Research and Publications - Department of Health Science

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Patterns of autism spectrum symptomatology in individuals with Down syndrome without comorbid autism spectrum disorder
(BMC, 2015) Channell, Marie Moore; Phillips, B. Allyson; Loveall, Susan J.; Conners, Frances A.; Bussanich, Paige M.; Klinger, Laura Grofer; University of Alabama Tuscaloosa; University of California Davis; University of Kansas; University of Wisconsin Madison; University of North Carolina; University of North Carolina Chapel Hill
Background: Prevalence estimates of autism spectrum disorder (ASD) in Down syndrome (DS) are highly varied. This variation is partly due to the difficulty of screening for and diagnosing comorbid ASD in individuals with a syndrome that carries its own set of social communicative and behavioral difficulties that are not well documented. The aim of this study was to identify the typical range of social communicative impairments observed in children, adolescents, and young adults with DS who do not have comorbid ASD. Methods: We examined patterns of scores from the five subscales of the Social Responsiveness Scale (SRS) in 46 individuals with DS (ages 10-21 years) without comorbid ASD relative to the published normative sample. We also explored the correlations between SRS symptomatology and age, nonverbal cognition, and receptive language. Results: SRS scores were elevated (i.e., more ASD symptoms endorsed), with mean scores falling into the clinically significant range. Analysis by subscale revealed a specific pattern, with Autistic Mannerisms and Social Cognition scores significantly more elevated than Social Communication scores, which were significantly more elevated than Social Awareness and Social Motivation scores. Correlations between SRS scores and the other measures varied by subscale. Conclusions: General elevated ASD symptomatology on the SRS indicates the need for developing population-based norms specific to DS. The pattern of scores across subscales should inform clinicians of the typical range of behaviors observed in DS so that individuals with atypical patterns of behavior can be more easily identified and considered for a full ASD evaluation.
Drosophila Muller F Elements Maintain a Distinct Set of Genomic Properties Over 40 Million Years of Evolution
(Oxford University Press, 2015) Participating Students Fac Genomic; Washington University (WUSTL); University of Alabama Tuscaloosa; Albion College; Amherst College; California Lutheran University; California Polytechnic State University San Luis Obispo; Calvin University; Cardinal Stritch University; William & Mary; Denison University; Duke University; Georgetown University; Grand Valley State University; Hofstra University; Johnson C Smith University; Longwood University; Loyola Marymount University; Macalester College; Montclair State University; University of North Carolina; North Carolina A&T State University; North Carolina Central University; Oberlin College; Claremont Colleges; Pomona College; Prairie View A&M University; Saint Joseph's University; Saint Mary's College of California; San Francisco State University; Simmons University; City College of New York (CUNY); George Washington University; University of California San Diego; University of Evansville; University of Nebraska Lincoln; University of Pittsburgh; University of Puerto Rico; University of Puerto Rico at Cayey; University of Puerto Rico Mayaguez; University Incarnate Word; University of West Florida; Utah Valley University; Webster University; Widener University; Wilkes University; William Woods University; Worcester State University; York College NY (CUNY)
The Muller F element (4.2 Mb, similar to 80 protein-coding genes) is an unusual autosome of Drosophila melanogaster; it is mostly heterochromatic with a low recombination rate. To investigate how these properties impact the evolution of repeats and genes, we manually improved the sequence and annotated the genes on the D. erecta, D. mojavensis, and D. grimshawi F elements and euchromatic domains from the Muller D element. We find that F elements have greater transposon density (25-50%) than euchromatic reference regions (3-11%). Among the F elements, D. grimshawi has the lowest transposon density (particularly DINE-1: 2% vs. 11-27%). F element genes have larger coding spans, more coding exons, larger introns, and lower codon bias. Comparison of the Effective Number of Codons with the Codon Adaptation Index shows that, in contrast to the other species, codon bias in D. grimshawi F element genes can be attributed primarily to selection instead of mutational biases, suggesting that density and types of transposons affect the degree of local heterochromatin formation. F element genes have lower estimated DNA melting temperatures than D element genes, potentially facilitating transcription through heterochromatin. Most F element genes (similar to 90%) have remained on that element, but the F element has smaller syntenic blocks than genome averages (3.4-3.6 vs. 8.4-8.8 genes per block), indicating greater rates of inversion despite lower rates of recombination. Overall, the F element has maintained characteristics that are distinct from other autosomes in the Drosophila lineage, illuminating the constraints imposed by a heterochromatic milieu.
