General cross-coupling reactions with adaptive dynamic homogeneous catalysis.

Cross-coupling reactions are among the most important transformations in modern organic synthesis1-3. Although the range of reported (het)aryl halides and nucleophile coupling partners is very large considering various protocols, the reaction conditions vary considerably between compound classes, necessitating renewed case-by-case optimization of the reaction conditions4. Here we introduce adaptive dynamic homogeneous catalysis (AD-HoC) with nickel under visible-light-driven redox reaction conditions for general C(sp2)-(hetero)atom coupling reactions. The self-adjustive nature of the catalytic system allowed the simple classification of dozens of various classes of nucleophiles in cross-coupling reactions. This is synthetically demonstrated in nine different bond-forming reactions (in this case, C(sp2)-S, Se, N, P, B, O, C(sp3, sp2, sp), Si, Cl) with hundreds of synthetic examples under predictable reaction conditions. The catalytic reaction centre(s) and conditions differ from one another by the added nucleophile, or if required, a commercially available inexpensive amine base.

The roles of calcium and ATP in the physiology and pathology of the exocrine pancreas.

This review deals with the roles of calcium ions and ATP in the control of the normal functions of the different cell types in the exocrine pancreas as well as the roles of these molecules in the pathophysiology of acute pancreatitis. Repetitive rises in the local cytosolic calcium ion concentration in the apical part of the acinar cells not only activate exocytosis but also, via an increase in the intramitochondrial calcium ion concentration, stimulate the ATP formation that is needed to fuel the energy-requiring secretion process. However, intracellular calcium overload, resulting in a global sustained elevation of the cytosolic calcium ion concentration, has the opposite effect of decreasing mitochondrial ATP production, and this initiates processes that lead to necrosis. In the last few years it has become possible to image calcium signaling events simultaneously in acinar, stellate, and immune cells in intact lobules of the exocrine pancreas. This has disclosed processes by which these cells interact with each other, particularly in relation to the initiation and development of acute pancreatitis. By unraveling the molecular mechanisms underlying this disease, several promising therapeutic intervention sites have been identified. This provides hope that we may soon be able to effectively treat this often fatal disease.

Expression and high levels of insertional polymorphism of an endogenous gammaretrovirus lineage in dogs.

Despite the absence of a confirmed exogenously replicating retrovirus in Canis lupus familiaris (C. familiaris), past retroviral infections are evident in the genomes of living animals via the presence of endogenous retroviruses (ERVs). Although gammaretrovirus-like transcripts and enzyme activities were previously reported to be present in canine leukemias and lymphomas, those findings were not further explored. Initial analysis of the C. familiaris reference genome revealed a minor subset of one ERV lineage, classified as CfERV-Fc1(a), or Fc1(a) here, with features characteristic of recent integration, including the presence of ORFs and identical or nearly identical LTRs. Our previous analysis of whole genome sequence data belonging to extant Canidae revealed a burst of past infections in Canis ancestors resulting in numerous young, polymorphic, and highly intact loci now segregating in dogs. Here, we demonstrate the expression of full-length Fc1(a) proviruses in tissues collected from healthy animals and from animals with cancer. We observed significantly higher expression in samples of dogs with various cancer diagnoses when compared to samples from healthy dogs. Genotyping of insertionally polymorphic Fc1(a) loci identified candidate expressed proviruses and delineated distributions over sample groups. Collectively, the data show that Fc1(a) proviruses retain biological activity in the domestic dog and provides a means to examine potential genetic links with disease states in this species.

When van der Waals Met Kagome: A 2D Antimonide with a Vanadium-Kagome Network.

