bluuebunny/crossref_metadata_2025 huggingface dataset:
HDL and persistent inflammation immunosuppression and catabolism syndrome
Authors: Barker Grant , Winer Julia R. , Guirgis Faheem W. , Reddy Srinivasa
Published: August 2021

Purpose of review

This study reviews the mechanisms of HDL cholesterol immunomodulation in the context of the mechanisms of chronic inflammation and immunosuppression causing persistent inflammation, immunosuppression and catabolism syndrome (PICS) and describes potential therapies and gaps in current research.

Recent findings

Low HDL cholesterol is predictive of acute sepsis severity and outcome. Recent research has indicated apolipoprotein is a prognostic indicator of long-term outcomes. The pathobiologic mechanisms of PICS have been elucidated in the past several years. Recent research of the interaction of HDL pathways in related chronic inflammatory diseases may provide insights into further mechanisms and therapeutic targets.

HDL significantly influences innate and adaptive immune pathways relating to chronic disease and inflammation. Further research is needed to better characterize these interactions in the setting of PICS.
Insights into the molecular mechanisms regulating mammalian hair cell regeneration
Authors: Hu Zhengqing , Singh Aditi , Bojrab Dennis , Sim Nathan
Published: August 2021

Purpose of review

To give an overview of recent advances in mammalian auditory hair cell regeneration.

Recent findings

Supporting cells act as progenitors to regenerate hair cells in the prehearing mammalian cochlea but not in the mature cochlea. To overcome this developmental obstacle, manipulation of multiple genes and intracellular pathways has been investigated, which has obtained promising data. This review focuses on recent advances in auditory hair cell regeneration, including synergic gene regulation associated with Atoh1 and Notch signaling, epigenetics, and functional recovery of regenerated hair cells. Co-manipulation of genes critical for hair cell development and cell cycle re-entry, including Atoh1, Isl1, Pou4f3, Gata3, Gfi1, P27

kip1
, RB, Myc, and Notch-signaling genes, has generated hair cell-like cells in the adult cochlea both in vitro and in vivo. The epigenetic mechanism has been studied in hair cell development and regeneration. Regeneration of hair cell function has a very limited progress, which lacks in-vitro and in-vivo electrophysiology data.

Regeneration of adult auditory hair cells remains a major challenge. Manipulation of multiple genes and pathways together with epigenetic regulation might potentially regenerate functional hair cells in the adult mammalian cochlea.
Kidney transplant outcomes in minority populations: can we close the gap?
Authors: Desai Amishi , Sodhi Rupinder K. , Akkina Sanjeev
Published: August 2021

Purpose of review

Health disparity in minority populations has been increasingly recognized over the last decade. The COVID-19 pandemic sheds a bright light on this very issue impressing upon the need for more research regarding healthcare in disparate populations. Although kidney transplantation remains the treatment of choice for end-stage renal disease management and longevity of life, access to transplantation remains a critical barrier in minority populations. The literature on disparity in access abounds but remains limited with regards to posttransplantation outcomes. The purpose of this review is to draw attention to existing research and literature in posttransplant outcomes and highlight the overall knowledge gap that persists in postkidney transplant care among disparate populations.

Recent findings

The current review focuses on important paradigm shifts in the determinants of outcomes in posttransplantation care in minority populations. It emphasizes a departure from immune mediated causes to more salient health inequities and socioeconomic factors contributing to patient and graft survival which require further investigation.

Despite increased awareness of health disparity in minority populations, outcomes data postkidney transplantation remains sparse. Critical to the future of kidney transplantation and improved healthcare coordination in minority populations will be a deeper understanding of contributing socio-economic variables in disparate outcomes.
Disparities in living donation
Authors: Lopez-Soler Reynold I. , Garcia-Roca Raquel , Lee David D.
Published: August 2021

Purpose of review

Living organ donation provides improved access to transplantation, thereby shortening transplant wait times and allowing for more deceased organ transplants. However, disparity in access to living donation has resulted in decreased rates of living donor transplants for some populations of patients.

Recent findings

Though there have been marked improvements in deceased donor equity, there are still challenges as it relates to gender, racial/ethnic, and socio-economic disparity. Improvements in living donation rates in Hispanic and Asian populations are tempered by challenges in African American rates of organ donation. Socio-economic disparity may drive gender disparities in organ donation resulting in disproportionate female living donors. Tailored approaches relating to language-specific interventions as well as directed educational efforts have helped mitigate disparity. Additionally, the use of apolipoprotein1 testing and modifications of glomerular filtration rate calculators may improve rates of African American donation. This review will evaluate recent data in living donor disparity as well as highlight successes in mitigating disparity.

Though there are still challenges in living donor disparity, many efforts at tailoring education and access as well as modifying living donor evaluation and identifying systemic policy changes may result in improvements in living donation rates.
An open-source pipeline for analysing changes in microglial morphology
Authors: Clarke Devin , Crombag Hans S. , Hall Catherine N.
Published: August 2021