Using linkage maps to correct and scaffold de novo genome assemblies: methods, challenges, and computational tools
(Frontiers, 2015) Fierst, Janna L.; University of Alabama Tuscaloosa
Modern high-throughput DNA sequencing has made it possible to inexpensively produce genome sequences, but in practice many of these draft genomes are fragmented and incomplete. Genetic linkage maps based on recombination rates between physical markers have been used in biology for over 100 years and a linkage map, when paired with a de novo sequencing project, can resolve mis-assemblies and anchor chromosome-scale sequences. Here, I summarize the methodology behind integrating de novo assemblies and genetic linkage maps, outline the current challenges, review the available software tools, and discuss new mapping technologies.
Metabolomic and Gene Expression Profiles Exhibit Modular Genetic and Dietary Structure Linking Metabolic Syndrome Phenotypes in Drosophila
(Genetics Society of America, 2015) Williams, Stephanie; Dew-Budd, Kelly; Davis, Kristen; Anderson, Julie; Bishop, Ruth; Freeman, Kenda; Davis, Dana; Bray, Katherine; Perkins, Lauren; Hubickey, Joana; Reed, Laura K.; North Carolina State University; University of Alabama Tuscaloosa
Genetic and environmental factors influence complex disease in humans, such as metabolic syndrome, and Drosophila melanogaster serves as an excellent model in which to test these factors experimentally. Here we explore the modularity of endophenotypes with an in-depth reanalysis of a previous study by Reed et al. (2014), where we raised 20 wild-type genetic lines of Drosophila larvae on four diets and measured gross phenotypes of body weight, total sugar, and total triglycerides, as well as the endophenotypes of metabolomic and whole-genome expression profiles. We then perform new gene expression experiments to test for conservation of phenotype-expression correlations across different diets and populations. We find that transcript levels correlated with gross phenotypes were enriched for puparial adhesion, metamorphosis, and central energy metabolism functions. The specific metabolites L-DOPA and N-arachidonoyl dopamine make physiological links between the gross phenotypes across diets, whereas leucine and isoleucine thus exhibit genotype-by-diet interactions. Between diets, we find low conservation of the endophenotypes that correlate with the gross phenotypes. Through the follow-up expression study, we found that transcript-trait correlations are well conserved across populations raised on a familiar diet, but on a novel diet, the transcript-trait correlations are no longer conserved. Thus, physiological canalization of metabolic phenotypes breaks down in a novel environment exposing cryptic variation. We cannot predict the physiological basis of disease in a perturbing environment from profiles observed in the ancestral environment. This study demonstrates that variation for disease traits within a population is acquired through a multitude of physiological mechanisms, some of which transcend genetic and environmental influences, and others that are specific to an individual's genetic and environmental context.
Retrotransposons Are the Major Contributors to the Expansion of the Drosophila ananassae Muller F Element
(Oxford University Press, 2017) Participating Students Fac; Washington University (WUSTL); Saint Joseph's University; Illinois State University; University of Alabama Tuscaloosa; Albion College; California Lutheran University; California Polytechnic State University San Luis Obispo; California State University Stanislaus; Cardinal Stritch University; Duke University; Grand Valley State University; Hofstra University; Longwood University; University of North Carolina; North Carolina Central University; Oberlin College; Rochester Institute of Technology; Simmons University; George Washington University; University of Evansville; University of Northern Colorado; University of Puerto Rico; University of Puerto Rico at Cayey; University of the Cumberlands; York College NY (CUNY); Pennsylvania State University; University of San Diego; Nanjing Agricultural University; Ohio State University; Nationwide Childrens Hospital; Research Institute at Nationwide Children's Hospital
The discordance between genome size and the complexity of eukaryotes can partly be attributed to differences in repeat density. The Muller F element (similar to 5.2 Mb) is the smallest chromosome in Drosophila melanogaster, but it is substantially larger (>18.7 Mb) in D. ananassae. To identify the major contributors to the expansion of the F element and to assess their impact, we improved the genome sequence and annotated the genes in a 1.4-Mb region of the D. ananassae F element, and a 1.7-Mb region from the D element for comparison. We find that transposons (particularly LTR and LINE retrotransposons) are major contributors to this expansion (78.6%), while Wolbachia sequences integrated into the D. ananassae genome are minor contributors (0.02%). Both D. melanogaster and D. ananassae F-element genes exhibit distinct characteristics compared to D-element genes (e.g., larger coding spans, larger introns, more coding exons, and lower codon bias), but these differences are exaggerated in D. ananassae. Compared to D. melanogaster, the codon bias observed in D. ananassae F-element genes can primarily be attributed to mutational biases instead of selection. The 59 ends of F-element genes in both species are enriched in dimethylation of lysine 4 on histone 3 (H3K4me2), while the coding spans are enriched in H3K9me2. Despite differences in repeat density and gene characteristics, D. ananassae F-element genes show a similar range of expression levels compared to genes in euchromatic domains. This study improves our understanding of how transposons can affect genome size and how genes can function within highly repetitive domains.
