bluuebunny/crossref_metadata_2025 huggingface dataset:
MicroRNAs (miRNAs) role in hypertension: pathogenesis and promising therapeutics
Authors: Shaheen Nour , Shaheen Ahmed , Diab Rehab Adel , Desouki Mariam Tarek
Published: November 2023

Background:

MicroRNAs (miRNAs) are small, non-coding RNA molecules that play a crucial role in regulating various cellular processes, including cell proliferation, differentiation, apoptosis, and disease development. Recent studies have highlighted the importance of miRNAs in the development and progression of essential hypertension, a common form of high blood pressure that affects millions of individuals worldwide. The molecular mechanisms by which miRNAs regulate hypertension are complex and multifaceted. MiRNAs target the 3’ untranslated regions of mRNA molecules, thereby regulating the synthesis of specific proteins involved in cardiovascular function. For instance, miRNAs are known to regulate the expression of genes involved in blood vessel tone, cardiac function, and inflammation. The growing body of research on miRNAs in hypertension has highlighted their potential as therapeutic targets for managing this condition. Studies have shown that miRNA-based therapies can modulate the expression of key genes involved in hypertension, leading to improvements in blood pressure and cardiovascular function. However, more research is needed to fully understand the mechanisms of miRNA-mediated hypertension and to develop effective therapeutic strategies.

Conclusions:

In summary, this review highlights the current understanding of the role of miRNAs in essential hypertension, including their molecular mechanisms and potential therapeutic applications. Further research is needed to fully understand the impact of miRNAs on hypertension and to develop new treatments for this common and debilitating condition.
Meningitis in Niger Republic amidst COVID-19: current issues and novel recommendations
Authors: Oduoye Malik Olatunde , Akanbi-Hakeem Hauwa Bolanle , Muzammil Muhammad Ali , Arama Umulkhairah Onyioiza , Abbasi Haleema Qayyum , Farhan Kanza , Fariha FNU , Modupeoluwa Olajide O. , Paul Houessou W. , Badarou Achiraf-deen E. , Akilimali Aymar
Published: November 2023

Amidst coronavirus disease 2019 (COVID-19), there has been a misplaced priority on meningitis in the Niger Republic, thus refocusing resources and attention away from the continuing meningitis campaign in the Niger Republic. The over-strained state of public health resources and staff has also led to decreased surveillance, postponed diagnoses, and constrained immunization efforts in Niger Republic. This review aims to bridge the gaps regarding meningitis amid COVID-19 in Niger Republic and offer recommendations to government to mitigate meningitis in the country, with the hope of finding a permanent solution to this debilitating disease. The authors reviewed 45 past and present pieces of literature on meningitis and COVID-19 from 2013 to 2023 in well-renowned scientific databases such as PubMed, ResearchGate, Google Scholar, African Journals Online, Medline, and Embase. Since 2015, Niger Republic has experienced multiple meningitis epidemics that have resulted in 20, 789 cases and 1, 369 deaths [a case fatality rate (CFR) of 6.6%]. A total of 231 cases of meningitis were reported from 1 November 2021 to 31 January 2022. And recently, 559 cases of meningitis (of which 111 are laboratory confirmed), including 18 deaths (overall CFR 3.2%), occurred in the Zinder region, southeast of Niger Republic, from 1 November 2022 to 27 January 2023. Meningitis remains a public health concern in the world, especially in Niger Republic, which could lead to serious long-term complications. Therefore, adequate and novel measures and therapeutic actions should be implemented by the Niger Government to lessen the burden of the disease in the country.
Complete androgen insensitivity syndrome diagnosed after inguinal surgery in era of modern technology: a case report
Authors: Shrestha Anup , Thapa Anup , Bohara Keshav , Simkhada Suman
Published: November 2023

Introduction:

Androgen Insensitivity Syndrome (AIS) is a rare X-linked recessive disorder of sexual development. It results from mutations in the Androgen Receptor (AR) gene located on chromosome Xq11–12. Affected individuals have a male genotype but a female phenotype.

Case presentation:

A 20-year-old female presented to the emergency room with a history of pain in the bilateral inguinal region. In ultrasonography (USG), bilateral inguinal hernia was suspected. While performing an emergency operation for hernia repair, hernia was revealed as bilateral abdominal testis. Then, after a gynecology consultation, a bilateral orchidectomy was done. Postoperative karyotyping showed a male genotype. Then the patient was discharged on hormone replacement therapy to maintain normal bone mineral density and secondary sexual characteristics.

Discussion:

AIS presents with primary amenorrhea in pubertal females. The growth spurt and secondary sexual characteristics are normal except for absent axillary and pubic hair. There is a short-blind vagina, but the uterus is absent, and the abdominal testis presents as an inguinal hernia. Serum gonadotropin level, karyotyping, and imaging studies are done to reach a diagnosis. Management includes gonadectomy, genitoplasty, and hormone replacement therapy.

Conclusion:

The objective of this report was to make clinicians aware that AIS can present as a bilateral inguinal hernia. In acute presentations, it can be misdiagnosed as a strangulated femoral hernia only later to be identified as an undescended abdominal testis during surgery. An absence of proper clinical judgment and reliance on USG for imaging can often lead to misdiagnosis in acute settings.
Diagnosis of a pulmonary hydatid cyst by fine needle aspiration: a case report with literature review
Authors: Abdullah Ari M. , Rashid Rezheen J. , Tahir Soran H. , Fattah Fattah H. , Hama Jihad Ibrahim , Abdullah Hiwa O. , Kakamad Suhaib H. , Kakamad Fahmi H. , Abdalla Berun A.
Published: November 2023

Introduction and importance:

Hydatid cysts are seldom identified in cytologic smears and are often incidental. This report highlights a case where fine needle aspiration cytology was unintentionally utilized to diagnose a pulmonary hydatid cyst clinically mistaken for an abscess.

