bluuebunny/crossref_metadata_2025 huggingface dataset:
A High Flavonoid Diet Reduces Gut Permeability, Short Chain Fatty Acid Production and Decreases Gut Inflammation in Overweight and Obese Men and Women
Authors: Ward Robert Edwin , Bergerson Janet , Hergert Nancie , Hergert John , Aguilar Sheryl , Khan Abdullah , Kung Stephanie , Lefevre Michael
Published: June 2021

We hypothesized that providing a diet high in flavonoids would reduce gut permeability, and gut inflammation, and possibly differentially affect the fecal concentrations of short chain fatty acids (SCFA). To test this hypothesis, 29 overweight/obese (BMI; 25.2–34.5 kg/m2) men (N=16) and women (N=16) were provided two well‐controlled diets that were identical in macronutrient content (Protein 17% en; Fat, 30% en, Carbohydrate, 53% en), but formulated to have large differences in the flavonoid content. The Low Flavonoid Diet (LFD) contained 10 mg/1000 Kcals, while the High Flavonoid Diet (HFD) contained 340 mg/1000 Kcals. The study was a randomized cross‐over design with six weeks for each arm, and subjects were provided all meals. Endpoints were determined in duplicate during the last week of each diet period. Gut permeability was assessed by the differential sugar test using mannitol, sucrose, lactulose and sucralose which were measured after ingestion and 24h collection by gas chromatography. Fecal SCFA (acetic, butyric, proprionic, valeric, caproic, isovaleric and isobutyric acids) were measured using gas chromatography. Gut inflammation was determined by measure of fecal calprotectin (Calp), myeloperoxidase (MPO) and eosinophil derived neurotoxin (EDN). Food was well tolerated by participants; compliance was assessed by questionnaires and direct observation and was deemed to be excellent. Compared to the LFD, the HFD significantly reduced gut permeability, with differential effects along the length of the GI tract. Compared to the LFD, sucrose recovery was reduced 45% by the HFD, whereas lactulose and sucralose were reduced by 34% and 22%. Collectively, these data indicate the HFD has a greater effect on gut permeability in proximal gastrointestinal tract. The HFD also significantly reduced the fecal concentration of all seven SCFA in the range of 15 to 50%. For the three most abundant SCFA the reductions were 24% (acetic), 20% (butyric) and 34% (proprionic). Lastly, the HFD also significantly reduced markers of intestinal inflammation by 53% to 72%. Despite significant reductions in both intestinal permeability and inflammation, there was no effect on plasma lipopolysaccharide. Collectively, these data indicate dietary flavonoids have a substantial effect on the barrier properties of the gut, metabolic activity of the microbiome and intestinal inflammation.

Support or Funding Information

This work was supported by USDA/NIFA grant 2014‐67017‐21749.
Use of Skin Carotenoids as a Biomarker for Fruit and Vegetable Intake Among Mexican‐Origin Children in a Community Setting
Authors: Aguilera Alberto Leopoldo , de la Torre Adela , Kaiser Lucia Lynn
Published: June 2021

Measuring fruit and vegetable (F/V) consumption in individuals is important for evaluating nutrition interventions and population‐based studies. Traditional methods of assessing F/V intake rely on participant recall, which raises concerns of accuracy. Recently, clinical studies using skin carotenoid levels show promising results as an objective measure of F/V intake. However, there is a need to further develop this method in community‐based studies with hard to reach populations. The Niños Sanos, Familia Sana (Healthy Children, Healthy Family) study is a multi‐year, multi‐faceted intervention aimed at reducing obesity rates and increasing F/V consumption among Mexican‐origin children. The purpose of this study was to compare skin carotenoid levels to F/V intake as measured by a food frequency questionnaire (FFQ) and 24‐hour dietary recalls (24HDR). Participants included 51 Mexican‐origin children (ages 3–8 years) from a rural, Central Valley community in California. The researchers measured the skin carotenoid levels of the children were using the Pharmanex BioPhotonic Scanner. Trained bilingual university students interviewed parents in person and over the phone to collect three 24HDR recalls of their children's dietary intake. The researchers calculated the children's F/V intake over 30 previous days a 26‐item, parent‐reported FFQ (including fresh fruit, canned fruit, vegetable soup, other cooked vegetables, salsa, lettuce or cabbage, and other vegetables). Preliminary results of the study demonstrate a significant positive correlation between skin carotenoid levels and parent‐reported 24HDR vegetable consumption (r=0.41, p=0.003) but not with 24HDR fruit, FFQ fruit, or FFQ vegetable consumption. The use of skin carotenoid measurements may be more indicative of vegetable consumption than overall fruit and vegetable consumption in this population of Mexican‐origin children.

