bluuebunny/crossref_metadata_2025 huggingface dataset:
Apilactobacillus nanyangensis sp. nov., Secundilactobacillus hailunensis sp. nov., Secundilactobacillus yichangensis sp. nov., Levilactobacillus andaensis sp. nov., Levilactobacillus wangkuiensis sp. nov., Levilactobacillus lanxiensis sp. nov., Lacticaseibacillus mingshuiensis sp. nov. and Lacticaseibacillus suilingensis sp. nov., isolated from traditional Chinese pickle and the gut of honeybee (Apis mellifera)
Authors: Liu Dan Dan , Li Yu Qin , Zhang Li Ping , Ding Wei , Tian Wen Li , Gu Chun Tao
Published: July 2021

Thirteen Gram-stain-positive bacterial strains were isolated from Chinese traditional pickle and the gut of honeybee (Apis mellifera). These strains were characterized using a polyphasic taxonomic approach. The data demonstrated that 12 of the 13 strains represented eight novel species belonging to the genera

Apilactobacillus

,

Secundilactobacillus

,

Levilactobacillus

and

Lacticaseibacillus

; strains HN36-1T, 887-11T, F79-211-2T, 866-3T, 6-5(1)T, 13B17T, 117-1T and ZW152T were designated as the type strains. Based upon the data of polyphasic characterization obtained in the present study, eight novel species, Apilactobacillus nanyangensis sp. nov., Secundilactobacillus hailunensis sp. nov., Secundilactobacillus yichangensis sp. nov., Levilactobacillus andaensis sp. nov., Levilactobacillus wangkuiensis sp. nov., Levilactobacillus lanxiensis sp. nov., Lacticaseibacillus mingshuiensis sp. nov. and Lacticaseibacillus suilingensis sp. nov., are proposed and the type strains are HN36-1T (=JCM 33867T=CCTCC AB 2019385T), 887-11T (=NCIMB 15201T=CCM 8950T=JCM 33864T=CCTCC AB 2018396T), F79-211-2T (=NCIMB 15254T=JCM 33866T=CCTCC AB 2019384T), 866-3T (=JCM 33863T=CCTCC AB 2019383T), 6-5(1)T (=NCIMB 15229T=CCM 8977T=JCM 33564T=CCTCC AB 2019168T), 13B17T (=NCIMB 15230T=CCM 8979T=JCM 33565T=CCTCC AB 2019167T), 117-1T (=NCIMB 15232T=CCM 8980T=JCM 33567T) and ZW152T (=JCM 34363T=CCTCC AB 2020299T=LMG 32143T=CCM 9110T), respectively.
Early multidrug treatment of SARS-CoV-2 (COVID-19) and decreased case fatality rates in Honduras
Authors: Ontai Sidney , Zeng Li , Hoffman Miguel Sierra , Pascua Fernando Valerio , VanBuren Vincent , McCullough Peter A
Published: July 2021

INTRODUCTION

Within 2 months of first detection of SARS-CoV-2 in Honduras, its government promoted nationwide implementation of multi-drug COVID-19 inpatient and outpatient treatment protocols. This was associated with a case fatality rate decrease from 9.33% to 2.97%. No decrease was seen in Mexico, a similar Latin American country that did not introduce multi-drug treatment protocols at that time.

OBJECTIVE

The primary objective of the study was to use statistical process control to assess the likelihood that the decrease in case fatality rate in Honduras was due to chance, using Mexico as a control country.

METHODS

Fourteen day running average COVID-19 case fatality rates in Honduras and Mexico were used to create Shewhart control charts during the first 6 months of the epidemic. The date of implementation in Honduras of the inpatient and outpatient multi-drug COVID-19 protocols were plotted on control charts, with a Mexican COVID-19 case fatality control chart for comparison.

RESULTS

The case fatality rate for COVID-19 in Honduras dropped below the lower control limit 9 days after implementation of an inpatient and outpatient multi-drug therapeutic protocol, from an average 9.33% case fatality rate to 5.01%. The Honduran COVID-19 case fatality rate again dropped below the lower control limit to 2.97%, 17 days after launching a substantial government program to make the protocol medications accessible to underserved areas. Shewhart control chart plots of case fatality rates in Honduras suggest a plausible temporal association between the implementation dates of both the initial protocol implementation on May 3, 2020, and the outreach effort on June 10, 2020, and statistically significant control chart anomalies. No control chart anomalies were seen during that time in Mexico.

CONCLUSION

Decreases in COVID-19 case fatality rates in Honduras were associated with both the initial publication a multi-drug COVID-19 therapeutic protocol and a subsequent outreach program.
Epithelial-mesenchymal plasticity determines estrogen receptor positive (ER+) breast cancer dormancy and reacquisition of an epithelial state drives awakening
Authors: Aouad Patrick , Zhang Yueyun , Stibolt Céline , Mani Sendurai A. , Sflomos George , Brisken Cathrin
Published: July 2021

