bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalence and acceptability of psychological and/or economic intimate partner violence, and utilization of mental health services by its survivors in Lithuania
Authors: Grigaitė Ugnė , Azeredo-Lopes Sofia , Žeimė Eglė , Slotkus Paulius Yamin , Heitmayer Maxi , Aluh Deborah Oyine , Pedrosa Bárbara , Silva Manuela , Santos-Dias Margarida , Cardoso Graça , Caldas-de-Almeida José Miguel
Published: February 2024

Background

Lithuania has one of the highest averages in the European Union when it comes to psychological and/or economic intimate partner violence (PE-IPV). IPV survivors are several times more likely to have mental health conditions than those without IPV experiences. The aim of this article is to study the prevalence, characteristics and attitudes of PE-IPV survivors in Lithuania, and the predictors of them accessing mental health services.

Methods

A cross-sectional study based on a national survey representative of the adult population. The survey was implemented by a third-party independent market research company employing an online survey panel. Logistic regression models were used in the analysis.

Results

Almost 50% of women in Lithuania experience PE-IPV. Females are significantly more likely to experience it than males. The vast majority of women find PE-IPV unacceptable; however, only one-third of survivors seek any type of help. Only one-tenth approach mental health services, with divorcees being at higher odds of doing so.

Conclusions

Further research is needed to explore predictors and contextual factors of why IPV survivors seek mental healthcare, or not. Policy implications include the need to eliminate IPV and mental health stigma; develop accessible mental health services and effective treatment approaches.
Effectiveness and safety of treat-to-target strategy for methotrexate-naïve rheumatoid arthritis patients >75 years of age
Authors: Matsumoto Takumi , Sugihara Takahiko , Hosoya Tadashi , Ishizaki Tatsuro , Kubo Kanae , Kamiya Mari , Baba Hiroyuki , Tsuchida Marina , Hirano Fumio , Kojima Masayo , Miyasaka Nobuyuki , Harigai Masayoshi
Published: February 2024

Objectives

To identify differences in effectiveness and safety of a treat-to-target (T2T) strategy comparing late-onset MTX-naïve RA patients (LORA) ≥75 or <75 years of age.

Methods

Treatment was adjusted to target low disease activity with conventional synthetic DMARDs followed by biologic DMARDs (bDMARDs) in LORA ≥75 years (n = 98, mean age 80.0 years) and LORA <75 years (n = 99) with moderate–high disease activity. Achievement of Simplified Disease Activity Index (SDAI) remission at week 156 by non-responder imputation analysis was evaluated as a primary outcome.

Results

LORA ≥75 years had more comorbidities than LORA <75 years, but SDAI and ACPA positivity were similar at baseline. Of the LORA ≥75 years, 70.4% started MTX and 34.1% and 37.1% received a bDMARD at week 52 and 156, respectively (very similar to the LORA <75 years). Glucocorticoid use was more frequent in the LORA ≥75 years than in the LORA <75 years. Comorbidities/adverse events more frequently contributed to the reasons for non-adherence to T2T in the LORA ≥75 than in the LORA <75. At week 156, 32.7% of the LORA ≥75 and 66.7% of the LORA <75 achieved SDAI remission (P < 0.001). The cumulative incidence of serious adverse events (SAEs) over 156 weeks was 42.8% in the LORA ≥75 and 22.1% in the LORA <75. Multivariable analysis indicated an increased risk of SDAI non-remission at week 156 in the LORA ≥75 [odds ratio 2.82 (95% CI 1.29. 6.14)] after adjusting for comorbidities at baseline, non-adherence to T2T and SAEs.

Conclusions

It was more difficult to achieve remission in the LORA ≥75 patients than in the LORA <75 patients due to both poor treatment response and safety issues.
Microbiome-friendly PS/PVP electrospun fibrous membrane with antibiofilm properties for dental engineering
Authors: Chen Jiamin , Guo Jia , Lu Xueyun , Yin Derong , Zhou Cuisong , Li Yuqing , Zhou Xuedong
Published: February 2024

Dental caries is one of the most prevalent and biofilm-associated oral diseases in humans. Streptococcus mutans, with a high ability to form biofilms by adhering to hard surfaces, has been established as an important etiological agent for dental caries. Therefore, it is crucial to find a way to prevent the formation of cariogenic biofilm. Here, we report an electrospun fibrous membrane that could inhibit the adhesion and biofilm formation of S. mutans. Also, the polystyrene (PS)/polyvinyl pyrrolidone (PVP) electrospun fibrous membrane altered the 3D biofilm architecture and decreased water-insoluble extracellular polysaccharide production. Notably, the anti-adhesion mechanism which laid in Coulomb repulsion between the negatively charged PS/PVP electrospun fibrous membrane and S. mutans was detected by zeta potential. Furthermore, metagenomics sequencing analysis and CCK-8 assay indicated that PS/PVP electrospun fibrous membrane was microbiome-friendly and displayed no influence on the cell viability of human gingival epithelial cells and human oral keratinocytes. Moreover, an in vitro simulation experiment demonstrated that PS/PVP electrospun fibrous membrane could decrease colony-forming unit counts of S. mutans effectively, and PS/PVP electrospun fibrous membrane carrying calcium fluoride displayed better anti-adhesion ability than that of PS/PVP electrospun fibrous membrane alone. Collectively, this research showed that the PS/PVP electrospun fibrous membrane has potential applications in controlling and preventing dental caries.
3D printing sequentially strengthening high-strength natural polymer hydrogel bilayer scaffold for cornea regeneration
Authors: Nie Xiongfeng , Tang Yong , Wu Tengling , Zhao Xinrui , Xu Ziyang , Yang Rong , Sun Yage , Wu Bin , Han Quanhong , Hui Jingwen , Liu Wenguang
Published: February 2024

