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Schistosomiasis, otherwise known as bilharzia or snail fever, is a disease that usually affects poor people and people exposed to poor sanitation. The disease affects over 200 million people worldwide annually. Schistosomiasis has been treated using a single drug, praziquantel, since the 1970s and this is resulting in schistosomes becoming resistant. Therefore, there is an urgent need to develop new antischistosoma drugs and vaccines. This study focuses on identifying potential antischistosomal compounds from the plant Salvia fruticosa . We virtually screened a library of 163 S fruticosa compounds by docking against Schistosoma mansoni sulfotransferase ( Sm SULT) using the PyRx software. Docking scores ranged from −4.7 to −9.3 kcal/mol. Compounds with binding affinity of −7.6 or stronger were subjected to drug-likeness assessments using the DataWarrior software. We also employed the PAINS removal tool to filter off false-positive results. Twelve compounds passed the drug-likeness screen, and these were subjected to in silico toxicity predictions to determine their mutagenic, tumorigenic and reproductive potential. Seven compounds were predicted to be nontoxic. After considering the toxicity analysis results and drug scores of the compounds, we identified rosmarinic acid and hispidulin as qualifying for further evaluation as potential drugs against schistosomiasis. Free energy calculations using the fastDRH webserver and molecular dynamics simulations using CABS-flex showed that the receptor-ligand complexes for the 2 lead compounds are stable under physiological conditions. We recommend that rosmarinic acid and hispidulin be used as hit compounds for the development of potential antischistosomal drugs.

The survival of the malaria parasite is highly dependent on withstanding physiological stresses, which are a proportional response to parasite invasion within the hostile human host environment. Plasmodium falciparum heat shock protein 70-1 (PfHSP70-1) plays a significant role through its network of interactions with the substrate scanners PfHSP40s, the functional maturation protein PfHSP90, the nucleotide exchange factor PfHSP110c/PfHSP70-z, apoptosis and parasite homeostasis agent PfHSP60, also the Clp machinery for the unfolding and degrading of misfolded proteins PfHSP100. These proteins work together to maintain the health and function of the parasite, but also possess individual functionalities. Here, we review the functional interplay between these heat shock proteins (HSPs), highlighting the central role of PfHSP70-1, its prospects in antimalarial drug discovery and possible implications in drug resistance.

ABSTRACTIn order to understand the mechanism of desiccation tolerance in Xerophyta schlechteri, we carried out an in silico study to identify hub proteins and functional modules in the nuclear proteome of the leaves. Protein–protein interaction networks were constructed and analyzed from proteome data obtained from Abdalla and Rafudeen. We constructed networks in Cytoscape using the GeneMania software and analyzed them using a Network Analyzer. Functional enrichment analysis of key proteins in the respective networks was done using GeneMania network enrichment analysis, and GO (Gene Ontology) terms were summarized using REViGO. Also, community analysis of differentially expressed proteins was conducted using the Cytoscape Apps, GeneMania and ClusterMaker. Functional modules associated with the communities were identified using an online tool, ShinyGO. We identified HSP 70–2 as the super-hub protein among the up-regulated proteins. On the other hand, 40S ribosomal protein S2–3 (a protein added by GeneMANIA) was identified as a super-hub protein associated with the down-regulated proteins. For up-regulated proteins, the enriched biological process terms were those associated with chromatin organization and negative regulation of transcription. In the down-regulated protein-set, terms associated with protein synthesis were significantly enriched. Community analysis identified three functional modules that can be categorized as chromatin organization, anti-oxidant activity and metabolic processes.

AbstractThe use of native microalgal strains, which are well adapted to local environmental conditions, for sustainable biofuels production has largely been marred by photonics-related challenges. To date, most photobioreactor systems make use of artificial sources of illumination thus increasing the overall costs of biomass production. Solar energy, although sustainable and cost-effective, is difficult to manage and control. It also contains other wavelengths which are detrimental to microalgae. Thus, this study sought to make use of spectral filters for optimal outdoor algaculture. Hence, solar energy was used in wastewater-mediated algaculture of native and imported Chlorella sp. under blue, green, red and yellow coloured spectral filters. The native Chlorella sp. had the highest growth rate of 0.892 d−1 and 0.754 d−1 under green and blue coloured filters, respectively. In comparison, the imported Chlorella strain had a growth rate of 0.379 d−1 and 0.267 d−1 under green and blue filters, respectively. Both strains produced high lipid yields under the blue coloured filter, with the native and imported Chlorella strains managing lipid yields of 41.87% dry cell weight (dcw) and 32.29% dcw, respectively. The native Chlorella strain also significantly lowered (p

