bluuebunny/crossref_metadata_2025 huggingface dataset:
Evolution of the grain size distribution in Milky Way-like galaxies in post-processed IllustrisTNG simulations
Authors: Huang Yu-Hsiu , Hirashita Hiroyuki , Hsu Yun-Hsin , Lin Yen-Ting , Nelson Dylan , Cooper Andrew P
Published: November 2020

We model dust evolution in Milky Way-like galaxies by post-processing the IllustrisTNG cosmological hydrodynamical simulations in order to predict dust-to-gas ratios and grain size distributions. We treat grain-size-dependent dust growth and destruction processes using a 64-bin discrete grain size evolution model without spatially resolving each galaxy. Our model broadly reproduces the observed dust–metallicity scaling relation in nearby galaxies. The grain size distribution is dominated by large grains at z ≳ 3 and the small-grain abundance rapidly increases by shattering and accretion (dust growth) at z ≲ 2. The grain size distribution approaches the so-called MRN distribution at z ∼ 1, but a suppression of large-grain abundances occurs at z < 1. Based on the computed grain size distributions and grain compositions, we also calculate the evolution of the extinction curve for each Milky Way analogue. Extinction curves are initially flat at z > 2, and become consistent with the Milky Way extinction curve at z ≲ 1 at $1/\lambda \lt 6~\rm{\mu m}^{-1}$. However, typical extinction curves predicted by our model have a steeper slope at short wavelengths than is observed in the Milky Way. This is due to the low-redshift decline of gas-phase metallicity and the dense gas fraction in our TNG Milky Way analogues that suppresses the formation of large grains through coagulation.
WD 1856 b: a close giant planet around a white dwarf that could have survived a common envelope phase
Authors: Lagos F , Schreiber M R , Zorotovic M , Gänsicke B T , Ronco M P , Hamers Adrian S
Published: November 2020

The discovery of a giant planet candidate orbiting the white dwarf WD 1856+534 with an orbital period of 1.4 d poses the questions of how the planet reached its current position. We here reconstruct the evolutionary history of the system assuming common envelope evolution as the main mechanism that brought the planet to its current position. We find that common envelope evolution can explain the present configuration if it was initiated when the host star was on the asymptotic giant branch, the separation of the planet at the onset of mass transfer was in the range 1.69–2.35 au, and if in addition to the orbital energy of the surviving planet either recombination energy stored in the envelope or another source of additional energy contributed to expelling the envelope. We also discuss the evolution of the planet prior to and following common envelope evolution. Finally, we find that if the system formed through common envelope evolution, its total age is in agreement with its membership to the Galactic thin disc. We therefore conclude that common envelope evolution is at least as likely as alternative formation scenarios previously suggested such as planet–planet scattering or Kozai–Lidov oscillations.
Chemical abundances of Seyfert 2 AGNs – IV. Composite models calculated by photoionization + shocks
Authors: Dors O L , Contini M , Riffel R A , Pérez-Montero E , Krabbe A C , Cardaci M V , Hägele G F
Published: November 2020

We build detailed composite models of photoionization and shock ionization based on the suma code to reproduce emission lines emitted from the Narrow Line Regions (NLR) of Seyfert 2 nuclei. The aim of this work is to investigate diagram active galactic nucleus (AGN) positions according to shock parameters, shock effects on the gas temperature and ionization structures and derive a semi-empirical abundance calibration based on emission-line ratios little sensitive to the shock presence. The models were used to reproduce optical (3000 < λ(Å) < 7000) emission line intensities of 244 local ($z \: \lesssim \: 0.4$) Seyfert 2s, whose observational data were selected from Sloan Digital Sky Survey DR7. Our models suggest that shocks in Seyfert 2 nuclei have velocities in the range of 50–300 $\rm km \: s^{-1}$ and imply a narrower metallicity range ($0.6 \: \lesssim \: (Z/Z_{\odot }) \: \lesssim \: 1.6$) than those derived using pure photoionization models. Our results indicate that shock velocity in AGNs cannot be estimated using standard optical line ratio diagrams, based on integrated spectra. Our models predict a different temperature structure and $\rm O^{+}$/O and $\rm O^{2+}$/O fractional abundances throughout the NLR clouds than those derived from pure photoionization models, mainly in shock-dominated objects. This suggests that, in order to minimize the shock effects, the combination of emission-lines emitted by ions with similar intermediate ionization potential could be good metallicity indicators. Finally, we derive two calibrations between the N/O abundance ratio and the N2O2 = log([N ii]λ6584/[O ii]λ3727) and N2 = log([N ii]λ6584/H α) indexes which agree with that derived from pure photoionization models.
DNA damage alters nuclear mechanics through chromatin reorganization
Authors: dos Santos Ália , Cook Alexander W , Gough Rosemarie E , Schilling Martin , Olszok Nora A , Brown Ian , Wang Lin , Aaron Jesse , Martin-Fernandez Marisa L , Rehfeldt Florian , Toseland Christopher P
Published: November 2020

