A comparison of the venom proteomes and potential therapeutics of 3 African naja subgenera.

African cobras (Naja species) represent one of the most encountered medically important snakes in Africa. They are classified as African spitting (Afronaja subgenus) and non-spitting cobras (Uraeus and Boulengerina subgenera) with similar and different characteristics. Snake venom toxins including three-finger toxin (3FTx), phospholipase A2 (PLA2), and snake venom metalloproteinase (SVMP) cause snakebite envenomation leading to morbidity and mortality. The profile of the proteome of African cobra venoms will help to develop safer and more effective antivenoms. The approval of Captopril by the US Food and Drug Administration (FDA) for the treatment of cardiovascular diseases, has led to intensified research towards possible use of venom toxins as therapeutics. In this review, we compare the venom proteome profile of 3 African Naja subgenera. In both Afronaja and Boulengerina subgenera, 3FTx (Afronaja-69.79%; Boulengerina-60.56%) followed by PLA2 (Afronaja-21.15%; Boulengerina-20.21%) dominated the venoms compared to the Uraeus subgenus dominated by 3FTx (84.55%) with little to no PLA2 abundance (0.8%). The venom of subgenus Uraeus was distinct from the other two subgenera by the almost total absence of PLA2, thus indicating little or no contribution of PLA2 in the envenomation caused by Uraeus compared to Afronaja and Boulengerina. Furthermore, we report studies on the experimental testing of African cobra venoms and toxins against diseases including anti-cancer properties.

Decoding the language of first impressions: Comparing models of first impressions of faces derived from free-text descriptions and trait ratings.

First impressions formed from facial appearance predict important social outcomes. Existing models of these impressions indicate they are underpinned by dimensions of Valence and Dominance, and are typically derived by applying data reduction methods to explicit ratings of faces for a range of traits. However, this approach is potentially problematic because the trait ratings may not fully capture the dimensions on which people spontaneously assess faces. Here, we used natural language processing to extract 'topics' directly from participants' free-text descriptions (i.e., their first impressions) of 2222 face images. Two topics emerged, reflecting first impressions related to positive emotional valence and warmth (Topic 1) and negative emotional valence and potential threat (Topic 2). Next, we investigated how these topics were related to Valence and Dominance components derived from explicit trait ratings. Collectively, these components explained only ~44% of the variance in the topics extracted from free-text descriptions and suggested that first impressions are underpinned by correlated valence dimensions that subsume the content of existing trait-rating-based models. Natural language offers a promising new avenue for understanding social cognition, and future work can examine the predictive utility of natural language and traditional data-driven models for impressions in varying social contexts.

Exploring okra-derived compounds as prospective aromatase inhibitors: a computational study for enhanced breast cancer therapy.

Estrogen receptor-positive breast cancer represents itself as the most prevalent malignancy among postmenopausal women. One of the promising therapeutic approaches involves the use of Aromatase inhibitors, which competitively bind to Aromatase, reducing estrone and estradiol levels. While current drugs have improved survival rates, they are not without adverse effects. Consequently, this study explores the computational screening of medicinally relevant compounds derived from okra (Abelmoschus esculentus) for potential Aromatase inhibition. Molecular docking employing AMDock v1.5.2 was utilized to assess binding affinities with Aromatase (PDB:3EQM). Subsequently, in-depth molecular interactions were examined using Discovery Studio Visualizer v4.5, and the stability of docked complexes was evaluated via molecular dynamics with the GROMACS package, focusing on RMSD, RMSF, H-bond count, SASA, Free energy landscape, Principal Component Analysis and binding affinity assessment. The pharmacokinetic properties of the okra compounds were predicted using admetSAR v2.0. Our findings highlight Quercetin 3-gentiobioside as a standout candidate, demonstrating superior binding affinity (-10 kcal/mol) and an estimated Ki of 46.77 nM compared to letrozole and other okra compounds. Molecular dynamic analysis confirms the stability of Quercetin 3-gentiobioside binding in terms of H-bonds and conformational integrity. In conclusion, our computational investigation identifies Quercetin 3-gentiobioside, along with Quercetin 3-O-rutinoside and Hyperin, as promising candidates for preclinical studies in the pursuit of potential Aromatase inhibitors.Communicated by Ramaswamy H. Sarma.

