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Deep sequencing of wastewater to detect SARS-CoV-2 has been used during the COVID-19 pandemic to monitor viral variants as they appear and circulate in communities. SARS-CoV-2 lineages of an unknown source that have not been detected in clinical samples, referred to as cryptic lineages, are sometimes repeatedly detected from specific locations. We have continued to detect one such lineage previously seen in a Missouri site. This cryptic lineage has continued to evolve, indicating continued selective pressure similar to that observed in Omicron lineages.

The intracellular bacterium Wolbachia is increasingly being utilised in control programs to limit the spread of arboviruses by Aedes mosquitoes. Achieving a better understanding of how Wolbachia strains can reduce viral replication/spread could be important for the long-term success of such programs. Previous studies have indicated that for some strains of Wolbachia, perturbations in lipid metabolism and cholesterol storage are vital in Wolbachia-mediated antiviral activity against the flaviviruses dengue and Zika; however, it has not yet been examined whether arboviruses in the alphavirus group are affected in the same way. Here, using the reporters for the alphavirus Semliki Forest virus (SFV) in Aedes albopictus cells, we found that Wolbachia strains wMel, wAu and wAlbB blocked viral replication/translation early in infection and that storage of cholesterol in lipid droplets is not key to this inhibition. Another alphavirus, o’nyong nyong virus (ONNV), was tested in both Aedes albopictus cells and in vivo in stable, transinfected Aedes aegypti mosquito lines. The strains wMel, wAu and wAlbB show strong antiviral activity against ONNV both in vitro and in vivo. Again, 2-hydroxypropyl-β-cyclodextrin (2HPCD) was not able to rescue ONNV replication in cell lines, suggesting that the release of stored cholesterol caused by wMel is not able to rescue blockage of ONNV. Taken together, this study shows that alphaviruses appear to be inhibited early in replication/translation and that there may be differences in how alphaviruses are inhibited by Wolbachia in comparison to flaviviruses.

ABSTRACT A sensitive and quantitative fluorescence-based approach is presented for characterizing fatty acid acquisition and lipid biosynthesis by asexually replicating, intraerythrocytic Plasmodium falciparum. We show that a BODIPY-containing, green-fluorescent fatty acid analog is efficiently and rapidly incorporated into parasite neutral lipids and phospholipids. Prelabeling with a red-fluorescent ceramide analog permits normalization and enables reliable quantitation of glycerolipid labeling. Inhibition of lipid labeling by competition with natural fatty acids and by acyl-coenzyme A synthetase and diacylglycerol acyltransferase inhibitors demonstrates that the fluorescent fatty acid probe is acquired, activated, and transferred to lipids through physiologically-relevant pathways. To assess its utility in discovering small molecules that block parasite lipid biosynthesis, the lipid labeling assay was used to screen a panel of mammalian lipase inhibitors and a selection of compounds from the “Malaria Box” anti-malarial collection. Several compounds were identified that inhibited the incorporation of the fluorescent fatty acid probe into lipids in cultured parasites at low micromolar concentrations. Two contrasting profiles of suppression of neutral lipid and phospholipid synthesis were observed, which implies the inhibition of distinct pathways. IMPORTANCE The human malaria parasite Plasmodium falciparum relies on fatty acid scavenging to supply this essential precursor of lipid synthesis during its asexual replication cycle in human erythrocytes. This dependence on host fatty acids represents a potential vulnerability that can be exploited to develop new anti-malarial therapies. The quantitative experimental approach described here provides a platform for simultaneously interrogating multiple facets of lipid metabolism- fatty acid uptake, fatty acyl-CoA synthesis, and neutral lipid and phospholipid biosynthesis- and of identifying cell-permeable inhibitors that are active in situ.

Wiele dowcipów wykorzystuje jako dodatkowy element humorystyczny stylizację na rozmowę osób o różnym statusie społecznym, mówiących różnymi odmianami tego samego języka. Osoba o wyższej pozycji używa standardowej odmiany języka (w tym przypadku angielskiego), natomiast osoba o niższym statusie społecznym posługuje się w większym lub mniejszym zakresie formą lokalnego dialektu (w tym przypadku szkockiego-angielskiego). Efektywność tego rodzaju stylizacji zależy od tego, na ile lokalna odmiana języka znana jest odbiorcy.

