Interpersonal Media and Face-to-Face Communication: Relationship with Life Satisfaction and Loneliness.

Framed by need to belong theory, this study considers the role of communication modality, geographic proximity, and the number of close relationship partners to predict life satisfaction and loneliness. A quota sample of American adults (N = 1,869) completed four name generation tasks to identify up to 16 alters, resulting in four alters per participant (n = 7,471). Participants reported the frequency with which they communicated with each alter in the past year in person and through eight interpersonal media. Results suggest that number of relationship partners and frequency of face-to-face interaction were robust predictors of life satisfaction and loneliness. Those living alone faced significant threats to well-being. Video chat and voice call frequency were also associated with greater life satisfaction. Mediation analyses showed voice call frequency was indirectly associated with less loneliness through greater relationship maintenance satisfaction, while lean media was indirectly associated with greater loneliness through relationship maintenance frustration. Supplementary Information: The online version contains supplementary material available at 10.1007/s10902-022-00581-8.

Developmental trajectory of oligodendrocyte progenitor cells in the human brain revealed by single cell RNA sequencing.

Characterizing the developmental trajectory of oligodendrocyte progenitor cells (OPC) is of great interest given the importance of these cells in the remyelination process. However, studies of human OPC development remain limited by the availability of whole cell samples and material that encompasses a wide age range, including time of peak myelination. In this study, we apply single cell RNA sequencing to viable whole cells across the age span and link transcriptomic signatures of oligodendrocyte-lineage cells with stage-specific functional properties. Cells were isolated from surgical tissue samples of second-trimester fetal, 2-year-old pediatric, 13-year-old adolescent, and adult donors by mechanical and enzymatic digestion, followed by percoll gradient centrifugation. Gene expression was analyzed using droplet-based RNA sequencing (10X Chromium). Louvain clustering analysis identified three distinct cellular subpopulations based on 5,613 genes, comprised of an early OPC (e-OPC) group, a late OPC group (l-OPC), and a mature OL (MOL) group. Gene ontology terms enriched for e-OPCs included cell cycle and development, for l-OPCs included extracellular matrix and cell adhesion, and for MOLs included myelination and cytoskeleton. The e-OPCs were mostly confined to the premyelinating fetal group, and the l-OPCs were most highly represented in the pediatric age group, corresponding to the peak age of myelination. Cells expressing a signature characteristic of l-OPCs were identified in the adult brain in situ using RNAScope. These findings highlight the transcriptomic variability in OL-lineage cells before, during, and after peak myelination and contribute to identifying novel pathways required to achieve remyelination.

Use of Whole-Genome Phylogeny and Comparisons for Development of a Multiplex PCR Assay To Identify Sequence Type 36 Vibrio parahaemolyticus.

Vibrio parahaemolyticus sequence type 36 (ST36) strains that are native to the Pacific Ocean have recently caused multistate outbreaks of gastroenteritis linked to shellfish harvested from the Atlantic Ocean. Whole-genome comparisons of 295 genomes of V. parahaemolyticus, including several traced to northeastern U.S. sources, were used to identify diagnostic loci, one putatively encoding an endonuclease (prp), and two others potentially conferring O-antigenic properties (cps and flp). The combination of all three loci was present in only one clade of closely related strains of ST36, ST59, and one additional unknown sequence type. However, each locus was also identified outside this clade, with prp and flp occurring in only two nonclade isolates and cps in four. Based on the distribution of these loci in sequenced genomes, prp identified clade strains with >99% accuracy, but the addition of one more locus increased accuracy to 100%. Oligonucleotide primers targeting prp and cps were combined in a multiplex PCR method that defines species using the tlh locus and determines the presence of both the tdh and trh hemolysin-encoding genes, which are also present in ST36. Application of the method in vitro to a collection of 94 clinical isolates collected over a 4-year period in three northeastern U.S. states and 87 environmental isolates revealed that the prp and cps amplicons were detected only in clinical isolates identified as belonging to the ST36 clade and in no environmental isolates from the region. The assay should improve detection and surveillance, thereby reducing infections.

Inoviridae prophage and bacterial host dynamics during diversification, succession, and Atlantic invasion of Pacific-native Vibrio parahaemolyticus.