Re-evaluating the Role of Partnership-Related Perceptions in Women's Preferences for Men with Masculine Face Shapes.

Many researchers have proposed that women perceive men with masculine face shapes to be less suitable as parents and long-term partners than men with feminine face shapes, causing women to find masculine men more attractive for short-term than long-term relationships. However, recent work shows that results obtained using the type of experimentally manipulated stimuli that were employed in studies presenting evidence for these claims are not necessarily observed when natural (i.e., unmanipulated) face stimuli were used to suggest that the evidence for these claims may need to be revaluated. Consequently, we tested for possible relationships between ratings of natural male faces for parenting- and relationship-related traits and shape masculinity (Study 1) and also tested whether women's preferences for shape masculinity were stronger when natural male faces were rated for short-term relationships than when natural male faces were rated for long-term relationships (Studies 2 and 3). We saw no evidence for either of these predictions, instead finding that men with more attractive faces were perceived to be better parents and better long-term partners. Thus, our findings do not support the widely held view that masculine men are more attractive for short-term relationships because they are perceived to be unlikely to invest time and effort in their romantic partners and offspring.

Heterobimetallic 3d-4f complexes supported by a Schiff-base tripodal ligand.

Complexes featuring multiple metal centres are of growing interest regarding metal-metal cooperation and its tuneability. Here the synthesis and characterisation of heterobimetallic complexes of a 3d metal (4: Mn, 5: Co) and lanthanum supported by a (1,1,1-tris[(3-methoxysalicylideneamino)methyl]ethane) ligand is reported, as well as discussion of their electronic structure via electron paramagnetic resonance (EPR) spectroscopy, electrochemical experiments and computational studies. Competitive binding experiments of the ligand and various metal salts unequivocally demonstrate that in these heterobimetallic complexes the 3d metal (Mn, Co) selectively occupies the κ6-N3O3 binding site of the ligand, whilst La occupies the κ6-O6 metal binding site in line with their relative oxophilicities. EPR spectroscopy supported by density functional theory analysis indicates that the 3d metal is high spin in both cases (S = 5/2 (Mn), 3/2 (Co)). Cyclic voltammetry studies on the Mn/La and Co/La bimetallic complexes revealed a quasi-reversible Mn2+/3+ redox process and poorly-defined irreversible oxidation events respectively.

No evidence that averaging voices influences attractiveness.

Vocal attractiveness influences important social outcomes. While most research on the acoustic parameters that influence vocal attractiveness has focused on the possible roles of sexually dimorphic characteristics of voices, such as fundamental frequency (i.e., pitch) and formant frequencies (i.e., a correlate of body size), other work has reported that increasing vocal averageness increases attractiveness. Here we investigated the roles these three characteristics play in judgments of the attractiveness of male and female voices. In Study 1, we found that increasing vocal averageness significantly decreased distinctiveness ratings, demonstrating that participants could detect manipulations of vocal averageness in this stimulus set and using this testing paradigm. However, in Study 2, we found no evidence that increasing averageness significantly increased attractiveness ratings of voices. In Study 3, we found that fundamental frequency was negatively correlated with male vocal attractiveness and positively correlated with female vocal attractiveness. By contrast with these results for fundamental frequency, vocal attractiveness and formant frequencies were not significantly correlated. Collectively, our results suggest that averageness may not necessarily significantly increase attractiveness judgments of voices and are consistent with previous work reporting significant associations between attractiveness and voice pitch.

Economic impacts of marine debris encounters on commercial shrimping.

The commercial shrimping industry is subjected to myriad stressors that have led to financial hardships among industry members. One of these stressors is marine debris; however, there is limited understanding of the type and magnitude of impacts. Quantitative methods of estimating the economic impacts of marine debris on the commercial shrimping industry were developed. From June to December 2019, participating shrimpers submitted 393 daily summaries, including shrimping activities, marine debris encounters, damages, and impacts. The impacts of marine debris encounters were assessed from reports of daily damages to fishing assets, daily lost fishing time, daily loss-catch ratios, and daily catch losses. The results of this study demonstrate substantial negative economic impacts on commercial shrimpers related to marine debris encounters. About 17 % of shrimp caught were lost due to marine debris encounters, resulting in foregone total sales and job impacts of $3.2 million and 33 jobs in shrimping and associated businesses.