Estrogen receptor α-positive (ER+) breast cancers (BCs) represent more than 70% of all breast cancers and pose a particular clinical challenge because they recur up to decades after initial diagnosis and treatment. The mechanisms governing tumor cell dormancy and latent disease remain elusive due to a lack of adequate models. Here, we compare tumor progression of ER+ and triple-negative (TN) BC subtypes with a clinically relevant mouse intraductal xenografting approach (MIND). Both ER+ and TN BC cells disseminate already during thein situstage. However, TN disseminated tumor cells (DTCs) proliferate at the same rate as cells at the primary site and give rise to macro-metastases. ER+ DTCs have low proliferative indices, form only micro-metastases and lose epithelial characteristics. Expression ofCDH1is decreased whereas the mesenchymal markerVIMand the transcription factors,ZEB1/ZEB2,which control epithelial-mesenchymal plasticity (EMP) are increased. EMP is not detected earlier during ER+ BC development and not required for invasion or metastasis.In vivo, forced transition to the epithelial state through ectopic E-cadherin expression overcomes dormancy with increased growth of lung metastases. We conclude that EMP is essential for the generation of a dormant cell state and the development of latent disease. Targeting exit from EMP is of therapeutic potential.
Echocardiographic characterisation in critical Covid19 - an observational study
Authors: Isackson Henrik , Larsson Anders , Lipcsey Miklos , Frithiof Robert , Flachskampf Frank A. , Hultström Michael
Published: July 2021

Objective

We aimed to investigate the acute cardiac effects of severe SARS-CoV-2.

Methods

This is an observational study generated from the first 79 patients admitted to Uppsala intensive care due to respiratory failure with SARS-CoV-2 infection. 34 underwent echocardiography of which 25 were included in the study and compared to 44 non-echo patients. Exclusion was based on absence of normofrequent sinus rhythm and mechanical respiratory support. Biomarker analysis was carried out on all patients.

Results

Mortality was increased in the echo compared to non-echo group (44 % vs. 16%, p<0.05). Right sided dimensions and functional parameters were not affected. Tricuspid regurgitation velocity indicated how increased pulmonary artery pressure was associated with mortality (survivors (n=5): 2.51 ± 0.01 m/s vs. non-survivors (n=5): 3.06 ± 0.11 m/s, p<0.05). Cardiac markers and D-dimer correlated to initiation of echocardiography (hs-TnI (ng/L): echo (n=23): 133 ± 45 vs. non-echo (n=41): 81.3 ± 45, p<0.01; NTproBNP (ng/L): echo (n=25): 2959 ± 573 vs. non-echo (n=42): 1641 ± 420, p<0.001; D-dimer (mg/L): echo (n=25): 16.1 ± 3.7 vs. non-echo (n=43: 6.1 ± 1.5, p<0.01) and mortality (hs-TnI (ng/L): survivors (n=48): 59.1 ± 21 vs. non-survivors (n=17): 211 ± 105, p<0.0001; NT-proBNP (ng/L): survivors (n=47): 1310 ± 314 vs. non-survivors (n=20): 4065 ± 740, p<0.0001; D-dimer (mg/L): survivors (n=50): 7.2 ± 1.5 vs. non-survivors (n=18): 17.1 ± 4.8, p<0.01). All intervals refer to standard error of the mean. Tricuspid regurgitation velocity was correlated with troponin I (r=0.93, r2=0.74, p<0.001, n=10).

Conclusions

These results suggest that there is no clear negative effect on cardiac function in critical SARS-CoV-2. There are indications that pulmonary pressure elevation carries a negative predictive outcome suggesting pulmonary disease as the driver of mortality. Cardiac biomarkers as well as D-dimer carry predictive value.

Trial registration number

Patients were included in “Clinical trials NCT04316884”

Article summary

Strength and limitations of this study

-

The patient body is recruited from all patients admitted to ICU in need of mechanical respiratory support independent of background which makes it relevant to clinical practice.

-

The echocardiographic image acquisition was carried out by hospital assigned agents on clinical indication, which makes the results applicable in a clinical setting.

-

Since the image acquisition was carried out on a clinical indication, the results may be skewed towards the false positive if applied to all Covid19 patients.
Robust antibody levels in both diabetic and non-diabetic individuals after BNT162b2 mRNA COVID-19 vaccination
Authors: Ali Hamad , AlTerki Abdelmohsen , Sindhu Sardar , Alahmad Barrak , Hammad Maha , Al-Sabah Salman , Alghounaim Mohammad , Jamal Mohammad H. , Aldei Ali , Mairza Mohammad J. , Husain Maitham , Deverajan Sriraman , Ahmad Rasheed , Cherian Preethi , Alkhairi Irina , Alkandari Abdullah , Abubaker Jehad , Abu-Farha Mohamed , Al-Mulla Fahd
Published: July 2021

The emergence of effective vaccines for COVID-19 has been welcomed by the world with great optimism. Given their increased susceptibility to COVID-19, the question arises whether individuals with type-2 diabetes mellitus (T2DM) and other metabolic conditions can respond effectively to the mRNA-based vaccine. We aimed to evaluate the levels of anti-SARS-CoV-2 IgG and neutralizing antibodies in people with T2DM and/or other metabolic risk factors (hypertension and obesity) compared to those without. This study included 262 people that took two doses of BNT162b2 (Pfizer–BioNTech) mRNA vaccine. Both T2DM and non-diabetic individuals had a robust response to vaccination as demonstrated by their high antibody titers. However, both SARS-CoV-2 IgG and neutralizing antibodies titers were lower in people with T2DM. Their levels were 154±49.1 vs. 138±59.4BAU/mL for IgG and 87.1±11.6 vs. 79.7±19.5% for neutralizing antibodies in individuals without diabetes compared to those with T2DM, respectively. In a multiple linear regression adjusted for individual characteristics, comorbidities, previous COVID-19 infection and duration since second vaccine dose, diabetics had 13.86 BAU/ml (95%CI: -27.08 to -0.64BAU/ml, p=0.041) less IgG antibodies and 4.42% (95%CI: -8.53 to -0.32%, p=0.036) less neutralizing antibodies than non-diabetics. Hypertension and obesity did not show significant changes in antibody titers. Taken together, both type-2 diabetic and non-diabetic individuals elicited strong immune responses to SARS-CoV-2 BNT162b2 mRNA vaccine; nonetheless, lower levels were seen in people with diabetes. Continuous monitoring of the antibody levels might be a good indicator to guide personalized needs for further booster shots to maintain adaptive immunity.
PCRMS: a database of predicted cis-regulatory modules and constituent transcription factor binding sites in genomes
Authors: Ni Pengyu , Su Zhengchang
Published: July 2021

