bluuebunny/crossref_metadata_2025 huggingface dataset:
The German version of the Oxford Cognitive Screen (D‐OCS): Normative data and validation in acute stroke and a mixed neurological sample
Authors: Bormann Tobias , Kaller Christoph P. , Kulyk Caterina , Demeyere Nele , Weiller Cornelius
Published: January 2024

Given the frequency of stroke worldwide, tools for neuropsychological assessment of patients with acute stroke are needed to identify cognitive impairments, guide rehabilitation efforts and allow for a prognosis of outcome. However, requirements for assessment tools for acute cognitive deficits differ substantially from tests for chronic neuropsychological impairments and screening tools for suspected dementia. The Oxford Cognitive Screen (OCS) has been developed as a quick to administer neurocognitive screening for acute neurological patients providing information on various cognitive domains. It is available in different languages. The present study reports cut‐off scores, parallel‐test reliability and concurrent validity of the German version (D‐OCS). Following standardized language adaptation and translation, the D‐OCS was administered to 100 healthy individuals to generate cut‐off scores (5th percentile). Subsequently, 88 neurological patients were assessed with both versions of the D‐OCS as well as other tests to evaluate reliability and validity of the D‐OCS subscales. In a further study, the D‐OCS was compared to the MoCA test in 65 acute stroke patients revealing comparable sensitivity but also differences between both tools. The cut‐off scores were comparable to other international versions of the OCS. Intraclass correlations were highly significant and document reliability of the D‐OCS subtests. Scores on subtests correlated significantly with independent tests securing validity. Comparison with the MoCA revealed comparable sensitivity and specificity. The D‐OCS is a reliable and valid assessment tool well suited for patients with acute stroke. Differences to the MoCA test are discussed.
Role of melanocortin system in the locomotor activity rhythms and melatonin secretion as revealed by agouti‐signalling protein (asip1) overexpression in zebrafish
Authors: Godino‐Gimeno Alejandra , Leal Esther , Chivite Mauro , Tormos Elisabeth , Rotllant Josep , Vallone Daniela , Foulkes Nicholas S. , Míguez Jesús M. , Cerdá‐Reverter Jose Miguel
Published: January 2024

Temporal signals such as light and temperature cycles profoundly modulate animal physiology and behaviour. Via endogenous timing mechanisms which are regulated by these signals, organisms can anticipate cyclic environmental changes and thereby enhance their fitness. The pineal gland in fish, through the secretion of melatonin, appears to play a critical role in the circadian system, most likely acting as an element of the circadian clock system. An important output of this circadian clock is the locomotor activity circadian rhythm which is adapted to the photoperiod and thus determines whether animals are diurnal or nocturnal. By using a genetically modified zebrafish strain known as Tg (Xla.Eef1a1:Cau.asip1)iim04, which expresses a higher level of the agouti signalling protein 1 (Asip1), an endogenous antagonist of the melanocortin system, we observed a complete disruption of locomotor activity patterns, which correlates with the ablation of the melatonin daily rhythm. Consistent with this, in vitro experiments also demonstrated that Asip1 inhibits melatonin secretion from the zebrafish pineal gland, most likely through the melanocortin receptors expressed in this gland. Asip1 overexpression also disrupted the expression of core clock genes, including per1a and clock1a, thus blunting circadian oscillation. Collectively, these results implicate the melanocortin system as playing an important role in modulating pineal physiology and, therefore, circadian organisation in zebrafish.
Chlorophyll‐a variation in response to precipitation in a tropical urban lake
Authors: Hamdhani Hamdhani , Sharaha Musyiir , Eppehimer Drew E. , Rizal Samsul
Published: January 2024

With increasing urbanization, urban lakes are becoming more common and serve as important flood control infrastructure, recreational uses, as well as habitat for a variety of biota. However, given their construction, function and location, urban lakes are susceptible to disturbances including stormwater runoff from metropolitan catchment areas. For example, nutrient loading from stormwater runoff can cause eutrophication. Chlorophyll‐a concentration is an important water quality parameter because it is used to assess water quality and determine trophic state. Chlorophyll‐a is known to be impacted by a number of environmental factors including precipitation and associated runoff. Previous studies indicate that the relationship between precipitation and chlorophyll‐a is complex and often site‐specific. In this study, we examined the relationship between chlorophyll‐a and precipitation in an urban, tropical lake located in East Kalimantan Province, Indonesia. From October through December 2022, chlorophyll‐a, turbidity, phosphate (PO4), pH, dissolved oxygen, temperature, total dissolved solids and conductivity were measured at five sampling sites in Air Hitam Lake, and precipitation was measured adjacent to the lake. These data indicated that chlorophyll‐a concentrations were negatively correlated with recent precipitation (r2 = .71, p < .05). This relationship was likely a result of dilution from increased lake volume. Although urban runoff is expected to increase nutrient loading, our monitoring indicated that dilution can mediate this process in the short‐term. Our findings suggest that timing matters when monitoring water quality in tropical, urban lakes. Sampling immediately following heavy precipitation and stormwater runoff can lead to an underestimation of normal chlorophyll‐a concentrations due to dilution. As a result, dilution effects should be examined when studying and managing urban lentic ecosystems with strong precipitation dynamics. Further studies are necessary to better understand these urban aquatic ecosystems to continue to improve future management efforts.
Community‐level post‐hazard functionality methodology for buildings exposed to floods
Authors: Nofal Omar , Rosenheim Nathanael , Kameshwar Sabarethinam , Patil Jayant , Zhou Xiangnan , van de Lindt John W. , Duenas‐Osorio Leonardo , Cha Eun Jeong , Endrami Amin , Sutley Elaina , Cutler Harvey , Lu Tao , Wang Chen , Jeon Hwayoung
Published: January 2024

