bluuebunny/crossref_metadata_2025 huggingface dataset:
The role of the PIK3CA gene in the development and aging of the brain
Authors: Xie Shaozhen , Ni Jing , Guo Hanbing , Luu Victor , Wang Yanzhi , Zhao Jean J. , Roberts Thomas M.
Published: January 2021

The CLOVES syndrome is an overgrowth disease arising from mosaic activating somatic mutations in the PIK3CA gene. These mutations occur during fetal development producing malformation and overgrowth of a variety of tissues. It has recently been shown that treatment with low doses of a selective inhibitor of Class I PI3K catalytic subunit p110α, the protein product of the PIK3CA gene, can yield dramatic therapeutic benefits for patients with CLOVES and PROS (a spectrum of PIK3CA-related overgrowth syndromes). To assess the long-term effects of moderate loses of p110α activity, we followed development and growth of mice with heterozygous loss of p110α (Pik3ca+/−) over their entire lifetimes, paying particular attention to effects on the brain. While homozygous deletion of the Pik3ca gene is known to result in early embryonic lethality, these Pik3ca+/− mice displayed a longer lifespan compared to their wild-type littermates. These mice appeared normal, exhibited no obvious behavioral abnormalities, and no body weight changes. However, their brains showed a significant reduction in size and weight. Notably, mice featuring deletion of one allele of Pik3ca only in the brain also showed gradually reduced brain size and weight. Mechanistically, either deletion of p110α or pharmacological inhibition of p110α activity reduced neurosphere size, but not numbers, in vitro, suggesting that p110α activity is critical for neuronal stem cells. The phenotypes observed in our two genetically engineered mouse models suggest that the sustained pharmacological inhibition of the PIK3CA activity in human patients might have both beneficial and harmful effects, and future treatments may need to be deployed in a way to avoid or minimize adverse effects.
Bromelain reduced pro-inflammatory mediators as a common pathway that mediate antinociceptive and anti-anxiety effects in sciatic nerve ligated Wistar rats
Authors: Bakare Ahmed O. , Owoyele Bamidele V.
Published: January 2021

The involvement of pro-inflammatory mediators complicates the complex mechanism in neuropathic pain (NP). This study investigated the roles of bromelain against pro-inflammatory mediators as a mechanism that underpins its antinociceptive and anti-anxiety effects in the peripheral model of NP. Sixty-four male Wistar rats randomly divided into eight groups, were used for the study. A chronic constriction injury model of peripheral neuropathy was used to induce NP. Tail-immersion and von Frey filaments tests were used to assess hyperalgesia while open field and elevated plus mazes were used to assess anxiety-like behaviour. NF-кB, iNOS, nitrate, and pro-inflammatory cytokines were investigated in the plasma, sciatic nerve, and brain tissues using ELISA, spectrophotometer, and immunohistochemistry techniques after twenty-one days of treatment. Bromelain significantly (p < 0.05) improved the cardinal signs of NP and inhibited anxiety-like behaviours in ligated Wistar rats. It mitigated the increases in cerebral cortex interleukin (IL) -1β, IL-6, and PGE2 levels. Bromelain reduced NF-кB, IL-1β, IL-6, TNF-α, PGE2, and nitrate concentrations as well as the expression of iNOS in the sciatic nerve. Hence, the antinociceptive and anxiolytic effects of bromelain in the sciatic nerve ligation model of NP is in part due to its ability to reduce nitrosative and inflammatory activities.
Transcriptomic analysis of early stages of intestinal regeneration in Holothuria glaberrima
Authors: Quispe-Parra David J. , Medina-Feliciano Joshua G. , Cruz-González Sebastián , Ortiz-Zuazaga Humberto , García-Arrarás José E.
Published: January 2021

Echinoderms comprise a group of animals with impressive regenerative capabilities. They can replace complex internal organs following injury or autotomy. In holothurians or sea cucumbers, cellular processes of intestinal regeneration have been extensively studied. The molecular machinery behind this faculty, however, remains to be understood. Here we assembled and annotated a de novo transcriptome using RNA-seq data consisting of regenerating and non-regenerating intestinal tissues from the sea cucumber Holothuria glaberrima. Comparisons of differential expression were made using the mesentery as a reference against 24 h and 3 days regenerating intestine, revealing a large number of differentially expressed transcripts. Gene ontology and pathway enrichment analysis showed evidence of increasing transcriptional activity. Further analysis of transcripts associated with transcription factors revealed diverse expression patterns with mechanisms involving developmental and cancer-related activity that could be related to the regenerative process. Our study demonstrates the broad and diversified gene expression profile during the early stages of the process using the mesentery as the focal point of intestinal regeneration. It also establishes the genes that are the most important candidates in the cellular processes that underlie regenerative responses.
Plasma and follicular fluid osteopontin levels during ovarian cycle and their correlation with follicular fluid vascular endothelial growth factor levels
Authors: Kuwabara Yoshimitsu , Ono Shuichi , Katayama Akira , Kurihara Sachiko , Oishi Yumiko , Takeshita Toshiyuki
Published: January 2021

