Miracle-dz/UniFAR-FTUs huggingface dataset:
Monodopsis and Vischeria Genomes Shed New Light on the Biology of Eustigmatophyte Algae

Abstract Members of eustigmatophyte algae, especially Nannochloropsis and Microchloropsis, have been tapped for biofuel production owing to their exceptionally high lipid content. Although extensive genomic, transcriptomic, and synthetic biology toolkits have been made available for Nannochloropsis and Microchloropsis, very little is known about other eustigmatophytes. Here we present three near-chromosomal and gapless genome assemblies of Monodopsis strains C73 and C141 (60 Mb) and Vischeria strain C74 (106 Mb), which are the sister groups to Nannochloropsis and Microchloropsis in the order Eustigmatales. These genomes contain unusually high percentages of simple repeats, ranging from 12% to 21% of the total assembly size. Unlike Nannochloropsis and Microchloropsis, long interspersed nuclear element repeats are abundant in Monodopsis and Vischeria and might constitute the centromeric regions. We found that both mevalonate and nonmevalonate pathways for terpenoid biosynthesis are present in Monodopsis and Vischeria, which is different from Nannochloropsis and Microchloropsis that have only the latter. Our analysis further revealed extensive spliced leader trans-splicing in Monodopsis and Vischeria at 36–61% of genes. Altogether, the high-quality genomes of Monodopsis and Vischeria not only serve as the much-needed outgroups to advance Nannochloropsis and Microchloropsis research, but also shed new light on the biology and evolution of eustigmatophyte algae.
Oxidative degradation perturbs physico-chemical properties of hemoglobin in cigarette smokers: a threat to different biomolecules

Abstract Context Cigarette smokers develop structural modification in hemoglobin (Hb) and this modification enable Hb to undergo higher rate of auto-oxidation, leading to generation of further intracellular ROS. Objective In this study, we exhibited the possible cause and consequences of Hb modification in cigarette smokers. Methods Twenty-two smokers and 16 nonsmokers, aged 25 to 35 years, having a smoking history of 7–10 years were recruited in this study. Carbonyl content, ferryl form, peroxidase-like and esterase-like activities of Hb were assayed. Free iron release by Hb, erythrocyte membrane-bound Hb and plasma Hb were also measured along with assessment of important biomolecular degradations by Hb. Results and discussion Increase in carbonyl content in Hb indicates its oxidative degradation. Increase in ferryl Hb formation, peroxidase-like activity and decrease in esterase like activity of Hb along with increased release of nonheme iron (from Hb) clearly indicates alteration in physico-chemical properties of Hb in smokers. Moreover, increase in erythrocyte membrane-bound Hb and plasma-free Hb provide further evidences for higher rate of Hb oxidation in smokers’ erythrocyte. The rates of protein, lipid, sugar and DNA degradation were noticed to be higher by smokers’ Hb; and were further attenuated by desferrioxamine as well as mannitol. Conclusion We conclude that in cigarette smokers, there is oxidative degradation of Hb and the degradation causes alteration in its physico-chemical properties, which in turn may degrade different biomolecules in its close vicinity by releasing more iron and production of more superoxide as well as hydroxyl radical.
Effect of ground technicity on cardio-respiratory and biomechanical parameters in uphill trail running

