bluuebunny/crossref_metadata_2025 huggingface dataset:
Curable sexually transmitted infections among women with HIV in sub-Saharan Africa
Authors: Jarolimova Jana , Platt Laura R. , Curtis Megan R. , Philpotts Lisa L. , Bekker Linda-Gail , Morroni Chelsea , Shahmanesh Maryam , Mussa Aamirah , Barracks Khallela , Ciaranello Andrea L. , Parker Robert A. , Bassett Ingrid V. , Dugdale Caitlin M.
Published: January 2022

Objectives:

Sexually transmitted infections (STIs) cause significant morbidity among women with HIV and increase HIV transmission. We estimated the prevalence of four STIs among women with HIV in sub-Saharan Africa (SSA) and compared prevalence among women with and without HIV.

Design:

Systematic review and meta-analysis.

Methods:

We searched for studies published 1 January 1999 to 19 December 2019 reporting prevalence of gonorrhea, chlamydia, trichomoniasis, or Mycoplasma genitalium among women with HIV in SSA. We excluded studies conducted in high-risk groups (e.g. female sex workers). We extracted data on laboratory-confirmed STIs among women with HIV, and when included, among women without HIV. We estimated pooled prevalence for each STI among women with HIV using inverse variance heterogeneity meta-analysis, compared prevalence to women without HIV, and examined the influences of region, clinical setting, and pregnancy status in subgroup analyses.

Results:

We identified 3756 unique records; 67 studies were included in the meta-analysis. Prevalence of gonorrhea, chlamydia, trichomoniasis, and M. genitalium was 3.5, 4, 15.6, and 10.2%, respectively. Chlamydia prevalence was lower in Eastern (2.8%) than in Southern (12.5%) and West/Central (19.1%) Africa combined. Prevalence of chlamydia and trichomoniasis was higher among pregnant (8.1%, 17.6%) than nonpregnant (1.7%, 12.3%) women. All STIs were more prevalent among women with than without HIV (relative risks ranging 1.54–1.89).

Conclusion:

STIs are common among women with HIV in SSA, and more common among women with than without HIV. Integrated STI and HIV care could substantially impact STI burden among women with HIV, with potential downstream impacts on HIV transmission.
Comparison of T2 Quantification Strategies in the Abdominal-Pelvic Region for Clinical Use
Authors: Draveny Robin , Ambarki Khalid , Han Fei , Hilbert Tom , Laurent Valérie , Morel Olivier , Bertholdt Charline , Beaumont Marine
Published: January 2022

Objectives

The aim of the study was to compare different magnetic resonance imaging (MRI) acquisition strategies appropriate for T2 quantification in the abdominal-pelvic area. The different techniques targeted in the study were chosen according to 2 main considerations: performing T2 measurement in an acceptable time for clinical use and preventing/correcting respiratory motion.

Materials and Methods

Acquisitions were performed at 3 T. To select sequences for in vivo measurements, a phantom experiment was conducted, for which the T2 values obtained with the different techniques of interest were compared with the criterion standard (single-echo SE sequence, multiple acquisitions with varying echo time). Repeatability and temporal reproducibility studies for the different techniques were also conducted on the phantom. Finally, an in vivo study was conducted on 12 volunteers to compare the techniques that offer acceptable acquisition time for clinical use and either address or correct respiratory motion.

Results

For the phantom study, the DESS and T2-preparation techniques presented the lowest precision (ρ
2 = 0.9504 and ρ
2 = 0.9849 respectively), and showed a poor repeatability/reproducibility compared with the other techniques. The strategy relying on SE-EPI showed the best precision and accuracy (ρ
2 = 0.9994 and Cb
= 0.9995). GRAPPATINI exhibited a very good precision (ρ
2 = 0.9984). For the technique relying on radial TSE, the precision was not as good as GRAPPATINI (ρ
2 = 0.9872). The in vivo study demonstrated good respiratory motion management for all of the selected techniques. It also showed that T2 estimate ranges were different from one method to another. For GRAPPATINI and radial TSE techniques, there were significant differences between all the different types of organs of interest.

Conclusions

To perform T2 measurement in the abdominal-pelvic region, one should favor a technique with acceptable acquisition time for clinical use, with proper respiratory motion management, with good repeatability, reproducibility, and precision. In this study, the techniques relying respectively on SE-EPI, radial TSE, and GRAPPATINI appeared as good candidates.
Customized and Navigated Primary Orbital Fracture Reconstruction: Computerized Operation Neuronavigated Surgery Orbital Recent Trauma (CONSORT) Protocol
Authors: Consorti Giuseppe , Betti Enrico , Catarzi Lisa
Published: January 2022

