bluuebunny/crossref_metadata_2025 huggingface dataset:
Epidemiological Relevance of Colletotrichum Species Isolated from Glomerella Leaf Spot Causing Symptoms in Apple Fruit
Authors: Castellar Camilla , Petermann Débora , May De Mio Louise Larissa
Published: May 2023

Colletotrichum isolates from apple leaves with symptoms of Glomerella leaf spot (GLS) can cause fruit rot and several small lesion spots, here called Colletotrichum fruit spot (CFS). This work investigated the epidemiological relevance of Colletotrichum species obtained from leaves with GLS in causing diseases in immature apple fruit by comparing different fruit sizes (phenological stages) for symptom development. In the first experiment, five Colletotrichum species were inoculated in ‘Gala’ (Ø = 5.5 cm) and ‘Eva’ (Ø = 4.8 cm) fruit in the field (2016/17 season). Subsequently, C. chrysophilum and C. nymphaeae were inoculated in fruit of different sizes (Ø = 2.4 to 6.3 cm) in the field (2017/18 and 2021/22 seasons) and in the laboratory according to the phenological stages of growing fruit. At harvest of the immature inoculated fruit in the field, only CFS symptoms were observed in both cultivars. For Gala, the CFS incidence reached 50% regardless of season, pathogen species, and fruit size. For Eva, CFS symptoms were observed after inoculation with C. melonis in the 2016/17 season and in smaller fruit inoculated with C. chrysophilum and C. nymphaeae in 2021/22. During postharvest, bitter rot symptoms developed, but did not seem to come from CFS symptoms. It can be concluded that the Gala cultivar has a high susceptibility to CFS caused by the two Colletotrichum species of the greatest epidemiological importance for GLS in Brazil in all fruit sizes tested.
Transcranial Direct Current Stimulation for Global Cognitive Functioning and Ability in Daily Life Activities in Post-stroke Cognitive Impairment: A Systematic Review and Meta-Analysis
Authors: Lyu Zecai , Liu Fang , Xiu Huoqin , Tu Shuzhen , Lin Ruhui
Published: May 2023

Objective

To determine the efficacy of transcranial direct current stimulation (tDCS) on global cognition and ability in daily life activities (ADL) of patients with Post-stroke cognitive impairment (PSCI).

Design

Nine electronic databases were searched from their respective inceptions through Jan 2022. We included the randomized controlled trials (RCTs) that used tDCS for PSCI and included at least one global cognitive function or ADL outcome indicators. Two reviewers appraised the risks of bias through the Cochrane Collaboration's tool and performed the meta-analysis. We followed the PRISMA 2020 guidelines.

Results

Twenty-two studies (1198 participants) were included. Most studies had no significant bias in the quality of the methodology. Meta-analyses found that compared with the control group, tDCS increased Montreal cognitive assessment (MoCA), Mini-mental state examination (MMSE), Loewenstein occupational therapy cognitive assessment (LOTCA), total effective rate of cognition, modified Barthel index (MBI) and decreased P300 latency (all P < 0.05). These results showed tDCS can improve cognitive function and ADL in PSCI.

Conclusion

The tDCS may have a significant rehabilitation effect on global cognitive functioning and ADL of patients with PSCI.
DEVELOPMENT OF SCORE SYSTEM BASED ON POINT-OF-CARE ULTRASOUND TO PREDICT VASOPRESSOR REQUIREMENT FOR EMERGENCY PATIENTS WITH CARDIOPULMONARY SYMPTOMS
Authors: Kim Hayoung , Kim Ki Hong , Park Yun Seong , Kim Jin Hee , Choi Yun Ang , Park Joong Wan , Lee Yong Hee , Jung Jae Yun
Published: May 2023

Objectives: Patients with cardiopulmonary symptoms admitted to the emergency department (ED) have high mortality and intensive care unit admission rates. We developed a new scoring system comprising concise triage information, point-of-care ultrasound, and lactate levels to predict vasopressor requirements. Methods: This retrospective observational study was conducted at a tertiary academic hospital. Patients with cardiopulmonary symptoms who visited the ED and underwent point-of-care ultrasound between January 2018 and December 2021 were enrolled. The influence of demographic and clinical findings on the requirement for vasopressor support within 24 h of ED admission was investigated. A new scoring system was developed using key components after stepwise multivariable logistic regression analysis. Prediction performance was evaluated using the area under the receiver operating characteristic curve (AUC), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Results: A total of 2,057 patients were analyzed. A stepwise multivariable logistic regression model showed high predictive performance in the validation cohort (AUC, 0.87). Eight key components were selected: hypotension, chief complaint, and fever at ED admission, and way of ED visit, systolic dysfunction, regional wall motion abnormalities, inferior vena cava status, and serum lactate level. The scoring system was developed based on the β coefficients of each component: accuracy, 0.8079; sensitivity, 0.8057; specificity, 0.8214; PPV, 0.9658; and NPV, 0.4035, with a cutoff value according to the Youden index. Conclusions: A new scoring system was developed to predict vasopressor requirements in adult ED patients with cardiopulmonary symptoms. This system can serve as a decision-support tool to guide efficient assignment of emergency medical resources.
Impact of intensive care-related factors on outcome in stroke patients, results from the population-based Brest Stroke Registry: an observational study
Authors: Ariès Philippe , Bailly Pierre , Baudic Thibaut , Garrec Fanny Le , Consigny Maëlys , L’Her Erwan , Timsit Serge , Huet Olivier
Published: May 2023

Background

Little is known on the burden of ICU care for stroke patients. The aim of this study was to provide a description of management strategies, resource use, complications and their association with prognosis of stroke patients admitted to ICU.

