Specialization of actin isoforms derived from the loss of key interactions with regulatory factors.

A paradox of eukaryotic cells is that while some species assemble a complex actin cytoskeleton from a single ortholog, other species utilize a greater diversity of actin isoforms. The physiological consequences of using different actin isoforms, and the molecular mechanisms by which highly conserved actin isoforms are segregated into distinct networks, are poorly known. Here, we sought to understand how a simple biological system, composed of a unique actin and a limited set of actin-binding proteins, reacts to a switch to heterologous actin expression. Using yeast as a model system and biomimetic assays, we show that such perturbation causes drastic reorganization of the actin cytoskeleton. Our results indicate that defective interaction of a heterologous actin for important regulators of actin assembly limits certain actin assembly pathways while reinforcing others. Expression of two heterologous actin variants, each specialized in assembling a different network, rescues cytoskeletal organization and confers resistance to external perturbation. Hence, while species using a unique actin have homeostatic actin networks, actin assembly pathways in species using several actin isoforms may act more independently.

Germline homozygous missense DEPDC5 variants cause severe refractory early-onset epilepsy, macrocephaly and bilateral polymicrogyria.

DEPDC5 (DEP Domain-Containing Protein 5) encodes an inhibitory component of the mammalian target of rapamycin (mTOR) pathway and is commonly implicated in sporadic and familial focal epilepsies, both non-lesional and in association with focal cortical dysplasia. Germline pathogenic variants are typically heterozygous and inactivating. We describe a novel phenotype caused by germline biallelic missense variants in DEPDC5. Cases were identified clinically. Available records, including magnetic resonance imaging and electroencephalography, were reviewed. Genetic testing was performed by whole exome and whole-genome sequencing and cascade screening. In addition, immunohistochemistry was performed on skin biopsy. The phenotype was identified in nine children, eight of which are described in detail herein. Six of the children were of Irish Traveller, two of Tunisian and one of Lebanese origin. The Irish Traveller children shared the same DEPDC5 germline homozygous missense variant (p.Thr337Arg), whereas the Lebanese and Tunisian children shared a different germline homozygous variant (p.Arg806Cys). Consistent phenotypic features included extensive bilateral polymicrogyria, congenital macrocephaly and early-onset refractory epilepsy, in keeping with other mTOR-opathies. Eye and cardiac involvement and severe neutropenia were also observed in one or more patients. Five of the children died in infancy or childhood; the other four are currently aged between 5 months and 6 years. Skin biopsy immunohistochemistry was supportive of hyperactivation of the mTOR pathway. The clinical, histopathological and genetic evidence supports a causal role for the homozygous DEPDC5 variants, expanding our understanding of the biology of this gene.

AlphaFold2: A versatile tool to predict the appearance of functional adaptations in evolution: Profilin interactions in uncultured Asgard archaea: Profilin interactions in uncultured Asgard archaea.

The release of AlphaFold2 (AF2), a deep-learning-aided, open-source protein structure prediction program, from DeepMind, opened a new era of molecular biology. The astonishing improvement in the accuracy of the structure predictions provides the opportunity to characterize protein systems from uncultured Asgard archaea, key organisms in evolutionary biology. Despite the accumulation in metagenomics-derived Asgard archaea eukaryotic-like protein sequences, limited structural and biochemical information have restricted the insight in their potential functions. In this review, we focus on profilin, an actin-dynamics regulating protein, which in eukaryotes, modulates actin polymerization through (1) direct actin interaction, (2) polyproline binding, and (3) phospholipid binding. We assess AF2-predicted profilin structures in their potential abilities to participate in these activities. We demonstrate that AF2 is a powerful new tool for understanding the emergence of biological functional traits in evolution.

Structural displacement model of chitooligosaccharide transport through chitoporin.