Support or Funding Information

Funded by USDA‐NIFA Fund number: 82705
Genetic Ablation of TNF‐α Attenuates High Fat Diet‐induced Obesity Potentially via Diminishing Wnt‐signaling and Determinant Genes of Adipogenesis
Authors: Li Jinchao , Frederick Armina‐Lyn , Kim Young‐Cheul , Wood Richard J. , Liu Zhenhua
Published: June 2021

Recent decades have seen a rapid increase in obesity, which is associated with increased risk of multiple medical complications including diabetes, cardiovascular disease, and some cancers. As obesity has reached an epidemic level and no decrease is projected in the near future, new prevention and medication strategies are needed for obesity and related disorders. Tumor necrosis factor alpha (TNF‐α), a critical pro‐inflammatory cytokine, is elevated in adipose tissue and its expression level correlates with the degree of obesity. Impressive evidence shows that diets or drugs, which are used to reduce inflammation, can ameliorate obesity. The objective of the study was to investigate the role of TNF‐α in high‐fat diet‐induced obesity and thereby to examine the potential implication of targeting TNF‐α in obesity and obesity‐related complications. Fifty‐two wildtype and 52 TNF‐α knockout mice (male and female evenly) with the same C57BL6 genetic background were randomly divided into two groups receiving either a high‐fat diet (HFD, 60% fat) or a low fat diet (LFD, 10% fat) for 16 weeks. Body weight were monitored weekly and body composition were determined by Magnetic Resonance Imaging (MRI), The expression of pro‐inflammatory cytokines, key components within Wnt pathway and determinants of adipogenesis in the visceral adipose tissue were also measured. The results shows that, while there are no significant differences among the LFD groups (p > 0.05), wildtype HFD group has significantly higher body weight and fat composition compared to TNF‐α knockout HFD group. In addition to TNF‐α itself, the expressions of IL‐6 and IFNγ, as measured by chemiluminescent immunoassay, were also significantly lower in the HFD‐induced obese animals with TNF‐α knockout when comparing to the wildtype HFD group (p < 0.05). In the obese state, the genetic ablation of TNF‐α significantly reduced Wnt‐signaling, as indicated by decreased phospho‐GSK3β and active β‐catenin as well as Wnt pathway downstream genes (p < 0.05). The deletion of TNF‐α significantly increased both mRNA and protein expression of PPARγ and C/EBPα, two critical genes which are key determinants of adipogenesis. All these data collectively indicate that depletion of TNF‐α may ameliorate HFD‐induced obesity, potentially via altering Wnt‐signaling and determinants of adipogenesis.

Support or Funding Information

This project is supported by USDA grants (2014‐67017‐21762 and MAS00454) and the Pilot grant from Rays of Hope Center for Breast Cancer Research
Increasing Physical Activity in American Indian Adults: Preliminary Results from a Multi‐institutional Obesity Prevention Program
Authors: Redmond Leslie , Eckmann Thomas , Pardilla Marla , Swartz Jacqueline , Platero Harrison , Gittelsohn Joel
Published: June 2021

Background

Prevalence of obesity is disproportionately high among American Indians (AIs) and is associated with increased prevalence of diabetes, hypertension, and cardiovascular disease. Increasing physical activity (PA) is associated with weight loss and maintenance of a healthy body weight.

Objective

The objective of this study was to decrease obesity and promote healthier bodyweights using a multi‐level, multi‐institutional obesity intervention designed to increase knowledge, build self‐efficacy, and influence intentions for improved behavior change at multiple levels. Primary areas of focus were nutrition, PA, and behaviors related to food consumption and purchasing. The aim of this analysis was to determine whether or not participants in the intervention communities engaged in a greater amount of PA versus comparison at follow‐up.

Methods

A randomized controlled community‐based program (OPREVENT) was developed, implemented, and evaluated within five AI communities. The five communities were randomly assigned to intervention (n=3) or delayed intervention (comparison; n=2)in New Mexico and Michigan. A modified International Physical Activity Questionnaire‐Short Form (IPAQ‐SF) was administered to 180 randomly selected community members at baseline and follow‐up from intervention and comparison communities.

Results

Total days per week participating in vigorous PA was significantly different between intervention and comparison at follow‐up (p<0.05). Total Metabolic Equivalents(METs) of vigorous PA was significantly different between intervention and comparison at follow‐up (p<0.05).

Conclusions

OPREVENT was associated with an increase in days per week engaged invigorous PA as well as an increase in total METs vigorous PA in communities that received the OPREVENT program.

Support or Funding Information

The USDA provided funding for this project. Approval and support was obtained from all participating tribal communities.
Level of tool‐use proficiency in chimpanzees is associated with differences in gray matter distribution in the inferior parietal cortex: a voxel‐based morphometry study
Authors: Reyes Laura Denise , Hopkins William D , Sherwood Chet C
Published: June 2021

Evidence from paleoneurology and neuroimaging studies suggests that the inferior parietal region expanded in the human lineage. We compared gray matter distribution in MRI scans of chimpanzees with high and low proficiency at tool‐use with voxel‐based morphometry (VBM) to assess the link between tool‐use and structural differences in the inferior parietal cortex (IPC). The sample consisted of nine high proficiency (HP) and nine low proficiency (LP) female chimpanzee tool‐users to avoid a possible sex bias. Tool‐use proficiency was based on Z‐scores for average performance time on a simulated termite‐fishing task; Z‐scores greater than or equal to 0.5 standard deviations above and below the mean were classified as HP and LP, respectively. A VBM analysis focused on the IPC showed significantly increased gray matter in HP compared to LP tool‐users in the left supramarginal gyrus (SMG; X=43, Y=75, Z=79; p < 0.05). The left SMG is part of a left‐lateralized network involved in human tool‐use, and its anterior portion is activated during tool‐use in humans but not macaques. SMG activation is also observed during expert stone tool‐making in humans. These results indicate that there are structural differences in the IPC based on tool‐use proficiency in this sample of chimpanzees, suggesting that cortical variation associated with tool‐use and tool‐making predated the evolution of the genus Homo. and could have provided a basis for the evolution of stone tool‐making in the human lineage.

