bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evolutionary and biochemical analyses reveal conservation of the Brassicaceae telomerase ribonucleoprotein complex
Authors: Dew-Budd Kelly , Cheung Julie , Palos Kyle , Forsythe Evan S. , Beilstein Mark A. 
Published: September 2019

AbstractThe telomerase ribonucleoprotein complex (RNP) is essential for genome stability and performs this role through the addition of repetitive DNA to the ends of chromosomes. The telomerase enzyme is composed of a reverse transcriptase (TERT), which utilizes a template domain in an RNA subunit (TER) to reiteratively add telomeric DNA at the ends of chromosomes. Multiple TERs have been identified in the model plant Arabidopsis thaliana. Here we combine a phylogenetic and biochemical approach to understand how the telomerase RNP has evolved in Brassicaceae, the family that includes A. thaliana. Because of the complex phylogenetic pattern of template domain loss and alteration at the previously characterized A. thaliana TER loci, TER1 and TER2, across the plant family Brassicaceae, we bred double mutants from plants with a template deletion at AtTER1 and T-DNA insertion at AtTER2. These double mutants exhibited no telomere length deficiency, a definitive indication that neither of these loci encode a functional telomerase RNA. Moreover, we determined that the telomerase components TERT, Dyskerin, and the KU heterodimer are under strong purifying selection, consistent with the idea that the TER with which they interact is also conserved. To test this hypothesis further, we analyzed the substrate specificity of telomerase from species across Brassicaceae and determined that telomerase from close relatives bind and extend substrates in a similar manner, supporting the idea that TERs in different species are highly similar to one another and are likely encoded from an orthologous locus. Lastly, TERT proteins from across Brassicaceae were able to complement loss of function tert mutants in vivo, indicating TERTs from other species have the ability to recognize the native TER of A. thaliana. Finally, we immunoprecipitated the telomerase complex and identified associated RNAs via RNA-seq. Using our evolutionary data we constrained our analyses to conserved RNAs within Brassicaceae that contained a template domain. These analyses revealed a highly expressed locus whose disruption by a T-DNA resulted in a telomeric phenotype similar to the loss of other telomerase core proteins, indicating that the RNA has an important function in telomere maintenance.
Structural changes in secondary, but not primary, sensory cortex in individuals with congenital olfactory sensory loss
Authors: Peter Moa G. , Mårtensson Gustav , Postma Elbrich M. , Nordin Love Engström , Westman Eric , Boesveldt Sanne , Lundström Johan N. 
Published: September 2019

ABSTRACTIndividuals with congenital sensory loss usually demonstrate altered brain morphology in areas associated with early processing of the lost sense. Here, we aimed to establish whether this also applies to individuals born without a sense of smell (congenital anosmia) by comparing cortical morphology between 33 individuals with isolated congenital anosmia and matched controls. We detected no structural alterations in the primary olfactory (piriform) cortex. However, individuals with anosmia demonstrated gray matter volume atrophy in bilateral olfactory sulci, explained by decreased cortical area, curvature, and sulcus depth. They further demonstrated increased gray matter volume and cortical thickness in the medial orbital gyri; regions closely associated with olfactory processing, sensory integration, and value-coding. Our results suggest that a lifelong absence of sensory input does not necessarily lead to morphological alterations in primary sensory cortex and extend previous findings with divergent morphological alterations in bilateral orbitofrontal cortex, indicating influences of different plastic processes.
Epigenetic Memory Independent of Symmetric Histone Inheritance
Authors: Saxton Daniel S , Rine Jasper 
Published: September 2019

