bluuebunny/crossref_metadata_2025 huggingface dataset:
The prevalence of dyslipidemia in patients on hemodialysis: a cross-sectional study from Syria
Authors: Hasan Yasmeen Kamel , Alsultan Mohammad , Anan Mohamed Taher , Hassn Qussai , Basha Kassem
Published: August 2023

Introduction:

Dyslipidemia is an established risk factor for cardiovascular disease (CVD), which is the main cause of mortality among haemodialysis (HD) patients. We investigate the prevalence and characteristics of dyslipidemia in HD patients. Also, we aimed to study the prediction scores; Framingham risk score (FRS), and the atherosclerotic cardiovascular disease risk score; among this population.

Methods:

One hundred fifty-three HD patients were enroled in this retrospective cross-sectional study from two HD centres in Syria, from March 2021 to March 2022. Dyslipidemia is considered as follows; hyper-total cholesterol (TC) (≥200 mg/dl), hyper-triglycerides (TG), (≥150 mg/dl), hyper-low-density lipoprotein (LDL) (≥100 mg/dl), hypo-high-density lipoprotein (HDL) (<40 mg/dl), hyper-Non-HDL (≥130 mg/dl).

Results:

The most prevalent dyslipidemic parameter was low HDL (72.50%) followed by increased TGs (37.30%). TC, LDL, HDL, and Non-HDL showed differences between males and females (P=0.001, 0.015, 0.024, and 0.025; respectively). These parameters were higher in females. History of CVD showed associations with TC, LDL, HDL, and non-HDL (P=0.003, 0.007, 0.004, and 0.004; respectively). Additionally, statins showed effects on TC, LDL, and non-HDL (P=0.003, 0.0002, and 0.002; respectively); however, no relation with TG and HDL (P=0.9 and 0.4). HDL level showed differences in low (7.5%) and intermediate (10%) FRS (P=0.01 and 0.028; respectively); however, it did not show a difference in high (20%) FRS (P=0.68). The lipids profile did not show differences in different thresholds of atherosclerotic cardiovascular disease scores.

Conclusion:

The prevalence of dyslipidemia was high in HD patients in Syria. All lipid parameters except TG showed differences between males and females. Comparisons of lipid parameters with CVD risk stratifications support the need for further studies to prove the benefits of these scores in CVD prediction among the dialysis population.
The devastating effect of cyclone Freddy amidst the deadliest cholera outbreak in Malawi: a double burden for an already weak healthcare system—short communication
Authors: Focus Adriano Lubanga , Nazir Abubakar , Uwishema Olivier
Published: August 2023

Cholera outbreaks cause significant disease burden, especially in developing countries. While the disease is largely eliminated in developed countries, it still remains a huge burden to Sub-Saharan Africa. Lack of access to clean water, hygiene and sanitation facilities remains a huge risk factor for disease transmission and persistence. These outbreaks in Africa are usually associated with high case fatality rates. While many risk factors exist for the spread of the disease, climate change poses a huge challenge to the fight and spread of the disease. Most countries in southern Africa including Malawi and Mozambique have been experiencing the direct and indirect impact of climate change. Climate change can affect the epidemiological dynamics of multiple infectious agents, including vector-borne, water-borne, and food-borne pathogens. The aftermaths effects of flooding and droughts can largely be felt in seasonality changes in the spread of Cholera. Having an in-depth understanding of multiple factors that influence the patterns of spread of climate change related diseases combined with robust surveillance systems could help detect environmental changes in high-risk areas and result in early public health interventions that can alleviate potential outbreaks.
Not every twist is ovarian torsion: a case report of isolated torsion of the fallopian tube in a child
Authors: Awal Shila , Regmi Pradeep Raj , Prajapati Nabin
Published: August 2023

Introduction:

Isolated fallopian tube torsion is a rare condition presenting with abdomen pain. The diagnosis is challenging because the clinical findings mimic several other conditions. In this article, we present a case of an adolescent girl who was diagnosed with the condition during laparoscopy.

Presentation of the case:

A 15-year-old girl presented with complaints of sudden onset left lower quadrant pain, nausea, and vomiting. There was tenderness in the left iliac fossa. Ultrasonography revealed inconclusive findings and contrast-enhanced computed tomography of the abdomen and pelvis suggested possible left adnexal torsion. Hence, she underwent a diagnostic laparoscopy which revealed a twisted, edematous, and congested left fallopian tube. The diagnosis of isolated left fallopian tube torsion was made and she was managed with unilateral salpingectomy.

Discussion:

Women of the reproductive age group are usually affected by this condition. The common presentations are abdominal pain, nausea, and vomiting. The physical examination may reveal abdominal and cervical motion tenderness. Per abdominal ultrasound is the first go-to modality in children. Magnetic resonance imaging, if available, is advised in children if the ultrasound is inconclusive because of the absence of radiation. However, it may require sedation. Therefore, contrast-enhanced computed tomography abdomen gives an added advantage in such scenarios as in our case. This condition is managed by surgery with salpingectomy or tube detorsion with preservation of the tube, depending on the intraoperative findings.

Conclusion:

Clinicians should be aware of the condition given the rarity and challenges in the diagnosis of isolated fallopian tube torsion.
Hemodynamic Characteristics of Intracranial Atherosclerotic Stenosis: A Pilot Study of Contrast Enhancement Time-Density Curves Based on Regions of Interest
Authors: Yu Xiang , Dong Aijing , Zhang Weiguo , Chen Ping
Published: August 2023

Objective

The present study aimed to analyze the hemodynamic characteristics of occluded vessels responsible for acute ischemic stroke and to diagnose the occlusion types.

