bluuebunny/crossref_metadata_2025 huggingface dataset:
Fish gut-associated bacterial communities in a tropical lagoon (Aghien lagoon, Ivory Coast)
Authors: Gallet Alison , Yao Eric Kouamé , Foucault Pierre , Bernard Cécile , Quiblier Catherine , Humbert Jean-François , Coulibaly Julien Kalpy , Troussellier Marc , Marie Benjamin , Duperron Sébastien
Published: September 2022

Aghien lagoon (Ivory Coast) is a eutrophic freshwater lagoon that harbors high biomasses of phytoplankton. Despite Increasing interest in fish gut microbiomes diversity and functions, little data is currently available regarding wild species from tropical west African lakes. Here, gut-associated bacterial communities are investigated in four fish species that are consumed by locale populations, namely the Cichlidae Hemichromis fasciatus, Tilapia guineensis and Sarotherodon melanotheron, and the Claroteidae Chrysichthys nigrodigitatus. Species-related differences are identified, that can be attributed to host phylogeny and diet. Important variations throughout the year are observed in T. guineensis and C. nigrodigitatus. This result emphasized the importance of time-series sampling and comparison with environmental variables even in tropical regions, that are not often conducted in wild populations. Effects of environmental factors (anthropogenic or not) on the microbiota and potential outcomes for fish health and populations sustainability need to be further explored. Interestingly, fish appear as major reservoirs of bacterial diversity, suggesting that they could contribute to the overall stability and resilience of bacterial communities present in the Aghien lagoon.
Molecular diagnostics in neurotrauma: Are there reliable biomarkers and effective methods for their detection?
Authors: Sabirov Davran , Ogurcov Sergei , Baichurina Irina , Blatt Nataliya , Rizvanov Albert , Mukhamedshina Yana
Published: September 2022

To date, a large number of studies are being carried out in the field of neurotrauma, researchers not only establish the molecular mechanisms of the course of the disorders, but are also involved in the search for effective biomarkers for early prediction of the outcome and therapeutic intervention. Particular attention is paid to traumatic brain injury and spinal cord injury, due to the complex cascade of reactions in primary and secondary injury that affect pathophysiological processes and regenerative potential of the central nervous system. Despite a wide range of methods available methods to study biomarkers that correlate with the severity and degree of recovery in traumatic brain injury and spinal cord injury, development of reliable test systems for clinical use continues. In this review, we evaluate the results of recent studies looking for various molecules acting as biomarkers in the abovementioned neurotrauma. We also summarize the current knowledge of new methods for studying biological molecules, analyzing their sensitivity and limitations, as well as reproducibility of results. In this review, we also highlight the importance of developing reliable and reproducible protocols to identify diagnostic and prognostic biomolecules.
Insights Into the Role of Matrix Metalloproteinases in Cancer and its Various Therapeutic Aspects: A Review
Authors: Mustafa Sabeena , Koran Sheeja , AlOmair Lamya
Published: September 2022

Matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases that regulate the turnover of extracellular matrix (ECM) components. Gross and La Piere discovered MMPs in 1962 during an experiment on tissue samples from a tadpole’s tail. Several subtypes of MMPs have been identified, depending on their substrate specificity and localization. MMPs are involved as essential molecules in multiple and diverse physiological processes, such as reproduction, embryonic development, bone remodeling, tissue repair, and regulation of inflammatory processes. Its activity is controlled at various levels such as at transcription level, pro-peptide activation level and by the activity of a family of tissue inhibitors of metalloproteinase, endogenous inhibitors of MMPs. Cancer metastasis, which is the spread of a tumor to a distant site, is a complex process that is responsible for the majority of cancer-related death It is considered to be an indicator of cancer metastasis. During metastasis, the tumor cells have to invade the blood vessel and degrade the ECM to make a path to new loci in distant places. The degradation of blood vessels and ECM is mediated through the activity of MMPs. Hence, the MMP activity is critical to determining the metastatic potential of a cancer cell. Evasion of apoptosis is one of the hallmarks of cancer that are found to be correlated with the expression of MMPs. As a result, given the importance of MMPs in cancer, we describe the role of these multifunctional enzymes MMPs in various aspects of cancer formation and their rising possibilities as a novel therapeutic target in this review. There is also a brief discussion of various types of therapeutic components and drugs that function against MMPs.
Saliva tau and phospho-tau-181 measured by Lumipulse in patients with Alzheimer’s disease
Authors: Marksteiner Josef , Defrancesco Michaela , Humpel Christian
Published: September 2022

