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A fundamental goal in evolutionary biology and population genetics is to understand how selection shapes the fate of new mutations. Here, we test the null hypothesis that insertion-deletion (indel) events in protein-coding regions occur randomly with respect to secondary structures. We identified indels across 11,444 sequence alignments in mouse, rat, human, chimp, and dog genomes and then quantified their overlap with four different types of secondary structure-alpha helices, beta strands, protein bends, and protein turns-predicted by deep-learning methods of AlphaFold2. Indels overlapped secondary structures 54% as much as expected and were especially underrepresented over beta strands, which tend to form internal, stable regions of proteins. In contrast, indels were enriched by 155% over regions without any predicted secondary structures. These skews were stronger in the rodent lineages compared to the primate lineages, consistent with population genetic theory predicting that natural selection will be more efficient in species with larger effective population sizes. Nonsynonymous substitutions were also less common in regions of protein secondary structure, although not as strongly reduced as in indels. In a complementary analysis of thousands of human genomes, we showed that indels overlapping secondary structure segregated at significantly lower frequency than indels outside of secondary structure. Taken together, our study shows that indels are selected against if they overlap secondary structure, presumably because they disrupt the tertiary structure and function of a protein., (© The Author(s) 2024. Published by Oxford University Press on behalf of Society for Molecular Biology and Evolution.)

Here we examine whether our impressive ability to perceive upright faces arises from evolved orientation-specific mechanisms, our extensive experience with upright faces, or both factors. To do so, we tested Claudio, a man with a congenital joint disorder causing his head to be rotated back so that it is positioned between his shoulder blades. As a result, Claudio has seen more faces reversed in orientation to his own face than matched to it. Controls exhibited large inversion effects on all tasks, but Claudio performed similarly with upright and inverted faces in both detection and identity-matching tasks, indicating these abilities are the product of evolved mechanisms and experience. In contrast, he showed clear upright superiority when detecting "Thatcherized" faces (faces with vertically flipped features), suggesting experience plays a greater role in this judgment. Together, these findings indicate that both evolved orientation-specific mechanisms and experience contribute to our proficiency with upright faces., Competing Interests: The authors declare no competing interests., (© 2023 The Authors.)

