Miracle-dz/UniFAR-FTUs huggingface dataset:
Individual Goffin´s cockatoos (Cacatua goffiniana) show flexible targeted helping in a tool transfer task

Flexible targeted helping is considered an advanced form of prosocial behavior in hominoids, as it requires the actor to assess different situations that a conspecific may be in, and to subsequently flexibly satisfy different needs of that partner depending on the nature of those situations. So far, apart from humans such behaviour has only been experimentally shown in chimpanzees and in Eurasian jays. Recent studies highlight the prosocial tendencies of several bird species, yet flexible targeted helping remained untested, largely due to methodological issues as such tasks are generally designed around tool-use, and very few bird species are capable of tool-use. Here, we tested Goffin’s cockatoos, which proved to be skilled tool innovators in captivity, in a tool transfer task in which an actor had access to four different objects/tools and a partner to one of two different apparatuses that each required one of these tools to retrieve a reward. As expected from this species, we recorded playful object transfers across all conditions. Yet, importantly and similar to apes, three out of eight birds transferred the correct tool more often in the test condition than in a condition that also featured an apparatus but no partner. Furthermore, one of these birds transferred that correct tool first more often before transferring any other object in the test condition than in the no-partner condition, while the other two cockatoos were marginally non-significantly more likely to do so. Additionally, there was no difference in the likelihood of the correct tool being transferred first for either of the two apparatuses, suggesting that these birds flexibly adjusted what to transfer based on their partner´s need. Future studies should focus on explanations for the intra-specific variation of this behaviour, and should test other parrots and other large-brained birds to see how this can be generalized across the class and to investigate the evolutionary history of this trait.
A T cell redirection platform for co-targeting dual antigens on solid tumors

ABSTRACT In order to direct T cells to specific features of solid cancer cells, we engineered a bispecific antibody format, named Dual Antigen T cell Engager (DATE), by fusing a single-chain variable fragment targeting CD3 to a tumor-targeting antigen-binding fragment. In this format, multiple novel paratopes against different tumor antigens were able to recruit T-cell cytotoxicity to tumor cells in vitro and in an in vivo pancreatic ductal adenocarcinoma xenograft model. Since unique surface antigens in solid tumors are limited, in order to enhance selectivity, we further engineered “double-DATEs” targeting two tumor antigens simultaneously. The double-DATE contains an additional autonomous variable heavy-chain domain, which binds a second tumor antigen without itself eliciting a cytotoxic response. This novel modality provides a strategy to enhance the selectivity of immune redirection through binary targeting of native tumor antigens. The modularity and use of a common, stable human framework for all components enables a pipeline approach to rapidly develop a broad repertoire of tailored DATEs and double-DATEs with favorable biophysical properties and high potencies and selectivities.
Selection and thermostability suggest G-quadruplexes are novel functional elements of the human genome

Approximately 1% of the human genome has the ability to fold into G-quadruplexes (G4s)—noncanonical strand-specific DNA structures forming at G-rich motifs. G4s regulate several key cellular processes (e.g., transcription) and have been hypothesized to participate in others (e.g., firing of replication origins). Moreover, G4s differ in their thermostability, and this may affect their function. Yet, G4s may also hinder replication, transcription, and translation and may increase genome instability and mutation rates. Therefore, depending on their genomic location, thermostability, and functionality, G4 loci might evolve under different selective pressures, which has never been investigated. Here we conducted the first genome-wide analysis of G4 distribution, thermostability, and selection. We found an overrepresentation, high thermostability, and purifying selection for G4s within genic components in which they are expected to be functional—promoters, CpG islands, and 5′ and 3′ UTRs. A similar pattern was observed for G4s within replication origins, enhancers, eQTLs, and TAD boundary regions, strongly suggesting their functionality. In contrast, G4s on the nontranscribed strand of exons were underrepresented, were unstable, and evolved neutrally. In general, G4s on the nontranscribed strand of genic components had lower density and were less stable than those on the transcribed strand, suggesting that the former are avoided at the RNA level. Across the genome, purifying selection was stronger at stable G4s. Our results suggest that purifying selection preserves the sequences of functional G4s, whereas nonfunctional G4s are too costly to be tolerated in the genome. Thus, G4s are emerging as fundamental, functional genomic elements.
Environmental and Spatial Predictors of the Distribution Patterns of the Host-Seeking Black Fly, Simulium jenningsi (Diptera: Simuliidae)