Osteopontin (OPN) is a multifunctional secreted glycoprotein. We evaluated OPN concentrations in blood and follicular fluid (FF) during the ovarian cycle and their relationship with the production of vascular endothelial growth factor (VEGF), which is involved in the pathophysiology of ovarian hyperstimulation syndrome (OHSS). Twenty-two women undergoing in vitro fertilization (minimal stimulation protocol with clomiphene citrate) were enrolled. Samples were collected (a) on the third day of withdrawal bleeding, (b) 2 days before oocyte retrieval, and (c) on the day of oocyte retrieval. FF was collected during oocyte retrieval. The OPN concentration in each specimen and the VEGF concentration in FF was measured by enzyme-linked immunosorbent assays. Plasma OPN concentrations were (in ng/mL): (a) 416 ± 37.2, (b) 378 ± 35.8, and (c) 390 ± 40.0, with no significant differences between the groups. The OPN concentration in FF was 106 ± 13.4 ng/mL. A positive correlation was found between OPN concentrations in FF and plasma samples. A positive correlation was also found between plasma OPN and FF VEGF concentrations, irrespective of the blood-sampling period. Plasma OPN concentration is suggested to reflect the FF VEGF level at oocyte retrieval and maybe a novel clinical marker for predicting the risk for OHSS.
Source dipole analysis reveals a new brain response to visual symmetry
Authors: Tyson-Carr John , Bertamini Marco , Rampone Giulia , Makin Alexis
Published: January 2021

Visual regularity activates a network of brain regions in the extrastriate cortex. Previous EEG studies have found that this response scales parametrically with proportion of symmetry in symmetry + noise displays. The parametric symmetry response happens in many tasks, but it is enhanced during active regularity discrimination. However, the origins and time course of this selective enhancement are unclear. Here we answered remaining questions with new source dipole analysis. As assumed, the parametric symmetry response found at the sensor level was generated by a pair of dipoles in the left and right extrastriate cortex. This bilateral activity was itself enhanced during regularity discrimination. However, we identified a third, and later, symmetry response in the posterior cingulate during regularity discrimination. Unlike the extrastriate response, this previously unknown activation only indexes strong, task relevant regularity signals. This clarifies the neural circuits which mediate the perceptual and cognitive aspects of symmetry discrimination.
Quantitative proteomics analysis of Angiostrongylus vasorum-induced alterations in dog serum sheds light on the pathogenesis of canine angiostrongylosis
Authors: Tritten Lucienne , Gillis-Germitsch Nina , Kockmann Tobias , Schnyder Manuela
Published: January 2021

Blood contains hundreds of proteins, reflecting ongoing cellular processes and immune reactions. Infections with the blood-dwelling cardiopulmonary nematode Angiostrongylus vasorum in dogs manifest with a broad spectrum of clinical signs including respiratory distress, bleeding diathesis and neurological signs, and are associated with a perturbed blood protein profile in dogs. However, current knowledge does not completely explain the observed pathologies induced by A. vasorum infections, including bleeding disorders. Using sera from experimentally infected dogs, dog serum proteome was analysed by quantitative mass spectrometry methods over several time points before and after inoculation. Following computational analysis, we identified 139 up- and downregulated proteins after infection (log2 ratio cut-off ≥ 1.0; q-value ≤ 0.05). Among upregulated proteins were chitinase 3-like 1 and pulmonary surfactant-associated protein B (log2 fold-changes ≥ 5). Pathway enrichment revealed the complement (especially the lectin pathway) and coagulation cascades as significantly affected upon analysis of downregulated proteins. Among them were mannan-binding lectin serine peptidases, ficolin, and coagulation factor XIII-B. These results bring new elements towards understanding the underlying pathomechanisms of bleeding diatheses observed in some A. vasorum-infected dogs.
A threshold mechanism ensures minimum-path flow in lightning discharge
Authors: Blanchini Franco , Casagrande Daniele , Fabiani Filippo , Giordano Giulia , Palma David , Pesenti Raffaele
Published: January 2021

A well-known property of linear resistive electrical networks is that the current distribution minimizes the total dissipated power. When the circuit includes resistors with nonlinear monotonic characteristic, the current distribution minimizes in general a different functional. We show that, if the nonlinear characteristic is a threshold-like function and the current generator is concentrated in a single point, as in the case of lightning or dielectric discharge, then the current flow is concentrated along a single path, which is a minimum path to the ground with respect to the threshold. We also propose a dynamic model that explains and qualitatively reproduces the lightning transient behavior: initial generation of several plasma branches and subsequent dismissal of all branches but the one reaching the ground first, which is the optimal one.
Optimal body size adjustment of L3 CT skeletal muscle area for sarcopenia assessment
Authors: Derstine Brian A. , Holcombe Sven A. , Ross Brian E. , Wang Nicholas C. , Su Grace L. , Wang Stewart C.
Published: January 2021

Measurements of skeletal muscle cross-sectional area (SMA) at the level of the third lumbar (L3) vertebra derived from clinical computed tomography (CT) scans are commonly used in assessments of sarcopenia, the loss of skeletal muscle mass and function associated with aging. As SMA is correlated with height and Body Mass Index (BMI), body size adjustment is necessary to fairly assess sarcopenic low muscle mass in individuals of different height and BMI. The skeletal muscle index, a widely used measure, adjusts for height as $$(SMA/height^2)$$

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but uses no BMI adjustment. There is no agreed upon standard for body size adjustment. We extracted L3 SMA using non-contrast-enhanced CT scans from healthy adults, split into ‘Under-40’ and ‘Over-40’ cohorts. Sex-specific allometric analysis showed that height to the power of one was the optimal integer coefficient for height adjusted SMA in both males and females. We computed two height-adjusted measures $$SMA_{HT}=SMA/height$$

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HT

=
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and $$SMA_{HT2}=SMA/height^2$$

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=
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, comparing their Pearson correlations versus age, height, weight, and BMI separately by sex and cohort. Finally, in the ‘Under-40’ cohort, we used linear regression to convert each height-adjusted measure into a z-score ($$z(SMA_{HT})$$

z
(
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M

A

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)

, $$z(SMA_{HT2})$$

z
(
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M

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) adjusted for BMI. $$SMA_{HT}$$

