Miracle-dz/UniFAR-FTUs huggingface dataset:
Electrophysiology of cerebral ischemia and reperfusion: First evidence for the role of synapse in ischemic tolerance

Objective: The subthreshold brain‐damaging stimulus may protect the brain from subsequent ischemia; this phenomenon has been named “ischemic tolerance” (IT). We focused on the synaptic properties of the neurons after mild and severe ischemia to determine the association between IT and synaptic efficacy. Experimental design: Adult male rats were randomly divided into four experimental groups including control, sham, permanent ischemia (pI/R), and mild ischemia (mI/R). Middle cerebral artery occlusion (MCAO) method was applied to induce brain ischemia. Seven days after the insult, long‐term potentiation (LTP) induced by high‐frequency stimulation (HFS) and paired‐pulse ratio (PPR) were monitored before and after the HFS delivery. Results: The field potential recording demonstrated that mild ischemia significantly increased the basal synaptic transmission. Additionally, the HFS produced a significant potentiation compared to its baseline level in the mI/R group. Moreover, mild ischemia prevented depression of PPR by HFS. This effect was accompanied by a significant increase in the normalized PPR (PPR after HFS/PPR before HFS) in this group. Conclusions: Our data indicated that a mild reduction in brain perfusion without permanent lesion can dramatically increase the basal synaptic transmission. This effect may be associated with an increase in the neurotransmitter content of the pre‐synaptic neurons. This hypothesis could provide a new insight into the relationship between IT and synaptic efficacy. Synapse 70:351–360, 2016. © 2016 Wiley Periodicals, Inc.
Informatics and machine learning to define the phenotype

ABSTRACT Introduction: For the past decade, the focus of complex disease research has been the genotype. From technological advancements to the development of analysis methods, great progress has been made. However, advances in our definition of the phenotype have remained stagnant. Phenotype characterization has recently emerged as an exciting area of informatics and machine learning. The copious amounts of diverse biomedical data that have been collected may be leveraged with data-driven approaches to elucidate trait-related features and patterns. Areas covered: In this review, the authors discuss the phenotype in traditional genetic associations and the challenges this has imposed.Approaches for phenotype refinement that can aid in more accurate characterization of traits are also discussed. Further, the authors highlight promising machine learning approaches for establishing a phenotype and the challenges of electronic health record (EHR)-derived data. Expert commentary: The authors hypothesize that through unsupervised machine learning, data-driven approaches can be used to define phenotypes rather than relying on expert clinician knowledge. Through the use of machine learning and an unbiased set of features extracted from clinical repositories, researchers will have the potential to further understand complex traits and identify patient subgroups. This knowledge may lead to more preventative and precise clinical care.
Layer-by-layer gelatin/chitosan polyelectrolyte coated nanoparticles on Ti implants for prevention of implant-associated infections

Gelatin nanoparticles (Gb-NP) and layer-by-layer (LBL) coated NPs were developed to modify a Ti substrate surface to prevent implant-associated infections. Vancomycin (Van) was loaded into these materials to obtain GbV-NP and LBL-GbV-NP. The size of the GbV-NP (277.4±1.4 nm) was smaller than that of LBL-GbV-NP (710.2±4.6 nm) but both had a spherical shape. These coated materials showed no cytotoxicity and facilitated better cell proliferation by osteoblast-like cells compared to the bare Ti. This was probably due to the roughness of the coated NP that enhanced cell attachement to the surface. Both coated materials showed antibacterial activity against S. aureus. The release of Van from GbV-NP was higher from LBL-GbV-NP and this corresponded to their antibacterial activity. Furthermore the release profile of Van showed a sustained release. Thus both materials should be able to prolong the protection of implant-associated infections to the bone.
Spatial clustering of childhood leukaemia in Switzerland: A nationwide study

