bluuebunny/crossref_metadata_2025 huggingface dataset:
-gravity in the context of dark energy with power law expansion and energy conditions*
Authors: Manna Goutam , Panda Arijit , Karmakar Aninda , Ray Saibal , Islam Md. Rabiul
Published: November 2022

The objective of this work is to generate a general formalism of

gravity in the context of dark energy under the framework of K-essence emergent geometry with the Dirac-Born-Infeld (DBI) variety of action, where

is the familiar Ricci scalar,

is the DBI type non-canonical Lagrangian with

, and ϕ is the K-essence scalar field. The emergent gravity metric (

) and the well known gravitational metric (

) are not conformally equivalent. We have constructed a modified field equation using the metric formalism in

-gravity incorporating the corresponding Friedmann equations into the framework of the background gravitational metric, which is of Friedmann-Lemaître-Robertson-Walker (FLRW) type. The solution of the modified Friedmann equations have been deduced for the specific choice of

, which is of Starobinsky-type, using the power law expansion method. The consistency of the model with the accelerating phase of the universe has been shown when we restrict ourselves to consider the value of the dark energy density as

, which indicates that the present universe is dark-energy dominated. Graphical plots for the energy density (ρ), pressure (p), and equation of state parameter (

) with respect to (w.r.t.) time (t) based on parametric values are interestingly consistent with the dark energy domination theory, and hence the accelerating features. We also highlight the corresponding energy conditions and constraints of the

theory with a basic example.
Bioscaffold developed with decellularized human amniotic membrane seeded with mesenchymal stromal cells: assessment of efficacy and safety profiles in a second-degree burn preclinical model
Authors: Naasani Liliana Ivet Sous , Pretto Luiza , Zanatelli Carla , Paim Thaís Casagrande , Souza Aline Francielle Damo , Pase Pablo Fagundes , Fernandes Marilda Da Cruz , Sévigny Jean , Wink Márcia Rosângela
Published: November 2022

Therapies to deep burn injuries remain a global challenge. Human amniotic membrane (hAM) is a biomaterial that has been increasingly explored by the field of regenerative medicine. A decellularized hAM (DhAM) can be used as scaffold for mesenchymal stromal cells (MSCs) to grow without the loss of their stemness potential, allowing its application as cell therapy for wound healing. In this work, we associated DhAM with adipose-derived MSCs (DhAM + AD-MSCs), as a therapy strategy for second-degree burns in a preclinical model. Animals with induced second-degree burns were divided into four groups: control, which consists of a non-adherent gauze; a synthetic commercial dressing as the positive control (Control+); DhAM; and DhAM plus rat AD-MSCs (DhAM + AD-MSCs), followed by detailed and long term analysis (5 weeks). The macroscopical analysis showed the healing improvement in the wound area after the DhAM + AD-MSC treatment. Histological analysis also showed no alteration in the animal organs and a regular epithelial progression in comparison to the control. This observation was also confirmed by the analysis of suprabasal layers in the neoepidermis with CK10, showing a stratified and differentiated epithelium, when compared to Control and Control+. A strong CD73 (ecto-5′-nucleotidase) labeling was observed in the first 2 weeks postburn in dermis and epidermis. The expression in dermis was stronger in the second week in the middle of the wound, when comparing the Control+ with DhAM + AD-MSCs (p = 0.0238). In the epidermis the expression of CD73 was increased in all regions when compared to the control. This data suggests the involvement of this protein on wound healing. A low CD11b labeling was observed in DhAM + AD-MSCs treatment group mainly in the last treatment week, in comparison to Control and Control+ (p < 0.0001), which indicates a reduction in the inflammatory process. MSCs through CD73 can release high concentrations of adenosine, an immunosuppressive molecule, suggesting that this could be the mechanism by which the inflammation was better modulated in the DhAM + AD-MSCs group. The results obtained with this preclinical model confirm the effectiveness and safety of this low-cost and highly available dressing for future clinical application as a therapy for burn treatments.
Dynamics on nilpotent character varieties
Authors: Burelle Jean-Philippe , Lawton Sean
Published: November 2022

Let

H
o
m

0

(
Γ
,
G
)

\mathsf {Hom}^{0}(\Gamma ,G)

be the connected component of the identity of the variety of representations of a finitely generated nilpotent group

Γ
\Gamma

into a connected compact Lie group

G
G

, and let

X

0

(
Γ
,
G
)

\mathsf {X}^0(\Gamma ,G)

be the corresponding moduli space. We show that there exists a natural

O
u
t

(
Γ
)

\mathsf {Out}(\Gamma )

-invariant measure on

X

0

(
Γ
,
G
)

\mathsf {X}^0(\Gamma ,G)

and that whenever

O
u
t

(
Γ
)

\mathsf {Out}(\Gamma )

has at least one hyperbolic element, the action of

O
u
t

(
Γ
)

\mathsf {Out}(\Gamma )

on

X

0

(
Γ
,
G
)

\mathsf {X}^0(\Gamma , G)

is mixing with respect to this measure.
Cross-sectional and longitudinal association of sleep and Alzheimer biomarkers in cognitively unimpaired adults
Authors: Blackman Jonathan , Stankeviciute Laura , Arenaza-Urquijo Eider M , Suárez-Calvet Marc , Sánchez-Benavides Gonzalo , Vilor-Tejedor Natalia , Iranzo Alejandro , Molinuevo José Luis , Gispert Juan Domingo , Coulthard Elizabeth , Grau-Rivera Oriol ,   for the European Prevention of Alzheimer’s Disease (EPAD) Consortium
Published: November 2022

