bluuebunny/crossref_metadata_2025 huggingface dataset:
BRCA1/BRC-1 and SMC-5/6 regulate DNA repair pathway engagement during Caenorhabditis elegans meiosis
Authors: Toraason Erik , Salagean Alina , Almanzar David E , Brown Jordan E , Richter Colette M , Kurhanewicz Nicole A , Rog Ofer , Libuda Diana E
Published: August 2024

The preservation of genome integrity during sperm and egg development is vital for reproductive success. During meiosis, the tumor suppressor BRCA1/BRC-1 and structural maintenance of chromosomes 5/6 (SMC-5/6) complex genetically interact to promote high fidelity DNA double strand break (DSB) repair, but the specific DSB repair outcomes these proteins regulate remain unknown. Using genetic and cytological methods to monitor resolution of DSBs with different repair partners in Caenorhabditis elegans, we demonstrate that both BRC-1 and SMC-5 repress intersister crossover recombination events. Sequencing analysis of conversion tracts from homolog-independent DSB repair events further indicates that BRC-1 regulates intersister/intrachromatid noncrossover conversion tract length. Moreover, we find that BRC-1 specifically inhibits error prone repair of DSBs induced at mid-pachytene. Finally, we reveal functional interactions of BRC-1 and SMC-5/6 in regulating repair pathway engagement: BRC-1 is required for localization of recombinase proteins to DSBs in smc-5 mutants and enhances DSB repair defects in smc-5 mutants by repressing theta-mediated end joining (TMEJ). These results are consistent with a model in which some functions of BRC-1 act upstream of SMC-5/6 to promote recombination and inhibit error-prone DSB repair, while SMC-5/6 acts downstream of BRC-1 to regulate the formation or resolution of recombination intermediates. Taken together, our study illuminates the coordinated interplay of BRC-1 and SMC-5/6 to regulate DSB repair outcomes in the germline.
Differential conformational dynamics in two type-A RNA-binding domains drive the double-stranded RNA recognition and binding
Authors: Parvez Firdousi , Sangpal Devika , Paithankar Harshad , Amin Zainab , Chugh Jeetender
Published: August 2024

Trans-activation response (TAR) RNA-binding protein (TRBP) has emerged as a key player in the RNA interference pathway, wherein it binds to different pre-microRNAs (miRNAs) and small interfering RNAs (siRNAs), each varying in sequence and/or structure. We hypothesize that TRBP displays dynamic adaptability to accommodate heterogeneity in target RNA structures. Thus, it is crucial to ascertain the role of intrinsic and RNA-induced protein dynamics in RNA recognition and binding. We have previously elucidated the role of intrinsic and RNA-induced conformational exchange in the double-stranded RNA-binding domain 1 (dsRBD1) of TRBP in shape-dependent RNA recognition. The current study delves into the intrinsic and RNA-induced conformational dynamics of the TRBP-dsRBD2 and then compares it with the dsRBD1 study carried out previously. Remarkably, the two domains exhibit differential binding affinity to a 12-bp dsRNA owing to the presence of critical residues and structural plasticity. Furthermore, we report that dsRBD2 depicts constrained conformational plasticity when compared to dsRBD1. Although, in the presence of RNA, dsRBD2 undergoes induced conformational exchange within the designated RNA-binding regions and other residues, the amplitude of the motions remains modest when compared to those observed in dsRBD1. We propose a dynamics-driven model of the two tandem domains of TRBP, substantiating their contributions to the versatility of dsRNA recognition and binding.
JAK inhibition decreases the autoimmune burden in Down syndrome
Authors: Rachubinski Angela L , Wallace Elizabeth , Gurnee Emily , Enriquez Estrada Belinda A , Worek Kayleigh R , Smith Keith P , Araya Paula , Waugh Katherine A , Granrath Ross E , Britton Eleanor , Lyford Hannah R , Donovan Micah G , Eduthan Neetha Paul , Hill Amanda A , Martin Barry , Sullivan Kelly D , Patel Lina , Fidler Deborah J , Galbraith Matthew D , Dunnick Cory A , Norris David A , Espinosa Joaquin M
Published: August 2024

Individuals with Down syndrome (DS), the genetic condition caused by trisomy 21 (T21), display clear signs of immune dysregulation, including high rates of autoimmune disorders and severe complications from infections. Although it is well established that T21 causes increased interferon responses and JAK/STAT signaling, elevated autoantibodies, global immune remodeling, and hypercytokinemia, the interplay between these processes, the clinical manifestations of DS, and potential therapeutic interventions remain ill defined. Here, we report a comprehensive analysis of immune dysregulation at the clinical, cellular, and molecular level in hundreds of individuals with DS. We demonstrate multi-organ autoimmunity of pediatric onset concurrent with unexpected autoantibody-phenotype associations. Importantly, constitutive immune remodeling and hypercytokinemia occur from an early age prior to autoimmune diagnoses or autoantibody production. We then report the interim analysis of a Phase II clinical trial investigating the safety and efficacy of the JAK inhibitor tofacitinib through multiple clinical and molecular endpoints. Analysis of the first 10 participants to complete the 16-week study shows a good safety profile and no serious adverse events. Treatment reduced skin pathology in alopecia areata, psoriasis, and atopic dermatitis, while decreasing interferon scores, cytokine scores, and levels of pathogenic autoantibodies without overt immune suppression. Additional research is needed to define the effects of JAK inhibition on the broader developmental and clinical hallmarks of DS. ClinicalTrials.gov identifier: NCT04246372.
Growth consequences of the inhomogeneous organization of the bacterial cytoplasm
Authors: van Heerden Johan H , Berkvens Alicia , de Groot Daan H , Bruggeman Frank J
Published: August 2024