Objective: The aims of this cross-sectional study were to evaluate the prevalence of MetS in PsA patients compared with sex- and age-matched healthy controls and to test possible associations with clinical and laboratory variables., Methods: The prevalence of MetS was determined for 76 PsA patients and 76 sex- and age-matched healthy controls, using the criteria of NCEP/ATPIII and Harmonizing, adjusted for South Americans. Multivariate logistic regression analysis was used to identify independent risk factors for MetS., Results: Metabolic syndrome was significantly more prevalent in the PsA group than in the control group (53.9% vs 18.4%, p < 0.001). Psoriatic arthritis was associated with hypertension, diabetes mellitus, increased waist circumference (WC), elevated body mass index, and raised levels of blood glucose and triglycerides. When comparing MetS and non-Mets PsA patients, MetS was not significantly associated with disease activity, skin involvement, or quality of life. In the logistic regression model, the variables independently associated with MetS were use of biologic disease-modifying antirheumatic drugs (p = 0.001), elevated arterial pressure (p = 0.006), age (p = 0.0015), WC (p = 0.004), and low HDL (p = 0.042)., Conclusions: In this study on PsA patients from Northeastern Brazil, MetS was highly prevalent and associated with biologic disease-modifying antirheumatic drugs use, increased WC, and low HDL., Competing Interests: The authors declare no conflict of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Musca domestica (Linnaeus, 1758) is a muscoid species that is widespread throughout the world and acts as a mechanical vector of different enteropathogens primarily in underdeveloped countries. The adult and its immature forms are associated with decaying organic matter and can be seen visiting human corpses and animal carcass, and the larvae can also cause an infestation on human and animal wounds, feeding on the tissues. These characteristics make them have a forensic significance and, mainly, a great sanitary importance. This study aimed to analyze and describe morphological aspects of their immature stages of M. domestica, including the eggs, the first-, second-, and third-instar larvae, and the puparium using scanning electron microscopy (SEM). The eggs have standard format that all muscoid flies shared. The exochorion has some modified cells that were used for embryonic respiration. The first-instar larvae present two openings on the posterior spiracle as in the second-instar larvae, but with the last one, we can observe the anterior spiracle structure. The third-instar larvae, as in some other Muscidae species, have a posterior spiracular opening with a sinuous form that is located near the edge of the spiracular plate. The puparium morphology is equal to the third instar with a respiratory structure that helps the breathing during the metamorphosis process. This article supports the need for knowledge over the morphological characteristics of the immature forms of the muscoid Diptera (Linnaeus, 1758) at the same time helping with the correct identification of this insect phase., (© The Author(s) 2020. Published by Oxford University Press on behalf of Entomological Society of America.All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Sacroiliac joint involvement is one of the earliest manifestations of psoriatic arthritis (PsA). Magnetic resonance imaging (MRI) is a useful tool in the early diagnosis of axial disease due to its sensitivity for detecting acute and chronic changes associated with sacroiliitis. In this study, we evaluated the prevalence of sacroiliitis, acute and structural image changes on MRI in PsA patients and identified predictive clinical, laboratory and disease activity factors. Cross-sectional study on PsA patients submitted to MRI of the sacroiliac joints. The scans were evaluated by two blinded radiologists and the level of agreement was calculated (kappa). Clinical, disease activity and quality-of-life indices (DAS28, BASDAI, PASI, MASES, HAQ, CRP, ESR) were estimated. The sample consisted of 45 PsA patients with a mean age of 50.1 ± 11.5 years. The prevalence of sacroiliitis was 37.8% (n = 17), 47% of which was unilateral. The kappa coefficient was 0.64. Only 5 (29.4%) of the 17 patients with sacroiliitis on MRI had back pain. The most prevalent acute and chronic changes on MRI were, respectively, subchondral bone edema (26.7%) and enthesitis (20%), periarticular erosions (26.7%) and fat metaplasia (13.3%). CRP levels were higher among sacroiliitis patients (p = 0.028), and time of psoriasis was positively associated with chronic lesions (p = 0.006). Sacroiliitis on MRI was highly prevalent in our sample of PsA patients. Raised CRP levels were significantly associated with sacroiliitis, and longer time of psoriasis was predictive of chronic sacroiliitis lesions. Most sacroiliitis patients displayed no clinical symptoms.

Small for gestational age (SGA) newborns have increased neonatal morbidity and mortality besides having a high risk of contracting chronic diseases during adult life. We compared foot length among 700 SGA and AGA newborns. Foot length was shorter in SGA newborns, both in term and preterm babies. Fetal growth restriction may impair foot growth and this finding may contribute to identify SGA newborns., (© The Author(s) 2015.)

A species-specific complex mixture of highly stable cuticular hydrocarbons (CHCs) covers the external surface of all insects. Components can be readily analyzed by gas chromatography coupled to mass spectrometry (GC-MS) to obtain a cuticular hydrocarbon profile, which may be used as an additional tool for the taxonomic differentiation of insect species and also for the determination of the age and sex of adult and immature forms. We used GC-MS to identify and quantify the CHCs of female and male Chrysomya putoria (Wiedemann, 1818) (Diptera: Calliphoridae) from one to five days old. CHCs ranged from C21 to C35 for females and from C21 to C37 in males. Major compounds were the same for both sexes and were 2-MeC28, C29:1, n-C29, 15-,13-MeC29, 2-MeC30, C31:1, n-C31 and 15-,13-MeC31. The relative abundance of each component, however, varied with age. Cluster Analysis using Bray-Curtis measure for abundance showed that cuticular hydrocarbon profiles are a strong and useful tool for the determination of age in adult C. putoria., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