3D printing of high-strength natural polymer biodegradable hydrogel scaffolds simultaneously resembling the biomechanics of corneal tissue and facilitating tissue regeneration remains a huge challenge due to the inherent brittleness of natural polymer hydrogels and the demanding requirements of printing. Herein, concentrated aqueous solutions of gelatin and carbohydrazide-modified alginate (Gel/Alg-CDH) are blended to form a natural polymer hydrogel ink, where the hydrazides in Alg-CDH are found to form strong hydrogen bonds with the gelatin. The hydrogen-bonding-strengthened Gel/Alg-CDH hydrogel demonstrates an appropriate thickened viscosity and shear thinning for extrusion printing. The strong hydrogen bonds contribute to remarkably increased mechanical properties of Gel/Alg-CDH hydrogel with a maximum elongation of over 400%. In addition, sequentially Ca2+-physical crosslinking and then moderately chemical crosslinking significantly enhance the mechanical properties of Gel/Alg-CDH hydrogels that ultimately exhibit an intriguing J-shaped stress–strain curve (tensile strength of 1.068 MPa and the toughness of 677.6 kJ/m2). The dually crosslinked Gel-Alg-CDH-Ca2+-EDC hydrogels demonstrate a high transparency, physiological swelling stability and rapid enzymatic degradability, as well as suturability. The growth factor and drug-loaded biomimetic bilayer hydrogel scaffold are customized via a multi-nozzle printing system. This bioactive bilayer hydrogel scaffold considerably promotes regeneration of corneal epithelium and stroma and inhibits cornea scarring in rabbit cornea keratoplasty.
Lung imaging patterns in connective tissue disease–associated interstitial lung disease impact prognosis and immunosuppression response
Authors: Zheng Boyang , Marinescu Daniel-Costin , Hague Cameron J , Muller Nestor L , Murphy Darra , Churg Andrew , Wright Joanne L , Al-Arnawoot Amna , Bilawich Ana-Maria , Bourgouin Patrick , Cox Gerard , Durand Celine , Elliot Tracy , Ellis Jennifer , Fisher Jolene H , Fladeland Derek , Grant-Orser Amanda , Goobie Gillian C , Guenther Zachary , Haider Ehsan , Hambly Nathan , Huynh James , Johannson Kerri A , Karjala Geoffrey , Khalil Nasreen , Kolb Martin , Leipsic Jonathon , Lok Stacey D , MacIsaac Sarah , McInnis Micheal , Manganas Helene , Marcoux Veronica , Mayo John , Morisset Julie , Scallan Ciaran , Sedlic Tony , Shapera Shane , Sun Kelly , Tan Victoria , Wong Alyson W , Ryerson Christopher J
Published: February 2024

Objectives

Interstitial lung disease (ILD) in CTDs has highly variable morphology. We aimed to identify imaging features and their impact on ILD progression, mortality, and immunosuppression response.

Methods

Patients with CTD-ILD had high-resolution chest CT (HRCT) reviewed by expert radiologists blinded to clinical data for overall imaging pattern [usual interstitial pneumonia (UIP); non-specific interstitial pneumonia (NSIP); organizing pneumonia (OP); fibrotic hypersensitivity pneumonitis (fHP); and other]. Transplant-free survival and change in percent-predicted forced vital capacity (FVC) were compared using Cox and linear mixed-effects models adjusted for age, sex, smoking, and baseline FVC. FVC decline after immunosuppression was compared with pre-treatment.

Results

Among 645 CTD-ILD patients, the most frequent CTDs were SSc (n = 215), RA (n = 127), and inflammatory myopathies (n = 100). NSIP was the most common pattern (54%), followed by UIP (20%), fHP (9%), and OP (5%). Compared with the case for patients with UIP, FVC decline was slower in patients with NSIP (by 1.1%/year, 95% CI 0.2, 1.9) or OP (by 3.5%/year, 95% CI 2.0, 4.9), and mortality was lower in patients with NSIP [hazard ratio (HR) 0.65, 95% CI 0.45, 0.93] or OP (HR 0.18, 95% CI 0.05, 0.57), but higher in fHP (HR 1.58, 95% CI 1.01, 2.40). The extent of fibrosis also predicted FVC decline and mortality. After immunosuppression, FVC decline was slower compared with pre-treatment in NSIP (by 2.1%/year, 95% CI 1.4, 2.8), with no change for UIP or fHP.

Conclusion

Multiple radiologic patterns are possible in CTD-ILD, including a fHP pattern. NSIP and OP were associated with better outcomes and response to immunosuppression, while fHP had worse survival compared with UIP.
The problem of calculating the prevalence of sexual dysfunction: a meta-analysis attending gender
Authors: Ramírez-Santos Javier , Cristóbal-Cañadas Delia , Parron-Carreño Tesifón , Lozano-Paniagua David , Nievas-Soriano Bruno José
Published: February 2024

Introduction

Sexuality is an integral part of human health, and sexual dysfunctions are prevalent issues that affect men and women. While reviews on sexual dysfunctions in various diseases have been conducted, overall data are scarce.