Brachystegia boehmii leaf extracts are ethnopharmacological known to treat microbial infections in burn wounds. Coupling the action of the traditional plant medicine and nanotechnology gives rise to innovative strategies for healing burn wounds. This study aimed to determine the effect of B. boehmii extracts and their green synthesised nanoparticles on bacteria which infect burn wounds. The effects of water, chloroform and methanolic leaf extracts were compared with the effects of the phytosynthesised silver nanoparticles on burn wound infectious bacteria. Dried leaves were extracted using the maceration technique, followed by filtration and concentration of the filtrate using a rotavapor. Drying was achieved by using a centrivap and appropriate masses were dissolved in dimethyl sulfoxide to achieve 100 mg/ml concentrations. Silver nanoparticles were synthesised using the methanol extract of the plant leaves and characterised using a UV–VIS spectrophotometer. The disc diffusion method was used to assess the bacterial susceptibility levels with Ciprofloxacin as the positive control and DMSO and 1 mM silver nitrate as the negative controls. The green synthesised silver nanoparticles produced a yellowish colour with a peak at 420 nm wavelength. They exhibited antibacterial activity against all five bacteria; Pseudomonas aeruginosa, Klebsiella pneumoniae, Escherichia coli, Staphylococcus aureus and Staphylococcus epidermidis comparable to those of the B. boehmii leaf solvent extracts. A zone of inhibition of 20 ± 1.00 mm was obtained on the action of B. boehmii leaf extract against P. aeruginosa. Plant synthesised nanoparticles exhibited broad spectrum antibacterial activity and hence are potential future burn wound antibacterial therapeutics.

Synthetic biology (SynBio) is an interdisciplinary field that has developed rapidly in the last two decades. It involves the design and construction of new biological systems and processes from standardized biological components, networks and synthetic pathways. The goal of Synbio is to create logical forms of cellular control. Biological systems and their parts can be redesigned to carry out completely new functions. SynBio is poised to greatly impact human health, the environment, biofuels and chemical production with huge economic benefits. SynBio presents opportunities for the highly agro-based African economies to overcome setbacks that threaten food security: The setbacks are brought about by climate change, land degradation, over-reliance on food imports, global competition, and water and energy security issues among others. With appropriate regulatory frameworks and systems in place, the benefits of harnessing SynBio to boost development in African economies by far potentially outweigh the risks. Countries that are already using GMOs such as South Africa and Kenya should find the application of SynBio seamless, as it would be a matter of expanding the already existing regulations and policies for GMO use.

Natural compounds are increasingly becoming an important source of drug leads for computer-aided drug design approaches. Cucurbita maxima has been observed to have medicinal properties and can, therefore, be a potential source of novel drug leads. However, before compounds can be synthesized in the lab for tests, modern approaches require that the candidate compounds be screened for drug-likeness characteristics and toxicity, among others. In this work, the computational tools, SwissADME and DataWarrior were used to screen C. maxima compounds for their potential consideration as drug leads. A total of 130 compounds, downloaded from the LOTUS natural products database, were computationally analysed. The data set presented in this work will be useful to researchers searching for novel drug leads based on natural compounds.

Gene drives are being used to enhance a DNA sequence’s likelihood of passing between generations via sexual reproduction. Gene drives can be deployed to manipulate natural populations. They can be used to suppress populations by reducing the number of individuals in a population or to modify populations. There are more than 3000 mosquito species in the world, some of which are vectors of diseases. Malaria is a typical disease whose vectors are mosquitoes. It affects mostly tropical countries. It kills many people annually, many of whom are children. Interventions currently in use, such as indoor residual spraying and mosquito nets, are proving insufficient to eradicate malaria. Gene drives can be used in different ways to control mosquito populations or to eliminate mosquito species, thereby reducing malaria cases and deaths. This can occur through population replacement or suppression. However, before the elimination of any mosquito species for malaria control, it is necessary to consider the effects of such an action. Additionally, there is a need to review the options available for the control of mosquitoes and to create awareness of the benefits and risks of such an action. This paper, therefore, looks at the role of mosquitoes in the environment, the methods of controlling mosquitoes and malaria and necessary considerations when using gene drives inter alia.

