bluuebunny/crossref_metadata_2025 huggingface dataset:
Sexual Dimorphism in Innate Immunity: The Role of Sex Hormones and Epigenetics
Authors: Shepherd Rebecca , Cheung Ada S. , Pang Ken , Saffery Richard , Novakovic Boris
Published: January 2021

Sexual dimorphism refers to differences between biological sexes that extend beyond sexual characteristics. In humans, sexual dimorphism in the immune response has been well demonstrated, with females exhibiting lower infection rates than males for a variety of bacterial, viral, and parasitic pathogens. There is also a substantially increased incidence of autoimmune disease in females compared to males. Together, these trends indicate that females have a heightened immune reactogenicity to both self and non-self-molecular patterns. However, the molecular mechanisms driving the sexually dimorphic immune response are not fully understood. The female sex hormones estrogen and progesterone, as well as the male androgens, such as testosterone, elicit direct effects on the function and inflammatory capacity of immune cells. Several studies have identified a sex-specific transcriptome and methylome, independent of the well-described phenomenon of X-chromosome inactivation, suggesting that sexual dimorphism also occurs at the epigenetic level. Moreover, distinct alterations to the transcriptome and epigenetic landscape occur in synchrony with periods of hormonal change, such as puberty, pregnancy, menopause, and exogenous hormone therapy. These changes are also mirrored by changes in immune cell function. This review will outline the evidence for sex hormones and pregnancy-associated hormones as drivers of epigenetic change, and how this may contribute to the sexual dimorphism. Determining the effects of sex hormones on innate immune function is important for understanding sexually dimorphic autoimmune diseases, sex-specific responses to pathogens and vaccines, and how innate immunity is altered during periods of hormonal change (endogenous or exogenous).
A Glance at the Use of Glucocorticoids in Rare Inflammatory and Autoimmune Diseases: Still an Indispensable Pharmacological Tool?
Authors: Ronchetti Simona , Ayroldi Emira , Ricci Erika , Gentili Marco , Migliorati Graziella , Riccardi Carlo
Published: January 2021

Since their discovery, glucocorticoids (GCs) have been used to treat almost all autoimmune and chronic inflammatory diseases, as well as allergies and some forms of malignancies, because of their immunosuppressive and anti-inflammatory effects. Although GCs provide only symptomatic relief and do not eliminate the cause of the pathology, in the majority of treatments, GCs frequently cannot be replaced by other classes of drugs. Consequently, long-term treatments cause adverse effects that may, in turn, lead to new pathologies that sometimes require the withdrawal of GC therapy. Therefore, thus far, researchers have focused their efforts on molecules that have the same efficacy as that of GCs but cause fewer adverse effects. To this end, some GC-induced proteins, such as glucocorticoid-induced leucine zipper (GILZ), have been used as drugs in mouse models of inflammatory pathologies. In this review, we focus on some important but rare autoimmune and chronic inflammatory diseases for which the biomedical research investment in new therapies is less likely. Additionally, we critically evaluate the possibility of treating such diseases with other drugs, either GC-related or unrelated.
Bactericidal Permeability Increasing Protein Deficiency Aggravates Acute Colitis in Mice by Increasing the Serum Levels of Lipopolysaccharide
Authors: Kong Qingli , Lv Zhe , Kang Yun , An Yunqing , Liu Zhenlong , Zhang Jianmin
Published: January 2021

Objective

The objective of this study was to understand the role of bactericidal permeability increasing protein (BPI) in the pathogenesis of experimental murine colitis.

Methods

We used the Cre-LoxP system to generate BPI knockout (BPI KO) mice. Acute colitis was induced in BPI KO mice and wild-type (WT) mice by subjecting the mice to 5% dextran sulfate sodium (DSS). Mice were observed for symptoms of experimental colitis. The survival of BPI KO mice to infection with Acinetobacter baumannii, a gram-negative bacterium, was also assessed.

Results

Southern blot, RT-PCR, and western blot results showed that the 2nd and 3rd exons of the murine Bpi gene were knocked out systemically, confirming successful construction of the BPI KO mouse. BPI KO mice subjected to DSS showed increased symptoms of experimental colitis, increased colonic mucosal damage, increased epithelial permeability, elevated levels of serum LPS, and a disrupted fecal microbiome as compared with WT mice. Furthermore, BPI KO mice challenged intraperitoneally with A. baumannii died sooner than WT mice, and the total number of bacteria in the abdominal cavity, spleen, and liver was increased in BPI KO mice as compared to WT mice.

Conclusions

We successfully generated BPI KO mice. The BPI KO mice developed worse colitis than WT mice by increased colitis symptoms and colonic mucosal damage, elevated levels of serum LPS, and a disrupted microbiome. BPI could be a potential target for treatment of ulcerative colitis in humans.
Selective Host Cell Death by Staphylococcus aureus: A Strategy for Bacterial Persistence
Authors: Missiakas Dominique , Winstel Volker
Published: January 2021

