Miracle-dz/UniFAR-FTUs huggingface dataset:
The symbioses of endophytic fungi shaped the metabolic profiles in grape leaves of different varieties

Endophytic fungi produce many novel bioactive metabolites that are directly used as drugs or that function as the precursor structures of other chemicals. The metabolic shaping of endophytes on grape cells was reported previously. However, there are no reports on the interactions and metabolic impact of endophyte symbiosis on in vitro vine leaves, which may be examined under well-controlled conditions that are more representative of the natural situation of endophytes within grapevines. The present study used an in vitro leaf method to establish endophyte symbiosis of grapevines and analyze the effects on the metabolic profiles of grape leaves from two different cultivars, ‘Rose honey’ (RH) and ‘Cabernet sauvignon’ (CS). The effects of endophytic fungi on the metabolic profiles of grape leaves exhibited host selectivity and fungal strain specificity. Most of the endophytic fungal strains introduced novel metabolites into the two varieties of grape leaves according to the contents of the detected metabolites and composition of metabolites. Strains RH49 and MDR36, with high or moderate symbiosis rates, triggered an increased response in terms of the detected metabolites, and the strains MDR1 and MDR33 suppressed the detected metabolites in CS and RH leaves despite having strong or moderate symbiosis ability. However, the strain RH12 significantly induced the production of novel metabolites in RH leaves due to its high symbiosis ability and suppression of metabolites in CS leaves.
Bone biomarkers in koalas: validation of assays and preliminary analyses

Traumatic injury, including bone fracture, is, to date, one of the leading causes of koala mortality in the South East Queensland region of Australia. Further, the specialist diet of koalas, which is restricted to certain Eucalyptus spp. , may impact their normal bone physiology. Considering the dramatic koala population decline and high incidence of trauma, a greater understanding of koala bone physiology may support conservation. We retrieved from GenBank the protein sequences of parathyroid hormone (PTH), osteocalcin (OCN), and tissue-nonspecific alkaline phosphatase (TNALP) in human, dog, cattle, horse, koala, and gray short-tailed opossum. After homology was determined, plasma samples from 13 koalas were analyzed with human PTH, OCN, and bone-specific ALP (BALP) assay kits. Although koala PTH exhibited relatively low sequence homology with placental mammals, high sequence homology between humans and koalas was observed for both OCN and TNALP, and successful cross-reactivity was achieved using human enzyme immunoassay kits for detection of OCN and BALP biomarkers in koala plasma. However, we identified no correlation between OCN and BALP concentrations of healthy and trauma-affected koalas (p = 0.66 and p = 0.79, respectively). Further analysis of OCN and BALP in healthy and diseased koalas will allow a better understanding of bone physiology in this unique marsupial.
Elevated levels of δ15N in riverine Painted Turtles (Chrysemys picta): trophic enrichment or anthropogenic input?

The natural abundance of stable isotopes of elements in animal tissue is influenced by both biotic and abiotic factors. Biotically, animals feeding at higher trophic levels are enriched in the ratio of 15N:14N (δ15N) relative to their food resources owing to the preferential excretion of 14N. Abiotically, increases in δ15N may also reflect different sources of biologically available nitrogen, including nitrogen resulting from denitrification of inorganic fertilizer. We studied variation in δ15N among freshwater turtle populations to assess spatial variation in δ15N and to determine whether this variation can be attributed to differences in nitrogen source or trophic enrichment. We examined nitrogen and carbon stable isotope ratios in duckweed (genus Lemna L.) and in Painted Turtles (Chrysemys picta (Schneider, 1783)) in aquatic ecosystems expected to be differentially affected by agricultural activity and denitrification of inorganic fertilizer. Across sites, C. picta δ15N was strongly correlated with Lem.
Outcomes of lenalidomide‐ or bortezomib‐based regimens in older patients with plasma cell myeloma