Methods

Using a population-based stroke registry, we analyzed consecutive stroke patients admitted to 3 ICU with at least one organ failure between 2008 and 2017. The study period was divided into two periods corresponding to the arrival of mechanical reperfusion technique.

Predictors of ICU mortality were separately assessed in two multivariable logistic regression models, a “clinical model” and an “intervention model”. The same analysis was performed for predictors of functional status at hospital discharge.

Results

215 patients were included. Stroke etiology was ischemia in 109 patients (50.7%) and hemorrhage in 106 patients (49.3%). Median NIHSS score was 20.0 (9.0; 40.0). The most common reason for ICU admission was coma (41.2%) followed by acute circulatory failure (41%) and respiratory failure (27.4%). 112 patients (52%) died in the ICU and 20 patients (11.2%) had a good functional outcome (mRS≤3) at hospital discharge.

In the “clinical model,” factors independently associated with ICU mortality were: age (OR = 1.03 [95%CI, 1.0 to 1.06];p=0.04) and intracranial hypertension (OR = 6.89 [95%CI, 3.55 to 13.38];p<0.0001). In the “intervention model,” the need for invasive mechanical ventilation (OR = 7.39 [95%CI, 1.93 to 28.23];p=0.004), the need for vasopressor therapy (OR = 3.36 [95%CI, 1.5 to 7.53];p=0.003) and decision of withholding life support treatments (OR = 19.24 [95%CI, 7.6 to 48.65];p<0.0001) were associated with bad outcome.

Conclusion

Our study showed the very poor prognosis of acute stroke patients admitted to ICU. These results also suggest that the clinical evolution of these patients during ICU hospitalization may provide important information for prognostication.
Accuracy of Expired BinaxNOW Rapid Antigen Tests
Authors: Vaeth Mary Jane E. , Abdullah Omar , Cheema Minahil , Sun Kristie , Elhabashy Maryam , Mitchell Asia , Foyez Maisha , Talla Mahita , Cheema Aamna , Locke Charles , Kantsiper Melinda , Pekosz Andrew , Mostafa Heba H. , Siddiqui Zishan K.
Published: May 2023

The widespread existence of expired antigen testing kits in households and potential coronavirus outbreaks necessitate evaluating the reliability of these expired kits. Our study examined BinaxNOW COVID-19 rapid antigen tests 27 months post-manufacture and 5 months past their FDA extended expiration dates, using SARS-CoV-2 variant XBB.1.5 viral stock. We conducted testing at two concentrations: the Limit of Detection (LoD) and 10 times the LoD. 100 expired and unexpired kits were tested at each concentration for a total of 400 antigen tests. At the LoD (2.32x10^2 TCID50/mL), both expired and unexpired tests displayed 100% sensitivity (95% CI 96.38% to 100%), with no statistical difference (95% CI -3.92% to 3.92%). Similarly, at 10 times the LoD, unexpired tests retained 100% sensitivity (95% CI 96.38% to 100%), while expired tests exhibited 99% sensitivity (95% CI 94.61% to 99.99%), demonstrating a statistically insignificant 1% difference (95% CI -2.49% to 4.49%, p=0.56). Expired rapid antigen tests had fainter lines than the unexpired tests at each viral concentration. The expired rapid antigens tests at LoD were only just visible. These findings carry significant implications for waste management, cost efficiency, and supply chain resilience in pandemic readiness efforts. They also provide critical insights for formulating clinical guidelines for interpreting results from expired kits. In light of expert warnings of a potential outbreak of a severity rivaling the Omicron variant, our study underscores the importance of maximizing the utility of expired antigen testing kits in managing future health emergencies.
Combining rare and common genetic variants improves population risk stratification for breast cancer
Authors: Bolze Alexandre , Kiser Daniel , Schiabor Barrett Kelly M. , Elhanan Gai , Schnell Blitstein Jamie M. , Neveux Iva , Dabe Shaun , Reed Harry , Anderson Alexa , Metcalf William J. , Orlova Ekaterina , Thibodeau Ildiko , Telis Natalie , Jiang Ruomu , Washington Nicole L. , Ferber Matthew J. , Hajek Catherine , Cirulli Elizabeth T. , Grzymski Joseph J.
Published: May 2023

Purpose

In the United States, breast cancer clinical risk assessments are inconsistent and inequitable. The previous success ofBRCA1andBRCA2screening has demonstrated that genetics could be used to reduce these inequities, if they are available and accessible across the population. The aim of this study is to evaluate the performance of different genetic screening approaches to identify women at high-risk of breast cancer in the general population.

Methods

We did a retrospective study on 25,591 women participating in the Healthy Nevada Project. Electronic Health Records (EHR) data were used to identify women with a family history of, and women who were diagnosed with breast cancer. The genetic analysis assessed the role of rare predicted loss-of-function (pLOF) variants inBRCA1,BRCA2,PALB2,ATMandCHEK2, as well as the combined role of common variants via a polygenic risk score. Women were considered at high-risk of breast cancer if they had greater than 20% probability of being diagnosed with breast cancer by age 70.