Host cell death programs are fundamental processes that shape cellular homeostasis, embryonic development, and tissue regeneration. Death signaling and downstream host cell responses are not only critical to guide mammalian development, they often act as terminal responses to invading pathogens. Here, we briefly review and contrast how invading pathogens and specificallyStaphylococcus aureusmanipulate apoptotic, necroptotic, and pyroptotic cell death modes to establish infection. Rather than invading host cells,S. aureussubverts these cells to produce diffusible molecules that cause death of neighboring hematopoietic cells and thus shapes an immune environment conducive to persistence. The exploitation of cell death pathways byS. aureusis yet another virulence strategy that must be juxtaposed to mechanisms of immune evasion, autophagy escape, and tolerance to intracellular killing, and brings us closer to the true portrait of this pathogen for the design of effective therapeutics and intervention strategies.
Variable Expression of Programmed Cell Death Protein 1-Ligand 1 in Kidneys Independent of Immune Checkpoint Inhibition
Authors: Hakroush Samy , Kopp Sarah Birgit , Tampe Désirée , Gersmann Ann-Kathrin , Korsten Peter , Zeisberg Michael , Tampe Björn
Published: January 2021

Context

Due to recent advantages in cancer therapy, immune checkpoint inhibitors (ICIs) are new classes of drugs targeting programmed cell death protein 1 (PD-1) or its ligand programmed cell death protein 1-ligand 1 (PD-L1) used in many cancer therapies. Acute interstitial nephritis (AIN) is a potential and deleterious immune-related adverse events (irAE) in the kidney observed in patients receiving ICIs and the most common biopsy-proven diagnosis in patients who develop acute kidney injury (AKI). Based on previous reports, AIN in patients receiving ICIs is associated with tubular positivity for PD-L1, implicating that PD-L1 positivity reflects susceptibility to develop renal complications with these agents. It remains unclear if PD-L1 positivity is acquired specifically during ICI therapy or expressed independently in the kidney.

Methods

PD-L1 was analyzed in experimental mouse models of ischemia-reperfusion injury (IRI), folic acid-induced nephropathy (FAN), unilateral ureteral obstruction (UUO), and nephrotoxic serum nephritis (NTN) by immunostaining, SDS-PAGE, and subsequent immunoblotting. In addition, we included a total number of 87 human kidney samples (six renal biopsies with AIN related to ICI therapy, 13 nephrectomy control kidneys, and 68 ICI-naïve renal biopsies with various underlying kidney diseases to describe PD-L1 expression.

Results

We here report distinct PD-L1 expression in renal compartments in multiple murine models of kidney injury and human cases with various underlying kidney diseases, including ICI-related AIN and renal pathologies independent of ICI therapy. PD-L1 is frequently expressed in various renal pathologies independent of ICI therapy and could potentially be a pre-requisit for susceptibility to develop AKI and deleterious immune-related AIN. In addition, we provide evidence that tubular PD-L1 positivity in the kidney is associated with detection of urinary PD-L1+ tubular epithelial cells.

Conclusion

Our study implicates that PD-L1 is frequently expressed in various renal pathologies independent of ICI therapy and could potentially be a pre-requisit for susceptibility to develop AKI and deleterious immune-related AIN. Because non-invasive detection of PD-L1+ cells in corresponding urine samples correlates with intrarenal PD-L1 positivity, it is attractive to speculate that further non-invasive detection of PD-L1+ cells may identify patients at risk for ICI-related AIN.
SNRNP200 Mutations Cause Autosomal Dominant Retinitis Pigmentosa
Authors: Zhang Tao , Bai Jingshan , Zhang Xinyi , Zheng Xiaowei , Lu Nan , Liang Zhongyin , Lin Ling , Chen Yongsong
Published: January 2021

The small nuclear ribonucleoprotein 200 kDa (SNRNP200) gene plays a key role in the maturation of pre-message RNA (pre-mRNA) splicing with the indication for the etiology of retinitis pigmentosa (RP). Gene recognition can facilitate the diagnosis of these patients for better clinical management, treatment and counseling. This study aimed to outline the causative mutation in a Chinese family and the pathogenic mechanism of this SNRNP200 mutation in RP. Eighteen individuals from the affected family underwent a complete ophthalmic examination. Whole exome sequencing (WES) was conducted to identify the pathogenic variant in the proband, which was then confirmed by Sanger sequencing. Expression of the SNRNP200 transcript in zebrafish was identified via whole mountin situhybridization. Morpholino oligonucleotide (MO) and SNRNP200 wild and mutant mRNA were injected into zebrafish embryos followed by analyses of the systemic changes and retinal phenotypes using immunofluorescence. Heterozygous SNRNP200c.C6088T(p.Arg2030Cys) mutation was ascertained in two members of this family: the proband and his father (II-2). Overexpression of SNRNP200Arg2030Cys, but not SNRNP200WTcaused systemic deformities in the wild-type zebrafish embryos with the retina primarily injured, and significantly increased death rates in the morphant embryos, in which the orthologous zebrafish SNRNP200 gene was blocked. In conclusion, this study reports a novel heterozygous SNRNP200c.C6088Tmutation, which is evidenced to cause RP via a dominant-negative effect.
Optical Coherence Tomography Angiography Findings After Intravitreal Ranibizumab in Patients With Coats Disease
Authors: Cennamo Gilda , Montorio Daniela , Comune Chiara , Laezza Maria Paola , Fallico Matteo , Lionetti Maria Elena , Reibaldi Michele
Published: January 2021