Dopamine induces soluble alpha-synuclein oligomers and nigrostriatal degeneration
(Nature Portfolio, 2017) Mor, Danielle E.; Tsika, Elpida; Mazzulli, Joseph R.; Gould, Neal S.; Kim, Hanna; Daniels, Malcolm J.; Doshi, Shachee; Gupta, Preetika; Grossman, Jennifer L.; Tan, Victor X.; Kalb, Robert G.; Caldwell, Kim A.; Caldwell, Guy A.; Wolfe, John H.; Ischiropoulos, Harry; University of Pennsylvania; Pennsylvania Medicine; Swiss Federal Institutes of Technology Domain; Ecole Polytechnique Federale de Lausanne; Northwestern University; Feinberg School of Medicine; Childrens Hospital of Philadelphia; University of Alabama Tuscaloosa; State University of New York (SUNY) Downstate Medical Center
Parkinson's disease (PD) is defined by the loss of dopaminergic neurons in the substantia nigra and the formation of Lewy body inclusions containing aggregated alpha-synuclein. Efforts to explain dopamine neuron vulnerability are hindered by the lack of dopaminergic cell death in a-synuclein transgenic mice. To address this, we manipulated both dopamine levels and alpha-synuclein expression. Nigrally targeted expression of mutant tyrosine hydroxylase with enhanced catalytic activity increased dopamine levels without damaging neurons in non-transgenic mice. In contrast, raising dopamine levels in mice expressing human A53T mutant alpha-synuclein induced progressive nigrostriatal degeneration and reduced locomotion. Dopamine elevation in A53T mice increased levels of potentially toxic alpha-synuclein oligomers, resulting in conformationally and functionally modified species. Moreover, in genetically tractable Caenorhabditis elegans models, expression of alpha-synuclein mutated at the site of interaction with dopamine prevented dopamine-induced toxicity. These data suggest that a unique mechanism links two cardinal features of PD: dopaminergic cell death and alpha-synuclein aggregation.
The Prevalence and Severity of Tooth Wear in Type 2 Diabetic Patients
(Hindawi, 2018) Srisilapanan, Patcharawan; Jindarat, Matee; Roseman, Jeffrey; Chiang Mai University; University of Alabama Tuscaloosa
Objective. To assess the prevalence and severity of tooth wear in type 2 diabetic patients. Methods. Attendees at a diabetic clinic at Wiang Pa Pao Hospital in Chiang Rai province, Thailand, were invited to take part in this cross-sectional study. All participants were aged 35-74 and had type 2 diabetes. Participants were required to have been diagnosed with diabetes for at least three months. 179 subjects accepted a clinical oral examination and completed the questionnaire. Tooth wear was assessed clinically using the Smith and Knight Tooth Wear Index. Results. The mean age of diabetic patients was 56.5 +/- 7.8 years. The majority (44.1%) had diabetes more than 5 years. The average years of having had diabetes was 6.5 +/- 6.3 years. The most prevalent type of tooth wear was attrition (99.4%). The prevalence of erosion, abrasion, and abfraction were 64.8%, 31.3%, and 7.3%, respectively. The majority of the tooth wear was moderate to high severity (62.1%). Erosion and abfraction showed significant association with age group (p < 0.05). Age group was significantly associated with the severity level (p = 0.017). Mild tooth wear severity was the highest in age groups 35-44 and 45-54 (53.8% and 41.2%, respectively). Moderate tooth wear was the highest proportion in age groups 55-65 and 65-74 (52.2% and 44.0%, respectively). There were no significant differences between specific diabetic symptoms and types of tooth wear. Conclusion. There was a high prevalence of tooth wear among diabetic patients. The role of prevention is vital in maintaining the integrity of the teeth and to avoid treating these worn teeth in diabetic patients.
