bluuebunny/crossref_metadata_2025 huggingface dataset:
Trends in utilization of whole-body computed tomography in blunt trauma after MVC: Analysis of the Trauma Quality Improvement Program database
Authors: Bunn Corinne , Ringhouse Brendan , Patel Purvi , Baker Marshall , Gonzalez Richard , Abdelsattar Zaid M. , Luchette Fred A.
Published: February 2021

BACKGROUND

The use of whole-body computed tomography (WBCT) in awake, clinically stable injured patients is controversial. It is associated with unnecessary radiation exposure and increased cost. We evaluate use of computed tomography (CT) imaging during the initial evaluation of injured patients at American College of Surgeons Levels I and II trauma centers (TCs) after blunt trauma.

METHODS

We identified adult blunt trauma patients after motor vehicle crash (MVC) from the American College of Surgeons Trauma Quality Improvement Program (TQIP) database between 2007 and 2016 at Level I or II TCs. We defined awake clinically stable patients as those with systolic blood pressure of 100 mm Hg or higher with a Glasgow Coma Scale score of 15. Computed tomography imaging had to have been performed within 2 hours of arrival. Whole-body computed tomography was defined as simultaneous CT of the head, chest and abdomen, and selective CT if only one to two aforementioned regions were imaged. Patients were stratified by Injury Severity Score (ISS).

RESULTS

There were 217,870 records for analysis; 131,434 (60.3%) had selective CT, and 86,436 (39.7%) had WBCT. Overall, there was an increasing trend in WBCT utilization over the study period (p < 0.001). In patients with ISS less than 10, WBCT was utilized more commonly at Level II versus Level I TCs in patients discharged from the emergency department (26.9% vs. 18.3%, p < 0.001), which had no surgical procedure(s) (81.4% vs. 80.3%, p < 0.001) and no injury of the head (53.7% vs. 52.4%, p = 0.008) or abdomen (83.8% vs. 82.1%, p = 0.001). The risk-adjusted odds of WBCT was two times higher at Level II TC vs. Level I (odds ratio, 1.88; 95% confidence interval 1.82–1.94; p < 0.001).

CONCLUSION

Whole-body computed tomography utilization is increasing relative to selective CT. This increasing utilization is highest at Level II TCs in patients with low ISSs, and in patients without associated head or abdominal injury. The findings have implications for quality improvement and cost reduction.

LEVEL OF EVIDENCE

Care management, Level IV.
Insult to injury: National analysis of return to work and financial outcomes of trauma patients
Authors: Neiman Pooja U. , Taylor Kathryn K. , Sinco Brandy , Anderson Geoffrey A. , Sangji Naveen F. , Hemmila Mark R. , Scott John W.
Published: February 2021

BACKGROUND

While much of trauma care is rightly focused on improving inpatient survival, the ultimate goal of recovery is to help patients return to their daily lives after injury. Although the overwhelming majority of trauma patients in the United States survive to hospital discharge, little is known nationally regarding the postdischarge economic burden of injuries among trauma survivors.

METHODS

We used the National Health Interview Survey from 2008 to 2017 to identify working-age trauma patients, aged 18 to 64 years, who sustained injuries requiring hospitalization. We used propensity score matching to identify noninjured respondents. Our primary outcome measure was postinjury return to work among trauma patients. Our secondary outcomes included measures of food insecurity, medical debt, accessibility and affordability of health care, and disability.

RESULTS

A nationally weighted sample of 319,580 working-age trauma patients were identified. Of these patients, 51.7% were employed at the time of injury, and 58.9% of them had returned to work at the time of interview, at a median of 47 days postdischarge. Higher rates of returning to work were associated with shorter length of hospital stay, higher education level, and private health insurance. Injury was associated with food insecurity at an adjusted odds ratio (aOR) of 1.8 (95% confidence interval, 1.40–2.37), with difficulty affording health care at aOR of 1.6 (1.00–2.47), with medical debt at aOR of 2.6 (2.11–3.20), and with foregoing care due to cost at aOR of 2.0 (1.52–2.63). Working-age trauma patients had disability at an aOR of 17.6 (12.93–24.05).

CONCLUSION

The postdischarge burden of injury among working-age US trauma survivors is profound—patients report significant limitations in employment, financial security, disability, and functional independence. A better understanding of the long-term impact of injury is necessary to design the interventions needed to optimize postinjury recovery so that trauma survivors can lead productive and fulfilling lives after injury.

LEVEL OF EVIDENCE

Economic & Value-Based Evaluations, level II; Prognostic, level II.
Effect of injury location and severity on opioid use after trauma
Authors: Baker Rachel C. , Brown Craig S. , Montgomery John R. , Mouch Charles A. , Kenney Brooke C. , Englesbe Michael J. , Waljee Jennifer F. , Hemmila Mark R.
Published: February 2021

OBJECTIVE

Recent data have suggested that persistent opioid use is prevalent following trauma. The effect of type of injury and total injury burden is not known. We sought to characterize the relationship between injury location and severity and risk of persistent opioid use.

METHODS

We investigated postdischarge opioid utilization among patients who were admitted for trauma between January 2010 and June 2017 using the Optum Clinformatics Database. New persistent opioid use (NPOU) was defined as one of the following scenarios: (1) two separate opioid prescription fills between 0 and 14 days postdischarge and having 1+ fills in the 91 to 180 days following discharge or (2) filling a prescription in the 15 to 90 days following discharge in addition to a filling in the 91 to 180 day postdischarge period. Multivariable logistic regression was used to assess the relationship between injury type and severity with new persistent opioid use development.