Changes in microglial morphology are powerful indicators of the inflammatory state of the brain. Here, we provide an open-source microglia morphology analysis pipeline that first cleans and registers images of microglia, before extracting 62 parameters describing microglial morphology. It then compares control and ‘inflammation’ training data and uses dimensionality reduction to generate a single metric of morphological change (an ‘inflammation index’). This index can then be calculated for test data to assess inflammation, as we demonstrate by investigating the effect of short-term high-fat diet consumption in heterozygous Cx3CR1-GFP mice, finding no significant effects of diet. Our pipeline represents the first open-source microglia morphology pipeline combining semi-automated image processing and dimensionality reduction. It uses free software (ImageJ and R) and can be applied to a wide variety of experimental paradigms. We anticipate it will enable others to more easily take advantage of the powerful insights microglial morphology analysis provides.
Bdellovibrio bacteriovorus
phosphoglucose isomerase structures reveal novel rigidity in the active site of a selected subset of enzymes upon substrate binding
Authors: Meek R. W. , Cadby I. T. , Lovering A. L.
Published: August 2021

Glycolysis and gluconeogenesis are central pathways of metabolism across all domains of life. A prominent enzyme in these pathways is phosphoglucose isomerase (PGI), which mediates the interconversion of glucose-6-phosphate and fructose-6-phosphate. The predatory bacterium
Bdellovibrio bacteriovorus
leads a complex life cycle, switching between intraperiplasmic replicative and extracellular ‘hunter’ attack-phase stages. Passage through this complex life cycle involves different metabolic states. Here we present the unliganded and substrate-bound structures of the
B. bacteriovorus
PGI, solved to 1.74 Å and 1.67 Å, respectively. These structures reveal that an induced-fit conformational change within the active site is not a prerequisite for the binding of substrates in some PGIs. Crucially, we suggest a phenylalanine residue, conserved across most PGI enzymes but substituted for glycine in
B. bacteriovorus
and other select organisms, is central to the induced-fit mode of substrate recognition for PGIs. This enzyme also represents the smallest conventional PGI characterized to date and probably represents the minimal requirements for a functional PGI.
The intrinsically disorderly story of Ki-67
Authors: Remnant Lucy , Kochanova Natalia Y. , Reid Caitlin , Cisneros-Soberanis Fernanda , Earnshaw William C.
Published: August 2021

Ki-67 is one of the most famous marker proteins used by histologists to identify proliferating cells. Indeed, over 30 000 articles referring to Ki-67 are listed on PubMed. Here, we review some of the current literature regarding the protein. Despite its clinical importance, our knowledge of the molecular biology and biochemistry of Ki-67 is far from complete, and its exact molecular function(s) remain enigmatic. Furthermore, reports describing Ki-67 function are often contradictory, and it has only recently become clear that this proliferation marker is itself dispensable for cell proliferation. We discuss the unusual organization of the protein and its mRNA and how they relate to various models for its function. In particular, we focus on ways in which the intrinsically disordered structure of Ki-67 might aid in the assembly of the still-mysterious mitotic chromosome periphery compartment by controlling liquid–liquid phase separation of nucleolar proteins and RNAs.
Fruit odorants mediate co-specialization in a multispecies plant–animal mutualism
Authors: Santana Sharlene E. , Kaliszewska Zofia A. , Leiser-Miller Leith B. , Lauterbur M. Elise , Arbour Jessica H. , Dávalos Liliana M. , Riffell Jeffrey A.
Published: August 2021

Despite the widespread notion that animal-mediated seed dispersal led to the evolution of fruit traits that attract mutualistic frugivores, the dispersal syndrome hypothesis remains controversial, particularly for complex traits such as fruit scent. Here, we test this hypothesis in a community of mutualistic, ecologically important neotropical bats (Carolliaspp.) and plants (Piperspp.) that communicate primarily via chemical signals. We found greater bat consumption is significantly associated with scent chemical diversity and presence of specific compounds, which fit multi-peak selective regime models inPiper. Through behavioural assays, we foundCarolliaprefer certain compounds, particularly 2-heptanol, which evolved as a unique feature of twoPiperspecies highly consumed by these bats. Thus, we demonstrate that volatile compounds emitted by neotropicalPiperfruits evolved in tandem with seed dispersal by scent-orientedCarolliabats. Specifically, fruit scent chemistry in somePiperspecies fits adaptive evolutionary scenarios consistent with a dispersal syndrome hypothesis. While other abiotic and biotic processes likely shaped the chemical composition of ripe fruit scent inPiper, our results provide some of the first evidence of the effect of bat frugivory on plant chemical diversity.
Contributions of environmental and maternal transmission to the assembly of leaf fungal endophyte communities
Authors: Bell-Dereske Lukas P. , Evans Sarah E.
Published: August 2021

Leaf fungal endophytes (LFEs) contribute to plant growth and responses to stress. Fungi colonize leaves through maternal transmission, e.g. via the seed, and through environmental transmission, e.g. via aerial dispersal. The relative importance of these two pathways in assembly and function of the LFE community is poorly understood. We used amplicon sequencing to track switchgrass (
Panicum virgatum
) LFEs in a greenhouse and field experiment as communities assembled from seed endophytes and rain fungi (integration of wet and dry aerial dispersal) in germinating seeds, seedlings, and adult plants. Rain fungi varied temporally and hosted a greater portion of switchgrass LFE richness (greater than 65%) than were found in seed endophytes (greater than 25%). Exposure of germinating seeds to rain inoculum increased dissimilarity between LFE communities and seed endophytes, increasing the abundance of rain-derived taxa, but did not change diversity. In the field, seedling LFE composition changed more over time, with a decline in seed-derived taxa and an increase in richness, in response to environmental transmission than LFEs of adult plants. We show that environmental transmission is an important driver of LFE assembly, and likely plant growth, but its influence depends on both the conditions at the time of colonization and plant life stage.
Using the Goldilocks Principle to model coral ecosystem engineering
Authors: Hennige S. J. , Larsson A. I. , Orejas C. , Gori A. , De Clippele L. H. , Lee Y. C. , Jimeno G. , Georgoulas K. , Kamenos N. A. , Roberts J. M.
Published: August 2021

