bluuebunny/crossref_metadata_2025 huggingface dataset:
On possible proxies of AGN light-curves cadence selection in future time domain surveys
Authors: Kovačević Andjelka B , Ilić Dragana , Popović Luka Č , Radović Viktor , Jankov Isidora , Yoon Ilsang , Caplar Neven , Čvorović-Hajdinjak Iva , Simić Saša
Published: June 2021

Motivated by upcoming photometric and spectroscopic surveys [Vera C. Rubin Observatory Legacy Survey of Space and Time (LSST), Manuakea Spectroscopic Explorer], we design the statistical proxies to measure the cadence effects on active galactic nuclei (AGNs) variability-observables [time-lags, periodicity, and structure-function (SF)]. We constructed a multiple-regression model to statistically identify the cadence-formal error pattern knowing AGN time-lags and periodicity from different surveys. We defined the simple metric for the SF’s properties, accounting for the ‘observed’ SF’s deviation relative to those obtained from the homogenously sampled light curves. We tested the regression models on different observing strategies: the optical data set of long light curves of eight AGN with peculiarities and the artificial data sets based on several idealized and LSST-like cadences. The SFs metric is assessed on synthetic data sets. The regression models (for both data types) predict similar cadences for time-lags and oscillation detection, whereas for light curves with low variability (${\sim}10{{\ \rm per\ cent}}$), cadences for oscillation detection differ. For higher variability (${\sim}20{{\ \rm per\ cent}}$), predicted cadences are larger than for $F_{var}\sim 10{{\ \rm per\ cent}}$. The predicted cadences are decreasing with redshift. SFs with dense and homogenous cadences are more likely to behave similarly. SFs with oscillatory signals are sensitive to the cadences, possibly impacting LSST-like operation strategy. The proposed proxies can help to select spectroscopic and photometric-surveys cadence strategies, and they will be tested further in larger samples of objects.
HIV-Infected Individuals on ART With Impaired Immune Recovery Have Altered Plasma Metabolite Profiles
Authors: Nyström Sofia , Govender Melissa , Yap Siew Hwei , Kamarulzaman Adeeba , Rajasuriar Reena , Larsson Marie
Published: June 2021

Background

Multiple host factors may influence immune reconstitution in HIV-infected people after the initiation of suppressive antiretroviral therapy (ART). Aberrant metabolic pathways have been reported in people with HIV (PWH) on ART. We hypothesized that alterations in plasma metabolites were associated with immune recovery following ART.

Methods

In this cross-sectional study, the plasma metabolomic profiles of PWH on ART were evaluated. PWH of slow and fast immune recovery were classified by increase in CD4 T cells following 2 years of ART. Targeted plasma metabolite profiling by liquid chromatography–mass spectrometry and gas chromatography–mass spectrometry to determine metabolite signatures for HIV recovery identified >200 metabolites.

Results

Notably, indole-3-propionic acid was downregulated during HIV, possibly reflecting impaired gastrointestinal epithelium homeostasis. The most important metabolite discriminating between the PWH with fast and slow immune recovery was cysteine. Upregulated cysteine and cysteine pathways may contribute to redox-balance maintenance and T-cell function in PWH with fast immune recovery. Additionally, serine and glycine metabolism and bile acid biosynthesis were the most perturbed metabolic pathways in PWH.

Conclusions

These results provide a starting point for developing biomarker candidates for immune recovery in PWH on ART and provide insight into the interplay of metabolism and immune response in HIV infection.
Infected Nonunion of the Tibia Due to Paenibacillus turicensis in a Healthy Young Adult After an All-Terrain Vehicle Accident
Authors: Schade Meredith , French Cristy N
Published: June 2021

We present the case of a 19-year-old man with an open fracture of the tibia and fibula secondary to an accident with an all-terrain vehicle. He underwent operative excisional irrigation, debridement, and fixation on the day of injury. His course was complicated by nonunion of the tibia fracture. Infection is a common factor in fracture nonunion, even in patients who receive appropriate surgical and antimicrobial management. Paenibacillus turicensis, an organism adapted to survive in the environment via spore formation, was responsible for nonunion in our patient. A brief discussion of this unusual organism, fracture nonunion, and the role of infection in etiology of nonunion follows.
Validation of fetal microchimerism after pregnancy in the ovine using qPCR
Authors: Brown J Alison , Niland Erika S , Pierce Natalie L , Taylor J Bret
Published: June 2021