Case presentation:

A 29-year-old female presented with intermittent respiratory symptoms, including a mild cough and sputum, that she has been complaining of since 2020. A blood investigation revealed an elevated erythrocyte sedimentation rate (25 mm/h), C-reactive protein (>5 mg/dl), and white blood cells (>11×109/l). A high-resolution computed tomography scan of the chest revealed an irregular pulmonary opacity in the right lower lobe with central fluid attenuation, suspecting an abscess or, less likely, a pulmonary neoplasm. The patient underwent fine needle aspiration cytology, which was diagnosed as a hydatid cyst. A thoracotomy was performed, and the cyst was totally excised. Histopathological results of the specimen confirmed the previous diagnosis.

Clinical discussion:

Various diagnostic modalities have been discussed for diagnosing hydatid cysts, including radiology, serology tests, and fine needle aspiration. These modalities have been evaluated in terms of their respective advantages and drawbacks.

Conclusion:

Hydatid cysts can be challenging to diagnose based on imaging findings and may be misidentified as abscesses or masses. Despite the risk of anaphylaxis, fine needle aspiration cytology can be a reliable diagnostic method if performed meticulously by experienced radiologists.
Impact of Immune Checkpoint Inhibitor Therapy on Quality of Life in Patients With Advanced Melanoma
Authors: Jackson-Carroll Natalie , Whisenant Meagan , Crane Stacey , Johnson Constance
Published: November 2023

Background

Immune checkpoint inhibitors (ICIs) were approved to treat advanced melanoma (AM) because of meaningful clinical benefit. These early data reported that ICI therapy is generally well tolerated, and despite symptoms, patients reported a high global health-related quality of life (HRQOL).

Objective

Immune checkpoint inhibitors are widely used in the oncology community; the aim of this systematic review was to evaluate current data on ICI therapy and its impact on HRQOL of patients with AM.

Methods

The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed during this systematic review to identify and select studies from the PubMed, OVID, EMBASE, and Cochrane databases. Selected studies were downloaded into Covidence and analyzed for trends in how ICI therapy impacts HRQOL in patients with AM. Multiple tools were used to assess the quality of the studies.

Results

The 16 studies included 12 quantitative, 2 qualitative, and 2 mixed-methods studies. The quality of the studies was moderate (n = 7) or strong (n = 9). Symptoms that impacted HRQOL were fatigue, endocrine dysfunction, rash, diarrhea, cognitive impairment, emotional impact (anxiety and depression), and financial toxicity. Suicidal ideation and 1 attempt were reported in 2 studies, which had not been previously published.

Conclusion

Patient-reported symptoms due to ICI negatively impacted HRQOL. Anxiety and depression are prevalent. Current QOL instruments do not capture the entire patient experience.

Implications for Practice

Patients need to be asked if their symptoms are impacting their HRQOL. Further prospective research is needed to develop or adjust current patient-reported outcome instruments to adequately capture the impact of ICIs on HRQOL.
Incidental Detection of 68Ga-DOTA-RGD-2 Uptake in Uterine Fibroid
Authors: Solanki Ritanshu , Mittal Bhagwant Rai , Kumar Rajender , Singh Harmandeep , Sharma Aman
Published: November 2023

Uterine fibroids are benign tumors originating from the smooth muscle cells of the myometrium seen in approximately 20%–50% of women of reproductive age. The Arg-Gly-Asp (RGD) binds to αvβ3 integrin expressed on the surface of angiogenic blood vessels or tumor cells. 18F-FDG PET/CT has been used to evaluate uterine fibroids, with moderate 18F-FDG uptake. However, angiogenesis imaging in uterine fibroids has not been evaluated. The present case presents a rare finding of RGD uptake in the uterine fibroid on 68Ga-DOTA-RGD-2 PET/CT in a patient who underwent angiogenesis imaging for left ankle joint pain and swelling.
Colorectal Adenocarcinoma Mimicking Neuroendocrine Neoplasia on 18F-FDOPA PET/CT
Authors: Moreau Aurélie , Isnardi Vanina , Mognetti Thomas , Meurgey Alexandra , Kryza David
Published: November 2023

We present a case of a 48-year-old woman who had previously undergone surgical resection for bladder paraganglioma. An 18F-FDOPA PET/CT scan performed for suspected colorectal paraganglioma showed intense colorectal uptake associated with adenopathy. Histological examination did not support the presence of a neuroendocrine tumor but instead confirmed the presence of moderately differentiated colorectal adenocarcinoma. Colorectal adenocarcinoma belongs to the list of nonneuroendocrine false-positive tumors that can be detected using 18F-FDOPA. Therefore, a morphological analysis is important. Thus, 18F-FDOPA may be a marker for the aggressiveness of colorectal adenocarcinoma.
“Wandering Spleen” With Lymphomatous Involvement
Authors: Cagliyan Feyza , Balaban Genc Zeynep Ceren , Dede Fuat , Erdil Tanju Yusuf
Published: November 2023