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M

A

HT

was less correlated with height in both males and females ($$r=0.005$$

r
=
0.005

, $$p=0.91$$

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=
0.91

and $$r=0.1$$

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=
0.1

, $$p=0.01$$

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=
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) than $$SMA_{HT2}$$

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($$r=-\,0.30$$

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=
-

0.30

and $$r=-\,0.21$$

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=
-

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, $$p<0.001$$

p
<
0.001

). $$z(SMA_{HT})$$

z
(
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M

A

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)

was uncorrelated with BMI and weight, and minimally correlated with height in males and females ($$r=-\,0.01$$

r
=
-

0.01

, $$p=0.85$$

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=
0.85

and $$r=0.15$$

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=
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, $$p<0.001$$

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<
0.001

). The final $$z(SMA_{HT})$$

z
(
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M

A

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equation was: $$z = (I - {\widehat{I}}) / SD(I)$$

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=

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I
-

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^

)

/
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D

(
I
)

, where $$I = SMA/height$$

I
=
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M
A
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, $${\widehat{I}} = 50 + BMI + 13 \times sex + 0.6 \times BMI \times sex$$

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^

=
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+
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I
+
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×
s
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x
+
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×
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M
I
×
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, $$SD(I) = 8.8 + 2.6 \times sex$$

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D
(
I
)
=
8.8
+
2.6
×
s
e
x

, and sex = 1 if male, 0 if female. We propose $$SMA_{HT}$$

S
M

A

HT

for optimal height adjustment and the $$z(SMA_{HT})$$

z
(
S
M

A

HT

)

score for optimal height and BMI adjustment. By minimizing correlations with height and BMI, the $$z(SMA_{HT})$$

z
(
S
M

A

HT

)

score produces unbiased assessments of relative L3 skeletal muscle area across the full range of body sizes.
Regional homogeneity abnormalities of resting state brain activities in children with growth hormone deficiency
Authors: Zhang Fanyu , Hua Bo , Wang Mei , Wang Tengfei , Ding Zhongxiang , Ding Ju-Rong
Published: January 2021

Growth hormone deficiency (GHD) is a common developmental disorder in children characterized by low levels of growth hormone secretion, short stature, and multiple cognitive and behavioral problems, including hyperactivity, anxiety, and depression. However, the pathophysiology of this disorder remains unclear. In order to investigate abnormalities of brain functioning in children with GHD, we preformed functional magnetic resonance imaging and regional homogeneity (ReHo) analysis in 26 children with GHD and 15 age- and sex-matched healthy controls (HCs) in a resting state. Compared with HCs, children with GHD exhibited increased ReHo in the left putamen and decreased ReHo in the right precentral gyrus, reflecting a dysfunction of inhibitory control. Decreased ReHo was also identified in the orbital parts of the bilateral superior frontal gyrus and the medial part of the left superior frontal gyrus, a finding that correlated with the inappropriate anxiety and depression that are observed in this patient population. Our results provide imaging evidence of potential pathophysiologic mechanisms for the cognitive and behavioral abnormalities of children with GHD.
Weather radar detection of planetary boundary layer and smoke layer top of peatland fire in Central Kalimantan, Indonesia
Authors: Rahman Muhammad Arif , Nugroho Devis Styo , Yamanaka Manabu D. , Kawasaki Masahiro , Kozan Osamu , Ohashi Masafumi , Hashiguchi Hiroyuki , Mori Shuichi
Published: January 2021

During the dry period of August–October 2015, a C-band Doppler weather radar of the BMKG station in a fire-prone peatland area, Palangka Raya, detected echoes with reflectivity values between − 19 and + 34 dBZ at a height below 2–3 km and a slant range of 100 km. The MERRA-2/NASA atmospheric reanalysis database is used to obtain the vertical profiles of refractive index and equivalent potential temperature of the air. The temporal variation of the radar image is due to the tropical diurnal cycle of planetary boundary layer formation, which is consistent with the results of the database analysis. The echo images are discussed in terms of Bragg scattering of microwaves at the top of the planetary boundary layer. Weather radar monitoring of the fire smoke layer-top images has a potential feasibility to support real-time management of peatland fires.
Associating cryptogenic ischemic stroke in the young with cardiovascular risk factor phenotypes
Authors: Dardick Joseph M. , Flomenbaum David , Labovitz Daniel L. , Cheng Natalie , Liberman Ava L. , Esenwa Charles
Published: January 2021

Acute Ischemic Stroke (AIS) in the young is increasing in prevalence and the largest subtype within this cohort is cryptogenic. To curb this trend, new ways of defining cryptogenic stroke and associated risk factors are needed. We aimed to gain insights into the presence or absence of cardiovascular risk factors in cases of cryptogenic stroke. We conducted a retrospective cohort study of patients aged 18–49 who presented to an urban tertiary care center with AIS. We manually collected predefined demographic, clinical, laboratory and radiological variables. Clinical risk phenotypes were determined using these variables through multivariate analysis of patients with the small and large vessel disease subtypes (vascular phenotype) and cardioembolic subtype (cardiac phenotype). The resultant phenotype models were applied to cases deemed cryptogenic. Within the 449 patients who met criteria, patients with small and large vessel disease (vascular phenotype) had higher rates of hypertension, intracranial atherosclerosis, and diabetes mellitus, and higher admission glucose, HbA1c, admission blood pressure, and cholesterol compared to the patients with cardioembolic AIS. The cardioembolic subgroup (cardiac phenotype) had significantly higher rates of congestive heart failure (CHF), rheumatic heart disease, atrial fibrillation, clotting disorders, left ventricular hypertrophy, larger left atrial sizes, lower ejection fractions, and higher B-type natriuretic peptide and troponin levels. Adjusted multivariate analysis produced six variables independently associated with the vascular phenotype (age, male sex, hemoglobin A1c, ejection fraction (EF), low-density lipoprotein (LDL) cholesterol, and family history of AIS) and five independently associated with the cardiac phenotype (age, female sex, decreased EF, CHF, and absence of intracranial atherosclerosis). Applying these models to cryptogenic stroke cases yielded that 51.5% fit the vascular phenotype and 3.1% fit the cardiac phenotype. In our cohort, half of young patients with cryptogenic stroke fit the risk factor phenotype of small and large vessel strokes.
Single-photon frequency shifting with a quadrature phase-shift keying modulator
Authors: Chen Changchen , Heyes Jane E. , Shapiro Jeffrey H. , Wong Franco N. C.
Published: January 2021