RESULTS

A total of 26,437 opioid-naive patients were included in the analysis. Overall, 2,277 patients (8.6%) met the criteria for NPOU. After adjustment for confounding, NPOU was significantly more common for patients with injury to the extremities (adjusted odds ratio [aOR], 1.75; 95% confidence interval [CI], 1.57–1.94) or abdomen (adjusted odds ratio [aOR], 1.42; 95% CI, 1.22–1.64). Importantly, patients with maximum Abbreviated Injury Scale score of ≥2 for any body region had 1.49-fold odds of NPOU compared with patients with score of 1 (95% CI, 1.28–1.73), while no difference was seen across groupings of total injury burden based on Injury Severity Score.

CONCLUSION

New persistent opioid use is common among patients suffering from trauma. In addition, patients suffering from extremity and abdominal injuries are at highest risk. Maximum individual region injury severity predicts development of new persistent use, whereas total injury severity does not.

LEVEL OF EVIDENCE

Prognostic and epidemiological, level III.
Surgical stabilization of rib fractures in octogenarians and beyond—what are the outcomes?
Authors: Pieracci Fredric M. , Leasia Kiara , Hernandez Matthew C. , Kim Brian , Cantrell Emily , Bauman Zachary , Gardner Scott , Majercik Sarah , White Thomas , Dieffenbaugher Sean , Eriksson Evert , Barns Matthew , Benjamin Christie D. , Lasso Erika Tay , Schubl Sebastian , Sauaia Angela , Doben Andrew R.
Published: February 2021

BACKGROUND

Prospective studies of surgical stabilization of rib fractures (SSRF) have excluded elderly patients, and no study has exclusively addressed the ≥80-year-old subgroup. We hypothesized that SSRF is associated with decreased mortality in trauma patients 80 years or older.

METHODS

Multicenter retrospective cohort study involving eight centers. Patients who underwent SSRF from 2015 to 2020 were matched to controls by study center, age, injury severity score, and presence of intracranial hemorrhage. Patients with chest Abbreviated Injury Scale score less than 3, head Abbreviated Injury Scale score greater than 2, death within 24 hours, and desire for no escalation of care were excluded. A subgroup analysis compared early (0–2 days postinjury) to late (3–7 days postinjury) SSRF. Poisson regression accounting for clustered data by center calculated the relative risk (RR) of the primary outcome of mortality for SSRF versus nonoperative management.

RESULTS

Of 360 patients, 133 (36.9%) underwent SSRF. Compared with nonoperative patients, SSRF patients were more severely injured and more likely to receive locoregional analgesia. There were 31 hospital deaths among the entire sample (8.6%). Multivariable regression demonstrated a decreased risk of mortality for the SSRF group, as compared with the nonoperative group (RR, 0.41; 95% confidence interval, 0.24–0.69; p < 0.01). However, SSRF patients were more likely to develop pneumonia, and had an increased duration of both mechanical ventilation and intensive care unit stay. There were no differences in discharge destination, although the SSRF group was less likely to be discharged on narcotics (RR, 0.66; 95% confidence interval, 0.48–0.90; p = 0.01). There was no difference in adjusted mortality between the early and late SSRF subgroups.

CONCLUSION

Patients selected for SSRF were substantially more injured versus those managed nonoperatively. Despite this, SSRF was independently associated with decreased mortality. With careful patient selection, SSRF may be considered a viable treatment option in octogenarian/nonagenarians.

LEVEL OF EVIDENCE

Therapeutic, Level IV
Outcome of Liver Transplantation for Neonatal-onset Citrullinemia Type I
Authors: Liu Yuan , Luo Yi , Xia Lei , Qiu Bijun , Zhou Tao , Feng Mingxuan , Wang Chenchen , Xue Feng , Chen Xiaosong , Han Longzhi , Zhang Jianjun , Xia Qiang
Published: February 2021

Background.

We evaluated the outcome of liver transplantation (LT) in neonatal-onset citrullinemia type I patients, especially its impact on neurological deficits and developmental retardation.

Methods.

From October 2006 to October 2019, 5 of the 2003 children who received LT at Ren Ji Hospital had been diagnosed with citrullinemia type I. The primary indication for transplantation was repeated metabolic compensation and developmental retardation in 4 patients and prophylactic transplantation in the other. Among them, 3 patients received living donor LT and 2 received orthotopic LT.

Results.

All recipients had successfully recovered within the median follow-up period of 32 months (range, 6–54 mo). Transplantation restored citrulline metabolism and liver function. Plasma ammonia and citrulline concentration decreased to normal levels with no further hyperammonemic episodes being reported, even after normal diet intake began. Meanwhile, uracil-2 and orotic acid were not detected in urinary excretion. Strikingly, patients suffered developmental retardation before LT showed improved psychomotor ability and significant catch-up growth during the follow-up period. Cognitive ability, including language skills and academic performance, also greatly improved. Three patients had sustained brain injuries and exhibited severe neurological deficits before transplantation, especially repeated generalized tonic-clonic seizures. LT halted neurological deterioration and controlled seizure episodes, which further facilitated the intellectual development and improvement of life quality.

Conclusions.

LT is an effective treatment for neonatal-onset citrullinemia type I patients, which reverses metabolism decompensation and improves quality of life. For patients who have suffered severe hyperammonemic insults, LT should be conducted at an early age to avoid further neurological or developmental deficits.
Lung Transplantation for Severe Post–coronavirus Disease 2019 Respiratory Failure
Authors: Hawkins Robert B. , Mehaffey J. Hunter , Charles Eric J. , Mannem Hannah C. , Roeser Mark
Published: February 2021

Background.