Wandering spleen is a rare condition caused by either lack or the laxity of ligaments, which results malposition in the lower abdomen or pelvis. FDG PET/CT is the cornerstone of the staging procedures in the management of lymphomas leading to upstaging and picking up occult lesions in the spleen and extranodal sites. Herein, we reported initial staging 18F-FDG PET/CT findings of a woman with Hodgkin lymphoma whose spleen was absent in normal position and multiple intense heterogenous hypermetabolism in a pelvic mass raised a suspicion of wandering splenic involvement. The confirmation was made with selective spleen SPECT/CT images thereafter.
Vagal nerve stimulation for headache
Authors: Venkatakrishnan Srikant , Thomas Pravin
Published: November 2023

Purpose of review

Vagal nerve stimulation (VNS) is emerging as a probable therapeutic option for headache. Several questions remain on the mechanism of action, device parameters, efficacy, duration of treatment and long-term safety. This review aims at describing findings of recent literature pertaining to VNS for headache, to put these findings into the perspective of our current fund of knowledge and future scope of work on the topic.

Recent findings

Several studies on functional magnetic resonance imaging patterns following VNS in patients with headache have been published, revealing potential biomarkers of headache and possible treatment effects. A study on post-COVID-19 headache and its management with noninvasive cervical VNS adds to the body of original studies. Meta-analyses and systematic reviews outlining previous work have been published. The collection of these studies adds some data to mechanisms of VNS without adding much insight to differential effects of sub-types of VNS and possible device settings that could prove to be beneficial for headache management.

Well designed studies are needed to identify mechanisms of action, elicit differential effects of various stimulation parameters, and to demonstrate long-term therapeutic effects and safety of VNS in headache.
Fast evolution of SARS-CoV-2 BA.2.86 to JN.1 under heavy immune pressure
Authors: Yang Sijie , Yu Yuanling , Xu Yanli , Jian Fanchong , Song Weiliang , Yisimayi Ayijiang , Wang Peng , Wang Jing , Liu Jingyi , Yu Lingling , Niu Xiao , Wang Jing , Wang Yao , Shao Fei , Jin Ronghua , Wang Youchun , Cao Yunlong
Published: November 2023

While the BA.2.86 variant demonstrated significant antigenic drift and enhanced ACE2 binding affinity, its ability to evade humoral immunity was relatively moderate compared to dominant strains like EG.5 and HK.3. However, the emergence of a new subvariant, JN.1 (BA.2.86.1.1), which possesses an additional spike mutation, L455S, compared to BA.2.86, showed a markedly increased prevalence in Europe and North America, especially in France. Here, we found that L455S of JN.1 significantly enhances immune evasion capabilities at the expense of reduced ACE2 binding affinity. This mutation enables JN.1 to effectively evade Class 1 neutralizing antibodies, offsetting BA.2.86’s susceptibility and thus allowing it to outcompete both its precursor BA.2.86 and the prevailing variants HV.1 (XBB.1.5+L452R+F456L) and JD.1.1 (XBB.1.5+L455F+F456L+A475V) in terms of humoral immune evasion. The rapid evolution from BA.2.86 to JN.1, similar to the earlier transition from BA.2.75 to CH.1.1, highlights the importance of closely monitoring strains with high ACE2 binding affinity and distinct antigenicity, despite their temporarily unremarkable immune evasion capabilities. Such strains could survive and transmit at low levels, since their large antigenic distance to dominant strains allow them to target distinct populations and accumulate immune-evasive mutations rapidly, often at the cost of receptor binding affinity.
Phylogenetic and protein structure analyses provide insight into the evolution and diversification of the CD36 domain ‘apex’ among scavenger receptor class B proteins across Eukarya
Authors: Boohar Reed T. , Vandepas Lauren E. , Traylor-Knowles Nikki , Browne William E.
Published: November 2023

The cluster of differentiation 36 (CD36) domain defines the characteristic ectodomain associated with scavenger receptor class B (SR-B) proteins. In bilaterians, SR-Bs play critical roles in diverse biological processes including innate immunity functions such as pathogen recognition and apoptotic cell clearance, as well as metabolic sensing associated with fatty acid uptake and cholesterol transport. While previous studies suggest this protein family is ancient, SR-B diversity across Eukarya has not been robustly characterized. We analyzed SR-B homologs identified from the genomes and transcriptomes of 165 diverse eukaryotic species. The presence of highly conserved amino acid motifs across major eukaryotic supergroups supports the presence of a SR-B homolog in the last eukaryotic common ancestor (LECA). Our comparative analyses of SR-B protein structure identifies the retention of a canonical asymmetric beta barrel tertiary structure within the CD36 ectodomain across Eukarya. We also identify multiple instances of independent lineage-specific sequence expansions in the apex region of the CD36 ectodomain — a region functionally associated with ligand-sensing. We hypothesize that a combination of both sequence expansion and structural variation in the CD36 apex region may reflect the evolution of SR-B ligand sensing specificity between diverse eukaryotic clades.