More accurate and more complete predictions of cis-regulatory modules (CRMs) and constituent transcriptional factor (TF) binding sites (TFBSs) in genomes can facilitate characterizing functions of regulatory sequences. Here, we developed a database PCRMS (https://cci-bioinfo.uncc.edu) that stores highly accurate and unprecedentedly complete maps of predicted CRMs and TFBSs in the human and mouse genomes. The web interface allows the user to browse CRMs and TFBSs in an organism, find the closest CRMs to a gene, search CRMs around a gene, and find all TFBSs of a TF. PCRMS can be a useful resource for the research community to characterize regulatory genomes.
Tropomyosin isoforms segregate into distinct clusters on single actin filaments
Authors: Obeidy Peyman , Sobey Thomas , Nicovich Philip R. , Coster Adelle C. F. , Pandzic Elvis
Published: July 2021

Tropomyosins (Tpm) are rod-shaped proteins that interact head-to-tail to form a continuous polymer along both sides of most cellular actin filaments. Head-to-tail interaction between adjacent Tpm molecules and the formation of an overlap complex between them leads to the assembly of actin filaments with one type of Tpm isoform in time and space. Variations in the affinity of tropomyosin isoforms for different actin structures are proposed as a potential sorting mechanism. However, the detailed mechanisms of spatio-temporal sorting of Tpms remain elusive. In this study, we investigated the early intermediates during actin-tropomyosin filament assembly, using skeletal/cardiac Tpm isoform (Tpm1.1) and a cytoskeletal isoform (Tpm1.6) that differ only in the last 27 amino acids. We investigated how the muscle isoform Tpm1.1 and the cytoskeletal isoform Tpm1.6 nucleate domains on the actin filament and tested whether (1) recruitment is affected by the actin isoform (muscle vs cytoskeletal) and (2) whether there is specificity in recruiting the same isoform to a domain at these early stages. To address these questions, actin filaments were exposed to low concentrations of fluorescent tropomyosins in solution. The filaments were immobilized onto glass coverslips and the pattern of decoration was visualized by TIRF microscopy. We show that at the early assembly stage, tropomyosins formed multiple distinct fluorescent domains (here termed “cluster“) on the actin filaments. An automated image analysis algorithm was developed and validated to identify clusters and estimate the number of tropomyosins in each cluster. The analysis showed that tropomyosin isoform sorting onto an actin filament is unlikely to be driven by a preference for nucleating on the corresponding muscle or cytoskeletal actin isoforms but rather is facilitated by a higher probability of incorporating the same tropomyosin isoforms into an early assembly intermediate. We showed that the 27 amino acids at the end of each tropomyosin seem to provide enough molecular information for attachment of the same tropomyosin isoforms adjacent to each other on an actin filament. This results in the formation of homogeneous clusters composed of the same isoform rather than clusters with mixed isoforms.
PiRATeMC: A highly flexible, scalable, and affordable system for obtaining high quality video recordings for behavioral neuroscience
Authors: Centanni Samuel W. , Smith Alexander C.W.
Published: July 2021

With the recent development and rapidly accelerating adoption of machine-learning based rodent behavioral tracking tools such as DeepLabCut, there is an unmet need for a method of acquiring video data that is scalable, flexible, and affordable. Many experimenters use webcams, GoPros, or other commercially available cameras that are not only relatively expensive, but offer very little flexibility over recording parameters. These cameras are not ideal for recording many types of behavioral experiments, and can lead to suboptimal video quality. Furthermore when using relatively affordable commercially available products, it is a challenge, if not impossible, to synchronize multiple cameras with each other, or to interface with third-party equipment (for example, receiving a simple trigger to simultaneously start recording, or acting as a microcontroller for closed-loop experiments). We have developed an affordable ecosystem of behavioral recording equipment, PiRATeMC (Pi-basedRemoteAcquisitionTechnology forMotionCapture), that relies on Raspberry Pi Camera Boards that are able to acquire high quality recordings in bright light, low light, or dark conditions under infrared light. PiRATeMC offers users control over nearly every recording parameter, and can be fine-tuned to produce optimal video data in any behavioral arena. This setup can easily be scaled up and synchronously controlled in clusters via a self-contained network to record a large number of simultaneous behavioral sessions without burdening institutional network infrastructure. Furthermore, the Raspberry Pi is an excellent platform for novice and inexperienced programmers interested in using an open-source recording system, with a large online community that is very active in developing novel open-source tools. It easily interfaces with Arduinos and other microcontrollers, allowing simple synchronization and interfacing of video recording with nearly any behavioral equipment using GPIO pins to send or receive 3.3V or 5V (TTL) signals, I2C, or serial communication.
Taxonomic repositioning of twelveXanthomonas campestris, sevenXanthomonas axonopodisand onePseudomonas cissicolareference pathovars toXanthomonas citri
Authors: Bansal Kanika , Kumar Sanjeet , Patil Prabhu B.
Published: July 2021

