bluuebunny/crossref_metadata_2025 huggingface dataset:
Subcutaneous Leiomyosarcoma
Authors: Bresler Scott C. , Gosnell Hailey L. , Ko Jennifer S. , Angeles Christina V. , Ronen Shira , Billings Steven D. , Patel Rajiv M.
Published: September 2023

Subcutaneous leiomyosarcoma (LMS) is a rare, poorly understood variant. The current literature on the subject is sparse, consisting of isolated case reports and small clinicopathologic studies compromised by the inclusion of both its more common and indolent counterpart, cutaneous LMS (atypical intradermal smooth muscle neoplasm), as well as highly aggressive deep-seated tumors. Thus, precise clinicopathologic characterization is limited. Cases of subcutaneous LMS reviewed at the University of Michigan and Cleveland Clinic from 1994 to 2022 were included in this retrospective study. A total of 39 cases were identified. The mean age was 61 years, and the cohort was predominantly male (23/39; 59%). Tumors averaged 4.2 cm and most commonly arose on the extremities (32/39; 82%). The majority (38/39; 97%) were diagnosed at an early pathologic stage (pT1 or pT2). Histopathologically, most tumors were well-circumscribed and were assigned a Fédération Nationale des Centers de Lutte Contre le Cancer grade of either 1 or 2 (24/39; 62%). The majority (22/39; 56%) appeared to arise in association with a blood vessel. Of the 36 cases with accessible clinical data and follow-up (mean 34 mo, range 0 to 94 mo), 12 (33%) were noted to have metastasized, with the lung representing the most common anatomic location. One case recurred locally. Six of 36 patients (17%) died from the disease at an average of 47 months after diagnosis (range 16 to 94 mo). Metastasis or death from disease was significantly associated with the Fédération Nationale des Centers de Lutte Contre le Cancer grade (P=0.0015), the presence of necrosis (P=0.032), tumor size (P=0.049), and AJCC tumor stage (P=0.036). These data demonstrate that subcutaneous LMS are more aggressive than dermal-based tumors and have a prognosis akin to that of deep-seated LMS.
Standardization and Visualization of the Surgical Time-Out
Authors: Levy Brittany E. , Wilt Wesley S. , Lantz Sherry , Ballert Erik , Harris Andrew
Published: September 2023

Introduction

The time-out (TO) can prevent adverse events but is subject to TO engagement. We hypothesize transforming the TO to an auditable, active process will improve compliance and engagement.

Methods

The passive nature of the current TO was identified as a potential safety issue on staff patient safety culture surveys. Subsequently, the Time Out Engagement and Standardization quality improvement initiative was developed and included a whiteboard checklist to be used in the operating room. As a baseline, 11 TOs were audited concerning engagement and content. Key stakeholders were engaged to determine potential interventions. A TO consisting of 15 elements using a TO whiteboard checklist with role-specific objectives was developed. Plan, Do, Study, Act cycles commenced. After implementation, 17 TOs were audited based on engagement and content.

Results

Before intervention, engagement varied with nurse participating in 100% compared with anesthesia provider or surgeon participating in 18%. No TO included all 15 elements and only 13% of elements included in all TOs. After implementation of Time Out Engagement and Standardization, anesthesia and surgeon who participated increased to 100% and 76.5%, respectively (P < 0.0001, P = 0.006). The 15 standardized elements of the TO were discussed in 90% of cases. Overall, preintervention 88 elements (57.1%) were completed across all TOs, while postintervention 243 elements (98.8%) were completed (P < 0.001).

Conclusions

We identified a need for increased engagement of the TO based on staff concerns, which were verified through auditing. Implementation of a team-driven intervention and 3 rapid Plan, Do, Study, Act cycles led to measurable improvement of the surgical TO.
Duration of antifungal treatment in mold infection: when is enough?
Authors: Portillo Vera , Neofytos Dionysios
Published: September 2023

Purpose of review

Although invasive mold infections (IMI) are a major complication in high-risk populations, treatment duration has not yet been well defined.

Recent findings

Guidelines suggest documenting clinical/radiological resolution and immunological recovery before stopping antifungal treatment, after a minimum duration of treatment of 3 months for invasive pulmonary aspergillosis, while longer (up to 6 months) duration is proposed for the treatment of invasive mucormycosis. However, data on and definitions of clinical/radiological resolution and immune recovery remain scarce. Limited real-life data suggest that often much longer courses of treatment are given, generally in the context of continuous immunosuppression, occasionally defined as secondary prophylaxis. However, clearcut definition and distinction of secondary prophylaxis from antifungal treatment remain to be defined.

Decisions to stop antifungal treatment are based on poorly defined treatment responses and immune reconstitution and experts’ opinions. More evidence is needed to determine the optimal duration of treatment of IMI. Well designed, easy to use, and realistic algorithms to help clinicians decide when to stop antifungal treatment are urgently needed.
Thermoablative Treatment of De Novo Tumor in Kidney Allograft
Authors: Bodard Sylvain , Boudhabhay Idris , Dariane Charles , Delavaud Christophe , Guinebert Sylvain , Guétat Pierre , Mejean Arnaud , Timsit Marc-Olivier , Anglicheau Dany , Joly Dominique , Hélénon Olivier , Correas Jean-Michel
Published: September 2023

Background.

The overall cancer risk increases in transplant patients, including in kidney allografts. This study aimed to analyze the outcome of patients with kidney allograft malignant tumors who underwent percutaneous thermal ablation.

Methods.