Combined orbital medial wall and floor fractures and large isolated orbital floor fractures commonly require surgical treatment due to the high probability of diplopia and enophthal-mos. Primary reconstruction of these orbital fractures requires a high-level surgeon with a great amount of technical surgical skill. The use of novel technology can greatly improve the accuracy of reconstruction and achieve satisfactory clinical outcomes. Hence, the authors aimed to present our findings and overall experience with respect to extensive floor and medial wall orbital fracture reconstruction according to the Computerized Operation Neuronavigated Surgery Orbital Recent Trauma (CONSORT) protocol, a workflow designed for the primary reconstruction of orbital fractures with customized mesh and intraoperative navigation. A total of 25 consecutively presenting patients presenting with unilateral extensive orbital floor fractures and orbital floor and medial wall fractures were treated following the CONSORT workflow from January 2017 to March 2020. Fractures were surgically treated with a customized implant and intraoperative navigation. Patients underwent surgery within 14 days of the trauma injury. Preopera-tive and postoperative functional and aesthetic outcomes are described herein. All fractures were successfully reconstructed. Postoperatively, all 19 patients with preoperative diplopia reported the resolution of diplopia. Enophthalmos resolved in 18/20 cases. No patients had major complications during follow-up. Thus, the authors conclude that the CONSORT protocol introduced by the authors is an adaptable and reliable workflow for the early treatment of orbital fractures and can clearly optimize functional and aesthetic outcomes, reduce costs and intensive time commitments, and make customized and navigated surgery more available for institutions.
Consensus Statement on Hemostatic Management, Anticoagulation, and Antiplatelet Therapy in Liver Transplantation
Authors: Montalvá Eva , Rodríguez-Perálvarez Manuel , Blasi Annabel , Bonanad Santiago , Gavín Olga , Hierro Loreto , Lladó Laura , Llop Elba , Pozo-Laderas Juan Carlos , Colmenero Jordi ,   on behalf of the Spanish Society of Liver Transplantation and the Spanish Society of Thrombosis and Haemostasis
Published: January 2022

Anticoagulation and antiplatelet therapies are increasingly used in liver transplant (LT) candidates and recipients due to cardiovascular comorbidities, portal vein thrombosis, or to manage posttransplant complications. The implementation of the new direct-acting oral anticoagulants and the recently developed antiplatelet drugs is a great challenge for transplant teams worldwide, as their activity must be monitored and their complications managed, in the absence of robust scientific evidence. In this changing and clinically heterogeneous scenario, the Spanish Society of Liver Transplantation and the Spanish Society of Thrombosis and Haemostasis aimed to achieve consensus regarding the indications, drugs, dosing, and timing of anticoagulation and antiplatelet therapies initiated from the inclusion of the patient on the waiting list to post-LT surveillance. A multidisciplinary group of experts composed by transplant hepatologists, surgeons, hematologists, transplant-specialized anesthesiologists, and intensivists performed a comprehensive review of the literature and identified 21 clinically relevant questions using the patient-intervention-comparison-outcome format. A preliminary list of recommendations was drafted and further validated using a modified Delphi approach by a panel of 24 transplant delegates, each representing a LT institution in Spain. The present consensus statement contains the key recommendations together with the core supporting scientific evidence, which will provide guidance for improved and more homogeneous clinical decision making.
Determinants of Immune Response to Anti–SARS-CoV-2 mRNA Vaccines in Kidney Transplant Recipients: A Prospective Cohort Study
Authors: Magicova Maria , Zahradka Ivan , Fialova Martina , Neskudla Tomas , Gurka Jiri , Modos Istvan , Hojny Michal , Raska Petr , Smejkal Petr , Striz Ilja , Viklicky Ondrej
Published: January 2022

Background.

Immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination has been recently shown to be impaired in kidney transplant recipients (KTRs), but the underlying factors affecting vaccine effectiveness need to be further elucidated.

Methods.

In this prospective cohort study, antibodies against S1 and S2 subunits of SARS-CoV-2 were evaluated using an immunochemiluminescent assay (cutoff 9.5 AU/mL, sensitivity 91.2%, and specificity 90.2%) in 736 KTRs, who were previously either naive or infected with SARS-CoV-2 and vaccinated before or after transplantation. Cellular response was analyzed in a subset of patients using an interferon gamma release assay (cutoff 0.15 IU/mL, sensitivity 92%, and specificity 100%).

Results.

Seroconversion was significantly more impaired in SARS-CoV-2–naive KTRs than in those previously infected (40.1% versus 97.1%; P < 0.001). Mycophenolate use (odds ratio, 0.15; 95% confidence interval, 0.09-0.24; P < 0.001) and depleting therapy in the past year (odds ratio, 0.19; 95% confidence interval, 0.05-0.8; P = 0.023) were found to be among independent factors associated with impaired humoral response. Similarly, the interferon gamma release assay tested in 50 KTRs (cutoff 0.15 IU/mL, sensitivity 92%, specificity 100%) showed that specific T-cell responses against spike protein epitopes are impaired in SARS-CoV-2–naive KTRs, as compared to previously infected KTRs (9.4% versus 90%, P < 0.001). All 35 KTRs vaccinated on the waiting list before transplantation exhibited sustained seroconversion persisting after transplantation.

Conclusions.

Survivors of coronavirus disease 2019 and those vaccinated while on the waiting list exhibited a marked immune response to mRNA vaccines, contrary to poor response in naive KTRs vaccinated after transplantation (NCT04832841).
Invasive Fungal Sinusitis in Patients With Coronavirus Disease 2019 Seen in South India
Authors: Hema V. K. , Kumar Karthik , Shah Virna M.
Published: January 2022

Background:

Coronavirus disease 2019 (COVID-19) has a vast array of presentations and associations with neuro-ophthalmic diseases. There has been a recent surge in ophthalmic manifestations secondary to fungal sinus infections in India especially in diabetic patients who were given systemic steroids. We present our COVID-19–related cranial neuropathies presenting in our clinic.

