bluuebunny/crossref_metadata_2025 huggingface dataset:
Symptoms of Pediatric Feeding Disorders Among Individuals with 3q29 Deletion Syndrome: A Case-Control Study
Authors: Wawrzonek Addam J. , Sharp William , Burrell Teresa Lindsey , Gillespie Scott E. , Pollak Rebecca M. ,   The Emory 3q29 Project,, Murphy Melissa M. , Mulle Jennifer G.
Published: October 2021

Objective:

The goal of this study was to evaluate symptoms of pediatric feeding disorder in a sample of individuals with 3q29 deletion syndrome (3q29Del). Previous research has found that individuals with 3q29Del may experience elevated feeding concerns in early childhood; however, the specificity of these feeding concerns is not well understood.

Methods:

We compared individuals with 3q29Del (N = 83) with controls (N = 59) using an 11-item survey that assessed commonly reported symptoms associated with pediatric feeding disorders. An exploratory analysis also examined individuals with 3q29Del with and without a comorbid global developmental delay (GDD) or an autism spectrum disorder diagnosis.

Results:

Caregivers of 3q29Del cases reported higher incidences of feeding concerns on 10 of the 11 items included in the survey. This included statistically significant differences in food refusal behaviors, rejection of 1 or more food groups, and a history of failure to thrive. Parents of children with comorbid GDD were more likely to report concerns regarding food selectivity and problem behaviors during mealtime.

Conclusion:

The results suggest individuals with 3q29Del experience increased symptoms of pediatric feeding disorder that may require targeted evaluation and intervention for optimal outcomes. Future research should include a more thorough multidisciplinary evaluation to further elucidate symptom severity and optimal treatment strategies.
Children's Attention and Self-Regulatory Behavior Before and During the COVID-19 Pandemic
Authors: Raghunathan Radhika S. , Musci Rashelle J. , Voegtline Kristin M. , Chambers Thomas Tracey , Johnson Sara B.
Published: October 2021

Objective:

The goal of this study was to investigate changes in children's self-regulatory behavior before and during the COVID-19 pandemic.

Method:

Participants were parents of children aged 4 to 13 years (n = 45, mean 7.5, SD: 2.6) who participated in the Baltimore Generations Study before the pandemic. They reported on their child's self-regulation (SR) using the Parent Observation of Child Adaptation. During the pandemic, they were recontacted to report on child SR, disruptions to family life (Coronavirus Impact Scale), and parenting stress (Parenting Stress Index). Prepandemic to pandemic changes in SR were compared with repeated measures analysis of variance.

Results:

There were significant decreases in child SR (poorer concentration, attention, task engagement and persistence, and greater impulsivity) prepandemic to pandemic. During the pandemic, parenting stress was correlated with lower child SR (r range = −0.52 to −0.34, p < 0.05). Pandemic-related family disruptions were associated with changes in children's impulsivity (F [1, 42] = 5.28, p = 0.03); children with 4 or more disruptions (67%) showed less ability to wait their turn during the pandemic compared with prepandemic (M [SD] = 3.34 [0.93] vs. 4.41 [1.21], t [28] = 3.93, p < 0.001). There was no change in SR for children with fewer than 4 disruptions.

Conclusion:

Results highlight modest pandemic-associated decreases in child attention, task persistence, and task engagement alongside increases in impulsivity. We did not find evidence of broad or severe impacts; however, children whose families have been disproportionately affected by the pandemic may need focused support in school and at home to avoid widening prepandemic health and educational disparities.
Postoperative ICU admission following major elective surgery
Authors: Ohbe Hiroyuki , Matsui Hiroki , Kumazawa Ryosuke , Yasunaga Hideo
Published: October 2021

BACKGROUND

Whether the routine use of the ICU after major elective surgery improves postoperative outcomes is not well established.

OBJECTIVES

To describe the association between use of postoperative ICU admission and clinical outcomes for patients undergoing major elective surgery.

DESIGN

Observational study.

SETTING

Nationwide inpatient database in Japan, July 2010 to March 2018.

PATIENTS

Patients undergoing one of 15 major elective orthopaedic, gastrointestinal, neurological, thoracic or cardiovascular surgical procedures.

INTERVENTION

ICU admission on the day of surgery. ICU was defined as a separate unit providing critical care services with around-the-clock physician staffing and nursing, the equipment necessary for critical care and a nurse-to-patient ratio at least one to two.

MAIN OUTCOME

In-hospital mortality. Patient-level and hospital-level analyses were performed.

RESULTS

Overall, 2 011 265 patients from 1524 hospitals were assessed. The cohort size ranged from 38 547 patients in 467 hospitals for surgical clipping for cerebral aneurysms to 308 952 patients in 599 hospitals for spinal fixation, laminectomy or laminoplasty. In the patient-level analyses, there were no significant mortality differences among patients undergoing the 12 major noncardiovascular surgical procedures, whereas postoperative ICU admission was associated with trends towards lower in-hospital mortality among patients undergoing coronary artery bypass grafting, risk difference −1.0% (95% CI −1.8 to −0.1) open aortic aneurysm repair, risk difference −0.6% (95% CI −1.3 to 0.1), and heart valve replacement, risk difference −0.7% (95% CI − 1.6 to 0.1). In the hospital-level analyses, similar to the results of the patient-level analyses, a higher proportion of postoperative ICU admission at hospital level was associated with trends toward lower in-hospital mortality for patients undergoing the three cardiovascular surgical procedures.