VhChiP is a chitooligosaccharide-specific porin identified in the outer membrane of Vibrio campbellii type strain American Type Culture Collection BAA 1116. VhChiP contains three identical subunits, and in each subunit, the 19-amino acid N-terminal segment serves as a molecular plug (the "N-plug") that controls the closed/open dynamics of the neighboring pores. In this study, the crystal structures of VhChiP lacking the N-plug were determined in the absence and presence of chitohexaose. Binding studies of sugar-ligand interactions by single-channel recordings and isothermal microcalorimetry experiments suggested that the deletion of the N-plug peptide significantly weakened the sugar-binding affinity due to the loss of hydrogen bonds around the central affinity sites. Steered molecular dynamic simulations revealed that the movement of the sugar chain along the sugar passage triggered the ejection of the N-plug, while the H-bonds transiently formed between the reducing end GlcNAc units of the sugar chain with the N-plug peptide may help to facilitate sugar translocation. The findings enable us to propose the structural displacement model, which enables us to understand the molecular basis of chitooligosaccharide uptake by marine Vibrio bacteria.

Poststroke Depression: An Update.

The presence of neuropsychiatric disorders after stroke has been recognized for more than 100 years, but controlled systematic studies did not begin until the 1970s. The most clinically important advances, however, have been in the treatment and prevention of poststroke depression (PSD). Recent meta-analyses of randomized controlled trials (RCTs) for the treatment of PSD have demonstrated the efficacy of antidepressants. Similarly, RCTs for the prevention of PSD have shown that antidepressants significantly decrease the incidence of PSD compared with placebo. Early treatment of PSD with antidepressants also appears to enhance both physical and cognitive recovery from stroke and may increase survival up to 10 years. Genetic and epigenetic variations, white matter disease, cerebrovascular deregulation, altered neuroplasticity, and changes in glutamate neurotransmission may be relevant etiological factors.

Genomes of Asgard archaea encode profilins that regulate actin.

The origin of the eukaryotic cell is unresolved1,2. Metagenomics sequencing has recently identified several potential eukaryotic gene homologues in Asgard archaea3,4, consistent with the hypothesis that the eukaryotic cell evolved from within the Archaea domain. However, many of these eukaryotic-like sequences are highly divergent and the organisms have yet to be imaged or cultivated, which brings into question the extent to which these archaeal proteins represent functional equivalents of their eukaryotic counterparts. Here we show that Asgard archaea encode functional profilins and thereby establish that this archaeal superphylum has a regulated actin cytoskeleton, one of the hallmarks of the eukaryotic cell5. Loki profilin-1, Loki profilin-2 and Odin profilin adopt the typical profilin fold and are able to interact with rabbit actin-an interaction that involves proteins from species that diverged more than 1.2 billion years ago6. Biochemical experiments reveal that mammalian actin polymerizes in the presence of Asgard profilins; however, Loki, Odin and Heimdall profilins impede pointed-end elongation. These archaeal profilins also retard the spontaneous nucleation of actin filaments, an effect that is reduced in the presence of phospholipids. Asgard profilins do not interact with polyproline motifs and the profilin-polyproline interaction therefore probably evolved later in the Eukarya lineage. These results suggest that Asgard archaea possess a primordial, polar, profilin-regulated actin system, which may be localized to membranes owing to the sensitivity of Asgard profilins to phospholipids. Because Asgard archaea are also predicted to encode potential eukaryotic-like genes involved in membrane-trafficking and endocytosis3,4, imaging is now necessary to elucidate whether these organisms are capable of generating eukaryotic-like membrane dynamics that are regulated by actin, such as are observed in eukaryotic cell movement, podosomes and endocytosis.

Mechanisms underpinning community stability along a latitudinal gradient: Insights from a niche-based approach.

At large scales, the mechanisms underpinning stability in natural communities may vary in importance due to changes in species composition, mean abundance, and species richness. Here we link species characteristics (niche positions) and community characteristics (richness and abundance) to evaluate the importance of stability mechanisms in 156 butterfly communities monitored across three European countries and spanning five bioclimatic regions. We construct niche-based hierarchical structural Bayesian models to explain first differences in abundance, population stability, and species richness between the countries, and then explore how these factors impact community stability both directly and indirectly (via synchrony and population stability). Species richness was partially explained by the position of a site relative to the niches of the species pool, and species near the centre of their niche had higher average population stability. The differences in mean abundance, population stability, and species richness then influenced how much variation in community stability they explained across the countries. We found, using variance partitioning, that community stability in Finnish communities was most influenced by community abundance, whereas this aspect was unimportant in Spain with species synchrony explaining most variation; the UK was somewhat intermediate with both factors explaining variation. Across all countries, the diversity-stability relationship was indirect with species richness reducing synchrony which increased community stability, with no direct effects of species richness. Our results suggest that in natural communities, biogeographical variation observed in key drivers of stability, such as population abundance and species richness, leads to community stability being limited by different factors and that this can partially be explained due to the niche characteristics of the European butterfly assemblage.

