Miracle-dz/UniFAR-FTUs huggingface dataset:
Diversity and sex differences in rectal gland volatiles of Queensland fruit fly, Bactrocera tryoni (Diptera: Tephritidae)

Rectal gland volatiles are key mediators of sexual interactions in tephritid fruit flies. We used solid-phase microextraction (SPME) plus gas chromatography-mass spectrometry (GC-MS) and gas chromatography-flame ionization detection (GC-FID) to substantially expand rectal gland chemical characterisation of the Queensland fruit fly (Bactrocera tryoni (Diptera: Tephritidae); Qfly). The SPME GC-MS analysis identified 24 of the 30 compounds previously recorded from Qfly rectal glands, plus another 21 compounds that had not previously been reported. A few amides and fatty acid esters dominated the chromatograms of males and females respectively, but we also found other esters, alcohols and aldehydes and a ketone. The GC-FID analyses also revealed over 150 others, as yet unidentified, volatiles, generally in lesser amounts. The GC-FID analyses also showed 49 and 12 compounds were male- and female-specific, respectively, both in single sex (virgin) and mixed sex (mostly mated) groups. Another ten compounds were male-specific among virgins but undetected in mixed sex groups, and 29 were undetected in virgins but male-specific in mixed sex groups. The corresponding figures for females were four and zero, respectively. Most short retention time peaks (including a ketone and an ester) were male-specific, whereas most female-biased peaks (including five fatty acid esters) had long retention times. Our results indicate previously unsuspected diversity of rectal gland volatiles that might have pheromone functions in males, but far fewer in females.
The APP intracellular domain promotes LRRK2 expression to enable feed-forward neurodegenerative mechanisms in Parkinson’s disease

Gain-of-function mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are common in familial forms of Parkinson’s disease (PD), which is characterized by progressive neurodegeneration that impairs motor and cognitive function. We previously demonstrated that LRRK2-mediated phosphorylation of β-amyloid precursor protein (APP) triggers the production and nuclear translocation of the APP intracellular domain (AICD). Here, we connected LRRK2 to AICD in a feed-forward cycle that enhanced LRRK2-mediated neurotoxicity. In cooperation with the transcription factor FOXO3a, AICD promoted LRRK2 expression, thus increasing the abundance of LRRK2 that promotes AICD activation. APP deficiency in LRRK2G2019S mice suppressed LRRK2 expression, LRRK2-mediated mitochondrial dysfunction, α-synuclein accumulation, and tyrosine hydroxylase (TH) loss in the brain, phenotypes associated with toxicity and loss of dopaminergic neurons in PD. Conversely, AICD overexpression increased LRRK2 expression and LRRK2-mediated neurotoxicity in LRRK2G2019S mice. In LRRK2G2019S mice or cultured dopaminergic neurons from LRRK2G2019S patients, treatment with itanapraced reduced LRRK2 expression and was neuroprotective. Itanapraced showed similar effects in a neurotoxin-induced PD mouse model, suggesting that inhibiting the AICD may also have therapeutic benefits in idiopathic PD. Our findings reveal a therapeutically targetable, feed-forward mechanism through which AICD promotes LRRK2-mediated neurotoxicity in PD. Description A feed-forward loop between an APP fragment and the kinase LRRK2 promotes Parkinson’s disease pathology. Spiraling into neurodegeneration Activating mutations in the kinase LRRK2 cause Parkinson’s disease (PD) in some patients. Mutant LRRK2 can promote the processing of APP into its transcriptionally active form, the APP intracellular domain (AICD). Zhang et al. showed that these proteins are linked in a self-perpetuating cycle. In cultured neurons and brain tissue from mouse models of PD, LRRK2-mediated phosphorylation of APP increased the abundance and activity of the AICD that then directly mediated LRRK2 transcription. Pathological markers in LRRK2-mutant PD models were reduced by targeting the AICD with itanapraced, a small-molecule inhibitor that is currently in trials to treat Alzheimer’s disease. The findings reveal that LRRK2 and the AICD are reciprocally linked and that itanapraced may be therapeutically beneficial in PD.
Conformer‐RL: A deep reinforcement learning library for conformer generation