Objectives

To update the overall prevalence of sexual dysfunctions from available prevalence studies on both sexes.

Methods

We used a 2-phase selection process to include cross-sectional studies that were conducted on the adult population and published between 2017 and 2022. The extracted data were prevalence, methodology, sample size, and location. Sensitivity and subgroup analyses were conducted to assess heterogeneity.

Results

This review analyzed 4407 studies. Twenty-three met the established criteria: 9 on the male population and 14 on the female population. The meta-analysis included 7 articles on males and 13 on females. The prevalence of sexual dysfunction was 31% in men and 41% in women, with significant heterogeneity among the studies. Sociocultural differences and use of varying measurement methods were identified as the main factors contributing to heterogeneity. Subgroup analysis revealed decreased heterogeneity among studies that used the Female Sexual Function Index as a diagnostic tool for females.

Conclusions

The review highlights the notable variability in results due to methodological and geographic variations. Therefore, enhancing the training of professionals and standardizing the recording of patient data—through the Female Sexual Function Index and Male Sexual Health Questionnaire or by developing new ones for this purpose—could improve the consistency of research on sexual health.
What contributes to promote sexual health in cancer palliative care? A realist review
Authors: Donz Roxane , Russia Bruno , Barbaret Cécile , Braybrook Debbie , Perceau-Chambard Elise , Reverdy Thibaut , Economos Guillaume
Published: February 2024

Introduction

Sexuality is an important determinant of the overall health of a population and remains so at the end of life and in patients with advanced cancers. Despite the abundant literature on sexuality and intimacy, these topics have been rarely discussed in the context of cancer palliative care, and very few interventions to promote sexual health in patients undergoing cancer palliative care have been explored.

Objectives

In this study we sought to identify which factors and mechanisms contribute to promoting sexual health in cancer palliative care.

Methods

A realist review was performed according to the guidelines of the realist and meta-narrative evidence synthesis method guidelines. Articles published between January 2010 and June 2021 were searched in 4 databases. Records were screened for their relevance regarding a predefined list of context–mechanism–outcome (CMO) configurations. Abstracts were independently screened by 2 authors before the data were extracted from the full-text articles selected for inclusion. With the use of abductive and retroductive reasoning techniques, each article was examined for evidence of its contribution to one of the CMO configurations, which could be refined when relevant. The data were summarized according to the final CMO configurations.

Results

Of the 2056 articles identified, 38 articles were included in the review. The data reported in these articles contributed to 7 CMO hypotheses: (1) improving communication skills, (2) healthcare provider training, (3) reorganizing the patient environment in care settings or at home, (4) managing sexual symptoms and also general symptoms, (5 and 6) patient-centered counseling or couple counseling, and (7) lifting the taboo.

Conclusions

The findings reported here highlight various ways to improve sexual health for patients in cancer palliative care but are limited to genital cancers. Further research should consider all types of cancer rather than being restricted to genital cancers.
Influence of particle size and origin of field peas on apparent ileal digestibility of starch and amino acids and standardized ileal digestibility of amino acids when fed to growing pigs
Authors: Ibagon Jimena A , Lee Su A , Nyachoti C Martin , Stein Hans H
Published: February 2024

The objective was to test the hypothesis that particle size and origin of field peas influence the apparent ileal digestibility (AID) of starch, crude protein (CP), and amino acids (AA) and the standardized ileal digestibility (SID) of AA. Three sources of field peas were procured. One source was from the United States and two sources were from Canada. The U.S. source and one of the sources from Canada (i.e., Canada 1) were each divided into two batches and ground to achieve a target particle size of 250 or 450 µm, whereas the other source from Canada (i.e., Canada 2) was only ground to a target particle size of 250 µm. Each batch of field peas was included in one diet as the only source of AA. An N-free diet was used to determine the basal endogenous losses of CP and AA. Six barrows (initial weight: 50.5 kg; SD = 3.7) that had a T-cannula installed in the distal ileum were randomly allotted to a 6 × 6 Latin square design with six diets and six 7-d periods. Ileal digesta from pigs were collected for 2 d after 5 d of adaptation. Data were analyzed using a statistical model that included batch of field peas as the fixed effect and animal and period as the random effects. Contrast statements were used to analyze the effects of particle size, origin, and the interaction between particle size and origin. Results indicated that the AID of starch was increased by reducing the particle size in the U.S. source of field peas, but that was not the case for the Canada 1 source (interaction; P < 0.001). Particle size did not influence the AID of CP or AA, but the Canada 2 source of field peas had greater (P < 0.05) AID of Trp, Ala, Cys, Gly, and Tyr than the field peas from the United States. The SID of CP and AA was also not affected by the particle size of field peas. The SID of CP and Trp was greater (P < 0.05), and the SID of His, Ile, and Thr tended (P < 0.10) to be greater in the Canada 2 source compared with the U.S. source, but no differences between the two Canada sources were observed. In conclusion, a few differences in SID of AA between field peas produced in the United States and peas produced in Canada were observed, but there was no effect on SID of AA of reducing the particle size of field peas from 450 to 250 µm, whereas the AID of starch increased by reducing the particle size only in the field peas from the United States.
Ecological and phylogenetic influences on limb joint kinematics in wild primates
Authors: Janisch Judith , McNamara Allison , Myers Lydia C , Schapker Nicole , Dunham Noah T , Phelps Taylor , Mundry Roger , Hieronymus Tobin , Shapiro Liza J , Young Jesse W
Published: February 2024