The external surface of all insects is covered by a species-specific complex mixture of highly stable, very long chain cuticular hydrocarbons (CHCs). Gas chromatography coupled to mass spectrometry was used to identify CHCs from four species of Sarcophagidae, Peckia (Peckia) chrysostoma, Peckia (Pattonella) intermutans, Sarcophaga (Liopygia) ruficornis and Sarcodexia lambens. The identified CHCs were mostly a mixture of n-alkanes, monomethylalkanes and dimethylalkanes with linear chain lengths varying from 23 to 33 carbons. Only two alkenes were found in all four species. S. lambens had a composition of CHCs with linear chain lengths varying from C23 to C33, while the other three species linear chain lengths from 24 to 31 carbons. n-Heptacosane, n-nonacosane and 3-methylnonacosane, n-triacontane and n-hentriacontane occurred in all four species. The results show that these hydrocarbon profiles may be used for the taxonomic differentiation of insect species and are a useful additional tool for taxonomic classification, especially when only parts of the insect specimen are available., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Trypanosoma cruzi is the ethiological agent for Chagas disease in Latin America. This study aimed to test the trypanocidal effect of licarin A and burchellin isolated from plants in northeastern Brazil. These neolignans were tested on T. cruzi and on peritoneal macrophages, to evaluate drug toxicity. Epimastigote growth was inhibited in 45% with licarin A and 20% with burchellin with an IC(50)/96 h of 462.7 microM and 756 microM, respectively. Epimastigotes treated with licarin A presented swollen mitochondria and disorganized mitochondrial cristae, kDNA and Golgi complex. When treated with burchellin, they presented enormous autophagosomes and chromatin disorganization. Licarin A and burchellin were able to induce trypomastigote death with IC(50)/24 h of 960 microM and 520 microM, respectively. Although licarin A presented an IC(50) for trypomastigotes higher than for epimastigotes, both substances acted as therapeutic trypanocidal agents, because they were able to kill parasites without affecting macrophages. Due to our results, burchellin and licarin A need to be further analysed to observe if they may be used as alternative blood additive prophylaxis against Chagas disease, since it has been established that blood transfusion is an important mechanism in the transmission process., (Copyright 2009 Elsevier Inc. All rights reserved.)

Leishmaniasis is an important disease in widely dispersed regions of the world. In South America, visceral leishmaniasis (VL) is mainly caused by Leishmania chagasi. The morbidity associated with the infection is high, and death may occur in some untreated patients. Treatment has been based upon pentavalent antimonial drugs for more than half a century and problems, including development of resistance to antimonials and lack of efficacy against VL/HIV co-infections, have emphasized the need for new drugs. Squalene synthase (SQS) is an essential enzyme for the biosynthesis of protozoal sterol molecules. In this work, nineteen synthetic quinuclidines, potentially inhibitors of SQS, were tested against promastigote forms of L. chagasi and the IC50 values of the compounds were determined. The most active compounds had IC50 values of around 30 nM and induced complete growth arrest and cell lysis at sub-micromolar concentrations. We analyzed the morphological structure of the parasites treated with these compounds by transmission electron microscopy of thin sections. Treated parasites showed significant ultrastructural changes, which varied from discrete alterations to total destruction of the cells, depending on the drug concentration and the time of incubation. One important change observed was a typical swelling of the unique and highly branched mitochondrion, where the inner membrane lost its organization. There was an increase in the number of autophagosomal structures. Changes in the organization of the nuclear chromatin and alterations in the flagellar pocket and flagellar membrane were also observed.