The coronavirus disease 2019 (COVID-19) pandemic has resulted in >72 million cases and 1.6 million deaths. End-stage lung disease from COVID-19 is a new and growing entity that may benefit from lung transplant; however, there are limited data on the patient selection, perioperative management, and expected outcomes of transplantation for this indication.

Methods.

A systematic review of the literature was performed with searches of MEDLINE and Web of Science databases as well as the gray literature. All manuscripts, editorials, commentaries, and gray literature reports of lung transplantation for COVID-related respiratory failure were included. A case from the University of Virginia is described and included in the review.

Results.

A total of 27 studies were included: 11 manuscripts, 5 commentaries, and 11 gray literature reports. The total number of transplantations for COVID-related lung disease was 21. The mean age was 55±12 years, 16 (76%) were male individuals, and the acuity was high, with 85% on extracorporeal membrane oxygenation preoperatively. There was a 95% early survival rate, with 1 additional late death. There is growing histopathologic evidence for permanent structural damage with no replicating virus at the time of transplantation.

Conclusions.

Bilateral lung transplantation is an effective treatment option with reasonable short-term outcomes for patients with end-stage lung failure secondary to COVID-19. However, specific considerations in this new population require a multidisciplinary approach. As we move into the second wave of the COVID-19 global pandemic, lung transplantation will likely have a growing role in management of these complex patients.
Uterine Transplantation Using Living Donation: A Cross-sectional Study Assessing Perceptions, Acceptability, and Suitability
Authors: Jones Benjamin P. , Rajamanoharan Abirami , Williams Nicola J. , Vali Saaliha , Saso Srdjan , Mantrali Ifigenia , Jalmbrant Maria , Thum Meen-Yau , Diaz-Garcia Cesar , Ghaem-Maghami Sadaf , Wilkinson Stephen , Quiroga Isabel , Friend Peter , Yazbek Joseph , Smith J. Richard
Published: February 2021

Background.

A uterine transplantation is a nonvital, quality-of-life–enhancing solid organ transplant. Given improvements in donor risk profile and the anticipated shortage of suitable deceased donors, nondirected donation could facilitate sustainability as uterine transplantation moves from research into the clinical realm. The aim of this article is to determine perceptions and identify motivations of potential nondirected living uterus donors and assess acceptability and suitability.

Methods.

A cross-sectional survey using an electronic questionnaire among women who have inquired about donating their uterus for uterine transplantation.

Results.

The majority of respondents “strongly agreed” or “agreed” that the most prevalent motivations to donate their uterus include helping someone carry and give birth to their own baby (n = 150; 99%), helping others (n = 147; 97%), and because they no longer need their womb (n = 147; 97%). After considering risks of uterus donation, the majority were still keen to donate their uterus (n = 144; 95%), but following a process of exclusion using donor selection criteria, less than a third (n = 42; 29%) were found to be suitable to proceed.

Conclusions.

This study demonstrates novel insight into the motivations of women who wish to donate their uterus and displays high levels of acceptability after consideration of the risks involved. Despite the physical risk and transient impact upon ability to undertake activities of daily living, women who donate their uterus expect to gain psychological and emotional benefits from enabling another woman to gestate and give birth to their own future children. However, currently used selection criteria reduce the number of potential donors significantly.
Cerebral small vessel disease and vascular cognitive impairment: from diagnosis to management
Authors: Zanon Zotin Maria Clara , Sveikata Lukas , Viswanathan Anand , Yilmaz Pinar
Published: February 2021

Purpose of review

We present recent developments in the field of small vessel disease (SVD)-related vascular cognitive impairment, including pathological mechanisms, updated diagnostic criteria, cognitive profile, neuroimaging markers and risk factors. We further address available management and therapeutic strategies.

Recent findings

Vascular and neurodegenerative pathologies often co-occur and share similar risk factors. The updated consensus criteria aim to standardize vascular cognitive impairment (VCI) diagnosis, relying strongly on cognitive profile and MRI findings. Aggressive blood pressure control and multidomain lifestyle interventions are associated with decreased risk of cognitive impairment, but disease-modifying treatments are still lacking. Recent research has led to a better understanding of mechanisms leading to SVD-related cognitive decline, such as blood-brain barrier dysfunction, reduced cerebrovascular reactivity and impaired perivascular clearance.

SVD is the leading cause of VCI and is associated with substantial morbidity. Tackling cardiovascular risk factors is currently the most effective approach to prevent cognitive decline in the elderly. Advanced imaging techniques provide tools for early diagnosis and may play an important role as surrogate markers for cognitive endpoints in clinical trials. Designing and testing disease-modifying interventions for VCI remains a key priority in healthcare.
Paraneoplastic Progressive Downbeat Nystagmus, Ataxia and Sensorineural Hearing Loss due to the ANTI-Kelch-11 Protein Antibody
Authors: Kattah Jorge C. , Eggers Scott D. , Bach Sarah E. , Dubey Divyanshu , McKeon Andrew B.
Published: February 2021