Methods

Multimodal computed tomography (CT) was used to accurately identify the range of occlusion of large intracranial vessels. Regions of interest (ROI1–3) were manually delineated at sites 2 mm away from the proximal, middle, and distal portions of each occlusion, generating 3 contrast enhancement time-density curves. The peak CT attenuation values, or Hounsfield units (H1–3), and time-to-peak values (T1–3) were extracted from each curve. H0 and T0 of the time-density curve, based on ROI0 of the automatically recognized input artery, were used as the baseline values with which the odds ratios of each parameter, H1–3/0 and T1–3/0, were obtained. The present study aimed to establish prediction models for intracranial atherosclerotic stenosis (ICAS) based on each ROI's time-density curve.

Results

Among the 33 acutely occluded intracranial vessels, 10 were found to have ICAS, whereas 23 did not, based on the diagnostic criteria. Significant differences were observed in patient sex, neutrophil-to-lymphocyte ratio upon admission, Alberta Stroke Program Early CT Score 24–48 hours after reperfusion therapy, and H1/0, H3/0, and T3/0 between the ICAS and non-ICAS groups (P < 0.05). The prediction model (model 3) based on the ROI3 time-density curve showed the best performance for the diagnosis of ICAS (area under the curve, 0.944; 95% confidence interval, 0.854–1.000). The prediction models based on ROI1 (model 1) and ROI2 (model 2) showed moderate diagnostic performance (area under the curve, 0.817 vs 0.822, respectively). The best visualization for proximal occlusions was in the first phase (arterial phase) of multiphase CT angiography, and in the second phase (early venous phase) for distal occlusions.

Conclusions

The contrast enhancement time-density curves of the ROIs at all evaluated portions of the acute ischemic stroke occlusions provided a visual display of the blood flow characteristics of the responsible vessels. The time-density curve of the ROI placed 2 mm from the distal occlusion was a combined effect of residual blood flow and collateral establishment, thus providing good performance for the diagnosis of ICAS.
Autologous Fat Versus Hydroxyapatite Cement for Use in Frontal Sinus Obliteration
Authors: Martinez O. Parker , Le Paulina B. , Martinez Carlos R. , Chen Elliott
Published: August 2023

Background

Frontal sinus obliteration is a possible terminus for the management of chronic sinusitis, frontal bone trauma, cancer extirpation, or mucocele. The mucosa of the sinus is stripped and space obliterated with either autogenic, allopathic, or synthetic materials. This study aimed to compare the outcomes of autologous fat and hydroxyapatite cement (HAC) for frontal sinus obliteration.

Methods

A multidatabase systematic review was conducted to collect outcomes on frontal sinus obliterations with either autologous fat or HAC. Outcomes collected included infection of the frontal sinus or obliteration material, mucocele formation, skin infection at the operative site, hematoma or seroma, cosmetic defect, donor site infection, and need for revision procedure. Prevalence of outcomes was analyzed through meta-analysis of proportions.

Results

Twenty studies were ultimately included in the meta-analysis. Sixteen studies reported outcomes for 667 patients obliterated with autologous fat, and 7 studies reported outcomes for 100 patients obliterated with HAC. Prevalence of infection of the frontal sinus or obliteration material, mucocele formation, skin infection at the operative site, hematoma or seroma, and cosmetic defect did not differ statistically between the cohorts. Donor site infection secondary to fat harvesting for fat obliteration had a prevalence of <0.01. Revision rate was 0.04 (95% confidence interval, 0.01–0.8) for fat obliteration and 0.10 (95% confidence interval, 0.00–0.33) for HAC obliteration.

Conclusions

No statistically significant differences in the studied outcomes were detected between obliterations with autologous fat and HAC, suggesting that either is equally suitable and may be up to the surgeon's preference.
Psychosocial and Behavioral Outcomes for Persons With Cognitive Impairment and Caregivers Following Amyloid-β PET Scan Disclosure
Authors: Couch Elyse , Ashford Miriam T. , Zhang Wenhan , Prina Matthew
Published: August 2023

Background:

Positron emission tomography (PET) scans for amyloid-β can aid in the early and accurate detection of Alzheimer disease. The results of amyloid PET scans could help people with cognitive impairment and caregivers better understand their diagnosis; however, there are concerns that they could also cause psychological harm.

Methods:

A systematic review of psychosocial and behavioral quantitative outcomes following the disclosure of an amyloid PET scan for persons living with cognitive impairment (subjective cognitive decline, mild cognitive impairment, Alzheimer’s Disease, and other dementias) and caregivers.

Findings:

Ten papers were identified from 7 studies. There was little evidence of an association between disclosure and depression. However, persons with mild cognitive impairment and their caregivers with elevated levels of amyloid had an increased risk of distress or anxiety compared with those without elevated amyloid. Participants correctly recalled the scan results; however, it is unclear whether this led to an increased understanding of their diagnosis. We did not identify any studies measuring behavioral outcomes.