2D materials showcase unconventional properties emerging from quantum confinement effects. In this work, a "soft chemical" route allows for the deintercalation of K+ from the layered antimonide KV6Sb6, resulting in the discovery of a new metastable 2D-Kagome antimonide K0.1(1)V6Sb6 with a van der Waals gap of 3.2 Å. The structure of K0.1(1)V6Sb6 was determined via the synergistic techniques, including X-ray pair distribution function analysis, advanced transmission electron microscopy, and density functional theory calculations. The K0.1(1)V6Sb6 compound crystallizes in the monoclinic space group C2/m (a = 9.57(2) Å, b = 5.502(8) Å, c = 10.23(2) Å, ß = 97.6(2)°, Z = 2). The [V6Sb6] layers in K0.1(1)V6Sb6 are retained upon deintercalation and closely resemble the layers in the parent compound, yet deintercalation results in a relative shift of the adjacent [V6Sb6] layers. The magnetic properties of the K0.1(1)V6Sb6 phase in the 2-300 K range are comparable to those of KV6Sb6 and another Kagome antimonide KV3Sb5, consistent with nearly temperature-independent paramagnetism. Electronic band structure calculation suggests a nontrivial band topology with flat bands and opening of band crossing afforded by deintercalation. Transport property measurements reveal a metallic nature for K0.1(1)V6Sb6 and a low thermal conductivity of 0.6 W K-1 m-1 at 300 K. Additionally, ion exchange in KV6Sb6 via a solvothermal route leads to a successful partial exchange of K+ with A+ (A = Na, Rb, and Cs). This study highlights the tunability of the layered structure of the KV6Sb6 compound, providing a rich playground for the realization of new 2D materials.

Toward New Horizons in Verdazyl-Nitroxide High-Spin Systems: Thermally Robust Tetraradical with Quintet Ground State.

High-spin organic tetraradicals with significant intramolecular exchange interactions have high potential for advanced technological applications and fundamental research, but examples reported to date exhibit limited stability and processability. In this work, we designed the first tetraradical based on an oxoverdazyl core and nitronyl nitroxide radicals and successfully synthesized it using a palladium-catalyzed cross-coupling reaction of an oxoverdazyl radical bearing three iodo-phenylene moieties with a gold(I) nitronyl nitroxide-2-ide complex in the presence of a recently developed efficient catalytic system. The molecular and crystal structures of the tetraradical were confirmed by single crystal X-ray diffraction analysis. The tetraradical possesses good thermal stability with decomposition onset at ∼125 °C in an inert atmosphere; in a toluene solution upon prolonged heating at 90 °C in air, no decomposition was observed. The resulting unique verdazyl-nitroxide conjugate was thoroughly studied using a range of experimental and theoretical techniques, such as SQUID magnetometry of polycrystalline powders, EPR spectroscopy in various matrices, cyclic voltammetry, and high-level quantum chemical calculations. All collected data confirm the high thermal stability of the resulting tetraradical and quintet multiplicity of its ground state, which makes the synthesis of this important paramagnet a new milestone in the field of creating high-spin systems.

Delineating three-dimensional behavior of uveal melanoma cells under anchorage independent or dependent conditions.

BACKGROUND: Although rare, uveal melanoma (UM) is a life-threatening malignancy. Understanding its biology is necessary to improve disease outcome. Three-dimensional (3D) in vitro culture methods have emerged as tools that incorporate physical and spatial cues that better mimic tumor biology and in turn deliver more predictive preclinical data. Herein, we comprehensively characterize UM cells under different 3D culture settings as a suitable model to study tumor cell behavior and therapeutic intervention. METHODS: Six UM cell lines were tested in two-dimensional (2D) and 3D-culture conditions. For 3D cultures, we used anchorage-dependent (AD) methods where cells were embedded or seeded on top of basement membrane extracts and anchorage-free (AF) methods where cells were seeded on agarose pre-coated plates, ultra-low attachment plates, and on hanging drops, with or without methylcellulose. Cultures were analyzed for multicellular tumor structures (MCTs) development by phase contrast and confocal imaging, and cell wellbeing was assessed based on viability, membrane integrity, vitality, apoptotic features, and DNA synthesis. Vascular endothelial growth factor (VEGF) production was evaluated under hypoxic conditions for cell function analysis. RESULTS: UM cells cultured following anchorage-free methods developed MCTs shaped as spheres. Regardless of their sizes and degree of compaction, these spheres displayed an outer ring of viable and proliferating cells, and a core with less proliferating and apoptotic cells. In contrast, UM cells maintained under anchorage-dependent conditions established several morphological adaptations. Some remained isolated and rounded, formed multi-size irregular aggregates, or adopted a 2D-like flat appearance. These cells invariably conserved their metabolic activity and conserved melanocytic markers (i.e., expression of Melan A/Mart-1 and HMB45). Notably, under hypoxia, cells maintained under 3D conditions secrete more VEGF compared to cells cultured under 2D conditions. CONCLUSIONS: Under an anchorage-free environment, UM cells form sphere-like MCTs that acquire attributes reminiscent of abnormal vascularized solid tumors. UM cells behavior in anchorage-dependent manner exposed diverse cells populations in response to cues from an enriched extracellular matrix proteins (ECM) environment, highlighting the plasticity of UM cells. This study provides a 3D cell culture platform that is more predictive of the biology of UM. The integration of such platforms to explore mechanisms of ECM-mediated tumor resistance, metastatic abilities, and to test novel therapeutics (i.e., anti-angiogenics and immunomodulators) would benefit UM care.

