0.80 and 0.74). Our results add to the growing body of experimental work indicating that aggressive signals have relatively high informational value.
Modelling effects of inter-group contact on links between population size and cultural complexity
Authors: Ben-Oren Yotam , Strassberg Sarah Saxton , Hovers Erella , Kolodny Oren , Creanza Nicole
Published: April 2023

Human populations rely on cultural artefacts for their survival. Populations vary dramatically in the size of their tool repertoires, and the determinants of these cultural repertoire sizes have been the focus of extensive study. A prominent hypothesis, supported by computational models of cultural evolution, asserts that tool repertoire size increases with population size. However, not all empirical studies have found such a correlation, leading to a contentious and ongoing debate. As a possible resolution to this longstanding controversy, we suggest that accounting for even rare cultural migration events that allow sharing of knowledge between different-sized populations may help explain why a population’s size might not always predict its cultural repertoire size. Using an agent-based model to test assumptions about the effects of population size and connectivity on tool repertoires, we find that cultural exchange between a focal population and others, particularly with large populations, may significantly boost its tool repertoire size. Thus, two populations of identical size may have drastically different tool repertoire sizes, hinging upon their access to other groups’ knowledge. Intermittent contact between populations boosts cultural repertoire size and still allows for the development of unique tool repertoires that have limited overlap between populations.
Deployment of biologging tags on free swimming large whales using uncrewed aerial systems
Authors: Wiley David N. , Zadra Christopher J. , Friedlaender Ari S. , Parks Susan E. , Pensarosa Alicia , Rogan Andy , Alex Shorter K. , Urbán Jorge , Kerr Iain
Published: April 2023

Suction-cup-attached biologging tags have led to major advances in our understanding of large whale behaviour. Getting close enough to a whale at sea to safely attach a tag is a major limiting factor when deploying these systems. Here we present an uncrewed aerial system (UAS)-based tagging technique for free-swimming large whales and provide data on efficacy from field testing on blue (
Balaenoptera musculus
) and fin (
B. physalus
) whales. Rapid transit speed and the bird's-eye view of the animal during UAS tagging contributed to the technique's success. During 8 days of field testing, we had 29 occasions when a focal animal was identified for attempted tagging and tags were successfully attached 21 times. The technique was efficient, with mean flight time of 2 min 45 s from launch to deployment and a mean distance of 490 m from the launch vessel to tagged animal, reducing potential adverse effects resulting from close approaches for tagging. These data indicate that UAS are capable of attaching biologging tags to free-swimming large whales quickly and from large distances, potentially increasing success rates, decreasing attempt times, and reducing animal disruption during tagging.
Causal evidence for the role of the sensory visual cortex in visual short-term memory maintenance
Authors: Phylactou Phivos , Shimi Andria , Konstantinou Nikos
Published: April 2023

The role of the sensory visual cortex during visual short-term memory (VSTM) remains controversial. This controversy is possibly due to methodological issues in previous attempts to investigate the effects of transcranial magnetic stimulation (TMS) on VSTM. The aim of this study was to use TMS, while covering previous methodological deficits. Sixty-four young adults were recruited to participate in two experiments (Experiment 1:n= 36; Experiment 2:n= 28) using a VSTM orientation change-detection task under TMS. Monocular vision was ensured using red-blue goggles combined with red-blue stimuli. Double-pulse TMS was delivered at different times (Experiment 1: 0, 200 or 1000 ms; Experiment 2: 200, 1000 ms) during a 2 s maintenance phase, on one side of the occipital hemisphere. In Experiment 2, a sham TMS condition was introduced. Decreased detection sensitivity (d′) in the ipsilateral occipital hemisphere to visual hemifield, and in the real TMS (compared with sham TMS) condition indicated inhibitory TMS effects, and thus, a causal involvement of the sensory visual cortex during early (200 ms) and late (1000 ms) maintenance in VSTM. These findings are aligned with sensory recruitment, which proposes that both perceptual and memory processes rely upon the same neural substrates in the sensory visual cortex. The methods used in this study were preregistered and had received in-principle acceptance on 6 June 2022 (Stage 1 protocol can be found in:https://doi.org/10.17605/OSF.IO/EMPDT).
A thermodynamic framework for non-isothermal phenomenological models of isotropic Mullins effect
Authors: Cichra David , Alexei Gazca-Orozco Pablo , Průša Vít , Tůma Karel
Published: April 2023

The Mullins effect is a common name for a family of intriguing inelastic responses of various solid materials, in particular filled rubbers. Given the importance of the Mullins effect, there have been many attempts to develop mathematical models describing the effect. However, most of the available models focus exclusively on the mechanical response and are restricted to the idealized isothermal setting. We lift the restriction to isothermal processes, and we propose a full thermodynamic framework for a class of phenomenological models of the Mullins effect. In particular, we identify energy storage mechanisms (Helmholtz free energy) and entropy production mechanisms that on the level of stress–strain relation lead to the idealized Mullins effect or to the Mullins effect with permanent strain. The models constructed within the proposed framework can be used in the modelling of fully coupled thermo-mechanical processes, and the models are guaranteed to be consistent with the laws of thermodynamics.
Structural function from sequential, interacting elastic instabilities
Authors: Wheatcroft E. D. , Shen J. , Groh R. M. J. , Pirrera A. , Schenk M.
Published: April 2023

