bluuebunny/crossref_metadata_2025 huggingface dataset:
Russell on Experience and Egocentricity
Authors: Wishon Donovan
Published: July 2024

Neutral monism is the view that ‘mind’ and ‘matter’ are composed of, or grounded in, more basic elements of reality that are intrinsically neither mental nor material. Before adopting this view in 1918, Russell was a mind–matter dualist and a pointed critic of it. His most ‘decisive’ objection concerns whether it can provide an adequate analysis of egocentricity and our use of indexical expressions such as ‘I’, ‘this’, ‘now’, and so on. I argue that M. G. F. Martin (2024) and other recent interpreters cannot make proper sense of Russell’s shifting views about egocentricity because they misascribe to his early dualism the thesis that experience is in some sense ‘diaphanous’ or ‘transparent’. Against this, I make the case that (1) Russell rejected the diaphaneity of experience as a dualist, (2) this rejection played a key role in his early objections to neutral monism, and (3) several decades later Russell takes his neutral monism to have key resources for answering his prior objections.
Horkheimer, Habermas, Foucault as Political Epistemologists
Authors: Alcoff Linda Martín
Published: July 2024

This paper reorients the problematic of political epistemology to put power at the centre of analysis, through an analysis of writings on the relationship between power and knowledge by Horkheimer, Habermas and Foucault. In their work, political epistemology was pursued analogously to the development of political economy, which explored the background conditions and assumptions of economic research. I also show that Horkheimer, Habermas and Foucault each had normative aims intended to improve both epistemology and knowing practices. Though their approaches are distinct, the shared element was a concern with redefining truth.
Genetic variation mining of the Chinese mitten crab (Eriocheir sinensis) based on transcriptome data from public databases
Authors: Xu Yuanfeng , Yu Fan , Feng Wenrong , Wei Jia , Su Shengyan , Li Jianlin , Hua Guoan , Li Wenjing , Tang Yongkai
Published: July 2024

At present, public databases house an extensive repository of transcriptome data, with the volume continuing to grow at an accelerated pace. Utilizing these data effectively is a shared interest within the scientific community. In this study, we introduced a novel strategy that harnesses SNPs and InDels identified from transcriptome data, combined with sample metadata from databases, to effectively screen for molecular markers correlated with traits. We utilized 228 transcriptome datasets of Eriocheir sinensis from the NCBI database and employed the Genome Analysis Toolkit software to identify 96 388 SNPs and 20 645 InDels. Employing the genome-wide association study analysis, in conjunction with the gender information from databases, we identified 3456 sex-biased SNPs and 639 sex-biased InDels. The KOG and KEGG annotations of the sex-biased SNPs and InDels revealed that these genes were primarily involved in the metabolic processes of E. sinensis. Combined with SnpEff annotation and PCR experimental validation, a highly sex-biased SNP located in the Kelch domain containing 4 (Klhdc4) gene, CHR67-6415071, was found to alter the splicing sites of Klhdc4, generating two splice variants, Klhdc4_a and Klhdc4_b. Additionally, Klhdc4 exhibited robust expression across the ovaries, testes, and accessory glands. The sex-biased SNPs and InDels identified in this study are conducive to the development of unisexual cultivation methods for E. sinensis, and the alternative splicing event caused by the sex-biased SNP in Klhdc4 may serve as a potential mechanism for sex regulation in E. sinensis. The analysis strategy employed in this study represents a new direction for the rational exploitation and utilization of transcriptome data in public databases.
Fine-tuning protein embeddings for functional similarity evaluation
Authors: Dickson Andrew , Mofrad Mohammad R K
Published: July 2024

Motivation

Proteins with unknown function are frequently compared to better characterized relatives, either using sequence similarity, or recently through similarity in a learned embedding space. Through comparison, protein sequence embeddings allow for interpretable and accurate annotation of proteins, as well as for downstream tasks such as clustering for unsupervised discovery of protein families. However, it is unclear whether embeddings can be deliberately designed to improve their use in these downstream tasks.

Results

We find that for functional annotation of proteins, as represented by Gene Ontology (GO) terms, direct fine-tuning of language models on a simple classification loss has an immediate positive impact on protein embedding quality. Fine-tuned embeddings show stronger performance as representations for K-nearest neighbor classifiers, reaching stronger performance for GO annotation than even directly comparable fine-tuned classifiers, while maintaining interpretability through protein similarity comparisons. They also maintain their quality in related tasks, such as rediscovering protein families with clustering.

Availability and implementation

github.com/mofradlab/go_metric
Minimally Invasive transCervical oEsophagectomy (MICE) for oesophageal cancer: prospective cohort study (IDEAL stage 2A)
Authors: Vercoulen Richard J M T , van Veenendaal Linde , Kramer Irene F , Hutteman Merlijn , Shiozaki Atsushi , Fujiwara Hitoshi , Rosman Camiel , Klarenbeek Bastiaan R
Published: July 2024

Background

Minimally invasive transcervical oesophagectomy is a surgical technique that offers radical oesophagectomy without the need for transthoracic access. The aim of this study was to evaluate the safety and feasibility of the minimally invasive transcervical oesophagectomy procedure and to report the refinement of this technique in a Western cohort.