Here on the basis of phylo-taxonogenomics criteria we present amended description of 20 pathovars toXanthomonas citrimajority (18/20) of which were first reported from India. 7/20 are currently classified asX. axonopodis, 12/20 asX. campestrisand 1/20 asPseudomonas cissicola. Here, we have generated genome sequence data for 4 pathovars and genomes of remaining 16 were used from the published data. Genome based investigation reveals that all these pathovars belong toX. citriand not toX. axonopodisorX. campestrisas previously reported. Present proposal is to aid in resolving the taxonomic confusion of theX. ctiripathovars and prevent future usage of invalid names.
Differential Interactions Between Human ACE2 and Spike RBD of SARS-CoV-2 Variants of Concern
Authors: Kim Seonghan , Liu Yi , Lei Zewei , Dicker Jeffrey , Cao Yiwei , Zhang X. Frank , Im Wonpil
Published: July 2021

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the current coronavirus disease 2019 (COVID-19) pandemic. It is known that the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2 interacts with the human angiotensin-converting enzyme 2 (ACE2) receptor, initiating the entry of SARS-CoV-2. Since its emergence, a number of SARS-CoV-2 variants have been reported, and the variants that show high infectivity are classified as the variants of concern according to the US CDC. In this study, we performed both all-atom steered molecular dynamics (SMD) simulations and microscale thermophoresis (MST) experiments to characterize the binding interactions between ACE2 and RBD of all current variants of concern (Alpha, Beta, Gamma, and Delta) and two variants of interest (Epsilon and Kappa). We report that the RBD of the Alpha (N501Y) variant requires the highest amount of force initially to be detached from ACE2 due to the N501Y mutation in addition to the role of N90-glycan, followed by Beta/Gamma (K417N/T, E484K, and N501Y) or Delta (L452R and T478K) variant. Among all variants investigated in this work, the RBD of the Epsilon (L452R) variant is relatively easily detached from ACE2. Our results combined SMD simulations and MST experiments indicate what makes each variant more contagious in terms of RBD and ACE2 interactions. This study could help develop new drugs to inhibit SARS-CoV-2 entry effectively.

Abstract Figure

TOC Graphic
Metabolite patterns of patients with peripheral arterial disease in response to exercise
Authors: Bellomo Tiffany R. , Tsao Noah L. , Johnston-Cox Hillary , Borkowski Kamil , Shakt Gabrielle , Judy Renae , Moore Jonni S. , Ractcliffe Sarah J. , Fiehn Oliver , Mohler Emile , Newman John W. , Damrauer Scott M.
Published: July 2021

Supervised exercise therapy (SET) is an effective intervention for symptomatic peripheral artery disease. Its effect on metabolism, measured by the circulating metabolome is not well understood. Participants underwent the Gardner graded treadmill test before and after SET and blood was sampled before and after each treadmill test. We tested the average association of metabolite levels with timing of blood draws. We used five models to identify metabolites or changes in metabolites at specific time points that associate with treadmill test performance or inter-individual variability in functional performance after SET. When analyzing individual time points, high levels of anandamide (AEA) before any exercise interventions were associated with shorter, or worse, walking time. Increased arachidonic acid (AA) and decreased levels of AA precursors (dihomo-γ-linolenic acid and diacylglycerol) before any exercise was associated with shorter walking times. Participants who tolerated large increases in AA during acute exercise had longer, or better, walking times before and after SET. We identified two pathways of relevance to individual response to SET: AEA synthesis may increase the activity at endocannabinoid receptors, resulting in worse treadmill test performance. SET may help train patients withstand higher levels of AA and inflammatory signaling, resulting in longer walking times.
Unraveling the regulatory role of miRNAs responsible for proanthocyanidin biosynthesis in the underutilized legume Psophocarpus tetragonolobus (L.) DC
Authors: Nayak Sagar Prasad , Prasad Priti , Singh Vinayak , Tripathi Abhinandan Mani , Bag Sumit Kumar , Mohanty Chandra Sekhar
Published: July 2021

The underutilized legume winged bean (Psophocarpus tetragonolobus (L.) DC.) is deposited with various degrees of proanathocyanidin (PA) or condensed tannin (CT) on its seed-coat. PA content of two different lines of P. tetragonolobus was estimated and accordingly they were denoted as high-proanthocyanidin containing winged bean (HPW) and low-proanthocyanidin containing winged bean (LPW). The level of PA-content varied as 59.23 mg/g in HPW and 8.68 mg/g in LPW when estimated through vanillin-HCl assay. The identification and quantification of catechin and epigallocatechin gallate were estimated in a range of 63.8 mg/g and 2.3mg/g respectively in HPW whereas only epigallocatechin gallate was reported in LPW line with a value of 3 mg/g. A comparative miRNA profiling of the leaf-tissues of these contrasting lines of P. tetragonolobus revealed a total of 139 mature miRNAs. Isoforms of known novel miRNAs were also identified in this study. Differentially expressed miRNAs e.g., miR156, miR396, miR4414b, miR4416c, miR894, miR2111 and miR5139 were validated through qRT-PCR analysis. Target prediction of the identified miRNAs especially miR156, miR396, miR4416b shows that they have a potential role in the proanthocyanidin biosynthesis of P. tetragonolobus. The study will provide the basis for understanding the role of miRNAs in regulating the biosynthesis of proanthocyanidin.
Important Docking study of Structure of Plasmodium falciparum thioredoxin reductase-thioredoxin complex: the case of potent drug Telatinib, a small molecule angiogenesis inhibitor
Authors: Ferrari Ivan Vito
Published: July 2021