Schistosomiasis, a disease usually related to poverty and poor sanitation, affects more than 200 million people worldwide. Since the 1970s, the medical sector has depended on a single drug, praziquantel, for the treatment of the disease. The emerging evidence of resistance of the Schistosoma parasite to praziquantel and the drug’s inefficacy against juvenile stages of the parasite makes the need to find alternative drugs an urgent matter. In this study, we explored the inhibition potential of compounds from Cucurbita maxima using molecular docking studies on Schistosoma mansoni purine nucleoside phosphorylase ( Sm PNP) and Schistosoma haematobium 28-kDa glutathione S-transferase ( Sh 28kDaGST). Following molecular docking studies and analysis of the active sites, the primary amino acids that were observed and shown to be involved in the Sm PNP-ligand interaction are CYS 33, ARG 86, HIS 88, TYR 90, ALA 118, ALA 119, PRO 200, TYR 202, GLU 203, VAL 219, MET 221, THR 244, ASN 245, PRO 257 and HIS 259. For the Sh2 8dKa-ligand interaction, the primary amino acids were PHE 11, ARG 16, TRP 41, LEU 53, GLU 70 and SER 71. Momordicoside I aglycone binds to Sm PNP with the lowest binding affinity of -7.9 kcal/mol by pi sigma bond interactions with HIS 88. Balsaminoside B binds to Sh 28kDaGST with a binding affinity of −7.6 kcal/mol by hydrogen bond interaction with TRP 41, LEU 53 and SER 71. Pharmacokinetic studies showed favourable drug-like properties for the 10 compounds that exhibited the lowest binding energies. Therefore, we propose that bioactive compounds from C. maxima be considered as potential novel drug hits in the treatment of schistosomiasis.

Speech impediments are a prominent yet understudied symptom of Parkinson's disease (PD). While the subthalamic nucleus (STN) is an established clinical target for treating motor symptoms, these interventions can lead to further worsening of speech. The interplay between dopaminergic medication, STN circuitry, and their downstream effects on speech in PD is not yet fully understood. Here, we investigate the effect of dopaminergic medication on STN circuitry and probe its association with speech and cognitive functions in PD patients. We found that changes in intrinsic functional connectivity of the STN were associated with alterations in speech functions in PD. Interestingly, this relationship was characterized by altered functional connectivity of the dorsolateral and ventromedial subdivisions of the STN with the language network. Crucially, medication-induced changes in functional connectivity between the STN's dorsolateral subdivision and key regions in the language network, including the left inferior frontal cortex and the left superior temporal gyrus, correlated with alterations on a standardized neuropsychological test requiring oral responses. This relation was not observed in the written version of the same test. Furthermore, changes in functional connectivity between STN and language regions predicted the medication's downstream effects on speech-related cognitive performance. These findings reveal a previously unidentified brain mechanism through which dopaminergic medication influences speech function in PD. Our study sheds light into the subcortical-cortical circuit mechanisms underlying impaired speech control in PD. The insights gained here could inform treatment strategies aimed at mitigating speech deficits in PD and enhancing the quality of life for affected individuals., Competing Interests: Competing interests statement:The authors declare no competing interest.

Parkinson's disease (PD) starts at the molecular and cellular level long before motor symptoms appear, yet there are no early-stage molecular biomarkers for diagnosis, prognosis prediction, or monitoring therapeutic response. This lack of biomarkers greatly impedes patient care and translational research-L-DOPA remains the standard of care more than 50 years after its introduction. Here, we performed a large-scale, multi-tissue, and multi-platform proteomics study to identify new biomarkers for early diagnosis and disease monitoring in PD. We analyzed 4877 cerebrospinal fluid, blood plasma, and urine samples from participants across seven cohorts using three orthogonal proteomics methods: Olink proximity extension assay, SomaScan aptamer precipitation assay, and liquid chromatography-mass spectrometry proteomics. We discovered that hundreds of proteins were upregulated in the CSF, blood, or urine of PD patients, prodromal PD patients with DAT deficit and REM sleep behavior disorder or anosmia, and non-manifesting genetic carriers of LRRK2 and GBA mutations. We nominate multiple novel hits across our analyses as promising markers of early PD, including DOPA decarboxylase (DDC), also known as L-aromatic acid decarboxylase (AADC), sulfatase-modifying factor 1 (SUMF1), dipeptidyl peptidase 2/7 (DPP7), glutamyl aminopeptidase (ENPEP), WAP four-disulfide core domain 2 (WFDC2), and others. DDC, which catalyzes the final step in dopamine synthesis, particularly stands out as a novel hit with a compelling mechanistic link to PD pathogenesis. DDC is consistently upregulated in the CSF and urine of treatment-naïve PD, prodromal PD, and GBA or LRRK2 carrier participants by all three proteomics methods. We show that CSF DDC levels correlate with clinical symptom severity in treatment-naïve PD patients and can be used to accurately diagnose PD and prodromal PD. This suggests that urine and CSF DDC could be a promising diagnostic and prognostic marker with utility in both clinical care and translational research., (© 2024. The Author(s).)

