bluuebunny/crossref_metadata_2025 huggingface dataset:
A viral movement protein co-opts endoplasmic reticulum luminal-binding protein and calreticulin to promote intracellular movement
Authors: Huang Ying-Wen , Sun Chu-I , Hu Chung-Chi , Tsai Ching-Hsiu , Meng Menghsiao , Lin Na-Sheng , Dinesh-Kumar Savithramma P , Hsu Yau-Heiu
Published: December 2022

Intracellular movement is an important step for the initial spread of virus in plants during infection. This process requires virus-encoded movement proteins (MPs) and their interaction with host factors. Despite the large number of known host factors involved in the movement of different viruses, little is known about host proteins that interact with one of the MPs encoded by potexviruses, the triple-gene-block protein 3 (TGBp3). The main obstacle lies in the relatively low expression level of potexviral TGBp3 in hosts and the weak or transient nature of interactions. Here, we used TurboID-based proximity labeling to identify the network of proteins directly or indirectly interacting with the TGBp3 of a potexvirus, Bamboo mosaic virus (BaMV). Endoplasmic reticulum (ER) luminal-binding protein 4 and calreticulin 3 of Nicotiana benthamiana (NbBiP4 and NbCRT3, respectively) associated with the functional TGBp3-containing BaMV movement complexes, but not the movement-defective mutant, TGBp3M. Fluorescent microscopy revealed that TGBp3 colocalizes with NbBiP4 or NbCRT3 and the complexes move together along ER networks to cell periphery in N. benthamiana. Loss- and gain-of-function experiments revealed that NbBiP4 or NbCRT3 is required for the efficient spread and accumulation of BaMV in infected leaves. In addition, overexpression of NbBiP4 or NbCRT3 enhanced the targeting of BaMV TGBp1 to plasmodesmata (PD), indicating that NbBiP4 and NbCRT3 interact with TGBp3 to promote the intracellular transport of virion cargo to PD that facilitates virus cell-to-cell movement. Our findings revealed additional roles for NbBiP4 and NbCRT3 in BaMV intracellular movement through ER networks or ER-derived vesicles to PD, which enhances the spread of BaMV in N. benthamiana.
Varieties of Mobility Measures: Comparing Survey and Mobile Phone Data during the COVID-19 Pandemic
Authors: Kalleitner Fabian , Schiestl David W , Heiler Georg
Published: December 2022

Human mobility has become a major variable of interest during the COVID-19 pandemic and central to policy decisions all around the world. To measure individual mobility, research relies on a variety of indicators that commonly stem from two main data sources: survey self-reports and behavioral mobility data from mobile phones. However, little is known about how mobility from survey self-reports relates to popular mobility estimates using data from the Global System for Mobile Communications (GSM) and the Global Positioning System (GPS). Spanning March 2020 until April 2021, this study compares self-reported mobility from a panel survey in Austria to aggregated mobility estimates utilizing (1) GSM data and (2) Google’s GPS-based Community Mobility Reports. Our analyses show that correlations in mobility changes over time are high, both in general and when comparing subgroups by age, gender, and mobility category. However, while these trends are similar, the size of relative mobility changes over time differs substantially between different mobility estimates. Overall, while our findings suggest that these mobility estimates manage to capture similar latent variables, especially when focusing on changes in mobility over time, researchers should be aware of the specific form of mobility different data sources capture.
Validation of methods to identify people with idiopathic inflammatory myopathies using hospital episode statistics
Authors: Hannah Jennifer R , Gordon Patrick A , Galloway James , Rutter Megan , Peach Emily J , Rooney Michael , Stilwell Peter , Grainge Matthew J , Lanyon Peter C , Bythell Mary , Pearce Fiona A
Published: December 2022

Objective

Hospital episode statistics (HES) are routinely recorded at every hospital admission within the National Health Service (NHS) in England. This study validates diagnostic ICD-10 codes within HES as a method of identifying cases of idiopathic inflammatory myopathies (IIMs).

Methods

All inpatient admissions at one NHS Trust between 2010 and 2020 with relevant diagnostic ICD-10 codes were extracted from HES. Hospital databases were used to identify all outpatients with IIM, and electronic care records were reviewed to confirm coding accuracy. Total hospital admissions were calculated from NHS Digital reports. The sensitivity and specificity of each code and code combinations were calculated to develop an optimal algorithm. The optimal algorithm was tested in a sample of admissions at another NHS Trust.

Results

Of the 672 individuals identified by HES, 510 were confirmed to have IIM. Overall, the positive predictive value (PPV) was 76% and sensitivity 89%. Combination algorithms achieved PPVs between 89 and 94%. HES can also predict the presence of IIM-associated interstitial lung disease (ILD) with a PPV of 79% and sensitivity of 71%. The optimal algorithm excluded children (except JDM code M33.0), combined M33.0, M33.1, M33.9, M36.0, G72.4, M60.8 and M33.2, and included M60.9 only if it occurred alongside an ILD code (J84.1, J84.9 or J99.1). This produced a PPV of 88.9% and sensitivity of 84.2%. Retesting this algorithm at another NHS Trust confirmed a high PPV (94.4%).