Deterministic frequency manipulation of single photons is an essential tool for quantum communications and quantum networks. We demonstrate a 15.65 GHz frequency shift for classical and nonclassical light using a commercially available quadrature phase-shift keying modulator. The measured spectrum of frequency-shifted single photons indicates a high carrier-to-sideband ratio of 30 dB. We illustrate our frequency shifter’s utility in quantum photonics by performing Hong–Ou–Mandel quantum interference between two photons whose initial frequency spectra overlap only partially, and showing visibility improvement from 62.7 to 89.1% after one of the photons undergoes a corrective frequency shift.
Carbon dioxide inhibits UVB-induced inflammatory response by activating the proton-sensing receptor, GPR65, in human keratinocytes
Authors: Sayama Keimon , Yuki Katsuyuki , Sugata Keiichi , Fukagawa Satoko , Yamamoto Tetsuji , Ikeda Shigaku , Murase Takatoshi
Published: January 2021

Carbon dioxide (CO2) is the predominant gas molecule emitted during aerobic respiration. Although CO2 can improve blood circulation in the skin via its vasodilatory effects, its effects on skin inflammation remain unclear. The present study aimed to examine the anti-inflammatory effects of CO2 in human keratinocytes and skin. Keratinocytes were cultured under 15% CO2, irradiated with ultraviolet B (UVB), and their inflammatory cytokine production was analyzed. Using multiphoton laser microscopy, the effect of CO2 on pH was observed by loading a three-dimensional (3D)-cultured epidermis with a high-CO2 concentration formulation. Finally, the effect of CO2 on UVB-induced erythema was confirmed. CO2 suppressed the UVB-induced production of tumor necrosis factor-α (TNFα) and interleukin-6 (IL-6) in keratinocytes and the 3D epidermis. Correcting medium acidification with NaOH inhibited the CO2-induced suppression of TNFα and IL-6 expression in keratinocytes. Moreover, the knockdown of H+-sensing G protein-coupled receptor 65 inhibited the CO2-induced suppression of inflammatory cytokine expression and NF-κB activation and reduced CO2-induced cyclic adenosine monophosphate production. Furthermore, the high-CO2 concentration formulation suppressed UVB-induced erythema in human skin. Hence, CO2 suppresses skin inflammation and can be employed as a potential therapeutic agent in restoring skin immune homeostasis.
Mid-regional pro-adrenomedullin is a novel biomarker for arterial stiffness as the criterion for vascular failure in a cross-sectional study
Authors: Koyama Teruhide , Kuriyama Nagato , Suzuki Yosuke , Saito Satoshi , Tanaka Ryota , Iwao Motoshi , Tanaka Megumu , Maki Takakuni , Itoh Hiroki , Ihara Masafumi , Shindo Takayuki , Uehara Ritei
Published: January 2021

We investigated the potential of mid-regional pro-adrenomedullin (MR-proADM) for use as a novel biomarker for arterial stiffness as the criterion for vascular failure and cardiometabolic disease (obesity, hypertension, dyslipidemia, diabetes, and metabolic syndrome) compared with high-sensitivity C-reactive protein (hsCRP). Overall, 2169 individuals (702 men and 1467 women) were enrolled. Multiple regression analysis was performed to assess the association of MR-proADM and hsCRP with brachial-ankle pulse wave velocity (baPWV), adjusting for other variables. The diagnostic performance (accuracy) of MR-proADM with regard to the index of vascular failure was tested with the help of receiver operating characteristic curve analysis in the models. MR-proADM was significantly higher in participants with vascular failure, as defined by baPWV and/or its risk factors (obesity, hypertension, dyslipidemia, diabetes, and metabolic syndrome), than in control groups. Independent of cardiovascular risk factors (age, drinking, smoking, body mass index, systolic blood pressure, lipid and glycol metabolism), MR-proADM was significantly associated with baPWV, and MR-proADM showed higher areas under the curve of baPWV than hsCRP showed. MR-proADM is more suitable for the diagnosis of higher arterial stiffness as the criterion for vascular failure than hsCRP. Because vascular assessment is important to mitigate the most significant modifiable cardiovascular risk factors, MR-proADM may be useful as a novel biomarker on routine blood examination.
Gut microbiome partially mediates and coordinates the effects of genetics on anxiety-like behavior in Collaborative Cross mice
Authors: Jin X. , Zhang Y. , Celniker S. E. , Xia Y. , Mao J.-H. , Snijders A. M. , Chang H.
Published: January 2021

