bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identifying carbohydrate-active enzymes of Cutaneotrichosporon oleaginosus using systems biology
Authors: Fuchs Tobias , Melcher Felix , Rerop Zora Selina , Lorenzen Jan , Shaigani Pariya , Awad Dania , Haack Martina , Prem Sophia Alice , Masri Mahmoud , Mehlmer Norbert , Brueck Thomas B. 
Published: October 2021

Abstract
Background
The oleaginous yeast Cutaneotrichosporon oleaginosus represents one of the most promising microbial platforms for resource-efficient and scalable lipid production, with the capacity to accept a wide range of carbohydrates encapsulated in complex biomass waste or lignocellulosic hydrolysates. Currently, data related to molecular aspects of the metabolic utilisation of oligomeric carbohydrates are sparse. In addition, comprehensive proteomic information for C. oleaginosus focusing on carbohydrate metabolism is not available.

Results
In this study, we conducted a systematic analysis of carbohydrate intake and utilisation by C. oleaginosus and investigated the influence of different di- and trisaccharide as carbon sources. Changes in the cellular growth and morphology could be observed, depending on the selected carbon source. The greatest changes in morphology were observed in media containing trehalose. A comprehensive proteomic analysis of secreted, cell wall-associated, and cytoplasmatic proteins was performed, which highlighted differences in the composition and quantity of secreted proteins, when grown on different disaccharides. Based on the proteomic data, we performed a relative quantitative analysis of the identified proteins (using glucose as the reference carbon source) and observed carbohydrate-specific protein distributions. When using cellobiose or lactose as the carbon source, we detected three- and five-fold higher diversity in terms of the respective hydrolases released. Furthermore, the analysis of the secreted enzymes enabled identification of the motif with the consensus sequence LALL[LA]L[LA][LA]AAAAAAA as a potential signal peptide.

Conclusions
Relative quantification of spectral intensities from crude proteomic datasets enabled the identification of new enzymes and provided new insights into protein secretion, as well as the molecular mechanisms of carbo-hydrolases involved in the cleavage of the selected carbon oligomers. These insights can help unlock new substrate sources for C. oleaginosus, such as low-cost by-products containing difficult to utilize carbohydrates. In addition, information regarding the carbo-hydrolytic potential of C. oleaginosus facilitates a more precise engineering approach when using targeted genetic approaches. This information could be used to find new and more cost-effective carbon sources for microbial lipid production by the oleaginous yeast C. oleaginosus.
Whole-cell catalysis by surface display of fluorinase on Escherichia coli using N-terminal domain of ice nucleation protein
Authors: Feng Xinming , Jin Miaomiao , Huang Wei , Liu Wei , Xian Mo 
Published: October 2021

Abstract
Background
Fluorinases play a unique role in the production of fluorine-containing organic molecules by biological methods. Whole-cell catalysis is a better choice in the large-scale fermentation processes, and over 60% of industrial biocatalysis uses this method. However, the in vivo catalytic efficiency of fluorinases is stuck with the mass transfer of the substrates.

Results
A gene sequence encoding a protein with fluorinase function was fused to the N-terminal of ice nucleation protein, and the fused fluorinase was expressed in Escherichia coli BL21(DE3) cells. SDS-PAGE and immunofluorescence microscopy were used to demonstrate the surface localization of the fusion protein. The fluorinase displayed on the surface showed good stability while retaining the catalytic activity. The engineered E.coli with surface-displayed fluorinase could be cultured to obtain a larger cell density, which was beneficial for industrial application. And 55% yield of 5′-fluorodeoxyadenosine (5′-FDA) from S-adenosyl-L-methionine (SAM) was achieved by using the whole-cell catalyst.

Conclusions
Here, we created the fluorinase-containing surface display system on E.coli cells for the first time. The fluorinase was successfully displayed on the surface of E.coli and maintained its catalytic activity. The surface display provides a new solution for the industrial application of biological fluorination.

Graphical Abstract
Carboxypeptidase N1 is anticipated to be a synergy metrics for chemotherapy effectiveness and prognostic significance in invasive breast cancer
Authors: Cui Ranliang , Wang Chaomin , Li Tiantian , Hua Jialei , Zhao Ting , Ren Li , Wang Yichao , Li Yueguo 
Published: October 2021

Abstract
Background
The incidence and mortality of invasive breast cancer (IBC) are increasing annually. Hence, it is urgently needed to determine reliable biomarkers for not only monitoring curative effects, but evaluating prognosis. In present study, we aim to determine the potential role of Carboxypeptidase N1 (CPN1) in IBC tissues on chemotherapeutic efficacy and poor prognosis.