An increasing number of protein kinases (PKs) of parasitic protozoa are being evaluated as drug targets. Some PK inhibitors display antiproliferative effects on protozoa. We tested three PK inhibitors on the growth and ultrastructure of epimastigotes of Trypanosoma cruzi and the effect of these drugs on intracellular amastigotes. They were staurosporine (serine/threonine kinase inhibitor), genistein (tyrosine kinase inhibitor), and wortmannin (phosphatidylinositol 3' (PI3) kinase inhibitor). All drugs inhibited epimastigote growth at the concentrations tested. Wortmannin inhibited parasite growth at the lowest concentrations. However, staurosporine was the most effective after 24 h treatment and genistein caused the stronger inhibition during the whole treatment (60-70% inhibition). The IC50 were: staurosporine: 6.43+/-1.28 microM; genistein: 6.54+/-1.86 microM; and wortmannin: 0.056+/-0.014 microM. These PK inhibitors had strong ultrastructural effects on the epimastigotes: abnormal chromatin condensation of the nucleus; loose flagellar membrane with the formation of blebs; incomplete cell division; autophagosomes and myelin-like figures. These drugs did not interfere with the division of intracellular amastigotes or with its differentiation to trypomastigotes. However, as trypanosomes have kinomes that contain a large set of protein kinases and phosphatases, PKs should not be disregarded as an important target for chemotherapy of Chagas disease.

Trypanosoma cruzi is the ethiological agent of Chagas disease. New compounds are being developed based on the biosynthesis and function of sterols, because T. cruzi has a requirement for specific endogenous sterols for growth and survival. Sterol biosynthesis inhibitors (SBIs) are drugs commonly used against fungal diseases. These drugs act by depleting essential and specific membrane components and/or inducing the accumulation of toxic intermediary or lateral products of the biosynthetic pathway. In this work we present the effects of WSP488, WSP501, and WSP561, specific inhibitors of Delta24(25)-sterol methyl transferase, on the ultrastructure of T. cruzi epimastigotes. All three drugs inhibited parasite multiplication at low concentrations, with IC50 values of 0.48, 0.44, and 0.48 muM, respectively, and induced marked morphological changes including (a) blockage of cell division; (b) swelling of the mitochondrion, with several projections and depressions; (c) swelling of the perinuclear space; (d) presence of autophagosomes and myelin-like figures; (e) enlargement of the flagellar pocket and of a cytoplasmic vacuole located in close association with the flagellar pocket; (f) detachment of the membrane of the cell body; and (g) formation of a vesicle at the surface of the parasite between the flagellar pocket and the cytostome. Our results show that these drugs are potent in vitro inhibitors of growth of T. cruzi.

Squalene synthase (SQS) catalyses the first committed step of sterol biosynthesis; a blockade of this enzyme does not affect the production of other essential isoprenoids. In the present study, 3-(biphenyl-4-yl)-3-hydroxyquinuclidine (BPQ-OH) and ER27856, two specific inhibitors of SQS, were tested against epimastigote forms of Trypanosoma cruzi. Both compounds inhibited parasite multiplication with IC(50) values of 24.3 and 4.5 microM, respectively and induced marked morphological changes. These changes included: (a) detachment of the plasma membrane from the cell body, forming blebs; (b) detachment of the membrane lining the cell body and the flagellum from the sub-pellicular and axonemal microtubules; (c) enlargement of the flagellar pocket; (d) enlargement of a vacuole localised close to the flagellar pocket, which may correspond to a contractile vacuole; (e) mitochondrial swelling, with the appearance of concentric structures formed by invaginations of the inner mitochondrial membrane; (f) alterations in the nucleus of some cells, where the chromatin appears in clumps, as described for apoptotic cells; and (g) blockage of cytokinesis. These alterations are interpreted as a consequence of the depletion of essential parasite sterols induced by the experimental compounds and the concomitant alteration of the physical properties of the parasite membranes.

This paper describes the synthesis of some novel azasterols based on (20R,22xi)-5alpha-pregnan-20-(piperidin-2-yl)-3beta,20-diol. These compounds are potential inhibitors of the enzyme sterol 24-methyltransferase (24-SMT), which is a vital enzyme in the biosynthesis of ergosterol and related 24-alkyl sterols. Structure-activity studies were undertaken to understand the important features for activity against the enzyme, with the aim of increasing activity and selectivity. The compounds were evaluated for inhibition of recombinant Leishmania major 24-SMT and the effect of compounds on sterol composition and parasite proliferation. Essentially, compounds which showed good activity against the recombinant enzyme had a significant effect on the sterol composition and growth of parasites. The activity of compounds was found to be related to the basicity and stereochemical location of the nitrogen. Also, presence of an unprotected 3beta-OH seemed to be important for activity. However, some azasterols which were not good inhibitors of 24-SMT also showed antiproliferative activity, suggesting that there may be other modes of actions of these compounds.