Fetal microchimerism has been detected in maternal tissues of humans and rodents during and after pregnancy. Studies focusing on fetal DNA transfer to maternal tissues in domestic animals are limited, especially in sheep. Fetal ram DNA was observed in the maternal circulation during pregnancy, but it is not known if this chimerism persists in soft tissues after parturition. The objectives of this exploratory study were to: 1) determine if male fetal DNA is detectable in soft tissues of mature ewes after parturition and if so, determine if detection repeatability differed with lifetime offspring sex ratio and 2) determine if male fetal DNA was present in soft tissues of yearling (primiparous) ewes shortly after parturition. Eight mature (open, non-lactating) and 8 yearling (primiparous, periparturient) Rambouillet ewes were used. Mature ewes (5- to 7-yr old) had given birth to primarily 82% males (n = 4) or 71% female (n = 4) over a lifetime. Yearling ewes had birthed either a singleton male (n = 4) or female (n = 4) lambs. DNA was extracted from 10 and 11 different soft tissues from the mature and yearling ewes, respectively. Real-time PCR (qPCR) was used to identify the presence of the SRY gene in each tissue sample. Male DNA was detected in the brain and liver from one mature open ewe that had given birth to two males and six females during her lifetime. In younger ewes that gave birth to a ram lamb, male DNA was observed in the thyroid of one ewe and the pancreas and brain of a second ewe. Male DNA was detected in the ovary of one ewe that had given birth to a female lamb. Based on these data, we suggest fetal microchimerism in soft maternal tissues is possible in sheep and may remain after pregnancy has ended. The detection repeatability of male fetal DNA was not associated with sex ratio of lifetime offspring. Male DNA was observed in maternal soft tissues collected shortly after parturition. The greater detection of fetal male DNA found in younger ewes shortly after parturition may be due to not having enough time for fetal DNA clearance to occur. Future studies are warranted to further study XY chimerism in maternal tissues of the ewe and its potential role in ovine physiology.
OsRAM2 Function in Lipid Biosynthesis Is Required for Arbuscular Mycorrhizal Symbiosis in Rice
Authors: Liu Ying-Na , Liu Cheng-Chen , Zhu An-Qi , Niu Ke-Xin , Guo Rui , Tian Li , Wu Ya-Nan , Sun Bo , Wang Bin
Published: June 2021

Arbuscular mycorrhiza (AM) is a mutualistic symbiosis formed between most land plants and Glomeromycotina fungi. During symbiosis, plants provide organic carbon to fungi in exchange for mineral nutrients. Previous legume studies showed that the required for arbuscular mycorrhization2 (RAM2) gene is necessary for transferring lipids from plants to AM fungi (AMF) and is also likely to play a “signaling” role at the root surface. To further explore RAM2 functions in other plant lineages, in this study, two rice (Oryza sativa) genes, OsRAM2 and OsRAM2L, were identified as orthologs of legume RAM2. Examining their expression patterns during symbiosis revealed that only OsRAM2 was strongly upregulated upon AMF inoculation. CRISPR/Cas9 mutagenesis was then performed to obtain three Osram2 mutant lines (-1, -2, and -3). After inoculation by AMF Rhizophagus irregularis or Funneliformis mosseae, all of the mutant lines showed extremely low colonization rates and the rarely observed arbuscules were all defective, thus supporting a conserved “nutritional” role of RAM2 between monocot and dicot lineages. As for the signaling role, although the hyphopodia numbers formed by both AMF on Osram2 mutants were indeed reduced, their morphology showed no abnormality, with fungal hyphae invading roots successfully. Promoter activities further indicated that OsRAM2 was not expressed in epidermal cells below hyphopodia or outer cortical cells enclosing fungal hyphae but instead expressed exclusively in cortical cells containing arbuscules. Therefore, this suggested an indirect role of RAM2 rather than a direct involvement in determining the symbiosis signals at the root surface.

[Formula: see text] The author(s) have dedicated the work to the public domain under the Creative Commons CC0 “No Rights Reserved” license by waiving all of his or her rights to the work worldwide under copyright law, including all related and neighboring rights, to the extent allowed by law, 2022.
Ligamentum-preserved/Temporary Preserved Minimally Invasive Transforaminal Lumbar Interbody Fusion for Lumbar Spondylolisthesis: Technical Note and 2-year Follow-up
Authors: Wang Lianlei , Li Hao , Zhao Yiwei , Yuan Suomao , Tian Yonghao , Liu Xinyu
Published: June 2021

Study Design.

Prospective study.

Objective.

The aim of this study was to prospectively assess the clinical outcomes of modified minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) for the treatment of singlesegment lumbar spondylolisthesis.

Summary of Background Data.

MIS-TLIF is a safe and effective procedure in the treatment of lumbar degenerative disease. To avoid durotomy and nerve root injury, we modified the surgical order of MIS-TLIF such that the interbody fusion procedure was performed before the decompression procedure.

Methods.

One hundred thirty-nine patients with single-segment lumbar spondylolisthesis were separated into two groups. Sixty-seven patients underwent modified MIS-TLIF (group A). In group B, 72 patients underwent routine MIS-TLIF. The Japanese Orthopedic Association (JOA) score and the visual analogue scale (VAS) scores for lower back pain (LBP) and leg pain were assessed during the postoperative follow-up, and the lumbar interbody fusion rate was evaluated by CT scanning.

Results.

The mean operative time, incision length, average blood loss, and incision pain level were not significantly different (P 
> 0.05) between the two groups. No nerve root or dural injuries were observed in group A. In group B, there were two cases of dural injury and three cases of nerve root injury. One patient experienced temporary numbness and weakness on dorsiflexion of the foot, which recovered in 3 months. No differences were identified between the two groups when postoperative JOA scores, back pain, leg pain VAS scores, or the lumbar interbody fusion rate.

Conclusion.

Both methods are effective in the treatment of lumbar degenerative disease. Modified MIS-TLIF is a safe and effective procedure that can significantly reduce the occurrence of injury to the dura and nerve root during decompression and the interbody fusion procedure.

Level of Evidence: 3
Ambulatory blood pressure changes with lung ultrasound-guided dry-weight reduction in hypertensive hemodialysis patients: 12-month results of a randomized controlled trial
Authors: Loutradis Charalampos , Sarafidis Pantelis A. , Ekart Robert , Tsouchnikas Ioannis , Papadopoulos Christodoulos , Kamperidis Vasileios , Alexandrou Maria Eleni , Ferro Charles J. , Papagianni Aikaterini , London Gerard , Mallamaci Francesca , Zoccali Carmine
Published: June 2021

Objectives:

Hypertension is highly prevalent and independently associated with adverse outcomes in patients undergoing hemodialysis. Volume overload is the main mechanism of increased blood pressure (BP) in these individuals. This study examines the long-term effects of dry-weight reduction with a standardized lung-ultrasound (US)-guided strategy on ambulatory BP in hypertensive hemodialysis patients.