TLR4-mediated autophagic impairment contributes to neuropathic pain in chronic constriction injury mice
(Biomed Central, 2018) Piao, Yibo; Gwon, Do Hyeong; Kang, Dong-Wook; Hwang, Tae Woong; Shin, Nara; Kwon, Hyeok Hee; Shin, Hyo Jung; Yin, Yuhua; Kim, Jwa-Jin; Hong, Jinpyo; Kim, Hyun-Woo; Kim, Yonghyun; Kim, Sang Ryong; Oh, Sang-Ha; Kim, Dong Woon; Chungnam National University; Chungnam National University Hospital; University of Alabama Tuscaloosa; Kyungpook National University
Neuropathic pain is a complex, chronic pain state characterized by hyperalgesia, allodynia, and spontaneous pain. Accumulating evidence has indicated that the microglial Toll-like receptor 4 (TLR4) and autophagy are implicated in neurodegenerative diseases, but their relationship and role in neuropathic pain remain unclear. In this study, we examined TLR4 and its association with autophagic activity using a chronic constriction injury (CCI)-induced neuropathic pain model in wild-type (WT) and TLR4-knockout (KO) mice. The mice were assigned into four groups: WT-Contralateral (Contra), WT-Ipsilateral (Ipsi), TLR4 KO-Contra, and TLR4 KO-Ipsi. Behavioral and mechanical allodynia tests and biochemical analysis of spinal cord tissue were conducted following CCI to the sciatic nerve. Compared with the Contra group, mechanical allodynia in both the WT-and TLR4 KO-Ipsi groups was significantly increased, and a marked decrease of allodynia was observed in the TLR4 KO-Ipsi group. Although glial cells were upregulated in the WT-Ipsi group, no significant change was observed in the TLR4 KO groups. Moreover, protein expression and immunoreactive cell regulation of autophagy (Beclin 1, p62) were significantly increased in the neurons, but not microglia, of WT-Ipsi group compared with the WT-Contra group. The level of PINK1, a marker for mitophagy was increased in the neurons of WT, but not in TLR4 KO mice. Together, these results show that TLR4-mediated p62 autophagic impairment plays an important role in the occurrence and development of neuropathic pain. And what is more, microglial TLR4-mediated microglial activation might be indirectly coupled to neuronal autophage.
The Small GTPase RAC1/CED-10 Is Essential in Maintaining Dopaminergic Neuron Function and Survival Against alpha-Synuclein-Induced Toxicity (vol 55, pg 7533, 2018)
(Springer, 2018) Kim, Hanna; Calatayud, Carles; Guha, Sanjib; Fernandez-Carasa, Irene; Berkowitz, Laura; Carballo-Carbajal, Iria; Ezquerra, Mario; Fernandez-Santiago, Ruben; Kapahi, Pankaj; Raya, Angel; Miranda-Vizuete, Antonio; Miguel Lizcano, Jose; Vila, Miquel; Caldwell, Kim A.; Caldwell, Guy A.; Consiglio, Antonella; Dalfo, Esther; University of Alabama Tuscaloosa; Institut d'Investigacio Biomedica de Bellvitge (IDIBELL); Bellvitge University Hospital; University of Barcelona; Hospital Duran i Reynals; CIBER - Centro de Investigacion Biomedica en Red; CIBERBBN; Centro de Medicina Regenerativa de Barcelona; Buck Institute for Research on Aging; Hospital Clinic de Barcelona; IDIBAPS; ICREA; Consejo Superior de Investigaciones Cientificas (CSIC); University of Sevilla; CSIC-JA-USE - Instituto de Biomedicina de Sevilla (IBIS); Virgen del Rocio University Hospital; Autonomous University of Barcelona; Universitat de Vic - Universitat Central de Catalunya (UVic-UCC)
With the author(s)' decision to opt for Open Choice the copyright of the article changed on March 2018 to A (c) The Author(s) 2018 and the name of one of the author was changed to "Sanjib Guha".