CONCLUSION

This nationwide observational study showed that postoperative ICU admission was associated with improved survival outcomes among patients undergoing three types of cardiac surgery but not among patients undergoing low-risk elective surgery.
A predictive model of choosing pessary type for women with symptomatic pelvic organ prolapse
Authors: Xu Hainan , Wu Wenjing , Wang Xinlu , Xia Zhijun
Published: October 2021

Objective:

To investigate clinical factors including translabial ultrasound parameters, which are predictive for choosing pessary type (Ring or Gellhorn) in the fitting trial, and to establish a predictive model.

Methods:

A retrospective study was conducted on symptomatic women with pelvic organ prolapse (POP) at the Pelvic Floor Disease Diagnosis and Treatment Center (Liaoning Province, China) between May 2018 and December 2020 who were successfully fitted with pessaries. This retrospective study was supplemented with a prospective cohort study on women seeking pessary for first-line treatment of POP at the above tertiary center between December 2020 and April 2021 for validation. Enrolled participants were grouped by their fitted type of pessary. Demographic and clinical parameters between groups, including pelvic organ prolapse quantification and translabial ultrasound, were analyzed using logistic regression. A receiver operating characteristic curve was calculated using predictive values obtained by regression as the predictor for choosing pessary type in the pessary fitting trial.

Results:

The 181 participants included in the retrospective analysis were randomly divided into the “Development” and “Validation” datasets. In the “Development” set, multivariable logistic regression analyses showed that a younger age (odds ratio [OR]: 0.950; 95% confidence interval [CI]: 0.908-0.995; P = 0.026), a larger hiatal circumference on Valsalva (OR: 1.348; 95% CI: 1.103-1.647; P = 0.004), and a higher POP-Q stage (OR: 2.963; 95% CI: 1.210-7.255; P = 0.017) were independent predictors for successful fitting with the Gellhorn pessary. The predictive model was P = exp(Z)/[1 + exp(Z)], Z = −0.051 × Age (y) + 0.298 × hiatal circumference on Valsalva (cm) + 1.086 × pelvic organ prolapse stage (2, 3, or 4) − 5.490. The area under the receiver operating characteristic curves (AUC) was 0.776 (P < 0.001) and 0.705 (P < 0.001) based on the “Development” dataset and “Validation” datasets, respectively. The AUC was 0.815 (P < 0.001) based on the prospective cohort validation.

Conclusions:

For severe POP, women with younger age and larger hiatal circumference, Gellhorn pessaries should be their first choice instead of ring ones in pessary fitting trials.
Treatment of menopausal symptoms: concomitant modification of cortisol
Authors: Cagnacci Angelo , Xholli Anjeza , Fontanesi Francesca , Neri Isabella , Facchinetti Fabio , Palma Federica
Published: October 2021

Objectives:

To evaluate whether change in menopausal symptoms is related to modification of 24-hour urinary cortisol.

Methods:

Sixty-nine postmenopausal women were treated for their menopausal symptoms with either estrogen progestin therapy (0.3 mg conjugate equine estrogens and 1.5 mg medroxyprogesterone acetate; n = 25), phytoestrogens (75 mg isoflavones, twice daily; n = 21) or acupuncture (once a week; n = 23). Baseline and treatment-induced changes of total and subscale scores (vasomotor, depression, anxiety, somatization, sexuality) of the Greene's Climacteric Scale and of 24-hour urinary cortisol were evaluated.

Results:

At baseline, 24-hour urinary cortisol was related to Greene's Climacteric Scale score (P < 0.0001). Independent determinants (R2 = 0.319) were the Greene's subscales scores of depression (with a mean difference of 24-h cortisol for score unit expressed as beta coefficient of regression (b) of 4.91, 95% CI 2.14-7.7; P = 0.0007), and of somatization (b 3.04 95% CI 0.69-5.4; P = 0.012). The Greene's Climacteric Scale score (−5.67 ± 6.8; P = 0.0001) and 24-hour cortisol (−23.6 ± 45.7 μg/24 h; P = 0.0001) declined after 3 months of treatment. Changes of 24-hour cortisol values were linearly related to changes of total Greene's Climacteric Scale score with a mean change for unit score (b) of 2.10, 95% CI 0.47-3.73; P = 0.012).