A 45-year-old man with a history of testicular seminoma treated 8 years earlier presented with chronic progressive truncal and limb ataxia, progressive sensorineural hearing loss, and episodic vertigo. Eye movement and neuro-otology examinations showed localizing abnormalities to the bilateral cerebellar flocculus, vermis, and bilateral cerebellar hemispheres. Audiometric testing showed bilateral symmetric sensorineural hearing loss. There was a normal MRI of the brain. Cerebrospinal fluid (CSF) showed modest lymphocytic pleocytosis, and there was an elevated serum choriogonadotrophic hormone. An abdominal CT scan showed a solitary, large retroperitoneal lymph node, and histopathologic examination of the node biopsy showed granulomatous inflammation without microorganisms; eventually, immunohistochemical markers confirmed the diagnosis of metastatic seminoma. Although normal neuroimaging and inflammatory CSF reaction suggested a paraneoplastic etiology, the initial paraneoplastic antibody testing was negative. Subsequent investigation identified a positive kelch-11 protein antibody, thus confirming the paraneoplastic connection between the metastatic seminoma and the subacute neurologic–cochleovestibular syndrome.
Neural electrophysiological mechanism of joint hierarchical rule shifting: an event-related potential study
Authors: Han Jiahui , Liu Jie , Guan Lei , Luo Wenpei
Published: February 2021

Although previous studies have explored the brain mechanism by which an individual independently accomplishes task switching or rule shifting with different hierarchical structures, electrophysiological evidence indicating that two actors cooperate to complete the hierarchical rule shift remains unclear. This study adopts a modified joint hierarchical rule shifting paradigm in which one actor judged the parity task and the other decided the magnitude task. Results demonstrated that cues in high- and low-shift conditions elicited larger P2 amplitudes and that low-shift had a larger P3 amplitude than high-shift. Results further indicated that participants required more attention resources to ascertain who would make a judgment for the current trial and that low hierarchical features were superior in reconfiguring changed rules. Regarding the target, the high-shift condition evoked smaller P2 and larger N2 amplitudes when compared to low-shift and repeat conditions, whereas when compared to high- and low-shifts, the repeat condition elicited a larger P3 amplitude. The findings revealed that participants required more control resources to process the varied features and that repeat condition required the least cognitive resources to update rules. Thus, participants had different process patterns between cues and targets when cooperating with their co-actors.
Long noncoding RNA H19 contributes to the proliferation and autophagy of glioma cells through mTOR/ULK1 pathway
Authors: Zhao Wei , Lin Xiaoyan , Han Han , Zhang Hongxu , Li Xiaoli , Jiang Chunming , Feng Mei
Published: February 2021

Long noncoding RNA (LncRNA) H19 has been proven to be involved in many kinds of cancers including glioma, and a previous study has shown an autophagy regulation of H19. The mammalian target of rapamycin (mTOR) signaling pathway plays a key role in autophagy and Unc-51 like autophagy activating kinase 1 (ULK1) is also thought to be involved in autophagy signaling. In our study, we investigated the role of mTOR/ULK1 autophagy signaling in the H19-mediated promotion of glioma proliferation. Human glioma cells U87 and U251 and normal human astrocytes HA1800 were used in the study. First, the expression of H19 was determined in U87, U251, and HA1800 cells. Then, the cell proliferation and migration of glioma cells were detected, while the protein levels of main molecules of the mTOR/ULK1 pathway and autophagy-related proteins were also examined. Rapamycin, an inhibitor of mTOR, was used to further study the role of H19 in autophagy. We observed that overexpressed H19 promoted the proliferation and migration in glioma cells. The autophagy of U87 cells was suppressed when H19 was overexpressed and enhanced when H19 was silenced. H19 overexpression inhibited mTOR phosphorylation and promoted ULK1 phosphorylation. H19 promoted proliferation, migration, and autophagy by regulating mTOR signaling. In conclusion, we validate that H19 contributes to the proliferation and autophagy of glioma cells through the mTOR/ULK1 pathway.
An update on psychotic spectrum disorders and disasters
Authors: Jing Genevieve P. , Katz Craig L.
Published: February 2021

Purpose of review

The aim of this study is to review the recent literature on disasters’ impact on the course of psychotic spectrum disorders (PSDs) and how people with PSD fare during a disaster, including the effects of COVID-19.

Recent findings

Several, but not all, studies examining disasters including earthquake-affected communities and refugee populations have found increased incidence of PSDs. Studies have been inconsistent regarding psychosis incidence in COVID-19 patients. Meanwhile, patients with PSD have been found to cope poorly in recent disasters including flooding and a nuclear accident. Patients with schizophrenia appear to be at particular risk during COVID-19 due to such issues as poor awareness of health precautions and the psychiatric impact of lockdown. However, novel methods including telepsychiatry have allowed care of this population to remain consistent during COVID-19.

There is conflicting evidence as to the association between disasters and onset of PSD, and further study is needed to elucidate this link. Patients with PSDs are more likely to fare worse during disasters. Novel approaches to delivery of care have helped offset the psychiatric risks to PSD patients during the COVID-19 pandemic. These approaches may be applicable to other disaster scenarios or to general outpatient care.
TRPV1 in arteries enables a rapid myogenic tone
Authors: Phan Thieu X. , Ton Hoai T. , Gulyás Hajnalka , Pórszász Róbert , Tóth Attila , Russo Rebekah , Kay Matthew W. , Sahibzada Niaz , Ahern Gerard P.
Published: February 2021