Growing evidence suggests that the gut microbiome (GM) plays a critical role in health and disease. However, the contribution of GM to psychiatric disorders, especially anxiety, remains unclear. We used the Collaborative Cross (CC) mouse population-based model to identify anxiety associated host genetic and GM factors. Anxiety-like behavior of 445 mice across 30 CC strains was measured using the light/dark box assay and documented by video. A custom tracking system was developed to quantify seven anxiety-related phenotypes based on video. Mice were assigned to a low or high anxiety group by consensus clustering using seven anxiety-related phenotypes. Genome-wide association analysis (GWAS) identified 141 genes (264 SNPs) significantly enriched for anxiety and depression related functions. In the same CC cohort, we measured GM composition and identified five families that differ between high and low anxiety mice. Anxiety level was predicted with 79% accuracy and an AUC of 0.81. Mediation analyses revealed that the genetic contribution to anxiety was partially mediated by the GM. Our findings indicate that GM partially mediates and coordinates the effects of genetics on anxiety.
Surface hydrophobics mediate functional dimerization of CYP121A1 of Mycobacterium tuberculosis
Authors: Kumar Amit , Campomizzi Christopher S. , Jay Natalie , Ferguson Shaun , Scheffler Emelie-Jo , Lioi James , Tu Chengjian , Qu Jun , Simons Claire , Estrada D. Fernando
Published: January 2021

Tuberculosis is caused by the pathogenic bacterium Mycobacterium tuberculosis (Mtb) and remains the leading cause of death by infection world-wide. The Mtb genome encodes a disproportionate number of twenty cytochrome P450 enzymes, of which the essential enzyme cytochrome P450 121A1 (CYP121A1) remains a target of drug design efforts. CYP121A1 mediates a phenol coupling reaction of the tyrosine dipeptide cyclo-L-Tyr-L-Tyr (cYY). In this work, a structure and function investigation of dimerization was performed as an overlooked feature of CYP121A1 function. This investigation showed that CYP121A1 dimers form via intermolecular contacts on the distal surface and are mediated by a network of solvent-exposed hydrophobic residues. Disruption of CYP121A1 dimers by site-directed mutagenesis leads to a partial loss of specificity for cYY, resulting in an approximate 75% decrease in catalysis. 19F labeling and nuclear magnetic resonance of the enzyme FG-loop was also combined with protein docking to develop a working model of a functional CYP121A1 dimer. The results obtained suggest that participation of a homodimer interface in substrate selectivity represents a novel paradigm of substrate binding in CYPs, while also providing important mechanistic insight regarding a relevant drug target in the development of novel anti-tuberculosis agents.
An optomechanogram for assessment of the structural and mechanical properties of tissues
Authors: Lee W. , Ostadi Moghaddam A. , Shen S. , Phillips H. , McFarlin B. L. , Wagoner Johnson A. J. , Toussaint K. C.
Published: January 2021

The structural and mechanical properties of tissue and the interplay between them play a critical role in tissue function. We introduce the optomechanogram, a combined quantitative and qualitative visualization of spatially co-registered measurements of the microstructural and micromechanical properties of any tissue. Our approach relies on the co-registration of two independent platforms, second-harmonic generation (SHG) microscopy for quantitative assessment of 3D collagen-fiber microstructural organization, and nanoindentation (NI) for local micromechanical properties. We experimentally validate our method by applying to uterine cervix tissue, which exhibits structural and mechanical complexity. We find statistically significant agreement between the micromechanical and microstructural data, and confirm that the distinct tissue regions are distinguishable using either the SHG or NI measurements. Our method could potentially be used for research in pregnancy maintenance, mechanobiological studies of tissues and their constitutive modeling and more generally for the optomechanical metrology of materials.
Phylogenomics of the Hyalella amphipod species-flock of the Andean Altiplano
Authors: Zapelloni Francesco , Pons Joan , Jurado-Rivera José A. , Jaume Damià , Juan Carlos
Published: January 2021

Species diversification in ancient lakes has enabled essential insights into evolutionary theory as they embody an evolutionary microcosm compared to continental terrestrial habitats. We have studied the high-altitude amphipods of the Andes Altiplano using mitogenomic, nuclear ribosomal and single-copy nuclear gene sequences obtained from 36Hyalellagenomic libraries, focusing on species of the Lake Titicaca and other water bodies of the Altiplano northern plateau. Results show that early Miocene South American lineages have recently (late Pliocene or early Pleistocene) diversified in the Andes with a striking morphological convergence among lineages. This pattern is consistent with the ecological opportunities (access to unoccupied resources, initial relaxed selection on ecologically-significant traits and low competition) offered by the lacustrine habitats established after the Andean uplift.
Preparation and characterization of nanocurcumin based hybrid virosomes as a drug delivery vehicle with enhanced anticancerous activity and reduced toxicity
Authors: Kumar Varun , Kumar Ramesh , Jain V. K. , Nagpal Suman
Published: January 2021

The present study represents a formulation of nanocurcumin based hybrid virosomes (NC-virosome) to deliver drugs at targeted sites. Curcumin is a bioactive component derived from Curcuma longa and well-known for its medicinal property, but it exhibits poor solubility and rapid metabolism, which led to low bioavailability and hence limits its applications. Nanocurcumin was prepared to increase the aqueous solubility and to overcome all the limitations associated with curcumin. Influenza virosomes were prepared by solubilization of the viral membrane with 1,2-distearoyl-sn-glycerol-3-phosphocholine (DSPC). During membrane reconstitution, the hydrophilic nanocurcumin was added to the solvent system, followed by overnight dialysis to obtain NC-virosomes. The same was characterized using a transmission electron microscope (TEM) and scanning electron microscope (SEM), MTT assay was used to evaluate it's in vitro-cytotoxicity using MDA-MB231 and Mesenchyme stem cells (MSCs). The results showed NC-virosomes has spherical morphology with size ranging between 60 and 90 nm. It showed 82.6% drug encapsulation efficiency. The viability of MDA-MB231 cells was significantly inhibited by NC-virosome in a concentration-dependent manner at a specific time. The IC50 for nanocurcumin and NC-virosome was 79.49 and 54.23 µg/ml, respectively. The site-specific drug-targeting, high efficacy and non- toxicity of NC-virosomes proves its future potential as drug delivery vehicles.
Linker histone defines structure and self-association behaviour of the 177 bp human chromatosome
Authors: Wang Sai , Vogirala Vinod K. , Soman Aghil , Berezhnoy Nikolay V. , Liu Zhehui Barry , Wong Andrew S. W. , Korolev Nikolay , Su Chun-Jen , Sandin Sara , Nordenskiöld Lars
Published: January 2021

