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The methylotrophic yeast Komagataella phaffii is a popular host system for the pharmaceutical and biotechnological production of recombinant proteins. CRISPR-Cas9 and its derivative CRISPR interference (CRISPRi) offer a promising avenue to further enhance and exploit the full capabilities of this host. MAD7 and its catalytically inactive variant "dead" MAD7 (dMAD7) represent an interesting alternative to established CRISPR-Cas9 systems and are free to use for industrial and academic research. CRISPRi utilizing dMAD7 does not introduce double-strand breaks but only binds to the DNA to regulate gene expression. Here, we report the first use of dMAD7 in K. phaffii to regulate the expression of the enhanced green fluorescent protein (eGFP). A reduction of eGFP fluorescence level (up to 88 %) was achieved in random integration experiments using dMAD7 plasmids. Integration loci/events of investigated strains were assessed through whole genome sequencing. Additionally, RNA-sequencing experiments corroborated the whole genome sequencing results and showed a significantly reduced expression of eGFP in strains containing a dMAD7 plasmid, among others. Our findings conclusively demonstrate the utility of dMAD7 in K. phaffii through successfully regulating eGFP expression. • We report the first use of dMAD7 in K. phaffii to regulate the expression of enhanced green fluorescent protein (eGFP). • A reduction of eGFP fluorescence level (up to 88 %) was achieved in random integration experiments using dMAD7 plasmids. • Whole genome sequencing and RNA-sequencing were used to assess the integration events and to characterize the strains. • Our findings conclusively demonstrate the utility of the dMAD7 system in K. phaffii. [ABSTRACT FROM AUTHOR]

Exaggerated blood pressure (BP) responses during exercise are independently associated with future development of hypertension. Partial sleep deprivation (PSD) can increase 24-h ambulatory BP, but the effects on exercise BP are unclear. We hypothesized that acute PSD would augment the BP response to constant load cycling exercise and a 20-min time trial. Twenty-two healthy adults (22 ± 3 yr old; 13 males; V̇ o 2peak, 43.6 ± 8.2 mL·kg−1·min−1) completed a randomized crossover trial in which they either slept normally (normal sleep-wake schedule for each participant) or sleep was partially deprived (early awakening, 40% of normal sleep duration). Each participant completed a 12-min warm-up consisting of two 6-min steps (step 1, 62 ± 25 W; step 2, 137 ± 60 W) followed by a 20-min time trial on a cycle ergometer. PSD did not alter power output during the 20-min time trial [(control vs. PSD) 170 ± 68 vs. 168 ± 68 W, P = 0.65]. Systolic BP did not differ during step 1 of the warm-up (141 ± 15 vs. 137 ± 12 mmHg, P = 0.39) but was lower following PSD during step 2 (165 ± 21 vs. 159 ± 22 mmHg, P = 0.004) and the 20-min time trial (171 ± 20 vs. 164 ± 23 mmHg, P < 0.001). These results were maintained when peak oxygen uptake (V̇ o 2peak) was included as a covariate. Systolic BP responses were modulated by sex (time × visit × sex interaction P = 0.03), with attenuated systolic BP during the warm-up and the 20-min time trial in males but not in females. In contrast to our hypothesis, acute PSD attenuates systolic BP responses during constant load and 20-min time trial cycling exercise; however, these observations appear to be primarily driven by changes in males. NEW & NOTEWORTHY: A single night of partial sleep deprivation (PSD) can increase ambulatory blood pressure (BP) the following day. Despite this phenomenon, the present study found that acute PSD attenuates systolic BP responses to both constant load cycling and a 20-min cycling time trial in young healthy adults. Interestingly, the attenuated systolic BP responses following PSD appeared to be modulated by sex such that attenuations were observed in males but not in females. [ABSTRACT FROM AUTHOR]

The demand for highly sensitive methods of pathogen detection drives the development of new diagnostic assays. While nucleic acid amplification methods such as PCR are very sensitive and remain widely used, they may be limited in complex sample matrices due to the presence of polymerase inhibitors. On the other hand, the direct detection of nucleic acids by DNA hybridization assays is simple but typically less sensitive. This work combines a branched DNA (bDNA) hybridization assay with upconversion nanoparticle (UCNP) labels to enhance the sensitivity of DNA detection. The anti‐Stokes emission of UCNP labels enables measurements without optical background interference. The bDNA assay relies on a series of oligonucleotide probes creating a branched structure with several binding sites for biotinylated amplification probes and streptavidin‐conjugated UCNPs. Several configurations of the bDNA assay are investigated to achieve the highest signal amplification and the lowest background signal. The optimal configuration of bDNA assay yields a limit of detection (LOD) of 5.9 × 104 cfu mL−1 for the target DNA of the bacteriophage M13. The upconversion‐linked bDNA assay is easily adaptable to other target DNAs by adjusting the oligonucleotide probes. [ABSTRACT FROM AUTHOR]

Linear growth during three distinct stages of life determines attained stature in adulthood: namely, in utero, early postnatal life, and puberty and the adolescent period. Individual host factors, genetics, and the environment, including nutrition, influence attained human stature. Each period of physical growth has its specific biological and environmental considerations. Recent epidemiologic investigations reveal a strong influence of prenatal factors on linear size at birth that in turn influence the postnatal growth trajectory. Although average population height changes have been documented in high-income regions, stature as a complex human trait is not well understood or easily modified. This review summarizes the biology of linear growth and its major drivers, including nutrition from a life-course perspective, the genetics of programmed growth patterns or height, and gene–environment interactions that determine human stature in toto over the life span. Implications for public health interventions and knowledge gaps are discussed. [ABSTRACT FROM AUTHOR]

Background Although genome-wide association studies (GWAS) of breast cancer (BC) identified common variants which differ between intrinsic subtypes, genes through which these variants act to impact BC risk have not been fully established. Transcriptome-wide association studies (TWAS) have identified genes associated with overall BC risk, but subtype-specific differences are largely unknown. Methods We performed two multi-tissue TWAS for each BC intrinsic subtype, including an expression-based approach that collated TWAS signals from expression quantitative trait loci (eQTLs) across multiple tissues and a novel splicing-based approach that collated signals from splicing QTLs (sQTLs) across intron clusters and subsequently across tissues. We used summary statistics for five intrinsic subtypes including Luminal A-like, Luminal B-like, Luminal B/HER2-negative-like, HER2-enriched-like, and triple-negative BC, generated from 106 278 BC cases and 91 477 controls in the Breast Cancer Association Consortium. Results Overall, we identified 235 genes in 88 loci that were associated with at least one of the five intrinsic subtypes. Most genes were subtype-specific, and many have not been reported in previous TWAS. We discovered common variants that modulate expression of CHEK2 confer increased risk to Luminal A-like BC, in contrast to the viewpoint that CHEK2 primarily harbors rare, penetrant mutations. Additionally, our splicing-based TWAS provided population-level support for MDM4 splice variants that increased the risk of triple-negative BC. Conclusion Our comprehensive, multi-tissue TWAS corroborated previous GWAS loci for overall BC risk and intrinsic subtypes, while underscoring how common variation that impacts expression and splicing of genes in multiple tissue types can be used to further elucidate the etiology of BC. [ABSTRACT FROM AUTHOR]