Abstract Black flies are nuisance pests as adults, yet they are best managed in the larval stage in flowing waters. As a result, more effort is put into understanding the distribution of the immature life stages than the blood-seeking females that form nuisance. The seemingly localized nature of Simulium jenningsi Malloch (Diptera: Simuliidae) pest problems in western Maryland offered a study system to investigate the spatial and environmental correlates to their severity. Collections of adult black flies were taken at 260 sites within a 2,000 km2 region centered on Washington County, Maryland, during June, July, and August of 2 yr. Average S. jenningsi counts were greater in the June of both years compared to July and August. Although S. jenningsi was found at the majority of sampling sites, higher fly counts were significantly clustered in the southern portion of the county where the majority of resident complaints originated. A generalized linear mixed-model (GLMM) approach was used to determine the correlates to S. jenningsi abundance. The highest performing model showed a negative relationship of S. jenningsi counts with the amount of surrounding impervious surface, distance to the riffles along the confluence of the Shenandoah and Potomac Rivers, distance to the closest body of flowing water, and light intensity, as well as a positive relationship with elevation and air temperature. The results suggest S. jenningsi females are not readily found in urban environments in this study region, and the most relevant monitoring locations for S. jenningsi may be outside of human population centers.
Impact of beta‐blocker use on the long‐term outcomes of heart failure patients with chronic obstructive pulmonary disease

The number of patients with both chronic obstructive pulmonary disease (COPD) and heart failure (HF) is increasing in Asia, and these conditions often coexist. We previously revealed a tendency of beta‐blocker underuse among patients with HF with reduced ejection fraction (HFrEF) and COPD in Asian countries other than Japan. Here, we evaluated the impact of cardio‐selective beta‐blocker use on the long‐term outcomes of patients with HF and COPD.
Monitoring Insect Transposable Elements in Large Double-Stranded DNA Viruses Reveals Host-to-Virus and Virus-to-Virus Transposition

Abstract The mechanisms by which transposable elements (TEs) can be horizontally transferred between animals are unknown, but viruses are possible candidate vectors. Here, we surveyed the presence of host-derived TEs in viral genomes in 35 deep sequencing data sets produced from 11 host–virus systems, encompassing nine arthropod host species (five lepidopterans, two dipterans, and two crustaceans) and six different double-stranded (ds) DNA viruses (four baculoviruses and two iridoviruses). We found evidence of viral-borne TEs in 14 data sets, with frequencies of viral genomes carrying a TE ranging from 0.01% to 26.33% for baculoviruses and from 0.45% to 7.36% for iridoviruses. The analysis of viral populations separated by a single replication cycle revealed that viral-borne TEs originating from an initial host species can be retrieved after viral replication in another host species, sometimes at higher frequencies. Furthermore, we detected a strong increase in the number of integrations in a viral population for a TE absent from the hosts’ genomes, indicating that this TE has undergone intense transposition within the viral population. Finally, we provide evidence that many TEs found integrated in viral genomes (15/41) have been horizontally transferred in insects. Altogether, our results indicate that multiple large dsDNA viruses have the capacity to shuttle TEs in insects and they underline the potential of viruses to act as vectors of horizontal transfer of TEs. Furthermore, the finding that TEs can transpose between viral genomes of a viral species sets viruses as possible new niches in which TEs can persist and evolve.
A whole-body physiologically-based pharmacokinetic model for alpha particle emitting bismuth in rats