Conclusions:

Present data indicate that greater reduction in menopausal symptoms is associated with a larger decrease in cortisol levels. Possible implication of this finding on the long-term consequences for women's health needs to be explored.
Peak shifts and extinction under sex-specific selection
Authors: De Lisle Stephen P.
Published: October 2021

A well-known property of sexual selection combined with a cross-sex genetic correlation (
r
mf
) is that it can facilitate a peak shift on the adaptive landscape. How do these diversifying effects of sexual selection +
r
mf
balance with the constraints imposed by such sexual antagonism, to affect the macroevolution of sexual dimorphism? Here, I extend existing quantitative genetic models of evolution on complex adaptive landscapes. Beyond recovering classical predictions for the conditions promoting a peak shift, I show that when
r
mf
is moderate to strong, relatively weak sexual selection is required to induce a peak shift in males only. Increasing the strength of sexual selection leads to a sexually concordant peak shift, suggesting that macroevolutionary rates of sexual dimorphism may be largely decoupled from the strength of within-population sexual selection. Accounting explicitly for demography further reveals that sex-specific peak shifts may be more likely to be successful than concordant shifts in the face of extinction, especially when natural selection is strong. An overarching conclusion is that macroevolutionary patterns of sexual dimorphism are unlikely to be readily explained by within-population estimates of selection or constraint alone.
Gut microbiome and telomere length in gull hatchlings
Authors: Velando Alberto , Noguera Jose Carlos , Aira Manuel , Domínguez Jorge
Published: October 2021

In many animals, recent evidence indicates that the gut microbiome may be acquired during early development, with possible consequences on newborns' health. Thus, it has been hypothesized that a healthy microbiome protects telomeres and genomic integrity against cellular stress. However, the link between the early acquired microbiome and telomere dynamics has not hitherto been investigated. In birds, this link may also be potentially modulated by the transfer of maternal glucocorticoids, since these substances dysregulate microbiome composition during postnatal development. Here, we examined the effect of the interplay between the microbiome and stress hormones on the telomere length of yellow-legged gull hatchlings by using a field experiment in which we manipulated the corticosterone content in eggs. We found that the hatchling telomere length was related to microbiome composition, but this relationship was not affected by the corticosterone treatment. Hatchlings with a microbiome dominated by potential commensal bacteria (i.e.
Catellicoccus
and
Cetobacterium
) had larger telomeres, suggesting that an early establishment of the species-specific microbiome during development may have important consequences on offspring health and survival.
Immunity to SARS-CoV-2 up to 15 months after infection
Authors: Marcotte Harold , Piralla Antonio , Zuo Fanglei , Du Likun , Cassaniti Irene , Wan Hui , Kumagai-Braesh Makiko , Andréll Juni , Percivalle Elena , Sammartino Josè Camilla , Wang Yating , Vlachiotis Stelios , Attevall Janine , Bergami Federica , Ferrari Alessandro , Colaneri Marta , Vecchia Marco , Sambo Margherita , Zuccaro Valentina , Asperges Erika , Bruno Raffaele , Oggionni Tiberio , Meloni Federica , Abolhassanni Hassan , Bertoglio Federico , Schubert Maren , Calzolai Luigi , Varani Luca , Hust Michael , Xue Yintong , Hammarström Lennart , Baldanti Fausto , Pan-Hammarström Qiang
Published: October 2021

Background

Information concerning the longevity of immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) following natural infection may have considerable implications for durability of immunity induced by vaccines. Here, we monitored the SARS-CoV-2 specific immune response in convalescent coronavirus disease-2019 (COVID-19) patients up to 15 months after symptoms onset.

Methods

The levels of anti-spike and anti-receptor binding domain antibodies and neutralizing activities were tested in a total of 188 samples from 136 convalescent patients who experience mild to critical COVID-19. Specific memory B and T cell responses were measured in 76 peripheral blood mononuclear cell samples collected from 54 patients. Twenty-three vaccinated individuals were included for comparison.

Findings

Following a peak at day 15-28 post-infection, the IgG antibody response and plasma neutralizing titers gradually decreased over time but stabilized after 6 months. Plasma neutralizing activity against G614 was still detected in 87% of the patients at 6-15 months. Compared to G614, the median neutralizing titers against Beta, Gamma and Delta variants in plasma collected at early (15-103 days) and late (9-15 month) convalescence were 16- and 8-fold lower, respectively. SARS-CoV-2-specific memory B and T cells reached a peak at 3-6 months and persisted in the majority of patients up to 15 months although a significant decrease in specific T cells was observed between 6 and 15 months.

Conclusion

The data suggest that antiviral specific immunity especially memory B cells in COVID-19 convalescent patients is long-lasting, but some variants of concern, including the fast-spreading Delta variant, may at least partially escape the neutralizing activity of plasma antibodies.

Funding

EU-ATAC consortium, the Italian Ministry of Health, the Swedish Research Council, SciLifeLab, and KAW.
Persistent Activity in Human Parietal Cortex Mediates Perceptual Choice Repetition Bias
Authors: Urai Anne E. , Donner Tobias H.
Published: October 2021

Abstract

Humans and other animals tend to repeat or alternate their previous choices, even when judging sensory stimuli presented in a random sequence. It is unclear if and how sensory, associative, and motor cortical circuits produce these idiosyncratic behavioral biases. Here, we combined behavioral modeling of a visual perceptual decision with magnetoencephalographic (MEG) analyses of neural dynamics, across multiple regions of the human cerebral cortex. We identified distinct history-dependent neural signals in motor and posterior parietal cortex. Gamma-band activity in parietal cortex tracked previous choices in a sustained fashion, and biased evidence accumulation toward choice repetition; sustained beta-band activity in motor cortex inversely reflected the previous motor action, and biased the accumulation starting point toward alternation. The parietal, not motor, signal mediated the impact of previous on current choice and reflected individual differences in choice repetition. In sum, parietal cortical signals seem to play a key role in shaping choice sequences.
Is there magnocellular facilitation of early neural processes underlying visual word recognition? Evidence from masked repetition priming with ERPs
Authors: Huang Xin , Wong Wai Leung , Tse Chun-Yu , Sommer Werner , Dimigen Olaf , Maurer Urs
Published: October 2021

