bluuebunny/crossref_metadata_2025 huggingface dataset:
Ecogeography of group size suggests differences in drivers of sociality among cooperatively breeding fairywrens
Authors: Johnson Allison E. , Welklin Joseph F. , Hoppe Ian R. , Shizuka Daizaburo
Published: March 2023

Cooperatively breeding species exhibit a range of social behaviours associated with different costs and benefits to group living, often in association with different environmental conditions. For example, recent phylogenetic studies have collectively shown that the evolution and distribution of cooperative breeding behaviour is related to the environment. However, little is known about how environmental variation may drive differences in social systems across populations within species, and how the relationship between environmental conditions and sociality may differ across species. Here, we examine variation in social group size along a steep environmental gradient for two congeneric cooperatively breeding species of fairywrens (Maluridae) and show that they exhibit opposing ecogeographic patterns. Purple-backed fairywrens, a species in which helpers increase group productivity, have larger groups in hot, dry environments and smaller groups in cool, wet environments. By contrast, superb fairywrens, a species with helpers that do not increase group productivity despite the presence of alloparental care, exhibit the opposite trend. We suggest differences in the costs and benefits of sociality contribute to these opposing ecogeographical patterns and demonstrate that comparisons of intraspecific patterns of social variation across species can provide insight into how ecology shapes social systems.
Direct quantification of skeletal pneumaticity illuminates ecological drivers of a key avian trait
Authors: Burton Maria Grace P. , Benson Roger B. J. , Field Daniel J.
Published: March 2023

Skeletal pneumaticity is a key feature of extant avian structure and biology, which first evolved among the non-flying archosaurian ancestors of birds. The widespread presence of air-filled bones across the postcranial skeleton is unique to birds among living vertebrates, but the true extent of skeletal pneumaticity has never been quantitatively investigated—hindering fundamental insights into the evolution of this key avian feature. Here, we use microCT scans of fresh, frozen birds to directly quantify the fraction of humerus volume occupied by air across a phylogenetically diverse taxon sample to test longstanding hypotheses regarding the evolution and function of avian skeletal pneumatization. Among other insights, we document weak positive allometry of internal air volume with humeral size among pneumatized humeri and provide strong support that humeral size, body mass, aquatic diving, and the presence or absence of pneumaticity all have independent effects on cortical bone thickness. Our quantitative evaluation of humeral pneumaticity across extant avian phylogeny sheds new light on the evolution and ontogenetic progression of an important aspect of avian skeletal architecture, and suggests that the last common ancestor of crown birds possessed a highly pneumatized humerus.
Production of highly enriched GABA through Lactobacillus
plantarum fermentation of katsuobushi protein
hydrolyzate made from Dendropanax morbiferus extract
fermented by Bacillus subtilis
Authors: An Yu-Jeong , Sung Nak-Ju , Lee Sam-Pin
Published: March 2023

To develop a multi-functional ingredient, the bioconversion of
katsuobushi protein was optimized using Bacillus
subtilis HA and Lactobacillus plantarum KS2020.
The Dendropanax morbiferus extract (DME) culture with protease
activity (102 unit/mL) was prepared by B. subtilis with
2% glucose and 1% skim milk through one day of alkaline
fermentation. Katsuobushi protein was effectively hydrolyzed by
the DME culture at 60°C for 3 hours, resulting in a tyrosine content of
156.85 mg%. Subsequently, a second lactic acid fermentation was carried
out with 10% monosodium glutamate (MSG) using L.
plantarum KS2020 to produce higher levels of GABA. Following
co-cultivation for three days, DME exhibited a pH of 8.3 (0% acidity).
After seven days, the viable cell count of L. plantarum
increased to 9.33 CFU/mL, but viable Bacillus cells were not
detected. Taken together, a multi-functional ingredient with enriched GABA,
peptides, probiotics, and umami flavor was developed through lactic acid
fermentation using hydrolyzed katsuobushi protein. These
results indicate that katsuobushi protein could be used as a
byproduct to produce a palatable protein hydrolysate using alkaline-fermented
DME culture as a proteolytic enzyme source.
Effects of Sasa borealis silage on proximate
composition, amino acid and fatty acid contents, and antioxidant activity in
fresh meat of Korean native goat fed with total mixed ration
Authors: Choi Young-Jin , Chung Sang Uk , Kim Na Yeon , Oh Mirae , Jang Se Young , Yun Young Sik , Moon Sang Ho
Published: March 2023

Jeju Sasa borealis (S. borealis) is indigenous
to the Halla Mountain area of Jeju Island, Republic of Korea. However, its
dominance has retarded the development of other plant species and lowered
biodiversity in this region. The aim of this study was to determine whether
S. borealis silage (SS) supplementation affects the
chemical composition and antioxidant activity in the fresh meat of Korean native
goats (Capra hircus coreanae). The experiment was conducted on
12 Korean native goats at the finisher stage. The feeding groups were the
Control (total mixed ration, TMR) and the Treatment (80% TMR + 20%
SS). The animals were adapted for two weeks and then subjected to a six-month
breeding experiment. Meat samples were excised from the neck, loin, rib, front
leg, and hind leg of the slaughtered animals. The meat derived from the
treatment group contained more taurine and anserine than that derived from the
control group. Both groups did not significantly differ in terms of
ω-6/ω-3 fatty acid ratio.
The loin and front leg of the treatment group contained significantly higher
vitamin E levels than those of the control group. DPPH, ABTS, and FRAP analyses
disclosed that the loin and front leg had significantly higher antioxidant
activity (p⟨0.05) than the other parts. Moreover, the loin and front leg
cuts of the treatment group had higher antioxidant activity than those of the
control group. The present study demonstrated that S. borealis
supplementation could effectively improve Korean native goat meat quality.
Evaluation of radical scavenging and diasestive enzyme inhibitory
capacities of peach twigs fraction extract (Prunus persica
L. Bastch)
Authors: Lee Youjeoung , Jeong Gyeong Han , Hong Ju Yeon , Kim Tae Hoon
Published: March 2023