The occurrence and proliferation of reef-forming corals is of vast importance in terms of the biodiversity they support and the ecosystem services they provide. The complex three-dimensional structures engineered by corals are comprised of both live and dead coral, and the function, growth and stability of these systems will depend on the ratio of both. To model how the ratio of live : dead coral may change, the ‘Goldilocks Principle’ can be used, where organisms will only flourish if conditions are ‘just right’. With data from particle imaging velocimetry and numerical smooth particle hydrodynamic modelling with two simple rules, we demonstrate how this principle can be applied to a model reef system, and how corals are effectively optimizing their own local flow requirements through habitat engineering. Building on advances here, these approaches can be used in conjunction with numerical modelling to investigate the growth and mortality of biodiversity supporting framework in present-day and future coral reef structures.
Indirect interactions among co-infecting parasites and a microbial mutualist impact disease progression
Authors: O'Keeffe Kayleigh R. , Simha Anita , Mitchell Charles E.
Published: August 2021

Interactions among parasites and other microbes within hosts can impact disease progression, yet study of such interactions has been mostly limited to pairwise combinations of microbes. Given the diversity of microbes within hosts, indirect interactions among more than two microbial species may also impact disease. To test this hypothesis, we performed inoculation experiments that investigated interactions among two fungal parasites,Rhizoctonia solaniandColletotrichum cereale,and a systemic fungal endophyte,Epichloë coenophiala,within the grass, tall fescue (Lolium arundinaceum). Both direct and indirect interactions impacted disease progression. While the endophyte did not directly influenceR. solanidisease progression orC. cerealesymptom development, the endophyte modified the interaction between the two parasites.The magnitude of the facilitative effect ofC. cerealeon the growth ofR. solanitended to be greater when the endophyte was present. Moreover, this interaction modification strongly affected leaf mortality. For plants lacking the endophyte, parasite co-inoculation did not increase leaf mortality compared to single-parasite inoculations. By contrast, for endophyte-infected plants, parasite co-inoculation increased leaf mortality compared to inoculation withR. solaniorC. cerealealone by 1.9 or 4.9 times, respectively. Together, these results show that disease progression can be strongly impacted by indirect interactions among microbial symbionts.
Hyperspectral imaging technigue for monitoring moisture content of
blueberry during the drying process
Authors: Choi Ji-Young , Kim Jiyoon , Kim Jungsoo , Jeong Saeul , Kim Minhyun , Park Sanghyeok , Moon Kwang-Deog
Published: August 2021

Changes in the moisture content (MC) of blueberries during drying was monitored
by hyperspectral image analysis, and the degree of drying was determined using
the partial least squares (PLS) model. Blueberries (n=820) were dried at
35°C for 0 (control), 3, 6, 9 and 12 days. The PLS discriminant analysis
prediction accuracy of smoothing the pre-processed data was the highest.
Regression coefficients were high at 706, 790, 827, 868, and 894 nm,
corresponding to water molecules and carbohydrates (830-840 nm). To develop a
prediction model for blueberry MC, 150 hyperspectral images were obtained from
30 samples per group. The MC of each group was also analyzed. The accuracy of
the MC prediction model pretreated by the multiplicative scatter correction
method was the highest at 0.9302. As indicated by Pearson’s correlation
analysis, the blueberry MC showed a high correlation of 0.95 with the total
soluble solid contents, brightness, and total flavonoid contents. These results
suggest that hyperspectral imaging techniques can be used to predict and monitor
various quality characteristics as well as the MC of blueberries during
drying.
Phenylpropanoids, lignan glucosides, feruloyltyramines, and flavonoid
glycosides, as antioxidative compounds from aerial parts of Suaeda
japonica
Authors: Oh Gyu-Yeon , Lee Young-Seung , Jeon Tae-Il , Ham Kyung-Sik , Moon Jae-Hak , Cho Jeong-Yong
Published: August 2021

Sixteen antioxidative compounds were purified and isolated from the aerial parts
of Suaeda japonica by column chromatography using Amberlite
XAD-2 and octadecylsilane columns and high-performance liquid chromatography.
These compounds, esculin (1), citrusin D (2), scopolin (3), cichoriin (4),
isorhamnetin 3-O-rutinoside-7-O-β-
D-glucopyranoside (5), 3'-methoxytaxifolin
7-O-β-D-glucopyranoside (6), (+)-lyoniresinol
3a-O-β-D-glucopyranoside (7),
(2R,3R,4S)-isolariciresinol
3a-O-β-D-glucopyranoside (8),
N-cis-feruloyltyramine
4-O-β-D-glucopyranoside (9),
N-cis-feruloylmethoxytyramine
4-O-β-D-glucopyranoside (10),
trans-icariside H1 (11),
cis-icariside H1 (12),
N-trans- feruloyltyramine
4-O-β-D-glucopyranoside (13), rutin (14),
kaempferol-3-O-rutinoside (15), and narcissin (16), were
identified for the firtst time in S. japonica. The structures
of these compounds were determined by mass spectrometry and nuclear magnetic
resonance spectroscopic analyses. Among the compounds, 14 showed the highest
1,1-diphenyl- 2-picrylhydrazyl free radical-scavenging activity and 8 exhibited
the highest reactive oxygen species-scavenging activity in Huh7 cells.
Optimization of ultrasonic-assisted extraction of polyphenols and
antioxidants from cumin (Cuminum cyminum L.)
Authors: Shamsiev Anvar , Park Jongjin , Olawuyi Ibukunoluwa Fola , Odey Golden , Lee Wonyoung
Published: August 2021