Electroconvulsive therapy (ECT) pulse amplitude, which dictates the induced electric field (E-field) magnitude in the brain, is presently fixed at 800 or 900 milliamperes (mA) without clinical or scientific rationale. We have previously demonstrated that increased E-field strength improves ECT's antidepressant effect but worsens cognitive outcomes. Amplitude-determined seizure titration may reduce the E-field variability relative to fixed amplitude ECT. In this investigation, we assessed the relationships among amplitude-determined seizure-threshold (ST a ), E-field magnitude, and clinical outcomes in older adults (age range 50 to 80 years) with depression. Subjects received brain imaging, depression assessment, and neuropsychological assessment pre-, mid-, and post-ECT. ST a was determined during the first treatment with a Soterix Medical 4×1 High Definition ECT Multi-channel Stimulation Interface (Investigation Device Exemption: G200123). Subsequent treatments were completed with right unilateral electrode placement (RUL) and 800 mA. We calculated E brain defined as the 90th percentile of E-field magnitude in the whole brain for RUL electrode placement. Twenty-nine subjects were included in the final analyses. E brain per unit electrode current, E brain /I, was associated with ST a . ST a was associated with antidepressant outcomes at the mid-ECT assessment and bitemporal electrode placement switch. E brain /I was associated with changes in category fluency with a large effect size. The relationship between ST a and E brain /I extends work from preclinical models and provides a validation step for ECT E-field modeling. ECT with individualized amplitude based on E-field modeling or ST a has the potential to enhance neuroscience-based ECT parameter selection and improve clinical outcomes., (© 2024. The Author(s).)

Apraxia of eyelid opening (or eye-opening apraxia) is characterized by the inability to voluntarily open the eyes because of impaired supranuclear control. Here, we examined the neural substrates implicated in eye-opening apraxia through lesion network mapping. We analysed brain lesions from 27 eye-opening apraxia stroke patients and compared them with lesions from 20 aphasia and 45 hemiballismus patients serving as controls. Lesions were mapped onto a standard brain atlas using resting-state functional MRI data derived from 966 healthy adults in the Harvard Dataverse. Our analyses revealed that most eye-opening apraxia-associated lesions occurred in the right hemisphere, with subcortical or mixed cortical/subcortical involvement. Despite their anatomical heterogeneity, these lesions functionally converged on the bilateral dorsal anterior and posterior insula. The functional connectivity map for eye-opening apraxia was distinct from those for aphasia and hemiballismus. Hemiballismus lesions predominantly mapped onto the putamen, particularly the posterolateral region, while aphasia lesions were localized to language-processing regions, primarily within the frontal operculum. In summary, in patients with eye-opening apraxia, disruptions in the dorsal anterior and posterior insula may compromise their capacity to initiate the appropriate eyelid-opening response to relevant interoceptive and exteroceptive stimuli, implicating a complex interplay between salience detection and motor execution., Competing Interests: The authors report no conflicts of interests., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Objective: Hippocampal atrophy is an indicator of emerging dementia in PD, though it is unclear whether cerebral spinal fluid (CSF) Abeta-42, t-tau, or alpha-syn predict hippocampal subfield atrophy in a de novo cohort of PD patients. To examine whether levels of CSF alpha-synuclein (alpha-syn), beta-amyloid 1-42 (Abeta-42) , or total-tau (t-tau) are associated with hippocampal subfield volumes over time., Methods: We identified a subset of Parkinson's Progression Markers Initiative (PPMI) de novo PD patients with longitudinal T1-weighted imaging (baseline plus at least two additional visits across 12, 24, and 48 months) and CSF biomarkers available at baseline. We performed cross-sectional, regression, and linear mixed model analyses to evaluate the baseline and longitudinal CSF biomarkers, hippocampal subfields, and cognition. A false discovery rate (FDR) was used to correct for multiple comparisons., Results: 88 PD-CN and 21 PD-MCI had high quality longitudinal data. PD-MCI patients exhibited reduced bilateral CA1 volumes relative to PD-CN, though there were no significant differences in CSF biomarkers between these groups. Relationships between CSF biomarkers and hippocampal subfields changed over time, with a general pattern that lower CSF Abeta-42, higher t-tau and higher alpha-syn were associated with smaller hippocampal subfields, primarily in the right hemisphere., Conclusion: We replicated prior reports that demonstrated reduced CA1 volumes in PD-MCI in a de novo PD cohort. CSF biomarkers were associated with individual subfields, with evidence that the increased CSF t-tau was associated with smaller subiculum volumes at baseline and over time, though there was no clear indication that the subfields associated with cognition (CA1 and HATA) were associated with CSF biomarkers., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Author(s).)

