bluuebunny/crossref_metadata_2025 huggingface dataset:
Sexually dimorphic impact of the iron-regulating gene, HFE, on survival in glioblastoma
Authors: Nesterova Darya S , Midya Vishal , Zacharia Brad E , Proctor Elizabeth A , Lee Sang Y , Stetson Lindsay C , Lathia Justin D , Rubin Joshua B , Waite Kristin A , Berens Michael E , Barnholtz-Sloan Jill S , Connor James R
Published: January 2020

Background

The median survival for patients with glioblastoma (GBM), the most common primary malignant brain tumor in adults, has remained approximately 1 year for more than 2 decades. Recent advances in the field have identified GBM as a sexually dimorphic disease. It is less prevalent in females and they have better survival compared to males. The molecular mechanism of this difference has not yet been established. Iron is essential for many biological processes supporting tumor growth and its regulation is impacted by sex. Therefore, we interrogated the expression of a key component of cellular iron regulation, the HFE (homeostatic iron regulatory) gene, on sexually dimorphic survival in GBM.

Methods

We analyzed TCGA microarray gene expression and clinical data of all primary GBM patients (IDH-wild type) to compare tumor mRNA expression of HFE with overall survival, stratified by sex.

Results

In low HFE expressing tumors (below median expression, n = 220), survival is modulated by both sex and MGMT status, with the combination of female sex and MGMT methylation resulting in over a 10-month survival advantage (P < .0001) over the other groups. Alternatively, expression of HFE above the median (high HFE, n = 240) is associated with significantly worse overall survival in GBM, regardless of MGMT methylation status or patient sex. Gene expression analysis uncovered a correlation between high HFE expression and expression of genes associated with immune function.

Conclusions

The level of HFE expression in GBM has a sexually dimorphic impact on survival. Whereas HFE expression below the median imparts a survival benefit to females, high HFE expression is associated with significantly worse overall survival regardless of established prognostic factors such as sex or MGMT methylation.
Comparison of Multiplex Gastrointestinal Pathogen Panel and Conventional Stool Testing for Evaluation of Patients With HIV Infection
Authors: Sobczyk Juliana , Jain Sonia , Sun Xiaoying , Karris Maile , Wooten Darcy , Stagnaro Janet , Reed Sharon
Published: January 2020

Background

Gastrointestinal pathogen panels (GPPs) are increasingly used to identify stool pathogens, but their impact in people with HIV (PWH) is unknown. We performed a retrospective cohort study comparing GPP and conventional stool evaluation in PWH.

Methods

We included all PWH who underwent GPP (Biofire Diagnostics; implemented September 15, 2015) or conventional testing, including stool culture, Clostridium difficile polymerase chain reaction testing, fluorescent smears for Cryptosporidium or Giardia, and ova and parasite exams (O&P) from 2013 to 2017. A total of 1941 specimens were tested, with 169 positive specimens detected in 144 patients. We compared result turnaround time, pathogen co-infection, antibiotic treatment, and treatment outcomes between positive specimens detected by conventional testing vs GPP.

Results

Overall, 124 patient samples tested positive by GPP, compared with 45 patient specimens by conventional testing. The GPP group demonstrated a higher co-infection rate (48.4% vs 13.3%; P < .001) and quicker turnaround time (23.4 vs 71.4 hours; P < .001). The GPP identified 29 potential viral infections that were undetectable by conventional stool tests. Unnecessary anti-infective therapy was avoided in 9 of 11 exclusively viral infections. Exclusively nonpathogenic parasites (n = 13) were detected by conventional stool tests, the majority of which were treated with metronidazole. There were no significant differences in clinical outcomes between groups.

Conclusions

In PWH, GPP implementation improved antibiotic stewardship through shorter turnaround times and detection of enteric viral pathogens.
Evaluating Inoculation Methods to Infect Sugar Beet with Fusarium oxysporum f. betae and F. secorum
Authors: Lai X. , Qi A. , Liu Y. , Mendoza L. E. Del Río , Liu Z. , Lin Z. , Khan M. F. R.
Published: January 2020

Minnesota and North Dakota combined contain 55% of the sugar beet production area in the United States, contributing to 49% of the nation’s sugar beet production in 2018. Fusarium diseases caused by Fusarium oxysporum f. betae and F. secorum on sugar beet can cause significant reduction in both root yield and sucrose concentration and purity. The objective of this research was to identify an alternative artificial inoculation method to induce Fusarium diseases on sugar beet leaves and roots caused by both Fusarium spp. in greenhouse conditions to better aid in research efforts. We tested four inoculation methods, including barley to seed, barley to root, drenching, and cutting. and compared them with the conventional root-dipping inoculation method. The inoculation method of placing Fusarium-colonized barley seed close to sugar beet seed (barley to seed) caused levels of symptom severities on both leaves and roots similar to the root-dipping method. Because the traditional root-dipping method involves a laborious transplant process, use of infected barley seed as inoculum may serve as an alternative method in the evaluation of host resistance and pathogen virulence among Fusarium diseases by Fusarium spp. on sugar beet at the seed or seedling stage.
Heparin sensitivity and postoperative blood loss in patients undergoing cardiac surgery with cardiopulmonary bypass
Authors: Ma Hai-Ping , Xu Wei-Fang , Yu Jin , Wang Jiang , Zheng Hong
Published: January 2020

BACKGROUND

Heparin-associated coagulation disorder is an important factor related to postoperative bleeding in patients undergoing cardiac surgery with cardiopulmonary bypass. Currently, the relationship between heparin sensitivity and postoperative bleeding is unknown.