Methods:

This is the report of the 12-month follow-up of a randomized controlled trial in 71 clinically euvolemic, hemodialysis patients with hypertension. Patients were randomized to dry-weight reduction guided by prehemodialysis lung ultrasound and to standard care. A 48-h ambulatory BP monitoring (ABPM) was performed in all study participants at baseline and after 12 months.

Results:

During follow-up, a greater proportion of patients in the active group underwent dry-weight reduction compared with the control group (71.4% vs. 22.2%; P < 0.001). The number of lung US-B lines (a metric of lung water) reduced in the active (−4.83 ± 13.73) and increased in the control arm (+5.53 ± 16.01; P = 0.005) paralleling dry-weight changes (−1.68 ± 2.38 vs. 0.54 ± 2.32 kg; P < 0.001). At 12 months, 48-h systolic BP (136.19 ± 14.78 vs. 130.31 ± 13.57 mmHg; P = 0.034) and diastolic BP (80.72 ± 9.83 vs. 76.82 ± 8.97 mmHg; P = 0.008) were lower compared to baseline in the active but similar in the control group. Changes in 48-h systolic BP (−7.78 ± 13.29 vs. −0.10 ± 14.75 mmHg; P = 0.021) were significantly greater in the active compared to the control group. The proportion of patients experiencing ≥1 episode of intradialytic hypotension was nominally lower in the active group (71.4% vs. 88.9%, P = 0.065).

Conclusions:

Lung-US-guided dry-weight reduction can effectively and safely decrease ambulatory BP levels in the long-term.
Associations of serum apolipoprotein A1, B levels and their ratio with blood pressure in Chinese adults with coronary artery disease
Authors: Dong Hongli , Yang Xuemei , Zhang Yaju , Hu Ping , Liu Yang , Liang Shuxia
Published: June 2021

Objective

We examined the relationships of apolipoprotein A1 (ApoA1), ApoB levels and ApoB/A1 ratio with blood pressure (BP) in Chinese adults with coronary artery disease (CAD).

Methods

This cross-sectional study included 4921 adults with CAD. SBP, DBP, serum ApoA1 and ApoB levels were measured. The associations between Apo and BP were assessed by analyses of covariance.

Results

Serum ApoA1 was inversely associated with BP, whereas ApoB and the ApoB/A1 ratio exhibited positive associations with BP. For all subjects, a higher ApoA1 level was associated with lower SBP. Subjects in the fourth quartile for ApoA1 exhibited − 2.85 and − 2.63% lower DBP and mean arterial pressure (MAP), respectively than those in the third quartile. In contrast, higher ApoB and ApoB/A1 ratios were associated with higher SBP, DBP and MAP. The mean differences between ApoB quartiles 4 and 1 were 1.54% for SBP, 2.92% for DBP and 2.29% for MAP. The mean differences between the ApoB/A1 ratio quartiles 4 and 1 were 1.94% for SBP, 3.53% for DBP and 2.80% for MAP. In analyses stratified by gender, graded and inverse associations of ApoA1 with SBP, DBP and MAP were observed in both men and women, but positive associations were observed for ApoB and the ApoB/A1 ratio. Path analysis showed that BMI mediated the associations between ApoB and the ApoB/A1 ratio and SBP.

Conclusions

In general, serum ApoA1 was inversely associated with BP in persons with CAD. In contrast, serum ApoB and the ApoB/A1 ratio were positively associated with BP, and these associations were mediated by BMI.
Aphasia Induced by Infratentorial Ischemic Stroke: Two Case Reports
Authors: Inatomi Yuichiro , Nakajima Makoto , Yonehara Toshiro
Published: June 2021

Aphasia induced by an infratentorial stroke has rarely been reported, and its mechanism has not been fully identified. We evaluated two individuals who had been admitted to Saiseikai Kumamoto Hospital in Kumamoto, Japan, due to acute ischemic stroke in order to determine whether their aphasia was induced by an infratentorial stroke. The first patient, a 59-year-old man with a history of left parietal embolic stroke with very mild sequelae of anomia, developed Wernicke’s aphasia, nonfluent speech, and right limb ataxia as a result of the stroke. The second patient, a 76-year-old woman with a history of chronic renal failure, experienced transcortical sensory aphasia and right one-and-a-half syndrome as a result of the stroke. Both patients’ recent ischemic lesions were limited to the right cerebellar hemisphere and the right medial portion of the midbrain. However, SPECT showed low-uptake lesions in both patients’ left cerebral hemisphere that did not include the recent ischemic lesions but that had spread to an extent that was difficult to be explained by the old or recent ischemic lesions and that might be responsible for their recent aphasia. We believe that the aphasia experienced by these two patients may have been caused by crossed cerebello-cerebral diaschisis.
Structure determination of oleanolic and ursolic acids: a combined density functional theory/vibrational spectroscopy methodology
Authors: Gómez-Pulido Luz D. M. , González-Cano Rafael C. , Domínguez Eva , Heredia Antonio
Published: June 2021

Raw samples of oleanolic and ursolic acids, a class of terpenoid acids mainly found in the leaf and fruit cuticles of some plant species, can be defined as a blend of clusters of different conformers aggregated in dimers and tetramers by means of hydrogen bonds and stabilized by non-electrostatic interactions.
A local-realistic model for quantum theory
Authors: Raymond-Robichaud Paul
Published: June 2021