Ultrasonic-assisted extraction (UAE) using response surface methodology (RSM) was
employed for the highly efficient extraction of bioactive compounds such as
polyphenols and antioxidants from cumin (Cuminum cyminum L.)
seeds. A central composite design (CCD) consisting of three variables and five
levels was used to estimate the significance of each process variable in the
application of UAE for cumin seed extraction. Process variables optimized were
ethanol concentration (0-80%, v/v), extraction time (15-75 min), and extraction
temperature (15-75°C). RSM was employed to determine the optimal
extraction conditions for the bioactive compounds. Four-dimensional surface
plots were generated to indicate polynomial equations of good-fit models. The
optimal conditions were then predicted by superimposing these four-dimensional
surface plots. Based on the graph for the overlapped contour plots, the optimal
UAE conditions: ethanol concentration of 40% v/v, extraction time of 51 min, and
temperature of 39°C, were found to give predicted maximal values for
yield (20.31%), total polyphenol content (27.11 mg GAE/g), antioxidant activity
DPPH (52.47%), and ABTS (41.04%). Verification experiments were carried out
under optimal conditions, and there was a good fit between the estimated and
experimental values, suggesting that the model was valid and accurate for the
design of UAE process. In conclusion, UAE showed effectiveness in the recovery
of valuable antioxidant compounds from cumin.
Effect of particle size on the physicochemical and morphological
properties of Hypsizygus marmoreus mushroom powder and its
hot-water extracts
Authors: Hitayezu Emmanuel , Kang Yoon-Han
Published: August 2021

Hypsizygus marmoreus, an edible mushroom with various functional
properties, was prepared to obtain coarse and superfine powders. We evaluated
the effect of particle size on mushroom powder quality. The water absorption
index and total dietary fiber contents of superfine powders (average median
diameter, 4.791 μm) were 5.79 g/g and 28.50 g/100 g, respectively, which
were higher than the corresponding values of coarse powder (average median
diameter, 168.085 μm). Similarly, extracts prepared from the superfine
mushroom powders exhibited higher total polyphenolics contents (83.91 mgGAE/100
g), total sugar contents (5,138.50 mg/100 g), and total flavonoid contents
(43.99 mgNE/100 g) compared with those prepared from coarse mushroom powders.
The extraction yield and pH were higher for superfine powder concentrates than
for coarse powder concentrates. According to the electronic tongue results,
superfine powder extracts had high scores for umami, sourness, and sweetness,
while coarse powder extracts scored high in bitterness. Furthermore, SEM images
indicated that both powders differed in either the shape or size of the
particles; coarse powder particles exhibited irregular shapes and high porosity,
while superfine powder particles represented a uniform shape and lower porosity.
Particle size reduction through superfine grinding improved the physicochemical
and morphological properties of the mushroom powder samples and their hot-water
extracts.
A new species of the genusMicrohylaTschudi, 1838 (Amphibia: Anura: Microhylidae) from eastern India with notes on Indian species
Authors: Bhakat Somnath , Bhakat Soumendranath
Published: August 2021

A new species of the genusMicrohyla,Microhyla bengalensissp. nov., described from West Bengal state, India. The new species is distinguished from its congeners by a combination of the following morphological characters: 1) Small in size (SVL= 16.2 mm. in male); 2) truncated snout in dorsal view; 3) head wider than long (HW: HL= 1.36); 4) canthus rostralis and tympanum are indistinct; 5) nostril placed on the dorsal side of the snout; 6) tibiotarsal articulation not reaching the eye; 7) fingers and toes without disc; 8) toe webbing basal; 9) thigh and foot length are equal and smaller than shank; 10) skin tuberculated on dorsum; 11) ‘teddy bear’ dark brown mark on dorsum; 12) an inverted ‘V’-shaped dark brown mark above the vent.

A comparative morphological data of all the 14 Indian species ofMicrohylais also provided.
Broad neutralizing nanobody against SARS-CoV-2 engineered from pre-designed synthetic library
Authors: Liu Qianyun , Cai Chenguang , Huang Yanyan , Zhou Li , Guan Yanbin , Fu Shiying , Lin Youyou , Yang Ting , Wan Nanyan , Zhang Fengzhi , Sun Qi , Bai Ying , Chen Yu , Liang Xiaohua , Yan Huan , Zhang Zhen , Lan Ke , Chen Yu , Li Xiang , Hou Shin-Chen , Xiong Yi
Published: August 2021

SARS-CoV-2 infection is initiated with Spike glycoprotein binding to the receptor of human angiotensin converting enzyme 2 via its receptor binding domain. Blocking this interaction is considered as an effective approach to inhibit virus infection. Here we report the discovery of a neutralizing nanobody, VHH60, directly produced from a humanized synthetic nanobody library. VHH60 competes with human ACE2 to bind the receptor binding domain of the Spike protein with a KDof 2.56 nM, inhibits infections of both live SARS-CoV-2 and pseudotyped viruses harboring wildtype, escape mutations and prevailing variants at nanomolar level. VHH60 also suppresses SARS-CoV-2 infection and propagation 50-fold better and protects mice from death two times longer than that of control group after live virus inoculation on mice. VHH60 therefore is a powerful synthetic nanobody with a promising profile for disease control against COVID19.
Evaluation of the Liberty16 mobile real time PCR device for use with the SalivaDirect assay for SARS-CoV-2 testing
Authors: Yolda-Carr Devyn , Thammavongsa Darani A. , Vega Noel , Turner Susan J. , Pickering Paul J. , Wyllie Anne L.
Published: August 2021