Methods

A single-centre prospective cohort study was designed as an IDEAL stage 2A study. Patients with oesophageal cancer (cT1b–4a N0–3 M0) who were scheduled for oesophagectomy with curative intent were eligible for inclusion in the study. The main outcome parameter was the postoperative pulmonary complication rate and the secondary outcomes were the anastomotic leakage, recurrent laryngeal nerve palsy, and R0 resection rates, as well as the lymph node yield.

Results

In total, 75 patients underwent minimally invasive transcervical oesophagectomy between January 2021 and November 2023. Several modifications to the surgical technique were registered, evaluated, and implemented in the context of IDEAL stage 2A. A total of 12 patients (16%) had postoperative pulmonary complications, including pneumonia (4 patients) and pleural effusion with drainage or aspiration (8 patients). Recurrent laryngeal nerve palsy was observed in 33 of 75 patients (44%), with recovery in 30 of 33 patients (91%). A total of 5 of 75 patients (7%) had anastomotic leakage. The median number of resected lymph nodes was 29 (interquartile range 22–37) and the R0 resection rate was 96% (72 patients).

Conclusion

Introducing minimally invasive transcervical oesophagectomy for oesophageal cancer in a Dutch institution is associated with a low rate of postoperative pulmonary complications and a high rate of temporary recurrent laryngeal nerve palsy.
Improved sliding-mode control for tracking global maximum power of triple-series–parallel ladder photovoltaic arrays under uneven shadowing
Authors: Alla RamaKoteswaraRao , Rajani Kandipati , Yadlapalli Ravindranath Tagore
Published: July 2024

This paper presents an innovative way to enhance the performance of photovoltaic (PV) arrays under uneven shadowing conditions. The study focuses on a triple-series–parallel ladder configuration to exploit the benefits of increased power generation while addressing the challenges associated with uneven shadowing. The proposed methodology focuses on the implementation of improved sliding-mode control technique for efficient global maximum power point tracking. Sliding-mode control is known for its robustness in the presence of uncertainties and disturbances, making it suitable for dynamic and complex systems such as PV arrays. This work employs a comprehensive simulation framework to comment on the performance of the suggested improved sliding-mode control strategy in uneven shadowing scenarios. Comparative analysis has been done to show the better effectiveness of the suggested method than the traditional control strategies. The results demonstrate a remarkable enhancement in the tracking accuracy of the global maximum power point, leading to enhanced energy-harvesting capabilities under challenging environmental conditions. Furthermore, the proposed approach exhibits robustness and adaptability in mitigating the effect of shading on the PV array, thereby increasing overall system efficiency. This research contributes valuable insights into the development of advanced control strategies for PV arrays, particularly in the context of triple-series–parallel ladder configurations operating under uneven shadowing conditions. Under short narrow shading conditions, the improved sliding-mode control method tracks the maximum power better compared with perturb & observe at 20.68%, incremental-conductance at 68.78%, fuzzy incremental-conductance at 19.8%, and constant-velocity sliding-mode control at 1.25%. The improved sliding-mode control method has 60% less chattering than constant-velocity sliding-mode control under shading conditions.
MRI resting-state signature of the propensity to experience meaningful coincidences: a functional coupling analysis
Authors: Rominger Christian , Koschutnig Karl , Fink Andreas , Perchtold-Stefan Corinna M
Published: July 2024

The propensity to experience meaningful patterns in random arrangements and unrelated events shows considerable interindividual differences. Reduced inhibitory control (over sensory processes) and decreased working memory capacities are associated with this trait, which implies that the activation of frontal as well as posterior brain regions may be altered during rest and working memory tasks. In addition, people experiencing more meaningful coincidences showed reduced gray matter of the left inferior frontal gyrus (IFG), which is linked to the inhibition of irrelevant information in working memory and the control and integration of multisensory information. To study deviations in the functional connectivity of the IFG with posterior associative areas, the present study investigated the fMRI resting state in a large sample of n = 101 participants. We applied seed-to-voxel analysis and found that people who perceive more meaningful coincidences showed negative functional connectivity of the left IFG (i.e. pars triangularis) with areas of the left posterior associative cortex (e.g. superior parietal cortex). A data-driven multivoxel pattern analysis further indicated that functional connectivity of a cluster located in the right cerebellum with a cluster including parts of the left middle frontal gyrus, left precentral gyrus, and the left IFG (pars opercularis) was associated with meaningful coincidences. These findings add evidence to the neurocognitive foundations of the propensity to experience meaningful coincidences, which strengthens the idea that deviations of working memory functions and inhibition of sensory and motor information explain why people experience more meaning in meaningless noise.
A case report of Löffler’s endocarditis with right ventricular outflow obstruction in idiopathic hypereosinophilic syndrome: timely surgical intervention is crucial
Authors: Zeng Decai , Peng Ziyu , Guan Xuechun , Wu Ji
Published: July 2024

Background

Löffler’s endocarditis (LE) is a frequently encountered condition in hypereosinophilic syndrome and is associated with a significant morbidity and mortality rate.