Exercise has long been known for its beneficial effects on insulin sensitivity (IS) and glucose handling with both moderate-intensity continuous (MIC) exercise and resistance exercise (RE) inducing beneficial effects. In recent years, low-load, high-repetition (LLHR) RE has emerged as a strategy to increase muscle mass and strength to levels similar to traditional RE; however, the effects of LLHR RE on glucose handling has yet to be investigated. The purpose of this trial was to compare the acute effects of LLHR RE to MIC exercise on post-exercise glycemic control and insulin sensitivity in males and females. Twenty-four (n = 12/sex) participants completed acute bouts of MIC exercise (30 min at 65% V̇O₂peak) and LLHR (3 circuits, 6 exercises/circuit, 25–35 repetitions/exercise/circuit) matched for time with muscle biopsies immediately pre and post exercise and an oral glucose tolerance test (OGTT) 90 min following exercise. Blood glucose concentrations (p = 0.002, ηp2 = 0.37), glucose AUC (p = 0.002, ηp2 = 0.35) and max glucose concentration (p = 0.003, ηp2 = 0.34) were lower during the post exercise OGTT following LLHR RE compared to MIC exercise. There was a main effect of trial on TBC1D1 Ser237 phosphorylation (p = 0.04, ηp2 = 0.19) such that it was greater following MIC exercise compared to LLHR RE. Furthermore, phosphorylated ACC Ser79 increased following MIC exercise with no change following LLHR RE (p < 0.001, ηp2 = 0.50). Phosphorylation of PTEN Ser380 was greater in males than females during LLHR RE (p = 0.01, ηp2 = 0.27). These findings suggest that LLHR RE is a feasible exercise modality to improve post-exercise glycemic control in both males and females. Trial registration number: NCT06217679. [ABSTRACT FROM AUTHOR]

Headsprout Early Reading is a computer-based program designed on behavioral principles to enhance the basic skills that underpin the initial development of reading. In a within and between groups design, and using primary schools within Northern Ireland that had a currently high proportion of disadvantaged pupils, children who were behind their peers in progress with reading were randomly allocated to an intervention group (n = 79), where the target was to work through 80 reading training episodes within a school year, or a teaching as usual group (n = 44). Reading skills were assessed in all children before, at the midpoint, and after the intervention using a flashcard-based phonics identification test with three levels of difficulty, and before and after intervention using a standardized reading assessment, which generated a sentence reading age and a phonics reading age. Both groups showed increased scores on all measures over the 6 months of the study, but the intervention group showed markedly greater improvement. Importantly, the mean scores on sentence reading age and phonics reading age for the intervention group increased by over 17 months and 12.1 months, respectively, as opposed to 7.6 months and 7.8 months with the control group. These findings also validated the use of the flashcard-based phonics identification test with this population. This study indicates that widespread use of Headsprout Early Reading in mainstream education could be highly effective. [ABSTRACT FROM AUTHOR]

Childhood stunting and wasting, or decreased linear and ponderal growth associated with undernutrition, continue to be a major global public health challenge. Although many of the current therapeutic and dietary interventions have significantly reduced childhood mortality caused by undernutrition, there remain great inefficacies in improving childhood stunting. Longitudinal bone growth in children is governed by different genetic, nutritional and other environmental factors acting systemically on the endocrine system and locally at the growth plate. Recent studies have shown that this intricate interplay between nutritional and hormonal regulation of the growth plate could involve the gut microbiota, highlighting the importance of a holistic approach in tackling childhood undernutrition. In this review, I focus on the mechanistic insights provided by these recent advances in gut microbiota research and discuss ongoing development of microbiota‐based therapeutics in humans, which could be the missing link in solving undernutrition and childhood stunting. What is the topic of this review?This review is about the mechanisms by which the gut microbiota regulates bone growth.What advances does it highlight?There is in vivo evidence for regulation of the gut microbiota on the growth hormone–insulin‐like growth factor I axis. An association exists between gut microbiota immaturity and undernutrition. Clinical trials of microbiota‐based therapeutics are underway. [ABSTRACT FROM AUTHOR]

In 2004 the first annual BioMalPar meeting was held at EMBL Heidelberg, bringing together researchers from around the world with the goal of building connections between malaria research groups in Europe. Twenty years on it is time to reflect on what was achieved and to look ahead to the future. [ABSTRACT FROM AUTHOR]

Blood pressure (BP) follows a circadian rhythm intertwined with the sleep-wake cycle. Acute partial sleep deprivation (PSD; sleep = 6 h) can increase BP, associated with increased cardiovascular risk. Acute exercise can reduce BP for up to 24 h, a phenomenon termed postexercise hypotension. The present study tested whether aerobic exercise could mitigate the augmented 24-h ambulatory BP caused by acute PSD. Twenty-four young otherwise healthy adults (22 ± 3 yr; 14 females; selfreported chronotypes: 6 early/10 intermediate/8 late; Pittsburgh sleep quality index: 17 good/7 poor sleepers) completed a randomized crossover trial in which, on different days, they slept normally (2300-0700), restricted sleep [0330-0700 (PSD)], and cycled for 50 min (70-80% predicted heart rate maximum) before PSD. Ambulatory BP was assessed every 30 min until 2100 the next day. Acute PSD increased 24-h systolic BP (control 117 ± 9 mmHg, PSD 122 ± 9 mmHg; P < 0.001) and prior exercise attenuated (exercise þ PSD 120 ± 9 mmHg; P = 0.04 vs. PSD) but did not fully reverse this response (exercise þ PSD, P = 0.02 vs. control). Subgroup analysis revealed that the 24-h systolic BP reduction following exercise was specific to late types (PSD 119 ± 7 vs. exercise þ PSD 116 ± 6 mmHg; P < 0.05). Overall, habitual sleep quality was negatively correlated with the change in daytime systolic BP following PSD (r = -0.56, P < 0.01). These findings suggest that the ability of aerobic cycling exercise to counteract the hemodynamic effects of acute PSD in young adults may be dependent on chronotype and that habitual sleep quality can predict the daytime BP response to acute PSD. [ABSTRACT FROM AUTHOR]

In recent years, biblicists have argued that the "judge of Israel" and the "era of judges" are simply the editorial invention of the Deuteronomist(s). Central to the debate is the place of Judg 2:11-19, the only passage within the book of Judges where the leaders of early Israel are specifically designated with the Hebrew title טפש, conventionally translated "judge." Since, according to recent scholarship, םיטפש never existed in Israel's premonarchic past, their biblical attestation in Judg 2:11-19 demands an explanation. Over the past several decades, scholars have offered various ideas, none of which has been fully satisfactory. In this article, I challenge prevailing claims about the טפש of premonarchic Israel through a reexamination of the composition history of Judg 2:11-19. I argue that this literary unit underwent two phases of editing--one in Israelite circles, and another in Judahite (Deuteronomistic) circles. Behind these editorial layers of Judg 2:11-19 is what I propose may have been a substratum on which later editors built. Notwithstanding the hypothetical nature of this substratum, I show how it corresponds to certain sociopolitical realities that would have been foreign at later times of writing and how it coheres with recent models of composition history for the book of Judges. Thus, I argue that the טפש of Israel was not the invention of the Deuteronomist(s). Moreover, the findings suggest that Judg 2:11-19 may preserve a genuine memory of םיטפש in premonarchic Israel. While recent scholarship has sought to explain cultural phenomena of early Israel (e.g., the םיטפש) as the product of later writings, my study invites a discussion of possible links with older cultural settings. [ABSTRACT FROM AUTHOR]