Sleep abnormalities are prevalent in Alzheimer’s disease, with sleep quality already impaired at its preclinical stage. Epidemiological and experimental data point to sleep abnormalities contributing to the risk of Alzheimer’s disease. However, previous studies are limited by either a lack of Alzheimer’s disease biomarkers, reduced sample size or cross-sectional design. Understanding if, when, and how poor sleep contributes to Alzheimer’s disease progression is important so that therapies can be targeted to the right phase of the disease. Using the largest cohort to date, the European Prevention of Alzheimer’s Dementia Longitudinal Cohort Study, we test the hypotheses that poor sleep is associated with core Alzheimer’s disease CSF biomarkers cross-sectionally and predicts future increments of Alzheimer’s disease pathology in people without identifiable symptoms of Alzheimer’s disease at baseline. This study included 1168 adults aged over 50 years with CSF core Alzheimer’s disease biomarkers (total tau, phosphorylated tau and amyloid-beta), cognitive performance, and sleep quality (Pittsburgh sleep quality index questionnaire) data. We used multivariate linear regressions to analyse associations between core Alzheimer’s disease biomarkers and the following Pittsburgh sleep quality index measures: total score of sleep quality, binarized score (poor sleep categorized as Pittsburgh sleep quality index > 5), sleep latency, duration, efficiency and disturbance. On a subsample of 332 participants with CSF taken at baseline and after an average period of 1.5 years, we assessed the effect of baseline sleep quality on change in Alzheimer’s disease biomarkers over time. Cross-sectional analyses revealed that poor sleep quality (Pittsburgh sleep quality index total > 5) was significantly associated with higher CSF t-tau; shorter sleep duration (<7 h) was associated with higher CSF p-tau and t-tau; and a higher degree of sleep disturbance (1–9 versus 0 and >9 versus 0) was associated with lower CSF amyloid-beta. Longitudinal analyses showed that greater sleep disturbances (1–9 versus 0 and >9 versus 0) were associated with a decrease in CSF Aβ42 over time. This study demonstrates that self-reported poor sleep quality is associated with greater Alzheimer’s disease-related pathology in cognitively unimpaired individuals, with longitudinal results further strengthening the hypothesis that disrupted sleep may represent a risk factor for Alzheimer’s disease. This highlights the need for future work to test the efficacy of preventive practices, designed to improve sleep at pre-symptomatic stages of disease, on reducing Alzheimer’s disease pathology.
Efficient method for wind velocity estimation and power-extraction maximization using a fourth-order Luenberger observer in a wind-energy-conversion system
Authors: Azelhak Younes , Voyer Damien , Medromi Hicham
Published: November 2022

This paper proposes an advanced method for estimating numerous parameters in a wind-energy-conversion system with high precision, especially in a transient state, including the rotation speed and mechanical torque of the turbine as well as wind velocity. The suggested approach is designed into two parts. First, a fourth-order Luenberger observer is proposed to take into account the significant fluctuations of the mechanical torque that can be caused by wind gusts. This observer provides an accurate estimate of speed and mechanical torque in all weather conditions and especially when the wind is gusting. At the same time, the wind velocity is calculated using the Luenberger observer outputs and a model of the mechanical power generated by the turbine. Second, these estimated parameters are exploited as input in a maximum-power-point tracking (MPPT) algorithm using the tip-speed ratio (TSR) to improve the sensorless strategy control. Simulation results were performed using MATLAB®/Simulink® for both wind gust and real wind profiles. We have verified that for wind gusts with jumps ranging from 3 to 7 m/s, the new observer manages to better follow the rotation speed and the torque of the turbine compared to a usual observer. In addition, we demonstrated that by applying the proposed estimator in the improved TSR-MPPT strategy, it is possible to extract 3.3% more energy compared to traditional approaches.
Odor-induced sound localization bias under unilateral intranasal trigeminal stimulation
Authors: Liang Kun , Wang Wu , Lei Xiao , Zeng Huanke , Gong Wenxiao , Lou Chunmiao , Chen Lihan
Published: November 2022

As a stereo odor cue, internostril odor influx could help us in many spatial tasks, including localization and navigation. Studies have also revealed that this benefit could be modulated by the asymmetric concentrations of both influxes (left nose vs right nose). The interaction between olfaction and vision, such as in object recognition and visual direction judgment, has been documented; however, little has been revealed about the impact of odor cues on sound localization. Here we adopted the ventriloquist paradigm in auditory–odor interactions and investigated sound localization with the concurrent unilateral odor influx. Specifically, we teased apart both the “nature” of the odors (pure olfactory stimulus vs. mixed olfactory/trigeminal stimulus) and the location of influx (left nose vs. right nose) and examined sound localization with the method of constant stimuli. Forty-one participants, who passed the Chinese Smell Identification Test, perceived sounds with different azimuths (0°, 5°, 10°, and 20° unilaterally deflected from the sagittal plane by head-related transfer function) and performed sound localization (leftward or rightward) tasks under concurrent, different unilateral odor influxes (10% v/v phenylethyl alcohol, PEA, as pure olfactory stimulus, 1% m/v menthol as mixed olfactory/trigeminal stimulus, and propylene glycol as the control). Meanwhile, they reported confidence levels of the judgments. Results suggested that unilateral PEA influx did not affect human sound localization judgments. However, unilateral menthol influx systematically biased the perceived sound localization, shifting toward the odor source. Our study provides evidence that unilateral odor influx could bias perceived sound localization only when the odor activates the trigeminal nerves.
Usefulness of the Optimal Cutoff Value and Delta Value of Leucine-Rich Alpha 2 Glycoprotein in Ulcerative Colitis
Authors: Matsumoto Satohiro , Mashima Hirosato
Published: November 2022