AbstractHeterochromatic gene silencing is an important form of gene regulation that usually requires specific histone modifications. A popular model posits that inheritance of modified histones, especially in the form of H3-H4 tetramers, underlies inheritance of heterochromatin. Because H3-H4 tetramers are randomly distributed between daughter chromatids during DNA replication, rare occurrences of asymmetric tetramer inheritance within a heterochromatic domain would have the potential to destabilize heterochromatin. This model makes a prediction that shorter heterochromatic domains would experience unbalanced tetramer inheritance more frequently, and thereby be less stable. In contrast to this prediction, we found that shortening a heterochromatic domain in Saccharomyces had no impact on the strength of silencing nor its heritability. Additionally, we found that replisome mutations that disrupt inheritance of H3-H4 tetramers had only minor effects on heterochromatin stability. These findings suggest that histones carry little or no memory of the heterochromatin state through DNA replication.
Genetic diversity and haplotypic structure of a Saudi population sample using Investigator Argus X-12 amplification kit
Authors: Messaoudi Safia A. , Babu Saranya R. , Alsaleh Abrar B. , Albajjah Mohamed , AlSnan Noora , Chaudhary Abdul Rauf 
Published: September 2019

AbstractX-chromosome short tandem repeat (X-STR) markers have shown a great capability in forensic identity investigations and paternity testing involving kinship analysis.In the current study, the distribution of 12 X-STR loci located in four linkage groups was evaluated using Investigator® Argus X-12 Amplification Kit in 200 unrelated healthy individuals (105 males and 95 females) from the central region of the Saudi Arabia in order to create a DNA database.Our results indicated that DXS10146 locus was the most informative with 21 alleles while DXS8378 locus was the least with five alleles. Forensic parameters showed that all X-STRs loci either as individual markers or as linkage groups provide genetic information with high discrimination that is appropriate for forensic purposes with Paternity Informed Consent (PIC), Power of exclusion (PE), and Paternity index (PI) varied from 0.61211 to 0.917979, 0.38722 to 0.842949, and 0.038416 to 0.16367, respectively. A significant Linkage disequilibrium (LD) with p-value after Bonferroni correction p ≤ 0.05/66= 0.0008 was observed for 17 pairs of loci in male samples and 4 pairs of loci in female. In the male group, LG3 showed relatively high values of Haplotype diversity. The pairwise genetic distance fixation index (Fst) results showed that the Saudi population is genetically close to the Egyptian and Emirati populations and distant to the Turkish population.The current study revealed that Investigator® Argus 12 X-STR kit would support forensic application, kinship testing involving female offspring, and human identification in Saudi populations.
Sex differences in autoimmunity could be associated with altered regulatory T cell phenotype and lipoprotein metabolism
Authors: Robinson George A , Waddington Kirsty E , Adriani Marsilio , Radziszewska Anna , Peckham Hannah , Isenberg David. A , Ioannou Yiannis , Ciurtin Coziana , Pineda-Torra Ines , Jury Elizabeth C 
Published: September 2019

ABSTRACTMale and female immune responses are known to differ resulting in an increased prevalence of autoimmunity in women. Here sex differences in T-cell subset frequency and function during adolescence were examined in healthy donors and patients with the autoimmune disease juvenile (J)SLE; onset of JSLE commonly occurs during puberty suggesting a strong hormonal influence. Healthy adolescent males had increased regulatory T-cell (Treg) frequency, and increased Treg suppressive capacity and IL-4 production compared to healthy adolescent females. The T-helper 2-like profile in male Tregs was associated with increased expression of GATA3 which correlated significantly with elevated Treg plasma membrane glycosphingolipid expression. Differential Treg phenotype was associated with unique serum metabolomic profiles in males compared to female adolescents. Notably, very low density lipoprotein (VLDL) metabolomic signatures correlated positively with activated Tregs in males but with resting Tregs in females. Consistently, only VLDL isolated from male serum was able to induce increased Treg IL-4 production and glycosphingolipid expression following in cultured cells. Remarkably, gender differences in Treg frequency, phenotype and function and serum metabolomic profiles were lost in adolescents with JSLE. This work provides evidence that a combination of pubertal development, immune cell defects and dyslipidemia may contribute to JSLE pathogenesis.
Dysregulated cell signalling and reduced satellite cell potential in ageing muscle
Authors: Patel Ketan , Simbi Biggy , Ritvos Olli , Vaiyapuri Sakthivel , Dhoot Gurtej K 
Published: September 2019