The aetiology of childhood leukaemia remains largely unknown. Several hypotheses involve environmental exposures that could implicate spatial clustering of cases. The evidence from previous clustering studies is inconclusive. Most of them used areal data and thus had limited spatial resolution. We investigated whether childhood leukaemia tends to cluster in space using exact geocodes of place of residence both at the time of birth or diagnosis. We included 1,871 leukaemia cases diagnosed between 1985 and 2015 at age 0–15 years from the Swiss Childhood Cancer Registry. For each case, we randomly sampled 10 age and sex matched controls from national censuses closest in time. We used the difference of k‐functions, Cuzick‐Edwards' test and Tango's index for point data to assess spatial clustering and Kulldorff's circular scan to detect clusters. We separately investigated acute lymphoid leukaemia (ALL), acute myeloid leukaemia (AML), different age groups at diagnosis (0–4, 5–15 years) and adjusted for multiple testing. After adjusting for multiple testing, we found no evidence of spatial clustering of childhood leukaemia neither around time of birth (p = 0.52) nor diagnosis (p = 0.51). Individual tests indicated spatial clustering for leukaemia diagnosed at age 5–15 years, p k‐functions = 0.05 and p Cuzick‐Edwards' = 0.04 and a cluster of ALL cases diagnosed at age 0–4 years in a small rural area (p = 0.05). This study provides little evidence of spatial clustering of childhood leukaemia in Switzerland and highlights the importance of accounting for multiple testing in clustering studies.
Localisation and substrate specificities of transglycanases in charophyte algae relate to development and morphology

ABSTRACT Cell wall-modifying enzymes have been previously investigated in charophyte green algae (CGA) in cultures of uniform age, giving limited insight into their roles. Therefore, we investigated the in situ localisation and specificity of enzymes acting on hemicelluloses in CGA genera of different morphologies and developmental stages. In vivo transglycosylation between xyloglucan and an endogenous donor in filamentous Klebsormidium and Zygnema was observed in longitudinal cell walls of young (1 month) but not old cells (1 year), suggesting that it has a role in cell growth. By contrast, in parenchymatous Chara, transglycanase action occurred in all cell planes. In Klebsormidium and Zygnema, the location of enzyme action mainly occurred in regions where xyloglucans and mannans, and to a lesser extent mixed-linkage β-glucan (MLG), were present, indicating predominantly xyloglucan:xyloglucan endotransglucosylase (XET) activity. Novel transglycosylation activities between xyloglucan and xylan, and xyloglucan and galactomannan were identified in vitro in both genera. Our results show that several cell wall-modifying enzymes are present in CGA, and that differences in morphology and cell age are related to enzyme localisation and specificity. This indicates an evolutionary significance of cell wall modifications, as similar changes are known in their immediate descendants, the land plants. This article has an associated First Person interview with the first author of the paper. Summary: The distribution of major hemicelluloses and cell wall-modifying enzymes in three charophyte green algae (CGA), representing the ancestors of land plants, relate to algal morphology and developmental stage.
Patterns and Implications of Gene Gain and Loss in the Evolution of Prochlorococcus

Prochlorococcus is a marine cyanobacterium that numerically dominates the mid-latitude oceans and is the smallest known oxygenic phototroph. Numerous isolates from diverse areas of the world's oceans have been studied and shown to be physiologically and genetically distinct. All isolates described thus far can be assigned to either a tightly clustered high-light (HL)-adapted clade, or a more divergent low-light (LL)-adapted group. The 16S rRNA sequences of the entire Prochlorococcus group differ by at most 3%, and the four initially published genomes revealed patterns of genetic differentiation that help explain physiological differences among the isolates. Here we describe the genomes of eight newly sequenced isolates and combine them with the first four genomes for a comprehensive analysis of the core (shared by all isolates) and flexible genes of the Prochlorococcus group, and the patterns of loss and gain of the flexible genes over the course of evolution. There are 1,273 genes that represent the core shared by all 12 genomes. They are apparently sufficient, according to metabolic reconstruction, to encode a functional cell. We describe a phylogeny for all 12 isolates by subjecting their complete proteomes to three different phylogenetic analyses. For each non-core gene, we used a maximum parsimony method to estimate which ancestor likely first acquired or lost each gene. Many of the genetic differences among isolates, especially for genes involved in outer membrane synthesis and nutrient transport, are found within the same clade. Nevertheless, we identified some genes defining HL and LL ecotypes, and clades within these broad ecotypes, helping to demonstrate the basis of HL and LL adaptations in Prochlorococcus. Furthermore, our estimates of gene gain events allow us to identify highly variable genomic islands that are not apparent through simple pairwise comparisons. These results emphasize the functional roles, especially those connected to outer membrane synthesis and transport that dominate the flexible genome and set it apart from the core. Besides identifying islands and demonstrating their role throughout the history of Prochlorococcus, reconstruction of past gene gains and losses shows that much of the variability exists at the “leaves of the tree,” between the most closely related strains. Finally, the identification of core and flexible genes from this 12-genome comparison is largely consistent with the relative frequency of Prochlorococcus genes found in global ocean metagenomic databases, further closing the gap between our understanding of these organisms in the lab and the wild.
Neonatal hypothyroidism affects testicular glucose homeostasis through increased oxidative stress in prepubertal mice: effects on GLUT3, GLUT8 and Cx43