We investigated the free radical scavenging and digestive enzyme inhibitory
activities of the hot water extract of peach twig (Prunus
persica L. Bastch). This extract of the peach twigs was further
split up into n-hexane, ethyl acetate (EtOAc), and n-butyl
alcohol(n-BuOH), which resulted in three solvent-soluble
fractions. Free radical scavenging activity was evaluated using
2,2-diphenyl-1-picrylhydrazyl (DPPH) and
2,2’-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)
(ABTS+) assay systems, while hypoglycemic effect of the
peach twig extract and the solvent-soluble fractions were tested using
α-glucosidase and α-amylase
inhibition assays. Accordingly, the EtOAc layer showed a greater free radical
scavenging activity compared to other solvent-soluble fractions. Furthermore,
based on the α-glucosidase and
α-amylase assays, the IC50 values were
determined to be 38.2±1.6 and 69.6±6.1
μg/mL for the EtOAc-soluble fractions, respectively.
Taken together, these results suggest that the fractions obtained from the peach
twig extract can be considered as a potential source of natural antioxidant and
hypoglycaemic constituents.
Kiwi-persimmon wine produced using wild Saccharomyces
cerevisiae strains with sugar, acid, and alcohol
tolerance
Authors: Lee Hee Yul , Cho Kye Man , Joo Ok Soo
Published: March 2023

100 different yeast colonies were isolated from spontaneously fermented kiwis,
persimmons, apples, pears, watermelons, grapes, grape fruits, peachs, and plums,
and selected yeast strains were used to produce kiwi-persimmon mixed wine
(KPMW). Among the isolates, five representative strains exhibited tolerance to
sucrose, alcohol, pH, and potassium metabisulfite when compared with the control
yeast strain (Saccharomyces cerevisiae KCCM 12615). All five
yeast strains (Y4, Y10, Y28, Y78, and Y81) exhibited 99% 26S rDNA
sequence similarity to S. cerevisiae. The pH, acidity, Brix,
reducing sugar, alcohol, and organic acid contents were consistent in KPMW
prepared from the S. cerevisiae KCCM 12615 and Y28 strains.
KPMW made from the Y4, Y10, and Y28 strains exhibited lower quantities of free
sugars than those of the KPMW made from the other yeast strains. The level of
ethyl esters in KPMW prepared from the Y28 was higher than that in the other
KPMWs. All strains, except for Y28, produced lower concentrations of sulfur and
ketone compounds. Furthermore, the KPMW produced by the Y28 strains had total
phenolic contents with 1.1 g/L, with DPPH and ABTS radical scavenging activities
of 57.06% and 55.62%, respectively, and a FRAP assay value of
0.72. Our results suggest that Y28 is a promising yeast strain for producing
high-quality wines.
Immunomodulatory effects of six Acetobacter
pasteurianus strains in RAW-Blue macrophage
Authors: Kim Sun Hee , Jeong Woo Soo , Kim So-Young , Yeo Soo-Hwan
Published: March 2023

In this study, we investigated the immunological properties of six strains of
Acetobacter pasteurianus through nuclear factor-kappa
B/activator protein-1 (NF-κB/AP-1) transcription factor activation and
nitric oxide (NO) and cytokine production in macrophages. We found that the six
A. pasteurianus strains had no significant inhibitory
effect on the cell viability of RAW-Blue™ cells at the concentration of
(25, 50, 100 CFU/macrophage). The production of NO and cytokines (TNF-α,
IL-1β, and IL-6) showed different abilities of immune activation for each
strain, and it was 0.7 to 0.9 times higher than that of the LPS (100 ng/mL, v/v)
positive control and 7 to 8 times superior to that of the negative control
group. To explore the underlying mechanism, we evaluated the mRNA expression of
pro-inflammatory genes. Consequently, we found that inducible nitric oxide
synthase (iNOS) and cyclooxygenase (COX)-2 expression including
genes expression of cytokines were elevated by the six A.
pasteurianus treatment. These results suggested that the six
strains of A. pasteurianus have an excellent industrial
application value as a functional material for the purpose of enhancing immune
function.
Effects of 1-methylcyclopropene (1-MCP) treatment on the maintenance of fruit quality of RubyS apples during cold storage
Authors: Yoo Jingi , Yoo Hwajong , Win Nay Myo , Jung Hee-Young , Cho Young-Je , Kang In-Kyu
Published: March 2023

