bluuebunny/crossref_metadata_2025 huggingface dataset:
A-41 Not Just a “Clumsy” Kid: A Case Study of Developmental Coordination Disorder
Authors: Del Pozzo Jill , Weiss Erica F , Bronshteyn Diana , Masur David M , McGinley John J , Facchini Ronda F
Published: August 2021

Objective

Developmental Discoordination Disorder (DCD) is an often overlooked and seldom diagnosed neurodevelopmental condition marked by impairments in motor skills. Lacking identifiable medical or neurological etiology, children with DCD often have preserved intellectual abilities. Comorbidity is common, including ADHD and specific learning disability. Despite extensive evidence of significant impact on daily activities and academics due to differences in motor behaviors, DCD difficulties are regularly treated as behavioral problems.

Method

Neuropsychological evaluation of an 8-year-old boy with a possible reading delay and inability to perform some age-appropriate academic and self-care tasks.

Results

Average overall ability with very strong verbal performances; intact visual perceptual processing, memory, and non-written language. Academics are within expected range, although graphomotor weakness impacted academic performances on tasks with written demands. Patient appeared clumsy and awkward with low muscle tone, poor balance, and difficulty learning new motor skills. Impaired fine motor control, handwriting, gait, gross motor skills, motor planning, coordination, and oromotor weakness as well as inferior verbal language abilities were evident. Impulsivity, inattention, poor planning, and poor self-monitoring were also evident.

Conclusions

DCD is evidenced by impairment in fine and gross motor skills, oromotor skills, motor planning, energy, and coordination with clear discrepancy between motor abilities and abilities in other areas, specifically language. In our case, DCD features were overlooked despite wide ranging impact. ADHD and SLD with impairment in written expression were concurrent. This case highlights the need for greater appreciation of DCD so that children can benefit from early detection and intervention considering the life-long implications of the disorder.
A-45 Closing the Gap in the Neuropsychology Pipeline Via Mentorship Focusing on African American Students
Authors: Reyes Anny , McBride Willie F , Anderson Kendra , Montgomery Valencia , Ray Courtney
Published: August 2021

Objective

A core mission of the Society for Black Neuropsychology (SBN) is to increase the representation of neuropsychologists, students, and scholars from diverse backgrounds. As such, SBN developed a 12-month mentoring program for trainees at all levels. The SBN Mentorship Program includes four components: mentoring where mentees are paired with a mentor based on interest and needs; professional development webinars; application materials resources; virtual social hours.

Methods

First, a call for mentors and mentees was distributed via SBN’s and related listservs and social media. Second, pairings were based on mentee training level, clinical/research interest, needs (e.g., applying to doctoral programs, cultural competency, securing funding), and additional preferences (e.g., matched on the same racial/ethnic background, sex/gender, geographical location). Surveys will be distributed at 6-months and upon completion of the mentorship program to evaluate pairings, webinars, and overall impact of the program.

Results

A total of 60 mentors from diverse backgrounds and different levels of training enrolled. Thirty-five underrepresented minority (URM) trainees were matched with mentors based on their level of training, interest, and needs. The mentee cohort comprised of undergraduate/post-baccalaureate (30%), masters (5%), and doctoral students (60%), and post-doctoral fellows (5%). The cohort was approximately 77% female and all mentees identified as an URM in academia (URM: 85.7% Black, 14.3% Latinx).

Conclusion

Mentorship programs represent a vital but often overlooked component of trainee success. Mentorship programs sponsored by organizations such as SBN can help increase the number of URM students in neuropsychology and provide the mentorship needed to navigate barriers URM students often encounter in academia.
A-47 The Interplay between Achievement Scores in Math Ability, Visual Working Memory, and Perceptual Reasoning across Race in an Adult Population
Authors: Harrigan D'Shawn L , Kotalik Kayla , Arias Brittny , Golden Charles J
Published: August 2021

Objective

The aim of this study is to measure the associations between overall math ability, visual working memory, and perceptual reasoning.

Method

Data stemmed from an ongoing de-identified database aof clinical adults. Participants were administered the WAIS-IV, KM-3, and WMS-IV. The sample consisted of Caucasians (N = 671, M_edu = 14,45.7% males & 52.5% females), African Americans (N = 154, M_edu = 13, 43.5% males & 56.5% females), and Hispanic (N = 194, M_edu = 13,44.8% males & 53.6% females). Participant’s age ranged from 16 to 81, with a mean of 31.06.

Results

The analysis corrected for age, education, and gender. The relationship between PR and KM-3 was 0.505 for Caucasians, 0.782 for African Americans, and 0.769 for Hispanics, all p < 0.05. A Fisher Z transformation indicated significance on PR and KM-3 between Caucasians and Hispanics, p < 0.001. The relationship between KM-3 and VWM was 0.408 for Caucasians, 0.828 for African Americans, and 0.591 for Hispanics, all p < 0.05. A Fisher Z transformation indicated significance on KM-3 and VWM between Caucasians and African Americans, p = 0.020. The relationship between KM-3 and VP was 0.349 for Caucasians, 0.584 for African Americans, and.733 for Hispanics, all p < 0.05. A Fisher Z transformation indicated significance on KM-3 and VP between Caucasians and Hispanics, p = 0.04.