Conclusion

IIM ICD-10 code combinations in HES have high PPVs and sensitivities. Algorithms tested in this study could be applied across all NHS Trusts to enable robust and cost-effective whole-population research into the epidemiology of IIM.
Positron Emission Tomography Assessments of Phosphodiesterase 10A in Patients With Schizophrenia
Authors: Kubota Manabu , Takahata Keisuke , Matsuoka Kiwamu , Sano Yasunori , Yamamoto Yasuharu , Tagai Kenji , Tarumi Ryosuke , Suzuki Hisaomi , Kurose Shin , Nakajima Shinichiro , Shiwaku Hiroki , Seki Chie , Kawamura Kazunori , Zhang Ming-Rong , Takahashi Hidehiko , Takado Yuhei , Higuchi Makoto
Published: December 2022

Background and hypothesis

Phosphodiesterase 10A (PDE10A) is a highly expressed enzyme in the basal ganglia, where cortical glutamatergic and midbrain dopaminergic inputs are integrated. Therapeutic PDE10A inhibition effects on schizophrenia have been reported previously, but the status of this molecule in the living patients with schizophrenia remains elusive. Therefore, this study aimed to investigate the central PDE10A status in patients with schizophrenia and examine its relationship with psychopathology, cognition, and corticostriatal glutamate levels.

Study design

This study included 27 patients with schizophrenia, with 5 antipsychotic-free cases, and 27 healthy controls. Positron emission tomography with [18F]MNI-659, a specific PDE10A radioligand, was employed to quantify PDE10A availability by measuring non-displaceable binding potential (BPND) of the ligand in the limbic, executive, and sensorimotor striatal functional subregions, and in the pallidum. BPND estimates were compared between patients and controls while controlling for age and gender. BPND correlations were examined with behavioral and clinical measures, along with regional glutamate levels quantified by the magnetic resonance spectroscopy.

Study results

Multivariate analysis of covariance demonstrated a significant main effect of diagnosis on BPND (p = .03). A posthoc test showed a trend-level higher sensorimotor striatal BPND in patients, although it did not survive multiple comparison corrections. BPND in controls in this subregion was significantly and negatively correlated with the Tower of London scores, a cognitive subtest. Striatal or dorsolateral prefrontal glutamate levels did not correlate significantly with BPND in either group.

Conclusions

The results suggest altered striatal PDE10A availability and associated local neural dysfunctions in patients with schizophrenia.
An economy of details: standards and data reusability
Authors: Delgado Ana
Published: December 2022

Reusability has been a key issue since the origins of the parts-based approach to synthetic biology. Starting with the BioBrick™ standard part, multiple efforts have aimed to make biology more exchangeable. The reusability of parts and other deoxyribonucleic acid-based data has proven over time to be challenging, however. Drawing on a series of qualitative interviews and an international workshop, this article explores the challenges of reusability in real laboratory practice. It shows particular ways that standards are experienced as presenting shortcomings for capturing the kinds of contextual information crucial for scientists to be able to reuse biological parts and data. I argue that researchers in specific laboratories develop a sense of how much circumstantial detail they need to share for others to be able to make sense of their data and possibly reuse it. When choosing particular reporting formats, recharacterizing data to gain closer knowledge or requesting additional information, researchers enact an ‘economy of details’. The farther apart two laboratories are in disciplinary, epistemological, technical and geographical terms, the more detailed information needs to be captured for data to be reusable across contexts. In synthetic biology, disciplinary distance between computing science and engineering researchers and experimentalist biologists is reflected in diverging views on standards: what kind of information should be included to enable reusability, what kind of information can be captured by standards at all and how they may serve to produce and circulate knowledge. I argue that such interdisciplinary tensions lie at the core of difficulties in setting standards in synthetic biology.
Sural Nerve Vertical Cross-Face Graft for Lacrimal Gland Neurotization to Improve Tear Secretion in Neurodeprivative Dry Eye
Authors: Giannaccare Giuseppe , Bolognesi Federico , Fogagnolo Paolo , Allevi Fabiana , Ruggiero Federica , Filipov Iulian , Marchetti Claudio , Scorcia Vincenzo , Biglioli Federico
Published: December 2022

Purpose:

No specific interventions have been reported for the treatment of severe neurodeprivative dry eye disease owing to facial nerve palsy. We describe herein the feasibility of a novel surgical procedure to reinnervate the lacrimal gland and report the preliminary outcomes of the first series of patients who were treated accordingly.

Methods:

Prospective interventional case series including consecutive patients affected by facial palsy with absolute deficiency of tear secretion who underwent lacrimal gland neurotization. A sural nerve vertical cross-face graft was used to connect the lacrimal gland with the parasympathetic branch of the lingual nerve directed to the contralateral submandibular gland.

Results:

Lacrimal neurotization was performed uneventfully in 10 patients (4 M, 6 F; mean age 47.1 ± 17.1 years). In all cases, the procedure was combined with facial reanimation, while corneal neurotization was performed in 4 cases. One year postoperatively, mean values of a Schirmer test increased significantly compared with baseline values (7.56 ± 7.84 vs. 0 ± 0 mm/5 min; P = 0.02), while the mean daily number of instillation of tear substitutes decreased significantly (21.8 ± 4.5 vs. 7.1 ± 2.2; P = 0.009). Overall, all patients were satisfied with surgery (very satisfied: n = 7 and satisfied: n = 2). No major postoperative complications occurred.