DNA double-strand breaks drive genomic instability. However, it remains unknown how these processes may affect the biomechanical properties of the nucleus and what role nuclear mechanics play in DNA damage and repair efficiency. Here, we have used Atomic Force Microscopy to investigate nuclear mechanical changes, arising from externally induced DNA damage. We found that nuclear stiffness is significantly reduced after cisplatin treatment, as a consequence of DNA damage signalling. This softening was linked to global chromatin decondensation, which improves molecular diffusion within the organelle. We propose that this can increase recruitment for repair factors. Interestingly, we also found that reduction of nuclear tension, through cytoskeletal relaxation, has a protective role to the cell and reduces accumulation of DNA damage. Overall, these changes protect against further genomic instability and promote DNA repair. We propose that these processes may underpin the development of drug resistance.
A pathway for error-free non-homologous end joining of resected meiotic double-strand breaks
Authors: Hatkevich Talia , Miller Danny E , Turcotte Carolyn A , Miller Margaret C , Sekelsky Jeff
Published: November 2020

Programmed DNA double-strand breaks (DSBs) made during meiosis are repaired by recombination with the homologous chromosome to generate, at selected sites, reciprocal crossovers that are critical for the proper separation of homologs in the first meiotic division. Backup repair processes can compensate when the normal meiotic recombination processes are non-functional. We describe a novel backup repair mechanism that occurs when the homologous chromosome is not available in Drosophila melanogaster meiosis. In the presence of a previously described mutation (Mcm5A7) that disrupts chromosome pairing, DSB repair is initiated by homologous recombination but is completed by non-homologous end joining (NHEJ). Remarkably, this process yields precise repair products. Our results provide support for a recombination intermediate recently proposed in mouse meiosis, in which an oligonucleotide bound to the Spo11 protein that catalyzes DSB formation remains bound after resection. We propose that this oligonucleotide functions as a primer for fill-in synthesis to allow scarless repair by NHEJ. We argue that this is a conserved repair mechanism that is likely to be invoked to overcome occasional challenges in normal meiosis.
Results of the European EDITH nephrologist survey on factors influencing treatment modality choice for end-stage kidney disease
Authors: de Jong Rianne W , Jager Kitty J , Vanholder Raymond C , Couchoud Cécile , Murphy Mark , Rahmel Axel , Massy Ziad A , Stel Vianda S
Published: November 2020

Background

Access to forms of dialysis, kidney transplantation (Tx) and comprehensive conservative management (CCM) for patients with end-stage kidney disease (ESKD) varies across European countries. Attitudes of nephrologists, information provision and decision-making may influence this access and nephrologists may experience several barriers when providing treatments for ESKD.

Methods

We surveyed European nephrologists and kidney transplant surgeons treating adults with ESKD about factors influencing modality choice. Descriptive statistics were used to compare the opinions of professionals from European countries with low–, middle– and high–gross domestic product purchasing power parity (GDP PPP).

Results

In total, 681 professionals from 33 European countries participated. Respondents from all GDP categories indicated that ∼10% of patients received no information before the start of renal replacement therapy (RRT) (P = 0.106). Early information provision and more involvement of patients in decision-making were more frequently reported in middle- and high-GDP countries (P < 0.05). Professionals’ attitudes towards several treatments became more positive with increasing GDP (P < 0.05). Uptake of in-centre haemodialysis was sufficient to 73% of respondents, but many wanted increased uptake of home dialysis, Tx and CCM. Respondents experienced different barriers according to availability of specific treatments in their centre. The occurrence of barriers (financial, staff shortage, lack of space/supplies and patient related) decreased with increasing GDP (P < 0.05).

Conclusions

Differences in factors influencing modality choice when providing RRT or CCM to adults with ESKD were found among low-, middle- and high-GDP countries in Europe. Therefore a unique pan-European policy to improve access to treatments may be inefficient. Different policies for clusters of countries could be more useful.
Association of substance use disorders and drug overdose with adverse COVID-19 outcomes in New York City: January–October 2020
Authors: Allen Bennett , El Shahawy Omar , Rogers Erin S , Hochman Sarah , Khan Maria R , Krawczyk Noa
Published: November 2020

Background

Evidence suggests that individuals with history of substance use disorder (SUD) are at increased risk of COVID-19, but little is known about relationships between SUDs, overdose and COVID-19 severity and mortality. This study investigated risks of severe COVID-19 among patients with SUDs.

Methods

We conducted a retrospective review of data from a hospital system in New York City. Patient records from 1 January to 26 October 2020 were included. We assessed positive COVID-19 tests, hospitalizations, intensive care unit (ICU) admissions and death. Descriptive statistics and bivariable analyses compared the prevalence of COVID-19 by baseline characteristics. Logistic regression estimated unadjusted and sex-, age-, race- and comorbidity-adjusted odds ratios (AORs) for associations between SUD history, overdose history and outcomes.

Results

Of patients tested for COVID-19 (n = 188 653), 2.7% (n = 5107) had any history of SUD. Associations with hospitalization [AORs (95% confidence interval)] ranged from 1.78 (0.85–3.74) for cocaine use disorder (COUD) to 6.68 (4.33–10.33) for alcohol use disorder. Associations with ICU admission ranged from 0.57 (0.17–1.93) for COUD to 5.00 (3.02–8.30) for overdose. Associations with death ranged from 0.64 (0.14–2.84) for COUD to 3.03 (1.70–5.43) for overdose.

Discussion

Patients with histories of SUD and drug overdose may be at elevated risk of adverse COVID-19 outcomes.
Health in Men Study: is frailty a predictor of medication-related hospitalization?
Authors: Athuraliya N , Etherton-Beer C
Published: November 2020

Background

Older adults are at high risk of medication-related hospitalizations. Frailty is a phenotype commonly observed in older people due to declining physiological functions.