Discussion

Closer analysis of performance between race reveals statistically stronger associations between mathematical ability and perceptual/memory tasks that are visuoconstructional in nature for African Americans and Hispanics when compared to Caucasians. The findings of this study may allude to different approach’s African Americans and Hispanics may use (e.g., mental rotation) when solving mathematical computations.
A-53 The Relationship between Age and TMT-A Performance in Patients with Heart Failure
Authors: Lackey Nicholas S , Nemanim Natasha , Hauson Alexander O , Connors Eric J , Pollard Anna , Flora-Tostado Christopher , Stelmach Nicholas , Sarkissians Sharis , Walker Alyssa , Barlet Brianna
Published: August 2021

Objective

A previous meta-analysis utilized the Trail Making Test A (TMT-A) to measure the impact of heart failure (HF) on attention. A near medium effect size with moderate heterogeneity was observed, the HF group performed worse than healthy controls (HC). This study explores if the age of the HF group moderates differences in the performance of individuals with HF versus HC on TMT-A.

Data Selection

Two researchers searched eight databases, extracted data, and calculated effect sizes as part of a larger study. Inclusion criteria were: (a) adults with HF (New York Heart Association severity II or higher), (b) comparison to a HC group, (c) standardized neuropsychological/cognitive testing, and (d) adequate data to calculate effect sizes. Exclusion criteria were: (a) participants had other types of major organ failure, (b) the article was not in English, or (c) there was a risk of sample overlap with another included study. A total of six articles were included in this sub-study (Total HF n = 602 and HC n = 342). The unrestricted maximum likelihood computational model was used for the meta-regression.

Data Synthesis

Studies included in the meta-regression evidenced a statistically significant medium effect size estimate with moderate heterogeneity (k = 6, g = 0.636, p < 0.001, I2 = 56.85%). The meta-regression was statistically significant (slope = −0.0515, p = 0.0016, Qmodel = 9.86, df = 1, p = 0.0016).

Conclusions

Individuals with HF performed worse on the TMT-A than HC. Age accounted for a significant proportion of the observed heterogeneity in the meta-regression. Future research should examine the relationship of age on cognition in individuals with HF.
A-55 Neuropsychological Findings Associated with Progressive Lesion Development in Cerebral Cavernous Malformation Secondary to PDCD10 Mutation
Authors: Phillips Matthew , Wisinger Amanda , Fink Joseph
Published: August 2021

Objective

A rare mutation in the PDCD10 gene causes cerebral cavernous malformations, which can result in multiple brain hemorrhages and hundreds of lesions. Up to 50% of individuals with the PDCD10 mutation remain symptom-free throughout their lives; however, others can suffer from seizures or focal neurologic deficits. Participant: A 67-year-old Caucasian male presented for a neuropsychological re-evaluation (2020) following a progressive decline in his memory and attention dating back 20 years. A baseline neuropsychological evaluation was obtained 7 years ago. Relevant medical history included a 5 mm left falcine meningioma, epilepsy, obstructive sleep apnea, hypertension, and type II diabetes. Neuroimaging revealed over 250 scattered lesions that had advanced over the past 7 years, particularly in the paramedian pontine reticular formation, left inferior cerebellum, and right middle frontal gyrus.

Results

His neurocognitive profile was marked by mild impairments in immediate verbal memory. The remainder of his cognitive profile was average. Compared to his 2013 evaluation, he showed only a minimal decline in verbal memory, but he showed slight improvements in the domains of executive functioning, visuospatial abilities, and language.

Conclusion

Despite the marked progression of lesions documented on current neuroimaging, aside from immediate verbal memory problems the patient’s neurocognitive functioning was relatively well-preserved. He even exhibited minor improvements within several domains. Given the patient’s current neurocognitive status, this case illustrates the importance of comprehensive neuropsychological testing in cases that would appear more severe based on neuroimaging data alone. Relatedly, progression of neuropathological disease burden on neuroimaging is not necessarily accompanied by consistent progression of neuropsychological dysfunction.
A-58 Unusual Presentation of Anti-NMDAR Encephalitis in a Young Adult Male: A Case Study
Authors: Smetana Racheal , Broshek Donna
Published: August 2021

Objective

To illustrate an unusual presentation of anti-n-methyl-D-aspartate-receptor (anti-NMDAR) encephalitis in a young adult male. Anti-NMDAR encephalitis is an autoimmune-mediated disorder with psychiatric and neurological features that can have lasting impact on cognition. Unique presentation, diagnosis, and assessment are presented.

Method

Patient is a 28-year-old, Caucasian male with a history of bipolar disorder. Initial hospital presentation was characterized by headache, tremor, and acute altered mental status. Imaging revealed chronic meningitis with diffuse leptomeningeal enhancement/multiple cranial nerve enhancement, hydrocephalus, and Chiari I malformation. He underwent external ventricular drain (EVD) placement and was discharged upon stabilization. He presented 1 month later with symptom recurrence and interval development of hydrocephalus. CSF studies were positive for NMDAR antibody. He was treated with immunotherapy. His 3-month long hospitalization was complicated by acute respiratory failure and intracerebral and intraventricular hemorrhages. He was discharged to 1 month of inpatient rehabilitation.

Results

Neuropsychological assessment was completed 4 months following discharge from rehabilitation. Visual deficits due to grade 1 papilledema complicated testing. Results revealed frontal deficits (focused attention, processing, and executive functions), with intact verbal learning/memory. This deviates from previous literature that specify verbal memory dysfunction as a core long-term outcome of anti-NMDAR encephalitis.