The aim of this retrospective study was to describe the vascular features in eyes with Coats disease, using optical coherence tomography angiography (OCTA), at baseline and after 3 monthly intravitreal injections of ranibizumab. Fifteen eyes of 15 consecutive patients affected by Coats' disease were recruited in this study. All patients underwent the best-corrected visual acuity (BCVA) evaluation, fundus examination, fluorescein angiography (FA), indocyanine green angiography (ICGA), multicolor imaging, structural Spectral Domain (SD)-OCT and OCTA at baseline and 1 month after the third monthly ranibizumab injection (loading phase). Fifteen patients completed the study, of whom nine were males and six females. Mean age was 20.4 ± 2 years. BCVA was 0.46 ± 0.11 logMar and 0.47 ± 0.12 logMar at baseline and after treatment, respectively (p = 0.164). SD-OCT revealed no significant decrease in central macular thickness (486.33 μm ± 93.37 at baseline vs. 483.4 μm ± 80.97 after treatment; p = 0.915). The subretinal exudates persisted in macular region after intravitreal injections. OCTA showed a general vascular rarefaction in superficial capillary plexus (SCP), deep capillary plexus (DCP), and choriocapillary (CC) that did not change after loading phase. This study showed no functional and vascular improvement following 3 monthly ranibizumab injections. OCTA, non-invasive technique, could be useful during follow up of these patients and provide a better understand of pathogenesis of this disorder.
Focus on the Gut–Kidney Axis in Health and Disease
Authors: Stavropoulou Elisavet , Kantartzi Konstantia , Tsigalou Christina , Konstantinidis Theoharis , Romanidou Gioulia , Voidarou Chrysa , Bezirtzoglou Eugenia
Published: January 2021

The recent new developments in technology with culture-independent techniques including genome sequencing methodologies shed light on the identification of microbiota bacterial species and their role in health and disease. Microbiome is actually reported as an important predictive tool for evaluating characteristic shifts in case of disease. Our present review states the development of different renal diseases and pathologies linked to the intestinal dysbiosis, which impacts on host homeostasis. The gastrointestinal–kidney dialogue provides intriguing features in the pathogenesis of several renal diseases. Without any doubt, investigation of this interconnection consists one of the most cutting-edge areas of research with potential implications on our health.
Cilomilast Ameliorates Renal Tubulointerstitial Fibrosis by Inhibiting the TGF-β1-Smad2/3 Signaling Pathway
Authors: Xu Man , Li Shumin , Wang Jiajia , Huang Songming , Zhang Aihua , Zhang Yue , Gu Wei , Yu Xiaowen , Jia Zhanjun
Published: January 2021

Background: Renal tubulointerstitial fibrosis is the key pathological feature in chronic kidney diseases (CKDs) with no satisfactory therapies in clinic. Cilomilast is a second-generation, selective phosphodiesterase-4 inhibitor, but its role in renal tubulointerstitial fibrosis in CKD remains unclear.

Material and Methods: Cilomilast was applied to the mice with unilateral ureteric obstruction (UUO) and renal fibroblast cells (NRK-49F) stimulated by TGF-β1. Renal tubulointerstitial fibrosis and inflammation after UUO or TGF-β1 stimulation were examined by histology, Western blotting, real-time PCR and immunohistochemistry. KIM-1 and NGAL were detected to evaluate tubular injury in UUO mice.

Results:In vivo, immunohistochemistry and western blot data demonstrated that cilomilast treatment inhibited extracellular matrix deposition, profibrotic gene expression, and the inflammatory response. Furthermore, cilomilast prevented tubular injury in UUO mice, as manifested by reduced expression of KIM-1 and NGAL in the kidney. In vitro, cilomilast attenuated the activation of fibroblast cells stimulated by TGF-β1, as shown by the reduced expression of fibronectin, α-SMA, collagen I, and collagen III. Cilomilast also inhibited the activation of TGF-β1-Smad2/3 signaling in TGF-β1-treated fibroblast cells.

Conclusion: The findings of this study suggest that cilomilast is protective against renal tubulointerstitial fibrosis in CKD, possibly through the inhibition of TGF-β1-Smad2/3 signaling, indicating the translational potential of this drug in treating CKD.
Muffin Technique Micrographic Surgery for Non-melanoma Skin Cancer
Authors: Surmanowicz Philip , Sivanand Arunima , Du Amy X. , Mahmood Muhammad N. , Gniadecki Robert
Published: January 2021

Background: Mohs micrographic surgery (MMS) is the gold standard treatment for high-risk facial non-melanoma skin cancer. However, patients' access to MMS is limited by cost. The muffin technique micrographic surgery (MTMS) is an alternative micrographic technique wherein the entire excised margin is evaluated post-operatively by a pathologist using paraffin-embedded material. Herein, we describe the implementation and the preliminary results of MTMS in an academic dermatology center.

Objective: To describe the MTMS and outline its efficacy and safety in a real-world clinical academic setting.

Methods: A retrospective chart review was conducted of all patients with basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) who underwent MTMS at the University of Alberta Dermatology Center from June 2016 until July 2019.

Results: A total of 69 patients were included (64 BCCs and 5 SCCs). 68.1% of surgeries had clear margins following the first incision, 100% after second round re-excisions. There were no observed cases of tumor recurrence after a median 40 months of follow-up. There were no major adverse events or complications.

Conclusions: MTMS is a superior alternative to simple excision of skin cancer by providing full margin control and residual tumor mapping.
A Machine-Learning Approach for Dynamic Prediction of Sepsis-Induced Coagulopathy in Critically Ill Patients With Sepsis
Authors: Zhao Qin-Yu , Liu Le-Ping , Luo Jing-Chao , Luo Yan-Wei , Wang Huan , Zhang Yi-Jie , Gui Rong , Tu Guo-Wei , Luo Zhe
Published: January 2021

Background: Sepsis-induced coagulopathy (SIC) denotes an increased mortality rate and poorer prognosis in septic patients.