Alzheimer’s disease (AD) is a severe neurodegenerative brain disorder. The determination of beta-amyloid (Aβ)-40, –42, total tau, and phospho-tau-181 (pTau181) in cerebrospinal fluid (CSF) using Lumipulse technology has been established as biomarkers for AD in recent years. As CSF collection is an invasive procedure, one aims to find biomarkers in blood or other human fluids, such as saliva. In the present study, we aim to measure these markers in human saliva. Using Salivettes, we collected saliva samples from healthy controls (n = 27), patients with AD dementia (n = 44), mild cognitive impairment (MCI) (n = 45), depression (n = 31), and 21 blinded samples, all older than 60 years. Lumipulse technology with a G600II was used to detect all four biomarkers. Our data show that the levels of total protein were highly variable and thus biomarker levels were corrected to 1 mg/ml of total protein. Saliva Aβ−40 and –42 were not detectable, because it was not recovered from the Salivettes. However, saliva total tau (577 ± 134 pg/mg, n = 22) and phospho-tau-181 (9.7 ± 1.3 pg/mg, n = 21) could be analyzed by Lumipulse technology. Saliva total tau levels were significantly decreased in patients with AD (≤ 300 pg/mg protein), while pTau181 levels (≥ 18 pg/mg protein) were significantly enhanced in patients with MCI compared to controls. Laboratory diagnosis with a cut-off of ≥ 18 pg/mg protein pTau181 (for MCI) and ≤ 300 pg/mg protein tau (for AD) for blinded samples could diagnose MCI and AD with an accuracy of 71.4%. Despite these initial promising results, the findings must be replicated in larger cohorts, and several technical problems due to saliva processing must be solved and Salivettes should not be used.
Nilotinib in Parkinson's disease: A systematic review and meta-analysis
Authors: Xie Xiaolu , Yuan Ping , Kou Liqiu , Chen Xiu , Li Jun , Li Yaling
Published: September 2022

Background

Nilotinib, which inhibits cellular Abelson tyrosine kinase, may be an effective treatment for patients with Parkinson's disease (PD). The purpose of this study is to evaluate the outcomes of different doses of nilotinib in patients with PD.

Methods

We searched PubMed, Embase, Web of Science, and Cochrane Central Register of Controlled Clinical Trials from inception to 7 March 2022 to identify all randomized controlled trials (RCTs) of nilotinib reporting outcomes of interest in patients with PD. Outcomes included tolerability, efficacy, safety, and CSF biomarker levels. Review manager 5.4 software was used to analyze all data.

Results

Three RCTs with a total of 163 patients were included. No significant difference was found between 150 mg nilotinib or 300 mg nilotinib and placebo in terms of tolerability, adverse events, or HVA levels. 300 mg nilotinib showed significantly higher Movement Disorder Society Unified Parkinson's Disease Rating Scale III (MDS-UPDRS III) scores [SMD = 0.52, 95%CI = (0.12, 0.92), P = 0.01] and 3,4-dihydroxyphenylacetic acid (DOPAC) levels [SMD = 0.52, 95%CI = (0.12, 0.92), P = 0.01], and lower α-synuclein levels [SMD = −2.16, 95%CI = (−3.38, −1.84), P < 0.00001] compared with placebo. And compared with 150 mg nilotinib, 300 mg nilotinib showed significantly lower α-synuclein levels [SMD = −1.16, 95%CI = (−1.70, −0.61), P < 0.0001].

Conclusions

Although our study demonstrated favorable tolerability and safety of different doses of nilotinib, and improvement in part of CSF biomarker levels of 300 mg nilotinib, the poor efficacy on motor outcomes indicated that nilotinib had no advantages in the clinic.
The influence of continuous prenatal exposure to valproic acid on physical, nociceptive, emotional and psychomotor responses during adolescence in mice: Dose-related effects within sexes
Authors: Podgorac Jelena , Sekulić Slobodan , Petković Branka , Stojadinović Gordana , Martać Ljiljana , Pešić Vesna
Published: September 2022

Clinical findings show that the use of valproic acid (VPA) during pregnancy increases the risk of birth defects and autism spectrum disorder in offspring. Although there is a consensus that monitoring of potential long-term outcomes of VPA exposure is needed, especially in undiagnosed individuals, preclinical studies addressing this issue are rare. The present study examined the effects of continuous intrauterine exposure to a wide dose range of VPA (50, 100, 200, and 400 mg/kg/day) on the physical and behavioral response in peripubertal mice as a rodent model of adolescence. Body weight and the hot plate test [on postnatal days (PND) 25 and 32], the elevated plus-maze test (on PND35), and the open field test (on PND40) served to examine physical growth, the supraspinal reflex response to a painful thermal stimulus and conditional learning, anxiety-like/risk-assessment behavior, as well as novelty-induced psychomotor activity, respectively. VPA exposure produced the following responses: (i) a negative effect on body weight, except for the dose of 100 mg/kg/day in both sexes; (ii) an increase in the percentage of animals that responded to the thermal stimulus above the defined cut-off time interval and the response latency in both sexes; (iii) dose-specific changes within sexes in behavior provoked by a novel anxiogenic environment, i.e., in females less anxiety-like/risk-assessment behavior in response to the lowest exposure dose, and in males more pronounced anxiety-like/risk-assessment behavior after exposure to the highest dose and 100 mg/kg/day; (iv) dose-specific changes within sexes in novelty-induced psychomotor activity, i.e., in females a decrease in stereotypy-like activity along with an increase in rearing, and in males a decrease in stereotypy-like activity only. These findings show that continuous intrauterine exposure to VPA produces maladaptive functioning in different behavioral domains in adolescence and that the consequences are delicate to assess as they are dose-related within sexes.
Cholinergic regulation of object recognition memory
Authors: Okada Kana , Hashimoto Kouichi , Kobayashi Kazuto
Published: September 2022