IMPORTANCE: An understanding of the processes that contribute to the emergence of pathogens from environmental reservoirs is critical as changing climate precipitates pathogen evolution and population expansion. Phylogeographic analysis of Vibrio parahaemolyticus hosts combined with the analysis of their Inoviridae phage resolved ambiguities of diversification dynamics which preceded successful Atlantic invasion by the epidemiologically predominant ST36 lineage. It has been established experimentally that filamentous phage can limit host recombination, but here, we show that phage loss is linked to rapid bacterial host diversification during epidemic spread in natural ecosystems alluding to a potential role for ubiquitous inoviruses in the adaptability of pathogens. This work paves the way for functional analyses to define the contribution of inoviruses in the evolutionary dynamics of environmentally transmitted pathogens.

An adapted protocol to derive microglia from stem cells and its application in the study of CSF1R-related disorders.

BACKGROUND: Induced pluripotent stem cell-derived microglia (iMGL) represent an excellent tool in studying microglial function in health and disease. Yet, since differentiation and survival of iMGL are highly reliant on colony-stimulating factor 1 receptor (CSF1R) signaling, it is difficult to use iMGL to study microglial dysfunction associated with pathogenic defects in CSF1R. METHODS: Serial modifications to an existing iMGL protocol were made, including but not limited to changes in growth factor combination to drive microglial differentiation, until successful derivation of microglia-like cells from an adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) patient carrying a c.2350G > A (p.V784M) CSF1R variant. Using healthy control lines, the quality of the new iMGL protocol was validated through cell yield assessment, measurement of microglia marker expression, transcriptomic comparison to primary microglia, and evaluation of inflammatory and phagocytic activities. Similarly, molecular and functional characterization of the ALSP patient-derived iMGL was carried out in comparison to healthy control iMGL. RESULTS: The newly devised protocol allowed the generation of iMGL with enhanced transcriptomic similarity to cultured primary human microglia and with higher scavenging and inflammatory competence at ~ threefold greater yield compared to the original protocol. Using this protocol, decreased CSF1R autophosphorylation and cell surface expression was observed in iMGL derived from the ALSP patient compared to those derived from healthy controls. Additionally, ALSP patient-derived iMGL presented a migratory defect accompanying a temporal reduction in purinergic receptor P2Y12 (P2RY12) expression, a heightened capacity to internalize myelin, as well as heightened inflammatory response to Pam3CSK4. Poor P2RY12 expression was confirmed to be a consequence of CSF1R haploinsufficiency, as this feature was also observed following CSF1R knockdown or inhibition in mature control iMGL, and in CSF1RWT/KO and CSF1RWT/E633K iMGL compared to their respective isogenic controls. CONCLUSIONS: We optimized a pre-existing iMGL protocol, generating a powerful tool to study microglial involvement in human neurological diseases. Using the optimized protocol, we have generated for the first time iMGL from an ALSP patient carrying a pathogenic CSF1R variant, with preliminary characterization pointing toward functional alterations in migratory, phagocytic and inflammatory activities.

Insight from the lamprey genome: glimpsing early vertebrate development via neuroendocrine-associated genes and shared synteny of gonadotropin-releasing hormone (GnRH).

Study of the ancient lineage of jawless vertebrates is key to understanding the origins of vertebrate biology. The establishment of the neuroendocrine system with the hypothalamic-pituitary axis at its crux is of particular interest. Key neuroendocrine hormones in this system include the pivotal gonadotropin-releasing hormones (GnRHs) responsible for controlling reproduction via the pituitary. Previous data incorporating several lines of evidence showed all known vertebrate GnRHs were grouped into four paralogous lineages: GnRH1, 2, 3 and 4; with proposed evolutionary paths. Using the currently available lamprey genome assembly, we searched genes of the neuroendocrine system and summarize here the details representing the state of the current lamprey genome assembly. Additionally, we have analyzed in greater detail the evolutionary history of the GnRHs based on the information of the genomic neighborhood of the paralogs in lamprey as compared to other gnathostomes. Significantly, the current evidence suggests that two genome duplication events (both 1R and 2R) that generated the different fish and tetrapod paralogs took place before the divergence of the ancestral agnathans and gnathostome lineages. Syntenic analysis supports this evidence in that the previously-classified type IV GnRHs in lamprey (lGnRH-I and -III) share a common ancestry with GnRH2 and 3, and thus are no longer considered type IV GnRHs. Given the single amino acid difference between lGnRH-II and GnRH2 we propose that a GnRH2-like gene existed before the lamprey/gnathostome split giving rise to lGnRH-II and GnRH2. Furthermore, paralogous type 3 genes (lGnRH-I/III and GnRH3) evolved divergent structure/function in lamprey and gnathostome lineages.

