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N-methyl-D-aspartate receptors (NMDARs) mediate slow excitatory postsynaptic transmission in the central nervous system, thereby exerting a critical role in neuronal development and brain function. Rare genetic variants in the GRIN genes encoding NMDAR subunits segregated with neurological disorders. Here, we summarize the clinical presentations for 18 patients harboring 12 de novo missense variants in GRIN1, GRIN2A, and GRIN2B that alter residues in the M2 re-entrant loop, a region that lines the pore and is intolerant to missense variation. These de novo variants were identified in children with a set of neurological and neuropsychiatric conditions. Evaluation of the receptor cell surface expression, pharmacological properties, and biophysical characteristics show that these variants can have modest changes in agonist potency, proton inhibition, and surface expression. However, voltage-dependent magnesium inhibition is significantly reduced in all variants. The NMDARs hosting a single copy of a mutant subunit showed a dominant reduction in magnesium inhibition for some variants. These variant NMDARs also show reduced calcium permeability and single-channel conductance, as well as altered open probability. The data suggest that M2 missense variants increase NMDAR charge transfer in addition to varied and complex influences on NMDAR functional properties, which may underlie the patients' phenotypes.

Preclinical studies indicate that (2R,6R)-hydroxynorketamine (HNK) is a putative fast-acting antidepressant candidate. Although inhibition of NMDA-type glutamate receptors (NMDARs) is one mechanism proposed to underlie ketamine’s antidepressant and adverse effects, the potency of (2R,6R)-HNK to inhibit NMDARs has not been established. We used a multidisciplinary approach to determine the effects of (2R,6R)-HNK on NMDAR function. Antidepressant-relevant behavioral responses and (2R,6R)-HNK levels in the extracellular compartment of the hippocampus were measured following systemic (2R,6R)-HNK administration in mice. The effects of ketamine, (2R,6R)-HNK, and, in some cases, the (2S,6S)-HNK stereoisomer were evaluated on the following: (i) NMDA-induced lethality in mice, (ii) NMDAR-mediated field excitatory postsynaptic potentials (fEPSPs) in the CA1 field of mouse hippocampal slices, (iii) NMDAR-mediated miniature excitatory postsynaptic currents (mEPSCs) and NMDA-evoked currents in CA1 pyramidal neurons of rat hippocampal slices, and (iv) recombinant NMDARs expressed in Xenopus oocytes. While a single i.p. injection of 10 mg/kg (2R,6R)-HNK exerted antidepressant-related behavioral and cellular responses in mice, the ED(50) of (2R,6R)-HNK to prevent NMDA-induced lethality was found to be 228 mg/kg, compared with 6.4 mg/kg for ketamine. The 10 mg/kg (2R,6R)-HNK dose generated maximal hippocampal extracellular concentrations of ∼8 µM, which were well below concentrations required to inhibit synaptic and extrasynaptic NMDARs in vitro. (2S,6S)-HNK was more potent than (2R,6R)-HNK, but less potent than ketamine at inhibiting NMDARs. These data demonstrate the stereoselectivity of NMDAR inhibition by (2R,6R;2S,6S)-HNK and support the conclusion that direct NMDAR inhibition does not contribute to antidepressant-relevant effects of (2R,6R)-HNK.

This study examined two effective teaching behaviors traditionally considered by instructional communication scholars to associate positively with students’ academic experiences: instructor clarity and immediacy. Our study situated these teaching behaviors in a conditional process model that integrated two key assumptions about student learning: (a) the process by which student learning occurs is due, in part, to the sustained attention that students give to effective instructors (a mediated test of learning) and (b) some students self-regulate their learning despite the (in)effectiveness of the teaching they receive (a moderated test of learning). Three hundred and sixty-two college students were randomly assigned to one of four lecture conditions that manipulated instructor clarity and nonverbal immediacy in a 2 × 2 factorial experiment and completed post-test assessments including a test of cognitive learning. Results indicated that: (a) clear instruction with or without nonverbal immediacy cue...

The purpose of this study was to investigate the enactment of relational maintenance behaviors across three types of adult friendship. Participants (N = 139) completed an online questionnaire in which they were randomly assigned to an active, dormant, or commemorative friendship condition. After reading a description of the friendship type, participants identified one friend who met this description and indicated their use of relational maintenance behaviors with this friend. The results of multivariate analysis of covariance treating age as a covariate indicated that individuals reporting on an active friendship used the understanding, self-disclosure, assurances, and tasks relational maintenance behaviors at a higher rate than individuals reporting on a commemorative friendship.

The development of whole exome/genome sequencing technologies has given rise to an unprecedented volume of data linking patient genomic variability to brain disorder phenotypes. A surprising number of variants have been found in the N-methyl-d-aspartate receptor (NMDAR) gene family, with the GRIN2B gene encoding the GluN2B subunit being implicated in many cases of neurodevelopmental disorders, which are psychiatric conditions originating in childhood and include language, motor, and learning disorders, autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), developmental delay, epilepsy, and schizophrenia. The GRIN2B gene plays a crucial role in normal neuronal development and is important for learning and memory. Mutations in human GRIN2B were distributed throughout the entire gene in a number of patients with various neuropsychiatric and developmental disorders. Studies that provide functional analysis of variants are still lacking, however current analysis of de novo variants that segregate with disease cases such as intellectual disability, developmental delay, ASD or epileptic encephalopathies reveal altered NMDAR function. Here, we summarize the current reports of disease-associated variants in GRIN2B from patients with multiple neurodevelopmental disorders, and discuss implications, highlighting the importance of functional analysis and precision medicine therapies.