OBJECTIVE

To investigate the relationship between individual heparin sensitivity and postoperative blood loss in patients undergoing cardiac surgery.

DESIGN

Prospective controlled study.

SETTING

Tertiary teaching hospital, Urumqi, Xinjiang, PR China. The study was conducted from January 2016 to August 2018.

PATIENTS

A total of 195 adult patients undergoing cardiac valve replacement surgery were included.

INTERVENTION

After initial heparin dosing (2.5 mg kg−1), patients were divided into three groups according to the whole blood activated clotting time (ACT): group A, insensitive group (ACT < 480 s); group B, sensitive group (480 s < ACT < 750 s); group C, hypersensitive group (ACT > 750 s).

MAIN OUTCOME MEASURES

First, intra-operative and 24-h postoperative blood loss. Second, antithrombin (AT) and factor X mRNA levels. Third, the plasma levels of AT-III and factor X. Fourth, heparin sensitivity index.

RESULTS

Blood loss was approximately 20 to 25% lower in group B than in groups A and C, which was statistically significant (P < 0.01). The AT-III mRNA levels increased from groups A to C and was positively associated with heparin sensitivity; the factor X mRNA levels changed in the opposite direction; a significant difference was observed between groups A and C (P < 0.05). The factor X plasma level showed the same trend as its mRNA. The AT-III plasma level was significantly lower in group B than in groups A and C (P < 0.05).

CONCLUSION

Postoperative blood loss is related to heparin sensitivity in patients undergoing cardiac surgery, and the moderately sensitive patients have the least postoperative bleeding. Individual variation in heparin sensitivity is related to the mRNA and plasma levels of AT-III and factor X.

TRIAL REGISTRATION

Registration number ChiCTR-RPC-17012259.
Serpentinite and the search for life beyond Earth
Authors: Vance S. D. , Melwani Daswani M.
Published: January 2020

Hydrogen from serpentinization is a source of chemical energy for some life forms on Earth. It is a potential fuel for life in the subsurface of Mars and in the icy ocean worlds in the outer solar system. Serpentinization is also implicated in life’s origin. Planetary exploration offers a way to investigate such theories by characterizing and ultimately searching for life in geochemical settings that no longer exist on Earth. At present, much of the current context of serpentinization on other worlds relies on inference from modelling and studies on Earth. While there is evidence from orbital spectral imaging and martian meteorites that serpentinization has occurred on Mars, the extent and duration of that activity has not been constrained. Similarly, ongoing serpentinization might explain hydrogen found in the ocean of Saturn’s tiny moon Enceladus, but this raises questions about how long such activity has persisted. Titan’s hydrocarbon-rich atmosphere may derive from ancient or present-day serpentinization at the bottom of its ocean. In Europa, volcanism or serpentinization may provide hydrogen as a redox couple to oxygen generated at the moon’s surface. We assess the potential extent of serpentinization in the solar system’s wet and rocky worlds, assuming that microfracturing from thermal expansion anisotropy sets an upper limit on the percolation depth of surface water into the rocky interiors. In this bulk geophysical model, planetary cooling from radiogenic decay implies the infiltration of water to greater depths through time, continuing to the present. The serpentinization of this newly exposed rock is assessed as a significant source of global hydrogen. Comparing the computed hydrogen and surface-generated oxygen delivered to Europa’s ocean reveals redox fluxes similar to Earth’s. Planned robotic exploration missions to other worlds can aid in understanding the planetary context of serpentinization, testing the predictions herein.

This article is part of a discussion meeting issue ‘Serpentinite in the Earth System’.
Formation and loss of metastable brucite: does Fe(II)-bearing brucite support microbial activity in serpentinizing ecosystems?
Authors: Templeton A. S. , Ellison E. T.
Published: January 2020

Ultramafic rocks undergo successive stages of hydration and oxidation during water/rock interaction, giving rise to secondary minerals such as brucite, serpentine, magnetite and the production of H
2(g)
. Ferroan brucite

(

M

g

x

Fe

(

1
−

x

)

2
+

(

OH

)

2

)

often forms under low water/rock ratios early during the ‘serpentinization’ process. The formation of ferroan brucite sequesters Fe(II) and suppresses the production of H
2
, thereby limiting the flux of reductants suitable for sustaining microbial metabolism. Yet ferroan brucite is a relatively soluble mineral ‘reservoir’ for reactive Fe(II). Brucite is often metastable and can be lost at later stages of peridotite hydration when there is a significant increase in the water/rock ratio or the activity of SiO
2
or CO
2
. The Fe(OH)
2
component of brucite has the thermodynamic potential to reduce most aqueous oxidants. Therefore, ferroan brucite may reduce water and/or dissolved carbon, nitrogen and sulfur species, while the Fe(II) is converted into more stable secondary minerals such as Fe(II/III)-oxides and hydroxides (e.g. green-rust, magnetite, iowaite and pyroaurite) and ferric serpentine. The reactivity of ferroan brucite, and the associated rate of Fe solubilization and oxidation in subsurface fluids, could be a key regulator on the rate of electron transfer from serpentinites to the rock-hosted biosphere. Aqueous alteration of ferroan brucite may significantly modulate the H
2
activity in fluids circulating within partially serpentinized rocks, and buffer H
2
as it is lost by advection or
in situ
consumption by a hydrogenotrophic microbial community. Moreover, there may be microbial organisms that specifically colonize and use ferroan brucite as an electron donor for their metabolism. The energy fluxes sustained by localized brucite oxidation may often be sufficiently large to sustain abundant microbial communities; water/rock reaction zones where brucite is consumed could serve as environments to search for extant or fossil serpentinite-hosted life.