We provide a rigorous definition of local realism. We show that the universal wave function cannot be a complete description of a local reality. Finally, we construct a local-realistic model for quantum theory.
Nonlinear stochastic modelling with Langevin regression
Authors: Callaham J. L. , Loiseau J.-C. , Rigas G. , Brunton S. L.
Published: June 2021

Many physical systems characterized by nonlinear multiscale interactions can be modelled by treating unresolved degrees of freedom as random fluctuations. However, even when the microscopic governing equations and qualitative macroscopic behaviour are known, it is often difficult to derive a stochastic model that is consistent with observations. This is especially true for systems such as turbulence where the perturbations do not behave like Gaussian white noise, introducing non-Markovian behaviour to the dynamics. We address these challenges with a framework for identifying interpretable stochastic nonlinear dynamics from experimental data, using forward and adjoint Fokker–Planck equations to enforce statistical consistency. If the form of the Langevin equation is unknown, a simple sparsifying procedure can provide an appropriate functional form. We demonstrate that this method can learn stochastic models in two artificial examples: recovering a nonlinear Langevin equation forced by coloured noise and approximating the second-order dynamics of a particle in a double-well potential with the corresponding first-order bifurcation normal form. Finally, we apply Langevin regression to experimental measurements of a turbulent bluff body wake and show that the statistical behaviour of the centre of pressure can be described by the dynamics of the corresponding laminar flow driven by nonlinear state-dependent noise.
Times of arrival and gauge invariance
Authors: Das Siddhant , Nöth Markus
Published: June 2021

We revisit the arguments underlying two well-known arrival-time distributions in quantum mechanics, viz., the Aharonov–Bohm–Kijowski (ABK) distribution, applicable for freely moving particles, and the quantum flux (QF) distribution. An inconsistency in the original axiomatic derivation of Kijowski’s result is pointed out, along with an inescapable consequence of the ‘negative arrival times’ inherent to this proposal (and generalizations thereof). The ABK free-particle restriction is lifted in a discussion of an explicit arrival-time set-up featuring a charged particle moving in a constant magnetic field. A natural generalization of the ABK distribution is in this case shown to be critically gauge-dependent. A direct comparison to the QF distribution, which does not exhibit this flaw, is drawn (its acknowledged drawback concerning the quantum backflow effect notwithstanding).
Evolutionary drivers, morphological evolution and diversity dynamics of a surviving mammal clade: cainotherioids at the Eocene–Oligocene transition
Authors: Weppe R. , Orliac M. J. , Guinot G. , Condamine F. L.
Published: June 2021

The Eocene–Oligocene transition (EOT) represents a period of global environmental changes particularly marked in Europe and coincides with a dramatic biotic turnover. Here, using an exceptional fossil preservation, we document and analyse the diversity dynamics of a mammal clade, Cainotherioidea (Artiodactyla), that survived the EOT and radiated rapidly immediately after. We infer their diversification history from Quercy Konzentrat–Lagerstätte (south-west France) at the species level using Bayesian birth–death models. We show that cainotherioid diversity fluctuated through time, with extinction events at the EOT and in the late Oligocene, and a major speciation burst in the early Oligocene. The latter is in line with our finding that cainotherioids had a high morphological adaptability following environmental changes throughout the EOT, which probably played a key role in the survival and evolutionary success of this clade in the aftermath. Speciation is positively associated with temperature and continental fragmentation in a time-continuous way, while extinction seems to synchronize with environmental change in a punctuated way. Within-clade interactions negatively affected the cainotherioid diversification, while inter-clade competition might explain their final decline during the late Oligocene. Our results provide a detailed dynamic picture of the evolutionary history of a mammal clade in a context of global change.
Long-term gene–culture coevolution and the human evolutionary transition
Authors: Waring Timothy M. , Wood Zachary T.
Published: June 2021

It has been suggested that the human species may be undergoing an evolutionary transition in individuality (ETI). But there is disagreement about how to apply the ETI framework to our species, and whether culture is implicated as either cause or consequence. Long-term gene–culture coevolution (GCC) is also poorly understood. Some have argued that culture steers human evolution, while others proposed that genes hold culture on a leash. We review the literature and evidence on long-term GCC in humans and find a set of common themes. First, culture appears to hold greater adaptive potential than genetic inheritance and is probably driving human evolution. The evolutionary impact of culture occurs mainly through culturally organized groups, which have come to dominate human affairs in recent millennia. Second, the role of culture appears to be growing, increasingly bypassing genetic evolution and weakening genetic adaptive potential. Taken together, these findings suggest that human long-term GCC is characterized by an evolutionary transition in inheritance (from genes to culture) which entails a transition in individuality (from genetic individual to cultural group). Thus, research on GCC should focus on the possibility of an ongoing transition in the human inheritance system.
GRP78 binds SARS-CoV-2 Spike protein and ACE2 and GRP78 depleting antibody
blocks viral entry and infection in vitro
Authors: Carlos Anthony J. , Ha Dat P. , Yeh Da-Wei , Van Krieken Richard , Gill Parkash , Machida Keigo , Lee Amy S.
Published: June 2021