Objective: This study was undertaken to study pareidolias, or perceived meaningful objects in a meaningless stimulus, in patients across the Lewy body (LB) disease spectrum, where most do not report hallucinations or delusions., Methods: We studied illusory responses on the Noise Pareidolia Task in 300 participants (38 cognitively impaired LB, 65 cognitively unimpaired LB, 51 Alzheimer disease spectrum [AD-s], 146 controls). Pairwise between-group comparisons examined how diagnosis impacts the number of illusory responses. Ordinal regression analysis compared the number of illusory responses across diagnosis groups, adjusting for age, sex, and education. Analyses were repeated after removing participants with reported hallucinations or delusions., Results: Cognitively impaired LB participants were 12.3, 4.9, and 4.6 times more likely than control, cognitively unimpaired LB, and AD-s participants, respectively, to endorse illusory responses. After adjusting for age, sex, and education, the probability of endorsing 1 or more illusory responses was 61% in the cognitively impaired LB group, compared to 26% in AD-s, 25% in cognitively unimpaired LB, and 12% in control participants. All results were similar after repeated analysis only in participants without hallucinations or delusions. In LB without hallucinations or delusions, 52% with mild cognitive impairment and 66.7% with dementia endorsed at least 1 illusory response., Interpretation: We found illusory responses are common in cognitively impaired LB patients, including those without any reported psychosis. Our data suggest that, prior to the onset of hallucinations and delusions, the Noise Pareidolia Task can easily be used to screen for unobtrusive pareidolias in all LB patients. ANN NEUROL 2023;93:702-714., (© 2022 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Lewy body diseases, such as Parkinson's disease and dementia with Lewy bodies, vary in their clinical phenotype but exhibit the same defining pathological feature, α-synuclein aggregation. Microbiome-gut-brain dysfunction may play a role in the initiation or progression of disease processes, though there are multiple potential mechanisms. We discuss the need to evaluate gastrointestinal mechanisms of pathogenesis across Lewy body diseases, as disease mechanisms likely span across diagnostic categories and a 'body first' clinical syndrome may better account for the heterogeneity of clinical presentations across the disorders. We discuss two primary hypotheses that suggest that either α-synuclein aggregation occurs in the gut and spreads in a prion-like fashion to the brain or systemic inflammatory processes driven by gastrointestinal dysfunction contribute to the pathophysiology of Lewy body diseases. Both of these hypotheses posit that dysbiosis and intestinal permeability are key mechanisms and potential treatment targets. Ultimately, this work can identify early interventions targeting initial disease pathogenic processes before the development of overt motor and cognitive symptoms., (© 2022. The Author(s).)