Arterioles maintain blow flow by adjusting their diameter in response to changes in local blood pressure. In this process called the myogenic response, a vascular smooth muscle mechanosensor controls tone predominantly through altering the membrane potential. In general, myogenic responses occur slowly, reaching a plateau in minutes. In the heart and skeletal muscle, however, myogenic tone is rapid; activation occurs in tens of seconds and arterial constrictions or raised extravascular pressure as brief as 100 ms remove tone. Previously, we identified extensive expression of TRPV1 in the smooth muscle of arterioles supplying skeletal muscle, heart and the adipose. Here we reveal a critical role for TRPV1 in the myogenic tone of these tissues. TRPV1 antagonists dilated skeletal muscle arteriolesin vitroandin vivo, increased coronary flow in isolated hearts, and transiently decreased blood pressure. All of these effects of TRPV1 antagonists were abolished by genetic disruption of TRPV1. Stretch of isolated vascular smooth muscle cells, or raised intravascular pressure in arteries (with or without endothelium), triggered Ca2+signaling and vasoconstriction. The majority of these stretch-responses were TRPV1-mediated, with the remaining tone being inhibited by the TRPM4 antagonist, 9-phenantrol. Notably, tone developed more quickly in arteries from wild-type compared with TRPV1-null mice. Furthermore, the rapid vasodilation following brief constriction of arterioles was also dependent on TRPV1, consistent with a rapid deactivation or inactivation of TRPV1. Pharmacologic experiments revealed that membrane stretch activates a phospholipase C/protein kinase C signaling pathway to activate TRPV1, and in turn, L-type Ca2+channels. These results suggest a critical role, for TRPV1 in the dynamic regulation of myogenic tone and blood flow in the heart and skeletal muscle.
Simulating rhizodeposition patterns around growing and exuding root systems
Authors: Landl Magdalena , Haupenthal Adrian , Leitner Daniel , Kroener Eva , Vetterlein Doris , Bol Roland , Vereecken Harry , Vanderborght Jan , Schnepf Andrea
Published: February 2021

1

In this study, we developed a novel model approach to compute the spatio-temporal distribution patterns of rhizodeposits around growing root systems in three dimensions. This model approach allows us for the first time to study the evolution of rhizodeposition patterns around complex three-dimensional root systems. Root systems were generated using the root architecture model CPlantBox. The concentration of rhizodeposits at a given location in the soil domain was computed analytically. To simulate the spread of rhizodeposits in the soil, we considered rhizodeposit release from the roots, rhizodeposit diffusion into the soil, rhizodeposit sorption to soil particles, and rhizodeposit degradation by microorganisms. To demonstrate the capabilities of our new model approach, we performed simulations for the two example rhizodeposits mucilage and cit-rate and the example root systemVicia faba. The rhizodeposition model was parameterized using values from the literature. Our simulations showed that the rhizosphere soil volume with rhizodeposit concentrations above a defined threshold value (i.e., the rhizodeposit hotspot volume), exhibited a maximum at intermediate root growth rates. Root branching allowed the rhizospheres of individual roots to overlap, resulting in a greater volume of rhizodeposit hotspots. This was particularly important in the case of citrate, where overlap of rhizodeposition zones accounted for more than half of the total rhizodeposit hotspot volumes. Coupling a root architecture model with a rhizodeposition model allowed us to get a better understanding of the influence of root architecture as well as rhizodeposit properties on the evolution of the spatio-temporal distribution patterns of rhizodeposits around growing root systems.
Alternative electron pathways of photosynthesis drive the algal CO2concentrating mechanism
Authors: Burlacot Adrien , Dao Ousmane , Auroy Pascaline , Cuiné Stephan , Li-Beisson Yonghua , Peltier Gilles
Published: February 2021

Global photosynthesis consumes ten times more CO2than net anthropogenic emissions, and microalgae account for nearly half of this consumption1. The great efficiency of algal photosynthesis relies on a mechanism concentrating CO2(CCM) at the catalytic site of the carboxylating enzyme RuBisCO, thus enhancing CO2fixation2. While many cellular components involved in the transport and sequestration of inorganic carbon (Ci) have been uncovered3,4, the way microalgae supply energy to concentrate CO2against a thermodynamic gradient remains elusive4-6. Here, by monitoring dissolved CO2consumption, unidirectional O2exchange and the chlorophyll fluorescence parameter NPQ in the green algaChlamydomonas, we show that the complementary effects of cyclic electron flow and O2photoreduction, respectively mediated by PGRL1 and flavodiiron proteins, generate the proton motive force (pmf) required by Citransport across thylakoid membranes. We demonstrate that the trans-thylakoidpmfis used by bestrophin-like Citransporters and further establish that a chloroplast-to-mitochondria electron flow contributes to energize non-thylakoid Citransporters, most likely by supplying ATP. We propose an integrated view of the CCM energy supply network, describing how algal cells distribute photosynthesis energy to power different Citransporters, thus paving the way to the transfer of a functional algal CCM in plants towards improving crop productivity.

One sentence summary

Photosynthetic alternative electron flows and mitochondrial respiration drive the algal CO2concentrating mechanism
Ionotropic receptors in the turnip mothAgrotis segetumrespond to repellent medium-chain fatty acids
Authors: Hou Xiao-Qing , Zhang Dan-Dan , Powell Daniel , Wang Hong-Lei , Andersson Martin N. , Löfstedt Christer
Published: February 2021

Background

In insects, airborne chemical signals are mainly detected by two receptor families, odorant receptors (ORs) and ionotropic receptors (IRs). Functions of ORs have been intensively investigated in Diptera and Lepidoptera, while the functions and evolution of the more ancient IR family remain largely unexplored beyond Diptera.