We included 26 renal allograft tumors, including 7 clear-cell renal cell carcinoma (RCCs), 16 papillary RCCs, 1 clear-cell papillary RCC, and 2 tubulocystic RCCs, treated in 19 ablation sessions. Outcomes of thermal ablation therapy were assessed, including technical success, adverse events, local tumor progression, development of metastases, survival after thermal ablation, and changes in renal function.

Results.

Success rate was achieved in all ablation sessions (primary success rate: 96%; secondary success rate: 100%). No adverse events were observed in grades 3, 4, or 5. The median follow-up period was of 34 mo (15–69 mo). Two patients died during follow-up from a cause independent of renal cancer. The median decrease in estimated glomerular filtration rate 1 y after procedure was −4 (interquartile range, −7 to 0) mL/min/1.73 m2. One patient returned to dialysis within the year of the procedure.

Conclusions.

Percutaneous thermal ablation shows convincing results for treating malignant renal graft tumors and should be a useful treatment option. The shorter hospitalization time, the advantage of avoiding a potentially challenging dissection of the transplant, and the excellent preservation of allograft function appear encouraging to extend this indication.
Coupling of coastal activity with tidal cycles is stronger in tool-using capuchins (
Cebus capucinus imitator
)
Authors: Goldsborough Zoë , Crofoot Margaret C. , Alavi Shauhin E. , Del Rosario-Vargas Evelyn , Garza Sylvia F. , Tiedeman Kate , Barrett Brendan J.
Published: September 2023

Terrestrial mammals exploiting coastal resources must cope with the challenge that resource availability and accessibility fluctuate with tidal cycles. Tool use can improve foraging efficiency and provide access to structurally protected resources that are otherwise unavailable (e.g. molluscs and fruits). To understand how variable accessibility of valuable resources shapes behavioural patterns, and whether tool use aids in the efficient exploitation of intertidal resources, we compared the relationship between tidal cycles and activity patterns of tool-using versus non-tool-using groups of white-faced capuchin monkeys on Jicarón Island in Coiba National Park, Panama. Although tool use on Jicarón is localized to a small stretch of coast (approx. 1 km), all coastal groups forage on intertidal resources. Using more than 5 years of camera trap data at varying distances from the coast, we found that capuchins on Jicarón showed increased coastal activity during specific parts of the tidal cycle, and that this relationship differed between tool-using and non-tool-using groups, as well as between seasons. Activity patterns of tool-using capuchins were more strongly and consistently tied to tidal cycles compared with non-tool-users, indicating that tool use might allow for more efficient exploitation of tidal resources. Our findings highlight the potential of tool use to aid niche expansion.
Interindividual differences in Pavlovian influence on learning are consistent
Authors: Saeedpour Sepehr , Hossein Mostafa Minadari , Deroy Ophelia , Bahrami Bahador
Published: September 2023

Pavlovian influences impair instrumental learning. It is easier to learn to approach reward-predictive signals and avoid punishment-predictive cues than their contrary. Whether the interindividual variability in this Pavlovian influence is consistent across time has been examined by a number of recent studies and met with mixed results. Here we introduce an open-source, web-based instance of a well-established Go–NoGo paradigm for measuring Pavlovian influence. We closely replicated the previous laboratory-based results. Moreover, the interindividual differences in Pavlovian influence were consistent across a two-week time window at the level of (i) raw measures of learning (i.e. performance accuracy), (ii) linear, descriptive estimates of Pavlovian bias (test–retest reliability: 0.40), and (iii) parameters obtained from reinforcement learning model fitting and model selection (test–retest reliability: 0.25). Nonetheless, the correlations reported here are still lower than the standards (i.e. 0.7) employed in psychometrics and self-reported measures. Our results provide support for trusting Pavlovian bias as a relatively stable individual characteristic and for using its measure in the computational understanding of human mental health.
The relationship between body dissatisfaction and attentional bias to thin bodies in Malaysian Chinese and White Australian women: a dot probe study
Authors: House T. , Wong H. K. , Samuel N. W. , Stephen I. D. , Brooks K. R. , Bould H. , Attwood A. S. , Penton-Voak I. S.
Published: September 2023

Studies suggest that an attentional bias to thin bodies is common among those with high levels of body dissatisfaction, which is a risk factor for, and symptom of, various eating disorders. However, these studies have predominantly been conducted in Western countries with body stimuli involving images of White people. In a preregistered study, we recruited 150 Malaysian Chinese women and 150 White Australian women for a study using standardized images of East Asian and White Australian bodies. To measure attentional bias to thin bodies, participants completed a dot probe task which presented images of women who self-identified their ethnicity as East Asian or as White Australian. Contrary to previous findings, we found no evidence for an association between body dissatisfaction and attentional bias to thin bodies. This lack of association was not affected by participant ethnicity (Malaysian Chinese versus White Australian) or ethnic congruency between participants and body stimuli (own-ethnicity versus other-ethnicity). However, the internal consistency of the dot probe task was poor. These results suggest that either the relationship between body dissatisfaction and attentional bias to thin bodies is not robust, or the dot probe task may not be a reliable measure of attentional bias to body size.
Principal component and linear discriminant analyses for the classification of hominoid primate specimens based on bone shape data
Authors: Vanhoof Marie J. M. , Croquet Balder , De Groote Isabelle , Vereecke Evie E.
Published: September 2023