Background

Over the last decades, malaria parasites have been rapidly developing resistance against antimalarial drugs, which underlines the need for novel drug targets. Thioredoxin reductase (TrxR) is crucially involved in redox homeostasis and essential for Plasmodium falciparum. In this communication, we report first time important Docking study by in Silico approach, using AutoDock Vina. After a selective analysis of over 300 drugs, processed with Pyrx (a Virtual Screening software into the active site of protein (ID PDB 4J56 Thioredoxin reductase 2 Chain A), we noticed excellent value of Binding Energy of Telatinib estimated by Pyrx software. These results are comparable to the crystallized ligand FAD (FLAVIN-ADENINE DINUCLEOTIDE) completed in the above-mentioned protein. Indeed, from the results of Autodock Vina, Telatinib an inhibitor of tyrosine kinases, has excellent a Binding affinity value, ca. −12 kcal/mol.
High consistency of trophic niches in soil microarthropod species (Oribatida, Acari) across soil depth and forest type
Authors: Lu Jing-Zhong , Cordes Peter , Maraun Mark , Scheu Stefan
Published: July 2021

Individuals of species may differ in resource use within and between populations. High intraspecific variation in resource use may hamper the co-existence of species in natural communities. To better understand the intraspecific variation in trophic niches of oribatid mites (Oribatida, Acari), we quantified stable isotope ratios of carbon (δ13C) and nitrogen (δ15N) of 40 Oribatida species that co-occurred in litter and soil of five forest types (European beech, Douglas fir, Norway spruce, two beech–conifer mixed forests) covering a range of environmental conditions. We found that although stable isotopes in litter and soil varied among forest types, δ13C and δ15N values of Oribatida and their trophic niches were remarkably stable between litter and soil, and also among forest types. We considered four trophic guilds of Oribatida representing the guild composition of the regional species pool; notably, trophic niches of Oribatida guilds also did not vary with soil depth. Furthermore, δ13C of Oribatida was more enriched (detrital shift) in European beech than in coniferous forests, but δ15N of Oribatida did not vary among forest types, indicating that basal resources of Oribatida are variable, but trophic positions are highly consistent across forest ecosystems. We conclude that trophic positions of Oribatida species and guilds are consistent across different forest types, and Oribatida species occupy virtually identical trophic niches irrespective of the soil depth they are colonizing. Overall, the results suggest that low intraspecific variability facilitates Oribatida niche differentiation and species coexistence.
Variability of pollen grains quality in oat amphiploids and their parental species
Authors: Tomaszewska Paulina , Kosina Romuald
Published: July 2021

The reproductive potential of oat species and their hybrid progeny (amphiploids) was evaluated during three vegetation seasons. Morphotypes and viability of pollen grains were described by means of correlations and regression, while relationships between taxa were analysed with the use of numerical taxonomy methods. Size of pollen grains varied between the growing seasons, but the relations between the taxa appeared to be stable. Viability of pollen grains was environmentally modified and showed no correlation with pollen length. In an ordination space, amphiploids were discriminated from parental species. In both group of plants, a positive correlation between the pollen size and the level of ploidy was maintained; however, along a regression line, amphiploids were located among species with a high level of ploidy and were extreme units deviating from the regression line. Developmental anomalies of pollen grains had a low frequency, with the formation of micrograins being the most common event. Such a pattern of development can prove that some pollen grains were chromosomally unbalanced. Anomalous morphotypes of pollen were more common in hybrid types than in species, including pollens with many poruses, which were found only in amphiploids. Frequencies of multiporate grains and micropollens were strongly correlated. In an ordination space, monoporate types (species) were discriminated from multiporate types (amphiploids). In general, the high level of pollen viability in amphiploids can prove their genomic stabilisation through many generations of their reproduction.
Modelling time evolution of in blood alcohol concentration
Authors: Gelabert Antoni Oliver
Published: July 2021

A theoretical model based on mass conservation is proposed to predict blood alcohol concentration (BAC) over time. The proposed model takes as input the body parameters, the data timing for each drink, as well as his alcoholic strength and ingested amount. Three test cases with variations are presented and discussed. The results given are obtained by solving numerically the equation proposed. The solution predicts a well located alcohol peak and a reasonable time of alcohol body cleaning. This model represents a first order approach to a complex problem. Similar scenarios, like, for instance, drug concentrations can be modelled by using the same concept. The proposed model has been implemented on easy-to-use program COGORZA, which source code is available online at https://github.com/tonibois/Cogorza.
IRI-CCE: A Platform for Evaluating CRISPR-based Base Editing Tools and Its Components
Authors: Shelake Rahul Mahadev , Pramanik Dibyajyoti , Kim Jae-Yean
Published: July 2021