An influential theory in the field of visual object recognition proposes that fast magnocellular (M) information facilitates neural processing of spatially more fine-grained but slower parvocellular (P) information. While written words can be considered as a special type of visual objects, it is unknown whether magnocellular facilitation also plays a role in reading. We used a masked priming paradigm that has been shown to result in neural facilitation in visual word processing and tested whether these facilitating effects are mediated by the magnocellular system. In two experiments, we manipulated the influence of magnocellular and parvocellular systems on visual processing of a contextually predictable target character by contrasting high versus low spatial frequency and luminance versus color contrast, respectively. In addition, unchanged (normal) primes were included in both experiments as a manipulation check. As expected, unchanged primes elicited typical repetition effects in the N1, N250 and P3 components of the ERP in both experiments. In the experiment manipulating spatial contrast, we obtained repetition effects only for the N1 component for both M- and P-biased primes. In the luminance versus color contrast experiment, repetition effects were found in N1 and N250 for both M- and P- biased primes. Furthermore, no interactions were found between M- vs. P-biased prime types and repetition. Together these results indicate that M- and P- information contributes jointly to early neural processes underlying visual word recognition.
Age-related intrinsic functional connectivity changes of locus coeruleus from childhood to older adults
Authors: Song Inuk , Neal Joshua , Lee Tae-Ho
Published: October 2021

The locus coeruleus is critical for selective information processing by modulating brain’s connectivity configuration. Increasingly studies have suggested that LC controls sensory inputs at the sensory gating stage. Furthermore, accumulating evidence has examined that young children and older adults are more prone to distraction and filter out irrelevant information less efficiently, possibly due to the impaired LC connectivity. However, the LC connectivity pattern across the life span is not fully examined yet, hampering our ability to understand the relationship between LC development and the distractibility. In this study, we examined the intrinsic network connectivity of the LC using resting-state fMRI from the enhanced NKI dataset with wide-range age samples. Based on LC-seed functional connectivity maps, we examined the age-related variation in the LC connectivity with a quadratic model. The analyses revealed two connectivity patterns explicitly. The sensory-related brain regions showed a positive quadratic age effect (u-shape), and the frontal regions for the cognitive control showed a negative quadratic age effect (inverted u-shape). Our results imply that such age-related distractibility is possibly due to the impaired sensory gating by the LC and the insufficient top-down controls by the frontal regions. We discuss the underlying neural mechanisms and limitations of our study.
Assessing The Repeatability of Multi-Frequency Multi-Layer Brain Network Topologies Across Alternative Researcher’s Choice Paths
Authors: Dimitriadis Stavros I.
Published: October 2021

There is a growing interest in the neuroscience community on the advantages of multilayer functional brain networks. Researchers usually treated different frequencies separately at distinct functional brain networks. However, there is strong evidence that these networks share complementary information while their interdependencies could reveal novel findings. For this purpose, neuroscientists adopt multilayer networks, which can be described mathematically as an extension of trivial single-layer networks. Multilayer networks have become popular in neuroscience due to their advantage to integrate different sources of information. Here, we will focus on the multi-frequency multilayer functional connectivity analysis on resting-state fMRI recordings. However, constructing a multilayer network depends on selecting multiple pre-processing steps that can affect the final network topology. Here, I analyzed the fMRI dataset from a single human performing scanning over a period of 18 months (84 scans in total), and the second dataset of 25 subjects with 3 repeat scans. I focused on assessing the reproducibility of multi-frequency multilayer topologies exploring the effect of two filtering methods for extracting frequencies from BOLD activity, three connectivity estimators, with or without a topological filtering scheme, and two spatial scales. Finally, I untangled specific combinations of researchers’ choices that yield consistently brain networks with repeatable topologies, giving us the chance to recommend best practices over consistent topologies.
Extracellular Fluid Flow Induces Shallow Quiescence through Physical and Biochemical Cues
Authors: Liu Bi , Wang Xia , Jiang Linan , Xu Jianhua , Zohar Yitshak , Yao Guang
Published: October 2021

The balance between cell quiescence and proliferation is fundamental to tissue physiology and homeostasis. Recent studies have shown that quiescence is not a passive and homogeneous state but actively maintained and heterogeneous. These cellular characteristics associated with quiescence were observed primarily in cultured cells under a static medium. However, cells in vivo face different microenvironmental conditions, particularly, under interstitial fluid flows distributed through extracellular matrices. Interstitial fluid flow exerts shear stress on cells and matrix strain, and results in continuous replacement of extracellular factors. In this study, by analyzing individual cells under varying fluid flow rates in microfluidic devices, we found that extracellular fluid flow alters cellular quiescence depth through flow-induced physical and biochemical cues. Specifically, increasing the flow rate drives cells to shallower quiescence and become more likely to reenter the cell cycle upon growth stimulation. Furthermore, we found that increasing shear stress or extracellular factor replacement individually, without altering other parameters, also results in shallow quiescence. We integrated the experimental results into a mathematical model to gain insight and predict the effects of varying extracellular fluid flow conditions on cellular quiescence depth. Our findings uncover a previously unappreciated mechanism that likely underlies the heterogeneous responses of quiescent cells for tissue repair and regeneration in physiological tissue microenvironments.
Feasibility conditions of ecological models: Unfolding links between model parameters
Authors: AlAdwani Mohammad , Saavedra Serguei
Published: October 2021