Aim

To examine the association of frailty with medication-related hospitalization among community dwelling older men.

Methods

A prospective observational cohort study was conducted among community dwelling older men (mean age 75.6 years SD 5.9) from Western Australia (4324) who participated in the Health in Men Study. Participants were followed-up at 12 and 24 months to determine adverse drug event-related hospitalization, hospitalizations for other causes and mortality.

Results and Discussion

The prevalence of frailty was 13.2%. At baseline, frailty was associated with exposure to polypharmacy, potentially inappropriate medication use and potential adverse drug–drug interactions with unadjusted odds ratios; [4.13 (3.48–4.89) P < 0.001], [2.46 (1.91–3.17) P < 0.001], [3.85 (3.03–4.90) P < 0.001], respectively. In unadjusted models, frail men were more likely to have non-accidental falls [OR 3.16 (2.51–3.99) P < 0.001], acute kidney injury [OR 3.37 (2.35–4.82) P < 0.001], ADE-related hospitalizations at 12 months [OR 6.83 (4.91–9.51)] and non-ADE-related hospitalizations [OR 2.63 (2.01–3.45)], or to be dead at 12 months [OR 2.97 (1.79–4.92)] and at 24 months [OR 3.14 (2.28–4.33)] when compared with non-frail men. After adjusting for age, living alone, cognitive decline, smoking status and comorbidity, frailty remained associated with ADE-related hospitalization [OR 3.60 (2.41–5.37)], non-ADE-related hospitalizations [OR 1.74 (1.29–2.36)] and death [OR 1.67 (1.15–2.41)].

Conclusion

The study suggests that frailty is a predictor of medication-related harm with poorer clinical outcomes including mortality.
Effectiveness of initial methotrexate-based treatment approaches in early rheumatoid arthritis: an elicitation of rheumatologists’ beliefs
Authors: Pokharel Gyanendra , Deardon Rob , Johnson Sindhu R , Tomlinson George , Hull Pauline M , Hazlewood Glen S
Published: November 2020

Objectives

To quantify rheumatologists’ beliefs about the effectiveness of triple therapy (MTX + HCQ + SSZ) and other commonly used initial treatments for RA.

Methods

In a Bayesian belief elicitation exercise, 40 rheumatologists distributed 20 chips, each representing 5% of their total weight of belief on the probability that a typical patient with moderate–severe early RA would have an ACR50 response within 6 months with MTX (oral and s.c.), MTX + HCQ (dual therapy) and triple therapy. Parametric distributions were fit, and used to calculate pairwise median relative risks (RR), with 95% credible intervals, and estimate sample sizes for new trials to shift these beliefs.

Results

In the pooled analysis, triple therapy was perceived to be superior to MTX (RR 1.97; 1.35, 2.89) and dual therapy (RR 1.32; 1.03, 1.73). A pessimistic subgroup (n = 10) perceived all treatments to be similar, whereas an optimistic subgroup (n = 10) believed triple therapy to be most effective of all (RR 4.03; 2.22, 10.12). Similar variability was seen for the comparison between oral and s.c. MTX. Assuming triple therapy is truly more effective than MTX, a trial of 100 patients would be required to convince the pessimists; if triple therapy truly has no–modest effect (RR <1.5), a non-inferiority trial of 475 patients would be required to convince the optimists.

Conclusion

Rheumatologists’ beliefs regarding the effectiveness of triple therapy vary, which may partially explain the variability in its use. Owing to the strength of beliefs, some may be reluctant to shift, even with new evidence.
Childhood trauma, brain structure and emotion recognition in patients with schizophrenia and healthy participants
Authors: Rokita Karolina I , Holleran Laurena , Dauvermann Maria R , Mothersill David , Holland Jessica , Costello Laura , Kane Ruán , McKernan Declan , Morris Derek W , Kelly John P , Corvin Aiden , Hallahan Brian , McDonald Colm , Donohoe Gary
Published: November 2020

Childhood trauma, and in particular physical neglect, has been repeatedly associated with lower performance on measures of social cognition (e.g. emotion recognition tasks) in both psychiatric and non-clinical populations. The neural mechanisms underpinning this association have remained unclear. Here, we investigated whether volumetric changes in three stress-sensitive regions—the amygdala, hippocampus and anterior cingulate cortex (ACC)—mediate the association between childhood trauma and emotion recognition in a healthy participant sample (N = 112) and a clinical sample of patients with schizophrenia (N = 46). Direct effects of childhood trauma, specifically physical neglect, on Emotion Recognition Task were observed in the whole sample. In healthy participants, reduced total and left ACC volumes were observed to fully mediate the association between both physical neglect and total childhood trauma score, and emotion recognition. No mediating effects of the hippocampus and amygdala volumes were observed for either group. These results suggest that reduced ACC volume may represent part of the mechanism by which early life adversity results in poorer social cognitive function. Confirmation of the causal basis of this association would highlight the importance of resilience-building interventions to mitigate the detrimental effects of childhood trauma on brain structure and function.
Somatic Growth of Enteral-Only Fed Extremely Low Birth Weight Infants in a Resource-Restricted Setting
Authors: Kombo Lena , Smith Johan , Van Wyk Lizelle
Published: November 2020

Aim

To determine the growth and prevalence of extrauterine growth restriction (EUGR) in extremely low birth weight (ELBW) infants receiving enteral-only nutrition in a resource-restricted (RR) environment.