This study was conducted to evaluate the effect of different 1-methylcyclopropene (1-MCP) concentrations on fruit quality of small-sized RubyS apples during cold storage. After harvesting, the fruits were treated with 1-MCP at 0.5 or 1 μL/L concentrations and, subsequently, stored at 0°C for 6 months. After 6 months, the flesh firmness of untreated fruits, which was 85.4 N at harvest, had gradually decreased to 46.5 N; however, that of 1-MCP-treated fruits was maintained at 59.1 and 59.5 N. Titratable acidity (TA) of untreated fruits had also decreased from 0.42 to 0.24%, whereas that of 1-MCP-treated fruits was maintained at 0.26 and 0.27%. Soluble solids content (SSC) did not differ in all fruits. However, the 1-MCP-treated fruits had lower levels of SSC/TA ratio than untreated fruits. Moreover, after 6 months, the ethylene production had increased to 47.0 μL/kg/h in the untreated fruits, whereas 1-MCP blocked the ethylene production at 1.4 and 1.7 μL/kg/h. The weight loss and peel color variables remained unaffected by 1-MCP treatments. Thus, these results indicated that, for RubyS apples, the storability was only 2 months at 0°C without treatment, which can be extended to 6 months with 1-MCP treatments. The application of 1-MCP at 0.5 μL/L concentration is effectively and economically sufficient to maintain the quality of RubyS apples.
Influence of low-pressure tumbling on the quality characteristics
of thawed pork
Authors: Hong Won-Ho , Kim Jeong , Gwak Yu-Jeong , Chun Jiyeon
Published: March 2023

As livestock consumption in Korea has been gradually increasing, the quality of
the final products has been improved to meet this increased demand. In
particular, maintaining the water holding capacity (WHC) and minimizing the drip
loss during the thawing of frozen meat are of utmost importance. This study
investigated the physicochemical properties of frozen pork subjected to thawing
under different conditions: at room temperature (20°C, under air), at a
low temperature (4°C refrigerator, under air), under water (20°C,
under water in a vacuum bag), under microwave (microwave-thawing, 260 W), and
under low-pressure tumbling (20°C, 0.015 bar, tumbling). The shortest
thawing time for frozen pork was recorded upon low-pressure tumbling thus
indicating a fast heat transfer. The lowest drip loss (0.2%) and highest
WHC (94.5%) were also recorded under this condition. A significantly
higher drip loss was observed upon microwave-(1.0%) and water-thawing
(1.2%), which resulted in the lowest WHC in microwave thawing
(87.2%). The highest total count of aerobic bacteria and coliform group
were observed upon room temp thawing while the low pressure tumbling and thawing
resulted in the lowest aerobic bacteria (1.90 log CFU/g) and coliform (0.78 log
CFU/g) count. Consequently, thawing by low pressure tumbling afforded the best
food quality.
The Rho GAP RRC-1 is required for the assembly or stability of integrin adhesion complexes and is a member of the PIX pathway in muscle
Authors: Moody Jasmine C. , Qadota Hiroshi , Benian Guy M.
Published: March 2023

GTPases cycle between active GTP bound and inactive GDP bound forms. Exchange of GDP for GTP is catalyzed by guanine nucleotide exchange factors (GEFs). GTPase activating proteins (GAPs) accelerate GTP hydrolysis, to promote the GDP bound form. Recently, we reported that the GEF called PIX is required for assembly or stability of integrin adhesion complexes (IAC) in striated muscle. A GAP for the PIX pathway had not been identified in any cell type or organism. A screen inC. elegansof mutants in 18 proteins containing Rho GAP domains and expressed in muscle revealed that loss of function ofrrc-1results in loss of IAC components at the muscle cell boundary (MCB). RRC-1 contains an SH3 domain and a Rho GAP domain, and is localized to the IACs of MCBs, like PIX-1.rrc-1mutants show reduced accumulation of IAC components at the MCB, sarcomere disorganization, and reduced whole animal locomotion. Knockdown ofgit-1, which encodes a PIX scaffold protein, reduces the level of RRC-1. Localization at MCBs of RRC-1 depends onpix-1, and the localization of PIX-1 depends onrrc-1. These results suggest that RRC-1 is a RhoGAP for the PIX pathway in muscle.
Histological examination of choroid plexus epithelia changes in schizophrenia
Authors: Williams MR , Macdonald CM , Turkheimer F
Published: March 2023

Background

The choroid plexus (CP) is suggested to be involved in neuroimmune regulation avia the interaction between central and peripheral inflammation. Quantitative imaging has demonstrated volumetric CP change in psychosis, schizophrenia and depression. This study histologically examines CP epithelial cell morphology in these illnesses to identify the biological source of such volumetric changes.

Methods

Formalin-fixed paraffin-embedded FFPE blocks were obtained bilaterally from the lateral ventricles of 13 cases of sex- and age-matched brains from each of schizophrenia (SZ) with psychosis, major depressive disorder (MDD) and matched controls. FFPE blocks were sectioned at 7μm and routinely stained for H&E. Morphological analysis of 180 CP epithelia/case was conducted blindly on digital images collected x600 magnification. Calcification was assessed in all CP regions manually.

Results

Linear General Model analysis shows a significant effect of diagnosis on somal width (p=0.006, r2=0.33, adj=0.25), with a significant difference between SZ non-medicated v non-medicated NPD controls (p=0.032), demonstrating increased somal width in SZ with psychotic medication but not in unmedicated SZ cases. No effects were observed in calcification.