In many bacteria, translating ribosomes are excluded from the nucleoid, while amino-acid and energy-supplying metabolic enzymes spread evenly throughout the cytoplasm. Here we show with time-lapse fluorescence microscopy that this inhomogeneous organisation of the cytoplasm can cause single
Escherichia coli
cells to experience an imbalance between biosynthesis and metabolism when they divide, resulting in cell size-dependent growth rate perturbations. After division, specific growth rate and ribosome concentration correlates negatively with birthsize, and positively with each other. These deviations are compensated during the cell-cycle, but smaller-than-average cells do so with qualitatively different dynamics than larger-thanaverage cells. A mathematical model of cell growth, division and regulation of biosynthetic and metabolic resource allocation reproduces our experimental findings, suggesting a simple mechanism through which long-term growth rate homeostasis is maintained while heterogeneity is continuously generated. This work shows that the life of single bacterial cells is intrinsically out-of-steady-state, dynamic and reliant on cytoplasmic organization.
Predicting the satisfiability of Boolean formulas by incorporating gated recurrent unit (GRU) in the Transformer framework
Authors: Chang Wenjing , Guo Mengyu , Luo Junwei
Published: August 2024

The Boolean satisfiability (SAT) problem exhibits different structural features in various domains. Neural network models can be used as more generalized algorithms that can be learned to solve specific problems based on different domain data than traditional rule-based approaches. How to accurately identify these structural features is crucial for neural networks to solve the SAT problem. Currently, learning-based SAT solvers, whether they are end-to-end models or enhancements to traditional heuristic algorithms, have achieved significant progress. In this article, we propose TG-SAT, an end-to-end framework based on Transformer and gated recurrent neural network (GRU) for predicting the satisfiability of SAT problems. TG-SAT can learn the structural features of SAT problems in a weakly supervised environment. To capture the structural information of the SAT problem, we encodes a SAT problem as an undirected graph and integrates GRU into the Transformer structure to update the node embeddings. By computing cross-attention scores between literals and clauses, a weighted representation of nodes is obtained. The model is eventually trained as a classifier to predict the satisfiability of the SAT problem. Experimental results demonstrate that TG-SAT achieves a 2%–5% improvement in accuracy on random 3-SAT problems compared to NeuroSAT. It also outperforms in SR(N), especially in handling more complex SAT problems, where our model achieves higher prediction accuracy.
Tree regeneration and ontogenetic strategies of northern European hemiboreal forests: transitioning towards closer-to-nature forest management
Authors: Petrokas Raimundas , Manton Michael , Kavaliauskas Darius
Published: August 2024

Background

Tree ontogeny is the genetic trajectories of regenerative processes in trees, repeating in time and space, including both development and reproduction. Understanding the principles of tree ontogeny is a key priority in emulating natural ecological patterns and processes that fall within the calls for closer-to-nature forest management. By recognizing and respecting the growth and development of individual trees and forest stands, forest managers can implement strategies that align with the inherent dynamics of forest ecosystem. Therefore, this study aims to determine the ontogenetic characteristics of tree regeneration and growth in northern European hemiboreal forests.

Methodology

We applied a three-step process to review i) the ontogenetic characteristics of forest trees, ii) ontogenetic strategies of trees for stand-forming species, and iii) summarise the review findings of points i and ii to propose a conceptual framework for transitioning towards closer-to-nature management of hemiboreal forest trees. To achieve this, we applied the super-organism approach to forest development as a holistic progression towards the establishment of natural stand forming ecosystems.

Results

The review showed multiple aspects; first, there are unique growth and development characteristics of individual trees at the pre-generative and generative stages of ontogenesis under full and minimal light conditions. Second, there are four main modes of tree establishment, growth and development related to the light requirements of trees; they were described as ontogenetic strategies of stand-forming tree species: gap colonisers, gap successors, gap fillers and gap competitors. Third, the summary of our analysis of the ontogenetic characteristics of tree regeneration and growth in northern European hemiboreal forests shows that stand-forming species occupy multiple niche positions relative to forest dynamics modes.