Conformer‐RL is an open‐source Python package for applying deep reinforcement learning (RL) to the task of generating a diverse set of low‐energy conformations for a single molecule. The library features a simple interface to train a deep RL conformer generation model on any covalently bonded molecule or polymer, including most drug‐like molecules. Under the hood, it implements state‐of‐the‐art RL algorithms and graph neural network architectures tuned specifically for molecular structures. Conformer‐RL is also a platform for researching new algorithms and neural network architectures for conformer generation, as the library contains modular class interfaces for RL environments and agents, allowing users to easily swap components with their own implementations. Additionally, it comes with tools to visualize and save generated conformers for further analysis. Conformer‐RL is well‐tested and thoroughly documented with tutorials for each of the functionalities mentioned above, and is available on PyPi and Github: https://github.com/ZimmermanGroup/conformer-rl.
Impact of Icerya purchasi (Hempitera: Monophlebidae) on Navel Orange, Citrus sinensis, Production and Fruit Quality

Abstract Cottony cushion scale, Icerya purchasi Maskell, is an occasional pest of citrus, especially when insecticides disrupt vedalia beetle, Novius cardinalis (Mulsant) (Coleoptera: Coccinellidae). In two field tests conducted in successive years, navel orange trees were artificially infested with I. purchasi to determine the impact of I. purchasi on fruit yield and quality. In the first year, for which adult scale densities ranged between 0 and > 45 per branch and between 0 and > 500 on trunk counts, there was a highly significant negative linear relationship between the number of I. purchasi adults on branches or the trunk and its effect on fruit number, the percentage of large fruit, and the mass of fruit, and a highly significant positive relationship for the percentage of sooty mold-affected fruit and the percentage of juice grade fruit. In the second year, in which adult scale densities ranged between 0 and 10.5 per branch and between 0 and 35 on trunk counts, only the percentage of sooty mold-affected fruit showed a relationship. Damage to fruit was better predicted by population estimates from branch samples versus trunk counts. Analysis of the two years, estimated significant damage ranging from 2 adults per branch to no detectable effects of insect density, depending on the given metric of fruit number or quality, at the time that treatment decisions would be made. These results support May–June monitoring of branches for adult scales and application of treatments at an action threshold of <2 adult females/branch to prevent damage to navel orange trees.
Betacyanins are plant-based dyes with potential as histological stains

ABSTRACT Interest is increasing in certain parts of the world in replacing synthetic dyes with dyes from natural sources, particularly from plants. Although textile dyers have used various groups of natural dyes, microscopists generally have restricted their use to anthocyanins. Recently, however, another class of plant-based dyes has found some favor, the betacyanins. Betacyanins are a group of red and violet betalain dyes found only in certain plants of the order Caryophyalles and in Basidiomycetes mushrooms. Although the chemical structures of betacyanins are known, little use has been made of that information to understand or predict their behavior with biomedical specimens. We investigated two common, widely distributed betacyanin-containing plants, edible beets (Beta vulgaris) and wild pokeweed (Phytolacca americana). Aqueous alcoholic extracts were made from beet root and pokeweed berries, adjusted to pH 4.1 or 5.3 and used together with Harris’ hematoxylin to stain histological sections. We used a methanolic extract of pokeweed berries, pH 3.0, to stain cultured mycological specimens. Both extracts produced satisfactory staining that was equivalent to that of eosin Y, although the colors were more muted with the beet root extract. Epithelial cytoplasm, muscle, collagen and erythrocytes were well demonstrated. Betanin is the predominant component of beet root extract; it possesses one delocalized positive charge and three carboxylic acid substituents. The dyes are weak acids and the carboxylate anions are more diffuse than for eosin Y; this produces weaker bonding to tissue cations. The principal colored component of pokeweed berries, prebetanin, possesses a sulfonic acid group as well as carboxylic acids, which favors acid dyeing and more intense coloration. Both dyes show potential for hydrogen bonding and to a much lesser extent for some types of van der Waals forces. Complex formation with metals such as aluminum to create a nuclear stain is not likely with beet root dyes nor is it possible with pokeweed dyes. Betacyanins are suitable for staining microscopy preparations in place of other red acid dyes such as eosin. Of the two dyes tested here, prebetanin from pokeweed berries was superior to betanin from red beet roots. These berries are widely distributed and readily collected; the extraction procedure is simple and does not require expensive solvents.
Genome-wide analyses of individual differences in quantitatively assessed reading- and language-related skills in up to 34,000 people