The COVID-19 pandemic has highlighted the need and benefits for all communities to be permitted timely access to on-demand screening for infectious respiratory diseases. This can be achieved with simplified testing approaches and affordable access to core resources. While RT-qPCR-based tests remain the gold standard for SARS-CoV-2 detection due to their high sensitivity, implementation of testing requires high upfront costs to obtain the necessary instrumentation. This is particularly restrictive in low-resource settings. The Ubiquitome Liberty16 system was developed as an inexpensive, portable, battery-operated single-channel RT-qPCR device with an associated iPhone app to simplify assay set-up and data reporting. When coupled with the SalivaDirect protocol for testing saliva samples for SARS-CoV-2, the Liberty16 device yielded a limit of detection (LOD) of 12 SARS-CoV-2 RNA copies/µL, comparable to the upper end of the LOD range for the standard SalivaDirect protocol when performed on larger RT-qPCR instruments. While further optimization may deliver even greater sensitivity and assay speed, findings from this study indicate that small portable devices such as the Liberty16 can deliver reliable results and provide the opportunity to further increase access to gold standard SARS-CoV-2 testing.
Comparison of Ferroptosis Related Genes expression in Human Oral Squamous Cell Carcinoma and Normal oral tissues
Authors: Thavarajah Rooban , Joshua Elizabeth , Ranganathan Kannan
Published: August 2021

Introduction

Evasion of programmed cell death (PCD) is a hall mark of oncogenesis. There are different types of PCD. Iron related PCD, ferroptosis is being increasingly associated with neoplastic process. There are very few reports that investigate the role of ferroptosis in Oral Squamous Cell Carcinoma (OSCC). An attempt is made to compare the ferroptosis related genes(FRGs) expression in human OSCC and normal oral tissues.

Materials and Methods

Gene Expression Omnibus repository was scanned for OSCC mRNA datasets along with normal control tissues. Datasets fulfilling inclusion and exclusion criteria as well as that fulfilled the statistical correlation requirements were considered for this study. Differentially expressed mRNAs were identified. From the literature and ferroptosis database, FRGs were identified and those FRGs were differentially expressed were validated using The Human Cancer Genome dataset.

Results

In all 44 FRGs were identified to be differentially expressed between OSCC and control tissues. Of the 44, 21 were that promoted ferroptosis including 18 drivers of ferroptosis. Of the 21 FRGs that drives ferroptosis, 9 were found significantly elevated in controls while the remaining 12 were elevated in OSCC. The role of the differentially expressed FRGs were also studied. Of the 44 FRGs, 36 were validated using the human cancer genome dataset.

Discussion and Conclusion

Drivers and suppressors of ferroptosis were differentially expressed in OSCC and controls. This reflects that ferroptosis has a dual role in oncogenesis – both as a promoter and a suppressor. The identified specific FRGs in this studied would help to understand the role of PCD in OSCC progression and help in designing better treatment.
The Normative Modeling Framework for Computational Psychiatry
Authors: Rutherford Saige , Kia Seyed Mostafa , Wolfers Thomas , Fraza Charlotte , Zabihi Mariam , Dinga Richard , Berthet Pierre , Worker Amanda , Verdi Serena , Ruhe Henricus G. , Beckmann Christian F. , Marquand Andre F.
Published: August 2021

Normative modeling is an emerging and innovative framework for mapping individual differences at the level of a single subject or observation in relation to a reference model. It involves charting centiles of variation across a population in terms of mappings between biology and behavior which can then be used to make statistical inferences at the level of the individual. The fields of computational psychiatry and clinical neuroscience have been slow to transition away from patient versus “healthy” control analytic approaches, likely due to a lack of tools designed to properly model biological heterogeneity of mental disorders. Normative modeling provides a solution to address this issue and moves analysis away from case-control comparisons that rely on potentially noisy clinical labels. In this article, we define a standardized protocol to guide users through, from start to finish, normative modeling analysis using the Predictive Clinical Neuroscience toolkit (PCNtoolkit). We describe the input data selection process, provide intuition behind the various modeling choices, and conclude by demonstrating several examples of down-stream analyses the normative model results may facilitate, such as stratification of high-risk individuals, subtyping, and behavioral predictive modeling. The protocol takes approximately 1-3 hours to complete.
Suppression of influenza virus infection by rhinovirus interference at the population, individual and cellular levels
Authors: Tao Kin P , Chong Marc , Pun Jason CS , Tsun Joseph GS , Chow Samuel MW , Ng Calvin SH , Wang Maggie HT , Chan Zigui , Chan Paul KS , Li Albert M , Chan Renee WY
Published: August 2021

Background

Investigations of the natural viral interference effect between rhinovirus (RV) and influenza virus (IV) were conducted in temperate regions. We conducted an epidemiological study in Hong Kong, a major epicentre of influenza virus in the sub-tropical region. RV is the most prevalent respiratory virus year-round and causes asymptomatic to mild symptoms while IV infection exerts a great burden of public health. We aimed to examine the correlation of RV prevalence against IV activity.