Object recognition memory refers to a basic memory mechanism to identify and recall various features of objects. This memory has been investigated by numerous studies in human, primates and rodents to elucidate the neuropsychological underpinnings in mammalian memory, as well as provide the diagnosis of dementia in some neurological diseases, such as Alzheimer’s disease and Parkinson’s disease. Since Alzheimer’s disease at the early stage is reported to be accompanied with cholinergic cell loss and impairment in recognition memory, the central cholinergic system has been studied to investigate the neural mechanism underlying recognition memory. Previous studies have suggested an important role of cholinergic neurons in the acquisition of some variants of object recognition memory in rodents. Cholinergic neurons in the medial septum and ventral diagonal band of Broca that project mainly to the hippocampus and parahippocampal area are related to recognition memory for object location. Cholinergic projections from the nucleus basalis magnocellularis innervating the entire cortex are associated with recognition memory for object identification. Especially, the brain regions that receive cholinergic projections, such as the perirhinal cortex and prefrontal cortex, are involved in recognition memory for object-in-place memory and object recency. In addition, experimental studies using rodent models for Alzheimer’s disease have reported that neurodegeneration within the central cholinergic system causes a deficit in object recognition memory. Elucidating how various types of object recognition memory are regulated by distinct cholinergic cell groups is necessary to clarify the neuronal mechanism for recognition memory and the development of therapeutic treatments for dementia.
The effects and mechanism of environmental enrichment on MK-801 induced cognitive impairment in rodents with schizophrenia
Authors: Xu Jinwei , Li Yaohao , Tian Biqing , Liu Haiying , Wu Shengxi , Wang Wenting
Published: September 2022

Schizophrenia is a severe mental disorder characterized by positive, negative, and cognitive symptoms. Cognitive symptoms are a kind of symptoms with high incidence and great impact on patients. There is no effective treatment in clinical practice. N-methyl-d-aspartic acid (NMDA) receptor hypofunction may be an important cause of cognitive symptoms. MK-801 (also named Dizocilpine), a noncompetitive antagonist of NMDA receptor, is often used to construct a model of NMDA receptor dysfunction. In terms of treatment, environmental enrichment (EE) as an environmental intervention can effectively improve the symptoms of cognitive impairment in rodents. In this paper, we first briefly introduce the background of cognitive symptoms and EE in schizophrenia, and then investigate the manifestations of MK-801 induced cognitive impairment, the improvement of EE on these cognitive impairments based on the MK-801 induced schizophrenia rodent models, and the possible mechanism of EE in improving cognitive symptoms. This article reviews the literature in recent years, which provides an important reference for MK-801 to construct a cognitive symptom model of schizophrenia and the mechanism of EE in improving cognitive symptoms of schizophrenia.
The neural circuits of monogamous behavior
Authors: López-Gutiérrez María Fernanda , Mejía-Chávez Sara , Alcauter Sarael , Portillo Wendy
Published: September 2022

The interest in studying the neural circuits related to mating behavior and mate choice in monogamous species lies in the parallels found between human social structure and sexual behavior and that of other mammals that exhibit social monogamy, potentially expanding our understanding of human neurobiology and its underlying mechanisms. Extensive research has suggested that social monogamy, as opposed to non-monogamy in mammals, is a consequence of the neural encoding of sociosensory information from the sexual partner with an increased reward value. Thus, the reinforced value of the mate outweighs the reward value of mating with any other potential sexual partners. This mechanism reinforces the social relationship of a breeding pair, commonly defined as a pair bond. In addition to accentuated prosocial behaviors toward the partner, other characteristic behaviors may appear, such as territorial and partner guarding, selective aggression toward unfamiliar conspecifics, and biparental care. Concomitantly, social buffering and distress upon partner separation are also observed. The following work intends to overview and compare known neural and functional circuits that are related to mating and sexual behavior in monogamous mammals. We will particularly discuss reports on Cricetid rodents of the Microtus and Peromyscus genus, and New World primates (NWP), such as the Callicebinae subfamily of the titi monkey and the marmoset (Callithrix spp.). In addition, we will mention the main factors that modulate the neural circuits related to social monogamy and how that modulation may reflect phenotypic differences, ultimately creating the widely observed diversity in social behavior.
The first report on brain sagging dementia caused by a cranial leak: A case report
Authors: Lashkarivand Aslan , Eide Per Kristian
Published: September 2022

Objective

Brain Sagging Dementia (BSD) is an increasingly recognized syndrome for which diagnostic criteria recently were proposed. There have been no reports on BSD caused by a cranial leak. Here we present the first report on a patient with BSD caused by a cranial leak.

Case description

A 60-year old male patient was admitted with a 2-year history of orthostatic headache and gradually progressive cognitive and behavioral changes. Traditional treatments for spontaneous intracranial hypotension, including repeated epidural blood patches, failed. Brain imaging showed severe brain sagging, and intracranial pressure monitoring demonstrated intracranial hypotension. No leakage site was found. His past medical history revealed an accident where a ski pole struck his head at age ten. Due to progressive clinical decline, surgery was pursued. A cranial defect with an accompanying cerebrospinal fluid leak site representing the trauma from his childhood was found and repaired. He also was in need of a ventriculoperitoneal shunt. Following surgery, he improved and recovered completely.