Methods:

This is a retrospective case series of 10 patients affected with COVID-19 disease and who presented with cranial nerve palsies at the neuro-ophthalmic department of a tertiary eye care hospital in South India. An analysis of electronic medical records data was performed, including their comorbidities, symptoms, cranial nerves involved, ocular and neuroimaging findings, site of lesion, etiology, and prognosis.

Results:

Most of the patients (7 of 10) presented with multiple cranial nerve palsies (MCNP) with poor visual acuity. 2 of the 10 cases succumbed to death due to the intracranial involvement. All MCNP cases had uncontrolled diabetes with a history of systemic steroids, and neuroimaging of these cases showed sinusitis of varying severity most of which were suggestive of fungal invasive type.

Conclusion:

Our study emphasizes the need to screen for fungal involvement in COVID-19 cases presenting with MCNP especially on diabetic patients on systemic steroids so that an early diagnosis may reduce visual loss and mortality. Physicians treating COVID-19 cases need to be aware of this dreadful complication.
Clinical Neurophysiology of Zika Virus–Related Disorders of the Peripheral Nervous System in Adults
Authors: González-Salazar Carelis , Tartaglia Jordana Sartori , Teixeira Dourado Mario Emilio , França Marcondes C.
Published: January 2022

During the 2013 to 2016 outbreak in the Pacific and Americas, Zika virus infection resulted not only in febrile and cutaneous manifestations but also in (severe) neurologic complications. These included both central and peripheral nervous system disorders. The most frequent was Guillain–Barré syndrome that typically developed 1 to 2 weeks after the acute infection. Later, other peripheral nervous system syndromes were recognized in association with the viral infection, broadening the spectrum of Zika virus–related peripheral nervous system syndromes. In the current article, the authors review all available clinical neurophysiology data on Guillain–Barré syndrome and other peripheral nervous system syndromes in an attempt to characterize the major patterns of involvement related to Zika virus. The authors also highlight the clinical usefulness of nerve conduction studies and needle EMG in the investigation of suspected Zika virus–related Guillain–Barré syndrome.
Epilepsy and EEG Abnormalities in Congenital Zika Syndrome
Authors: van der Linden Hélio , Pessoa André , van der Linden Ana , Florêncio Rodrigo Neves , Carvalho Maria Durce C. G. , van der Linden Vanessa
Published: January 2022

The congenital Zika syndrome is a new entity of a group of etiologies that can lead to microcephaly and other brain damages during pregnancy, such as toxoplasmosis, rubeola, cytomegalovirus, and herpes simplex. The Zika virus crosses the placental barrier and, predominantly, affects neuronal progenitor cells. This disruptive process results in severe cortical developmental disorder, calcifications, cortical and subcortical atrophies, and malformations of the cerebellum, brain stem, and spinal cord. Children with congenital Zika syndrome have a set of clinical findings, such as cerebral palsy, dysphagia, orthopedic deformities, visual and auditory impairment, and, rarely, hydrocephalus. Because of the severity of brain lesions, epilepsy is a common finding and a frequent cause of increased morbidity. The prevalence of epilepsy in different series of patients ranges from 37.7% to 71.4%. The aim of this study is to review the studies published so far regarding epilepsy and the EEG pattern in series of patients with congenital Zika syndrome.
Prevalence, characteristics, and predictors of Long COVID among diagnosed cases of COVID-19
Authors: Arjun M. C. , Singh Arvind Kumar , Pal Debkumar , Das Kajal , Gajjala Alekhya , Venkateshan Mahalingam , Mishra Baijayantimala , Patro Binod Kumar , Mohapatra Prasanta Raghab , Subba Sonu Hangma
Published: January 2022

Background

Long COVID or long-term complication after COVID-19 has the ability to affect health and quality of life. Knowledge about the burden and predictors could aid in their prevention and management. Most of the studies are from high-income countries and focus on severe cases. We did this study to estimate the prevalence and identify the characteristics and predictors of Long COVID among our patients.

Methodology

We recruited adult (≥18 years) patients who were diagnosed as Reverse Transcription Polymerase Chain Reaction (RTPCR) confirmed SARS-COV-2 infection and were either hospitalized or tested on outpatient basis. Eligible participants were followed up telephonically after four weeks of diagnosis of SARS-COV-2 infection to collect data on sociodemographic, clinical history, vaccination history, Cycle threshold (Ct) values during diagnosis and other variables. Characteristics of Long COVID were elicited, and multivariable logistic regression was done to find the predictors of Long COVID.

Results

We have analyzed 487 individual data with a median follow-up of 44 days (Inter quartile range (IQR): 39,47). Overall, Long COVID was reported by 29.2% (95% Confidence interval (CI): 25.3%,33.4%) participants. Prevalence of Long COVID among patients with mild/moderate disease (n = 415) was 23.4% (95% CI: 19.5%,27.7%) as compared to 62.5% (95% CI: 50.7%,73%) in severe/critical cases(n=72). The most common Long COVID symptom was fatigue (64.8%) followed by cough (32.4%). Statistically significant predictors of Long COVID were - Pre-existing medical conditions (Adjusted Odds ratio (aOR)=2.00, 95% CI: 1.16,3.44), having a more significant number of symptoms during acute phase of COVID-19 disease (aOR=11.24, 95% CI: 4.00,31.51), two doses of COVID-19 vaccination (aOR=2.32, 95% CI: 1.17,4.58), the severity of illness (aOR=5.71, 95% CI: 3.00,10.89) and being admitted to hospital (Odds ratio (OR)=3.89, 95% CI: 2.49,6.08).