Conclusions

This case highlights an unusual presentation and neuropsychological assessment of anti-NMDAR encephalitis. Rare presentations of anti-NMDAR encephalitis can preclude clinical diagnosis and compromise long-term cognitive outcomes if not rapidly and effectively treated. Additionally, mood symptoms may have been early manifestation of the patient’s disease process. Despite acute complications, he demonstrated remarkable functional and cognitive recovery.
A-61 Predictors of Subjective and Objective Everyday Functioning in Middle-Aged and Older Adults with HIV
Authors: Jacob Alexandra E , Crowe Michael , Fazeli Pariya L , Vance David E
Published: August 2021

Objective

Older adults with HIV are at increased risk for difficulties with instrumental activities of daily living (IADLs). Awareness of their functional capacity has emerged as an important area for research, but it is not well studied in PWH. The purpose of this study is: (1) to identify factors associated with subjective and objective IADL difficulty in PWH and (2) to identify factors associated with under- or over-reporting of IADL difficulties.

Methods

This cross-sectional study included 261 adults with HIV. Participants completed a neuropsychological battery, self-report and performance-based measures of IADLs. Self-report measures included the Patient’s Assessment of Own Functioning Inventory (PAOFI) and the Lawton and Brody IADL Questionnaire. The Timed Instrumental Activities of Daily Living (TIADL) task was used as an objective measure. Hierarchical multiple regressions were performed to identify factors associated with subjective and objective assessment of everyday functioning as well as factors associated with discrepancy between self-report and actual performance of IADLS.

Results

On the PAOFI, higher depression (p = 0.001), lower conscientiousness (p > 0.001), and better processing speed (p = 0.017) predicted worse functioning. On the Lawton and Brody, higher depression (p = 0.049) predicted of worse functioning. On the TIADL, older age (p = 0.1), lower WRAT-4 score (p > 0.001), worse processing speed (p > 0.001), and worse motor function (p = 0.1) were associated with worse performance. Processing speed predicted discrepancy between subjective and objective performance of IADLs (p = 0.1).

Conclusions

Several demographic, cognitive, and personality variables are associated with worse subjective and objective everyday functioning, as well as an individual’s ability to accurately self-appraise their functional capacity.
A-64 Neuropsychological Assessment in Bilateral Perisylvian Polymicrogyria: A Tool for Data-Driven Intervention
Authors: Grow Melissa , Culotta Stephanie
Published: August 2021

Objective

This case study examined neurocognitive features associated with a rare genetic/neurological disorder impacting the cerebral cortex. Bilateral perisylvian polymicrogyria (BPP) is characterized by abnormal embryonic growth affecting both sides of the brain near the Sylvian fissure. BPP occurs randomly though researchers suspect an underlying genetic abnormality that may have autosomal recessive inheritance. Neurodevelopmental manifestations include neurocognition marked by EEG abnormalities, impaired motor function, and deficits in speech articulation, language development, learning and memory, and adaptive skills.

Method

A 13-year 7-month-old male with BPP, detected at 24 months by MRI, was seen for neuropsychological assessment to guide habilitative, academic and adaptive interventions. Relevant medical history includes stimulant medication and pharyngeal flap surgery. Parental concerns include the provision of appropriate special education services and withdrawal behaviors.

Results

Assessment revealed a complex neuropsychological profile characterized by nonverbal versus verbal intellectual strengths, receptive-expressive language impairment, underlying deficits in phonemic awareness, diminished fine motor speed, and diminished verbal fluency. Verbal list learning, semantic memory, and attention were intact. Mild elevations were evident for anxiety symptoms.

Conclusion

BPP, a rare genetic disorder, represents significant challenges for affected children. In this case study, a 13-year 7-month-old youngster’s assessment revealed underlying neurocognitive and neuromotor deficits most pronounced in aspects of language, speech articulation, select domains of executive functioning and academic skills. Areas of strength, including verbal memory and semantic recall, were indicated and merit consideration in developing appropriate interventions. This case study illustrates the value of neuropsychological assessment in guiding therapeutic interventions, pharmacotherapy, and appropriate educational services in this rare neurological disorder.
A-69 Baseline Predictors of Longitudinal SDMT Performance in Individuals with Multiple Sclerosis
Authors: Cadden Margaret , Barker Lindsay , Healy Brian , Chitnis Tanuja , Weiner Howard , Glanz Bonnie
Published: August 2021

Objective

More than half of persons with MS (PwMS) experience cognitive difficulties during the course of their illness. However, not everyone develops cognitive problems suggesting a role for important moderating factors. The object of the current study was to identify baseline predictors of cognitive trajectories in PwMS.

Methods

680 PwMS completed the Symbol Digit Modalities Test (SDMT) and a battery of patient-reported outcome (PRO) measures as part their participation in The Comprehensive Longitudinal Investigation of Multiple Sclerosis at Brigham and Women’s Hospital (CLIMB). Each participant had at least 2 SDMT measurements as well as demographic (age, sex), clinical (EDSS, disease duration, course type), and PRO (fatigue, depression, and quality of life) data. Participants had a concurrent brain MRI scan at the time of the baseline SDMT measurement; intracranial cavity (ICC) was calculated for each participant as a proxy of brain reserve. The association between each baseline measure and the longitudinal change in the SDMT over the course of the follow-up period was calculated using a linear mixed effects model.