Conclusions:

Vertical cross-face using a sural nerve graft to connect the lacrimal gland with the contralateral submandibular gland is a novel technique for treating patients with facial nerve palsy and severe neurodeprivative dry eye disease. This surgery both performed alone and combined with corneal neurotization is able to improve tear secretion and decrease the need for frequent instillations of tear substitutes.
Clinically Based Automated Tracing and Tortuosity Estimation of Corneal Nerve Fibers From Confocal Microscopy Images
Authors: Colonna Alessia , Scarpa Fabio
Published: December 2022

Purpose:

The purpose of this study was the development of an algorithm able to automatically trace corneal nerves and to estimate a nerve tortuosity index that is useful in clinical practice.

Methods:

In vivo confocal microscopy is an imaging technique that allows the clinical assessment of corneal and systemic diseases. Many studies have demonstrated a correlation between the tortuosity level of nerve fibers in the subbasal plexus layer and some pathologies. We developed an algorithm that provides fully automatic tracing of nerve fibers. It also includes a new way of dealing with bifurcations, separating the main paths from the secondary ones. Based on this automated tracing, the tortuosity was estimated as the absolute curvature, tortuosity density, and fractal dimension. These metrics were considered first individually and then as a linear combination of 2 or 3 of them. We investigated the capability of the estimated tortuosity to emulate the clinical classification into low, mid, and high tortuosity levels. Furthermore, we investigated its ability to distinguish healthy subjects from pathological subjects.

Results:

Excellent agreement between manual and automated grouping of tortuosity (96.6% accuracy) was obtained. Moreover, the proposed algorithm could differentiate between healthy and pathological subjects with an accuracy of 77.1% by analyzing each image individually. The accuracy improved to 86.31% by considering 3 images of the same subject simultaneously.

Conclusions:

The proposed framework provides completely automated analysis of corneal nerve images. The results demonstrate the ability of our method to emulate the clinical classification of tortuosity levels and its potential for identifying healthy and pathological subjects.
Vergence and Accommodation Deficits in Children and Adolescents with Vestibular Disorders
Authors: Chinn Ryan N. , Marusic Sophia , Wang Alicia , Vyas Neerali , Staffa Steven J. , Brodsky Jacob R. , Raghuram Aparna
Published: December 2022

Significance

The high frequency of vergence and accommodation deficits coexisting in patients with a vestibular diagnosis merits a detailed visual function examination.

Purpose

Deficits in vergence and saccades have been reported in patients with vestibular symptomatology. We retrospectively evaluated visual function deficits in adolescents with vestibular diagnoses and concussion.

Methods

Inclusion criteria: vestibular and optometric evaluations between 2014 and 2020; 6 to <22 years old; 20/25 best-corrected vision or better. Clinical criteria assigned vestibular diagnoses and concussion diagnoses. Vestibular diagnoses included vestibular migraine, benign paroxysmal positional vertigo, and persistent postural perceptual dizziness. Visual function deficits were compared to a pediatric control group (30). Non-parametric statistics assessed differences in group distribution.

Results

153 patients were included: 18 had vestibular diagnoses only, 62 had vestibular diagnoses related to concussion, and 73 had concussion only. Vergence deficits were more frequent in patients with vestibular diagnoses and concussion (42%) and concussion only (34%) compared to controls (3%; all P = .02). Accommodation deficits were more frequent in patients with vestibular diagnoses only (67%), vestibular diagnoses and concussion (71%), and concussion (58%) compared to controls (13%; all P = .002). Patients with vestibular migraine and concussion (21) had more vergence deficits (62%) and accommodation insufficiency (52%) than concussion only patients (47%; P = .02; 29%; P = .04). Patients with benign paroxysmal positional vertigo and concussion (20) had lower positive fusional vergence and failed near vergence facility (35%) more than concussion only patients (16%; P = .03).

Conclusions

Visual function deficits were observed at a high frequency in patients with a vestibular diagnosis with or without a concussion and particularly in vestibular migraine or benign paroxysmal positional vertigo. Visual function assessments may be important for patients with vestibular diagnoses.
Effects of Disease-Worsening Following Withdrawal of Etanercept or Methotrexate on Patient-Reported Outcomes in Patients With Rheumatoid Arthritis
Authors: Curtis Jeffrey R. , Stolshek Bradley , Emery Paul , Haraoui Boulos , Karis Elaine , Kricorian Greg , Collier David H. , Yen Priscilla K. , Bykerk Vivian P.
Published: December 2022

Background/Objective

The effect of treatment withdrawal on patient-reported outcomes (PROs) in patients with rheumatoid arthritis (RA) whose disease is in sustained remission has not been well described. This analysis aimed to compare PRO changes in patients with RA following medication withdrawal and disease worsening.

Methods

SEAM-RA (Study of Etanercept and Methotrexate in Combination or as Monotherapy in Subjects With Rheumatoid Arthritis) was a phase 3, multicenter, randomized withdrawal, double-blind controlled study in patients with RA taking methotrexate plus etanercept and in remission (Simple Disease Activity Index ≤3.3). Patient's Global Assessment of Disease Activity, Patient's Assessment of Joint Pain, Health Assessment Questionnaire–Disability Index, and 36-Item Short-Form Health Survey were evaluated for 48 weeks following methotrexate or etanercept withdrawal. Treatment differences for patients with versus without disease worsening were evaluated using a 2-sample t test for continuous end points and log-rank test for time-to-event end points.