Conclusions

This study demonstrates the importance of understanding tree ontogeny under the pretext of closer-to-nature forest management, and its potential towards formulating sustainable forest management that emulates the natural dynamics of forest structure. We suggest that scientists and foresters can adapt closer-to-nature management strategies, such as assisted natural regeneration of trees, to improve the vitality of tree communities and overall forest health. The presented approach prioritizes ecological integrity and forest resilience, promoting assisted natural regeneration, and fostering adaptability and connectivity among plant populations in hemiboreal tree communities.
Museomics allows comparative analyses of mitochondrial genomes in the family Gryllidae (Insecta, Orthoptera) and confirms its phylogenetic relationships
Authors: Dong Jiajia , Liu Yong , Tan Ming Kai , Wahab Rodzay Abdul , Nattier Romain , Chifflet-Belle Pascaline , Robillard Tony
Published: August 2024

Background

Next-generation sequencing technology can now be used to sequence historical specimens from natural history collections, an approach referred to as museomics. The museomics allows obtaining molecular data from old museum-preserved specimens, a resource of biomolecules largely underexploited despite the fact that these specimens are often unique samples of nomenclatural types that can be crucial for resolving scientific questions. Despite recent technical progress, cricket mitogenomes are still scarce in the databases, with only a handful of new ones generated each year from freshly collected material.

Methods

In this study, we used the genome skimming method to sequence and assemble three new complete mitogenomes representing two tribes of the cricket subfamily Eneopterinae: two were obtained from old, historical type material of Xenogryllus lamottei (68 years old) and X. maniema (80 years old), the third one from a freshly collected specimen of Nisitrus vittatus. We compared their genome organization and base composition, and reconstructed the molecular phylogeny of the family Gryllidae.

Results

Our study not only confirmed that the genome skimming method used by next generation sequencing allows us to efficiently obtain the whole mitogenome from dry-pinned historical specimens, but we also confirmed how promising it is for large-scale comparative studies of mitogenomes using resources from natural history collections. Used in a phylogenetic context the new mitogenomes attest that the mitogenomic data contain valuable information and also strongly support phylogenetic relationships at multiple time scales.
Representación de estudiantes con necesidades educativas especiales en educación escolar técnico profesional a partir de las prácticas de evaluación diferenciada
Authors:   , Dreau Virot Zenaida Andrea
Published: August 2024

Esta investigación busca caracterizar los modos de representación y problematización de la presencia y participación de estudiantes con necesidades educativas especiales (NEE), a partir de las prácticas de evaluación diferenciada que se realizan en un instituto comercial de administración delegada de la comuna de Santiago. Este trabajo se aproxima a la producción de estudiantes con NEE desde los estudios críticos de discapacidad, los cuales se utilizan para comprender la producción de estudiantes a partir de los discursos docentes y la legislación, tanto nacional como interna del establecimiento, de las evaluaciones diferenciadas. Para ello, se analizan políticas públicas, documentos internos del establecimiento y entrevista semiestructurada a actores del proceso evaluativo de la institución. Además, a través de un análisis postestructuralista del discurso y análisis temático, se realiza una triangulación de los datos obtenidos a partir de las tres fuentes interrogadas para lograr la caracterización buscada. Dentro de los resultados de la presente investigación se encuentra el esfuerzo como pilar para lograr la inclusión esperada, la calificación como motivación del aprendizaje y la educación superior como gran expectativa de las y los docentes para sus estudiantes.
Comparison of Physiochemical Properties and Biocompatiblity of Two Commercially Available Natural Xenogeneic Collagen Membranes: In-vitro Study
Authors: Gnanamani A , Lavu Vamsi , Joseph Reshma Achu , Thilagam R , Balaji SK
Published: August 2024

Introduction: Physical factors like stiffness and surface features are among the characteristics that affect the performance of barrier membranes and determine the results of regenerative processes. A perfect equilibrium between the membrane’s rigidity and mechanical stability guarantees effective periodontal regeneration. The study’s novelty lies in comparing the physical characteristics, namely morphology, tensile strength, wettability, and biological characteristics, namely biocompatibility and enzyme resistance properties, of the Fix-GideTM membrane against the gold standard membrane, Bio-Gide®. Aim: To explore the physical and biological properties of two commercially available barrier membranes in oral tissue regeneration. Materials and Methods: The present in-vitro study compared two commercially available membranes, namely Bio-Gide® and Fix-GideTM. Both membranes are bilayered resorbable membranes, with Bio-Gide composed of porcine dermis Type-I and III collagen and Fix-GideTM of bovine origin. The study was conducted at the Central Leather Research Institute, and the membranes were procured from Sri Ramachandra Institute of Higher Education and Research. Morphological characterisation was done using Scanning Electron Microscopy (SEM). Physical properties were evaluated using a tensile strength test, enzyme resistance test, and wettability measurement. Biocompatibility assessment was also performed. The Statistical Package for Social Sciences (SPSS) software was used to run the MannWhitney U test to analyse the statistical data obtained in the enzyme resistance test. Results: Biocompatibility assessment showed no cytotoxic profile of both membranes, portraying their biocompatible nature. Morphological analysis using SEM showed the surface of the Bio-Gide® membrane to be considerably smoother than the Fix-GideTM membrane. Both membranes, however, have fibrous and porous features on their inner surfaces. Tensile strength assessment found that the percentage of elongation was better with Bio-Gide (1.7±0.4 and 4.8±0.4) when compared to Fix-Gide (15.8±0.2 and 2.2±0.2) in both wet and dry states, respectively. The enzyme resistance test evaluated in dry and wet settings showed that the membranes, namely, Bio-Gide® membrane exhibited around 29±2% of degradation, whereas the Fix-GideTM exhibited only 18±2%. These mechanical profiles exhibited that the membranes has appreciable differences, although there wasn’t a statistically significant difference between them (p=0.68). According to wettability studies, BioGide is hydrophilic, but Fix-GideTM is hydrophobic. Conclusion: The observations of the present study showed that Fix-Gide had comparable physio-biological properties to that of the Bio-Gide membrane. This supports the suitability of the use of both membranes for various oral tissue regeneration procedures.
Corporate Citizenship and Wealth Maximisation: A Re-evaluation of Stakeholder Theory Using Evidence from Listed Industrial Goods Firms in Nigeria
Authors: Anaike Chiamaka L. , Nworie Gilbert Ogechukwu , Ochuka Chekwube Esther
Published: August 2024