Results

Increased baseline age (95% CI: −0.29, −0.06; p = 0.002), increased baseline EDSS (95% CI: −0.24, −0.01; p = 0.037), and decreased baseline ICC (95% CI: 0.02, 0.25; p = 0.023) were each associated with a greater decline in the SDMT score longitudinally. Although most PRO measures were cross-sectionally correlated with SDMT performance, none were associated with longitudinal change.

Discussion

Older individuals and those with more clinical disability are likely to experience declines in SDMT performance over time. Individuals with high baseline brain reserve tend to have more favorable SDMT trajectories.
A-71 Subjective Employment Concerns: Correlates and Impact on Employment Status One Year Later in Women with Multiple Sclerosis
Authors: Cohen Jenna N , Stimmel Marnina , Foley Frederick
Published: August 2021

Objective

Loss of employment is common in multiple sclerosis (MS) and is associated with fatigue, depression, and cognitive dysfunction. This study looked at a “low-risk” group of women, with subclinical levels of these factors, to evaluate whether subjective concerns about employment would relate to decreased employment status over time. Secondarily, fatigue, depressive symptoms, and cognition were also examined in relation to employment concerns at baseline, to determine whether subjective concerns might indicate prodromal psychiatric and cognitive dysfunction.

Methods

Our sample includes 52 employed women with MS who participated in a larger quasi-experimental employment study. Screening included open-ended questions about employment concerns and measures of fatigue (Fatigue Severity Scale), depression (Patient Health Questionnaire), and cognitive functioning (Symbol-Digit Modalities Test). Because this subset of women were considered “low-risk,” they were followed over time (1 year) with no active intervention.

Results

Overall, 16/52 women (44%) voiced employment concerns. A chi-square analysis revealed that 5 (31.3%) of those women had decreased employment status at one year, while only 3 (8.3%) women without employment concerns had decreased employment status (p = 0.049, Fisher’s exact). Comparison of women with and without employment concerns (independent t-tests), indicated that those with concerns had higher depressive symptoms (p = 0.017); groups did not differ in cognitive functioning or fatigue at baseline.

Conclusions

Findings suggest that women with MS who were previously thought to be “low-risk” may still experience negative functional outcomes such as decreased employment status, when they voice subjective employment concerns. Employment concerns may also indicate prodromal depressive symptoms.
Soluble adenylyl cyclase inhibition prevents human sperm functions essential for fertilization
Authors: Balbach Melanie , Ghanem Lubna , Rossetti Thomas , Kaur Navpreet , Ritagliati Carla , Ferreira Jacob , Krapf Dario , Puga Molina Lis C , Santi Celia Maria , Hansen Jan Niklas , Wachten Dagmar , Fushimi Makoto , Meinke Peter T , Buck Jochen , Levin Lonny R
Published: August 2021

Soluble adenylyl cyclase (sAC: ADCY10) has been genetically confirmed to be essential for male fertility in mice and humans. In mice, ex vivo studies of dormant, caudal epididymal sperm demonstrated that sAC is required for initiating capacitation and activating motility. We now use an improved sAC inhibitor, TDI-10229, for a comprehensive analysis of sAC function in mouse and human sperm. In contrast to caudal epididymal mouse sperm, human sperm are collected post-ejaculation, after sAC activity has already been stimulated. In addition to preventing the capacitation-induced stimulation of sAC and protein kinase A activities, tyrosine phosphorylation, alkalinization, beat frequency and acrosome reaction in dormant mouse sperm, sAC inhibitors interrupt each of these capacitation-induced changes in ejaculated human sperm. Furthermore, we show for the first time that sAC is required during acrosomal exocytosis in mouse and human sperm. These data define sAC inhibitors as candidates for non-hormonal, on-demand contraceptives suitable for delivery via intravaginal devices in women.
Intragenic tRNA-promoted R-loops orchestrate transcription interference for plant oxidative stress responses
Authors: Liu Kunpeng , Sun Qianwen
Published: August 2021

Eukaryotic genomes are transcribed by at least three RNA polymerases, RNAPI, II, and III. Co-transcriptional R-loops play diverse roles in genome regulation and maintenance. However, little is known about how R-loops regulate transcription interference, the transcriptional event that is caused by different RNA polymerases transcribing the same genomic templates. Here, we established that the intragenic transfer RNA (tRNA) genes can promote sense R-loop enrichment (named intra-tR-loops) in Arabidopsis thaliana, and found that intra-tR-loops are decreased in an RNAPIII mutant, NUCLEAR RNA POLYMERASE C, SUBUNIT 7(nrpc7-1). NRPC7 is co-localized with RNAPIIS2P at intragenic tRNA genes and interferes with RNAPIIS2P elongation. Conversely, the binding of NRPC7 at intragenic tRNA genes is increased following inhibition of RNAPII elongation. The transcription of specific tRNA host genes is inhibited by RNAPIII, and the inhibition of tRNA host genes is intra-tR-loop dependent. Moreover, alleviating the inhibition of tRNAPro-induced intra-tR-loops on its host gene AtNUDX1 promotes oxidative stress tolerance in A. thaliana. Our work suggests intra-tR-loops regulate host gene expression by modulating RNA polymerases interference.
Identifying and tackling racial disparities in healthcare
Authors: Butler Anisa , Covington Kyla , Parsh Bridget
Published: August 2021

The US healthcare system is plagued with inequities that disproportionately impact people of color and other marginalized communities. This article discusses some of the key reasons behind these historic and current health disparities, identifies key terms, and discusses strategies for nurses who are interested in allying with efforts to tackle inequity and racism in American healthcare.
Hybrid immunity versus vaccine-induced immunity against SARS CoV2 in Patients with Autoimmune Rheumatic Diseases
Authors: Shenoy Padmanabha , Ahmed Sakir , Paul Aby , Cherian Somy , Umesh Rashwith , shenoy Veena , Vijayan Anuroopa , Babu Sageer , Nivin S , Thambi Arya
Published: August 2021

Introduction

Single-dose COVID-19 vaccines in healthy individuals with past COVID-19 infections seem to provide better immunity than double doses in COVID-19 unexposed individuals. However, it is not known whether the same is true for patients with autoimmune rheumatic diseases (AIRD) who are on immunosuppressants.