ABSTRACT The human malaria parasite Plasmodium falciparum causes disease as it replicates within the host’s erythrocytes. We have found that an erythrocyte serine hydrolase, acylpeptide hydrolase (APEH), accumulates within developing asexual parasites. Internalization of APEH was associated with a proteolytic event that reduced the size of the catalytic polypeptide from 80 to 55 kDa. A triazole urea APEH inhibitor, termed AA74-1, was employed to characterize the role of parasite-internalized APEH. In cell lysates, AA74-1 was a potent and highly selective inhibitor of both host erythrocyte and parasite-internalized APEH. When added to cultures of ring-stage parasites, AA74-1 was a poor inhibitor of replication over one asexual replication cycle; however, its potency increased dramatically after a second cycle. This enhancement of potency was not abrogated by the addition of exogenous isopentenyl pyrophosphate, the sole essential product of apicoplast metabolism. High-potency inhibition of parasite growth could be effected by adding AA74-1 to schizont-stage parasites, which resulted in parasite death at the early trophozoite stage of the ensuing replication cycle. Analysis of APEH inhibition in intact cultured cells revealed that host erythrocyte APEH, but not the parasite-internalized APEH pool, was inhibited by exogenous AA74-1. Our data support a model for the mode of parasiticidal activity of AA74-1 whereby sustained inactivation of host erythrocyte APEH is required prior to merozoite invasion and during parasite asexual development. Together, these findings provide evidence for an essential catalytic role for parasite-internalized APEH. IMPORTANCE Nearly half a million deaths were attributed to malaria in 2017. Protozoan parasites of the genus Plasmodium cause disease in humans while replicating asexually within the host’s erythrocytes, with P. falciparum responsible for most of the mortality. Understanding how Plasmodium spp. have adapted to their unique host erythrocyte environment is important for developing malaria control strategies. Here, we demonstrate that P. falciparum coopts a host erythrocyte serine hydrolase termed acylpeptide hydrolase. By showing that the parasite requires acylpeptide hydrolase activity for replication, we expand our knowledge of host cell factors that contribute to robust parasite growth.

Many excellent jokes can pose potential difficulties for tellers and listeners since they require considerable knowledge of the subject of the joke and have a long and elaborate narrative structure such that only a very skilled joke-teller can do justice to them. In a democratic, fast-moving, plural, urban world such features can create problems since they mean that on a particular occasion when jokes are being told some of the listeners may miss the point of the joke and others will feel inhibited from telling a joke. Jokes with seemingly pointless endings may likewise disappoint the broad masse, who like clear, well structured jokes with a strong resolution and who may be bored by one that disappears into nonsense. Each of these points will be considered in turn, partly from an analytical point of view and partly in relation to empirical observations of how jokes in the English language have evolved in the course of the twentieth century.

Socialism produces distinct forms of humorous ridicule that are relatively rare in capitalist, bourgeois democracies. These forms are arranged in a hierarchy that reflects the distribution of power in this type of social and political order, one which differs markedly from a bourgeois democracy or indeed even a traditional or dictatorial authoritarian society. Merely authoritarian societies lack the kind of over-riding ideology and central control of economic and cultural life that are the defining characteristics of socialism. Socialist humorous ridicule is cruel at the top; then comes an aggressive and admonishing, but in intention humorous, official ridicule employed by the state in pursuit of centrally defined political ends. Finally, there is the ridicule by ordinary people of the elite and the social order they have imposed on the masses who respond by spontaneously and autonomously inventing and circulating innumerable jokes and anecdotes. This pattern is a product of the exercise of a monopoly of political and economic power by the leaders of the Communist Party and the distinctive political inequality that characterises socialism, an inequality based not on ownership but on differential access to the power of the state. The rulers of merely authoritarian societies that were not socialist such as Franco’s Spain, Pinochet’s Chile or Afrikaner South Africa did not and could not attain the same kind of hegemony that was possible under socialism because there existed economic, religious, scientific and even legal institutions that enjoyed a substantial degree of independence from their political rulers. Accordingly, they did not exhibit to anything like the full extent the patterns of humour to be found under socialism. The aggregate patterns of humour in socialist societies must be treated not as interactions between individuals but as ‘social facts’ to be understood in relation to other social facts, notably the nature of political power, with both sets of social facts being contrasted with those to be found in the capitalist democracies that are the antithesis of socialism.