The “triplet” regimen of lenalidomide, bortezomib, and dexamethasone (RVD) showed survival advantage over lenalidomide‐dexamethasone (RD) in clinical trials, but older patients with myeloma often receive doublet regimens (RD or bortezomib‐dexamethasone, VD), or VD plus cyclophosphamide (VCD). We compared these first‐line regimens using real‐world data from Medicare beneficiaries receiving therapy between 2007 and 2015. In each comparative analysis, we balanced confounding characteristics using a propensity score. Outcomes included overall (OS) and event‐free survival (EFS, reporting hazard ratios [HR] with 95% confidence intervals [CI]), adverse events, and costs. We identified 6076 patients with median age 76 and median OS of 2.6 years. In the comparison of RVD vs RD/VD doublets, RVD showed significantly better OS (HR = 0.83; 95% CI, 0.72‐0.95) and EFS (HR = 0.68; 95% CI, 0.61‐0.76). So, RVD was associated with more frequent hospitalizations, anemia, and neuropathy, but no increase in thromboembolism or secondary cancers. Costs were higher with RVD. In the comparison of RD vs VD, RD demonstrated better EFS (HR = 0.74; 95% CI, 0.68‐0.81) and marginally better OS (HR = 0.91; 95% CI, 0.83‐0.99). And, RD resulted in significantly more thromboembolic events, less neuropathy, and no significant difference in hospitalizations, transfusions, or secondary cancers. In the comparison of VCD vs VD, we observed no significant difference in any outcome. Superior survival favors RVD over doublet regimens, but even in 2015 RVD was applied for only about 25% of Medicare beneficiaries with myeloma. For patients not eligible for RVD due to toxicity, VCD offers no survival benefit over VD. Lenalidomide‐dexamethasone may be the preferred line doublet considering its advantage over VD.
Analysis of Gal4 Expression Patterns in Adult Drosophila Females

Precise genetic manipulation of specific cell types or tissues to pinpoint gene function requirement is a critical step in studies aimed at unraveling the intricacies of organismal physiology. Drosophila researchers heavily rely on the UAS/Gal4/Gal80 system for tissue-specific manipulations; however, it is often unclear whether the reported Gal4 expression patterns are indeed specific to the tissue of interest such that experimental results are not confounded by secondary sites of Gal4 expression. Here, we surveyed the expression patterns of commonly used Gal4 drivers in adult Drosophila female tissues under optimal conditions and found that multiple drivers have unreported secondary sites of expression beyond their published cell type/tissue expression pattern. These results underscore the importance of thoroughly characterizing Gal4 tools as part of a rigorous experimental design that avoids potential misinterpretation of results as we strive for understanding how the function of a specific gene/pathway in one tissue contributes to whole-body physiology.
Using an aquatic model, Xenopus laevis, to uncover the role of chromodomain 1 in craniofacial disorders

The chromodomain family member chromodomain 1 (CHD1) has been shown to have numerous critical molecular functions including transcriptional regulation, splicing, and DNA repair. Complete loss of function of this gene is not compatible with life. On the other hand, missense and copy number variants of CHD1 can result in intellectual disabilities and craniofacial malformations in human patients including cleft palate and Pilarowski–Bjornsson Syndrome. We have used the aquatic developmental model organism Xenopus laevis, to determine a specific role for Chd1 in such cranioafcial disorders. Protein and gene knockdown techniques in Xenopus, including antisense oligos and mosaic Crispr/Cas9‐mediated mutagenesis, recapitulated the craniofacial defects observed in humans. Further analysis indicated that embryos deficient in Chd1 had defects in cranial neural crest development and jaw cartilage morphology. Additionally, flow cytometry and immunohistochemistry revealed that decreased Chd1 resulted in increased in apoptosis in the developing head. Together, these experiments demonstrate that Chd1 is critical for fundamental processes and cell survival in craniofacial development. We also presented evidence that Chd1 is regulated by retinoic acid signaling during craniofacial development. Expression levels of chd1 mRNA, specifically in the head, were increased by RAR agonist exposure and decreased upon antagonist treatment. Subphenotypic levels of an RAR antagonist and Chd1 morpholinos synergized to result in orofacial defects. Further, RAR DNA binding sequences (RAREs) were detected in chd1 regulatory regions by bioinformatic analysis. In summary, by combining human genetics and experiments in an aquatic model we now have a better understanding of the role of CHD1 in craniofacial disorders.
Biaxiality-driven twist-bend to splay-bend nematic phase transition induced by an electric field