Methods

We identified 30 patients with AIRD who took a single dose of the ChAdOx1 vaccine post-COVID-19 infection. Age, sex and disease similar patients were enrolled in to three groups of 30 each who had (1) past infection with COVID-19 but no vaccine, (2) a single dose of ChAdOx1 and (3) double doses of ChAdOx1. Sera were collected from each patient approximately 30 days after last vaccine dose or since the onset of COVID19 symptoms (in the unvaccinated group). Antibodies to spike protein were estimated and virus neutralization potential of sera was tested.

Results

Baseline characteristics including drug usage was similar betweenthe groups. Seroconversion occurred in 25(83%), 23(77%), 27(90%), and 30(100%) in natural infection, single-dose vaccine, double dose vaccine, and infection +single dose vaccine groups respectively. Mean antibody titres (10076.8±8998) in the last group were at least 6-100x higher than in the other 3 groups. Also, the infection +vaccine group had the highest neutralization potential of 83.37 % as compared to 45.4% in the fully vaccinated group.

Conclusion

The hybrid immunity with a single dose of the vector-based vaccine post-infection seems to be superior to double dosage of the vaccine in patients with AIRD. A universal vaccination strategy involving a single dose of vaccine for all individuals with previous COVID-19 infection seems to be effective in these patients also.

What is already known about this subject?

A single dose of an RNA based COVID-19 vaccine after COVID-19 natural infection provides superior immune protection as compared to double doses of vaccines in infection naïve persons

A second dose of vaccine in healthy people who had infection previously does not increase the immune protection but may paradoxically induce tolerance

Vaccine responses in patients with autoimmune rheumatic diseases(AIRD) may be suboptimal due to underlying disease or the use of immunosuppressants.

What does this study add?

Hybrid-induced immunity (single vaccine post COVID-19 infection) produces adequate vaccine responses in patients with AIRD, non-inferior to double dose of vaccine

Besides mRNA vaccines, the adenoviral vector vaccine AZD1222 also demonstrates this hybrid phenomenon.

How might this impact on clinical practice?

Vaccination policies can consider providing only a single vaccine in those who had previous COVID-19 infection. This strategy has been shown not to be harmful for patients with AIRD. This will help reduce vaccine shortages.
May a Strain Chlamydia Isolated From SARS Patient’s Autopsy Issues Inhibit the Proliferation of SARS-CoV? An Early Observation in Vitro
Authors: Quan Xing , Liu Weifei
Published: August 2021

We found that a strain chlamydia isolated from SARS patient’s autopsy issues could decrease the proliferation of SARS-CoV in vitro; The inhibitory factors distribute both in the extracellular and intracellular cultures.
S-acylation stabilizes ligand-induced receptor kinase complex formation during plant pattern-triggered immune signalling
Authors: Hurst Charlotte H. , Turnbull Dionne , Xhelilaj Kaltra , Myles Sally , Pflughaupt Robin L. , Kopischke Michaela , Davies Paul , Jones Susan , Robatzek Silke , Zipfel Cyril , Gronnier Julien , Hemsley Piers A.
Published: August 2021

Plant receptor kinases are key transducers of extracellular stimuli, such as the presence of beneficial or pathogenic microbes or secreted signalling molecules. Receptor kinases are regulated by numerous post-translational modifications. Here, using the immune receptor kinases FLS2 and EFR, we show that S-acylation at a cysteine conserved in all plant receptor kinases is crucial for function. S-acylation involves the addition of long-chain fatty acids to cysteine residues within proteins, altering their biophysical properties and behaviour within the membrane environment. We observe S-acylation of FLS2 at C-terminal kinase domain cysteine residues within minutes following perception of its ligand flg22, in a BAK1 co-receptor dependent manner. We demonstrate that S-acylation is essential for FLS2-mediated immune signalling and resistance to bacterial infection. Similarly, mutating the corresponding conserved cysteine residue in EFR supressed elf18 triggered signalling. Analysis of unstimulated and activated FLS2-containing complexes using microscopy, detergents and native membrane DIBMA nanodiscs indicates that S-acylation stabilises and promotes retention of activated receptor kinase complexes at the plasma membrane to increase signalling efficiency.
Flanking sequences regulate the toxicity, non-ATG translation, and aggregation of RNA with tandem CAG Repeats
Authors: Das Michael R. , Chang Yeonji , Saunders Reuben , Zhang Nan , Tomberlin Colson , Vale Ronald D. , Jain Ankur
Published: August 2021