Background

Leucine-rich alpha 2 glycoprotein (LRG) is a novel serum biomarker used to determine disease activity in inflammatory bowel disease. We investigated the association between endoscopic scores based on the Ulcerative Colitis Endoscopic Index of Severity (UCEIS) and LRG in ulcerative colitis (UC).

Methods

A total of 1019 LRG measurements were obtained from 358 patients with UC. This study included 190 patients (199 measurements) who underwent colonoscopy within 3 months before and after LRG measurement with unchanged disease status or treatment during the same period. The patients were divided into those with and without UC relapse. We evaluated the correlation between LRG levels and UCEIS scores and performed a receiver operating characteristic curve analysis to determine the optimal LRG cutoff value. Delta values of LRG were then analyzed.

Results

LRG levels were positively correlated with UCEIS scores (correlation coefficient: 0.638; 95% CI: 0.548–0.714; P < .0001) in all disease types. The LRG cutoff value for mucosal healing was 12.6 µg mL−1 (area under the curve: 0.736; 95% CI: 0.651–0.821); this value had a sensitivity of 0.72 and a specificity of 0.66. In patients with UC relapse, the median delta value of LRG before and after relapse was 5 µg mL−1.

Conclusions

LRG levels were positively correlated with the UCEIS scores. The optimal LRG cutoff value for determining mucosal healing was 12.6 µg mL−1. The median delta value of LRG before and after relapse was 5 µg mL−1.
Acute Microcirculatory Effects of Remote Ischemic Conditioning in Superficial Partial Thickness Burn Wounds
Authors: Lucius Julia , Jensen Jan-Oluf , Tasar Raphael R , Schleusser Sophie , Stang Felix H , Mailänder Peter , Kisch Tobias
Published: November 2022

Microcirculation is a critical factor in burn wound healing. Remote ischemic conditioning (RIC) has been shown to improve microcirculation in healthy skin and demonstrated ischemic protective effects on heart, kidney, and liver cells. Therefore, we examined microcirculatory effects of RIC in partial thickness burn wounds. The hypothesis of this study is that RIC improves cutaneous microcirculation in partial thickness burn wounds. Twenty patients with partial thickness burn wounds within 48 hours after trauma were included in this study. RIC was performed with an upper arm blood pressure cuff on a healthy upper arm using three ischemia cycles (5 min inflation to 200 mm Hg) followed by 10-minute reperfusion phases. The third and final reperfusion phase lasted 20 minutes. Microcirculation of the remote (lower/upper extremities or torso) burn wound was continuously quantified, using a combined Laser Doppler and white light spectrometry. The capillary blood flow in the burn wounds increased by a maximum of 9.6% after RIC (percentage change from baseline; P < .01). Relative hemoglobin was increased by a maximum of 2.8% (vs. baseline; P < .01), while cutaneous tissue oxygen saturation remained constant (P > .05). RIC improves microcirculation in partial thickness burn wounds by improving blood flow and elevating relative hemoglobin.
The Interpretation of Mirror Pattern Bands During Oligoclonal Immunoglobulin Isoelectric Focusing Electrophoresis: A Retrospective Study
Authors: Wang JinLing , Li Lei , Zhang YanBing , Wang PeiChang
Published: November 2022

Objective

Mirror patterns are incidental types that accompany the analysis of the oligoclonal band (OCB) in cerebrospinal fluid (CSF). However, their interpretation remains controversial. In this study, we analyzed all graphic results of mirror patterns from 86 patients to provide an optimal interpretation scheme for mirror patterns.

Methods

Matched CSF and serum specimens were obtained from patients with various neurological disorders that required OCB analysis. A total of 86 patients were screened and serum immunofixation electrophoresis (IFE) was performed in all 86. The interobserver agreement for interpreting mirror patterns by visual inspection was tested. The method agreement between the visual inspection and IFE was also evaluated. The CSF/serum albumin quotient (QALB) was calculated to determine the blood-brain barrier integrity of all patients.

Results

Of the 86 patients with mirror patterns, 19.8% (17/86) had typical mirror bands and most (80.2%) had atypical mirror bands. There was a good agreement between the 2 observers in interpreting typical mirror patterns. However, kappa statistics analysis showed poor agreement regarding the interpretation of atypical mirror bands by visual observation alone (kappa value, −0.026 to 0.314 between 2 observers). The disagreement was pronounced between the visual inspection and validation of IFE (kappa value, −0.0238 to 0.176 between the first observer and IFE; −0.322 to 0.118 between the second observer and IFE). The normal QALB rates in the type V groups were significantly higher than those in the type IV group and the positive QALB rates in the type IV were significantly higher than those in the type V.

