bluuebunny/crossref_metadata_2025 huggingface dataset:
Human African Trypanosomiasis (sleeping sickness): Current knowledge and future challenges
Authors: Papagni Roberta , Novara Roberta , Minardi Maria Letizia , Frallonardo Luisa , Panico Gianfranco Giorgio , Pallara Elisabetta , Cotugno Sergio , Ascoli Bartoli Tommaso , Guido Giacomo , De Vita Elda , Ricciardi Aurelia , Totaro Valentina , Camporeale Michele , Segala Francesco Vladimiro , Bavaro Davide Fiore , Patti Giulia , Brindicci Gaetano , Pellegrino Carmen , Mariani Michele Fabio , Putoto Giovanni , Sarmati Loredana , Castellani Chiara , Saracino Annalisa , Di Gennaro Francesco , Nicastri Emanuele
Published: May 2023

According to both definitions of US Centers for Disease Control and Prevention and World Health Organization, Neglected Tropical Diseases (NTDs) are a group of preventable and treatable parasitic, viral, and bacterial diseases that affect more than one billion people globally. They generally afflict the more indigent patients of the world and historically have not received as much attention as other diseases. NTDs tend to thrive in low-income regions, where water quality, sanitation and access to health care are substandard. They are common in several countries of Africa, Asia, and Latin America. In this literature review, we want to focus on Human African Trypanosomiasis (HAT), also known as “sleeping sickness”, one of the most common neglected diseases in Africa. It is caused by infection with the subspecies of the parasitic protozoan Trypanosoma brucei, and it is transmitted by the bite of the tsetse fly. It puts 70 million people at risk throughout sub-Saharan Africa and it is usually fatal if untreated or inadequately treated. This review covers several aspects of the disease. We focused our interests on most recent epidemiological data, novel diagnostic methods with their advantages and limitations, new improved treatment and orphan drugs and eradication programs, including vector control, according to a “One Health” approach, to achieve the new goals recently set by WHO.
Global ocean reanalysis CORA2 and its inter comparison with a set of other reanalysis products
Authors: Fu Hongli , Dan Bo , Gao Zhigang , Wu Xinrong , Chao Guofang , Zhang Lianxin , Zhang Yinquan , Liu Kexiu , Zhang Xiaoshuang , Li Wei
Published: May 2023

We present the China Ocean ReAnalysis version 2 (CORA2) in this paper. We compare CORA2 with its predecessor, CORA1, and with other ocean reanalysis products created between 2004 and 2019 [GLORYS12v1 (Global Ocean reanalysis and Simulation), HYCOM (HYbrid Coordinate Ocean Model), GREP (Global ocean Reanalysis Ensemble Product), SODA3 (Simple Ocean Data Assimilation, version 3), and ECCO4 (Estimating the Circulation and Climate of the Ocean, version 4)], to demonstrate its improvements and reliability. In addition to providing tide and sea ice signals, the accuracy and eddy kinetic energy (EKE) of CORA2 are also improved owing to an enhanced resolution of 9 km and updated data assimilation scheme compared with CORA1. Error analysis shows that the root-mean-square error (RMSE) of CORA2 sea-surface temperature (SST) remains around 0.3°C, which is comparable to that of GREP and smaller than those of the other products studied. The subsurface temperature (salinity) RMSE of CORA2, at 0.87°C (0.15 psu), is comparable to that of SODA3, smaller than that of ECCO4, and larger than those of GLORYS12v1, HYCOM, and GREP. CORA2 and GLORYS12v1 can better represent sub-monthly-scale variations in subsurface temperature and salinity than the other products. Although the correlation coefficient of sea-level anomaly (SLA) in CORA2 does not exceed 0.8 in the whole region, as those of GREP and GLORYS12v1 do, it is more effective than ECCO4 and SODA3 in the Indian Ocean and Pacific Ocean. CORA2 can reproduce the variations in steric sea level and ocean heat content (OHC) on the multiple timescales as the other products. The linear trend of the steric sea level of CORA2 is closer to that of GREP than that of the other products, and the long-term warming trends of global OHC in the high-resolution CORA2 and GLORYS12v1 are greater than those in the low-resolution EN4 and GREP. Although CORA2 shows overall poorer performance in the Atlantic Ocean, it still achieves good results from 2009 onward. We plan to further improve CORA2 by assimilating the best available observation data using the incremental analysis update (IAU) procedure and improving the SLA assimilation method.
SIPN South: six years of coordinated seasonal Antarctic sea ice predictions
Authors: Massonnet François , Barreira Sandra , Barthélemy Antoine , Bilbao Roberto , Blanchard-Wrigglesworth Edward , Blockley Ed , Bromwich David H. , Bushuk Mitchell , Dong Xiaoran , Goessling Helge F. , Hobbs Will , Iovino Doroteaciro , Lee Woo-Sung , Li Cuihua , Meier Walter N. , Merryfield William J. , Moreno-Chamarro Eduardo , Morioka Yushi , Li Xuewei , Niraula Bimochan , Petty Alek , Sanna Antonella , Scilingo Mariana , Shu Qi , Sigmond Michael , Sun Nico , Tietsche Steffen , Wu Xingren , Yang Qinghua , Yuan Xiaojun
Published: May 2023