Based on stakeholder theory, the study examined the extent to which firm involvement in corporate citizenship influences the wealth maximisation of listed industrial goods firms in Nigeria. While corporate citizenship was measured using corporate donations, the proxy for wealth maximisation was market value of the firms. Ex-post facto research design was used on a population of thirteen listed industrial goods firms in Nigeria, from which a sample size of nine was purposively selected. Secondary data were gleaned from the firms’ annual reports from 2013 to 2023 (11 year interval). Panel Cross-section Heteroskedasticity LR Test was conducted while White cross-section standard errors and covariance was applied to correct the heteroskedasticity anomaly. In addition, Residual Cross-Section Dependence Test was carried out of which Cross-section Seemingly Unrelated Regression was used to address the issue of cross-sectional dependence. Therefore, the hypothesis were tested using estimates from Panel Estimated Generalised Least Squares, which revealed that involvement in corporate citizenship significantly and positively influences wealth maximisation among listed industrial goods firms in Nigeria (β = 32.79912; p-value = 0.000). In conclusion, firms that engage in meaningful corporate citizenship are likely to build stronger relationships and this, in turn, contributes to increased sustainable wealth creation. We recommend that senior management of listed industrial goods firms in Nigeria should prioritise and formalise their corporate citizenship initiatives as integral parts of their corporate strategies in order to ensure that the community development efforts they make are not ad hoc but embedded in the firm's strategic planning and operations.
Effect of Liquid and Single Compound NPK Fertilizer on Soil and Plant Nitrogen Content and Yield of Sweet Corn (Zea mays L. Saccharata) in Inceptisols of Jatinangor
Authors: Sofyan Emma Trinurani , Yuniarti Anni , Alparidzy Mohammad
Published: August 2024

The main problem in Inceptisols soil is its low fertility level. One of the efforts to overcome this problem is by providing additional nutrients that can be absorbed by the soil through compound NPK fertilization, which supplies available nutrients to optimize soil fertility, thereby improving the quality and quantity of sweet corn plants. This research aims to determine the effect of liquid compound NPK fertilizer and single fertilizer on total soil N content, plant N content, and yields of sweet corn crops; and to obtain a combination of compound NPK inorganic fertilizer and single fertilizer that provides the highest yield of sweet corn on Inceptisols soil from Jatinangor. The experiment was carried out in the experimental garden of the soil chemistry and plant nutrition laboratory, Faculty of Agriculture, Universitas Padjadjaran, Jatinangor, from July 2023 to December 2023. The research design used was a Completely Randomized Block Design (CRBD) consisting of nine treatments and three replications, namely: A (control); B (1 dose NPK fertilizer standard);  C (¾ NPK compound + ¾ NPK standard); D (1 NPK compound + ¾ NPK standard); E (1½ NPK compound  + ¾ NPK standard); F (½ NPK compound + 1 NPK standard); G (¾ NPK compound + 1 NPK standard); H (1 NPK compound + 1 NPK standard), and I (1½ NPK Compound  + 1 NPK standard). The data collected were initial soil yield before treatment, soil N-total content, N-plant content, cob diameter, cob length, husked cob weight, peeled cob weight, and cob weight per plot. Data analysis was carried out using variance analysis and continued with the 5% level Duncan’s Mutiple Range Test (DMRT). Data analysis using SPSS software. The research results show that the application of liquid and single compound NPK fertilizer had a significant effect on increasing soil N-total, N-plant content, and yields of sweet corn on Inceptisols soil from Jatinangor; and the combination dose of 1 NPK compound (8 L ha-1) + 1 dose of NPK standard (Urea 300 kg ha-1, TSP 100 kg ha-1, and KCl 50 kg ha-1) provides the best sweet corn crop results on Inceptisols soil from Jatinangor.
Effect of Organic Manure and NPK Consortium on Growth, Yield and Quality of Beetroot (Beta vulgaris L.) in Southern Rajasthan Condition
Authors: Chandel Rajesh , Bairwa H.L , Pilania Shalini , Saharan Vinod , Rawal Pokhar , Meena R. L , Ajmeri Aamir Shohel , Dulani Varun
Published: August 2024