Discussion

Epithelial cells examined were adhered to CP fibrous surface so width expansion describes the primary methods for these cells to expand with adherence to this surface. The interaction of antipsychotic medication and diagnosis demonstrates that this is an illness-specific change and mediated through the DA-system, although the mechanism is unclear at present.
Spatial architecture of high-grade glioma reveals tumor heterogeneity within distinct domains
Authors: Moffet J.J.D. , Fatunla O.E. , Freytag L. , Jones J.J. , Roberts-Thomson S. , Pavenko A. , Scoville D. , Zhang L. , Liang Y. , Morokoff A. , Whittle J.R. , Freytag S. , Best S.A.
Published: March 2023

High-grade gliomas are aggressive primary brain cancers with poor response to standard regimens, driven by immense heterogeneity. In isocitrate dehydrogenase (IDH) wild-type high-grade glioma (glioblastoma, GBM), increased intra-tumoral heterogeneity is associated with more aggressive disease. Recently, spatial technologies have emerged to dissect this complex heterogeneity within the tumor ecosystem by preserving cellular organizationin situ. Here, we construct a high-resolution molecular landscape of GBM andIDH-mutant high-grade glioma patient samples to investigate the cellular subtypes and spatial communities that compose high-grade glioma using digital spatial profiling and spatial molecular imaging. This uncovered striking diversity of the tumor and immune microenvironment, that is embodied by the heterogeneity of the inferred copy-number alterations in the tumor. Reconstructing the tumor architecture revealed two distinct niches, one composed of tumor cell states that most closely resemble normal glial cells, associated with microglia; and the other niche populated by monocytes and mesenchymal tumor cells. We further reveal that communication between tumor and immune cells is underpinned by tumor-specific ligands, such as TGFβ signaling in astrocyte-like tumor cells. This primary study reveals high levels of intra-tumoral heterogeneity in high-grade gliomas, associated with a diverse immune landscape within spatially localized regions.
Functional connectomics reveals general wiring rule in mouse visual cortex
Authors: Ding Zhuokun , Fahey Paul G. , Papadopoulos Stelios , Wang Eric Y. , Celii Brendan , Papadopoulos Christos , Chang Andersen , Kunin Alexander B. , Tran Dat , Fu Jiakun , Ding Zhiwei , Patel Saumil , Ntanavara Lydia , Froebe Rachel , Ponder Kayla , Muhammad Taliah , Bae J. Alexander , Bodor Agnes L. , Brittain Derrick , Buchanan JoAnn , Bumbarger Daniel J. , Castro Manuel A. , Cobos Erick , Dorkenwald Sven , Elabbady Leila , Halageri Akhilesh , Jia Zhen , Jordan Chris , Kapner Dan , Kemnitz Nico , Kinn Sam , Lee Kisuk , Li Kai , Lu Ran , Macrina Thomas , Mahalingam Gayathri , Mitchell Eric , Mondal Shanka Subhra , Mu Shang , Nehoran Barak , Popovych Sergiy , Schneider-Mizell Casey M. , Silversmith William , Takeno Marc , Torres Russel , Turner Nicholas L. , Wong William , Wu Jingpeng , Yin Wenjing , Yu Szi-chieh , Yatsenko Dimitri , Froudarakis Emmanouil , Sinz Fabian , Josić Krešimir , Rosenbaum Robert , Seung H. Sebastian , Collman Forrest , da Costa Nuno Maçarico , Reid R. Clay , Walker Edgar Y. , Pitkow Xaq , Reimer Jacob , Tolias Andreas S.
Published: March 2023

Understanding the relationship between circuit connectivity and function is crucial for uncovering how the brain implements computation. In the mouse primary visual cortex (V1), excitatory neurons with similar response properties are more likely to be synaptically connected, but previous studies have been limited to within V1, leaving much unknown about broader connectivity rules. In this study, we leverage the millimeter-scale MICrONS dataset to analyze synaptic connectivity and functional properties of individual neurons across cortical layers and areas. Our results reveal that neurons with similar responses are preferentially connected both within and across layers and areas — including feedback connections — suggesting the universality of the ‘like-to-like’ connectivity across the visual hierarchy. Using a validated digital twin model, we separated neuronal tuning into feature (what neurons respond to) and spatial (receptive field location) components. We found that only the feature component predicts fine-scale synaptic connections, beyond what could be explained by the physical proximity of axons and dendrites. We also found a higher-order rule where postsynaptic neuron cohorts downstream of individual presynaptic cells show greater functional similarity than predicted by a pairwise like-to-like rule. Notably, recurrent neural networks (RNNs) trained on a simple classification task develop connectivity patterns mirroring both pairwise and higher-order rules, with magnitude similar to those in the MICrONS data. Lesion studies in these RNNs reveal that disrupting ‘like-to-like’ connections has a significantly greater impact on performance compared to lesions of random connections. These findings suggest that these connectivity principles may play a functional role in sensory processing and learning, highlighting shared principles between biological and artificial systems.
Whole-genome duplications and the long-term evolution of gene regulatory networks in angiosperms
Authors: Almeida-Silva Fabricio , Van de Peer Yves
Published: March 2023