In this study, we tested the hypothesis that machine learning methods can accurately classify extant primates based on triquetrum shape data. We then used this classification tool to observe the affinities between extant primates and fossil hominoids. We assessed the discrimination accuracy for an unsupervised and supervised learning pipeline, i.e. with principal component analysis (PCA) and linear discriminant analysis (LDA) feature extraction, when tasked with the classification of extant primates. The trained algorithm is used to classify a sample of known fossil hominoids. For the visualization, PCA and uniform manifold approximation and projection (UMAP) are used. The results show that the discriminant function correctly classified the extant specimens with an F1-score of 0.90 for both PCA and LDA. In addition, the classification of fossil hominoids reflects taxonomy and locomotor behaviour reported in literature. This classification based on shape data using PCA and LDA is a powerful tool that can discriminate between the triquetrum shape of extant primates with high accuracy and quantitatively compare fossil and extant morphology. It can be used to support taxonomic differentiation and aid the further interpretation of fossil remains. Further testing is necessary by including other bones and more species and specimens per species extinct primates.
Chryseobacterium luquanense sp. nov., a casein-hydrolysing bacterium from the Jiaozi Mountain in Yunnan, PR China
Authors: Zhu Guo-Xing , Chen Xiu , Wu Ya-Jie , Wang Hai-Long , Jiao Yu , Liu Zi-Chao , Zhang Yue , Tang Shu-Kun , Kong De-Jun , Cao Yan-Ru
Published: September 2023

Strain KC 927T was isolated during an investigation of the soil bacteria diversity on Jiaozi Mountain, central Yunnan, Southwest China. The strain was Gram-stain-negative, rod-shaped, non-motile, oxidase-negative, catalase-positive and aerobic. Results of 16S rRNA gene alignment and phylogenetic analysis indicated that strain KC 927T was a member of the genus

Chryseobacterium

and closely related to

Chryseobacterium caseinilyticum

GCR10T (98.4%),

Chryseobacterium piscicola

DSM 21068T (98.3 %) and ‘

Chryseobacterium formosus

’ CCTCC AB 2015118T (97.9 %). With a genome size of 4 348 708 bp, strain KC 927T had 33.5 mol% DNA G+C content and contained 4012 protein-coding genes and 77 RNA genes. The average nucleotide identity and digital DNA–DNA hybridization values between strain KC 927T and

C. caseinilyticum

GCR10T,

C. piscicola

DSM 21068T and ‘

C. formosus

’ CCTCC AB 2015118T were 80.1, 79.6 and 90.7 %, and 25.5, 23.6 and 42.0 %, respectively. The main polar lipid of strain KC 927T was phosphatidylethanolamine and the respiratory quinone was MK-6. The major fatty acids (≥10 %) were iso-C15 : 0, iso-C17 : 1
 ω9c and iso-C17 : 0 3-OH. Evidence from phenotypic, phylogenetic and chemotaxonomic analyses support that strain KC 927T represents a new species of the genus

Chryseobacterium

, for which the name Chryseobacterium luquanense sp. nov. is proposed. The type strain is KC 927T (=CGMCC 1.18760T=JCM 35707T).
Cold Storage and Cryopreservation Methods For Spermatozoa of the sea urchinLytechinus pictus
Authors: Vacquier Victor D. , Hamdoun Amro
Published: September 2023

Sea urchins have contributed greatly to knowledge of fertilization, embryogenesis and cell biology. However, until now, they have not been a genetic model organism because of the long generation times of commonly used species, and lack of tools for husbandry and genetic manipulation. We recently establishedLytechinus pictus, as a multigenerational sea urchin model, because of its relatively short generation time of 4-6 months and ease of laboratory culture. To take full advantage of this new multigenerational species, methods are needed to biobank and share mutantL. pictussperm. Here, we describe a new extender based on sperm ion physiology before spawning of sperm into seawater. This extender maintains sperm capable of fertilization for at least 5-10 weeks when stored at 0 °C. We use the extender, and the cryoprotectant dimethyl sulfoxide (DMSO), to cryopreserve sperm of bothL. pictus, and the widely used sea urchin,Strongylocentrotus purpuratus. The simple methods we describe work well for both species, achieving > 90% development and producing larvae that successfully undergo metamorphosis to juvenile sea urchins. Sperm of these two species can be frozen and thawed at least twice and still give rise to larvae that undergo metamorphosis.

Main Points

Sperm can maintain fertilizing capacityex vivofor 5-10 weeks when stored at 0°C.

When freezing in liquid nitrogen no stepwise addition of cryoprotectant, or stepwise drop in temperature are required.

A standard fertilization assay is presented to score cleavage stage sea urchin embryos produced by cryopreserved sperm.

Sperm frozen and thawed more than once can produce larvae.
Prediction of body weight from body volume of Savanna goats in Limpopo province, South Africa
Authors: Mathapo Madumetja Cyril , Tyasi Thobela Louis , Mugwabana Thinawanga Joseph
Published: September 2023