The present investigation was carried out at Horticulture Farm, Department of Horticulture, Rajasthan College of Agriculture, MPUAT, Udaipur. The nine treatments for the beetroot crop were evaluated with three replications under randomized block design. Variety “Detroit dark red” of beetroot was used in this experiment. The results exhibit the significant effect of various treatments on growth, yield and quality of beetroot. The growth parameters viz., Maximum germination percentage (72.23), maximum plant height at 25 DAS, 50 DAS and at harvesting (16.00, 31.77 and 32.30 cm), respectively, Number of leave per plant (6.58, 9.23 and 13.13), respectively,leaf area (195.47 cm),root length (16.30 cm), maximum root diameter (7.32 cm), Maximum root weight (147.90 g), Maximum yield per plot (7.10 kg) maximum TSS (8.59 0Brix), highest reducing sugar content (5.23 %), highest total sugar content (7.30%), highest betanine (1.96 mg/100g).
Bamboo’s Role in Climate Change Adaptation and Mitigation: An Analysis of Biomass, Carbon Stock, and Economic Potential in Tanzania
Authors: Zella Adili Y.
Published: August 2024

Bamboo, a rapidly growing member of the grass family, thrives across diverse climates worldwide and offers vital ecosystem services essential for human well-being and economic development. Notably, bamboo releases 35% more oxygen than other trees and sequesters an average of 12 tons of carbon dioxide per hectare, highlighting its significant ecological benefits. This study analyses the contribution of bamboo to climate change adaptation and mitigation, focusing on Tanzania as a case study. Specifically, the study aims to determine the amount of biomass and carbon stock of bamboo in Tanzania, and estimate the financial benefits from including bamboo in carbon payment projects like REDD+. Utilizing adapted allometric models and data from the National Forest Resources Monitoring and Assessment (NAFORMA) of 2015, the study reveals that Tanzania possesses 4.04 billion tons of stored bamboo biomass and 1.9 billion tons of stored bamboo carbon, translating to an estimated 7.6 billion US dollars in unutilized conservation profit from carbon trading. The findings indicate that 51.4% of the stored bamboo biomass, carbon, and potential conservation profit are concentrated in the genus Bambusa, with nearly half of these resources located in the southern regions of Lindi and Mtwara. These results underscore the substantial ecological and economic benefits of bamboo ecosystem services, emphasizing the need for stakeholders to formulate strategies for the sustainable production, conservation, and management of bamboo in Tanzania. The study provides a benchmark for developing policies and plans that leverage bamboo's potential in climate change adaptation and mitigation, promoting environmental sustainability and economic growth.
The significance of the episodic nature of atmospheric deposition to Low Nutrient Low Chlorophyll regions
Authors: Guieu C. , Aumont O. , Paytan A. , Bopp L. , Law C. S. , Mahowald N. , Achterberg E. P. , Marañón E. , Salihoglu B. , Crise A. , Wagener T. , Herut B. , Desboeufs K. , Kanakidou M. , Olgun N. , Peters F. , Pulido‐Villena E. , Tovar‐Sanchez A. , Völker C.
Published: October 2014

In the vast Low Nutrient Low‐Chlorophyll (LNLC) Ocean, the vertical nutrient supply from the subsurface to the sunlit surface waters is low, and atmospheric contribution of nutrients may be one order of magnitude greater over short timescales. The short turnover time of atmospheric Fe and N supply (<1 month for nitrate) further supports deposition being an important source of nutrients in LNLC regions. Yet, the extent to which atmospheric inputs are impacting biological activity and modifying the carbon balance in oligotrophic environments has not been constrained. Here, we quantify and compare the biogeochemical impacts of atmospheric deposition in LNLC regions using both a compilation of experimental data and model outputs. A metadata‐analysis of recently conducted field and laboratory bioassay experiments reveals complex responses, and the overall impact is not a simple “fertilization effect of increasing phytoplankton biomass” as observed in HNLC regions. Although phytoplankton growth may be enhanced, increases in bacterial activity and respiration result in weakening of biological carbon sequestration. The application of models using climatological or time‐averaged non‐synoptic deposition rates produced responses that were generally much lower than observed in the bioassay experiments. We demonstrate that experimental data and model outputs show better agreement on short timescale (days to weeks) when strong synoptic pulse of aerosols deposition, similar in magnitude to those observed in the field and introduced in bioassay experiments, is superimposed over the mean atmospheric deposition fields. These results suggest that atmospheric impacts in LNLC regions have been underestimated by models, at least at daily to weekly timescales, as they typically overlook large synoptic variations in atmospheric deposition and associated nutrient and particle inputs. Inclusion of the large synoptic variability of atmospheric input, and improved representation and parameterization of key processes that respond to atmospheric deposition, is required to better constrain impacts in ocean biogeochemical models. This is critical for understanding and prediction of current and future functioning of LNLC regions and their contribution to the global carbon cycle.
Slime Moulds
Authors: Blanton Richard L
Published: October 2014

Slime moulds are organisms that feed and grow like protozoa but reproduce like fungi. No single taxonomic group encompasses all slime moulds. Instead, the slime mould habit appears to have arisen multiple times across a number of different groups. Their unusual name belies the importance of some species as experimental research organisms.

Dictyostelium discoideum

has provided significant insights into cell differentiation and pattern formation, cell motility, cell signalling, gene expression and cell adhesion and in recent years has also been employed in studies of the mechanism of action of pharmaceuticals, the cellular effects of pathogenic microorganisms and the evolution of social behaviour.