Conclusion

Visual inspection to interpret mirror pattern bands is unreliable. Considering the completely different clinical significance between type IV and type V and high risk of potential misinterpretations, it is necessary to perform IFE on all the atypical mirror types to discriminate atypical type IV from atypical type V.
Race, Labor, and the Future of Work
Authors: Ajunwa Ifeoma
Published: November 2022

Amidst the full-throttle optimism surrounding the promise of automation to revolutionize the workplace and transform society for the better, there are concerns about its potential to also widen the gulf of economic inequality, as Dr. Martin Luther King, Jr. warned. While undoubtedly new labor markets and novel work opportunities are created by the technological capability for decentralized management and remote work, the rhetoric around automation tends to elide the disparities between those who enjoy its benefits and those who bear the burden of being its draught horses. This chapter examines how race factors into the demographics of the workforce of the gig economy and other precarious jobs that are creating a planetary labor market—opening up new labor markets in developing nations, but without the same labor protections as those in economically privileged countries. This chapter observes that racial minorities disproportionately perform the precarious work created by the gig economy and that the jobs at danger for full automation, such as retail and care work, are those held by White women and racial minorities. Meanwhile, technological advancements such as automated hiring and wearable technologies also portend that the future of work may have lopsided benefits. Governmental action is necessary to ensure that the future of work is not a dystopia for all workers, but especially for more vulnerable workers of color.
Changes in anti-MDA5 antibody titres and serum cytokine levels before and after diagnosis of anti-MDA5 antibody-positive dermatomyositis
Authors: Kogami Masahiro , Abe Yoshiyuki , Ando Taiki , Makiyama Ayako , Yamaji Ken , Tamura Naoto
Published: November 2022

Objectives

Anti-melanoma differentiation-associated gene 5 (MDA5) antibody-positive DM is characterized by rapidly progressive interstitial lung disease and has a poor prognosis. We aimed to investigate whether anti-MDA5 antibody titres and cytokine levels predict clinical course, and evaluate changes in both parameters before and after diagnosis.

Methods

This was a retrospective, single-centre study in 38 patients with anti-MDA5 antibody-positive DM. We compared clinical characteristics and laboratory data at diagnosis between patients in the treatment response (n = 23) and non-response (n = 15) groups, and between those in the relapse (n = 5) and non-relapse (n = 24) groups. We also measured serum anti-MDA5 antibody titres and cytokine levels before and after diagnosis.

Results

The non-response group was older, had a higher ground-glass opacity score, lower PaO2/FiO2, higher CRP level, and higher anti-MDA5 antibody titre than the response group. No cytokines significantly differed between groups at diagnosis. The relapse group had a significantly higher anti-MDA5 antibody titre than the non-relapse group. In the survivor group, the anti-MDA5 antibody titre and levels of IFN-α, IFN-γ, monocyte chemotactic protein-1 (MCP-1), IL-6, IL-33, CRP, and ferritin were significantly lower 6 months post-treatment than at diagnosis. Macrophage-associated cytokines such as IL-6, IL-8, IL-18 and MCP-1 increased after anti-MDA5 antibody positivity in three patients who were anti-MDA5 antibody-positive before diagnosis.

Conclusion

The anti-MDA5 antibody titre at diagnosis may predict the clinical course. Levels of macrophage-associated cytokines significantly declined at 6 months post-treatment, and they may have increased after anti-MDA5 antibody titre positivity.
Two CandidateMeloidogyne javanicaEffector Genes,MjShKTandMjPUT3: A Functional Investigation of Their Roles in Regulating Nematode Parasitism
Authors: Kumar Anil , Fitoussi Nathalia , Sanadhya Payal , Sichov Natalia , Bucki Patricia , Bornstein Menachem , Belausuv Eduard , Brown Miyara Sigal
Published: November 2022

During parasitism, root-knot nematode Meloidogyne spp. inject molecules termed effectors that have multifunctional roles in construction and maintenance of nematode feeding sites. As an outcome of transcriptomic analysis of Meloidogyne javanica, we identified and characterized two differentially expressed genes encoding the predicted proteins MjShKT, carrying a Stichodactyla toxin (ShKT) domain, and MjPUT3, carrying a ground-like domain, both expressed during nematode parasitism of the tomato plant. Fluorescence in-situ hybridization revealed expression of MjShKT and MjPUT3 in the dorsal esophageal glands, suggesting their injection into host cells. MjShKT expression was upregulated during the parasitic life stages, to a maximum at the mature female stage, whereas MjPUT3 expression increased in third- to fourth-stage juveniles. Subcellular in-planta localization of MjShKT and MjPUT3 using a fused fluorescence marker indicated MjShKT co-occurrence with the endoplasmic reticulum, the perinuclear endoplasmatic reticulum, and the Golgi organelle markers, while MjPUT3 localized, to some extent, within the endoplasmatic reticulum and was clearly observed within the nucleoplasm. MjShKT inhibited programmed cell death induced by overexpression of MAPKKKα and Gpa2/RBP-1. Overexpression of MjShKT in tomato hairy roots allowed an increase in nematode reproduction, as indicated by the high number of eggs produced on roots overexpressing MjShKT. Roots overexpressing MjPUT3 were characterized by enhanced root growth, with no effect on nematode development on those roots. Investigation of the two candidate effectors suggested that MjShKT is mainly involved in manipulating the plant effector-triggered immune response toward establishment and maintenance of active feeding sites, whereas MjPUT3 might modulate roots morphology in favor of nematode fitness in the host roots.