Elastic instabilities have traditionally been considered a failure mechanism; however, recent years have seen numerous studies exploiting instabilities as a means to achieve structural functionality. By contrast, interacting instabilities and compound buckling are still largely viewed as a failure mechanism. In this paper, we show that interacting instabilities can also be exploited to achieve bespoke functionality. We focus on ‘sequential instabilities’, whose associated critical points cannot both lie on a fundamental equilibrium path. We obtain sequential instabilities by combining canonical bifurcations, (e.g. limit point, pitchfork) as building-blocks. Initially, this concept is explored through simple bar-and-spring models that are found to have several properties not exhibited by the building blocks from which they are constructed. Further, the utility of the building block approach, and that of sequential, interacting instabilities, is demonstrated through the development of a morphing structure which must rapidly deploy after a critical input displacement is attained, and meet specific post-deployment stiffness requirements. Two design concepts are proposed, each comprising building blocks to mirror the fundamental working principles identified through the bar-and-spring models. Finite-element models of the design solutions are presented, demonstrating how the designs positively use sequential, interacting instabilities in order to meet the challenging requirements of the application. This work extends the contextual framework of instabilities that can be used to create structures with novel functionality.
Aridibaculum aurantiacum gen. nov., sp. nov., isolated from the Kumtag Desert soil
Authors: Dong Lei , Li Shuai , Shi Guo-Yuan , Han Jia-Rui , Lu Chun-Yan , Lian Wen-Hui , Yue Ling-Xiang , Alkhalifah Dalal Hussien M. , Hozzein Wael N. , Li Wen-Jun
Published: April 2023

A novel orange-coloured bacterium, designated strain SYSU D00508T, was isolated from a sandy soil sampled from the Kumtag Desert in China. Strain SYSU D00508T was aerobic, Gram-stain-negative, oxidase-positive, catalase-positive and non-motile. Growth occurred at 4–45°C (optimum 28–30°C), pH 6.0–9.0 (optimum pH 7.0–8.0) and with 0–2.5 % NaCl (w/v, optimum 0–1.0 %). The major polar lipids consisted of phosphatidylethanolamine (PE), unidentified aminolipids (AL1-3) and unidentified polar lipids (L1-5) were also detected. The major respiratory quinone was MK-7 and the major fatty acids (>10 %) were iso-C17 : 0 3-OH, iso-C15 : 0 and iso-C15 : 1 G. The genomic DNA G+C content was 42.6 %. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain SYSU D00508T belonged to the family

Chitinophagaceae

and showed 93.9 % (

Segetibacter koreensis

DSM18137T), 92.9 % (

Segetibacter aerophilus

NBRC 106135T), 93.0 % (

Terrimonas soli

JCM 32095T) and 92.8 % (

Parasegetibacter terrae

JCM 19942T) similarities. Based on the phylogenetic, phenotypic and chemotaxonomic data, strain SYSU D00508T is proposed to represent a novel species of a new genus, named Aridibaculum aurantiacum gen. nov., sp. nov., within the family

Chitinophagaceae

. The type strain is SYSU D00508T (=KCTC 82286T=CGMCC 1.18648T=MCCC 1K05005T).
Microbulbifer zhoushanensis sp. nov., Microbulbifer sediminum sp. nov. and Microbulbifer guangxiensis sp. nov., three marine bacteria isolated from a tidal flat
Authors: Fu Yun-Han , Wu Zhi-Cheng , Kong Yan-Hui , Xu Xue-Wei , Sun Cong , Wu Yue-Hong
Published: April 2023

Three strains, TT30T, TT37T and L3T, were isolated from tidal flat samples. Cells were Gram-stain-negative, non-motile and rod shaped. Cells of strains TT30T and TT37T were able to grow in a medium containing 1.0–15.0 % (w/v) NaCl (optimum, 3.0 and 4.0 %, respectively), and cells of strain L3T was able to grow in a medium containing 1.0–10.0 % (w/v) NaCl (optimum, 1.0 %). Growth of the three strains was observed at pH 6.0–10.0 and at 10–40 °C. Strains TT30T, TT37T and L3T showed the highest similarity to

Microbulbifer hydrolyticus

DSM 11525T (97.7 %),

M

.

yueqingensis

CGMCC 1.10658T (98.0 %) and

M. elongatus

DSM 6810T (97.9 %), respectively. Results of phylogenetic analyses indicated that the three isolates represented two distinct lineages within the genus

Microbulbifer

. The DNA G+C contents of strains TT30T, TT37T and L3T were 61.3, 60.9 and 60.2%, respectively. The average nucleotide identity and in silico DNA–DNA hybridization values among strains TT30T, TT37T and L3T and the reference strains were 84.4–87.4 and 19.6–28.9 %, respectively. Differential phenotypic properties, chemotaxonomic differences, phylogenetic distinctiveness, together with the genomic data, demonstrated that strains TT30T, TT37 T and L3T represent novel species of the genus