Evolutionary origin and divergence of the growth hormone receptor family: insight from studies on sea lamprey.

Sea lamprey, one of the oldest extant lineages of vertebrates, Agnatha, was used to clarify the evolutionary origin and divergence of the growth hormone receptor (GHR) family. A single full-length cDNA encoding a protein that shares amino acid identity with GHRs and prolactin receptors (PRLRs) previously characterized from teleost fish was identified. Expression of the GHR/PRLR-like transcript was widespread among tissues, including brain, pituitary, heart, liver, and skeletal muscle, which is consistent with the broad physiological roles of GH-family peptides. Phylogenetic analysis suggests that the lamprey possess an ancestral gene encoding a common GHR/PRLR that diverged to give rise to distinct GHRs and PRLRs later in the course of vertebrate evolution. After the divergence of the Actinopterygian and Sarcopterygian lineages, the GHR gene was duplicated in the Actinopterygian lineage during the fish-specific genome duplication event giving rise to two GHRs in teleosts, type 1 GHR and type 2 GHR. A single GHR gene orthologous to the teleost type 1 GHR persisted in the Sarcopterygian lineage, including the common ancestor of tetrapods. Within the teleosts, several subsequent independent duplication events occurred that led to several GHR subtypes. A revised nomenclature for vertebrate GHRs is proposed that represents the evolutionary history of the receptor family. Structural features of the receptor influence ligand binding, receptor dimerization, linkage to signal effector pathways, and, ultimately, hormone function.

Social media use, social displacement, and well-being.

Social displacement is the proposition that time spent on social media replaces time spent in face-to-face interaction, particularly with close friends and family, thus reducing well-being. There is clear evidence of growing mobile and social media use, and some evidence of a decline in face-to-face communication. This essay concludes, however, there is very little direct or causal evidence of social media time displacing face-to-face time. This article concludes that increasing social media use most likely displaces other media activities. To explain findings that seem to support social displacement, this essay examines the difference between population-level trends and within-individual behavior, and the difference between within-person and between-person displacement.

Development and initial evaluation of a multidimensional digital stress scale.

Digital stress is believed to play a role in the association between social media use and psychosocial outcomes. However, the literature is limited by a lack of measures that conform to published theoretical models of the construct. The present investigation details the development of a new multidimensional measure of digital stress. Based on an earlier conceptualization of Digital Stress (Steele et al., 2020), Study 1 identified items from extant measures of digital stress, conducted a qualitative review of the literature to compose new items, and conducted focus groups with young adults and adolescents (N = 23) to improve item wording and interpretation. Study 2 conducted an exploratory factor analysis (EFA) of items with a young adult sample (N = 247) collected online, yielding support for four hypothesized factors (i.e., availability stress, approval anxiety, fear of missing out [FoMO], and connection overload) plus one unanticipated factor (i.e., online vigilance). In Study 3, college students (N = 174) completed paper-and-pencil surveys, and EFA results showed a similar structure as detected in Study 2. In Study 4, confirmatory factor analysis examining the five-factor model was conducted on data from adolescents (N = 163) and college students (N = 152). These procedures yielded 24 items measuring 5 components of digital stress: availability stress, approval anxiety, FoMO, connection overload, and online vigilance. Associations between digital stress and psychosocial distress and functioning are reported to demonstrate convergent and divergent validity. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

An exploratory study of communication, gender-role conflict, and social support of parents of children treated at children's hospital.

This article explores the relationships between communication and social support of parents of children with cancer (N = 44), and the importance of gender-role conflict in fathers. Structural equation modeling and the Actor-Partner Interdependence Model were used to test the expected relationships between communication, social support, gender-role conflict, and anxiety, and to control for sample nonindependence. Results suggest communication increases perceived emotional and instrumental social support between parents, and instrumental support from fathers results in less anxiety for mothers. When fathers experienced more conflict about their role as financial supporter for the family (i.e., career achievement gender-role conflict), fathers perceived less instrumental and emotional support from their wives. However, fathers who experienced more conflict about career achievement were also less anxious. A second measure of fathers' gender-role conflict (i.e., emotional expression) was unrelated to either mothers' or fathers' outcomes. The role of gender, communication, and social support in the context of pediatric oncology is discussed.