Conclusions:

We found mixed evidence on the relationship between amyloid scans and psychosocial and behavioral outcomes in people with cognitive impairment and caregivers. These findings highlight the need for more methodologically rigorous research on this topic.
Cognitive functioning in anxiety and depression: results from the ALSPAC cohort
Authors: Suddell Steph , Mahedy Liam , Skirrow Caroline , Penton-Voak Ian S. , Munafò Marcus R. , Wootton Robyn E.
Published: August 2023

Anxiety and depression are associated with a range of impairments in cognitive functioning. Understanding the nature of these deficits may identify targets for intervention and prevent functional decline. We used observational and genetic methods to investigate the relationship of anxiety and depression with three cognitive domains: emotion recognition, response inhibition, and working memory, in the Avon Longitudinal Study of Parents and Children (ALSPAC). We examined: (i) cross-sectional associations between anxiety, depression, and cognition at age 24 (
n
= 2187), (ii) prospective associations between anxiety and depression at age 18 and cognition at age 24 (
n
= 1855), and (iii) the casual effect of anxiety and depression on cognition using Mendelian randomization (MR). Both disorders were associated with altered emotion recognition; anxiety with decreased happiness recognition (
b = −
0.27 [−0.54,0.01],
p
= 0.045), and depression with increased sadness recognition (
b =
0.35 [0.07,0.64],
p
= 0.016). Anxiety was also associated with poorer working memory (
b = −
0.14 [−0.24,0.04],
p
= 0.005). There was no evidence for an association with response inhibition. MR provided no clear evidence of causal relationships between mental health and cognition, but these analyses were underpowered. Overall, there was little evidence for impairments in executive functioning, but moderate alterations in emotion recognition. This may inform the development of psychosocial interventions.
Near-optimal integration of the magnitude information of time and numerosity
Authors: Otsuka Taku , Yotsumoto Yuko
Published: August 2023

Magnitude information is often correlated in the external world, providing complementary information about the environment. As if to reflect this relationship, the perceptions of different magnitudes (e.g. time and numerosity) are known to influence one another. Recent studies suggest that such magnitude interaction is similar to cue integration, such as multisensory integration. Here, we tested whether human observers could integrate the magnitudes of two quantities with distinct physical units (i.e. time and numerosity) as abstract magnitude information. The participants compared the magnitudes of two visual stimuli based on time, numerosity, or both. Consistent with the predictions of the maximum-likelihood estimation model, the participants integrated time and numerosity in a near-optimal manner; the weight of each dimension was proportional to their relative reliability, and the integrated estimate was more reliable than either the time or numerosity estimate. Furthermore, the integration approached a statistical optimum as the temporal discrepancy of the acquisition of each piece of information became smaller. These results suggest that magnitude interaction arises through a similar computational mechanism to cue integration. They are also consistent with the idea that different magnitudes are processed by a generalized magnitude system.
A nutrition–defence trade-off drives diet choice in a toxic plant generalist
Authors: Carlson Nathaniel J. , Agrawal Anurag A.
Published: August 2023

Plant toxicity shapes the dietary choices of herbivores. Especially when herbivores sequester plant toxins, they may experience a trade-off between gaining protection from natural enemies and avoiding toxicity. The availability of toxins for sequestration may additionally trade off with the nutritional quality of a potential food source for sequestering herbivores. We hypothesized that diet mixing might allow a sequestering herbivore to balance nutrition and defence (via sequestration of plant toxins). Accordingly, here we address diet mixing and sequestration of large milkweed bugs (
Oncopeltus fasciatus
) when they have differential access to toxins (cardenolides) in their diet. In the absence of toxins from a preferred food (milkweed seeds), large milkweed bugs fed on nutritionally adequate non-toxic seeds, but supplemented their diet by feeding on nutritionally poor, but cardenolide-rich milkweed leaf and stem tissues. This dietary shift corresponded to reduced insect growth but facilitated sequestration of defensive toxins. Plant production of cardenolides was also substantially induced by bug feeding on leaf and stem tissues, perhaps benefitting this cardenolide-resistant herbivore. Thus, sequestration appears to drive diet mixing in this toxic plant generalist, even at the cost of feeding on nutritionally poor plant tissue.
Examination of SARS-CoV-2 serological test results from multiple commercial and laboratory platforms with an in-house serum panel
Authors: Lester Sandra N. , Stumpf Megan , Freeman Brandi D. , Mills Lisa , Schiffer Jarad , Semenova Vera , Jia Tao , Desai Rita , Browning Peter , Alston Bailey , Ategbole Muyiwa , Bolcen Shanna , Chen Alexander , David Ebenezer , Manitis Panagiotis , Tatum Heather , Qin Yunlong , Zellner Briana , Drobeniuc Jan , Tejada-Strop Alexandra , Chatterjee Payel , Shrivastava-Ranjan Punya , Jenks M. Harley , McMullan Laura K. , Flint Mike , Spiropoulou Christina F. , Niemeyer Glenn P. , Werner Bonnie J. , Bean Christopher J. , Johnson Jeffrey A. , Hoffmaster Alex R. , Satheshkumar Panayampalli S. , Schuh Amy J. , Owen S. Michele , Thornburg Natalie J.
Published: August 2023

Severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2) is a novel human coronavirus that was identified in 2019. SARS-CoV-2 infection results in an acute, severe respiratory disease called coronavirus disease 2019 (COVID-19).  The emergence and rapid spread of SARS-CoV-2 has led to a global public health crisis, which continues to affect populations across the globe. Real time reverse transcription polymerase chain reaction (rRT-PCR) is the reference standard test for COVID-19 diagnosis. Serological tests are valuable tools for serosurveillance programs and establishing correlates of protection from disease. This study evaluated the performance of one in-house enzyme linked immunosorbent assay (ELISA) utilizing the pre-fusion stabilized ectodomain of SARS-CoV-2 spike (S), two commercially available chemiluminescence assays Ortho VITROS Immunodiagnostic Products Anti-SARS-CoV-2 Total Reagent Pack and Abbott SARS-CoV-2 IgG assay and one commercially available Surrogate Virus Neutralization Test (sVNT), GenScript USA Inc., cPass SARS-CoV-2 Neutralization Antibody Detection Kit for the detection of SARS-CoV-2 specific antibodies.  Using a panel of rRT-PCR confirmed COVID-19 patients’ sera and a negative control group as a reference standard, all three immunoassays demonstrated high comparable positivity rates and low discordant rates.  All three immunoassays were highly sensitive with estimated sensitivities ranging from 95.4%-96.6%. ROC curve analysis indicated that all three immunoassays had high diagnostic accuracies with area under the curve (AUC) values ranging from 0.9698-0.9807. High positive correlation was demonstrated among the conventional microneutralization test (MNT) titers and the sVNT inhibition percent values.  Our study indicates that independent evaluations are necessary to optimize the overall utility and the interpretation of the results of serological tests.  Overall, we demonstrate that all serological tests evaluated in this study are suitable for the detection of SARS-CoV-2 antibodies.
Antimicrobial activity of Serratia marcescens endosymbionts of Rhabditis nematodes against selected antibiotic resistant bacteria
Authors: Aleyo Roselyne , Wagacha John M. , Amugune Nelson O. , Waturu Charles N.
Published: August 2023

Serratia marcescens is a gram-negative non-sporulating gamma proteobacteria of the family Enterobacteriaceae. It is a symbiont of the Oscheius nematodes. The bacterium has shown capacity to kill insect pests, thus the need to evaluate its efficacy against antibiotic tolerant bacterial pathogens. Serratia marcescens bacteria were isolated from hemolymph of previously nematode-infected Galleria mellonella larvae. Cultures were made by streaking on selective media then incubated at 28°C for 48hrs. Antimicrobial bioassays were then performed on Staphylococcus aureus, Methicillin-resistant S. aureus (MRSA), Escherichia coli, Bacillus cereus and Pseudomonas aeruginosa. Genomic DNA was isolated using the Cetyl Trimethyl Ammonium Bromide method followed by amplification of the 16S rRNA gene using B27F and 1492R primers. The two strains scored 99.26% and 98.22% identity to Serratia marcescens strains B195 and RS, respectively. No significant differences were observed between the two isolates with respect to antimicrobial efficacy towards the test pathogens. In general, the least susceptible pathogen was P. aeruginosa with a mean diameter of 13.00 mm followed by MRSA (14.83 mm), S. aureus (15.92 mm), E. coli (21.09 mm) and B. cereus (26.92 mm). Serratia marcescens should be exploited in the management of antibiotic resistant human pathogens.
Ruegeria spongiae sp. nov., isolated from Callyspongia elongata
Authors: Han Seung-Min , Park Jin-Sook
Published: August 2023

A Gram-stain-negative, rod-shaped, polar flagellated, aerobic, light-yellow bacterium, designated as 2012CJ41-6T, was isolated from a sponge sample of Callyspongia elongata from Chuja-myeon, Jeju-si, Jeju-do, Republic of Korea. On the basis of 16S rRNA gene sequencing, strain 2012CJ41-6T clustered with species of the genus

Ruegeria

and appeared closely related to

R

.

halocynthiae

DSM 27839T (96.46 % similarity),

R

.

denitrificans

CECT 4357T (96.32 %),

R

.

profundi

ZGT108T (96.32 %),

R. litorea

CECT 7639T (96.32 %) and

R

.

atlantica

CECT 4292T (96.16 %). The average nucleotide identity and digital DNA–DNA hybridization between strain 2012CJ41-6T and the most closely related strain was 75.3 % and 19.6 %, indicating that 2012CJ41-6T represents a novel species of the genus

Ruegeria

. Growth occurred at 15–37 °C on marine medium in the presence of 0.5–10 % (w/v) NaCl and at pH 5.5–8.5. The DNA G+C content of the genomic DNA was 60.80 mol%, and ubiquinone-10 (Q-10) was the major respiratory quinone. The major cellular fatty acids (>5 %) were C18 : 1
ω7c and/or C18:1
ω6c (summed feature 8). The polar lipids consisted of phosphatidylglycerol, diphosphatidylglycerol, phosphatidylcholine, one unidentified phospholipid, one unidentified aminolipid, one unidentified aminophospholipid and five unidentified lipids. Physiological and biochemical characteristics indicated that strain 2012CJ41-6T represents a novel species of the genus

Ruegeria

, for which the name Ruegeria spongiae sp. nov. is proposed. The type strain is 2012CJ41-6T (=KACC 22645T=LMG 32585T).
NVX-CoV2373 ancestral and NVX-CoV2540 BA.5 protein nanoparticle vaccines protect against Omicron BA.5 variant in Syrian hamsters
Authors: Bricker Traci L. , Joshi Astha , Soudani Nadia , Scheaffer Suzanne M. , Patel Nita , Guebre-Xabier Mimi , Smith Gale , Diamond Michael S. , Boon Adrianus C. M.
Published: August 2023