Conclusion

A considerable proportion of COVID-19 cases reported Long COVID symptoms. More research is needed in Long COVID to objectively assess the symptoms and find the biological and radiological markers.
basicsynbio and the BASIC SEVA collection: Software and vectors for an established DNA assembly method
Authors: Haines Matthew C. , Carling Benedict , Marshall James , Shenshin Vasily A. , Baldwin Geoff S. , Storch Marko , Freemont Paul
Published: January 2022

Standardized DNA assembly methods utilizing modular components provide a powerful framework to explore design spaces and iterate through Design-Build-Test-Learn cycles. Biopart Assembly Standard for Idempotent Cloning (BASIC) DNA assembly uses modular parts and linkers, is highly accurate, easy to automate, free for academic and commercial use, while enabling simple hierarchical assemblies through an idempotent format. These features facilitate various applications including pathway engineering, ribosome binding site tuning, fusion protein engineering and multiplexed gRNA expression. In this work we present basicsynbio, an open-source software encompassing a Web App (https://basicsynbio.web.app/) and Python Package (https://github.com/LondonBiofoundry/basicsynbio). With basicsynbio, users can access commonly used BASIC parts and linkers while robustly designing new parts and assemblies with exception handling for common design errors. Users can export sequence data and create build instructions for manual or acoustic liquid-handling platforms. The generation of build instructions relies on the BasicBuild Open Standard which is easily parsed for bespoke workflows and is serializable in Java Script Object Notation for transfer and storage. We demonstrate basicsynbio by assembling a collection of 30 vectors using various sequences including modules from the Standard European Vector Architecture (SEVA). The BASIC SEVA collection is compatible with BASIC and Golden Gate using BsaI. It encompasses vectors containing six antibiotic resistance markers and five origins of replication from different compatibility groups, including a temperature-sensitive variant. To make the collection accessible we deposited it on Addgene under an OpenMTA agreement. Furthermore, vector sequences are accessible from within the basicsynbio application programming interface along with other collections of parts and linkers, providing an ideal environment to design assemblies for bioengineering applications using BASIC.
Loss-of-function of OTUD7A in the schizophrenia-associated 15q13.3 deletion impairs synapse development and function in human neurons
Authors: Kozlova Alena , Zhang Siwei , Kotlar Alex V. , Jamison Brendan , Zhang Hanwen , Shi Serena , Forrest Marc P. , McDaid John , Cutler David J. , Epstein Michael P. , Zwick Michael E. , Pang Zhiping P. , Sanders Alan R. , Warren Stephen T. , Gejman Pablo V. , Mulle Jennifer G. , Duan Jubao
Published: January 2022

Identifying causative gene(s) within disease-associated large genomic regions of copy number variants (CNVs) is challenging. Here, by targeted sequencing of genes within schizophrenia (SZ)-associated CNVs in 1,779 SZ cases and 1,418 controls, we identified three rare putative loss-of-function (LoF) mutations in OTU deubiquitinase 7A (OTUD7A) within the 15q13.3 deletion in cases, but none in controls. To tie OTUD7A LoF with any SZ-relevant cellular phenotypes, we modeled the OTUD7A LoF mutation, rs757148409, in human induced pluripotent stem cell (hiPSC)-derived induced excitatory neurons (iNs) by CRISPR/Cas9 engineering. The mutant iNs showed a ∼50% decrease in OTUD7A expression without undergoing nonsense-mediated mRNA decay. The mutant iNs also exhibited marked reduction of dendritic complexity, density of synaptic proteins GluA1 and PSD-95, and neuronal network activity. Congruent with the neuronal phenotypes in mutant iNs, our transcriptomic analysis showed that the set of OTUD7A LoF-downregulated genes was enriched for those relating to synapse development and function, and was associated with SZ and other neuropsychiatric disorders. These results suggest that OTUD7A LoF impairs synapse development and neuronal function in human neurons, providing mechanistic insight into the possible role of OTUD7A in driving neuropsychiatric phenotypes associated with the 15q13.3 deletion.
Phylogenomics reveals the evolutionary origins of lichenization in chlorophyte algae
Authors: Puginier Camille , Libourel Cyril , Otte Juergen , Skaloud Pavel , Haon Mireille , Grisel Sacha , Petersen Malte , Berrin Jean-Guy , Delaux Pierre-Marc , Dal Grande Francesco , Keller Jean
Published: January 2022

Mutualistic symbioses have contributed to major transitions in the evolution of life. Here, we investigate the evolutionary history and the molecular innovations at the origin of lichens, which are a symbiosis established between fungi and green algae or cyanobacteria. Wede novosequence the genomes or transcriptomes of 12 lichen algal symbiont (LAS) and closely related non-symbiotic algae (NSA) to improve the genomic coverage of Chlorophyte algae. We then perform ancestral state reconstruction and comparative phylogenomics. We identify at least three independent gains of the ability to engage in the lichen symbiosis, one in Trebouxiophyceae and two in Ulvophyceae, confirming the convergent evolution of the lichen symbioses. A carbohydrate-active enzyme from the glycoside hydrolase 8 (GH8) family was identified as a top candidate for the molecular-mechanism underlying lichen symbiosis in Trebouxiophyceae. This GH8 was acquired in lichenizing Trebouxiophyceae by horizontal gene transfer, concomitantly with the ability to associate with lichens fungal symbionts (LFS) and is able to degrade polysaccharides found in the cell wall of LFS. These findings indicate that a combination of gene family expansion and horizontal gene transfer provided the basis for lichenization to evolve in chlorophyte algae.
CHDbase: A Comprehensive Knowledgebase for Congenital Heart Disease-related Genes and Clinical Manifestations
Authors: Zhou Wei-Zhen , Li Wenke , Shen Huayan , Wang Ruby W. , Chen Wen , Zhang Yujing , Zeng Qingyi , Wang Hao , Yuan Meng , Zeng Ziyi , Cui Jinhui , Li Chuan-Yun , Ye Fred Y. , Zhou Zhou
Published: January 2022