Antarctic sea ice prediction has garnered increasing attention in recent years, particularly in the context of the recent record lows of February 2022 and 2023. As Antarctica becomes a climate change hotspot, as polar tourism booms, and as scientific expeditions continue to explore this remote continent, the capacity to anticipate sea ice conditions weeks to months in advance is in increasing demand. Spurred by recent studies that uncovered physical mechanisms of Antarctic sea ice predictability and by the intriguing large variations of the observed sea ice extent in recent years, the Sea Ice Prediction Network South (SIPN South) project was initiated in 2017, building upon the Arctic Sea Ice Prediction Network. The SIPN South project annually coordinates spring-to-summer predictions of Antarctic sea ice conditions, to allow robust evaluation and intercomparison, and to guide future development in polar prediction systems. In this paper, we present and discuss the initial SIPN South results collected over six summer seasons (December-February 2017-2018 to 2022-2023). We use data from 22 unique contributors spanning five continents that have together delivered more than 3000 individual forecasts of sea ice area and concentration. The SIPN South median forecast of the circumpolar sea ice area captures the sign of the recent negative anomalies, and the verifying observations are systematically included in the 10-90% range of the forecast distribution. These statements also hold at the regional level except in the Ross Sea where the systematic biases and the ensemble spread are the largest. A notable finding is that the group forecast, constructed by aggregating the data provided by each contributor, outperforms most of the individual forecasts, both at the circumpolar and regional levels. This indicates the value of combining predictions to average out model-specific errors. Finally, we find that dynamical model predictions (i.e., based on process-based general circulation models) generally perform worse than statistical model predictions (i.e., data-driven empirical models including machine learning) in representing the regional variability of sea ice concentration in summer. SIPN South is a collaborative community project that is hosted on a shared public repository. The forecast and verification data used in SIPN South are publicly available in near-real time for further use by the polar research community, and eventually, policymakers.
g-C3N4/Fe3O4 composites synthesized via solid-state reaction and photocatalytic activity evaluation of methyl blue degradation under visible light irradiation
Authors: Ali Asghar , Amin Muhammad , Tahir Muhammad , Ali S. S. , Hussain Asif , Ahmad Imtiaz , Mahmood Asif , Farooq M. Umer , Farid Muhammad Asim
Published: May 2023

This study applied the solid-state reaction technique to synthesize g-C3N4, Fe3O4, and g-C3N4/Fe3O4composites in various ratios. XRD confirmed the formation of g-C3N4, Fe3O4, and a g-C3N4/Fe3O4heterostructure. SEM confirmed the rod-shaped structure of Fe2O3and the layered-like fabrication of g-C3N4. The Egof g-C3N4/Fe3O4was approximately 1.9 eV, making it a beneficial composite material for visible response in photocatalysis activity, which was confirmed by UV-Vis spectroscopy. Dielectrics were used to study ferrite nanoparticles and provide information on the mechanism of conductivity in the parts of the dielectric that responded to an applied alternating electric field. In polycrystalline ceramics, the resistive and capacitive grains, contributions, electrode specimen interfaces, and grain boundaries may all be distinguished using impedance analysis, a crucial tool for the study of complicated electrical performance. The g-C3N4/Fe3O4composite material showed high photocatalytic activity against methylene blue (MB) dye.
A novel homozygous variant of TMEM260 induced cardiac malformation and neurodevelopmental abnormality: case report and literature review
Authors: Peng Mou , Jing Siyuan , Duan Sichen , Lu Guoyan , Zhou Kaiyu , Hua Yimin , Wang Tao , Yue Peng , Li Yifei
Published: May 2023

Background

Congenital heart disease (CHD) represents the most widespread congenital birth defect among neonates worldwide, leading to substantial expenses and contributing significantly to premature death caused by birth defects. Despite the significance of CHD, research on its etiology remains limited and has failed to provide substantial evidence for the molecular basis of the disease. With the advancement of next-generation sequencing (NGS), genetic screening has become increasingly accessible, offering a greater capability for identifying potential genetic variants associated with CHD.

Case presentation

Exome sequencing and variant analysis of TMEM260 were performed to obtain genetic data, and clinical characteristics were determined. A complex and severe form of CHD, comprising a persistent truncus arteriosus type I, ventricular septal defect, right aortic arch, as well as critical neurodevelopmental delay and neurological dysfunction, was observed in a patient. This proband presented global muscle hypotonia and a significant delay in gross and fine motor development. Cranial computed tomography scanning showed the presence of bilateral apical, occipital, and temporal subdural effusions; slightly wider bilateral lateral ventricles and annular cisterns; and bilateral cerebral hemispheric parenchyma atrophy. Upon genetic analysis of the patient, a novel homozygous mutation was identified in the TMEM260 gene. The mutation, c.1336_1339DEL, was found to be homozygous and resulted in a frameshift mutation, causing a p.L447Vfs*9 amino acid change. This mutation led to the deletion of a TCTC sequence from positions 1336 to 1339 in the TMEM260 gene, changing leucine to valine at amino acid 447 and introducing a stop codon after the ninth amino acid. This structural deletion in the TMEM260 protein resulted in the loss of gene function.

Conclusion

This case report presents a newly discovered variant site in the TMEM260 gene and reinforces the relationship between TMEM260 molecular function and differentiation of mesoderm and ectoderm. Furthermore, our findings broaden the spectrum of variants in the TMEM260 gene and contribute to advancing the genetic understanding of CHD.
The impact of guided self-study on knowledge and skills in Swiss pre-clinical physiotherapy students – a feasibility study protocol
Authors: Schenk Elisabeth , Taeymans Jan , Rogan Slavko
Published: May 2023