The Small GTPase RAC1/CED-10 Is Essential in Maintaining Dopaminergic Neuron Function and Survival Against alpha-Synuclein-Induced Toxicity
(Springer, 2018) Kim, Hanna; Calatayud, Caries; Guha, Sanjib; Fernandez-Carasa, Irene; Berkowitz, Laura; Carballo-Carbajal, Iria; Ezquerra, Mario; Fernandez-Santiago, Ruben; Kapahi, Pankaj; Raya, Angel; Miranda-Vizuete, Antonio; Miguel Lizcano, Jose; Vila, Miquel; Caldwell, Kim A.; Caldwell, Guy A.; Consiglio, Antonella; Dalfo, Esther; University of Alabama Tuscaloosa; Institut d'Investigacio Biomedica de Bellvitge (IDIBELL); Bellvitge University Hospital; University of Barcelona; Hospital Duran i Reynals; Centro de Medicina Regenerativa de Barcelona; Buck Institute for Research on Aging; Autonomous University of Barcelona; Hospital Universitari Vall d'Hebron; Vall d'Hebron Institut de Recerca (VHIR); Hospital Clinic de Barcelona; IDIBAPS; ICREA; Consejo Superior de Investigaciones Cientificas (CSIC); University of Sevilla; CSIC-JA-USE - Instituto de Biomedicina de Sevilla (IBIS); Virgen del Rocio University Hospital; Universitat de Vic - Universitat Central de Catalunya (UVic-UCC)
Parkinson's disease is associated with intracellular alpha-synuclein accumulation and ventral midbrain dopaminergic neuronal death in the Substantia Nigra of brain patients. The Rho GTPase pathway, mainly linking surface receptors to the organization of the actin and microtubule cytoskeletons, has been suggested to participate to Parkinson's disease pathogenesis. Nevertheless, its exact contribution remains obscure. To unveil the participation of the Rho GTPase family to the molecular pathogenesis of Parkinson's disease, we first used C elegans to demonstrate the role of the small GTPase RACI (ced-10 in the worm) in maintaining dopaminergic function and survival in the presence of alpha-synuclein. In addition, ced-10 mutant worms determined an increase of alpha-synuclein inclusions in comparison to control worms as well as an increase in autophagic vesicles. We then used a human neuroblastoma cells (M17) stably over-expressing alpha-synuclein and found that RAC1 function decreased the amount of amyloidogenic alpha-synuclein. Further, by using dopaminergic neurons derived firm patients of familial LRRIC2-Parkinson's disease we report that human RAC1 activity is essential in the regulation of dopaminergic cell death, alpha-synuclein accumulation, participates in neurite arborization and modulates autophagy. Thus, we determined for the first time that RAC1/ced-10 participates in Parkinson's disease associated pathogenesis and established RAC1/ced-10 as a new candidate for further investigation of Parkinson's disease associated mechanisms, mainly focused on dopaminergic function and survival against alpha-synuclein-induced toxicity.
A Novel Mutation in Brain Tumor Causes Both Neural Over-Proliferation and Neurodegeneration in Adult Drosophila
(Genetics Society of America, 2018) Loewen, Carin; Boekhoff-Falk, Grace; Ganetzky, Barry; Chtarbanova, Stanislava; University of Wisconsin Madison; University of Alabama Tuscaloosa
A screen for neuroprotective genes in Drosophila melanogaster led to the identification of a mutation that causes extreme, progressive loss of adult brain neuropil in conjunction with massive brain overgrowth. We mapped the mutation to the brain tumor (brat) locus, which encodes a tripartite motif-NCL-1, HT2A, and LIN-41 (TRIM-NHL) RNA-binding protein with established roles limiting stem cell proliferation in developing brain and ovary. However, a neuroprotective role for brat in the adult Drosophila brain has not been described previously. The new allele, brat(cheesehead) (brat(chs)), carries a mutation in the coiled-coil domain of the TRIM motif, and is temperature-sensitive. We demonstrate that mRNA and protein levels of neural stem cell genes are increased in heads of adult brat(chs) mutants and that the over-proliferation phenotype initiates prior to adult eclosion. We also report that disruption of an uncharacterized gene coding for a presumptive prolyl-4-hydroxylase strongly enhances the over-proliferation and neurodegeneration phenotypes. Together, our results reveal an unexpected role for brat that could be relevant to human cancer and neurodegenerative diseases.