Results

Of 253 patients, 121 experienced disease worsening and 132 did not. All PRO scores were similar to those of a general population at baseline and deteriorated over time across the study population. The PtGA and Patient's Assessment of Joint Pain values deteriorated less in those on etanercept monotherapy compared with methotrexate monotherapy. More patients with versus without disease worsening experienced deterioration that was greater than the minimal clinically important difference (MCID) for all PROs tested. In patients with disease worsening, PtGA deterioration more than the MCID preceded Simple Disease Activity Index disease worsening.

Conclusions

Etanercept monotherapy showed benefit over methotrexate in maintaining PRO scores. Patients with disease worsening experienced a more rapid worsening of PtGA beyond the MCID versus patients without disease worsening.

Categories: autoinflammatory disease, biological therapy, DMARDs, rheumatoid arthritis
Bacteriophage and antibiotic combination therapy for recurrentEnterococcus faeciumbacteremia
Authors: Stellfox Madison E. , Fernandes Carolyn , Shields Ryan K. , Haidar Ghady , Hughes Kramer Kailey , Dembinski Emily , Mangalea Mihnea R. , Canfield Gregory S. , Duerkop Breck A. , Van Tyne Daria
Published: December 2022

Enterococcus faeciumis a member of the human gastrointestinal (GI) tract microbiota but can also cause invasive infections, especially in immunocompromised hosts. Enterococci display intrinsic resistance to many antibiotics, and most clinicalE. faeciumisolates have acquired vancomycin resistance, leaving clinicians with a limited repertoire of effective antibiotics. As such, vancomycin-resistantE. faecium(VREfm) has become an increasingly difficult to treat nosocomial pathogen that is often associated with treatment failure and recurrent infections. We followed a patient with recurrentE. faeciumbloodstream infections (BSIs) of increasing severity that ultimately became unresponsive to antibiotic combination therapy over the course of 7 years. Whole genome sequencing (WGS) showed that the patient was colonized with closely relatedE. faeciumstrains for at least two years, and that invasive isolates likely emerged from a largeE. faeciumpopulation in the patient’s GI tract. The addition of bacteriophage (phage) therapy to the patient’s antimicrobial regimen was associated with several months of clinical improvement and reduced intestinal burden of VRE andE. faecium. Eventual recurrence ofE. faeciumBSI was not associated with the development of antibiotic or phage resistance in post-treatment isolates. However, an anti-phage neutralizing antibody response occurred simultaneously with an increased relative abundance of VRE in the GI tract, both of which may have contributed to clinical failure. Taken together, these findings highlight the potential utility and limitations of phage therapy to treat antibiotic-resistant enterococcal infections.

Importance

Phage therapy is an emerging therapeutic approach for treating bacterial infections that do not respond to traditional antibiotics. The addition of phage therapy to systemic antibiotics to treat a patient with recurrentE. faeciuminfections that were non-responsive to antibiotics alone resulted in fewer hospitalizations and improved the patient’s quality of life. Combination phage and antibiotic therapy reducedE. faeciumand VRE abundance in the patient’s stool. Eventually an anti-phage antibody response emerged that was able to neutralize phage activity, which may have limited clinical efficacy. This study demonstrates the potential of phages as an additional option in the antimicrobial toolbox for treating invasive enterococcal infections and highlights the need for further investigation to ensure phage therapy can be deployed for maximum clinical benefit.
The dependence of the amino acid backbone conformation on the translated synonymous codon is not statistically significant
Authors: González-Delgado Javier , Mier Pablo , Bernadó Pau , Neuvial Pierre , Cortés Juan
Published: December 2022

In their recent work, Rosenberget al. [1] studied the dependence between the identity of synonymous codons and the distribution of the backbone dihedral angles of the translated amino acids. In the past, it has been shown that the use of synonymous codons is highly relevant in multiple biological processes including, among others, mRNA splicing, translational rates and protein folding [2, 3]. While the correlation between synonymous codons and secondary structure in translated proteins has been widely studied [4–6], Rosenberget al. evaluated the effect of codon identity on a finer scale, analyzing whether the distribution of (ϕ, ψ) dihedral angles within secondary structure elements is significantly altered when synonymous codons are used. Their conclusion, showing significant differences, particularly for amino acid residues involved inβ-strands, would represent a new paradigm for the role played by synonymous codons in defining protein structure. However, the statistical methodology used in that study was formally incorrect, casting doubt on the obtained results. Besides, it is based on density estimates that might be imprecise for small sample sizes, yielding misleading comparisons. These methodological errors are described in the following section. Then, using an appropriate methodology, we reanalyzed the data presented in [1]. Our results show that the influence of the codon on the distribution of the dihedral angles is statistically non-significant for all types of secondary structures, contradicting the conclusion by Rosenberget al.. These results were corroborated by repeating the analysis on structures extracted from the AlphaFold Database [7, 8] for the same set of proteins, and shown to be robust with respect to the definition secondary structural classes and also when considering the nature of the neighbor residues. Overall, our observations demonstrate that the influence of the synonymous codons on the backbone dihedral angles can not be inferred with current data.
Synergizing algorithmic design, photoclick chemistry and multi-material volumetric printing for accelerating complex shape engineering
Authors: Chansoria Parth , Rütsche Dominic , Wang Anny , Liu Hao , D’Angella Davide , Rizzo Riccardo , Hasenauer Amelia , Weber Patrick , Ibrahim Nafeesah Bte Mohamed , Korshunova Nina , Zenobi-Wong Marcy
Published: December 2022