Two separate nonlinear differential systems are investigated in the frequency and time domains using plots generated by Mathematica. Spectral density plots are of particular interest as they can conveniently demonstrate the effect on a system of changing one of the parameters. The effects of the starting displacement on the nonlinear pendulum, and the behavior of the Lorenz system when the Rayleigh number is varied, are considered in this way.

We demonstrate that in many cases, known frame-dependent transport equations for a propagating electromagnetic 2-form in an arbitrarily curved space-time can be replaced by a much simpler set of frame-independent equations. The frame-dependent equations can then be more easily recovered from the simpler set presented here if required. The relationship of such transport equations to the WKB approximation is also briefly discussed.

Socialism produces distinct forms of humorous ridicule that are relatively rare in capitalist, bourgeois democracies. These forms are arranged in a hierarchy that reflects the distribution of power in this type of social and political order, one which differs markedly from a bourgeois democracy or indeed even a traditional or dictatorial authoritarian society. Merely authoritarian societies lack the kind of over-riding ideology and central control of economic and cultural life that are the defining characteristics of socialism. Socialist humorous ridicule is cruel at the top; then comes an aggressive and admonishing, but in intention humorous, official ridicule employed by the state in pursuit of centrally defined political ends. Finally, there is the ridicule by ordinary people of the elite and the social order they have imposed on the masses who respond by spontaneously and autonomously inventing and circulating innumerable jokes and anecdotes. This pattern is a product of the exercise of a monopoly of political and economic power by the leaders of the Communist Party and the distinctive political inequality that characterises socialism, an inequality based not on ownership but on differential access to the power of the state. The rulers of merely authoritarian societies that were not socialist such as Franco’s Spain, Pinochet’s Chile or Afrikaner South Africa did not and could not attain the same kind of hegemony that was possible under socialism because there existed economic, religious, scientific and even legal institutions that enjoyed a substantial degree of independence from their political rulers. Accordingly, they did not exhibit to anything like the full extent the patterns of humour to be found under socialism. The aggregate patterns of humour in socialist societies must be treated not as interactions between individuals but as ‘social facts’ to be understood in relation to other social facts, notably the nature of political power, with both sets of social facts being contrasted with those to be found in the capitalist democracies that are the antithesis of socialism.

Historically a much greater range of styles of literary humour were to be found in Bri[1]t sun than in the United States because Bi „.n was a much more hierarchical society with a divined elite and an aristocratic as well as a bourgeois aesthetic. In America there was a single dominant class, that of independent farmers and the businessmen and professional people of medium sized cities whose optimistic, egalitarian, moralistic, culture restricted the range of styles an aspiring American humorous writer could use. This restnctiveness remained long after American had become the world’s leading, richest and most techno[1]logically advanced economy. British humour alone was able to use styles that valued de[1]tachment from conventional morality and also took inequality for granted and hence devi[1]sed torms of aggressive mockery that could be directed downwards. British humour was also able to emplo> a greater reach of allusw eness, vocabulary and sophistication than was possible in America. It was the rise of Jev sh humour in America from a new initially immigrant population that valued things of the intellect for their own sake and which had also mastered the arts of detachment that enabled American literary humour to achieve a comparable degree of vanety and sophistication to that of Britain in the course of the twentith century.

Electrospinning, an economical technique, is widely used for biomedical scaffold fabrication, crucial in tissue and organ regeneration, particularly with biomaterials. Polymers, either pure or reinforced with ceramics, aid in cell proliferation and tissue formation. Polyhydroxybutyrate (PHB) is a promising biopolymer for tissue engineering, offering biocompatibility comparable to petroleum-derived polymers. Combining PHB with hydroxyapatite (HAp) enhances mechanical strength and osteoconductivity. This study aims to produce electrospun PHB microfibrous webs reinforced with HAp for scaffold fabrication. Morphological variations are analyzed through manipulation of electrospinning parameters. The study observed microfibrous webs with diameters ranging from 2 to 9 µm. Mechanical and microstructural evaluations demonstrate superior strength of PHB/HAp microfibrous webs compared to pure PHB, 1.23 MPa and 0.58 MPa respectively, demonstrating the efficacy of HAp reinforcement. These findings highlight the potential of PHB/HAp microfibrous webs in bone tissue engineering.