[Formula: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Academic Medicine’s Fourth Mission: Building on Community-Oriented Primary Care to Achieve Community-Engaged Health Care
Authors: Savage Hoggard Courtney L. , Kaufman Arthur , Michener J. Lloyd , Phillips Robert L.
Published: November 2022

A 2021 article, “Now is our time to act: Why academic medicine must embrace community collaboration as its fourth mission,” by Association of American Medical Colleges (AAMC) authors, including AAMC president and CEO Dr. David J. Skorton, offers 2 aims that are highly related: community collaboration and health equity. The AAMC’s call to prioritize community collaboration and health equity as pillars of the academic medicine mission echo earlier work on community-oriented primary care (COPC) and an even more robust model that builds on COPC, community-engaged health care (CEHC). COPC is a tested, systematic approach to health care by which a health clinic or system collaborates with a community to reshape priorities and services based on assessed health needs and determinants of health. COPC affirms health inequities’ socioeconomic and political roots, emphasizing health care as a relationship, not a transaction or commodity. Communities where COPC is implemented often see reductions in health inequities, especially those related to socioeconomic, structural, and environmental factors. COPC was the foundation on which community health centers were built, and early models had demonstrable effects on community health and engagement. Several academic health centers build on COPC to achieve CEHC. In CEHC, primary care remains critical, but more of the academic health center’s functions are pulled into community engagement and trust building. Thus, the AAMC has described and embraced a care and training model for which there are good, longitudinal examples among medical schools and teaching hospitals. Spreading CEHC and aligning the Community Health Needs Assessment requirements of academic health centers with the fourth mission could go a long way to improving equity, building trust, and repairing the social contract for health care.
Association Between Obesity and Fetal Acidosis at Scheduled Cesarean Delivery
Authors: DeBolt Chelsea A. , Sarker Minhazur , Trejo Fatima Estrada , Feldman Kristina , Kaplowitz Elianna , Rattner Paige , Paul Keisha , Jagannatham Shobha , Ferrara Lauren , Doulaveris Georgios , Bernstein Peter S. , Brustman Lois , Glazer Kimberly B. , Stone Joanne , Bianco Angela
Published: November 2022

OBJECTIVE:

To evaluate whether patients with obesity who undergo scheduled cesarean delivery under neuraxial anesthesia are at increased risk for umbilical artery pH less than 7.1 and base deficit 12 mmol or greater.

METHODS:

We conducted a multicenter, retrospective cohort study of individuals who delivered a term, singleton, nonanomalous neonate at one of four academic medical centers in New York City from 2013 to 2019 by scheduled cesarean under neuraxial anesthesia for whom fetal cord blood gas results were available. The primary study outcome was rate of fetal acidosis, defined as umbilical artery pH less than 7.1. This was compared between patients with obesity (body mass index [BMI] 30 or higher) and those without obesity (BMI lower than 30). Base deficit 12 mmol or greater and a composite of fetal acidosis and base deficit 12 mmol or greater were also compared. Secondary outcomes included neonatal intensive care unit admission rate, 5-minute Apgar score less than 7, and neonatal morbidity. Associations between maternal BMI and study outcomes were assessed using multivariable logistic or linear regression and adjusted for age, race and ethnicity, insurance type, cesarean delivery order number, and neuraxial anesthesia type.

RESULTS:

Of the 6,264 individuals who met inclusion criteria during the study interval, 3,098 had obesity and 3,166 did not. The overall rate of umbilical artery cord pH less than 7.1 was 2.5%, and the overall rate of umbilical artery base deficit 12 mmol or greater was 1.5%. Patients with obesity were more likely to have umbilical artery cord pH less than 7.1 (adjusted odds ratio [aOR] 2.7, 95% CI 1.8–4.2) and umbilical artery base deficit 12 mmol or greater (aOR 3.2, 95% CI 1.9–5.3). This association was not significantly attenuated after additional adjustments for potential mediators, including maternal medical comorbidities. We found no differences in secondary outcomes between groups.

CONCLUSION:

Maternal obesity is associated with increased odds of arterial pH less than 7.1 and base deficit 12 mmol or greater at the time of scheduled cesarean delivery under neuraxial anesthesia.
“Bowing Technique” for Using a HeartMate 3 Mini-Apical Cuff
Authors: Ohira Suguru , Grunfeld Matan , Levine Avi , De La Pena Corazon , Spielvogel David , Kai Masashi
Published: November 2022

A HeartMate 3 mini-apical cuff is designed to facilitate minimally invasive left ventricular assist implantation. A possible problem of using a mini-apical cuff is that multiple buttress braided sutures can interfere with a HeartMate 3 pump when locking the pump. If this happens in a minimally invasive approach, multiple manipulations to engage the pump can cause catastrophic myocardial injury and uncontrollable bleeding, especially in patients with a fragile myocardium. We are reporting a simple and effective technique to prevent suture jamming in the setting of mini-apical cuff implantation utilizing multiple buttress sutures.
High-throughput single-cell sequencing of multiple invertible promoters reveals a strong determinant of bacterial population heterogeneity
Authors: Lan Freeman , Saba Jason , Qian Yili , Ross Tyler , Landick Robert , Venturelli Ophelia S
Published: November 2022

Population heterogeneity can promote bacterial fitness in response to unpredictable environmental conditions. Human gut symbiontBacteroidesspp., displays variability in single cell surface architectures by combinatorial regulation of promoter inversions that drive expression of capsular polysaccharides (CPS). Using high-throughput single-cell sequencing, we reveal population heterogeneity generated through combinatorial promoter inversion and show thatB. fragilispopulations can access diverse CPS promoter states. Combining our data with stochastic computational modeling, we demonstrate that the rates of promoter inversion regulated by a broadly conserved serine recombinase are a major mechanism shaping population heterogeneity. Exploiting control over the expression of the recombinase, we devise a method for creating phase-locked variants and show that populations with different initial compositions converge to a similar steady-state composition over time. Our approach can be used to interrogate single-cell phase variable states of diverse microbes including bacterial pathogens.