This paper presents a building‐level post‐hazard functionality model for communities exposed to flood hazards including the interdependencies between the population, buildings, and infrastructure. An existing portfolio of building archetypes is used to model the post‐hazard physical flood functionality of different building typologies within the community with the goal of supporting resilience‐informed decision‐making. Specific fragility‐based flood functionality curves were developed for this portfolio to quantify the exceedance probability of a prescribed set of functionality states. While the physical functionality of buildings is significant to the total functionality of a building and community resilience assessment, the functionality of utilities such as power and water along with the accessibility of the household to essential services such as schools and hospitals is crucial to measure their total functionality. Therefore, functionality models for essential infrastructure were developed to assess housing unit‐ and building‐level functionality following flood hazards. This model also accounts for the functionality of the road network following a flood hazard to identify the level of accessibility of households to different services (e.g., schools, hospitals, gas stations, shopping centers, etc.). The main novelty of this paper is the ability to quantify the total functionality of buildings based on a socio‐physical formulation after including the interdependencies between the functionality of the physical systems and the subsequent functionality of the socio‐economic systems, which is key to measuring resilience at the community level. This was evident from the analysis results using a testbed community of Lumberton, NC, showing that the physical functionality is not sufficient to quantify the total post‐hazard functionality of buildings and that the functionality of other subsystems such as utilities and accessibility to essential services are also needed to quantify the total functionality of buildings and the livability of households.
Endoplasmic reticulum localized TMEM33 domain‐containing protein is crucial for all life cycle stages of the malaria parasite
Authors: Kamil Mohd , Kina Umit Yasar , Atmaca Habibe Nur , Unal Sinem , Deveci Gozde , Burak Pinar , Aly Ahmed S. I.
Published: January 2024

Endoplasmic reticulum (ER) plays a pivotal role in the regulation of stress responses in multiple eukaryotic cells. However, little is known about the effector mechanisms that regulate stress responses in ER of the malaria parasite. Herein, we aimed to identify the importance of a transmembrane protein 33 (TMEM33)‐domain‐containing protein in life cycle of the rodent malaria parasite Plasmodium berghei. TMEM33 is an ER membrane‐resident protein that is involved in regulating stress responses in various eukaryotic cells. A C‐terminal tagged TMEM33 was localized in the ER throughout the blood and mosquito stages of development. Targeted deletion of TMEM33 confirmed its importance for asexual blood stages and ookinete development, in addition to its essential role for sporozoite infectivity in the mammalian host. Pilot scale analysis shows that the loss of TMEM33 results in the initiation of ER stress response and induction of autophagy. Our findings conclude an important role of TMEM33 in the development of all life cycle stages of the malaria parasite, which indicates its potential as an antimalarial target.
Investigation of the relationship between spiritual care needs of relatives of patients hospitalized in intensive care unit and intensive care satisfaction in Turkey
Authors: Kaplan Ebubekir , Sir Özkan , Özakgül Aylin
Published: January 2024

Background

Relatives of patients admitted to the intensive care unit (ICU) play a crucial role in the care of their loved ones. After a patient's admission to the ICU, family members may be vulnerable to conditions such as depression, anxiety or post‐traumatic stress disorder, which can lead to moral concerns.

Aim

The aim of this study was to determine the relationship between the spiritual care needs of family members of patients hospitalized in the ICU and their satisfaction with the ICU.

Study Design

In this study, a cross‐sectional and correlational design was used. The study was conducted with 291 patient relatives who could be reached by face‐to‐face questionnaire. Data were collected using the ‘Personal Information Form’, ‘Family Satisfaction Scale in Intensive Care Unit (FS‐ICU‐24)’ and ‘Spiritual Care Needs Inventory’.

Results

Spiritual Care Needs Inventory (SCNI) total score was determined as 58.00 ± 15.91. The mean total score of FS‐ICU‐24 was 86.38 ± 7.12. No significant correlation was found between the mean SCNI total score and the FS‐ICU‐24 total score (r = .084; p > .05).

Conclusions

As a result of this research, it was determined that the spiritual care needs of the patients' relatives were at a medium level and their satisfaction with intensive care was high.

Relevance to Clinical Practice

Institutions should establish spiritual care support units for individuals with patients in ICUs and examine the effects of this on individuals.
Anatomical variation of femoral vessels and ultrasound‐guided femoral vein puncture for catheter ablation of arrhythmias
Authors: Guan Wenchi , Li Xiaofeng , Chen Keping , Yao Yan , Liu Jun
Published: January 2024

Objective

This study aims to investigate the anatomical variations in femoral vasculature and evaluate the clinical value of ultrasound‐guided femoral vein puncture in catheter ablation procedures.

Methods

In this retrospective analysis conducted from January 2023 to March 2023, we examined data from patients who underwent catheter ablation with ultrasound‐guided femoral venipuncture. We evaluated the anatomy of the femoral vasculature at both high and low inguinal levels. Based on the relationship between the femoral vein and artery, we classified the anatomy into four types: Type I (vein parallel to artery without overlap), Type II (vein medial to artery with lumen overlap ≤50%), Type III (vein posterior to artery with lumen overlap > 50%), and Type IV (vein lateral to artery). Additionally, we assessed procedure‐related vascular complications that required interventions or prolonged hospital stays.