This article is part of a discussion meeting issue ‘Serpentinite in the Earth System’.
Chemical and isotopic analyses of hydrocarbon-bearing fluid inclusions in olivine-rich rocks
Authors: Grozeva Niya G. , Klein Frieder , Seewald Jeffrey S. , Sylva Sean P.
Published: January 2020

We examined the mineralogical, chemical and isotopic compositions of secondary fluid inclusions in olivine-rich rocks from two active serpentinization systems: the Von Damm hydrothermal field (Mid-Cayman Rise) and the Zambales ophiolite (Philippines). Peridotite, troctolite and gabbroic rocks in these systems contain abundant CH
4
-rich secondary inclusions in olivine, with less abundant inclusions in plagioclase and clinopyroxene. Olivine-hosted secondary inclusions are chiefly composed of CH
4
and minor H
2
, in addition to secondary minerals including serpentine, brucite, magnetite and carbonates. Secondary inclusions in plagioclase are dominated by CH
4
with variable amounts of H
2
and H
2
O, while those in clinopyroxene contain only CH
4
. We determined hydrocarbon abundances and stable carbon isotope compositions by crushing whole rocks and analysing the released volatiles using isotope ratio monitoring—gas chromatography mass spectrometry. Bulk rock gas analyses yielded appreciable quantities of CH
4
and C
2
H
6
in samples from Cayman (4–313 nmol g
−1
CH
4
and 0.02–0.99 nmol g
−1
C
2
H
6
), with lesser amounts in samples from Zambales (2–37 nmol g
−1
CH
4
and 0.004–0.082 nmol g
−1
C
2
H
6
). Mafic and ultramafic rocks at Cayman exhibit δ
13
C

CH
4

values of −16.7‰ to −4.4‰ and δ
13
C

C
2
H
6

values of −20.3‰ to +0.7‰. Ultramafic rocks from Zambales exhibit δ
13
C

CH
4

values of −12.4‰ to −2.8‰ and δ
13
C

C
2
H
6

values of −1.2‰ to −0.9‰. Similarities in the carbon isotopic compositions of CH
4
and C
2
H
6
in plutonic rocks, Von Damm hydrothermal fluids, and Zambales gas seeps suggest that leaching of fluid inclusions may provide a significant contribution of abiotic hydrocarbons to deep-sea vent fluids and ophiolite-hosted gas seeps. Isotopic compositions of CH
4
and C
2
H
6
from a variety of hydrothermal fields hosted in olivine-rich rocks that are similar to those in Von Damm vent fluids further support the idea that a significant portion of abiotic hydrocarbons in ultramafic-influenced vent fluids is derived from fluid inclusions.

This article is part of a discussion meeting issue ‘Serpentinite in the Earth system’.
Major element mobility during serpentinization, oxidation and weathering of mantle peridotite at low temperatures
Authors: de Obeso Juan Carlos , Kelemen Peter B.
Published: January 2020

Mantle peridotite in Wadi Fins in eastern Oman exhibits three concentric alteration zones with oxide and sulfide mineralogy recording gradients in
f
O
2
and
f
S
2
(fugacity) of more than 20 orders of magnitude over 15–20 cm. The black cores of samples (approx. 5 cm in diameter) exhibit incomplete, nearly isochemical serpentinization, with relict primary mantle minerals (olivine, orthopyroxene and clinopyroxene) along with sulfide assemblages (pentlandite/heazlewoodite/bornite) recording low
f
O
2
and moderate
f
S
2
. In addition to the black cores, two alteration zones are evident from their colouration in outcrop and hand samples: green and red. These zones exhibit non-isochemical alteration characterized by intergrowths of stevensite/lizardite. All three reaction zones are cut by calcite ± serpentine veins, which are most abundant in the outer, red zones, sometimes are flanked by narrow red and/or green zones where they cut the black zones, and thus may be approximately coeval with all three alteration zones. The alteration zones record progressively higher 
f
O
2
recorded by Ni-rich sulfides and iron oxides/hydroxides. These alteration zones lost 20–30% of their initial magnesium content, together with mobilization of iron over short distances from inner green zones into outer red zones, where iron is reprecipitated in goethite intermixed with silicates due to higher
f
O
2
. Thermodynamic modelling at 60°C and 50 MPa (estimated alteration conditions) reproduces sulfide assemblages,
f
O
2
changes and Mg and Fe mobility.

This article is part of a discussion meeting issue ‘Serpentinite in the Earth system’.
Sphingorhabdus soli sp. nov., isolated from Arctic soil
Authors: Liu Yang , Du Juan , Zhang Jun , Lai Qiliang , Shao Zongze , Zhu Honghui
Published: January 2020

A Gram-stain-negative, strictly aerobic, rod-shaped and non-motile bacterial strain, designated D-2Q-5-6T, was isolated from a soil sample collected from the Arctic region. Strain D-2Q-5-6T was found to grow at 10–43 °C (optimum, 28 °C), at pH 6.0–9.0 (pH 7.0) and in 0–5 % (w/v) NaCl (0–1 %). Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain D-2Q-5-6T fell into the genus