Significance Statement

SR-Bs are well-described in bilaterians, however the diversity and evolution of this ancient receptor protein family is poorly understood across Eukarya. Our analyses reveal a conserved beta barrel tertiary structure across eukaryotic SR-Bs that correlates with the presence of an intramolecular tunnel. In contrast, the putative ligand-sensing region associated with the apex of the protein can be highly divergent in both sequence and structure within and between taxa. Our data confirm the antiquity of the SR-B receptor protein family in Eukaryota and improve characterization of SR-B diversity outside of Metazoa. We hypothesize that eukaryotic SR-B diversity may be used as a model to explore receptor protein evolution driven by lineage-specific ligand specificity.
Cholinergic mu-opioid receptor deletion alters reward preference and aversion-resistance
Authors: Beane Cambria R. , Lewis Delainey G. , VI Nicolaus Bruns , Pikus Kat L. , Durfee Mary H. , Zegarelli Roman A. , Perry Thomas W. , Sandoval Oscar , Radke Anna K.
Published: November 2023

Abstract

Heavy alcohol use and binge drinking are important contributors to alcohol use disorder (AUD). The endogenous opioid system has been implicated in alcohol consumption and preference in both humans and animals. The mu opioid receptor (MOR) is expressed on multiple cells in the striatum, however little is known about the contributions of specific MOR populations to alcohol drinking behaviors. The current study used mice with a genetic deletion of MOR in cholinergic cells (ChAT- Cre/Oprm1fl/fl) to examine the role of MORs expressed in cholinergic interneurons (CINs) in home cage self-administration paradigms. Male and female ChAT-Cre/Oprm1fl/flmice were generated and heterozygous Cre+ (knockout) and Cre- (control) mice were tested for alcohol and nicotine consumption. In Experiment 1, binge-like and quinine-resistant drinking was tested using 15% ethanol (EtOH) in a two- bottle, limited-access Drinking in the Dark paradigm. Experiment 2 involved a six-week intermittent access paradigm in which mice received 20% EtOH, nicotine, and then a combination of the two drugs.

Experiment 3 assessed locomotor activity, sucrose preference, and quinine sensitivity. Deleting MORs in cholinergic cells did not alter consumption of EtOH in Experiment 1 or 2. In Experiment 1, the MOR deletion resulted in greater consumption of quinine-adulterated EtOH in male Cre+ mice (vs. Cre-). In Experiment 2, Cre+ mice demonstrated a significantly lower preference for nicotine but did not differ from Cre- mice in nicotine or nicotine + EtOH consumption. Overall fluid consumption was also heightened in the Cre+ mice. In Experiment 3, Cre+ females were found to have greater locomotor activity and preference for sucrose vs. Cre- mice. These data suggest that cholinergic MORs are not required for EtOH, drinking behaviors but may contribute to aversion resistant EtOH drinking in a sex- dependent manner.
Mutation Impact on mRNA Versus Protein Expression across Human Cancers
Authors: Liu Yuqi , Elmas Abdulkadir , Huang Kuan-lin
Published: November 2023

Cancer mutations are often assumed to alter proteins, thus promoting tumorigenesis. However, how mutations affect protein expression has rarely been systematically investigated. We conduct a comprehensive analysis of mutation impacts on mRNA- and protein-level expressions of 953 cancer cases with paired genomics and global proteomic profiling across six cancer types. Protein-level impacts are validated for 47.2% of the somatic expression quantitative trait loci (seQTLs), including mutations from likely “long-tail” driver genes. Devising a statistical pipeline for identifying somatic protein-specific QTLs (spsQTLs), we reveal several gene mutations, includingNF1andMAP2K4truncations andTP53missenses showing disproportional influence on protein abundance not readily explained by transcriptomics. Cross-validating with data from massively parallel assays of variant effects (MAVE),TP53missenses associated with high tumor TP53 proteins were experimentally confirmed as functional. Our study demonstrates the importance of considering protein-level expression to validate mutation impacts and identify functional genes and mutations.
High-sensitivity whole-genome recovery of single viral species in environmental samples
Authors: Chen Liyin , Chen Anqi , Zhang Xinge Diana , T. Robles Maria Saenz , Han Hee-Sun , Xiao Yi , Xiao Gao , Pipas James M. , Weitz David A.
Published: November 2023

Characterizing unknown viruses is essential for understanding viral ecology and preparing against viral outbreaks. Recovering complete genome sequences from environmental samples remains computationally challenging using metagenomics, especially for low-abundance species with uneven coverage. This work presents a method for reliably recovering complete viral genomes from complex environmental samples. Individual genomes are encapsulated into droplets and amplified using multiple displacement amplification. A novel gene detection assay, which employs an RNA-based probe and an exonuclease, selectively identifies droplets containing the target viral genome. Labeled droplets are sorted using a microfluidic sorter, and genomes are extracted for sequencing. Validation experiments using a sewage sample spiked with two known viruses demonstrate the method’s efficacy. We achieve 100% recovery of the spiked-in SV40 (Simian virus 40, 5243bp) genome sequence with uniform coverage distribution, and approximately 99.4% for the larger HAd5 genome (Human Adenovirus 5, 35938bp).