To compare relative cold treatment tolerance across the economically important tephritid fruit flies (Diptera: Tephritidae), Bactrocera carambolae Drew & Hancock, Bactrocera correcta (Bezzi), Bactrocera cucurbitae (Coquillett), four populations of Bactrocera dorsalis (Hendel), Bactrocera zonata (Saunders), and Bactrocera tryoni (Froggatt), eggs (in vitro), and larvae (in infested fruit or on carrot diet) were cold treated at 2.0 ± 0.2 °C for selected durations. The study was performed to assess whether a single (i.e., generic) cold treatment could be developed that would control the entire group of fruit flies that were tested. Probit regression models showed that the hierarchy of cold resistance was third-instar larvae reared on carrot diet > third-instar larvae reared on orange > eggs test in vitro. Differences in mortality responses of third-instar larvae reared in oranges across populations of B. dorsalis were observed only at subefficacious levels of control. The majority of Bactrocera species responded the same at the high levels of control demanded of phytosanitary treatments, which indicated that cold treatments would be similarly effective across the species and populations tested. B. cucurbitae was found to be the most cold tolerant of all the species tested.

This article reviews all historical literature in which rodent-derived myelinating cells have been engrafted into the contused adult rodent spinal cord. From 2500 initial PubMed citations identified, human cells grafts, bone mesenchymal stem cells, olfactory ensheathing cells, non-myelinating cell grafts, and rodent grafts into hemisection or transection models were excluded, resulting in the 67 studies encompassed in this review. Forty five of those involved central nervous system (CNS)-derived cells, including neural stem progenitor cells (NSPCs), neural restricted precursor cells (NRPs) or oligodendrocyte precursor cells (OPCs), and 22 studies involved Schwann cells (SC). Of the NSPC/NPC/OPC grafts, there was no consistency with respect to the types of cells grafted and/or the additional growth factors or cells co-grafted. Enhanced functional recovery was reported in 31/45 studies, but only 20 of those had appropriate controls making conclusive interpretation of the remaining studies impossible. Of those 20, 19 were properly powered and utilized appropriate statistical analyses. Ten of those 19 studies reported the presence of graft-derived myelin, 3 reported evidence of endogenous remyelination or myelin sparing, and 2 reported both. For the SC grafts, 16/21 reported functional improvement, with 11 having appropriate cellular controls and 9/11 using proper statistical analyses. Of those 9, increased myelin was reported in 6 studies. The lack of consistency and replication among these preclinical studies are discussed with respect to the progression of myelinating cell transplantation therapies into the clinic.

This study explored the socialization of 118 Division-I student-athletes via the topics of memorable messages that they received prior to their arrival on campus. Ten topics were identified (i.e., desirable attitudes, hard work, physical skill or ability, opportunities, pride, inclusion, challenges, athletes as symbols, the importance of education, and the duration of college athletics) using first cycle coding and were subsequently categorized as either addressing the characteristics or experiences of collegiate student-athletes using second cycle coding. These findings continue to demonstrate that characteristics and experiences associated with roles are prevalent within athletes’ memorable messages but also highlight the inherent ambiguity and the contradictions regarding how to use these messages and balance the dual roles of being a student-athlete. This study provides a novel communicative lens for understanding athlete socialization but underscores the need to recognize receivers’ processing and ap...

The purpose of this study was to examine the extent to which doctoral faculty advisors’ reports of their advisees’ use of relational maintenance behaviors are associated with the advisors’ perceived relational characteristics (i.e., liking, communication satisfaction, relational satisfaction, trust, and control mutuality) and relational uncertainty (i.e., behavioral, mutuality, definitional, and future uncertainty). Doctoral faculty advisors (N = 141) completed a questionnaire in reference to their relationships with a specific doctoral student advisee. The results of canonical correlations largely supported the predictions in that the advisors’ reports of their advisees’ use of relational maintenance behaviors were associated positively with the five relational characteristics but associated negatively with the four types of relational uncertainty. These findings extend both extant relational maintenance and advisor-advisee research.

Purpose of Review Psychiatry is steadily moving toward a new conceptualization of brain disorders that blurs long-held diagnostic distinctions among neurodevelopmental and psychiatric conditions, including autism. Genomic discoveries are driving these changing perceptions, yet there has so far been minimal impact on traditional genetic counseling practices that continue to view autism through the lens of a dichotomous, all-or-none risk model. Recent Findings High rates of comorbidity exist across autism spectrum disorder, schizophrenia, intellectual disability, and other brain-based disorders. Recent epidemiological studies have shown that co-occurrence of neurodevelopmental and psychiatric disorders is the rule, rather than the exception, in affected individuals and within families. Moreover, studies of chromosomal microarray analysis and whole exome sequencing have now detected many of the same pathogenic copy number and sequence-level variants across cohorts with different clinical presentations. Summary Going forward, the genetic counseling field will need to significantly adapt its approaches to pedigree interpretation, variant analysis, and patient education to more precisely describe both the chance and the nature of autism recurrence in terms of a continuum of brain dysfunction. These efforts will have implications for multiple practice areas and require philosophical changes for experienced practitioners and for the training of new genetic counselors. Resetting entrenched dichotomous notions about autism and other brain-based manifestations of genetic conditions will require a strategic educational effort on the part of the genetic counseling profession.