Sphingorhabdus

and shared less than 95.8 % identity with all type strains of recognized species of this genus. The major cellular fatty acids of strain D-2Q-5-6T were summed feature 8 (C18 : 1
ω7c and/or C18 : 1
ω6c; 31.4 %), summed feature 3 (C16 : 1
ω7c and/or C16 : 1
ω6c; 26.8 %) and C14 : 0 2OH (11.7 %). The polar lipids consisted of diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, phosphatidylcholine and sphingoglycolipid. The predominant quinone was identified as Q10. The DNA G+C content of strain D-2Q-5-6T was 64.5 mol%. Based on the results of phylogenetic analysis and distinctive phenotypic characteristics, strain D-2Q-5-6T is concluded to represent a novel species of the genus

Sphingorhabdus

, for which the name Sphingorhabdus soli sp. nov. is proposed. The type strain of the species is D-2Q-5-6T (=MCCC 1A06070T=KCTC 52311T).
Performance of FRAX in predicting fracture in the US postmenopausal women with varied race and genetic profiles
Authors: Wu Qing , Xiao Xiangxue , Xu Yingke
Published: January 2020

Background

Whether the Fracture Risk Assessment Tool (FRAX) performed differently in estimating the 10-year fracture probability in women of different genetic profiling and race remained unclear.

Methods

The genomic data in the Women’s Health Initiative study was analyzed (n=23,981). the genetic risk score (GRS) was calculated from 14 fracture-associated single nucleotide polymorphisms (SNPs) for each participant. FRAX without bone mineral density (BMD) was used to estimate fracture probability.

Results

FRAX significantly overestimated the risk of major osteoporotic fracture (MOF) in the WHI study. The most enormous overestimation was observed in women with low GRS (predicted/observed ratio [POR]: 1.61, 95% CI: 1.45-1.79), in Asian women (POR: 3.5, 95% CI 2.48-4.81), and in African American women (POR: 2.59, 95% CI: 2.33-2.87). Compared to the low GRS group, the 10-year probability of MOF adjusted for the FRAX score was 21% and 30% higher in median GRS group and high GRS group, respectively. Asian, African American, and Hispanic women respectively had a 78%, 76%, and 56% lower hazard than Caucasian women after the FRAX score was adjusted for. The results were similar when for hip fractures.

Conclusions

Our study suggested the FRAX performance varies significantly by both genetic profiling and race in postmenopausal women.
Thrombospondin-4 mediates hyperglycemia- and TGF-beta-induced inflammation in breast cancer
Authors: Muppala Santoshi , Xiao Roy , Gajeton Jasmine , Krukovets Irene , Verbovetskiy Dmitriy , Stenina-Adognravi Olga
Published: January 2020

Inflammation drives the growth of tumors and is an important predictor of cancer aggressiveness. CD68, a marker of tumor-associated macrophages (TAM), is routinely used as a marker to aid in prognosis and treatment choices for breast cancer.

We report that thrombospondin-4 (TSP-4) mediates breast cancer inflammation and growth in mouse models in response to hyperglycemia and TGF-beta by increasing TAM infiltration and production of inflammatory signals in tumors. Analysis of breast cancers and non-cancerous tissue specimens from hyperglycemic patients revealed that levels of TSP-4 and of macrophage marker CD68 are upregulated in diabetic tissues. TSP-4 was co-localized with macrophages in cancer tissues. Bone-marrow-derived macrophages (BMDM) responded to high glucose and TGF-beta by upregulating TSP-4 production and expression, as well as the expression of inflammatory markers.

We report a novel function for TSP-4 in breast cancer: regulation of TAM infiltration and inflammation. The results of our study provide new insights into regulation of cancer growth by hyperglycemia and TGF-beta and suggest TSP-4 as a potential therapeutic target.

Novelty and Impact

Thrombospondin-4 (TSP-4) is a secreted extracellular protein that belongs to the family of matricellular proteins. TSP-4 is one of the top 1% of proteins upregulated in several cancers, including breast cancer. Inflammation and infiltration of macrophages drive cancer progression and metastasis and are clinically important markers of cancer aggressiveness and critical consideration in the process of selection of the appropriate therapeutic approaches. We report that TSP-4 promotes breast cancer inflammation and infiltration of macrophages and mediates the effects of hyperglycemia and TGF-beta on cancer growth and inflammation. Our work describes a role for TSP-4 in cancer inflammation and identifies the pathways, in which increased levels of TSP-4 mediate cancer growth.
Alzheimer’s Disease Neuropathological Comorbidities Are Common in the Younger-Old
Authors: Beach Thomas G. , Malek-Ahmadi Michael
Published: January 2020