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the
causative agent of the current COVID-19 global pandemic, utilizes the host
receptor angiotensin-converting enzyme 2 (ACE2) for viral entry. However, other
host factors may also play major roles in viral infection. Here we report that
the stress-inducible molecular chaperone GRP78 can form a complex with the
SARS-CoV-2 Spike protein and ACE2 intracellularly and on the cell surface, and
that the substrate binding domain of GRP78 is critical for this function.
Knock-down of GRP78 by siRNA dramatically reduced cell surface ACE2 expression.
Treatment of lung epithelial cells with a humanized monoclonal antibody
(hMAb159), selected for its ability to cause GRP78 endocytosis and its safe
clinical profile in preclinical models, reduces cell surface ACE2 expression,
SARS-CoV-2 Spike-driven viral entry, and significantly inhibits SARS-CoV-2
infection in vitro. Our data suggest that GRP78 is an
important host auxiliary factor for SARS-CoV-2 entry and infection and a
potential target to combat this novel pathogen and other viruses that utilize
GRP78.
Genomic epidemiology and associated clinical outcomes of a SARS-CoV-2 outbreak in a general adult hospital in Quebec
Authors: Paré Bastien , Rozendaal Marieke , Morin Sacha , Poujol Raphaël , Mostefai Fatima , Grenier Jean-Christophe , Kaufmann Léa , Xing Henry , Sanchez Miguelle , Yechouron Ariane , Racette Ronald , Hussin Julie , Wolf Guy , Pavlov Ivan , Smith Martin A.
Published: June 2021

The first confirmed case of COVID-19 in Quebec, Canada, occurred at Verdun Hospital on February 25, 2020. A month later, a localized outbreak was observed at this hospital. We performed tiled amplicon whole genome nanopore sequencing on nasopharyngeal swabs from all SARS-CoV-2 positive samples from 31 March to 17 April 2020 in 2 local hospitals to assess the viral diversity of the outbreak. We report 264 viral genomes from 242 individuals (both staff and patients) with associated clinical features and outcomes, as well as longitudinal samples, technical replicates and the first publicly disseminated SARS-CoV-2 genomes in Quebec. Viral lineage assessment identified multiple subclades in both hospitals, with a predominant subclade in the Verdun outbreak, indicative of hospital-acquired transmission. Dimensionality reduction identified two subclades that evaded supervised lineage assignment methods, including Pangolin, and identified certain symptoms (headache, myalgia and sore throat) that are significantly associated with favorable patient outcomes. We also address certain limitations of standard SARS-CoV-2 bioinformatics procedures, notably when presented with multiple viral haplotypes.
Epidemiological profile study of COVID-19 in West African countries: Nigeria, Senegal, Mauritania, Cape Verde and Mali
Authors: Ba Mouhamadou Faly , Diop Boly , Bassoum Oumar , Sougou Ndèye Marème , Niang Khadim , Bonnet Emmanuel , Ridde Valéry , Faye Adama
Published: June 2021

Introduction

The COVID-19 pandemic was first reported in West Africa on 27 February 2020 in Nigeria. It subsequently spread to other countries in the region. The objective of this study is to analyze the epidemiological profile of COVID-19 in West Africa from the first reported case to 31 January 2021.

Method

We publicly used available data from reliable sources and from the “COVID-19R” package. We used epidemic curves to describe the trends in the daily evolution of confirmed cases and deaths of COVID-19 in West Africa and specifically in the five countries. The reproduction rate and evolution rates were calculated from these trends.

Results

As of 31 January 2021, West Africa had 342,938 confirmed cases of COVID-19 with 4,496 deaths. Nigeria had 131,242 cases with 1,586 deaths. Senegal had 26,523 cases with 628 deaths. The case-fatality rate in Mali was 4.08% and the attack rate in Cape Verde was 2587 cases per 100,000 inhabitants. In Nigeria, Senegal, Mauritania and Mali, the epidemic curves supported by the evolution rates showed an increase in confirmed cases and deaths of COVID-19 during December 2020 and January 2021 compared to the last two months. The effective reproduction rates (Re) inferred a slowdown in virus transmission (Re < 1) in these countries except for Senegal.

Conclusion

The results showed that COVID-19 was still circulating in some West African countries in late 2020 and early 2021. By improving the health system and with context-specific public health interventions and vaccination, these countries should effectively control COVID-19.
TransportTools: a library for high-throughput analyses of internal voids in biomolecules and ligand transport through them
Authors: Brezovsky Jan , Thirunavukarasu Aravind Selvaram , Surpeta Bartlomiej , Sequeiros-Borja Carlos Eduardo , Mandal Nishita , Sarkar Dheeraj Kumar , Dongmo Foumthuim Cedrix J. , Agrawal Nikhil
Published: June 2021

Information regarding pathways through voids in biomolecules and their roles in ligand transport is critical to our understanding of the function of many biomolecules. Recently, the advent of high-throughput molecular dynamics simulations has enabled the study of these pathways, and of rare transport events. However, the scale and intricacy of the data produced requires dedicated tools in order to conduct analyses efficiently and without excessive demand on users. To fill this gap, we developed the TransportTools, which allows the investigation of pathways and their utilization across large, simulated datasets. TransportTools also facilitates the development of custom-made analyses. TransportTools is implemented in Python3 and distributed as pip and conda packages. The source code is available at https://github.com/labbit-eu/transport_tools.
Inducible and reversible inhibition of miRNA-mediated gene repression in vivo
Authors: La Rocca Gaspare , King Bryan , Shui Bing , Li Xiaoyi , Zhang Minsi , Akat Kemal , Ogrodowski Paul , Mastroleo Chiara , Chen Kevin , Cavalieri Vincenzo , Ma Yilun , Anelli Viviana , Betel Doron , Vidigal Joana A. , Tuschl Thomas , Meister Gunter , Thompson Craig B. , Lindsten Tullia , Haigis Kevin M. , Ventura Andrea
Published: June 2021