Microbulbifer

, which are named Microbulbifer zhoushanensis sp. nov. (TT30T=KCTC 92167T=MCCC 1K07276T), Microbulbifer sediminum sp. nov. (TT37T=KCTC 92168T=MCCC 1K07277T) and Microbulbifer guangxiensis sp. nov. (L3T=KCTC 92165T=MCCC 1K07278T).
An HMM approach expands the landscape of sesquiterpene cyclases across the kingdom Fungi
Authors: Hage Hayat , Couillaud Julie , Salamov Asaf , Loussouarn-Yvon Margot , Durbesson Fabien , Ormeño Elena , Grisel Sacha , Duquesne Katia , Vincentelli Renaud , Grigoriev Igor , Iacazio Gilles , Rosso Marie-Noëlle
Published: April 2023

Sesquiterpene cyclases (STC) catalyse the cyclization of the C15 molecule farnesyl diphosphate into a vast variety of mono- or polycyclic hydrocarbons and, for a few enzymes, oxygenated structures, with diverse stereogenic centres. The huge diversity in sesquiterpene skeleton structures in nature is primarily the result of the type of cyclization driven by the STC. Despite the phenomenal impact of fungal sesquiterpenes on the ecology of fungi and their potentials for applications, the fungal sesquiterpenome is largely untapped. The identification of fungal STC is generally based on protein sequence similarity with characterized enzymes. This approach has improved our knowledge on STC in a few fungal species, but it has limited success for the discovery of distant sequences. Besides, the tools based on secondary metabolite biosynthesis gene clusters have shown poor performance for terpene cyclases. Here, we used four sets of sequences of fungal STC that catalyse four types of cyclization, and specific amino acid motives to identify phylogenetically related sequences in the genomes of basidiomycetes fungi from the order Polyporales. We validated that four STC genes newly identified from the genome sequence of Leiotrametes menziesii, each classified in a different phylogenetic clade, catalysed a predicted cyclization of farnesyl diphosphate. We built HMM models and searched STC genes in 656 fungal genomes genomes. We identified 5605 STC genes, which were classified in one of the four clades and had a predicted cyclization mechanism. We noticed that the HMM models were more accurate for the prediction of the type of cyclization catalysed by basidiomycete STC than for ascomycete STC.
Ultrastructure of the nebenkern during spermatogenesis in the praying mantidHierodula membranacea
Authors: Köckert Maria , Okafornta Chukwuebuka William , Hill Charlice , Ryndyk Anne , Striese Cynthia , Müller-Reichert Thomas , Paliulis Leocadia , Fabig Gunar
Published: April 2023

Spermatogenesis leads to the formation of functional sperm cells. Here we have applied high-pressure freezing in combination with transmission electron microscopy (TEM) to study the ultrastructure of sperm development in subadult males of the praying mantidHierodula membranacea. We show the ultrastructure of different stages of sperm development in this species. In addition, we have applied serial-section electron tomography of the nebenkern to demonstrate in three dimensions (3D) that this organelle is composed of two interwoven segments that are connected by a zipper-like structure at opposing positions. Our approach will enable further ultrastructural analyses of the nebenkern also in other organisms.
Genetic Mapping of SNP Markers and Candidate Genes Associated with Day-Neutral Flowering inCannabis sativaL.
Authors: Garfinkel Andrea R , Wilkerson Dustin G , Chen Hsuan , Smart Lawrence B , Rojas Brendan M , Getty Brooke A , Michael Todd P , Crawford Seth
Published: April 2023

Hemp (Cannabis sativaL.) is a primarily short-day crop grown for grain, fiber, and secondary metabolites. Although terminal flowering of most non-domesticated hemp is regarded as photoperiod sensitive, limited germplasm is available for the development of day-neutral hemp. Day-neutral plants experience flower maturation independently of the short-day photoperiod cue which is typically triggered by photoperiods of less than 14 hours. The day-neutral trait is the subject of increased commercial interest for the purpose of breeding varieties with accelerated flowering time or cultivars that do not require labor- and cost-intensive light deprivation production systems. Genetic markers for the photoperiodic response would help breeders make early selection in the design of suitable cultivars for specific environments and cultivation calendars. Limited refereed information has been produced regarding the genetic regulation of photoperiodism inC. sativa. A population of 318 F2 individuals segregating for day-neutral flowering was developed, phenotyped, and genotyped. Genome-wide association analysis identified markers associated with the day-neutral trait indicating that a single recessive gene controlling photoperiod sensitivity is located within a large region of Chromosome 1. Flanking region sequence data of linked SNP markers was used in the development and validation of a TaqMan-based qPCR assay for the day-neutral trait. A genetic linkage map was produced, and QTL mapping identified two additional markers on Chromosome 1. Candidate genes,TARGET OF EARLY ACTIVATION TAGGED (TOE)/APETALA2 (AP2), andPSEUDO-RESPONSE REGULATOR 3 (PRR3), may work together to impact phase transition and photoperiodic flowering respectively and have key domains that are disrupted in day-neutral plants.
Informing Extinction Risk: Summarizing Population Viability through a Meta-analysis of Multiple Long-term Monitoring Programs for a Declining Estuarine Fish Species
Authors: Tobias Vanessa D. , Chen Ernest , Hobbs James , Eakin Michael , Detwiler Steven
Published: April 2023