Results

A total of 254 patients were included in this study. At the upper inguinal level, most cases (92.5%) exhibited Type II, followed by Type I (6.5%), while Type III (0.6%) and IV (0.4%) were less common. At the lower inguinal level, Type II accounted for 70.7%, there was a significantly higher proportion of Type III (23.4%) and Type IV (5.9%). The overall complication rate was 0.4%, no pseudoaneurysm or hematoma was observed in our study.

Conclusion

Our study revealed significant anatomical variations in the relationship between the femoral vein and femoral artery. Ultrasound‐guided femoral venipuncture significantly reduced vascular complication rate, making it a valuable tool for guiding puncture procedures.
The signalling pathways, calcineurin B‐like protein 5 (CBL5)‐CBL‐interacting protein kinase 8 (CIPK8)/CIPK24‐salt overly sensitive 1 (SOS1), transduce salt signals in seed germination in Arabidopsis
Authors: Xie Qing , Yin Xiaochang , Wang Yu , Qi Yuting , Pan Chengcai , Sulaymanov Sunnatulla , Qiu Quan‐Sheng , Zhou Yang , Jiang Xingyu
Published: January 2024

For plant growth under salt stress, sensing and transducing salt signals are central to cellular Na+ homoeostasis. The calcineurin B‐like protein (CBL)‐CBL‐interacting protein kinase (CIPK) complexes play critical roles in transducing salt signals in plants. Here, we show that CBL5, an ortholog of CBL4 and CBL10 in Arabidopsis, interacts with and recruits CIPK8/CIPK24 to the plasma membrane. Yeast cells coexpressing CBL5, CIPK8/CIPK24 and SOS1 demonstrated lesser Na+ accumulation and a better growth phenotype than the untransformed or SOS1 transgenic yeast cells under salinity. Overexpression of CBL5 improved the growth of the cipk8 or cipk24 single mutant but not the cipk8 cipk24 double mutant under salt stress, suggesting that CIPK8 and CIPK24 were the downstream targets of CBL5. Interestingly, seed germination in cbl5 was severely inhibited by NaCl, which was recovered by the overexpression of CBL5. Furthermore, CBL5 was mainly expressed in the cotyledons and hypocotyls, which are essential to seed germination. Na+ efflux activity in the hypocotyls of cbl5 was reduced relative to the wild‐type under salt stress, enhancing Na+ accumulation. These findings indicate that CBL5 functions in seed germination and protects seeds and germinating seedlings from salt stress through the CBL5‐CIPK8/CIPK24‐SOS1 pathways.
Enterocolic granulomatous phlebitis associated with epidermal growth factor‐containing fibulin‐like extracellular matrix protein 1 deposition and focal amyloid properties: A case report
Authors: Ichimata Shojiro , Aikawa Akane , Sugishita Naonori , Katoh Nagaaki , Kametani Fuyuki , Tagawa Hibiki , Handa Yusuke , Yazaki Masahide , Sekijima Yoshiki , Ehara Takashi , Nishida Naoki , Ishizawa Shin
Published: January 2024

A woman in her 60s with rheumatoid arthritis was admitted with fever and abdominal pain. Laparoscopic examination with the differential diagnosis of peritoneal neoplasm and infection revealed granulomatous phlebitis in the resected greater omentum. Amorphous eosinophilic deposits observed in the resected tissue exhibited focal, weak positivity for Congo red but were strongly positive for thioflavin S, confirming their focal amyloid properties. Marked degeneration of elastic fibers was also evident. Electron microscopy revealed deposits around the affected elastic fibers. Immunohistochemistry revealed the deposition of epidermal growth factor‐containing fibulin‐like extracellular matrix protein 1 (EFEMP1) along with T‐cell‐predominant lymphocytic inflammation. The definitive diagnosis was granulomatous enterocolic lymphocytic phlebitis (ELP) associated with EFEMP1 deposition exhibiting focal amyloid properties (EFEMP1/AEFEMP1), supported by proteomics analysis. This type of vasculitis is similar to amyloid‐β‐related angiitis of the central nervous system. Thus, we speculate that granulomatous ELP also results from an immune response that recognizes EFEMP1/AEFEMP1 deposits as foreign material and attempts to remove them. Confirmation of EFEMP1/AEFEMP1 deposition with Congo red staining is challenging, particularly in the presence of inflammation, and warrants comprehensive evaluation.
Multidimensional preference for technology risk regulation: The role of political beliefs, technology attitudes, and national innovation cultures
Authors: Hemesath Sebastian , Tepe Markus
Published: January 2024

Building on the concept of participatory regulation, this study emphasizes recognizing the multidimensional character of citizens' risk regulation preferences. Using the case of autonomous vehicles, we specify six technology‐related risks: product safety, regulatory oversight, legal liability, ethical prioritization, data protection, and human supervision. We argue that differences in these multidimensional risk regulation preferences are shaped by citizens' political beliefs, technology attitudes, and national innovation cultures. To test these hypotheses, a conjoint experiment was conducted in the United States (1188 participants), Japan (1135 participants), and Germany (1174 participants) in which respondents compared hypothetical regulation regimes for self‐driving cars, varying alongside the six regulatory risk dimensions. The findings show a universal preference for increased legal responsibility of manufacturers and more stringent safety regulations for autonomous vehicles. Political beliefs and technological attitudes had minimal impact on these preferences. Although there were some cultural differences in privacy and ethical prioritization, no systematic differences were noted across countries, suggesting the possibility of finding common ground in standardizing risk regulations for self‐driving cars.
Changes in running economy and running technique following 6 months of running with and without wearable‐based real‐time feedback
Authors: Van Hooren Bas , Willems Paul , Plasqui Guy , Meijer Kenneth
Published: January 2024

Background

An increasing number of commercially available wearables provide real‐time feedback on running biomechanics with the aim to reduce injury risk or improve performance.