Clinicopathological studies have demonstrated that Alzheimer’s disease dementia (ADD) is often accompanied by clinically undetectable comorbid neurodegenerative and cerebrovascular disease that alter the presence and rate of cognitive decline in aging and ADD. Aside from causing increased variability in clinical response, it is possible that the major ADD comorbidities may not respond to ADD-specific molecular therapeutics. As most reports have focused on comorbidity in the oldest-old, its extent in younger age groups that are more likely to be involved in clinical trials is largely unknown. We conducted a survey of neuropathological comorbidities in sporadic ADD using data from the US National Alzheimer’s Coordinating Center. Subject data was restricted to those with dementia and meeting National Institute on Aging-Alzheimer’s Association (NIA-AA) intermediate or high AD Neuropathological Change (ADNC) levels, excluding those with known autosomal dominant AD-related mutations. Subjects were divided into age-at-death categories for analysis: under 60, 60-69, 70-79, 80-89, 90-99 and 100 or over. Confirmatory of earlier reports, ADD histopathology is less severe with advancing age, effectively increasing the relative contribution of comorbidities, most of which rise in prevalence with age. Highly prevalent ADD comorbidities are not restricted to the oldest-old but are common even in early-onset ADD. The percentage of cases with ADD as the sole major neuropathological diagnosis is highest in the under-60 group, where “pure” ADD cases are still in the minority at 44%. After this AD as a sole major pathology in ADD declines to roughly 20% in the 70s and beyond. Comorbidity rates for some pathologies, especially LBD, are high even in subjects in their 60s and 70s, at nearly 60%, but for most others, their prevalence increases with age. TDP-43 pathology affects more than 35% of ADD subjects 80 and over while microscopic infarcts reach this rate a decade later. Gross infarcts rise more slowly and affect fewer subjects but still involve 15-20% of ADD after age 80. White matter rarefaction may be underestimated in the NACC database but is present in almost 70% of centenarians with ADD. Effective clinical trials depend on accurate estimates of required subject numbers, which are dependent on observed effect size and clinical response variability. Comorbidities are likely to affect both, leading to lower probability of clinical trial success. Stratifying ADD clinical trial analyses by presence and types of accompanying comorbidities might identify subgroups with higher effect sizes and greater clinical response rates, but accurate in-vivo diagnostic methods for most comorbidities are still lacking.
NMR Line Shapes in Molecular Mechanisms with Ligand Binding and Multiple Conformers
Authors: Kovrigin Evgenii L
Published: January 2020

Interactions of ligands with biological macromolecules are sensitively detected through changes of chemical shifts and line shapes of the NMR signals. This paper reports a mathematical analysis and simulations of NMR line shapes expected in titrations when ligand binding is coupled to multiple isomerization transitions. Such molecular mechanisms may correspond to ligand binding by intrinsically disordered proteins or by autoinhibited enzymes. Based on the simulation results, we anticipate several specific effects that may be observed in practice. First, the presence of non-binding conformers of the receptor molecule leads to a remarkable broadening in the binding transition even if the exchange between binding and non-binding conformers is very slow. Second, the ligand-binding mechanisms involving induced fit are expected to demonstrate deceptively decelerated exchange regimes even when the underlying kinetics are very fast. Conversely, the observation of fast-exchange shifting resonances with modest line-broadening (“marching peaks”) in practical NMR titrations may involve conformational selection transitions but less likely to be observed for the induced fit. Finally, in auto-inhibited molecules that open to form multiple binding-competent conformers, the fast dynamics of opening/closing transition are capable of masking the true kinetics of interconversion among transiently open forms of the receptor.
Repetitive DNA profiles Reveal Evidence of Rapid Genome Evolution and Reflect Species Boundaries in Ground Beetles
Authors: Sproul John S. , Barton Lindsey M. , Maddison David R.
Published: January 2020

Abstract

Genome architecture is a complex, multidimensional property of an organism defined by the content and spatial organization of the genome’s component parts. Comparative study of entire genome architecture in model organisms is shedding light on mechanisms underlying genome regulation, evolution, and diversification; but such studies require costly analytical approaches which make extensive comparative study impractical for most groups. However, lower-cost methods that measure a single architectural component (e.g., distribution of one class of repeats) have potential as a new data source for evolutionary studies insofar as that measure correlates with more complex biological phenomena, and for which it could serve as part of an explanatory framework. We investigated copy number variation (CNV) profiles in ribosomal DNA (rDNA) as a simple measure reflecting the distribution of rDNA subcomponents across the genome. We find that signatures present in rDNA CNV profiles strongly correlate with species boundaries in thebrevespecies group ofBembidion, and vary across broader taxonomic sampling inBembidionsubgenusPlataphus. Profiles of several species show evidence of re-patterning of rDNA-like sequences throughout the genome, revealing evidence of rapid genome evolution (including among sister pairs) not evident from analysis of traditional data sources such as multi-gene data sets. Major re-patterning of rDNA-like sequences has occurred frequently within the evolutionary history ofPlataphus. We confirm that CNV profiles represent an aspect of genomic architecture (i.e., the linear distribution of rDNA components across the genome) via fluorescencein-situhybridization. In at least one species, novel rDNA-like elements are spread throughout all chromosomes. We discuss the potential of copy number profiles of rDNA, or other repeats, as a low-cost tool for incorporating signal of genomic architecture variation in studies of species delimitation and genome evolution.
Bee and Flowering Plant Communities in a Riparian Corridor of the Lower Rio Grande River (Texas, USA)
Authors: Rubio Amede , Wright Karen , Longing Scott
Published: January 2020

The Rio Grande in Texas serves as the geo-political boundary between the United States and Mexico. It is considered one of the world’s most at-risk rivers and has been the subject of intensified management by the inhabitants of both countries lining its banks. Additionally, invasion by non-native Arundo donax (Linnaeus) (Cyperales: Poaceae), giant reed, has been extensive in the riparian corridor, with potential impacts to native wildlife. Locally, there remains a significant lack of ecological community data of riparian and upland habitats parallel to the river. We sampled bee and flowering plant communities monthly over two years, along a 3.22 km stretch of the lower Rio Grande in Webb County, TX. Data show that bee and plant richness and abundance was highest during March-April and September among both habitat types. Analysis of bee communities showed low spatial and temporal variation at the habitat level. Although common bee taxa (Halictidae and Apidae) were numerically dominant, NMS and ISA found key bee species driving community patterns. This included higher abundances of two species in the riparian habitat Anthophora occidentalis (Cresson) (Hymenoptera: Apidae) and Lasioglossum sp.L (Curtis) (Hymenoptera: Apidae) and one showing affinity for the upland habitat Halictus ligatus (Say) (Hymenoptera: Halictidae). Additionally, ISA analysis of plant data revealed that three species were significant indicator taxa in riparian habitats. Further analysis showed a positive correlation between bee generic richness and abundance with various climate attributes. Management of the riparian corridor and associated watershed could include significant areas for ecological restoration to assist pollinators.
ZEAMAP, a comprehensive database adapted to the maize multi-omics era
Authors: Gui Songtao , Yang Linfeng , Li Jianbo , Luo Jingyun , Xu Xiaokai , Yuan Jianyu , Chen Lu , Li Wenqiang , Yang Xin , Wu Shenshen , Li Shuyan , Wang Yuebin , Zhu Yabing , Gao Qiang , Yang Ning , Yan Jianbing
Published: January 2020