Arboreal locomotion is precarious and places multiple challenges upon stability. Studies have shown that captive primates respond to narrower and steeper supports by flexing limb joints and adopting a compliant gait. We tested whether these same kinematic responses are adopted by wild primates freely ranging over a variety of supports in their natural habitats. We recorded five species of platyrrhines, five species of catarrhines, and four species of strepsirrhines with modified GoPro cameras and used remote measurement to quantify substrate characteristics. Video images were imported into ImageJ to measure the angular kinematics of limb joints during quadrupedal locomotion on a variety of arboreal supports. We statistically tested for associations between joint posture and substrate characteristics, and then disentangled the influence of phylogeny and substrate on limb joint kinematics using variation partitioning and redundancy analysis. Our results partially confirm previous kinematic studies and suggest variation in support orientation, more than diameter or compliance, influences quadrupedal gait kinematics. Phylogenetic relatedness explained more variation in the data than substrate properties. This suggests primates either prospectively choose relatively ‘safe’ substrates for locomotion, or that they possess locomotor adaptations independent of limb joint kinematics per se to overcome the challenges of the precarious arboreal environment.
Plasmonic Enhancement of Protein Function
Authors: Locarno Marco , Dong Qiangrui , Meng Xin , Glessi Cristiano , Hettema Nynke Marije , Brandsma Nidas , Blokhuizen Sebbe , Garcia Alejandro Castañeda , Ganapathy Srividya , Post Marco , Schmidt Thieme , van Roemburg Lars , Xu Bing , Cho Chun-Ting , Laan Liedewij , Chien Miao-Ping , Brinks Daan
Published: February 2024

Plasmonic nanoparticles are key components in nanophotonics1–11and have applications in molecular detection and diagnostic platforms.12–14Coupling of dipoles to plasmonic antennas has allowed engineering of qualitatively altered behavior in isolated quantum systems,8,15but this promise has not been fulfilled in living systems, where the use of plasmonics is limited to tissue level applications of plasmonic particles as contrast agents16or heat sources.17Here we show that coupling to designed plasmonic nanoparticles can control the electrophysiological function of proteins in living cells. We designed nanostar geometries and achieved robust near-field coupling of these optimized nanoparticles to plasma membrane-localized Archaerhodopsin proteins. We enhanced the fluorescence of the coupled rhodopsins and increased their response speed to membrane voltage. We incorporated this plasmonic enhancement into a Markov chain photocycle model of the Archaerhodopsin mutant QuasAr6a, showing an increased fluorescence emission rate and manipulation of the protein dynamics through a combination of photocycle transition rate enhancements. These results represent the first scalable near-field coupling between plasmonic particles and fluorescent proteins in living cells. They show enhancement of protein function beyond what has been achievable through genetic engineering. This opens up a range of possibilities for engineering biological functionality through plasmonics.
Cortistatin exerts an immunomodulatory and neuroprotective role in a preclinical model of ischemic stroke
Authors: Castillo-González J , Buscemi L , Vargas-Rodríguez P , Serrano-Martínez I , Forte-Lago I , Price M , Hernández-Cortés P , Hirt L , González-Rey E
Published: February 2024

Ischemic stroke is the result of a permanent or transient occlusion of a brain artery, leading to irreversible tissue injury and long-term sequelae. Despite ongoing advancements in revascularization techniques, stroke remains the second leading cause of death worldwide. A comprehensive understanding of the complex and interconnected mechanisms, along with the endogenous mediators that modulate stroke responses is essential for the development of effective interventions. Our study investigates cortistatin, a neuropeptide extensively distributed in the immune and central nervous systems, known for its immunomodulatory properties. With neuroinflammation and peripheral immune deregulation as key pathological features of brain ischemia, cortistatin emerges as a promising therapeutic candidate. To this aim, we evaluated its potential effect in a well-established middle cerebral artery occlusion (MCAO) preclinical stroke model. Our findings indicate that the peripheral administration of cortistatin at 24 hours post-stroke significantly reduces neurological damage and enhances recovery. Importantly, cortistatin-induced neuroprotection was multitargeted, as it modulated the glial reactivity and astrocytic scar formation, facilitated blood-brain barrier recovery, and regulated local and systemic immune dysfunction. Surprisingly, administration of cortistatin at immediate and early post-stroke time points proved to be not beneficial and even detrimental. These results emphasize the importance of understanding the spatio-temporal dynamics of stroke pathology to develop innovative therapeutic strategies. Premature interruption of certain neuroinflammatory processes might inadvertently compromise neuroprotective mechanisms. In summary, our study highlights cortistatin as a novel pleiotropic therapeutic approach against ischemic stroke, offering new treatment options for patients for whom early revascularization intervention is unsuccessful.