Results

Family history of breast cancer (FHx-BrCa) was ascertained on or after the record of breast cancer for 78% of women with both, indicating that this method for risk assessment is not being properly utilized for early screening. Genetics offered an alternative method for risk assessment. 11.4% of women in HNP were at high-risk of breast cancer based on their genetic risk: having a pLOF variant inBRCA1,BRCA2orPALB2(hazard ratio = 10.4, 95% confidence interval: 8.1-13.5), or a pLOF variant inATMorCHEK2(HR = 3.4, CI: 2.4-4.8), or being in the top 10% of the polygenic risk score distribution (HR = 2.4, CI: 2.0-2.8). We also showed that combining PRS with pLOF inATMandCHEK2allowed a better identification of participants with high risk while minimizing false positives. Women with a pLOF inATMorCHEK2and in the top 50% of the PRS are at high risk (39.2% probability of breast cancer at age 70), while those with a pLOF inATMorCHEK2and in the bottom 50% of the PRS are not at high risk (14.4% probability of breast cancer at age 70).

Conclusion

These results suggest that a combined monogenic and polygenic approach may best capture the inherited risk for breast cancer across the population.
Creation of data-driven low-order predictive cardiac excitation models at the tissue scale in augmented state space⋆
Authors: Kabus Desmond , De Coster Tim , de Vries Antoine A.F. , Pijnappels Daniël A. , Dierckx Hans
Published: May 2023

The quick and easy creation of fast in-silico models of excitable media is, for instance, needed for patient-specific predictions in diagnostics and decision making in cardiac electrophysiology. We here present a model creation pipeline that not only generates new models quickly, but also only requires data from one easily measurable spatio-temporal variable. These data may, for instance, be an optical voltage mapping recording of the electrical waves in cardiac muscle tissue controlling the heart beat. We use exponential moving averages and compute standard deviations to extract additional states from this one variable to span a sparse discretised state space. The standard deviation in a neighbourhood can be used as a proxy for the gradient. To this augmented state space, we fit a simple polynomial model to predict the evolution of this one state variable. For optical voltage mapping data of human atrial myocyte monolayers electrically stimulated by stochastic burst pacing, the data-driven model is able to describe the excitation and recovery of the system, as well as wave propagation. The data-driven model is also able to predict spiral waves only based on data from focal waves. In contrast to conventional models, with our model creation pipeline new models can be generated in a matter of hours from experiment to fitting, rather than months or years.

Highlights

Models of excitation waves can be created in minutes from experiment to fitting.

One variable in space and time is sufficient to create a working excitation model.

A polynomial can predict excitation waves based on useful extracted features.

Spiral waves in heart muscle tissue can be predicted from focal wave data.

Graphical Abstract
Subtype-specific circadian clock dysregulation modulates breast cancer biology, invasiveness, and prognosis
Authors: Hammarlund Jan A , Li Shi-Yang , Wu Gang , Lian Jia-wen , Howell Sacha J , Clarke Rob , Adamson Antony , Gonçalves Cátia F. , Hogenesch John B , Meng Qing-Jun , Anafi Ron C
Published: May 2023

Studies in shift workers and model organisms link circadian disruption to breast cancer. However, molecular rhythms in non-cancerous and cancerous human breast tissues are largely unknown. We reconstructed rhythms informatically, integrating locally collected, time-stamped biopsies with public datasets. For non-cancerous tissue, the inferred order of core-circadian genes matches established physiology. Inflammatory, epithelial-mesenchymal transition (EMT), and estrogen responsiveness pathways show circadian modulation. Among tumors, clock correlation analysis demonstrates subtype-specific changes in circadian organization. Luminal A organoids and informatic ordering of Luminal A samples exhibit continued, albeit disrupted rhythms. However, CYCLOPS magnitude, a measure of global rhythm strength, varied widely among Luminal A samples. Cycling of EMT pathway genes was markedly increased in high-magnitude Luminal A tumors. Patients with high-magnitude tumors had reduced 5-year survival. Correspondingly, 3D Luminal A cultures show reduced invasion following molecular clock disruption. This study links subtype-specific circadian disruption in breast cancer to EMT, metastatic potential, and prognosis.
Engineering 3D neuronal networks with directional endogenous neuronal plasticity pathways
Authors: Pagan-Diaz Gelson J , Kilacarslan Evin , Wester Matthew , Rahman Saeedur , Aydin Onur , Gapinske Lauren , Kim Yongdeok , Buoros Daniel , Taher M Saif A , Bashir Rashid
Published: May 2023

The forward engineering of the structure and function of three-dimensional millimeter to centimeter scale living Neuronal Tissue Mimics (NTMs) can advance many engineering and biomedical applications. While hydrogels and 3D printing have achieved major breakthroughs in the development of cm-scale neural tissues that mimic structural morphologies in native neural networks, controlling and programming the resulting function of these NTMs have remained elusive. In this work, using human embryonic stem cell derived optogenetic neurons, we report the in-situ formation of the NTMs on a 2-dimensional micro electrode array with an intimate electrical contact between the electrodes and the tissue. These NTMs were optimized during the differentiation phase of the cells to enrich for neuronal populations that expressed receptors responsible for activating spike-timing dependent plasticity (STDP). Using an optical stimulation regiment with millisecond temporal and micrometer spatial resolution, we were able to program the otherwise omnidirectional spontaneous firing in the NTMs to demonstrate directional firing across different shapes of the NTMs. Our work can pave the way for developing cellular based computational devices, bio-processors, and biological memories.
Analysis of the Confidence in the Prediction of the Protein Folding by Artificial Intelligence
Authors: Tejera-Nevado Paloma , Serrano Emilio , González-Herrero Ana , Bermejo-Moreno Rodrigo , Rodríguez-González Alejandro
Published: May 2023