Objective

Investigate whether real‐time feedback by wearable insoles (ARION) alters running biomechanics and improves running economy more as compared to unsupervised running training. We also explored the correlation between changes in running biomechanics and running economy.

Methods

Forty recreational runners were randomized to an intervention and control group and performed ~6 months of in‐field training with or without wearable‐based real‐time feedback on running technique and speed. Running economy and running biomechanics were measured in lab conditions without feedback pre and post intervention at four speeds.

Results

Twenty‐two individuals (13 control, 9 intervention) completed both tests. Both groups significantly reduced their energetic cost by an average of −6.1% and −7.7% for the control and intervention groups, respectively. The reduction in energy cost did not significantly differ between groups overall (−0.07 ± 0.14 J∙kg∙m−1, −1.5%, p = 0.63). There were significant changes in spatiotemporal metrics, but their magnitude was minor and did not differ between the groups. There were no significant changes in running kinematics within or between groups. However, alterations in running biomechanics beyond typical session‐to‐session variation were observed during some in‐field sessions for individuals that received real‐time feedback.

Conclusion

Alterations in running biomechanics as observed during some in‐field sessions for individuals receiving wearable‐based real‐time feedback did not result in significant differences in running economy or running biomechanics when measured in controlled lab conditions without feedback.
Antibody verification of HLA class I and class II eplets by human monoclonal HLA antibodies
Authors: Kramer Cynthia S. M. , Bezstarosti Suzanne , Franke‐van Dijk Marry E. I. , Vergunst Manon , Roelen Dave L. , Uyar‐Mercankaya Merve , Voogt‐Bakker Kim H. , Heidt Sebastiaan
Published: January 2024

In solid organ transplantation, formation of de novo donor‐specific HLA antibodies is induced by mismatched eplets on donor HLA molecules. While several studies have shown a strong correlation between the number of eplet mismatches and inferior outcomes, not every eplet mismatch is immunogenic. Eplets are theoretically defined entities, necessitating formal proof that they can be recognised and bound by antibodies. This antibody verification is pivotal to ensure that clinically relevant eplets are considered in studies on molecular matching. Recombinant human HLA‐specific monoclonal antibodies (mAbs) were generated from HLA‐reactive B cell clones isolated from HLA immunised individuals using recombinant HLA molecules. Subsequently, the reactivity patterns of the mAbs obtained from single antigen bead assay were analysed using HLA‐EMMA software to identify single or configurations of solvent accessible amino acids uniquely present on the reactive HLA alleles and were mapped to eplets. Two HLA class I and seven HLA class II‐specific human mAbs were generated from four individuals. Extensive mAb reactivity analysis, led to antibody verification of three HLA‐DR‐specific eplets, and conversion of five eplets (one HLA‐A, one HLA‐B, two HLA‐DR, and one HLA‐DP), from provisionally verified to truly antibody‐verified. Finally, one HLA‐DQ‐specific eplet was upgraded from level A2 to level A1 verification evidence. The generation of recombinant human HLA‐specific mAbs with different specificities contributes significantly to the antibody verification of eplets and therefore is instrumental for implementation of eplet matching in the clinical setting.
Testing precision and accuracy of weak value measurements in an IBM quantum system
Authors: Ruelas Paredes David R. A. , Uria Mariano , Massoni Eduardo , De Zela Francisco
Published: January 2024

Historically, weak values have been associated with weak measurements performed on quantum systems. Over the past two decades, a series of works have shown that weak values can be determined via measurements of arbitrary strength. One such proposal by Denkmayr et al. [Phys. Rev. Lett. 118, 010402 (2017)], carried out in neutron interferometry experiments, yielded better outcomes for strong than for weak measurements. We extend this scheme and explain how to implement it in an optical setting as well as in a quantum computational context. Our implementation in a quantum computing system provided by IBM confirms that weak values can be measured, with varying degrees of performance, over a range of measurement strengths. However, at least for this model, strong measurements do not always perform better than weak ones.
Similar susceptibility to temporary hearing threshold shifts despite different audiograms in harbor porpoises and harbor seals
Authors: Gransier Robin , Kastelein Ronald A.
Published: January 2024

When they are exposed to loud fatiguing sounds in the oceans, marine mammals are susceptible to hearing damage in the form of temporary hearing threshold shifts (TTSs) or permanent hearing threshold shifts. We compared the level-dependent and frequency-dependent susceptibility to TTSs in harbor seals and harbor porpoises, species with different hearing sensitivities in the low- and high-frequency regions. Both species were exposed to 100% duty cycle one-sixth-octave noise bands at frequencies that covered their entire hearing range. In the case of the 6.5 kHz exposure for the harbor seals, a pure tone (continuous wave) was used. TTS was quantified as a function of sound pressure level (SPL) half an octave above the center frequency of the fatiguing sound. The species have different audiograms, but their frequency-specific susceptibility to TTS was more similar. The hearing frequency range in which both species were most susceptible to TTS was 22.5–50 kHz. Furthermore, the frequency ranges were characterized by having similar critical levels (defined as the SPL of the fatiguing sound above which the magnitude of TTS induced as a function of SPL increases more strongly). This standardized between-species comparison indicates that the audiogram is not a good predictor of frequency-dependent susceptibility to TTS.
On phase recovery and preserving early reflections for deep-learning speech dereverberation
Authors: Luo Xiaoxue , Ke Yuxuan , Li Xiaodong , Zheng Chengshi
Published: January 2024