Savanna goats is one of the South African commercial meat breeds. This study was conducted to predict body weight from body volume (BV), heart girth (HG) and body length (BL). A total of 139 savanna goats of the age between 1 and 5 years old of different sex (male and female) were used in the study for collection of body weight, body length and heart girth. The animals were kept under semi-intensive production system, where they were supplemented in the afternoon. Body volume was derived using cylinder volume formula from body length and heart girth as the components of model. R-studio software was employed for Pearson correlation matrix to assess the association between body weight, body length, heart girth and body volume. Simple linear regression was used to establish model to predict body weight. Pearson correlation results indicated that BW had a highly statistical significant (p<0.01) correlation with HG (r = 0.90), BV (r = 0.84) and BL (r = 0.66), respectively. Regression model findings indicated that HG had highest coefficient of determination (R2= 0.81) and lowest mean square error (MSE = 24.85), and BV indicated highest coefficient of determination (R2= 0.76) and low mean square error of (MSE = 35.07) while BL indicated lowest coefficient determination of (R2= 0.45) and high mean square error (MSE = 70.80). In conclusion, correlation result suggests that by improving HG, BV and BL will result in improving BW of Savanna goats. Simple linear regression suggest that HG and BV can be used to estimate BW of Savanna goats.
Documented Goals of Care Conversations with Hospitalized Patients after Severe Stroke
Authors: Comer Amber R. , Bartlett Stephanie , Holloway Robert , Creutzfeldt Claire J. , Williams Linda S. , Slaven James E. , D’Cruz Lynn , Endris Katlyn , Marchand McKenzie , Zepeda Isabel , Toor Sumeet , Waite Carly , Jawed Areeba , Torke Alexia M.
Published: September 2023

Documented Goals of Care Conversations with Hospitalized Patients after Severe Stroke

Background

Identifying goals of care is important for patients suffering severe ischemic stroke (SIS) and their caregivers to ensure patient- and family-centered treatment decisions. This study sought to determine the prevalence and patient predictors associated with having a documented goals-of-care conversation (dGOCC) after SIS.

Methods

We reviewed the medical charts of all patients with National Institutes of Health Stroke Scale (NIHSS) ≥10 admitted to four hospitals in the Midwestern US. In addition to sociodemographic and clinical characteristics, we searched for dGOCC during the acute stroke hospitalization, defined as any documented conversation or meeting that addressed one or more of the following domains: prognostic information, treatment plan, patient preferences and values, quality of life, or establishing goals. We determined prevalence, frequency, timing, and content of dGOCC’s. Additionally, we obtained information on treatment utilization and outcomes.

Results

Among 1297 patients, 26.5% (n=344) had at least one dGOCC. Treatment plan was the most discussed domain (n=264, 20% of all patients) and was the most common first dGOCC (n=207, 60% of first conversations). Median day for first dGOCC was on hospital day zero. Patient preferences, values, and goals were documented in 112 (8.6%) of all patients’ charts and quality of life conversations were documented in only 61 (4.7%) charts. In multivariate analysis, having a NIHSS ≥21 (OR 1.46, p-value.01) was associated with having a dGOCC.

Conclusion

After severe stroke, most patients do not have a dGOCC, despite the important decisions that often arise about treatment and rehabilitation. Documentation of patient preferences, values and goals are even rarer. This suggests missed opportunities for high quality decision making informed by patient goals to improve person centered care.
The paradox of plant preference: the malaria vectorsAnopheles gambiaeandAnopheles coluzziiselect suboptimal food sources for their survival and reproduction
Authors: Paré Prisca S. L. , Hien Domonbabele F. D. S. , Youba Mariam , Yerbanga Rakiswendé S. , Cohuet Anna , Gouagna Louis-Clément , Diabaté Abdoulaye , Ignell Rickard , Dabiré Roch K. , Gnankiné Olivier , Lefèvre Thierry
Published: September 2023

Anopheles gambiae s.l.mosquitoes, the primary malaria vectors in sub-Saharan Africa, exhibit selectivity among plant species as potential food sources. However, it remains unclear if their preference aligns with optimal nutrient intake and survival. Following an extensive screening of the effects of 31 plant species onAn. coluzziiin Burkina Faso, we selected three species for their contrasting effects on mosquito survival, namelyIxora coccinea, Caesalpinia pulcherrima and Combretum indicum. We assessed the sugar content of these plants and their impact on mosquito fructose-positivity, survival, and insemination rate, usingAnopheles coluzziiandAnopheles gambiae, and with glucose 5% and water as controls. Plants displayed varying sugar content and differentially affected the survival, sugar intake and insemination rate of mosquitoes. All three plants were more attractive to mosquitoes than controls, withAn. gambiaebeing more responsive thanAn. coluzzii. Notably,C. indicumwas the most attractive but had the lowest sugar content and offered the lowest survival, insemination rate, and fructose positivity. Our findings unveil a performance-preference mismatch inAn. coluzziiandAn. gambiaeregarding plant food sources. Several possible reasons for this negative correlation between performance and preference are discussed.
Cohesin organizes 3D DNA contacts surrounding active enhancers inC. elegans
Authors: Kim Jun , Wang Haoyu , Ercan Sevinç
Published: September 2023

In mammals, cohesin and CTCF organize the 3D genome into topologically associated domains (TADs) to regulate communication betweencis-regulatory elements. Many organisms, includingS. cerevisiae,C. elegans, andA. thalianacontain cohesin but lack CTCF. Here, we usedC. elegansto investigate the function of cohesin in 3D genome organization in the absence of CTCF. Using Hi-C data, we observe cohesin-dependent features called “fountains”, which are also reported in zebrafish and mice. These are population average reflections of DNA loops originating from distinct genomic regions and are ∼20-40 kb inC. elegans. Hi-C analysis upon cohesin and WAPL depletion support the idea that cohesin is preferentially loaded at NIPBL occupied sites and loop extrudes in an effectively two-sided manner. ChIP-seq analyses show that cohesin translocation along the fountain trajectory depends on a fully intact complex and is extended upon WAPL-1 depletion. Hi-C contact patterns at individual fountains suggest that cohesin processivity is unequal on each side, possibly due to collision with cohesin loaded from surrounding sites. The putative cohesin loading sites are closest to active enhancers and fountain strength is associated with transcription. Compared to mammals, average processivity ofC. eleganscohesin is ∼10-fold shorter and NIPBL binding does not depend on cohesin. We propose that preferential loading and loop extrusion by cohesin is an evolutionarily conserved mechanism that regulates the 3D interactions of enhancers in animal genomes.
RATTACA: Genetic predictions in Heterogeneous Stock rats offer a new tool for genetic correlation and experimental design
Authors: Johnson Benjamin B. , Sanches Thiago M. , Okamoto Mika H. , Nguyen Khai-Min , Ortez Clara A. , Polesskaya Oksana , Palmer Abraham A.
Published: September 2023