Methods

Information on nutritional intake, provided largely from fortified breastmilk, was collected retrospectively for 72 ELBW (<1000 g) infants admitted to Tygerberg Hospital, Cape Town, South Africa over a 1 year period. Anthropometric data for the first 49 postnatal days were compared to gender-specific INTERGROWTH-21st standards.

Results

Full enteral feeds (150 ml/kg) were reached by Day 10–14 with energy >100 Kcal/kg/day from Day 10, and protein >3.5 mg/kg/day from Day 14, onwards. Growth velocity remained below 15 g/kg/day at Day 49. INTERGROWTH-21st Z-scores decreased from −0.8 ± 1.1 at birth to −2.4 ± 1.5 at Day 49. Adequate weight growth velocity (≥15 g/kg/day) was associated with maternal hypertension, completed antenatal steroids, caesarean section delivery and small for gestational age status.

Conclusion

This is the first study to evaluate growth of ELBW infants in a RR setting where enteral-only nutrition, principally from fortified breastmilk, was the primary feeding option. The incidence of EUGR, although high, was similar to the incidence in well-resourced settings, where total parenteral nutrition is routinely provided.

Lay summary

Extra-uterine growth restriction (EUGR) is high in extremely low birth weight infants receiving enteral-only nutrition. However, EUGR rates are similar to infants receiving parenteral nutrition. Despite developmental immaturity, it is possible for these infants to achieve fetal growth rates. More aggressive feeding and fortification strategies may be necessary and will need to be balanced against the risk and fear of necrotizing enterocolitis. Enteral-only feeding regimens, especially in resource-restricted environments, should be audited regularly to ensure provision of feeds with the most optimal protein, and protein to energy ratios possible.
Possible host-adaptation of SARS-CoV-2 due to improved ACE2 receptor binding in mink
Authors: Welkers Matthijs R A , Han Alvin X , Reusken Chantal B E M , Eggink Dirk
Published: November 2020

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections on mink farms are increasingly observed in several countries, leading to the massive culling of animals on affected farms. Recent studies showed multiple (anthropo)zoonotic transmission events between humans and mink on these farms. Mink-derived SARS-CoV-2 sequences from The Netherlands and Denmark contain multiple substitutions in the S protein receptor binding domain (RBD). Molecular modeling showed that these substitutions increase the mean binding energy, suggestive of potential adaptation of the SARS-CoV-2 S protein to the mink angiotensin-converting enzyme 2 (ACE2) receptor. These substitutions could possibly also impact human ACE2 binding affinity as well as humoral immune responses directed to the RBD region of the SARS-CoV-2 S protein in humans. We wish to highlight these observations to raise awareness and urge for the continued surveillance of mink (and other animal)-related infections.
Prognostic impact of short-term ambulatory blood pressure variability for microvascular and macrovascular outcomes in patients with type 2 diabetes: the Rio de Janeiro Type 2 Diabetes Cohort Study
Authors: Cardoso Claudia R.L. , Salles Guilherme C. , Leite Nathalie C. , Salles Gil F.
Published: November 2020

Objective:

To evaluate the prognostic importance of short-term blood pressure variability (BPV) for the occurrence of macrovascular and microvascular complications in individuals with type 2 diabetes.

Methods:

Six hundred and forty patients had 24-h ambulatory BP monitoring performed at baseline and were followed-up over a median of 11.2 years. Daytime, night-time and 24-h SBP and DBPV parameters (standard deviations and variation coefficients) were calculated. Multivariate Cox analysis, adjusted for risk factors and mean BPs, examined the associations between BPV and the occurrence of microvascular (retinopathy, microalbuminuria, renal function deterioration, peripheral neuropathy) and macrovascular complications [total cardiovascular events (CVEs), major adverse CVEs [MACEs]), and cardiovascular and all-cause mortalities. Improvements in risk discrimination were assessed by the C-statistic and Integrated Discrimination Improvement (IDI) index.

Results:

During follow-up, 186 patients had a CVE (150 MACEs), and 237 patients died (107 from cardiovascular diseases); 155 newly developed or worsened diabetic retinopathy, 200 achieved the renal composite outcome (124 newly developed microalbuminuria and 102 deteriorated renal function), and 170 newly developed or worsened peripheral neuropathy. Daytime DBPV was the best predictor for all cardiovascular outcomes and mortality, with hazard ratios (for increments of 1SD) ranging from 1.27 (95% CI 1.09–1.48) for all-cause mortality to 1.55 (1.29–1.85) for MACEs, and it improved cardiovascular risk discrimination (with increases in C-statistic of up to 0.026, and IDIs of up to 22.8%). No BPV parameter predicted any microvascular outcome.