In indoor environments, reverberation often distorts clean speech. Although deep learning-based speech dereverberation approaches have shown much better performance than traditional ones, the inferior speech quality of the dereverberated speech caused by magnitude distortion and limited phase recovery is still a serious problem for practical applications. This paper improves the performance of deep learning-based speech dereverberation from the perspectives of both network design and mapping target optimization. Specifically, on the one hand, a bifurcated-and-fusion network and its guidance loss functions were designed to help reduce the magnitude distortion while enhancing the phase recovery. On the other hand, the time boundary between the early and late reflections in the mapped speech was investigated, so as to make a balance between the reverberation tailing effect and the difficulty of magnitude/phase recovery. Mathematical derivations were provided to show the rationality of the specially designed loss functions. Geometric illustrations were given to explain the importance of preserving early reflections in reducing the difficulty of phase recovery. Ablation study results confirmed the validity of the proposed network topology and the importance of preserving 20 ms early reflections in the mapped speech. Objective and subjective test results showed that the proposed system outperformed other baselines in the speech dereverberation task.
The Effects of Virtual Reality Training on Cognition in Older Adults: A Systematic Review, Meta-Analysis, and Meta-Regression of Randomized Controlled Trials
Authors: Kantola Mirjami , Ilves Outi , Honkanen Sari , Hakonen Harto , Yli-Ikkelä Riku , Köyhäjoki Anna , Anttila Marjo-Riitta , Rintala Aki , Korpi Hilkka , Sjögren Tuulikki , Karvanen Juha , Aartolahti Eeva
Published: January 2024

The aim of this systematic review, meta-analysis, and meta-regression was to examine the effects of virtual reality–based training on global cognition and executive function compared with conventional training or information-based treatment in older adults, regardless of cognitive level. A systematic literature search was conducted using four databases. A total of 31 randomized controlled trials were identified. Pooled effect sizes were calculated, the risk of bias was assessed, and evidence was graded. The primary analyses showed a small but statistically significant effect of virtual reality–based training compared with control on global cognition (Hedges’ g 0.42, 95% confidence interval [0.17, 0.68], I2 = 70.1%, n = 876, 20 randomized controlled trials, low evidence) and executive function (Hedges’ g 0.35, 95% confidence interval [0.06, 0.65], I2 = 68.4%, n = 810, 16 randomized controlled trials, very low evidence). Meta-regression yielded inconclusive results. Virtual reality–based training may be more effective than control in improving cognition in older adults; however, more high-quality studies are needed.
Multicultural Training and Program Climate in Master’s Degree Sport Psychology Programs
Authors: Arnold Macey , Petrie Trent
Published: January 2024

Key governing bodies (e.g., Association for Applied Sport Psychology) recognize that graduate programs must prepare multiculturally competent practitioners. Students and recent graduates of sport psychology master’s degree programs (N = 107, Mage = 26.32, SD = 5.19) reported moderate levels of feeling safe, valued, and comfortable within their program; low to moderate levels of multicultural training integration; and low to moderate satisfaction with their multicultural training. Students of Color (n = 42) compared to White students (n = 63) reported less satisfaction with their multicultural training; felt less safe, comfortable, and valued; and perceived less multicultural integration. Furthermore, perceptions of multicultural training integration and of feeling safe, comfortable, and valued were significantly related to satisfaction with their multicultural training. Training programs are advised to improve integration of multicultural training, invest in program climate to help students feel safe and valued, and ensure continuing education of faculty members.
Enhanced NF-κB activation via HIV-1 Tat-TRAF6 cross-talk
Authors: Li Yang , Liu Xi , Fujinaga Koh , Gross John D. , Frankel Alan D.
Published: January 2024

The Tat proteins of HIV-1 and simian immunodeficiency virus (SIV) are essential for activating viral transcription. In addition, Tat stimulates nuclear factor κB (NF-κB) signaling pathways to regulate viral gene expression although its molecular mechanism is unclear. Here, we report that Tat directly activates NF-κB through the interaction with TRAF6, which is an essential upstream signaling molecule of the canonical NF-κB pathway. This interaction increases TRAF6 oligomerization and auto-ubiquitination, as well as the synthesis of K63-linked polyubiquitin chains to further activate the NF-κB pathway and HIV-1 transcription. Moreover, ectopic expression of TRAF6 significantly activates HIV-1 transcription, whereas TRAF6 knockdown inhibits transcription. Furthermore, Tat-mediated activation of NF-κB through TRAF6 is conserved among HIV-1, HIV-2, and SIV isolates. Our study uncovers yet another mechanism by which HIV-1 subverts host transcriptional pathways to enhance its own transcription.
Fiberbots: Robotic fibers for high-precision minimally invasive surgery
Authors: Abdelaziz Mohamed E. M. K. , Zhao Jinshi , Gil Rosa Bruno , Lee Hyun-Taek , Simon Daniel , Vyas Khushi , Li Bing , Koguna Hanifa , Li Yue , Demircali Ali Anil , Uvet Huseyin , Gencoglan Gulsum , Akcay Arzu , Elriedy Mohamed , Kinross James , Dasgupta Ranan , Takats Zoltan , Yeatman Eric , Yang Guang-Zhong , Temelkuran Burak
Published: January 2024