Trogroderma variabile Ballion, warehouse beetle, and Trogoderma inclusum LeConte, larger cabinet beetle, are dermestid pests of stored products. A series of laboratory bioassays were conducted to evaluate residual toxicity of the pyrethroids deltamethrin and β-cyfluthrin, applied on a concrete surface substrate for control of adults and larvae of both species, to provide initial baseline susceptibility data for dermestids. Commercial formulations were applied at calculated deposition rates of 8, 16, and 24 mg active ingredient [AI] per m2 for deltamethrin and 10 and 20 mg active ingredient [AI] per m2 for β-cyfluthrin. Ten adults or larvae of either species were introduced to individual untreated and treated arenas at 0, 0.5, 1, 2, and 3 mo post-treatment. Adult mortality was evaluated after 4 d of exposure with no food provided, and larval mortality was assessed 30 d after exposure with provision of food. Adult mortality of both species exposed to both insecticides ranged from 72.4 ± 6.9 to 100% depending on exposure interval. Larval mortality ranged from 18.3 ± 5.4 to 96.7 ± 2.1% on arenas treated with deltamethrin, and was significantly lower than adult mortality (P

The purpose of this study was to explore young adults’ motives for and content of extradyadic interactions with friends following a negative relational event in a romantic relationship. Focus group discussions with young adults revealed the following partner motives: improving affect, managing uncertainty, obtaining clarity, and entertainment. In turn, friends were motivated by issues of honesty, friendship quality, and a desire to protect or comfort their friend. Both partners and friends discussed the use of a variety of negative, neutral, and positive message content. Results provide an exploratory look at extradyadic interactions that may have important implications for relationship functioning.

Long-lasting insecticide treated netting (LLIN) has a number of potential uses for the control of insect pests. Using such netting, stored products may be protected from insects including the khapra beetle (Trogoderma granarium Everts, Coleoptera: Dermestidae) a widespread pest of many agricultural commodities. Here we first examined whether brief exposures of larvae to LLIN, for less than 30 min, decreased the chance of eventual adult emergence compared to larvae exposed on untreated netting. Next, we observed the responses of larvae that were either not exposed to any netting, exposed to untreated netting, or exposed to LLIN for 10 min and then placed in a wind tunnel and monitored for movement toward a stimulus. The wind-tunnel assay was performed either with or without a lure containing kairomones and pheromones known to be attractive to larvae of this species. There was little effect of the LLIN on adult emergence of exposed larvae. However, there were interacting effects of untreated netting and LLIN relating to thigmotaxis and anemotaxis. Larvae not exposed to netting showed increased likelihood of walking upwind if the semiochemical lure was provided, as expected. A similar pattern was observed when the untreated netting was used, but the larvae became more likely to remain stationary in the assay after acclimating to the net. When LLIN was used, the larvae became more likely to move and there was a baseline increase in the likelihood of moving upwind. However, upwind walking was no longer related to semiochemical presentation. These observations suggest that particular care should be used in relation to the airflow patterns and semiochemical landscape of the warehouse settings in which LLIN is deployed.

Anastrepha grandis (Macquart) (Diptera: Tephritidae) is endemic to the lowland Andean region of South America and considered a quarantine pest of cucurbits by most tropical and subtropical countries outside of the infested region. Despite its regulatory significance, the only phytosanitary treatment available is a generic phytosanitary irradiation dose of 150 Gy that is accepted for all Tephritidae but that was developed without any data on radiotolerance of A. grandis. The objectives of this research were to determine the most cold-tolerant developmental stage of A. grandis and to estimate a time period required for a phytosanitary cold treatment in zucchini squash, Cucurbita pepo L. (Cucurbitaceae). The most cold-tolerant developmental stage of A. grandis in fruit was the 3rd instar, and the time required for a phytosanitary cold treatment in zucchini squash when treated at a minimum of 1.0 °C was estimated at ~23 d. This indicates that A. grandis is approximately as cold tolerant as the most cold-tolerant Anastrepha species known, i.e., Anastrepha ludens (Loew). However, in small-scale testing, no survivors were found at 14 d (n = 340) and the estimated time of 23 d needs to be confirmed by large-scale testing before it should be used commercially. As statistical estimates of extreme values (>99.9%) are not very reliable, and data from 3rd instars did not fit the model well, large-scale testing should be initiated at a treatment time