Conclusion:

Short-term BPV, particularly daytime DBPV, predicts future development of macrovascular complications and mortality and improves cardiovascular risk discrimination in patients with diabetes.
Increase in trigeminal ganglion neurons that respond to both calcitonin gene–related peptide and pituitary adenylate cyclase–activating polypeptide in mouse models of chronic migraine and posttraumatic headache
Authors: Guo Zhaohua , Czerpaniak Katherine , Zhang Jintao , Cao Yu-Qing
Published: November 2020

A large body of animal and human studies indicates that blocking peripheral calcitonin gene–related peptide (CGRP) and pituitary adenylate cyclase–activating polypeptide (PACAP) signaling pathways may prevent migraine episodes and reduce headache frequency. To investigate whether recurring migraine episodes alter the strength of CGRP and PACAP signaling in trigeminal ganglion (TG) neurons, we compared the number of TG neurons that respond to CGRP and to PACAP (CGRP-R and PACAP-R, respectively) under normal and chronic migraine-like conditions. In a mouse model of chronic migraine, repeated nitroglycerin (NTG) administration significantly increased the number of CGRP-R and PACAP-R neurons in TG but not dorsal root ganglia. In TG neurons that express endogenous αCGRP, repeated NTG led to a 7-fold increase in the number of neurons that respond to both CGRP and PACAP (CGRP-R&PACAP-R). Most of these neurons were unmyelinated C-fiber nociceptors. This suggests that a larger fraction of CGRP signaling in TG nociceptors may be mediated through the autocrine mechanism, and the release of endogenous αCGRP can be enhanced by both CGRP and PACAP signaling pathways under chronic migraine condition. The number of CGRP-R&PACAP-R TG neurons was also increased in a mouse model of posttraumatic headache (PTH). Interestingly, low-dose interleukin-2 treatment, which completely reverses chronic migraine-related and PTH-related behaviors in mouse models, also blocked the increase in both CGRP-R and PACAP-R TG neurons. Together, these results suggest that inhibition of both CGRP and PACAP signaling in TG neurons may be more effective in treating chronic migraine and PTH than targeting individual signaling pathways.
Feasibility of Predicting In-Season Mental Health Problems in College Student-Athletes From Pre-season Assessment
Authors: Leonelli Brooke R. , Kuhn Tyler , Sanborn Victoria , Gunstad John
Published: November 2020

Objective:

To examine whether pre-season assessment using a validated assessment tool, the Minnesota Multiphasic Personality Inventory-2-Restructured Form (MMPI-2-RF), could predict college student-athletes identified as experiencing in-season mental health (MH) problems.

Design:

A prospective study of athletes who completed a pre-season evaluation in August 2018.

Setting and Participants:

A total of 195 National Collegiate Athletic Association Division 1 student-athletes from a large midwestern university in northeast Ohio.

Independent Variable:

The MMPI-2-RF, a 338-item self-report measure of constructs relevant to the assessment of psychopathology and personality.

Main Outcome Measure:

Mental health problems of student-athletes tracked throughout the competitive season (August 2018-May 2019) by a team of athletic department personnel who met weekly with a licensed clinical psychologist.

Results:

In pre-season assessment, 71.8% of athletes clinically elevated at least one MMPI-2-RF scale and underreporting was higher in student-athletes than normative controls. Pre-season levels of internalizing psychopathology, diffuse physical symptoms, and unusual thoughts predicted increased likelihood of experiencing MH problems during the competitive season.

Conclusions:

The current findings suggest that the MMPI-2-RF may be a promising tool for identifying student-athletes at risk for MH concerns.
Combining longitudinal data from different cohorts to examine the life-course trajectory
Authors: Hughes Rachael A. , Tilling Kate , Lawlor Deborah A.
Published: November 2020

Longitudinal data are necessary to reveal changes within the same individual as they age. However, rarely will a single cohort capture data throughout the lifespan. We describe in detail the steps needed to develop life-course trajectories from cohorts that cover different and overlapping periods of life. Such independent studies are likely from heterogenous populations which raises several challenges including: data harmonisation (deriving new harmonised variables from differently measured variables by identifying common elements across all studies); systematically missing data (variables not measured are missing for all participants of a cohort); and model selection with differing age ranges and measurement schedules. We illustrate how to overcome these challenges using an example which examines the effects of parental education, sex, and ethnicity on weight trajectories. Data were from five prospective cohorts (Belarus and four UK regions), spanning from birth to early adulthood during differing calendar periods. Key strengths of our approach include modelling trajectories over wide age ranges, sharing of information across studies and direct comparison of the same parts of the life-course in different geographical regions and time periods. We also introduce a novel approach of imputing individual-level covariates of a multilevel model with a nonlinear growth trajectory and interactions.
Sleep is required for odor exposure to consolidate memory and remodel olfactory synapses
Authors: Chandra Rashmi , Farah Fatima , Muñoz-Lobato Fernando , Bokka Anirudh , Benedetti Kelli L. , Brueggemann Chantal , Saifuddin Fatema , Miller Julia M. , Li Joy , Chang Eric , Varshney Aruna , Jimenez Vanessa , Baradwaj Anjana , Nassif Cibelle , Alladin Sara , Andersen Kristine , Garcia Angel J. , Bi Veronica , Nordquist Sarah K. , Dunn Raymond L. , Tokalenko Kateryna , Soohoo Emily , Garcia Vanessa , Kaur Sukhdeep , Harris Malcolm , Briseno Fabiola , Fung Brandon , Bykov Andrew , Guillen Hazel , Byrd Decklin , Odisho Emma , Tsujimoto Bryan , Tran Alan , Duong Alex , Daigle Kevin C. , Paisner Rebekka , Zuazo Carlos E. , Churgin Matthew A. , Fang-Yen Christopher , Bremer Martina , Kato Saul , L’Étoile Noëlle D. , VanHoven Miri K.
Published: November 2020