ABSTRACTAberrant activation of signalling pathways has been postulated to promote age related changes in skeletal muscle. Cell signalling activation requires not only the expression of ligands and receptors but also an appropriate environment that facilitates their interaction. Here we first examined the expression of SULF1/SULF2 and members of RTK and the Wnt family in skeletal muscle of normal and a mouse model of accelerated ageing. We show that SULF1/SULF2 and these signalling components, a feature of early muscle development are barely detectable in early postnatal muscle. Real time qPCR and immunocytochemical analysis showed gradual but progressive up-regulation of SULF1/SULF2 and RTK/Wnt proteins not only in the activated satellite cells but also on muscle fibres that gradually increased with age. Satellite cells on isolated muscle fibres showed spontaneous in vivo satellite cell activation and progressive reduction in proliferative potential and responsiveness to HGF and dysregulated myogenic differentiation with age. Finally, we show that SULF1/SULF2 and RTK/Wnt signalling components are expressed in progeric mouse muscles at earlier stage but their expression is attenuated by an intervention that promotes muscle repair and growth.
Design and assembly of DNA molecules using multi-objective optimisation
Authors: Gaeta Angelo , Zulkower Valentin , Stracquadanio Giovanni 
Published: September 2019

AbstractRapid engineering of biological systems is currently hindered by limited integration of manufacturing constraints into the design process, ultimately limiting the yield of many synthetic biology workflows.Here we tackle DNA engineering as a multi-objective optimization problem aiming at finding the best tradeoff between design requirements and manufacturing constraints. We developed a new open-source algorithm for DNA engineering, called Multi-Objective Optimisation algorithm for DNA Design and Assembly (MOODA), available as a Python package and web application athttp://mooda.stracquadaniolab.org.Experimental results show that our method provides near optimal constructs and scales linearly with design complexity, effectively paving the way to rational engineering of DNA molecules from genes to genomes.
NNT Regulates Mitochondrial Metabolism in NSCLC Through Maintenance of Fe-S Protein Function
Authors: Ward Nathan P. , Kang Yun Pyo , Falzone Aimee , Boyle Terry A. , DeNicola Gina M. 
Published: September 2019

AbstractHuman lung tumors exhibit robust and complex mitochondrial metabolism, likely precipitated by the highly oxygenated nature of pulmonary tissue. As ROS generation is a byproduct of this metabolism, reducing power in the form of nicotinamide adenine dinucleotide phosphate (NADPH) is required to mitigate oxidative stress in response to this heightened mitochondrial activity. Nicotinamide nucleotide transhydrogenase (NNT) is known to sustain mitochondrial antioxidant capacity through the generation of NADPH, however its function in non-small cell lung cancer (NSCLC) has not been established. We found that NNT expression significantly enhances tumor formation and aggressiveness in mouse models of lung tumor initiation and progression. We further show that NNT loss elicits mitochondrial dysfunction independent of substantial increases in oxidative stress, but rather marked by the diminished activities of proteins dependent on resident iron-sulfur clusters. These defects were associated with both NADPH availability and ROS accumulation, suggesting that NNT serves a specific role in mitigating the oxidation of these critical protein cofactors.
Homeostatic recovery of embryonic spinal activity initiated by compensatory changes in resting membrane potential
Authors: Gonzalez-Islas Carlos , Garcia-Bereguiain Miguel Angel , Wenner Peter 
Published: September 2019