Importance Population screening for medically relevant genomic variants that cause diseases such as hereditary cancer and cardiovascular disorders is increasing to facilitate early disease detection or prevention. Neuropsychiatric disorders (NPDs) are common, complex disorders with clear genetic causes; yet, access to genetic diagnosis is limited. We explored whether inclusion of NPD in population-based genomic screening programs is warranted by assessing 3 key factors: prevalence, penetrance, and personal utility. Objective To evaluate the suitability of including pathogenic copy number variants (CNVs) associated with NPD in population screening by determining their prevalence and penetrance and exploring the personal utility of disclosing results. Design, Setting, and Participants In this cohort study, the frequency of 31 NPD CNVs was determined in patient-participants via exome data. Associated clinical phenotypes were assessed using linked electronic health records. Nine CNVs were selected for disclosure by licensed genetic counselors, and participants’ psychosocial reactions were evaluated using a mixed-methods approach. A primarily adult population receiving medical care at Geisinger, a large integrated health care system in the United States with the only population-based genomic screening program approved for medically relevant results disclosure, was included. The cohort was identified from the Geisinger MyCode Community Health Initiative. Exome and linked electronic health record data were available for this cohort, which was recruited from February 2007 to April 2017. Data were collected for the qualitative analysis April 2017 through February 2018. Analysis began February 2018 and ended December 2019. Main Outcomes and Measures The planned outcomes of this study include (1) prevalence estimate of NPD-associated CNVs in an unselected health care system population; (2) penetrance estimate of NPD diagnoses in CNV-positive individuals; and (3) qualitative themes that describe participants’ responses to receiving NPD-associated genomic results. Results Of 90 595 participants with CNV data, a pathogenic CNV was identified in 708 (0.8%; 436 women [61.6%]; mean [SD] age, 50.04 [18.74] years). Seventy percent (n = 494) had at least 1 associated clinical symptom. Of these, 28.8% (204) of CNV-positive individuals had an NPD code in their electronic health record, compared with 13.3% (11 835 of 89 887) of CNV-negative individuals (odds ratio, 2.21; 95% CI, 1.86-2.61;P Conclusions and Relevance This study informs critical factors central to the development of population-based genomic screening programs and supports the inclusion of NPD in future designs to promote equitable access to clinically useful genomic information.

NMDA receptors are ligand-gated ion channels that mediate excitatory neurotransmission. Most native NMDA receptors are tetrameric assemblies of two glycine-binding GluN1 and two glutamate-binding GluN2 subunits. Co-assembly of the glycine-binding GluN1 with glycine-binding GluN3 subunits (GluN3A-B) creates glycine activated receptors that possess strikingly different functional and pharmacological properties compared to GluN1/GluN2 NMDA receptors. The role of GluN1/GluN3 receptors in neuronal function remains unknown, in part due to lack of pharmacological tools with which to explore their physiological roles. We have identified the negative allosteric modulator EU1180-438, which is selective for GluN1/GluN3 receptors over GluN1/GluN2 NMDA receptors, AMPA, and kainate receptors. EU1180-438 is also inactive at GABA, glycine, and P2X receptors, but displays inhibition of some nicotinic acetylcholine receptors. Furthermore, we demonstrate that EU1180-438 produces robust inhibition of glycine-activated current responses mediated by native GluN1/GluN3A receptors in hippocampal CA1 pyramidal neurons. EU1180-438 is a non-competitive antagonist with activity that is independent of membrane potential (i.e. voltage-independent), glycine concentration, and extracellular pH. Non-stationary fluctuation analysis of neuronal current responses provided an estimated weighted mean unitary conductance of 6.1 pS for GluN1/GluN3A channels, and showed that EU1180-438 has no effect on conductance. Site-directed mutagenesis suggests that structural determinants of EU1180-438 activity reside near a short pre-M1 helix that lies parallel to the plane of the membrane below the agonist binding domain. These findings demonstrate that structural differences between GluN3 and other glutamate receptor subunits can be exploited to generate subunit-selective ligands with utility in exploring the roles GluN3 in neuronal function.

OBJECTIVE: To determine how gestational age relates to research-identified autism spectrum disorder (ASD-R) in the context of perinatal risk factors STUDY DESIGN: This is a population-based cohort study using the 1994–2000 Olmsted County Birth Cohort. Children included were born and remained in Olmsted County after age 3 years. ASD-R status was determined from signs and symptoms abstracted from medical and educational records. Cox proportional hazards models were fit to identify associations between perinatal characteristics and ASD-R. RESULTS: The incidence of preterm birth (

Context-dependent inhibition of N-methyl-D-aspartate (NMDA) receptors has important therapeutic implications for the treatment of neurological diseases that are associated with altered neuronal firing and signaling. This is especially true in stroke, where the proton concentration in the afflicted area can increase by an order of magnitude. A class of allosteric inhibitors, the 93-series, shows greater potency against GluN1-GluN2B NMDA receptors in such low pH environments, allowing targeted therapy only within the ischemic region. Here we map the 93-series compound binding site in the GluN1-GluN2B NMDA receptor amino terminal domain and show that the interaction of the N-alkyl group with a hydrophobic cage of the binding site is critical for pH-dependent inhibition. Mutation of residues in the hydrophobic cage alters pH-dependent potency, and remarkably, can convert inhibitors into potentiators. Our study provides a foundation for the development of highly specific neuroprotective compounds for the treatment of neurological diseases., Context-dependent inhibition of NMDA receptors has important therapeutic implications for treatment of neurological diseases. Here, the authors use structural biology and biophysics to describe the basis for pH-dependent inhibition for a class of allosteric NMDAR inhibitors, called the 93-series.