Genetic correlations between traits are a common first step in studies identifying causal genetic pathways and mechanisms. Using this framework with inbred or selected lines, however, requires intensive labor investment through breeding and phenotyping, and is prone to confounding, as observed trait correlations do not necessarily reflect a causative genetic architecture shared between distinct populations. When drawn from a single outbred population, genetic trait predictions offer a viable alternative to experimental phenotyping and can be used to identify putative genetic correlations when samples with divergent trait predictions also diverge in a second measured trait. Here, we present a novel research paradigm and service called RATTACA, in which genotypes from Heterogenous Stock (HS) rats are used to predict trait values using linear mixed models. These predictions are used to select samples of individuals with high and low extreme trait values, facilitating (1)a priorisampling of desired trait values without oversampling across phenotypic space and (2) easy identification of putative genetic correlations between predicted and newly measured traits. We validated prediction models using four example phenotypes with measured trait values and found sufficient accuracy to distinguish extreme trait samples, even when using a small number of genome-wide variants (n = 50,000) for traits with modest heritability (h2= 0.13). Given genotypes and trait measurements available through previous research in HS rats, we propose RATTACA as a service to reliably predict more than 80 behavioral and physiological traits.
Plant-based production of diverse human milk oligosaccharides
Authors: Barnum Collin R. , Paviani Bruna , Couture Garret , Masarweh Chad , Chen Ye , Huang Yu-Ping , Mills David A. , Lebrilla Carlito B. , Barile Daniela , Yang Minliang , Shih Patrick M.
Published: September 2023

Human milk oligosaccharides (HMOs) are a diverse class of carbohydrates that aid in the health and development of infants. The vast health benefits of HMOs have made them a commercial target for microbial production; however, producing the ∼130 structurally diverse HMOs at scale has proven difficult. Here, we produce a vast diversity of HMOs by leveraging the robust carbohydrate anabolism of plants. This diversity includes high value HMOs, such as lacto-N-fucopentaose I, that have not yet been commercially produced using state-of-the-art microbial fermentative processes. HMOs produced in transgenic plants provided strong bifidogenic properties, indicating their ability to serve as a prebiotic supplement. Technoeconomic analyses demonstrate that producing HMOs in plants provides a path to the large-scale production of specific HMOs at lower prices than microbial production platforms. Our work demonstrates the promise in leveraging plants for the cheap and sustainable production of HMOs.
Expanding the toolbox for phycobiliprotein assembly: phycoerythrobilin biosynthesis inSynechocystis
Authors: Heck Steffen , Sommer Frederik , Zehner Susanne , Schroda Michael , Gehringer Michelle M. , Frankenberg-Dinkel Nicole
Published: September 2023

Phycobiliproteins (PBPs) play a vital role in light harvesting by cyanobacteria, which enables efficient utilization of photon energy for oxygenic photosynthesis. The PBPs carry phycobilins, open-chain tetrapyrrole chromophores derived from heme. The structure and chromophore composition of PBPs is dependent on the organism’s ecological niche. In cyanobacteria, these holo-proteins typically form large, macromolecular antenna complexes called phycobilisomes (PBSs). The PBS ofSynechocystissp. PCC 6803 (hereafterSynechocystis) consists of allophycocyanin (APC) and phycocyanin (PC), which exclusively harbor phycocyanobilin (PCB) as a chromophore. Investigations into heterologous PBP biosynthesis inE. colihave proven limiting with respect to PBP assembly and their functional characterization. Consequently, we wanted to engineer a platform for the investigation of heterologously produced PBPs, focusing on unusual, phycoerythrobilin (PEB)-containing light-harvesting proteins called phycoerythrins (PEs) inSynechocystis. As a first step, a gene encoding for the synthesis of the natural cyanobacterial chromophore, PEB, was introduced intoSynechocystis. We provide spectroscopic evidence for heterologous PEB formation and show covalent attachment of PEB to the α-subunit of PC, CpcA, by HPLC and LC-MS/MS analyses. Fluorescence microscopy and PBS isolation demonstrate a cellular dispersal of PBPs with modified phycobilin content. However, these modifications have minor effects on physiological responses, as demonstrated by growth rates, oxygen evolution, nutrient accumulation, and PBP content analyses. As a result,Synechocystisdemonstrates the capacity to efficiently manage PEB biosynthesis and therefore reflects a promising platform for both biochemical and physiological investigations of foreign and unusual PEs.
Optimal Decoding of Neural Dynamics Occurs at Mesoscale Spatial and Temporal Resolutions
Authors: Samiei Toktam , Zou Zhuowen , Imani Mohsen , Nozari Erfan
Published: September 2023

Introduction

Understanding the neural code has been one of the central aims of neuroscience research for decades. Spikes are commonly referred to as the units of information transfer, but multi-unit activity (MUA) recordings are routinely analyzed in aggregate forms such as binned spike counts, peri-stimulus time histograms, firing rates, or population codes. Various forms of averaging also occur in the brain, from the spatial averaging of spikes within dendritic trees to their temporal averaging through synaptic dynamics. However, how these forms of averaging are related to each other or to the spatial and temporal units of information representation within the neural code has remained poorly understood.