Physarum polycephalum

has provided insights into cytoplasmic streaming and control of nuclear division and more recently has been employed in practical and theoretical studies of path‐finding. The comparative genomics of the multicellular slime moulds has the potential to provide insights into the evolution of multicellularity.

Key Concepts:

‘Slime moulds’ is a descriptive term rather than a systematic category.

The slime mould habit of protozoan‐like feeding stages alternating with fungus‐like reproductive stages has arisen independently in a wide variety of microorganisms embracing four of the five major supergroups of Eukaryotes.

The multicellular slime moulds include the well‐known social amoeba
Dictyostelium discoideum
, which has had broad application as a model research organism in the study of fundamental cellular processes.

Complete genome sequences are available for some of the multicellular slime moulds and their non‐aggregative and nonfruiting amoebal relatives. This presents intriguing prospects for exploring the evolution of multicellularity using comparative genomics.
Huxley, Andrew Fielding
Authors: Huang Christopher L‐H
Published: October 2014

Andrew Huxley (1917–2012) graduated in Natural Sciences at Cambridge (1935–1939), beginning research on nerve excitation with Alan Hodgkin in 1939. During World War II he worked on operational anti‐aircraft and naval gunnery. He returned to Cambridge in 1945, moved to University College London in 1960 and returned to Cambridge as Master of Trinity College (1984–1990). Huxley made major contributions on nerve conduction and muscle activation. He analysed nerve action potentials invoking underlying transmembrane ion movements, and their saltatory propagation in myelinated nerves. His muscle work demonstrated the action of the transverse tubules conveying surface excitation to the interior thereby initiating contraction. He established the sliding filament theory for actin–myosin interaction involving actions of cross‐bridges formed between them. Huxley was awarded the 1963 Nobel Prize in Physiology or Medicine with Hodgkin and John Eccles, elected to the Royal Society in 1955, knighted in 1974 and created Order of Merit in 1983.
Integrated Pest Management
Authors: Philips Christopher R , Kuhar Thomas P , Hoffmann Michael P , Zalom Frank G , Hallberg Rosemary , Herbert D Ames , Gonzales Christopher , Elliott Steve
Published: October 2014

Defining integrated pest management (IPM) is not easy. Although numerous definitions can be found, the goal is usually the same, to coordinate pest biology, environmental information and available technology to prevent unacceptable levels of pest damage by the most economical means, while posing the least possible risk to people, property, and the environment. IPM is a science‐based decision‐making process that identifies and reduces risks from unwanted pests and the control strategies used in all arenas from agricultural, residential and public areas to wild lands. The IPM ‘tool box’ has almost limitless combinations of options and applying multiple tactics minimises the chance that a pest will adapt to any one tactic. However, new programmes will only succeed if they meet the economic goals of the growers, are socially accepted and are ecologically based. Herein the authors discuss the concept of IPM; available strategies; examples of successful implementation; and potential new tools. The advancement of IPM will hinge on new technology, and a more fundamental understanding of organisms and ecosystems.

Key Concepts:

Integrated pest management (IPM) is a science‐based and sustainable approach to managing pests.

The goal of IPM is to suppress pest abundance and damage to acceptable or tolerable levels.

IPM tactics include pest‐resistant or pest‐tolerant plants, and cultural, physical, mechanical, genetic, biological and chemical controls.

IPM is a complex decision‐making process based on numerous factors.

Measuring IPM successes can be difficult, but there are clear successes.

Technological advances will play a major role in future IPM programs.
Metabolic Effects of Caloric Restriction
Authors: Lamming Dudley W , Anderson Rozalyn M
Published: October 2014

Caloric restriction (CR) is a dietary intervention that robustly extends lifespan in diverse species. In mammals CR extends the period in which the animal is fit and vigorous, and attenuates age‐related disease vulnerability. Benefits of CR include reduced incidence of cancer, improved cardiovascular health, increased insulin sensitivity, and resistance to neurodegenerative diseases. The fact that CR extends not only average lifespan but also maximum lifespan has led to the consensus that an optimised CR diet slows the aging process itself. Here we outline the effects of CR on physiology and metabolism and where these may fit with current theories of aging. The authors describe factors that are likely to mediate the physiological adaptations to CR, placing an emphasis on nutrient sensitive regulators of metabolism. A major incentive for research into the mechanisms of CR is the promise of novel treatments for age‐related diseases and disorders that are relevant to human aging.

Key Concepts:

CR has a system‐wide physiological impact.

Metabolic factors are responsive to CR.

Metabolism and aging are tightly linked.

Growth factor signalling impacts metabolism.

CR research is highly relevant for human aging.
Virus Discovery in the 21st Century
Authors: Kapoor Amit , Lipkin W Ian
Published: October 2014

Viral discovery poses challenges distinct from those associated with other microbial agents, such as bacteria, fungi and parasites. With the exception of mimiviruses and megaviruses, where imaging is feasible by optical microscopy, viruses cannot be detected without resorting to specialized electron microscopy. Furthermore, viruses lack correlates of the conserved bacterial 16S
ribosomal ribonucleic acid (rRNA)
gene sequences and fungi's 18S rRNA or internal transcribed spacer gene sequences that facilitate detection and phylogenetic characterisation through polymerase chain reaction (PCR) amplification. Virus discovery during most of the twentieth century followed a classical approach comprising isolation in cell culture or animal models, followed by morphological classification by electron microscopy and studies of serological properties. In the late twentieth century, advances in nucleic acid sequencing have revolutionised virus discovery by enabling cultivation‐independent methods for virus detection and classification. Here, we review current methods for virus discovery and characterisation and provide our perspective on likely future advances in this field.