Rapid assessment of CRISPR/Cas (Clustered Regularly Interspaced Short Palindromic Repeats/CRISPR associated Cas protein)-based genome editing (GE) tools and their components are critical aspects for successful applications in different organisms. In many bacteria, double-stranded breaks (DSBs) generated by CRISPR/Cas tool generally cause cell death due to the lack of an efficient non-homologous end-joining pathway and restricts its use. CRISPR-based DSB-free base editors (BEs) have been applied for precise nucleotide editing in bacteria, which does not need to make DSBs. However, optimization of newer BE tools in bacteria is challenging owing to the toxic effects of BE reagents expressed using strong promoters. Improved variants of two main BEs capable of converting C-to-T (CBE) and A-to-G (ABE) have been recently developed but yet to be tested in bacteria. Here, we report a platform for in vivo rapid investigation of CRISPR-BE components in Escherichia coli (IRI-CCE) comprising different combinations of promoters/terminators. We demonstrate the use of IRI-CEE to characterize different variants of CBEs (PmCDA1, evoCDA1, APOBEC3A) and ABEs (ABE8e, ABE9e), exhibiting that each independent BE has its specific editing pattern for a given target site and promoter type. Additionally, the IRI-CCE platform offers a rapid way to screen functional gRNAs. In summary, CRISPR-BE components expressed by promoters of different strengths in the IRI-CCE allow an analysis of various BE tools, including cloned biopart modules and gRNAs.
A General Biphasic-Bodyweight Model for Scaling Basal Metabolic Rate, Glomerular Filtration Rate and Drug Clearance from Birth to Adulthood
Authors: Hu Teh-Min
Published: July 2021

Understanding the maturation process of human physiology and metabolism has broad medical and pharmaceutical implications. Age and bodyweight are frequently considered as separate variables in modeling the dynamical changes of human organ functions and of drug clearance from birth to adulthood. The objective of this study is to propose a unified, continuous and bodyweight-only equation to quantify the changes of human basal metabolic rate (BMR), glomerular filtration rate (GFR) and drug clearance (CL) from infancy to adulthood. The BMR datasets were retrieved from a comprehensive historical database of male and female subjects (0.02 to 64 years). The CL datasets for 17 drugs and the GFR dataset were generated from age-incorporated maturation-and-growth models with reported parameter values. The model used in the simulation is independent of the proposed model. A statistical approach was used to simulate the model generated CL and GFR data for a hypothetical population with 26 age groups (ranging from 0 to 20 years). Besides, individual CL data for one drug, and sparse PBPK-modeled CL values for two drugs were also included for analysis. A 4-parameter, mixed-allometry equation with two power-law functions of bodyweight was proposed and evaluated as a general model using nonlinear regression and dimensionless analysis. All datasets universally reveal biphasic curves with two distinct linear segments on log-log plots. Compared with simple allometry, the biphasic model fits satisfactorily to all datasets (based on Akaike’s Information Criterion and residual plots). The biphasic equation consists of two reciprocal allometric terms that asymptotically determine the overall curvature. The fitting results show a superlinear scaling phase (slope >1; ca. 1.5 – 3.5) below the characteristic bodyweight at the phase transition; and above which, a sublinear scaling phase (slope <1; ca. 0.5 – 0.7) is evident. The phase-transition bodyweight is ranging from 5 to 20 kg (corresponding to 0.5 – 9 years) and the mean value is around 10 kg (∼2 years) for all data sets. The dimensionless analysis generalizes, and offers quantitative realization of, the maturation and growth process. In conclusion, the proposed mixed-allometry equation is a generic model that quantitatively describes the phase transition occurring in the human maturation process of BMR, GFR and drug CL.
MetaBinner: a high-performance and stand-alone ensemble binning method to recover individual genomes from complex microbial communities
Authors: Wang Ziye , Huang Pingqin , You Ronghui , Sun Fengzhu , Zhu Shanfeng
Published: July 2021

Binning is an essential procedure during metagenomic data analysis. However, the available individual binning methods usually do not simultaneously fully use different features or biological information. Furthermore, it is challenging to integrate multiple binning results efficiently and effectively. Therefore, we developed an ensemble binner, MetaBinner, which generates component results with multiple types of features and utilizes single-copy gene (SCG) information for k-means initialization. It then utilizes a two-step ensemble strategy based on SCGs to integrate the component results. Extensive experimental results over three large-scale simulated datasets and one real-world dataset demonstrate that MetaBinner outperforms other state-of-the-art individual binners and ensemble binners. MetaBinner is freely available athttps://github.com/ziyewang/MetaBinner.
The northern gene flow into southeastern East Asians inferred from genome-wide array genotyping
Authors: He Guanglin , Li Yingxiang , Zou Xing , Yeh Hui-Yuan , Tang Renkuan , Wang Peixin , Bai Jingya , Yang Xiaomin , Wang Zheng , Guo Jianxin , Chen Jinwen , Chen Jing , Yang Meiqing , Zhao Jing , Sun Jin , Zhu Kongyang , Ma Hao , Wang Rui , Yang Wenjiao , Hu Rong , Wei Lan-Hai , Hou Yiping , Wang Mengge , Chen Gang , Wang Chuan-Chao
Published: July 2021