Decisions about whether to designate a species for conservation and protection depend on the ability to summarize their population trajectories and their risk of extinction. Such decisions may rely on quantitative population viability analyses based on a time series of abundance index values that are derived from a monitoring program. In the case of the Longfin Smelt (Spirinchus thaleichthys), a decision to protect a distinct population segment of the species under the U.S. Endangered Species Act was informed by several indices of population abundance. In this paper, we combined individual population viability analyses into a single metric for extinction risk using a meta-analysis framework. Individual monitoring surveys for this species generally agreed that the trajectory of abundance was downward and combining data from all of the surveys produced a better summary of the population growth rate. We also used the population growth rates in a simulation to estimate the probability that the abundance of Longfin Smelt dropped too low to recover. We found that this probability of quasi-extinction was substantial, exceeding 20% over two decades. This study demonstrates a practical way that having multiple sources of information creates better information about the trajectory of a population. Individually, the surveys contribute information about specific life stages or ages to our understanding of the population. Combined into one metric and an associated graphical summary, this analysis succinctly communicates risk and creates a benchmark for evaluating future management decisions.
Anticipatory Biogenesis of Hepatic Fed MicroRNAs is Regulated by Metabolic and Circadian Inputs
Authors: Sandra U.S. , Chowdhury Shreyam , Kolthur-Seetharam Ullas
Published: April 2023

Starvation and refeeding are mostly unanticipated in the wild in terms of duration, frequency, and nutritional value of the refed state. Notwithstanding this, organisms mount efficient and reproducible responses to restore metabolic homeostasis. Hence, it is intuitive to invoke expectant molecular mechanisms that build anticipatory responses to enable physiological toggling during fed-fast cycles. In this regard, we report anticipatory biogenesis of oscillatory hepatic microRNAs, which were earlier shown to peak during a fed state to inhibit starvation-responsive genes. Results presented in this study clearly demonstrate that the levels of primary and precursor microRNA transcripts increase during a fasting state, in anticipation of a fed response. We delineate the importance of both metabolic inputs and circadian cues in orchestrating microRNA homeostasis in a physiological setting, using the most prominent hepatic fed-miRNAs as candidates. Besides illustrating the metabo-endocrine control, our findings provide a mechanistic basis for the overarching influence of starvation on anticipatory biogenesis. Importantly, by employing pharmacological agents that are widely used in the clinics, we point out the high potential of interventions to restore homeostasis of hepatic microRNAs, whose deregulated expression is otherwise well established to cause metabolic diseases.
A novel simian adenovirus vectored COVID-19 vaccine elicits effective mucosal and systemic immunity in mice by intranasal and intramuscular vaccination regimens
Authors: Zhang Panli , Luo Shengxue , Zou Peng , Deng Qitao , Wang Cong , Li Jinfeng , Cai Peiqiao , Zhang Ling , Li Chengyao , Li Tingting
Published: April 2023

The failure of COVID-19 vaccines to prevent SARS-CoV-2 infection and transmission, a possibly critical reason was the lack of protective mucosal immunity in respiratory tract. Here, we evaluated the effects of mucosal and systemic immunity from a novel simian adenovirus vectored COVID-19 vaccine (Sad23L- nCoV-S) in mice in comparison with Ad5-nCoV-S by intranasal (IN) drip and intramuscular (IM) injection vaccinations. As good as the well-known Ad5-nCoV-S vaccine, a single-dose IN inoculation of 1×109PFU Sad23L-nCoV-S vaccine induced a similar level of IgG S-binding antibody (S-BAb) and neutralizing antibody (NAb) and higher IgA in serum, while IN route raised significantly higher IgG and IgA S- BAb and NAb in bronchoalveolar lavage (BAL), and specific IFN-γ secreting T cell response in lung compared with IM route, but lower T cell response in spleen. By prime-boost vaccination regimens with different combination of IN and IM inoculations of Sad23L-nCoV-S vaccine, the IN involved vaccinations stimulated higher protective mucosal or local immunity in BAL and lung, while the IM involved immunizations induced higher systemic immunity in serum and spleen. A long-term sustained systemic and mucosal NAb and T cell immunity to SARS-CoV-2 was maintained at high levels over 32 weeks by prime-boost vaccination regimens with IN and IM routes. In conclusion, priming or boosting immunization with IN inoculation of Sad23L-nCoV-S vaccine could induced effective mucosal immunity and in combination of IM route could additionally achieve systemic immunity, which provided an important reference for vaccination regimens against respiratory virus infection.