Angiosperms have a complex history of whole-genome duplications (WGDs), with varying numbers and ages of WGD events across clades. These WGDs have greatly affected the composition of plant genomes due to the biased retention of genes belonging to certain functional categories following their duplication. In particular, regulatory genes and genes encoding proteins that act in multiprotein complexes have been retained in excess following WGD. Here, we inferred protein-protein interaction (PPI) networks and gene regulatory networks (GRNs) for seven well-characterized angiosperm species and explored the impact of both WGD and small-scale duplications (SSD) in network topology by analyzing changes in frequency of network motifs. We found that PPI networks are enriched in WGD-derived genes associated with dosage-sensitive intricate systems, and strong selection pressures constrain the divergence of WGD-derived genes at the sequence and PPI levels. WGD-derived genes in network motifs are mostly associated with dosage-sensitive processes, such as regulation of transcription and cell cycle, translation, photosynthesis, and carbon metabolism, while SSD-derived genes in motifs are associated with response to biotic and abiotic stress. Recent polyploids have higher motif frequencies than ancient polyploids, while WGD-derived network motifs tend to be disrupted on the longer term. Our findings demonstrate that both WGD and SSD have contributed to the evolution of angiosperm GRNs, but in different ways, with WGD events likely having a more significant impact on the short-term evolution of polyploids.
Effects of selfing on speciation through the accumulation of Dobzhansky-Muller incompatibilities
Authors: Xu Kuangyi
Published: March 2023

Phylogenetic analyses suggest that self-compatible lineages have higher speciation rates than self-incompatible lineages. However, the effects of selfing on speciation remain unclear. Although a selfing population can resist gene flow from other populations, selfing may increase gene flow from a focal population to other populations. This study investigates the effects of selfing rates of two populations on the waiting time to speciation through the accumulation of Dobzhansky-Muller incompatibilities (DMI). Generally, a higher mean selfing rate of two populations facilitates speciation when incompatibility-controlling alleles are recessive and are weakly selected, and when gene flow is mainly through pollen dispersal instead of seed dispersal. However, the selfing rate difference between two populations can retard speciation, especially when the selfing rate of immigrants remains unchanged after migration. When the selfing rates of two populations differ, speciation may be fastest when the mean selfing rate is intermediate. Given that selfing rates often vary among conspecific populations in plant species, the results indicate that lineages with higher mean selfing rates may not necessarily have higher rates of speciation through the accumulation of DMI, and also call for an estimation of the dependency of speciation rates on selfing rates.
Using Recognition Testing to Support Semantic Learning in Developmental Amnesia
Authors: Elward Rachael , Limond Jennifer , Chareyron Loïc , Ethapemi Janice , Vargha-Khadem Faraneh
Published: March 2023

Patients with developmental amnesia (DA) have suffered hippocampal damage in infancy and subsequently shown poor episodic memory, but good semantic memory. It is not clear how patients with DA learn semantic information in the presence of episodic amnesia. However, patients with DA show well-developed recognition memory and these recognition abilities may support semantic learning. We present data from three experiments (two previously described in Elward & Vargha-Khadem, 2018). The first experiment showed that recall tests did not facilitate semantic learning. Patients with DA recalled only 35% of the learned information (controls recalled 80%). The second experiment indicated that multiple-choice recognition tests may facilitate learning. Patients with DA recalled 85% of the learned information. In experiment three, a patient with DA (aged 8 years) took part in a repeated-measures test so that recall learning and recognition learning could be directly compared. The results showed a clear benefit of recognition learning compared to recall learning (76% v. 35%). This finding indicates that young people with extensive hippocampal damage indeed utilise their recognition memory to support the integration of new information into their semantic system. This has important implications for the support of school-aged children with episodic memory difficulties.
The role of self-fertilization in plant colony establishment
Authors: Xu Kuangyi , Reatini Bryan
Published: March 2023

Increased rates of self-fertilization are often found in plant colonies, but the factors driving the observed higher selfing rates remain unclear. Specifically, the higher selfing rates in colonist populations may be due to 1) source populations with a higher selfing rate being more likely to successfully establish colonies (a filter effect), 2) thein situevolution of selfing rate or a plastic selfing rate increase rescuing the colony from extinction, 3) selfing rate evolution post establishment. Using individual-based simulations and eco-evo models, we show that under both single and multiple dispersal, colony establishment may often be driven by a filter effect, due to a higher initial selfing rate and lower genetic load, which are correlated since selfing can purge deleterious mutations. Moreover, the role of the filter effect is weaker under multiple dispersal than single dispersal. The evolution of a higher selfing rate is unlikely to contribute directly to colony establishment. Although selfing rate evolution occurs during the colonization process, most of the selfing rate evolution may occur post establishment. Plasticity in selfing rates is more effective in facilitating colony establishment than the evolution of selfing.
The origin and structural evolution ofde novogenes inDrosophila
Authors: Peng Junhui , Zhao Li
Published: March 2023