Graphical abstract
ABCC10 roles in plant development and the transport of indole-3-butyric acid
Authors: Homayouni Arielle L. , Damodaran Suresh , Schreiber Katherine , Michniewicz Marta , Gunther Lauren K. , Strader Lucia C.
Published: February 2024

Proper spatiotemporal distribution of the phytohormone auxin throughout plant tissues mediates a variety of developmental processes. Auxin levels are tightly regulated viade novosynthesis, transport, and conversion from its conjugated forms and precursors. These levels can be regulated through conversion of the auxin precursor, indole 3-butyric acid (IBA), into the active auxin, indole-3-acetic acid (IAA), in a peroxisomal β-oxidation process. Defects in IBA-to-IAA conversion cause multiple developmental defects in Arabidopsis, demonstrating IBA-derived IAA is physiologically important to the active auxin pool. Similar to IAA, transport of IBA modulates development. However, the mechanisms governing transport of this molecule remain largely unknown. Here, we identify a mutation in theABCC10gene of Arabidopsis that suppresses theabcg36hypersensitivity to IBA and its synthetic analog, 2,4-dichlorophenoxy butyric acid (2,4-DB) and theabcg36hyperaccumulation of [3H]-IBA. We found that ABCC10 acts as a direct vacuolar transporter of IBA. Further,ABCC10is necessary for proper development of the root apical meristem and leaf tissue. Our findings uncover a previously uncharacterized method of IBA transport that regulates aspects of plant development.
The intensity of supplementary feeding in an urban environment impacts overwintering MallardsAnas platyrchynhosas wintering conditions get harsher
Authors: Witkowska Marta , Wesołowski Wojciech , Markiewicz Martyna , Pakizer Jonasz , Neumann Julia , Ożarowska Agnieszka , Meissner Włodzimierz
Published: February 2024

Although urbanization poses various threats to avifauna, some bird species, including Mallards, are attracted to towns and cities as their winter habitats due to favourable temperatures and abundant anthropogenic food. In this study, we investigated how population dynamics changed in relation to winter harshness and intensity of supplementary feeding. The results indicated that the number of Mallards increased with the feeding intensity but the pattern differed in response to worsening of wintering conditions on water bodies with distinct supplementary feeding intensity. The ponds with low feeding intensity were occupied by fewer but more stable populations, suggesting the presence of natural food resources there, available for small number of individuals, regardless of winter conditions. On the ponds with medium feeding intensity, we observed a bell-shaped relationship between the number of ducks and ice cover. Unpredictable anthropogenic food on those ponds might not provide sufficient food resources, forcing birds to relocate when wintering conditions worsen. In such conditions, the ponds with a high feeding intensity attracted more ducks. We demonstrated that the wintering population of Mallards in urban areas is not solely influenced by ambient temperature but is also significantly affected by the intensity of supplementary feeding.
TheXanthomonas fragariaeeffector XopK suppresses stomatal immunity by perturbing abscisic acid accumulation and signaling pathways in strawberry
Authors: Cai Xiao-lin , Zhang Wenyao , Yu Haiyan , Wen Ying-qiang , Feng Jia-yue
Published: February 2024

Xanthomonas fragariae(Xaf) usually causes angular leaf spot (ALS) in strawberry all over the world. Recently, we isolated a new strain ofXafcalledXafYL19. This strain causes not only typical ALS symptoms, but also dry cavity rot in the crown tissues of strawberries. This was the first time aXafstrain had both of these effects in strawberries. Pathogen effectors play a crucial role in plant colonization and infection. Understanding how effector proteins escape from plant surveillance is important for plant breeding and resistance deployment. In this study, thirty-three putative effectors were predicted inXafYL19, and a virulent secreted effector called XopK was identified. XopK has a robust capacity for suppressing plant cell death and transcript response to infection host. Transgenic strawberries expressing XopK exhibit more susceptibility toXafYL19, and this was associated with weakened stomatal immunity. Additionally abscisic acid (ABA) accumulation and signaling were mainly suppressed in the presence of XopK. XopK also inhibited ABA- and methyl jasmonate (MeJA)-induced stomatal closure, and ABA- but not MeJA-induced reactive oxygen species (ROS) production. Moreover, endogenous ABA is critical forXaf-induced ROS burst and stomatal closure. These results suggested thatXafYL19 uses XopK to suppress JA, especially ABA signaling, for disrupting stomatal closure, and allowing its colonization for disease development. Taken together, our results provide a novel virulent mechanism byXafand an available strategy for resistant breeding in strawberries.
Enhancing Portability of Trans-Ancestral Polygenic Risk Scores through Tissue-Specific Functional Genomic Data Integration
Authors: Crone Bradley , Boyle Alan P.
Published: February 2024

Portability of trans-ancestral polygenic risk scores is often confounded by differences in linkage disequilibrium and genetic architecture between ancestries. Recent literature has shown that prioritizing GWAS SNPs with functional genomic evidence over strong association signals can improve model portability. We leveraged three RegulomeDB-derived functional regulatory annotations - SURF, TURF, and TLand - to construct polygenic risk models across a set of quantitative and binary traits highlighting functional mutations tagged by trait-associated tissue annotations. Tissue-specific prioritization by TURF and TLand provide a significant improvement in model accuracy over standard polygenic risk score (PRS) models across all traits. We developed the Trans-ancestral Iterative Tissue Refinement (TITR) algorithm to construct PRS models that prioritize functional mutations across multiple trait-implicated tissues. TITR-constructed PRS models show increased predictive accuracy over single tissue prioritization. This indicates our TITR approach captures a more comprehensive view of regulatory systems across implicated tissues that contribute to variance in trait expression.
Internal structure ofMycoplasma mobilegliding machinery analyzed by negative staining electron tomography
Authors: Fukushima Minoru , Toyonaga Takuma , Tahara Yuhei O. , Nakane Daisuke , Miyata Makoto
Published: February 2024