Linker histones play essential roles in the regulation and maintenance of the dynamic chromatin structure of higher eukaryotes. The influence of human histone H1.0 on the nucleosome structure and biophysical properties of the resulting chromatosome were investigated and compared with the 177-bp nucleosome using Cryo-EM and SAXS. The 4.5 Å Cryo-EM chromatosome structure showed that the linker histone binds at the nucleosome dyad interacting with both linker DNA arms but in a tilted manner leaning towards one of the linker sides. The chromatosome is laterally compacted and rigid in the dyad and linker DNA area, in comparison with the nucleosome where linker DNA region is more flexible and displays structural variability. In solution, the chromatosomes appear slightly larger than the nucleosomes, with the volume increase compared to the bound linker histone, according to solution SAXS measurements. SAXS X-ray diffraction characterisation of Mg-precipitated samples showed that the different shapes of the 177 chromatosome enabled the formation of a highly ordered lamello-columnar phase when precipitated by Mg2+, indicating the influence of linker histone on the nucleosome stacking. The biological significance of linker histone, therefore, may be affected by the change in the polyelectrolyte and DNA conformation properties of the chromatosomes, in comparison to nucleosomes.
Effect of gravity on brain structure as indicated on upright computed tomography
Authors: Yokoyama Yoichi , Yamada Yoshitake , Kosugi Kenzo , Yamada Minoru , Narita Keiichi , Nakahara Takehiro , Fujiwara Hirokazu , Toda Masahiro , Jinzaki Masahiro
Published: January 2021

We aimed to use upright computed tomography (CT) to depict posture-related changes in the brain tissue under normal gravity. Thirty-two asymptomatic volunteers underwent upright CT in the sitting position and conventional CT in the supine position on the same day. We compared the shift of the pineal body, cerebellar tonsil, the length of pituitary stalk, optic nerve sheath area and perimeter (ONSA and ONSP, respectively), and lateral ventricular volume between the supine and sitting positions. We also compared shape changes of the cerebrospinal fluid (CSF) spaces at different sites between both positions. In the sitting position, the pineal body shifted 0.68 ± 0.27 mm in the ventral direction and 0.76 ± 0.24 mm in the caudal direction, the length of pituitary stalk decreased by 1.23 ± 0.71 mm, the cerebellar tonsil descended by 2.10 ± 0.86 mm, the right ONSA decreased by 15.21 ± 6.54%, the left ONSA decreased by 15.30 ± 7.37%, the right ONSP decreased by 8.52 ± 3.91%, the left ONSP decreased by 8.20 ± 4.38%, and the lateral ventricular volume decreased by 5.07 ± 3.24% (all P < 0.001). We also observed changes in the shape of CSF spaces with changes in posture. We concluded that the intracranial structure of healthy subjects and volume of ventricles changed according to posture on Earth.
Reference standards for accurate validation and optimization of assays that determine integrated lentiviral vector copy number in transduced cells
Authors: Paugh Barbara S. , Baranyi Lajos , Roy Andre , He Hua-Jun , Harris Lindsay , Cole Kenneth D. , Artlip Moria , Raimund Caroline , Langan Patricia S. , Jana Srikanta , Orentas Rimas J. , Lin-Gibson Sheng , Krueger Winfried , Dropulić Boro
Published: January 2021

Lentiviral vectors (LV) have emerged as a robust technology for therapeutic gene delivery into human cells as advanced medicinal products. As these products are increasingly commercialized, there are concomitant demands for their characterization to ensure safety, efficacy and consistency. Standards are essential for accurately measuring parameters for such product characterization. A critical parameter is the vector copy number (VCN) which measures the genetic dose of a transgene present in gene-modified cells. Here we describe a set of clonal Jurkat cell lines with defined copy numbers of a reference lentiviral vector integrated into their genomes. Genomic DNA was characterized for copy number, genomic integrity and integration coordinates and showed uniform performance across independent quantitative PCR assays. Stability studies during continuous long-term culture demonstrated sustained renewability of the reference standard source material. DNA from the Jurkat VCN standards would be useful for control of quantitative PCR assays for VCN determination in LV gene-modified cellular products and clinical samples.
Association of GZMB polymorphisms and susceptibility to non-segmental vitiligo in a Korean population
Authors: Jeong Ki-Heon , Kim Su Kang , Seo Jong-Kil , Shin Min Kyung , Lee Mu-Hyoung
Published: January 2021