The emergence of SARS-CoV-2 variants with greater transmissibility or immune evasion properties has jeopardized the existing vaccine and antibody-based countermeasures. Here, we evaluated the efficacy of boosting with the protein nanoparticle NVX-CoV2373 or NVX-CoV2540 vaccines containing ancestral or BA.5 S proteins, respectively, in mRNA-immunized pre-immune hamsters, against challenge with the Omicron BA.5 variant of SARS-CoV-2. Serum antibody binding and neutralization titers were quantified before challenge, and viral loads were measured 3 days after challenge. Compared to an mRNA vaccine boost, NVX-CoV2373 or NVX-CoV2540 induced higher serum antibody binding responses against ancestral Wuhan-1 or BA.5 spike proteins, and greater neutralization of Omicron BA.1 and BA.5 variants. One and three months after vaccine boosting, hamsters were challenged with the Omicron BA.5 variant. NVX-CoV2373 and NVX-CoV2540 boosted hamsters showed reduced viral infection in the nasal washes, nasal turbinates, and lungs compared to unvaccinated animals. Also, NVX-CoV2540 BA.5 boosted animals had fewer breakthrough infections than NVX-CoV2373 or mRNA-vaccinated hamsters. Thus, immunity induced by NVX-CoV2373 or NVX-CoV2540 boosting can protect against the Omicron BA.5 variant in the Syrian hamster model.

IMPORTANCE

As SARS-CoV-2 variants continue to emergence, the efficacy of prior and updated COVID-19 vaccines need to be tested. Here, we tested the efficacy of two nanoparticle protein-based vaccines in pre-immune hamsters against a challenge with the BA.5 Omicron variant of SARS-CoV-2. Compared to an mRNA vaccine boost, the nanoparticle vaccine NVX-CoV2373 and NVX-CoV2540 induced higher serum antibody binding and neutralization responses against ancestral Wuhan-1 or BA.5 variants. One and three months after the last immunization, hamsters were challenged with the Omicron BA.5 variant. NVX-CoV2373 and NVX-CoV2540 boosted hamsters showed reduced viral infection in the nasal washes, nasal turbinates, and lungs compared to unvaccinated animals. Animals that received the homologous vaccine, NVX-CoV2540, had fewer breakthrough infections than NVX-CoV2373 or mRNA-vaccinated hamsters. Together, our data shows that the BA.5 nanoparticle vaccine is effective and that it is important to update the COVID-19 vaccine to match currently circulating strains of SARS-CoV-2.
A genotype-first approach identifies high incidence ofNF1pathogenic variants with distinct disease associations
Authors: Safonov Anton , Nomakuchi Tomoki T , Chao Elizabeth , Horton Carrie , Dolinsky Jill S , Yussuf Amal , Richardson Marcy , Speare Virginia , Li Shuwei , Bogus Zoe C , Bonanni Maria , Raper Anna , Kallish Staci , Ritchie Marylyn D ,   Regeneron Genetics Center,   Penn Medicine BioBank, Nathanson Katherine L , Drivas Theodore G
Published: August 2023

Loss of function variants in theNF1gene cause neurofibromatosis type 1 (NF1), a genetic disorder characterized by complete penetrance, prevalence of 1 in 3,000, characteristic physical exam findings, and a substantially increased risk for malignancy. However, our understanding of the disorder is entirely based on patients ascertained through phenotype-first approaches. Leveraging a genotype-first approach in two large patient cohorts, we demonstrate unexpectedly high prevalence (1 in 450-750) ofNF1pathogenic variants. Half were identified in individuals lacking clinical features of NF1, with many appearing to have post-zygotic mosaicism for the identified variant. Incidentally discovered variants were not associated with classic NF1 features but were associated with an increased incidence of malignancy compared to a control population. Our findings suggest thatNF1pathogenic variants are substantially more common than previously thought, often characterized by somatic mosaicism and reduced penetrance, and are important contributors to cancer risk in the general population.
Climatic and biogeographic processes underlying the diversification of the pantropical and early divergent angiosperm family Annonaceae
Authors: Li Weixi , Wang Runxi , Liu Ming-Fai , Folk Ryan A. , Xue Bine , Saunders Richard M.K.
Published: August 2023

Aim

Tropical rainforests harbour the richest biodiversity among terrestrial ecosystems, but few studies have addressed underlying processes of species diversification in these ecosystems. We use the pantropical and early divergent flowering plant family Annonaceae as a model system to investigate how abiotic factors such as climate and biogeographic events contribute to the diversification process and lead to its high diversity across a long evolutionary history.

Location

Tropics and subtropics

Taxon

Annonaceae

Methods

A super-matrix was constructed for 835 taxa (34% of Annonaceae species), based on eight chloroplast regions. To understand the patterns of diversification, we reconstructed climatic niche evolution and historical biogeographical events, and tested their association with diversification rates.

Results

The analysis of temperature-dependent models in Annonaceae lineages provides strong support for the significant influence of global temperature on net diversification and accumulation of species diversity. The pattern of lineage accumulation in the initial radiation is better aligned with the “museum model,” followed by later accumulation consistent with the “recent cradle model” from the late Oligocene to the present. The increase in the diversification rate of the family (around 25 Ma) lags behind the accumulation of niche divergences (around 15 Ma). Biogeographic events are related to only two of the five diversification rate shifts detected. While no direct relationship to shifts in the diversification rate was uncovered, shifts in niche evolution appear to be associated with increasingly seasonal environments.