Physiotherapy education in Europe must incorporate self-study units in the curriculum due to the bologna reform. Studies investigating the impact of guided self-study (G-SS) on knowledge and skills in pre-clinical Swiss physiotherapy students are scarce. This study protocol describes a prospective randomized feasibility education study that will primarily examine the feasibility of establishing G-SS using retired physiotherapists as tutors in undergraduate physiotherapy students at the Bern University of Applied Sciences, School of Health Professions. Secondary objective will be to evaluate the effectiveness of six G-SS cycles with retired physiotherapists as tutors on knowledge and skills of pre-clinical undergraduate physiotherapy students. Students of the physiotherapy degree course will be allocated into a G-SS group or control group (CG). G-SS consists of an 8-day cycle. Feasibility outcome are the fidelity of implementation that include exposure dosage and students’ responsiveness, and the degree of acceptability. Success criteria of feasibility are (1) exposure dosage calculated as the number of 90-min presentations that are conducted, and the content of cases and competences and (2) students’ responsiveness, with at least a 83% willingness to participate. Acceptability of intervention from the undergraduate students’ perspective will be evaluated by a questionnaire with open, semi-structured questions (post intervention). This study will provide new information regarding the feasibility of embedding G-SS in the curriculum and about the students’ responsiveness and their acceptability for G-SS.

Study protocol version 1

Trial registration:German Register of Clinical Studies (DKRS: DRKS00015518).
Effects of insecticidal proteins of Enterobacter cloacae NK on cellular immunity of Galleria mellonella larvae
Authors: Liao Chunli , Huang Ran , Yang Yi , Huang Yapeng , Zhang Kai , Ma Liang , Li Taotao , Wang Lianzhe , Zhang Huamin , Li Bingbing
Published: May 2023

Enterobacter cloacae produces insecticidal proteins capable of causing toxicity in pests, but the insecticidal mechanisms of these proteins for insect control remain unclear. To elucidate the mechanisms, the purified insecticidal protein from E. cloacae NK was administered to Galleria mellonella larvae either by intraperitoneal injection or by feeding. The number of hemocytes, apoptosis in immune cells, and polyphenol oxidase (PO) activity of G. mellonella larvae were detected by hemocytometer, Annexin V-FITC/PI, and UV–vis spectrophotometer, respectively. With the extension of the invasion time of NK insecticidal protein, the number of hemocytes in G. mellonella larvae decreased significantly (p < 0.05), whereas the apoptosis rate of hemocytes increased. The activity of PO showed a trend of rising-peak-sharp decline and the melanization reaction was deepened simultaneously. Moreover, the phagocytosis and coating capabilities of hemocytes decreased, and the intraperitoneal injection method was more effective than the feeding method. Taking together, the insecticidal protein of E. cloacae NK inhibits and destroys the cellular immune response of G. mellonella larvae, which suggests an important role in killing the host insect.
Maternal HIV infection drives altered placental Mtb-specific antibody transfer
Authors: Nziza Nadege , Jung Wonyeong , Mendu Maanasa , Chen Tina , McNamara Ryan P. , Fortune Sarah M. , Franken Kees L. M. C. , Ottenhoff Tom H. M. , Bryson Bryan , Ngonzi Joseph , Bebell Lisa M. , Alter Galit
Published: May 2023

Introduction

Placental transfer of maternal antibodies is essential for neonatal immunity over the first months of life. In the setting of maternal HIV infection, HIV-exposed uninfected (HEU) infants are at higher risk of developing severe infections, including active tuberculosis (TB). Given our emerging appreciation for the potential role of antibodies in the control of Mycobacterium tuberculosis (Mtb), the bacteria that causes TB, here we aimed to determine whether maternal HIV status altered the quality of Mtb-specific placental antibody transfer.

Methods

Antigen-specific antibody systems serology was performed to comprehensively characterize the Mtb-specific humoral immune response in maternal and umbilical cord blood from HIV infected and uninfected pregnant people in Uganda.

Results

Significant differences were noted in overall antibody profiles in HIV positive and negative maternal plasma, resulting in heterogeneous transfer of Mtb-specific antibodies. Altered antibody transfer in HIV infected dyads was associated with impaired binding to IgG Fc-receptors, which was directly linked to HIV viral loads and CD4 counts.

Conclusions

These results highlight the importance of maternal HIV status on antibody transfer, providing clues related to alterations in transferred maternal immunity that may render HEU infants more vulnerable to TB than their HIV-unexposed peers.
Comparison of salivary gland and midgut microbiome in the soft ticks Ornithodoros erraticus and Ornithodoros moubata
Authors: Piloto-Sardiñas Elianne , Cano-Argüelles Ana Laura , Maitre Apolline , Wu-Chuang Alejandra , Mateos-Hernández Lourdes , Corduneanu Alexandra , Obregón Dasiel , Oleaga Ana , Pérez-Sánchez Ricardo , Cabezas-Cruz Alejandro
Published: May 2023

Introduction

Ornithodoros erraticus and Ornithodoros moubata are the main vectors of African swine fever virus (ASFV) and the human relapsing fever spirochetes Borrelia hispanica and Borrelia crocidurae in the Mediterranean region and Borrelia duttoni in continental Africa. Manipulation of the tick microbiome has been shown to reduce vector fitness and competence in tick vectors, suggesting that the identification of key microbial players associated with tick tissues can inform interventions such as anti-microbiota vaccines to block pathogen development in the midgut and/or salivary glands.

Methods

In this study, we analyzed and compared the microbiome of the salivary glands and midgut of O. erraticus and O. moubata. For the taxonomic and functional characterization of the tissue-specific microbiome, we used 16S rRNA amplicon sequencing and prediction of metabolic profiles using PICRUSt2. Co-occurrence networks were built to characterize the community assembly and identify keystone taxa in each tick species.