Key Concepts:

Recent advances in nucleic acid sequencing enable cultivation‐independent methods for microbial diagnosis surveillance and discovery.

Viruses are ubiquitous and play important roles in global ecology and evolution as well as in disease.

Classical methods such as culture and serology remain important despite the increasing emphasis on molecular assays in microbiology.

Zoonoses, infections that jump from domestic animals and wildlife to humans, account for the majority of emerging infectious diseases.

Microbial discovery must be linked to rigorous validation strategies to reduce risks for errors that can profoundly impact public health.
Transhumanism and Enhancement
Authors: Levin Susan B
Published: October 2014

Humans have always sought to elevate the conditions of their existence. While ancient writers noted limited human contact with the divine, transhumanists believe that crossing from our ontological status to a higher plane is possible, even inevitable, through human technological ingenuity. Given their content and implications, further scrutiny of transhumanists' views is essential. Areas that should be addressed include transhumanists' own essentialism, the implications of existing brain science for transhumanists' more extravagant claims, and their constricted notions of knowledge and education. Further, not only would posthuman existence not be ours, but exuberant visions of that existence do not adequately heed the irreducible context in which humans pursue desires' fulfillment. Finally, when defending their positions, transhumanists must attend further to potentially grave risks, which, even where acknowledged, are downplayed.

Key Concepts:

Notwithstanding key differences, conservatives and transhumanists concur on significant points.

While proponents of strong enhancement challenge conservatives' views of human nature, they too are essentialists.

Transhumanists aim to shift humans' ontological status to a plane on which posthumans would be like the divine on two different ancient views.

Since posthuman existence could not be ours, questions of personal identity involving that stage are moot.

Current knowledge of the brain does not support extravagant claims about biotechnological boosts, whether cognitive or moral, and uploads.

Transhumanists' constricted views of human knowledge and education would extend to posthumans.

Our categorical incapacity to meaningfully anticipate what posthuman existence would be like deeply impacts the tenability of transhumanists' claims.

Even where transhumanists acknowledge the existence, even likelihood, of serious risks, they do not adequately attend to them.
Recent Advances on 5‐Lipoxygenase Biochemistry
Authors: Werz Oliver , Rådmark Olof , Steinhilber Dieter
Published: October 2014

5‐Lipoxygenase (5‐LOX) catalyses two steps in the biosynthesis of leukotrienes (LTs), lipid mediators of inflammation derived from arachidonic acid. LTs function in normal host defence, and have pathophysiological roles in chronic inflammatory diseases, as asthma and atherosclerosis. Also, possible effects of 5‐LOX products in relation to tumorigenesis have been described. 5‐LOX is also involved in the biosynthesis of anti‐inflammatory/pro‐resolving lipoxins. 5‐LOX is mainly expressed in myeloid and lymphoid cells and its expression is upregulated during cell differentiation. Cellular 5‐LOX activity is regulated in a complex manner and depends on cellular localisation, phosphorylation, the intracellular calcium concentration and the redox status of the cell. Thus, insight regarding the biochemistry of 5‐LOX is relevant for better understanding of normal physiology, and for development of pharmacotherapy.

Key Concepts:

Lipoxygenases oxygenate polyunsaturated fatty acids.

5‐LOX produces 5‐HPETE, leukotrienes and together with other dioxygenases lipoxins.

The regulatory C2‐like domain binds Ca
2+
, diacylglycerols and phosphatidylcholine and regulates the activity of the catalytic domain.

5‐LOX interacts with various proteins such as FLAP, CLP and Dicer.

The 5‐lipoxygenase pathway is part of the innate immune system.

5‐LOX products are involved in inflammation, allergic reactions, development of cardiovascular disease as well as certain types of cancer.
The Immunogenetics of the Autoimmune Myasthenias
Authors: Willcox Nick
Published: October 2014

The autoimmune myasthenias are prototypes of an emerging group of autoantibody‐mediated neurological diseases, mostly with very well defined target molecules, whether receptors or ion channels (or both). At the neuromuscular junction, these include presynaptic calcium channels in the Lambert–Eaton myasthenic syndrome (LEMS) and postsynaptic acetyl‐choline receptors (AChR) in myasthenia gravis (MG). These disorders are particularly informative because of the distinct aetiological factors in the several patient subgroups, including characteristic associations with small cell lung cancers in the LEMS or with thymomas in MG; also – but mainly in other subgroups – with certain immuno‐genetic variants, both in the HLA region and at other immuno‐regulatory loci. Here, I briefly summarise current knowledge in these areas and discuss its implications.
New Roles for
MHC
Class I Immune Molecules in the Healthy and Diseased Nervous System
Authors: Tyler Carolyn M , Boulanger Lisa M
Published: October 2014

Proteins of the major histocompatibility complex class I (MHC class I) are best known for their central role in the immune response. However, accumulating evidence shows that MHC class I proteins also have nonimmune roles in the healthy nervous system. MHC class I is expressed by developing and adult neurons, and is required for the proper establishment, function and modification of synaptic connections. The newly discovered, critical functions of MHC class I in the healthy nervous system suggest that MHC class I could directly link the immune response to changes in brain structure and function in diverse neurological disorders.