Methods
The expression level of CPN1 in IBC tissue samples (n = 123) was quantified by tissue microarray technique and immunohistochemical staining. Moreover, sera of IBC patients (n = 34) that underwent three to five consecutive chemotherapy sessions were collected. The patients were randomly stratified into a training (n = 15) as well as a validation group (n = 19). The expression of serum CA153 and CPN1 was quantified by electrochemiluminescence and ELISA assay, respectively.

Results
By univariate and multivariate Cox regression analysis, we show that CPN1 expression in IBC tissues, as an independent risk factor, is related to a poor overall survival (OS) and progression-free survival (PFS) (P < 0.05). Analysis of the data revealed that CPN1 over-expression could be consistently linked to adverse clinicopathological features such as lymph node metastasis and the pathological stage (pTNM) (P < 0.05). The serum CPN1 level trajectory of individual patients generally decreased during chemotherapy. In line with these findings were changes in the follow-up ultrasonography and a consistent decrease in serum CPN1 levels. The comparison of the area under the receiver operating curves (ROC) revealed that CPN1 has a better surveillance value than CA153 in the training (AUCCPN1 = 0.834 vs. AUCCA153 = 0.724) as well as the validation set (AUCCPN1 = 0.860 vs. AUCCA153 = 0.720) when comparing cycle2 versus cycle3.

Conclusions
CPN1 is a suitable potential biomarker for chemotherapeutic surveillance purposes as well as being an appropriate prognostic indicator which would support an improved chemotherapy regimen.
Proteo-transcriptomics meta-analysis identifies SUMO2 as a promising target in glioblastoma multiforme therapeutics
Authors: Krishna Aswani P. , John Sebastian , Shinde Puja Laxmanrao , Mishra Rashmi 
Published: October 2021

Abstract
Background
Glioblastoma multiforme (GBM) is a deadly brain tumour with minimal survival rates due to the ever-expanding heterogeneity, chemo and radioresistance. Kinases are known to crucially drive GBM pathology; however, a rationale therapeutic combination that can simultaneously inhibit multiple kinases has not yet emerged successfully.

Results
Here, we analyzed the GBM patient data from several publicly available repositories and deduced hub GBM kinases, most of which were identified to be SUMOylated by SUMO2/3 isoforms. Not only the hub kinases but a significant proportion of GBM upregulated genes involved in proliferation, metastasis, invasion, epithelial-mesenchymal transition, stemness, DNA repair, stromal and macrophages maintenance were also identified to be the targets of SUMO2 isoform. Correlatively, high expression of SUMO2 isoform was found to be significantly associated with poor patient survival.

Conclusions
Although many natural products and drugs are evidenced to target general SUMOylation, however, our meta-analysis strongly calls for the need to design SUMO2/3 or even better SUMO2 specific inhibitors and also explore the SUMO2 transcription inhibitors for universally potential, physiologically non-toxic anti-GBM drug therapy.

Graphical Abstract
Effect of roof colour on indoor temperature and human comfort levels, with implications for malaria control: a pilot study using experimental houses in rural Gambia
Authors: Carrasco-Tenezaca Majo , Jatta Ebrima , Jawara Musa , Bradley John , Pinder Margaret , D’Alessandro Umberto , Knudsen Jakob , Lindsay Steve W. 
Published: October 2021

Abstract
Background
In rural sub-Saharan Africa, thatch roofs are being replaced by metal roofs. Metal roofing, however, increases indoor temperatures above human comfort levels, and thus makes it more likely that residents will not use an insecticide-treated bed net (ITN) at night. Whether the colour of a metal roof affects indoor temperature and human comfort was assessed.

Methods
Two identical, experimental houses were constructed with metal roofs in rural Gambia. Roof types were: (1) original bare-metal, (2) painted with red oxide primer or (3) white gloss, to reflect solar radiation. Pairwise comparisons were run in six, five-night blocks during the malaria season 2018. Indoor climate was measured in each house and multivariate analysis used to compare indoor temperatures during the day and night.