The coronavirus (COVID-19) has spread quickly across the nation with a disproportionate impact on Black Americans. Many college-aged students receive their COVID-19-related information through social media and television even though research suggests that social media sources are more likely to be incorrect. Some students report trusting these sources over government sources such as the CDC and WHO. The purpose of this study was to understand Historically Black College and University (HBCU) students' COVID-19 knowledge, sources of information, and planned precautions. There were 21 in-depth interviews conducted with students attending a large southern HBCU during Spring 2020. Themes regarding knowledge included the following: it is a flu-like condition, it has international roots, there is inaccurate and changing information, and it is a pandemic. Themes regarding sources included: the news, US government and related officials, social media, interactions with family, and other social interactions. Themes regarding severity included the following: statistics, a distrust for hospital reporting, a belief that COVID-19 deaths were conflated with baseline health, peer influence, and familial influence. Themes regarding precautions included the following: proper mask use, hand washing/ sanitizing, avoiding large crowds/small crowds only, physical distancing, COVID-19 testing/symptom monitoring, and COVID-19 vaccination., (© 2021. W. Montague Cobb-NMA Health Institute.)

Dopaminergic medication is widely used to alleviate motor symptoms of Parkinson's disease, but these medications also impact cognition with significant variability across patients. It is hypothesized that dopaminergic medication impacts cognition and working memory in Parkinson's disease by modulating frontoparietal-basal ganglia cognitive control circuits, but little is known about the underlying causal signalling mechanisms and their relation to individual differences in response to dopaminergic medication. Here we use a novel state-space computational model with ultra-fast (490 ms resolution) functional MRI to investigate dynamic causal signalling in frontoparietal-basal ganglia circuits associated with working memory in 44 Parkinson's disease patients ON and OFF dopaminergic medication, as well as matched 36 healthy controls. Our analysis revealed aberrant causal signalling in frontoparietal-basal ganglia circuits in Parkinson's disease patients OFF medication. Importantly, aberrant signalling was normalized by dopaminergic medication and a novel quantitative distance measure predicted individual differences in cognitive change associated with medication in Parkinson's disease patients. These findings were specific to causal signalling measures, as no such effects were detected with conventional non-causal connectivity measures. Our analysis also identified a specific frontoparietal causal signalling pathway from right middle frontal gyrus to right posterior parietal cortex that is impaired in Parkinson's disease. Unlike in healthy controls, the strength of causal interactions in this pathway did not increase with working memory load and the strength of load-dependent causal weights was not related to individual differences in working memory task performance in Parkinson's disease patients OFF medication. However, dopaminergic medication in Parkinson's disease patients reinstated the relation with working memory performance. Our findings provide new insights into aberrant causal brain circuit dynamics during working memory and identify mechanisms by which dopaminergic medication normalizes cognitive control circuits., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: Electroconvulsive therapy (ECT) remains the benchmark for treatment resistant depression, yet its cognitive adverse effects have a negative impact on treatment. A predictive safety biomarker early in ECT treatment is needed to identify patients at cognitive risk to maximize therapeutic outcomes and minimize adverse effects. We used ictal electroencephalography frequency analysis from suprathreshold treatments to assess the relationships between ECT dose, ictal power across different frequency domains, and cognitive outcomes., Methods: Seventeen subjects with treatment resistant depression received right unilateral ECT. Structural magnetic resonance imaging was obtained pre-ECT for electric field modeling to assess ECT dose. Serial assessments with 24-lead electroencephalography captured ictal activity. Clinical and cognitive assessments were performed before and after ECT. The primary cognitive outcome was the change in Delis Kaplan Executive Function Verbal Fluency Letter Fluency., Results: Ictal theta (4-8 Hz) power in the Fp1/Fp2 channels was associated with both whole-brain electric field strength (t(2,12) = 19.5, P = 0.007)/(t(2,10) = 21.85, P = 0.02) and Delis Kaplan Executive Function Verbal Fluency Letter Fluency scores (t(2,12) = -2.05, P = 0.05)/(t(2,10) = -2.20, P = 0.01). Other frequency bands (beta, alpha, delta, and gamma) did not demonstrate this relationship., Conclusions: This pilot data identify ictal theta power as a potential safety biomarker in ECT and is related to the strength of the ECT dose. Ictal theta power could prove to be a convenient and powerful tool for clinicians to identify those patients most susceptible to cognitive impairment early in the treatment series. Additional studies are needed to assess the role of longitudinal changes in ictal theta power throughout the ECT series., Competing Interests: S.W.M. is a consultant to Pearson Assessment. The other authors have no conflicts of interest or financial disclosures to report., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc.)