Discussion

This case report illustrates that a cranial leak may cause BSD, even with a “lucid interval” between trauma and symptom debut spanning many years. Moreover, this report validates well the recently proposed BSD diagnostic criteria.
Difficult to treat absence seizures in children: A single-center retrospective study
Authors: Gregorčič Samo , Hrovat Jaka , Bizjak Neli , Rener Primec Zvonka , Hostnik Tadeja , Stres Blaž , Perković Benedik Mirjana , Osredkar Damjan
Published: September 2022

Objectives

The aim of this study was to analyse the characteristics of typical absence seizures (AS), myoclonic AS and AS with eyelid myoclonia in children and to find associations between these characteristics and difficult to treat absence seizures (DTAS).

Methods

This was a single-center retrospective study. Electronic health records of pediatric patients with a clinical diagnosis of AS treated at a single tertiary epilepsy center between January 2013 and June 2020 were reviewed. Clinical characteristics, seizure information, ASM, and therapeutic response of patients were recorded. All patients were followed up for at least 1 year. DTAS were defined as failure to achieve remission after treatment with at least 2 anti-seizure medications (ASM), regardless of whether remission was achieved eventually in the study period.

Results

Data from 131 patients were available for analysis. Remission was achieved after the first ASM treatment in 81 (61.8%) patients, and eventually in 120 (91.6%) during the study period. Epilepsy was classified as DTAS in 18 (13.7%) patients. AS were more often difficult to treat in patients with myoclonic AS and AS with eyelid myoclonia (40.0%), compared with patients with typical AS (11.4%; p = 0.012, 95% CI 1.480–25.732). A positive family history of epilepsy (p = 0.046; 95% CI 1.021–8.572), a higher seizure frequency (p = 0.023, 95% CI 1.009–1.126) prior to ASM treatment, and longer time between seizure onset and treatment onset (p = 0.026; 95% CI 1.006–1.099) were also associated with DTAS.

Significance

Our study suggests that several clinical characteristics of AS are associated with DTAS. One of these was the time between onset of AS and initiation of ASM treatment, which can be shortened with better care, suggesting that early diagnosis and treatment may improve prognosis in pediatric patients with AS. These findings remain to be confirmed in larger prospective studies.
Increased variability of mean arterial pressure is associated with increased risk of short-term mortality in intensive care unit: A retrospective study
Authors: Yao Jia , Liu Dandan , Huang Weifeng , Fang Yuexin , Yang Yifan , Li Yingchuan , Liu Pengyuan , Pan Xiaoqing
Published: September 2022

Background

In intensive care unit (ICU), what thresholds of MAP variability are effective in distinguishing low- and high-risk patients for short-term mortality (in-hospital and 28-day) remains unclear.

Methods

Fifteen thousand five hundred sixty adult subjects admitted to ICU at Beth Israel Deaconess Medical Center (Boston, USA) between 2001 and 2012 were included in this retrospective study from MIMIC-III database. MAP within the first 24 h after admission were collected. Quantiles of MAP variability from 10% to 90% with 10% increasement each were considered to divide study participants into two groups, either having coefficients of variation of MAP greater or less than the given threshold. The threshold of MAP variability was identified by maximizing the odds ratio associated with increased risk of short-term mortality (in-hospital and 28-day). Logistic regression and Cox regression models were further applied to evaluate the association between increased variability of MAP and short-term mortality (in-hospital and 28-day).

Results

90% quantile of MAP variability was determined as the threshold generating the largest odds ratio associated with the increased risk of short-term mortality. Increased MAP variability, especially over 90% of MAP variability, was associated with increased risk of in-hospital mortality (odds ratio: 2.351, 95% CI: 2.064–2.673), and 28-day mortality (hazard ratio: 2.064, 95% CI: 1.820–2.337).

Conclusion

Increased MAP variability, especially over 90% of MAP variability, is associated with short-term mortality. Our proposed threshold of MAP variability may aid in the early identification of critically ill patients with a high risk of mortality.
Proteomic and metabolomic profiling of acupuncture for migraine reveals a correlative link via energy metabolism
Authors: Liu Lu , Li Weizheng , Wang Linpeng , Gong Pengyun , Lyu Tianli , Liu Dapeng , Zhang Yajie , Guo Yijie , Liu Xiang , Tang Min , Hu Hongke , Liu Chao , Li Bin
Published: September 2022

Migraine is a neurovascular disease with a high disability rate. Acupuncture treatment has emerged as a safe and viable alternative prophylactic therapy that can effectively alleviate the duration and frequency of migraine attacks. However, the therapeutic mechanisms underlying the effects of acupuncture are yet to be systematically elucidated. In this study, we enrolled female patients with migraine without aura (n = 20) and healthy controls (n = 10). Patients received acupuncture treatment on DU20, DU24, bilateral GB13, GB8, and GB20, applied three times per week over the course of 4 weeks for 12 sessions in total. Blood samples were collected from the median cubital vein before and after acupuncture treatment. Proteomic and metabolomic profiling was performed using liquid chromatography-mass spectrometry to determine the characteristics of differentially expressed molecules and expression of their corresponding biological pathways as well as to elucidate the pathogenesis of migraine and the biological effects underlying the treatment of migraine with acupuncture. Proteomic and metabolomic profiling of plasma samples from patients with migraine without aura before and after acupuncture treatment revealed enrichment of immune-related pathway functions and the arginine synthesis pathway. Joint pathway analyses revealed significant enrichment of the pentose phosphate and glycolysis/gluconeogenesis pathways in patients with migraine. The glycolysis/gluconeogenesis and riboflavin metabolism pathways were significantly enriched after acupuncture treatment. The expression levels of various key proteins and metabolites, including α-D-glucose, flavin adenine dinucleotide, biliverdin reductase B, and L-glutamate, were significantly differentially expressed before and after acupuncture treatment in patients with migraine without aura. Treatment of migraine with acupuncture was associated with significant changes in key molecules and pathways, indicative of physiological changes in the trigeminovascular system, glutamate neurotoxicity, and other migraine-related physiological changes. Overall, our comprehensive analysis using proteomic and metabolomic profiling demonstrates that energy metabolism may serve as a key correlative link in the occurrence of migraine and the therapeutic effects of acupuncture treatment. Our findings may facilitate the identification of diagnostic and therapeutic modalities in the ongoing search for effective treatments for migraine attacks.
From Bayes-optimal to heuristic decision-making in a two-alternative forced choice task with an information-theoretic bounded rationality model
Authors: Lindig-León Cecilia , Kaur Nehchal , Braun Daniel A.
Published: September 2022