"What's Going to Happen?": Internal Medicine Resident Experiences of Uncertainty in the Care of Older Adults.

PURPOSE: Internal medicine residents care for clinically complex older adults and may experience increased moral distress due to knowledge gaps, time constraints, and institutional barriers. We conducted a phenomenological study to explore residents' experiences and challenges through the lens of uncertainty. METHODS: Between January and March 2022, six focus groups were conducted comprising a total of 13 internal medicine residents in postgraduate years 2 and 3, who had completed a required 2-week geriatrics rotation. Applying the Beresford taxonomy of uncertainty as a conceptual model, data were analyzed using the framework method. RESULTS: All challenging experiences described by residents caring for older adults were linked to uncertainty. Sources of uncertainty were categorized and mapped to the Beresford taxonomy: (1) lack of geriatrics knowledge or clinical guidelines (technical); (2) difficulty applying knowledge to complex older adults (conceptual); and (3) lack of longitudinal relationship with the older patient (personal). Residents identified capacity evaluation and discharge planning as two major geriatric knowledge areas linked with uncertainty. While the majority of residents reacted to uncertainty with some degree of distress, several reported positive coping strategies. CONCLUSIONS: Internal medicine residents face uncertainty when caring for older adults, particularly related to technical and conceptual factors. Strategies for mitigating uncertainty in the care of older adults are needed given links with moral distress and trainee well-being.

Bayesian total-evidence dating revisits sloth phylogeny and biogeography: a cautionary tale on morphological clock analyses.

Combining morphological and molecular characters through Bayesian total-evidence dating allows inferring the phylogenetic and timescale framework of both extant and fossil taxa, while accounting for the stochasticity and incompleteness of the fossil record. Such an integrative approach is particularly needed when dealing with clades such as sloths (Mammalia: Folivora), for which developmental and biomechanical studies have shown high levels of morphological convergence whereas molecular data can only account for a limited percentage of their total species richness. Here, we propose an alternative hypothesis of sloth evolution that emphasizes the pervasiveness of morphological convergence and the importance of considering the fossil record and an adequate taxon sampling in both phylogenetic and biogeographic inferences. Regardless of different clock models and morphological datasets, the extant sloth Bradypus is consistently recovered as a megatherioid, and Choloepus as a mylodontoid, in agreement with molecular-only analyses. The recently extinct Caribbean sloths (Megalocnoidea) are found to be a monophyletic sister-clade of Megatherioidea, in contrast to previous phylogenetic hypotheses. Our results contradict previous morphological analyses and further support the polyphyly of "Megalonychidae", whose members were found in five different clades. Regardless of taxon sampling and clock models, the Caribbean colonization of sloths is compatible with the exhumation of islands along Aves Ridge and its geological time frame. Overall, our total-evidence analysis illustrates the difficulty of positioning highly incomplete fossils, although a robust phylogenetic framework was recovered by an a posteriori removal of taxa with high percentages of missing characters. Elimination of these taxa improved topological resolution by reducing polytomies and increasing node support. However, it introduced a systematic and geographic bias because most of these incomplete specimens are from northern South America. This is evident in biogeographic reconstructions, which suggest Patagonia as the area of origin of many clades when taxa are underrepresented, but Amazonia and/or Central and Southern Andes when all taxa are included. More generally, our analyses demonstrate the instability of topology and divergence time estimates when using different morphological datasets and clock models, and thus caution against making macroevolutionary inferences when node support is weak or when uncertainties in the fossil record are not considered.