Accelerating the designing and manufacturing of complex shapes has been a driving factor of modern industrialization. This has led to numerous advances in computational design and modeling and novel additive manufacturing (AM) techniques that can create complex shapes for bespoke applications. By combining a new coding-based design approach with high-throughput volumetric printing, we envision a new approach to transform the way we design and fabricate complex shapes. Here, we demonstrate an algorithmic voxel-based approach, which can rapidly generate and analyze porous structures, auxetic meshes and cylinders, or perfusable constructs. We use this design scheme in conjunction with new approaches for multi-material volumetric printing based on thiol-ene photoclick chemistry to rapidly fabricate complex heterogeneous structures. Collectively, the new design and fabrication technique we demonstrate can be used across a wide-spectrum of products such as actuators, biomedical implants and grafts, or tissue and disease models.

Teaser

A new scheme of rapidly designing and printing complex multi-material structures for implant and tissue graft applications.
Single cell gene set scoring with nearest neighbor graph smoothed data (gssnng)
Authors: Gibbs David L , Strasser Michael K , Huang Sui
Published: December 2022

Gene set scoring (or enrichment) is a common dimension reduction task in bioinformatics that can be focused on differences between groups or at the single sample level. Gene sets can represent biological functions, molecular pathways, cell identities, and more. Gene set scores are context dependent values that are useful for interpreting biological changes following experiments or perturbations. Single sample scoring produces a set of scores, one for each member of a group, which can be analyzed with statistical models that can include additional clinically important factors such as gender or age. However, the sparsity and technical noise of single cell expression measures create difficulties for these methods, which were originally designed for bulk expression profiling (microarrays, RNAseq). This can be greatly remedied by first applying a smoothing transformation that shares gene measure information within transcriptomic neighborhoods. In this work, we use the nearest neighbor graph of cells for matrix smoothing to produce high quality gene set scores on a per-cell, per-group, level which is useful for visualization and statistical analysis.

Availability and implementation

The gssnng software is available using the python package index (PyPI) and works with Scanpy AnnData objects. It can be installed using ‘pip install gssnng’. More information and demo notebooks: Seehttps://github.com/IlyaLab/gssnng
A data-driven approach to establishing cell motility patterns as predictors of macrophage subtypes and their relation to cell morphology
Authors: Kesapragada Manasa , Sun Yao-Hui , Zhu Kan , Recendez Cynthia , Fregoso Daniel , Yang Hsin-ya , Rolandi Marco , Isseroff Rivkah Roslyn , Zhao Min , Gomez Marcella
Published: December 2022

The motility of macrophages in response to microenvironment stimuli is a hallmark of innate immunity, where macrophages play pro-inflammatory or pro-reparatory roles depending on their activation status during wound healing. Cell size and shape have been informative in defining macrophage subtypes. Studies show pro and anti-inflammatory macrophages exhibit distinct migratory behaviors, in vitro, in 3D and in vivo but this link has not been rigorously studied. We apply both morphology and motility-based image processing approaches to analyze live cell images consisting of macrophage phenotypes. Macrophage subtypes are differentiated from primary murine bone marrow derived macrophages using a potent lipopolysaccharide (LPS) or cytokine interleukin-4 (IL-4). We show that morphology is tightly linked to motility, which leads to our hypothesis that motility analysis could be used alone or in conjunction with morphological features for improved prediction of macrophage subtypes. We train a support vector machine (SVM) classifier to predict macrophage subtypes based on morphology alone, motility alone, and both morphology and motility combined. We show that motility has comparable predictive capabilities as morphology. However, using both measures can enhance predictive capabilities. While motility and morphological features can be individually ambiguous identifiers, together they provide significantly improved prediction accuracies (75%) from a training dataset of 1000 cells tracked over time using only phase contrast time-lapse microscopy. Thus, the approach combining cell motility and cell morphology information can lead to methods that accurately assess functionally diverse macrophage phenotypes quickly and efficiently. This can support the development of cost efficient and high through-put methods for screening biochemicals targeting macrophage polarization.
High frequency monitoring of feeding activity in benthic suspension feeders
Authors: Agüera Antonio , Strohmeier Tore , Krogness Cathinka , Strand Øivind
Published: December 2022

Suspension feeders ecosystem role and services are mainly driven by their efficiency in clearing particles from the water column. As such there is an interest on suspension feeders feeding activity and how they interact with the ecosystem. Advancing research on feeding response requires experimental designs where individuals can be exposed to continuously changing environments and where feeding activity can be monitored at a high frequency and at different time scales. There are several methods to monitor feeding activity (as clearance rate (CR) and particle capture efficiency (CE)) of suspension feeders. Among them, the flow-through method is most often used and it allows individuals to be exposed to changing conditions. However, as with the other existing methods, the flow-through method is labor intensive and time consuming limiting both the number of individuals that could be observed simultaneously and the resolution at which measurements can be taken. The flow-through method is constrained by the need to measure the flow rate through the chambers and to take samples to determine particle concentration in the water. In this work we automated the standard flow-through method using micro-controller based prototyping. The result is a methodological approach that continuously monitor feeding at high frequency and on a larger number of individuals while reducing handling and measurement errors. This work provides the description and assessment of the automated set-up, which is an end to end solution that can readily assembled and configured.
Nigral-specific increase in ser31 tyrosine hydroxylase phosphorylation offsets dopamine loss and forestalls hypokinesia onset during progressive nigrostriatal neuron loss
Authors: Kasanga Ella A. , Han Yoonhee , Shifflet Marla K. , Navarrete Walter , McManus Robert , Parry Caleb , Barahona Arturo , Nejtek Vicki A. , Richardson Jason R. , Salvatore Michael F.
Published: December 2022