Animals with complex nervous systems demand sleep for memory consolidation and synaptic remodeling. Here we show that though theCaenorhabditis elegansnervous system has a limited number of neurons, sleep is necessary for both processes. In addition, it is unclear in any system if sleep collaborates with experience to alter synapses between specific neurons and whether this ultimately affects behavior.C. elegansneurons have defined connections and well-described contributions to behavior. We show that spaced odor-training and post-training sleep induce long-term memory. Memory consolidation, but not acquisition, requires a pair of interneurons, the AIYs, which play a role in odor-seeking behavior. In worms that consolidate memory, both sleep and odor conditioning are required to diminish inhibitory synaptic connections between the AWC chemosensory neurons and the AIYs. Thus, we demonstrate in a living organism that sleep is required for events immediately after training that drive memory consolidation and alter synaptic structures.
Neuroskeletal effects of chronic bioelectric nerve stimulation in health and diabetes
Authors: Beeve Alec T , Shen Ivana , Zhang Xiao , Magee Kristann , Yan Ying , MacEwan Matthew , Scheller Erica L
Published: November 2020

Background/Aims

Bioelectric nerve stimulation (eStim) is a novel clinical paradigm that can promote nerve regeneration after trauma, including within the context of diabetes. However, its ability to prevent the onset of diabetic peripheral neuropathy (DPN) has not yet been evaluated. Beyond the nerve itself, DPN has emerged as a potential contributor to sarcopenia and bone disease; thus, we hypothesized that eStim could serve as a strategy to simultaneously promote neural and musculoskeletal health in diabetes.

Methods

To address this question, an eStim paradigm pre-optimized to promote nerve regeneration was applied to the sciatic nerve, which directly innervates the tibia and lower limb, for 8-weeks in control and streptozotocin-induced type 1 diabetic (T1D) rats. Metabolic, gait, nerve and bone assessments were used to evaluate the progression of diabetes and the effect of sciatic nerve eStim on neuropathy and musculoskeletal disease, while also considering the effects of cuff placement and chronic eStim in otherwise healthy animals.

Results

Rats with T1D exhibited increased mechanical allodynia in the hindpaw, reduced muscle mass, decreased cortical and cancellous bone volume fraction (BVF), reduced cortical bone tissue mineral density (TMD), and decreased bone marrow adiposity. T1D also had an independent effect on gait. Placement of the cuff electrode alone was sufficient to alter gait patterns and to promote unilateral reductions in tibia length, cortical BVF, and bone marrow adiposity. Alterations in gait patterns and left-right balance to tibia length were restored with eStim, but it did not prevent T1D-induced changes in muscle, bone, marrow adiposity or mechanical sensitivity. Beyond this, chronic eStim resulted in an independent, bilateral reduction in cortical TMD.

Conclusion

Overall, these results provide new insight into the pathogenesis of diabetic neuroskeletal disease and its regulation by eStim. Though eStim did not prevent neural or musculoskeletal complications in T1D, our results demonstrate that clinical applications of peripheral neuromodulation ought to consider the impact of device placement and eStim on long-term skeletal health in both healthy individuals and those with metabolic disease. This includes monitoring for compounded bone loss to prevent unintended consequences including decreased bone mineral density and increased fracture risk.
A method to quantify autonomic nervous system function in healthy, able-bodied individuals
Authors: Debnath Shubham , Levy Todd J. , Bellehsen Mayer , Schwartz Rebecca M. , Barnaby Douglas P. , Zanos Stavros , Volpe Bruce T. , Zanos Theodoros P.
Published: November 2020

The autonomic nervous system (ANS), which maintains physiological homeostasis in various organ systems via parasympathetic and sympathetic branches, is altered in common diffuse and focal conditions. Sensitive, quantitative biomarkers could detect changes in ANS function, first here in healthy participants and eventually in patients displaying dysautonomia. This framework combines controlled autonomic testing with feature extraction from physiological responses. Twenty-one individuals were assessed in two morning and two afternoon sessions over two weeks. Each session included five standard clinical tests probing autonomic function: squat test, cold pressor test, diving reflex test, deep breathing, and Valsalva maneuver. Noninvasive sensors captured continuous electrocardiography, blood pressure, breathing, electrodermal activity, and pupil diameter. Heart rate, heart rate variability, mean arterial pressure, electrodermal activity, and pupil diameter responses to the perturbations were extracted, and averages across participants were computed. A template matching algorithm calculated scaling and stretching features that optimally fit the average to an individual response. These features were grouped based on test and modality to derive sympathetic and parasympathetic indices for this healthy population. A significant positive correlation (p= 0.000377) was found between sympathetic amplitude response and body mass index. Additionally, longer duration and larger amplitude sympathetic and longer duration parasympathetic responses occurred in afternoon testing sessions; larger amplitude parasympathetic responses occurred in morning sessions. These results demonstrate the robustness and sensitivity of an algorithmic approach to extract multimodal responses from standard tests. This novel method of quantifying ANS function can be used for early diagnosis, measurement of disease progression, or treatment evaluation.
What are the demographic consequences of a seed bank stage for columnar cacti?
Authors: Arroyo-Cosultchi Gabriel , Mandujano María C. , Salguero-Gómez Roberto , Martínez Armando J. , Golubov Jordan
Published: November 2020