Nucleotide repeat-expansions cause several neurodegenerative disorders, including Huntington’s disease and spinocerebellar ataxia. The expanded repeat-containing RNA transcribed from the affected loci agglomerate in the nucleus as pathogenic foci. Here we demonstrate that depending on their surrounding sequence context, RNAs with expanded CAG repeats can also undergo nuclear export and aggregate in the cytoplasm. Cytoplasmic aggregation of repeat-containing RNA coincides with several disease hallmarks, including repeat-associated non-AUG (RAN) translation, mislocalization of RNA binding proteins, and cell toxicity. Interestingly, the repeat-containing RNA co-aggregate with RAN translation products. Inhibition of RAN translation prevents cytoplasmic RNA aggregation and also alleviates cell toxicity. Our findings provide a cogent explanation for aberrant cytoplasmic localization of RNA binding proteins and implicate cis-acting flanking sequences in mediating RAN translation and disease.
Elevation of major constitutive heat shock proteins is heat shock factor independent and essential for establishment and growth of Lgl loss and Yorkie gain mediated tumors in Drosophila
Authors: Singh Gunjan , Chakraborty Saptomee , Lakhotia Subhash C.
Published: August 2021

Cancer cells generally overexpress heat shock proteins (Hsps), the major components of cellular stress response, to overcome and survive the diverse stresses. However, the specific roles of Hsps in initiation and establishment of cancers remain unclear. Using loss of Lgl-mediated epithelial tumorigenesis in Drosophila, we induced tumorigenic somatic clones of different genetic backgrounds to examine the temporal and spatial expression and roles of major heat shock proteins in tumor growth. The constitutively expressed Hsp83, Hsc70 (heat shock cognate), Hsp60 and Hsp27 show elevated levels in all cells of the tumorigenic clone since early stages, which persists till their transformation. However, the stress-inducible Hsp70 is expressd only in a few cells at later stage of established tumorous clones that show high F-actin aggregation. Intriguingly, levels of heat shock factor (HSF), the master regulator of Hsps, remain unaltered in these tumorous cells and its down-regulation does not affect tumorigenic growth of lgl− clones overexpressing Yorkie, although down-regulation of Hsp83 prevents their survival and growth. Interestingly, overexpression of HSF or Hsp83 in lgl− cells makes them competitively successfully in establishing tumorous clones. These results show that the major constitutively expressed Hsps, but not the stress-inducible Hsp70, are involved in early as well as late stages of epithelial tumors and their elevated expression in lgl− clones co-overexpressing Yorkie is independent of HSF.
Effects of intra-hippocampal corticosterone and sleep on consolidation of complex memory of aversive experience in rats
Authors: Brukhnová Alena , Szczurowska Ewa , Vejmola Čestmír , Horsley Rachel R. , Kelemen Eduard
Published: August 2021

Formation and consolidation of memories for highly stressful (traumatic) events is a complex process that involves interplay between multiple memory systems and has implications for etiology and treatment of stress- and trauma-related disorders. Here we study effects of sleep/wake state and high intra-hippocampal corticosterone on consolidation of aversive contextual memories as well as consolidation of association between simple trauma-related cues and fear response in rats. Animals were implanted with EEG and EMG electrodes for sleep assessment and cannulas for intra-hippocampal corticosterone application. They were familiarized to a “safe box” and then trained in fear conditioning paradigm in a distinct “shock box” with a prominent simple auditory cue serving as a phasic background cue. Immediately after conditioning, animals received bilateral intra-hippocampal saline (1μl) or corticosterone (10ng in 1μl saline) injection and were either allowed to sleep or were kept awake for a following two-hour consolidation period. Memory test twenty-four hours later revealed that the saline-injected animals with sleep during consolidation had significantly stronger freezing response in the shock box compared to the safe box as well as increased freezing in response to the tone. Lack of post-learning sleep in saline injected animals led to generalization of fear response to the safe context, while association between simple cue and fear response was preserved. High intra-hippocampal corticosterone level during memory consolidation led to generalization of fear response to the safe context, regardless of sleep/wake state, while enhancement of response to single stimulus was not observed. Our results show how manipulation of conditions during consolidation can lead to greatly variable complex memories for a traumatic episode and distinct behavioral outcomes.

Highlights

We studied effect of sleep and intrahippocampal corticosterone on consolidation of memories surrounding stressful event modeled by fear conditioning in rats.

Sleep following traumatic fear conditioning event is important for subsequent manifestation of fear response (freezing) specifically in the context of traumatic event but not in a neutral safe context.

Lack of sleep or high intra-hippocampal corticosterone level during memory consolidation leads to generalization of fear response to both the traumatic and safe context.

Increased freezing in response to a trauma-related auditory cue was observed in saline injected rats regardless of wake/sleep state during consolidation.

Post-learning intra-hippocampal corticosterone injection blocked response to a trauma-related auditory cue regardless of wake/sleep state during consolidation.
Plus and minus ends of microtubule respond asymmetrically to kinesin binding by a long range directionally driven allosteric mechanism
Authors: Vu Huong T. , Zhang Zhechun , Tehver Riina , Thirumalai D.
Published: August 2021