Mechanisms that augment dopamine (DA) signaling to compensate for tyrosine hydroxylase (TH) loss and delay motor impairment in Parkinson’s disease remain unidentified. The rat nigrostriatal pathway was unilaterally-lesioned by 6-OHDA to determine whether differences in DA content, TH protein, TH phosphorylation, or D1receptor expression in striatum or substantia nigra (SN) aligned with onset of hypokinesia at two time points. At 7 days, DA and TH loss in striatum exceeded 95%, whereas DA was unaffected in SN, despite ∼60% TH loss. At 28 days, hypokinesia was established. At both time points, ser31 TH phosphorylation increased only in SN, corresponding to less DA versus TH loss. ser40 TH phosphorylation was unaffected in striatum or SN. By day 28, D1receptor expression increased only in lesioned SN. These results indicate that increased ser31 TH phosphorylation and D1receptor in the SN, not striatum, augment DA signaling against TH loss to mitigate hypokinesia.

Highlights

–Despite >90% TH and DA loss in striatum, open-field locomotor activity did not decrease

–Early after lesion, DA and TH loss in striatum exceeded 90%. In contrast, DA loss did not occur despite 60% TH loss in substantia nigra (SN).

–TH loss was progressive in the SN, with loss also spreading contralateral to lesion.

–Loss of TH protein in SN preceded cell loss ipsilateral and contralateral to lesion, indicating first stages of nigrostriatal neuron loss begin with loss of TH protein loss.

–TH phosphorylation at ser31 in SN was associated with less, if any, DA loss compared to TH protein loss.

–TH phosphorylation at ser40 did not change in either region and at any time during TH loss, suggesting no contribution to differences in DA loss against TH loss.

–Expression of the D1 receptor increased 2.5-fold in the SN late, but not early, after lesion, suggesting a post-synaptic receptor response to offset DA loss in SN.

–No increases in TH phosphorylation or D1 receptor expression in striatum at any time after lesion induction, indicating that compensatory mechanisms occur only in substantia nigra, but not in striatum, to delay onset of hypokinesia.
Does Inter-Protein Contact Prediction Benefit from Multi-Modal Data and Auxiliary Tasks?
Authors: Talukder Arghamitra , Yin Rujie , Sun Yuanfei , Shen Yang , You Yuning
Published: December 2022

Approaches toin silicoprediction of protein structures have been revolutionized by AlphaFold2, while those topredict interfaces between proteinsare relatively underdeveloped, owing to the overly complicated yet relatively limited data of protein–protein complexes. In short, proteins are 1D sequences of amino acids folding into 3D structures, and interact to form assemblies to function. We believe that such intricate scenarios are better modeled with additional indicative information that reflects their multi-modality nature and multi-scale functionality. To improve binary prediction of inter-protein residue-residue contacts, we propose to augment input features with multi-modal representations and to synergize the objective with auxiliary predictive tasks. (i) We first progressively add three protein modalities into models: protein sequences, sequences with evolutionary information, and structure-aware intra-protein residue contact maps. We observe thatutilizing all data modalities delivers the best prediction precision. Analysis reveals that evolutionary and structural information benefit predictions on the difficult and rigid protein complexes, respectively, assessed by the resemblance to native residue contacts in bound complex structures. (ii) We next introduce three auxiliary tasks via self-supervised pre-training (binary prediction of protein-protein interaction (PPI)) and multi-task learning (prediction of inter-protein residue–residue distances and angles). Although PPI prediction is reported to benefit from predicting inter-contacts (as causal interpretations), it is not found vice versa in our study. Similarly, the finer-grained distance and angle predictions did not appear to uniformly improve contact prediction either. This again reflects the high complexity of protein–protein complex data, for whichdesigning and incorporating synergistic auxiliary tasks remains challenging.
SARS-CoV-2 Antibody response to the Sputnik Vaccine in previous infected Patients and non-infected one
Authors: Abdulsammad Mohamed , Ebrahim Fawzi , Tabal Salah , Bashir Sedigh , Aburgiga Ashraf , Milad Mohamed , Bareem Mohamed
Published: December 2022

At the begging of 2020 saw the development and trials of vaccines against Covid-19 at an unprecedented pace. The first half of 2021 has seen vaccine rollout in many countries, on the other hand, Immunity to covid-19 has exhibited to minimize the risk of having a severe infection and initiate an excellent degree against the disease. This study focuses on the comparison of Anti-Spike IgG antibodies among vaccinated people with or without previous exposure to the coronavirus. To determine whether a single dose of sputnik V can produce significant antibody titer amongst previously infected cases and design vaccine dosage regimens accordingly. This study was performed at Libyan biotechnology research Centre from August 2021 to December 2021. Blood samples were collected from 1811 adult males and females vaccinated with and without a history of exposure to covid-19. Previously infected individuals’ record was noted separately. Samples were immediately analyzed by Beckman Unicel Dxl 600, Access immunoassay system. Data were analyzed using GraphPad Prism 9 Software. A P-value >0.5 was not significant. The Majority of candidates 60% of the total samples were males and on analysis, it was found that 72% of patients were seropositive, on the other hand, individuals who vaccinated and have naïve antibodies from the previous infection showed slightly higher immunological response rather than vaccinated patients without previous infection and this finding can help the policymakers to design a single-dose vaccine regimen for the former category.
Whole-genome sequencing identifies variants inANK1,LRRN1,HAS1,and other genes and regulatory regions for stroke in type 1 diabetes
Authors: Antikainen Anni A. , Haukka Jani K. , Kumar Anmol , Syreeni Anna , Hägg-Holmberg Stefanie , Ylinen Anni , Kilpeläinen Elina , Kytölä Anastasia , Palotie Aarno , Putaala Jukka , Thorn Lena M. , Harjutsalo Valma , Groop Per-Henrik , Sandholm Niina
Published: December 2022