N-methyl D-aspartate receptors are ligand-gated ionotropic receptors mediating a slow, calcium-permeable component of excitatory synaptic transmission in the CNS. Variants in genes encoding NMDAR subunits have been associated with a spectrum of neurodevelopmental disorders. Here we report six novel GRIN2D variants and one previously-described disease-associated GRIN2D variant in two patients with developmental and epileptic encephalopathy. GRIN2D encodes for the GluN2D subunit protein; the GluN2D amino acids affected by the variants in this report are located in the pre-M1 helix, transmembrane domain M3, and the intracellular carboxyl terminal domain. Functional analysis in vitro reveals that all six variants decreased receptor surface expression, which may underline some shared clinical symptoms. In addition the GluN2D(Leu670Phe), (Ala675Thr) and (Ala678Asp) substitutions confer significantly enhanced agonist potency, and/or increased channel open probability, while the GluN2D(Ser573Phe), (Ser1271Phe) and (Arg1313Trp) substitutions result in a mild increase of agonist potency, reduced sensitivity to endogenous protons, and decreased channel open probability. The GluN2D(Ser573Phe), (Ala675Thr), and (Ala678Asp) substitutions significantly decrease current amplitude, consistent with reduced surface expression. The GluN2D(Leu670Phe) variant slows current response deactivation time course and increased charge transfer. GluN2D(Ala678Asp) transfection significantly decreased cell viability of rat cultured cortical neurons. In addition, we evaluated a set of FDA-approved NMDAR channel blockers to rescue functional changes of mutant receptors. This work suggests the complexity of the pathological mechanisms of GRIN2D-mediated developmental and epileptic encephalopathy, as well as the potential benefit of precision medicine.

We retrospectively identified autism spectrum disorder (ASD) incident cases among 31,220 individuals in a population-based birth cohort based on signs and symptoms uniformly abstracted from medical and educational records. Inclusive and narrow research definitions of ASD (ASD-R(I) and ASD-R(N), respectively) were explored, along with clinical diagnoses of ASD (ASD-C) obtained from the records. The incidence of ASD-R(I,) ASD-R(N), and ASD-C increased significantly from 1985–1998, then ASD-R(I) and ASD-R(N) plateaued while the rate of ASD-C continued to increase during 1998–2004. The rising incidence of research-defined ASD may reflect improved recognition and documentation of ASD signs and symptoms. Although the frequency of threshold ASD symptoms stabilized, the rate of ASD-C continued to increase, narrowing the gap between clinical ascertainment and symptom documentation.

Autosomal dominant or benign osteopetrosis is a rare genetic disorder of osteoclasts that results in dense but brittle bone structures. Patients with osteopetrosis may be scheduled for total knee arthroplasty to treat painful and functionally limiting osteoarthrosis. A search of the published literature produced no citation concerning anesthesia for patients with autosomal dominant osteopetrosis undergoing total knee arthroplasty. We present a case report detailing our experience and discuss considerations for the care of future patients with autosomal dominant osteopetrosis.

The khapra beetle, Trogoderma granarium Everts (Coleoptera: Dermestidae), is a serious pest of stored products and is the only stored product insect pest that triggers a quarantine response when it is found in the United States. The larvae of T. granarium feed on a wide range of dry food products of plant and animal origin, including cereals, dried fish, and museum specimens. In this study, we evaluated the residual efficacy of two pyrethroid insecticides, deltamethrin and cyfluthrin, applied on concrete, wood, painted wood, vinyl flooring tile, and metal surfaces using small and large T. granarium larvae. Residual efficacy of two insect growth regulators (IGRs), methoprene and pyriproxyfen was also evaluated on concrete, metal, and wood surfaces. In both studies, larvae were exposed with provision of a food source on the treated surfaces and residual assays were conducted at 0 months (1 d), 1, 2, and 3 months post treatment. In general, both of the pyrethroids provided a high level of control of T. granarium larvae, though small larvae were much more susceptible than large larvae. The IGRs were comparatively less effective, with more larval survival and adult emergence of exposed larvae compared with the pyrethroids. Residues of the pyrethroids and IGRs were most persistent on the metal surface. Results can be used to help to control and eradicate infestations of T. granarium when they are detected in the United States.

Studies on family–work conflict among higher education faculty focus exclusively on research or promotion-related work outcomes and find significant challenges in balancing these two spheres. To ex...

ASD and ADHD are regarded as distinct disorders in the current DSM-5. However, recent research and the RDoC initiative are recognizing considerable overlap in the clinical presentation of ASD, ADHD, and other neurodevelopmental disorders. In spite of numerous neuroimaging findings in ASD and ADHD, the extent to which either of the above views are supported remains equivocal. Here we compare structural MRI and DTI literature in ASD and ADHD. Our main findings reveal both distinct and shared neural features. Distinct expressions were in total brain volume (ASD: increased volume, ADHD: decreased volume), amygdala (ASD: overgrowth, ADHD: normal), and internal capsule (ASD: unclear, ADHD: reduced FA in DTI). Considerable overlap was noted in the corpus callosum and cerebellum (lower volume in structural MRI and decreased FA in DTI), and superior longitudinal fasciculus (reduced FA in DTI). In addition, we identify brain regions which have not been studied in depth and require more research. We discuss relationships between brain features and symptomatology. We conclude by addressing limitations of current neuroimaging research and offer approaches that account for clinical heterogeneity to better distinguish brain-behavior relationships.

Since the introduction of the student affect construct to the instructional communication field by both Scott and Wheeless (1977) and Andersen (1979), their work has heavily influenced the manner i...

This study gathered longitudinal and descriptive data on the nature of the basic communication course, continuing a tradition dating back to 1968. Now in its ninth iteration, convenience sampling and hard copy distribution of the survey instrument resulted in a total of 188 respondents (21 from two-year schools, 167 from four-year schools). This study reports and discusses data in the following categories: (a) general description of the course; (b) course administration; (c) assessment, standardization, and assignments and grading; (d) course content and pedagogy; and (e) media, technology, and online teaching. General reflections are provided about the results in light of changing landscapes in the U.S. educational system and recent research and other activities of communication scholars related to the basic communication course. Recommendations are offered for future scholarship about the communication discipline's “front porch.”