The effects of various levels of food deprivation on the oogenesis of P. megistus was studied. Immediately after the imaginal ecdysis, six groups (GI to GVI) of 15 couples each were formed. Each group was fed as follows: GI -- on days 5 and 25; G-II -- on days 5 and 35; GIII -- on days 5 and 45; GIV -- on day 20; GV -- on day 30; GVI -- on day 40 after the imaginal ecdysis. After the established fasting period, all groups were fed fortnightly. Fifteen couples were in the control group (CG), which was fed on the day 5 after the imaginal ecdysis and subsequently fortnightly. GI produced more eggs, matings and fertile eggs. GII had longer life spans, higher fecundity and hatchings. GIII had a shorter life span, low fecundity, fertility and hatchings. GVI presented the least favorable results for all parameters, except for the pre-oviposition period. The CG had the best results in all parameters when compared with all experimental groups.

Schistosomiasis mansoni affects the hepatic functional reserve. Clinical treatment with oxamniquine is not 100% effective and there has been found strain of this parasite resistant to this drug. The aims of this investigation were: (1) to examine the presence of residual parasite burden after medical and surgical treatment on adolescents with surgical schistosomiasis mansoni and (2) to assess the effect on the hepatic functional reserve in patients with and without residual infection. Twenty nine children with hepatosplenic schistosomiasis mansoni and bleeding esophageal varices were treated with oxamniquine. They underwent splenectomy, ligature of the left gastric vein and autologous implantation of spleen tissue into the greater omentum. After a mean post-operative follow up of five years they underwent rectal biopsy for schistosomotic egg search. They were divided in patients with and without infection. In 20 patients the submucosal egg search was negative, however, in 9 it was positive. The hepatic functional reserve in the patients without infection was as follows: 17 were Child-Pugh A and 3 Child-Pugh B. In the patients who were still infected 6 were Child-Pugh A and 3 Child-Pugh B. The chi2 analysis of the hepatic functional reserve showed chi2 = 3.19 - p= 0.07. From the results the following conclusion can be drawn: residual infection or reinfection in the follow up period had not interfered with the distribution of the hepatic functional reserve of the patients in this series. However, there was a trend for a decrease of this parameter in patients with residual infection.

The duration of the life cycle of Rhodnius robustus Larrousse, 1927 as well as the mortality rate of each nymphal instar were studied comparing groups fed on pigeon or on mouse blood weekly or fortnightly. This species showed a better development and lower mortality rate when fed on swiss mouse. The intervals between feedings apparently did not have influence on the shortening of the cycle. We suggest that laboratory colonies and experiments with R. robustus are better maintained when these triatomines are fed on swiss mouse.

The life cycle and reproductive patterns of Triatoma rubrofasciata were studied along with laboratory conditions for the establishment of a prolific colony. The insects were divided into four groups: two of them were maintained at room temperature (20.5 degrees C to 33 degrees C and 85% +/- 5% of relative humidity), the other two in a climatic chamber (CC) (temperature: 29 degrees C, humidity: 80% +/- 5%). The groups were fed weekly or fortnightly on Swiss mice. The females from the group kept in the CC and fed weekly had longer life span, as well as a higher number of eggs, fertile eggs and hatchings; the group kept in the CC and fed fortnightly had a shorter life span for the 1st, 2nd and 3rd instars and a lower mortality rate for all instars. It was concluded that a constant high temperature (CC at 29 degrees C) is the most suitable condition for the maintenance of a colony of T. rubrofasciata regardless of the interval between repasts.