Aims

Individuals with type 1 diabetes (T1D) carry a markedly increased risk of stroke, with distinct clinical and neuroimaging characteristics as compared to those without diabetes. Using whole-genome sequencing (WGS) and whole-exome sequencing (WES), we aimed to find rare and low-frequency genomic variants associated with stroke in T1D. The lead findings were followed up in various datasets to replicate the findings and to assess their specificity to diabetes.

Methods and Results

We studied stroke genetics in 1,051 individuals with T1D using WGS or WES. We analysed the genome with single-variant analyses, gene aggregate analyses, and aggregate analyses on genomic windows, enhancers and promoters. Furthermore, we attempted replication in T1D using a genome-wide association study (N=3,945) and direct genotyping (N=3,600), and in the general population from the FinnGen project and UK Biobank summary statistics. We identified a rare missense mutation onSREBF1associated with hemorrhagic stroke (rs114001633, p.Pro227Leu,p-value=8.96×10-9), which further replicated in T1D. Using gene aggregate analysis with protein altering or protein truncating variants, we identified exome-wide significant genes:ANK1andLRRN1displayed replication evidence in T1D, whileLRRN1,HAS1andUACAreplicated in the general population (UK Biobank). Furthermore, we performed sliding-window analyses and identified 14 genome-wide significant windows for stroke on 4q33-34.1, of which two replicated in T1D, and a suggestive genomic window onLINC01500, which replicated in T1D. Finally, with the regulatory region aggregate analyses, we identified a stroke-associatedTRPM2-ASpromoter (p-value=5.78×10-6), which we validated with an in vitro cell-based assay.TRPM2has been previously linked to ischemic stroke.

Conclusions

Here, we report the first genome-wide analysis on stroke in individuals with diabetes. We identified multiple stroke risk loci with evidence of replication: 4q33-34.1,SREBF1, andANK1for stroke in T1D; andHAS1,UACA,LRRN1,LINC01500, andTRPM2-ASpromoter for stroke potentially generalizable to the non-diabetic population.
Severe acute infection and chronic pulmonary disease are risk factors for developing post-COVID-19 conditions
Authors: Ghosh Pritha , Niesen Michiel J.M. , Pawlowski Colin , Bandi Hari , Yoo Unice , Lenehan Patrick J. , Kumar M. Praveen , Nadig Mihika , Ross Jason , Ardhanari Sankar , O’Horo John C. , Venkatakrishnan AJ , Rosen Clifford J. , Telenti Amalio , Hurt Ryan T. , Soundararajan Venky
Published: December 2022

Post-COVID-19 conditions, also known as “long COVID”, has significantly impacted the lives of many individuals, but the risk factors for this condition are poorly understood. In this study, we performed a retrospective EHR analysis of 89,843 individuals at a multi-state health system in the United States with PCR-confirmed COVID-19, including 1,086 patients diagnosed with long COVID and 1,086 matched controls not diagnosed with long COVID. For these two cohorts, we evaluated a wide range of clinical covariates, including laboratory tests, medication orders, phenotypes recorded in the clinical notes, and outcomes. We found that chronic pulmonary disease (CPD) was significantly more common as a pre-existing condition for the long COVID cohort than the control cohort (odds ratio: 1.9, 95% CI: [1.5, 2.6]). Additionally, long-COVID patients were more likely to have a history of migraine (odds ratio: 2.2, 95% CI: [1.6, 3.1]) and fibromyalgia (odds ratio: 2.3, 95% CI: [1.3, 3.8]). During the acute infection phase, the following lab measurements were abnormal in the long COVID cohort: high triglycerides (meanlongCOVID: 278.5 mg/dL vs. meancontrol: 141.4 mg/dL), low HDL cholesterol levels (meanlongCOVID: 38.4 mg/dL vs. meancontrol: 52.5 mg/dL), and high neutrophil-lymphocyte ratio (meanlongCOVID: 10.7 vs. meancontrol: 7.2). The hospitalization rate during the acute infection phase was also higher in the long COVID cohort compared to the control cohort (ratelongCOVID: 5% vs. ratecontrol: 1%). Overall, this study suggests that the severity of acute infection and a history of CPD, migraine, CFS, or fibromyalgia may be risk factors for long COVID symptoms. Our findings motivate clinical studies to evaluate whether suppressing acute disease severity proactively, especially in patients at high risk, can reduce incidence of long COVID.
Trends in patients’ willingness for cancer care and the number of registered cancer cases in Ehime Prefecture during the COVID-19 pandemic
Authors: Teramoto Norihiro , Yamashita Natsumi , Ohira Yutsuko
Published: December 2022

Background

The COVID-19 pandemic has reduced diagnosed cancer cases worldwide. This study aimed to elucidate the recovery of cancer care from the COVID-19 pandemic in Ehime Prefecture, Japan.