Precise manipulation of flexible surgical tools is crucial in minimally invasive surgical procedures, necessitating a miniature and flexible robotic probe that can precisely direct the surgical instruments. In this work, we developed a polymer-based robotic fiber with a thermal actuation mechanism by local heating along the sides of a single fiber. The fiber robot was fabricated by highly scalable fiber drawing technology using common low-cost materials. This low-profile (below 2 millimeters in diameter) robotic fiber exhibits remarkable motion precision (below 50 micrometers) and repeatability. We developed control algorithms coupling the robot with endoscopic instruments, demonstrating high-resolution in situ molecular and morphological tissue mapping. We assess its practicality and safety during in vivo laparoscopic surgery on a porcine model. High-precision motion of the fiber robot delivered endoscopically facilitates the effective use of cellular-level intraoperative tissue identification and ablation technologies, potentially enabling precise removal of cancer in challenging surgical sites.
Hox
genes control homocercal caudal fin development and evolution
Authors: Cumplido Nicolás , Arratia Gloria , Desvignes Thomas , Muñoz-Sánchez Salomé , Postlethwait John H. , Allende Miguel L.
Published: January 2024

Ancient bony fishes had heterocercal tails, like modern sharks and sturgeons, with asymmetric caudal fins and a vertebral column extending into an elongated upper lobe. Teleost fishes, in contrast, developed a homocercal tail characterized by two separate equal-sized fin lobes and the body axis not extending into the caudal fin. A similar heterocercal-to-homocercal transition occurs during teleost ontogeny, although the underlying genetic and developmental mechanisms for either transition remain unresolved. Here, we investigated the role of
hox13
genes in caudal fin formation as these genes control posterior identity in animals. Analysis of expression profiles of zebrafish
hox13
paralogs and phenotypes of CRISPR/Cas9-induced mutants showed that double
hoxb13a
and
hoxc13a
mutants fail to form a caudal fin. Furthermore, single mutants display heterocercal-like morphologies not seen since Mesozoic fossil teleosteomorphs. Relaxation of functional constraints after the teleost genome duplication may have allowed
hox13
duplicates to neo- or subfunctionalize, ultimately contributing to the evolution of a homocercal tail in teleost fishes.
TGFβ prevents IgE-mediated allergic disease by restraining T follicular helper 2 differentiation
Authors: Haque Tamara T. , Weissler Katherine A. , Schmiechen Zoe , Laky Karen , Schwartz Daniella M. , Li Jenny , Locci Michela , Turfkruyer Mathilde , Yao Chen , Schaughency Paul , Leak Lashawna , Lack Justin , Kanno Yuka , O’Shea John , Frischmeyer-Guerrerio Pamela A.
Published: January 2024

Allergic diseases are common, affecting more than 20% of the population. Genetic variants in the TGFβ pathway are strongly associated with atopy. To interrogate the mechanisms underlying this association, we examined patients and mice with Loeys-Dietz syndrome (LDS) who harbor missense mutations in the kinase domain of
TGFΒR1/2
. We demonstrate that LDS mutations lead to reduced TGFβ signaling and elevated total and allergen-specific IgE, despite the presence of wild-type T regulatory cells in a chimera model. Germinal center activity was enhanced in LDS and characterized by a selective increase in type 2 follicular helper T cells (T
FH
2). Expression of
Pik3cg
was increased in LDS T
FH
cells and associated with reduced levels of the transcriptional repressor SnoN. PI3Kγ/mTOR signaling in LDS naïve CD4
+
T cells was elevated after T cell receptor cross-linking, and pharmacologic inhibition of PI3Kγ or mTOR prevented exaggerated T
FH
2 and antigen-specific IgE responses after oral antigen exposure in an adoptive transfer model. Naïve CD4
+
T cells from nonsyndromic allergic individuals also displayed decreased TGFβ signaling, suggesting that our mechanistic discoveries may be broadly relevant to allergic patients in general. Thus, TGFβ plays a conserved, T cell–intrinsic, and nonredundant role in restraining T
FH
2 development via the PI3Kγ/mTOR pathway and thereby protects against allergic disease.
CD4
+
T cell immunity against cutaneous melanoma encompasses multifaceted MHC II–dependent responses
Authors: Bawden Emma G. , Wagner Teagan , Schröder Jan , Effern Maike , Hinze Daniel , Newland Lewis , Attrill Grace H. , Lee Ariane R. , Engel Sven , Freestone David , de Lima Moreira Marcela , Gressier Elise , McBain Nathan , Bachem Annabell , Haque Ashraful , Dong Ruining , Ferguson Angela L. , Edwards Jarem J. , Ferguson Peter M. , Scolyer Richard A. , Wilmott James S. , Jewell Christopher M. , Brooks Andrew G. , Gyorki David E. , Palendira Umaimainthan , Bedoui Sammy , Waithman Jason , Hochheiser Katharina , Hölzel Michael , Gebhardt Thomas
Published: January 2024