Many members in the kinesin superfamily walk predominantly towards the plus end of the micro-tubule (MT) in a hand-over-hand manner. Despite great progress in elucidating the mechanism of stepping kinetics, the origin of stepping directionality is not fully understood. To provide quantitative insights into this important issue, we represent the structures of conventional kinesin (Kin1), MT, and the Kin1-MT complex using the elastic network model, and calculate the residue-dependent responses to a local perturbation in these constructs. Fluctuations in the residues in the β domain of the α/β-tubulin are distinct from the α domain. Surprisingly, the Kin1-induced asymmetry, which is more pronounced in α/β-tubulin in the plus end of MT than in the minus end, propagates spatially across multiple α/β-tubulin dimers. Kin1 binding expands the MT lattice by mechanical stresses, resulting in a transition in the cleft of α/β tubulin dimer between a closed (CC for closed cleft) state (not poised for Kin1 to bind) to an open (OC for open cleft) binding competent state. The long-range asymmetric responses in the MT, leading to the creation of OC states with high probability in several α/β dimers on the plus end of the bound Kin1, is needed for the motor to take multiple steps towards the plus end of the MT. Reciprocally, kinesin binding to the MT stiffens the residues in the MT binding region, induces correlations between switches I and II in the motor, and enhances fluctuations in ADP and the residues in the binding pocket. Our findings explain both the directionality of stepping and MT effects on a key step in the catalytic cycle of Kin1.
Profiling ofN6-methyladenosine dynamics indicates regulation of oyster development by m6A-RNA epitranscriptomes
Authors: Franc Lorane Le , Petton Bruno , Favrel Pascal , Rivière Guillaume
Published: August 2021

TheN6-methylation of RNA adenosines (m6A) is an important regulator of gene expression with critical implications in vertebrate and insect development. However, the developmental significance of epitranscriptomes in lophotrochozoan organisms remains unknown.

Using MeRIP-seq, we generated transcriptome-wide m6A-RNA methylomes covering the whole development of the oyster from oocytes to juveniles. Oyster RNA classes display specific m6A signatures, with mRNAs and lncRNAs exhibiting distinct profiles and being highly methylated compared to transposon transcripts. Epitranscriptomes are dynamic and correspond to chronological steps of development (cleavage, gastrulation, organogenesis and metamorphosis), with a minimal mRNA and lncRNA methylation at the morula stage followed by a global increase. mRNA m6A levels are correlated to transcript levels and shifts in methyladenine profiles correspond to expression kinetics. Differentially methylated transcripts cluster according to embryo-larval stages and bear the corresponding developmental functions (cell division, signal transduction, morphogenesis and cell differentiation). The m6A level of transposon transcripts is also regulated and peaks during the gastrulation.

We demonstrate that m6A-RNA methylomes are dynamic and associated to gene expression regulation during oyster development. The putative epitranscriptome implication in the cleavage, maternal-to-zygotic transition and cell differentiation in a lophotrochozoan model brings new insights into the control and evolution of developmental processes
Critical period for vision-dependent modulation of postnatal retinal neurogenesis
Authors: Tkatchenko Tatiana V. , Michurina Tatyana V. , Tomarev Stanislav I. , Nakaya Naoki , Enikolopov Grigori N. , Tkatchenko Andrei V.
Published: August 2021

It is generally accepted that retinal neurogenesis in mammals ceases shortly after birth and that stem/progenitor cells found in the postnatal eyes of mice and humans are in the quiescent state. In the present study, we have investigated postnatal retinal neurogenesis and its modulation by visual experience in the mouse model. Four age groups (P26, P45, P72, and P94) of transgenic mice expressing green fluorescent protein (GFP) in the retinal progenitor cells under the control of nestin regulatory elements were examined for the presence of nestin-GFP-positive proliferating progenitor cells in the retina. Contrary to the previously held belief, we found a significant number of proliferating progenitors at the retinal periphery in all age groups examined. The majority of these cells gave rise to photoreceptors as revealed by the genetic cell fate mapping experiments. The intensity of neurogenesis was declining with age, and strongly correlated with eye growth. Visual form deprivation resulted in a significant increase in the intensity of peripheral neurogenesis, which correlated strongly with the induced ocular growth. The susceptibility to both form-deprivation-induced increase in the peripheral neurogenesis and form-deprivation-induced increase in the ocular growth declined with age ceasing completely around P70, which marked the end of the critical period for the vision-dependent modulation of both ocular growth and postnatal retinal neurogenesis. Thus, neurogenesis in the peripheral retina of young mice is modulated by visual input, but only during a critical period in postnatal development.
Liquid-crystalline lipid phase transitions in lipid droplets selectively remodel the LD proteome
Authors: Rogers Sean , Gui Long , Kovalenko Anastasiia , Reetz Evan , Nicastro Daniela , Henne W. Mike
Published: August 2021

Lipid droplets (LDs) are reservoirs for triglycerides (TGs) and sterol-esters (SEs). How lipids are organized within LDs and influence the LD proteome remains unclear. Using in situ cryo-electron tomography, we show that glucose restriction triggers lipid phase transitions within LDs generating liquid-crystalline lattices inside them. Mechanistically, this requires TG lipolysis, which alters LD neutral lipid composition and promotes SE transition to a liquid-crystalline phase. Fluorescence imaging and proteomics further reveal that LD liquid-crystalline lattices selectively remodel the LD proteome. Some canonical LD proteins including Erg6 re-localize to the ER network, whereas others remain on LDs. Model peptide LiveDrop also redistributes from LDs to the ER, suggesting liquid-crystalline-phases influence ER-LD inter-organelle transport. Proteomics also indicates glucose restriction elevates peroxisome lipid oxidation, suggesting TG mobilization provides fatty acids for cellular energetics. This suggests glucose restriction drives TG mobilization, which alters the phase properties of LD lipids and selectively remodels the LD proteome.
The MIDAS domain of AAA mechanoenzyme Mdn1 forms catch bonds with two different substrates
Authors: Mickolajczyk Keith J. , Olinares Paul Dominic B. , Chait Brian T. , Liu Shixin , Kapoor Tarun M.
Published: August 2021