Standardised empirical dispersal kernels emphasise the pervasiveness of long-distance dispersal in European birds.

Dispersal is a key life-history trait for most species and is essential to ensure connectivity and gene flow between populations and facilitate population viability in variable environments. Despite the increasing importance of range shifts due to global change, dispersal has proved difficult to quantify, limiting empirical understanding of this phenotypic trait and wider synthesis. Here, we introduce a statistical framework to estimate standardised dispersal kernels from biased data. Based on this, we compare empirical dispersal kernels for European breeding birds considering age (average dispersal; natal, before first breeding; and breeding dispersal, between subsequent breeding attempts) and sex (females and males) and test whether different dispersal properties are phylogenetically conserved. We standardised and analysed data from an extensive volunteer-based bird ring-recoveries database in Europe (EURING) by accounting for biases related to different censoring thresholds in reporting between countries and to migratory movements. Then, we fitted four widely used probability density functions in a Bayesian framework to compare and provide the best statistical descriptions of the different age and sex-specific dispersal kernels for each bird species. The dispersal movements of the 234 European bird species analysed were statistically best explained by heavy-tailed kernels, meaning that while most individuals disperse over short distances, long-distance dispersal is a prevalent phenomenon in almost all bird species. The phylogenetic signal in both median and long dispersal distances estimated from the best-fitted kernel was low (Pagel's λ < 0.25), while it reached high values (Pagel's λ >0.7) when comparing dispersal distance estimates for fat-tailed dispersal kernels. As expected in birds, natal dispersal was on average 5 km greater than breeding dispersal, but sex-biased dispersal was not detected. Our robust analytical framework allows sound use of widely available mark-recapture data in standardised dispersal estimates. We found strong evidence that long-distance dispersal is common among European breeding bird species and across life stages. The dispersal estimates offer a first guide to selecting appropriate dispersal kernels in range expansion studies and provide new avenues to improve our understanding of the mechanisms and rules underlying dispersal events.

La dispersión es un rasgo clave del ciclo vital de la mayoría de las especies y es esencial para garantizar la conectividad y el flujo genético entre poblaciones y contribuir a la viabilidad de la población en contextos de ambiente variable. A pesar de que la dispersión es clave para estudiar los cambios en el área de distribución de las especies debido al cambio global, la dispersión es difícil de cuantificar, lo que limita la comprensión empírica de este rasgo fenotípico y su síntesis más amplia. Aquí introducimos un marco de trabajo estadístico para estimar de manera estandarizada los kernels de dispersión a partir de datos sesgados. Basándonos en este marco, comparamos los kernels de dispersión empíricos para las aves reproductoras europeas considerando la edad (dispersión media vital; natal, antes de la primera reproducción; y dispersión reproductora, entre los intentos de reproducción posteriores) y el sexo (hembras y machos), además de explorar si las diferentes propiedades de dispersión se conservan filogenéticamente. Estandarizamos y analizamos los datos de una extensa base de datos de anillamiento de aves en Europa (EURING), basada en voluntarios, teniendo en cuenta los sesgos relacionados con los diferentes umbrales de comunicación de las anillas entre países y con los movimientos migratorios. A continuación, ajustamos, en un marco bayesiano, cuatro funciones de probabilidad ampliamente utilizadas para comparar y proporcionar las mejores descripciones estadísticas de los diferentes kernels de dispersión por edad y sexo para cada especie de ave. Los movimientos de dispersión de las 234 especies de aves europeas analizadas se explicaron estadísticamente mejor mediante kernels de cola pesada, lo que significa que, aunque la mayoría de los individuos se dispersan en distancias cortas, la dispersión a larga distancia es un fenómeno prevalente en casi todas las especies de aves. La señal filogenética tanto en las distancias de dispersión medias como en las largas estimadas a partir del kernel mejor ajustado fue baja (λ de Pagel < 0,25), mientras que alcanzó valores altos (λ de Pagel >0,7) al comparar las estimas de distancia de dispersión para los kernels de cola pesada. Como se esperaba en las aves, la dispersión natal fue en promedio 5 km mayor que la dispersión reproductiva, pero no se detectó una dispersión sesgada por sexo. Nuestro robusto marco analítico permite un buen uso de los datos de marcaje y recaptura disponibles para la estimación estandarizada de las distancias de dispersión. Hemos encontrado pruebas sólidas de que la dispersión a larga distancia es común entre las especies de aves reproductoras europeas y en todas las etapas de la vida. Las estimas de dispersión ofrecen un primer paso para seleccionar los kernels de dispersión adecuados para los estudios de expansión del rango de distribución y proporcionar nuevas vías de investigación para mejorar nuestra comprensión de los mecanismos y procesos que subyacen a los eventos de dispersión.