AbstractWhen baseline activity in a neuronal network is modified by external challenges, a set of mechanisms is prompted to homeostatically restore activity levels. These homeostatic mechanisms are thought to be profoundly important in the maturation of the network. We have previously shown that 2-day blockade of either excitatory GABAergic or glutamatergic transmission in the living embryo transiently blocks the movements generated by spontaneous network activity (SNA) in the spinal cord. However, by 2 hours of persistent receptor blockade embryonic movements begin to recover, and by 12 hours we observe a complete homeostatic recovery in vivo. Compensatory changes in voltage-gated conductances in motoneurons were observed by 12 hours of blockade, but not changes in synaptic strength. It was unclear whether changes in voltage-gated conductances were observed by 2 hours of blockade when the recovery actually begins. Further, compensatory changes in voltage-gated conductances were not observed following glutamatergic blockade where embryonic movements were blocked but then recovered in a similar manner to GABAergic blockade. In this study, we discover a mechanism for homeostatic recovery in these first hours of neurotransmitter receptor blockade. In the first 6 hours of GABAergic or glutamatergic blockade there was a clear depolarization of resting membrane potential in both motoneurons and interneurons. These changes reduced action potential threshold and were mainly observed in the continued presence of the antagonist. Therefore, it appears that fast changes in resting membrane potential represent a key fast homeostatic mechanism for the maintenance of network activity in the living embryonic nervous system.SignificanceHomeostatic plasticity represents a set of mechanisms that act to recover cellular or network activity following a challenge to that activity and is thought to be critical for the developmental construction of the nervous system. The chick embryo afforded us the opportunity to observe in a living developing system the timing of the homeostatic recovery of network activity following 2 distinct perturbations. Because of this advantage, we have identified a novel homeostatic mechanism that actually occurs as the network recovers and is therefore likely to contribute to nervous system homeostasis. We found that a depolarization of the resting membrane potential in the first hour of the perturbations enhances excitability and supports the recovery of embryonic spinal network activity.
A novel xenograft model of human HCC in immunocompetent mouse
Authors: Bi Yanzhen , Shi Jun , Li Shanshan , Wang Quanyi , Wang Quanquan , Wen Xinyuan , Yang Feng , Duan Zhongping , Yang Yonghong , Zhang Xiaobei , Zhang Yongchao , Shu Zhenfeng , Chen Yu , Hong Feng 
Published: September 2019

ABSTRACTHepatocellular carcinoma (HCC) is one of the most common malignant tumors that threaten human health; thus, the establishment of an animal model with clinical features similar to human liver cancer is of important practical significance. Taking advantage of the novel microcarrier-6, human HCC cells was injected into immunocompetent mice to establish a novel human HCC patient-derived xenograft (PDX) model. Primary HCC cells were isolated from fresh liver cancer tissues, which were subsequently co-cultured with microcarrier-6 to construct a three-dimensional tumor cell culture model in vitro. The HCC-microcarrier complex was implanted into mice by subcutaneous inoculation, and the tumor formation time, tumor formation rate, and pathological manifestation were recorded. Changes of immune parameters in mice were detected by flow cytometry. The success rate was 60% (6/10) in the establishment of liver cancer PDX mouse model, and the total tumor formation rate of the tumor-forming model is 80-100%. H&E staining and immunohistochemical experiments indicate that the model well retained the characteristics of the primary tumor. Interestingly, M2 macrophages in tumor-bearing mice increased significantly, and the levels of CD4+ T cells were significantly reduced. Through the application of the microcarrier-6 in immunocompetent mice, we successfully established a novel human HCC PDX model, which can be used to better study and further elucidate the occurrence and pathogenic mechanism of HCC.
Intraspecific niche partitioning in macrodetritivores enhances mixed leaf litter decomposition
Authors: Fontana Simone , Berg Matty P. , Moretti Marco 
Published: September 2019

Abstract

In biodiversity and ecosystem functioning research, the consideration of intraspecific trait variation and multiple trophic levels – both largely overlooked so far – has been proposed as a promising step towards a consensus about causal relationships and mechanisms.

Soil invertebrates contribute crucially to leaf litter decomposition and thus to the functioning of one of the most diverse ecosystem components on Earth. On the one hand, a positive effect of leaf litter diversity on decomposition was shown by several studies. On the other hand, at the interspecific level, differences in body size and feeding traits of consumers influence this process by interacting with leaf litter traits that define decomposability, such as nutrient content and physical properties. It is also known that the feeding niche of consumers can vary during their ontogeny as it depends on individual body size, metabolism and physiology. However, whether and how intraspecific trait variation of macrodetritivores contributes through niche partitioning to the positive effect of litter combinations on decomposition was never investigated.

Here, we tested experimentally the effect of intraspecific body size differences in the common terrestrial isopod species Oniscus asellus on the decomposition of the two co‐occurring litter species Acer platanoides and Betula pendula. We hypothesized complementary resource use by two distinct isopod body size classes, leading to decreased competition and higher overall litter decomposition.