In vivo deuterated water (2H2O) labeling leads to deuterium (2H) incorporation into biomolecules of proliferating cells and provides the basis for its use in cell kinetics research. We hypothesized that rapidly proliferating cancer cells would become preferentially labeled with 2H and, therefore, could be visualized by deuterium magnetic resonance imaging (dMRI) following a brief period of in vivo systemic 2H2O administration. We initiated systemic 2H2O administration in two xenograft mouse models harboring either human colorectal, HT-29, or pancreatic, MiaPaCa-2, tumors and 2H2O level of ~ 8% in total body water (TBW). Three schemas of 2H2O administration were tested: (1) starting at tumor seeding and continuing for 7 days of in vivo growth with imaging on day 7, (2) starting at tumor seeding and continuing for 14 days of in vivo growth with imaging on day 14, and (3) initiation of labeling following a week of in vivo tumor growth and continuing until imaging was performed on day 14. Deuterium chemical shift imaging of the tumor bearing limb and contralateral control was performed on either day 7 of 14 after tumor seeding, as described. After 14 days of in vivo tumor growth and 7 days of systemic labeling with 2H2O, a clear deuterium contrast was demonstrated between the xenografts and normal tissue. Labeling in the second week after tumor implantation afforded the highest contrast between neoplastic and healthy tissue in both models. Systemic labeling with 2H2O can be used to create imaging contrast between tumor and healthy issue, providing a non-radioactive method for in vivo cancer imaging. [ABSTRACT FROM AUTHOR]

Over the past two decades, there has been a renewed interest in the analysis of character and characterization in the Hebrew Bible. Many studies have focused on the major characters and their company. However, insufficient attention has been given to characters on the margins of the narrative I identify as 'marginal characters'. In this paper, I investigate the narratological function of these characters through an examination of select marginal characters in 1–2 Samuel. Drawing upon a conceptual framework for analyzing anonymous characters in Greek Tragedy, I propose two functions for these marginal characters: 1) they serve as a reflection of the narrator's disposition toward the complex characters of Saul and David; 2) they serve as manifestations of divine providence. These functions are not mutually exclusive. In both cases, however, the marginal characters contribute to a strategy of narrative persuasion, leading the audience to certain ideological and theological conclusions. [ABSTRACT FROM AUTHOR]

The role of C‐type natriuretic peptide (CNP) in the regulation of cardiac function in humans remains to be established as previous investigations have been confined to animal model systems. Here, we used well‐characterized engineered cardiac tissues (ECTs) generated from human stem cell‐derived cardiomyocytes and fibroblasts to study the acute effects of CNP on contractility. Application of CNP elicited a positive inotropic response as evidenced by increases in maximum twitch amplitude, maximum contraction slope and maximum calcium amplitude. This inotropic response was accompanied by a positive lusitropic response as demonstrated by reductions in time from peak contraction to 90% of relaxation and time from peak calcium transient to 90% of decay that paralleled increases in maximum contraction decay slope and maximum calcium decay slope. To establish translatability, CNP‐induced changes in contractility were also assessed in rat ex vivo (isolated heart) and in vivo models. Here, the effects on force kinetics observed in ECTs mirrored those observed in both the ex vivo and in vivo model systems, whereas the increase in maximal force generation with CNP application was only detected in ECTs. In conclusion, CNP induces a positive inotropic and lusitropic response in ECTs, thus supporting an important role for CNP in the regulation of human cardiac function. The high degree of translatability between ECTs, ex vivo and in vivo models further supports a regulatory role for CNP and expands the current understanding of the translational value of human ECTs. New Findings: What is the central question of this study?What are the acute responses to C‐type natriuretic peptide (CNP) in human‐engineered cardiac tissues (ECTs) on cardiac function and how well do they translate to matched concentrations in animal ex vivo and in vivo models?What is the main finding and its importance?Acute stimulation of ECTs with CNP induced positive lusitropic and inotropic effects on cardiac contractility, which closely reflected the changes observed in rat ex vivo and in vivo cardiac models. These findings support an important role for CNP in the regulation of human cardiac function and highlight the translational value of ECTs. [ABSTRACT FROM AUTHOR]

This case characterizes the clinical motor, perceived fatigue, gait and balance, cardiovascular, neuromuscular, and cardiopulmonary responses after cycling 7850 km over 85 days in a physically active 57‐year‐old male with idiopathic Parkinson's disease (PD). The participant cycled 73/85 days (86%); averaging 107.5 ± 48.9 km/day over 255.4 ± 108.8 min. Average cycling heart rate was 117 ± 11 bpm. The Unified Parkinson Disease Rating Scale (UPDRS) Part III motor score decreased from 46 to 26 (−44%), while the mean Parkinson Fatigue Scale (PFS‐16) score decreased from 3.4 to 2.3 (−32%). Peak power output on a maximal aerobic exercise test increased from 326 to 357 W (+10%), while peak isotonic power of single‐leg knee extension increased from 312 to 350 W (+12%). Maximal oxygen uptake following the trip was 53.1 mL/min/kg or 151% of predicted. Resting heart rate increased from 48 to 71 bpm (+48%). The systolic and diastolic blood pressure responses to a 2‐min submaximal static handgrip exercise were near absent at baseline (∆2/∆2 mm Hg) but appeared normal post‐trip (∆17/∆9 mm Hg). Gait and static balance measures were unchanged. This case report demonstrates the capacity for physiological and clinical adaptations to a high‐volume, high‐intensity cycling regiment in a physically active middle‐aged male with PD. [ABSTRACT FROM AUTHOR]

Interval training has been found to lower glucose concentrations and increase insulin sensitivity in males but not in females, which may be due to inherent sex-based differences in metabolism. Twenty-four (12/sex) participants completed a bout of highintensity interval exercise (HIIE, 10 x 1 min at 90% HRmax) to evaluate whether sex influenced the physiological effects of HIIE on postexercise glycemic control during an oral glucose tolerance test (OGTT). Given that body anthropometrics influence postprandial glucose, data were also expressed as a function of the normalized glucose dose. In addition, we examined whether sex differences in postexercise glycemic control were related to sex differences in muscle metabolism and/or insulin signaling proteins. HIIE increased insulin sensitivity in both sexes as characterized by the Matsuda (P = 0.03, ɳp²= 0.20) and HOMA-IR (P = 0.047, ɳp² = 0.17) indices. HIIE also lowered insulin concentration during the OGTT (P = 0.04, ɳp² = 0.18) as compared with control. When normalized for glucose dose relative to lean mass, glucose area under the curve (AUC) was lower in females than inmales (P < 0.001, ɳp² = 0.47). TBC1D1 Ser237 phosphorylation increased in males, but not in females, postexercise (P = 0.03, ɳp² = 0.19). There was no difference in total insulin signaling protein content, muscle glycogen utilization, or AMPK activation during exercise between the sexes. These findings indicate that when the glucose dose is normalized for differences in body composition glycemic handling is better in females and that an acute bout of HIIE improves insulin sensitivity equally in healthy males and females. [ABSTRACT FROM AUTHOR]

Micellar photocatalysis has been used to overcome oxygen quenching and enable a [2+2] photocycloaddition through triplet‐energy transfer in water under aerobic conditions. The cheap and commercially available self‐assembling sodium dodecyl sulfate (SDS) micelles were found to increase the oxygen tolerance of a typically oxygen‐sensitive reaction. Furthermore, the use of the micellar solution was found to activate α,β‐unsaturated carbonyl compounds to energy transfer and allow [2+2] photocycloadditions to take place. Our preliminary studies of micellar effects on energy‐transfer‐based reactions demonstrate the reaction between α,β‐unsaturated carbonyl compounds and activated alkenes in a mixture of SDS, water and [Ru(bpy)3](PF6)2. [ABSTRACT FROM AUTHOR]