IMPORTANCE

The essential goal of vaccination is to generate potent and long-term protection against diseases. Several factors including type of vector, delivery route, boosting regimen influence the outcome of prime-boost immunization approaches. The immunization regimen by constructing a novel simian adenovirus vectored COVID-19 vaccine and employing combination of intranasal and intramuscular inoculations, could elicit mucosal neutralizing antibodies against five mutant strains in the respiratory tract, and strong systemic immunity. Immune protection could last for more than 32 weeks. Vectored vaccine construction and immunization regimens have positively impacted respiratory disease prevention.
Do glucocorticoids indicate stress? Meta-analysis reveals a tight association between glucocorticoids and metabolic rate
Authors: Jimeno Blanca , Verhulst Simon
Published: April 2023

Glucocorticoid (GC) variation has long been thought to reflect variation in organismal ‘stress’, but associations between GCs and Darwinian fitness components are diverse in magnitude, direction, and highly context-dependent. This paradox reveals our poor understanding of the causes of GC variation, contrasting with the detailed knowledge of the functional consequences of GC variation. Amongst an array of effects in many physiological systems, GCs orchestrate energy availability to anticipate and recover from predictable and unpredictable environmental fluctuations and challenges. Although this is mechanistically well-known, the extent to which GC levels are quantitatively explained by energy metabolism is unresolved. We investigated this association through meta-analysis, selecting studies of endotherms in which (1) an experiment was performed that affected metabolic rate and (2) metabolic rate and GC-levels were measured simultaneously. We found that an increase in metabolic rate was associated with an increase in GC levels in 20 out of 21 studies (32 out of 35 effect sizes). More importantly, there was a strong positive correlation between the increases in metabolic rate and GCs (p=0.003). This pattern was similar in birds and mammals, and independent of the nature of the experimental treatment. We conclude that metabolic rate is a major driver of GC variation within individuals. Stressors often affect metabolic rate, leading us to question whether GC levels provide information on ‘stress’ beyond the stressor’s effect on metabolic rate.
Spatial phylogenetics of Fagales: Investigating the history of temperate forests
Authors: Folk R.A. , Siniscalchi C.M. , Doby J. , Kates H.R. , Manchester S.R. , Soltis P.S. , Soltis D.E. , Guralnick R.P. , Belitz M.
Published: April 2023

Aim

Quantifying the phylogenetic diversity of temperate trees is essential for understanding what processes are implicated in shaping the modern distribution of temperate broadleaf forest and other major forest biomes. Here we focus on Fagales, an iconic member of forests worldwide, to uncover global diversity and endemism patterns and investigate potential drivers responsible for the spatial distribution of fagalean forest communities.

Location

Global.

Taxon

Fagales.

Methods

We combined phylogenetic data covering 60.2% of living species, fine-scale distribution models covering 90% of species, and nodulation data covering all species to investigate the distribution of species richness at fine spatial scales and compare this to relative phylogenetic diversity (RPD) and phylogenetic endemism. Further, we quantify phylogenetic betadiversity and bioregionalization of Fagales and determine hotspots of Fagales species engaging in root nodule symbiosis (RNS) with nitrogen-fixing actinomycetes.

Results

We find the highest richness in temperate east Asia, eastern North America, and equatorial montane regions of Asia and Central America. By contrast, RPD is highest at higher latitudes, where RNS also predominates. We found a strong spatial structuring of regionalizations of Fagales floras as defined by phylogeny and traits related to RNS, reflecting distinct Northern and Southern Hemisphere floras (with the exception of a unique Afro-Boreal region) and highly distinct tropical montane communities.

Main conclusions

Species richness and phylogenetic regionalization accord well with traditional biogeographic concepts for temperate forests, but RPD does not. This may reflect ecological filtering specific to Fagales, as RNS strategies are almost universal in the highest RPD regions. Our results highlight the importance of global-scale, clade-specific spatial phylogenetics and its utility for understanding the history behind temperate forest diversity.
PTPN1/2 inhibition induces highly functional terminal effector CD8 T cells through autocrine IL-10
Authors: Perez-Quintero Luis-Alberto , Poirier Alexandre , Martinez-Cordoba Zuzet , Feng Chu-Han , Aubry Isabelle , Carli Cedric , Kamyabiazar Samaneh , Pacis Alain , Zolotarov Yevgen , Pike Kelly-Anne , Delisle Jean-Sebastien , Tremblay Michel L.
Published: April 2023

Increased understanding of the modulatory pathways controlling CD8 T cell responses has led to the formulation of successful checkpoint inhibitor-based immunotherapies against cancer. However, their effectiveness is limited to a few tumor types, motivating the search for novel combinatorial strategies. PTPN1 and PTPN2 are two homologous protein tyrosine phosphatases recently proposed as potent intracellular checkpoints. Furthermore, their catalytic domain is a propitious target for small-molecule pharmacological intervention. Herein we investigated the potential effects of conditional genetic deletion of either or both phosphatases in mouse CD8 T cells, one of the main effectors in cancer immunotherapy. Our results demonstrated that hemizygous deletion of PTPN1 in a PTPN2 deficient background heightens the enhanced effector phenotype already observed in PTPN2 defective CD8 T cells. This functional gain is mediated by an autocrine IL-10 positive feedback loop. Pharmacological inhibition with a PTPN1/2 small-molecule inhibitor yielded similar results, highlighting the importance of simultaneously inhibiting both phosphatases. Our study uncovers a novel mechanism by which the downregulation of PTPN1 and PTPN2 act as a powerful tool for potentiating CD8 cytotoxic responses.
RGS6 mediates exercise-induced recovery of hippocampal neurogenesis, learning, and memory in an Alzheimer’s mouse model
Authors: Spicer Mackenzie M. , Yang Jianqi , Fu Daniel , DeVore Alison N. , Lauffer Marisol , Atasoy Nilufer S. , Atasoy Deniz , Fisher Rory A.
Published: April 2023