Notably, genome recovery is achieved with as few as one sorted droplet, which enables the recovery of any desired genomes in complex environmental samples, regardless of their abundance. This method enables targeted characterizations of rare viral species and whole-genome amplification of single genomes for accessing the mutational profile in single virus genomes, contributing to an improved understanding of viral ecology.
Causal interpretations of family GWAS in the presence of heterogeneous effects
Authors: Veller Carl , Przeworski Molly , Coop Graham
Published: November 2023

Family-based genome-wide association studies (GWAS) have emerged as a gold standard for assessing causal effects of alleles and polygenic scores. Notably, family studies are often claimed to provide an unbiased estimate of the average causal effect (or average treatment effect; ATE) of an allele, on the basis of an analogy between the random transmission of alleles from parents to children and a randomized controlled trial. Here, we show that this interpretation does not hold in general. Because Mendelian segregation only randomizes alleles among children of heterozygotes, the effects of alleles in the children of homozygotes are not observable. Consequently, if an allele has different average effects in the children of homozygotes and heterozygotes, as can arise in the presence of gene-by-environment interactions, gene-by-gene interactions, or differences in LD patterns, family studies provide a biased estimate of the average effect in the sample. At a single locus, family-based association studies can be thought of as providing an unbiased estimate of the average effect in the children of heterozygotes (i.e., a local average treatment effect; LATE). This interpretation does not extend to polygenic scores, however, because different sets of SNPs are heterozygous in each family. Therefore, other than under specific conditions, the within-family regression slope of a PGS cannot be assumed to provide an un-biased estimate for any subset or weighted average of families. Instead, family-based studies can be reinterpreted as enabling an unbiased estimate of the extent to which Mendelian segregation at loci in the PGS contributes to the population-level variance in the trait. Because this estimate does not include the between-family variance, however, this interpretation applies to only (roughly) half of the sample PGS variance. In practice, the potential biases of a family-based GWAS are likely smaller than those arising from confounding in a standard, population-based GWAS, and so family studies remain important for the dissection of genetic contributions to phenotypic variation. Nonetheless, the causal interpretation of family-based GWAS estimates is less straightforward than has been widely appreciated.
Xanthomonas citri subsp. citri type III effector PthA4 directs the dynamical expression of a putative citrus carbohydrate-binding protein gene for canker formation
Authors: Chen Xinyu , Zou Huasong , Zhuo Tao , Rou Wei , Wu Wei , Fan Xiaojing
Published: November 2023

Xanthomonas citrisubsp.citri(Xcc), the causal agent of citrus canker, elicits canker symptoms in citrus plants because of the transcriptional activator-like (TAL) effector PthA4, which activates the expression of the citrus susceptibility geneCsLOB1. This study reports the regulation of the putative carbohydrate-binding protein geneCs9g12620by PthA4-mediated induction of CsLOB1 duringXccinfection. We found that the transcription ofCs9g12620was induced by infection withXccin a PthA4-dependent manner. Even though it specifically bound to a putative TAL effector-binding element in theCs9g12620promoter, PthA4 exerted a suppressive effect on the promoter activity. In contrast, CsLOB1 bound to theCs9g12620promoter to activate its expression. The silencing ofCsLOB1significantly reduced the level of expression ofCs9g12620, which demonstrated thatCs9g12620was directly regulated by CsLOB1. Intriguingly, PhtA4 interacted with CsLOB1 and exerted feedback control that suppressed the induction of expression ofCs9g12620by CsLOB1. Transient overexpression and gene silencing revealed thatCs9g12620was required for the optimal development of canker symptoms. These results support the hypothesis that the expression ofCs9g12620is dynamically directed by PthA4 for canker formation through the PthA4-mediated induction of CsLOB1.
Latitudinal gradients in predation persist in urban environments
Authors: Hargreaves Anna L , Ensing John , Rahn Olivia , Oliveira Fernanda M. P. , Burkiewicz Jérôme , Lafond Joëlle , Haeussler Sybille , Byerley-Best M. Brooke , Lazda Kira , Slinn Heather L. , Martin Ella , Carlson Matthew L. , Sformo Todd L. , Dawson-Glass Emma , Chiuffo Mariana C. , Vargas-Rodriguez Yalma L. , García-Jiménez Carlos I. , Gomes Inácio J. M. T. , Klemet-N’Guessan Sandra , Paolucci Lucas , Joly Simon , Mehltreter Klaus , Muñoz Jenny , Buono Carmela , Brodie Jedediah F. , Rodriguez-Campbell Antonio , Veen Thor , Freeman Ben , Lee-Yaw Julie , Muñoz Juan Camilo , Paquette Alexandra , Butler Jennifer , Suaréz Esteban
Published: November 2023

Urbanization can profoundly disrupt local ecology. But while urban areas now stretch across latitudes, little is known about urbanization’s effects on macroecological patterns. We used standardized experiments to test whether urbanization disrupts latitudinal gradients in seed predation, a macroecological pattern that shapes community assembly and diversity. Using >56,000 seeds, we compared predation in urbanized and natural areas across 14,000 km of latitude, spanning the Americas. Predation increased 5-fold from high latitudes to the tropics, and latitudinal gradients in predation persisted in urban areas despite significant habitat modification. Urbanization reduced predation by vertebrates, but not invertebrates, and seemed to increase ant predation specifically. Our results show that macroecological patterns in predation intensity can persist in urbanized environments, even as urbanization alters the relative importance of predators.

One-Sentence Summary

Across 56,000 seeds and 112° of latitude, latitudinal gradients in seed predation are equally strong in natural vs. urban areas
Reproducible Neuronal Components found using Group Independent Component Analysis in Resting State Electroencephalographic Data
Authors: Ochoa-Gómez John Fredy , Mantilla-Ramos Yorguin-José , Isaza Verónica Henao , Tobón Carlos Andrés , Lopera Francisco , Aguillón David , Suárez Jazmín Ximena
Published: November 2023

Objective

Evaluate the reliability of neural components obtained from the appli-cation of the group ICA (gICA) methodology to resting-state EEG datasets acquired from multiple sites.