Over more than 100 years, ecological research has been striving to derive internal and external conditions compatible with the coexistence of a given group of interacting species. To address this challenge, numerous studies have focused on developing ecological models and deriving the necessary conditions for species coexistence under equilibrium dynamics, namely feasibility. However, due to mathematical limitations, it has been impossible to derive analytic expressions if the isocline equations have five or more roots, which can be easily reached even in 2-species models. Here, we propose a general formalism to obtain the set of analytical conditions of feasibility for any polynomial population dynamics model of any dimension without the need to solve for the equilibrium locations. We additionally illustrate the application of our methodology by showing how it is possible to derive mathematical relationships between model parameters, while maintaining feasibility in modified Lotka-Volterra models with functional responses and higher-order interactions (model systems with at least five equilibrium points)—a task that is impossible to do with simulations. This work unlocks the opportunity to increase our systematic understanding of species coexistence.
Losses and gains of fallows impact farmland bird populations over three funding periods of the EU Common Agricultural Policy
Authors: Hertzog Lionel R. , Röder Norbert , Frank Claudia , Böhner Hannah G. S. , Kamp Johannes , Klimek Sebastian
Published: October 2021

Fallow land provides habitat for threatened and declining farmland biodiversity. Policy change under the EU’s Common Agricultural Policy (CAP) has been driving the area of fallows over the past decades and influenced trends in farmland biodiversity.

We analyzed the relationships between fallow land area across Germany over three CAP funding periods and species richness and abundance of farmland birds. We examined whether the strength of the relationships with fallow land area were moderated by species habitat preferences and landscape configurational complexity (edge density). We combined spatial data on fallow land area from three agricultural censuses in Germany (2007, 2010 and 2016) with country-wide farmland bird monitoring data.

Farmland bird species richness and the abundance of the majority of the studied farmland bird species were positively related to increases in fallows across three CAP funding periods. The relationship of fallows with bird richness was strongest at intermediate levels of edge density. There was generally little support for a moderating effect of edge density on the relations between fallows and bird abundance.

We conclude that the loss of fallows in the period 2007 to 2016 resulted in strong declines of farmland birds. We predict that a future increase of the proportion of fallow land to 4% of the arable land, as envisaged in the German 2023-2027 CAP strategic plans, or to 10%, as foreseen in the EU Biodiversity Strategy, will lead to increases in farmland bird species richness and abundance depending on the landscape context and species-specific habitat preferences.

Policy implications

Increasing the proportion of fallow land will likely be a key lever to stabilize and revert negative farmland bird population trends. An increase of fallow area in all but the least complex landscapes will boost farmland bird richness and abundance. Increasing the proportion of fallow land to 4% should bring farmland bird richness and abundance back to the levels observed in 2007 acknowledging that farmland bird populations were already severely depleted in 2007. A more ambitious expansion of fallow land towards 10% should be targeted towards areas that experienced the strongest loss of fallows and towards landscapes with intermediate levels of edge density.
HIF1α-AS1 is a DNA:DNA:RNA triplex-forming lncRNA interacting with the HUSH complex
Authors: Leisegang Matthias S. , Bains Jasleen Kaur , Seredinski Sandra , Oo James A. , Krause Nina M. , Kuo Chao-Chung , Günther Stefan , Cetin Nevcin Sentürk , Warwick Timothy , Cao Can , Boos Frederike , Ponce Judit Izquierdo , Bednarz Rebecca , Valasarajan Chanil , Fuhrmann Dominik , Preussner Jens , Looso Mario , Pullamsetti Soni S. , Schulz Marcel H. , Rezende Flávia , Gilsbach Ralf , Pflüger-Müller Beatrice , Wittig Ilka , Grummt Ingrid , Ribarska Teodora , Costa Ivan G. , Schwalbe Harald , Brandes Ralf P.
Published: October 2021

DNA:DNA:RNA triplexes that are formed through Hoogsteen base-pairing have been observed in vitro, but the extent to which these interactions occur in cells and how they impact cellular functions remains elusive. Using a combination of bioinformatic techniques, RNA/DNA pulldown and biophysical studies, we set out to identify functionally important DNA:DNA:RNA triplex-forming long non-coding RNAs (lncRNA) in human endothelial cells. The lncRNA HIF1α-AS1 was retrieved as a top hit. Endogenous HIF1α-AS1 reduced the expression of numerous genes, including EPH Receptor A2 and Adrenomedullin through DNA:DNA:RNA triplex formation by acting as an adapter for the repressive human silencing hub complex (HUSH). Moreover, the oxygen-sensitive HIF1α-AS1 was down-regulated in pulmonary hypertension and loss-of-function approaches not only resulted in gene de-repression but also enhanced angiogenic capacity. As exemplified here with HIF1α-AS1, DNA:DNA:RNA triplex formation is a functionally important mechanism of trans-acting gene expression control.
Neuronal Dot1l is a broad mitochondrial gene-repressor associated with human brain aging via H3K79 hypermethylation
Authors: Van Heesbeen H.J , Von Oerthel L , De Vries P.M , Wagemans M.R.J , Smidt M.P.
Published: October 2021