Simple Summary: The cytoplasm of a living cell is a crowded place, containing hundreds of types of protein and other macromolecules. Cells reliably and continually perform thousands of biochemical reactions to maintain their health. Biomolecular condensates are fluid protein compartments that provide distinct local environments, within which they carry out cellular functions. How they prevent their contents mixing with the external environment without being encapsulated inside a lipid membrane is not fully understood. Many researchers approach this question by studying simpler systems in a test tube that contain only a few protein types although it is hard to relate their results to the complex cellular milieu. Computer simulations are used to explore the predictions of simple models of cellular behavior, but are also limited by the ability of human experimenters to recreate important aspects of the cytoplasm, in particular, its crowded nature. We have used a novel computer framework to perform dozens of simultaneous simulations that map out the influence of macromolecular crowding on the formation and structure of a biomolecular condensate. We find that the spatial structure of the model condensate is surprisingly insensitive to the composition and concentration of external macromolecules, even when its formation is assisted by steric repulsion from its environment. The crowded interior of a living cell makes performing experiments on simpler in vitro systems attractive. Although these reveal interesting phenomena, their biological relevance can be questionable. A topical example is the phase separation of intrinsically disordered proteins into biomolecular condensates, which is proposed to underlie the membrane-less compartmentalization of many cellular functions. How a cell reliably controls biochemical reactions in compartments open to the compositionally-varying cytoplasm is an important question for understanding cellular homeostasis. Computer simulations are often used to study the phase behavior of model biomolecular condensates, but the number of relevant parameters increases as the number of protein components increases. It is unfeasible to exhaustively simulate such models for all parameter combinations, although interesting phenomena are almost certainly hidden in their high-dimensional parameter space. Here, we have studied the phase behavior of a model biomolecular condensate in the presence of a polymeric crowding agent. We used a novel compute framework to execute dozens of simultaneous simulations spanning the protein/crowder concentration space. We then combined the results into a graphical representation for human interpretation, which provided an efficient way to search the model's high-dimensional parameter space. We found that steric repulsion from the crowder drives a near-critical system across the phase boundary, but the molecular arrangement within the resulting biomolecular condensate is rather insensitive to the crowder concentration and molecular weight. We propose that a cell may use the local cytoplasmic concentration to assist the formation of biomolecular condensates, while relying on the dense phase to reliably provide a stable, structured, fluid milieu for cellular biochemistry despite being open to its changing environment. [ABSTRACT FROM AUTHOR]

The essay also addresses the implications of Fenstad's understanding of the development of human knowledge for the training of future scientists. By contrast, in Part 2, Fenstad provides more detailed and technical discussions of the mathematical modeling of human language and cognition, and defends a cultural account of mathematics. Like the fourth essay, the primary purpose of this essay is to demonstrate the importance of mathematical modeling to the human sciences, ensuring that no one can take Fenstad's reflections on human knowledge to apply only to the natural and social sciences. While I could devote significantly more space to exploring Fenstad's overall project, instead, I will proceed by outlining the content of each essay in the collection[1] and providing a sense of how it relates to Fenstad's overall project. [Extracted from the article]

Theology as a story of doubt and imagination is to be understood against the background of interdisciplinary social science and in contrast to the traditional paradigm of theology as a system of propositional certainty. The concepts of doubt and imagination are part and parcel of narrative research and can also be linked to postfoundational philosophy. The relevancy of this theological paradigm will be discussed on the basis of the following: (1) It is in touch with its own doubt, (2) It is in touch with its own story (tradition), (3) It can therefore interact with other stories, stories of hope and despair, stories of suffering, stories of power and of marginalisation, (4) It can also imagine alternative stories. Intradisciplinary and/or interdisciplinary implications: The interaction with 'other stories', which is one of the important outcomes of this postfoundational approach, makes it possible for theology to be a humble but important participant at the interdisciplinary conversational table. [ABSTRACT FROM AUTHOR]

Describes a study called the "National Monument Audit" produced by Monument Lab in partnership with The Andrew W. Mellon Foundation for the purpose of assessing monuments across the United States.

This paper reports on a study which examined the notions of authenticity and citizenship for people living with cognitive impairment or dementia in a care home in the North-East of England. We demonstrated that both notions were present and were encouraged by engagement with an artist, where this involved audio and visual recordings and the creation of a film. The artist's interactions were observed by a non-participant observer using ethnographic techniques, including interviews with the residents, their families and the staff of the care home. The data were analysed using grounded theory and the constant comparative method of qualitative analysis. Our findings suggest that participatory art might help to maintain and encourage authenticity and citizenship in people living with dementia in a care home. Certainly, authenticity and citizenship are notions worth pursuing in the context of dementia generally, but especially in care homes. [ABSTRACT FROM AUTHOR]

Management of cucurbit downy mildew (CDM) caused by Pseudoperonospora cubensis, relies on an intensive fungicide program. In Michigan, CDM occurs annually due to an influx of airborne sporangia and timely alerts of airborne inoculum can assist growers in assessing the need to initiate fungicide sprays. This research aimed to improve the specific detection of airborne P. cubensis sporangia by adapting quantitative real-time polymerase chain reaction (qPCR) assays to distinguish among P. cubensis clades I and II and P. humuli in spore trap samples from commercial production sites and research plots. We also evaluated the suitability of impaction spore traps compared with Burkard traps for detection of airborne sporangia. A multiplex qPCR assay improved the specificity of P. cubensis clade II detection accelerating the assessment of field spore trap samples. After 2 years of monitoring, P. cubensis clade II DNA was detected in spore trap samples before CDM symptoms were first observed in cucumber fields (July and August), while P. cubensis clade I DNA was not detected in air samples before or after the disease onset. In some commercial cucumber fields, P. humuli DNA was detected throughout the growing season. The Burkard spore trap appeared to be better suited for recovery of sporangia at low concentrations than the impaction spore trap. This improved methodology for the monitoring of airborne Pseudoperonospora spp. sporangia could be used as part of a CDM risk advisory system to time fungicide applications that protect cucurbit crops in Michigan. [ABSTRACT FROM AUTHOR]

Background: Artificial intelligence (AI) and machine learning (ML) have resulted in significant enthusiasm for their promise in healthcare. Despite this, prospective randomized controlled trials and successful clinical implementation remain limited. One clinical application of ML is mitigation of the increased risk for acute care during outpatient cancer therapy. We previously reported the results of the System for High Intensity EvaLuation During Radiation Therapy (SHIELD-RT) study (NCT04277650), which was a prospective, randomized quality improvement study demonstrating that ML based on electronic health record (EHR) data can direct supplemental clinical evaluations and reduce the rate of acute care during cancer radiotherapy with and without chemotherapy. The objective of this study is to report the workflow and operational challenges encountered during ML implementation on the SHIELD-RT study. Results: Data extraction and manual review steps in the workflow represented significant time commitments for implementation of clinical ML on a prospective, randomized study. Barriers include limited data availability through the standard clinical workflow and commercial products, the need to aggregate data from multiple sources, and logistical challenges from altering the standard clinical workflow to deliver adaptive care. Conclusions: The SHIELD-RT study was an early randomized controlled study which enabled assessment of barriers to clinical ML implementation, specifically those which leverage the EHR. These challenges build on a growing body of literature and may provide lessons for future healthcare ML adoption. Trial registration: NCT04277650. Registered 20 February 2020. Retrospectively registered quality improvement study. [ABSTRACT FROM AUTHOR]