Methods

Five databases from three sites, covering a total of 292 healthy subjects, were analyzed. Each dataset was segmented into groups of 15 subjects, for a total of 19 groups. Data were pre-processed using an automatic pipeline leveraging robust average referencing, wavelet-ICA and automatic rejection of epochs. On each group, stable gICA decompositions were calculated using the ICASSO methodology through a range of orders of decompositions. Each order was characterized by reliability and neuralness metrics, which were evaluated to select a single order of decomposition. Finally, using the decompositions of the selected order, a clustering analysis was performed to find the common components across the 19 groups. Each cluster was characterized by the mean scalp map, its dipole generator with its localization in Talairach coordinates, the spectral behavior of the associated time-series of the components, the assigned ICLabel class and metrics that reflected their reproducibility.

Results

Lower order of decompositions benefits the gICA methodology. At this, using an order of ten, the number of reproducible components with high neuronal information tends to be around nine. Of these, the bilateral motor, frontal medial, and occipital neuronal components were the most reproducible across the different datasets, appearing in more than 89% of the 19 groups evaluated.

Conclusion

We developed a workflow that allows finding reproducible spatial filters between different data sets. This contributes to the improvement of the spatial resolution of the EEG as a brain mapping technique.
Perigestational Opioid Exposure Alters Alcohol-Driven Reward Behaviors in Adolescent Rats
Authors: Searles Christopher T. , Harder Hannah J. , Vogt Meghan E. , Murphy Anne Z.
Published: November 2023

Every fifteen minutes, a baby is born in the U.S. experiencing neonatal opioid withdrawal syndrome (NOWS). Since 2004, the rate of NOWS has increased 7-fold. Clinical studies have established intrauterine exposure to drugs of abuse as a risk factor for adverse health outcomes in adult life, including the propensity for future illicit drug use. Despite extensive knowledge about common mechanisms of action in the neural circuitry that drives opioid and alcohol reward, there is little data on the risks that those born with NOWS face regarding alcohol use later in life. Here, we investigate the impact of perigestational opioid exposure (POE) on the mesolimbic reward system of male and female Sprague Dawley rats at postnatal and adolescent ages. Our laboratory has developed a clinically relevant model for morphine exposure spanning pre-conception to the first week of life. Using this model, we found that POE increased alcohol consumption in female rats under noncontingent conditions, and inversely, reduced alcohol consumption in both male and female rats during operant conditioning sessions. Operant responding was also reduced for sucrose, suggesting that the impact of POE on reward-seeking behaviors is not limited to drugs of abuse. Expression of µ-opioid receptors was also significantly altered in the nucleus accumbens and medial habenula, regions previously shown to play a significant role in reward/aversion circuitry.

Significance Statement

Early life exposure to opioids is known to alter future drug behavior in rats. In the present study, female rats exposed to morphine via their mothers throughout and after pregnancy exhibited increased alcohol consumption when allowed to consume freely. During operant conditioning, however, male and female rats exposed to gestational morphine decreased consumption of alcohol as well as sucrose. We also observed that gestational morphine exposure altered µ-opioid receptor expression in reward-related brain regions. Our study provides the first evidence of changes in alcohol-directed reward behavior in a gestational opioid exposure rat model.
Injectable borax-loaded alginate hydrogels reduce muscle atrophy, modulate inflammation, and generate neuroprotection in the SOD1G93Amouse model of ALS via activation of the IGF–Akt–mTOR axis pathway
Authors: Rodriguez-Romano Ana , Gonzalez-Valdivieso Juan , Moreno-Martinez Laura , Costa Juan Francisco Vázquez , Osta Rosario , Rico Patricia
Published: November 2023

Amyotrophic Lateral Sclerosis (ALS) is the most frequent and fatal condition that causes motor neuron loss and skeletal muscle paralysis. Although ALS is associated with mutations in over 40 genes, its etiology remains largely elusive without a cure or effective treatment. Historically considered the prototype of motor neuron diseases, ALS is defined today as a multisystem disorder that presents several changes in non-neuronal cell types, such as pathological changes in muscle occurring before disease onset and independent from motor neuron degeneration (dying back hypothesis). We base on the hypothesis that skeletal muscle may have an active contribution to disease pathology and thus we consider skeletal muscle tissue as a therapeutic target for ALS.

In previous works, we have demonstrated that boron transporter NaBC1 (encoded by theSLC4A11gene), after activation co-localizes with integrins and growth factor receptors producing a functional cluster that synergistically enhances crosstalk mechanisms accelerating muscle repair. In this work, we aimed to study the effects of borax (B) in a SOD1 mouse model of ALS targeting muscle. We have engineered and characterized injectable alginate-based hydrogels with controlled local borax release to effectively activate muscle NaBC1in vivo. Treated mice presented improved motor function and extended survival correlated with the activation of essential muscle metabolic pathways, resulting in an enhanced muscle repair response and reduced muscle atrophy and inflammation. Interestingly, the activation of muscle repair mechanisms at the local level produced retrograde neuroprotection by motor neuron preservation and reduction in neuroinflammation. Altogether, this work presents evidence supporting the involvement of muscle tissue in ALS pathology, reinforcing skeletal muscle as a primary target to develop new therapies for ALS. We propose a novel strategy based on NaBC1 activation for ALS muscle regeneration.