Snake venom toxins: Potential anticancer therapeutics.

Snake venom contains a cocktail of compounds dominated by proteins and peptides, which make up the toxin. The toxin components of snake venom attack several targets in the human body including the neuromuscular system, kidney and blood coagulation system and cause pathologies. As such, the venom toxins can be managed and used for the treatment of these diseases. In this regard, Captopril used in the treatment of cardiovascular diseases was the first animal venom toxin-based drug approved by the US Food and Drug Administration and the European Medicines Agency. Cancers cause morbidity and mortality worldwide. Due to side effects associated with the current cancer treatments including chemotherapy, radiotherapy, immunotherapy, hormonal therapy and surgery, there is a need to improve the efficacy of current treatments and/or develop novel drugs from natural sources including animal toxin-based drugs. There is a long history of earlier and ongoing studies implicating snake venom toxins as potential anticancer therapies. Here, we review the role of crude snake venoms and toxins including phospholipase A2, L-amino acid oxidase, C-type lectin and disintegrin as potential anticancer agents tested in cancer cell lines and animal tumour models in comparison to normal cell lines. Some of the anti-tumour activities of snake venom toxins include induction of cytotoxicity, apoptosis, cell cycle arrest and inhibition of metastasis, angiogenesis and tumour growth. We thus propose the advancement of multidisciplinary approaches to more pre-clinical and clinical studies for enhanced bioavailability and targeted delivery of snake venom toxin-based anticancer drugs.

Correction: Academic global surgical competencies: A modified Delphi consensus study.

[This corrects the article DOI: 10.1371/journal.pgph.0002102.].

Assessing the roles of shape prototypicality and sexual dimorphism in ratings of the trustworthiness of faces.

Perceptions of the trustworthiness of faces predict important social outcomes, including economic exchange and criminal sentencing decisions. However, the specific facial characteristics that drive trustworthiness perceptions remain poorly understood. Here we investigated this issue by exploring possible relationships between ratings of the trustworthiness of face images and objective assessments of two aspects of face shape that researchers have previously argued are important for perceptions of trustworthiness: distinctiveness and sexual dimorphism. Here we report that faces with more distinctive shapes are rated as less trustworthy, but that sexual dimorphism of face shape is not significantly correlated with trustworthiness ratings. These results suggest that distinctiveness of face shape plays a more important role in trustworthiness perceptions than does sexual dimorphism and suggest that perceptions of trustworthiness may stem, at least in part, from the 'anomalous-is-bad' stereotype.

The importance of face-shape masculinity for perceptions of male dominance depends on study design.

Dominance perceptions play an important role in social interactions. Although many researchers have proposed that shape masculinity is an important facial cue for dominance perceptions, evidence for this claim has come almost exclusively from studies that assessed perceptions of experimentally manipulated faces using forced-choice paradigms. Consequently, we investigated the role of masculine shape characteristics in perceptions of men's facial dominance (1) when shape-manipulated stimuli were presented in a forced-choice paradigm and (2) when unmanipulated face images were rated for dominance and shape masculinity was measured from face images. Although we observed large effects of masculinity on dominance perceptions when we used the forced-choice method (Cohen's ds = 2.51 and 3.28), the effect of masculinity on dominance perceptions was considerably smaller when unmanipulated face images were rated and shape masculinity measured from face images (Cohen's ds = 0.44 and 0.62). This pattern was observed when faces were rated separately for physical dominance, social dominance, and masculinity, and was seen for two different sets of stimuli. Collectively, these results suggest that shape masculinity may not be a particularly important cue for dominance perceptions when faces vary simultaneously on multiple dimensions, as is the case during everyday social interactions.

Academic global surgical competencies: A modified Delphi consensus study.