Significance Our unique capacities for spoken and written language are fundamental features of what makes us human, yet the biological bases remain largely mysterious. We present a large-scale well-powered genome-wide association study meta-analysis of individual differences in reading- and language-related skills (word reading, nonword reading, spelling, phoneme awareness, and nonword repetition) in tens of thousands of participants. The findings prompt a major reevaluation of prior literature claiming candidate gene associations in much smaller samples. Moreover, we use the novel genetic data as windows into multiple aspects of the biology of these important abilities, revealing molecular links to individual differences in neuroanatomy of language-related brain areas and enriched heritability in archaic deserts of the human genome as well as in fetal brain enhancer regions.
The new French kidney allocation system for donations after brain death: Rationale, implementation, and evaluation

In recent decades, the allocation policies of many countries have moved from center‐based to patient‐based approaches. The new French kidney allocation system (KAS) of donations after brain death for adult recipients, implemented in 2015, was principally designed to introduce a unified allocation score (UAS) to be applied locally for one kidney and nationally for the other and to replace regional borders by a new geographical model. The new KAS balances dialysis duration and waiting time to compensate for listing delays and provides more effective longevity matching between donors and recipients with better HLA and age matching. We report these changes, with their rationale and main results. Results show improved HLA matching for young recipients and more rapid access to transplant for older recipients. Young recipients also had better access to transplantation. Transplant access decreased for recipients aged 60–69 and required tuning of KAS parameters. In conclusion, our results strongly indicate that national or adequately broad geographic allocation areas, combined with multiplicative interactions between allocation criteria, permit multivariate optimization of organ allocation and thus improve national kidney sharing and balance HLA matching and age matching, at the price of longer cold ischemic times and more logistical constraints than with local allocation.
β‐catenin cancer–enhancing genomic regions axis is involved in the development of fibrolamellar hepatocellular carcinoma

Fibrolamellar hepatocellular carcinoma (FLC) is a disease that occurs in children and young adults. The development of FLC is associated with creation of a fusion oncoprotein DNAJB1‐PKAc kinase, which activates multiple cancer‐associated pathways. The aim of this study was to examine the role of human genomic regions, called cancer‐enhancing genomic regions or aggressive liver cancer domains (CEGRs/ALCDs), in the development of FLC. Previous studies revealed that CEGRs/ALCDs are located in multiple oncogenes and cancer‐associated genes, regularly silenced in normal tissues. Using the regulatory element locus intersection (RELI) algorithm, we searched a large compendium of chromatin immunoprecipitation–sequencing (ChIP) data sets and found that CEGRs/ALCDs contain regulatory elements in several human cancers outside of pediatric hepatic neoplasms. The RELI algorithm further identified components of the β‐catenin–TCF7L2/TCF4 pathway, which interacts with CEGRs/ALCDs in several human cancers. Particularly, the RELI algorithm found interactions of transcription factors and chromatin remodelers with many genes that are activated in patients with FLC. We found that these FLC‐specific genes contain CEGRs/ALCDs, and that the driver of FLC, fusion oncoprotein DNAJB1‐PKAc, phosphorylates β‐catenin at Ser675, resulting in an increase of β‐catenin–TCF7L2/TCF4 complexes. These complexes increase a large family of CEGR/ALCD‐dependent collagens and oncogenes. The DNAJB1‐PKAc–β‐catenin–CEGR/ALCD pathway is preserved in lung metastasis. The inhibition of β‐catenin in FLC organoids inhibited the expression of CEGRs/ALCDs‐dependent collagens and oncogenes, preventing the formation of the organoid's structure. Conclusion: This study provides a rationale for the development of β‐catenin‐based therapy for patients with FLC.
Comparative Genomics Analysis and Outer Membrane Vesicle-Mediated Horizontal Antibiotic-Resistance Gene Transfer in Avibacterium paragallinarum