Age-dependent impairment of disease tolerance is associated with a robust transcriptional response following RNA virus infection in Drosophila
(Oxford University Press, 2021) Sheffield, Lakbira; Sciambra, Noah; Evans, Alysa; Hagedorn, Eli; Goltz, Casey; Delfeld, Megan; Kuhns, Haley; Fierst, Janna L.; Chtarbanova, Stanislava; University of Alabama Tuscaloosa; University of Alabama Birmingham
Advanced age in humans is associated with greater susceptibility to and higher mortality rates from infections, including infections with some RNA viruses. The underlying innate immune mechanisms, which represent the first line of defense against pathogens, remain incompletely understood. Drosophila melanogaster is able to mount potent and evolutionarily conserved innate immune defenses against a variety of microorganisms including viruses and serves as an excellent model organism for studying host-pathogen interactions. With its relatively short lifespan, Drosophila also is an organism of choice for aging studies. Despite numerous advantages that this model offers, Drosophila has not been used to its full potential to investigate the response of the aged host to viral infection. Here, we show that, in comparison to younger flies, aged Drosophila succumb more rapidly to infection with the RNA-containing Flock House virus due to an age-dependent defect in disease tolerance. Relative to younger individuals, we find that older Drosophila mount transcriptional responses characterized by differential regulation of more genes and genes regulated to a greater extent. We show that loss of disease tolerance to Flock House virus with age associates with a stronger regulation of genes involved in apoptosis, some genes of the Drosophila immune deficiency NF-kappa B pathway, and genes whose products function in mitochondria and mitochondrial respiration. Our work shows that Drosophila can serve as a model to investigate host-virus interactions during aging and furthermore sets the stage for future analysis of the age-dependent mechanisms that govern survival and control of virus infections at older age.
Everyday Memory in People with Down Syndrome
(MDPI, 2021) Yang, Yingying; Himmelberger, Zachary M.; Robinson, Trent; Davis, Megan; Conners, Frances; Merrill, Edward; Montclair State University; University of Alabama Tuscaloosa
Although memory functions in people with Down Syndrome (DS) have been studied extensively, how well people with DS remember things about everyday life is not well understood. In the current study, 31 adolescents/young adults with DS and 26 with intellectual disabilities (ID) of mixed etiology (not DS) participated. They completed an everyday memory questionnaire about personal facts and recent events (e.g., school name, breakfast). They also completed a standard laboratory task of verbal long-term memory (LTM) where they recalled a list of unrelated words over trials. Results did not indicate impaired everyday memory, but impaired verbal LTM, in people with DS relative to people with mixed ID. Furthermore, the laboratory verbal LTM task predicted everyday memory for both groups after taking into account mental age equivalent. Our research showed both an independence and a connection between everyday memory and the standard laboratory memory task and has important research and clinical implications.
Chromosome-Scale Genome for a Red-Fruited, Perpetual Flowering and Runnerless Woodland Strawberry (Fragaria vesca)
(Frontiers, 2021) Alger, Elizabeth I.; Platts, Adrian E.; Deb, Sontosh K.; Luo, Xi; Ou, Shujun; Cao, Yao; Hummer, Kim E.; Xiong, Zhiyong; Knapp, Steven J.; Liu, Zhongchi; McKain, Michael R.; Edger, Patrick P.; Michigan State University; University of Alabama Tuscaloosa; Shahjalal University of Science & Technology (SUST); University of Maryland College Park; Iowa State University; Inner Mongolia University; United States Department of Agriculture (USDA); University of California Davis
Mindful Coping Power: Comparative Effects on Children's Reactive Aggression and Self-Regulation
(MDPI, 2021) Boxmeyer, Caroline L.; Miller, Shari; Romero, Devon E.; Powell, Nicole P.; Jones, Shannon; Qu, Lixin; Tueller, Stephen; Lochman, John E.; University of Alabama Tuscaloosa; University of Texas at San Antonio (UTSA); Research Triangle Institute
Coping Power (CP) is an evidence-based preventive intervention for youth with disruptive behavior problems. This study examined whether Mindful Coping Power (MCP), a novel adaptation which integrates mindfulness into CP, enhances program effects on children's reactive aggression and self-regulation. A pilot randomized design was utilized to estimate the effect sizes for MCP versus CP in a sample of 102 child participants (fifth grade students, predominantly low-middle income, 87% Black). MCP produced significantly greater improvement in children's self-reported dysregulation (emotional, behavioral, cognitive) than CP, including children's perceived anger modulation. Small to moderate effects favoring MCP were also observed for improvements in child-reported inhibitory control and breath awareness and parent-reported child attentional capacity and social skills. MCP did not yield a differential effect on teacher-rated reactive aggression. CP produced a stronger effect than MCP on parent-reported externalizing behavior problems. Although MCP did not enhance program effects on children's reactive aggression as expected, it did have enhancing effects on children's internal, embodied experiences (self-regulation, anger modulation, breath awareness). Future studies are needed to compare MCP and CP in a large scale, controlled efficacy trial and to examine whether MCP-produced improvements in children's internal experiences lead to improvements in their observable behavior over time.