Spatial consistency in drivers of population dynamics of a declining migratory bird.

Many migratory species are in decline across their geographical ranges. Single-population studies can provide important insights into drivers at a local scale, but effective conservation requires multi-population perspectives. This is challenging because relevant data are often hard to consolidate, and state-of-the-art analytical tools are typically tailored to specific datasets. We capitalized on a recent data harmonization initiative (SPI-Birds) and linked it to a generalized modelling framework to identify the demographic and environmental drivers of large-scale population decline in migratory pied flycatchers (Ficedula hypoleuca) breeding across Britain. We implemented a generalized integrated population model (IPM) to estimate age-specific vital rates, including their dependency on environmental conditions, and total and breeding population size of pied flycatchers using long-term (34-64 years) monitoring data from seven locations representative of the British breeding range. We then quantified the relative contributions of different vital rates and population structure to changes in short- and long-term population growth rate using transient life table response experiments (LTREs). Substantial covariation in population sizes across breeding locations suggested that change was the result of large-scale drivers. This was supported by LTRE analyses, which attributed past changes in short-term population growth rates and long-term population trends primarily to variation in annual survival and dispersal dynamics, which largely act during migration and/or nonbreeding season. Contributions of variation in local reproductive parameters were small in comparison, despite sensitivity to local temperature and rainfall within the breeding period. We show that both short- and long-term population changes of British breeding pied flycatchers are likely linked to factors acting during migration and in nonbreeding areas, where future research should be prioritized. We illustrate the potential of multi-population analyses for informing management at (inter)national scales and highlight the importance of data standardization, generalized and accessible analytical tools, and reproducible workflows to achieve them.

Insights into the evolution of regulated actin dynamics via characterization of primitive gelsolin/cofilin proteins from Asgard archaea.

Asgard archaea genomes contain potential eukaryotic-like genes that provide intriguing insight for the evolution of eukaryotes. The eukaryotic actin polymerization/depolymerization cycle is critical for providing force and structure in many processes, including membrane remodeling. In general, Asgard genomes encode two classes of actin-regulating proteins from sequence analysis, profilins and gelsolins. Asgard profilins were demonstrated to regulate actin filament nucleation. Here, we identify actin filament severing, capping, annealing and bundling, and monomer sequestration activities by gelsolin proteins from Thorarchaeota (Thor), which complete a eukaryotic-like actin depolymerization cycle, and indicate complex actin cytoskeleton regulation in Asgard organisms. Thor gelsolins have homologs in other Asgard archaea and comprise one or two copies of the prototypical gelsolin domain. This appears to be a record of an initial preeukaryotic gene duplication event, since eukaryotic gelsolins are generally comprise three to six domains. X-ray structures of these proteins in complex with mammalian actin revealed similar interactions to the first domain of human gelsolin or cofilin with actin. Asgard two-domain, but not one-domain, gelsolins contain calcium-binding sites, which is manifested in calcium-controlled activities. Expression of two-domain gelsolins in mammalian cells enhanced actin filament disassembly on ionomycin-triggered calcium release. This functional demonstration, at the cellular level, provides evidence for a calcium-controlled Asgard actin cytoskeleton, indicating that the calcium-regulated actin cytoskeleton predates eukaryotes. In eukaryotes, dynamic bundled actin filaments are responsible for shaping filopodia and microvilli. By correlation, we hypothesize that the formation of the protrusions observed from Lokiarchaeota cell bodies may involve the gelsolin-regulated actin structures.