Key Concepts:

MHC class I is expressed by developing and mature neurons in the healthy nervous system.

Endogenous MHC class I limits neurite outgrowth, limits synapse density and promotes synapse elimination in multiple brain regions.

MHC class I limits synaptic transmission mediated by NMDA‐type glutamate receptors in the hippocampus, regulates NMDAR‐dependent synaptic plasticity, and is required for normal NMDAR‐dependent learning and memory.

The receptors and signalling pathways that mediate MHC class I's effects on neurons remain largely unknown.

Disruption of the nonimmune functions of MHC class I may be an unexpected contributor to diverse neurological disorders.
Genetics of Cerebellar and Vestibular Disorders
Authors: Martin‐Sierra Carmen , Requena Teresa , Lopez‐Escamez Jose A
Published: October 2014

Cerebellar and vestibular disorders are two groups of rare diseases with overlapping phenotypes with a strong genetic component. Previous studies had shown familial aggregation and few genes had been identified by segregation in large pedigrees. So, causal genes have remained unknown until the recent advances in next‐generation sequencing technologies, including whole‐exome sequencing (WES) as well as different bioinformatics approaches to elucidate and increase the lists of rare variants and novel genes associated with these disorders. WES have defined new genes as CLIC5 causing of DFNB102 and novel variants in
TGM6
, ELOVL4 or FXN genes associated with autosomal dominant and autosomal recessive hereditary ataxias. Vestibular disorders such as Meniere's disease or vestibular migraine also have a strong familial clustering with autosomal dominant inheritance, but no candidate genes have been identified in familial cases.

Key Concepts:

Cerebellar and vestibular disorders are two groups of rare diseases with a strong genetic component.

The clinical heterogeneity and the very low frequency of the causal variants can explain the slow progress in the knowledge of molecular genetics of vestibular and cerebellar disorders.

The bioinformatics analysis of rare variants and synonymous variants identified by NGS technology in multicase families is the best strategy to find out new genes associated with cerebellar and vestibular disorders.

Different bioinformatics approaches are needed to elucidate the genetic basis of cerebellar and vestibular disorders in order to find out causal variants leading to the development of new treatments.

A large number of causal mutations and genes will be described using NGS in vestibular and cerebellar disorders, but functional studies will be required to assess their impact on the phenotype.
Genotoxicity and Epigenetic Modifications in Response to Atmospheric and Engineered Nanoparticles
Authors: Des Marais Thomas L , Costa Max
Published: October 2014

Nanoparticles are of increasing interest and concern as they become more widely used in consumer products, industry and medicine. Nanoparticles differ from their ‘bulk’ materials in physiochemical properties, creating interest and further applications. In addition to being engineered, humans are constantly exposed to nanoparticles (NPs) through ambient air pollution. There is a need for toxicological assessment of these particles as humans come into contact with them every day. The toxicological mechanism and biological fate of these particles are not well known. Findings in the fields of genotoxicity and epigenetics shed light on potential mechanisms for adverse human health effects when exposed to these particles. There is still much work to be done in order to properly assess the risk of NP exposure.

Key Concepts:

Nanoparticles have different inherent physiochemical properties from bulk materials of the same composition.

Studies show that nanoparticles at smaller dimensions induce stronger toxic effects than the same particles at larger dimensions

Oxidative stress is increased when exposed to nanoparticles, more free radicals will cause more cellular and DNA damage.

Nanoparticles are being investigated for use in clinical settings, specifically diagnostic procedures and drug delivery.

Epigenetic modifications are those in which there is no genetic mutation or DNA damage present.

Nanoparticles will be constituents of ambient particulate matter, therefore, all life is exposed to varying amounts of nanoparticles daily.

Government organisations are working to increase research and development involving nanoparticles in order to better understand their mechanisms of action.
Lies, Damn Lies, and Expectations: How Base Rates Inform Lie–Truth Judgments
Authors: Street Chris N. H. , Richardson Daniel C.
Published: October 2014

We are biased towards thinking that people are telling the truth. Our study represents the first test of how beliefs about the base rate of truths and lies affect this truth bias. Raters were told either 20, 50 or 80% of the speakers would be telling the truth. As the speaker delivered their statement, participants indicated moment by moment whether they thought the speaker was lying or being truthful. At the end of the statement, they made a final lie–truth judgment and indicated their confidence. While viewing the statement, base rate beliefs had an early influence, but as time progressed, all conditions showed a truth bias. In the final judgment at the end of the statement, raters were truth biased when expecting mostly truths but did not show a lie bias when expecting mostly lies. We conclude base rate beliefs have an early influence, but over time, a truth bias dominates. Copyright © 2014 John Wiley & Sons, Ltd.