The determination of protein structure has been facilitated using deep learning models, which can predict protein folding from protein sequences. In some cases, the predicted structure can be compared to the already-known distribution if there is information from classic methods such as nuclear magnetic resonance (NMR) spectroscopy, X-ray crystallography, or electron microscopy (EM). However, challenges arise when the proteins are not abundant, their structure is heterogeneous, and protein sample preparation is difficult. To determine the level of confidence that supports the prediction, different metrics are provided. These values are important in two ways: they offer information about the strength of the result and can supply an overall picture of the structure when different models are combined. This work provides an overview of the different deep-learning methods used to predict protein folding and the metrics that support their outputs. The confidence of the model is evaluated in detail using two proteins that contain four domains of unknown function.
Genome-wide association and environmental suppression of the mortal germline phenotype of wildC. elegans
Authors: Frézal Lise , Saglio Marie , Zhang Gaotian , Noble Luke , Richaud Aurélien , Félix Marie-Anne
Published: May 2023

The animal germline lineage needs to be maintained along generations. However, someCaenorhabditis eleganswild isolates display a mortal germline phenotype, whereby the lineage becomes sterile after several generations at 25°C. We used a genome-wide association approach to study the genetic basis for this phenotype inC. eleganspopulations. We detected a significant peak on chromosome III around 5 Mb, which was confirmed using introgression lines. These results indicate that a seemingly deleterious genotype is maintained at intermediate frequency in the species. Environmental rescue is a likely explanation and we indeed find that naturally associated bacteria and microsporidia suppressed the phenotype. The tested bacteria also suppressed the temperature-sensitive mortal germline phenotype of mutants in small RNA inheritance (nrde-2) and histone modifications (set-2). EvenEscherichia colistrains of the K-12 lineage suppressed the phenotype compared to B strains. By shifting a strain cultured onE. coliK-12 back toE. coliB, we found thatC. eleganscan keep over several generations the memory of the suppressing conditions. Thus, the mortal germline phenotype of wildC. elegansis lin part revealed by laboratory conditions and may represent variation in epigenetic inheritance and environmental interactions. This study also points to the importance of non-genetic memory in the face of environmental variation.
Registration of sugar beet genetic stocks FC308 (PI701378) and FC309 (PI700990)
Authors: Todd Olivia E , Nielson Amy L , Fenwick Ann , Hanson Linda E , Richardson Kelley L , Dorn Kevin M
Published: May 2023

Sugar beet (Beta vulgarisL.) genetic stock lines FC308 (PI701378) and FC309 (PI700990) are two highly homozygous and phenotypically homogenous sources of resistance to two sugar beet pests. FC308 is resistant to sugar beet cyst nematode (Heterodera schachtii), but susceptible to Fusarium yellows, while FC309 is Fusarium yellows resistant, but sugar beet cyst nematode susceptible. These two populations were developed by the USDA-ARS in Fort Collins, CO, derived from unreleased USDA-ARS Salinas germplasm lines. Multiple field and greenhouse trials for Fusarium yellows and nematode resistance confirmed the uniform phenotypes of both lines for each disease. To enable molecular breeders to rapidly screen proprietary markers in silico, gene space assemblies for each line were also developed. Genome sequencing of individual plants from each line, as well as pooled sequencing of sub-populations of both lines indicated fixation of a previously reported genetic variant linked to sugar beet cyst nematode resistance in FC308. However, two previously reported variants linked to Fusarium resistance appear to be unlinked to the resistance found in FC309. Collectively, these two new genetic stocks should prove useful as sources of resistance to Fusarium yellows and sugar beet cyst nematode, as model genetic backgrounds for studying plant-pathogen interactions, and for mapping the resistance genes present in these lines.
A severe bottleneck impacted the genomic structure of egg-eating cichlids
Authors: Imamoto Minami , Nakamura Haruna , Aibara Mitsuto , Hatashima Ryo , Itoh Takehiko , Nikaido Masato
Published: May 2023

The explosive adaptive radiation of Haplochromine cichlids in Lake Victoria, East Africa, produced 500 endemic species within only 15,000 years. A paedophage or an egg-eater is considered a unique example of trophic adaptation. Many field studies reported that more than 200 cichlids have extinct due to the upsurge of Nile perch, a carnivorous species introduced to the lake in the 1950s. Especially, piscivorous cichlids like paedophages were critically damaged by Nile perch predation. Here, we performed a genome-wide evolutionary study of the paedophages in Lake Victoria to understand their past demographic events and phylogenetic relationships. We discovered evidence of a recent, short-period, and severe bottleneck in a paedophage “matumbi hunter”. Interestingly, the signature of a strong bottleneck, as observed in matumbi hunter, was not detected in other species including paedophagus species. In addition, it was revealed that the population size of matumbi hunter started to decline 30 years ago and recover from 20 to 10 years ago, corresponding to the time of both disappearance and resurgence of Lake Victoria Haplochromines were reported. Although population structure analyses showed that matumbi hunter is composed of a unique genetic component, phylogenetic analyses supported its strong monophyly with other paedophagus species. These results suggest that the paedophages originated only once in Lake Victoria followed by the decline of genetic diversity in matumbi hunter. This study succeeded to demonstrate the demographic events triggered by invasive species and associated genomic consequences of the unique trophic group, promoting a holistic understanding of adaptive radiation.
Tomato CYP94C1 terminates jasmonate signaling during fruit ripening by inactivating bioactive jasmonoyl-L-isoleucine
Authors: Yang Tianxia , Deng Lei , Sun Chuanlong , Ali Muhammad , Wu Fangming , Zhai Huawei , Xu Qian , Xin Peiyong , Chu Jinfang , Huang Tingting , Li Chang-Bao , Li Chuanyou
Published: May 2023