Support or Funding Information

NSF BCS‐1455629, NSF DGE‐0801634, James S. McDonnell Foundation 22002078, James S. McDonnell Foundation 220020293, NIH NS‐ 73134, NIH NS ‐ 42867
Regulation of the Development of Human Neurons by Substratum Elasticity
Authors: Rivera‐Pérez Luis Miguel , Nichol Robert , Gomez Timothy
Published: June 2021

Growth cones, the sensory tips of developing axons, respond to molecular cues present in the environment. Additionally, recent studies suggest local differences in environmental rigidity affect axon development via mechanosensitive protein regulation in growth cones, and is dependent upon neuronal subtype. Neurites innervating the Central Nervous System (CNS) grow more rapidly on flexible substrata. Conversely, neurites projecting into the Peripheral Nervous System (PNS) prefer rigid substrata. By using human forebrain (hFBs) and motor neurons (hMNs) differentiated from Induced Pluripotent Stem Cells (IPSCs), we compared growth rates and morphology of CNS and PNS neurons on varying substrata stiffnesses. We found MNs prefer more rigid substrata, while forebrain neurons do not have a strong preference for rigidity. Finally, we found both hFBs and hMNs express mechanosensitive ion channels. Future studies should investigate differential expression patterns of these ion channels on different rigidities as a possible mechanism for the differential growth we observed.

Support or Funding Information

NIH RO1NS41564‐10 (to T.M.G)

NIH T32GM007507 (to UW‐NTP)

IBS‐SRP at UW‐Madison (NSF grant NSF‐DBI 1063085)

NIH‐NIGMS R25GM096955 (to Edu B. Suarez‐Martinez)
The Influence Of Progerin Expression On The Nature Of DNA Double‐Strand Break Repair
Authors: Waldman Alan S. , Chowdhary Sona , Patrick Andrew , Hersey Melinda , Waldman Barbara Criscuolo
Published: June 2021

Hutchinson‐Gilford Progeria Syndrome (HGPS) is a rare, fatal autosomal dominant genetic condition characterized by many features of accelerated aging in children. Children with HGPS die at an average age of fourteen, usually from heart disease. It has been known for some time that the syndrome is most commonly caused by a point mutation in the LMNA gene which normally codes for lamin A and its splice variant lamin C. The LMNA mutation commonly associated with HGPS leads to increased usage of a cryptic splice site which leads to the production of a truncated, farnesylated form of lamin A referred to as “progerin.” Interestingly, and quite significantly, progerin is also expressed at very low levels in healthy individuals and has been implicated in the normal aging process, possibly by increased expression over time. Progerin overexpression in progeria disrupts nuclear architecture and chromatin organization. Previous studies by others have indicated that progerin slows the kinetics of DNA double‐strand break (DSB) repair and leads to the accumulation of spontaneous DSBs. Strikingly, there has been little investigation into how progerin expression may alter the nature of DSB repair. DSB repair may occur through one of two ways: homologous recombination (HR), which is accurate, or non‐homologous end joining (NHEJ), which is intrinsically mutagenic. We aimed to assess whether progerin expression alters the DSB repair pathway of choice or whether it alters the nature of individual repair events. To do so, we stably expressed a GFP‐progerin fusion protein, or GFP alone, in a human cell line containing an integrated DNA substrate that served as a reporter for DSB repair. A DSB was introduced in the integrated substrate by transient expression of endonuclease I‐SceI. Events involving DSB repair via HR or NHEJ were recoverable by selection for G418‐resistant clones, and these events were analyzed at the nucleotide level and by Southern blotting analysis. We present results indicating there was an increased frequency of DSB events occurring via NHEJ in cells expressing GFP‐progerin in comparison to those expressing GFP alone, and the difference in pathway usage was highly significant (p < 0.004 by a two‐sided Fisher exact test). There was no evidence that progerin impacted the accuracy of HR events. In future work, the finding that progerin expression appears to alter the DSB repair pathway of choice within the human genome will be explored further, as will the possibility that progerin alters the homology requirements for HR. Our long‐term goal is to better understand the relationship between aging and the corruption of genome maintenance pathways.

Support or Funding Information

This work was supported by grant MCB‐1157416 from the NSF to ASW and BCW, and from an ASPIRE grant from the University of South Carolina to ASW.
Distal Radius Physeal Bar and Ulnar Overgrowth: Indications for Treatment
Authors: Samora Julie Balch
Published: June 2021

Background:

Distal radius physeal bar with associated growth arrest can occur because of fractures, ischemia, infection, radiation, tumor, blood dyscrasias, and repetitive stress injuries. The age of the patient as well as the size, shape, and location of the bony bridge determines the deformity and associated pathology that will develop.

Methods:

A search of the English literature was performed using PubMed and multiple search terms to identify manuscripts dealing with the evaluation and treatment of distal radius physeal bars and ulnar overgrowth. Single case reports and level V studies were excluded.