Hippocampal neuronal loss causes cognitive dysfunction in Alzheimer’s disease (AD). Adult hippocampal neurogenesis (AHN) is reduced in AD patients. Exercise stimulates AHN in rodents and improves memory and slows cognitive decline in AD patients. However, the molecular pathways for exercise-induced AHN and improved cognition in AD are poorly understood. Here, we show that voluntary running in APPSWEmice restores their hippocampal cognitive impairments to that of control mice. This cognitive rescue was abolished by RGS6 deletion in dentate gyrus (DG) neuronal progenitors (NPs), which also abolished running-mediated increases in AHN. AHN was reduced in sedentary APPSWEmice versus control mice, with basal AHN reduced by RGS6 deletion in DG NPs. RGS6 expression is significantly lower in the DG of AD patients. Thus, RGS6 mediates exercise-induced rescue of impaired cognition and AHN in AD mice, identifying RGS6 in DG NPs as a potential target to combat hippocampal neuron loss in AD.

Teaser

RGS6 expression in hippocampal NPCs promotes voluntary running-induced neurogenesis and restored cognition in APPSWEmice.

Field Codes

RGS6, Alzheimer’s disease, adult hippocampal neurogenesis, neural precursor cells, dentate gyrus, exercise, learning/memory
ER-dependent membrane repair of mycobacteria-induced vacuole damage
Authors: Anand Aby , Mazur Anna-Carina , Rosell-Arevalo Patricia , Franzkoch Rico , Breitsprecher Leonhard , Listian Stevanus A. , Hüttel Sylvana V. , Müller Danica , Schäfer Deise G. , Vormittag Simone , Hilbi Hubert , Maniak Markus , G. Gutierrez Maximiliano , Barisch Caroline
Published: April 2023

Several intracellular pathogens, such asMycobacterium tuberculosis,damage endomembranes to access the cytosol and subvert innate immune responses. The host counteracts endomembrane damage by recruiting repair machineries that retain the pathogen inside the vacuole.

Here, we show that the endoplasmic reticulum (ER)-Golgi protein oxysterol binding protein (OSBP) and itsDictyostelium discoideumhomologue OSBP8 are recruited to theMycobacterium-containing vacuole (MCV) after ESX-1-dependent membrane damage. Lack of OSBP8 causes a hyperaccumulation of phosphatidylinositol-4-phosphate (PI4P) on the MCV and decreased cell viability. OSBP8-depleted cells had reduced lysosomal and degradative capabilities of their vacuoles that favoured mycobacterial growth. In agreement with a function of OSBP8 in membrane repair, human macrophages infected withM. tuberculosisrecruited OSBP in an ESX-1 dependent manner. These findings identified an ER-dependent repair mechanism for restoring MCVs in which OSBP8 functions to equilibrate PI4P levels on damaged membranes.

Importance

Tuberculosis still remains a global burden and is one of the top infectious diseases from a single pathogen.Mycobacterium tuberculosis, the causative agent, has perfected many ways to replicate and persist within its host. While mycobacteria induce vacuole damage to evade the toxic environment and eventually escape into the cytosol, the host recruits repair machineries to restore the MCV membrane. However, how lipids are delivered for membrane repair is poorly understood. Using advanced fluorescence imaging and volumetric correlative approaches, we demonstrate that this involves the recruitment of the ER-Golgi lipid transfer protein OSBP8 in theD. discoideum/M. marinumsystem. Strikingly, depletion of OSBP8 affects lysosomal function accelerating mycobacterial growth. This indicates that an ER-dependent repair pathway constitutes a host defence mechanism against intracellular pathogens such asM. tuberculosis.
Barley HvNIP2;1 aquaporin permeates water, metalloids, saccharides, and ion pairs due to structural plasticity and diversification
Authors: Venkataraghavan Akshayaa , Kim Hoshin , Schwerdt Julian G. , Gulyuk Alexey V. , Singh Abhishek , Yingling Yaroslava G. , Tyerman Stephen D. , Hrmova Maria
Published: April 2023

Aquaporins can facilitate the passive movement of water and small polar molecules and some ions. The barley Nodulin 26-like Intrinsic Protein (HvNIP2;1) embedded in liposomes and examined through stopped-flow light scattering spectrophotometry andXenopusoocyte swelling assays was found to permeate water, boric and germanic acids, sucrose and L-arabinose but not D-glucose or D-fructose. Other saccharides, such as neutral (D-mannose, D-galactose, D-xylose, D-mannoheptaose) and charged (N-acetyl D-glucosamine, D-glucosamine, D-glucuronic acid) aldoses, disaccharides (lactose, cellobiose, gentiobiose, trehalose), trisaccharide raffinose, and urea, glycerol, and acyclic polyols were permeated to a much lower extent. Apparent permeation of hydrated KCl and MgSO4ion pairs was observed, while CH3COONa and NaNO3permeated at significantly lower rates. Experiments with boric acid and sucrose revealed no apparent interaction between solutes when permeated together, and AgNO3blocked the permeation of all solutes. Full-scale steered molecular dynamics simulations of HvNIP2;1 and spinach SoPIP2;1 revealed possible rectification for water, boric acid, and sucrose transport, and defined key residues interacting with permeants. In a biological context, the simulated sucrose rectification could mediate its apoplastic-to-intracellular transport but not the reverse, thus, constituting a novel element of plant saccharide-transporting machinery. Phylogenomic analyses of 164 Viridiplantae and 2,993 Archaean, bacterial, fungal, and Metazoan aquaporins rationalised solute poly-selectivity in NIP3 sub-clade entries and suggested that they diversified from other sub-clades to acquire a unique specificity of saccharide transporters. Solute specificity definition in NIP aquaporins could inspire developing plants for sustained food production.