Ripe fruits are more susceptible to necrotrophic pathogens than unripe fruits. Although this phenomenon is widespread across different fruit species and results in substantial economic losses, the underlying mechanism is still poorly understood. Previous studies revealed that ethylene (ET) is a key signal controlling climacteric fruit ripening and that jasmonate (JA) regulates plant resistance to necrotrophs. We investigated the function of tomato cytochrome P450 94 (CYP94) family genes in JA signaling and report here that ET-mediated ripening suppresses JA-mediated defense by promoting the deactivation of bioactive JA-Ile. ETHYLENE-INSENSITIVE 3 (EIN3)/EIN3-LIKE (EIL) transcription factors directly activatedCYP94C1to convert JA-Ile to its inactive form 12-COOH-JA-Ile, thereby terminating JA signaling during fruit ripening. Mutation ofCYP94C1led to increased resistance of ripe fruits to the necrotrophic pathogenBotrytis cinereawithout affecting the ripening process. Additionally, the master transcription factor MYC2 directly activated two other CYP94 membersCYP94B1andCYP94B2to convert JA-Ile to its less active form 12-OH-JA-Ile, thereby attenuating JA signaling in wounded leaves. Simultaneous mutation ofCYP94B1andCYP94B2increased the resistance of leaves toB. cinerea. Thus, differences in the expression and enzymatic activities ofCYP94family gene members precisely control JA-mediated defense responses in tomato.
On the mechanical origins of waving, coiling and skewing inArabidopsis thalianaroots
Authors: Porat Amir , Tekinalp Arman , Bhosale Yashraj , Gazzola Mattia , Meroz Yasmine
Published: May 2023

By masterfully balancing directed growth and passive mechanics, plant roots are remarkably capable of navigating complex heterogeneous environments to find resources. Here we present a theoretical and numerical framework which allows us to interrogate and simulate the mechanical impact of solid interfaces on the growth pattern of plant organs. We focus on the well-known waving, coiling and skewing patterns exhibited by roots ofArabidopsis thalianawhen grown on inclined surfaces, serving as a minimal model of the intricate interplay with solid substrates. By modelling growing slender organs as Cosserat rods that mechanically interact with the environment, our simulations verify hypotheses of waving and coiling arising from the combination of active gravitropism and passive root-plane responses. Skewing is instead related to intrinsic twist due to cell file rotation. Numerical investigations are outfitted with an analytical framework that consistently relates transitions between straight, waving, coiling and skewing patterns with substrate tilt angle. Simulations are found to corroborate theory and recapitulate a host of reported experimental observations, thus providing a systematic approach for studyingin silicoplant organs behavior in relation to their environment.

Significance

Plant roots exhibit an exceptional ability to navigate in heterogeneous soil environments while overcoming obstacles. Our study combines theory and experimental observations to interrogate and simulate the mechanical impact of obstacles on organ growth. As a test case we focus on well-known observations of waving, coiling and skewing growth patterns ofArabidopsis thalianaroots grown on inclined substrates. Overall, our study explains a broad set of experimental observations through the minimal ingredients of gravitropism and passive mechanics. Our numerical framework provides anin silicolaboratory, yielding quantitative insight into the dynamics of growing organs at the intersection of active processes and passive mechanics, applicable beyond plants to any slender growing system, from neurons or fungal hyphae to novel soft robots.
Altered glucose utilization and disrupted mitochondrial homeostasis in CD4+T cells from HIV-positive women on combination anti-retroviral therapy
Authors: Akiso Matrona , Ameka Magdalene , Naidoo Kewreshini K , Langat Robert , Kombo Janet , Sikuku Delories , Ndung’u Thumbi , Altfeld Marcus , Anzala Omu , Mureithi Marianne
Published: May 2023

Background

For optimal functionality, immune cells require a robust and adaptable metabolic program that is fueled by dynamic mitochondrial activity. In this study, we investigate the metabolic alterations occurring in immune cells during HIV infection and antiretroviral therapy by analyzing the uptake of metabolic substrates and mitochondrial homeostasis. By delineating changes in immune cell metabolic programming during HIV, we may identify novel potential therapeutic targets to improve antiviral immune responses.