The population history of Southeast China remains poorly understood due to the sparse sampling of present-day populations and far less modeling with ancient genomic data. We here newly reported genome-wide genotyping data from 207 present-day Han Chinese and Hmong-Mien-speaking She people from Fujian and Taiwan, southeast China. We co-analyzed with 66 early-Neolithic to Iron-Age ancient Fujian and Taiwan individuals obtained from literature to explore the genetic continuity and admixture based on the genetic variations of high-resolution time transect. We found the genetic differentiation between northern and southern East Asians defined by a north-south East Asian genetic cline and the studied southern East Asians were clustered in the southern end of this cline. We also found that southeastern coastal continental modern East Asians harbored the genetic differentiation with other southern Tai-Kadai, Hmong-Mien, Austronesian and Austroasiatic speakers, as well as geographically close Neolithic-to-Iron Age populations, but relatedly close to post-Neolithic Yellow River ancients, which suggested the influence of southward gene flow on the modern southern coastal gene pool. Besides, we also identified one new Hmong-Mien genetic cline in East Asia with the coastal Fujian She localizing at the intersection position between Hmong-Mien and Han clines in the principal component analysis. She people show stronger genetic affinity with southern East Asian indigenous populations with the main ancestry deriving from Hanben-related populations. The southeastern Han Chinese could be modeled with the primary ancestry deriving from the group related to the Yellow River Basin millet farmers and the remaining from groups related to southeastern ancient indigenous rice farmers, which was consistent with the northern China origin of modern southeastern Han Chinese and in line with the historically and archaeologically attested southward migrations of Han people and their ancestors. Interestingly, f4-statistics and three-way admixture model results showed both coastal ancient sources related to Austronesian speakers and inland ancient sources related to Austroasiatic speakers complexed the modern observed fine-scale genetic structure here. Our estimated north-south admixture time ranges based on the decay of the linkage disequilibrium spanned from the Bronze age to historic periods, suggesting the recent large-scale population migrations and subsequent admixture participated in the formation of modern Han in Southeast Asia.
Functional asymmetry and chemical reactivity of CsoR family persulfide sensors
Authors: Fakhoury Joseph N. , Zhang Yifan , Edmonds Katherine A. , Bringas Mauro , Luebke Justin L. , Gonzalez-Gutierrez Giovanni , Capdevila Daiana A. , Giedroc David P.
Published: July 2021

CstR is a persulfide-sensing member of the functionally diverse copper-sensitive operon repressor (CsoR) superfamily that regulates the bacterial response to hydrogen sulfide (H2S) and more oxidized reactive sulfur species (RSS) in Gram-positive pathogens. A cysteine thiol pair on CstR reacts with RSS to form a mixture of interprotomer di-, tri- and tetrasulfide crosslinks, which drives transcriptional derepression of CstR-regulated genes. In some bacteria, notably methicillin-resistant Staphylococcus aureus (MRSA), CstR and CsoR, a Cu(I)-sensor, exhibit no regulatory crosstalk in cells, despite maintaining an identical pair of cysteines. We report a sequence similarity network (SSN) analysis of the entire CsoR superfamily, together with the first crystallographic structure of a CstR protein and mass spectrometry-based kinetic profiling experiments to obtain new insights into the molecular basis of RSS specificity in CstRs. The more N-terminal cysteine is the attacking Cys in CstR and is far more nucleophilic than in a CsoR. This cysteine, C30 in SpCstR, is separated from the resolving thiol, C59’, by an Asn55’ wedge. Chemical reactivity experiments reveal a striking asymmetry of reactivity, preserved in all CstRs and with all oxidants tested; however, the distribution of crosslinked products varies markedly among CstRs. Substitution of N55 with Ala in SpCstR significantly impacts the distribution of species, despite adopting the same structure as the parent repressor. We show that CstRs react with hydrogen peroxide, a finding that contrasts sharply with other structurally distinct persulfide sensors from Gram-negative bacteria. This suggests that other factors may enhance the specificity and repressor activity of CstRs in cells.
Towards an integrative multi-omics workflow
Authors: Jeanneret Florian , Gazut Stéphane
Published: July 2021

The advent of high-throughput techniques has greatly enhanced biological discovery. Last years, analysis of multi-omics data has taken the front seat to improve physiological understanding. Handling functional enrichment results from various biological data raises practical questions.

We propose an integrative workflow to better interpret biological process insights in a multi-omics approach applied to breast cancer data from The Cancer Genome Atlas (TCGA) related to Invasive Ductal Carcinoma (IDC) and Invasive Lobular Carcinoma (ILC). Pathway enrichment by Over Representation Analysis (ORA) and Gene Set Enrichment Analysis (GSEA) has been conducted with both features information from differential expression analysis or selected features from multi-block sPLS-DA methods. Then, comprehensive comparisons of enrichment results have been carried out by looking at classical enrichment analysis, probabilities pooling by Stouffer’s Z scores method and pathways clustering in biological themes.