Results

Our results revealed differences in the composition, diversity, and assembly of the bacterial microbiome of salivary glands and midgut within each tick species, but differences were more noticeable in O. moubata. Differences were also found in the microbiome of each tissue, salivary gland and midgut, between species. However, the ‘Core Association Networks (CAN)’ analysis revealed conserved patterns of interacting taxa in tissues within and between tick species. Different keystone taxa were identified in O. erraticus and O. moubata tissues, but Muribaculaceae and Alistipes were found as keystone taxa in the salivary glands of both tick species which justifies their use as anti-microbiota vaccine candidates to alter the microbiome and reduce tick fitness and/or block pathogen transmission. The high similarity of predicted metabolic pathways profiles between tissues of the two tick species suggests that taxonomic variability of the microbiome is not associated with significant changes in microbial functional profiles.

Conclusion

We conclude that the taxonomic structure of the microbiome in O. erraticus and O. moubata is tissue-specific, suggesting niche partitioning of bacterial communities associated to these soft ticks. However, shared keystone taxa and conserved patterns of interacting taxa between tissues and tick species suggest the presence of key microbial players that could be used as anti-microbiota vaccine candidates to affect tick physiology and/or pathogen colonization.
Size-fractionated N2 fixation off the Changjiang Estuary during summer
Authors: Jiang Zhibing , Zhu Yuanli , Sun Zhenhao , Zhai Hongchang , Zhou Feng , Yan Xiaojun , Chen Quanzhen , Chen Jianfang , Zeng Jiangning
Published: May 2023

Recent evidence has shown active N2 fixation in coastal eutrophic waters, yet the rate and controlling factors remain poorly understood, particularly in large estuaries. The Changjiang Estuary (CE) and adjacent shelf are characterized by fresh, nitrogen-replete Changjiang Diluted Water (CDW) and saline, nitrogen-depletion intruded Kuroshio water (Taiwan Warm Current and nearshore Kuroshio Branch Current), where N2 fixation may be contributed by different groups (i.e., Trichodesmium and heterotrophic diazotrophs). Here, for the first time, we provide direct measurement of size-fractionated N2 fixation rates (NFRs) off the CE during summer 2014 using the 15N2 bubble tracer method. The results demonstrated considerable spatial variations (southern > northern; offshore > inshore) in surface and depth-integrated NFRs, averaging 0.83 nmol N L−1 d−1 and 24.3 μmol N m−2 d−1, respectively. The highest bulk NFR (99.9 μmol N m−2 d−1; mostly contributed by >10 μm fraction) occurred in the southeastern East China Sea, where suffered from strong intrusion of the Kuroshio water characterized by low N/P ratio (<10) and abundant Trichodesmium (up to 10.23 × 106 trichomes m−2). However, low NFR (mostly contributed by <10 μm fraction) was detected in the CE controlled by the CDW, where NOx concentration (up to 80 μmol L−1) and N/P ratio (>100) were high and Trichodesmium abundance was low. The >10 μm fraction accounted for 60% of depth-integrated bulk NFR over the CE and adjacent shelf. We speculated that the present NFR of >10 μm fraction was mostly supported by Trichodesmium. Spearman rank correlation indicated that the NFR was significantly positively correlated with Trichodesmium abundance, salinity, temperature and Secchi depth, but was negatively with turbidity, N/P ratio, NOx, and chlorophyll a concentration. Our study suggests that distribution and size structure of N2 fixation off the CE are largely regulated by water mass (intruded Kuroshio water and CDW) movement and associated diazotrophs (particularly Trichodesmium) and nutrient conditions.
A step into the rare biosphere: genomic features of the new genus Terrihalobacillus and the new species Aquibacillus salsiterrae from hypersaline soils
Authors: Galisteo Cristina , de la Haba Rafael R. , Sánchez-Porro Cristina , Ventosa Antonio
Published: May 2023

Hypersaline soils are a source of prokaryotic diversity that has been overlooked until very recently. The phylum Bacillota, which includes the genus Aquibacillus, is one of the 26 phyla that inhabit the heavy metal contaminated soils of the Odiel Saltmarshers Natural Area (Southwest Spain), according to previous research. In this study, we isolated a total of 32 strains closely related to the genus Aquibacillus by the traditional dilution-plating technique. Phylogenetic studies clustered them into two groups, and comparative genomic analyses revealed that one of them represents a new species within the genus Aquibacillus, whereas the other cluster constitutes a novel genus of the family Bacillaceae. We propose the designations Aquibacillus salsiterrae sp. nov. and Terrihalobacillus insolitus gen. nov., sp. nov., respectively, for these two new taxa. Genome mining analysis revealed dissimilitude in the metabolic traits of the isolates and their closest related genera, remarkably the distinctive presence of the well-conserved pathway for the biosynthesis of molybdenum cofactor in the species of the genera Aquibacillus and Terrihalobacillus, along with genes that encode molybdoenzymes and molybdate transporters, scarcely found in metagenomic dataset from this area. In-silico studies of the osmoregulatory strategy revealed a salt-out mechanism in the new species, which harbor the genes for biosynthesis and transport of the compatible solutes ectoine and glycine betaine. Comparative genomics showed genes related to heavy metal resistance, which seem required due to the contamination in the sampling area. The low values in the genome recruitment analysis indicate that the new species of the two genera, Terrihalobacillus and Aquibacillus, belong to the rare biosphere of representative hypersaline environments.
A synthetic lethal screen for Snail-induced enzalutamide resistance identifies JAK/STAT signaling as a therapeutic vulnerability in prostate cancer
Authors: Ware Kathryn E. , Thomas Beatrice C. , Olawuni Pelumi D. , Sheth Maya U. , Hawkey Nathan , Yeshwanth M. , Miller Brian C. , Vietor Katherine J. , Jolly Mohit Kumar , Kim So Young , Armstrong Andrew J. , Somarelli Jason A.
Published: May 2023