ABSTRACT The goal of this study was to analyse the effects of ground technicity on cardio-respiratory and biomechanical responses during uphill running. Ten experienced male trail-runners ran ∼10.5 min at racing pace on two trails with different (high and low) a priori technicity levels. These two runs were replicated (same slope, velocity, and distance) indoor on a motor-driven treadmill. Oxygen uptake, minute ventilation (V̇E), heart rate as well as step frequency and medio-lateral feet accelerations (i.e. objective indices of uneven terrain running patterns adjustments) were continuously measured throughout all sessions. Rating of perceived exertion (RPE) and perceived technicity were assessed at the end of each bout. Oxygen cost of running (O2Cr) (+10.5%; p < 0.001), V̇E (+21%; p < 0.004) and the range and variability of feet medio-lateral accelerations (+116% and +134%, respectively; p < 0.001), were significantly greater when running on trail compared to the treadmill, regardless of the a priori technicity level. Despite perceived technicity being lower on treadmill (p < 0.001), RPE was not different between trail and treadmill runs (p < 0.68). It is concluded that running uphill on a trail vs. a treadmill significantly elevates both O2Cr and magnitude/variability of feet medio-lateral accelerations but no difference could be identified between trails of different a priori technicities. These results strengthen the need for trainers and race organisers to consider terrain technicity per se as a challenging cardio-respiratory and biomechanical component in uphill trail running. Highlights Ten experienced male trail-runners ran ∼10.5 min at racing pace on two trails with different a priori technicity levels. The two runs were replicated (same slope, velocity, and distance) indoor on a motor-driven treadmill. Oxygen cost of running (O2Cr), minute ventilation (V̇E) as well as medio-lateral feet accelerations (i.e. objective indices of uneven terrain running patterns adjustments) were continuously measured throughout all sessions. Rating of perceived exertion (RPE) and perceived technicity were assessed at the end of each bout. O2Cr (+10.5%; p < 0.001), V̇E (+21%; p < 0.004) and the magnitude and variability of feet medio-lateral accelerations (+116% and +134%, respectively; p < 0.001) were significantly greater when running on trail compared to treadmill, regardless of the a priori technicity level. Despite O2Cr being different between trail and treadmill runs, RPE was not. Thus, running uphill on a trail vs. on a treadmill significantly elevates both O2Cr and magnitude/variability of feet medio-lateral accelerations but no difference could be identified between trails of different a priori technicities.
Identification of Indole-3-Acetic Acid-Regulated Genes in Pseudomonas syringae pv. tomato Strain DC3000

Indole-3-acetic acid (IAA), a form of the plant hormone auxin, is used by many plant-associated bacteria as a cue to sense the plant environment. Previously, we showed that IAA can promote disease in interactions between the plant pathogen Pseudomonas syringae strain PtoDC000 and one of its hosts, Arabidopsis thaliana. ABSTRACT The auxin indole-3-acetic acid (IAA) is a plant hormone that not only regulates plant growth and development but also plays important roles in plant-microbe interactions. We previously reported that IAA alters expression of several virulence-related genes in the plant pathogen Pseudomonas syringae pv. tomato strain DC3000 (PtoDC3000). To learn more about the impact of IAA on regulation of PtoDC3000 gene expression, we performed a global transcriptomic analysis of bacteria grown in culture, in the presence or absence of exogenous IAA. We observed that IAA repressed expression of genes involved in the type III secretion (T3S) system and motility and promoted expression of several known and putative transcriptional regulators. Several of these regulators are orthologs of factors known to regulate stress responses and accordingly expression of several stress response-related genes was also upregulated by IAA. Similar trends in expression for several genes were also observed by quantitative reverse transcription PCR. Using an Arabidopsis thaliana auxin receptor mutant that accumulates elevated auxin, we found that many of the P. syringae genes regulated by IAA in vitro were also regulated by auxin in planta. Collectively the data indicate that IAA modulates many aspects of PtoDC3000 biology, presumably to promote both virulence and survival under stressful conditions, including those encountered in or on plant leaves. IMPORTANCE Indole-3-acetic acid (IAA), a form of the plant hormone auxin, is used by many plant-associated bacteria as a cue to sense the plant environment. Previously, we showed that IAA can promote disease in interactions between the plant pathogen Pseudomonas syringae strain PtoDC000 and one of its hosts, Arabidopsis thaliana. However, the mechanisms by which IAA impacts the biology of PtoDC3000 and promotes disease are not well understood. Here, we demonstrate that IAA is a signal molecule that regulates gene expression in PtoDC3000. The presence of exogenous IAA affects expression of over 700 genes in the bacteria, including genes involved in type III secretion and genes involved in stress response. This work offers insight into the roles of auxin-promoting pathogenesis.
Novel cubosome based system for ocular delivery of acetazolamide