Neurophotonic methods in approach to in vivo animal epileptic models: Advantages and limitations.

Neurophotonic technology is a rapidly growing group of techniques that are based on the interactions of light with natural or genetically modified cells of the neural system. New optical technologies make it possible to considerably extend the tools of neurophysiological research, from the visualization of functional activity changes to control of brain tissue excitability. This opens new perspectives for studying the mechanisms underlying the development of human neurological diseases. Epilepsy is one of the most common brain disorders; it is characterized by recurrent seizures and affects >1% of the world's population. However, how seizures occur, spread, and terminate in a healthy brain is still unclear. Therefore, it is extremely important to develop appropriate models to accurately explore the causal relationship of epileptic activity. The use of neurophotonic technologies in epilepsy research falls into two broad categories: the visualization of neural epileptic activity, and the direct optical influence on neurons to induce or suppress epileptic activity. An optogenetic variant of the classical kindling model of epileptic seizures, in which activatable cells are genetically defined, is called optokindling. Research is also underway concerning the application of neurophotonic techniques for suppressing epileptic activity, aiming to bring these methods into clinical practice. This review aims to systematize and describe new approaches that use combinations of different neurophotonic methods to work with in vivo models of epilepsy. These approaches overcome many of the shortcomings associated with classical animal models of epilepsy and thus increase the effectiveness of developing new diagnostic methods and antiepileptic therapy.

Synaptic weights that correlate with presynaptic selectivity increase decoding performance.

The activity of neurons in the visual cortex is often characterized by tuning curves, which are thought to be shaped by Hebbian plasticity during development and sensory experience. This leads to the prediction that neural circuits should be organized such that neurons with similar functional preference are connected with stronger weights. In support of this idea, previous experimental and theoretical work have provided evidence for a model of the visual cortex characterized by such functional subnetworks. A recent experimental study, however, have found that the postsynaptic preferred stimulus was defined by the total number of spines activated by a given stimulus and independent of their individual strength. While this result might seem to contradict previous literature, there are many factors that define how a given synaptic input influences postsynaptic selectivity. Here, we designed a computational model in which postsynaptic functional preference is defined by the number of inputs activated by a given stimulus. Using a plasticity rule where synaptic weights tend to correlate with presynaptic selectivity, and is independent of functional-similarity between pre- and postsynaptic activity, we find that this model can be used to decode presented stimuli in a manner that is comparable to maximum likelihood inference.

Associations between the resting EEG aperiodic slope and broad domains of cognitive ability.

Recent studies suggest that the EEG aperiodic exponent (often represented as a slope in log-log space) is sensitive to individual differences in momentary cognitive skills such as selective attention and information processing speed. However, findings are mixed, and most of the studies have focused on just a narrow range of cognitive domains. This study used an archival dataset to help clarify associations between resting aperiodic features and broad domains of cognitive ability, which vary in their demands on momentary processing. Undergraduates (N = 166) of age 18-52 years completed a resting EEG session as well as a standardized, individually administered assessment of cognitive ability that included measures of processing speed, working memory, and higher-order visuospatial and verbal skills. A subsample (n = 110) also completed a computerized reaction time task with three difficulty levels. Data reduction analyses revealed strong correlations between the aperiodic offset and slope across electrodes, and a single component accounted for ~60% of variance in slopes across the scalp, in both eyes-closed and eyes-open conditions. Structural equation models did not support relations between the slope and specific domains tapping momentary processes. However, secondary analyses indicated that the eyes-open slope was related to higher overall performance, as represented by a single general ability factor. A latent reaction time variable was significantly inversely related to both eyes-closed and eyes-open resting exponents, such that faster reaction times were associated with steeper slopes. These findings support and help clarify the relation of the resting EEG exponent to individual differences in cognitive skills.