A structural model for (GlcNAc)2 translocation via a periplasmic chitooligosaccharide-binding protein from marine Vibrio bacteria.

VhCBP is a periplasmic chitooligosaccharide-binding protein mainly responsible for translocation of the chitooligosaccharide (GlcNAc)2 across the double membranes of marine bacteria. However, structural and thermodynamic understanding of the sugar-binding/-release processes of VhCBP is relatively less. VhCBP displayed the greatest affinity toward (GlcNAc)2, with lower affinity for longer-chain chitooligosaccharides [(GlcNAc)3-4]. (GlcNAc)4 partially occupied the closed sugar-binding groove, with two reducing-end GlcNAc units extending beyond the sugar-binding groove and barely characterized by weak electron density. Mutation of three conserved residues (Trp363, Asp365, and Trp513) to Ala resulted in drastic decreases in the binding affinity toward the preferred substrate (GlcNAc)2, indicating their significant contributions to sugar binding. The structure of the W513A-(GlcNAc)2 complex in a 'half-open' conformation unveiled the intermediary step of the (GlcNAc)2 translocation from the soluble CBP in the periplasm to the inner membrane-transporting components. Isothermal calorimetry data suggested that VhCBP adopts the high-affinity conformation to bind (GlcNAc)2, while its low-affinity conformation facilitated sugar release. Thus, chitooligosaccharide translocation, conferred by periplasmic VhCBP, is a crucial step in the chitin catabolic pathway, allowing Vibrio bacteria to thrive in oceans where chitin is their major source of nutrients.

Differential changes in life cycle-event phenology provide a window into regional population declines.

Climate change affects the phenology of annual life cycle events of organisms, such as reproduction and migration. Shifts in the timing of these events could have important population implications directly, or provide information about the mechanisms driving population trajectories, especially if they differ between life cycle event. We examine if such shifts occur in a declining migratory passerine bird (willow warbler, Phylloscopus trochilus), which exhibits latitudinally diverging population trajectories. We find evidence of phenological shifts in breeding initiation, breeding progression and moult that differ across geographic and spring temperature gradients. Moult initiation following warmer springs advances faster in the south than in the north, resulting in proportionally shorter breeding seasons, reflecting higher nest failure rates in the south and in warmer years. Tracking shifts in multiple life cycle events allowed us to identify points of failure in the breeding cycle in regions where the species has negative population trends, thereby demonstrating the utility of phenology analyses for illuminating mechanistic pathways underlying observed population trajectories.

The role of gelsolin domain 3 in familial amyloidosis (Finnish type).

In the disease familial amyloidosis, Finnish type (FAF), also known as AGel amyloidosis (AGel), the mechanism by which point mutations in the calcium-regulated actin-severing protein gelsolin lead to furin cleavage is not understood in the intact protein. Here, we provide a structural and biochemical characterization of the FAF variants. X-ray crystallography structures of the FAF mutant gelsolins demonstrate that the mutations do not significantly disrupt the calcium-free conformations of gelsolin. Small-angle X-ray-scattering (SAXS) studies indicate that the FAF calcium-binding site mutants are slower to activate, whereas G167R is as efficient as the wild type. Actin-regulating studies of the gelsolins at the furin cleavage pH (6.5) show that the mutant gelsolins are functional, suggesting that they also adopt relatively normal active conformations. Deletion of gelsolin domains leads to sensitization to furin cleavage, and nanobody-binding protects against furin cleavage. These data indicate instability in the second domain of gelsolin (G2), since loss or gain of G2-stabilizing interactions impacts the efficiency of cleavage by furin. To demonstrate this principle, we engineered non-FAF mutations in G3 that disrupt the G2-G3 interface in the calcium-activated structure. These mutants led to increased furin cleavage. We carried out molecular dynamics (MD) simulations on the FAF and non-FAF mutant G2-G3 fragments of gelsolin. All mutants showed an increase in the distance between the center of masses of the 2 domains (G2 and G3). Since G3 covers the furin cleavage site on G2 in calcium-activated gelsolin, this suggests that destabilization of this interface is a critical step in cleavage.