Case Summary

A 22-year-old man presented with acute dyspnoea, recurring wheezing, and cough, leading to his hospital admission. Multimodal diagnostic imaging revealed a manifestation of eosinophil-mediated cardiac injury in the thrombus formation stage. Moreover, a mural thrombus and thickened endocardium had caused severe obstruction of the right ventricular outflow tract (RVOT) and complete obliteration of the right ventricular apex, resulting in a significant reduction in right ventricular cardiac output. The patient received a diagnosis of LE and was treated with high-dose corticosteroids and anticoagulants. To alleviate the RVOT obstruction, an emergency surgical intervention was conducted through median sternotomy to the removal of the mural thrombus and resection of the thickened endocardium. Subsequently, eosinophil counts normalized within 1 month. Follow-up imaging examination demonstrated the existence of a residual section of thickened endocardium within the right ventricular free wall. Importantly, no mural thrombus was detected with complete relief of the RVOT obstruction. Notably, a transthoracic echocardiography examination at the 3-month postoperative unveiled a significant regression in right ventricular endomyocardial fibrosis. The patient’s condition exhibited tangible improvement, with no adverse events observed.

Discussion

Multimodal imaging is essential for the early diagnosis and accurate staging of LE. Timely surgical intervention, combined with corticosteroid therapy, is an effective therapeutic approach in selected patients with LE. This approach is crucial to achieve remission of acute phase symptoms and improve prognosis.
Left ventricular apical pacing-induced heart failure in a child after congenital heart surgery: a case report
Authors: De Wolf Rik , van der Palen Roel L F , ten Harkel Arend D J , Hazekamp Mark G , Blom Nico A
Published: July 2024

Background

Left ventricular apical pacing (LVAP) is considered to preserve left ventricular (LV) systolic function in both patients with and without congenital heart disease. However, sporadic LVAP-associated cardiac dysfunction in children with complex structural heart disease was recently reported. We present the case of a 2.5-year-old child with complex congenital heart disease and LVAP-induced cardiomyopathy.

Case summary

Corrective surgery for double outlet right ventricle, subpulmonary ventricular septal defect, and transposition of the great arteries was done at the age of 1.5 months. Late complete atrioventricular block occurred, necessitating VVI pacemaker insertion with LV apical epicardial leads. He presented with heart failure and dilated cardiomyopathy 1.5 years after pacemaker insertion and required persistent circulatory support with intravenous inotropes. Speckle tracking echocardiography identified an important LV apical to basal dyssynchrony. After excluding any coronary artery involvement, cardiac resynchronization therapy was performed. Speckle tracking echocardiography guided lead placement resulted in improved LV contraction synchrony. Cardiac function recovered progressively in combination with oral heart failure medication and is almost normal at 10-month follow-up.

Discussion

Right ventricular pacing is a well-known cause of pacing-induced cardiomyopathy. The LV apex and LV free wall are thought to be most optimal locations for ventricular pacing in children. However, LVAP can also be the cause of a pacing-induced cardiomyopathy and decreased systolic LV function in children with complex congenital heart disease due to lack of LV contraction synchrony. Cardiac resynchronization therapy can reverse this LV dysfunction and remodelling.
Estimated impact of guidelines-based initiation of dual antihypertensive therapy on long-term cardiovascular outcomes in 1.1 million individuals
Authors: Coca Antonio , Borghi Claudio , Stergiou George S , Khan Irfan , Koumas Alexandra , Blacher Jacques , Abdel-Moneim Mohamed
Published: July 2024

Aims

Guidelines recommend initiation of dual combination antihypertensive therapy, preferably single-pill combination (SPC), in most patients with hypertension. Evidence on narrowing gaps in clinical practice relative to guidelines is limited.

Methods and results

Monte Carlo simulation was applied to 1.1 million patients qualifying for dual combination therapy from a previously conducted retrospective analysis of clinical practice, hospital statistics, and national statistics in the UK. We provide 10-year Kaplan–Meier event rates for the primary endpoint representing a composite of non-fatal myocardial infarction, non-fatal stroke (ischaemic or haemorrhagic), non-fatal heart failure hospitalization, or cardiovascular death. Cox model results from a previously conducted study were utilized to estimate baseline risk, together with evidence on risk reduction from the Blood Pressure Lowering Treatment Trialists’ Collaboration (BPLTTC) meta-analysis and published evidence on blood pressure-lowering efficacy of antihypertensive therapies. In the overall population, estimated 10-year event rates for the primary endpoint in patients with 100% persistence in monotherapy were 17.0% for irbesartan and 17.6% for ramipril. These rates were only modestly better than those observed in clinical practice (17.8%). In patients with 100% persistence in dual therapy, estimated event rates were 13.6% for combinations of irbesartan + amlodipine [absolute risk reduction (ARR) = 8.7% compared with untreated] and 14.3% for ramipril + amlodipine (ARR = 8.0% compared with untreated). The absolute risk of the primary endpoint was reduced by 15.9% in patients with atherosclerotic cardiovascular disease (ASCVD) and 6.6% in those without ASCVD. Similarly, the absolute risk was reduced by 11.7% in patients with diabetes and 7.8% in those without diabetes.