Although previously thought to be unlikely, recent studies have shown thatde novogene origination from previously non-genic sequences is a relatively common mechanism for gene innovation in many species and taxa. These young genes provide a unique set of candidates to study the structural and functional origination of proteins. However, our understanding of their protein structures and how these structures originate and evolve are still limited, due to a lack of systematic studies. Here, we combined high-quality base-level whole genome alignments, bioinformatic analysis, and computational structure modeling to study the origination, evolution, and protein structure of lineage-specificde novogenes. We identified 555de novogene candidates inD. melanogasterthat originated within theDrosophilinaelineage. We found a gradual shift in sequence composition, evolutionary rates, and expression patterns with their gene ages, which indicates possible gradual shifts or adaptations of their functions. Surprisingly, we found little overall protein structural changes forde novogenes in theDrosophilinaelineage. Using Alphafold2, ESMFold, and molecular dynamics, we identified a number ofde novogene candidates with protein products that are potentially well-folded, many of which are more likely to contain transmembrane and signal proteins compared to other annotated protein-coding genes. Using ancestral sequence reconstruction, we found that most potentially well-folded proteins are often born folded. Interestingly, we observed one case where disordered ancestral proteins become ordered within a relatively short evolutionary time. Single-cell RNA-seq analysis in testis showed that although mostde novogenes are enriched in spermatocytes, several youngde novogenes are biased in the early spermatogenesis stage, indicating potentially important but less emphasized roles of early germline cells in thede novogene origination in testis. This study provides a systematic overview of the origin, evolution, and structural changes ofDrosophilinae-specificde novogenes.
Contribution of Implicit Memory to Adaptation of Movement Extent During Reaching Against Unpredictable Spring-Like Loads: Insensitivity to Intentional Suppression of Kinematic Performance
Authors: Lantagne Devon D , Mrotek Leigh Ann , Hoelzle James B , Thomas Danny G , Scheidt Robert A
Published: March 2023

We examined the extent to which intentionally underperforming a goal-directed reaching task impacts how memories of recent performance contribute to sensorimotor adaptation. Healthy human subjects performed computerized cognition testing and an assessment of sensorimotor adaptation wherein they grasped the handle of a horizontal planar robot while making goal-directed out-and-back reaching movements. The robot exerted forces that resisted hand motion with a spring-like load that changed unpredictably between movements. The robotic test assessed how implicit and explicit memories of sensorimotor performance contribute to the compensation for the unpredictable changes in the hand-held load. After each movement, subjects were to recall and report peak movement extent from the previous trial. Subjects performed the tests under two counterbalanced conditions: one where they performed with their best effort, and one where they intentionally suppressed performance. Results from the computerized cognition tests confirmed that subjects understood and complied with task instructions. When suppressing performance during the robotic assessment, subjects demonstrated marked changes in reach precision, time to capture the target, and reaction time. We fit a set of limited memory models to the data to identify how subjects used implicit and explicit memories of recent performance to compensate for the changing loads. In both sessions, subjects used implicit, but not explicit, memories from the most recent trial to adapt reaches to unpredictable spring-like loads. Subjects did not “give up” on large errors, nor did they discount small errors deemed “good enough.” Although subjects clearly suppressed kinematic performance (response timing, movement variability, and self-reporting of reach error), the relative contributions of sensorimotor memories to trial-by-trial variations in task performance did not differ significantly between the two testing conditions. We conclude that intentional performance suppression had minimal impact on how implicit sensorimotor memories contribute to adaptation of unpredictable mechanical loads applied to the hand.
Modeling Tick Populations: An Ecological Test Case for Gradient Boosted Trees
Authors: Manley William , Tran Tam , Prusinski Melissa , Brisson Dustin
Published: March 2023

General linear models have been the foundational statistical framework used to discover the ecological processes that explain the distribution and abundance of natural populations. Analyses of the rapidly expanding cache of environmental and ecological data, however, require advanced statistical methods to contend with complexities inherent to extremely large natural data sets. Modern machine learning frameworks such as gradient boosted trees efficiently identify complex ecological relationships in massive data sets, which are expected to result in accurate predictions of the distribution and abundance of organisms in nature. However, rigorous assessments of the theoretical advantages of these methodologies on natural data sets are rare. Here we compare the abilities of gradient boosted and linear models to identify environmental features that explain observed variations in the distribution and abundance of blacklegged tick (Ixodes scapularis) populations in a data set collected across New York State over a ten-year period. The gradient boosted and linear models use similar environmental features to explain tick demography, although the gradient boosted models found non-linear relationships and interactions that are difficult to anticipate and often impractical to identify with a linear modeling framework. Further, the gradient boosted models predicted the distribution and abundance of ticks in years and areas beyond the training data with much greater accuracy than their linear model counterparts. The flexible gradient boosting framework also permitted additional model types that provide practical advantages for tick surveillance and public health. The results highlight the potential of gradient boosted models to discover novel ecological phenomena affecting pathogen demography and as a powerful public health tool to mitigate disease risks.
BioConvert: a comprehensive format converter for life sciences
Authors: Caro Hugo , Dollin Sulyvan , Biton Anne , Brancotte Bryan , Desvillechabrol Dimitri , Dufresne Yoann , Li Blaise , Kornobis Etienne , Lemoine Frédéric , Maillet Nicolas , Perrin Amandine , Traut Nicolas , Néron Bertrand , Cokelaer Thomas
Published: March 2023