Despite substantial improvements in the treatment landscape of prostate cancer, the evolution of hormone therapy-resistant and metastatic prostate cancer remains a major cause of cancer-related death globally. The mainstay of treatment for advanced prostate cancer is targeting of androgen receptor signaling, including androgen deprivation therapy plus second-generation androgen receptor blockade (e.g., enzalutamide, apalutamide, darolutamide), and/or androgen synthesis inhibition (abiraterone). While these agents have significantly prolonged the lives of patients with advanced prostate cancer, is nearly universal. This therapy resistance is mediated by diverse mechanisms, including both androgen receptor-dependent mechanisms, such as androgen receptor mutations, amplifications, alternative splicing, and amplification, as well as non-androgen receptor-mediated mechanisms, such as lineage plasticity toward neuroendocrine-like or epithelial-mesenchymal transition (EMT)-like lineages. Our prior work identified the EMT transcriptional regulator Snail as critical to hormonal therapy resistance and is commonly detected in human metastatic prostate cancer. In the current study, we sought to interrogate the actionable landscape of EMT-mediated hormone therapy resistant prostate cancer to identify synthetic lethality and collateral sensitivity approaches to treating this aggressive, therapy-resistant disease state. Using a combination of high-throughput drug screens and multi-parameter phenotyping by confluence imaging, ATP production, and phenotypic plasticity reporters of EMT, we identified candidate synthetic lethalities to Snail-mediated EMT in prostate cancer. These analyses identified multiple actionable targets, such as XPO1, PI3K/mTOR, aurora kinases, c-MET, polo-like kinases, and JAK/STAT as synthetic lethalities in Snail+ prostate cancer. We validated these targets in a subsequent validation screen in an LNCaP-derived model of resistance to sequential androgen deprivation and enzalutamide. This follow-up screen provided validation of inhibitors of JAK/STAT and PI3K/mTOR as therapeutic vulnerabilities for both Snail+ and enzalutamide-resistant prostate cancer.
Reversible binding of divalent cations to Ductin protein assemblies—A putative new regulatory mechanism of membrane traffic processes
Authors: Sebők-Nagy Krisztina , Blastyák András , Juhász Gábor , Páli Tibor
Published: May 2023

Ductins are a family of homologous and structurally similar membrane proteins with 2 or 4 trans-membrane alpha-helices. The active forms of the Ductins are membranous ring- or star-shaped oligomeric assemblies and they provide various pore, channel, gap-junction functions, assist in membrane fusion processes and also serve as the rotor c-ring domain of V-and F-ATPases. All functions of the Ductins have been reported to be sensitive to the presence of certain divalent metal cations (Me2+), most frequently Cu2+ or Ca2+ ions, for most of the better known members of the family, and the mechanism of this effect is not yet known. Given that we have earlier found a prominent Me2+ binding site in a well-characterised Ductin protein, we hypothesise that certain divalent cations can structurally modulate the various functions of Ductin assemblies via affecting their stability by reversible non-covalent binding to them. A fine control of the stability of the assembly ranging from separated monomers through a loosely/weakly to tightly/strongly assembled ring might render precise regulation of Ductin functions possible. The putative role of direct binding of Me2+ to the c-ring subunit of active ATP hydrolase in autophagy and the mechanism of Ca2+-dependent formation of the mitochondrial permeability transition pore are also discussed.
Visuomotor interactions in the mouse forebrain mediated by extrastriate cortico-cortical pathways
Authors: Hovde Karoline , Rautio Ida V. , Hegstad Andrea M. , Witter Menno P. , Whitlock Jonathan R.
Published: May 2023

Introduction

The mammalian visual system can be broadly divided into two functional processing pathways: a dorsal stream supporting visually and spatially guided actions, and a ventral stream enabling object recognition. In rodents, the majority of visual signaling in the dorsal stream is transmitted to frontal motor cortices via extrastriate visual areas surrounding V1, but exactly where and to what extent V1 feeds into motor-projecting visual regions is not well known.

Methods

We employed a dual labeling strategy in male and female mice in which efferent projections from V1 were labeled anterogradely, and motor-projecting neurons in higher visual areas were labeled with retrogradely traveling adeno-associated virus (rAAV-retro) injected in M2. We characterized the labeling in both flattened and coronal sections of dorsal cortex and made high-resolution 3D reconstructions to count putative synaptic contacts in different extrastriate areas.

Results

The most pronounced colocalization V1 output and M2 input occurred in extrastriate areas AM, PM, RL and AL. Neurons in both superficial and deep layers in each project to M2, but high resolution volumetric reconstructions indicated that the majority of putative synaptic contacts from V1 onto M2-projecting neurons occurred in layer 2/3.

Discussion

These findings support the existence of a dorsal processing stream in the mouse visual system, where visual signals reach motor cortex largely via feedforward projections in anteriorly and medially located extrastriate areas.
Epileptiform activity influences theta-burst induced LTP in the adult hippocampus: a role for synaptic lipid raft disruption in early metaplasticity?
Authors: Carvalho-Rosa José D. , Rodrigues Nádia C. , Silva-Cruz Armando , Vaz Sandra H. , Cunha-Reis Diana
Published: May 2023