Cognitive control is the ability to act according to plan. Problems with cognitive control are a primary symptom and a major decrement of quality of life in Parkinson's disease (PD). Individuals with PD have problems with seemingly different controlled processes (e.g., task switching, impulsivity, gait disturbance, apathetic motivation). We review how these varied processes all rely upon disease-related alteration of common neural substrates, particularly due to dopaminergic imbalance. A comprehensive understanding of the neural systems underlying cognitive control will hopefully lead to more concise and reliable explanations of distributed deficits. However, high levels of clinical heterogeneity and medication-invariant control deficiencies suggest the need for increasingly detailed elaboration of the neural systems underlying control in PD., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Cognitive impairment in older adults is a rapidly growing public health concern as the elderly population dramatically grows worldwide. While it is generally assumed that cognitive deficits in older adults are associated with reduced brain flexibility, quantitative evidence has been lacking. Here, we investigate brain flexibility in healthy older adults (ages 60-85) using a novel Bayesian switching dynamical system algorithm and ultrafast temporal resolution (TR = 490 ms) whole-brain fMRI data during performance of a Sternberg working memory task. We identify latent brain states and characterize their dynamic temporal properties, including state transitions, associated with encoding, maintenance, and retrieval. Crucially, we demonstrate that brain inflexibility is associated with slower and more fragmented transitions between latent brain states, and that brain inflexibility mediates the relation between age and cognitive inflexibility. Our study provides a novel neurocomputational framework for investigating latent dynamic circuit processes underlying brain flexibility and cognition in the context of aging., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Attention is inherently biased towards the visual modality during most multisensory scenarios in adults, but the developmental trajectory towards visual dominance has not been fully elucidated. More recent evidence in primates and adult humans suggests a modality-specific stratification of the prefrontal cortex. The current study therefore used functional magnetic resonance imaging (fMRI) to investigate the neuronal correlates of proactive (following cues) and reactive (following probes) cognitive control for simultaneous audio-visual stimulation in 67 healthy adolescents (13-18 years old). Behavioral results were only partially supportive of visual dominance in adolescents, with both reduced response times and accuracy during attend-visual relative to attend-auditory trials. Differential activation of medial and lateral prefrontal cortex for processing incongruent relative to congruent stimuli (reactive control) was also only observed during attend-visual trials. There was no evidence of modality-specific prefrontal cortex stratification during the active processing of multisensory stimuli or during separate functional connectivity analyses. Attention-related modulations were also greater within visual relative to auditory cortex, but were less robust than observed in previous adult studies. Collectively, current results suggest a continued transition towards visual dominance in adolescence, as well as limited modality-specific specialization of prefrontal cortex and attentional modulations of unisensory cortex., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Affinity maturation is a powerful technique in antibody engineering for the in vitro evolution of antigen binding interactions. Key to the success of this process is the expansion of sequence and combinatorial diversity to increase the structural repertoire from which superior binding variants may be selected. However, conventional strategies are often restrictive and only focus on small regions of the antibody at a time. In this study, we used a method that combined antibody chain shuffling and a staggered-extension process to produce unbiased libraries, which recombined beneficial mutations from all six complementarity-determining regions (CDRs) in the affinity maturation of an inhibitory antibody to Arginase 2 (ARG2). We made use of the vast display capacity of ribosome display to accommodate the sequence space required for the diverse library builds. Further diversity was introduced through pool maturation to optimize seven leads of interest simultaneously. This resulted in antibodies with substantial improvements in binding properties and inhibition potency. The extensive sequence changes resulting from this approach were translated into striking structural changes for parent and affinity-matured antibodies bound to ARG2, with a large reorientation of the binding paratope facilitating increases in contact surface and shape complementarity to the antigen. The considerable gains in therapeutic properties seen from extensive sequence and structural evolution of the parent ARG2 inhibitory antibody clearly illustrate the advantages of the unbiased approach developed, which was key to the identification of high-affinity antibodies with the desired inhibitory potency and specificity., Competing Interests: Competing interest statement: A patent application has been filed on antibodies related to this work (UK Patent Application No. GB1912030.2 filed on 21 August 2019: Binding Molecules [ARG2]).The authors declare no competing interest.