Methods

This study collected data from the hospital-based cancer registry (HBCR) as well as the number of outpatients, medical information provision fee payments (MIP2), and second opinion patients (SOP) from the Council of Ehime Cancer Care Hospitals (ECCH). Then cancer care and patient requests for hospital transfers before and during the COVID-19 pandemic were analyzed.

Result

The HBCR from the ECCH comprises >80% of cancer cases in Ehime Prefecture. In 2020, the numbers of all registered cases, first-line treatment cases, and cases detected by cancer screening in the HBCR decreased from those in 2018–2019. In 2021, they increased to almost the same levels as those in 2020. In contrast, the number of registered patients that changed hospitals (hospital-change cases) after first-line treatments, patients who lived outside the metropolitan area of Ehime but registered in metropolitan hospitals, MIP2, and SOP remained low in 2021 after decreasing in 2020. Furthermore, using the Wilcoxon rank sum test, the monthly numbers of hospital-change cases, MIP2, and SOP were significantly smaller in 2021 than in 2018–2019.

Conclusion

The assessed indicators suggest that the willingness of cancer patients to improve and/or advance cancer care had not returned to pre-pandemic levels by 2021. Hence, psychological measures in society and support for patient caregivers are necessary to prevent self-restraint in patients receiving cancer care.

Mini-abstract

The number of registered cases in hospital-based cancer registries returned to pre-COVID-19 levels by 2021, cancer patients’ willingness to further their care did not return to pre-pandemic levels.
G2019S selective LRRK2 kinase inhibitor abrogates mitochondrial DNA damage
Authors: Pena Nicholas , Gonzalez-Hunt Claudia P. , Qi Rui , Barlow Carrolee , Shanks Natalie F. , Carlisle Holly J. , Sanders Laurie H.
Published: December 2022

Pathogenic mutations inLRRK2cause Parkinson’s disease (PD). The G2019S variant is the most common, which results in abnormally high kinase activity. Compounds that target LRRK2 kinase activity are currently being developed and tested in clinical trials. We recently found that G2019S LRRK2 causes mitochondrial DNA (mtDNA) damage and treatment with multiple classes of LRRK2 kinase inhibitors at concentrations associated with dephosphorylation of LRRK2 reversed mtDNA damage to healthy control levels. Because maintaining the normal function of LRRK2 in heterozygous G2019SLRRK2carriers while specifically targeting the G2019S LRRK2 activity could have an advantageous safety profile, we explored the efficacy of a G2019S mutant selective LRRK2 inhibitor to reverse mtDNA damage in G2019S LRRK2 models and patient cells relative to non-selective LRRK2 inhibitors. Potency of LRRK2 kinase inhibition by EB-42168, a G2019S mutant LRRK2 kinase inhibitor, and MLi-2, a nonselective inhibitor, was determined by measuring phosphorylation of LRRK2 at Ser935 and/or Ser1292 using quantitative western immunoblot analysis. The Mito DNADXassay, a novel system that allows for the accurate real-time quantification of mtDNA damage in a 96-well platform, was performed in parallel. We confirmed that EB-42168 selectively inhibits LRRK2 phosphorylation on G2019S LRRK2 relative to wild-type LRRK2. On the other hand, MLi-2 was equipotent for wild-type and G2019S LRRK2. Acute treatment with EB-42168 inhibited LRRK2 phosphorylation and also restored mtDNA damage to healthy control levels. Precision medicine is a common approach in modern day cancer research that is not yet routinely applied to neurodegenerative diseases. Abrogation of mtDNA damage with mutant selective tool inhibitor EB-42168 demonstrates the promise of a precision medicine approach for LRRK2 G2019S PD. Levels of mtDNA damage may serve as a potential pharmacodynamic biomarker of altered kinase activity that could be useful for small molecule development and clinical trials.
Moving and static faces, bodies, objects and scenes are differentially represented across the three visual pathways
Authors: Küçük Emel , Foxwell Matthew , Kaiser Daniel , Pitcher David
Published: December 2022

Models of human cortex propose the existence of neuroanatomical pathways specialised for different behavioural functions. These pathways include a ventral pathway for object recognition, a dorsal pathway for performing visually guided physical actions and a recently proposed third pathway for social perception. In the current study we tested the hypothesis that different categories of moving stimuli are differentially processed across the dorsal and third pathways according to their behavioural implications. Human participants (N=30) were scanned with functional magnetic resonance imaging (fMRI) while viewing moving and static stimuli from five categories (faces, bodies, scenes, objects, and scrambled objects). Whole brain group analyses showed that moving bodies and moving objects increased neural responses in bilateral V5/MT+ and intraparietal sulcus (IPS), parts of the dorsal pathway. In addition, moving faces and moving bodies increased neural responses in bilateral V5/MT+ and the right posterior superior temporal sulcus (rpSTS), parts of the third pathway. This pattern of results was also supported by a separate region of interest (ROI) analysis showing that moving stimuli produced more robust neural responses for all visual object categories, particularly in lateral and dorsal brain areas. Our results suggest that dynamic naturalistic stimuli from different categories are routed along specific visual pathways that process their unique behavioural implications.