Abstract Acetazolamide is the drug of choice for glaucoma treatment in an emergency. However, it is not available in any topical formulation and it is available only as systemic tablets. Despite its efficiency as a drug in decreasing intraocular pressure, it has negative systemic effects as renal toxicity and metabolic acidosis. Moreover, it suffers from poor aqueous solubility and low corneal permeability limiting its ocular bioavailability and its use topically. Cubosomes have enormous advantages as a drug delivery system, most importantly, high surface area, thermal stability, and ability to encapsulate hydrophobic, amhiphilic, and hydrophilic molecules. Herein, we have exploited the unique properties of cubosomes as a novel nano-delivery system for acetazolamide as eye drops dosage form for glaucoma treatment. Different acetazolamide-loaded cubosomes have been developed and evaluated. The best-optimized formulation (F5), was cubic shaped structure, with an average particle size of 359.5 ± 2.8 nm, surface charge −10.8 ± 3.2 mV, and 59.8% entrapment efficiency. Ex-vivo corneal permeation studies have revealed a 4-fold increase in acetazolamide permeability coefficient compared to that stated in the literature. F5 showed superior therapeutic efficacy represented by a 38.22% maximum decrease in intraocular pressure vs. 31.14 and 21.99% decrease for the commercial Azopt® eye drops and Cidamex® tablets, respectively. It also exhibited higher (AUC0–10) compared to Azopt® eye drops and Cidamex® tablets by 2.3 and 3 times, respectively. F5 showed mean residence time 4.22 h vs. 2.36 and 2.62 h for Azopt® and Cidamex® with no eye irritation observed according to the modified Draize test. To the best of our knowledge, this is the first study for developing acetazolamide-loaded cubosomes as the topical delivery system for glaucoma treatment.
Relationship of Purpose in Life to Dementia in Older Black and White Brazilians

Abstract Objectives: To test the hypothesis that higher level of purpose in life is associated with lower likelihood of dementia and mild cognitive impairment (MCI) in older Brazilians. Methods: As part of the Pathology, Alzheimer’s and Related Dementias Study (PARDoS), informants of 1,514 older deceased Brazilians underwent a uniform structured interview. The informant interview included demographic data, the Clinical Dementia Rating scale to diagnose dementia and MCI, the National Institute of Mental Health Diagnostic Interview Schedule for depression, and a 6-item measure of purpose in life, a component of well-being. Results: Purpose scores ranged from 1.5 to 5.0 with higher values indicating higher levels of purpose. On the Clinical Dementia Rating Scale, 940 persons (62.1%) had no cognitive impairment, 121 (8.0%) had MCI, and 453 (29.9%) had dementia. In logistic regression models adjusted for age at death, sex, education, and race, higher purpose was associated with lower likelihood of MCI (odds ratio = .58; 95% confidence interval [CI]: .43, .79) and dementia (odds ratio = .49, 95% CI: .41, .59). Results were comparable after adjusting for depression (identified in 161 [10.6%]). Neither race nor education modified the association of purpose with cognitive diagnoses. Conclusions: Higher purpose in life is associated with lower likelihood of MCI and dementia in older black and white Brazilians.
Magnetic Topological Insulator Heterostructures: A Review

Topological insulators (TIs) provide intriguing prospects for the future of spintronics due to their large spin–orbit coupling and dissipationless, counter‐propagating conduction channels in the surface state. The combination of topological properties and magnetic order can lead to new quantum states including the quantum anomalous Hall effect that was first experimentally realized in Cr‐doped (Bi,Sb)2Te3 films. Since magnetic doping can introduce detrimental effects, requiring very low operational temperatures, alternative approaches are explored. Proximity coupling to magnetically ordered systems is an obvious option, with the prospect to raise the temperature for observing the various quantum effects. Here, an overview of proximity coupling and interfacial effects in TI heterostructures is presented, which provides a versatile materials platform for tuning the magnetic and topological properties of these exciting materials. An introduction is first given to the heterostructure growth by molecular beam epitaxy and suitable structural, electronic, and magnetic characterization techniques. Going beyond transition‐metal‐doped and undoped TI heterostructures, examples of heterostructures are discussed, including rare‐earth‐doped TIs, magnetic insulators, and antiferromagnets, which lead to exotic phenomena such as skyrmions and exchange bias. Finally, an outlook on novel heterostructures such as intrinsic magnetic TIs and systems including 2D materials is given.
Projection-based dynamic tomography