Non-epileptic seizures are identified as a common epileptogenic trigger. Early metaplasticity following seizures may contribute to epileptogenesis by abnormally altering synaptic strength and homeostatic plasticity. We now studied how in vitro epileptiform activity (EA) triggers early changes in CA1 long-term potentiation (LTP) induced by theta-burst stimulation (TBS) in rat hippocampal slices and the involvement of lipid rafts in these early metaplasticity events. Two forms of EA were induced: (1) interictal-like EA evoked by Mg2+ withdrawal and K+ elevation to 6 mM in the superfusion medium or (2) ictal-like EA induced by bicuculline (10 μM). Both EA patterns induced and LTP-like effect on CA1 synaptic transmission prior to LTP induction. LTP induced 30 min post EA was impaired, an effect more pronounced after ictal-like EA. LTP recovered to control levels 60 min post interictal-like EA but was still impaired 60 min after ictal-like EA. The synaptic molecular events underlying this altered LTP were investigated 30 min post EA in synaptosomes isolated from these slices. EA enhanced AMPA GluA1 Ser831 phosphorylation but decreased Ser845 phosphorylation and the GluA1/GluA2 ratio. Flotillin-1 and caveolin-1 were markedly decreased concomitantly with a marked increase in gephyrin levels and a less prominent increase in PSD-95. Altogether, EA differentially influences hippocampal CA1 LTP thorough regulation of GluA1/GluA2 levels and AMPA GluA1 phosphorylation suggesting that altered LTP post-seizures is a relevant target for antiepileptogenic therapies. In addition, this metaplasticity is also associated with marked alterations in classic and synaptic lipid raft markers, suggesting these may also constitute promising targets in epileptogenesis prevention.
The pathogenesis of DLD-mediated cuproptosis induced spinal cord injury and its regulation on immune microenvironment
Authors: Li Chaochen , Wu Chunshuai , Ji Chunyan , Xu Guanhua , Chen Jiajia , Zhang Jinlong , Hong Hongxiang , Liu Yang , Cui Zhiming
Published: May 2023

Introduction

Spinal cord injury (SCI) is a severe central nervous system injury that leads to significant sensory and motor impairment. Copper, an essential trace element in the human body, plays a vital role in various biological functions and is strictly regulated by copper chaperones and transporters. Cuproptosis, a novel type of metal ion-induced cell death, is distinct from iron deprivation. Copper deprivation is closely associated with mitochondrial metabolism and mediated by protein fatty acid acylation.

Methods

In this study, we investigated the effects of cuproptosis-related genes (CRGs) on disease progression and the immune microenvironment in acute spinal cord injury (ASCI) patients. We obtained the gene expression profiles of peripheral blood leukocytes from ASCI patients using the Gene Expression Omnibus (GEO) database. We performed differential gene analysis, constructed protein-protein interaction networks, conducted weighted gene co-expression network analysis (WGCNA), and built a risk model.

Results

Our analysis revealed that dihydrolipoamide dehydrogenase (DLD), a regulator of copper toxicity, was significantly associated with ASCI, and DLD expression was significantly upregulated after ASCI. Furthermore, gene ontology (GO) enrichment analysis and gene set variation analysis (GSVA) showed abnormal activation of metabolism-related processes. Immune infiltration analysis indicated a significant decrease in T cell numbers in ASCI patients, while M2 macrophage numbers were significantly increased and positively correlated with DLD expression.

Discussion

In summary, our study demonstrated that DLD affects the ASCI immune microenvironment by promoting copper toxicity, leading to increased peripheral M2 macrophage polarization and systemic immunosuppression. Thus, DLD has potential as a promising biomarker for ASCI, providing a foundation for future clinical interventions.
Seizure after chronic subdural hematoma evacuation: associated factors and effect on clinical outcome
Authors: Wu Liang , Guo Xufei , Ou Yunwei , Yu Xiaofan , Zhu Bingcheng , Li Yunfei , Liu Weiming
Published: May 2023

Objective

Chronic subdural hematoma (CSDH) is a common disease in neurosurgery, which usually occurs in the elderly. Seizure is one of the postoperative complications in CSDH patients and can affect patient outcomes. There is currently no consensus on whether antiepileptic drugs should be prescribed prophylactically. The aim of this study was to evaluate independent risk factors for postoperative seizures and unfavorable outcomes in CSDH patients.

Methods

We reviewed 1,244 CSDH patients who had undergone burr-hole craniotomy in this study. Patient clinical data, CT scan results, recurrence and outcome data were collected. We divided the patients into two groups based on whether they had a postoperative seizure. Percentages and χ2 tests were applied for categorical variables. Standard deviations and two-sided unpaired t-tests were applied for continuous variables. Stepwise logistic regression analyses were performed to identify the independent factors of postoperative seizures and unfavorable outcomes.

Results

The incidence of seizures after CSDH surgery was 4.2% in this study. There was no significant difference in recurrence rate between seizure and non-seizure patients (p = 0.948), and the outcome of seizure patients was significantly poor (p < 0.001). There are more postoperative complications in seizure patients (p < 0.001). Logistic regression analysis showed that the independent risk factors for postoperative seizures included drinking history (p = 0.031), cardiac disease (p = 0.037), brain infarction (p = 0.001) and trabecular hematoma (p < 0.001). The use of urokinase is a protective factor for postoperative seizures (p = 0.028). Hypertension is an independent risk factor for unfavorable outcome in seizure patients (p = 0.038).