Although virtually all gene networks are predicted to be controlled by miRNAs, the contribution of this important layer of gene regulation to tissue homeostasis in adult animals remains unclear. Gain and loss of function experiments have provided key insights into the specific function of individual miRNAs, but effective genetic tools to study the functional consequences of global inhibition of miRNA activity in vivo are lacking. Here we report the generation and characterization of a genetically engineered mouse strain in which miRNA-mediated gene repression can be reversibly inhibited without affecting miRNA biogenesis or abundance. We demonstrate the usefulness of this strategy by investigating the consequences of acute inhibition of miRNA function in adult animals. We find that different tissues and organs respond differently to global loss of miRNA function. While miRNA-mediated gene repression is essential for the homeostasis of the heart and the skeletal muscle, it is largely dispensable in the majority of other organs. Even in tissues where it is not required for homeostasis, such as the intestine and hematopoietic system, miRNA activity can become essential during regeneration following acute injury. These data support a model where many metazoan tissues primarily rely on miRNA function to respond to potentially pathogenic events.
Experimental Urolithiasis Model to assess Phyto-fractions as Anti-lithiatic Contributors: A Herbaceutical Approach
Authors: Devi Aishwarya Tripurasundari , Yashaswini N , Zameer Farhan , Nagendra Prasad MN
Published: June 2021

Life-style disorders have bought a serious burden on the maintenance of health in animals and humans. Lithiasis specifically nephro- and urolithiasis is no exception and needs urgent attention. Currently, only semi-invasive and surgical methods are widely employed which leads to trauma and reoccurrence of kidney stones. Hence complementary and alternative herbal medicine could pave newer ways in exploring anti-lithiatic contributors. The current study attempts to screen twenty herbal hot aqueous leaf extracts for assessing their antioxidant potency (anti-stress) and efficiency against urolithiasis in an experimental calcium oxalate-inducedin vitro(chicken egg membrane) model. The study was further validated byIn silicomolecular docking studies using the Molegro software package on enzymatic biomarkers involved in scavenging oxidants in the host and regulating oxalate metabolism at a cellular level. Among the screened botanicalsKalanchoe pinnataexhibited promising results compared to the standard chemical (potassium-magnesium citrate) and phyto-formulation drug (cystone) currently used by clinicians for treating urolithiasis. The phytochemical profiling (qualitative and quantitative) and virtual studies indicated rutin fromKalanchoe pinnataas a potential candidate for preventing kidney stones. The results of the current study provide better insights into the design and development of newer, smart, and cost-effective herbal therapeutics making food as medicine.

Graphical Abstract
Genomic Abelian Finite Groups
Authors: Sanchez Robersy , Barreto Jesús
Published: June 2021

Experimental studies reveal that genome architecture splits into DNA sequence domains suggesting a well-structured genomic architecture, where, for each species, genome populations are integrated by individual mutational variants. Herein, we show that, consistent with the fundamental theorem of Abelian finite groups, the architecture of population genomes from the same or closed related species can be quantitatively represented in terms of the direct sum of homocyclic Abelian groups of prime-power order defined on the genetic code and on the set of DNA bases, where populations can be stratified into subpopulations with the same canonical decomposition intop-groups. Through concrete examples we show that the architectures of current annotated genomic regions including (but not limited to) transcription factors binding-motif, promoter regulatory boxes, exon and intron arrangement associated to gene splicing are subjects for feasible modeling as decomposable Abelianp-groups. Moreover, we show that the epigenomic variations induced by diseases or environmental changes also can be represented as an Abelian group decomposable into homocyclic Abelianp-groups. The nexus between the direct sum of homocycle Abelianp-groups and the endomorphism ring paved the ways to unveil unsuspected stochastic-deterministic logical propositions ruling the ensemble of genomic regions. Our study aims to set the basis for concrete applications of the theory in computational biology and bioinformatics. Consistently with this goal, a computational tool designed for the analysis of fixed mutational events in gene/genome populations represented as endomorphisms and automorphisms is provided. Results suggest that complex local architectures and evolutionary features no evident through the direct experimentation can be unveiled through the analysis of the endomorphism ring and the subsequent application of machine learning approaches for the identification of stochastic-deterministic logical rules (reflecting the evolutionary pressure on the region) constraining the set of possible mutational events (represented as homomorphisms) and the evolutionary paths.
Imprecise recombinant viruses evolve via a fitness-driven, iterative process of polymerase template-switching events
Authors: Bentley Kirsten , Alnaji Fadi G. , Woodford Luke , Jones Siân , Woodman Andrew , Evans David
Published: June 2021

Recombination is a common feature of many positive-strand RNA viruses, playing an important role in virus evolution. However, to date, there is limited understanding of the mechanisms behind the process. Utilising in vitro assays, we have previously shown that the template-switching event of recombination is a random and ubiquitous process that often leads to recombinant viruses with imprecise genomes containing sequence duplications. Subsequently, a process termed resolution, that has yet to be mechanistically studied, removes these duplicated sequences resulting in a virus population of wild type length genomes. Using defined imprecise recombinant viruses together with Oxford Nanopore and Illumina high throughput next generation sequencing technologies we have investigated the process of resolution. We show that genome resolution involves subsequent rounds of template-switching recombination with viral fitness resulting in the survival of a small subset of recombinant genomes. This alters our previously held understanding that recombination and resolution are independent steps of the process, and instead demonstrates that viruses undergo frequent and continuous recombination events over a prolonged period until the fittest viruses, predominantly those with wild type length genomes, dominate the population.