Objective. This paper proposes a 4D dynamic tomography framework that allows a moving sample to be imaged in a tomograph as well as the associated space-time kinematics to be measured with nothing more than a single conventional x-ray scan. Approach. The method exploits the consistency of the projection/reconstruction operations through a multi-scale procedure. The procedure is composed of two main parts solved alternatively: a motion-compensated reconstruction algorithm and a projection-based measurement procedure that estimates the displacement field directly on each projection. Main results. The method is applied to two studies: a numerical simulation of breathing from chest computed tomography (4D-CT) and a clinical cone-beam CT of a breathing patient acquired for image guidance of radiotherapy. The reconstructed volume, initially blurred by the motion, is cleaned from motion artifacts. Significance. Applying the proposed approach results in an improved reconstruction quality showing sharper edges and finer details.
Effects of Combined Varenicline With Nicotine Patch and of Extended Treatment Duration on Smoking Cessation: A Randomized Clinical Trial.

Importance Smoking cessation medications are routinely used in health care. Research suggests that combining varenicline with the nicotine patch, extending the duration of varenicline treatment, or both, may increase cessation effectiveness. Objective To compare combinations of varenicline plus the nicotine or placebo patch vs combinations used for either 12 weeks (standard duration) or 24 weeks (extended duration). Design, Settings, and Participants Double-blind, 2 × 2 factorial randomized clinical trial conducted from November 11, 2017, to July 9, 2020, at 1 research clinic in Madison, Wisconsin, and at 1 clinic in Milwaukee, Wisconsin. Of the 5836 adults asked to participate in the study, 1251 who smoked 5 cigarettes/d or more were randomized. Interventions All participants received cessation counseling and were randomized to 1 of 4 medication groups: varenicline monotherapy for 12 weeks (n = 315), varenicline plus nicotine patch for 12 weeks (n = 314), varenicline monotherapy for 24 weeks (n = 311), or varenicline plus nicotine patch for 24 weeks (n = 311). Main Outcomes and Measures The primary outcome was carbon monoxide-confirmed self-reported 7-day point prevalence abstinence at 52 weeks. Results Among 1251 patients who were randomized (mean [SD] age, 49.1 [11.9] years; 675 [54.0%] women), 751 (60.0%) completed treatment and 881 (70.4%) provided final follow-up. For the primary outcome, there was no significant interaction between the 2 treatment factors of medication type and medication duration (odds ratio [OR], 1.03 [95% CI, 0.91 to 1.17]; P = .66). For patients randomized to 24-week vs 12-week treatment duration, the primary outcome occurred in 24.8% (154/622) vs 24.3% (153/629), respectively (risk difference, -0.4% [95% CI, -5.2% to 4.3%]; OR, 1.01 [95% CI, 0.89 to 1.15]). For patients randomized to varenicline combination therapy vs varenicline monotherapy, the primary outcome occurred in 24.3% (152/625) vs 24.8% (155/626), respectively (risk difference, 0.4% [95% CI, -4.3% to 5.2%]; OR, 0.99 [95% CI, 0.87 to 1.12]). Nausea occurrence ranged from 24.0% to 30.9% and insomnia occurrence ranged from 24.4% to 30.5% across the 4 groups. Conclusions and Relevance Among adults smoking 5 cigarettes/d or more, there were no significant differences in 7-day point prevalence abstinence at 52 weeks among those treated with combined varenicline plus nicotine patch therapy vs varenicline monotherapy, or among those treated for 24 weeks vs 12 weeks. These findings do not support the use of combined therapy or of extended treatment duration. Trial Registration ClinicalTrials.gov Identifier: NCT03176784.
Co-evolutionary Signals Identify Burkholderia pseudomallei Survival Strategies in a Hostile Environment