Academic global surgery is a rapidly growing field that aims to improve access to safe surgical care worldwide. However, no universally accepted competencies exist to inform this developing field. A consensus-based approach, with input from a diverse group of experts, is needed to identify essential competencies that will lead to standardization in this field. A task force was set up using snowball sampling to recruit a broad group of content and context experts in global surgical and perioperative care. A draft set of competencies was revised through the modified Delphi process with two rounds of anonymous input. A threshold of 80% consensus was used to determine whether a competency or sub-competency learning objective was relevant to the skillset needed within academic global surgery and perioperative care. A diverse task force recruited experts from 22 countries to participate in both rounds of the Delphi process. Of the n = 59 respondents completing both rounds of iterative polling, 63% were from low- or middle-income countries. After two rounds of anonymous feedback, participants reached consensus on nine core competencies and 31 sub-competency objectives. The greatest consensus pertained to competency in ethics and professionalism in global surgery (100%) with emphasis on justice, equity, and decolonization across multiple competencies. This Delphi process, with input from experts worldwide, identified nine competencies which can be used to develop standardized academic global surgery and perioperative care curricula worldwide. Further work needs to be done to validate these competencies and establish assessments to ensure that they are taught effectively.

Loss of cholinergic receptor muscarinic 1 impairs cortical mitochondrial structure and function: implications in Alzheimer's disease.

Introduction: Cholinergic Receptor Muscarinic 1 (CHRM1) is a G protein-coupled acetylcholine (ACh) receptor predominantly expressed in the cerebral cortex. In a retrospective postmortem brain tissues-based study, we demonstrated that severely (≥50% decrease) reduced CHRM1 proteins in the temporal cortex of Alzheimer's patients significantly correlated with poor patient outcomes. The G protein-mediated CHRM1 signal transduction cannot sufficiently explain the mechanistic link between cortical CHRM1 loss and the appearance of hallmark Alzheimer's pathophysiologies, particularly mitochondrial structural and functional abnormalities. Therefore, the objective of this study was to analyze the molecular, ultrastructural, and functional properties of cortical mitochondria using CHRM1 knockout (Chrm1-/-) and wild-type mice to identify mitochondrial abnormalities. Methods: Isolated and enriched cortical mitochondrial fractions derived from wild-type and Chrm1-/- mice were assessed for respiratory deficits (oxygen consumption) following the addition of different substrates. The supramolecular assembly of mitochondrial oxidative phosphorylation (OXPHOS)-associated protein complexes (complex I-V) and cortical mitochondrial ultrastructure were investigated by blue native polyacrylamide gel electrophoresis and transmission electron microscopy (TEM), respectively. A cocktail of antibodies, specific to Ndufb8, Sdhb, Uqcrc2, Mtco1, and Atp5a proteins representing different subunits of complexes I-V, respectively was used to characterize different OXPHOS-associated protein complexes. Results: Loss of Chrm1 led to a significant reduction in cortical mitochondrial respiration (oxygen consumption) concomitantly associated with reduced oligomerization of ATP synthase (complex V) and supramolecular assembly of complexes I-IV (Respirasome). Overexpression of Chrm1 in transformed cells (lacking native Chrm1) significantly increased complex V oligomerization and respirasome assembly leading to enhanced respiration. TEM analysis revealed that Chrm1 loss led to mitochondrial ultrastructural defects and alteration in the tinctorial properties of cortical neurons causing a significant increase in the abundance of dark cortical neurons (Chrm1-/- 85% versus wild-type 2%). Discussion: Our findings indicate a hitherto unknown effect of Chrm1 deletion in cortical neurons affecting mitochondrial function by altering multiple interdependent factors including ATP synthase oligomerization, respirasome assembly, and mitochondrial ultrastructure. The appearance of dark neurons in Chrm1-/- cortices implies potentially enhanced glutamatergic signaling in pyramidal neurons under Chrm1 loss condition. The findings provide novel mechanistic insights into Chrm1 loss with the appearance of mitochondrial pathophysiological deficits in Alzheimer's disease.

The Impact of Global Collaboration on the Academic Focus of the West African College of Surgeons: Are Worldwide Efforts Aligning with Local Priorities?