During the second half of the first millennium BCE, innovative portrayals of Nebuchadnezzar began to emerge within Jewish circles that reshaped and reimagined his role in their history. Such reconstruals were part and parcel of the lively negotiations among Babylonian and Hellenistic scribes over the representation of bygone Mesopotamian monarchs. In this essay, I examine the reimagination of Nebuchadnezzar in the court tales of Dan 2–6 as a unique example of how scribes sought to reshape the haunting memory of Nebuchadnezzar. By comparing Nebuchadnezzar's narrative portrait with various texts from Jewish prophetic traditions, I argue that the redactor of the court tales constructed a counter-memory of Nebuchadnezzar in which the traumatic experience of Judah's humiliation, deportation, and restoration was creatively mapped onto Nebuchadnezzar. In order to construct this counter-memory, the redactor drew upon and repurposed specific language, imagery, and motifs borrowed from these textual traditions. [ABSTRACT FROM AUTHOR]

Type 2 diabetes (T2D) risk is lower in females than males. It has been reported that females have greater pancreatic 훽‐cell function than males, which may at least in part contribute to the T2D risk in females. 훽‐cell function is influenced by exercise training; however, previous trials comparing 훽‐cell function between the sexes have not included participants matched for training status. Furthermore, the acute effects of different modes of exercise on 훽‐cell function, and whether sex inherently influences these effects, are largely unexamined. Males and females (12/sex) completed a 120‐min oral glucose tolerance test (OGTT) at rest (CON) and following acute bouts of high‐intensity interval exercise (HIIE), moderate intensity continuous (MIC) exercise, and low‐load high‐repetition (LLHR) resistance exercise to assess whether sex inherently influences baseline and/or post‐exercise pancreatic function in the absence of pathology. We found no sex differences in basal pancreatic 훽‐cell function. Females had greater basal insulin clearance following MIC exercise compared to males (p = 0.01) and males tended to have a higher potentiation ratio following HIIE (p = 0.07). Females also had lower glucose sensitivity following MIC exercise compared to HIIE (p = 0.007) and LLHR (p = 0.003). Insulin clearance during the OGTT was greater following HIIE as compared with CON and MIC exercise (p = 0.02). 2‐H oral glucose insulin sensitivity was greater following LLHR compared to CON (p = 0.01). Acute bouts of different modes of exercise do not differentially influence 훽‐cell function but do influence insulin clearance and insulin sensitivity. Therefore, sex and exercise mode interact to differentially influence insulin clearance and glucose sensitivity. [ABSTRACT FROM AUTHOR]

Anthropogenic disturbances are widely recognized for their far-reaching consequences on the survival and reproduction of wildlife, but we understand comparatively little about their effects on the social lives of group-living animals. Here we examined these short-term changes in affiliative behavior as part of a long-term study on a human-tolerant and socially flexible population of California ground squirrels (Otospermophilus beecheyi). We used social network analysis to examine short-term changes in affiliative behavior and individual consistency in response to disturbances by humans, domestic dogs, or a natural predator (the coyote). Overall, juveniles were more involved than adults in affiliative interactions, but the short-term directional effects of these acute disturbances on social cohesion varied by disturbance type. Human and dog presence reduced aboveground connectivity, particularly for juveniles, whereas disturbances by coyotes generally promoted it. Beyond these effects, we also detected non-random responses to disturbances, though individuals were not very consistent in their directional response to different disturbance types. Our results demonstrate the flexible changes in social behavior triggered by short-term disturbances imposed by humans and other threats. More generally, our findings elucidate the underappreciated sensitivity of animal social interactions to short-term ecological disturbances, raising key questions about their consequences on the social lives of animals. [ABSTRACT FROM AUTHOR]

Patients with heart failure with preserved ejection fraction (HFpEF) and atherosclerosis-driven coronary artery disease (CAD) will have ongoing fibrotic remodeling both in the myocardium and in atherosclerotic plaques. However, the functional consequences of fibrosis differ for each location. Thus, cardiac fibrosis leads to myocardial stiffening, thereby compromising cardiac function, while fibrotic remodeling stabilizes the atherosclerotic plaque, thereby reducing the risk of plaque rupture. Although there are currently no drugs targeting cardiac fibrosis, it is a field under intense investigation, and future drugs must take these considerations into account. To explore similarities and differences of fibrotic remodeling at these two locations of the heart, we review the signaling pathways that are activated in the main extracellular matrix (ECM)-producing cells, namely human cardiac fibroblasts (CFs) and vascular smooth muscle cells (VSMCs). Although these signaling pathways are highly overlapping and context-dependent, effects on ECM remodeling mainly act through two core signaling cascades: TGF-β and Angiotensin II. We complete this by summarizing the knowledge gained from clinical trials targeting these two central fibrotic pathways. [ABSTRACT FROM AUTHOR]

Aeolosaurus is a late Cretaceous Titanosaur genus with two species discovered in Argentina and one in Brazil. Although the allocation of the Argentinean Aeolosaurus seems unequivocal, that is not the case for the Brazilian species Aeolosaurus maximus since several authors questioned its positioning into this genus, based on both anatomical and phylogenetic data. The revision of the diagnosis of Ae. maximus, with the proposition of a new autapomorphy, corroborates the anatomical uniqueness and our phylogenetic analysis stresses that the relation of Ae. maximus to the Argentinean Aeolosaurus is uncertain. Based upon that, we propose a new genus, Arrudatitan, to accommodate the Brazilian taxon. [ABSTRACT FROM AUTHOR]

The Gamma Factory (GF) is an ambitious proposal, currently explored within the CERN Physics Beyond Colliders program, for a source of photons with energies up to ≈400 MeV and photon fluxes (up to ≈1017 photons s−1) exceeding those of the currently available gamma sources by orders of magnitude. The high‐energy (secondary) photons are produced via resonant scattering of the primary laser photons by highly relativistic partially‐stripped ions circulating in the accelerator. The secondary photons are emitted in a narrow cone and the energy of the beam can be monochromatized, down to 10−3–10−6 level, via collimation, at the expense of the photon flux. This paper surveys the new opportunities that may be afforded by the GF in nuclear physics and related fields. [ABSTRACT FROM AUTHOR]

Background: Continuous relative phase and vector coding are two common approaches for quantifying lumbopelvic coordination and variability. Evaluating the application of such methodologies to the lower limb loss population is important for better understanding reported asymmetrical movement dynamics of the lumbopelvic region.Research Question: How do coordination variabilities derived from trunk-pelvic coupling angles and continuous relative phases compare among individuals with and without unilateral lower limb loss walking at self-selected speeds?Methods: Full-body kinematics were obtained from thirty-eight males with unilateral lower limb loss (23 transtibial and 15 transfemoral) and fifteen males without limb loss while walking along a 15 m walkway. Coordination variabilities were derived from trunk-pelvic coupling angles and continuous relative phases and compared using a multivariate approach, as well as in unilateral outcome measures between control participants and participants with lower limb loss.Results: Overall, tri-planar measures of continuous relative phase variability were 19-43% larger compared to coupling angle variabilities for individuals without limb loss and individuals with transtibial limb loss. Individuals with transfemoral limb loss had 27% and 31% larger sagittal and transverse variabilities from continuous relative phases compared to coupling angles, respectively. During both prosthetic and intact limb stance, individuals with transtibial limb loss had 19-35% greater tri-planar measures of continuous relative phase variability compared to coupling angle variabilities. During intact stance phase, tri-planar measures of continuous relative phase variability were 27%- 42% larger compared to coupling angle variabilities for individuals without limb loss.Significance: While both methods provide valid estimates of lumbopelvic movement variability during gait, continuous relative phase variability may provide a more sensitive estimate in the lower limb loss population capturing velocity-specific motions of the trunk and pelvis. [ABSTRACT FROM AUTHOR]