Conceptualizing Digital Stress in Adolescents and Young Adults: Toward the Development of an Empirically Based Model.

Existing literature provides a complicated picture of the relationship between digital media use and psychological outcomes. Both correlational and some experimental studies suggest that social media use specifically can be associated with diminished psychological functioning in adolescents and young adults. However, these effect sizes are not large, and must be considered in light of studies that suggest some positive outcomes associated with some uses of digital media, and a range of moderators of the identified associations. Although a growing body of evidence suggests that digital stress may be an important intervening factor between digital media use and psychosocial outcomes, this literature is complicated by multiple nomenclatures for similar or identical constructs. Our review of the literature suggests four potentially related components of digital stress, including availability stress, approval anxiety, fear of missing out, and communication overload. This conceptualization is consistent with recent published frameworks for understanding digital media's influence on peer relationships. Clinicians working with adolescents and young adults are encouraged to assess digital media use in the context of clients' overall psychological and social functioning, and in consideration of clients' specific uses of media. Future research is needed to examine the associations among components of digital stress and clinical outcomes, and to provide valid measures to assess digital stress in research and clinical settings.

Effects of PPAR-γ agonists on oral cancer cell lines: Potential horizons for chemopreventives and adjunctive therapies.

BACKGROUND: Peroxisome proliferator-activated receptor-gamma (PPAR-γ) activators have anti-cancer effects. Our objective was to determine the effect of PPAR-γ ligands 15-deoxy-D12,14 -Prostaglandin J2 (15-PGJ2 ) and ciglitazone on proliferation, apoptosis, and NF-κB in human oral squamous cell carcinoma cell lines. METHODS: NA and CA9-22 cells were treated in vitro with 15-PGJ2 and ciglitazone. Proliferation was measured by MTT colorimetric assay and cell cycle analysis performed via flow cytometry, apoptosis by caspase-3 colorimetric assay and poly-(ADP-ribose) polymerase cleavage on Western blot, and NF-κB activation by luciferase assays. RESULTS: MTT assays demonstrated dose-dependent decreases after 15-PGJ2 treatment in both cell lines, and S-phase cell cycle arrest was also demonstrated. NF-κB luciferase reporter gene activity decreased seven- and eightfold in NA and CA9-22 cells, respectively. Caspase-3 activity increased two- and eightfold in NA and CA9-22 cells, respectively. CONCLUSIONS: Our results suggest these agents, in addition to activating PPAR-γ, can downregulate NF-κB and potentiate apoptosis in oral cancer cells.

Mechanistic Physiologically Based Pharmacokinetic Modeling of the Dissolution and Food Effect of a Biopharmaceutics Classification System IV Compound-The Venetoclax Story.

Venetoclax, a selective B-cell lymphoma-2 inhibitor, is a biopharmaceutics classification system class IV compound. The aim of this study was to develop a physiologically based pharmacokinetic (PBPK) model to mechanistically describe absorption and disposition of an amorphous solid dispersion formulation of venetoclax in humans. A mechanistic PBPK model was developed incorporating measured amorphous solubility, dissolution, metabolism, and plasma protein binding. A middle-out approach was used to define permeability. Model predictions of oral venetoclax pharmacokinetics were verified against clinical studies of fed and fasted healthy volunteers, and clinical drug interaction studies with strong CYP3A inhibitor (ketoconazole) and inducer (rifampicin). Model verification demonstrated accurate prediction of the observed food effect following a low-fat diet. Ratios of predicted versus observed Cmax and area under the curve of venetoclax were within 0.8- to 1.25-fold of observed ratios for strong CYP3A inhibitor and inducer interactions, indicating that the venetoclax elimination pathway was correctly specified. The verified venetoclax PBPK model is one of the first examples mechanistically capturing absorption, food effect, and exposure of an amorphous solid dispersion formulated compound. This model allows evaluation of untested drug-drug interactions, especially those primarily occurring in the intestine, and paves the way for future modeling of biopharmaceutics classification system IV compounds.

Erratum: Author Correction: Biodiversity estimates and ecological interpretations of meiofaunal communities are biased by the taxonomic approach.