In vivo crystals reveal critical features of the interaction between cystic fibrosis transmembrane conductance regulator (CFTR) and the PDZ2 domain of Na+/H+ exchange cofactor NHERF1.

Crystallization of recombinant proteins has been fundamental to our understanding of protein function, dysfunction, and molecular recognition. However, this information has often been gleaned under extremely nonphysiological protein, salt, and H+ concentrations. Here, we describe the development of a robust Inka1-Box (iBox)-PAK4cat system that spontaneously crystallizes in several mammalian cell types. The semi-quantitative assay described here allows the measurement of in vivo protein-protein interactions using a novel GFP-linked reporter system that produces fluorescent readouts from protein crystals. We combined this assay with in vitro X-ray crystallography and molecular dynamics studies to characterize the molecular determinants of the interaction between the PDZ2 domain of Na+/H+ exchange regulatory cofactor NHE-RF1 (NHERF1) and cystic fibrosis transmembrane conductance regulator (CFTR), a protein complex pertinent to the genetic disease cystic fibrosis. These experiments revealed the crystal structure of the extended PDZ domain of NHERF1 and indicated, contrary to what has been previously reported, that residue selection at positions -1 and -3 of the PDZ-binding motif influences the affinity and specificity of the NHERF1 PDZ2-CFTR interaction. Our results suggest that this system could be utilized to screen additional protein-protein interactions, provided they can be accommodated within the spacious iBox-PAK4cat lattice.

Covariation in population trends and demography reveals targets for conservation action.

Wildlife conservation policies directed at common and widespread, but declining, species are difficult to design and implement effectively, as multiple environmental changes are likely to contribute to population declines. Conservation actions ultimately aim to influence demographic rates, but targeting actions towards feasible improvements in these is challenging in widespread species with ranges that encompass a wide range of environmental conditions. Across Europe, sharp declines in the abundance of migratory landbirds have driven international calls for action, but actions that could feasibly contribute to population recovery have yet to be identified. Targeted actions to improve conditions on poor-quality sites could be an effective approach, but only if local conditions consistently influence local demography and hence population trends. Using long-term measures of abundance and demography of breeding birds at survey sites across Europe, we show that co-occurring species with differing migration behaviours have similar directions of local population trends and magnitudes of productivity, but not survival rates. Targeted actions to boost local productivity within Europe, alongside large-scale (non-targeted) environmental protection across non-breeding ranges, could therefore help address the urgent need to halt migrant landbird declines. Such demographic routes to recovery are likely to be increasingly needed to address global wildlife declines.

Tree of motility - A proposed history of motility systems in the tree of life.

Motility often plays a decisive role in the survival of species. Five systems of motility have been studied in depth: those propelled by bacterial flagella, eukaryotic actin polymerization and the eukaryotic motor proteins myosin, kinesin and dynein. However, many organisms exhibit surprisingly diverse motilities, and advances in genomics, molecular biology and imaging have showed that those motilities have inherently independent mechanisms. This makes defining the breadth of motility nontrivial, because novel motilities may be driven by unknown mechanisms. Here, we classify the known motilities based on the unique classes of movement-producing protein architectures. Based on this criterion, the current total of independent motility systems stands at 18 types. In this perspective, we discuss these modes of motility relative to the latest phylogenetic Tree of Life and propose a history of motility. During the ~4 billion years since the emergence of life, motility arose in Bacteria with flagella and pili, and in Archaea with archaella. Newer modes of motility became possible in Eukarya with changes to the cell envelope. Presence or absence of a peptidoglycan layer, the acquisition of robust membrane dynamics, the enlargement of cells and environmental opportunities likely provided the context for the (co)evolution of novel types of motility.

Structure of a Minimal α-Carboxysome-Derived Shell and Its Utility in Enzyme Stabilization.

Bacterial microcompartments are proteinaceous shells that encase specialized metabolic processes in bacteria. Recent advances in simplification of these intricate shells have encouraged bioengineering efforts. Here, we construct minimal shells derived from the Halothiobacillus neapolitanus α-carboxysome, which we term Cso-shell. Using cryogenic electron microscopy, the atomic-level structures of two shell forms were obtained, reinforcing notions of evolutionarily conserved features in bacterial microcompartment shell architecture. Encapsulation peptide sequences that facilitate loading of heterologous protein cargo within the shells were identified. We further provide a first demonstration in utilizing minimal bacterial microcompartment-derived shells for hosting heterologous enzymes. Cso-shells were found to stabilize enzymatic activities against heat shock, presence of methanol co-solvent, consecutive freeze-thawing, and alkaline environments. This study yields insights into α-carboxysome assembly and advances the utility of synthetic bacterial microcompartments as nanoreactors capable of stabilizing enzymes with varied properties and reaction chemistries.