Summary sentence

High-throughput single cell sequencing of phase variation reveals regulation as a major driver of population diversification
Inhibition of the BMP pathway suppresses tumor growth via downregulation of EGFR in MEK/ERK-dependent colorectal cancer
Authors: Shimizu Shota , Kondo Jumpei , Onuma Kunishige , Ota Kasumi , Kamada Mayumi , Harada Yohei , Tanaka Yoshihisa , Nakazawa Mai Adachi , Tamada Yoshinori , Okuno Yasushi , Kawada Kenji , Obama Kazutaka , Coffey Robert J , Fujiwara Yoshiyuki , Inoue Masahiro
Published: November 2022

The bone morphogenetic protein (BMP) pathway promotes differentiation and induces apoptosis in normal colorectal epithelial cells. However, the effect of the BMP pathway in colorectal cancer (CRC) is controversial; it can either be tumor promoting or tumor suppressing, depending on the study. In this study, we found that CRC cells reside in a BMP-rich environment based on RNA-sequencing database analysis. Suppression of BMP using a specific BMP inhibitor, LDN193189, suppresses the growth of organoids in some CRC cases. CRC organoids treated with LDN193189 exhibited a decrease in epidermal growth factor receptor, which was, at least in part, mediated by protein degradation induced by leucine-rich repeats and immunoglobulin-like domains protein 1 (LRIG1). Among CRC organoid panels from 18 different patients, suppression of organoid growth by BMP inhibition correlated with the induction ofLRIG1gene expression. Notably, knockdown of LRIG1 in organoids diminished the growth-suppressive effect of LDN193189. Furthermore, simultaneous treatment with LDN192189 and trametinib, an FDA-approved MEK inhibitor, resulted in a combination effect in bothin vivoandin vitroxenograft tumor treatment in CRC organoids, which are susceptible to growth suppression by LDN193189. Taken together, the simultaneous inhibition of BMP and MEK can be a novel treatment option in CRC cases, and evaluatingin vitrogrowth suppression andLRIG1induction by BMP inhibition using patient-derived organoids could offer functional biomarkers for predicting potential responders.
Photocontrolled Release of Nitric Oxide for Precise Management of NO Concentration in a Solution
Authors: Zhermolenko Egor O. , Karogodina Tatyana Yu. , Vorobev Alexey Yu. , Panfilov Mikhail A. , Moskalensky Alexander E.
Published: November 2022

Nitric oxide (NO) is a unique biochemical mediator involved in the regulation of vital processes. Its short half-life and local action impede direct application in medical practice. Light-controllable NO releasers are promising for the development of smart therapies. Here we present novel aza-BODIPY derivative containingN-nitroso moiety, which shows efficient and reversible release of NO under red light. Using this molecule, we demonstrate a system for precise management of NO concentration in aqueous solutionin vitrousing the feedback loop with optical control. Our results could serve as the basis for the development of novel therapeutic methods.
HISS: Snakemake-based workflows for performing SMRT-RenSeq assembly, AgRenSeq and dRenSeq for the discovery of novel plant disease resistance genes
Authors: Adams Thomas M , Smith Moray , Wang Yuhan , Brown Lynn H , Bayer Micha M , Hein Ingo
Published: November 2022

Background

In the ten years since the initial publication of the RenSeq protocol, the method has proved to be a powerful tool for studying disease resistance in plants and providing target genes for breeding programmes. Since the initial publication of the methodology, it has continued to be developed as new technologies have become available and the increased availability of computing power has made new bioinformatic approaches possible. Most recently, this has included the development of ak-mer based association genetics approach, the use of PacBio HiFi data, and graphical genotyping with diagnostic RenSeq. However, there is not yet a unified workflow available and researchers must instead configure approaches from various sources themselves. This makes reproducibility and version control a challenge and limits the ability to perform these analyses to those with bioinformatics expertise.

Results

Here we present HISS, consisting of three workflows which take a user from raw RenSeq reads to the identification of candidates for disease resistance genes. These workflows conduct the assembly of enriched HiFi reads from an accession with the resistance phenotype of interest. A panel of accessions both possessing and lacking the resistance are then used in an association genetics approach (AgRenSeq) to identify contigs positively associated with the resistance phenotype. Candidate genes are then identified on these contigs and assessed for their presence or absence in the panel with a graphical genotyping approach that uses dRenSeq. These workflows are implemented via Snakemake, a python-based workflow manager. Software dependencies are either shipped with the release or handled with conda. All code is freely available and is distributed under the GNU GPL-3.0 license.