Mycoplasma mobileis a parasitic bacterium that forms gliding machinery on the cell pole and glides on a solid surface in the direction of the cell pole. The gliding machinery consists of both internal and surface structures. The internal structure is divided into a bell at the front and chain structure extending from the bell. In this study, the internal structures prepared under several conditions were analyzed using negative-staining electron microscopy and electron tomography. The chains were constructed by linked motors containing two complexes similar to ATP synthase. A cylindrical spacer with a maximum diameter of 6 nm and a height of 13 nm, and anonymous linkers with a diameter of 0.9–8.3 nm and length of 5–30 nm were found between motors. The bell is bowl-shaped and features a honeycomb surface with a periodicity of 8.4 nm. The chains of the motor are connected to the rim of the bell through a wedge-shaped structure. These structures may play roles in the assembly and cooperation of gliding machinery units.

Significance

Mycoplasma mobile, a parasitic bacterium, glides on solid surfaces at speeds of up to 4.0 μm per second through a specialized mechanism. The gliding machinery, located at one pole of the cell, is composed of surface legs and internal motor structures. The force generation unit within the internal structure evolved from ATP synthase. This study aimed to clarify the entire architecture of the gliding machinery using electron tomography.
Minimum Effective Dose of Clemastine in a Mouse Model of Preterm White Matter Injury
Authors: Odell Elizabeth , Jabassini Nora , Schniedewind Björn , Pease-Raissi Sarah E. , Frymoyer Adam , Christians Uwe , Green Ari J. , Chan Jonah R. , Ostrem Bridget E.L.
Published: February 2024

Background

Preterm white matter injury (PWMI) is the most common cause of brain injury in premature neonates. PWMI involves a differentiation arrest of oligodendrocytes, the myelinating cells of the central nervous system. Clemastine was previously shown to induce oligodendrocyte differentiation and myelination in mouse models of PWMI at a dose of 10 mg/kg/day. The minimum effective dose (MED) of clemastine is unknown. Identification if the MED is essential for maximizing safety and efficacy in neonatal clinical trials. We hypothesized that the MED in neonatal mice is lower than 10 mg/kg/day.

Methods

Mouse pups were exposed to normoxia or hypoxia (10% FiO2) from postnatal day 3 (P3) through P10. Vehicle or clemastine fumarate at one of four doses (0.5, 2, 7.5 or 10 mg/kg/day) was given orally to hypoxia-exposed pups. At P14, myelination was assessed by immunohistochemistry and electron microscopy to determine the MED. Clemastine pharmacokinetics were evaluated at steady-state on day 8 of treatment.

Results

Clemastine rescued hypoxia-induced hypomyelination with a MED of 7.5 mg/kg/day. Pharmacokinetic analysis of the MED revealed Cmax44.0 ng/mL, t1/24.6 hours, and AUC24280.1 ng*hr/mL.

Conclusion

Based on these results, myelination-promoting exposures should be achievable with oral doses of clemastine in neonates with PWMI.

Key Points

Preterm white matter injury (PWMI) is the most common cause of brain injury and cerebral palsy in premature neonates.

Clemastine, an FDA-approved antihistamine, was recently identified to strongly promote myelination in a mouse model of PWMI and is a possible treatment.

The minimum effective dose in neonatal rodents is unknown and is critical for guiding dose selection and balancing efficacy with toxicity in future clinical trials.

We identified the minimum effective dose of clemastine and the associated pharmacokinetics in a murine chronic hypoxia model of PWMI, paving the way for a future clinical trial in human neonates.
ChineseEEG: A Chinese Linguistic Corpora EEG Dataset for Semantic Alignment and Neural Decoding
Authors: Mou Xinyu , He Cuilin , Tan Liwei , Yu Junjie , Liang Huadong , Zhang Jianyu , Yan Tian , Yang Yu-Fang , Xu Ting , Wang Qing , Cao Miao , Chen Zijiao , Hu Chuan-Peng , Wang Xindi , Liu Quanying , Wu Haiyan
Published: February 2024

An Electroencephalography (EEG) dataset utilizing rich text stimuli can advance the understanding of how the brain encodes semantic information and contribute to semantic decoding in brain-computer interface (BCI). Addressing the scarcity of EEG datasets featuring Chinese linguistic stimuli, we present the ChineseEEG dataset, a high-density EEG dataset complemented by simultaneous eye-tracking recordings. This dataset was compiled while 10 participants silently read approximately 11 hours of Chinese text from two well-known novels. This dataset provides long-duration EEG recordings, along with pre-processed EEG sensor-level data and semantic embeddings of reading materials extracted by a pre-trained natural language processing (NLP) model. As a pilot EEG dataset derived from natural Chinese linguistic stimuli, ChineseEEG can significantly support research across neuroscience, NLP, and linguistics. It establishes a benchmark dataset for Chinese semantic decoding, aids in the development of BCIs, and facilitates the exploration of alignment between large language models and human cognitive processes. It can also aid research into the brain’s mechanisms of language processing within the context of the Chinese natural language.
Resource or slot model in visual working memory: Are they different?
Authors: Hojjati Fatemeh , Motahharynia Ali , Adibi Armin , Adibi Iman , Sanayei Mehdi
Published: February 2024