Graphical abstract
Host-microbiome mutualisms emerge from community interactions among microbes
Authors: Laurich Jason R. , Lash Emma , Frederickson Megan E.
Published: November 2023

Microbiomes often benefit plants, conferring resistance to pathogens, improving stress tolerance, or promoting plant growth. As potential plant mutualists, however, microbiomes are not a single organism but a community of species with complex interactions among microbial taxa and between microbes and their shared host. The nature of ecological interactions among microbes in the microbiome can have important consequences for the net effects of microbiomes on hosts. Here, we compared the effects of individual microbial strains and 10-strain synthetic communities on microbial productivity and host growth using the common duckweedLemna minorand a synthetic, simplified version of its native microbiome. Except forPseudomonas protegens, which was a mutualist when tested alone, all of the single strains we tested were commensals on hosts, benefiting from plant presence but not increasing host growth relative to uninoculated controls. However, 10-strain synthetic microbial communities increased both microbial productivity and duckweed growth more than the average single-strain inoculation and uninoculated controls, meaning that host-microbiome mutualisms can emerge from community interactions among microbes on hosts. The effects of community inoculation were sub-additive, suggesting at least some competition among microbes in the duckweed microbiome. We also investigated the relationship betweenL. minorfitness and that of its microbes, providing some of the first empirical estimates of broad fitness alignment between plants and members of their microbiomes; hosts grew faster with more productive microbes or microbiomes.
Precision data-driven modeling of cortical dynamics reveals idiosyncratic mechanisms underlying canonical oscillations
Authors: Singh Matthew F. , Braver Todd S. , Cole Michael W. , Ching ShiNung
Published: November 2023

Task-free brain activity affords unique insight into the functional structure of brain network dynamics and is a strong marker of individual differences. In this work, we present an algorithmic optimization framework that makes it possible to directly invert and parameterize brain-wide dynamical-systems models involving hundreds of interacting brain areas, from single-subject time-series recordings. This technique provides a powerful neurocomputational tool for interrogating mechanisms underlying individual brain dynamics (“precision brain models”) and making quantitative predictions. We extensively validate the models’ performance in forecasting future brain activity and predicting individual variability in key M/EEG markers. Lastly, we demonstrate the power of our technique in resolving individual differences in the generation of alpha and beta-frequency oscillations. We characterize subjects based upon model attractor topology and a dynamical-systems mechanism by which these topologies generate individual variation in the expression of alpha vs. beta rhythms. We trace these phenomena back to global variation in excitation-inhibition balance, highlighting the explanatory power of our framework in generating mechanistic insights.
Investigating Ecological Interactions in the Tumor Microenvironment using Joint Species Distribution Models for Point Patterns
Authors: Eliason Joel , Rao Arvind
Published: November 2023

The tumor microenvironment (TME) is a complex and dynamic ecosystem that involves interactions between different cell types, such as cancer cells, immune cells, and stromal cells. These interactions can promote or inhibit tumor growth and affect response to therapy. Multitype Gibbs point process (MGPP) models are statistical models used to study the spatial distribution and interaction of different types of objects, such as the distribution of cell types in a tissue sample. Such models are potentially useful for investigating the spatial relationships between different cell types in the tumor microenvironment, but so far studies of the TME using cell-resolution imaging have been largely limited to spatial descriptive statistics. However, MGPP models have many advantages over descriptive statistics, such as uncertainty quantification, incorporation of multiple covariates and the ability to make predictions. In this paper, we describe and apply a previously developed MGPP method, thesaturated pairwise interaction Gibbs point process model, to a publicly available multiplexed imaging dataset obtained from colorectal cancer patients. Importantly, we show how these methods can be used as joint species distribution models (JSDMs) to precisely frame and answer many relevant questions related to the ecology of the tumor microenvironment.
Extracellular Matrix Abnormalities Contribute to Cardiac Insulin Resistance and Associated Dysfunction in Diet-induced Obese Mice
Authors: Musale Vishal , Murdoch Colin E. , Banah Ayman K. , Hasib Annie , Hennayake Chandani K. , Dong Bo , Lang Chim C. , Wasserman David H. , Kang Li
Published: November 2023

Increased deposition of extracellular matrix (ECM) components such as collagens and hyaluronan contributes to the pathogenesis of obesity-associated insulin resistance in muscle, liver, and adipose tissue. Despite the significance of the heart in cardiovascular and metabolic diseases, maladaptive ECM remodelling in obesity-associated cardiac insulin resistance and cardiac dysfunction has not been studied. Using genetic and pharmacological approaches in mice fed a high fat (HF) diet, we demonstrated a tight association between increased ECM deposition with cardiac insulin resistance. Increased collagen deposition by genetic deletion of matrix metalloproteinase 9 (MMP9) exacerbated cardiac insulin resistance and decreased hyaluronan deposition by treatment with PEGylated human recombinant hyaluronidase PH20 (PEGPH20) improved cardiac insulin resistance in obese mice. These relationships corresponded to functional changes in the heart. PEGPH20 treatment in obese mice ameliorated HF diet-induced abnormal myocardial remodelling. In addition to hyaluronan, increased collagen deposition is a characteristic of the obese mouse heart. We further demonstrated that pirfenidone, a clinically available anti-fibrotic medication which inhibits collagen expression, improved cardiac insulin resistance and cardiac function in obese mice. Our results provide important new insights into the role of ECM remodelling in the pathogenesis of cardiac insulin resistance and associated dysfunction in obesity of distinct mouse models. These findings support the novel therapeutic potential of targeting early cardiac ECM abnormalities in the prevention and treatment of obesity-related cardiovascular complications.
The influence of cross-border mobility on the COVID-19 epidemic in Nordic countries
Authors: Shubin Mikhail , Brustad Hilde Kjelgaard , Midtbø Jørgen Eriksson , Günther Felix , Alessandretti Laura , Ala-Nissila Tapio , Tomba Gianpaolo Scalia , Kivelä Mikko , Hin Chan Louis Yat , Leskelä Lasse
Published: November 2023