Conclusions

HISS provides a user-friendly, portable, and easily customised approach for identifying novel disease resistance genes in plants. It is easily installed with all dependencies handled internally or shipped with the release and represents a significant improvement in the ease of use of these bioinformatics analyses.
A generalizable epigenetic clock captures aging in two nonhuman primates
Authors: Goldman Elisabeth A. , Chiou Kenneth L. , Watowich Marina M. , Mercer Arianne , Sams Sierra N. , Horvath Julie E. , Anderson Jordan A. ,   Cayo Biobank Research Unit, Tung Jenny , Higham James P. , Brent Lauren J.N. , Martínez Melween I. , Montague Michael J. , Platt Michael L. , Sterner Kirstin N. , Snyder-Mackler Noah
Published: November 2022

Epigenetic clocks generated from DNA methylation array data provide important insights into biological aging, disease susceptibility, and mortality risk. However, these clocks cannot be applied to high-throughput, sequence-based datasets more commonly used to study nonhuman animals. Here, we built a generalizable epigenetic clock using genome-wide DNA methylation data from 493 free-ranging rhesus macaques. Using a sliding-window approach that maximizes generalizability across datasets and species, this model predicted age with high accuracy (± 1.42 years) in held-out test samples, as well as in two independent test sets: rhesus macaques from a captive population (n=43) and wild baboons in Kenya (n=271). Our model can also be used to generate insight into the factors hypothesized to alter epigenetic aging, including social status and exposure to traumatic events. Our results thus provide a flexible tool for predicting age in other populations and species and illustrate how connecting behavioral data with the epigenetic clock can uncover social influences on biological age.
Accurate identification of de novo genes in plant genomes using machine learning algorithms
Authors: Casola Claudio , Owoyemi Adekola , Pepper Alan E. , Ioerger Thomas R.
Published: November 2022

De novo gene birth—the evolution of new protein-coding genes from ancestrally noncoding DNA—is increasingly appreciated as an important source of genetic and phenotypic innovation. However, the frequency and overall biological impact of de novo genes (DNGs) remain controversial. Large-scale surveys of de novo genes are critical to address these issues, but DNG identification represents a persistent challenge due to the lack of standardized protocols and the laborious analyses traditionally used to detect DNGs. Here, we introduced novel approaches to identify de novo genes that rely on Machine Learning Algorithms (MLAs) and are poised to accelerate DNG discovery. We specifically investigated if MLAs developed in one species using known DNGs can accurately predict de novo genes in other genomes. To maximize the applicability of these methods across species, we relied only on DNA and protein sequence features that can be easily obtained from annotation data. Using hundreds of published and newly annotated DNGs from three angiosperms, we trained and tested both Decision Tree (DT) and Neural Network (NN) algorithms. Both MLAs showed high levels of accuracy and recall within-genomes. Although accuracies and recall decreased in cross-species analyses, they remained elevated between evolutionary closely related species. A few training features, including presence of a protein domain and coding probability, held most of the MLAs predictive power. In analyses of all genes from a genome, recall was still elevated. Although false positive rates were relatively high, MLA screenings of whole-genome datasets reduced by up to ten-fold the number of genes to be examined by conventional comparative genomic methods. Thus, a combination of MLAs and traditional strategies can significantly accelerate the accurate discovery of DNG and the annotation in angiosperm genomes.
Exploring how ecological and epidemiological processes shape multi-host disease dynamics using global sensitivity analysis
Authors: Arachchilage Kalpana Hanthanan , Hussaini Mohammed Y. , Cogan N. G. , Cortez Michael H.
Published: November 2022

We use global sensitivity analysis (specifically, Partial Rank Correlation Coefficients) to explore the roles of ecological and epidemiological processes in shaping the temporal dynamics of a parameterized SIR-type model of two host species and an environmentally transmitted pathogen. We compute the sensitivities of disease prevalence in each host species to model parameters. Sensitivity rankings and subsequent biological interpretations are calculated and contrasted for cases were the pathogen is introduced into a disease-free community and where a second host species is introduced into an endemic single-host community. In some cases the magnitudes and dynamics of the sensitivities can be predicted only by knowing the host species characteristics (i.e., their competitive abilities and disease competence) whereas in other cases they can be predicted by factors independent of the species characteristics (specifically, intraspecific versus interspecific processes or the species’ roles of invader versus resident). For example, when a pathogen is initially introduced into a disease-free community, disease prevalence in both hosts is more sensitive to the burst size of the first host than the second host. In comparison, disease prevalence in each host is more sensitive to its own infection rate than the infection rate of the other host species. In total, this study illustrates that global sensitivity analysis can provide useful insight into how ecological and epidemiological processes shape disease dynamics and how those effects vary across time and system conditions. Our results show that sensitivity analysis can provide quantification and direction when exploring biological hypotheses.
Tomato geranylgeranyl diphosphate synthase isoform 1 specifically interacts with phytoene synthase isoform 3 to produce strigolactones in tomato roots
Authors: Ezquerro Miguel , Li Changsheng , Barja M. Victoria , Burbano-Erazo Esteban , Pérez-Pérez Julia , Wang Yanting , Dong Lemeng , Lisón Purificación , López-Gresa M. Pilar , Bouwmeester Harro J. , Rodríguez-Concepción Manuel
Published: November 2022

Carotenoids are photoprotectant pigments and precursors of the hormones abscisic acid (ABA) and strigolactones (SL). Carotenoids are produced in plastids from geranylgeranyl diphosphate (GGPP), which is diverted to the carotenoid pathway by phytoene synthase (PSY). In tomato (Solanum lycopersicum), 3 genes encode plastid-targeted GGPP synthases (SlG1 to 3) and 3 genes encode PSY isoforms (PSY1 to 3).