Non-segmental vitiligo (NSV) is the most common type of vitiligo, which is characterized by chronic and progressive loss of melanocytes. Genetic factors have been shown to play a key role in NSV in association and family studies. Granzyme B is a serine protease found in the cytoplasmic granules of cytotoxic T lymphocytes and natural killer cells that play an important role in inducing apoptotic changes of target cells. Several recent studies have provided evidence that polymorphism in the GZMB gene might be associated with autoimmune disease. A total of 249 NSV patients and 455 healthy controls were recruited to determine whether single nucleotide polymorphisms (SNPs) [rs2236337 (3′ untranslated region, UTR), rs2236338 (Tyr247His), rs11539752 (Pro94Ala), rs10909625 (Lys80Lys), rs8192917 (Arg55Gln), and rs7144366 (5′ near gene)] in GZMB gene contribute to the risk of developing NSV. Genotyping was performed using a single 192.24 Dynamic Array IFC. Data were analyzed using EP1 SNP Genotyping Analysis software to obtain genotype calls. Among the six SNPs tested, five SNPs (rs2236337, rs2236338, rs11539752, rs10909625, and rs8192917) showed significant association with NSV susceptibility. Among them, rs2236338, rs11539752, rs10909625, and rs8192917 remained a statistically significant association following multiple correction test. The five SNPs were located within a block of linkage disequilibrium. Haplotypes T–A–G–T–T and C–G–C–C–C consisting of rs2236337, rs2236338, rs11539752, rs10909625, and rs8192917 demonstrated significant association with NSV. Our results suggest that GZMB polymorphisms are associated with the development of NSV.
Neon-green fluorescence in the desert gecko Pachydactylus rangei caused by iridophores
Authors: Prötzel David , Heß Martin , Schwager Martina , Glaw Frank , Scherz Mark D.
Published: January 2021

Biofluorescence is widespread in the natural world, but only recently discovered in terrestrial vertebrates. Here, we report on the discovery of iridophore-based, neon-green flourescence in the gecko Pachydactylus rangei, localised to the skin around the eyes and along the flanks. The maximum emission of the fluorescence is at a wavelength of 516 nm in the green spectrum (excitation maximum 465 nm, blue) with another, smaller peak at 430 nm. The fluorescent regions of the skin show large numbers of iridophores, which are lacking in the non-fluorescent parts. Two types of iridophores are recognized, fluorescent iridophores and basal, non-fluorescent iridophores, the latter of which might function as a mirror, amplifying the omnidirectional fluorescence. The strong intensity of the fluorescence (quantum yield of 12.5%) indicates this to be a highly effective mechanism, unique among tetrapods. Although the fluorescence is associated with iridophores, the spectra of emission and excitation as well as the small Stokes shifts argue against guanine crystals as its source, but rather a rigid pair of fluorophores. Further studies are necessary to identify their morphology and chemical structures. We hypothesise that this nocturnal gecko uses the neon-green fluorescence, excited by moonlight, for intraspecific signalling in its open desert habitat.
Genetic and demographic history define a conservation strategy for earth’s most endangered pinniped, the Mediterranean monk seal Monachus monachus
Authors: Karamanlidis Alexandros A. , Skrbinšek Tomaž , Amato George , Dendrinos Panagiotis , Gaughran Stephen , Kasapidis Panagiotis , Kopatz Alexander , Stronen Astrid Vik
Published: January 2021

The Mediterranean monk seal (Monachus monachus) is a flagship species for marine conservation, but important aspects of its life history remain unknown. Concerns over imminent extinction motivated a nuclear DNA study of the species in its largest continuous subpopulation in the eastern Mediterranean Sea. Despite recent evidence of partial subpopulation recovery, we demonstrate that there is no reason for complacency, as the species still shares several traits that are characteristic of a critically endangered species: Mediterranean monk seals in the eastern Mediterranean survive in three isolated and genetically depauperate population clusters, with small effective population sizes and high levels of inbreeding. Our results indicated male philopatry over short distances, which is unexpected for a polygynous mammal. Such a pattern may be explained by the species’ unique breeding behavior, in which males defend aquatic territories near breeding sites, while females are often forced to search for new pupping areas. Immediate action is necessary to reverse the downward spiral of population decline, inbreeding accumulation and loss of genetic diversity. We propose concrete conservation measures for the Mediterranean monk seal focusing on reducing anthropogenic threats, increasing the population size and genetic diversity, and thus improving the long-term prospects of survival.
Combining microcavity size selection with Raman microscopy for the characterization of Nanoplastics in complex matrices
Authors: Valsesia Andrea , Quarato Monica , Ponti Jessica , Fumagalli Francesco , Gilliland Douglas , Colpo Pascal
Published: January 2021

Nanoplastic particulates (pNP) are widely considered as being potentially harmful to the environment and living organisms while also being technically difficult to detect and identify in the presence of biological matrices. In this study, we describe a method for the extraction and subsequent Raman analysis of pNP present in the tissues of salt-water mussels. The process combines a step of enzymatic digestion/filtering to eliminate the biological matrix with a detection/identification procedure, which uses a micro-machined surface, composed of arrays of cavities with well-defined sub-micron depths and diameters. This sensor surface, exploits capillary forces in a drying droplet of analyte solution to drive the self-assembly of suspended nanoparticles into the cavities leaving the individual particles isolated from each other over the surface. The resulting array, when analysed using confocal Raman microscopy, permits the size selective analysis of the individual sub-micron pNP trapped in the cavities structure.
Lipoxygenase catalyzed metabolites derived from docosahexaenoic acid are promising antitumor agents against breast cancer
Authors: Chen Kun-Ming , Thompson Henry , Vanden-Heuvel John P. , Sun Yuan-Wan , Trushin Neil , Aliaga Cesar , Gowda Krishne , Amin Shantu , Stanley Bruce , Manni Andrea , El-Bayoumy Karam
Published: January 2021