An electric field–induced, symmetry-breaking, transition from NTB to NSB nematics reveals the importance of local biaxiality. Although the existence of the twist-bend (NTB) and splay-bend (NSB) nematic phases was predicted long ago, only the former has as yet been observed experimentally, whereas the latter remains elusive. This is especially disappointing because the NSB nematic is promising for applications in electro-optic devices. By applying an electric field to a planar cell filled with the compound CB7CB, we have found an NTB-NSB phase transition using birefringence measurements. This field-induced transition to the biaxial NSB occurred, although the field was applied along the symmetry axis of the macroscopically uniaxial NTB. Therefore, this transition is a counterintuitive example of breaking of the macroscopic uniaxial symmetry. We show by theoretical modeling that the transition cannot be explained without considering explicitly the biaxiality of both phases at the microscopic scale. This strongly suggests that molecular biaxiality should be a key factor favoring the stability of the NSB phase.
Aerobic capacity and fatigability are associated with activity levels in women with hip osteoarthritis

Physical activity is important for physical function and pain relief in people with lower extremity osteoarthritis (OA). Unfortunately, people with OA are not as active as their peers without OA. The objective of this study was to determine whether aerobic capacity and fatigability are associated with physical activity in women with hip OA. We conducted a cross‐sectional analysis of 36 women with hip OA. We assessed aerobic fitness as predicted VO2max from a 6‐min walk test. We assessed fatigability using a treadmill test. Finally, we assessed self‐reported physical activity using the UCLA activity scale and quantified steps per day and activity intensity using accelerometers. We used Pearson correlations to determine associations. We used regression analysis to determine whether fatigability mediated the association between aerobic fitness and physical activity. On average, subjects were moderately active via the UCLA score (5.2 ± 1.3 out of 10). Aerobic fitness (R = 0.582, p < .001) and fatigability (R = 0.516, p =.003) were significantly correlated with UCLA scores. However, aerobic fitness was the best predictor of UCLA scores, as well as sedentary time, and time spent in light activity. Fatigability was not a mediator between aerobic fitness and UCLA scores. Aerobic fitness and fatigability may be modifiable barriers to physical activity in people with OA. Future interventional studies should examine whether improving aerobic fitness improves physical activity or fatigability.
The Value of Serum MicroRNA Expression Signature in Predicting Refractoriness to Bortezomib-Based Therapy in Multiple Myeloma Patients

Simple Summary The proteasome inhibitor bortezomib is currently commonly used for the treatment of multiple myeloma (MM). MicroRNAs (miRNAs) are small non-coding RNAs that play a crucial role in messenger RNA silencing and post-transcriptional regulation of gene expression. In MM, the expression of several miRNAs is markedly dysregulated suggesting their role in MM pathogenesis and drug resistance. The aim of our study was to assess miRNA expression patterns in the serum of MM patients treated with bortezomib. We have identified 21 serum miRNAs differentially expressed in patients refractory to bortezomib-based chemotherapy. A miRNAs-based prediction model was developed to assess the probability of refractoriness to bortezomib. Our findings, indicating the differential expression of miRNAs between bortezomib-refractory and bortezomib-sensitive patients, suggest that these circulating miRNAs may play an important role in personalized treatment of MM patients. Abstract Bortezomib is the first-in-class proteasome inhibitor, commonly used in the treatment of multiple myeloma (MM). The mechanisms underlying acquired bortezomib resistance in MM are poorly understood. Several cell-free miRNAs have been found to be aberrantly regulated in MM patients. The aim of this pilot study was to identify a blood-based miRNA signature that predicts bortezomib-based therapy efficacy in MM patients. Thirty MM patients treated with bortezomib-based regimens were studied, including 19 with refractory disease and 11 who were bortezomib sensitive. Serum miRNA expression patterns were identified with miRCURY LNA miRNA miRNome PCR Panels I+II (Exiqon/Qiagen). Univariate analysis found a total of 21 miRNAs to be differentially expressed in patients with MM according to bortezomib sensitivity. Multivariate logistic regression was created and allowed us to discriminate refractory from sensitive patients with a very high AUC of 0.95 (95%CI: 0.84–1.00); sensitivity, specificity and accuracy were estimated as 0.95, 0.91, and 0.93. The model used expression of 3 miRNAs: miR-215-5p, miR-181a-5p and miR-376c-3p. This study is the first to demonstrate that serum expression of several miRNAs differs between patients who are bortezomib refractory and those who are sensitive which may prove useful in studies aimed at overcoming drug resistance in MM treatment.
Cell-to-cell and genome-to-genome variability of adenovirus transcription tuned by the cell cycle.