Our work shows that ORA enrichment with selected sPLS-DA features and pathways probabilities pooling by Stouffer’s method lead to enrichment maps highly associated to physiological knowledge of IDC or ILC phenotypes, better than ORA and GSEA with differential expression driven features.
Connectivity between the hippocampus and default mode network during the relief – but not elicitation – of curiosity supports curiosity-enhanced memory enhancements
Authors: Murphy Charlotte , Ranganath Charan , Gruber Matthias J.
Published: July 2021

Consistent with the idea that curiosity enhances information seeking, it has been shown that activity within both the dopaminergic circuit and hippocampus supports curiosity-enhanced learning. However, the role of whole-brain mechanisms involved in cognitive control (fronto-parietal network; FPN) and memory integration (default mode network; DMN) that might underpin curiosity states and their effects on memory remain elusive. We hypothesised that the FPN and DMN should distinguish between high- and low-curiosity conditions and be recruited more heavily for later remembered information associated with high-curiosity. Here, we used functional magnetic resonance imaging whilst participants completed a trivia paradigm, in which we presented trivia questions associated with high- and low-curiosity, followed by the associated answer. After a short delay, we tested memory for trivia answers. We adopted a network-based parcellation of the brain into subnetworks of the FPN and DMN to examine how neural activity within, and functional connectivity between, each subnetwork predicts curiosity-enhanced memory. Across elicitation and relief of curiosity, we found focal recruitment of FPNA and widespread recruitment of DMN subnetworks in support of curiosity and curiosity-enhanced memory. Most importantly, during the elicitation of curiosity, functional subcortical connectivity and across cortical networks, but not subcortical-cortical coupling, correlated with curiosity-enhanced memory. However, during the relief of curiosity, coupling between subcortical regions and DMNA emerged in support of curiosity-enhanced memory. Taken together, our results provide the first evidence about how neuromodulatory mechanisms via the hippocampal-dopaminergic circuit trigger states of curiosity and thereby communicate to higher-order cortical regions to facilitate curiosity-enhanced memory.

Significant statement

Does neural activity within, and functional connectivity between, the dopaminergic-hippocampal network, fronto-parietal network (FPN), and default mode network (DMN) underpin curiosity states and their effects on memory? Here, we show how the dopaminergic system together with the hippocampus interact specifically with subnetwork DMNA potentially reflecting how subcortical regions support the enhancement of memory intergration of semantic information associated with curiosity. As DMNA (the core DMN subnetwork) was also functionally coupled with the whole DMN network and the semantic control network (FPNA), these findings provide a plausible neuromodulatory mechanism through which hippocampal-dopaminergic input triggers curiosity and then communicates to higher-order brain regions via DMNA to facilitate curiosity-enhanced memory.
The cryo-EM structure of the chloroplast ClpP complex reveals an interaction with the co-chaperonin complex that inhibits ClpP proteolytic activity
Authors: Wang Ning , Wang Yifan , Zhao Qian , Zhang Xiang , Peng Chao , Zhang Wenjuan , Liu Yanan , Vallon Olivier , Schroda Michael , Cong Yao , Liu Cuimin
Published: July 2021

Protein homeostasis in plastids is strategically regulated by the protein quality control system involving multiple chaperones and proteases, among them the Clp protease. We determined the structure of the chloroplast ClpP complex from Chlamydomonas reinhardtiiby cryo-EM. ClpP contains two heptameric catalytic rings without any symmetry. The top ring contains one ClpR6, three ClpP4 and three ClpP5 subunits while the bottom ring is composed of three ClpP1C subunits and one each of the ClpR1-4 subunits. ClpR3, ClpR4 and ClpT4 subunits connect the two rings and stabilize the complex. The chloroplast Cpn11/20/23 co-chaperonin, a co-factor of Cpn60, forms a cap on the top of ClpP by protruding mobile loops into hydrophobic clefts at the surface of the top ring. The co-chaperonin repressed ClpP proteolytic activity in vitro. By regulating Cpn60 chaperone and ClpP protease activity, the co-chaperonin may play a role in coordinating protein folding and degradation in the chloroplast.
COPILOT: a Containerised wOrkflow for Processing ILlumina genOtyping daTa
Authors: Patel Hamel , Lee Sang-hyuck , Breen Gerome , Menzel Stephen , Ojewunmi Oyesola , Dobson Richard J.B
Published: July 2021

Background

The Illumina genotyping microarrays generate data in image format, which is processed by the platform-specific software GenomeStudio, followed by an array of complex bioinformatics analyses. This process can be time-consuming, lead to reproducibility errors, and be a daunting task for novice bioinformaticians.

Results

Here we introduce the COPILOT (Containerised wOrkflow for Processing ILlumina genOtyping daTa) protocol, which provides an in-depth and clear guide to process raw Illumina genotype data in GenomeStudio, followed by a containerised workflow to automate an array of complex bioinformatics analyses involved in a GWAS quality control (QC). The COPILOT protocol was applied to two independent cohorts consisting of 2791 and 479 samples genotyped on the Infinium Global Screening (GSA) array with Multi-disease (MD) drop-in (~750,000 markers) and the Infinium H3Africa consortium array (~2,200,000 markers) respectively. Following the COPILOT protocol, an average sample quality improvement of 1.24% was observed across sample call rates, with notable improvement for low-quality samples. For example, from the 3270 samples processed, 141 samples had an initial sample call rate below 98%, averaging 96.6% (95% CI 95.6-97.7%), which is considered below the acceptable sample call rate threshold for a typical GWAS analysis. However, following the COPILOT protocol, all 141 samples had a call rate above 98% after QC and averaged 99.6% (95% CI 99.5-99.7%). In addition, the COPILOT pipeline automatically identified potential data issues, including gender discrepancies, heterozygosity outliers, related individuals, and population outliers through ancestry estimation.

Conclusions

The COPILOT protocol makes processing Illumina genotyping data transparent, effortless and reproducible. The container is deployable on multiple platforms, improves data quality, and the end product is analysis-ready PLINK formatted data, with a comprehensive and interactive summary report to guide the user for further data analyses.