Results:

Manuscripts evaluating distal radial physeal bars and their management were identified. A growth discrepancy between the radius and ulna can lead to distal radioulnar joint instability, ulnar impaction, and degenerative changes in the carpus and triangular fibrocartilage complex. Advanced imaging aids in the evaluation and mapping of a physeal bar. Treatment options for distal radius physeal bars include observation, bar resection±interposition, epiphysiodeses of the ulna±completion epiphysiodesis of the radius, ulnar shortening osteotomy±diagnostic arthroscopy to manage associated triangular fibrocartilage complex pathology, radius osteotomy, and distraction osteogenesis.

Conclusions:

Decision-making when presented with a distal radius physeal bar is multifactorial and should incorporate the age and remaining growth potential of the patient, the size and location of the bar, and patient and family expectations.
Operative Fixation Versus Cast Immobilization: Tibial Shaft Fractures in Adolescents
Authors: Martus Jeffrey E.
Published: June 2021

Introduction:

Tibial shaft fractures are common injuries in the adolescent age group. Potential complications from the injury or treatment include infection, implant migration, neurovascular injury, compartment syndrome, malunion, or nonunion.

Methods:

Published literature was reviewed to identify studies which describe the management options, complications, and outcome of tibial shaft fractures in adolescents.

Results:

Acceptable alignment parameters for tibial shaft fractures have been defined. Operative indications include open fractures and other severe soft tissue injuries, vascular injury, compartment syndrome, ipsilateral femoral fractures, and polytrauma. Relative indications for operative treatment are patient/family preference or morbid obesity. Closed reduction and cast immobilization necessitates radiographic observation for loss of reduction over the first 3 weeks. Cast change/wedging or conversion to operative management may be required in 25% to 40%. Flexible nailing provides relative fracture stability while avoiding the proximal tibial physis, but the fracture will still benefit from postoperative immobilization. Rigid nailing provides greater fracture stability and allows early weight bearing but violates the proximal tibial physis. Plate and screw osteosynthesis provide stable anatomic reduction, but there are concerns with delayed union and wound complications related to the dissection. External fixation is an excellent strategy for tibia fractures associated with complex wounds but also requires observation for loss of reduction.

Discussion and Conclusions:

The majority of adolescent tibia shaft fractures can be successfully managed with closed reduction and cast immobilization. Unstable fractures that have failed cast treatment should be treated operatively. Flexible intramedullary nailing, rigid intramedullary nailing, plate and screw osteosynthesis, and external fixation are acceptable treatment options that may be considered for an individual patient depending upon the clinical scenario.
Hematopoietic Stem Cell Transplantation Cures Therapy-refractory Aspergillosis in Chronic Granulomatous Disease
Authors: Dedieu Cinzia , Landwehr-Kenzel Sybille , Thee Stephanie , Oevermann Lena , Voigt Sebastian , Marggraf Katharina , Schulte Johannes , Lau Susanne , Roesler Joachim , Kuehl Jörn-Sven , von Bernuth Horst
Published: June 2021

Background:

Pulmonary invasive aspergillosis is a frequent and life-threatening complication for patients with chronic granulomatous disease (CGD). Despite combined treatment with several groups of antifungal agents, conservative treatment of invasive aspergillosis often remains refractory. Pulmonary invasive aspergillosis is often treated by surgical resection of consolidated lobes or segments, donor granulocyte transfusions and allogeneic hematopoietic stem cell transplantation (HSCT). These options are not mutually exclusive and often combined.

Methods and Results:

We here describe the treatment of 3 patients with CGD who received HSCT upon active pulmonary invasive aspergillosis: Two of them received HSCT as salvage therapy for refractory aspergillosis, and 1 patient received elective HSCT in infancy but developed pulmonary aspergillosis during secondary graft failure. Based on our experience and available literature, we discuss indication as well as timing of HSCT, granulocyte transfusions and surgery in patients with CGD and pulmonary invasive aspergillosis.

Conclusions:

Upon diagnosis with invasive aspergillosis in CGD, we propose to start antifungal treatment and preparation for HSCT at the same time. Remission of pulmonary invasive aspergillosis before HSCT remains preferable but is not mandatory. When pulmonary aspergillosis in patients with CGD remains refractory for longer than 3 months on conservative treatment, HSCT without prior surgery or accompanying granulocyte transfusions is a feasible option.
Unique Imaging Findings of Neurologic Phantosmia Following Pfizer-BioNtech COVID-19 Vaccination: A Case Report
Authors: Keir Graham , Maria Naomi I. , Kirsch Claudia F.E.
Published: June 2021

Olfactory dysfunction related to SARS-CoV-2 infection and COVID-19 disease is now well established in the literature. In December 2020, the FDA approved the Pfizer-BioNTech and Moderna vaccines for use in preventing COVID-19 in the United States. To the best of our knowledge, this is the first report of a phantosmia post-Pfizer COVID-19 vaccination, with positive magnetic resonance imaging radiographic findings in a patient with documented absence of infection by SARS-CoV-2 virus or concomitant sinonasal disease.
A discussion on electricity prices, or the two sides of the coin
Authors: Pablo Luna Juan , Sagastizábal Claudia , Silva Paulo J. S.
Published: June 2021

We examine how different pricing frameworks deal with non-convex features typical of day-ahead energy prices when the power system is hydro-dominated, like in Brazil. For the system operator, requirements of minimum generation translate into feasibility issues that are fundamental to carry the generated power through the network. When utilities are remunerated at a price depending on Lagrange multipliers computed for a system with fixed commitment, the corresponding values sometimes fail to capture a signal that recovers costs. Keeping in mind recent discussions for the Brazilian power system, we analyse mechanisms that provide a compromise between the needs of the generators and those of the system operator. After characterizing when a price supports a generation plan, we explain in simple terms dual prices and related concepts, such as minimal uplifts and bi-dual problems. We present a new pricing mechanism that guarantees cost recovery to all agents, without over-compensations. Instead of using Lagrange multipliers, the price is defined as the solution to an optimization problem. The behaviour of the new rule is compared to two other proposals in the literature on illustrative examples, including a small, yet representative, hydro-thermal system.