Whereas CD4
+
T cells conventionally mediate antitumor immunity by providing help to CD8
+
T cells, recent clinical studies have implied an important role for cytotoxic CD4
+
T cells in cancer immunity. Using an orthotopic melanoma model, we provide a detailed account of antitumoral CD4
+
T cell responses and their regulation by major histocompatibility complex class II (MHC II) in the skin. Intravital imaging revealed prominent interactions of CD4
+
T cells with tumor debris-laden MHC II
+
host antigen-presenting cells that accumulated around tumor cell nests, although direct recognition of MHC II
+
melanoma cells alone could also promote CD4
+
T cell control. CD4
+
T cells stably suppressed or eradicated tumors even in the absence of other lymphocytes by using tumor necrosis factor–α and Fas ligand (FasL) but not perforin-mediated cytotoxicity. Interferon-γ was critical for protection, acting both directly on melanoma cells and via induction of nitric oxide synthase in myeloid cells. Our results illustrate multifaceted and context-specific aspects of MHC II–dependent CD4
+
T cell immunity against cutaneous melanoma, emphasizing modulation of this axis as a potential avenue for immunotherapies.
Exposure to a fungicide for a field-realistic duration does not alter bumble bee fecal microbiota structure
Authors: Hotchkiss Michelle Z. , Forrest Jessica R. K. , Poulain Alexandre J.
Published: January 2024

Social bees are frequently exposed to pesticides when foraging on nectar and pollen. Recent research has shown that pesticide exposure not only impacts social bee host health but can also alter the community structure of social bee gut microbiotas. However, most research on pesticide–bee gut microbiota interactions has been conducted in honey bees; bumble bees, native North American pollinators, have received less attention and, due to differences in their ecology, may be exposed to certain pesticides for shorter durations than honey bees. Here, we examine how exposure to the fungicide chlorothalonil for a short, field-realistic duration alters bumble bee fecal microbiotas (used as a proxy for gut microbiotas) and host performance. We expose small groups of
Bombus impatiens
workers (microcolonies) to field-realistic chlorothalonil concentrations for 5 days, track changes in fecal microbiotas during the exposure period and a recovery period, and compare microcolony offspring production between treatments at the end of the experiment. We also assess the use of fecal microbiotas as a gut microbiota proxy by comparing community structures of fecal and gut microbiotas. We find that chlorothalonil exposure for a short duration does not alter bumble bee fecal microbiota structure or affect microcolony production at any concentration but that fecal and gut microbiotas differ significantly in community structure. Our results show that, at least when exposure durations are brief and unaccompanied by other stressors, bumble bee microbiotas are resilient to fungicide exposure. Additionally, our work highlights the importance of sampling gut microbiotas directly, when possible.

IMPORTANCE

With global pesticide use expected to increase in the coming decades, studies on how pesticides affect the health and performance of animals, including and perhaps especially pollinators, will be crucial to minimize negative environmental impacts of pesticides in agriculture. Here, we find no effect of exposure to chlorothalonil for a short, field-realistic period on bumble bee fecal microbiota community structure or microcolony production regardless of pesticide concentration. Our results can help inform pesticide use practices to minimize negative environmental impacts on the health and fitness of bumble bees, which are key native, commercial pollinators in North America. We also find that concurrently sampled bumble bee fecal and gut microbiotas contain similar microbes but differ from one another in community structure and consequently suggest that using fecal microbiotas as a proxy for gut microbiotas be done cautiously; this result contributes to our understanding of proxy use in gut microbiota research.
Non-purulent myositis caused by direct invasion of skeletal muscle tissue by
Leptospira
in a hamster model
Authors: Miyahara Satoshi , Mori Hiroshi , Fukuda Kazumasa , Ogawa Midori , Saito Mitsumasa
Published: January 2024

Myalgia is a common symptom of
Leptospira
infection in humans. Autopsies have reported that muscle tissue shows degeneration and necrosis of the myofibers and infiltration of inflammatory cells composed mainly of macrophages and lymphocytes. It remains unclear whether
Leptospira
directly infects the muscle and how the infiltrating inflammatory cells are involved in muscle fiber destruction. This study evaluated the relationship between histopathological changes and leptospiral localization in the muscle tissue of a hamster model. The influence of macrophages in skeletal muscle injury was also investigated, using selective depletion of macrophages by administration of liposomal clodronate. Hamsters infected subcutaneously with
Leptospira interrogans
serovar Manilae strain UP-MMC-SM showed myositis of the thighs adjacent to the inoculated area beginning at 6 days post-infection. The myositis was non-purulent and showed sporadic degeneration and necrosis of muscle fibers. The degeneration of myofibers was accompanied by aggregations of macrophages. Immunofluorescence staining revealed leptospires surrounding the damaged muscle fibers. Subcutaneous injection of formalin-killed
Leptospira
or intraperitoneal injection of live
Leptospira
caused no myositis in hamster thighs. Liposomal clodronate treatment in infected hamsters reduced macrophage infiltration in muscle tissue without impacting bacterial clearance. Muscle necrosis was still observed in the infected hamsters treated with liposomal clodronate, and there was no significant change in serum creatine kinase levels compared to those in animals treated with liposomes alone. Our findings suggest that leptospiral invasion of muscle tissue from an inoculation site leads to the destruction of muscle fibers and causes non-purulent myositis, whereas the infiltrating macrophages contribute less to muscle destruction.
Kaposi’s sarcoma-associated herpesvirus (KSHV) LANA prevents KSHV episomes from degradation
Authors: Nakajima Ken-ichi , Inagaki Tomoki , Espera Jonna Magdallene , Izumiya Yoshihiro
Published: January 2024