Abstract The soil bacterium Burkholderia pseudomallei is the causative agent of melioidosis and a significant cause of human morbidity and mortality in many tropical and subtropical countries. The species notoriously survives harsh environmental conditions but the genetic architecture for these adaptations remains unclear. Here we employed a powerful combination of genome-wide epistasis and co-selection studies (2,011 genomes), condition-wide transcriptome analyses (82 diverse conditions), and a gene knockout assay to uncover signals of “co-selection”—that is a combination of genetic markers that have been repeatedly selected together through B. pseudomallei evolution. These enabled us to identify 13,061 mutation pairs under co-selection in distinct genes and noncoding RNA. Genes under co-selection displayed marked expression correlation when B. pseudomallei was subjected to physical stress conditions, highlighting the conditions as one of the major evolutionary driving forces for this bacterium. We identified a putative adhesin (BPSL1661) as a hub of co-selection signals, experimentally confirmed a BPSL1661 role under nutrient deprivation, and explored the functional basis of co-selection gene network surrounding BPSL1661 in facilitating the bacterial survival under nutrient depletion. Our findings suggest that nutrient-limited conditions have been the common selection pressure acting on this species, and allelic variation of BPSL1661 may have promoted B. pseudomallei survival during harsh environmental conditions by facilitating bacterial adherence to different surfaces, cells, or living hosts.
COVID19 Disease Map, a computational knowledge repository of virus–host interaction mechanisms

We need to effectively combine the knowledge from surging literature with complex datasets to propose mechanistic models of SARS‐CoV‐2 infection, improving data interpretation and predicting key targets of intervention. Here, we describe a large‐scale community effort to build an open access, interoperable and computable repository of COVID‐19 molecular mechanisms. The COVID‐19 Disease Map (C19DMap) is a graphical, interactive representation of disease‐relevant molecular mechanisms linking many knowledge sources. Notably, it is a computational resource for graph‐based analyses and disease modelling. To this end, we established a framework of tools, platforms and guidelines necessary for a multifaceted community of biocurators, domain experts, bioinformaticians and computational biologists. The diagrams of the C19DMap, curated from the literature, are integrated with relevant interaction and text mining databases. We demonstrate the application of network analysis and modelling approaches by concrete examples to highlight new testable hypotheses. This framework helps to find signatures of SARS‐CoV‐2 predisposition, treatment response or prioritisation of drug candidates. Such an approach may help deal with new waves of COVID‐19 or similar pandemics in the long‐term perspective.
Aging at evolutionary crossroads: longitudinal gene co-expression network analyses of proximal and ultimate causes of aging in bats.

How, when and why do organisms, their tissues and their cells age remain challenging issues, although researchers have identified multiple mechanistic causes of aging, and three major evolutionary theories have been developed to unravel the ultimate causes of organismal aging. A central hypothesis of these theories is that the strength of natural selection decreases with age. However, empirical evidence on when, why and how organisms age is phylogenetically limited, especially in natural populations. Here, we developed generic comparisons of gene co-expression networks that quantify and dissect the heterogeneity of gene co-expression in conspecific individuals from different age-classes to provide topological evidence about some mechanical and fundamental causes of organismal aging. We applied this approach to investigate the complexity of some proximal and ultimate causes of aging phenotypes in a natural population of the greater mouse-eared bat Myotis myotis, a remarkably long-lived species given its body size and metabolic rate, with available longitudinal blood transcriptomes. Myotis gene co-expression networks become increasingly fragmented with age, suggesting an erosion of the strength of natural selection and a general dysregulation of gene co-expression in aging bats. However, selective pressures remain sufficiently strong to allow successive emergence of homogeneous age-specific gene co-expression patterns, for at least seven years. Thus, older individuals from long-lived species appear to sit at an evolutionary crossroad: as they age, they experience both a decrease in the strength of natural selection and a targeted selection for very specific biological processes, further inviting to refine a central hypothesis in evolutionary aging theories.
Dbf4-Dependent Kinase: DDK-ated to post-initiation events in DNA replication

ABSTRACT Dbf4-Dependent Kinase (DDK) has a well-established essential role at origins of DNA replication, where it phosphorylates and activates the replicative MCM helicase. It also acts in the response to mutagens and in DNA repair as well as in key steps during meiosis. Recent studies have indicated that, in addition to the MCM helicase, DDK phosphorylates several substrates during the elongation stage of DNA replication or upon replication stress. However, these activities of DDK are not essential for viability. Dbf4-Dependent Kinase is also emerging as a key factor in the regulation of genome-wide origin firing and in replication-coupled chromatin assembly. In this review, we summarize recent progress in our understanding of the diverse roles of DDK.