BACKGROUND: Global collaboration has the potential to induce a shift in research focus away from the priorities of those in low- and low-middle-income countries (LICs and LMICs). This study quantified international collaboration among surgery publications by Fellows of the West African College of Surgeons (WACS) and investigated if collaboration with upper-middle-income and high-income countries (UMICs and HICs) decreases the homophily of research focus. METHODS: Publications by WACS surgery Fellows from 1960 to 2019 were characterized as local WACS publications, collaborative publications without UMIC/HIC participation, or collaborative publications with UMIC/HIC participation. Research topics were determined for each publication, and topic percentages were compared between collaboration groups. RESULTS: We analyzed 5065 publications. Most (3690 publications, 73%) were local WACS publications, while 742 (15%) were collaborative publications with UMIC/HIC participation and 633 (12%) were collaborative publications without UMIC/HIC participation. UMIC/HIC collaborations contributed to 49% of the increase (378 out of 766 publications) from 2000 to 2019. Topic homophily was significantly lower between local WACS publications and collaborations with UMIC/HIC participation (differed in nine research topics) than it was between local WACS publications and collaborations without UMIC/HIC participation (differed in two research topics). CONCLUSIONS: Publications without international collaboration comprise most WACS research, but the rate of UMIC/HIC collaborations is rapidly increasing. We found that UMIC/HIC collaborations decreased the homophily of topic focus in WACS publications, indicating that global collaborations need to have greater emphasis on the priorities of those in LICs and LMICs.

No evidence that sociosexual orientation moderates effects of conception probability on women's preferences for male facial masculinity.

Although many researchers have proposed that women will show stronger preferences for male facial masculinity when conception probability is high, empirical tests of this hypothesis have produced mixed results. One possible explanation for these inconsistent findings is that effects of conception probability on women's preferences for facial masculinity are moderated by additional factors not typically considered in these empirical tests. One such potential moderator is individual differences in women's openness to uncommitted sexual relationships (i.e., individual differences in women's sociosexual orientation); women who are more open to uncommitted sexual relationships might show stronger positive effects of conception probability on masculinity preferences, as their sexuality is more overt and sexual attitudes and behaviours are more diversified. Consequently, we analysed data from three independent samples (N = 2304, N = 483, and N = 339) to assess whether sociosexual orientation moderates the hypothesised positive effect of conception probability on women's facial masculinity preferences. Analyses showed no evidence that higher conception probability increased preferences for facial masculinity or that sociosexual orientation moderated the effect of conception probability on women's preferences for facial masculinity. While it remains possible that factors other than sociosexual orientation moderate effects of conception probability on masculinity preferences, our null results suggest that the mixed results for the effects of conception probability on facial masculinity preferences in previous studies are unlikely to be a consequence of failing to consider the moderating role of sociosexual orientation.

Hippocampal versus cortical deletion of cholinergic receptor muscarinic 1 in mice differentially affects post-translational modifications and supramolecular assembly of respiratory chain-associated proteins, mitochondrial ultrastructure, and respiration: implications in Alzheimer's disease.

Introduction: In a previous retrospective study using postmortem human brain tissues, we demonstrated that loss of Cholinergic Receptor Muscarinic 1 (CHRM1) in the temporal cortex of a subset of Alzheimer's patients was associated with poor survival, whereas similar loss in the hippocampus showed no such association. Mitochondrial dysfunction underlies Alzheimer's pathogenesis. Therefore, to investigate the mechanistic basis of our findings, we evaluated cortical mitochondrial phenotypes in Chrm1 knockout (Chrm1-/-) mice. Cortical Chrm1 loss resulted in reduced respiration, reduced supramolecular assembly of respiratory protein complexes, and caused mitochondrial ultrastructural abnormalities. These mouse-based findings mechanistically linked cortical CHRM1 loss with poor survival of Alzheimer's patients. However, evaluation of the effect of Chrm1 loss on mouse hippocampal mitochondrial characteristics is necessary to fully understand our retrospective human tissue-based observations. This is the objective of this study. Methods: Enriched hippocampal and cortical mitochondrial fractions (EHMFs/ECMFs, respectively) derived from wild-type and Chrm1-/- mice were used to measure respiration by quantifying real-time oxygen consumption, supramolecular assembly of oxidative phosphorylation (OXPHOS)-associated proteins by blue native polyacrylamide gel electrophoresis, post-translational modifications (PTMs) by isoelectric focusing (IEF), and mitochondrial ultrastructure by electron microscopy. Results: In contrast to our previous observations in Chrm1-/- ECMFs, EHMFs of Chrm1-/- mice significantly increased respiration with a concomitant increase in the supramolecular assembly of OXPHOS-associated proteins, specifically Atp5a and Uqcrc2, with no mitochondrial ultrastructural alterations. IEF of ECMFs and EHMFs from Chrm1-/- mice showed a decrease and an increase, respectively in a negatively charged (pH∼3) fraction of Atp5a relative to the wild-type mice, with a corresponding decrease or increase in the supramolecular assembly of Atp5a and respiration indicating a tissue-specific signaling effect. Discussion: Our findings indicate that loss of Chrm1 in the cortex causes structural, and physiological alterations to mitochondria that compromise neuronal function, whereas Chrm1 loss in the hippocampus may benefit neuronal function by enhancing mitochondrial function. This brain region-specific differential effect of Chrm1 deletion on mitochondrial function supports our human brain region-based findings and Chrm1-/- mouse behavioral phenotypes. Furthermore, our study indicates that Chrm1-mediated brain region-specific differential PTMs of Atp5a may alter complex-V supramolecular assembly which in turn regulates mitochondrial structure-function.