As one of the most extensively cultivated crops, maize (Zea maysL.) has been extensively studied by researchers and breeders for over a century. With advances in high-throughput detection of various omics data, a wealth of multi-dimensional and multi-omics information has been accumulated for maize and its wild relative, teosinte. Integration of this information has the potential to accelerate genetic research and generate improvements in maize agronomic traits. To this end, we constructed ZEAMAP (http://www.zeamap.com), a comprehensive database incorporating multiple reference genomes, annotations, comparative genomics, transcriptomes, open chromatin regions, chromatin interactions, high-quality genetic variants, phenotypes, metabolomics, genetic maps, genetic mapping loci, population structures and domestication selection signals between teosinte and maize. ZEAMAP is user-friendly, with the ability to interactively integrate, visualize and cross-reference multiple different omics datasets.
Subcortical magnocellular visual system facilities object recognition by processing topological property
Authors: Wang Wenbo , Zhou Tiangang , Zhuo Yan , Chen Lin , Huang Yan
Published: January 2020

The Magnocellular (M) visual pathway is known as a fast route to convey coarse information and facilitates object recognition by initiating top-down processes. It is unclear what exact properties M pathway conveys to accelerate visual object processing. Previous studies suggest that visual systems are highly sensitive to the perception of topological property (TP), which remains unchanged under various shape changes, and the TP is probably processed through a fast subcortical pathway. Here we hypothesize that a subcortical M system contributes to the fast object recognition by processing TP first. We first demonstrate that the facilitation effect of TP processing on object perception occurs mainly in the M visual system, and then support the subcortical M hypothesis of TP processing by the evidence that the early processing of TP was not affected when cortical function was temporarily damaged by the transcranial magnetic stimulation and when stimuli were biased to M system.
A CSB-PAF1C axis restores processive transcription elongation after DNA damage repair
Authors: van den Heuvel Diana , Spruijt Cornelia G. , González-Prieto Román , Kragten Angela , Paulsen Michelle T. , Zhou Di , Wu Haoyu , Apelt Katja , van der Weegen Yana , Yang Kevin , Dijk Madelon , Daxinger Lucia , Marteijn Jurgen A. , Vertegaal Alfred C.O. , Ljungman Mats , Vermeulen Michiel , Luijsterburg Martijn S.
Published: January 2020

The coordinated transcription of genes involves the regulated release of RNA polymerase II (RNAPII) from promoter-proximal sites into active elongation. DNA lesions in transcribed strands block elongation and induce a strong transcriptional arrest. The transcription-coupled repair (TCR) pathway efficiently removes transcription-blocking DNA lesions, but this is not sufficient to resume transcription. Through proteomics screens, we find that the TCR-specific CSB protein loads the evolutionary conserved PAF1 complex (PAF1C) onto RNAPII in promoter-proximal regions in response to DNA damage. PAF1C is dispensable for TCR-mediated repair, but is essential for recovery of RNA synthesis after UV irradiation, suggesting an uncoupling between DNA repair and transcription recovery. Moreover, we find that PAF1C promotes RNAPII pause release in promoter-proximal regions and subsequently acts as a processivity factor that stimulates transcription elongation throughout genes. Our findings expose the molecular basis for a non-canonical PAF1C-dependent pathway that restores transcription throughout the human genome after genotoxic stress.
1-[(4-Nitrophenyl)sulfonyl]-4-phenylpiperazine Treatment After Brain Irradiation Preserves Cognitive Function in Mice
Authors: Bhat Kruttika , Medina Paul , He Ling , Zhang Le , Saki Mohammad , Ioannidis Angeliki , Nguyen Nhan T. , Sodhi Sirajbir S. , Sung David , Magyar Clara E. , Liau Linda M. , Kornblum Harley I. , Pajonk Frank
Published: January 2020

Background

Normal tissue toxicity to the CNS is an inevitable consequence of a successful radiotherapy of brain tumors or cancer metastases to the CNS. Cranial irradiation commonly leads to neurocognitive deficits that manifest months or years after treatment. Mechanistically, radiation-induced loss of neural stem/progenitor cells, neuro-inflammation and de-myelinization are contributing factors that lead to progressive cognitive decline.

Methods

The effects of Compound #5 on irradiated murine neurospheres, microglia cells and patients-derived gliomaspheres were assessed in sphere-formation assays, flow cytometry and IL-6 ELISAs, Activation of the Hedgehog pathway was studied by qRT-PCR. Thein vivoeffects of Compound #5 were analyzed using flow cytometry, sphere-formation assays, immune-histochemistry, behavioral testing and an intracranial mouse model of glioblastoma.