Bayes optimal and heuristic decision-making schemes are often considered fundamentally opposed to each other as a framework for studying human choice behavior, although recently it has been proposed that bounded rationality may provide a natural bridge between the two when varying information-processing resources. Here, we investigate a two-alternative forced choice task with varying time constraints, where subjects have to assign multi-component symbolic patterns to one of two stimulus classes. As expected, we find that subjects' response behavior becomes more imprecise with more time pressure. However, we also see that their response behavior changes qualitatively. By regressing subjects' decision weights, we find that decisions allowing for plenty of decision time rely on weighing multiple stimulus features, whereas decisions under high time pressure are made mostly based on a single feature. While the first response pattern is in line with a Bayes-optimal decision strategy, the latter could be considered as an instantiation of heuristic decision-making with cue discounting. When fitting a bounded rational decision model with multiple feature channels and varying information-processing capacity to subjects' responses, we find that the model is able to capture subjects' behavioral change. The model successfully reflects the simplicity of heuristics as well as the efficiency of optimal decision making, thus acting as a bridge between the two approaches.
High phenylalanine concentrations induce demyelination and microglial activation in mouse cerebellar organotypic slices
Authors: Thau-Zuchman Orli , Pallier Patrick N. , Savelkoul Paul J. M. , Kuipers Almar A. M. , Verkuyl J. Martin , Michael-Titus Adina T.
Published: September 2022

Phenylketonuria (PKU) is an inborn error of metabolism. Mutations in the enzyme phenylalanine hydroxylase (PAH)-encoding gene lead to a decreased metabolism of the amino acid phenylalanine (Phe). The deficiency in PAH increases Phe levels in blood and brain. Accumulation of Phe can lead to delayed development, psychiatric problems and cognitive impairment. White matter (WM) damage is a neuropathological hallmark of PKU and can be seen even in early detected and treated PKU patients. The mechanisms linking high Phe concentrations to WM abnormalities remain unclear. We tested the effects of high Phe concentrations on myelin in three in vitro models of increasing complexity: two simple cell culture models and one model that preserves local brain tissue architecture, a cerebellar organotypic slice culture prepared from postnatal day (P) 8 CD-1 mice. Various Phe concentrations (0.1–10 mM) and durations of exposure were tested. We found no toxic effect of high Phe in the cell culture models. On the contrary, the treatment promoted the maturation of oligodendrocytes, particularly at the highest, non-physiological Phe concentrations. Exposure of cerebellar organotypic slices to 2.4 mM Phe for 21 days in vitro (DIV), but not 7 or 10 DIV, resulted in a significant decrease in myelin basic protein (MBP), calbindin-stained neurites, and neurites co-stained with MBP. Following exposure to a toxic concentration of Phe, a switch to the control medium for 7 days did not lead to remyelination, while very active remyelination was seen in slices following demyelination with lysolecithin. An enhanced number of microglia, displaying an activated type morphology, was seen after exposure of the slices to 2.4 mM Phe for 10 or 21 DIV. The results suggest that prolonged exposure to high Phe concentrations can induce microglial activation preceding significant disruption of myelin.
miR-409-3p represses Cited2 to refine neocortical layer V projection neuron identity
Authors: Wagner Nikolaus R. , Sinha Ashis , Siththanandan Verl , Kowalchuk Angelica M. , MacDonald Jessica L. , Tharin Suzanne
Published: September 2022