Results
From 21.00 to 23.59 h, when most residents decide whether to use an ITN or not, the indoor temperature of a house with a bare metal roof was 31.5 °C (95% CI  31.2–31.8 °C), a red roof, 30.3 °C (95% CI 30.0–30.6) and a white roof, 29.8 °C (95% CI 29.4–30.1). During the same period, red-roofed houses were 1.23 °C cooler (95% CI 1.22–1.23) and white roofs 1.74 °C cooler (95% CI 1.70–1.79) than bare-metal roofed houses (p  < 0.001). Similar results were found from 00.00 to 06.00 h. Maximum daily temperatures were 0.93 °C lower in a white-roofed house (95% CI  0.10–0.30, p  < 0.001), but not a red roof (mean maximum temperature difference  = 0.44 °C warmer, 95% CI  0.43–0.45, p  = 0.081), compared with the bare-metal roofed houses. Human comfort analysis showed that from 21.00 to 23.59 h houses with white roofs (comfortable for 87% time) were more comfortable than bare-metal roofed houses (comfortable for 13% time; odds ratio  = 43.7, 95% CI 27.5–69.5, p  < 0.001). The cost of painting a metal roof white is approximately 31–68 USD.

Conclusions
Houses with a white roof were consistently cooler and more comfortable than those with a bare metal roof. Painting the roofs of houses white is a cheap way of making a dwelling more comfortable for the occupants and could potentially increase bed net use in hot humid countries.
Prevalence of asymptomatic malaria, submicroscopic parasitaemia and anaemia in Korogwe District, north-eastern Tanzania
Authors: Hayuma Paul M. , Wang Christian W. , Liheluka Edwin , Baraka Vito , Madebe Rashid A. , Minja Daniel T. R. , Misinzo Gerald , Alifrangis Michael , Lusingu John P. A. 
Published: October 2021

Abstract
Background
Asymptomatic malaria infections largely remain undetected and act as a reservoir for continuous transmission. The study assessed the prevalence of submicroscopic asymptomatic malaria infections and anaemia in two rural low (300 m above sea level) and highland (700 m asl) settings of Korogwe District north-eastern Tanzania.

Methods
A cross-sectional malariometric survey involving individuals aged 0–19 years was conducted in June 2018 in the two rural villages. Venous blood was collected from eligible study participants for estimation of haemoglobin level, detection of malaria by rapid diagnostic test (RDT), quantification of malaria parasitaemia by microscopy, as well as dried blood spot (DBS) for determining submicroscopic infections by PCR targeting the small subunit of the ribosomal ribonucleic acid (ssrRNA) of human Plasmodium.

Results
Out of 565 individuals tested, 211 (37.3%) were malaria positive based on RDT, whereas only 81 (14.3%) were positive by microscopy. There was no significant difference in the prevalence between the highland and the lowland village, p = 0.19 and p = 0.78 microscopy and RDT, respectively. Three out of 206 (1.5%) RDT/microscopy negative samples were P. falciparum positive by PCR. Of the 211 RDT and 81 microscopy positive, 130 (61.6%) and 33 (40.7%), respectively, were defined as being asymptomatic. Of the 565 individuals, 135 (23.9%) were anaemic (haemoglobin < 11 g/dL) out of which 5.2% were severely anaemic. The risk of being anaemic was significantly higher among individuals with asymptomatic malaria as compared to those without malaria as confirmed by RDT (AOR = 2.06 (95% CI 1.32–3.20) while based on microscopic results there was no significant differences observed (AOR = 2.09, 95% CI 0.98–4.47). Age and altitude had no effect on the risk of anaemia even after adjusting for asymptomatic malaria.

Conclusions
Asymptomatic malaria is associated with an increased risk of having anaemia in the study communities. The findings highlight the need for targeted interventions focusing on asymptomatic infections which is an important risks factor for anaemia in the community and act as a source of continued transmission of malaria in the study area.
Changes in dairy product consumption and subsequent type 2 diabetes among individuals with prediabetes: Tehran Lipid and Glucose Study
Authors: Yuzbashian Emad , Asghari Golaleh , Mirmiran Parvin , Chan Catherine B. , Azizi Fereidoun 
Published: October 2021