Docosahexaenoic acid (DHA) is known to inhibit breast cancer in the rat. Here we investigated whether DHA itself or select metabolites can account for its antitumor action. We focused on metabolites derived from the lipoxygenase (LOX) pathway since we previously showed that they were superior anti-proliferating agents compared to DHA; 4-OXO-DHA was the most potent. A lipidomics approach detected several LOX-metabolites in plasma and the mammary gland in rats fed DHA; we also identified for the first time, 4-OXO-DHA in rat plasma. In a reporter assay, 4-OXO-DHA and 4-HDHA were more effective activators of PPARɣ than DHA. In breast cancer cell lines, 4-OXO-DHA induced PPARɣ and 15-hydroxyprostaglandin dehydrogenase (15-PGDH) but inhibited the activity of NF-κB and suppressed PI3K and mTOR signaling. Because of the structural characteristics of 4-OXO-DHA (Michael acceptor), not shared by any of the other hydroxylated-DHA, we used MS and showed that it can covalently modify the cysteine residue of NF-κB. We have also shown that the chemopreventive effect of DHA is associated with significant reduction of PGE2 levels, in both rat mammary tumors induced by MNU and non-involved mammary tissues. Collectively, our results indicate that 4-OXO-DHA is the metabolite of choice in future chemoprevention studies.
A portable pen-sized instrumentation to measure stiffness of soft tissues in vivo
Authors: Li Zhengwei , Tofangchi Alireza , Stavins Robert A. , Emon Bashar , McKinney Ronald D. , Grippo Paul J. , Saif M. Taher A.
Published: January 2021

Quantitative assessment of soft tissue elasticity is crucial to a broad range of applications, such as biomechanical modeling, physiological monitoring, and tissue diseases diagnosing. However, the modulus measurement of soft tissues, particularly in vivo, has proved challenging since the instrument has to reach the site of soft tissue and be able to measure in a very short time. Here, we present a simple method to measure the elastic modulus of soft tissues on site by exploiting buckling of a long slender bar to quantify the applied force and a spherical indentation to extract the elastic modulus. The method is realized by developing a portable pen-sized instrument (EPen: Elastic modulus pen). The measurement accuracies are verified by independent modulus measures using commercial nanoindenter. Quantitative measurements of the elastic modulus of mouse pancreas, healthy and cancerous, surgically exposed but attached to the body further confirm the potential clinical utility of the EPen.
Electrical tuning effect for Schottky barrier and hot-electron harvest in a plasmonic Au/TiO2 nanostructure
Authors: Sun Zhiguang , Fang Yurui
Published: January 2021

Schottky barrier controls the transfer of hot carriers between contacted metal and semiconductor, and decides the performance of plasmonic metal–semiconductor devices in many applications. It is immensely valuable to actively tune the Schottky barrier. In this work, electrical tuning of Schottky barrier in an Au-nanodisk/TiO2-film structure was demonstrated using a simple three-electrode electrochemical cell. Photocurrents excited at different wavelength significantly increase as the applied bias voltage increases. Analyzing and fitting of experimental results indicate that the photocurrent is mainly affected by the bias tuning position of Schottky barrier maximum, which shifts to metal–semiconductor interface as applied voltage increases, and enhances the collection efficiency of the barrier for plasmonic hot electrons. The conduction band curvature of 0.13 eV was simultaneously obtained from the fitting. This work provides a new strategy for facile tuning of Schottky barrier and hot-electron transfer across the barrier.
Image compression-encryption method based on two-dimensional sparse recovery and chaotic system
Authors: Ghaffari Aboozar
Published: January 2021

In this paper, we propose an image compression-encryption method based on two-dimensional (2D) sparse representation and chaotic system. In the first step of this method, the input image is extended in a transform domain to obtain a sparse representation. To achieve better performance of image compression by 2D sparse recovery, the sparse representation is scrambled via a chaotic confusion. This step helps the satisfaction of the uniqueness conditions for sparse recovery, and the security level of encryption is increased. Then, two orthogonal measurement matrices are generated using the chaotic time series. The singular value decomposition is used to compress the sparse scrambled representation in two dimensions. Finally, to reduce the correlation between adjacent pixels in the compressed matrix, and obtain a uniform distribution in the encrypted image, a compressed scrambling matrix based on chaotic confusion is used. Then, XOR operation is applied for final encryption. In the decryption process, to improve the compression efficiency, the total variation constraint is added to the 2D sparse recovery problem based on the smoothed norm. The simulation results demonstrate the satisfying performance of the proposed method for different compression ratios. Security analysis describes the effectiveness of the proposed encryption approach.
Novel circRNA discovery in sheep shows evidence of high backsplice junction conservation
Authors: Varela-Martínez Endika , Corsi Giulia I. , Anthon Christian , Gorodkin Jan , Jugo Begoña M.
Published: January 2021

Circular RNAs (circRNAs) are covalently closed circular non-coding RNAs. Due to their structure, circRNAs are more stable and have longer half-lives than linear RNAs making them good candidates for disease biomarkers. Despite the scientific relevance of these molecules, the study of circRNAs in non-model organisms is still in its infancy. Here, we analyse total RNA-seq data to identify circRNAs in sheep from peripheral blood mononuclear cells (PBMCs) and parietal lobe cortex. Out of 2510 and 3403 circRNAs detected in parietal lobe cortex and in PBMCs, a total of 1379 novel circRNAs were discovered. Remarkably, around 63% of all detected circRNAs were found to be completely homologous to a circRNA annotated in human. Functional enrichment analysis was conducted for both tissues based on GO terms and KEGG pathways. The enriched terms suggest an important role of circRNAs from encephalon in synaptic functions and the involvement of circRNAs from PBMCs in basic immune system functions. In addition to this, we investigated the role of circRNAs in repetitive vaccination experiments via differential expression analysis and did not detect any significant relationship. At last, our results support both the miRNA sponge and the miRNA shuttle functions of CDR1-AS in sheep brain. To our knowledge, this is the first study on circRNA annotation in sheep PBMCs or parietal lobe cortex samples.