Methods

Nasopharyngeal aspirates (NPA) collected from patients hospitalized in the regional hospitals from 2015 to 2019 were examined for the presence of respiratory viruses. The correlation of the monthly prevalence between all pairs of virus infection, the co-infection rate and the temporal interference of RV and IV were tested. The viral interference was validatedin vitroby conducting sequential RV and IV infection in the well-differentiated primary human airway epithelial cells.

Findings

A total of 112,926 NPA were evaluated, and the Enterovirus/RV was the most prevalent respiratory virus detected. The negative correlation between EV/RV and IVs prevalence was independent of age and meteorological factors. Co-infection of EV/RV and IV was significantly less when compared with other virus pairs. Prior exposure to RV inhibited the replication of influenza A, B and oseltamivir-resistance stainin vitroand the inhibition is replication dependent.

Interpretation

Epidemiological surveillance and the sequential infectionin vitrosuggested viral interference between EV/RV and IV operated at the population, individual and cellular levels.

Funding

This study was supported by the General Research Fund (Ref: 24107017 and 14103119 to RWYC), Health and Medical Research Fund (Ref: COVID190112 to RWYC) and the Chinese University Direct Grant for Research (Ref: 2019.073 to RWYC).
Acute kidney injury after liver resection: A systematic review, meta-analysis and metaregression of factors affecting it
Authors: Vasavada Bhavin , Patel Hardik
Published: August 2021

Aim

This systematic review and meta-analysis aimed to study the incidence of acute kidney injury after liver resection and to analyze various factors affecting it by metaregression analysis.

Methods

The study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement (2020) and MOOSE guidelines. The meta-analysis was done using Review Manager 5.4 and the JASP Team (2020). JASP (Version 0.14.1)(University of Amsterdam). Weighted percentage incidence with 95% confidence intervals were used. Univariate metaregression was done by DerSimonian-Laird methods. Factors with a p-value less than 0.05 in the univariate metaregression model were entered in the multivariate metaregression model. Heterogeneity was assessed using the Higgins I2 test. The random-effects model was used in meta-analysis.

Results

Total 14 studies including 15510 patients were included in the final analysis. 1247 patients developed Acute Kidney Injury. Weighted Acute kidney injury percentage after liver resection was 15% with a 95% confidence interval of 11%-19%. On univariate metaregression analysis major hepatectomy (p=0.001), Underlying cirrhosis of liver (p=0.031), AKIN definition used (0.017), male sex (p<0.001), open surgery (p=0.032), underlying diabetes (0.026). On multivariate metaregression analysis major hepatectomy (p=0.003), underlying cirrhosis (p<0.001), male sex (p<0.001), AKIN classification used for defining acute kidney injury (p < 0.001, independently predicted heterogeneity and hence acute kidney injury.

Conclusion

Liver resection is associated with a high incidence of acute kidney injury. Major hepatectomy, male sex, underlying cirrhosis were independently predicting acute kidney injury.
Diagnosing COVID-19 in human serum using Raman spectroscopy: a preliminary study
Authors: Goulart Ana Cristina Castro , Silveira Landulfo , Carvalho Henrique Cunha , Dorta Cristiane Bissoli , Pacheco Marcos Tadeu T. , Zângaro Renato Amaro
Published: August 2021

This preliminary study proposed the diagnosis of COVID-19 by means of Raman spectroscopy. Samples of blood serum from 10 patients positive and 10 patients negative for COVID-19 by RT-PCR RNA and ELISA tests were analyzed. Raman spectra were obtained with a dispersive Raman spectrometer (830 nm, 350 mW) in triplicate, being submitted to exploratory analysis with principal component analysis (PCA) to identify the spectral differences and discriminant analysis with PCA (PCA-DA) and partial least squares (PLS-DA) for classification of the blood serum spectra into Control and COVID-19. The spectra of both groups positive and negative for COVID-19 showed peaks referred to the basal constitution of the serum (mainly albumin). The difference spectra showed decrease in the peaks referred to proteins and amino acids for the group positive. PCA variables showed more detailed spectral differences related to the biochemical alterations due to the COVID-19 such as increase in lipids, nitrogen compounds (urea and amines/amides) and nucleic acids, and decrease of proteins and amino acids (tryptophan) in the COVID-19 group. The discriminant analysis applied to the principal component loadings (PC 2, PC 4, PC 5 and PC 6) could classify spectra with 87% sensitivity and 100% specificity compared to 95% sensitivity and 100% specificity indicated in the RT-PCR kit leaflet, demonstrating the possibilities of a rapid, label-free and costless technique for diagnosing COVID-19 infection.
Fully Human Antibody Immunoglobulin from Transchromosomic Bovines is Potent Against SARS-CoV-2 Variant Pseudoviruses
Authors: Luke Thomas , Wu Hua , Egland Kristi A , Sullivan Eddie J , Bausch Christoph L
Published: August 2021

SAB-185 is a fully human polyclonal anti-SARS-CoV-2 immunoglobulin produced from the plasma of transchromosomic bovines that are hyperimmunized with recombinant SARS-CoV-2 Wuhan-Hu-1 Spike protein. SAB-185 is being evaluated for efficacy in aphase 3 clinical trial. The World Health Organization (WHO) has identified multiple Variants-of-Concern and Variants-of-Interest (VOC/VOI) that have mutations in their Spike protein that appear to increase transmissibility and/or reduce the effectiveness of therapeutics and vaccines, among other parameters of concern. SAB-185 was evaluated using lentiviral-based pseudovirus assays performed in a BSL2 environment that incorporates stable or transient cell lines that express human angiotensin converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2). The results indicate that SAB-185 retained neutralization potency against multiple SARS-CoV-2 pseudovirus variants, including the Delta, Kappa, Lambda and Omicron variants, that have or are supplanting other VOC/VOI in many countries and regions around the world.
3D single molecule localization microscopy reveals the topography of the immunological synapse at isotropic precision below 15 nm
Authors: Velas Lukas , Brameshuber Mario , Huppa Johannes B. , Kurz Elke , Dustin Michael L. , Zelger Philipp , Jesacher Alexander , Schütz Gerhard J.
Published: August 2021