The purpose of this investigation was to identify the types of citizenship behavior students use in the college classroom, and to examine the link between their use of citizenship behavior and their perceptions of classroom climate, interest, and self-reports of learning outcomes. Participants were 416 undergraduate students enrolled at a large Mid-Atlantic university. Three findings were obtained. First, participants use three types of citizenship behavior: involvement, affiliation, and courtesy. Second, involvement and courtesy are related positively to classroom climate, classroom connectedness, instructor rapport, emotional interest, and cognitive interest, whereas affiliation is related positively to classroom climate, classroom connectedness, instructor rapport, and emotional interest. Third, involvement and courtesy are related positively to three dimensions of affective learning, perceived cognitive learning, state motivation, and communication satisfaction, whereas affiliation is related positive...

Several North American walnut species (Juglans spp.) are threatened by thousand cankers disease which is caused by the walnut twig beetle (Pityophthorus juglandis Blackman) and its associated fungal plant pathogen, Geosmithia morbida M. Kolarík, E. Freeland, C. Utley and N. Tisserat sp. nov. Spread of this disease may occur via movement of infested black walnut (Juglans nigra L.) wood. This study evaluated the ability of P. juglandis to colonize J. nigra wood previously treated with various phytosanitation methods. Steam-heated and methyl bromide-fumigated J. nigra logs, as well as kiln-dried natural wane J. nigra lumber (with and without bark) were subsequently exposed to P. juglandis colonization pressure in two exposure scenarios. Following a pheromone-mediated, high-pressure scenario in the canopy of infested trees, beetles readily colonized the bark of steam-heated and methyl bromide-fumigated logs, and were also recovered from kiln-dried lumber on which a thin strip of bark was retained. In the simulated lumberyard exposure experiment, during which samples were exposed to lower P. juglandis populations, beetles were again recovered from bark-on steam-heated logs, but were not recovered from kiln-dried bark-on lumber. These data suggest logs and bark-on lumber treated with phytosanitation methods should not be subsequently exposed to P. juglandis populations. Further beetle exclusion efforts for phytosanitized, bark-on walnut wood products transported out of quarantined areas may be necessary to ensure that these products do not serve as a pathway for the spread of P. juglandis and thousand cankers disease.

This assessment examined the presence of anti-citizenship behavior (ACB) in the college classroom by (1) identifying the types of ACB college students use in their classes, (2) identifying the reasons why students use ACB, and (3) exploring the link between ACB and student learning outcomes. The results indicated that (1) participants report four types of ACB (i.e., participatory, technological, physical, and etiquette) used in their classes; (2) participants attribute the use of ACB to either their classmates or their instructors; and (3) perceived classmates’ use of ACB is negatively related to student affective learning, perceived cognitive learning, state motivation, and communication satisfaction.

This article reports the findings of two meta-analyses that explored the relationship between teacher clarity and student learning. Combined, the results suggest that teacher clarity has a larger effect for student affective learning than for cognitive learning. However, neither the effects for cognitive learning nor affective learning were homogeneous. Heterogeneous effects were observed for several additional subsets of the datasets. The first meta-analysis reviews the findings of 144 reported effects (N = 73,281) examining the relationship between teacher clarity and student learning outcomes. The cumulative evidence indicates that teacher clarity accounts for approximately 13% of the variance in student learning. The second meta-analysis reports a random-effects meta-analysis of 46 studies (N = 13,501). Moderators were examined and revealed that study design (i.e., survey versus experiment) moderated the impact of instructor clarity on affective learning. No significant moderators were found for cogni...

It is not much of a surprise that contemporary instructional communication scholars examine instructor–student interaction through an interpersonal communication lens. When the study of instruction...

The purpose of this investigation is to apply Gold's (1989) typology of sibling relationships to the study of adult-sibling use of relational maintenance behaviors and perceptions of relational characteristics. Participants were 196 adults who targeted a sibling whose birthday was closest to their own and completed a series of instruments in reference to the targeted sibling. It was found that whether individuals classified their sibling relationships as intimate, congenial, loyal, or apathetic/hostile was reflected in their self-reported use of relational maintenance behaviors, their perceptions of their targeted siblings' use of relational maintenance behaviors with them, and their perceptions of the relational characteristics associated with the sibling relationship.

To examine instructional communication behaviors in the medical context and to explore the role of health literacy in pediatrician-parent relationships, the current study assessed parents’ (N = 299) perceptions of their pediatricians’ nonverbal immediacy, clarity, and verbal receptivity and their own communication satisfaction, affective learning, and cognitive learning. Results demonstrated that when pediatricians are nonverbally immediate, clear, and verbally receptive, parents report that they are satisfied with their pediatricians’ communication, affectively predisposed toward their pediatricians, and able to recall their pediatricians’ medical directives. Further, health literacy moderates the relationships between pediatricians’ behaviors and parent outcomes such that for parents with low health literacy, pediatricians’ use of nonverbal immediacy and verbal receptivity was related to higher affective and cognitive learning.