Significance Statement

Aquaporins are fundamental to water and solute movements in nearly all living organisms. Solute selectivity inspections of the HvNIP2;1 aquaporin revealed that it transported water, hydroxylated metalloids boric and germanic acids, sucrose, L-arabinose, KCl, and MgSO4ion pairs, but not D-glucose or D-fructose and to lesser extent urea, and acyclic polyols. This poly-selective transport by HvNIP2;1 classified in the NIP3 sub-clade aquaporins may afford nutritional and protective roles during plant development and in response to abiotic stresses. It is anticipated that the solute specificity definition of HvNIP2;1 inspires protein engineering and in silico mining to develop plants, which when exposed to suboptimal soil conditions of high soil metalloids, would overcome toxicity for sustained food production.
Cell Type-Specific Regulation by a Heptad of Transcription Factors in Human Hematopoietic Stem and Progenitor Cells
Authors: Subramanian Shruthi , Thoms Julie A.I. , Huang Yizhou , Cornejo Paola , Koch Forrest C. , Jacquelin Sebastien , Shen Sylvie , Song Emma , Joshi Swapna , Brownlee Chris , Woll Petter S. , Fajardo Diego Chacon , Beck Dominik , Curtis David J. , Yehson Kenneth , Antonenas Vicki , Brien Tracey O’ , Trickett Annette , Powell Jason A. , Lewis Ian D. , Pitson Stuart M. , Gandhi Maher K. , Lane Steven W. , Vafaee Fatemeh , Wong Emily S. , Göttgens Berthold , Rokny Hamid Alinejad , Wong Jason W.H , Pimanda John E.
Published: April 2023

Hematopoietic stem and progenitor cells (HSPCs) rely on a complex interplay of transcription factors (TFs) to regulate differentiation into mature blood cells. A heptad of TFs - FLI1, ERG, GATA2, RUNX1, TAL1, LYL1, LMO2 - bind regulatory elements in bulk CD34+ HSPCs. However, whether specific heptad-TF combinations have distinct roles in regulating hematopoietic differentiation remained unknown. We mapped genome-wide chromatin contacts and TF binding profiles in HSPC subsets (HSC, CMP, GMP, MEP) and found that heptad occupancy and enhancer-promoter interactions varied significantly across cell types and were associated with cell-type-specific gene expression. Distinct regulatory elements were enriched with specific heptad-TF combinations, including stem-cell-specific elements with ERG, and myeloid- and erythroid-specific elements with combinations of FLI1, RUNX1, GATA2, TAL1, LYL1, and LMO2. These findings suggest that specific heptad-TF combinations play critical roles in regulating hematopoietic differentiation and provide a valuable resource for development of targeted therapies to manipulate specific HSPC subsets.
Plasma endocannabinoids in cocaine dependence and their interaction with cocaine craving and metabotropic glutamate receptor 5 density in the human brain
Authors: Kroll Sara L. , Hulka Lea M. , Kexel Ann-Kathrin , Vonmoos Matthias , Preller Katrin H. , Treyer Valerie , Ametamey Simon M. , Baumgartner Markus R. , Boost Carola , Pahlisch Franziska , Rohleder Cathrin , Leweke F. Markus , Quednow Boris B.
Published: April 2023

Animal models indicate that the endocannabinoid system (ECS) plays a modulatory role in stress and reward processing, both crucially impaired in addictive disorders. Preclinical findings showed endocannabinoid-modulated synaptic plasticity in reward brain networks linked to the metabotropic-glutamate-5 receptor (mGluR5), contributing to drug-reinforcing effects and drug-seeking behavior. Although animal models postulate a link between ECS and cocaine addiction, human translational studies are lacking. Here, we tested previous preclinical findings by investigating plasma endocannabinoids (eCBs) anandamide (AEA), 2-arachidonoylglycerol (2-AG), and the related N-acylethanolamines (NAEs) palmitoylethanolamide (PEA) and oleoylethanolamide (OEA), including their interaction with cerebral mGluR5, in chronic cocaine users (CU). We compared basal plasma concentrations between chronic CU (N=103; 69 recreational CU and 34 dependent CU) and stimulant-naïve healthy controls (N=92). Follow-up basal eCB/NAE plasma levels after 12 months were used for reliability and stability check (CU: N=33; controls: N=43). In an additional analysis using11C-ABP688 positron emission tomography (PET) in a male subsample (CU: N=18; controls: N=16), we investigated the relationships between eCBs/NAEs and mGluR5 density in the brain. We found higher 2-AG plasma levels in dependent CU compared to controls and recreational CU. 2-AG levels were stable over time across all groups. In the PET-subsample, a positive association between 2-AG and mGluR5 brain density only in CU was found. Our results corroborate animal findings suggesting an alteration of the ECS in cocaine dependence and an association between peripheral 2-AG levels and cerebral mGluR5 in humans. Therefore, the ECS might be a promising pharmaco-therapeutic target for novel treatments of cocaine dependence.
Organohalide respiration by aDesulforhopalus-dominated community
Authors: Zhang Chen , Atashgahi Siavash , Bosma Tom N.P. , Smidt Hauke
Published: April 2023