The dynamics of plants populations are often limited by the early stages in their life cycles. The question if the columnar cacti have or not a seed bank in predictable environments. Yet, information regarding seed bank dynamics and how these may influence the full life cycle of plant species is remarkably scarce or ignore. This lack of knowledge is mostly due to the challenges in quantifying seed vital rates. Studies of arid land plant species have historically been focused on the drivers of sporadic recruitment. However, little attention has been given to the demographic consequences of early developmental stages, including seed banks. Here, we evaluate the effects of seed bank survival and seedling recruitment vital rates on the population dynamics and viability of 12 columnar cacti species, recent evidence suggests that cacti seeds may remain viable for the short-term. We assess how changes in the vital rates of these processes, and the inclusion of a seed bank affect population growth rate (λ). We found that a seed bank in the examined matrix population models significantly increasedλas well as the vital rate elasticities ofλto growth and fecundity, whereas that of overall survival decreased. Our numerical simulations showed that seed survival had a larger effect onλthan seedling recruitment and establishment. We suggest that seed bank may explain the structure and population dynamics. Thus, we argue reconsider that this early stage in demographic models will generate more informed decisions on the conservation and management of columnar cacti.
Identifiability of speciation times under the multispecies coalescent
Authors: Kubatko Laura , Leonard Alexander , Chifman Julia
Published: November 2020

The advent of rapid and inexpensive sequencing technologies has necessitated the development of computationally efficient methods for analyzing sequence data for many genes simultaneously in a phylogenetic framework. The coalescent process is the most commonly used model for linking the underlying genealogies of individual genes with the global species-level phylogeny, but inference under the coalescent model is computationally daunting in the typical inference frameworks (e.g., the likelihood and Bayesian frameworks) due to the dimensionality of the space of both gene trees and species trees. Here we consider estimation of the branch lengths in fixed species trees with three or four taxa, and show that these branch lengths are identifiable. We also show that for three and four taxa simple estimators for the branch lengths can be derived based on observed site pattern frequencies. Properties of these estimators, such as their asymptotic variances and large-sample distributions, are examined, and performance of the estimators is assessed using simulation. Finally, we use these estimators to develop a hypothesis test that can be used to delimit species under the coalescent model for three or four putative taxa.
Cyto-nuclear linkage disequilibrium resulting from admixture
Authors: Fields Peter D. , McCauley David E. , Taylor Douglas R.
Published: November 2020

Previous studies of North American populations of the invasive plantSilene latifoliashowed significant cyto-nuclear linkage disequilibrium (CNLD) between SNP variants of a mitochondrial gene (atp1) and the most common allele at nuclear microsatellite loci. Fieldset al. (2014) hypothesized that this CNLD arose partially as a consequence of admixture that occurred during the colonization of North American (NA) populations ofS latifoliavia seed dispersal from genetically differentiated European populations that represent a portion of the native range of this species. In order to evaluate the plausibility of the admixture hypothesis, as opposed to metapopulation processes alone, we estimated CNLD for these same loci using data collected from eastern (EEU) and western (WEU) European populations ofS. latifoliaknown to be genetically differentiated and likely sources of the spread of the study species to North America. We show that the CNLD found previously in NA populations ofS. latifoliacan be attributed to admixture of the previously isolated European demes coupled with decay since that time. Our applied framework allows the separation of the forces generating and dissolving statistical associations between alleles in cytoplasmic organelles and the nuclear genome and may thus be of utility in the study of plant or animal microbiomes.
Cilia-independent requirements for Ccdc103 promoting proliferation and migration of myeloid cells
Authors: Falkenberg Lauren G. , Beckman Sarah A. , Ravisankar Padmapriyadarshini , Dohn Tracy E. , Waxman Joshua S.
Published: November 2020

The pathology of primary ciliary dyskinesia (PCD) is predominantly attributed to impairment of motile cilia. However, PCD patients also have perplexing functional defects in myeloid cells, which lack motile cilia. Here, we show Coiled-coiled domain containing protein 103 (CCDC103), mutations in which underlie PCD, is required for the proliferation and directed migration of myeloid cells. CCDC103 co-localizes with cytoplasmic microtubules in human myeloid cells. Zebrafishccdc103/schmalhans(smh) mutants have reduced macrophage and neutrophil proliferation, rounded cell morphology, and an inability to migrate efficiently to the site of sterile wounds. Furthermore, we demonstrate that direct interactions between CCDC103 and Sperm associated antigen 6 (SPAG6), which also promotes microtubule stability, are abrogated by CCDC103 mutations from PCD patients, and thatspag6zebrafish mutants recapitulate the myeloid defects ofsmhmutants. In summary, we have illuminated a mechanism, independent of motile cilia, to explain functional defects in myeloid cells from PCD patients.

Summary Statement

We show Ccdc103 regulates myeloid migration and proliferation independent of cilia in zebrafish and that mutations in CCDC103 that cause primary ciliary dyskinesia abrogate interactions with the microtubule-stabilizing protein SPAG6.
MIPMLP – Microbiome Preprocessing Machine Learning Pipeline
Authors: Jasner Yoel Y , Belogolovski Anna , Ben-Itzhak Meirav , Koren Omry , Louzoun Yoram
Published: November 2020

16S sequencing results are often used for Machine Learning (ML) tasks. 16S gene sequences are represented as feature counts, which are associated with taxonomic representation. Raw feature counts may not be the optimal representation for ML. We checked multiple preprocessing steps and tested the optimal combination for 16S sequencing-based classification tasks. We computed the contribution of each step to the accuracy as measured by the Area Under Curve (AUC) of the classification. We show that the log of the feature counts is much more informative than the relative counts. We further show that merging features associated with the same taxonomy at a given level, through a dimension reduction step for each group of bacteria improves the AUC. Finally, we show that z-scoring has a very limited effect on the results. These preprocessing steps are integrated into the MIPMLP - Microbiome Preprocessing Machine Learning Pipeline, which is available as a stand alone version athttps://github.com/louzounlab/microbiome/tree/master/Preprocessor as a service athttp://mip-mlp.math.biu.ac.il/Home

Importance

Microbiome composition has been proposed as a biomarker (mic-marker) for multiple diseases. However, a clear analysis of the optimal way to represent the gene sequence counts is still lacking.