Mass quarantine and mental health during COVID-19: A meta-analysis
(Elsevier, 2021) Jin, Yuchang; Sun, Tengwei; Zheng, Peixuan; An, Junxiu; Sichuan Normal University; University of Alabama Tuscaloosa; Chengdu University of Information Technology
To reveal the complex relationships between quarantine and mental health during COVID-19, a meta-analysis was conducted involving 34 articles and a total sample size of 134,061. As the relationship between quarantine and mental health was found to be affected by the sampling objects and national factors, a random-effects model was applied for the meta-analysis. First, a heterogeneity test and sensitivity analysis were conducted to determine whether there was heterogeneity in the samples, after which a funnel chart, Rosenthal's Classic Failsafe N test and Egger's test were applied to further determine whether there was publication bias in the included samples. Finally, a sub-group test was used to explore whether the sampling group and the country of origin had a moderating effect on the relationship between quarantine and mental health, which revealed that the relationship between quarantine and mental health was regulated and influenced by the sampled objects but was not affected by the country categories. The results indicated that: COVID-19 quarantine had varying impacts on individual anxiety, depression, and psychological stress; different groups had different regulatory effects on the relationship between quarantine and mental health; and country of origin had no moderating effect on quarantine and psychology. Background: COVID-19 is the most important topic in 2020, and mass quarantine is the measures for pandemic prevention and control around the world since 2020. To explore the relationships between mass quarantine and mental health during COVID-19, a meta-analysis was conducted involving 28 articles and a total sample size of 134,061. Method: As the relationship between mass quarantine and mental health was found to be affected by the sampling objects and national factors, a random-effects model was applied for the meta-analysis. First, a heterogeneity test and sensitivity analysis were conducted to determine whether there was heterogeneity in the samples, after which a funnel chart, Rosenthal's Classic Fail-safe N test and Egger's test were applied to further determine whether there was publication bias in the included samples. Finally, a sub-group test was used to explore whether the sampling group and the country of origin had a moderating effect on the relationship between mass quarantine and mental health. Results: COVID-19 quarantine had varying impacts on individual anxiety, depression, and psychological stress; different groups had different regulatory effects on the relationship between quarantine and mental health; and country of origin had no moderating effect on quarantine and mental health. Conclusions: This study employed a meta-analysis to examine the relationships between the COVID-19 pandemic mass quarantine measures and mental health factors such as anxiety, depression and stress, from which it was found that influence of quarantine on anxiety was stronger, the relationship between quarantine and mental health was affected by the sampled object, and there was no significant relationship between quarantine and country of origin in the sample population.
Motor Preparation and Execution for Performance Difficulty: Centroparietal Beta Activation during the Effort Expenditure for Rewards Task as a Function of Motivation
(MDPI, 2021) Wilhelm, Ricardo A.; Threadgill, A. Hunter; Gable, Philip A.; University of Alabama Tuscaloosa; Florida State University; University of Delaware
Debate exists as to the effects of anxiety in performance-based studies. However, no studies have examined the influence of motivation both in preparation of a motor movement and during movement performance. The present study measured beta activation in preparation for and during execution of the effort expenditure for rewards task (EEfRT), a button-pressing task consisting of easy and hard trials. Results indicated that motor preparation (i.e., reduced beta activation) was greater in preparation for hard trials than for easy trials. Additionally, motor preparation decreased (i.e., beta activation increased) over the course of hard trial execution. These results suggest that motor preparation is enhanced prior to more challenging tasks but that motor preparation declines as participants become closer to completing their goal in each challenging trial. These results provide insight into how beta activation facilitates effort expenditure for motor tasks varying in difficulty and motivation. The impact of these results on models of anxiety and performance is discussed.