Author Summary

Viruses with positive-sense RNA genomes, such as poliovirus, have several mechanisms by which they evolve. One of these is the process of recombination involving the large-scale exchange of genetic information. Recombination occurs during replication when the viral polymerase switches from copying one genome to another. However, the polymerase does not always accurately switch between the two, resulting in sequence duplications or deletions, and genomes that are referred to as imprecise. Over multiple rounds of replication sequence duplications are lost and genomes are resolved to wild type length, but it is unclear how this occurs. Here we used synthetic polioviruses containing defined sequence duplications to determine that the genome population undergoes repeated rounds of recombination until sequence duplications are lost and viruses with precise, wild type length genomes are selected for. This selection is based on the overall fitness of the virus population, with less fit imprecise viruses evolving more quickly. Our study suggests that recombination is a continual process where virus fitness drives the selection of a small subset of recombinant variants. These data are important for understanding how novel viruses evolve via recombination and how this process can be blocked to prevent novel and dangerous pathogens from arising.
Endomembrane systems are reorganized by ORF3a and Membrane (M) of SARS-CoV-2
Authors: Lee Yun-Bin , Jung Minkyo , Kim Jeesoo , Kang Myeong-Gyun , Kwak Chulhwan , Kim Jong-Seo , Mun Ji-Young , Rhee Hyun-Woo
Published: June 2021

The endomembrane reticulum (ER) is largely reorganized by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 ORF3a and membrane (M) protein expression affects ER-derived structures including cubic membrane and double membrane vesicles in coronavirus-infected cells; however, the molecular mechanisms underlying ER remodeling remain unclear. We introduced a “plug and playable” proximity labeling tool (TurboID-GBP) for interactome mapping of GFP-tagged SARS-CoV-2 ORF3a and M proteins. Through mass spectrometric identification of the biotinylated lysine residue (K+226 Da) on the viral proteins using Spot-TurboID workflow, 117 and 191 proteins were robustly determined as ORF3a and M interactomes, respectively, and many, including RNF5 (E3 ubiquitin ligase), overlap with the mitochondrial-associated membrane (MAM) proteome. RNF5 expression was correlated to ORF3a ubiquitination. MAM formation and secreted proteome profiles were largely affected by ORF3a expression. Thus, SARS-CoV-2 may utilize MAM as a viral assembly site, suggesting novel anti-viral treatment strategies for blocking viral replication in host cells.

Highlights

SARS-CoV-2 proteins ORF3a and M alter endoplasmic reticulum proteome profile

ORF3a affects mitochondrial-associated membrane formation

SARS-CoV-2 may utilize mitochondrial-associated membrane as viral assembly site

ORF3a and M interactome proteins may serve as targets for COVID-19 treatment

eTOC Blurb

ER remodelling by SARS-CoV-2 ORF3a and M protein
Two marine GH29 α-L-fucosidases from an uncultured Paraglaciecola sp. specifically hydrolyze fucosyl-N-acetylglucosamine regioisomers
Authors: Schultz-Johansen Mikkel , Stougaard Peter , Svensson Birte , Teze David
Published: June 2021

l-Fucose is the most widely distributed l-hexose in marine and terrestrial environments, and presents a variety of functional roles. l-Fucose is the major monosaccharide in the polysaccharide fucoidan from cell walls of brown algae, and is found in human milk oligosaccharides and the Lewis blood group system, where it is important in cell signaling and immune response stimulation. Removal of fucose from these biomolecules is catalyzed by fucosidases belonging to different carbohydrate-active enzyme (CAZy) families. Fucosidases of glycoside hydrolase family 29 (GH29) release α-l-fucose from non-reducing ends of glycans and display activities targeting different substrate compositions and linkage types. While several GH29 fucosidases from terrestrial environments have been characterized, much less is known about marine members of GH29 and their substrate specificities, as only four marine GH29 enzymes were previously characterized. Here, five GH29 fucosidases originating from an uncultured fucoidan-degrading marine bacterium (Paraglaciecola sp.) were cloned and produced recombinantly in E. coli. All five enzymes (Fp231, Fp239, Fp240, Fp251, Fp284) hydrolyzed the synthetic substrate CNP-α-l-fucose. By screening each of these enzymes against up to 17 fucose-containing oligosaccharides Fp231 and Fp284 showed strict substrate specificities against the fucosyl-N-acetylglucosamine regioisomers Fuc(α1,4)GlcNAc and Fuc(α1,6)GlcNAc, respectively, the former representing a new specificity. Fp231 is a monomeric enzyme with pH and temperature optima at pH 5.6–6.0 and 25°C, hydrolyzing Fuc(α1,4)GlcNAc with kcat = 1.3 s−1 and Km = 660 μM. Altogether, the findings extend our knowledge about GH29 family members from the marine environment, which are so far largely unexplored.
Efficacy of epetraborole against Mycobacterium abscessus is increased with norvaline
Authors: Sullivan Jaryd R. , Lupien Andréanne , Kalthoff Elias , Hamela Claire , Taylor Lorne , Munro Kim A. , Schmeing T. Martin , Kremer Laurent , Behr Marcel A.
Published: June 2021