Objectives: Our study aimed to develop and validate machine-learning models to dynamically predict the risk of SIC in critically ill patients with sepsis.

Methods: Machine-learning models were developed and validated based on two public databases named Medical Information Mart for Intensive Care (MIMIC)-IV and the eICU Collaborative Research Database (eICU-CRD). Dynamic prediction of SIC involved an evaluation of the risk of SIC each day after the diagnosis of sepsis using 15 predictive models. The best model was selected based on its accuracy and area under the receiver operating characteristic curve (AUC), followed by fine-grained hyperparameter adjustment using the Bayesian Optimization Algorithm. A compact model was developed, based on 15 features selected according to their importance and clinical availability. These two models were compared with Logistic Regression and SIC scores in terms of SIC prediction.

Results: Of 11,362 patients in MIMIC-IV included in the final cohort, a total of 6,744 (59%) patients developed SIC during sepsis. The model named Categorical Boosting (CatBoost) had the greatest AUC in our study (0.869; 95% CI: 0.850–0.886). Coagulation profile and renal function indicators were the most important features for predicting SIC. A compact model was developed with an AUC of 0.854 (95% CI: 0.832–0.872), while the AUCs of Logistic Regression and SIC scores were 0.746 (95% CI: 0.735–0.755) and 0.709 (95% CI: 0.687–0.733), respectively. A cohort of 35,252 septic patients in eICU-CRD was analyzed. The AUCs of the full and the compact models in the external validation were 0.842 (95% CI: 0.837–0.846) and 0.803 (95% CI: 0.798–0.809), respectively, which were still larger than those of Logistic Regression (0.660; 95% CI: 0.653–0.667) and SIC scores (0.752; 95% CI: 0.747–0.757). Prediction results were illustrated by SHapley Additive exPlanations (SHAP) values, which made our models clinically interpretable.

Conclusions: We developed two models which were able to dynamically predict the risk of SIC in septic patients better than conventional Logistic Regression and SIC scores.
Biodiversity of Aflatoxigenic Aspergillus Species in Dairy Feeds in Bulawayo, Zimbabwe
Authors: Nleya Nancy , Ngoma Lubanza , Adetunji Modupeade C. , Mwanza Mulunda
Published: January 2021

The presence of molds, especially certain species of Aspergillus, in food commodities may contribute to aflatoxin contamination. The aim of this study was to determine the biodiversity of Aspergillus species in dairy feeds from farms in select locations in Zimbabwe and assess their aflatoxin production potential using a polyphasic approach. A total of 96 feed samples were collected, which consisted of dairy feed concentrate, mixed ration, brewers’ spent grain, and grass from 13 farms during the dry season (August–October, 2016) and the following rainy season (January–March, 2017). A total of 199 presumptive isolates representing four sections from genus Aspergillus (Nigri, Fumigati, Flavi, and Circumdati) were recovered from the feeds. Section Flavi, which includes several aflatoxin producers, constituted 23% (n = 46) of the isolates. Species from this section were A. flavus, A. nomius, A. oryzae, A. parasiticus, and A. parvisclerotigenus, and 39 (84.4%) of these showed evidence of aflatoxin production in plate assays. Of the 46 section Flavi isolates examined, some lacked one or more of the five targeted aflatoxin cluster genes (aflD, aflR, aflS, aflM, and aflP). The presence of the five genes was as follows: aflD (76.9%), aflR (48.7%), aflS (74.4%), aflM (64.1%), and aflP (79.5%). This study highlights the species diversity of aflatoxigenic fungi that have the potential to contaminate different types of feed for dairy cows. Our findings underscore the importance of preventing contamination of feedstuffs by these fungi so that aflatoxins do not end up in the diets of consumers.
Patterns of Relative and Quantitative Abundances of Marine Bacteria in Surface Waters of the Subtropical Northwest Pacific Ocean Estimated With High-Throughput Quantification Sequencing
Authors: Kong Jie , Liu Xin , Wang Lei , Huang Hao , Ou Danyun , Guo Jiayu , Laws Edward A. , Huang Bangqin
Published: January 2021

Bacteria play a pivotal role in shaping ecosystems and contributing to elemental cycling and energy flow in the oceans. However, few studies have focused on bacteria at a trans-basin scale, and studies across the subtropical Northwest Pacific Ocean (NWPO), one of the largest biomes on Earth, have been especially lacking. Although the recently developed high-throughput quantitative sequencing methodology can simultaneously provide information on relative abundance, quantitative abundance, and taxonomic affiliations, it has not been thoroughly evaluated. We collected surface seawater samples for high-throughput, quantitative sequencing of 16S rRNA genes on a transect across the subtropical NWPO to elucidate the distribution of bacterial taxa, patterns of their community structure, and the factors that are potentially important regulators of that structure. We used the quantitative and relative abundances of bacterial taxa to test hypotheses related to their ecology. Total 16S rRNA gene copies ranged from 1.86 × 108to 1.14 × 109copies L−1. Bacterial communities were distributed in distinct geographical patterns with spatially adjacent stations clustered together. Spatial considerations may be more important determinants of bacterial community structures than measured environmental variables. The quantitative and relative abundances of bacterial communities exhibited similar distribution patterns and potentially important determinants at the whole-community level, but inner-community connections and correlations with variables differed at subgroup levels. This study advanced understanding of the community structure and distribution patterns of marine bacteria as well as some potentially important determinants thereof in a subtropical oligotrophic ocean system. Results highlighted the importance of considering both the quantitative and relative abundances of members of marine bacterial communities.
An Evolutionary Arms Race Between Burkholderia pseudomallei and Host Immune System: What Do We Know?
Authors: Chomkatekaew Chalita , Boonklang Phumrapee , Sangphukieo Apiwat , Chewapreecha Claire
Published: January 2021