AbstractBackgroundPeople with prediabetes can postpone or even reverse progression to type 2 diabetes (T2D) by making dietary changes. This study aimed to examine the association of changes in consumption of total and specific types of dairy products with the subsequent risk of incident T2D among individuals with prediabetes.MethodThis cohort study included 639 individuals (50% female, mean age 47.3 years) of the Tehran Lipid and Glucose Study (TLGS) who had prediabetes at baseline. We assessed 3-year changes in the consumption of dairy products using a food frequency questionnaire. Using multivariable logistic regression, odds ratios (OR) and 95% confidence intervals (CI) were calculated for the association of changes in intake of total and subtypes of dairy products during a 3-year interval with the risk of incident T2D in the subsequent 3 years.ResultsAfter almost 9 years of follow-up, the incidence of T2D was 25.2%. Compared with individuals whose intake remained relatively stable over 3 years, those who decreased consumption of total dairy (> 0.5 servings/day) had a higher T2D risk (OR = 1.56; 95% CI: 1.02 to 2.41). Increasing low-fat dairy consumption by 0.50 serving/d was associated with a lower risk of T2D (OR = 0.56; 95% CI: 0.35 to 0.90) compared with stable consumption. Those who increased consumption of low-fat milk (OR = 0.59; 95% CI: 0.37 to 0.92) and low-fat yogurt (OR = 0.55; 95% CI: 0.33 to 0.93) had a lower risk of T2D than those who were relatively stable in their consumption. Replacing low-fat milk and yogurt with regular cheese was associated with 66 and 47% higher risk of T2D, respectively.ConclusionIn individuals with prediabetes, increasing consumption of low-fat dairy, low-fat milk, and low-fat yogurt had reduced risk of subsequent T2D. These data suggest a role of low-fat dairy products in the prevention of T2D among prediabetes patients.
Domestic use of pesticides during early periods of development and risk of testicular germ cell tumors in adulthood: a French nationwide case-control study
Authors: Danjou Aurélie M. N. , Pérol Olivia , Coste Astrid , Faure Elodie , Béranger Rémi , Boyle Helen , Belladame Elodie , Grassot Lény , Dubuis Matthieu , Spinosi Johan , Bouaoun Liacine , Fléchon Aude , Bujan Louis , Drouineaud Véronique , Eustache Florence , Berthaut Isabelle , Perrin Jeanne , Brugnon Florence , Charbotel Barbara , Schüz Joachim , Fervers Béatrice ,   For the TESTIS study group
Published: October 2021

AbstractBackgroundTesticular germ cell tumours (TGCT) are the most frequent cancers in young men in developed countries and their incidence rate has doubled worldwide over the past 40 years. Early life exposures to pesticides are suspected to increase TGCT risk. Our research aimed at estimating adult TGCT risk associated with parental domestic use of pesticides during early periods of child development.MethodsWe conducted a case-control study of 304 TGCT cases, aged 18–45 years old, recruited in 20 French university hospitals, and 274 controls frequency-matched on hospital and birth year. Participants’ mothers provided information on their domestic use of pesticides from 1 year before start of pregnancy to 1 year after their son’s birth, for gardening activities, treatment of indoor plants, pets, wood and mold, and pest control. Odds ratios (OR) for TGCT (overall and by histological subtype) and 95% confidence intervals (CI) were estimated using conditional logistic regression.ResultsPrevalence of reported domestic use of pesticides was 77.3% for insecticides, 15.9% for fungicides and 12.1% for herbicides. While no association was found for any use of insecticides (OR = 1.27, CI = 0.80–2.01) or herbicides (OR = 1.15, CI = 0.67–2.00), elevated risks of TGCT overall (OR = 1.73, CI = 1.04–2.87) and non-seminoma subtype (OR = 2.44, CI = 1.26–4.74) were observed for any use of fungicides. When specific purposes were examined, using fungicides and/or insecticides for woodwork (OR = 2.35, CI = 1.06–5.20) and using insecticides on cats and dogs (OR = 1.95, CI = 1.12–3.40) were associated with increased risk of non-seminoma subtype. We found no association for seminoma subtype.ConclusionsAlthough recall bias may partially explain the elevated ORs, our study provides some evidence of a positive association between domestic use of pesticides during early periods of development, particularly fungicides and risk of adult TGCT and non-seminoma. Given the common domestic use of pesticides in France, further research on TGCT risk is warranted.
CXCR5 down-regulation alleviates cognitive dysfunction in a mouse model of sepsis-associated encephalopathy: potential role of microglial autophagy and the p38MAPK/NF-κB/STAT3 signaling pathway
Authors: Shen Yanan , Zhang Yuan , Du Jiayue , Jiang Baochun , Shan Tao , Li Haojia , Bao Hongguang , Si Yanna 
Published: October 2021

Abstract
Background
Cognitive deficits are common in patients with sepsis. Previous studies in sepsis-associated encephalopathy (SAE) implicated the C-X-C chemokine receptor type (CXCR) 5. The present study used a mouse model of SAE to examine whether CXCR5 down-regulation could attenuate cognitive deficits.