Certain aminoacyl-tRNA synthetases developed a proofreading mechanism to ensure aminoacylation of tRNAs with cognate amino acids. Epetraborole (EPT) was identified as an inhibitor of the leucyl-tRNA synthetase (LeuRS) editing site in Mycobacterium abscessus. EPT displayed enhanced activity against M. abscessus over Mycobacterium tuberculosis. Crystallographic and equilibrium binding data showed that EPT binds LeuRSMabs and LeuRSMtb with similar Kd. Proteomic analysis revealed that when M. abscessus LeuRS mutants were fed the non-proteinogenic amino acid norvaline, leucine residues in proteins were replaced by norvaline, inducing expression of GroEL chaperonins and Clp proteases. In vitro data revealed that supplementation of media with norvaline reduced the emergence of EPT mutants in both M. abscessus and M. tuberculosis. The combination of EPT and norvaline had improved in vivo efficacy compared to EPT in a murine model of M. abscessus infection.
Synergistic block of SARS-CoV-2 infection by combined drug inhibition of the host entry factors PIKfyve kinase and TMPRSS2 protease
Authors: Kreutzberger Alex J.B. , Sanyal Anwesha , Ojha Ravi , Pyle Jesse D. , Vapalahti Olli , Balistreri Giuseppe , Kirchhausen Tom
Published: June 2021

Repurposing FDA-approved inhibitors able to prevent infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) could provide a rapid path to establish new therapeutic options to mitigate the effects of coronavirus disease 2019 (COVID-19). Proteolytic cleavages of the spike S protein of SARS-CoV-2, mediated by the host cell proteases cathepsin and TMPRSS2, alone or in combination, are key early activation steps required for efficient infection. The PIKfyve kinase inhibitor apilimod interferes with late endosomal viral traffic, and through an ill-defined mechanism preventsin vitroinfection through late endosomes mediated by cathepsin. Similarly, inhibition of TMPRSS2 protease activity by camostat mesylate or nafamostat mesylate prevents infection mediated by the TMPRSS2-dependent and cathepsin-independent pathway. Here, we combined the use of apilimod with camostat mesylate or nafamostat mesylate and found an unexpected ~5-10-fold increase in their effectiveness to prevent SARS-CoV-2 infection in different cell types. Comparable synergism was observed using both, a chimeric vesicular stomatitis virus (VSV) containing S of SARS-CoV-2 (VSV-SARS-CoV-2) and SARS-CoV-2 virus. The substantial ~5-fold or more decrease of half maximal effective concentrations (EC50values) suggests a plausible treatment strategy based on the combined use of these inhibitors.

IMPORTANCE

Infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is causing the coronavirus disease 2019 (COVID-2019) global pandemic. There are ongoing efforts to uncover effective antiviral agents that could mitigate the severity of the disease by controlling the ensuing viral replication. Promising candidates include small molecules that inhibit the enzymatic activities of host proteins, thus preventing SARS-CoV-2 entry and infection. They include Apilimod, an inhibitor of PIKfyve kinase and camostat mesylate and nafamostat mesylate, inhibitors of TMPRSS2 protease. Our research is significant for having uncovered an unexpected synergism in the effective inhibitory activity of apilimod used together with camostat mesylate or with nafamostat mesylate.
The endemic plant species of Mt Kupe, Cameroon with a new Critically Endangered cloud-forest tree species,Vepris zapfackii(Rutaceae)
Authors: Cheek Martin , Onana Jean Michel
Published: June 2021

We revise and update the records of strict and near-endemic species of Mt Kupe, Cameroon respectively from 31 strict endemics in 2004, to 25 today, and with near-endemic species 30, unchanged in number but with turnover. The changes result from new collections, discoveries and taxonomic changes in the last 16 years. While 15 of the provisionally named putative endemic species have now been formally published, a further 18 have not. The majority of the 30 near-endemic species (18) are shared with the adjacent Bakossi Mts, far exceeding the numbers shared with the more distant Mt Etinde-Mt Cameroon, Rumpi Hills and Ebo forest areas (sharing three near-endemic species each with Mt Kupe). We test the hypothesis that a further one of the provisionally named putative Mt Kupe species,Veprissp. 1 from submontane forest near the summit, is indeed new to science. We compare it morphologically with the two other bicarpellate high altitude Cameroon Highland tree speciesVepris montisbambutensisOnana andVepris baliCheek, concluding that it is a new undescribed species here named asVepris zapfackii. The new species is illustrated, mapped and its conservation status assessed as Critically Endangered using the 2012 IUCN standard due to habitat clearance from agricultural pressures at its sole location which is unprotected.Vepris zapfackiiandV. baliappear unique in African trifoliolate species of the genus in having opposite leaves.Vepris zapfackiidiffers in having hairy petiolules and midribs and petiolules with the blade decurrent distally, narrowing towards a winged-canaliculate base (vs glabrous and petiolule long, terete), and sparsely golden hairy pistillodes and a glabrous calyx (vs densely black hairy pistillodes, and sepals hairy).
Immune dynamics in a time of covid
Authors: Shinbrot Troy
Published: June 2021

Motivated by curiosities of disease progression seen in the coronavirus pandemic, we analyze a minimalist predator-prey model for the immune system (predator) competing against a pathogen (prey). We find that the mathematical model alone accounts for numerous paradoxical behaviors observed in this and other infections. These include why an exponentially growing pathogen requires an exposure threshold to take hold, how chronic and recurrent infections can arise, and what can allow very sick patients to recover, while healthier patients succumb. We also examine the distinct dynamical roles that specific, “innate,” and nonspecific, “adaptive,” immunity play, and we describe mathematical effects of infection history on prognosis. Finally, we briefly discuss predictions for some of the effects of timing and strengths of antibiotics or immunomodulatory agents.