Conclusion

Seizures after CSDH surgery were associated with postoperative complications, higher mortality and poorer clinical outcomes at follow-up. We believe that alcohol consumption, cardiac disease, brain infarction and trabecular hematoma are independent risk factors for seizures. The use of urokinase is a protective factor against seizures. Patients with postoperative seizures need more stringent management of their blood pressure. A prospective randomized study is necessary to determine which subgroups of CSDH patients would benefit from antiepileptic drugs prophylaxis.
Influence of hypobaric hypoxic conditions on ocular structure and biological function at high attitudes: a narrative review
Authors: Wang Yuchen , Yu Xinli , Liu Ziyuan , Lv Zhongsheng , Xia Huaqin , Wang Yiren , Li Jiaxi , Li Xuemin
Published: May 2023

Background

With the development of science and technology, high-altitude environments, involving aviation, aerospace, and mountainous regions, have become the main areas for human exploration, while such complex environments can lead to rapid decreases in air and oxygen pressure. Although modern aircrafts have pressurized cabins and support equipment that allow passengers and crew to breathe normally, flight crew still face repeated exposure to hypobaric and hypoxic conditions. The eye is a sensory organ of the visual system that responds to light and oxygen plays a key role in the maintenance of normal visual function. Acute hypoxia changes ocular structure and function, such as the blood flow rate, and can cause retinal ischemia.

Methods

We reviewed researches, and summarized them briefly in a review.

Results

The acute hypobaric hypoxia affects corneal, anterior chamber angle and depth, pupils, crystal lens, vitreous body, and retina in structure; moreover, the acute hypoxia does obvious effect on visual function; for example, vision, intraocular pressure, oculometric features and dynamic visual performance, visual field, contrast sensitivity, and color perception.

Conclusion

We summarized the changes in the physiological structure and function of the eye in hypoxic conditions and to provide a biological basis for the response of the human eye at high-altitude.
Phase I trial outcome of amnion cell therapy in patients with ischemic stroke (I-ACT)
Authors: Phan Thanh G. , Lim Rebecca , Chan Siow T. , McDonald Hannah , Gan Poh-Yi , Zhang Shenpeng R. , Barreto Arce Liz J. , Vuong Jason , Thirugnanachandran Tharani , Clissold Benjamin , Ly John , Singhal Shaloo , Hervet Marie Veronic , Kim Hyun Ah , Drummond Grant R. , Wallace Euan M. , Ma Henry , Sobey Christopher G.
Published: May 2023

Background

We proposed a Phase I dose escalation trial to assess the safety of allogeneic human amniotic epithelial cells (hAECs) in stroke patients with a view to informing the design for a Phase II trial.

Methods

The design is based on 3 + 3 dose escalation design with additional components for measuring MR signal of efficacy as well as the effect of hAECs (2–8 × 106/kg, i.v.) on preventing immunosuppression after stroke.

Results

Eight patients (six males) were recruited within 24 h of ischemic stroke onset and were infused with hAECs. We were able to increase the dose of hAECs to 8 × 106 cells/kg (2 × 106/kg, n = 3; 4 × 106/kg, n = 3; 8 × 106/kg, n = 2). The mean age is 68.0 ± 10.9 (mean ± SD). The frequencies of hypertension and hyperlipidemia were 87.5%, diabetes was 37.5%, atrial fibrillation was 50%, ischemic heart disease was 37.5% and ever-smoker was 25%. Overall, baseline NIHSS was 7.5 ± 3.1, 7.8 ± 7.2 at 24 h, and 4.9 ± 5.4 at 1 week (n = 8). The modified Rankin scale at 90 days was 2.1 ± 1.2. Supplemental oxygen was given in five patients during hAEC infusion. Using pre-defined criteria, two serious adverse events occurred. One patient developed recurrent stroke and another developed pulmonary embolism whilst in rehabilitation. For the last four patients, infusion of hAECs was split across separate infusions on subsequent days to reduce the risk for fluid overload.

Conclusion

Our Phase I trial demonstrates that a maximal dose of 2 × 106/kg hAECs given intravenously each day over 2 days (a total of 4 × 106/kg) is safe and optimal for use in a Phase II trial.

Clinical trial registration

ClinicalTrials.gov, identifier ACTRN12618000076279P.
A comprehensive analysis of the hub genes for oxidative stress in ischemic stroke
Authors: Zhou Qing , Dong Yang , Wang Kun , Wang Ziyan , Ma Bingquan , Yang Bo
Published: May 2023

Ischemic stroke (IS), resulting from the occlusion of the cerebral artery and subsequent interruption of blood flow, represents a major and critical threat to public health. Oxidative stress (OS) has been confirmed to play a role in the IS pathological process and neural death. Understanding the essential role of OS-related genes in ischemic stroke is critical to understanding the current perception of the pathophysiological process in IS. Herein, by integrating three IS datasets (GSE16561, GSE22255, and GSE58294), we divided IS samples into the low- and high-OS groups by calculating the OS score identified by the oxidative stress gene set. The functional enrichment analysis of differentially expressed genes (DEGs) between the low- and high-OS groups indicated that DEGs were associated with hypoxia, the inflammatory response, and oxidative phosphorylation pathways. Furthermore, nine hub genes (namely TLR1, CXCL1, MMP9, TLR4, IL1R2, EGR1, FOS, CXCL10, and DUSP1) were identified through the Girvan–Newman algorithm and cytoHubba algorithms. Nine hub genes were highly expressed in IS samples and positively related to neutrophils and macrophages. Drug-sensitive analysis targeting hub genes defined allopurinol and nickel sulfate as potential candidates for impairing the neural death caused by oxidative stress in IS. Finally, we employed five machine learning methods to check the efficacy of the predictive model identified by nine hub genes. The results showed that our model had superior power for predicting the OS activity of IS patients. TLR4 was found to have excellent diagnostic value and a wide-spectrum interaction with other hub genes. Our research emphasized the impact of oxidative stress on ischemic stroke, which supports the idea that antioxidants hold great promise in ischemic stroke therapy.
Valorization and characterization of corn by-product polyphenols through green extraction technologies
Authors: Faiza Neelam , Imran Ali , Arshad Muhammad Umair , Arshad Muhammad Sajid , Shah Mohd Asif
Published: May 2023