Materials and Methods

In this work we developed NeuroPixelHD, a symbolic hyperdimensional model of MUA, and used it to decode the spatial location and identity of static images shown ton= 9 mice in the Allen Institute Visual Coding - NeuroPixels dataset from large-scale MUA recordings. We parametrically varied the spatial and temporal resolutions of the MUA data provided to the model, and compared its resulting decoding accuracy.

Results

For almost all subjects, we found 125ms temporal resolution to maximize decoding accuracy for both the spatial location of Gabor patches (81 classes for patches presented over a 9x9 grid) as well as the identity of natural images (118 classes corresponding to 118 images). The optimal spatial resolution was more heterogeneous among subjects, but was still found at either of two mesoscale levels in nearly all cases: the area level, where the spiking activity of neurons within each brain area are combined, and the population level, where the former are aggregated into two variables corresponding to fast spiking (putatively inhibitory) and regular spiking (putatively excitatory) neurons, respectively.

Discussion

Our findings corroborate existing empirical practices of spatiotemporal binning and averaging in MUA data analysis, and provide a rigorous computational framework for optimizing the level of such aggregations. Our findings can also synthesize these empirical practices with existing knowledge of the various sources of biological averaging in the brain into a new theory of neural information processing in which theunit of informationvaries dynamically based on neuronal signal and noise correlations across space and time.
Glutamylation of Npm2 and Nap1 acidic disordered regions increases DNA charge mimicry to enhance chaperone efficiency
Authors: Lorton Benjamin M. , Warren Christopher , Ilyas Humaira , Nandigrami Prithviraj , Hegde Subray , Cahill Sean , Lehman Stephanie M , Shabanowitz Jeffrey , Hunt Donald F. , Fiser Andras , Cowburn David , Shechter David
Published: September 2023

Histone chaperones–structurally diverse, non-catalytic proteins enriched with acidic intrinsically disordered regions (IDRs)–protect histones from spurious nucleic acid interactions and guide their deposition into and out of nucleosomes. Despite their conservation and ubiquity, the function of the chaperone acidic IDRs remains unclear. Here, we show that theXenopus laevisNpm2 and Nap1 acidic IDRs are substrates for TTLL4 (Tubulin Tyrosine Ligase Like 4)-catalyzed post-translational glutamate-glutamylation. We demonstrate that, to bind, stabilize, and deposit histones into nucleosomes, chaperone acidic IDRs function as DNA mimetics. Our biochemical, computational, and biophysical studies reveal that glutamylation of these chaperone polyelectrolyte acidic stretches functions to enhance DNA electrostatic mimicry, promoting the binding and stabilization of H2A/H2B heterodimers and facilitating nucleosome assembly. This discovery provides insights into both the previously unclear function of the acidic IDRs and the regulatory role of post-translational modifications in chromatin dynamics.
Bone marrow-derived CCR5-expressing macrophages promote venous thrombus resolution by up-regulating plasminogen activators and VEGF
Authors: Nosaka Mizuho , Ishida Yuko , Kuninaka Yumi , Ishigami Akiko , Kimura Akihiko , Taruya Akira , Tanaka Atsushi , Mukaida Naofumi , Kondo Toshikazu
Published: September 2023

Background

Deep vein thrombosis (DVT) is a common peripheral vascular disease arising from endothelial damage and can frequently result in pulmonary embolism. C-C chemokine receptor 5 (CCR5) is essentially involved in skin wound healing and pulmonary fibrosis, but the role of CCR5 still remains elusive.

Methods

Deep vein thrombus was induced by the ligation of the inferior vena cava (IVC) in wild-type (WT) mice andCcr5-/-mice, and thrombi were collected over time and various analyzes were performed.

Results

After ligation of the IVC in WT mice, a venous thrombus developed progressively until 5 days, and then resolved. Concomitantly, IVC ligation enhanced intrathrombotic gene and protein expression ofCcr5and its ligand,Ccl5, and both were expressed mainly by intrathrombotic macrophages. The same treatment ofCcr5-/-mice resulted in significantly greater thrombus mass than WT mice. Moreover, the administration of a specific CCR5 inhibitor to WT mice recapitulated similar phenotypes asCcr5-/-mice while that of CCL5 caused the opposite phenotypes. InCcr5-/-mice, the production of intrathrombotic vascular endothelial growth factor (VEGF), tissue plasminogen activator (tPA), and urokinase-type plasminogen activator (uPA) from macrophages was significantly reduced and intrathrombotic recanalization was also suppressed compared to WT mice. Moreover, CCL5 enhancedVegf, Plat,andPlaugene expression in WT-derived peritoneal macrophages by activating the ERK MAPK signaling pathway in vitro.