Results

Here, we identified a repertoire of 26 IRs from transcriptomes of female and male antennae, and ovipositors in the mothAgrotis segetum. We observed that a large clade formed by IR75p and IR75q expansions is closely related to the acid-sensing IRs identified in Diptera. We functionally assayed each of the five AsegIRs from this clade usingXenopusoocytes and found that two receptors responded to the tested ligands. AsegIR75p.1 responded to several compounds but hexanoic acid was revealed to be the primary ligand, and AsegIR75q.1 responded primarily to octanoic acid, and less so to nonanoic acid. It has been reported that the C6-C10medium-chain fatty acids repel various insects including many drosophilids and mosquitos. Our GC-EAD recordings showed that C6-C10medium-chain fatty acids elicited antennal responses of both sexes ofA. segetum, while only octanoic acid had repellent effect to the moths in a behavioural assay. In addition, using fluorescencein situhybridization, we demonstrated that the five IRs and their co-receptor AsegIR8a are not located in coeloconic sensilla as found inDrosophila, but in basiconic or trichoid sensilla.

Conclusions

Our results significantly expand the current knowledge of the insect IR family. Based on the functional data in combination with phylogenetic analysis, we propose that subfunctionalization after gene duplication plays an important role in the evolution of ligand specificities of the acid-sensing IRs in Lepidoptera.
Drivers of adaptive capacity in wild populations: implications for genetic interventions
Authors: Torda G , Quigley K
Published: February 2021

The unprecedented rate of environmental change in the Anthropocene poses evolutionary challenges for wild populations globally. Active human interventions are being increasingly considered to accelerate natural adaptive processes. Evolutionary models can evaluate how species may fare under future climate, elucidate which evolutionary processes are critical to rapid adaptation, and how active interventions may influence fitness trajectories of organisms. Here we use polygenic metapopulation adaptation models to quantify the relative importance (effect sizes) of different eco-evolutionary parameters on the rates of adaptation in wild populations i) without active interventions, and ii) under a subset of active interventions. We demonstrate that genetic diversity (heterozygosity, He), population connectivity and the effect size of additive genetic variance are the primary drivers of natural adaptation rates. We quantify the effect sizes of these parameters on population fitness across three proposed assisted evolution scenarios and identify critical thresholds for intervention effectiveness and implementation. Specifically, the interventions tested here were most effective at low levels of genetic diversity in target populations (He < 0.2) and when timed during a cold-to-warm phase of an ENSO-like oscillation. Beneficial levels of connectivity were highly dependent on desired outcomes for the meta-population. We also present a global meta-analysis of genetic diversity in tropical reef-building corals as a case study of how thresholds derived from evolutionary models can be used to guide decision making by managers. We find genetic diversity to be highly variable by coral taxon and region, highlighting how thresholds from evolutionary models can be used in conjunction with empirical data to assess intervention needs and priorities. Finally, we highlight the critical knowledge and data gaps to produce the next suite of applied models for conservation management decision-support.
Identification of theTMEM232 gene associated with atopic dermatitis through targeted capture sequencing
Authors: Zheng Jie , Wu Yuan-yuan , Fang Wen-liang , Cai Xin-ying , Zhang Zeng-yun-ou , Yu Chong-xian , Zheng Xiao-dong , Xiao Feng-li
Published: February 2021

BACKGROUND

Atopic dermatitis (AD) is a common and complex skin disorder, and the 5q22.1 region had been reported to be associated with AD.

OBJECTIVE

To identify the susceptibility gene for AD in the 5q22.1 region by haplotype and targeted capture sequencing.

METHODS

The haplotypes were reconstructed with our previously genotyping data of four SNPs and six deletions from 3055 Chinese Hans AD patients and 4346 controls. The targeted capture sequencing spanning 5q22.1 region was performed in the selected samples. The gene level enrichment analysis was done using loss of function variants.

RESULTS

A total of 60 haplotypes were found, and the H15 haplotype had the strongest association with AD (P= 2.72×10−10, OR = 0.14, 95%CI = 0.07-0.28). However, No co-segregation mutation sites were found in the sequencing analysis within the 16 selected samples, while the enrichment analysis indicated that TMEM232 was significantly associated with AD (P = 7.33×10-5, OR = 0.33, 95% CI = 0.19-0.58).

CONCLUSIONS

This study confirms previous findings that the TMEM232 gene is associated with AD by haplotype analysis and targeted capture sequencing.
Analyses of the complete genome sequence of 2,6-dichlorobenzamide (BAM) degraderAminobactersp. MSH1 suggests a polyploid chromosome, phylogenetic reassignment, and functions of (un)stable plasmids
Authors: Nielsen Tue Kjærgaard , Horemans Benjamin , Lood Cedric , T’Syen Jeroen , van Noort Vera , Lavigne Rob , Ellegaard-Jensen Lea , Hylling Ole , Aamand Jens , Springael Dirk , Hansen Lars Hestbjerg
Published: February 2021

Aminobactersp. MSH1 (CIP 110285) can use the pesticide dichlobenil and its transformation product, the recalcitrant groundwater micropollutant, 2,6-dichlorobenzamide (BAM) as sole source of carbon, nitrogen, and energy. The concentration of BAM in groundwater often exceeds the threshold limit for drinking water, resulting in the use of additional treatment in drinking water treatment plants (DWTPs) or closure of the affected abstraction wells. Biological treatment with MSH1 is considered a potential sustainable alternative to remediate BAM-contamination in drinking water production. Combining Illumina and Nanopore sequencing, we here present the complete genome of MSH1, which was determined independently in two different laboratories. Unexpectedly, divergences were observed between the two genomes, i.e. one of them lacked four plasmids compared to the other. Besides the circular chromosome and the two previously described plasmids involved in BAM catabolism pBAM1 (41 kb) and pBAM2 (54 kb), we observe that the genome of MSH1 contains two megaplasmids pUSP1 (367 kb) and pUSP2 (366 kb) and three smaller plasmids pUSP3 (97 kb), pUSP4 (64 kb), and pUSP5 (32 kb). The MSH1 substrain from KU Leuven showed a reduced genome lacking plasmids pUSP2 and the three smaller plasmids and was designated substrain MK1, whereas the variant with all plasmids was designated as substrain DK1. Results of a plasmid stability experiment, indicate that strain MSH1 may have a polyploid chromosome when growing in R2B medium with more chromosomes than plasmids per cell. Based on phylogenetic analyses, strain MSH1 is reassigned asAminobacter niigataensisMSH1.