Abstract

Restrictions of cross-border mobility are typically used to prevent an emerging disease from entering a country in order to slow down its spread. However, such interventions can come with a significant societal cost and should thus be based on careful analysis and quantitative understanding on their effects. To this end, we model the influence of cross-border mobility on the spread of COVID-19 during 2020 in the neighbouring Nordic countries of Denmark, Finland, Norway and Sweden. We investigate the immediate impact of cross-border travel on disease spread and employ counterfactual scenarios to explore the cumulative effects of introducing additional infected individuals into a population during the ongoing epidemic. Our results indicate that border restrictions can significantly influence the course of an epidemic, but this impact is highly contingent on the prevailing epidemic status of the involved countries. In particular, there are several instances in which the contribution of cross-border movement was found to be negligible. Our findings underscore the critical importance of accurate data and models on both epidemic progression and travel patterns in informing decisions related to inter-country mobility restrictions.
GPT-4V(ision) Unsuitable for Clinical Care and Education: A Clinician-Evaluated Assessment
Authors: Senkaiahliyan M. Senthujan , Toma Augustin , Ma Jun , Chan An-Wen , Ha Andrew , An Kevin R. , Suresh Hrishikesh , Rubin Barry , Wang Bo
Published: November 2023

OpenAI’s large multimodal model, GPT-4V(ision), was recently developed for general image interpretation. However, less is known about its capabilities with medical image interpretation and diagnosis. Board-certified physicians and senior residents assessed GPT-4V’s proficiency across a range of medical conditions using imaging modalities such as CT scans, MRIs, ECGs, and clinical photographs. Although GPT-4V is able to identify and explain medical images, its diagnostic accuracy and clinical decision-making abilities are poor, posing risks to patient safety. Despite the potential that large language models may have in enhancing medical education and delivery, the current limitations of GPT-4V in interpreting medical images reinforces the importance of appropriate caution when using it for clinical decision-making.
mRNA Vaccines Encoding Influenza Virus Hemagglutinin (HA) Elicits Immunity in Mice from Influenza A Virus Challenge
Authors: Reneer Z. Beau , Bergeron Harrison C. , Reynolds Stephen , Thornhill-Wadolowski Elena , Feng Lan , Bugno Marcin , Truax Agnieszka D. , Tripp Ralph A.
Published: November 2023

Influenza viruses cause epidemics and can cause pandemics with substantial morbidity with some mortality every year. Seasonal influenza vaccines have incomplete effectiveness and elicit a narrow antibody response that often does not protect against mutations occurring in influenza viruses. Thus, various vaccine approaches have been investigated to improve safety and efficacy. Here, we evaluate an mRNA influenza vaccine encoding hemagglutinin (HA) proteins in a BALB/c mouse model. The results show that mRNA vaccination elicits neutralizing and serum antibodies to each influenza virus strain contained in the current quadrivalent vaccine that is designed to protect against four different influenza viruses including two influenza A viruses (IAV) and two influenza B (IBV), as well as several antigenically distinct influenza virus strains in both hemagglutination inhibition assay (HAI) and virus neutralization assays. The quadrivalent mRNA vaccines had antibody titers comparable to the antibodies elicited by the monovalent vaccines to each tested virus regardless of dosage following an mRNA booster vaccine. Mice vaccinated with mRNA encoding an H1 HA had decreased weight loss and decreased lung viral titers compared to mice not vaccinated with an mRNA encoding an H1 HA. Overall, this study demonstrates the efficacy of mRNA-based seasonal influenza vaccines are their potential to replace both the currently available split-inactivated, and live-attenuated seasonal influenza vaccines.
Fast and scalable querying of eukaryotic linear motifs withgget elm
Authors: Luebbert Laura , Hoang Chi , Kumar Manjeet , Pachter Lior
Published: November 2023

Motivation

Eukaryotic linear motifs (ELMs), or Short Linear Motifs (SLiMs), are protein interaction modules that play an essential role in cellular processes and signaling networks and are often involved in diseases like cancer. The ELM database is a collection of manually curated motif knowledge from scientific papers. It has become a crucial resource for cataloging motif biology and recognizing candidate ELMs in novel amino acid sequences. Users can search amino acid sequences or UniProt IDs on the ELM resource web interface. However, as with many web services, there are limitations in the swift processing of large-scale queries through the ELM web interface or API calls, and, therefore, integration into protein function analysis pipelines is limited.

Results

To allow swift, large-scale motif analyses on protein sequences using ELMs curated on the ELM database, we have developed a Python and command line tool,gget elm, which relies on local computations for efficiently finding candidate ELMs in user-submitted amino acid sequences and UniProt identifiers.gget elmincreases accessibility to the information stored in the ELM database and allows scalable searches for motif-mediated interaction sites in the amino acid sequences.

Availability and implementation

The manual and source code are available athttps://github.com/pachterlab/gget.