Quantitative Determination of Active Species Transforming the R-NHC Coupling Process under Catalytic Conditions.

Palladium complexes with N-heterocyclic carbenes (Pd/NHC) serve as prominent precatalysts in numerous Pd-catalyzed organic reactions. While the evolution of Pd/NHC complexes, which involves the cleavage of the Pd-C(NHC) bond via reductive elimination and dissociation, is acknowledged to influence the catalysis mechanism and the performance of the catalytic systems, conventional analytic techniques [such as NMR, IR, UV-vis, gas chromatography-mass spectrometry (GC-MS), and high-performance liquid chromatography (HPLC)] frequently fail to quantitatively monitor the transformations of Pd/NHC complexes at catalyst concentrations typical of real-world conditions (below approximately 1 mol %). In this study, for the first time, we show the viability of using electrospray ionization mass spectrometry (ESI-MS). This approach was combined with the use of selectively deuterated H-NHC, Ph-NHC, and O-NHC coupling products as internal standards, allowing for an in-depth quantitative analysis of the evolution of Pd/NHC catalysts within actual catalytic systems. The reliability of this approach was affirmed by aligning the ESI-MS results with the NMR spectroscopy data obtained at greater Pd/NHC precatalyst concentrations (2-5 mol %) in the Mizoroki-Heck, Sonogashira, and alkyne transfer hydrogenation reactions. The efficacy of the ESI-MS methodology was further demonstrated through its application in the Mizoroki-Heck reaction at Pd/NHC loadings of 5, 0.5, 0.05, and 0.005 mol %. In this work, for the first time, we present a methodology for the quantitative characterization of pivotal catalyst transformation processes commonly observed in M/NHC systems.

Tridentate Nitrogen Ligand as a Tool for the Construction of Well-Defined Rare Earth Trichloride Complexes.

LnCl3(THF)3 (Ln = Y, La ÷ Nd, Sm ÷ Lu) readily react with the tridentate 1,3,5-trimethyl-1,3,5-triazacyclohexane (Me3tach) ligand to form mono- or binuclear lanthanide trichloride complexes, depending on the stoichiometry of the reaction and the ionic radius of the metal: mononuclear pseudosandwich [LnCl3(Me3tach)2], (Ln = Y, La ÷ Ho) or binuclear complexes [Ln2Cl6(Me3tach)3], or [LnCl3(Me3tach)(THF)]2 (Ln = Sm, Tb). Detailed analysis of the NMR data of [LnCl3(Me3tach)2] complexes with paramagnetic lanthanide ions showed that their structures remained unchanged in the toluene solution. A series of isomorphous complexes [LnCl3(Me3tach)(Py)2] (Ln = La, Sm, Tb, Er, Lu; Py = pyridine) have been obtained by the recrystallization of either mononuclear or binuclear complexes from pyridine. Complexes of terbium and europium ions with the Me3tach ligand exhibit relatively high quantum yields of metal-centered luminescence (0.39 and 0.32, respectively).

Patient reported outcomes of intermittent self-dilatation after direct vision internal urethrotomy.