Should artificial intelligence be used in conjunction with Neuroimaging in the diagnosis of Alzheimer's disease?

Alzheimer's disease (AD) is a progressive, neurodegenerative disorder that affects memory, thinking, behavior, and other cognitive functions. Although there is no cure, detecting AD early is important for the development of a therapeutic plan and a care plan that may preserve cognitive function and prevent irreversible damage. Neuroimaging, such as magnetic resonance imaging (MRI), computed tomography (CT), and positron emission tomography (PET), has served as a critical tool in establishing diagnostic indicators of AD during the preclinical stage. However, as neuroimaging technology quickly advances, there is a challenge in analyzing and interpreting vast amounts of brain imaging data. Given these limitations, there is great interest in using artificial Intelligence (AI) to assist in this process. AI introduces limitless possibilities in the future diagnosis of AD, yet there is still resistance from the healthcare community to incorporate AI in the clinical setting. The goal of this review is to answer the question of whether AI should be used in conjunction with neuroimaging in the diagnosis of AD. To answer the question, the possible benefits and disadvantages of AI are discussed. The main advantages of AI are its potential to improve diagnostic accuracy, improve the efficiency in analyzing radiographic data, reduce physician burnout, and advance precision medicine. The disadvantages include generalization and data shortage, lack of in vivo gold standard, skepticism in the medical community, potential for physician bias, and concerns over patient information, privacy, and safety. Although the challenges present fundamental concerns and must be addressed when the time comes, it would be unethical not to use AI if it can improve patient health and outcome.

Different Perspectives on Retest Effects in the Context of Spatial Thinking: Interplay of Behavioral Performance, Cognitive Processing, and Cognitive Workload.

Retest effects refer to performance improvements in a final test by completing previous tests with the same or similar testing materials. Improvements in test-related skills and/or increasing familiarity with the stimulus materials are considered sources of the retest effect. The present study analyzes retest effects in the context of spatial thinking, considering complementing perspectives (behavioral performance, cognitive processing, and cognitive workload). N = 141 participants completed a recently developed ability test for the visualization factor of spatial thinking (R-Cube-Vis Test). This test provides the opportunity to monitor the progression of changes in solving behavior from item to item within each of the six distinct difficulty levels. Items of one difficulty level all require the same spatial solving strategy but vary in visual appearance. Multi-level models were estimated, with items on level 1 and participants on level 2. Results demonstrated retest effects as changes from the beginning to the end of a set of items within each difficulty level by increasing accuracy. Gaze patterns showed the development of solving strategies by participants through, e.g., shifting the focus on relevant item parts. Increasing familiarity with the stimulus materials was indicated in reduced reaction times and increased confidence ratings, but also by the results of a pupillary-based cognitive workload measure. Furthermore, differences between participants with overall high vs. low spatial ability were considered. In addition to a deeper understanding of the underlying mechanisms of the retest effect, the complementing perspectives provide more detailed information about individual ability profiles for diagnostic purposes.