Congenital heart disease (CHD) is the most common cause of major birth defects, with a prevalence of 1%. Although an increasing number of studies reporting the etiology of CHD, the findings scattered throughout the literature are difficult to retrieve and utilize in research and clinical practice. We therefore developed CHDbase, an evidence-based knowledgebase with CHD-related genes and clinical manifestations manually curated from 1114 publications, linking 1124 susceptibility genes and 3591 variations to more than 300 CHD types and related syndromes. Metadata such as the information of each publication and the selected population and samples, the strategy of studies, and the major findings of study were integrated with each item of research record. We also integrated functional annotations through parsing ~50 databases/tools to facilitate the interpretation of these genes and variations in disease pathogenicity. We further prioritized the significance of these CHD-related genes with a gene interaction network approach, and extracted a core CHD sub-network with 163 genes. The clear genetic landscape of CHD enables the phenotype classification based on the shared genetic origin. Overall, CHDbase provides a comprehensive and freely available resource to study CHD susceptibility, supporting a wide range of users in the scientific and medical communities. CHDbase is accessible at http://chddb.fwgenetics.org/.
Climate Surveys of Biomedical PhD Students and Training Faculty Members in the Time of Covid
Authors: Ramadoss Deepti , McCord Meghan , Horn John P.
Published: January 2022

In July 2020, four months into the disruption of normal life caused by the Covid-19 pandemic, we assessed the institutional climate within the School of Medicine. Voluntary surveys were completed by 135 graduate students in 11 PhD-granting programs and by 83 members of the graduate training faculty. Several themes emerged. PhD students work hard, but the number of hours spent on research-related activities has declined during the pandemic. The students are worried about the pandemic’s impact on their research productivity, consequent delays in their graduation, and diminished future job prospects. Many late stage PhD students feel they do not have adequate time or resources to plan for their future careers. Symptoms of anxiety and/or depression are prevalent in 51% of the students, based on answers to standardized questions. Most students report they have strong mentoring relationships with their faculty advisors and like their programs, but they identify to a lesser extent with the medical school as a whole. Faculty think highly of their graduate students and are also worried about the pandemic’s impact upon productivity and the welfare of students. Students are interested in access to an Ombuds office, which is currently being organized by the medical school. Moving forward, the school needs to address issues of bias, faculty diversity, support for mentor training, professional development, and the imposter syndrome. We must also work to create a climate in which many more graduate students feel that they are valued members of the academic medicine community.
Thermal characterization and interaction of the subunits from the multimeric bacteriophage endolysin PlyC
Authors: Hoopes J. Todd , Heselpoth Ryan D. , Schwarz Frederick P. , Nelson Daniel C.
Published: January 2022

Bacteriophage endolysins degrade the bacterial peptidoglycan and are considered enzymatic alternatives to small molecule antibiotics. In particular, the multimeric streptococcal endolysin PlyC has appealing antibacterial properties. However, a comprehensive thermal analysis of PlyC is lacking, which is necessary for evaluating long-term stability and downstream therapeutic potential. Biochemical and kinetic-based methods were used in combination with differential scanning calorimetry to investigate the structural, kinetic and thermodynamic stability of PlyC and its various subunits and domains. The PlyC holoenzyme structure is irreversibly compromised due to partial unfolding and aggregation at 46°C. Unfolding of the catalytic subunit, PlyCA, instigates this event, resulting in the kinetic inactivation of the endolysin. In contrast to PlyCA, the PlyCB octamer (the cell wall binding domain) is thermostable, denaturing at ∼75°C. Isolation of PlyCA or PlyCB alone altered their thermal properties. Contrary to the holoenzyme, PlyCA alone unfolds uncooperatively and is thermodynamically destabilized whereas the PlyCB octamer reversibly dissociates into monomers and forms an intermediate state at 74°C in phosphate buffered saline, with each subunit subsequently denaturing at 92°C. Adding folded PlyCA to an intermediate state PlyCB, followed by cooling, allowed forin vitroreconstitution of the active holoenzyme.
Fluid-structure interaction analysis of eccentricity and leaflet rigidity on thrombosis biomarkers in bioprosthetic aortic valve replacements
Authors: Oks David , Vázquez Mariano , Houzeaux Guillaume , Butakoff Constantine , Samaniego Cristóbal
Published: January 2022