PURPOSE: Long-term results on quality of life (QoL) as well as clinical outcomes of intermittent self-dilatation (ISD) of the urethra after direct visual internal urethrotomy (DVIU) are scarce. The aim of this study was to prospectively evaluate patient reported outcomes (PROs) on voiding symptoms and QoL in a large cohort of urethral stricture patients performing ISD. METHODS: We identified a total of 121 patients who performed ISD following DVIU between 2008 and 2013. Baseline assessment was conducted for each patient before ISD was started. Follow-up visits were scheduled in 6-month intervals. Each assessment included the following questionnaires: International prostate symptom score (IPSS), IPSS quality of life index (IPSS-QoL), patient global impression of severity (PGI-S), and patient global impression of improvement (PGI-I). Additional parameters were maximum urinary flow rate (Qmax ), postvoid residual urine, rate of complications, and stricture recurrence. Linear mixed models were used to examine the change over the course of the follow-up visits to the baseline. RESULTS: The median age of the patients was 58 years (interquartile range [IQR]: 43-70). The median follow-up was 17 months (IQR: 7-30). Mean change from baseline IPSS was -6.1, -5.9, -4.2, and -4.8 points at 6, 24, 36, and 48 months. Mean change from baseline IPSS-QoL was -1.3, -1.4, -1.6, and -1.8 points, respectively. Mean PGI-I was 1.7 points at 6, 1.9 points at 24, 1.9 points at 36, and 2.2 points at 48 months after ISD initiation. Mean change of Qmax ranged from 1.7 at 6 to 2.2 mL/s at 48 months. The median complication rate was 3.3% per 6-month ISD interval. Overall, 11 patients developed stricture recurrence (9%). CONCLUSION: ISD after DVIU had no negative impact on patients' QoL (IPSS-QoL, PGI-I, PGI-S). Urodynamic parameters remained stable for up to 48 months with low complications and an acceptable stricture recurrence rate.

Harmonizing Energies: The Interplay Between a Nonplanar SalEn-Type Molecule and a TEMPO Moiety in a New Hybrid Energy-Storing Redox-Conducting Polymer.

Redox-conducting polymers based on SalEn-type complexes have attracted considerable attention due to their potential applications in electrochemical devices. However, their charge transfer mechanisms, physical and electrochemical properties remain unclear, hindering their rational design and optimization. This study aims to establish the influence of monomer geometry on the polymer's properties by investigating the properties of novel nonplanar SalEn-type complexes, poly[N,N'-bis(salicylidene)propylene-2-(hydroxy)diaminonickel(II)], and its analog with 2,2,6,6-tetramethylpiperidinyl-N-oxyl (TEMPO)-substituted bridge (MTS). To elucidate the charge transfer mechanism, operando UV-Vis spectroelectrochemical analysis, electrochemical impedance spectroscopy, and electron paramagnetic resonance are employed. Introducing TEMPO into the bridge moiety enhanced the specific capacity of the poly(MTS) material to 95 mA h g-1, attributed to TEMPO's and conductive backbone's charge storage capabilities. Replacement of the ethylenediimino-bridge with a 1,3-propylenediimino- bridge induced significant changes in the complex geometry and material's morphology, electrochemical, and spectral properties. At nearly the same potential, polaron and bipolaron particles emerged, suggesting intriguing features at the overlap point of the electroactivity potentials ranges of polaron-bipolaron and TEMPO, such as a disruption in the connection between TEMPO and the conjugation chain or intramolecular charge transfer. These results offer valuable insights for optimizing strategies to create organic materials with tailored properties for use in catalysis and battery applications.

Thermodynamic model for voltammetric responses in conducting redox polymers.

Electroactive polymer materials are known to play important roles in a vast spectrum of modern applications such as in supercapacitors, fuel cells, batteries, medicine, and smart materials, etc. They are usually divided into two main groups: first, conducting π-conjugated organic polymers, which conduct electricity by cation-radicals delocalized over a polymer chain; second, redox polymers, which conduct electricity via an electron-hopping mechanism. Polymer materials belonging to these two main groups have been thoroughly studied and their thermodynamic and kinetic models have been built. However, in recent decades a lot of mixed-type materials have been discovered and investigated. To the best of our knowledge, a thermodynamic-based description of conducting redox polymers (CRPs) has not been provided yet. In this work, we present a thermodynamic model for voltammetric responses of conducting redox polymers. The derived model allows one to extract thermodynamic parameters of a CRP including the polaron delocalization degree and redox active groups interaction constant. The model was verified with voltammetric experiments on three recently synthesized CRPs and showed a satisfactory predictive ability. The simulated data are in good agreement with the experiment. We believe that developing theoretical descriptions for CRPs and other types of electroactive materials with the ability to simulate their electrochemical responses may help in future realization of new systems with superior characteristics for electrochemical energy storage, chemical sensors, pharmacological applications, etc.