Thyroid hormones (THs) play an important role in maintaining the link between metabolism and reproduction and the altered THs status is associated with induction of oxidative stress in various organs like brain, heart, liver and testis. Further, reactive oxygen species play a pivotal role in regulation of glucose homeostasis in several organs, and glucose utilization by Leydig cells is essential for testosterone biosynthesis and thus is largely dependent on glucose transporter 8 (GLUT8). Glucose uptake by Sertoli cells is mediated through glucose transporter 3 (GLUT3) under the influence of THs to meet energy requirement of developing germ cells. THs also modulate level of gap junctional protein such as connexin 43 (Cx43), a potential regulator of cell proliferation and apoptosis in the seminiferous epithelium. Although the role of transient neonatal hypothyroidism in adult testis in terms of testosterone production is well documented, the effect of THs deficiency in early developmental period and its role in testicular glucose homeostasis and oxidative stress with reference to Cx43 in immature mice remain unknown. Therefore, the present study was conducted to evaluate the effect of neonatal hypothyroidism on testicular glucose homeostasis and oxidative stress at postnatal days (PND) 21 and 28 in relation to GLUT3, GLUT8 and Cx43. Hypothyroidism induced by 6‐propyl‐2‐thiouracil (PTU) markedly decreased testicular glucose level with considerable reduction in expression level of GLUT3 and GLUT8. Likewise, lactate dehydrogenase (LDH) activity and intratesticular concentration of lactate were also decreased in hypothyroid mice. There was also a rise in germ cell apoptosis with increased expression of caspase‐3 in PTU‐treated mice. Further, neonatal hypothyroidism affected germ cell proliferation with decreased expression of proliferating cell nuclear antigen (PCNA) and Cx43. In conclusion, our results suggest that neonatal hypothyroidism alters testicular glucose homeostasis via increased oxidative stress in prepubertal mice, thereby affecting germ cell survival and proliferation.
Psyllium Supplementation in Adolescents Improves Fat Distribution & Lipid Profile: A Randomized, Participant-Blinded, Placebo-Controlled, Crossover Trial

Aims We aimed to assess the effects of psyllium supplementation on insulin sensitivity and other parameters of the metabolic syndrome in an at risk adolescent population. Methods This study encompassed a participant-blinded, randomized, placebo-controlled, crossover trial. Subjects were 47 healthy adolescent males aged 15–16 years, recruited from secondary schools in lower socio-economic areas with high rates of obesity. Participants received 6 g/day of psyllium or placebo for 6 weeks, with a two-week washout before crossing over. Fasting lipid profiles, ambulatory blood pressure, auxological data, body composition, activity levels, and three-day food records were collected at baseline and after each 6-week intervention. Insulin sensitivity was measured by the Matsuda method using glucose and insulin values from an oral glucose tolerance test. Results 45 subjects completed the study, and compliance was very high: 87% of participants took >80% of prescribed capsules. At baseline, 44% of subjects were overweight or obese. 28% had decreased insulin sensitivity, but none had impaired glucose tolerance. Fibre supplementation led to a 4% reduction in android fat to gynoid fat ratio (p = 0.019), as well as a 0.12 mmol/l (6%) reduction in LDL cholesterol (p = 0.042). No associated adverse events were recorded. Conclusions Dietary supplementation with 6 g/day of psyllium over 6 weeks improves fat distribution and lipid profile (parameters of the metabolic syndrome) in an at risk population of adolescent males. Trial Registration Australian New Zealand Clinical Trials Registry ACTRN12609000888268
Application of stable‐isotope labelling techniques for the detection of active diazotrophs