This work introduces the first 2-way fluid-structure interaction (FSI) computational model to study the effect of aortic annulus eccentricity on the performance and thrombogenic risk of cardiac bioprostheses. The model predicts that increasing eccentricities yield lower geometric orifice areas (GOAs) and higher normalized transvalvular pressure gradients (TPGs) for healthy cardiac outputs during systole, agreeing with in vitro experiments. Regions with peak values of residence time and shear rate are observed to grow with eccentricity in the sinus of Valsalva, indicating an elevated risk of thrombus formation for eccentric configurations. In addition, the computational model is used to analyze the effect of varying leaflet rigidity on both performance, thrombogenic and calcification risks with applications to tissue-engineered prostheses, observing an increase in systolic and diastolic TPGs, and decrease in systolic GOA, which translates to decreased valve performance for more rigid leaflets. An increased thrombogenic risk is detected for the most rigid valves. Peak solid stresses are also analyzed, and observed to increase with rigidity, elevating risk of valve calcification and structural failure. The immersed FSI method was implemented in a high-performance computing multi-physics simulation software, and validated against a well known FSI benchmark. The aortic valve bioprosthesis model is qualitatively contrasted against experimental data, showing good agreement in closed and open states. To the authors’ knowledge this is the first computational FSI model to study the effect of eccentricity or leaflet rigidity on thrombogenic biomarkers, providing a novel tool to aid device manufacturers and clinical practitioners.
Impact of adolescent intermittent ethanol exposure on interneurons and their surrounding perineuronal nets in adulthood
Authors: Dannenhoffer Carol A. , Gómez-A Alexander , Macht Victoria A. , Jawad Rayyanoor , Sutherland E. Blake , Vetreno Ryan P. , Crews Fulton T. , Boettiger Charlotte A. , Robinson Donita L.
Published: January 2022

Background

Binge alcohol exposure during adolescence results in long-lasting alterations in brain and behavior. For example, adolescent intermittent ethanol (AIE) exposure in rodents results in long-term loss of functional connectivity among prefrontal cortex (PFC) and striatal regions as well as a variety of neurochemical, molecular, and epigenetic alterations. Interneurons in the PFC and striatum play critical roles in behavioral flexibility and functional connectivity. For example, parvalbumin (PV) interneurons are known to contribute to neural synchrony, and cholinergic interneurons contribute to strategy selection. Furthermore, extracellular perineuronal nets (PNNs) surround some interneurons, particularly PV+ interneurons, to further regulate cellular plasticity. The effect of AIE exposure on expression of these markers within the PFC is not well understood.

Methods

The present study tested the hypothesis that AIE exposure reduces expression of PV+ and ChAT+ interneurons in the adult PFC and striatum and increases related expression of PNNs (marked by binding ofWisteria Floribundaagglutinin lectin; WFA) in adulthood. Male rats were exposed to AIE (5 g/kg/day, 2-days-on/2-days-off,i.g., P25-P54) or water (CON), and brain tissue was harvested in adulthood (> P80). Immunohistochemistry and co-immunofluorescence were used to assess expression of ChAT, PV, and WFA labeling within the adult PFC and striatum following AIE exposure.

Results

ChAT and PV interneuron numbers in the striatum and PFC were unchanged after AIE exposure. However, WFA labeling in the PFC of AIE-exposed rats was increased compared to CON rats. Moreover, significantly more PV neurons were surrounded by WFA labeling in AIE-exposed subjects relative to controls in both PFC subregions assessed: the orbitofrontal cortex (CON = 34%; AIE = 40%) and the medial PFC (CON = 10%; AIE = 14%).

Conclusions

These findings indicate that while PV interneuron expression in the adult PFC and striatum is unaltered following AIE exposure, PNNs surrounding these neurons (indicated by extracellular WFA binding) are increased. This increase in PNNs may restrict plasticity of the ensheathed neurons, thus contributing to impaired microcircuitry in frontostriatal connectivity and related behavioral impairments.
Molecular convergence by differential domain acquisition is a hallmark of chromosomal passenger complex evolution
Authors: Komaki Shinichiro , Tromer Eelco C. , De Jaeger Geert , De Winne Nancy , Heese Maren , Schnittger Arp
Published: January 2022

The chromosomal passenger complex (CPC) is a heterotetrameric regulator of eukaryotic cell division, consisting of an Aurora-type kinase and a scaffold built of INCENP, Borealin and Survivin. While most CPC components are conserved across eukaryotes, orthologs of the chromatin reader Survivin have previously only been found in animals and fungi, raising the question of how its essential role is carried out in other eukaryotes. By characterizing proteins that bind to the Arabidopsis Borealin ortholog, we identified BOREALIN RELATED INTERACTOR 1 and 2 (BORI1 and BORI2) as redundant Survivin-like proteins in the context of the CPC in plants. Loss of BORI function is lethal and a reduced expression of BORIs causes severe developmental defects. Similar to Survivin, we find that the BORIs bind to phosphorylated histone H3, relevant for correct CPC association with chromatin. However, this interaction is not mediated by a BIR domain as in previously recognized Survivin orthologs, but by an FHA domain, a widely conserved phosphate-binding module. We propose that the unifying criterion of Survivin-type proteins is a helix that facilitates complex formation with the other two scaffold components, and that the addition of a phosphate-binding domain, necessary for concentration at the inner centromere, evolved in parallel in different eukaryotic groups. Using sensitive similarity searches, we indeed find conservation of this helical domain between animals and plants, and identify the missing CPC component in most eukaryotic supergroups. Interestingly, we also detect Survivin orthologs without a defined phosphate-binding domain, possibly reflecting the situation in the last eukaryotic common ancestor.