Conclusions

This study represents the first to investigate guidelines-based treatment in hypertensive patients and demonstrates the opportunity for considerable risk reduction by ensuring recommended dual therapy in clinical practice, particularly in the form of SPC with high persistence, relative to no treatment or monotherapy.
Genetics of hypertrophic cardiomyopathy: established and emerging implications for clinical practice
Authors: Lopes Luis R , Ho Carolyn Y , Elliott Perry M
Published: July 2024

Pathogenic variation in genes encoding proteins of the cardiac sarcomere is responsible for 30%–40% of cases of hypertrophic cardiomyopathy. The main clinical utility of genetic testing is to provide diagnostic confirmation and facilitation of family screening. It also assists in the detection of aetiologies, which require distinct monitoring and treatment approaches. Other clinical applications, including the use of genetic information to inform risk prediction models, have been limited by the challenge of establishing robust genotype–phenotype correlations with actionable consequences, but new data on the interaction between rare and common genetic variation, as well as the emergence of therapies targeting disease-specific pathogenic mechanisms, herald a new era for genetic testing in routine practice.
Global burden of atrial fibrillation/atrial flutter and its attributable risk factors from 1990 to 2021
Authors: Cheng Siyuan , He JinZheng , Han Yuchen , Han Shaojie , Li Panpan , Liao Huanyan , Guo Jun
Published: July 2024

Aims

To devise effective preventive measures, a profound understanding of the evolving patterns and trends in atrial fibrillation (AF) and atrial flutter (AFL) burdens is pivotal. Our study was designed to quantify the burden and delineate the risk factors associated with AF and AFL across 204 countries and territories spanning 1990–2021.

Methods and results

Data pertaining to AF and AFL were sourced from the Global Burden of Disease Study 2021. The burden of AF/AFL was evaluated using metrics such as incidence, disability-adjusted life years (DALYs), deaths, and their corresponding age-standardized rates (ASRs), stratified by age, sex, socio-demographic index (SDI), and human development index (HDI). The estimated annual percentage change was employed to quantify changes in ASRs. Population attributable fractions were calculated to determine the proportional contributions of major risk factors to age-standardized AF/AFL deaths. This analysis encompassed the period from 1990 to 2021. Globally, in 2021, there were 4.48 million incident cases [95% uncertainty interval (UI): 3.61–5.70], 8.36 million DALYs (95% UI: 6.97–10.13) and 0.34 million deaths (95% UI: 0.29–0.37) attributed to AF/AFL. The AF/AFL burden in 2021, as well as its trends from 1990 to 2021, displayed substantial variations based on gender, SDI quintiles, and geographical regions. High systolic blood pressure emerged as the leading contributor to age-standardized AF/AFL incidence, prevalence, death, and DALY rate globally among all potential risk factors, followed closely by high body mass index.

Conclusion

Our study underscores the enduring significance of AF/AFL as a prominent public health concern worldwide, marked by profound regional and national variations. Despite the substantial potential for prevention and management of AF/AFL, there is a pressing imperative to adopt more cost-effective strategies and interventions to target modifiable risk factors, particularly in areas where the burden of AF/AFL is high or escalating.
Complex vaccination strategies prevent the emergence of vaccine resistance
Authors: Rella Simon A , Kulikova Yuliya A , Minnegalieva Aygul R , Kondrashov Fyodor A
Published: July 2024

Vaccination is the most effective tool to control infectious diseases. However, the evolution of vaccine resistance, exemplified by vaccine resistance in SARS-CoV-2, remains a concern. Here, we model complex vaccination strategies against a pathogen with multiple epitopes—molecules targeted by the vaccine. We found that a vaccine targeting one epitope was ineffective in preventing vaccine escape. Vaccine resistance in highly infectious pathogens was prevented by the full-epitope vaccine, that is, one targeting all available epitopes, but only when the rate of pathogen evolution was low. Strikingly, a bet-hedging strategy of random administration of vaccines targeting different epitopes was the most effective in preventing vaccine resistance in pathogens with the low rate of infection and high rate of evolution. Thus, complex vaccination strategies, when biologically feasible, may be preferable to the currently used single-vaccine approaches for long-term control of disease outbreaks, especially when applied to livestock with near 100% vaccination rates.
Economic evaluation of reopening a dormant tree improvement programme: a case study with Scots pine in Scotland
Authors: Saraev Vadim , Ahtikoski Anssi , Whittet Richard , Ray Duncan
Published: July 2024

The deployment of improved forest reproductive material (FRM) selected to yield greater timber volume and quality than unimproved material could help to maintain productive, sustainable, and resilient forests and increase resistance to abiotic and biotic threats under extreme climate change events. In Scotland, Scots pine (Pinus sylvestris L.) is a productive species that aligns with these objectives. However, confidence in Scots pine has been low in recent years due to damage caused by the needle blight Dothistroma septosporum. Recent provenance/progeny trials using native Scots pine material from the Caledonian pine woods indicate a favourable genetic correlation between growth and resistance to D. septosporum, suggesting that simultaneous improvements are possible. The Scots pine breeding programme in Scotland was closed in 2002. Here, we present an economic case for reopening the breeding programme to further improve Scots pine FRM. Specifically, we evaluate the costs and potential benefits of supporting a new programme. We conduct an analysis using three improvement scenarios using a Faustmann formula (amended with thinnings) to maximize the land expectation value. Our results indicate that further improvement of Scots pine FRM would be cost-effective, outperforming the current Scots pine timber production and financial outcomes. The analysis shows that the Central scenario’s land expectation value rises by £883 ha−1 compared to the baseline of £79 ha−1, assuming a 3.5% interest rate. We employed both annuity calculations and a break-even analysis to show improved FRM could maintain a breeding programme investment of £3.5 million per year over a 30-year period with a break-even cost threshold increase of ~52% for purchasing improved planting materials from £0.33 to £0.50 per seedling. In conclusion, the study provides economic evidence of the commercial benefits for reopening the Scots pine breeding programme to increase timber production and financial returns.
Male-biased recombination at chromosome ends in a songbird revealed by precisely mapping crossover positions
Authors: Zhang Hongkai , Lundberg Max , Ponnikas Suvi , Hasselquist Dennis , Hansson Bengt
Published: July 2024