A better understanding of co-evolution between pathogens and hosts holds promise for better prevention and control strategies. This review will explore the interactions betweenBurkholderia pseudomallei, an environmental and opportunistic pathogen, and the human host immune system.B. pseudomalleicauses “Melioidosis,” a rapidly fatal tropical infectious disease predicted to affect 165,000 cases annually worldwide, of which 89,000 are fatal. Genetic heterogeneities were reported in bothB. pseudomalleiand human host population, some of which may, at least in part, contribute to inter-individual differences in disease susceptibility. Here, we review (i) a multi-host—pathogen characteristic of the interaction; (ii) selection pressures acting onB. pseudomalleiand human genomes with the former being driven by bacterial adaptation across ranges of ecological niches while the latter are driven by human encounter of broad ranges of pathogens; (iii) the mechanisms that generate genetic diversity in bacterial and host population particularly in sequences encoding proteins functioning in host—pathogen interaction; (iv) reported genetic and structural variations of proteins or molecules observed inB. pseudomallei—human host interactions and their implications in infection outcomes. Together, these predict bacterial and host evolutionary trajectory which continues to generate genetic diversity in bacterium and operates host immune selection at the molecular level.
Wickerhamomyces anomalus in Mosquitoes: A Promising Yeast-Based Tool for the “Symbiotic Control” of Mosquito-Borne Diseases
Authors: Cappelli Alessia , Favia Guido , Ricci Irene
Published: January 2021

The ascomycete yeast Wickerhamomyces anomalus is a mutualistic symbiont of different insects, including diptera vectors of diseases. Although fungal symbioses have been so far poorly characterized, the topic is gaining attention as yeast-insect interactions can provide pivotal information on insect biology, such as their environmental adaptation or vectorial capability. We review the symbiosis between W. anomalus and mosquitoes, which implies nutritional and protective functions. Furthermore, we focus on antiplasmodial effects of W. anomalus in malaria vectors and discuss the yeast potential for the “symbiotic control” (SC) of mosquito-borne diseases (MBDs).
Coupled Transcription-Translation in Prokaryotes: An Old Couple With New Surprises
Authors: Irastortza-Olaziregi Mikel , Amster-Choder Orna
Published: January 2021

Coupled transcription-translation (CTT) is a hallmark of prokaryotic gene expression. CTT occurs when ribosomes associate with and initiate translation of mRNAs whose transcription has not yet concluded, therefore forming “RNAP.mRNA.ribosome” complexes. CTT is a well-documented phenomenon that is involved in important gene regulation processes, such as attenuation and operon polarity. Despite the progress in our understanding of the cellular signals that coordinate CTT, certain aspects of its molecular architecture remain controversial. Additionally, new information on the spatial segregation between the transcriptional and the translational machineries in certain species, and on the capability of certain mRNAs to localize translation-independently, questions the unanimous occurrence of CTT. Furthermore, studies where transcription and translation were artificially uncoupled showed that transcription elongation can proceed in a translation-independent manner. Here, we review studies supporting the occurrence of CTT and findings questioning its extent, as well as discuss mechanisms that may explain both coupling and uncoupling, e.g., chromosome relocation and the involvement of cis- or trans-acting elements, such as small RNAs and RNA-binding proteins. These mechanisms impact RNA localization, stability, and translation. Understanding the two options by which genes can be expressed and their consequences should shed light on a new layer of control of bacterial transcripts fate.
Impact of Processed Food (Canteen and Oil Wastes) on the Development of Black Soldier Fly (Hermetia illucens) Larvae and Their Gut Microbiome Functions
Authors: Klammsteiner Thomas , Walter Andreas , Bogataj Tajda , Heussler Carina D. , Stres Blaž , Steiner Florian M. , Schlick-Steiner Birgit C. , Insam Heribert
Published: January 2021

Canteens represent an essential food supply hub for educational institutions, companies, and business parks. Many people in these locations rely on a guaranteed service with consistent quality. It is an ongoing challenge to satisfy the demand for sufficient serving numbers, portion sizes, and menu variations to cover food intolerances and different palates of customers. However, overestimating this demand or fluctuating quality of dishes leads to an inevitable loss of unconsumed food due to leftovers. In this study, the food waste fraction of canteen leftovers was identified as an optimal diet for black soldier fly (Hermetia illucens) larvae based on 50% higher consumption and 15% higher waste reduction indices compared with control chicken feed diet. Although the digestibility of food waste was nearly twice as high, the conversion efficiency of ingested and digested chicken feed remains unparalleled (17.9 ± 0.6 and 37.5 ± 0.9 in CFD and 7.9 ± 0.9 and 9.6 ± 1.0 in FWD, respectively). The oil separator waste fraction, however, inhibited biomass gain by at least 85% and ultimately led to a larval mortality of up to 96%. In addition to monitoring larval development, we characterized physicochemical properties of pre- and post-process food waste substrates. High-throughput amplicon sequencing identified Firmicutes, Proteobacteria, and Bacteroidota as the most abundant phyla, andMorganella,Acinetobacter, and certain Lactobacillales species were identified as indicator species. By using metagenome imputation, we additionally gained insights into the functional spectrum of gut microbial communities. We anticipate that the results will contribute to the development of decentralized waste-management sites that make use of larvae to process food waste as it has become common practice for biogas plants.
Different Biochemical Compositions of Particulate Organic Matter Driven by Major Phytoplankton Communities in the Northwestern Ross Sea
Authors: Jo Naeun , La Hyoung Sul , Kim Jeong-Hoon , Kim Kwanwoo , Kim Bo Kyung , Kim Myung Joon , Son Wuju , Lee Sang Heon
Published: January 2021