Methylation of histone 3 at lysine 79 (H3K79) and its catalyst, disrupter of telomeric silencing (Dot1l), have been coupled to multiple forms of stress like bioenergetic and ER challenges. However, studies on H3K79 methylation and Dot1l in the aging brain and neurons are very limited. This together with increasing evidence of a dynamic neuroepigenome made us wonder if H3K79 methylation and Dot1l could play unknown roles in brain aging and associated disorders. In aged humans, we found strong and consistent hypermethylation of H3K79 in neurons that accumulate lipofuscine, while neuronal Dot1l transcript abundance reacts to bioenergenic and oxidative challenges. Indeed, in dopaminergic neurons we found rapid global H3K79me turnover (<12h). While shortly after reduction of H3K79 methylation, synaptic transcripts decreased while mitochondrial genes, particularly respiratory chain transcripts increased. Strikingly, 6 months after reduction of Dot1l levels, almost solely a variety of mitochondrial genes linked to aging and Parkinsons disease remained increased. These profiles are in much detail inverse to those described in hallmark PD and aging studies and associate Dot1l and H3K79me with neuronal stress in the aging brain while putting Dot1l forward as dynamic master regulator of mitochondrial transcription in dopamine neurons.
Linking intrinsic scales of ecological processes to characteristic scales of biodiversity and functioning patterns
Authors: Zelnik Yuval R. , Barbier Matthieu , Shanafelt David W. , Loreau Michel , Germain Rachel M.
Published: October 2021

Ecology is a science of scale, which guides our description of both ecological processes and patterns, but we lack a systematic understanding of how process scale and pattern scale are connected. Recent calls for a synthesis between population ecology, community ecology, and ecosystem ecology motivate the integration of phenomena at multiple levels of organization. Furthermore, many studies leave out the scaling of a critical process: species interactions, which may be non-local through movement or foraging and must be distinguished from dispersal scales. Here, we use simulations to explore the consequences of three different process scales (species interactions, dispersal, and the environment) on emergent patterns of biodiversity, ecosystem functioning, and their relationship, in a spatially-explicit landscape and stable equilibrium setting. A major result of our study is that the spatial scales of dispersal and species interactions have opposite effects: a larger dispersal scale homogenizes spatial biomass patterns, while a larger interaction scale amplifies their heterogeneity. Interestingly, the specific scale at which dispersal and interaction scales begin to influence landscape patterns depends on the scale of environmental heterogeneity – in other words, the scale of one process allows important scales to emerge in other processes. This interplay between process scales, i.e., a situation where no single process dominates, can only occur when the environment is heterogeneous and the scale of dispersal small. Finally, contrary to our expectations, we observe that the spatial scale of ecological processes is more clearly reflected in landscape patterns (i.e., distribution of local outcomes) than in global patterns such as Species-Area Relationships or large-scale biodiversity-functioning relationships. Overall we conclude that long-range interactions often act differently and even in opposite ways to dispersal, and that the landscape patterns that emerge from the interplay of long-ranged interactions, dispersal and environmental heterogeneity are not well captured by often-used metrics like the Species-Area Relationship.
Catestatin selects for the colonization of antimicrobial-resistant gut bacterial communities
Authors: González-Dávila Pamela , Schwalbe Markus , Danewalia Arpit , Dalile Boushra , Verbeke Kristin , Mahata Sushil K , El Aidy Sahar
Published: October 2021

The gut microbiota is in continuous interaction with the innermost layer of the gut, namely the epithelium. One of the various functions of the gut epithelium, is to keep the microbes at bay to avoid overstimulation of the underlying mucosa immune cells. To do so, the gut epithelia secrete a variety of antimicrobial peptides, such as chromogranin A (CgA) peptide catestatin (CST: hCgA352-372). As a defense mechanism, gut microbes have evolved antimicrobial resistance mechanisms to counteract the killing effect of the secreted peptides. To this end, we treated wild-type mice and CST knockout (CST-KO) mice (where only the 63 nucleotides encoding CST have been deleted) with CST for 15 consecutive days. CST treatment was associated with a shift in the diversity and composition of the microbiota in the CST-KO mice. This effect was less prominent in WT mice. Levels of the microbiota-produced short-chain fatty acids, in particular, butyrate and acetate were significantly increased in CST-treated CST-KO mice but not the WT group. Both CST-treated CST-KO and WT mice showed a significant increase in microbiota-harboring phosphoethanolamine transferase-encoding genes, which facilitate their antimicrobial resistance. Finally, we show that CST was degraded by Escherichia coli via an omptin-protease and that the abundance of this gene was significantly higher in metagenomic datasets collected from patients with Crohn’s disease but not with ulcerative colitis. Overall, this study illustrates how the endogenous antimicrobial peptide, CST, shapes the microbiota composition in the gut and primes further research to uncover the role of bacterial resistance to CST in disease states such as inflammatory bowel disease.
Towards a machine-learning assisted diagnosis of psychiatric disorders and their operationalization in preclinical research: evidence from studies on addiction-like behaviour in individual rats
Authors: Jadhav Kshitij S , Jamot Benjamin Boury , Deroche-Gamonet Veronique , Belin David , Boutrel Benjamin
Published: October 2021