Catch bonds are a form of mechanoregulation wherein protein-ligand interactions are strengthened by the application of dissociative tension. Currently, the best-characterized examples of catch bonds are between single protein-ligand pairs. The essential AAA (ATPase associated with diverse cellular activities) mechanoenzyme Mdn1 drives two separate steps in ribosome biogenesis, using its MIDAS domain to extract the ubiquitin-like (UBL) domain-containing proteins Rsa4 and Ytm1 from ribosomal precursors. However, it must subsequently release these assembly factors to reinitiate the enzymatic cycle. The mechanism underlying MIDAS-UBL switching between strongly- and weakly-bound states is unknown. Here, we use single-molecule optical tweezers to investigate the force-dependence of MIDAS-UBL binding. Parallel experiments with Rsa4 and Ytm1 show that forces up to ~4 pN, matching the magnitude of force produced by AAA proteins similar to Mdn1, enhance the MIDAS domain binding lifetime up to tenfold, and higher forces accelerate dissociation. Together, our studies indicate that Mdn1’s MIDAS domain forms catch bonds with more than one UBL-substrate, and provide insights into how mechanoregulation may contribute to the Mdn1 enzymatic cycle during ribosome biogenesis.
Pulmonary tuberculosis among prisoners in Southern Thailand: prevalence and its association with imprisonment status
Authors: Bilmumad Bintinee , Liabsuetrakul Tippawan , Ngamtrairai Nipa , Chongsuvivatwong Virasakdi
Published: August 2021

Purpose

This study aims to measure the prevalence of pulmonary tuberculosis (PTB), its association with imprisonment status and to document the treatment success rate (TSR) among prisoners in Songkhla province, Southern Thailand.

Design/methodology/approach

A retrospective cross-sectional study was conducted in five prisons in Songkhla province, including all prisoners in the fiscal of year 2019, who had an annual chest radiography (CXR) screening result. Information of prisoners who had been imprisoned from 1 October 2018 to 30 September 2019, were reviewed for PTB diagnosis. Imprisonment status and other associated factors with PTB were analyzed using multiple logistic regression.

Findings

The prevalence of PTB was 2.72%. Prisoners having new or transfer-in status were more likely to have PTB. Those aged 40–80 years, who had smoked for ten years or more, or who were underweight, had higher odds of having PTB. TSR among prisoners with PTB in this study was 94.9%.

Originality/value

The prevalence of PTB among prisoners having annual CXR screening was high. Detection of PTB was higher among new or transfer-in prisoners; therefore, the CXR for PTB screening before admission to prison should be performed to prevent transmission to other prisoners.
Russian government quality award: 25 years towards organizational excellence
Authors: Salimova Tatiana , Dahlgaard-Park Su Mi , Biryukova Lyudmila , Palkina Julia , Vatolkina Natalia
Published: August 2021

Purpose

The purpose of this paper is to review the Russian Federation Government Quality Award (RFGQA) over its 25-year existence.

Design/methodology/approach

This paper looks into the evolution, model and key provisions of RFGQA, based on the authors’ long-time experience as an Award assessor. Apart from that, methodologically, this study uses the desktop research method, comparative literature review.

Findings

The research results show that RFGQA over its 25 years has become the most popular approach to the development of organizational excellence for Russian enterprises and organizations, regardless of the sphere of activity.

Research limitations/implications

This paper presents the core results of RFGQA’s 25-year existence. The comparison of the current Russian Quality Award model with the new European Foundation for Quality Management model is not analyzed.

Originality/value

This research paper extends current knowledge of national quality awards and presents an original set of information about RFGQA, its methodology and results.
Barriers and facilitators in the implementation of an evidence-based health promotion intervention in a primary care setting: a qualitative study
Authors: Rogers Heather L. , Pablo Hernando Susana , Núñez - Fernández Silvia , Sanchez Alvaro , Martos Carlos , Moreno Maribel , Grandes Gonzalo
Published: August 2021

Purpose

This study aims to elucidate the health care organization, management and policy barriers and facilitators associated with implementation of an evidence-based health promotion intervention in primary care centers in the Basque Country, Spain.

Design/methodology/approach

Seven focus groups were conducted with 49 health professionals from six primary care centers participating in the Prescribing Healthy Life program. Text was analyzed using the Consolidated Framework for Implementation Research (CFIR) focusing on those constructs related to health care organization, management and policy.

Findings

The health promotion intervention was found to be compatible with the values of primary care professionals. However, professionals at all centers reported barriers to implementation related to: (1) external policy and incentives, (2) compatibility with existing workflow and (3) available resources to carry out the program. Specific barriers in these areas related to lack of financial and political support, consultation time constraints and difficulty managing competing day-to-day demands. Other barriers and facilitators were related to the constructs networks and communication, culture, relative priority and leadership engagement. A set of six specific barrier-facilitator pairs emerged.

Originality/value

Implementation science and, specifically, the CFIR constructs were used as a guide. Barriers and facilitators related to the implementation of a health promotion program in primary care were identified. Healthcare managers and policy makers can modify these factors to foster a more propitious implementation environment. These factors should be appropriately monitored, both in pre-implementation phases and during the implementation process, in order to ensure effective integration of health promotion into the primary care setting.