Pure Primary Ovarian Carcinoid Tumor.

Primary ovarian carcinoid tumors are uncommon neoplasms that typically arise in the context of a mature cystic teratoma. Pure primary ovarian carcinoid tumors (PPOCTs) are rare and present as a solid ovarian mass in which, by definition, elements of an associated teratoma or other neoplasm are absent. We report a case of a middle-aged woman who presented with abdominal distension. Computed tomography identified a 20 cm abdominopelvic mass. The patient underwent exploratory laparotomy, hysterectomy, and bilateral salpingo-oophorectomy. A large, solid, yellow-tan ovarian mass was resected and diagnosed as a PPOCT. Para-aortic lymph node metastases were identified. This case highlights the gross and microscopic findings characteristic of PPOCTs. In addition, the large number of differential considerations for an insular PPOCT at intraoperative evaluation are discussed.

Effective Tools to Predict Depression in Acute and Subacute Phase of Ischemic Stroke.

OBJECTIVE: Despite the high frequency of depression in the first year following stroke, few studies have predicted risk of depression after the acute and subacute stroke periods. The aim of this study was to identify, in the acute and subacute periods, measures that would predict major depression during the first year after stroke. METHODS: Study subjects were inpatients with ischemic stroke aged 20-85 years within 6 weeks of onset. Patients were evaluated at baseline and at 3, 6, 9, and 12 months. Patients were diagnosed with major depression using the Structured Clinical Interview for DSM-IV. The severity of depressive symptoms was measured with the Patient Health Questionnaire-9 (PHQ-9) and the Montgomery-Åsberg Depression Rating Scale (MADRS). RESULTS: Of the 152 potential patients who met inclusion criteria, 49 had follow-up evaluations; one patient with major depression in the acute and subacute periods was excluded from the analysis. Among the remaining 48 patients, the number of those with major depression during the first year of stroke onset was five (10.4%). Patients who developed major depression had significantly more depressive symptoms in the acute and subacute stroke phase as assessed by both the PHQ-9 and MADRS. Patients with PHQ-9 scores ≥9 in the acute and subacute stroke phases were significantly more likely to develop major depression in a chronic phase of stroke. CONCLUSIONS: The self-administered PHQ-9 can identify patients in the acute and subacute stroke periods who are at increased risk for developing major depression during the first year after stroke.

Social Vulnerability Indices as a Risk Factor for Heart Failure Readmissions.

Objectives: The objective of our study was to use the parameters of social vulnerability index (SVI) to observe their association with the 30-day hospital readmissions in the heart failure population.Methods: Data required for analysis were extracted from the electronic medical record. The geographic SVI data was then merged with the clinical data. Qualitative variables and reported as frequency and quantitative variables and reported as the mean ± standard deviation. Variables from univariate analysis with a P value of ≤ 0.10 were evaluated using multivariate logistic regression with stepwise backward variable selection and receiver operating curve (ROC) analysis.Results: The odds ratio of readmission predicted by HOSPITAL score was 1.137 (P value = 0.004, 95% CI = 1.041-1.241). SVI parameter recording disability showed odds ratio of 1.521 (P value = 0.006, 95% CI = 1.125-2.058) and SVI parameter tracking vehicle ownership showed odds ratio of 15.355 (P value = 0.014, 95% CI = 1.755 - 134.383). The ROCs were generated for three scenarios: (i) HOSPITAL score only which had area under the curve (AUC) of 0.702 (P value = 0.015), (ii) SVI indicators tracking vehicle ownership and disability resulted in the AUC of 0.589 (P value = 0.016), and (iii) all of the above combined increased the AUC increased to 0.718 (P value = 0.015).Conclusions: Two social parameters (limited vehicle access and prevalence of disability) from the SVI showed a strong association with 30-day hospital readmissions.