FARCI: Fast and Robust Connectome Inference
(MDPI, 2021) Meamardoost, Saber; Bhattacharya, Mahasweta; Hwang, Eun Jung; Komiyama, Takaki; Mewes, Claudia; Wang, Linbing; Zhang, Ying; Gunawan, Rudiyanto; State University of New York (SUNY) Buffalo; University of California San Diego; Rosalind Franklin University Medical & Science; University of Alabama Tuscaloosa; Virginia Polytechnic Institute & State University; University of Rhode Island
The inference of neuronal connectome from large-scale neuronal activity recordings, such as two-photon Calcium imaging, represents an active area of research in computational neuroscience. In this work, we developed FARCI (Fast and Robust Connectome Inference), a MATLAB package for neuronal connectome inference from high-dimensional two-photon Calcium fluorescence data. We employed partial correlations as a measure of the functional association strength between pairs of neurons to reconstruct a neuronal connectome. We demonstrated using in silico datasets from the Neural Connectomics Challenge (NCC) and those generated using the state-of-the-art simulator of Neural Anatomy and Optimal Microscopy (NAOMi) that FARCI provides an accurate connectome and its performance is robust to network sizes, missing neurons, and noise levels. Moreover, FARCI is computationally efficient and highly scalable to large networks. In comparison with the best performing connectome inference algorithm in the NCC, Generalized Transfer Entropy (GTE), and Fluorescence Single Neuron and Network Analysis Package (FluoroSNNAP), FARCI produces more accurate networks over different network sizes, while providing significantly better computational speed and scaling.
Young Adults with a Parent with Dementia Show Early Abnormalities in Brain Activity and Brain Volume in the Hippocampus: A Matched Case-Control Study
(MDPI, 2022) McDonough, Ian M.; Mayhugh, Christopher; Moore, Mary Katherine; Brasfield, Mikenzi B.; Letang, Sarah K.; Madan, Christopher R.; Allen, Rebecca S.; University of Alabama Tuscaloosa; University of Nottingham
Having a parent with Alzheimer's disease (AD) and related dementias confers a risk for developing these types of neurocognitive disorders in old age, but the mechanisms underlying this risk are understudied. Although the hippocampus is often one of the earliest brain regions to undergo change in the AD process, we do not know how early in the lifespan such changes might occur or whether they differ early in the lifespan as a function of family history of AD. Using a rare sample, young adults with a parent with late-onset dementia, we investigated whether brain abnormalities could already be detected compared with a matched sample. Moreover, we employed simple yet novel techniques to characterize resting brain activity (mean and standard deviation) and brain volume in the hippocampus. Young adults with a parent with dementia showed greater resting mean activity and smaller volumes in the left hippocampus compared to young adults without a parent with dementia. Having a parent with AD or a related dementia was associated with early aberrations in brain function and structure. This early hippocampal dysfunction may be due to aberrant neural firing, which may increase the risk for a diagnosis of dementia in old age.
Lipase regulation of cellular fatty acid homeostasis as a Parkinson's disease therapeutic strategy
(Nature Portfolio, 2022) Fanning, Saranna; Cirka, Haley; Thies, Jennifer L.; Jeong, Jooyoung; Niemi, Sarah M.; Yoon, Joon; Ho, Gary P. H.; Pacheco, Julian A.; Dettmer, Ulf; Liu, Lei; Clish, Clary B.; Hodgetts, Kevin J.; Hutchinson, John N.; Muratore, Christina R.; Caldwell, Guy A.; Caldwell, Kim A.; Selkoe, Dennis; Harvard University; Brigham & Women's Hospital; Harvard Medical School; University of Alabama Tuscaloosa; Harvard T.H. Chan School of Public Health; Massachusetts Institute of Technology (MIT); Broad Institute
Synucleinopathy (Parkinson's disease (PD); Lewy body dementia) disease-modifying treatments represent a huge unmet medical need. Although the PD-causing protein alpha-synuclein (alpha S) interacts with lipids and fatty acids (FA) physiologically and pathologically, targeting FA homeostasis for therapeutics is in its infancy. We identified the PD-relevant target stearoyl-coA desaturase: inhibiting monounsaturated FA synthesis reversed PD phenotypes. However, lipid degradation also generates FA pools. Here, we identify the rate-limiting lipase enzyme, LIPE, as a candidate target. Decreasing LIPE in human neural cells reduced alpha S inclusions. Patient alpha S triplication vs. corrected neurons had increased pSer129 and insoluble alpha S and decreased alpha S tetramer:monomer ratios. LIPE inhibition rescued all these and the abnormal unfolded protein response. LIPE inhibitors decreased pSer129 and restored tetramer:monomer equilibrium in alpha S E46K-expressing human neurons. LIPE reduction in vivo alleviated alpha S-induced dopaminergic neurodegeneration in Caenorhabditis elegans. Co-regulating FA synthesis and degradation proved additive in rescuing PD phenotypes, signifying co-targeting as a therapeutic strategy.

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