We propose a simple and straight forward method that significantly improves the accuracy of mic-marker studies.

This method can be of use to merge two of the most important advances in biology in the last decade: Microbiome analysis, and the introduction of machine learning methods to biological studies.
Genetic links in angioimmunoblastic T-cell lymphoma (AITL), clonal hematopoiesis and concomitant hematologic malignancies provide insights into the cell of origin, etiology and biomarker discovery for AITL
Authors: Cheng Shuhua , Zhang Wei , Inghirami Giorgio , Tam Wayne
Published: November 2020

We generated and compared the mutation profiles through targeted sequencing of the primary tumors and matched bone marrow/peripheral blood samples in 25 patients with angioimmunoblastic T-cell lymphoma (AITL) and 2 with peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS). Our results provided strong evidence that AITL/PTCL-NOS, clonal hematopoiesis (CH) as well as other concomitant myeloid and even B-cell hematologic neoplasms (CHN), frequently arose from common mutated hematopoietic stem cell clones. Aberrant AID/APOBEC activity-associated substitutions and tobacco smoking-associated substitutions were enriched in the early CH-associated mutations and late non-CH associated mutations during AITL/PTCL-NOS development, respectively. Moreover, survival analysis showed that the presence of CH harboring ≥ 2 pathogenic TET2 variants with ≥ 15% of allele burden conferred higher risk for CHN (P = 0.0034, hazard ratio = 10.81). These findings provide insights into the cell origin and etiology of AITL, and provide a novel stratification biomarker for CHN risk in AITL/PTCL-NOS patients.
A convolutional neural-network framework for modelling auditory sensory cells and synapses
Authors: Drakopoulos Fotios , Baby Deepak , Verhulst Sarah
Published: November 2020

In classical computational neuroscience, analytical model descriptions are derived from neuronal recordings to mimic the underlying biological system. These neuronal models are typically slow to compute and cannot be integrated within large-scale neuronal simulation frameworks. We present a hybrid, machine-learning and computational-neuroscience approach that transforms analytical models of sensory neurons and synapses into deep-neural-network (DNN) neuronal units with the same biophysical properties. Our DNN-model architecture comprises parallel and differentiable equations that can be used for backpropagation in neuro-engineering applications, and offers a simulation run-time improvement factor of 70 and 280 on CPU or GPU systems respectively. We focussed our development on auditory neurons and synapses, and show that our DNN-model architecture can be extended to a variety of existing analytical models. We describe how our approach for auditory models can be applied to other neuron and synapse types to help accelerate the development of large-scale brain networks and DNN-based treatments of the pathological system.
Evaluation and refinement of sample preparation methods for extracellular matrix proteome coverage
Authors: McCabe Maxwell C. , Schmitt Lauren R. , Hill Ryan C. , Dzieciatkowska Monika , Maslanka Mark , Daamen Willeke F. , van Kuppevelt Toin H. , Hof Danique J. , Hansen Kirk C.
Published: November 2020

The extracellular matrix is a key component of tissues, yet it is under-represented in proteomic datasets. Identification and evaluation of proteins in the extracellular matrix (ECM) has proved challenging due to the insolubility of many ECM proteins in traditional protein extraction buffers. Here we separate the decellularization and ECM extraction steps of several prominent methods for evaluation under real-world conditions. The results are used to optimize a two-fraction ECM extraction method. Approximately one dozen additional parameters are tested and recommendations for analysis based on overall ECM coverage or specific ECM classes are given. Compared to a standard in-solution digest, the optimized method yielded a 4-fold improvement in unique ECM peptide identifications.

Abstract Figure
Monitoring single-cell dynamics of entry into quiescence during an unperturbed lifecycle
Authors: Jacquel Basile , Aspert Théo , Laporte Damien , Sagot Isabelle , Charvin Gilles
Published: November 2020

The life cycle of microorganisms is associated with dynamic metabolic transitions and complex cellular responses. In yeast, how metabolic signals control the progressive choreography of structural reorganizations observed in quiescent cells during a natural life cycle remains unclear. We have developed an integrated microfluidic device to address this question, enabling continuous single-cell tracking in a batch culture experiencing unperturbed nutrient exhaustion to unravel the coordination between metabolic and structural transitions within cells. Our technique reveals an abrupt fate divergence in the population, whereby a fraction of cells is unable to transition to respiratory metabolism and undergoes a reversible entry into a quiescence-like state leading to premature cell death. Further observations reveal that non-monotonous internal pH fluctuations in respiration-competent cells orchestrate the successive waves of protein super-assemblies formation that accompany the entry into abona fidequiescent state. This ultimately leads to an abrupt cytosolic glass transition that occurs stochastically long after proliferation cessation. This new experimental framework provides a unique way to track single-cell fate dynamics over a long timescale in a population of cells that continuously modify their ecological niche.