Main Conclusions

Global temperature plays a crucial role in driving recent rapid diversification in the Annonaceae. Our study challenges the prevailing assumption of the “museum model” alone and proposes instead a transition from the “museum model” to the “recent cradle model” during the diversification history of the family. However, our findings do not support the direct correlation of any particular climatic niche shifts or historical biogeographical events with shifts in diversification rate. Instead, Annonaceae diversification can lead to later niche divergence as a result of increasing interspecific competition arising from species accumulation. The evolutionary direction of niche shifts furthermore provides insight into the future expansion of Annonaceae into temperate regions. Our results highlight the complexity of the diversification process in taxa with long evolutionary histories, indicating that identifying isolated driving factors is simplistic and inadequate for explaining the observed patterns. Further comprehensive analyses of range evolution are necessary to delve deeper into the interplay among key opportunities, key innovation, and species diversification.
Trithoraxregulates long-term memory inDrosophilathrough epigenetic maintenance of mushroom body metabolic identity and translation capacity
Authors: Raun Nicholas , Jones Spencer G , Kerr Olivia , Keung Crystal , Ibrahim Veyan , Williams MacKayla , Top Deniz , Kramer Jamie M
Published: August 2023

The role of epigenetics and chromatin in the maintenance of postmitotic neuronal cell identities is not well understood. Here, we show that the histone methyltransferase trithorax (trx) is required in postmitotic memory neurons of theDrosophilamushroom body (MB) to enable their capacity for long-term memory (LTM), but not short-term memory (STM). Using MB-specific RNA-, ChIP-, and ATAC-sequencing, we find that trx maintains expression of several non-canonical MB-enriched transcripts, including the orphan nuclear receptorHr51, and the metabolic enzymelactate dehydrogenase. Through these key targets, trx establishes a metabolic state characterized by high lactate levels in MBγ neurons. This metabolic identity supports a high capacity for protein translation, a process that is essential for LTM, but not STM. These data suggest that trx, a classic regulator of cell type specification during development, has an alternative function in maintaining underappreciated aspects of postmitotic neuron identity, such as metabolic state. Our work supports a body of evidence suggesting that a high capacity for energy metabolism is an essential cell identity characteristic for neurons that mediate LTM.
Performing highly parallelized and reproducible GWAS analysis on biobank-scale data
Authors: Schönherr Sebastian , Schachtl-Riess Johanna , Maio Silvia Di , Filosi Michele , Mark Marvin , Lamina Claudia , Fuchsberger Christian , Kronenberg Florian , Forer Lukas
Published: August 2023

Motivation

Genome-wide association studies (GWAS) in large biobanks are transforming genetic research and enable the detection of novel genotype-phenotype relationships. In the last two decades, over 60,000 genetic associations across thousands of human diseases and traits have been discovered using a GWAS approach. Due to denser genotyping and increasing sample sizes, researchers are increasingly faced with computational challenges when executing GWAS analysis. A reproducible, modular and extensible pipeline with a focus on parallelization is essential to simplify data analysis and to allow researchers to devote their time to other essential tasks such as result interpretation and downstream analysis.

Results

Here we present nf-gwas, a Nextflow pipeline to run biobank-scale GWAS analysis. The pipeline automatically performs numerous pre- and post-processing steps, integrates regression modeling from the REGENIE package and currently supports single-variant, gene-based and interaction testing. nf-gwas also includes an extensive reporting functionality that allows to inspect thousands of phenotypes and navigate interactive Manhattan plots directly in the web browser. The pipeline is extensively tested using the unit-style testing framework nf-test to ensure code maintainability, a crucial requirement in clinical and pharmaceutical settings. Furthermore, we validated the pipeline against published GWAS datasets and benchmarked the pipeline on high-performance computing and cloud infrastructures to provide cost estimations to end users.

Availability

nf-gwas is free available athttps://github.com/genepi/nf-gwas.

Contact

lukas.forer@i-med.ac.at
ATRX guards against aberrant differentiation in mesenchymal progenitor cells
Authors: Fang Yan , Barrows Douglas , Dabas Yakshi , Carroll Thomas S , Tap William D. , Nacev Benjamin A.
Published: August 2023

Alterations in the tumor suppressorATRXare recurrently observed in several cancer types including sarcomas, which are mesenchymal neoplasms. ATRX has multiple epigenetic functions including heterochromatin formation and maintenance and regulation of transcription through modulation of chromatin accessibility. Here, we show in murine mesenchymal progenitor cells (MPCs) thatAtrxdeficiency aberrantly activated mesenchymal differentiation programs. This includes adipogenic pathways where ATRX loss induced expression of adipogenic transcription factors (PparγandCebpα) and enhanced adipogenic differentiation in response to differentiation stimuli. These changes are linked to loss of heterochromatin near mesenchymal lineage genes together with increased chromatin accessibility and gains of active chromatin marks at putative enhancer elements and promoters. Finally, we observed depletion of H3K9me3 at transposable elements, which are derepressed including near mesenchymal genes where they could serve as regulatory elements. Our results demonstrate that ATRX functions to buffer against differentiation in mesenchymal progenitor cells, which has implications for understanding ATRX loss of function in sarcomas.
Fecal microbiomes of laboratory beagles receiving antiparasitic formulations in an experimental setting
Authors: Ottesen Andrea , Kocurek Brandon , Deaver Christine , Chiesa Oscar , Cohen Rachael , Mammel Mark , Reed Elizabeth , McDermott Patrick , Strain Errol , Myers Michael
Published: August 2023

Here we describe the fecal microbiome of laboratory beagles in a non-invasive and humane experiment designed to contrast in vivo versus invitro bioequivalence in response to antiparasitic drug administration. The experiment provided a unique opportunity to describe the fecal microbiota of dogs in an experimental setting prior to their adoption. These data are contributed as a resource for the scientific community by the Center for Veterinary Medicine (CVM) of the U.S. Food and Drug Administration (FDA).
SHRIMP: Genetically Encoded mScarlet-derived Red Fluorescent Hydrogen Peroxide Sensor with High Brightness and Minimal Photoactivation
Authors: Pang Yu , Zhang Yiyu , Zhang Jing , Li Zefan , He Yi , Wang Yong , Oberholzer Jose , Ai Hui-wang
Published: August 2023