Summary Investigating active participants in the fixation of dinitrogen gas is vital as N is often a limiting factor for primary production. Biological nitrogen fixation is performed by a diverse guild of bacteria and archaea (diazotrophs), which can be free‐living or symbionts. Free‐living diazotrophs are widely distributed in the environment, yet our knowledge about their identity and ecophysiology is still limited. A major challenge in investigating this guild is inferring activity from genetic data as this process is highly regulated. To address this challenge, we evaluated and improved several 15N‐based methods for detecting N2 fixation activity (with a focus on soil samples) and studying active diazotrophs. We compared the acetylene reduction assay and the 15N2 tracer method and demonstrated that the latter is more sensitive in samples with low activity. Additionally, tracing 15N into microbial RNA provides much higher sensitivity compared to bulk soil analysis. Active soil diazotrophs were identified with a 15N‐RNA‐SIP approach optimized for environmental samples and benchmarked to 15N‐DNA‐SIP. Lastly, we investigated the feasibility of using SIP‐Raman microspectroscopy for detecting 15N‐labelled cells. Taken together, these tools allow identifying and investigating active free‐living diazotrophs in a highly sensitive manner in diverse environments, from bulk to the single‐cell level.
Amyloid fibril based bionanotechnologies.

Amyloid protein nanofibrils (PNFs) are self-assembling, misfolded structures formed by many proteins when exposed to denaturing conditions. PNFs offer several attractive features for utilisation in the creation of new bionanomaterials, such as nanometre dimensions, strength and stability, and ease of functionalisation through amino acid residues. However, if amyloid PNFs are to be used in bionanotechnology, then methods need to be developed to utilise inexpensive, crude proteins instead of pure protein preparations. This research focuses on utilising PNFs obtained from a low cost source, including fish eye lens crystallins, and whey protein isolate to develop novel PNFbased nanoscaffolds, with potential applications in bionanotechnology. To ensure that crystallin PNFs can be effectively used as a versatile bionanoscaffold, biocompatibility and stability studies were done using cell viability and Thioflavin T dye binding assays, Transmission electron microscopy, and Infrared microspectroscopy. Crystallin PNFs were shown to be stable over all the conditions studied (pH and temperature extremes, presence of proteases and solvents), and showed no evidence of cytotoxicity. The results obtained from IR microspectroscopy illustrated the long-term (up to 3 years) structural integrity of crystallin PNFs. To obtain PNF-based functional nanoscaffolds, several enzymes of industrial relevance were successfully immobilised onto the crystallin PNFs via a versatile glutaraldehyde-based crosslinking approach. Dualfunctionalised PNFs were also obtained by co-immobilising enzymes onto the whey PNF scaffold. The functional PNF-based nanoscaffolds provided a significant increase in thermostability and reusability of industrial enzymes relative to the free enzyme in solution under the same conditions. To demonstrate that PNF-based scaffolds can be potentially used for creating active bionanomaterials, electrochemistry, surface-assembly, and cell attachment and proliferation experiments were done. Electrochemistry studies demonstrated that functionalised PNFs can be successfully used to develop single enzyme-, or dual enzyme-based biosensing elements, for glucose and lactose analysis. Surface-assembly studies established that PNF scaffold provides more surface area for biomolecule immobilisation, and can be used to create PNF-based active surfaces. The use of PNF-based scaffold for cellular growth resulted in improved attachment and proliferation of fibroblasts, suggesting a role for PNFs obtained from crude protein sources in the biomedical field. This work demonstrated the potential of PNFs obtained from crude proteins to develop functional nanoscaffolds with broad applications. The described work contributes to the existing knowledge of PNF-based bionanomaterials, and is very significant for the technological development and future applications of PNF-based materials in bionanotechnology.
Role of Lgals9 Deficiency in Attenuating Nephritis and Arthritis in BALB/c Mice in a Pristane‐Induced Lupus Model