Arginase 2 (ARG2) is a binuclear manganese metalloenzyme that catalyzes the hydrolysis of L-arginine. The dysregulated expression of ARG2 within specific tumor microenvironments generates an immunosuppressive niche that effectively renders the tumor 'invisible' to the host's immune system. Increased ARG2 expression leads to a concomitant depletion of local L-arginine levels, which in turn leads to suppression of anti-tumor T-cell-mediated immune responses. Here we describe the isolation and characterization of a high affinity antibody (C0021158) that inhibits ARG2 enzymatic function completely, effectively restoring T-cell proliferation in vitro . Enzyme kinetic studies confirmed that C0021158 exhibits a noncompetitive mechanism of action, inhibiting ARG2 independently of L-arginine concentrations. To elucidate C0021158's inhibitory mechanism at a structural level, the co-crystal structure of the Fab in complex with trimeric ARG2 was solved. C0021158's epitope was consequently mapped to an area some distance from the enzyme's substrate binding cleft, indicating an allosteric mechanism was being employed. Following C0021158 binding, distinct regions of ARG2 undergo major conformational changes. Notably, the backbone structure of a surface-exposed loop is completely rearranged, leading to the formation of a new short helix structure at the Fab-ARG2 interface. Moreover, this large-scale structural remodeling at ARG2's epitope translates into more subtle changes within the enzyme's active site. An arginine residue at position 39 is reoriented inwards, sterically impeding the binding of L-arginine. Arg39 is also predicted to alter the p K of a key catalytic histidine residue at position 160, further attenuating ARG2's enzymatic function. A of a key catalytic histidine residue at position 160, further attenuating ARG2's enzymatic function. In silico molecular docking simulations predict that L-arginine is unable to bind effectively when antibody is bound, a prediction supported by isothermal calorimetry experiments using an L-arginine mimetic. Specifically, targeting ARG2 in the tumor microenvironment through the application of C0021158, potentially in combination with standard chemotherapy regimens or alternate immunotherapies, represents a potential new strategy to target immune cold tumors.

Nomenclatural type definitions are one of the most important concepts in biological nomenclature. Being physical objects that can be re-studied by other researchers, types permanently link taxonomy (an artificial agreement to classify biological diversity) with nomenclature (an artificial agreement to name biological diversity). Two proposals to amend the International Code of Nomenclature for algae, fungi, and plants (ICN), allowing DNA sequences alone (of any region and extent) to serve as types of taxon names for voucherless fungi (mainly putative taxa from environmental DNA sequences), have been submitted to be voted on at the 11 th International Mycological Congress (Puerto Rico, July 2018). We consider various genetic processes affecting the distribution of alleles among taxa and find that alleles may not consistently and uniquely represent the species within which they are contained. Should the proposals be accepted, the meaning of nomenclatural types would change in a fundamental way from physical objects as sources of data to the data themselves. Such changes are conducive to irreproducible science, the potential typification on artefactual data, and massive creation of names with low information content, ultimately causing nomenclatural instability and unnecessary work for future researchers that would stall future explorations of fungal diversity. We conclude that the acceptance of DNA sequences alone as types of names of taxa, under the terms used in the current proposals, is unnecessary and would not solve the problem of naming putative taxa known only from DNA sequences in a scientifically defensible way. As an alternative, we highlight the use of formulas for naming putative taxa (candidate taxa) that do not require any modification of the ICN.

This study examined the association between size of the caudate nuclei and intelligence. Based on the central role of the caudate in learning, as well as neuroimaging studies linking greater caudate volume to better attentional function, verbal ability, and dopamine receptor availability, we hypothesized the existence of a positive association between intelligence and caudate volume in three large independent samples of healthy adults (total N = 517). Regression of IQ onto bilateral caudate volume controlling for age, sex, and total brain volume indicated a significant positive correlation between caudate volume and intelligence, with a comparable magnitude of effect across each of the three samples. No other subcortical structures were independently associated with IQ, suggesting a specific biological link between caudate morphology and intelligence., (© 2014 Wiley Periodicals, Inc.)

There are no usable herbarium specimens for the type of Alpova rubescens; therefore a lectotype and an epitype are designated hereby to preserve current usage of the name. As lectotype the Vittadini's Fig. XII E/Tab. IV (from Monographia Tubera-cearum) was selected. The epitype chosen for A. rubescens is a recent large collection from Liguria (Italy). Furthermore to investigate the phylogenetic position of A. rubescens among Alpova spp. comparative 28S-rDNA gene sequence analyses were conducted. The new combination Rhizopogon alexsmithii (Trappe) Vizzini & Zotti is proposed.