The amount of food waste throughout the world has become quite alarming and is contributing to lower food resources. The study aimed to extract and characterize the polyphenols from corn silks at immature and mature stages through conventional and green extraction techniques. Purposely, corn silks, which are some of the by-products of corn, (Zea mays L.) were collected and subjected to proximate analysis including moisture, ash, protein, fiber, and minerals. Secondly, the antioxidants from both immature and mature corn silks were extracted by techniques involving supercritical and ultrasound extraction alongside conventional extraction. The results displayed a promising quantity of protein and fiber along with calcium, magnesium, sodium potassium, and copper. Among the extraction techniques, supercritical extraction at 3,000 Pa acquired the highest total phenolic contents (TPC), total flavonoids (TF), 2, 2-diphenylpicrylhydrazyl (DPPH), ferric-reducing antioxidant power (FRAP) activities as 128.08 ± 3.74 mg GAE/100 g, 86.73 ± 2.75 mg CE/100 g, 106.73 ± 5.10%, and 73.52 ± 2.33 μM Fe + 2/g, respectively, followed by the ultrasound and conventional extraction techniques. Between the immature and mature corn silks, the highest antioxidant activity was displayed by immature corn silks.
A holistic approach toward development of plant-based meat alternatives through incorporation of novel microalgae-based ingredients
Authors: Bakhsh Allah , Park Juhee , Baritugo Kei Anne , Kim Bosung , Sil Moon Sung , Rahman Attaur , Park Sungkwon
Published: May 2023

This study explored the changes in the physiochemical, textural, sensory, and functional characteristics of plant-based meat (PBM) after incorporating novel plant-based ingredients including spirulina (SPI), duck Weed (DW), and yellow Chlorella (YC). In the chromaticity evaluation, the YC group (YCI YC2, and YC3%) displayed significant differences (p < 0.05) in lightness (L*) indices as compared to the control. Whereas, based on concertation gradient of SPI microalgae (SP0.5, SP0.7, and SP1%) incorporated into PBM patties demonstrated that SPI 1 had the lowest values (p < 0.05) in redness (a*) and yellowness (b*) followed by SPI 0.7 and SPI 0.5% concentration, respectively. The concentration gradient of the YC group indicated that YC3 was intended to be the highest crude fat value followed by YC2 and YCI. The ash content in PBM patties increased considerably (p < 0.05) as the concentration level of microalgae advanced in all treated groups. Based on the concentration level of YC incorporated microalgae into PBM patties indicated that YC 3 had the highest (p < 0.05) gumminess and chewiness while YC 1 had the lowest reported values in terms of gumminess and chewiness. Moreover, springiness and cohesiveness showed considerable differences between SPI and YC groups. In the sensory evaluation, SPI 1 showed the lowest value only in color and appearance (p < 0.05), conversely, the other sensory parameters were non-significant among all treatment groups (p > 0.05). The micronutrient in PBM presented an irregular pattern after incorporating various ingredients. However, levels were higher (p < 0.05) in the DW group (DW 0.5 DW 0.7, and DW% 1) than those in the other groups. Moreover, the SPI and YC groups showed detectable levels of diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity with, SP 1 showing the highest level of antioxidant activity. Acknowledging the limited research on PBM production, extraction technologies, and selecting various novel suitable ingredients in meat substitutes. Hence, to fill this knowledge gap an attempt has been made to incorporate various concentrations of microalgae including SPI, YC, and DW to enhance the quality and functionality of meat alternatives. To the best of our knowledge, this is the first report that describes the physiochemical, textural, sensory, and nutritional attributes of PBM incorporated with novel microalgae. Collectively these results indicate that the incorporation of SPI, DW, and YC may improve the quality of PBM without showing deleterious outcomes on the quality and functionality of the ultimate PBM products.
Maternal monosaccharide diets evoke cognitive, locomotor, and emotional disturbances in adolescent and young adult offspring rats
Authors: Witek Kacper , Wydra Karolina , Suder Agata , Filip Małgorzata
Published: May 2023

Anxiety and depression are the most common mental disorders affecting people worldwide. Recent studies have highlighted that a maternal high-sugar diet (HSD) could be a risk factor for neurobehavioural dysregulations, including mood disorders. Increased consumption of added sugar in food such as refined fructose/glucose can increase the risk of metabolic disorders and impact susceptibility to mental disorders. Furthermore, a few papers have reported disabilities in learning and memory among offspring after maternal HSD, thus suggesting a relationship between maternal nutrition and offspring neurogenesis. In this study, we evaluated the impact of maternal monosaccharide consumption based on a glucose (GLU) or fructose (FRU) diet during pregnancy and lactation in adolescent and young adult offspring rats of both sexes on cognitive, locomotor, and emotional disturbances. Locomotor activity, short-term memory, anxiety-like and depressive-like behavior were evaluated in the offspring. We report for the first time that the maternal GLU or FRU diet is sufficient to evoke anxiety-like behavior among adolescent and young adult offspring. Moreover, we found that maternal monosaccharide diets lead to hyperactivity and depressive-like behavior in male adolescent rats. We also noticed that a maternal FRU diet significantly enhanced novelty-seeking behavior only in young adult male rats. Our novel findings indicated that the maternal monosaccharide diet, especially a diet enriched in FRU, resulted in strong behavioral alterations in offspring rats at early life stages. This study also revealed that male rats were more susceptible to hyperactivity and anxiety- and depressive-like phenotypes than female rats. These results suggest that maternal monosaccharide consumption during pregnancy and lactation is an important factor affecting the emotional status of offspring.