The evolutionary emergence of the corticospinal tract and corpus callosum are thought to underpin the expansion of complex motor and cognitive abilities in mammals. Molecular mechanisms regulating development of the neurons whose axons comprise these tracts, the corticospinal and callosal projection neurons, remain incompletely understood. Our previous work identified a genomic cluster of microRNAs (miRNAs), Mirg/12qF1, that is unique to placental mammals and specifically expressed by corticospinal neurons, and excluded from callosal projection neurons, during development. We found that one of these, miR-409-3p, can convert layer V callosal into corticospinal projection neurons, acting in part through repression of the transcriptional regulator Lmo4. Here we show that miR-409-3p also directly represses the transcriptional co-regulator Cited2, which is highly expressed by callosal projection neurons from the earliest stages of neurogenesis. Cited2 is highly expressed by intermediate progenitor cells (IPCs) in the embryonic neocortex while Mirg, which encodes miR-409-3p, is excluded from these progenitors. miR-409-3p gain-of-function (GOF) in IPCs results in a phenocopy of established Cited2 loss-of-function (LOF). At later developmental stages, both miR-409-3p GOF and Cited2 LOF promote the expression of corticospinal at the expense of callosal projection neuron markers in layer V. Taken together, this work identifies previously undescribed roles for miR-409-3p in controlling IPC numbers and for Cited2 in controlling callosal fate. Thus, miR-409-3p, possibly in cooperation with other Mirg/12qF1 miRNAs, represses Cited2 as part of the multifaceted regulation of the refinement of neuronal cell fate within layer V, combining molecular regulation at multiple levels in both progenitors and post-mitotic neurons.
Light-induced shifts in opsin gene expression in the four-eyed fish Anableps anableps
Authors: Salgado Daniele , Mariluz Bertha R. , Araujo Maysa , Lorena Jamily , Perez Louise N. , Ribeiro Rafaela de L. , Sousa Josane de F. , Schneider Patricia N.
Published: September 2022

The development of the vertebrate eye is a complex process orchestrated by several conserved transcriptional and signaling regulators. Aside from partial or complete loss, examples of exceptional modifications to this intricate organ are scarce. The unique eye of the four-eyed fish Anableps anableps is composed of duplicated corneas and pupils, as well as specialized retina regions associated with simultaneous aerial and aquatic vision. In a previous transcriptomic study of the A. anableps developing eye we identified expression of twenty non-visual and eleven visual opsin genes. Here, we surveyed the expression territories of three non-visual melanopsins genes (opn4×1, opn4×2, opn4m3), one teleost multiple tissue opsin (tmt1b) and two visual opsins (lws and rh2-1) in dorsal and ventral retinas. Our data showed that asymmetry of non-visual opsin expression is only established after birth. During embryonic development, while inside pregnant females, the expression of opn4×1, opn4×2, and tmt1b spans the whole retina. In juvenile fish (post birth), the expression of opn4×1, opn4×2, opn4m3, and tmt1b genes becomes restricted to the ventral retina, which receives aerial light. Raising juvenile fish in clear water instead of the murky waters found in its natural habitat is sufficient to change gene expression territories of opn4×1, opn4×2, opn4m3, tmt1b, and rh2-1, demonstrating that different lighting conditions can shift opsin expression and potentially contribute to changes in spectral sensitivity in the four eyed fish.
Molecular and cellular mechanisms leading to catatonia: an integrative approach from clinical and preclinical evidence
Authors: Ariza-Salamanca Daniel Felipe , Corrales-Hernández María Gabriela , Pachón-Londoño María José , Hernández-Duarte Isabella
Published: September 2022

This review aims to describe the clinical spectrum of catatonia, in order to carefully assess the involvement of astrocytes, neurons, oligodendrocytes, and microglia, and articulate the available preclinical and clinical evidence to achieve a translational understanding of the cellular and molecular mechanisms behind this disorder. Catatonia is highly common in psychiatric and acutely ill patients, with prevalence ranging from 7.6% to 38%. It is usually present in different psychiatric conditions such as mood and psychotic disorders; it is also a consequence of folate deficiency, autoimmunity, paraneoplastic disorders, and even autistic spectrum disorders. Few therapeutic options are available due to its complexity and poorly understood physiopathology. We briefly revisit the traditional treatments used in catatonia, such as antipsychotics, electroconvulsive therapy, and benzodiazepines, before assessing novel therapeutics which aim to modulate molecular pathways through different mechanisms, including NMDA antagonism and its allosteric modulation, and anti-inflammatory drugs to modulate microglia reaction and mitigate oxidative stress, such as lithium, vitamin B12, and NMDAr positive allosteric modulators.
Novel POU3F4 variants identified in patients with inner ear malformations exhibit aberrant cellular distribution and lack of SLC6A20 transcriptional upregulation
Authors: Bernardinelli Emanuele , Roesch Sebastian , Simoni Edi , Marino Angela , Rasp Gerd , Astolfi Laura , Sarikas Antonio , Dossena Silvia
Published: September 2022

Hearing loss (HL) is the most common sensory defect and affects 450 million people worldwide in a disabling form. Pathogenic sequence alterations in the POU3F4 gene, which encodes a transcription factor, are causative of the most common type of X-linked deafness (X-linked deafness type 3, DFN3, DFNX2). POU3F4-related deafness is characterized by a typical inner ear malformation, namely an incomplete partition of the cochlea type 3 (IP3), with or without an enlargement of the vestibular aqueduct (EVA). The pathomechanism underlying POU3F4-related deafness and the corresponding transcriptional targets are largely uncharacterized. Two male patients belonging to a Caucasian cohort with HL and EVA who presented with an IP3 were submitted to genetic analysis. Two novel sequence variants in POU3F4 were identified by Sanger sequencing. In cell-based assays, the corresponding protein variants (p.S74Afs*8 and p.C327*) showed an aberrant expression and subcellular distribution and lack of transcriptional activity. These two protein variants failed to upregulate the transcript levels of the amino acid transporter gene SLC6A20, which was identified as a novel transcriptional target of POU3F4 by RNA sequencing and RT-qPCR. Accordingly, POU3F4 silencing by siRNA resulted in downregulation of SLC6A20 in mouse embryonic fibroblasts. Moreover, we showed for the first time that SLC6A20 is expressed in the mouse cochlea, and co-localized with POU3F4 in the spiral ligament. The findings presented here point to a novel role of amino acid transporters in the inner ear and pave the way for mechanistic studies of POU3F4-related HL.
Regulation of amino acid metabolism in Aphis gossypii parasitized by Binodoxys communis
Authors: Xue Hui , Zhao Yunyun , Wang Li , Zhu Xiangzhen , Zhang Kaixin , Li Dongyang , Ji Jichao , Niu Lin , Cui Jinjie , Luo Junyu , Gao Xueke
Published: September 2022