Background: Trunk postural control (TPC) is critical in maintaining balance following perturbations (i.e., avoiding falls), and impaired among persons with lower extremity trauma, contributing to elevated fall risk. Previously, a fall-prevention program improved TPC in individuals with unilateral transtibial amputation following trip-inducing perturbations. However, it is presently unclear if these improvements are task specific.Research Question: Do improvements to TPC gained from a fall-prevention program translate to another task which assesses TPC in isolation (i.e., unstable sitting)? Secondarily, can isolated TPC be used to identify who would benefit most from the fall-prevention program?Methods: Twenty-five individuals (21 male/4 female) with lower extremity trauma, who participated in a larger fall-prevention program, were included in this analysis. Trunk flexion and flexion velocity quantified TPC following perturbation; accelerometer-based sway parameters quantified TPC during unstable sitting. A generalized linear mixed-effects model assessed training-induced differences in TPC after perturbation; a generalized linear model assessed differences in sway parameters following training. Spearman's rho related training-induced changes to TPC following perturbation (i.e., the difference in TPC measures at pre- and post-training assessments) with pre- vs. post-training changes to sway parameters during unstable sitting (i.e., the difference in sway parameters at pre- and post-training assessments) as well as pre-training sway parameters with the pre- vs. post-training differences in TPC following perturbation.Results: Following training, trunk flexion angles decreased, indicating improved TPC; however, sway parameters did not differ pre- and post-training. In addition, pre- vs. post-training differences in TPC following perturbation were neither strongly nor significantly correlated with sway parameters. Moreover, pre-training sway parameters did not correlate with pre- vs. post-training differences in trunk flexion/flexion velocity.Significance: Overall, these results indicate that improvements to TPC gained from fall-prevention training are task-specific and do not translate to other activities. Moreover, isolated TPC measures are not able to identify individuals that benefit most from the fall-prevention program. [ABSTRACT FROM AUTHOR]

Whether females breed in their natal group is an important factor in the evolution of extended families in animal sociality. Breeding in natal groups comes with costs and benefits, depending on group size and presence of older relatives, including mothers. Studying the consequences of breeding in the natal versus another group provides insight into the decisions and trade-offs governing the formation and structure of family groups. We investigated the family dynamics of a population of free-ranging commensal house mice. Using dynamic community detection on long-term datasets, we determined which females first bred in their natal group. We then looked at how this influenced breeding success. We found most females (77%) exhibited strong philopatry, breeding in their natal groups. Breeding elsewhere was only somewhat predictable at very large and very small group sizes. Despite their philopatric preference, breeding elsewhere made no difference in how quickly and successfully a female bred. However, presence of their mother did lead females to breed sooner when born during high breeding activity, when competition over reproduction is high. Based on these results, potential loss of reproductive success from leaving the natal group does not seem to be the main driver of philopatry in female house mice. The effect of the presence of mothers suggests that benefiting from established social connections promotes breeding in the natal group. Mothers providing benefits also implies a lack of conflict between generations, which will be important for the development of stable social groups. [ABSTRACT FROM AUTHOR]

Strike-slip faults can be nonplanar in both their strike and dip dimensions. While a large body of work has investigated the effects of changes in strike on earthquake rupture and arrest, no previous studies have investigated the role of along-strike variations in dip on strike-slip ruptures. Here, I use the three-dimensional finite-element method to conduct dynamic simulations of ruptures on strike-slip faults with linear surface traces and changes in dip along strike. I experiment with the amount of dip change as well as the abruptness of that change under a variety of initial stress conditions. In all of my initial stress cases, I find that a change in dip along strike can cause rupture to stop, and that larger dip changes over shorter distances are more likely to do so. This is largely due to the change in strike at depth that inherently comes from changing the dip; the majority of these behaviors are a result of the rupture front being forced to change direction mid-rupture. While some dip-slip movement does occur on the nonvertical parts of the model fault, it does not have a significant effect on rupture extent. However, linear-surface-trace, nonvertical-dip faults do produce different surface slip, stress, and ground motion patterns compared to corresponding nonlinear-strike, vertical-dip faults. Together, my results show that changes in dip along strike-slip faults do considerably impact the rupture process, suggesting that this type of geometrical complexity should be considered in rupture forecasts and hazard assessments. [ABSTRACT FROM AUTHOR]

• Critical discussion of the state of current annotations. • Methodological approaches to analyse non-coding natural antisense transcripts. • Summarization of the unique challenges posed in their analysis. • Discussion of their potential for biomarker and therapeutic applications. Non-coding natural antisense transcripts (ncNATs) are regulatory RNA molecules that are overlapping with as well as complementary to other transcripts. These transcripts are implicated in a broad variety of biological and pathological processes, including tumorigenesis and oncogenic progression. With this complex field still in its infancy, annotations, expression profiling and functional characterisations of ncNATs are far less comprehensive than those for protein-coding genes, pointing out substantial gaps in the analysis and characterisation of these regulatory transcripts. In this review, we discuss ncNATs from an analysis perspective, in particular regarding the use of high-throughput sequencing strategies, such as RNA-sequencing, and summarize the unique challenges of investigating the antisense transcriptome. Finally, we elaborate on their potential as biomarkers and future targets for treatment, focusing on cancer. [ABSTRACT FROM AUTHOR]

Material growth and etching processes that cause the formation or removal of one atomic or molecular layer at a time are becoming commonplace. Starting from the research labs, such atomic layer process technologies have now migrated to the fab floor. This compact review examines the reasons behind the popularity of these techniques through both a tutorial approach and by citing relevant works that show the practical uses of both additive and subtractive atomic layer processes. Succinct introductions to both atomic layer deposition (ALD) and atomic layer etching (ALE) have been provided. Beyond that, this review examines, in particular, seed layer growth and plasma-enhanced ALD (PEALD), as well as various applications of ALE for the removal of semiconductors, metals and dielectrics. [ABSTRACT FROM AUTHOR]

Recently described rhizolutin and collinolactone isolated from Streptomyces Gö 40/10 share the same novel carbon scaffold. Analyses by NMR and X‐Ray crystallography verify the structure of collinolactone and propose a revision of rhizolutin's stereochemistry. Isotope‐labeled precursor feeding shows that collinolactone is biosynthesized via type I polyketide synthase with Baeyer–Villiger oxidation. CRISPR‐based genetic strategies led to the identification of the biosynthetic gene cluster and a high‐production strain. Chemical semisyntheses yielded collinolactone analogues with inhibitory effects on L929 cell line. Fluorescence microscopy revealed that only particular analogues induce monopolar spindles impairing cell division in mitosis. Inspired by the Alzheimer‐protective activity of rhizolutin, we investigated the neuroprotective effects of collinolactone and its analogues on glutamate‐sensitive cells (HT22) and indeed, natural collinolactone displays distinct neuroprotection from intracellular oxidative stress. [ABSTRACT FROM AUTHOR]

Das kürzlich beschriebene Rhizolutin und Collinolacton, das aus Streptomyces Gö 40/10 isoliert wurde, besitzen dasselbe neuartige Kohlenstoffgerüst. Analysen mittels NMR und Kristallstrukturanalyse belegen die Struktur von Collinolacton und machen eine Korrektur der Stereochemie von Rhizolutin erforderlich. Fütterungsexperimente mit isotopenmarkierten Vorstufen zeigen, dass Collinolacton über eine Typ‐I‐Polyketidsynthase mit anschließender Baeyer‐Villiger‐Oxidation synthetisiert wird. CRISPR‐basierte genetische Arbeiten führten zur Entdeckung des Genclusters und einem optimierten Produktionsstamm. Chemische Semisynthesen lieferten Derivate von Collinolacton, welche die Viabilität von L929‐Zellen reduzieren. Fluoreszenzmikroskopie zeigte, dass diese Derivate während der Zellteilung monopolare Spindeln induzieren. Dem beschriebenen Schutz von Rhizolutin gegen Alzheimer folgend studierten wir die neuroprotektiven Eigenschaften von Collinolacton und dessen Derivaten an Glutamat‐sensitiven Zellen (HT22). Tatsächlich zeigt Collinolacton eine Schutzwirkung gegen intrazellulären oxidativen Stress. [ABSTRACT FROM AUTHOR]