Background and purpose To share our experience of a partnership created amongst students, staff, and faculty in order to address a gap in campus information technology (IT) customer services provided to students. Educational activity and setting Student reliance on a complex educational technology ecosystem requires a robust IT infrastructure; however, campus IT services are often stretched in terms of their capacity to deliver immediate customer support. Compounding this problem is the inability of campus IT services to address issues arising from pharmacy education specific hardware or software. A student help desk (SHD), a student-initiated technology user group was developed. The support provided by the SHD covers student devices to the level of ensuring access to required curriculum technological resources. Findings Over 24 months, a total of 259 cases were addressed by the SHD. When examining the type of submissions, the top five requested categories included computer-based assessment, e-mail synchronization, curricular management software synchronization, wireless printing and encryption. These results suggest the perceived value and confidence by students and faculty in the service provided by the SHD. Summary The use of a SHD helped to resolve technology issues faced by students for curriculum engagement. Regardless of the challenges institutions may face in delivering their curriculum, students have the desire to be engaged in the governance of their curriculum. By creating a collaborative triad, this represents one example of how student motivation can be leveraged to conquer not just gaps in IT customer service, but potentially other programmatic issues within an institution.

N-methyl-D-aspartate receptors (NMDARs) are ionotropic glutamate receptors that mediate excitatory synaptic transmission and have been implicated in numerous neurological disorders. NMDARs typically comprise two GluN1 and two GluN2 subunits. The four GluN2 subtypes (GluN2A-GluN2D) have distinct functional properties and gene expression patterns, which contribute to diverse functional roles for NMDARs in the brain. Here, we present a series of GluN2C/2D-selective negative allosteric modulators built around a N-aryl benzamide (NAB) core. The prototypical compound, NAB-14, is >800-fold selective for recombinant GluN2C/GluN2D over GluN2A/GluN2B in Xenopus oocytes and has an IC(50) value of 580 nM at recombinant GluN2D-containing receptors expressed in mammalian cells. NAB-14 inhibits triheteromeric (GluN1/GluN2A/GluN2C) NMDARs with modestly reduced potency and efficacy compared to diheteromeric (GluN1/GluN2C/GluN2C) receptors. Site-directed mutagenesis suggests that structural determinants for NAB-14 inhibition reside in the GluN2D M1 transmembrane helix. NAB-14 inhibits GluN2D-mediated synaptic currents in rat subthalamic neurons and mouse hippocampal interneurons, but has no effect on synaptic transmission in hippocampal pyramidal neurons, which do not express GluN2C or GluN2D. This series possesses some drug-like physical properties and modest brain permeability in rat and mouse. Altogether, this work identifies a new series of negative allosteric modulators that are valuable tools for studying GluN2C- and GluN2D-containing NMDAR function in brain circuits, and suggests that the series has the potential to be developed into therapies for selectively modulating brain circuits involving the GluN2C and GluN2D subunits.

It is increasingly evident that alcohol-induced, gut-mediated peripheral endotoxemia plays a significant role in glial cell activation and neuro-inflammation. Using a mouse model of chronic alcohol feeding, we examined the causal role of endotoxin- and cytokine-responsive Pde4 subfamily b (Pde4b) expression in alcohol-induced neuro-inflammation. Both pharmacologic and genetic approaches were used to determine the regulatory role of Pde4b. In C57Bl/6 wild type (WT) alcohol fed (WT-AF) animals, alcohol significantly induced peripheral endotoxemia and Pde4b expression in brain tissue, accompanied by a decrease in cAMP levels. Further, along with Pde4b, there was a robust activation of astrocytes and microglia accompanied by significant increases in the inflammatory cytokines (Tnfα, Il-1β, Mcp-1 and Il-17) and the generalized inflammatory marker Cox-2. At the cellular level, alcohol and inflammatory mediators, particularly LPS, Tnfα and Hmgb1 significantly activated microglial cells (Iba-1 expression) and selectively induced Pde4b expression with a minimal to no change in Pde4a and d isoforms. In comparison, the alcohol-induced decrease in brain cAMP levels was completely inhibited in WT mice treated with the Pde4 specific pharmacologic inhibitor rolipram and in Pde4b−/− mice. Moreover, all the observed markers of alcohol-induced brain inflammation were markedly attenuated. Importantly, glial cell activation induced by systemic endotoxemia (LPS administration) was also markedly decreased in Pde4b−/− mice. Taken together, these findings strongly support the notion that Pde4b plays a critical role in coordinating alcohol-induced, peripheral endotoxemia mediated neuro-inflammation and could serve as a significant therapeutic target.

Thousand cankers disease, caused by the invasive bark beetle Pityophthorus juglandis Blackman and an associated fungal pathogen Geosmithia morbida M.Kolařík, E. Freeland, C. Utley, N. Tisserat, currently threatens the health of eastern black walnut (Juglans nigra L.) in North America. Both the beetle and pathogen have expanded beyond their native range via transport of infested walnut wood. Geosmithia morbida can develop in seedlings following inoculation, but the ability of P. juglandis to colonize young, small diameter trees has not been investigated. This study assessed the beetle's colonization behavior on J. nigra nursery trees. Beetles were caged directly onto the stems of walnut seedlings from five nursery sources representing a range of basal stem diameter classes. Seedlings were also exposed to P. juglandis in a limited choice, field-based experiment comparing pheromone-baited and unbaited stems. When beetles were caged directly onto stems, they probed and attempted to colonize seedlings across the range of diameters and across sources tested, including stems as small as 0.5 cm in diameter. In the field experiment, beetles only attempted to colonize seedlings that were baited with a pheromone lure and appeared to prefer (though not statistically significant) the larger diameter trees. Despite several successful penetrations into the phloem, there was no evidence of successful progeny development within the young trees in either experiment. Further investigation is recommended to better elucidate the risk nursery stock poses as a pathway for thousand cankers disease causal organisms.