When studying the working memory (WM), the ‘slot model’ and the ‘resource model’ are two main theories used to describe how information retention occurs. The slot model shows that WM capacity consists of a certain number of predefined slots available for information storage. This theory explains that there is a binary condition during information recall in which information is either wholly maintained within a slot or forgotten. The resource model gives a resolution-based approach defining a continuous resource able to be distributed among an unlimited number of items in the WM capacity. With newer hybrid models suggesting that WM may not strictly conform to one model, this study aimed to understand the relationship between the original models. By implementing correlational assessments of subjects’ performances in two different psychophysics tasks (analog recall paradigm with sequential bar presentation and delayed match-to-sample task (DMS) with checkerboard stimuli which are representative for resource and slot models, respectively), our study revealed significant correlations between WM performance (measured by DMS tasks) with recall error, precision, and sources of error (measured by sequential paradigm). Overall, the findings emphasize the importance of considering both models in understanding WM processes, shedding light on the debate between slot and resource models by demonstrating overlap in elements of both models.
Cryo-EM structure of a conjugative T4SS identifies a molecular switch regulating pilus biogenesis
Authors: Macé Kévin , Waksman Gabriel
Published: February 2024

Conjugative Type IV Secretion Systems (T4SS) mediate bacterial conjugation, a process that enables the unidirectional exchange of genetic materials between a donor and a recipient bacterial cell. Bacterial conjugation is the primary means by which antibiotic resistance genes spread among bacterial populations (Barlow, 2009; Virolleet al, 2020). Conjugative T4SSs elaborate a long extracellular filament, termed “pilus” to connect with the recipient cell. Previously, we solved the cryo-EM structure of a conjugative T4SS. In this article, based on additional data, we present a more complete T4SS cryo-EM structure than that published earlier. Novel structural features include details of the mismatch symmetry within the OMCC, the presence of a 4thVirB8 subunit in the asymmetric unit of both the Arches and the IMC, and a hydrophobic VirB5 tip in the distal end of the stalk. However, more significantly, we provide previously-undescribed structural insights into the protein VirB10 and identify a novel regulation mechanism of T4SS-mediated pilus biogenesis by this protein, that we believe is a key checkpoint for this process.
Ungulate substrate use in fauna passages
Authors: Helldin Jan Olof , Niemi Milla
Published: February 2024

Fauna passages are increasingly constructed at major roads and railways to mitigate the negative effects of infrastructure and traffic on wildlife. The function of such passages depends on design, including the construction materials, soil and vegetation. Providing “naturalness” in fauna passages may entail significant costs, yet its benefits are unclear. By using camera trap data, we examined ungulate substrate use in seven passages serving both fauna and local roads (overpasses) and fauna and watercourses (underpasses) in boreal Sweden and Finland. While all substrates were used, during snow-free periods, ungulates used smoother surfaces (fine-grained topsoil, grass, artificial fiber mat, and dirt road) more than expected based on their availability. Coarser surface (stony/rocky ground), shrub, and water were used less than expected. The results for road and water were, however, inconsistent between passages; in one overpass road was instead used less than expected, and in one underpass the water section was used particularly during winter but also by moose wading or swimming through in summer and autumn. General patterns of use largely remained when analysed byspecies, although sample sizes were limited. Despite limitations, our study offers valuable insights for planning and constructing fauna passages. To our knowledge, this study was the first of its kind describing how ungulates use different substrates in fauna passages. We suggest to conduct further research on this issue, for example by more detailed study of animal trajectories through passages and by experimental modification of substrates.
Heat Conduction Simulation of Chondrocyte-Embedded Agarose Gels Suggests Negligible Impact of Viscoelastic Dissipation on Temperature Change
Authors: Myers Erik , Piazza Molly , Owkes Mark , June Ronald K.
Published: February 2024

Agarose is commonly used for 3D cell culture and to mimic the stiffness of the pericellular matrix of articular chondrocytes. Although it is known that both temperature and mechanical stimulation affect the metabolism of chondrocytes, little is known about the thermal properties of agarose hydrogels. Thermal properties of agarose are needed to analyze potential heat production by chondrocytes induced by various experimental stimuli (carbon source, cyclical compression, etc). Utilizing ASTM C177, a custom-built thermal conductivity measuring device was constructed and used to calculate the thermal conductivity of 4.5% low gelling temperature agarose hydrogels. Additionally, Differential Scanning Calorimetry was used to calculate the specific heat capacity of the agarose hydrogels. Testing of chondrocyte-embedded agarose hydrogels commonly occurs in Phosphate-Buffered Saline (PBS), and thermal analysis requires the free convection coefficient of PBS. This was calculated using a 2D heat conduction simulation within MATLAB in tandem with experimental data collected for known boundary and initial conditions. The specific heat capacity and thermal conductivity of 4.5% agarose hydrogels was calculated to be 2.85 J/g°C and 0.121 W/mK, respectively. The free convection coefficient of PBS was calculated to be 1000.1 W/m2K. The values of specific heat capacity and thermal conductivity for agarose are similar to the reported values for articular cartilage, which are 3.20 J/g°C and 0.21 W/mK (Moghadam, et al. 2014). This suggests that in addition to 4.5% agarose hydrogels mimicking the physiological stiffness of the cartilage PCM, they can also mimic the thermal properties of articular cartilage forin vitrostudies.
The Memorability of Voices is Predictable and Consistent across Listeners
Authors: Revsine Cambria , Goldberg Esther , Bainbridge Wilma A.
Published: February 2024