Marine particulate organic matter (POM) largely derived from phytoplankton is a primary food source for upper trophic consumers. Their biochemical compositions are important for heterotrophs. Especially, essential amino acids (EAAs) in phytoplankton are well known to have impacts on the survival and egg productions of herbivorous zooplankton. To estimate the nutritional quality of POM, the biochemical compositions [biomolecular and amino acid (AA) compositions] of POM were investigated in the northwestern Ross Sea during the late austral summer in 2018. Carbohydrates (CHO) accounted for the highest portion among different biomolecules [CHO, proteins (PRT), and lipids (LIP)] of POM. However, the higher contribution of PRT and lower contribution of CHO were observed in the southern section of our study area compared to those in the northern section. The spatial distribution of total hydrolyzable AAs in POM was considerably influenced by phytoplankton biomass, which indicates that the main source of particulate AA was generated by phytoplankton. Our results showed that the relative contribution of EAA to the total AAs was strongly associated with EAA index (EAAI) for determining protein quality. This result indicates that higher EAA contribution in POM suggests a better protein quality in consistency with high EAAI values. In this study, variations in the biochemical compositions in POM were principally determined by two different bloom-forming taxa (diatoms andPhaeocystis antarctica). The southern region dominated majorly by diatoms was positively correlated with PRT, EAA, and EAAI indicating a good protein quality, whileP. antarctica-abundant northern region with higher CHO contribution was negatively correlated with good protein quality factors. Climate-driven environmental changes could alter not only the phytoplankton community but also the physiological conditions of phytoplankton. Our findings could provide a better understanding for future climate-induced changes in the biochemical compositions of phytoplankton and consequently their potential impacts on higher trophic levels.
Accurate Neuronal Soma Segmentation Using 3D Multi-Task Learning U-Shaped Fully Convolutional Neural Networks
Authors: Hu Tianyu , Xu Xiaofeng , Chen Shangbin , Liu Qian
Published: January 2021

Neuronal soma segmentation is a crucial step for the quantitative analysis of neuronal morphology. Automated neuronal soma segmentation methods have opened up the opportunity to improve the time-consuming manual labeling required during the neuronal soma morphology reconstruction for large-scale images. However, the presence of touching neuronal somata and variable soma shapes in images brings challenges for automated algorithms. This study proposes a neuronal soma segmentation method combining 3D U-shaped fully convolutional neural networks with multi-task learning. Compared to existing methods, this technique applies multi-task learning to predict the soma boundary to split touching somata, and adopts U-shaped architecture convolutional neural network which is effective for a limited dataset. The contour-aware multi-task learning framework is applied to the proposed method to predict the masks of neuronal somata and boundaries simultaneously. In addition, a spatial attention module is embedded into the multi-task model to improve neuronal soma segmentation results. The Nissl-stained dataset captured by the micro-optical sectioning tomography system is used to validate the proposed method. Following comparison to four existing segmentation models, the proposed method outperforms the others notably in both localization and segmentation. The novel method has potential for high-throughput neuronal soma segmentation in large-scale optical imaging data for neuron morphology quantitative analysis.
Development of Locomotor-Related Movements in Early Infancy
Authors: Dewolf Arthur H. , Sylos Labini Francesca , Ivanenko Yury , Lacquaniti Francesco
Published: January 2021

This mini-review focuses on the emergence of locomotor-related movements in early infancy. In particular, we consider multiples precursor behaviors of locomotion as a manifestation of the development of the neuronal networks and their link in the establishment of precocious locomotor skills. Despite the large variability of motor behavior observed in human babies, as in animals, afferent information is already processed to shape the behavior to specific situations and environments. Specifically, we argue that the closed-loop interaction between the neural output and the physical dynamics of the mechanical system should be considered to explore the complexity and flexibility of pattern generation in human and animal neonates.
Alcohol-Specific Mortality in People With Epilepsy: Cohort Studies in Two Independent Population-Based Datasets
Authors: Gorton Hayley C. , Webb Roger T. , Parisi Rosa , Carr Matthew J. , DelPozo-Banos Marcos , Moriarty Kieran J. , Pickrell W. Owen , John Ann , Ashcroft Darren M.
Published: January 2021

Objectives: The risk of dying by alcohol-specific causes in people with epilepsy has seldom been reported from population-based studies. We aimed to estimate the relative risk of alcohol-specific mortality in people with epilepsy, and the extent to which problematic alcohol use was previously identified in the patients' medical records.

Method: We delineated cohort studies in two population-based datasets, the Clinical Practice Research Datalink (CPRD GOLD) in England (January 01, 2001–December 31, 2014) and the Secure Anonymised Information Linkage (SAIL) Databank in Wales (January 01, 2001–December 31, 2014), linked to hospitalization and mortality records. People with epilepsy were matched to up to 20 persons without epilepsy on gender, age (±2 years) and registered general practice. We identified alcohol-specific death from Office for National Statistics (ONS) records using specified ICD-10 codes. We further identified prescriptions, interventions and hospitalisations related to alcohol use.