The vast majority of parasitoids are capable of precise and meticulous regulation of nutrition and metabolism within the host. An important building block of life, amino acids are critical to the development of parasitoids. To date, research on how parasitoids regulate host amino acid metabolism remains limited. In this study, Aphis gossypii and its dominant parasitoid Binodoxys communis were used as a study system to explore how parasitism may change the regulation of amino acids in A. gossypii with UHPLC-MS/MS and RT-qPCR techniques. Here, for the first 8 h of parasitism the abundance of almost all amino acids in cotton aphids increased, and after 16 h most of the amino acids decreased. An amino acid of parasitic syndrome, the content of Tyr increased gradually after being parasitized. The expression of genes related to amino acid metabolism increased significantly in early stages of parasitism and then significantly decreased gradually. At the same time, the abundance of Buchnera, a cotton aphid specific symbiont increased significantly. Our comprehensive analyses reveal impacts of B. communis on the amino acid regulatory network in cotton aphid from three aspects: amino acid metabolism, gene expression, and bacterial symbionts. Therefore, this research provides an important theoretical basis for parasitoid nutritional regulation in host, which is highly significant as it may inform the artificial reproduction of parasitoids and the biological control of insect pests.
Flavor properties of Chinese noodles processed by dielectric drying
Authors: Lin Qian , Ren Aiqing , Liu Rui , Xing Yanan , Yu Xiuzhu , Jiang Hao
Published: September 2022

Volatile organic compounds (VOCs) significantly impact food flavor. In this work, Electron nose (E-nose), head space solid phase microextraction-gas chromatography-mass spectrometry (HS-SPME-GC-MS), and head space-gas chromatography-ion mobility spectrometry (HS-GC-IMS) techniques were applied to analyze different drying effects: microwave, hot air, and radio frequency on the aroma of Chinese noodles. E-nose analysis suggests that aromatic differences are mainly from broad range-methane. HS-SPME-GC-MS and HS-GC-IMS identified 47 and 26 VOCs in the fresh and dried noodles, respectively. The VOCs in the dried noodles were mainly aldehydes, alcohols, and esters. Drying significantly reduced the types of VOCs in Chinese dried noodles. Microwave dried noodles exhibited the strongest aroma after the shortest time of treatment, suggesting microwave drying may be the best drying method for noodles. Using aromatic analysis, this paper provides useful information for understanding the flavor of flour products and offers new ideas for drying noodles.
Acetyl-glucomannan from Dendrobium officinale: Structural modification and immunomodulatory activities
Authors: Guo Xiaoyu , Yang Mingguan , Wang Changlu , Nie Shaoping , Cui Steve W. , Guo Qingbin
Published: September 2022

To understand the mechanisms of immunomodulatory effect, Dendrobium Officinale polysaccharides (DOP) were treated by ultrasound and mild base separately to generate fractions of various weight-average molecular weight (Mw) and degrees of acetylation (DA). The structural features, conformational properties, functional properties and immunomodulatory activities of original and modified DOPs were investigated. Ultrasonic treatment decreased the Mw and apparent viscosity and improved the water solubility of DOP. Mild base treatment remarkably reduced the DA and the water solubility, while the overall apparent viscosity was increased. Conformational analysis by triple-detector high performance size-exclusion chromatography showed that the molecular chain of DOP turned more compact coil conformation with decreased DA. Results from the macrophages RAW 264.7 analysis showed that samples sonicated for 200 min (Mw 34.2 kDa) showed the highest immune-regulation effects. However, the immunomodulatory effects of the samples after de-acetylation were all compromised compared to the original DOP. This study inspires further research to establish the structural-immunomodulatory relationships, which promote the application of DOP in both the food and medicine fields.
Unpruning improvement the quality of tea through increasing the levels of amino acids and reducing contents of flavonoids and caffeine
Authors: Li Ruoyu , Liu Kunyi , Liang Zhengwei , Luo Hui , Wang Teng , An Jiangshan , Wang Qi , Li Xuedan , Guan Yanhui , Xiao Yanqin , Lv Caiyou , Zhao Ming
Published: September 2022