Background

Over the last few decades there is a progressive transition from a categorical to a dimensional approach to psychiatric disorders. Especially in case of substance use disorders, the increased interest in the individual vulnerability to transition from controlled to compulsive drug seeking and taking warrants the development of novel dimension-based objective diagnostic or stratification tools. Here we drew on a multidimensional preclinical model of addiction, namely the 3-criteria model, previously developed to identify the neurobehavioural basis of the individual vulnerability to switch from control to compulsive drug taking, to test the potential interest of a machine-learning assisted classifier objectively to identify individual subjects as vulnerable or resistant to addiction.

Methods

Large behavioural datasets from several of our previous studies on addiction-like behaviour for cocaine or alcohol were fed to a variety of machine-learning algorithms (each consisting of an unsupervised-clustering method combined with a supervised-prediction algorithm) to develop a classifier that identifies resilient and vulnerable rats with high precision and reproducibility irrespective of the cohort to which they belong.

Results

A classifier based on K-median or K-mean-clustering (for cocaine or alcohol, respectively) followed by Artificial Neural Networks emerged as a highly reliable and accurate tool to predict if a single rat is vulnerable or resilient to addiction. Thus, each of the rats previously characterized as displaying 0 criterion (i.e., resilient) or 3 criteria (i.e., vulnerable) in individual cohorts were correctly labelled by this classifier.

Conclusion

The present machine-learning-based classifier objectively labels single individuals as resilient or vulnerable to develop addiction-like behaviour in multisymptomatic preclinical models of cocaine or alcohol addiction-like behaviour in rats. This novel dimension-based classifier thereby increases the heuristic value and generalizability of these preclinical models while providing proof of principle for the deployment of similar tools for the future of diagnosis of psychiatric disorders.
Subcellular localization of mutant P23H rhodopsin in an RFP fusion knockin mouse model of retinitis pigmentosa
Authors: Robichaux Michael A. , Nguyen Vy , Chan Fung , Kailasam Lavanya , He Feng , Wilson John H. , Wensel Theodore G.
Published: October 2021

The P23H mutation in rhodopsin (Rho), the visual pigment protein in rod photoreceptor neurons, is the most common genetic cause of autosomal dominant retinitis pigmentosa (adRP), a retinal disease that causes blindness. Despite multiple studies in animal models, the subcellular details of the fate of misfolded mutant Rho in rod photoreceptors have not been completely defined. We generated a new mouse model of adRP, in which the P23H-Rho mutant allele is fused to the fluorescent protein Tag-RFP-T (P23HhRhoRFP). In heterozygotes, outer segments formed, and WT rhodopsin was properly localized there, but mutant P23H-Rho protein was specifically mislocalized in the inner segments of rods. Despite this cellular phenotype, the P23HhRhoRFP heterozygous mice exhibited only slowly progressing retinal degeneration; in ERG recordings, scotopic a-wave amplitudes were reduced by 24% and 26% at 30 days and 90 days respectively, and the corresponding scotopic b-waves by 18% and 24%. Outer nuclear layer thickness was still 80% of WT at 90 days, but at 364 days had declined to 40% of WT. Transmission electron microscopy revealed greatly expanded membrane lamellae in the inner segment, and by fluorescence imaging, we determined that the mislocalized P23HhRhoRFP was contained in greatly expanded endoplasmic reticulum (ER) membranes. TUNEL staining revealed a slow pace of cell death involving chromosomal endonucleolytic degradation. Quantification of mRNA for markers of ER stress and the unfolded protein response revealed little or no increases in levels of messages encoding the proteins BiP, CHOP, ATF6, XBP1, PERK, Eif2α and Derlin-1, but a decreased level of total Rhodopsin (mouse + human) mRNA levels. The decline in the rate of cell death after an initial burst suggests that P23HhRhoRFP mutant rods undergo an adaptative process that prolongs survival despite gross P23HhRhoRFP protein accumulation in the ER. Because of its slowly progressing nature, and easy visualization of the mutant protein, the P23H-Rho-RFP mouse may represent a useful tool for the future study of the pathology and treatment of P23H-Rho and adRP.
Rare instances of non-random dropout with the monochrome multiplex qPCR assay for mitochondrial DNA copy number
Authors: Yang Stephanie Y. , Newcomb Charles E. , Battle Stephanie L. , Hsieh Anthony YY. , Chapman Hailey L. , Côté Hélène C. F. , Arking Dan E.
Published: October 2021