Introduction/Aim: α particle emitting bismuth (212Bi) as decay product of 212Pb-labeled pharmaceuticals has been effective in targeted α particle therapy (TAT). Estimating the contribution of 212Bi released from its chelator to the absorbed doses in nontarget tissues is challenging in TAT. Physiologically based pharmacokinetic (PBPK) modeling can help overcome this limitation. Therefore, a whole-body 212Bi-PBPK model was developed to describe the pharmacokinetics (PKs) of 212Bi in rats. Materials and Methods: The rat 212Bi-PBPK model was implemented using the modeling software SAAM II with data and parameter values from the literature. Besides other mechanisms, 212Bi interactions with red blood cells, high molecular weight plasma protein, and intracellular biological thiols are described. Important PK parameters were fitted to time-activity data. Absorbed dose coefficients (ADCs) were calculated for injecting 0.774 fmol of 212Bi. Results: 212Bi uptake rates of liver, bone, small intestine, bone marrow, skin, and muscle were (0.86 ± 0.13), (3.85 ± 0.63), (0.27 ± 0.05), (1.44 ± 0.29), (0.04 ± 0.01), and (0.007 ± 0.007) per min with corresponding ADCs of 0.09, 0.03, 0.03, 0.07, 0.01, and 0.003 mGy/kBq, respectively. An ADC of 0.70 mGy/kBq was determined for kidneys. Conclusion: Kidneys are the dose-limiting organs in 212Bi-based TAT. The 212Bi-PBPK model is an effective tool to investigate the 212Bi biodistribution in murine models. Integrating the 212Bi-PBPK model into other murine and human PBPK models of α particle generators can help study the efficacy and safety of TAT.
Aromatic Side Chain at Position 412 of SERINC5 Exerts Restriction Activity toward HIV-1 and Other Retroviruses

The host protein SERINC5 is incorporated into progeny virions of certain retroviruses and restricts the infectivity of these viruses or sensitizes the envelope glycoprotein to a class of neutralizing antibodies. However, how and which part of SERINC5 engages with the diverse array of retroviral envelopes and exerts its antiretroviral functions remain elusive. ABSTRACT The host transmembrane protein SERINC5 is incorporated into viral particles and restricts infection by certain retroviruses. However, what motif of SERINC5 mediates this process remains elusive. By conducting mutagenesis analyses, we found that the substitution of phenylalanine with alanine at position 412 (F412A) resulted in a >75-fold reduction in SERINC5’s restriction function. The F412A substitution also resulted in the loss of SERINC5’s function to sensitize HIV-1 neutralization by antibodies recognizing the envelope’s membrane proximal region. A series of biochemical analyses revealed that F412A showed steady-state protein expression, localization at the cellular membrane, and incorporation into secreted virus particles to a greater extent than in the wild type. Furthermore, introduction of several amino acid mutations at this position revealed that the aromatic side chains, including phenylalanine, tyrosine, and tryptophan, were required to maintain SERINC5 functions to impair the virus-cell fusion process and virion infectivity. Moreover, the wild-type SERINC5 restricted infection of lentiviruses pseudotyped with envelopes of murine leukemia viruses, simian immunodeficiency virus, and HIV-2, and F412A abrogated this function. Taken together, our results highlight the importance of the aromatic side chain at SERINC5 position 412 to maintain its restriction function against diverse retrovirus envelopes. IMPORTANCE The host protein SERINC5 is incorporated into progeny virions of certain retroviruses and restricts the infectivity of these viruses or sensitizes the envelope glycoprotein to a class of neutralizing antibodies. However, how and which part of SERINC5 engages with the diverse array of retroviral envelopes and exerts its antiretroviral functions remain elusive. During mutagenesis analyses, we eventually found that the single substitution of phenylalanine with alanine, but not with tyrosine or tryptophan, at position 412 (F412A) resulted in the loss of SERINC5’s functions toward diverse retroviruses, whereas F412A showed steady-state protein expression, localization at the cellular membrane, and incorporation into progeny virions to a greater extent than the wild type. Results suggest that the aromatic side chain at position 412 of SERINC5 plays a critical role in mediating antiviral functions toward various retroviruses, thus providing additional important information regarding host and retrovirus interaction.
High-Performance Liquid Chromatography-Mass Spectrometry for the Determination of Flavonoids in G.biloba Leaves