Tea tree [Camellia sinensis var. sinensis or assamica (L.) O. Kuntze], an important crop worldwide, is usually pruned to heights of 70 to 80 cm, forming pruned tea tree (PTT) plantations. Currently, PTTs are transformed into unpruned tea tree (UPTT) plantations in Yunnan, China. This has improved the quality of tea products, but the underlying reasons have not been evaluated scientifically. Here, 12 samples of sun-dried green teas were manufactured using fresh leaves from an UPTT and the corresponding PTT. Using sensory evaluation, it was found that the change reduced the bitterness and astringency, while increasing sweetness and umami. Using high performance liquid chromatography detection showed that the contents of free amino acids (theanine, histidine, isoleucine and phenylalanine) and catechin gallate increased significantly (P < 0.05), whereas the content of alanine decreased significantly (P < 0.05). A liquid chromatography–mass spectrometry-based metabolomics analysis showed that the transformation to UPTT significantly decreased the relative levels of the majority of flavonols and tannins (P < 0.05), as well as γ-aminobutyric acid, caffeine and catechin (epigallocatechin, catechin, epigallocatechin gallate, gallocatechin gallate), while it significantly increased the relative contents of catechins (gallocatechin, epicatechin, epicatechin gallate and catechin gallate), phenolic acids and some amino acids (serine, oxidized glutathione, histidine, aspartic acid, glutamine, lysine, tryptophan, tyramine, pipecolic acid, and theanine) (P < 0.05). In summary, after transforming to UPTT, levels of amino acids, such as theanine increased significantly (P < 0.05), which enhanced the umami and sweetness of tea infusions, while the flavonoids (such as kaempferol, myricetin and glycosylated quercetin), and caffeine contents decreased significantly (P < 0.05), resulting in a reduction in the bitterness and astringency of tea infusions and an increase in tea quality.
Quercetin supplementation alters adipose tissue and hepatic transcriptomes and ameliorates adiposity, dyslipidemia, and glucose intolerance in adult male rats
Authors: Kábelová Adéla , Malínská Hana , Marková Irena , Hűttl Martina , Chylíková Blanka , Šeda Ondřej
Published: September 2022

Quercetin, a flavonoid present in many fruits and vegetables, exhibits beneficial effects toward abnormalities related to metabolic syndrome. In this study, to further investigate metabolic and transcriptomic responses to quercetin supplementation, we used a genetic model of metabolic syndrome. Adult male rats of the PD/Cub strain were fed either a high-sucrose diet (HSD; control PD rats) or HSD fortified with quercetin (10 g quercetin/kg diet; PD-Q rats). Morphometric and metabolic parameters, along with transcriptomic profiles of the liver and retroperitoneal fat, were assessed. The relative weights of epididymal and retroperitoneal fat were significantly decreased in quercetin-treated animals. Furthermore, a smaller area under the glycemic curve along with a decreased level of fasting insulin were detected in PD-Q rats. While no changes in total cholesterol levels were observed, the overall level of triglycerides decreased in the serum and the liver of the PD-Q rats. The transcriptomic profile of the liver and the adipose tissue corroborated the metabolic and morphometric findings, revealing the pattern consistent with insulin-sensitizing changes, with major regulator nodes being Pparg, Adipoq, Nos2, and Mir378. In conclusion, quercetin supplementation improves abnormalities related to metabolic syndrome, namely adiposity, dyslipidemia and glucose intolerance.
Validation and results of a novel survey assessing decisional balance for a whole food plant-based diet among US adults
Authors: Jovanovic Christine E. S. , Kalam Faiza , Granata Frank , Pfammatter Angela F. , Spring Bonnie
Published: September 2022

Importance

Consuming a whole food plant-based diet (WFPBD) is a promising, low-risk strategy for reducing risk of prevalent chronic disease and certain cancers, with synergistic benefits for climate and environment. However, few US adults report consuming a WFPBD. Understanding the reasons for this inconsistency is important for developing and implementing interventions for promoting a WFPBD. However, no research to elucidate decisional balance driving current consumption patterns in the US exists.

Objective

This research aims to validate an online survey to assess decisional balance for the consumption of a WFPBD, describe attitudes and beliefs toward adopting a WFPBD, and evaluate socio-demographic differences in decisional balance for consuming a WFPBD among a convenience sample of US adults.

Design

Online cross-sectional data collection followed by confirmatory factor analysis (CFA), validation of internal consistency, and examination of invariance across socio-demographic variables. Sensitivity analysis of full vs. truncated survey to predict self-reported dietary patterns and consumption behaviors were evaluated. Results of the survey and significant differences by socio-demographics were assessed.

Setting

Online survey based on previous research, createdviaQualtrics, and administered through MTurk.

Participants

A total of 412 US adults, majority female (66%), White (75%), 30–60 years old (54%), ≥ Bachelor’s degree (85%), and earning ≥ $45K (68%).

Main outcomes and measures

Factor loadings, covariance of survey items, associations with self-reported dietary pattern and consumption measures, and differences in pros, cons, and decisional balance across socio-demographic variables.

Results

CFA reduced the survey from 49 to 12 items and demonstrated invariance across socio-demographic variables. Pros and cons varied inversely and significantly (cov = –0.59), as expected. Cronbach’s α ’s for subscales in the final, reduced model were high (>0.80). Pros, cons, and decisional balance in both the full and the reduced model were significantly (p< 0.05) associated with self-reported dietary pattern and consumption.

Conclusion and relevance

Our analyses indicate the WFPBD Survey is a parsimonious and psychometrically sound instrument for evaluation of decisional balance to consume a WFPBD diet among our sample of US adults. These results may be instrumental for development and deployment of interventions intended to promote consumption of a WFPBD in the US.