Methods
Sepsis was induced in adult male C57BL/6 J and CXCR5−/− mice by cecal ligation and puncture (CLP). At 14–18 days after surgery, animals were tested in a Morris water maze, followed by a fear conditioning test. Transmission electron microscopy of hippocampal sections was used to assess levels of autophagy. Primary microglial cultures challenged with lipopolysaccharide (LPS) were used to examine the effects of short interfering RNA targeting CXCR5, and to investigate the possible involvement of the p38MAPK/NF-κB/STAT3 signaling pathway.

Results
CLP impaired learning and memory and up-regulated CXCR5 in hippocampal microglia. CLP activated hippocampal autophagy, as reflected by increases in numbers of autophagic vacuoles, conversion of microtubule-associated protein 1 light chain 3 (LC3) from form I to form II, accumulation of beclin-1 and autophagy-related gene-5, and a decrease in p62 expression. CLP also shifted microglial polarization to the M1 phenotype, and increased levels of IL-1β, IL-6 and phosphorylated p38MAPK. CXCR5 knockout further enhanced autophagy but partially reversed all the other CLP-induced effects, including cognitive deficits. Similar effects on autophagy and cytokine expression were observed after knocking down CXCR5 in LPS-challenged primary microglial cultures; this knockdown also partially reversed LPS-induced up-regulation of phosphorylated NF-κB and STAT3. The p38MAPK agonist P79350 partially reversed the effects of CXCR5 knockdown in microglial cultures.

Conclusions
CXCR5 may act via p38MAPK/NF-κB/STAT3 signaling to inhibit hippocampal autophagy during sepsis and thereby contribute to cognitive dysfunction. Down-regulating CXCR5 can restore autophagy and mitigate the proinflammatory microenvironment in the hippocampus.
Altered substrate metabolism in neurodegenerative disease: new insights from metabolic imaging
Authors: Cleland Nicholas R. W. , Al-Juboori Saif I. , Dobrinskikh Evgenia , Bruce Kimberley D. 
Published: October 2021

AbstractNeurodegenerative diseases (NDs), such as Alzheimer’s disease (AD), Parkinson’s disease (PD) and multiple sclerosis (MS), are relatively common and devastating neurological disorders. For example, there are 6 million individuals living with AD in the United States, a number that is projected to grow to 14 million by the year 2030. Importantly, AD, PD and MS are all characterized by the lack of a true disease-modifying therapy that is able to reverse or halt disease progression. In addition, the existing standard of care for most NDs only addresses the symptoms of the disease. Therefore, alternative strategies that target mechanisms underlying the neuropathogenesis of disease are much needed. Recent studies have indicated that metabolic alterations in neurons and glia are commonly observed in AD, PD and MS and lead to changes in cell function that can either precede or protect against disease onset and progression. Specifically, single-cell RNAseq studies have shown that AD progression is tightly linked to the metabolic phenotype of microglia, the key immune effector cells of the brain. However, these analyses involve removing cells from their native environment and performing measurements in vitro, influencing metabolic status. Therefore, technical approaches that can accurately assess cell-specific metabolism in situ have the potential to be transformative to our understanding of the mechanisms driving AD. Here, we review our current understanding of metabolism in both neurons and glia during homeostasis and disease. We also evaluate recent advances in metabolic imaging, and discuss how emerging modalities, such as fluorescence lifetime imaging microscopy (FLIM) have the potential to determine how metabolic perturbations may drive the progression of NDs. Finally, we propose that the temporal, regional, and cell-specific characterization of brain metabolism afforded by FLIM will be a critical first step in the rational design of metabolism-focused interventions that delay or even prevent NDs.
Integration of SARS-CoV-2 RNA in infected human cells by retrotransposons: an unlikely hypothesis and old viral relationships
Authors: Grandi Nicole , Tramontano Enzo , Berkhout Ben 
Published: October 2021

AbstractZhang et al. (Proc Natl Acad Sci 118:e2105968118, 2021) recently reported that SARS-CoV-2 RNA can be retrotranscribed and integrated into the DNA of human cells by the L1 retrotransposon machinery. This phenomenon could cause persistence of viral sequences in patients and may explain the prolonged PCR-positivity of SARS-CoV-2 infected patients, even long after the phase of active virus replication has ended. This commentary does critically review the available data on this topic and discusses them in the context of findings made for other exogenous viruses and ancestral endogenous retroviral elements.