In clonal cultures, not all cells are equally susceptible to virus infection and the underlying mechanisms are poorly understood. Here, we developed image-based single cell measurements to scrutinize the heterogeneity of adenovirus (AdV) infection. AdV delivers, transcribes and replicates a linear double-stranded DNA genome in the nucleus. We measured the abundance of viral transcripts by single-molecule RNA fluorescence in situ hybridization (FISH), and the incoming ethynyl-deoxy-cytidine (EdC)-tagged viral genomes by copper(I)-catalyzed azide-alkyne cycloaddition (click) reaction. Surprisingly, the expression of the immediate early gene E1A only moderately correlated with the number of viral genomes in the cell nucleus. Intranuclear genome-to-genome heterogeneity was found at the level of viral transcription and, in accordance, individual genomes exhibited heterogeneous replication activity. By analyzing the cell cycle state, we found that G1 cells exhibited the highest E1A expression and displayed increased correlation between E1A expression and viral genome copy numbers. The combined image-based single molecule procedures described here are ideally suited to explore the cell-to-cell variability in viral gene expression in a range of different settings, including innate immune response.
Are open-source approaches the most efficient way forward for COVID-19 drug discovery?

ABSTRACT Introduction: The COVID-19 pandemic has catalyzed the production of potential antivirals and vaccines from research organizations across the globe. The initial step for all drug discovery models is the identification of suitable targets. One approach organizations may take to tackle this involves issuing raw data publicly for collaboration with other organizations in order to spark discussion, collectively experiment and stay up to date with advances in scientific knowledge. Areas covered: Numerous organizations have released genomic data, amongst other tools, for the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and this has led to the development of growing datasets of knowledge for continued collaboration amongst different scientific communities. A different technique employs a more closed, market-driven method in order to stay ahead financially in the race for developing a suitable antiviral or vaccine. The latter allows sustained motivation for company ambitions and progress has been made toward clinical trials for potential drugs. Expert opinion: A case can be made for both open and closed drug discovery models; however, due to the rapidly evolving nature of this deadly virus, organizations should collate their research and support one another to ensure satisfactory treatment can be approved in a timely manner.
Corpus Callosum Agenesis: An Insight into the Etiology and Spectrum of Symptoms

Brain hemispheres are connected by commissural structures, which consist of white matter fiber tracts that spread excitatory stimuli to various regions of the cortex. This allows an interaction between the two cerebral halves. The largest commissure is the corpus callosum (CC) which is located inferior to the longitudinal fissure, serving as its lower border. Sometimes this structure is not completely developed, which results in the condition known as agenesis of the corpus callosum (ACC). The aim of this paper was to review the latest discoveries related to the genetic and metabolic background of ACC, including the genotype/phenotype correlations as well as the clinical and imaging symptomatology. Due to various factors, including genetic defects and metabolic diseases, the development of CC may be impaired in many ways, which results in complete or partial ACC. This creates several clinical implications, depending on the specificity of the malformation and other defects in patients. Epilepsy, motor impairment and intellectual disability are the most prevalent. However, an asymptomatic course of the disease is even more common. ACC presents with characteristic images on ultrasound and magnetic resonance imaging (MRI).
Reproductive Biology and Population Structure of the Western Red-backed Salamander, Plethodon vehiculum (Cooper)