Results

We report that 1-[(4-Nitrophenyl)sulfonyl]-4-phenylpiperazine (Compound #5) mitigates radiation-induced normal tissue toxicity in the brains of mice. Compound #5 treatment significantly increased the number of neural stem/progenitor cells after brain irradiation in female animals, inhibited radiation-induced microglia activation and expression of the pro-inflammatory cytokine interleukin-6. Behavioral testing revealed that treatment with Compound #5 after radiotherapy successfully mitigates radiation-induced decline in motor, sensory and memory function of the brain. In mouse models of glioblastoma, Compound #5 showed no toxicity and did not interfere with the growth-delaying effects of radiation.

Conclusions

We conclude that Compound #5 has the potential to mitigate cognitive decline in patients undergoing partial or whole brain irradiation without promoting tumor growth and that the use of this compound as a radiation mitigator of radiation late effects on the CNS warrants further investigation.

Importance of the Study

Successful radiotherapy of CNS malignancies inevitably lead to cognitive decline in cancer survivors and treatment options to mitigate this side effect are limited. We present evidence that a piperazine compound can prevent cognitive decline in mice after total brain irradiation without compromising the antitumor effect of radiation, suggesting that this compound could be used to mitigate radiation side effects in brain tumor patients undergoing radiotherapy.
In vivocommensal control ofClostridioides difficilevirulence
Authors: Girinathan Brintha P. , DiBenedetto Nicholas , Worley Jay N. , Peltier Johann , Arrieta-Ortiz Mario L. , Immanuel Rupa , Lavin Richard , Delaney Mary L. , Cummins Christopher , Hoffmann Maria , Luo Yan , Escalona Narjol Gonzalez , Allard Marc , Onderdonk Andrew B. , Gerber Georg K. , Sonenshein Abraham L. , Baliga Nitin , Dupuy Bruno , Bry Lynn
Published: January 2020

We define multiple mechanisms by which commensals protect against or worsenClostridioides difficileinfection. Leveraging new systems-level models we show how metabolically distinct species ofClostridiamodulate the pathogen’s colonization, growth, and virulence to impact host survival. Gnotobiotic mice colonized with the amino acid fermenterParaclostridium bifermentanssurvived infection while mice colonized with the butyrate- producer,Clostridium sardiniense,more rapidly succumbed. Systematicin vivoanalyses revealed how each commensal altered the gut nutrient environment, modulating the pathogen’s metabolism, regulatory networks, and toxin production. Oral administration ofP. bifermentansrescued conventional mice from lethalC. difficileinfection via mechanisms identified in specifically colonized mice. Our findings lay the foundation for mechanistically informed therapies to counterC. difficileinfections using systems biologic approaches to define host-commensal-pathogen interactionsin vivo.

Graphical Abstract
Monitoring the production of high diffraction-quality crystals of two enzymes in real time usingin situdynamic light scattering
Authors: de Wijn Raphaël , Rollet Kévin , Engilberge Sylvain , McEwen Alastair G. , Hennig Oliver , Betat Heike , Mörl Mario , Riobé François , Maury Olivier , Girard Eric , Bénas Philippe , Lorber Bernard , Sauter Claude
Published: January 2020

The reproducible preparation of well diffracting crystals is a prerequisite for every structural study based on crystallography. An instrument called the XtalController has recently been designed that allows the monitoring of crystallization assays using dynamic light scattering and microscopy, and integrates piezo pumps to alter the composition of the mother liquor during the experiment. We have applied this technology to study the crystallization of two enzymes, the CCA-adding enzyme of the psychrophilic bacteriumPlanococcus halocryophilusand the hen egg white lysozyme in the presence of a synthetic chemical nucleant. We were able to i) detect early nucleation events and ii) drive the crystallization system (through cycles of dissolution/crystallization) towards growth conditions yielding crystals with excellent diffraction properties. This technology opens a way to the rational production of samples for crystallography, ranging from nanocrystals for electron diffraction, microcrystals for serial or conventional X-ray diffraction, to larger crystals for neutron diffraction.
Co-option ofPlasmodium falciparumPP1 for egress from host erythrocytes
Authors: Paul Aditya S. , Miliu Alexandra , Paulo Joao A. , Goldberg Jonathan M. , Bonilla Arianna M. , Berry Laurence , Séveno Marie , Braun-Breton Catherine , Kosber Aziz L. , Elsworth Brendan , Arriola Jose S.N. , Lebrun Maryse , Gygi Steven P. , Lamarque Mauld H. , Duraisingh Manoj T.
Published: January 2020

Asexual proliferation of thePlasmodiumparasites that cause malaria follow a developmental program that alternates non-canonical intraerythrocytic replication with dissemination to new host cells. We carried out a functional analysis of thePlasmodium falciparumhomolog of Protein Phosphatase 1 (PfPP1), a universally conserved cell cycle factor in eukaryotes, to investigate regulation of parasite proliferation.PfPP1 is indeed required for efficient replication, but is absolutely essential for egress of parasites from host red blood cells. A phosphoproteomic screen and chemical-genetic analysis provided evidence for a HECT E3 protein-ubiquitin ligase, as well as a fusion protein with guanylyl cyclase and phospholipid transporter domains, as functional targets ofPfPP1. Extracellular phosphatidylcholine stimulatesPfPP1-dependent egress. ParasitePfPP1 acts as a master regulator that can integrate multiple cell-intrinsic pathways with external signals to direct parasite egress from host cells.
Synaptic vesicles dynamics in neocortical epilepsy
Authors: Vannini Eleonora , Restani Laura , Dilillo Marialaura , McDonnell Liam , Caleo Matteo , Marra Vincenzo
Published: January 2020