Recombination plays a crucial role in evolution by generating novel haplotypes and disrupting linkage between genes, thereby enhancing the efficiency of selection. Here, we analyze the genomes of 12 great reed warblers (Acrocephalus arundinaceus) in a 3-generation pedigree to identify precise crossover positions along the chromosomes. We located more than 200 crossovers and found that these were highly concentrated toward the telomeric ends of the chromosomes. Apart from this major pattern in the recombination landscape, we found significantly higher frequencies of crossovers in genic compared with intergenic regions, and in exons compared with introns. Moreover, while the number of recombination events was similar between the sexes, the crossovers were located significantly closer to the ends of paternal compared with maternal chromosomes. In conclusion, our study of the great reed warbler revealed substantial variation in crossover frequencies within chromosomes, with a distinct bias toward the sub-telomeric regions, particularly on the paternal side. These findings emphasize the importance of thoroughly screening the entire length of chromosomes to characterize the recombination landscape and uncover potential sex-biases in recombination.
Dynamic Expansions and Retinal Expression of Spectrally Distinct Short-Wavelength Opsin Genes in Sea Snakes
Authors: Rossetto Isaac H , Ludington Alastair J , Simões Bruno F , Van Cao Nguyen , Sanders Kate L
Published: July 2024

The photopigment-encoding visual opsin genes that mediate color perception show great variation in copy number and adaptive function across vertebrates. An open question is how this variation has been shaped by the interaction of lineage-specific structural genomic architecture and ecological selection pressures. We contribute to this issue by investigating the expansion dynamics and expression of the duplicated Short-Wavelength-Sensitive-1 opsin (SWS1) in sea snakes (Elapidae). We generated one new genome, 45 resequencing datasets, 10 retinal transcriptomes, and 81 SWS1 exon sequences for sea snakes, and analyzed these alongside 16 existing genomes for sea snakes and their terrestrial relatives. Our analyses revealed multiple independent transitions in SWS1 copy number in the marine Hydrophis clade, with at least three lineages having multiple intact SWS1 genes: the previously studied Hydrophis cyanocinctus and at least two close relatives of this species; Hydrophis atriceps and Hydrophis fasciatus; and an individual Hydrophis curtus. In each lineage, gene copy divergence at a key spectral tuning site resulted in distinct UV and Violet/Blue-sensitive SWS1 subtypes. Both spectral variants were simultaneously expressed in the retinae of H. cyanocinctus and H. atriceps, providing the first evidence that these SWS1 expansions confer novel phenotypes. Finally, chromosome annotation for nine species revealed shared structural features in proximity to SWS1 regardless of copy number. If these features are associated with SWS1 duplication, expanded opsin complements could be more common in snakes than is currently recognized. Alternatively, selection pressures specific to aquatic environments could favor improved chromatic distinction in just some lineages.
Build-A-Genome and the “awesome power of undergraduates”
Authors: Boeke Jef D ,   the Build-A-Genome Course, Bader Joel S , Basta Leighanne , Cai Yizhi , Chapman Carolyn , Cooper Eric , Dymond Jessica , Han Jeffrey , Jones Richard M , Lauer Stephanie , Li Bing-Zhi , Mathews Debra , Matinyan Nick , Muller Héloïse , Newman Robert , Ordoñez Ciriza Raquel , Payea Matthew , Qu Amanda , Sandmeier Franziska , Scheifele Lisa , Sikder Hashmat , Yuan Yingjin , Zeller Karen , Zhao Yu
Published: July 2024

The Elizabeth W. Jones Award for Excellence in Education recognizes individuals or groups who have had significant, sustained impact on genetics education at any level, from K-12 through graduate school and beyond. The 2024 Elizabeth W. Jones Award for Excellence in Education recipient Jef Boeke considers himself a geneticist turned engineer. He transformed his landmark synthetic yeast genome project into a research-heavy teaching course, revolutionizing molecular biology and genetics education.

The Build-A-Genome course was developed to teach students basic practical molecular genetics while also providing the raw materials for a global genome synthesis project, Yeast 2.0. The course evolved over two decades to reflect the changing needs and opportunities for the project and the development of new technologies. In addition to educating a generation of college and high school students in a new way, it also developed a cadre of educators who developed similar courses and projects at a wide variety of research and educational institutions.
The Drosophila tumor necrosis factor Eiger promotes Myc supercompetition independent of canonical Jun N-terminal kinase signaling
Authors: Kodra Albana L , Singh Aditi Sharma , de la Cova Claire , Ziosi Marcello , Johnston Laura A
Published: July 2024