Abstract

Bioinformatics is a field known for the numerous standards and formats that have been developed over the years. This plethora of formats, sometimes complementary, and often redundant, poses many challenges to bioinformatics data analysts. They constantly need to find the best tool to convert their data into the suitable format, which is often a complex, technical and time consuming task. Moreover, these small yet important tasks are often difficult to make reproducible. To over-come these difficulties, we initiatedBioConvert, a collaborative project to facilitate the conversion of life science data from one format to another.BioConvertaggregates existing software within a single framework and complemented them with original code when needed. It provides a common interface to make the user experience more streamlined instead of having to learn tens of them. Currently,BioConvertsupports about 50 formats and 100 direct conversions in areas such as alignment, sequencing, phylogeny, and variant calling. In addition to being useful for end-users,BioConvertcan also be utilized by developers as a universal benchmarking framework for evaluating and comparing numerous conversion tools. Additionally, we provide a web server implementing an online user-friendly interface toBioConvert, hence allowing direct use for the community.
The Adjuvant Effects of Amphipathic Helical Peptides
Authors: Lyu Jyun-Hong , Liou Gunn-Guang , Wang May , Kan Ming-Chung
Published: March 2023

Subunit vaccines are the focus of research in developing new vaccines against infectious diseases. Due to the low immunogenicity of recombinant proteins, adjuvants are required for the activation of humoral and cellular immunity against a protein antigen. In this study, we reported the identification of a novel pathway that can activate humoral immunity against a recombinant protein without inducing inflammatory responses. By fusing an amphipathic helical peptide to GFP, one can increases the immunogenicity of GFP by up to 1000 fold. This enhancement was correlated with the ability of amphipathic helical peptides to bind to cell membranes and cause lysosomal membrane permeabilization. We showed evidence that the amphipathic helical peptide may induce the delivery of antigen across the lysosomal membrane into cytosol. Amphipathic helical peptide fusion provided a new pathway for stimulating immune responses against recombinant proteins.
Functional aberration of cortical neuronal network induced by Aβ42 oligomer
Authors: Ganbat Dulguun , Jeon Jae Kyong , Kim Sang Seong
Published: March 2023

Alzheimer’s disease (AD) is a multifactorial disorder that affects cognitive functioning, behavior, and neuronal properties. The neuronal dysfunction is primarily responsible for cognitive decline in AD patients, with many causal factors including plaque accumulation of Aβ42. Neural hyperactivity induced by Aβ42 deposition cause abnormalities in neural networks, leading to alterations in synaptic activity and interneuron dysfunction. Even though neuroimaging techniques elucidated the underlying mechanism in the neural connectivity, precise understanding in cellular level is still elusive. Previously, a few multielectrode array studies examined the neuronal network modulationin vitrocultures revealing relevance of ion channels and the chemical modulators in the presence of Aβ42. In this study, we investigated neuronal connectivity and dynamic changes with high density multielectrode array, particularly in relation to network-wide parameter changes over time. By comparing the neuronal network between normal and Aβ42 treated neuronal cultures, it was possible to discover the direct pathological effect of the Aβ42 oligomer altering the network characteristics. The application of graph theory and center of activity trajectory analysis assessed the consolidation and disassociation of neural networks under Aβ42 oligomer exposure over time. This result can enhance our understanding of how neural networks are affected during AD progression.
A data-driven Boolean model explains memory subsets and evolution in CD8+ T cell exhaustion
Authors: Ildefonso Geena V. , Finley Stacey D.
Published: March 2023

T cells play a key role in a variety of immune responses, including infection and cancer. Upon stimulation, naïve CD8+ T cells proliferate and differentiate into a variety of memory and effector cell types; however, failure to clear antigens causes prolonged stimulation of CD8+ T cells, ultimately leading to T cell exhaustion (TCE). The functional and phenotypic changes that occur during CD8+ T cell differentiation are well characterized, but the underlying gene expression state changes are not completely understood. Here, we utilize a previously published data-driven Boolean model of gene regulatory interactions shown to mediate TCE. Our network analysis and modeling reveal the final gene expression states that correspond to TCE, along with the sequence of gene expression patterns that give rise to those final states. With a model that predicts the changes in gene expression that lead to TCE, we could evaluate strategies to inhibit the exhausted state. Overall, we demonstrate that a common pathway model of CD8+ T cell gene regulatory interactions can provide insights into the transcriptional changes underlying the evolution of cell states in TCE.
Downregulation of ribosomal RNA (rRNA) genes in human head and neck squamous cell carcinoma (HNSCC) cells is linked to rDNA promoter hypermethylation
Authors: Priyadarshini Neha , Puppala Navinchandra Venkatarama , Jayaprakash Jayasree Peroth , Khandelia Piyush , Sharma Vivek , Mohannath Gireesha
Published: March 2023

Eukaryotes carry hundreds of ribosomal RNA (rRNA) genes as tandem arrays, which generate rRNA for protein synthesis. Humans carry ~ 400 rRNA gene copies, which are epigenetically regulated. Dysregulation of rRNA synthesis and ribosome biogenesis are characteristic features of cancers. Targeting aberrant rRNA expression for cancer therapy is being explored. Head and neck squamous cell carcinoma (HNSCC) is among the most prevalent cancers globally. Using quantitative PCR and bisulfite sequencing, we show that rRNA genes are downregulated and their promoters are hypermethylated in HNSCC cell lines. These finding may have relevance for prognosis and diagnosis for HNSCC.
Principles of human pre-60Sbiogenesis
Authors: Broeck Arnaud Vanden , Klinge Sebastian
Published: March 2023