T-cells engage with antigen-presenting cells in search for antigenic peptides and form transient interfaces termed immunological synapses. A variety of protein-protein interactions in trans-configuration defines the topography of the synapse and orchestrates the antigen-recognition process. In turn, the synapse topography affects receptor binding rates and the mutual segregation of proteins due to size exclusion effects. For better understanding it is hence critical to map the 3D topography of the immunological synapse at high precision. Current methods, however, provide only rather coarse images of the protein distribution within the synapse, which do not reach the dimension of the protein ectodomains. Here, we applied supercritical angle fluorescence microscopy combined with defocused imaging, which allows 3-dimensional single molecule localization microscopy (3D-SMLM) at an isotropic localization precision below 15 nm. Experiments were performed on hybrid synapses between primary T-cells and functionalized glass-supported lipid bilayers. We used 3D-SMLM to quantify the cleft size within the synapse by mapping the position of the T-cell receptor (TCR) with respect to the supported lipid bilayer, yielding average distances of 18 nm up to 31 nm for activating and non-activating bilayers, respectively.
Glue genes are subjected to diverse selective forces during Drosophila development
Authors: Borne Flora , Kulathinal Rob J. , Courtier-Orgogozo Virginie
Published: August 2021

Molecular evolutionary studies usually focus on genes with clear roles in adult fitness or on developmental genes expressed at multiple time points during the life of the organism. Here, we examine the evolutionary dynamics of Drosophila glue genes, a set of eight genes tasked with a singular primary function during a specific developmental stage: the production of glue that allows animal pupa to attach to a substrate for several days during metamorphosis. Using phenotypic assays and available data from transcriptomics, PacBio genomes, and genetic variation from global populations, we explore the selective forces acting on the glue genes within the cosmopolitanD. melanogasterspecies and its five closely related species,D. simulans, D. sechellia, D. mauritiana, D. yakuba, andD. teissieri. We observe a three-fold difference in glue adhesion between the least and the most adhesiveD. melanogasterstrain, indicating a strong genetic component to phenotypic variation. These eight glue genes are among the most highly expressed genes in salivary glands yet they display no notable codon bias. New copies ofSgs3andSgs7are found inD. yakubaandD. teissieriwith theSgs3coding sequence evolving rapidly after duplication in theD. yakubabranch. Multiple sites along the various glue genes appear to be constrained. Our population genetics analysis inD. melanogastersuggests signs of local adaptive evolution forSgs3, Sgs5andSgs5bisand traces of selective sweeps forSgs1, Sgs3, Sgs7andSgs8. Our work shows that stage-specific genes can be subjected to various dynamic evolutionary forces. (249 words)

Significance statement

Drosophila larvae produce a glue to stick themselves to a substrate for several days during metamorphosis. Here we observe wide variation in stickiness amongDrosophila melanogasterstrains and we analyze the molecular evolution of eight glue genes. We find several recent gene duplications and heterogenous rates of evolution among these genes.
A photo-switchable assay system for dendrite degeneration and repair inDrosophila melanogaster
Authors: Liu Han-Hsuan , Hsu Chien-Hsiang , Jan Lily Y. , Jan Yuh-Nung
Published: August 2021

Neurodegeneration arising from aging, injury or disease has devastating health consequences. Whereas neuronal survival and axon degeneration have been studied extensively, much less is known about how neurodegeneration impacts dendrites. To develop an assay for dendrite degeneration and repair in theDrosophilaperipheral nervous system, we used photo-switchable caspase-3 (caspase-LOV) to induce neuronal damage with tunable severity by adjusting illumination duration, thereby revealing cell type-specific responses to caspase-3 induced dendrite degeneration in dendrite arborization (da) neurons. To ask whether mechanisms underlying axon degeneration also govern dendrite degeneration, we tested the involvement of the Wallerian degeneration pathway by examining the effects of expressing the mouse Wallerian degeneration slow (WldS) protein and knockdown of theDrosophilasterile alpha/Armadillo/Toll-Interleukin receptor homology domain protein (dSarm1) and Axundead (Axed) in class 4 da neurons. Here we report WldSexpression or knockdown of dSarm1 improved dendrite repair following caspase- 3 induced dendrite degeneration. Whereas both dSarm1 and Axed were required for thermal nocifensive behavior in uninjured animals, WldSexpression improved the recovery of thermal nocifensive behavior that was impaired by chronic low-level of caspase-LOV activity. By establishing ways to induce graded dendrite degeneration, we uncover a protective role of WldSin caspase-3 induced dendrite degeneration and repair.
OPAM, an Open source, 3D printed Low-cost Micro-Manipulator for Single Cell Manipulation
Authors: Xu Jiang , Du Zhuowei , Liu Paul , Kou Yi , Chen Lin
Published: August 2021