This article is part of the theme issue ‘The mathematics of energy systems’.
The energy distance for ensemble and scenario reduction
Authors: Ziel Florian
Published: June 2021

Scenario reduction techniques are widely applied for solving sophisticated dynamic and stochastic programs, especially in energy and power systems, but are also used in probabilistic forecasting, clustering and estimating generative adversarial networks. We propose a new method for ensemble and scenario reduction based on the energy distance which is a special case of the maximum mean discrepancy. We discuss the choice of energy distance in detail, especially in comparison to the popular Wasserstein distance which is dominating the scenario reduction literature. The energy distance is a metric between probability measures that allows for powerful tests for equality of arbitrary multivariate distributions or independence. Thanks to the latter, it is a suitable candidate for ensemble and scenario reduction problems. The theoretical properties and considered examples indicate clearly that the reduced scenario sets tend to exhibit better statistical properties for the energy distance than a corresponding reduction with respect to the Wasserstein distance. We show applications to a Bernoulli random walk and two real data-based examples for electricity demand profiles and day-ahead electricity prices.

This article is part of the theme issue ‘The mathematics of energy systems’.
Pseudomonas paraversuta sp. nov. isolated from refrigerated dry-aged beef
Authors: Lick Sonja , Wibberg Daniel , Winkler Annika , Blom Jochen , Grimmler Christina , Goesmann Alexander , Kalinowski Jörn , Kröckel Lothar
Published: June 2021

A polyphasic approach was applied to investigate the diversity of microbiota that evolved during cold storage beef ripening. Isolate V4/DAB/S4/2aT with a unique BOX-rep-PCR fingerprint profile revealed more than 99 % nucleotide identities upon pairwise comparisons of 16S rDNA sequences from the type strains

Pseudomonas versuta

DSM 101070T,

Pseudomonas saxonica

DSM 108989T,

Pseudomonas deceptionensis

DSM 26521T and

Pseudomonas weihenstephanensis

DSM 29166T, placing it within the

Pseudomonas fragi

/ lundensis branch of the genus

Pseudomonas

. Additional rpoB based comparison revealed

P. versuta

DSM 101070T as the nearest relative, with 98.5 % nucleotide identity. Calculation of ANIb values of the V4/DAB/S4/2aT draft genome identified

P. versuta

DSM 101070T with 90.1 %,

P. deceptionensis

DSM 26521T with 85.1 %,

P. fragi

DSM 3456T with 84.4 %,

Pseudomonas psychrophila

DSM 17535T and

Pseudomonas bubulae

DSM 107389T with 84.2 % similarities each. Pairwise genome-to-genome distance calculations [digital DNA–DNA hybridization (dDDH)] resulted in values of 47.1, 35.1, 34.8, 34.2 and 34.1 %, respectively. A second isolate was detected years later in ground beef and showed ANIb values of 99.3 % and dDDH of 96.1 % relatedness to V4/DAB/S4/2aT. The DNA G+C content was 58.6 mol% for both isolates. The predominant cellular fatty acids of V4/DAB/S4/2aT were C16 : 0, C18 : 1ω7c, C17 : 0 cyclo and a summed feature containing C16 : 1ω7c and/or C15 : 0 iso 2-OH. The major polar lipids were phosphatidylethanolamine, phosphatidylglycerol and diphosphatidylglycerol, the major respiratory quinone was Q9, with a small portion of Q8. The combined data on genotypic and phenotypic features support the proposal of a novel species, for which the name Pseudomonas paraversuta sp. nov. is proposed. The type strain is V4/DAB/S4/2aT (=DSM 111361T=LMG 31844T) and a second isolate is UBT376 (=DSM 111360=LMG 31845).
Alborzia kermanshahica gen. nov., sp. nov. (Chroococcales, Cyanobacteria), isolated from paddy fields in Iran
Authors: Nowruzi Bahareh , Soares Fabiana
Published: June 2021

In Iran, polyphasic studies of unicellular cyanobacteria are still scarce, with more emphasis being placed on filamentous cyanobacteria in paddy fields and fresh water regions. In an effort to increase the knowledge of the diversity of unicellular cyanobacteria from paddy fields in Iran, we have isolated and characterized a new unicellular cyanobacterium strain. The strain was studied using a polyphasic approach based on morphological, ecological and phylogenetic analyses of the 16S–23S ITS rRNA gene region. Complementarily, we have searched for the presence of cyanotoxin genes and analysed the pigment content of the strain. Results showed that the strain was morphologically indistinguishable from the genus

Chroococcus

, but phylogenetic analyses based on the Bayesian inference and maximum-likelihood methods placed the strain in a separated monophyletic and highly supported (0.99/98, posterior probability/maximum-likelihood) genus-level cluster, distant from Chroococcus sensu stricto and with