Importance

The complete genomes of the two MSH1 substrains, DK1 and MK1, provide further insight into this already well-studied organism with bioremediation potential. The varying plasmid contents in the two substrains suggest that some of the plasmids are unstable, although this is not supported by the herein described plasmid stability experiment. Instead, results suggest that MSH1 is polyploid with respect to its chromosome, at least under some growth conditions. As the essential BAM-degradation genes are found on some of these plasmids, stable inheritance is essential for continuous removal of BAM. Finally,Aminobactersp. MSH1 is reassigned asAminobacter niigataensisMSH1, based on phylogenetic evidence.
Increasing central serotonin with 5-HTP disrupts the inhibition of social gaze in non-human primates
Authors: Weinberg-Wolf Hannah , Fagan Nicholas A. , Dal Monte Olga , Chang Steve W. C.
Published: February 2021

To competently navigate the world, individuals must flexibly balance distinct aspects of social gaze, orienting toward others and inhibiting orienting responses, depending on the context. These behaviors are often disrupted in patient populations treated with serotonergic drugs. However, the field lacks a clear understanding of how the serotonergic system mediates social orienting and inhibiting behaviors. Here, we tested how increasing central concentrations of serotonin with the direct precursor 5-Hydroxytryptophan (5-HTP) would modulate the ability of rhesus macaques to use eye movements to flexibly orient to, or inhibit orienting to, faces. Systemic administrations of 5-HTP effectively increased central serotonin levels and impaired flexible orientation and inhibition. Critically, 5-HTP selectively impaired the ability of monkeys to inhibit orienting to face images, whereas it similarly impaired orienting to face and control images. 5-HTP also caused monkeys to perseverate on their gaze responses, making them worse at flexibly switching between orientating and inhibiting behaviors. Furthermore, the effects of 5-HTP on performance correlated with a constriction of the pupil, an increased time to initiate trials, and an increased reaction time, suggesting that the disruptive effects of 5-HTP on social gaze behaviors are likely driven by a downregulation of arousal and motivational states. Taken together, these findings provide causal evidence for a modulatory relationship between 5-HTP and social gaze behaviors in non-human primates and offer translational insights for the role of the serotonergic system in social gaze.
The Orb6-Sts5 Axis Regulates Stress Granule Formation and Heat Stress Response in Fission Yeast
Authors: Tams Robert N. , Chen Chuan , Nuñez Illyce , Haller Patrick Roman , Verde Fulvia
Published: February 2021

The NDR/LATS family kinases are a subclass of the AGC serine/threonine kinases which are important for morphogenesis and cell growth control. Using the model organismSchizosaccharomyces pombe, we previously reported that the NDR/LATS kinase Orb6 phosphorylates the RNA-binding protein (RBP) Sts5 serine 86 residue on its Intrinsically Disordered Domain (IDD). When dephosphorylated, Sts5 forms ribonucleoprotein (RNP) granules that colocalize with processing bodies (P-Bodies) and translationally repress mRNAs important for polarized cell growth. Here we report that Sts5 puncta colocalize with both P-Bodies and stress granules (SG) in response to glucose starvation, as well as heat, oxidative, and hyperosmotic stress. We find that loss of Sts5 decreases the number of stress granules, indicating that Sts5 has a role in promoting stress granule formation. Conversely, inhibition of Orb6 kinase promotes Sts5 aggregation and stress granule formation. In addition, loss of Sts5 decreases cell survival after heat stress, whereas decreasing Orb6 protein levels or including thests5S86Amutation, which promotes Sts5 aggregation, leads to increased survival. These data indicate that the Orb6-Sts5 axis is not only important for regulation of polarized growth but also for response to environmental stress, as dysregulation of the Orb6-Sts5 axis affects stress granule formation and cell survival.
A fungal powdery mildew pathogen induces extensive local and marginal systemic changes in theArabidopsis thalianamicrobiota
Authors: Durán Paloma , Reinstädler Anja , Rajakrut Anna Lisa , Hashimoto Masayoshi , Garrido-Oter Ruben , Schulze-Lefert Paul , Panstruga Ralph
Published: February 2021

Powdery mildew is a foliar disease caused by epiphytically growing obligate biotrophic ascomycete fungi. How powdery mildew colonization affects host resident microbial communities locally and systemically remains poorly explored.

We performed powdery mildew (Golovinomyces orontii) infection experiments withArabidopsis thalianagrown in either natural soil or a gnotobiotic system and studied the influence of pathogen invasion into standing natural multi-kingdom or synthetic bacterial communities (SynComs).

We found that after infection of soil-grown plants,G. orontiioutcompetes numerous resident leaf-associated fungi. We further detected a significant shift in foliar but not root-associated bacterial communities in this setup. Pre-colonization of germ-freeA. thalianaleaves with a bacterial leaf-SynCom, followed byG. orontiiinvasion, induced an overall similar shift in the foliar bacterial microbiota and minor changes in the root-associated bacterial assemblage. However, a standing root SynCom in root samples remained robust against foliar infection withG. orontii. Although pathogen growth was unaffected by the leaf SynCom, fungal infection caused a more than two-fold increase in leaf bacterial load.