In a full factorial design with all possible combinations of litter species and isopod body size classes, litter mixtures enhanced decomposition beyond the additive effect of each single species, especially in isopod mixed‐body size treatments. Our results suggest an interaction between litter and consumer diversity driving intraspecific feeding niche partitioning. Although the focus on a single detritivore species does not allow for generalizations, our results should stimulate the investigation of the mechanisms of biotic interactions among individual organisms.

A free Plain Language Summary can be found within the Supporting Information of this article.
Warm and out of breath: Thermal phenotypic plasticity in oxygen supply
Authors: Kielland Øystein Nordeide , Bech Claus , Einum Sigurd 
Published: September 2019

Abstract

Aquatic ectotherms face a challenge of obtaining sufficient oxygen, and it is commonly claimed that this challenge increases with increasing environmental temperature, causing concerns about the fate of aquatic ecosystems under climate change.

However, the oxygen challenge hypothesis often ignores the effect of known phenotypic plastic responses. These can occur on either a within‐ or multigenerational scale, where multiple reactions act in concert to increase oxygen supply in response to increased temperature in a wide range of traits (molecular, egg content, behavioural, cell structure, morphological).

Here, we combine a novel modelling approach with empirical measurements that enable quantification of how both the oxygen supply (maximum oxygen diffusion rate) and demand (metabolic rate) are affected by temperature while allowing for phenotypic plasticity.

We exposed the aquatic ectotherm Daphnia magna to a range of temperatures (17–28°C) over several asexual generations and confirm that phenotypic plasticity contributes to an increased ability to obtain oxygen on the whole‐organism level at high temperatures.

This response is strongest within the highest temperature range (22–28°C), where the change in oxygen challenge is expected to be most pronounced. However, the observed thermal plasticity in oxygen supply failed to compensate for the increased demand.

Thus, we provide empirical evidence that the oxygen challenge in aquatic ectotherms increases with increasing temperature, even in the presence of phenotypic plasticity in oxygen supply.

A free Plain Language Summary can be found within the Supporting Information of this article.
Field exclusion of large soil predators impacts lower trophic levels and decreases leaf‐litter decomposition in dry forests
Authors: Melguizo‐Ruiz Nereida , Jiménez‐Navarro Gerardo , De Mas Eva , Pato Joaquina , Scheu Stefan , Austin Amy T. , Wise David H. , Moya‐Laraño Jordi 
Published: September 2019

Abstract

Shifts in densities of apex predators may indirectly affect fundamental ecosystem processes, such as decomposition, by altering patterns of cascading effects propagating through lower trophic levels. These top–down effects may interact with anthropogenic impacts, such as climate change, in largely unknown ways.

We investigated how changes in densities of large predatory arthropods in forest leaf‐litter communities altered lower trophic levels and litter decomposition. We conducted our experiment in soil communities that had experienced different levels of long‐term average precipitation. We hypothesized that altering abundances of apex predators would have stronger effects on soil communities inhabiting dry forests, due to lower secondary productivity and greater resource overexploitation by lower trophic levels compared to wet forests.

We experimentally manipulated abundances of the largest arthropod predators (apex predators) in field mesocosms replicated in the leaf‐litter community of Iberian beech forests that differed in long‐term mean annual precipitation by 25% (three dry forests with MAP < 1,250 mm and four wet forests with MAP > 1,400 mm). After one year, we assessed abundances of soil fauna in lower trophic levels and indirect impacts on leaf‐litter decomposition using litter of understorey hazel, Corylus avellana.

Reducing densities of large predators had a consistently negative effect on final abundances of the different trophic groups and several taxa within each group. Moreover, large predatory arthropods strongly impacted litter decomposition, and their effect interacted with the long‐term annual rainfall experienced by the soil community. In the dry forests, a 50% reduction in the densities of apex predators was associated with a 50% reduction in decomposition. In wet forests, the same reduction in densities of apex soil predators did not alter the rate of litter decomposition.

Our results suggest that predators may facilitate lower trophic levels by indirectly reducing competition and resource overexploitation, cascading effects that may be more pronounced in drier forests where conditions have selected for greater competitive ability and more rapid resource utilization. These findings thus provide insights into the functioning of soil invertebrate communities and their role in decomposition, as well as potential consequences of soil community responses to climate change.