The functions and roles of OMVs on ARG and virulent gene transfer and dissemination have been reported in numerous Gram-negative bacteria. However, the role of OMVs in mediating antibiotic resistance in A. paragallinarum has not been reported. ABSTRACT Avibacterium paragallinarum is the etiological agent of infectious coryza, an acute respiratory disease of chickens that is globally distributed and causes serious economic losses for chicken production. A. paragallinarum is a Gram-negative bacterium that releases outer membrane vesicles (OMVs). In this study, a comparative genomic analysis of A. paragallinarum isolate P4chr1 and its OMVs was carried out, and the ability to transfer antibiotic resistance genes (ARGs) via the OMVs was studied. Sequencing and data analyses demonstrated that the genomic size of A. paragallinarum P4chr1 was approximately 2.77 Mb with a 25 kb tolerance island that covered six types of antibiotics and 11 ARGs. The genomic size of its OMVs was approximately 2.69 Mb, covering 97% of the genomic length and almost all the gene sequences of P4chr1. Purified and DNase-treated A. paragallinarum P4chr1 OMVs were cocultured with the antibiotic-sensitive A. paragallinarum Modesto strain on an antibiotic (chloramphenicol, erythromycin, tetracycline, or streptomycin)-containing plate, and the corresponding ARGs were detected in the colonies grown on the plates. However, using an antimicrobial susceptibility test, we found that ARGs delivered by OMVs were not persistent but only appeared transiently on the antibiotic-containing plates. Antibiotic resistance and ARGs were lost by the second bacterial passage. IMPORTANCE The functions and roles of OMVs on ARG and virulent gene transfer and dissemination have been reported in numerous Gram-negative bacteria. However, the role of OMVs in mediating antibiotic resistance in A. paragallinarum has not been reported. This study is the first report to compare the genomic characteristics of OMVs with its parent A. paragallinarum strain and to study A. paragallinarum ARG transfer via OMVs. This work has provided useful data for further studies focusing on nonplasmid ARG transfer mediated by A. paragallinarum OMVs.
Consideration of Solution for Enhancement of Frequency Converter Supply Power Parameters

Abstract The paper presents results of analysis of a possible solution for enhancement of frequency converter (FC) AC supply power parameters. The method proposed is based on switched stabilisation of DC current of FC front-end rectifier unit. Such stabilisation allows obtaining rather good AC supply power parameters, i.e., its power factor and total harmonics distortion (THD) indicator for phase current. The paper also demonstrates a possible realisation scheme, a simplified mathematical description of processes in the scheme, as well as methods for consideration of its parameters, accounting the rated power of FC and the appointed level of the rectifier DC current continuity ratio. The results of computer simulation, to a great extent, testify a possible enhancement level.
The Effects of the TSOL Knot on the Repair Strength and Gliding Resistance Following Flexor Tendon Repair

Background: The stability of a suture knot construct has been realized as an important parameter that affects the strength of flexor tendon repairs. A novel 2-strand-overhand-locking (TSOL) knot, which is not commonly used in the clinical setting, recently was reported to increase repair strength and to decrease tendon gliding resistance in a 2-strand repair technique. The purpose of the present study was to investigate the effect of the TSOL knot on tendon repair strength and gliding resistance compared with a typical surgical knot in both 2-strand and 4-strand repair techniques using an in vitro turkey flexor tendon model. Methods: Sixty flexor digitorum profundus tendons from the long digit of the turkey foot were divided evenly into 4 groups and repaired with the following techniques: (1) a 2-strand modified Pennington repair with a square knot, (2) a 2-strand modified Pennington repair with a TSOL knot, (3) a 4-strand grasping cruciate repair with a square knot, and (4) a 4-strand grasping cruciate repair with a TSOL knot. Repaired tendons were tested for failure mode, gliding resistance, and repair strength at failure. Results: The repair strength and stiffness of the 4-strand repairs were significantly higher than those of the 2-strand repairs, regardless of knot type (p < 0.05). The repair strength at failure of the TSOL knot was significantly greater than that of the square knot in 2-strand repairs (p < 0.05) but not in 4-strand repairs. The gliding resistance of the TSOL knot was significantly decreased compared with that of the square knot in both 2-strand and 4-stand repairs (p < 0.05). With regard to failure mode, the TSOL knot was less likely to fail due to knot unravelling. Conclusions: In this in vitro biomechanical study involving the use of turkey flexor tendons to compare gliding resistance and repair strength characteristics for knot-inside 2 and 4-strand repairs, the TSOL knot was associated with decreased repaired tendon gliding resistance, regardless of the number of strands used. Although the TSOL knot also increased the repair strength, the difference was only significant when 2-strand repairs were used. The results of our study support the use of the TSOL knot in the clinical setting of flexor tendon repair using 2 or 4-strand, knot-inside methods. Clinical Relevance: In surgical repair of flexor tendons, there is substantial interest in maximizing strength while minimizing friction. This study shows the potential utility of the TSOL knot to increase repair strength while decreasing gliding resistance, particularly in 2-strand repairs.
Is the narrative the message? The relationship between suicide-related narratives in media reports and subsequent suicides