Objective: Countries have adopted different approaches, at different times, to reduce the transmission of coronavirus disease 2019 (COVID-19). Cross-country comparison could indicate the relative efficacy of these approaches. We assess various nonpharmaceutical interventions (NPIs), comparing the effects of voluntary behavior change and of changes enforced via official regulations, by examining their impacts on subsequent death rates. Data Sources: Secondary data on COVID-19 deaths from 13 European countries, over March-May 2020. Study Design: We examine two types of NPI: the introduction of government-enforced closure policies and self-imposed alteration of individual behaviors in the period prior to regulations. Our proxy for the latter is Google mobility data, which captures voluntary behavior change when disease salience is sufficiently high. The primary outcome variable is the rate of change in COVID-19 fatalities per day, 16-20 days after interventions take place. Linear multivariate regression analysis is used to evaluate impacts. Data collection/extraction methods: publicly available. Principal Findings: Voluntarily reduced mobility, occurring prior to government policies, decreases the percent change in deaths per day by 9.2 percentage points (pp) (95% confidence interval [CI] 4.5-14.0 pp). Government closure policies decrease the percent change in deaths per day by 14.0 pp (95% CI 10.8-17.2 pp). Disaggregating government policies, the most beneficial for reducing fatality, are intercity travel restrictions, canceling public events, requiring face masks in some situations, and closing nonessential workplaces. Other sub-components, such as closing schools and imposing stay-at-home rules, show smaller and statistically insignificant impacts. Conclusions: NPIs have substantially reduced fatalities arising from COVID-19. Importantly, the effect of voluntary behavior change is of the same order of magnitude as government-mandated regulations. These findings, including the substantial variation across dimensions of closure, have implications for the optimal targeted mix of government policies as the pandemic waxes and wanes, especially given the economic and human welfare consequences of strict regulations. [ABSTRACT FROM AUTHOR]

Metabolomics is unique among omics technologies in being applicable to metabolism and toxicity studies broadly across organisms (e.g., humans, other mammals, model organisms, and even bacteria) and across biological materials (e.g., blood, urine, saliva, biopsy, and stool), including cultured cells and subcellular fractions. Metabolomics can be used to characterize biologic response patterns in humans as well as to support mechanistic studies in model systems and ex vivo studies. A broad range of resources are available, including publicly accessible data repositories (e.g., Metabolomics Workbench), tools for biostatistics and bioinformatics (e.g., MetaboAnalyst), metabolite identification (e.g., Metlin), and pathway analysis (e.g., Kyoto Encyclopedia of Genes and Genomes). Thus, metabolomics is more than a promise of the future; metabolomics is already available as a translational approach to facilitate precision medicine. This ACT Symposium review will contain an introduction to metabolomics in toxicity studies followed by sections on translational metabolic networks, translational metabolite biomarkers of acetaminophen-induced acute liver injury, translational framework using high-resolution metabolomics for integrated pharmacokinetics and pharmacodynamics, and precision medicine applications: extracting actionable targets from untargeted metabolomics data following one year in space. [ABSTRACT FROM AUTHOR]

With recent advances, nuclear genome data for phylogenomic analyses can now be sequenced from minuscule quantities of DNA 1 and from specimens that are more than a million years old. 2 DNA analysis from hair is a well-established approach 3 widely used in forensic science 4 and wildlife conservation. 5 Hair samples can be effectively decontaminated 6 and can be used to identify the mammalian species from which the hair was shed. 7,8 We aimed to use advances optimized for degraded DNA to systematically identify dietary prey species from hair compacted in the teeth of two Tsavo lions that lived during the 1890s in Kenya (see description of samples in the STAR Methods and Patterson 9 and Kerbis Peterhans and Gnoske 10 for background on the Tsavo "man-eaters"). Analysis of hair DNA identified giraffe, human, oryx, waterbuck, wildebeest, and zebra as prey and also identified hair that originated from lion. DNA preservation allowed for analyses of complete mitogenome profiles of zebra, giraffe, and lion. Giraffe mitogenomes are phylogeographically partitioned, and we found that the lions ate at least two individuals that belong to a subspecies of Masai giraffe (Giraffa tippelskirchi tippelskirchi) typically found in southeast Kenya. The lion mitogenome from a hair sample was identical to the Tsavo lion endogenous mitogenome and most closely matched other East African lions from Kenya and Tanzania. Our approach enables a better understanding of the hunting behaviors, diets, and ecology of historical individuals, populations, and species and holds promise for extinct populations and species. [Display omitted] • Prey hair in the Tsavo lions' tooth cavities contains complete mitogenomes • Cavities contained hair from giraffe, human, oryx, waterbuck, wildebeest, and zebra • A comparison of hair DNA to endogenous lion DNA indicates self- or allogrooming • At least two giraffes from a subspecies typical of Tsavo were eaten de Flamingh et al. use ancient DNA and bioinformatic methodologies to systematically identify dietary prey species from hair compacted in the teeth of two Tsavo "man-eating" lions that lived during the 1890s in Kenya. Analysis of hair DNA identified giraffe, human, oryx, waterbuck, wildebeest, and zebra as prey and also identified hair from lion. [ABSTRACT FROM AUTHOR]

The differential arbitrarily applicable relational responding effects (DAARRE) model explains two effects commonly observed with the implicit relational assessment procedure (IRAP): the single trial-type dominance effect (STTDE) and the dissonant-target trial-type effect (DTTTE). We sought to explore variables that modulate these effects. Forty-two participants who completed an IRAP met the practice criteria (median latency ≤ 2,000 ms and accuracy ≥ 80% correct) and thus proceeded to six test blocks of trials. The IRAP had four trial-types: trial-type 1: happy-face—happy-word; trial-type 2: happy-face—fear-word; trial-type 3: fear-face—happy-word; trial-type 4: fear-face—fear-word. Participants were randomly assigned to start with a consistent (respond True, False, False, True, respectively, to the four trial-types) or inconsistent (opposite responding) block. Difference (DIRAP) scores were calculated (inconsistent minus consistent latencies). A significantly larger DIRAP score was observed in trial-type 2 relative to trial-type 3 (a DTTTE), but only for participants who started with the inconsistent block. A "happiness superiority" STTDE (i.e., larger DIRAP score on trial-type 1 relative to trial-type 4) was observed, but only for participants who failed to maintain the criteria at the trial-type level (in any of the trial-types). Overall, the findings highlight the importance of distinguishing between the functional versus relational properties of the stimuli presented within an IRAP. The modulation of the DTTTE is interpreted in terms of functional coherence between the target and response option in inconsistent blocks. A novel data-analytic algorithm is presented to identify performance criteria violations at the trial-type level. The findings suggest that a greater focus is required in relational frame theory on the impact of the functional properties of stimuli on relational framing. [ABSTRACT FROM AUTHOR]