Our findings indicate thatG. orontiiinfection affects mainly microbial communities in local plant tissue, possibly driven by pathogen-induced changes in source-sink relationships and host immune status.
Ovarian Tumor Mitochondria Exhibit Abnormal Phenotypes and Blunted Associations with Biobehavioral Factors
Authors: Bindra Snehal , McGill Marlon A. , Triplett Marina K. , Tyagi Anisha , Thaker Premal H. , Dahmoush Laila , Goodheart Michael J. , Ogden R. Todd , Owusu-Ansah Edward , Karan Kalpita , Cole Steve , Sood Anil K. , Lutgendorf Susan K. , Picard Martin
Published: February 2021

Tumor cells exhibit mitochondrial alterations and are also influenced by biobehavioral processes, but the intersection of biobehavioral factors and tumor mitochondria remains unexplored. Here we examined multiple biochemical and molecular markers of mitochondrial content and function in benign and cancerous ovarian tissue in parallel with exploratory analyses of biobehavioral factors. First, analysis of a publicly-available database (n=1,435) showed that gene expression of specific mitochondrial proteins in ovarian tumors is associated with survival. Quantifying multiple biochemical and molecular markers of mitochondrial content and function in 51 benign and 128 high-grade epithelial ovarian tumors revealed that compared to benign tissue, tumors exhibit 3.3-8.4-fold higher mitochondrial content and respiratory chain enzymatic activities (P<0.001) but similar mitochondrial DNA levels (−3.1%), documenting abnormal mitochondrial phenotypes in tumors. Mitochondrial respiratory chain activity was also associated with interleukin-6 (IL-6) levels in ascites. In benign tissue, negative biobehavioral factors were inversely correlated with mitochondrial content and respiratory chain activities, whereas positive biobehavioral factors tended to be positively correlated with mitochondrial measures, although effect sizes were small to medium (r=-0.43 to 0.47). In contrast, serous tumors showed less pronounced biobehavioral-mitochondrial correlations. These results document abnormal mitochondrial functional phenotypes in ovarian tumors and warrant further research on the link between biobehavioral factors and mitochondria in cancer.
IL-10 driven memory T cell survival and Tfh differentiation promote HIV persistence
Authors: Ribeiro Susan Pereira , Aid Malika , Dupuy Frank P. , Chan Chi Ngai , Hultquist Judd , Delage Claire , Moysi Eirini , Kulpa Deanna , Li Lianghzu , Xu Xuan , Tamilselvan Banumathi , Tomalka Jeffrey , Nekorchuk Michael , Busman-Sahay Kathleen , Bordi Rebeka , Simoneau Camille , Goulet Jean Philippe , Marconi Vincent , Routy Jean Pierre , Balderas Robert , Micci Luca , Howell Bonnie , Barouch Dan H. , Krogan Nevan , Petrovas Constantinos , Paiardini Mirko , Deeks Steven G , Estes Jacob D. , Gorman Daniel , Hazuda Daria , Sekaly Rafick Pierre
Published: February 2021

Mechanisms regulating HIV persistence are complex and not well understood. Increased IL-10 levels were positively associated with HIV reservoir in blood and lymph nodes (LN) of treated HIV aviremic individuals. In LNs, B cells, regulatory T cells, follicular T helper cells (Tfh), monocytes and macrophages contributed to the frequencies of IL10+ cells. Cells with HIV DNA in LNs were in close proximity to IL-10+ cells and/or had the active form of STAT3, the transcription downstream of IL-10. Gene signatures and proteins associated to cell survival, Co-inhibitory receptors expression, maintenance of memory T cells, immune metabolism and Tfh frequencies were all modulated by IL-10 and associated with HIV reservoir persistence.In vitro,STAT3 knockout or neutralization of IL-10, reverted all the aforementioned pathways and resulted in 10-fold decay in HIV reservoir. Collectively, these results provide strong evidence for a pivotal role of IL-10 in HIV persistence, and a potential therapeutic strategy for HIV cure.
LSTM-PHV: Prediction of human-virus protein-protein interactions by LSTM with word2vec
Authors: Tsukiyama Sho , Hasan Md Mehedi , Fujii Satoshi , Kurata Hiroyuki
Published: February 2021

Viral infection involves a large number of protein-protein interactions (PPIs) between human and virus. The PPIs range from the initial binding of viral coat proteins to host membrane receptors to the hijacking of host transcription machinery. However, few interspecies PPIs have been identified, because experimental methods including mass spectrometry are time-consuming and expensive, and molecular dynamic simulation is limited only to the proteins whose 3D structures are solved. Sequence-based machine learning methods are expected to overcome these problems. We have first developed the LSTM model with word2vec to predict PPIs between human and virus, named LSTM-PHV, by using amino acid sequences alone. The LSTM-PHV effectively learnt the training data with a highly imbalanced ratio of positive to negative samples and achieved an AUC of 0.976 with an accuracy of 98.4% using 5-fold cross-validation. By using independent test dataset, we compared the LSTM-PHV with existing state-of-the-art PPI predictors including DeepViral. In predicting PPIs between human and unknown or new virus, the LSTM-PHV presented higher performance than the existing predictors when they were trained by multiple host protein-including datasets. LSTM-PHV learnt multiple host protein sequence contexts more efficiently than the DeepViral. Interestingly, learning of only sequence contexts as words presented remarkably high performances. Use of uniform manifold approximation and projection demonstrated that the LSTM-PHV clearly distinguished the positive PPI samples from the negative ones. We presented the LSTM-PHV online web server that is freely available athttp://kurata35.bio.kyutech.ac.jp/.