Biomolecular Condensates: Structure, Functions, Methods of Research.

The term "biomolecular condensates" is used to describe membraneless compartments in eukaryotic cells, accumulating proteins and nucleic acids. Biomolecular condensates are formed as a result of liquid-liquid phase separation (LLPS). Often, they demonstrate properties of liquid-like droplets or gel-like aggregates; however, some of them may appear to have a more complex structure and high-order organization. Membraneless microcompartments are involved in diverse processes both in cytoplasm and in nucleus, among them ribosome biogenesis, regulation of gene expression, cell signaling, and stress response. Condensates properties and structure could be highly dynamic and are affected by various internal and external factors, e.g., concentration and interactions of components, solution temperature, pH, osmolarity, etc. In this review, we discuss variety of biomolecular condensates and their functions in live cells, describe their structure variants, highlight domain and primary sequence organization of the constituent proteins and nucleic acids. Finally, we describe current advances in methods that characterize structure, properties, morphology, and dynamics of biomolecular condensates in vitro and in vivo.

Information accumulation on the item versus source test of source monitoring: Insights from diffusion modeling.

Source monitoring involves attributing previous experiences (e.g., studied words as items) to their origins (e.g., screen positions as sources). The present study aimed toward a better understanding of temporal aspects of item and source processing. Participants made source decisions for recognized items either in succession (i.e., the standard format) or in separate test blocks providing independent measures of item and source decision speed. Comparable speeds of item and source decision across the test formats would suggest a full separation between item and source processing, whereas different speeds would imply their (partial) temporal overlap. To test these alternatives, we used the drift rate parameter of the diffusion model (Ratcliff, Psychological Review, 85, 59-108, 1978). We examined whether the drift rates, together with the other parameters, assessed separately for the item and source decision varied as a function of the test format. Threshold separation and nondecision time differed between the test formats, but item and source decision speeds represented by drift rates did not change significantly. Thus, despite facilitation on the source decision when the item decision was immediately followed by a test for source memory than when item and source were tested in separate blocks, findings did not suggest that source information already begins accumulating in the item test in the standard format. We discuss the temporal sequence of item and source processing in light of different assumptions about the contribution of familiarity and recollection.

Long-read assembly of a Great Dane genome highlights the contribution of GC-rich sequence and mobile elements to canine genomes.

Technological advances have allowed improvements in genome reference sequence assemblies. Here, we combined long- and short-read sequence resources to assemble the genome of a female Great Dane dog. This assembly has improved continuity compared to the existing Boxer-derived (CanFam3.1) reference genome. Annotation of the Great Dane assembly identified 22,182 protein-coding gene models and 7,049 long noncoding RNAs, including 49 protein-coding genes not present in the CanFam3.1 reference. The Great Dane assembly spans the majority of sequence gaps in the CanFam3.1 reference and illustrates that 2,151 gaps overlap the transcription start site of a predicted protein-coding gene. Moreover, a subset of the resolved gaps, which have an 80.95% median GC content, localize to transcription start sites and recombination hotspots more often than expected by chance, suggesting the stable canine recombinational landscape has shaped genome architecture. Alignment of the Great Dane and CanFam3.1 assemblies identified 16,834 deletions and 15,621 insertions, as well as 2,665 deletions and 3,493 insertions located on secondary contigs. These structural variants are dominated by retrotransposon insertion/deletion polymorphisms and include 16,221 dimorphic canine short interspersed elements (SINECs) and 1,121 dimorphic long interspersed element-1 sequences (LINE-1_Cfs). Analysis of sequences flanking the 3' end of LINE-1_Cfs (i.e., LINE-1_Cf 3'-transductions) suggests multiple retrotransposition-competent LINE-1_Cfs segregate among dog populations. Consistent with this conclusion, we demonstrate that a canine LINE-1_Cf element with intact open reading frames can retrotranspose its own RNA and that of a SINEC_Cf consensus sequence in cultured human cells, implicating ongoing retrotransposon activity as a driver of canine genetic variation.