The aim of the present work was to develop a multimethod for the analysis of five flavonoids in G.biloba leaves. The selected flavonoids were rutin, quercetin 3-D-galactoside, baicalin, isorhamnetin and rhamnetin. Leaf extraction was sonicated by using ethanol. The extract was passed through solid-phase extraction columns. Then, the extract was analyzed by high-performance liquid chromatography coupled in line with mass spectrometry. Calibration was carried out over the concentration range of 0.5 to 50 mg/L. The calibration data presented high correlation coefficients (>0.99). The limits of detection were 4.7, 5.3, 9.7, 6.9 and 12.9 μg/L for rutin, quercetin 3-D-galactoside, baicalin, isorhamnetin and rhamnetin, respectively. Mean recoveries ranged from 66% to 72% for the HPLC–MS analysis. Reproducibility was estimated by the relative standard deviation (RSD) which ranged between 2.21 and 3.93%. Five flavonoids were found to be present in G.biloba leaves. The developed method was readily applied to quantify the flavonoids in some commercially available G.biloba leaves.
Effect of Liraglutide on Arterial Inflammation Assessed as [18F]FDG Uptake in Patients With Type 2 Diabetes: A Randomized, Double-Blind, Placebo-Controlled Trial

Supplemental Digital Content is available in the text. Background: The mechanism behind the cardiovascular protection observed with human GLP-1 RA (glucagon-like peptide-1 receptor agonists) in type 2 diabetes is unknown. We hypothesized that treatment with the GLP-1 RA liraglutide had a positive effect on vascular inflammation. Methods: LIRAFLAME (Effect of liraglutide on vascular inflammation in type-2 diabetes: A randomized, placebocontrolled, double-blind, parallel clinical PET/CT trial) was a double-blind, randomized controlled trial performed at a single university hospital clinic in Denmark. Patients with type 2 diabetes were via computer-generated randomization list assigned (1:1) liraglutide up to 1.8 mg or placebo once daily for 26 weeks. The primary end point was change in vascular inflammation over 26 weeks assessed by [18F]-fluorodeoxyglucose positron emission tomography/computed tomography. Analyses were based on intention-to-treat. Key secondary outcomes included change in other indices of atherosclerosis. Results: Between October 26, 2017, and August 16, 2019, 147 patients were screened and 102 were randomly assigned to liraglutide (n=51) or placebo (n=51) and 99 (97%) completed the trial. Change in the [18F]-fluorodeoxyglucose positron emission tomography measure of vascular inflammation (active-segment target-to-background ratio) did not differ between treatment groups: change from baseline to 26 weeks was −0.04 (95% CI, −0.17 to 0.08) in the liraglutide group compared with −0.09 (−0.19 to 0.01) in the placebo group (mean difference, 0.05 [95% CI, −0.11 to 0.21], P=0.53). Secondary analyses restricted to [18F]-fluorodeoxyglucose positron emission tomography of the carotid arteries as well as other indices of atherosclerosis confirmed the primary result. We performed an explorative analysis of interaction between treatment group and history of cardiovascular disease (P=0.052). Conclusions: In this low to moderate risk population with type 2 diabetes, liraglutide did not change vascular inflammation assessed as [18F]-fluorodeoxyglucose uptake compared with placebo. An explorative analysis indicated a possible effect in persons with history of cardiovascular disease, in line with current guidelines where liraglutide is recommended to patients with history of cardiovascular disease. Registration: URL: https://www.clinicaltrials. gov; Unique identifier: NCT03449654.
Prevention of eating disorders: 2020 in review