Despite the fact that several potential organohalide-respiring bacteria (OHRB) were discovered in metagenome-assembled genomes (MAGs) in our previous study of marine sediments from Aarhus Bay, delineation of their roles and interactions are yet to be disentangled. Henceforth, obtaining corresponding pure cultures or more defined consortia would be highly instrumental for more detailed eco-physiological studies. To this end, we isolated a colony from an anaerobic slant tube culture inoculated with a stable PCE dehalogenating enrichment. Intriguingly, the derived culture exhibited debromination only, instead of PCE dechlorination, under sulfate-reducing conditions. The culture was capable of conserving energy for growth via debromination of 2,6-dibromophenol (2,6-DBP). Analysis of 16S rRNA gene sequence data extracted from shot gun metagenome sequences revealed that a strain belonging toDesulforhopaluswas the predominant member of the consortium at a relative abundance of 29 %. Moreover, five bins (completeness > 85% and contamination < 3%) were assembled and all were identified as potentially new species (average nucleotide identity, ANI < 95%). Two bins from potential OHRB, bin.3 belonging toDesulfoplanes, and bin.4 belonging toMarinifilaceae, were found to encode reductive dehalogenase (RDase) genes, whereas bin.5 was found to contain a gene coding for thiolytic tetrachloro-p-hydroquinone (TPh-) RDase bearing 23.4 % identity to TPh-RDase ofSphingobium chlorophenolicum. The expression of all three RDase genes was strongly-induced after adding 2,6-DBP. Acetylene, a known inhibitor of different redox-active metalloenzymes, was found to inhibit methanogenesis as well as reductive dehalogenation without affecting gene expression, suggesting post-transcriptional inhibition. Phylogenomic analyses revealed the ecological importance of complementary roles of community members, including completede novovitamin B12 biosynthesis, which agreed with physiological data. Altogether, the findings presented here provided insight into the mutualism of the consortium and provided leads for synthetic OHR community optimization strategies forin situbioremediation.
Human fetal virtual histology with X-ray phase contrast imaging
Authors: Vérot Pierre-Louis , Charnay Laura , Tavakoli Clément , Singh Shifali , Quénot Laurène , Cruz Eva Solé , Barnat Monia , Humbert Sandrine , Dommergues Marc , Durr Alexandra , Piolat Christian , Rabattu Pierre-Yves , Brun Emmanuel
Published: April 2023

Human fetal analysis is of fundamental importance in understanding normal and pathological development. Congenital malformations and prenatal deaths are commonly linked to alterations of organs formation during embryonic and fetal life. Normal and pathological developments are not completely understood yet, because access to human fetal samples is difficult and exploratory means are scarce.

Here we show the first X-ray phase contrast images ofpost mortemhuman fetuses performed at the tissue scale. Imaging was performed on both an entire sample and isolated organs at higher resolution.

X-ray phase contrast imaging is based on the detection of refraction of a high energy X-ray beam after sample exposure. We were able to produce a tomographic imaging of human fetal tissues at the beginning of their second trimester at resolutions of 23 µm, 6 µm and 3 µm with high contrast on soft tissues.

Our results demonstrate how X-ray phase contrast imaging is a promising technique for human development analysis as it gives high-contrast and high-resolution results for soft and hard tissues.

We assume this technique to be a reference in the future of human development studies as it is conservative for rare and precious human specimens.
Spatiotemporal brain complexity quantifies consciousness outside of perturbation paradigms
Authors: Breyton Martin , Fousek Jan , Rabuffo Giovanni , Sorrentino Pierpaolo , Kusch Lionel , Massimini Marcello , Petkoski Spase , Jirsa Viktor
Published: April 2023

Signatures of consciousness are found in spectral and temporal properties of neuronal activity. Among these, spatiotemporal complexity after a perturbation has recently emerged as a robust metric to infer levels of consciousness. Perturbation paradigms remain, however, difficult to perform routinely. To discover alternative paradigms and metrics we systematically explore brain stimulation and resting-state activity in a digital brain twin model. We find that perturbational complexity only occurs when the brain model operates within a specific dynamical regime, in which spontaneous activity produces a large degree of functional network reorganizations referred to as being fluid. The regime of high brain fluidity is characterized by a small battery of metrics drawn from dynamical systems theory and predicts the impact of consciousness altering drugs (Xenon, Propofol and Ketamine). We validate the predictions in a cohort of 15 subjects at various stages of consciousness and demonstrate their agreement with previously reported perturbational complexity, but in a more accessible paradigm. Beyond the facilitation in clinical use, the metrics highlights complexity properties of brain dynamics in support of emergence of consciousness.