Red fluorescent protein (RFP) derived indicators are popular due to advantages such as increased imaging depth and reduced autofluorescence and cytotoxicity. However, most RFP-based indicators have low brightness and are susceptible to blue-light-induced photoactivation. In this study, we aimed to overcome the limitations of existing red fluorescent indicators. We utilized mScarlet-I, a highly bright and robust monomeric RFP, to develop a circularly permuted variant called cpmScarlet. We further engineered cpmScarlet into a novel red fluorescent indicator specifically for hydrogen peroxide (H2O2), a crucial reactive oxygen species (ROS) involved in redox signaling and oxidative stress. The resultant indicator, SHRIMP (mScarlet-derived H2O2Redox Indicator with Minimal Photoactivation), exhibited excitation and emission peaks at ∼570 and 595 nm, respectively, and demonstrated a maximum five-fold fluorescence turn-off response to H2O2. Importantly, SHRIMP was not susceptible to blue-light-induced photoactivation and showed high brightness both in its purified protein form and when expressed in mammalian cells. We successfully employed SHRIMP to visualize H2O2dynamics in mammalian cells with exogenously added H2O2and in activated macrophages. Additionally, we demonstrated its utility for multiparameter imaging by co-expressing SHRIMP with GCaMP6m, a green fluorescent calcium indicator, enabling simultaneous monitoring of H2O2and calcium dynamics in mammalian cells in response to thapsigargin (TG) and epidermal growth factor (EGF) stimulation. Furthermore, we expressed SHRIMP in isolated primary mouse islet tissue, and SHRIMP exhibited excellent brightness and capability for effective detection of H2O2production during streptozotocin (STZ)-induced β-cell damage. This study successfully transformed mScarlet-I, a bright and robust monomeric RFP, into a circularly permuted variant (cpmScarlet) and developed the first cpmScarlet-based genetically encoded fluorescent indicator called SHRIMP. SHRIMP exhibits high brightness and insensitivity to photoactivation and is a valuable tool for real-time monitoring of H2O2dynamics in various biological systems. Further research may yield an expanded family of cpmScarlet-based red fluorescent indicators with enhanced photophysical properties.
DHA shortage causes the early degeneration of photoreceptors and RPE in mice with peroxisomal β-oxidation deficiency
Authors: Swinkels Daniëlle , Kocherlakota Sai , Das Yannick , Dane Adriaan D. , Wever Eric J.M. , Vaz Frédéric M. , Bazan Nicolas G. , Van Veldhoven Paul P. , Baes Myriam
Published: August 2023

Purpose

Patients deficient in peroxisomal β-oxidation, which is essential for the synthesis of docosahexaenoic acid (DHA, C22:6n-3) and breakdown of very long-chain polyunsaturated fatty acids (VLC-PUFAs), both important components of photoreceptor outer segments, present with retinopathy. The representative mouse model lacking the central enzyme of this pathway, multifunctional protein 2 (Mfp2−/−), also develops early onset retinal decay and cell-autonomous retinal pigment epithelium (RPE) degeneration, accompanied by reduced plasma and retinal DHA levels. In this study, we investigated whether DHA supplementation can rescue the retinal degeneration ofMfp2−/−mice.

Methods

Mfp2+/−breeding pairs and their offspring were fed a 0.12% DHA or control diet during gestation, lactation and until sacrifice. Offspring were analysed for retinal function via electroretinograms, for lipid composition of neural retina and plasma with lipidome analysis and gas chromatography respectively, and histologically using retinal sections and RPE flatmounts at the age of 4, 8 and 16 weeks.

Results

DHA supplementation toMfp2−/−mice restored retinal DHA levels and prevented photoreceptor shortening, impaired functioning and death until 8 weeks. In addition, rescue of retinal DHA levels temporarily improved the ability of the RPE to phagocytose outer segments and delayed the RPE dedifferentiation. However, despite the initial rescue of retinal integrity, DHA supplementation could not prevent retinal degeneration at 16 weeks.

Conclusions

We reveal that the shortage of systemic supply of DHA is pivotal for the early retinal degeneration inMfp2−/−mice. Furthermore, we unveil that adequate retinal DHA levels are essential for both photoreceptor and RPE homeostasis.
Novel roles for the LRRC56 protein, an IFT cargo protein, in docking of dynein arms inTrypanosoma brucei
Authors: Bonnefoy Serge , Alves Aline Araujo , Bertiaux Eloïse , Bastin Philippe
Published: August 2023

Outer dynein arms (ODAs) are responsible for ciliary beating in eukaryotes. They are assembled in the cytoplasm and shipped by intraflagellar transport (IFT) before attachment to microtubule doublets via the docking complex. The LRRC56 protein has been proposed to contribute to ODAs maturation. Mutations or deletion of theLRRC56gene lead to reduced ciliary motility in all species investigated so far, but with variable impact on dynein arm presence. Here, we investigated the role of LRRC56 in the protistTrypanosoma brucei,where its absence results in distal loss of ODAs, mostly in growing flagella. We show that LRRC56 is a transient cargo of IFT trains during flagellum construction and surprisingly, is required for efficient attachment of a subset of docking complex proteins present in the distal portion of the organelle. This relation is interdependent since the knockdown of the distal docking complex prevents LRRC56’s association with the flagellum. Intriguingly,lrrc56-/-cells display shorter flagella whose maturation is delayed. Inhibition of cell division compensates for the distal ODAs absence thanks to the redistribution of the proximal docking complex, restoring ODAs attachment but not the flagellum length phenotype. This work reveals an unexpected connection between LRRC56 and the docking complex.
Erythroid differentiation dependent interaction of VPS13A with XK at the plasma membrane of K562 cells
Authors: Amos Chase , Xu Peng , De Camilli Pietro
Published: August 2023