Sensing of pathogens’ components is a fundamental cellular immune response. Pathogens have therefore evolved strategies to evade such cellular immune responses. KSHV LANA is a multifunctional protein and plays an essential role in maintaining the latent infection by tethering viral genomic DNA to the host chromosome. We adopted the inducible protein knockdown approach and found that depletion of LANA induced rapid degradation of viral genomic DNA, which is mediated by innate immune DNA sensors and autophagy pathway. These observations suggest that LANA may play a role in hiding KSHV episome from innate immune DNA sensors. Our study thus provides new insights into the role of LANA in latency maintenance.
Kaposi’s sarcoma-associated herpesvirus terminal repeat regulates inducible lytic gene promoters
Authors: Izumiya Yoshihiro , Algalil Adhraa , Espera Jonna M. , Miura Hiroki , Izumiya Chie , Inagaki Tomoki , Kumar Ashish
Published: January 2024

Enhancers are a crucial regulator of differential gene expression programs. Enhancers are the cis-regulatory sequences determining target genes’ spatiotemporal and quantitative expression. Here, we show that Kaposi’s sarcoma-associated herpesvirus (KSHV) terminal repeats fulfill the enhancer definition for KSHV inducible gene promoters. The KSHV enhancer is occupied by latency-associated nuclear antigen (LANA) and its interacting proteins, such as CHD4. Neighboring terminal repeat (TR) fragments to lytic gene promoters drastically enhanced KSHV replication and transcription activator and LANA transcription regulatory functions. This study, thus, proposes a new latency–lytic switch model in which TR accessibility to the KSHV gene promoters regulates viral inducible gene expression.
Multiple recombination events between endogenous retroviral elements and feline leukemia virus
Authors: Ngo Minh Ha , AbuEed Loai , Kawasaki Junna , Oishi Naoki , Pramono Didik , Kimura Tohru , Sakurai Masashi , Watanabe Kenji , Mizukami Yoichi , Ochi Haruyo , Anai Yukari , Odahara Yuka , Umehara Daigo , Kawamura Maki , Watanabe Shinya , Miyake Ariko , Nishigaki Kazuo
Published: January 2024

Feline leukemia virus (FeLV) is an exogenous retrovirus that causes malignant hematopoietic disorders in domestic cats, and its virulence may be closely associated with viral sequences. FeLV is classified into several subgroups, including A, B, C, D, E, and T, based on viral receptor interference properties or receptor usage. However, the transmission manner and disease specificity of the recombinant viruses FeLV-D and FeLV-B remain unclear. The aim of this study was to understand recombination events between exogenous and endogenous retroviruses within a host and elucidate the emergence and transmission of recombinant viruses. We observed multiple recombination events involving endogenous retroviruses (ERVs) in FeLV from a family of domestic cats kept in one house; two of these cats (ON-T and ON-C) presented with lymphoma and leukemia, respectively. Clonal integration of FeLV-D was observed in the ON-T case, suggesting an association with FeLV-D pathogenesis. Notably, the receptor usage of FeLV-B observed in ON-T was mediated by feline Pit1 and feline Pit2, whereas only feline Pit1 was used in ON-C. Furthermore, XR-FeLV, a recombinant FeLV containing an unrelated sequence referred to the X-region, which is homologous to a portion of the 5′-leader sequence of
Felis catus
endogenous gammaretrovirus 4 (FcERV-gamma4), was isolated. Genetic analysis suggested that most recombinant viruses occurred
de novo
; however, the possibility of FeLV-B transmission was also recognized in the family. This study demonstrated the occurrence of multiple recombination events between exogenous and endogenous retroviruses in domestic cats, highlighting the contribution of ERVs to pathogenic recombinant viruses.

IMPORTANCE

Feline leukemia virus subgroup A (FeLV-A) is primarily transmitted among cats. During viral transmission, genetic changes in the viral genome lead to the emergence of novel FeLV subgroups or variants with altered virulence. We isolated three FeLV subgroups (A, B, and D) and XR-FeLV from two cats and identified multiple recombination events in feline endogenous retroviruses (ERVs), such as enFeLV, ERV-DC, and FcERV-gamma4, which are present in the cat genome. This study highlights the pathogenic contribution of ERVs in the emergence of FeLV-B, FeLV-D, and XR-FeLV in a feline population.
Enterovirus D68 3C protease antagonizes type I interferon signaling by cleaving signal transducer and activator of transcription 1
Authors: Li Xiaohan , Guo Haoran , Yang Jiaxin , Liu Xize , Li Huili , Yang Wanying , Zhang Lili , Li Yan , Wei Wei
Published: January 2024

Enterovirus D68 (EV-D68) has significantly transformed over the past decade, evolving from a rare pathogen to a potential pandemic pathogen. The interferon (IFN) signaling pathway is an important defense mechanism and therapeutic target for the host to resist viral invasion. Previous studies have reported that the EV-D68 virus blocks or weakens immune recognition and IFN production in host cells through diverse strategies; however, the mechanisms of EV-D68 resistance to IFN signaling have not been fully elucidated. Our study revealed that EV-D68 relies on its own encoded protease, 3C, to directly cleave signal transducer and activator of transcription 1 (STAT1), a pivotal transduction component in the IFN signaling pathway, disrupting the IFN-mediated antiviral response. Previous studies on human enteroviruses have not documented direct cleavage of the STAT1 protein to evade cellular immune defenses. However, not all enteroviral 3C proteins can cleave STAT1. These findings highlight the diverse evolutionary strategies different human enteroviruses employ to evade host immunity.