Significance Statement

The identification of two SURVIVIN-type genes in the model plant Arabidopsis unfolded the evolutionary trajectories of this central chromosomal passenger complex component and led to the identification of SURVIVIN orthologs in almost the entire eukaryotic kingdom. Our work indicates that the central most aspect of the SURVIVIN gene family is a helix to make contact with two other core chromosomal passenger complex members whereas the addition of a phosphate-binding domain shown to bind to chromatin in animals and plants evolved in parallel at least 3 times in different eukaryotic branches.
Separable roles for RNAi in regulation of transposable elements and viability in the fission yeast Schizosaccharomyces japonicus
Authors: Chapman Elliott , Taglini Francesca , Bayne Elizabeth H.
Published: January 2022

RNA interference (RNAi) is a conserved mechanism of small RNA-mediated genome regulation commonly involved in suppression of transposable elements (TEs) through both post-transcriptional silencing, and transcriptional repression via heterochromatin assembly. The fission yeast Schizosaccharomyces pombe has been extensively utilised as a model for studying RNAi pathways. However, this species is somewhat atypical in that TEs are not major targets of RNAi, and instead small RNAs correspond primarily to non-coding pericentromeric repeat sequences, reflecting a specialised role for the pathway in promoting heterochromatin assembly in these regions. In contrast, in the related fission yeast Schizosaccharomyces japonicus, sequenced small RNAs correspond primarily to TEs. This suggests there may be fundamental differences in the operation of RNAi pathways in these two related species. To investigate these differences, we probed RNAi function in S. japonicus. Unexpectedly, and in contrast to S. pombe, we found that RNAi is essential in this species. Moreover, viability of RNAi mutants can be rescued by mutations implicated in enhanching RNAi-independent heterochromatin propagation. These rescued strains retain heterochromatic marks on TE sequences, but exhibit derepression of TEs at the post-transcriptional level. Our findings indicate that S. japonicus retains the ancestral role of RNAi in facilitating suppression of TEs via both post-transcriptional silencing and heterochromatin assembly, with specifically the heterochromatin pathway being essential for viability, likely due to a function in genome maintenance. The specialised role of RNAi in heterochromatin assembly in S. pombe appears to be a derived state that emerged after the divergence of S. japonicus.
Improved AlphaFold modeling with implicit experimental information
Authors: Terwilliger Thomas C. , Poon Billy K. , Afonine Pavel V. , Schlicksup Christopher J. , Croll Tristan I. , Millán Claudia , Richardson Jane. S. , Read Randy J. , Adams Paul D.
Published: January 2022

Machine learning prediction algorithms such as AlphaFold1and RoseTTAFold2can create remarkably accurate protein models, but these models usually have some regions that are predicted with low confidence or poor accuracy3–6. We hypothesized that by implicitly including experimental information, a greater portion of a model could be predicted accurately, and that this might synergistically improve parts of the model that were not fully addressed by either machine learning or experiment alone. An iterative procedure was developed in which AlphaFold models are automatically rebuilt based on experimental density maps and the rebuilt models are used as templates in new AlphaFold predictions. We find that including experimental information improves prediction beyond the improvement obtained with simple rebuilding guided by the experimental data. This procedure for AlphaFold modeling with density has been incorporated into an automated procedure for crystallographic and electron cryo-microscopy map interpretation.
The native - exotic plant choice in green roof design: using a multicriteria decision framework to foster urban biodiversity
Authors: Calviño Ana A. , Tavella Julia , Beccacece Hernán M. , Estallo Elizabet L. , Fabián Diego , Moreno María Laura , Salvo Adriana , Fenoglio María Silvina
Published: January 2022

Green roofs are considered key elements of the urban green infrastructure since they offer several environmental benefits, including habitat provision for arthropods. To achieve these benefits and ensure green roof success, an appropriate plant selection is an important step in the design of these infrastructures, especially where green roof technology is emerging like in South American cities. So far, decisions of using native or exotic plant species in green roofs had never been evaluated taking into account the plant potential to foster beneficial arthropods. By applying an integrative multicriteria decision framework that combined the habitat template hypothesis with the potential of plants to attract floral visitors and natural enemies, we obtained a ranked set of candidate native and exotic plant species. Among the best-ranked candidate species, we further compared the performance of six native and six exotic species in 30 experimental green roofs installed in Córdoba city, Argentina. To evaluate plant success, the occurrence and cover of each species were recorded one year after establishment under two management conditions: regular watering and weeding of spontaneous plants, and no management (15 roofs each). All selected species increased their vegetative cover one year after establishment. More interestingly, native plants had an advantage over exotic plant species as they exhibited a significantly higher occurrence and a slightly higher cover with no management than exotics. Native annuals were able to reseed the following season even in the absence of management, thus highlighting the relative importance of lifespan as a useful plant trait for future studies in green roof design. Given that green roofs are one of the possible solutions to ameliorate the negative effects of urban habitat loss on arthropod diversity, the development of an integrative multicriteria decision framework that takes into account the potential of native and exotic plant species for promoting beneficial arthropods would give a new twist in plant selection processes for green roofs.
Rnf149-related is an FGF/MAPK-independent regulator of pharyngeal muscle fate specification
Authors: Vitrinel Burcu , Vogel Christine , Christiaen Lionel
Published: January 2022