Chalicogloea cavernicola

as sister taxa. The calculated p-distance for the 16S rRNA gene also reinforced the presence of a new genus, by showing 92 % similarity to

C. cavernicola

. The D1–D1′, Box-B and V3 ITS secondary structures showed the uniqueness of this strain, as it shared no similar pattern with closest genera within the Chroococcales. For all these reasons, and in accordance with the International Code of Nomenclature for Algae, Fungi and Plants, we here proposed the description of a new genus with the name Alborzia gen. nov. along with the description of a new species, Alborzia kermanshahica sp. nov. (holotype: CCC1399-a; reference strains CCC1399-b; MCC 4116).
LPMX: A pure rootless composable container system
Authors: Yang Xu , Kasahara Masahiro
Published: June 2021

Delivering tools for genome analysis to users is often difficult given their complex dependencies and conflicts. Container virtualization systems such as Singularity isolate environments, helping developers avoid conflicts between tools. However, they lack composability, an easy way to integrate multiple tools in different containers or multiple tools both in a container and a host, which compromises the use of container systems in genome research. Another issue is that one may not be able to use a single container system of the same version at all sites they use, which discourages the use of container systems. To this end, we present a pure rootless composable container system, LPMX, that provides composability for letting developers easily integrate tools in different existing containers or on host, allowing researchers to compose existing containers. LPMX is pure rootless, so it does not require root privilege neither during installation nor at runtime, allowing researchers to use LPMX across sites without asking permissions from administrators. LPMX provides a pure userspace layered filesystem with at least an order of magnitude lower overhead for launching a new process than existing container systems. LPMX can import Docker and Singularity images.

Availability and Implementation

The source code of LPMX is available at https://github.com/jasonyangshadow/lpmx under Apache 2.0 License.

Contact

mkasa@k.u-tokyo.ac.jp

Supplementary information

Supplementary data are available at Bioinformaticsonline.
Accurate Virus Identification with Interpretable Raman Signatures by Machine Learning
Authors: Ye Jiarong , Yeh Yin-Ting , Xue Yuan , Wang Ziyang , Zhang Na , Liu He , Zhang Kunyan , Yu Zhuohang , Roder Allison , Lopez Nestor Perea , Organtini Lindsey , Greene Wallace , Hafenstein Susan , Lu Huaguang , Ghedin Elodie , Terrones Mauricio , Huang Shengxi , Huang Sharon Xiaolei
Published: June 2021

Rapid identification of newly emerging or circulating viruses is an important first step toward managing the public health response to potential outbreaks. A portable virus capture device coupled with label-free Raman Spectroscopy holds the promise of fast detection by rapidly obtaining the Raman signature of a virus followed by a machine learning approach applied to recognize the virus based on its Raman spectrum. In this paper, we present a machine learning analysis on Raman spectra of human and avian viruses. A Convolutional Neural Network (CNN) classifier specifically designed for spectral data achieves very high accuracy for a variety of virus type or subtype identification tasks. In particular, it achieves 99% accuracy for classifying influenza virus type A vs. type B, 96% accuracy for classifying four subtypes of influenza A, 95% accuracy for differentiating enveloped and non-enveloped viruses, and 99% for differentiating avian coronavirus (infectious bronchitis virus, IBV) from other avian viruses. Furthermore, interpretation of neural net responses in the trained CNN model using a full-gradient algorithm highlights Raman spectral ranges that are most important to virus identification. By correlating ML-selected salient Raman ranges with the signature ranges of known biomolecules and chemical functional groups (e.g. amide, amino acid, carboxylic acid) we verify that our ML model effectively recognizes the Raman signatures of proteins, lipids and other vital functional groups present in different viruses and uses a weighted combination of these signatures to identify viruses. The accurate and interpretable machine learning model developed for Raman virus identification presents promising potential in a real-time virus detection system.

Significance Statement

A portable micro-fluidic platform for virus capture promises rapid enrichment and label-free optical identification of viruses by Raman spectroscopy. A large Raman dataset collected on a variety of viruses enables the training of machine learning (ML) models capable of highly accurate and sensitive virus identification. The trained ML models can then be integrated with the portable device to provide real-time virus detection and identification capability. We validate this conceptual framework by presenting highly accurate virus type and subtype identification results using a convolutional neural network to classify Raman spectra of viruses.
Deep vascular imaging in the eye with flow-enhanced ultrasound
Authors: Damsgaard Christian , Lauridsen Henrik
Published: June 2021

The eye’s retina is one of the most energy-demanding tissues in the body and thus requires high rates of oxygen delivery from a rich blood supply. The capillary lamina of the choroid lines the outer surface of the retina and is the dominating source of oxygen in most vertebrates, but this vascular bed is challenging to image with traditional optical techniques due to its position behind the highly light-absorbing retina. Here we describe a high-frequency ultrasound technique with flow-enhancement to image deep vascular beds (0.5 – 3 cm) of the eye with a high spatiotemporal resolution. This non-invasive method works well in species with nucleated red blood cells (non-mammalian and fetal animal models), and it generates non-invasive three-dimensional angiographies without the use of contrast agents that is independent of blood flow angles and with a higher sensitivity than Doppler based ultrasound imaging techniques.
Selective pharmaceutical inhibition of PARP14 mitigates allergen-induced IgE and mucus overproduction in a mouse model of pulmonary allergic response
Authors: Eddie Alex M. , Chen Kevin , Schenkel Laurie B. , Swinger Kerren K. , Molina Jennifer R. , Kunii Kaiko , Raybuck Ariel L. , Keilhack Heike , Niepel Mario , Peebles R. Stokes , Boothby Mark R. , Cho Sung Hoon
Published: June 2021