Numerous factors have been implicated in the cell–cell interactions that lead to elimination of cells via cell competition, a context-dependent process of cell selection in somatic tissues that is based on comparisons of cellular fitness. Here, we use a series of genetic tests in Drosophila to explore the relative contribution of the pleiotropic cytokine tumor necrosis factor α (TNFα) in Myc-mediated cell competition (also known as Myc supercompetition or Myc cell competition). We find that the sole Drosophila TNF, Eiger (Egr), its receptor Grindelwald (Grnd/TNF receptor), and the adaptor proteins Traf4 and Traf6 are required to eliminate wild-type “loser” cells during Myc cell competition. Although typically the interaction between Egr and Grnd leads to cell death by activating the intracellular Jun N-terminal kinase (JNK) stress signaling pathway, our experiments reveal that many components of canonical JNK signaling are dispensable for cell death in Myc cell competition, including the JNKKK Tak1, the JNKK Hemipterous and the JNK Basket. Our results suggest that Egr/Grnd signaling participates in Myc cell competition but functions in a role that is largely independent of the JNK signaling pathway.
Inter domain linker region affects properties of CBM6 in GH5_34 arabinoxylanases and alters oligosaccharide product profile
Authors: Norlander Siri , Jasilionis Andrius , Allahgholi Leila , Wennerberg Christina , Grey Carl , Adlercreutz Patrick , Karlsson Eva Nordberg
Published: July 2024

Understanding the relation between enzyme domain structure and catalytic activity is crucial for optimal engineering of novel enzymes for lignocellulose bioconversion. Xylanases with varying specificities are commonly used to valorise the hemicellulose arabinoxylan (AX), yet characterization of specific arabinoxylanases remain limited. Two homologous GH5_34 arabinoxylanases, HhXyn5A and CtXyn5A, in which the two domains are connected by a 40-residue linker, exhibit distinct activity on AX, yielding different reaction product patterns, despite high sequence identity, conserved active sites and similar domain composition. In this study, the carbohydrate binding module 6 (CBM6), or the inter domain linker together with CBM6, were swapped to investigate their influence on hydrolytic activity and oligosaccharide product pattern on cereal AXs. The variants, with only CBM6 swapped, displayed reduced activity on commercial wheat and rye AX, as well as on extracted oat fibre, compared to the original enzymes. Additionally, exchange of both linker and CBM6 resulted in a reduced ratio of enzyme produced in soluble form in Escherichia coli cultivations, causing loss of activity of both HhXyn5A and CtXyn5A variants. Analysis of oligosaccharide product patterns applying HPAEC–PAD revealed a decreased number of reaction products for CtXyn5A with swapped CBM6, which resembled the product pattern of HhXyn5A. These findings emphasize the importance of the CBM6 interactions with the linker and the catalytic domain for enzyme activity and specificity, and underlines the role of the linker in enzyme structure organisation and product formation, where alterations in linker interactions with the catalytic and/or CBM6 domains, influence enzyme-substrate association and specificity.
Dynamic temporal transcriptome analysis reveals grape VlMYB59-VlCKX4 regulatory module controls fruit set
Authors: Shi Qiaofang , Li Xufei , Yang Shengdi , Zhao Xiaochun , Yue Yihan , Yang Yingjun , Yu Yihe
Published: July 2024

Fruit set is a key stage in determining yield potential and guaranteeing quality formation and regulation. N-(2-chloro-4-pyridyl)-N′-phenylurea (CPPU) has been widely applied in grape production, the most iconic of which is the promotion of grape fruit set. However, current studies still lack the molecular mechanism of CPPU-induced grape fruit set. Here, the dynamic, high-resolution stage-specific transcriptome profiles were generated based on two different treatments and five developmental periods during fruit set in ‘Kyoho’ grape (Vitis vinifera L. × V. labrusca L.). Pairwise comparison and functional category analysis showed that phytohormone action cytokinin was significantly enriched during the CPPU-induced grape fruit set, but not the natural one. Value differentially expressed gene (VDEG) was a newly proposed analysis strategy for mining genes related to the grape fruit set. Notably, the cytokinin metabolic process was significantly enriched among up-regulated VDEGs. Of importance, a key VDEG VlCKX4 related to the cytokinin metabolic process was identified as related to the grape fruit set. Overexpression of VlCKX4 gene promoted the Arabidopsis plants that produce more and heavier siliques. The transcription factor VlMYB59 directly bound to the promoter of VlCKX4 and activated its expression. Moreover, overexpression of VlMYB59 gene also promoted the Arabidopsis fruit set. Overall, VlMYB59 responded to CPPU treatment and directly activated the expression of VlCKX4, thus promoting the fruit set. A regulatory pathway of the VlMYB59-VlCKX4 module in the fruit set was uncovered, which provides important insights into the molecular mechanisms of the fruit set and good genetic resources for high fruit set rate breeding.
The gap-free genome of Forsythia suspensa illuminates the intricate landscape of centromeres
Authors: Cui Jian , Zhu Congle , Shen Lisha , Yi Congyang , Wu Rong , Sun Xiaoyang , Han Fangpu , Li Yong , Liu Yang
Published: July 2024