Certain aspects of the life history of Plethodon vehiculum from Benton and Lincoln Cos. , Oregon, were studied. Mating occurs primarily from November through January with oviposition in the spring. The number of yolky ovarian ova is a function of body size; the mean for all sizes was was 10.4/female. Incubation is in the summer, with hatching in the fall at 13 to 15 mm SVL. Growth rates for both sexes are about 10mm SVL/year for the first 3 years. Both sexes mature between their second and third years: males at 42 mm SVL and females at 44 mm SVL. Females have a biennial gonadal cycle as has been described for other species of Plethodon, and males have annual cycle. Spermatogenesis begins in the spring and culminates in the fall. Mature females are larger (mean SVL = 49.1 mm) than mature males (mean SVL -45.7 mm). In general, P. vehiculum, a western plethodon, has a life history similar to that of eastern small and eastern large plethodons. * * * The genus Plethodon can be divided into 3 natural groups (Grobman, 1944; Highton 1962a): the eastern large plethodons, the eastern small plethodons, and the western plethodons. Highton (1956, 1962b) and Pope and Pope (1949) described the reproductive cycle of the slimy salamander, Plethodon glutinosus, an eastern large plethodon; and Sayler (1966) studied the reproductive ecology of the red-backed salamander, Plethodon cinereus, an eastern small plethodon. Werner (1971) provided further notes on P. cinereus, and the reproductive biology of a second eastern small plethodon, the northern ravine salamander, Plethodon richmondi richmondi, was studied by Angle (1969). The geographically isolated Jemez Mountains salamander, Plethodon neomexicanus, is thought to be related to the eastern small plathodons
Adsorption Kinetics of Arsenic (V) on Nanoscale Zero-Valent Iron Supported by Activated Carbon

The presence of arsenic (As) in drinking water is of serious concern due to its negative impact on human health. This work reports on the kinetics of nanoscale zero-valent iron (Fe0) supported by activated carbon (NZVI/AC) for the removal of As (V) species from aqueous solutions. To better understand the factors affecting this process, we investigated the effects of various experimental parameters including initial As (V) concentration, adsorbent dosage, pH, temperature, and coexisting ions on the adsorption kinetics using a batch-adsorption method. The optimum conditions for As (V) removal by NZVI/AC were found to be: 318 K, pH 3.5, an adsorbent dosage of 1.5 g/L, and an equilibrium time of 72 h. A greater mass of NZVI/AC, lower concentration of As (V) and lower pH positively promoted adsorption kinetics. The presence of phosphate (PO43−) and silicate (SiO42−) markedly inhibited As (V) removal kinetics. However, in the presence of 4.5 g/L NZVI/AC, ≥99.9% of As (V) was removed from raw groundwater.
Evidence for limbic system links and neural plasticity

Article abstract—We used PET to map brain regions responding to changes in tinnitus loudness in four patients who could alter tinnitus loudness by performing voluntary oral facial movements (OFMs). Cerebral blood flow was measured in four patients and six controls at rest, during the OFM, and during stimulation with pure tones. OFM-induced loudness changes affected the auditory cortex contralateral to the ear in which tinnitus was perceived, whereas unilateral cochlear stimulation caused bilateral effects, suggesting a retrocochlear origin for their tinnitus. Patients, compared with controls, showed evidence for more widespread activation by the tones and aberrant links between the limbic and auditory systems. These abnormal patterns provide evidence for cortical plasticity that may account for tinnitus and associated symptoms. Although audiologic symptoms and examinations of these patients were typical, the unusual ability to modulate tinnitus loudness with an OFM suggests some caution may be warranted in generalizing these findings. NEUROLOGY 1998;50:114‐120