The type 2 cytokines IL-4 and IL-13, which share use of an IL-4 receptor alpha chain and its nuclear induction of the transcription factor STAT6, are crucial in elicitation and maintenance of allergic conditions that include asthma. Prior work has shown a physical and functional association of STAT6 with PARP14, an ADP-ribosyl monotransferase. Moreover, elimination of all PARP14 expression by gene targeting led to altered recall antibody responses and attenuation of ovalbumin-specific allergic lung inflammation with no apparent health issues for mice lacking this protein. However, an unanswered question is whether or not inhibition of the catalytic function has any biological consequence since PARP14 has multiple functional domains apart from the portion that catalyzes ADP-ribosylation. As reported separately, iterative structural analyses and medicinal chemistry fostered the generation of a compound, RBN2759, that is highly selective in its inhibition of PARP14 with negligible impact on other members of the PARP gene family. We show here that administration of this compound to mice previously sensitized to the allergenAlternaria alternataachieved biochemically active levels and altered physiological responses to the antigen. These results show for the first time that in vivo administration of a specific inhibitor of the ADP-ribosyltransferase activity encoded by PARP14 is sufficient to alter biological responses. Specifically, the orally absorbable pharmaceutical compound decreased allergen-induced mucus, blunted the induced increases in circulating IgE, and prevented suppression of IgG2a. We conclude that the catalytic activity can contribute to pathogenesis in allergic processes and propose that other biological endpoints that depend on ADP-ribosylation by PARP14 can be targeted using selective inhibition.
Single snapshot quantitative phase imaging with polarization differential interference contrast
Authors: Strassberg Mark , Shevtsova Yana , Kamel Domenick , Wagoner-oshima Kai , Zhong Hualin , Xu Min
Published: June 2021

We present quantitative phase imaging with polarization differential interference contrast (PDIC) realized on a slightly modified differential interference contrast (DIC) microscope. By recording the Stokes vector rather than the intensity of the differential interference pattern with a polarization camera, PDIC enables single snapshot quantitative phase imaging with high spatial resolution in real-time at speed limited by the camera frame rate alone. The approach applies to either absorptive or transparent samples and can integrate simply with fluorescence imaging for co-registered simultaneous measurements. Furthermore, an algorithm with total variation regularization is introduced to solve the quantitative phase map from partial derivatives. After quantifying the accuracy of PDIC phase imaging with numerical simulations and phantom measurements, we demonstrate the biomedical applications by imaging the quantitative phase of both stained and unstained histological tissue sections and visualizing the fission yeast Schizosaccharomyces pombe’s cytokinesis.
Modeling DNA opening in the eukaryotic transcription initiation complexes
Authors: Shino Genki , Takada Shoji
Published: June 2021

Recently, the molecular mechanisms of transcription initiation have been intensively studied. Especially, the cryo-electron microscopy revealed atomic structure details in key states in the eukaryotic transcription initiation. Yet, the dynamic processes of the promoter DNA opening in the pre-initiation complex remain obscured. In this study, based on the three cryo-electron microscopic yeast structures for the closed, open, and initially transcribing complexes, we performed multiscale molecular dynamics (MD) simulations to model structures and dynamic processes of DNA opening. Combining coarse-grained and all-atom MD simulations, we first obtained the atomic model for the DNA bubble in the open complexes. Then, in the MD simulation from the open to the initially transcribing complexes, we found a previously unidentified intermediate state which is formed by the bottleneck in the fork loop 1 of Pol II: The loop opening triggered the escape from the intermediate, serving as a gatekeeper of the promoter DNA opening. In the initially transcribing complex, the non-template DNA strand passes a groove made of the protrusion, the lobe, and the fork of Rpb2 subunit of Pol II, in which several positively charged and highly conserved residues exhibit key interactions to the non-template DNA strand.

Author Summary

Transcription is fundamental phenomenon in all species, and its regulation of the initiation process is important. In eukaryotes, multiple proteins, which is not only RNA polymerase but also transcription factors, assemble on the promotor to form the complex. After that, this complex open the part of DNA duplex, leading to forming single-stranded region for transcription. Previous study, including structural analysis and biochemical experiments, obtained the information about single-stranded region, but the structure is incomplete, so the details of the mechanism remains unclear. In this study, by the calculation using structural information about the protein-DNA complex, we obtained the structure of the complex with complete single-stranded region. As the result of the calculation, it found that the size of single-stranded region was fluctuated, which is related the sequence of the region. Furthermore, we found the intermediate state during the extended process of single-stranded region, which has not been reported in previous study. In this state, we found that the particular region of RNA polymerase is relevant to the extension of single-stranded region. These founding may contribute the understanding about the regulation of transcription initiation.
Siderophores drive invasion dynamics in bacterial communities through their dual role as public good versus public bad
Authors: Figueiredo Alexandre R. T. , Özkaya Özhan , Kümmerli Rolf , Kramer Jos
Published: June 2021