Forsythia suspensa, commonly known as weeping forsythia, holds significance in traditional medicine and horticulture. Despite its ecological and cultural importance, the existing reference genome presents challenges with duplications and gaps, hindering in-depth genomic analyses. Here, we present a Telomere-to-Telomere (T2T) assembly of the F. suspensa genome, integrating Oxford Nanopore Technologies (ONT) ultra-long, Hi-C datasets, and high-fidelity (HiFi) sequencing data. The T2T reference genome (Fsus-CHAU) consists of 14 chromosomes, totaling 688.79 Mb, and encompasses 33 932 predicted protein-coding genes. Additionally, we characterize functional centromeres in the F. suspensa genome by developing a specific CENH3 antibody. We demonstrate that centromeric regions in F. suspensa exhibit a diverse array of satellites, showcasing distinctive types with unconventional lengths across various chromosomes. This discovery offers implications for the adaptability of CENH3 and the potential influence on centromere dynamics. Furthermore, after assessing the insertion time of full-length LTRs within centromeric regions, we found that they are older compared to those across the entire genome, contrasting with observations in other species where centromeric retrotransposons are typically young. We hypothesize that asexual reproduction may impact retrotransposon dynamics, influencing centromere evolution. In conclusion, our T2T assembly of the F. suspensa genome, accompanied by detailed genomic annotations and centromere analysis, significantly enhances F. suspensa potential as a subject of study in fields ranging from ecology and horticulture to traditional medicine.
Treatment of Active Crohn’s Disease With Exclusive Enteral Nutrition Diminishes the Immunostimulatory Potential of Fecal Microbial Products
Authors: Kerbiriou Caroline , Dickson Caitlin , Nichols Ben , Logan Michael , Mascellani Anna , Havlik Jaroslav , Russell Richard K , Hansen Richard , Milling Simon , Gerasimidis Konstantinos
Published: July 2024

Background

Exclusive enteral nutrition (EEN) is an effective treatment for active Crohn’s disease (CD). This study explored the immunostimulatory potential of a cell-free fecal filtrate and related this with changes in the fecal microbiota and metabolites in children with active CD undertaking treatment with EEN.

Methods

Production of tumor necrosis factor α (TNFα) from peripheral blood mononuclear cells was measured following their stimulation with cell-free fecal slurries from children with CD, before, during, and at completion of EEN. The metabolomic profile of the feces used was quantified using proton nuclear magnetic resonance and their microbiota composition with 16S ribosomal RNA sequencing.

Results

Following treatment with EEN, 8 (72%) of 11 patients demonstrated a reduction in fecal calprotectin (FC) >50% and were subsequently labeled FC responders. In this subgroup, TNFα production from peripheral blood mononuclear cells was reduced during EEN (P = .008) and reached levels like healthy control subjects. In parallel to these changes, the fecal concentrations of acetate, butyrate, propionate, choline, and uracil significantly decreased in FC responders, and p-cresol significantly increased. At EEN completion, TNFα production from peripheral blood mononuclear cells was positively correlated with butyrate (rho = 0.70; P = .016). Microbiota structure (β diversity) was influenced by EEN treatment, and a total of 28 microbial taxa changed significantly in fecal calprotectin responders. At EEN completion, TNFα production positively correlated with the abundance of fiber fermenters from Lachnospiraceae_UCG-004 and Faecalibacterium prausnitzii and negatively with Hungatella and Eisenbergiella tayi.

Conclusions

This study offers proof-of concept data to suggest that the efficacy of EEN may result from modulation of diet-dependent microbes and their products that cause inflammation in patients with CD.
CRISPR/Cas9 Protocols for Disrupting Gene Function in the Non-vertebrate Chordate Ciona
Authors: Popsuj Sydney , Cohen Lindsey , Ward Sydney , Lewis Arabella , Yoshida Sean , Herrera R  Antonio , Cota Christina D , Stolfi Alberto
Published: July 2024

Synopsis

The evolutionary origins of chordates and their diversification into the three major subphyla of tunicates, vertebrates, and cephalochordates pose myriad questions about the genetic and developmental mechanisms underlying this radiation. Studies in non-vertebrate chordates have refined our model of what the ancestral chordate may have looked like, and have revealed the pre-vertebrate origins of key cellular and developmental traits. Work in the major tunicate laboratory model Ciona has benefitted greatly from the emergence of CRISPR/Cas9 techniques for targeted gene disruption. Here we review some of the important findings made possible by CRISPR in Ciona, and present our latest protocols and recommended practices for plasmid-based, tissue-specific CRISPR/Cas9-mediated mutagenesis.
Defined synthetic microbial communities colonize and benefit field-grown sorghum
Authors: Fonseca-García Citlali , Pettinga Dean , Wilson Andrew , Elmore Joshua R , McClure Ryan , Atim Jackie , Pedraza Julie , Hutmacher Robert , Turumtay Halbay , Tian Yang , Eudes Aymerick , Scheller Henrik V , Egbert Robert G , Coleman-Derr Devin
Published: July 2024

The rhizosphere constitutes a dynamic interface between plant hosts and their associated microbial communities. Despite the acknowledged potential for enhancing plant fitness by manipulating the rhizosphere, the engineering of the rhizosphere microbiome through inoculation has posed significant challenges. These challenges are thought to arise from the competitive microbial ecosystem where introduced microbes must survive, and the absence of adaptation to the specific metabolic and environmental demands of the rhizosphere. Here, we engineered a synthetic rhizosphere community (SRC1) with the anticipation that it would exhibit a selective advantage in colonizing the host Sorghum bicolor, thereby potentially fostering its growth. SRC1 was assembled from bacterial isolates identified either for their potential role in community cohesion through network analysis or for their ability to benefit from host-specific exudate compounds. The growth performance of SRC1 was assessed in vitro on solid media, in planta under gnotobiotic laboratory conditions, and in the field. Our findings reveal that SRC1 cohesion is most robust when cultivated in the presence of the plant host under laboratory conditions, with lineages being lost from the community when grown either in vitro or in a native field setting. We establish that SRC1 effectively promotes the growth of both above- and below-ground plant phenotypes in both laboratory and native field contexts. Furthermore, in laboratory conditions, these growth enhancements correlate with the transcriptional dampening of lignin biosynthesis in the host. Collectively, these results underscore the potential utility of synthetic microbial communities for modulating crop performance in controlled and native environments alike.
Effects of artificial light on foraging behavior of the Pacific Kangaroo Rat (Dipodomys agilis)
Authors: Berry Kaitlyn E , Stapp Paul
Published: July 2024