Here we investigated the function of SlG1 by generating loss-of-function lines and combining their metabolic and physiological phenotypes with gene co-expression and co-immunoprecipitation analyses.

Leaves and fruits ofslg1lines showed a wild-type phenotype in terms of isoprenoid accumulation, photosynthesis and development. Consistently,SlG1is co-expressed withPSY3and other genes involved in the production of carotenoids and SL (but not ABA) only in roots. SlG1 was also found to physically interact with the root-specific PSY3 isoform (and not with PSY1 and PSY2). Root SL (but not ABA) levels were reduced inslg1lines.

Our results confirm a specific role of SlG1 in SL production in combination with PSY3. This role appears to be restricted to roots asslg1plants do not exhibit the shoot phenotype displayed by other SL-deficient mutants.
Endoplasmic reticulum calnexins participate in the primary root growth response to phosphate deficiency
Authors: Montpetit Jonatan , Clúa Joaquín , Hsieh Yi-Fang , Vogiatzaki Evangelia , Müller Jens , Abel Steffen , Strasser Richard , Poirier Yves
Published: November 2022

Accumulation of incompletely folded proteins in the endoplasmic reticulum (ER) leads to ER stress, activates ER protein degradation pathways, and upregulates genes involved in protein folding (Unfolded Protein Response; UPR). ER stress has been associated with abiotic stress conditions that affect protein folding, including salt stress. However, the role of ER protein folding in plant responses to nutrient deficiencies is unclear. We analyzed severalArabidopsis thalianamutants affected in ER protein quality control and established that bothCALNEXIN(CNX) genes function in the primary root’s response to phosphate (Pi) deficiency. CNX and calreticulin (CRT) are homologous ER lectins that bind to N-glycosylated proteins to promote their folding. Growth ofcnx1-1andcnx2-2single mutants was similar to that of the wild type under high and low Pi conditions, but thecnx1-1 cnx2-2double mutant showed decreased primary root growth under low Pi conditions due to reduced meristematic cell division. This phenotype was specific to Pi deficiency; the double mutant responded normally to osmotic and salt stress. The root growth phenotype was Fe dependent and was associated with Fe accumulation in the root. Two genes involved in Fe-dependent inhibition of root growth under Pi deficiency, the ferroxidase geneLPR1and P5-type ATPasePDR2, are epistatic toCNX1/CNX2. OverexpressingPDR2failed to complement thecnx1-1 cnx2-2root phenotype.cnx1-1 cnx2-2showed no evidence of UPR activation, indicating a limited effect on ER protein folding. CNX might process a set of N-glycosylated proteins specifically involved in the response to Pi deficiency.

One sentence summary

Calnexin, a lectin chaperone engaged in the folding of N-glycosylated proteins in the ER, participates in primary root adaptation to low phosphate conditions.
A land plant specific VPS13 mediates polarized vesicle trafficking in germinating pollen
Authors: Tangpranomkorn Surachat , Igarashi Motoko , Ishizuna Fumiko , Kato Yoshinobu , Suzuki Takamasa , Fujii Sota , Takayama Seiji
Published: November 2022

Pollen has an extraordinary ability to convert from a dry state to an extremely rapidly growing state. During pollination, pollen receives water and Ca2+from the contacting pistil, which will be a directional cue for pollen tube germination. The subsequent rapid activation of directional vesicular transport must support the pollen tube growth, but the molecular mechanism leading to this process is largely unknown. Here we show that a plant-specific VPS13, AtVPS13a, mediates vesicle trafficking during the polarization process inArabidopsispollen.AtVPS13aknockout severely affected pollen germination and lipid droplet discharge, while Ca2+-dynamics after pollination was unchanged. Cellular distribution patterns of AtVPS13a and a secretory vesicle marker were synchronized, with a slight delay to the Ca2+-dynamics in polarizing pollen. The absence of AtVPS13a led to reduced cell wall deposition during pollen germination. These results suggest that AtVPS13a mediates pollen polarization, by regulating proper directional vesicular transport following Ca2+-signaling.
MORC proteins regulate transcription factor binding by mediating chromatin compaction in active chromatin regions
Authors: Zhong Zhenhui , Xue Yan , Harris C. Jake , Wang Ming , Li Zheng , Ke Yunqing , Jami-Alahmadi Yasaman , Feng Suhua , Wohlschlegel James A. , Jacobsen Steven E.
Published: November 2022

Background

The Microrchidia (MORC) proteins are a family of evolutionarily conserved GHKL-type ATPases involved in chromatin compaction and gene silencing. Arabidopsis MORC proteins act in the RNA-directed DNA methylation (RdDM) pathway, where they act as molecular tethers to ensure the efficient establishment of RdDM andde novogene silencing. However, MORC proteins also have RdDM-independent functions; although, their underlying mechanisms are unknown.

Results

In this study, we examined regions of MORC binding where RdDM does not occur in order to shed light on the RdDM-independent functions of MORC proteins. We found that MORC proteins compact chromatin and reduce DNA accessibility to transcription factors (TFs), thereby repressing gene expression. We also found that MORC-mediated repression of gene expression was particularly important under conditions of stress. We showed that MORC proteins regulate TFs through either direct or indirect interactions, and these TFs can in some cases regulate their own transcription, resulting in feedforward loops.

Conclusions

Our findings provide insights into the molecular mechanisms of MORC-mediated chromatin compaction and transcription regulation.