ABSTRACT Fifteen prevention-related publications in Eating Disorders during 2020 are reviewed. Two models frame this analysis: (1) the Mental Health Intervention Spectrum: health promotion → types of prevention → case identification and referral → treatment; and (2) parsing phases of prevention into a cycle: rationale, theory, and methodology, shaped by critical, integrative reviews → clarification of risk and protective factors → program innovation and feasibility studies → efficacy and effectiveness research → program dissemination. In this cycle the first two phases and the last phase inform advocacy for social policies supporting prevention. Ten articles comprising a special issue on yoga demonstrate the value of investing in translational prevention science that acknowledges (a) embodying experiences as a broad category of protective factors; (b) the utility of multidimensional theoretical models; and (c) social justice issues that advocacy efforts must address to make programs widely and equitably available. Other articles reviewed show, for example, that studies of emotion dysregulation and emotional eating are needed to enter a prevention cycle that moves us beyond body image (or weight/shape) concerns in defining high-risk groups and developing indicated prevention. Finally, implications of the absence of efficacy, effectiveness, dissemination, and advocacy studies are discussed.
A Small Regulatory RNA Generated from the malK 5′ Untranslated Region Targets Gluconeogenesis in Vibrio Species

Juvenile pacific oysters have been subject in recent years to summer mortality episodes with deep economic consequences. The pathogen Vibrio tasmaniensis has been associated with such mortality events. ABSTRACT Vsr217 is a small RNA from Vibrio tasmaniensis LGP32, a pathogen associated with mortality events affecting juvenile oysters. The vsr217 gene is located within the 5′ untranslated region (UTR) of malK, encoding the ATPase component of the maltose importer, and is conserved within the genus Vibrio. In the presence of maltose, vsr217 is regulated by MalT, the positive regulator of the maltose regulon. vsr217 is required in cis for the full expression of malK. In addition, Vsr217 acts in trans to downregulate the expression of fbp encoding fructose-1,6-bisphosphatase, an enzyme involved in gluconeogenesis. Thus, in the presence of maltose, the induction of Vsr217 is expected to promote glycolysis by negatively regulating the expression of a key enzyme of gluconeogenesis. IMPORTANCE Juvenile pacific oysters have been subject in recent years to summer mortality episodes with deep economic consequences. The pathogen Vibrio tasmaniensis has been associated with such mortality events. For bacterial pathogens, survival within the host requires profound metabolic adaptations according to available resources. All kinds of regulatory elements, including noncoding RNAs, orchestrate this response. Oysters are rich in glycogen, a precursor of maltose, and we previously reported that V. tasmaniensis maltose-regulated genes are strongly induced during oyster infection. Here, we report the dual mechanism by which a small regulatory RNA, generated from the 5′ untranslated region of a gene belonging to the maltose regulon, acts both in cis and trans. In cis, it stimulates growth on maltose, and in trans, it downregulates the expression of a gene associated with gluconeogenesis, thus coordinating maltose utilization with central carbon metabolism.
Social Support Promotes Mental Health During the COVID-19 Outbreak: A Cross-Sectional Study from Turkey.

BACKGROUND Coronavirus-19 (COVID-19) has several negative effects on mental health, given its rapid transmission, hygiene and isolation measures and associated social and financial difficulties. In this study, we aimed to investigate the mental health burden of the Turkish population and vulnerable groups during the COVID-19 outbreak, especially exploring the effects of social support. SUBJECTS AND METHODS We assessed depression, anxiety, stress symptoms and perceived social support among 894 people all over Turkey, using the Depression Anxiety Stress Scales (DASS-21) and Multidimensional Scale of Perceived Social Support (MSPSS) two months after the declaration of the first COVID-19 case in Turkey. RESULTS According to DASS-21 subscale scores, the findings showed that the prevalence of moderate to severe depression, anxiety and stress-related symptoms was 24.8%, 21.9% and 12.6%, respectively. Female gender, being single, having a lifetime psychiatric disorder, lower education level and financial concerns were significantly associated with higher DASS-21 scores. Also, there was a negative correlation between all subgroups of perceived social support, especially from the family, and the total DASS-21 score. CONCLUSIONS Vulnerable groups should be identified and protected to reduce adverse psychiatric outcomes of COVID-19. Besides, further strategies should be provided to maintain protective factors, such as social support, under stressful conditions.