Artificial light at night is increasingly recognized as a cause of habitat degradation, and as a conservation threat to wildlife species. We studied the behavioral response of Pacific kangaroo rats (Dipodomys agilis) to natural and artificial light in coastal sage scrub in southern California, United States. We used digital trail cameras to monitor visits to seed trays in shrub and open, intershrub microhabitats. Under natural-light conditions, kangaroo rats were more active on full- than new-moon nights, and concentrated foraging beneath shrubs. Surprisingly, kangaroo rats frequently interacted with other rodents in seed trays. Near to an artificial light source, kangaroo rats removed fewer seeds, had fewer foraging bouts, and spent less time in trays—especially in brightly lit open microhabitats—compared to distances farther from the light. Differences between the first and second nights of trials during both experiments suggested that kangaroo rats learned locations of resource-rich seed trays and modified their behavior accordingly. Our results are similar to recent studies showing that artificial light depresses foraging activity of rodents in the areas of highest illumination, and adds to evidence of the need to mitigate impacts of urban lighting in fragments of coastal sage scrub, especially along the urban–wildland interface.
In silico evidence of bitopertin’s broad interactions within the SLC6 transporter family
Authors: de Carvalho Gustavo Almeida , Tambwe Paul Magogo , Nascimento Lucas Rodrigues Couto , Campos Bruna Kelly Pedrosa , Chiareli Raphaela Almeida , Junior Guilhermino Pereira Nunes , Menegatti Ricardo , Gomez Renato Santiago , Pinto Mauro Cunha Xavier
Published: July 2024

The Glycine Transporter Type 1 (GlyT1) significantly impacts central nervous system functions, influencing glycinergic and glutamatergic neurotransmission. Bitopertin, the first GlyT1 inhibitor in clinical trials, was developed for schizophrenia treatment but showed limited efficacy. Despite this, bitopertin’s repositioning could advance treating various pathologies. This study aims to understand bitopertin’s mechanism of action using computational methods, exploring off-target effects, and providing a comprehensive pharmacological profile. Similarity Ensemble Approach (SEA) and SwissTargetPrediction initially predicted targets, followed by molecular modeling on SWISS-MODEL and GalaxyWeb servers. Binding sites were identified using PrankWeb, and molecular docking was performed with DockThor and GOLD software. Molecular dynamics analyses were conducted on the Visual Dynamics platform. Reverse screening on SEA and SwissTargetPrediction identified GlyT1 (SLC6A9), GlyT2 (SLC6A5), PROT (SLC6A7), and DAT (SLC6A3) as potential bitopertin targets. Homology modeling on SwissModel generated high-resolution models, optimized further on GalaxyWeb. PrankWeb identified similar binding sites in GlyT1, GlyT2, PROT, and DAT, indicating potential interaction. Docking studies suggested bitopertin’s interaction with GlyT1 and proximity to GlyT2 and PROT. Molecular dynamics confirmed docking results, highlighting bitopertin’s target stability beyond GlyT1. The study concludes that bitopertin potentially interacts with multiple SLC6 family targets, indicating a broader pharmacological property.
Overcoming drought: life traits driving tree strategies to confront drought stress
Authors: Nadal-Sala Daniel , Ruehr Nadine K , Sabaté Santiago
Published: July 2024

This insight article comments on:

Ziegler C, Cochard, H, Stahl C, Bastien Gérard LF, Goret J, Heuret P, Levionnois S, Maillard P, Bonal D, Coste S. 2024. Residual water losses mediate the trade-off between growth and drought survival across saplings of 12 tropical rainforest tree species with contrasting hydraulic strategies. Journal of Experimental Botany 75, 4128–4147.
Growth on Douglas fir media facilitatesCryptococcusvirulence factor production and enhances fungal survival against environmental and immune stressors
Authors: Stempinski Piotr R , Greengo Seth D , Casadevall Arturo
Published: July 2024

The yeasts Cryptococcus neoformans and Cryptococcus gattii are fungal pathogens that can be isolated from the environment, including the surfaces of many plants. Cryptococcus gattii caused an outbreak on Vancouver Island, British Columbia beginning in 1999 that has since spread to the Pacific Northwest of the United States. Coastal Douglas fir (Pseudotsuga menziesii) is an important lumber species and a major component of the ecosystems in this area. Previous research has explored Cryptococcus survival and mating on Douglas fir plants and plant-derived material, but no studies have been done on the production of cryptococcal virulence factors by cells grown on those media. Here, we investigated the effects of growth on Douglas fir-derived media on the production of the polysaccharide capsule and melanin, two of the most important cryptococcal virulence factors. We found that while the capsule was mostly unchanged by growth in Douglas fir media compared to cells grown in defined minimal media, Cryptococcus spp. can use substrates present in Douglas fir to synthesize functional and protective melanin. These results suggest mechanisms by which Cryptococcus species may survive in the environment and emphasize the need to explore how association with Douglas fir trees could affect its epidemiology for human cryptococcosis.