Methods

Whole blood was drawn from HIV uninfected female volunteers and women with chronic HIV infection on combination antiretroviral therapy. Peripheral blood mononuclear cells-derived immune cells were directly incubated with different fluorescent markers: FITC-2-NBDG (2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl) amino]-2-deoxy-D-glucose), FITC-BODIPY (4,4-Difluoro-5,7-Dimethyl-4-Bora-3a,4a-Diaza-s-Indacene-3-Hexadecanoic Acid), FITC-MitoTracker Green and APC-MitoTracker Deep Red. The uptake of glucose and fats and the mitochondrial mass and potential were measured using flow cytometry. All values are reported quantitatively as geometric means of fluorescence intensity.

Results

During chronic HIV infection, cellular uptake of glucose increases in HIV+dendritic cells (DCs) in particular. CD4+T cells had the lowest uptake of glucose and fats compared to all other cells regardless of HIV status, while CD8+T cells took up more fatty acids. Interestingly, despite the lower utilization of glucose and fats in CD4+T cells, mitochondrial mass increased in HIV+CD4+T cells compared to HIV negative CD4+T-cells. HIV+CD4+T cells also had the highest mitochondrial potential.

Conclusions

Significant disparities in the utilization of substrates by leukocytes during chronic HIV/cART exist. Innate immune cells increased utilization of sugars and fats while adaptive immune cells displayed lower glucose and fat utilization despite having a higher mitochondrial activity. Our findings suggest that cART treated HIV-infected CD4+T cells may prefer alternative fuel sources not included in these studies. This underscores the importance of understanding the metabolic effects of HIV treatment on immune function.
Nematostella vectensisexemplifies the exceptional expansion and diversity of opsins in the eyeless Hexacorallia
Authors: McCulloch Kyle J , Babonis Leslie S , Liu Alicia , Daly Christina M , Martindale Mark Q , Koenig Kristen M
Published: May 2023

Background

Opsins are the primary proteins responsible for light detection in animals. Cnidarians (jellyfish, sea anemones, corals) have diverse visual systems that have evolved in parallel with bilaterians (squid, flies, fish) for hundreds of millions of years. Medusozoans (e.g. jellyfish, hydroids) have evolved eyes multiple times, each time independently incorporating distinct opsin orthologs. Anthozoans (e.g. corals, sea anemones,) have diverse light-mediated behaviors and, despite being eyeless, exhibit more extensive opsin duplications than medusozoans. To better understand the evolution of photosensitivity in animals without eyes we increased anthozoan representation in the phylogeny of animal opsins and investigated the large but poorly characterized opsin family in the sea anemoneNematostella vectensis.

Results

We analyzed genomic and transcriptomic data from 16 species of cnidarians to generate a large opsin phylogeny (708 sequences) with the largest sampling of anthozoan sequences to date. We identified 29 opsins fromN. vectensis(NvOpsins) with high confidence, using transcriptomic and genomic datasets. We found that lineage-specific opsin duplications are common across Cnidaria, with anthozoan lineages exhibiting among the highest numbers of opsins in animals. To establish putative photosensory function ofNvOpsins, we identified canonically conserved protein domains and amino acid sequences essential for opsin function in other animal species. We show high sequence diversity amongNvOpsinsat sites important for photoreception and transduction, suggesting potentially diverse functions. We further examined the spatiotemporal expression ofNvOpsinsand found both dynamic expression of opsins during embryonic development and sexually dimorphic opsin expression in adults.

Conclusions

These data show that lineage-specific duplication and divergence has led to expansive diversity of opsins in eyeless cnidarians, suggesting opsins from these animals may exhibit novel biochemical functions. The variable expression patterns of opsins inN. vectensissuggest opsin gene duplications allowed for a radiation of unique sensory cell types with tissue-and stage-specific functions. This diffuse network of distinct sensory cell types could be an adaptive solution for varied sensory tasks experienced in distinct life history stages in Anthozoans.
Praziquantel inhibitsCaenorhabditis elegansdevelopment and species-wide differences might be cct-8-dependent
Authors: Wit Janneke , Dilks Clayton M. , Zhang Gaotian , Kim Guisbert Karen S. , Zdraljevic Stefan , Guisbert Eric , Andersen Erik C.
Published: May 2023

Anthelmintic drugs are used to treat parasitic roundworm and flatworm infections in humans and other animals.Caenorhabditis elegansis an established model to investigate anthelmintics used to treat roundworms. In this study, we useC. elegansto examine the mode of action and the mechanisms of resistance against the flatworm anthelmintic drug praziquantel (PZQ), used to treat trematode and cestode infections. We found that PZQ inhibited development and that this developmental delay varies by genetic background. Interestingly, both enantiomers of PZQ are equally effective againstC. elegans, but only the left-handed PZQ (S-PZQ) is effective against schistosome infections. We conducted a genome-wide association mapping with 74 wildC. elegansstrains to identify a region on chromosome IV that is correlated with differential PZQ susceptibility. Five candidate genes in this region:cct-8, znf-782, Y104H12D.4, Y104H12D.2, andcox-18, might underlie this variation. The genecct-8, a subunit of the protein folding complex TRiC, has variation that causes a putative protein coding change (G226V), which is correlated with reduced developmental delay. Gene expression analysis suggests that this variant correlates with slightly increased expression of bothcct-8andhsp-70. Acute exposure to PZQ caused increased expression ofhsp-70, indicating that altered TRiC function might be involved in PZQ responses. To test if this variant affects development upon exposure to PZQ, we used CRISPR-Cas9 genome editing to introduce the V226 allele into the N2 genetic background (G226) and the G226 allele into the JU775 genetic background (V226). These experiments revealed that this variant was not sufficient to explain the effects of PZQ on development. Nevertheless, this study shows thatC. eleganscan be used to study responses to PZQ to identify mode of action and resistance mechanisms. Additionally, we show that the TRiC complex requires further evaluation for PZQ responses inC. elegans.
Energy landscapes and heat capacity signatures for monomers and dimers of amyloid forming hexapeptides
Authors: Nicy  , Wales David J.
Published: May 2023