Conclusions

CCR5-deficient mice exhibited reduced expression ofVegf, Plat,andPlau,with concomitant attenuated neovascularization and reduced thrombus resolution. the Thus, the augmentation of the CCL5-CCR5 axis may be effective for DVT treatment by enhancing thrombolysis.
Identifying patients at risk for myasthenic crisis with hemogram and inflammation-related laboratory parameters – a pilot study
Authors: Mehnert Anne , Bershan Sivan , Kollmus-Heege Jil , Gerischer Lea , Herdick Meret Luise , Hoffmann Sarah , Lehnerer Sophie , Scheibe Franziska , Stascheit Frauke , Stein Maike , Buchan Alastair M. , Meisel Andreas , Aigner Annette , Mergenthaler Philipp
Published: September 2023

Background

Myasthenia gravis (MG) is a rare autoimmune disease characterized by fatigable weakness of the voluntary muscles and can exacerbate to life-threatening myasthenic crisis (MC), requiring intensive care treatment. Routine laboratory parameters are a cost-effective and widely available method for estimating clinical outcomes of several diseases, but so far such parameters have not been established to detect disease progression in MG.

Methods

We conducted a retrospective analysis of selected laboratory parameters related to inflammation and hemogram for MG patients with MC matched to MG patients without MC. To identify potential risk factors for MC, we applied time-varying Cox regression for time to MC, and as a sensitivity analysis generalized estimating equations logistic regression for the occurrence of MC at the next patient visit.

Results

15 of the 58 examined MG patients suffered at least one MC. There was no notable difference in the occurrence of MC by antibody status or sex. Both regression models showed that higher counts of basophils (per 0.01 units increase: HRlJ=lJ1.32, 95% CIlJ=1.02-1.70), neutrophils (per 1 unit increase: HRlJ=lJ1.40, 95% CIlJ=lJ1.14-1.72), and potentially leukocytes (per 1 unit increase: HR = 1.15, 95% CI = 0.99-1.34), and platelets (per 100 units increase: HR = 1.54, 95% CI = 0.99-2.38) may indicate increased risk for a myasthenic crisis.

Conclusion

This pilot study provides proof of concept that increased counts of basophils, neutrophils, leukocytes, and platelets may be associated with a higher risk for developing MC in patients with MG.
Sharps Injuries Among Healthcare Workers in Liberia and Ghana: A Cross-Sectional Survey
Authors: Ridge Laura Jean , Arko-Mensah John , Lambert Josh , Aziato Lydia , Zeantoe G Clinton , Duah Henry , McCullagh Marjorie
Published: September 2023

Objective

There is little data on sharps injuries among healthcare workers in West Africa, despite the region’s high rate of Hepatitis B and HIV. The purpose of this study is to investigate healthcare workers’ history of sharps injury in Liberia and Ghana.

Design

An electronic cross-sectional survey disseminated by local nursing, midwifery, physician assistant, and physician associations.

Setting

Healthcare workers in Liberia and Ghana from February to June 2022.

Participants

Participant were registered nurses, physician assistants, physicians, or midwives, and had been working in a patient care role for at least nine of the previous twelve months.

Methods

A link to the survey was texted to participants through their professional association membership lists, including nursing, midwifery, and physician assistant organizations in both Liberia and Ghana and a physician organization in Ghana only.

Results

509 participants reported an average of 1.8 injuries per year in Liberia and 1.1 in Ghana (p=<0.01). 15.1% of healthcare workers reported three or more injuries in the past year. Liberia had a higher proportion of frequently injured workers (p=<0.01). Frequently injured workers were evenly distributed across worker types.

Conclusions

Workers in this region are vulnerable to sharps injuries. A frequently injured subset of workers likely has distinctive risk factors and would benefit from further investigation and intervention.
Analysis of SARS-CoV-2 Ig seroprevalence in Northern Ireland
Authors: Greene Michelle K , Smyth Peter , English Andrew , McLaughlin Joseph , Bucholc Magda , Bailie Janice , McCarroll Julie , McDonnell Margaret , Watt Alison , Barnes George , Lynch Mark , Duffin Kevan , Duffy Gerard , Lewis Claire , James Jacqueline A , Ford Tom , O’Kane Maurice , Rai Taranjit Singh , Bjourson Anthony J , Cardwell Christopher , Elborn J Stuart , Gibson David S , Scott Christopher J
Published: September 2023

Background

With the impact of SARS-CoV-2 upon public health directly and socioeconomically, further information was required to inform policy decisions designed to limit virus spread. This study sought to contribute to serosurveillance work within Northern Ireland to track SARS-CoV-2 progression and guide health strategy.

Methods

Sera/plasma samples from clinical biochemistry laboratories were analysed for anti-SARS-CoV-2 immunoglobulins (Ig). Samples were assessed using an Elecsys anti-SARS-CoV-2 or anti-SARS-CoV-2 S ECLIA (Roche) on an automated Cobas-e-analyser. Samples were also assessed via ELISA (Euroimmun). A subset of samples assessed via Roche Elecsys anti-SARS-CoV-2 IgG assay were subsequently analysed in an ACE2 pseudoneutralisation assay using a V-PLEX SARS-CoV-2 Panel 7 for IgG and ACE2 by MesoScale Diagnostics Inc.

Results

Across three testing rounds (June-July 2020, November-December 2020 and June-July 2021 (rounds 1-3 respectively)), 4844 residual sera/plasma specimens were assayed for SARS-CoV-2 Ig. Seropositivity rates increased across the study, peaking at 11.6% during round 3. Varying trends in SARS-CoV-2 seropositivity were noted based on demographic factors. For instance, highest rates of seropositivity shifted from older to younger demographics across the study period. In round 3, alpha (B.1.1.7) variant neutralising antibodies were most frequently detected across age groups, with median concentration of anti-spike protein antibodies elevated in 50-69 year olds and anti-S1 RBD antibodies elevated in over 70s, relative to other age groups.