Memorability, the likelihood that a stimulus is remembered, is an intrinsic stimulus property that is highly consistent across people—participants tend to remember and forget the same faces, objects, and more. However, these consistencies in memory have thus far only been observed for visual stimuli. We provide the first study of auditory memorability, collecting recognition memory scores from over 3000 participants listening to a sequence of different speakers saying the same sentence. We found significant consistency across participants in their memory for voice clips and for speakers across different utterances. Next, we tested regression models incorporating both low-level (e.g., fundamental frequency) and high-level (e.g., dialect) voice properties to predict their memorability. These models were significantly predictive, and cross-validated out-of-sample, supporting an inherent memorability of speakers’ voices. These results provide the first evidence that listeners are similar in the voices they remember, which can be reliably predicted by quantifiable voice features.
Karyotype Description and Comparative Chromosomal Mapping of 5S rDNA in 21 species
Authors: Luo Xiaomei , Liu Yunke , Gong Xiao , Ye Meng , Xiao Qiangang , Zeng Zhen
Published: February 2024

5S rDNA is essential component of all cell types. A survey was conducted to study the 5S rDNA site number, position, and origin of signal pattern diversity in 64 plants using fluorescencein situhybridization. The species used for this experiment were chosen due to the discovery of karyotype rearrangement, and for species checked in which 5S rDNA has not yet been explored. The chromosome number was 14–160, while the chromosome length was 0.63–6.88 μm, with 37 plants (58%) had small chromosome (<3 μm). The chromosome numbers of three species and 5S rDNA loci of 19 species have been reported for the first time. 5S rDNA was varied and abundant in signal site number (2–18), position (e.g., interstitial, distal, and proximal position, occasionally, outside chromosome), and even as intense (e.g., strong, weak, and slight). Our results exposed modifiability in the number and location of 5S rDNA in 33 plants and demonstrated an extensive stable number and location of 5S rDNA in 31 plants. The potential origin of signal pattern diversity was probably caused by chromosome rearrangement (e.g., deletion, duplication, inversion, translocation), polyploidization, self-incompatibility, and chromosome satellites. These data characterized the variability of 5S rDNA within the karyotypes of the 64 plants that exhibited massive chromosomal rearrangements and provided anchor points for genetic physical maps. These data prove the utility of the 5S rDNA oligonucleotide as a chromosome marker in identifying plant chromosomes. This method provides a basis for developing similar applications for cytogenetic analysis in other species.

Article Summary

A survey was exploited to study 5S rDNA signal pattern diversity in 64 plants by FISH. The chromosome number of three species and 5S rDNA loci of 19 species have been reported by the first time. 5S rDNA was really rather various and abundant in signal site number (2–18), position (interstitial, distal, proximal position, occasionally, outside chromosome), even as the intense (strong, week, slight). These data prove the utility of 5S rDNA oligonucleotide as chromosome marker in identifying plant chromosomes.
Global neural encoding of model-free and inference-based strategies in mice
Authors: Wang Shuo , Gao Huayi , Ishizu Kotaro , Funamizu Akihiro
Published: February 2024

When a simple model-free strategy does not provide sufficient outcomes, an inference-based strategy estimating a hidden task structure becomes essential for optimizing choices. However, the neural circuitry involved in inference-based strategies is still unclear. We developed a tone frequency discrimination task in head-fixed mice in which the tone category of the current trial depended on the category of the previous trial. When the tone category was repeated every trial, the mice continued to use the default model-free strategy, as well as when tone was randomly presented, to bias the choices. In contrast, the default strategy gradually shifted to an inference-based strategy when the tone category was alternated in each trial. Brain-wide electrophysiological recording during the overtrained phase suggested that the neural activity of the frontal and sensory cortices, hippocampus, and striatum was correlated with the reward expectation of both the model-free and inference-based strategies. These results suggest the global encoding of multiple strategies in the brain.
Single-molecule observations of human small heat shock proteins in complex with aggregation-prone client proteins
Authors: Rice Lauren , Marzano Nicholas , Cox Dezerae , van Oijen Antoine , Ecroyd Heath
Published: February 2024

Small heat shock proteins (sHsps) are molecular chaperones that act to prevent the aberrant aggregation of misfolded proteins. Whilst it is widely suggested that sHsps prevent aggregation by binding to misfolded client proteins, the dynamic and heterogeneous nature of sHsps has hindered attempts to establish the mechanistic details of how sHsp-client protein complexes form. Single-molecule approaches have emerged as a powerful tool to investigate dynamic and heterogeneous interactions such as those that can occur between sHsps and their client proteins. Here, we use total internal reflection fluorescence microscopy to observe and characterise the complexes formed between model aggregation-prone client proteins [firefly luciferase (FLUC), rhodanese, and chloride intracellular channel 1 protein (CLIC)], and the human sHsps αB-crystallin (αB-c; HSPB1) and Hsp27 (HSPB5). We show that small (monomeric or dimeric) forms of both αB-c and Hsp27 bind to misfolded or oligomeric forms of the client proteins at early stages of aggregation, resulting in the formation of soluble sHsp-client complexes. Stoichiometric analysis of these complexes revealed that additional αB-c subunits accumulate onto pre-existing sHsp-client complexes to form larger species - this does not occur to the same extent for Hsp27. Instead, Hsp27-client interactions tend to be more transient than those of αB-c. Elucidating these mechanisms of sHsp function is crucial to our understanding of how these molecular chaperones act to inhibit protein aggregation and maintain cellular proteostasis.