Amyloid formation is a hallmark of various neurodegenerative disorders. In this contribution, energy landscapes are explored for various hexapeptides that are known to form amyloids. Heat capacity (CV) analysis at low temperature for these hexapeptides reveals that the low energy structures contributing to the first heat capacity feature above a threshold temperature exhibit a variety of backbone conformations for amyloid forming monomers. The corresponding control sequences do not exhibit such structural polymorphism, as diagnosed via end-to-end distance and a dihedral angle defined for the monomer. A similar heat capacity analysis for dimer conformations obtained using basin-hopping global optimisation, shows clear features in end-to-end distance versus dihedral correlation plots, where amyloid-forming sequences exhibit a preference for larger end-to-end distances and larger positive dihedrals. These results hold for sequences taken from tau, amylin, insulin A chain, a de-novo designed peptide, and various control sequences. While there is a little overall correlation between the aggregation propensity and the temperature at which the low-temperature CVfeature occurs, further analysis suggests that the amyloid forming sequences exhibit the key CVfeature at a lower temperature compared to control sequences derived from the same protein.
The health impact of wood dust in Kijishi: Yamanaka Kijishi Study
Authors: Nakao Yuki , Okada Kazuhiro , Goto Yasuhiro , Matsuda Yosuke , Fujimoto Kiyohiko , Okuhara Yoshiyasu
Published: May 2023

Objectives

It is well known that exposure to wood dust can cause Sinonasal carcinomas (SNC) and various respiratory diseases such as allergies. Japanese woodturners called kijishi work in an environment where wood dust is generated from lathes, and they are considered at risk for various diseases. However, there is a dearth of research on the health impacts of wood dust on kijishi. The purpose of this study is to understand the real situation of kijishi that are exposed to wood dust.

Methods

A questionnaire survey was conducted with 20 kijishi. We measured the amounts of wood dust two experienced kijishi were exposed to during a typical woodturning session.

Results

Approximately half the participants exhibited allergic symptoms such as rhinitis; however, this rate was equivalent to the result of the Japan Comprehensive Survey of Living Conditions 2019. SNC was not observed in any of the participants. The level of exposure to wood dust was low, that is, inhalable dust was 0.03 mg/m3, and total dust 0.22 mg/m3. The measured values were very low compared to the Occupational Safety and Health Administration (OSHA), National Institute for Occupational Safety and Health (NIOSH), American Conference of Governmental Industrial Hygienist (ACGIH), and Health and Safety Executive Control of Substances Hazardous to Health (HSE COSHH) standards.

Conclusions

We concluded that constant ventilation during woodturning reduces exposure to wood dust, thereby preventing harm to the health of kijishi to a considerable extent.
The indirect relationship between sleep and cognition in the PREVENT Cohort: Identifying targets for intervention
Authors: Tari Benjamin , Yehuda Michael Ben , Laurell Axel Anders Stefan , Ritchie Karen , Dauvilliers Yves , Ritchie Craig , Lawlor Brian , Naci Lorina , Terrera Graciela Muniz , Malhotra Paresh A. , Watermeyer Tam , Dudas Robert , Underwood Benjamin R. , O’Brien John T. , Raymont Vanessa , Koychev Ivan
Published: May 2023

Introduction

As the global population ages, the economic, societal, and personal burdens associated with worsening cognition and dementia onset are growing. It is therefore becoming ever more critical to understand the factors associated with cognitive decline. One such factor is sleep. Adequate sleep has been shown to maintain cognitive function and protect against the onset of chronic disease, whereas sleep deprivation has been linked to cognitive impairment and the onset of depression and dementia.

Objectives

Here, we aim to identify and explore mechanistic links between several sleep parameters, depressive symptoms and cognition in a cohort of middle-aged adults.

Methods

We investigated data from the PREVENT dementia programme via structural equation modelling to illustrate links between predictor variables, moderator variables, and two cognitive constructs (i.e., Executive Function and Memory).

Results

Our model demonstrated that sleep quality, and total hours of sleep were related to participants’ depressive symptoms, and that, participant apathy was related to higher scores on the Epworth Sleepiness and Lausanne NoSAS Scales. Subsequently, depressive symptoms, but not sleep or apathy ratings, were associated with Executive Function.

Conclusions

We provide evidence for an indirect relationship between sleep and cognition mediated by depressive symptoms in a middle-aged population. Our results provide a base from which cognition, dementia onset, and potential points of intervention, may be better understood.
Deep brain stimulation modulates directional limbic connectivity in major depressive disorder
Authors: Fridgeirsson Egill A. , Bergfeld I.O. , de Kwaasteniet B.P. , Luigjes J. , van Laarhoven J. , Notten P. , Beute G. , van den Munckhof P. , Schuurman P.R. , Denys D.A.J.P. , van Wingen G.A.
Published: May 2023

Deep brain stimulation (DBS) is being investigated as treatment for patients with refractory major depressive disorder (MDD). However, little is known about how DBS exerts its antidepressive effects. Here, we investigated whether ventral anterior limb of the internal capsule (vALIC) stimulation modulates a limbic network centered around the amygdala in patients with treatment resistant MDD.