The development of whole exome/genome sequencing technologies has given rise to an unprecedented volume of data linking patient genomic variability to brain disorder phenotypes. A surprising number of variants have been found in the N-methyl-D-aspartate receptor (NMDAR) gene family, with the GRIN2B gene encoding the GluN2B subunit being implicated in many cases of neurodevelopmental disorders, which are psychiatric conditions originating in childhood and include language, motor, and learning disorders, autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), developmental delay, epilepsy, and schizophrenia. The GRIN2B gene plays a crucial role in normal neuronal development and is important for learning and memory. Mutations in human GRIN2B were distributed throughout the entire gene in a number of patients with various neuropsychiatric and developmental disorders. Studies that provide functional analysis of variants are still lacking, however current analysis of de novo variants that segregate with disease cases such as intellectual disability, developmental delay, ASD or epileptic encephalopathies reveal altered NMDAR function. Here, we summarize the current reports of disease-associated variants in GRIN2B from patients with multiple neurodevelopmental disorders, and discuss implications, highlighting the importance of functional analysis and precision medicine therapies.

Importance It is critical to evaluate the risk of comorbid psychiatric diagnoses to meet the needs of individuals with autism spectrum disorder (ASD). Objective To examine whether individuals with ASD are at greater risk for comorbid diagnoses of depression, anxiety, or bipolar disorder. Design, Setting, and Participants This cohort study used data from a population-based birth cohort of 31 220 individuals born in Olmsted County, Minnesota, from January 1, 1976, to December 31, 2000. Patients with research-identified ASD were previously identified using a multistep process that evaluated signs and symptoms abstracted from medical and educational records. For each of the 1014 patients with ASD, 2 age- and sex-matched referents who did not meet criteria for ASD were randomly selected from the birth cohort (n = 2028). Diagnosis codes for anxiety, depression, and bipolar disorders were electronically obtained using the Rochester Epidemiological Project records-linkage system. Data analysis was performed from July 1, 2018, to April 1, 2019. Main Outcomes and Measures Cumulative incidence of clinically diagnosed depression, anxiety, and bipolar disorder through early adulthood in individuals with ASD compared with referents. Results A total of 1014 patients with ASD (median age at last follow-up, 22.8 years [interquartile range, 18.4-28.0 years]; 747 [73.7%] male; 902 [89.0%] white) and 2028 referents (median age at last follow-up, 22.4 years [interquartile range, 18.8-26.2 years]; 1494 [73.7%] male; 1780 [87.8%] white) participated in the study. Patients with ASD were significantly more likely to have clinically diagnosed bipolar disorder (hazard ratio [HR], 9.34; 95% CI, 4.57-19.06), depression (HR, 2.81; 95% CI, 2.45-3.22), and anxiety (HR, 3.45; 95% CI, 2.96-4.01) compared with referents. Among individuals with ASD, the estimates of cumulative incidence by 30 years of age were 7.3% (95% CI, 4.8%-9.7%) for bipolar disorder, 54.1% (95% CI, 49.8%-58.0%) for depression, and 50.0% (95% CI, 46.0%-53.7%) for anxiety. Among referents, cumulative incidence estimates by 30 years of age were 0.9% (95% CI, 0.1%-1.7%) for bipolar disorder, 28.9% (95% CI, 25.7%-32.0%) for depression, and 22.2% (95% CI, 19.3%-25.0%) for anxiety. Conclusions and Relevance The findings suggest that individuals with ASD may be at increased risk for clinically diagnosed depression, anxiety, and bipolar disorder compared with age- and sex-matched referents. This study supports the importance of early, ongoing surveillance and targeted treatments to address the psychiatric needs of individuals with ASD.

Three studies (N = 1119) were conducted to replicate and expand upon Kearney, Plax, Hays, and Ivey's seminal research on instructor misbehaviors. In study 1 (n = 233), a replication of Kearney et al.'s study revealed 43 categories of perceived instructor misbehaviors; 27 of the misbehaviors were originally identified by Kearney et al. and 16 new misbehaviors were identified in this study. In study 2 (n = 650), the Instructor Misbehavior Scale (IMS) was created to operationalize underlying dimensions of instructor misbehaviors; three dimensions (i.e., antagonism, lectures, and articulation) were uncovered through principal axis factoring. In study 3 (n = 236), a confirmatory factor analysis provided construct validity support for the three-factor IMS. Additionally, the antagonism and lectures dimensions of instructor misbehaviors were correlated negatively with student learning outcomes (i.e., affective learning, cognitive learning, state motivation, student communication satisfaction) and served as unique...

Peer coworkers exchange a variety of messages in their organizational experiences. However, little is known about how peer coworker relationship quality affects expression of organizational dissent. This study utilized Kram and Isabella's (1985) typology of peer coworker relationships to examine their impact on lateral dissent expression and dissent messages. The results revealed that special and collegial peers engage in greater amounts of lateral dissent expression than information peers. No differences emerged between the types of peer coworkers relationships in their use of dissent messages. The study lends support to the notion that organizational dissent is influenced by peer coworker relationships.