Conclusions

With seropositivity rates of <15% across the assessment period, it can be concluded that the significant proportion of the Northern Ireland population had not yet naturally contracted the virus by mid-2021.
Trends in Hepatitis C Virus Seroprevalence and Associated Risk Factors among MSM in Pakistan: Insights from a Community-Based Study
Authors: Tirmizi Raza , Munir Rimsha , Zaidi Nousheen
Published: September 2023

This community-based cross-sectional study investigates the seroprevalence of the Hepatitis C Virus (HCV) and its associated demographic and behavioral risk factors among the men who have sex with men (MSM) in Pakistan. The study reveals an HCV seroprevalence of 14.86%, significantly higher than global averages for the MSM population. Notably, HCV seroprevalence was associated with age, education level, self-identified sexual orientation, and self-reported HIV status. Furthermore, the study identified several risk factors positively associated with HCV seroprevalence, including sharing personal items such as razors and toothbrushes, histories of surgery, blood transfusion, dental procedures, intravenous drug use, and therapeutic injection histories. Interestingly, a lower HCV positivity rate was observed among self-reported HIV-positive individuals, contradicting previous research. The findings underscore the need for comprehensive, targeted prevention strategies tailored to the MSM population in Pakistan. Further research is warranted to validate these findings and to understand better the complex interplay of factors contributing to HCV seroprevalence in this high-risk population.
The nuclear PIWI-interacting protein Gtsf1 controls the selective degradation of small RNAs inParamecium
Authors: Charmant Olivia , Gruchota Julita , Arnaiz Olivier , Zangarelli Coralie , Bétermier Mireille , Nowak Katarzyna , Legros Véronique , Chevreux Guillaume , Nowak Jacek , Duharcourt Sandra
Published: September 2023

Ciliates undergo developmentally programmed genome elimination, in which small RNAs direct the removal of target DNA segments, including transposable elements. At each sexual generation, the development of the macronucleus (MAC) requires massive and reproducible elimination of a large proportion of the germline micronuclear (MIC) genome, leading to a highly streamlined somatic MAC genome. 25-nt long scnRNAs are produced from the entire germline MIC genome during meiosis, and this initial complex small RNA population is then transported to the maternal MAC, where selection of scnRNAs corresponding to germline (MIC)-specific sequences is thought to take place. Selected scnRNAs, loaded onto the PIWI protein Ptiwi09, guide the deposition of histone H3 post-translational modifications (H3K9me3 and H3K27me3) onto transposable elements in the developing macronucleus, ultimately triggering their specific elimination. How germline-specific MIC scnRNAs are selected remains to be determined. Here, we provide important mechanistic insights into the scnRNA selection pathway by identifying aParameciumhomolog of Gametocyte specific factor 1 (Gtsf1) as essential for the selective degradation of scnRNAs corresponding to retained somatic MAC sequences. Consistently, we also show that Gtsf1 is exclusively localized in the maternal macronucleus and associates with the scnRNA-binding protein Ptiwi09. Furthermore, Gtsf1 is necessary for DNA elimination and correct H3K9me3 and H3K27me3 localization in the new developing macronucleus, demonstrating that the scnRNA selection process is important for genome elimination. We propose that Gtsf1 is required for the coordinated degradation of Ptiwi09-scnRNA complexes that pair with nascent RNA transcribed from the maternal MAC genome, similarly to the mechanism suggested for microRNA target-directed degradation in metazoans.
High-resolution mapping ofRyd4Hb, a major resistance gene toBarley yellow dwarf virusfromHordeum bulbosum
Authors: Pidon Hélène , Ruge-Wehling Brigitte , Will Torsten , Habekuß Antje , Wendler Neele , Oldach Klaus , Maasberg-Prelle Anja , Korzun Viktor , Stein Nils
Published: September 2023

Virus diseases are causing high yield losses in crops worldwide. TheBarley yellow dwarf virus(BYDV) complex is responsible for one of the most widespread and economically important viral diseases of cereals. While no complete resistance gene has been uncovered in the primary genepool of barley, sources of resistance were identified in the wild relativeHordeum bulbosum, representing the secondary genepool of barley. One such locus,Ryd4Hb, has been previously introgressed into barley, and was allocated to chromosome 3H, but is tightly linked to a sublethality factor that prevents the incorporation and utilization ofRyd4Hbin barley varieties. To solve this problem, we fine-mappedRyd4Hband separated it from this negative factor. We narrowed theRyd4Hblocus to a 66.5 kbp physical interval in the barley ‘Morex’ reference genome. The region comprises one complete and one partial gene from the nucleotide-binding and leucine-rich repeat immune receptor family, typical of dominant virus resistance genes. The closest homolog to these twoRyd4Hbcandidate genes is the wheatSr35stem rust resistance gene. In addition to the fine mapping, we reduced the sublethality factor interval to 600 kbp in barley. Aphid feeding experiments demonstrated thatRyd4Hbprovides a direct resistance to BYDV rather than a resistance to its vector. The presented results, including the high-throughput molecular markers, will permit a more targeted selection of the resistance in breeding, enabling the use ofRyd4Hbin barley varieties.

Key message

We mappedRyd4Hbin a 66.5 kpb interval in barley and dissociated it from a sublethality factor. These results will enable a targeted selection of the resistance in barley breeding.