During embryonic development, cell fate specification gives rise to dedicated lineages that underlie tissue formation. In olfactores, which comprise tunicates and vertebrates, the cardiopharyngeal field is formed by multipotent progenitors to both cardiac and branchiomeric muscles. The ascidian Ciona is a powerful model to study the cardiopharyngeal fate specification with cellular resolution, as only 2 pairs of cardiopharyngeal multipotent progenitors give rise to the heart and to pharyngeal muscles (aka atrial siphon muscles, ASM). These progenitors are multilineage primed, in as much as they express a combination of early ASM- and heart-specific transcripts that become restricted to their corresponding precursors, following oriented asymmetric divisions. Here, we identify the primed gene Rnf149-related (Rnf149-r), which becomes restricted to the heart progenitors, but appears to regulate pharyngeal muscle fate specification in the cardiopharyngeal lineage. CRISPR/Cas9-mediated loss knock-out of Rnf149-r function impairs atrial siphon muscle morphogenesis, and down-regulates Tbx1/10 and Ebf, two key determinants of the pharyngeal muscle fate, while upregulating heart-specific gene expression. These phenotypes are reminiscent of loss of FGF-MAPK signaling in the cardiopharyngeal lineage, and integrated analysis of lineage-specific bulk RNA-seq profiling of loss-of-function perturbations identified a significant overlap between FGF-MAPK and Rnf149-r targets. However, functional interaction assays suggested the Rnf149-r does not directly modulate the activity of the FGF-MAPK-Ets1/2 pathway. Instead, we propose that Rnf149-r acts both in parallel to the FGF-MAPK signaling on shared targets, as well as on FGF-MAPK-independent targets through (a) separate pathway(s).
Relapse-like behavior and nAChR sensitization following intermittent access nicotine self-administration
Authors: Tapia Melissa A. , Jin Xiao-Tao , Tucker Brenton R. , Thomas Leanne N. , Walker Noah B. , Kim Veronica J. , Albertson Steven E. , Damuka Naresh , Krizan Ivan , Edassery Seby , Savas Jeffrey N. , Solingapuram Sai Kiran Kumar , Jones Sara R. , Drenan Ryan M.
Published: January 2022

ABSTRACT

Many tobacco smokers consume nicotine intermittently, but the underlying mechanisms and neurobiological changes associated with intermittent nicotine intake are unclear. Understanding intermittent nicotine intake is a high priority, as it could promote therapeutic strategies to attenuate tobacco consumption. We examined nicotine intake behavior and neurobiological changes in male rats that were trained to self-administer nicotine during brief (5 min) trials interspersed with longer (15 min) drug-free periods. Rats readily adapted to intermittent access (IntA) SA following acquisition on a continuous access (ContA) schedule. Probabilistic analysis of IntA nicotine SA suggested reduced nicotine loading behavior compared to ContA, and nicotine pharmacokinetic modeling revealed that rats taking nicotine intermittently may have increased intake to maintain blood levels of nicotine that are comparable to ContA SA. After IntA nicotine SA, rats exhibited an increase in unreinforced responses for nicotine-associated cues (incubation of craving) and specific alterations in the striatal proteome after 7 days without nicotine. IntA nicotine SA also induced nAChR functional upregulation in the interpeduncular nucleus (IPN), and it enhanced nicotine binding in the brain as determined via [11C]nicotine positron emission tomography. Reducing the saliency of the cue conditions during the 5 min access periods attenuated nicotine intake, but incubation of craving was preserved. Together, these results indicate that IntA conditions promote nicotine SA and nicotine seeking after a nicotine-free period.
Non-alcoholic components of Pelinkovac, a Croatian wormwood-based strong liquor, counteract the inhibitory effect of high ethanol concentration on catalasein vitro
Authors: Homolak Jan , Perhoc Ana Babic , Joja Mihovil , Kodvanj Ivan , Toljan Karlo , Virag Davor
Published: January 2022

Antioxidant enzyme catalase protects the cells against alcohol-induced oxidative stress by scavenging free radicals and metabolizing alcohol. Concentrations of ethanol present in alcoholic beverages can inhibit catalase and foster oxidative stress and alcohol-induced injury. Non-alcoholic components of pelinkovac counteract the inhibitory effects of high ethanol concentration and acidic pH on catalasein vitro.
Morphogenetic forces planar polarize LGN/Pins in the embryonic head during Drosophila gastrulation
Authors: Camuglia Jaclyn , Chanet Soline , Martin Adam C
Published: January 2022

Spindle orientation is often achieved by a complex of Pins/LGN, Mud/NuMa, Gαi, and Dynein, which interacts with astral microtubules to rotate the spindle. Cortical Pins/LGN recruitment serves as a critical step in this process. Here, we identify Pins-mediated planar cell polarized divisions in several of the mitotic domains of the early Drosophila embryo. We found that neither planar cell polarity pathways nor planar polarized myosin localization determined division orientation; instead, our findings strongly suggest that Pins planar polarity and force generated from mesoderm invagination are important. Disrupting Pins polarity via overexpression of a myristoylated version of Pins caused randomized division angles. We found that disrupting forces through chemical inhibitors, depletion of an adherens junction protein or blocking mesoderm invagination disrupted Pins planar polarity and spindle orientation. Furthermore, directional ablations that separated mesoderm from mitotic domains disrupted spindle orientation, suggesting that forces transmitted from mesoderm to mitotic domains can polarize Pins and orient division during gastrulation. To our knowledge, this is the first in vivo example where mechanical force has been shown to polarize Pins to mediate division orientation.