Nine patients underwent resting state functional magnetic resonance imaging (fMRI) before DBS surgery and after one year of treatment. In addition, they were scanned twice within two weeks during the subsequent double blind crossover phase with active and sham treatment. Eleven matched controls underwent fMRI scans at same time intervals to account for test-retest effects. The imaging data was investigated with functional connectivity analysis and dynamic causal modelling (DCM).

Results showed that one year of DBS treatment was associated with increased functional connectivity of the left amygdala with precentral cortex and left insula along with decreased bilateral connectivity between nucleus accumbens and ventromedial prefrontal cortex. No changes in functional connectivity were observed during the crossover phase. Effective connectivity analyses using DCM revealed widespread amygdala-centric changes between pre-surgery and one year follow-up, while the crossover phase was associated with insula-centric changes between active and sham stimulation.

These results suggest that vALIC DBS results in complex rebalancing of the limbic network involved in emotion, reward and interoceptive processing.
A protocol for a critical realist systematic synthesis of interventions to promote pupils’ wellbeing by improving the school climate in Low- and Middle-Income Countries
Authors: Abbott Pamela , Shanks Rachel , Stanley Isabel , D’Ambruoso Lucia
Published: May 2023

Introduction

The review described in this protocol will be the first critical realist review of the literature reporting on the impact of interventions to promote pupils’ wellbeing by improving the school climate in Low- and Middle-Income Countries. The review is being carried out to inform the programme theory for a critical realist evaluation of a whole school mindfulness intervention in Ethiopia and Rwanda to improve pupils’ mental wellbeing. Our initial programme theory hypothesises that pupils’ (and teachers’) responses to the mindfulness intervention as well as changing the behaviour and attitudes of individual pupils and teachers, will change the ‘school climate’ in ways that have a positive impact on mental wellbeing. This literature review will facilitate the identification of mechanisms for change working at the level of the whole school climate, something which is only infrequently discussed in evaluations of mindfulness interventions.

Methods and analysis

A critical realist review methodology will be used to provide a causal interdisciplinary understanding of how school climate can promote the wellbeing of pupils. This will be done through a systematic literature review and extrapolating context, agency, intervention, mechanisms, and outcome configurations and synthesising these to provide a conceptual understanding of the impact of interventions to improve school climate.

Discussion

The review findings will inform a critical realist evaluation of a mindfulness intervention in schools that we will be carrying out. The findings from the review will enable us to focus more precisely and transparently on what policymakers and other stakeholders need to know about how school climate changes due to introducing mindfulness to the curriculum and how this impacts pupils’ wellbeing [and for which pupils]. We will publish the findings from the review in academic and professional publications, policy briefs, workshops, conferences, and social media.

PROSPERO registration number

CRD42023417735
Aging modulates the effects of scene complexity on visual search and target selection in virtual environments
Authors: Lachica Isaiah J. , Kalkar Aniruddha , Finley James M.
Published: May 2023

Processing task-relevant visual information is important for successfully completing many everyday tasks. Prior work demonstrated that older adults are more susceptible to distraction by salient stimuli, leading to less efficient visual search. However, these studies often relied on simple stimuli, and little is known about how aging influences visual attention in environments more representative of real-world complexity. Here, we test the hypothesis that aging impacts how the visual complexity of the environment influences visual search. We asked young and older adults to complete a virtual reality-based visual search task with three levels of increasing visual complexity. As visual complexity increased, all participants took longer to complete the task. This increase in time to completion resulted from two factors: an increased time required to transfer gaze from one target to the next as participants re-fixated task-relevant objects and longer lags between when correct targets were fixated and selected. We also found that these changes in gaze trajectory were greater in older adults. In addition, we found that short-term and working memory capacities were positively associated with multiple performance measures in the visual search task. This suggests that visual search performance could be integrated into assessments of working memory in dynamic environments.
De novoassembly of the whole genome of Moth bean (Vigna aconitifolia), an underutilizedVignaspecies of India
Authors: Suranjika Sandhya , Pradhan Seema , Kalia Rajwant K. , Dey Nrisingha
Published: May 2023

As a fast-growing legume species, moth bean (Vigna aconitifolia)has a unique habit of sustaining in conditions of higher temperatures and drought. This grain legume is also valued for it seeds which have one of the highest contents of proteins amongst all grain legumes. This plant can be a rich source of genomic resources, which can be applied to improve abiotic stress response in allied grain legumes and also help understand the biological processes governing their overall development. Here we generate ade novogenome assembly ofVigna aconitifoliausing PacBio High-Fidelity reads and Hi-C sequencing data, with a total size of 409 Mb and contig N50 of more than 30Mb. We also annotated the genome for repeat sequences, found that the moth bean genome comprises of about 54% of repetitive sequences, and predicted 36950 protein-coding genes. Using the available RNA-Seq data for moth bean, we have developed a differential expression profile for various tissues of moth bean using the whole genome as a reference and identified simple sequence repeats that could be developed into viable molecular markers. This nascent study will provide insight into the identification of agronomically important genes and accelerate the genetic improvement of moth bean as well as other legume crops.