Results: In the CPRD GOLD, we identified 9,871 individuals in the incident epilepsy cohort and 185,800 in the comparison cohort and, in the SAIL Databank, these numbers were 5,569 and 110,021, respectively. We identified a five-fold increased risk of alcohol-specific mortality in people with epilepsy vs. those without the condition in our pooled estimate across the two datasets (deprivation-adjusted HR 4.85, 95%CI 3.46–6.79).

Conclusions: People with epilepsy are at increased risk of dying by an alcohol-specific cause than those without the disorder. It is plausible that serious alcohol misuse could either contribute to the development of epilepsy or it could commence subsequent to epilepsy being diagnosed. Regardless of the direction of the association, it is important that the risk of dying as a consequence of alcohol misuse is accurately quantified in people affected by epilepsy. Systematically-applied, sensitive assessment of alcohol consumption by healthcare professionals, at opportunistic, clinical contacts, with rapid access to quality treatment services, should be mandatory and play a key role in reduction of health harms and mortality.
Insights From Genetic Studies of Cerebral Palsy
Authors: Lewis Sara A. , Shetty Sheetal , Wilson Bryce A. , Huang Aris J. , Jin Sheng Chih , Smithers-Sheedy Hayley , Fahey Michael C. , Kruer Michael C.
Published: January 2021

Cohort-based whole exome and whole genome sequencing and copy number variant (CNV) studies have identified genetic etiologies for a sizable proportion of patients with cerebral palsy (CP). These findings indicate that genetic mutations collectively comprise an important cause of CP. We review findings in CP genomics and propose criteria for CP-associated genes at the level of gene discovery, research study, and clinical application. We review the published literature and report 18 genes and 5 CNVs from genomics studies with strong evidence of for the pathophysiology of CP. CP-associated genes often disrupt early brain developmental programming or predispose individuals to known environmental risk factors. We discuss the overlap of CP-associated genes with other neurodevelopmental disorders and related movement disorders. We revisit diagnostic criteria for CP and discuss how identification of genetic etiologies does not preclude CP as an appropriate diagnosis. The identification of genetic etiologies improves our understanding of the neurobiology of CP, providing opportunities to study CP pathogenesis and develop mechanism-based interventions.
An Evolutionary Perspective of Dyslexia, Stress, and Brain Network Homeostasis
Authors: Kershner John R.
Published: January 2021

Evolution fuels interindividual variability in neuroplasticity, reflected in brain anatomy and functional connectivity of the expanding neocortical regions subserving reading ability. Such variability is orchestrated by an evolutionarily conserved, competitive balance between epigenetic, stress-induced, and cognitive-growth gene expression programs. An evolutionary developmental model of dyslexia, suggests that prenatal and childhood subclinical stress becomes a risk factor for dyslexia when physiological adaptations to stress promoting adaptive fitness, may attenuate neuroplasticity in the brain regions recruited for reading. Stress has the potential to blunt the cognitive-growth functions of the predominantly right hemisphere Ventral and Dorsal attention networks, which are primed with high entropic levels of synaptic plasticity, and are critical for acquiring beginning reading skills. The attentional networks, in collaboration with the stress-responsive Default Mode network, modulate the entrainment and processing of the low frequency auditory oscillations (1–8 Hz) and visuospatial orienting linked etiologically to dyslexia. Thus, dyslexia may result from positive, but costly adaptations to stress system dysregulation: protective measures that reset the stress/growth balance of processing to favor the Default Mode network, compromising development of the attentional networks. Such a normal-variability conceptualization of dyslexia is at odds with the frequent assumption that dyslexia results from a neurological abnormality. To put the normal-variability model in the broader perspective of the state of the field, a traditional evolutionary account of dyslexia is presented to stimulate discussion of the scientific merits of the two approaches.
Formulation of the Challenges in Brain-Computer Interfaces as Optimization Problems—A Review
Authors: Fathima Shireen , Kore Sheela Kiran
Published: January 2021

Electroencephalogram (EEG) is one of the common modalities of monitoring the mental activities. Owing to the non-invasive availability of this system, its applicability has seen remarkable developments beyond medical use-cases. One such use case is brain-computer interfaces (BCI). Such systems require the usage of high resolution-based multi-channel EEG devices so that the data collection spans multiple locations of the brain like the occipital, frontal, temporal, and so on. This results in huge data (with high sampling rates) and with multiple EEG channels with inherent artifacts. Several challenges exist in analyzing data of this nature, for instance, selecting the optimal number of EEG channels or deciding what best features to rely on for achieving better performance. The selection of these variables is complicated and requires a lot of domain knowledge and non-invasive EEG monitoring, which is not feasible always. Hence, optimization serves to be an easy to access tool in deriving such parameters. Considerable efforts in formulating these issues as an optimization problem have been laid. As a result, various multi-objective and constrained optimization functions have been developed in BCI that has achieved reliable outcomes in device control like neuro-prosthetic arms, application control, gaming, and so on. This paper makes an attempt to study the usage of optimization techniques in formulating the issues in BCI. The outcomes, challenges, and major observations of these approaches are discussed in detail.
The Effects of Extracorporeal Shock Wave Therapy on Spastic Muscle of the Wrist Joint in Stroke Survivors: Evidence From Neuromechanical Analysis
Authors: Leng Yan , Lo Wai Leung Ambrose , Hu Chengpeng , Bian Ruihao , Xu Zhiqin , Shan Xiyao , Huang Dongfeng , Li Le
Published: January 2021

Background: This study combined neuromechanical modeling analysis, muscle tone measurement from mechanical indentation and electrical impedance myography to assess the neural and peripheral contribution to spasticity post stroke at wrist joint. It also investigated the training effects and explored the underlying mechanism of radial extracorporeal shock wave (rESW) on spasticity.