Mutations of the bridge-like lipid transport protein VPS13A and of the lipid scramblase XK result in Chorea Acanthocytosis (ChAc) and McLeod syndrome (MLS) respectively, two similar conditions involving neurodegeneration and deformed erythrocytes (acanthocytes). VPS13A binds XK, suggesting a model in which VPS13A forms a lipid transport bridge between the ER and the plasma membrane (PM) where XK resides. However, studies of VPS13A in HeLa and COS7 cells showed that this protein localizes primarily at contacts of the ER with mitochondria. Overexpression of XK in these cells redistributed VPS13A to the biosynthetic XK pool in the ER but not to PM localized XK. Colocalization of VPS13A with XK at the PM was only observed if overexpressed XK harbored mutations that disengage its VPS13A binding site from an intramolecular interaction. As the acanthocytosis phenotype of ChAc and MLS suggests a role of the two proteins in cells of the erythroid lineage, we explored their localization in K562 cells, which differentiate into erythroblasts upon hemin addition. When tagged VPS13A was overexpressed in hemin treated K562 cells, robust formation of ER-PM contacts positive for VPS13A were observed and their formation was abolished in XK KO cells. ER-PM contacts positive for VPS13A were seldomly observed in undifferentiated K562 cells, in spite of the presence of XK in these cells at concentrations similar to those observed after differentiation. These findings reveal that the interaction of VPS13A with XK at ER-PM contacts requires a permissive state which depends upon cell type and/or functional state of the cell.
CrWRKY42 positively regulates chlorophyll degradation and carotenoid biosynthesis in citrus
Authors: Chen Hongyan , Ji Huiyu , Huang Wenkai , Zhang Zhehui , Zhu Kaijie , Zhu Shiping , Chai Lijun , Ye Junli , Deng Xiuxin
Published: August 2023

Chlorophyll degradation and carotenoid biosynthesis, which occur almost simultaneously during fruit ripening, are essential for coloration and nutritional value of fruits. However, the synergistic regulation of these two processes at transcriptional level remains largely unknown. Here, we identified a novel WRKY transcription factor CrWRKY42 from the transcriptome data of the yellowish bud mutant ‘Jinlegan’ tangor (MT) and its wild type ‘Shiranuhi’ tangor (WT), which was involved in the transcriptional regulation of both chlorophyll degradation and carotenoid biosynthesis pathways. CrWRKY42 activated the expression ofβ-carotene hydroxylase 1(CrBCH1) by directly binding to its promoter. Overexpression and interference ofCrWRKY42in citrus calli demonstrated thatCrWRKY42promoted carotenoid accumulation by inducing the expression of multiple carotenoid biosynthetic genes. Further assays confirmed that CrWRKY42 also directly bound to and activated the promoters of the genes involved in the carotenoid biosynthesis, includingphytoene desaturase(CrPDS) andlycopene β-cyclase 2(CrLCYB2). In addition, CrWRKY42 could also bind to the promoter ofSTAY-GREEN(CrSGR) and activated its expression, thus promoting chlorophyll degradation. Overexpression and silencing ofCrWRKY42in citrus fruits indicated that CrWRKY42 positively regulated chlorophyll degradation and carotenoid biosynthesis by synergistically activating the expressions of genes involved in both pathways. In conclusion, our data revealed that CrWRKY42 acted as a positive regulator of chlorophyll degradation and carotenoid biosynthesis to alter the conversion of citrus fruit color. Our findings provide insight into the complex transcriptional regulation of chlorophyll and carotenoid metabolism during fruit ripening.

One Sentence Summary

The CrWRKY42 transcription factor coordinates chlorophyll degradation and carotenoid biosynthesis by directly regulating genes involved in these pathways to alter the conversion of citrus fruit color.
The roles of social media and mutual relationships between travel attitudes and brand equity
Authors: Huang Yung-Chuan
Published: August 2023

Purpose

The purpose of this study has to conduct an integrated effective evaluation system to discover consumers' travel attitudes of the culinary experiences or cuisines and establishing an optimal mutual relationship of a brand equity evaluation model.

Design/methodology/approach

Based on a sample of 624 participants, the results support that social media engagement has indirect effects on culinary brand equity development through travel attitudes and information sharing.

Findings

The study finds that values are expressed as foundational attributes that have indirect effects on brand equity through hedonic function, perceived quality, brand awareness and brand image. In contrast, the social interaction mechanism strengthens subdimensional relationships. These findings extend the customer brand equity literature and the nature of tourists' perspectives in the context of Taiwan's culinary destination brand equity.

Practical implications

It is a suggestion for tourism and hospitality managers to identify the different characteristics of attitudes towards visits and the customers' desert of participation in food-related activities when it derives to the classifications of food and culinary tourism.

Originality/value

The current study extended the findings and asserted that social interaction leads to and strengthens the relationships between memorable culinary hedonic experiences and perceived quality and improves tourists' positive awareness and image compared to other tourism experiences.