Microbial invasions can compromise ecosystem services and spur dysbiosis and disease in hosts. Nevertheless, the mechanisms determining invasion outcomes often remain unclear. Here, we examine the role of iron-scavenging siderophores in driving invasions of Pseudomonas aeruginosa into resident communities of environmental pseudomonads. Siderophores can be “public goods” by delivering iron to individuals possessing matching receptors; but they can also be “public bads” by withholding iron from competitors lacking these receptors. Accordingly, siderophores should either promote or impede invasion, depending on their dual effects on invader and resident growth. Using supernatant feeding and invasion assays, we show that invasion success indeed decreased when the invader was inhibited (public bad) rather than stimulated (public good) by the residents’ siderophores. Conversely, invasion success often increased when the invader could use its siderophore to inhibit the residents. Our findings identify siderophores as a major driver of invasion dynamics in bacterial communities.
Spatial-ATAC-seq: spatially resolved chromatin accessibility profiling of tissues at genome scale and cellular level
Authors: Deng Yanxiang , Bartosovic Marek , Ma Sai , Zhang Di , Liu Yang , Qin Xiaoyu , Su Graham , Xu Mina L. , Halene Stephanie , Craft Joseph E. , Castelo-Branco Gonçalo , Fan Rong
Published: June 2021

Cellular function in tissue is dependent upon the local environment, requiring new methods for spatial mapping of biomolecules and cells in the tissue context. The emergence of spatial transcriptomics has enabled genome-scale gene expression mapping, but it remains elusive to capture spatial epigenetic information of tissue at cellular level and genome scale. Here we report on spatial-ATAC-seq: spatially resolved chromatin accessibility profiling of tissue section via next-generation sequencing by combining in situ Tn5 transposition chemistry and microfluidic deterministic barcoding. Spatial chromatin accessibility profiling of mouse embryos delineated tissue region-specific epigenetic landscapes and identified gene regulators implicated in the central nerve system development. Mapping the accessible genome in human tonsil tissue with 20μm pixel size revealed spatially distinct organization of immune cell types and states in lymphoid follicles and extrafollicular zones. This technology takes spatial biology to a new realm by enabling spatially resolved epigenomics to improve our understanding of cell identity, state, and fate decision in relation to epigenetic underpinnings in development and disease.
A tug of war between filament treadmilling and myosin induced contractility generates actin ring
Authors: Ni Qin , Wagh Kaustubh , Pathni Aashli , Ni Haoran , Vashisht Vishavdeep , Upadhyaya Arpita , Papoian Garegin A.
Published: June 2021

In most eukaryotic cells, actin filaments assemble into a shell-like actin cortex under the plasma membrane, controlling cellular morphology, mechanics, and signaling. The actin cortex is highly polymorphic, adopting diverse forms such as the ring-like structures found in podosomes, axonal rings, and immune synapses. The biophysical principles that underlie the formation of actin rings and cortices remain unknown. Using a molecular simulation platform, called MEDYAN, we discovered that varying the filament treadmilling rate and myosin concentration induces a finite size phase transition in actomyosin network structures. We found that actomyosin networks condense into clusters at low treadmilling rates or high myosin concentration but form ring-like or cortex-like structures at high treadmilling rates and low myosin concentration. This mechanism is supported by our corroborating experiments on live T cells, which exhibit ring-like actin networks upon activation by stimulatory antibody. Upon disruption of filament treadmilling or enhancement of myosin activity, the pre-existing actin rings are disrupted into actin clusters or collapse towards the network center respectively. Our analyses suggest that the ring-like actin structure is a preferred state of low mechanical energy, which is, importantly, only reachable at sufficiently high treadmilling rates.
Heme oxygenase-2 (HO-2) binds and buffers labile heme, which is largely oxidized, in human embryonic kidney cells
Authors: Hanna David A. , Moore Courtney M. , Liu Liu , Yuan Xiaojing , Fleischhacker Angela S. , Hamza Iqbal , Ragsdale Stephen W. , Reddi Amit R.
Published: June 2021

Heme oxygenases (HO) detoxify heme by oxidatively degrading it into carbon monoxide, iron, and biliverdin, which is reduced to bilirubin and excreted. Humans express two isoforms: inducible HO-1, which is up-regulated in response to various stressors, including excess heme, and constitutive HO-2. While much is known about the regulation and physiological function of HO-1, comparatively little is known about the role of HO-2 in regulating heme homeostasis. The biochemical necessity for expressing constitutive HO-2 is largely dependent on whether heme is sufficiently abundant and accessible as a substrate under conditions in which HO-1 is not induced. By measuring labile heme, total heme, and bilirubin in human embryonic kidney HEK293 cells with silenced or over-expressed HO-2, and various HO-2 mutant alleles, we found that endogenous heme is too limiting to support HO-2 catalyzed heme degradation. Rather, we discovered that a novel role for HO-2 is to bind and buffer labile heme. Taken together, in the absence of excess heme, we propose that HO-2 regulates heme homeostasis by acting as a heme buffering factor in control of heme bioavailability. When heme is in excess, HO-1 is induced and both HO-2 and HO-1 can provide protection from heme toxicity by enzymatically degrading it. Our results explain why catalytically inactive mutants of HO-2 are cytoprotective against oxidative stress. Moreover, the change in bioavailable heme due to HO-2 overexpression, which selectively binds ferric over ferrous heme, is consistent with the labile heme pool being oxidized, thereby providing new insights into heme trafficking and signaling.