Conventional physicians or coffee-enema practitioners? If my refusal to entertain the idea of coffee enemas for cancer shows a lack of epistemic humility, then the concept seems to imply an "anything-goes eclecticism", but Waterman says this is not what he intends. First, in Shakespeare's time, "philosophy" would have included science; second, Shakespeare apparently contemplated using "our" rather than "your." Waterman is not, however, simply pointing out that there is a clash of cultures; and, I suspect, he'd rather avoid thinking in terms of a "clash.". [Extracted from the article]

There are currently no Food and Drug Administration-approved treatments for heart failure with preserved ejection fraction (HFpEF). Here we compared the effects of exercise with and without α/β-adrenergic blockade with carvedilol in Col4a3-/- Alport mice, a model of the phenogroup 3 subclass of HFpEF with underlying renal dysfunction. Alport mice were assigned to the following groups: no treatment control (n = 29), carvedilol (n = 11), voluntary exercise (n = 9), and combination carvedilol and exercise (n = 8). Cardiac function was assessed by echocardiography after 4-wk treatments. Running activity of Alport mice was similar to wild types at 1 mo of age but markedly reduced at 2 mo (1.3 ± 0.40 vs. 4.5 ± 1.02 km/day, P < 0.05). There was a nonsignificant trend for increased running activity at 2 mo by carvedilol in the combination treatment group. Combination treatments conferred increased body weight of Col4a3-/- mice (22.0 ± 1.18 vs. 17.8 ± 0.29 g in untreated mice, P < 0.01), suggesting improved physiology, and heart rates declined by similar increments in all carvedilol-treatment groups. The combination treatment improved systolic parameters; stroke volume (30.5 ± 1.99 vs. 17.8 ± 0.77 μL, P < 0.0001) as well as ejection fraction and global longitudinal strain compared with controls. Myocardial performance index was normalized by all interventions (P < 0.0001). Elevated osteopontin plasma levels in control Alport mice were significantly lowered only by combination treatment, and renal function of the Alport group assessed by urine albumin creatinine ratio was significantly improved by all treatments. The results support synergistic roles for exercise and carvedilol to augment cardiac systolic function of Alport mice with moderately improved renal functions but no change in diastole. [ABSTRACT FROM AUTHOR]

This article investigates two questions: (1) What is the significance of a typical western philosophical concept like postfoundationalism for the African context? (2) Can Ubuntu be the key or the bridge between two seemingly distant philosophical worlds? I have been involved in two major research projects: firstly, the exploration of the postfoundationalist paradigm and the significance of it for practical theology; secondly, a study of Ubuntu and its value for human and social development in Africa. Intradisciplinary and/or interdisciplinary implications: This article is an ethnographic journey in which I revisit and reflect on those two projects and the link between them. The reflection focuses on four concepts: interdisciplinary practice, colonialism and whiteness, fiction and research, and holism. [ABSTRACT FROM AUTHOR]

Understanding patient accumulation of comorbidities can facilitate healthcare strategy and personalized preventative care. We applied a directed network graph to electronic health record (EHR) data and characterized comorbidities in a cohort of healthy veterans undergoing screening colonoscopy. The Veterans Affairs Cooperative Studies Program #380 was a prospective longitudinal study of screening and surveillance colonoscopy. We identified initial instances of three-digit ICD-9 diagnoses for participants with at least 5 years of linked EHR history (October 1999 to December 2015). For diagnoses affecting at least 10% of patients, we calculated pairwise chronological relative risk (RR). iGraph was used to produce directed graphs of comorbidities with RR > 1, as well as summary statistics, key diseases, and communities. A directed graph based on 2210 patients visualized longitudinal development of comorbidities. Top hub (preceding) diseases included ischemic heart disease, inflammatory and toxic neuropathy, and diabetes. Top authority (subsequent) diagnoses were acute kidney failure and hypertensive chronic kidney failure. Four communities of correlated comorbidities were identified. Close analysis of top hub and authority diagnoses demonstrated known relationships, correlated sequelae, and novel hypotheses. Directed network graphs portray chronologic comorbidity relationships. We identified relationships between comorbid diagnoses in this aging veteran cohort. This may direct healthcare prioritization and personalized care. [ABSTRACT FROM AUTHOR]

Associating with relatives in social groups can bring benefits such as reduced risk of aggression and increased likelihood of cooperation. Competition among relatives over limited resources, on the other hand, can induce individuals to alter their patterns of association. Population density might further affect the costs and benefits of associating with relatives by altering resource competition or by changing the structure of social groups; preventing easy association with relatives. Consequently, the overlap between genetic and social structure is expected to decrease with increasing population size, as well as during times of increased breeding activity. Here, we use multi-layer network techniques to quantify the similarity between long-term, high resolution genetic, and behavioral data from a large population of free-ranging house mice (Mus musculus domesticus), studied over 10 years. We infer how the benefit of associating with genetically similar individuals might fluctuate in relation to breeding behavior and environmental conditions. We found a clear seasonal effect, with decreased overlap between social and genetic structure during summer months, characterized by high temperatures and high breeding activity. Though the effect of overall population size was relatively weak, we found a clear decrease in the overlap between genetic similarity and social associations within larger groups. As well as longer-term within-group changes, these results reveal population-wide short-term shifts in how individuals associate with relatives. Our study suggests that resource competition modifies the trade-off between the costs and benefits of interacting with relatives. [ABSTRACT FROM AUTHOR]

Tuberculosis (TB) is believed to affect around 10 million people worldwide. Treatment for TB includes isoniazid and rifampicin, with fixed-dose combination (FDC) recommended for improved patient compliance. Similarly, orally disintegrating tablets (ODTs) are an increasingly popular dosage form that aid compliance since they do not require swallowing. In this study ODTs of isoniazid and rifampicin, either as discrete or FDC doses, were formulated and bioequivalence between single and combination doses compared using in vitro and in silico approaches. Dissolution profiles were compared using FDA advised difference (f 1) and similarity (f 2) testing in biorelevant media. Rifampicin release from FDCs decreased by approximately 15% in fed-state media (failed f 1 and f 2), which was attributed to enhanced rifampicin degradation in the presence of isoniazid at lower pH. Apparent permeability (P app) values derived from Caco-2 transport studies were included alongside dissolution results into a physiologically based pharmacokinetic (PBPK) model, to simulate in vivo bioavailability in healthy subjects. Models showed no difference in bioavailability between formulations or dosing (fasted or fed) state, despite the failures in dissolution-based bioequivalence testing, highlighting shortcomings in f 1 and f 2 assessment and the strength of PBPK models. [ABSTRACT FROM AUTHOR]

Social network analysis is a suite of approaches for exploring relational data. Two approaches commonly used to analyze animal social network data are permutation-based tests of significance and exponential random graph models. However, the performance of these approaches when analyzing different types of network data has not been simultaneously evaluated. Here we test both approaches to determine their performance when analyzing a range of biologically realistic simulated animal social networks. We examined the false positive and false negative error rate of an effect of a two-level explanatory variable (e.g. sex) on the number and combined strength of an individual's network connections. We measured error rates for two types of simulated data collection methods in a range of network structures, and with/without a confounding effect and missing observations. Both methods performed consistently well in networks of dyadic interactions, and worse on networks constructed using observations of individuals in groups. Exponential random graph models had a marginally lower rate of false positives than permutations in most cases. Phenotypic assortativity had a large influence on the false positive rate, and a smaller effect on the false negative rate for both methods in all network types. Aspects of within- and between-group network structure influenced error rates, but not to the same extent. In "grouping event-based" networks, increased sampling effort marginally decreased rates of false negatives, but increased rates of false positives for both analysis methods. These results provide guidelines for biologists analyzing and interpreting their own network data using these methods. [ABSTRACT FROM AUTHOR]