Mitochondrial DNA copy number (mtDNA-CN) is a proxy for mitochondrial function and has been of increasing interest to the mitochondrial research community. There are a number of ways to measure mtDNA-CN, ranging from qPCR to whole genome sequencing [1]. A recent article in the Journal of Molecular Diagnostics [2] described a novel method for measuring mtDNA-CN that is both inexpensive and reproducible. After adapting the assay for use in our lab, we have found it to be reproducible and well-correlated with mtDNA-CN derived from whole genome sequencing. However, certain individuals show poor concordance between the two measures, particularly individuals with qPCR mtDNA-CN measurements >3 standard deviations below the sample mean, which corresponds to roughly 1% of assayed individuals (Figure 1). After examining whole genome sequencing data, this seems to be due to specific polymorphisms within the D-loop primer region, at positions MT 338, 340, 452, 457, 458, 460, 461, 466, and 467. All individuals with a variant in at least one of these positions have non-concordant mtDNA-CN measurements. Meanwhile, variants observed at other positions within the primer region do not appear to cause dropout.
Loss of TBK1 activity leads to TDP-43 proteinopathy through lysosomal dysfunction in human motor neurons
Authors: Hao Jin , Wells Michael F. , Niu Gengle , San Juan Irune Guerra , Limone Francesco , Fukuda Atsushi , Leyton-Jaimes Marcel F , Joseph Brian , Qian Menglu , Mordes Daniel A. , Budnik Bogdan , Dou Zhixun , Eggan Kevin
Published: October 2021

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by motor neuron loss accompanied by cytoplasmic localization of TDP-43 proteins and their insoluble accumulations. Haploinsufficiency of TBK1 has been found to associate with or cause ALS. However, the cell-autonomous mechanisms by which reduced TBK1 activity contributes to human motor neuron pathology remain elusive. Here, we generated a human cellular model harboring loss-of-function mutations of TBK1 by gene editing and found that TBK1 deficiency was sufficient to cause TDP-43 pathology in human motor neurons. In addition to its functions in autophagy, we found that TBK1 interacted with endosomes and was required for normal endosomal maturation and subsequent lysosomal acidification. Surprisingly, TDP-43 pathology resulted more from the dysfunctional endo-lysosomal pathway than the previously recognized autophagy inhibition mechanism. Restoring TBK1 levels ameliorated lysosomal dysfunction and TDP-43 pathology and maintained normal motor neuron homeostasis. Notably, using patient-derived motor neurons, we found that haploinsufficiency of TBK1 sensitized neurons to lysosomal stress, and chemical regulators of endosomal maturation rescued the neurodegenerative process. Together, our results revealed the mechanism of TBK1 in maintaining TDP-43 and motor neuron homeostasis and suggested that modulating endosomal maturation was able to rescue neurodegenerative disease phenotypes caused by TBK1 deficiency.
Experiencing success: an occupational therapy partnership programme. Gymnastics for children with attention deficit hyperactivity disorder
Authors: Ambrose Helen
Published: October 2021

Purpose

This paper aims to outline and evaluate a pilot partnership programme – an Occupational Therapy–led gymnastics group intervention for children aged eight to twelve with a diagnosis of attention deficit hyperactivity disorder (ADHD).

Design/methodology/approach

The overall aim of this programme was to increase participation in a valued leisure occupation. Based on the needs of the children, a physical-activity-based intervention was chosen that was challenging, novel and motivating. The intervention was then developed to target executive functioning and processing skills; enhance motor coordination skills; develop social skills; and primarily provide a positive experience. Seventeen children attended 75-minute sessions weekly for eight weeks. The programme was evaluated using non-standardised qualitative measures – parent, child and coach evaluation questionnaires were developed by the occupational therapist for this purpose.

Findings

Children engaged well in the programme with results showing increased participation and enjoyment of a new leisure occupation; improvement in social interaction levels and a sense of belonging; and development of motor and process skills. The results demonstrate the benefit of a partnership approach and suggest sustainability of the programme as well as the gains made.

Originality/value

The results of this evaluation suggest that the programme met its aims and supports further research into the efficacy of this type of partnership approach and intervention in supporting children with ADHD attending Child and Adolescent Mental Health Services.
Does structural capital count in human capital-corporate financial performance relationship? Evidence from deposit money banks in Nigeria
Authors: Onuoha Nnachi Egwu
Published: October 2021

Purpose

The purpose of this paper is to explore human capital and corporate financial performance link from the perspective of human capital theory, resources-based view and balanced score card approach, and the mediating role of structural capital in this relationship.

Design/methodology/approach

Overall, a data set was drawn from five-year annual reports of deposit money banks (DMBs) in Nigeria. Additionally, the bootstrap procedure was performed to test the mediating role of structural capital.

Findings

Specifically, the paper results indicate that whereas human capital has significant positive effect on corporate financial performance and structural capital, structural capital has significant positive effect on corporate financial performance. Additionally, the study finds structural capital to mediate the effect of human capital on organizational financial performance.

Research limitations/implications

This paper focused on 12 DMBs in Nigeria and their five year annual reports. Accordingly, future studies in this area should increase the number of banks and years, and include firms operating in insurance, manufacturing, telecommunication and oil and gas industries to permit comparability of results and broader basis for generalizability. Moreover, the study results provide insights that would serve as robust empirical basis for policy makers to insist on enhancement of the value of human and structural capital variables.

Practical implications

The managers of DMBs should commit to development of their employees through improvement in their training and health programs, among others. Also, they should ensure continuous improvement of their structural capital to enable the investments in their employee to translate to enhanced corporate financial performance.

Originality/value

To the best of the author’s knowledge, this is the first study to explore the mediation effect of structural capital on the human capital-corporate financial performance link using evidence from DMBs in Nigeria and, thus, extends and deepens extant literature on human capital-organizational performance nexus.