[This corrects the article DOI: 10.1038/s42003-018-0119-2.].

Biodiversity estimates and ecological interpretations of meiofaunal communities are biased by the taxonomic approach.

Accurate assessments of biodiversity are crucial to advising ecosystem-monitoring programs and understanding ecosystem function. Nevertheless, a standard operating procedure to assess biodiversity accurately and consistently has not been established. This is especially true for meiofauna, a diverse community (>20 phyla) of small benthic invertebrates that have fundamental ecological roles. Recent studies show that metabarcoding is a cost-effective and time-effective method to estimate meiofauna biodiversity, in contrast to morphological-based taxonomy. Here, we compare biodiversity assessments of a diverse meiofaunal community derived by applying multiple taxonomic methods based on comparative morphology, molecular phylogenetic analysis, DNA barcoding of individual specimens, and metabarcoding of environmental DNA. We show that biodiversity estimates are strongly biased across taxonomic methods and phyla. Such biases affect understanding of community structures and ecological interpretations. This study supports the urgency of improving aspects of environmental high-throughput sequencing and the value of taxonomists in correctly understanding biodiversity estimates.

Adolescent smoking networks: the effects of influence and selection on future smoking.

Peer influence and peer selection have both been linked to the smoking behavior of adolescents. The present investigation uses social network analysis methodology to explore the simultaneous effects of both processes on adolescent smoking and smoking susceptibility over two time periods. Results suggest the effects of friendship selection in 6th grade on smoking behavior in 7th grade were primarily direct. Selecting smokers as friends in 6th grade predicted both smoking and smoking susceptibility in 7th grade, and selecting susceptibles predicted future friendship selection and peer influence. Influence processes were indirectly related to smoking. Smokers' influence in 6th grade predicts the selection of smokers as friends in 7th grade. Smokers' influence also demonstrated a protective effect when ties were not reciprocated.

Sexual Selection and Humor in Courtship : A Case for Warmth and Extroversion.

This investigation examines a sexual selection-based argument regarding humor's role in courtship (i.e., humor production signals intelligence/creativity). Lens model (n =100) analyses suggest that humor production on Facebook profiles were self-reported and perceived to be associated with extroversion, not intelligence. Study 2 (n = 289) found that extroversion was associated humor production, but high school and college grade point average and American College Test (ACT) scores were not. In Study 3, pairs of opposite-sex strangers (n = 102) interacted for 10-12 min. Males' humor production and females' responsive laughter were both associated with females' dating interest. Both partners' dating interest was associated with simultaneous laughter. Without support for the sexual selection argument, three alternative explanations of humor's role in courtship are discussed.

Genetic characterization of clinical and environmental Vibrio parahaemolyticus from the Northeast USA reveals emerging resident and non-indigenous pathogen lineages.

Gastric infections caused by the environmentally transmitted pathogen, Vibrio parahaemolyticus, have increased over the last two decades, including in many parts of the United States (US). However, until recently, infections linked to shellfish from the cool northeastern US waters were rare. Cases have risen in the Northeast, consistent with changes in local V. parahaemolyticus populations toward greater abundance or a shift in constituent pathogens. We examined 94 clinical isolates from a period of increasing disease in the region and compared them to 200 environmental counterparts to identify resident and non-indigenous lineages and to gain insight into the emergence of pathogenic types. Genotyping and multi-locus sequence analysis (MLSA) of clinical isolates collected from 2010 to 2013 in Massachusetts, New Hampshire, and Maine revealed their polyphyletic nature. Although 80% of the clinical isolates harbored the trh hemolysin either alone or with tdh, and were urease positive, 14% harbored neither hemolysin exposing a limitation for these traits in pathogen detection. Resident sequence type (ST) 631 strains caused seven infections, and show a relatively recent history of recombination with other clinical and environmental lineages present in the region. ST34 and ST674 strains were each linked to a single infection and these strain types were also identified from the environment as isolates harboring hemolysin genes. Forty-two ST36 isolates were identified from the clinical collection, consistent with reports that this strain type caused a rise in regional infections starting in 2012. Whole-genome phylogenies that included three ST36 outbreak isolates traced to at least two local sources demonstrated that the US Atlantic coastal population of this strain type was indeed derived from the Pacific population. This study lays the foundation for understanding dynamics within natural populations associated with emergence and invasion of pathogenic strain types in the region.