Objectives: When journalists report on the details of a suicide, the way that they contextualize the meaning of the event (i.e. the ‘narrative’) can have significant consequences for readers. The ‘Werther’ and ‘Papageno’ narrative effects refer to increases and decreases in suicides across populations following media reports on suicidal acts or mastery of crises, respectively. The goal of this study was to investigate the impact of these different narrative constructs on subsequent suicides. Methods: This study examined the change in suicide counts over time in Toronto, Canada. It used latent difference score analysis, examining suicide-related print media reports in the Toronto media market (2011–2014). Articles (N = 6367) were coded as having a potentially harmful narrative if they described suicide in a celebrity or described a suicide death in a non-celebrity and included the suicide method. Articles were coded as having potentially protective narratives if they included at least one element of protective content (e.g. alternatives to suicide) without including any information about suicidal behaviour (i.e. suicide attempts or death). Results: Latent difference score longitudinal multigroup analyses identified a dose–response relationship in which the trajectory of suicides following harmful ‘Werther’ narrative reports increased over time, while protective ‘Papageno’ narrative reports declined. The latent difference score model demonstrated significant goodness of fit and parameter estimates, with each group demonstrating different trajectories of change in reported suicides over time: (χ2[6], N = 6367) = 13.16; χ2/df = 2.19; Akaike information criterion = 97.16, comparative fit index = 0.96, root mean square error of approximation = 0.03. Conclusion: Our findings support the notion that the ‘narrative’ matters when reporting on suicide. Specifically, ‘Werther’ narratives of suicides in celebrities and suicides in non-celebrities where the methods were described were associated with more subsequent suicides while ‘Papageno’ narratives of survival and crisis mastery without depictions of suicidal behaviours were associated with fewer subsequent suicides. These results may inform efforts to prevent imitation suicides.
Heme oxygenase-1 as an important predictor of the severity of COVID-19

Background and objective A cytokine storm is caused by inflammatory cells, including pro-inflammatory macrophage phenotype (M1), and play a critical role in the pathogenesis of COVID-19, in which diffuse alveolar damage occurs in the lungs due to oxidative stress exposure. Heme oxygenase (HO)-1 is a stress-induced protein produced by the anti-inflammatory / anti-oxidative macrophage phenotype (M2), which also produces soluble CD163 (sCD163). In our study, we investigated and determined that serum HO-1 can be a predictive biomarker for assessing both the severity and the outcome of COVID-19 patients. Method The serum concentrations of HO-1 and sCD163 of COVID-19 patients were measured on admission. The relationship between these biomarkers and other clinical parameters and outcomes were evaluated. Results Sixty-four COVID-19 patients (11 mild, 38 moderate, and 15 severe cases) were assessed. The serum HO-1 tended to increase (11.0 ng/mL vs. 24.3 ng/mL vs. 59.6 ng/mL with severity). Serum HO-1 correlated with serum lactate dehydrogenase (R = 0.422), C-reactive protein (R = 0.463), and the ground glass opacity (GGO) and consolidation score (R = 0.625) of chest computed tomography. The serum HO-1 showed a better area under the curve (AUC) for predicting ICU admission than the serum sCD163 (HO-1; 0.816 and sCD163; 0.743). In addition, composite parameters including serum HO-1 and the GGO and consolidation score showed a higher AUC for predicting ICU admission than the AUC of a single parameter. Conclusion Clinically, serum HO-1, reflecting the activation of M2, could be a very useful marker for evaluating disease severity and predicting prognoses for COVID-19 patients. In addition, controlling activated M2 might be a preventative COVID-19 therapeutic target.