Neuronal hyperexcitability often results from an unbalance between excitatory and inhibitory neurotransmission, but the synaptic alterations leading to enhanced seizure propensity are only partly understood. Taking advantage of a mouse model of neocortical epilepsy, we used a combination of photoconversion and electron microscopy to assess changes in synaptic vesicles poolsin vivo. Our analyses reveal that epileptic networks show an early onset lengthening of active zones at inhibitory synapses, together with a delayed spatial reorganization of recycled vesicles at excitatory synapses. Proteomics of synaptic content indicate that specific proteins were increased in epileptic mice. Altogether, our data reveal a complex landscape of nanoscale changes affecting the epileptic synaptic release machinery. In particular, our findings show that an altered positioning of release-competent vesicles represent a novel signature of epileptic networks.
The landscape of mouse epididymal cells defined by the single-cell RNA-Seq
Authors: Shi Jianwu , Sang Mengmeng , Xie Gangcai , Chen Hao
Published: January 2020

Spermatozoa acquire their fertilizing ability and forward motility properties during epididymal transit. Although lots of attempts elucidating the functions of different cell types in epididymis, the composition of epididymal tubal and cell types are still largely unknown. Using single-cell RNA sequence, we analyzed the cell constitutions and their gene expression profiles of adult epididymis derived from caput, corpus and cauda epididymis with a total of 12,597 cells. This allowed us to elucidate the full range of gene expression changes during epididymis and derive region-specific gene expression signatures along the epididymis. A total of 7 cell populations were identified with all known constituent cells of mouse epididymis, as well as two novel cell types. Our analyses revealed a segment to segment variation of the same cell type in the three different part of epididymis and generated a reference dataset of epididymal cell gene expression. Focused analyses uncovered nine subtypes of principal cell. Two subtypes of principal cell, c0.3 and c.6 respectively, in our results supported with previous finding that they mainly located in the caput of mouse epididymis and play important roles during sperm maturation. We also showed unique gene expression signatures of each cell population and key pathways that may concert epididymal epithelial cell-sperm interactions. Overall, our single-cell RNA seq datasets of epididymis provide a comprehensive potential cell types and information-rich resource for the studies of epididymal composition, epididymal microenvironment regulation by the specific cell type, or contraceptive development, as well as a gene expression roadmap to be emulated in efforts to achieve sperm maturation regulation in the epididymis.
A sample preparation protocol for high throughput immunofluorescence of suspension cells
Authors: Bäckström Anna , Kugel Laura , Gnann Christian , Xu Hao , Aslan Joseph E. , Lundberg Emma , Stadler Charlotte
Published: January 2020

Imaging is a powerful approach for studying protein expression and has the advantage over other methodologies in providing spatial informationin situat single cell level. Using immunofluorescence and confocal microscopy, detailed information of subcellular distribution of proteins can be obtained. While adherent cells of different tissue origin are relatively easy to prepare for imaging applications, nonadherent cells from hematopoietic origin, present a challenge due to their poor attachment to surfaces and subsequent loss of a substantial fraction of the cells. Still, these cell types represent an important part of the human proteome and express genes that are not expressed in adherent cell types. In the era of cell mapping efforts, overcoming the challenge with suspension cells for imaging applications would enable systematic profiling of hematopoietic cells. In this work, we successfully established an immunofluorescence protocol for preparation of suspension cell lines and peripheral blood mononucleated cells (PBMC) and human platelets. The protocol is based on a multi-well plate format with automated sample preparation, allowing for robust high throughput imaging applications. In combination with confocal microscopy, the protocol enables systematic exploration of protein localization to all major subcellular structures.
TGF-β-driven downregulation of the Wnt/β-Catenin transcription factor TCF7L2/TCF4 in PDGFRα+fibroblasts
Authors: Contreras Osvaldo , Soliman Hesham , Theret Marine , Rossi Fabio M.V. , Brandan Enrique
Published: January 2020

Mesenchymal stromal/stem cells (MSCs) are multipotent progenitors essential ororganogenesis, tissue homeostasis, regeneration, and scar formation. Tissue injury upregulates TGF-β signaling, which modulates myofibroblast fate, extracellular matrix remodeling, and fibrosis. However, the molecular determinants of MSCs differentiation and survival remain poorly understood. The canonical Wnt Tcf/Lef transcription factors regulate development and stemness, but the mechanisms by which injury-induced cues modulate their expression remain underexplored. Here, we studied the cell-specific gene expression of Tcf/Lef and, more specifically, we investigated whether damage-induced TGF-β impairs the expression and function of TCF7L2, using several models of MSCs, including skeletal muscle fibro-adipogenic progenitors. We show that Tcf/Lefs are differentially expressed and that TGF-β reduces the expression of TCF7L2 in MSCs but not in myoblasts. We also found that the ubiquitin-proteasome system regulates TCF7L2 proteostasis and participates in TGF-β-mediated TCF7L2 protein downregulation. Finally, we show that TGF-β requires HDACs activity to repress the expression of TCF7L2. Thus, our work found a novel interplay between TGF-β and Wnt canonical signaling cascades in PDGFRα+fibroblasts and suggests that this mechanism could be targeted in tissue repa ir and regeneration.

Summary statement

TGF-β signaling suppresses the expression of the Wnt transcription factor TCF7L2 and compromises TCF7L2-dependent functions in tissue-resident PDGFRα+fibroblasts.