During early stages of human large ribosomal subunit (60S) biogenesis, an ensemble of assembly factors establishes and fine-tunes the essential RNA functional centers of pre-60Sparticles by an unknown mechanism. Here, we report a series of cryo-electron microscopy structures of human nucleolar and nuclear pre-60Sassembly intermediates at resolutions of 2.5-3.2 Å. These structures show how protein interaction hubs tether assembly factor complexes to nucleolar particles and how GTPases and ATPases couple irreversible nucleotide hydrolysis steps to the installation of functional centers. Nuclear stages highlight how a conserved RNA processing complex, the rixosome, couples large-scale RNA conformational changes to pre-rRNA processing by the RNA degradation machinery. Our ensemble of human pre-60Sparticles provides a rich foundation to elucidate the molecular principles of ribosome formation.

One-Sentence Summary

High-resolution cryo-EM structures of human pre-60S particles reveal new principles of eukaryotic ribosome assembly.
Inhibitory input directs astrocyte morphogenesis through glial GABABR
Authors: Cheng Yi-Ting , Luna-Figueroa Estefania , Woo Junsung , Chen Hsiao-Chi , Lee Zhung-Fu , Harmanci Akdes Serin , Deneen Benjamin
Published: March 2023

Communication between neurons and glia plays an important role in establishing and maintaining higher order brain function. Astrocytes are endowed with complex morphologies which places their peripheral processes in close proximity to neuronal synapses and directly contributes to their regulation of brain circuits. Recent studies have shown that excitatory neuronal activity promotes oligodendrocyte differentiation; whether inhibitory neurotransmission regulates astrocyte morphogenesis during development is unknown. Here we show that inhibitory neuron activity is necessary and sufficient for astrocyte morphogenesis. We found that input from inhibitory neurons functions through astrocytic GABABR and that its deletion in astrocytes results in a loss of morphological complexity across a host of brain regions and disruption of circuit function. Expression of GABABR in developing astrocytes is regulated in a region-specific manner by SOX9 or NFIA and deletion of these transcription factors results in region-specific defects in astrocyte morphogenesis, which is conferred by interactions with transcription factors exhibiting region-restricted patterns of expression. Together our studies identify input from inhibitory neurons and astrocytic GABABR as universal regulators of morphogenesis, while further revealing a combinatorial code of region-specific transcriptional dependencies for astrocyte development that is intertwined with activity-dependent processes.
The RNA-DNA world and the emergence of DNA-encoded heritable traits
Authors: Roy Suvam , Sengupta Supratim
Published: March 2023

The RNA world hypothesis confers a central role to RNA molecules in information encoding and catalysis. Even though evidence in support of this hypothesis has accumulated from both experiments and computational modelling, the transition from an RNA world to a world where heritable genetic information is encoded in DNA remains an open question. Recent experiments show that both RNA and DNA templates can extend complementary primers using free RNA/DNA nucleotides, either non-enzymatically or in the presence of a replicase ribozyme. Guided by these experiments, we analyse protocellular evolution with an expanded set of reaction pathways made possible through the presence of DNA nucleotides. By en-capsulating these reactions inside three different types of protocellular compartments, each subject to distinct modes of selection, we show how protocells containing DNA-encoded replicases in low copy numbers and replicases in high copy numbers can dominate the population. This is facilitated by a reaction that leads to auto-catalytic synthesis of replicase ribozymes from DNA templates encoding the replicase, after the chance emergence of a replicase through non-enzymatic reactions. Our work unveils a pathway for the transition from an RNA world to a mixed RNA-DNA world characterized by Darwinian evolution, where DNA sequences encode heritable phenotypes.
The impact of uncertainty in hERG binding mechanism onin silicopredictions of drug-induced proarrhythmic risk
Authors: Lei Chon Lok , Whittaker Dominic G. , Mirams Gary R.
Published: March 2023

Background and Purpose

Drug-induced reduction of the rapid delayed rectifier potassium current carried by the human Ether-à-go-go-Related Gene (hERG) channel is associated with increased risk of arrhythmias. Recent updates to drug safety regulatory guidelines attempt to capture each drug’s hERG binding mechanism by combiningin vitroassays within silicosimulations. In this study, we investigate the impact onin silicoproarrhythmic risk predictions due to uncertainty in the hERG binding mechanism and physiological hERG current model.

Experimental Approach

Possible pharmacological binding models were designed for the hERG channel to account for known and postulated small molecule binding mechanisms. After selecting a subset of plausible binding models for each compound through calibration to available voltage-clamp electrophysiology data, we assessed their effects, and the effects of different physiological models, on proarrhythmic risk predictions.

Key Results

For some compounds, multiple binding mechanisms can explain the same data produced under the safety testing guidelines, which results in different inferred binding rates. This can result in substantial uncertainty in the predicted torsade risk, which often spans more than one risk category. By comparison, we found that the effect of a different hERG physiological current model on risk classification was subtle.

Conclusion and Implications

The approach developed in this study assesses the impact of uncertainty in hERG binding mechanisms on predictions of drug-induced proarrhythmic risk. For some compounds, these results imply the need for additional binding data to decrease uncertainty in safety-critical applications.