Methods: People with first occurrence of stroke were randomly allocated to rESW intervention or control group. The intervention group received one session of rESW therapy, followed by routine therapy which was the same frequency and intensity as the control group. Outcome measures were: (1) NeuroFlexor method measured neural component (NC), elastic component (EC) and viscosity component (VC), and (2) myotonometer measured muscle tone (F) and stiffness (S), (3) electrical impedance myography measured resistance (R), reactance (X) and phase angle (θ); (4) modified Asworth scale; (5) Fugl Meyer Upper limb scale. All outcome measures were recorded at baseline, immediately post rESW and at 1-week follow-up. The differences between the paretic and non-paretic side were assessed by t-test. The effectiveness of rESW treatment were analyzed by repeated-measures one-way analysis of variance (ANOVA) at different time points.

Results: Twenty-seven participants completed the study. NC, EC, and VC of the Neuroflexor method, F and S from myotonometer were all significantly higher on the paretic side than those from the non-paretic side. R, X, and θ from electrical impedance were significantly lower on the paretic side than the non-paretic side. Immediately after rESW intervention, VC, F, and S were significantly reduced, and X was significantly increased. The clinical scores showed improvements immediate post rESW and at 1-week follow-up.

Conclusions: The observed changes in upper limb muscle properties adds further support to the theory that both the neural and peripheral components play a role in muscle spasticity. ESW intervention may be more effective in addressing the peripheral component of spasticity in terms of muscle mechanical properties changes. The clinical management of post stroke spasticity should take into consideration of both the neural and non-neural factors in order to identify optimal intervention regime.
Evaluation of Functional Recovery in Rats After Median Nerve Resection and Autograft Repair Using Computerized Gait Analysis
Authors: Heinzel Johannes C. , Oberhauser Viola , Keibl Claudia , Swiadek Nicole , Längle Gregor , Frick Helen , Kolbenschlag Jonas , Prahm Cosima , Grillari Johannes , Hercher David
Published: January 2021

Computerized gait analysis is a common evaluation method in rat models of hind limb nerve injuries, but its use remains unpublished in models of segmental nerve injury of the forelimb. It was the aim of this work to investigate if computerized gait analysis is a feasible evaluation method in a rat model of segmental median nerve injury and autograft repair. Ten male Lewis rats underwent 7-mm resection of the right median nerve with immediate autograft repair. The left median nerve was resected without repair and served as an internal control. Animals were assessed for 12 weeks after surgery via CatWalk (CW) gait analysis every 2 weeks. Evaluation of motor recovery by means of the grasping test was performed weekly while electrophysiological measurements were performed at the end of the observation period. CW data were correlated with grasping strength at each post-operative time point. CW data were also correlated with electrophysiology using linear regression analysis. Principal component analysis was performed to identify clusters of outcome metrics. Recovery of motor function was observable 4 weeks after surgery, but grasping strength was significantly reduced (p < 0.01) compared to baseline values until post-operative week 6. In terms of sensory recovery, the pain-related parameter Duty Cycle showed significant (p < 0.05) recovery starting from post-operative week 8. The Print Area of the right paw was significantly (p < 0.05) increased compared to the left side starting from post-operative week 10. Various parameters of gait correlated significantly (p < 0.05) with mean and maximum grasping strength. However, only Stand Index showed a significant correlation with compound muscle action potential (CMAP) amplitude (p < 0.05). With this work, we prove that computerized gait analysis is a valid and feasible method to evaluate functional recovery after autograft repair of the rat median nerve. We were able to identify parameters such as Print Area, Duty Cycle, and Stand Index, which allow assessment of nerve regeneration. The course of these parameters following nerve resection without repair was also assessed. Additionally, external paw rotation was identified as a valid parameter to evaluate motor reinnervation. In summary, computerized gait analysis is a valuable additional tool to study nerve regeneration in rats with median nerve injury.
Interaction Between Mesenchymal Stem Cells and Retinal Degenerative Microenvironment
Authors: Lin Yu , Ren Xiang , Chen Yongjiang , Chen Danian
Published: January 2021

Retinal degenerative diseases (RDDs) are a group of diseases contributing to irreversible vision loss with yet limited therapies. Stem cell-based therapy is a promising novel therapeutic approach in RDD treatment. Mesenchymal stromal/stem cells (MSCs) have emerged as a leading cell source due to their neurotrophic and immunomodulatory capabilities, limited ethical concerns, and low risk of tumor formation. Several pre-clinical studies have shown that MSCs have the potential to delay retinal degeneration, and recent clinical trials have demonstrated promising safety profiles for the application of MSCs in retinal disease. However, some of the clinical-stage MSC therapies have been unable to meet primary efficacy end points, and severe side effects were reported in some retinal “stem cell” clinics. In this review, we provide an update of the interaction between MSCs and the RDD microenvironment and discuss how to balance the therapeutic potential and safety concerns of MSCs' ocular application.