In systemic lupus erythematosus (SLE), an autoimmune disease associated with multiple organ involvement, the development of lupus nephritis determines prognosis, and arthritis impairs quality of life. Galectin 9 (Gal‐9, Lgals9) is a β‐galactoside–binding lectin that has been used for clinical application in autoimmune diseases, since recombinant Gal‐9, as a ligand for T cell immunoglobulin and mucin domain–containing protein 3 (TIM‐3), induces apoptosis of activated CD4+TIM‐3+ Th1 cells. This study was undertaken to investigate whether deficiency of Lgals9 has beneficial or deleterious effects on lupus in a murine model.
The role of non-genetic inheritance in evolutionary rescue: epigenetic buffering, heritable bet hedging and epigenetic traps

Abstract Rapid environmental change is predicted to compromise population survival, and the resulting strong selective pressure can erode genetic variation, making evolutionary rescue unlikely. Non-genetic inheritance may provide a solution to this problem and help explain the current lack of fit between purely genetic evolutionary models and empirical data. We hypothesize that epigenetic modifications can facilitate evolutionary rescue through ‘epigenetic buffering’. By facilitating the inheritance of novel phenotypic variants that are generated by environmental change—a strategy we call ‘heritable bet hedging’—epigenetic modifications could maintain and increase the evolutionary potential of a population. This process may facilitate genetic adaptation by preserving existing genetic variation, releasing cryptic genetic variation and/or facilitating mutations in functional loci. Although we show that examples of non-genetic inheritance are often maladaptive in the short term, accounting for phenotypic variance and non-adaptive plasticity may reveal important evolutionary implications over longer time scales. We also discuss the possibility that maladaptive epigenetic responses may be due to ‘epigenetic traps’, whereby evolutionarily novel factors (e.g. endocrine disruptors) hack into the existing epigenetic machinery. We stress that more ecologically relevant work on transgenerational epigenetic inheritance is required. Researchers conducting studies on transgenerational environmental effects should report measures of phenotypic variance, so that the possibility of both bet hedging and heritable bet hedging can be assessed. Future empirical and theoretical work is required to assess the relative importance of genetic and epigenetic variation, and their interaction, for evolutionary rescue.
Strain measurement of softened Eucalyptus regnans wood during bending operation using a low-cost single camera optical method

An important requirement for developing an understanding of wood bending mechanics is to determine the mechanical response of softened wood during bending. This involves experimentally measuring wood's deformation or strain. Many wood bending studies have been conducted over the past 80 years to increase the understanding and investigate methods of ultimately improving the wood bending operation. The majority of these studies investigated the particular type of method of softening, using minimum bending radius and quality as a measured response. However, there is sparse literature in the public domain that offers a means of gaining an understanding of the mechanics of a wood specimen during a bending operation. This paper introduces a low-cost optical-based method for measuring engineering strain in softened wood. The method requires minimal specialised equipment and has been successfully used to determine the engineering strain response of Eucalyptus regnans during the bending process.
Trivializing and Orbifolding the Conifold ’ s Base

The conifold is a cone over the space T , which is known to be topologically S × S. The coordinates used in the literature describe a sphere-bundle which can be proven to be topologically trivializable. We provide an explicit trivialization of this bundle, with simultaneous global coordinates for both spheres. Using this trivialization we are able to describe the topology of the base of several infinite families of chiral and non-chiral orbifolds of the conifold. We demonstrate that in each case the 2nd Betti number of the base matches the number of independent ranks in the dual quiver gauge theory.