We introduce OPAM, an Open source, low-cost (under $150), 3D-Printed, stepper motor driven, Arduino based, single cell Micromanipulator (OPAM). Modification of a commercial stepper motor led to dramatically increased stability and maneuverability of the motor, based on which the micromanipulator was designed. All components of this micromanipulator can be 3D printed using an entry-level 3D printer and assembled with ease. With this single cell manipulator, successful targeted single cell capture and transfer was confirmed under the microscope, which showed great promise for single cell related experiments.
Sex-specific tuning of modular muscle activation patterns for locomotion in young and older adults
Authors: Santuz Alessandro , Janshen Lars , Brüll Leon , Munoz-Martel Victor , Taborri Juri , Rossi Stefano , Arampatzis Adamantios
Published: August 2021

There is increasing evidence that including sex as a biological variable is of crucial importance to promote rigorous, repeatable and reproducible science. In spite of this, the body of literature that accounts for the sex of participants in human locomotion studies is small and often produces controversial results. Here, we investigated the modular organization of muscle activation patterns for human locomotion using the concept of muscle synergies with a double purpose: i) uncover possible sex-specific characteristics of motor control and ii) assess whether these are maintained in older age. We recorded electromyographic activities from 13 ipsilateral muscles of the lower limb in young and older adults of both sexes walking (young and old) and running (young) on a treadmill. The data set obtained from the 215 participants was elaborated through non-negative matrix factorization to extract the time-independent (i.e., motor modules) and time-dependent (i.e., motor primitives) coefficients of muscle synergies. We found sparse sex-specific modulations of motor control. Motor modules showed a different contribution of hip extensors, knee extensors and foot dorsiflexors in various synergies. Motor primitives were wider (i.e., lasted longer) in males in the propulsion synergy for walking (but only in young and not in older adults) and in the weight acceptance synergy for running. Moreover, the complexity of motor primitives was similar in younger adults of both sexes, but lower in older females as compared to older males. In essence, our results revealed the existence of small but defined sex-specific differences in the way humans control locomotion and that these strategies are not entirely maintained in older age.
A DNA-structured mathematical model of cell-cycle progression in cyclic hypoxia
Authors: Celora Giulia L. , Bader Samuel B. , Hammond Ester M. , Maini Philip K. , Pitt-Francis Joe , Byrne Helen M.
Published: August 2021

New experimental data have shown how the periodic exposure of cells to low oxygen levels (i.e., cyclic hypoxia) impacts their progress through the cell-cycle. Cyclic hypoxia has been detected in tumours and linked to poor prognosis and treatment failure. While fluctuating oxygen environments can be reproducedin vitro, the range of oxygen cycles that can be tested is limited. By contrast, mathematical models can be used to predict the response to a wide range of cyclic dynamics. Accordingly, in this paper we develop a mechanistic model of the cell-cycle that can be combined within vitroexperiments, to better understand the link between cyclic hypoxia and cell-cycle dysregulation. A distinguishing feature of our model is the inclusion of impaired DNA synthesis and cell-cycle arrest due to periodic exposure to severely low oxygen levels. Our model decomposes the cell population into four compartments and a time-dependent delay accounts for the variability in the duration of the S phase which increases in severe hypoxia due to reduced rates of DNA synthesis. We calibrate our model against experimental data and show that it recapitulates the observed cell-cycle dynamics. We use the calibrated model to investigate the response of cells to oxygen cycles not yet tested experimentally. When the re-oxygenation phase is sufficiently long, our model predicts that cyclic hypoxia simply slows cell proliferation since cells spend more time in the S phase. On the contrary, cycles with short periods of re-oxygenation are predicted to lead to inhibition of proliferation, with cells arresting from the cell-cycle when they exit the S phase. While model predictions on short time scales (about a day) are fairly accurate (i.e, confidence intervals are small), the predictions become more uncertain over longer periods. Hence, we use our model to inform experimental design that can lead to improved model parameter estimates and validate model predictions.
Arabidopsisspliceosome factor SmD3 modulates immunity toPseudomonas syringaeinfection
Authors: Golisz Anna , Krzyszton Michal , Stepien Monika , Dolata Jakub , Piotrowska Justyna , Szweykowska-Kulinska Zofia , Jarmolowski Artur , Kufel Joanna
Published: August 2021

SmD3 is a core component of the small nuclear ribonucleoprotein (snRNP) that is essential for pre-mRNA splicing. The role ofArabidopsisSmD3 in plant immunity was assessed by testing sensitivity ofsmd3aandsmd3bmutants toPseudomonas syringaepv.tomato(Pst) DC3000 infection and its pathogenesis effectors flagellin (flg22), EF-Tu (elf18) and coronatine (COR). Bothsmd3mutants exhibited enhanced susceptibility toPstaccompanied by marked changes in the expression of key pathogenesis markers. mRNA levels of these factors were also altered upon treatment withPseudomonaseffectors. We showed that SmD3-b dysfunction impairs mainly stomatal immunity as a result of defects in stomatal development. Our genome-wide transcriptome analysis of thesmd3b-1mutant infected withPstrevealed that lack of SmD3-b deregulates defense againstPstinfection at the transcriptional and posttranscriptional levels including defects in splicing and an altered pattern of alternative splicing. Other changes in thesmd3b-1mutant involved enhanced elf18- and flg22-induced callose deposition, reduction of flg22-triggered production of early ROS and boost of secondary ROS caused byPstinfection. Together, our data indicate that SmD3 contributes to the plant immune response possibly via regulation of mRNA splicing of key pathogenesis factors.