Abstract Background Although it is well established that prostate cancer (PCa) patients are more likely to experience clinical depression than their age-matched non-prostate cancer peers, and that such depression can have negative effects upon survival, little is known about the underlying nature of the depressive symptomatology that these men experience. In particular, the incidence of melancholic symptoms of depression, which are signs of increased risk of suicide and resistance to treatment, has not previously been reported in PCa patients. The present study aimed to measure the incidence and nature of Melancholia in PCa depression. Method A sample of 507 PCa patients in Queensland, Australia, completed anonymous and confidential questionnaires about their background, treatment status, and depression. Data were analysed to select depressive symptoms that were part of the definition of Melancholia vs those which were not. Regression was used to determine the links between Melancholia and overall depressive status, and factor analysis revealed the underlying components of Melancholia, which were mapped over time since diagnosis for 3 years. Results Psychometric data were satisfactory. Melancholia significantly predicted depressive status for the most depressed subset of patients, but not for the total sample. Melancholia was factored into its components of Anhedonia and Agitation, and the first of these was more powerful in predicting Melancholia. Variability over the 3 years following diagnosis was noted for each of these two components of Melancholia. Conclusions The strong presence of Melancholia in the depressive symptomatology of this sample of PCa patients suggests that some forms of treatment for depression may be more likely to succeed than others. The dominance of Anhedonia and Agitation over other symptoms of Melancholia also holds implications for treatment options when assisting these men to cope with their depression.

Abstract Background Ovarian adenocarcinoma is not generally discovered in patients until there has been widespread intraperitoneal dissemination, which is why ovarian cancer is the deadliest gynecologic malignancy. Though incompletely understood, the mechanism of peritoneal metastasis relies on primary tumor cells being able to detach themselves from the tumor, escape normal apoptotic pathways while free floating, and adhere to, and eventually invade through, the peritoneal surface. Our laboratory has previously shown that the Golgi glycosyltransferase, ST6Gal-I, mediates the hypersialylation of β1 integrins in colon adenocarcinoma, which leads to a more metastatic tumor cell phenotype. Interestingly, ST6Gal-I mRNA is known to be upregulated in metastatic ovarian cancer, therefore the goal of the present study was to determine whether ST6Gal-I confers a similarly aggressive phenotype to ovarian tumor cells. Methods Three ovarian carcinoma cell lines were screened for ST6Gal-I expression, and two of these, PA-1 and SKOV3, were found to produce ST6Gal-I protein. The third cell line, OV4, lacked endogenous ST6Gal-I. In order to understand the effects of ST6Gal-I on cell behavior, OV4 cells were stably-transduced with ST6Gal-I using a lentiviral vector, and integrin-mediated responses were compared in parental and ST6Gal-I-expressing cells. Results Forced expression of ST6Gal-I in OV4 cells, resulting in sialylation of β1 integrins, induced greater cell adhesion to, and migration toward, collagen I. Similarly, ST6Gal-I expressing cells were more invasive through Matrigel. Conclusion ST6Gal-I mediated sialylation of β1 integrins in ovarian cancer cells may contribute to peritoneal metastasis by altering tumor cell adhesion and migration through extracellular matrix.

Esse trabalho tem como objetivo explorar a relação entre o desenvolvimento dos intermediários financeiros e a volatilidade do crescimento econômico dos estados brasileiros, diante de choques reais e monetários. O trabalho realiza uma análise empírica com dados para os Estados brasileiros entre 2004 e 2015, estruturados em um painel dividido em três períodos, que visa calcular o impacto na volatilidade regional em diferentes instantes do tempo. Os resultados obtidos mostram que, diante de choques reais nos Estados, os intermediários financeiros locais atuam de forma a absorver a volatilidade do crescimento econômico. Por outro lado, os impactos estimados do sistema financeiro locais sobre os choques monetários estaduais foram não significativos.

En este trabajo se caracteriza la respuesta mecánica del mango en función de los problemas encontrados durante las etapas de producción y comercialización. Problemas como daños físicos provocados por la manipulación inadecuada de la fruta, sea en el momento de la cosecha, almacenamiento, procesamiento o transporte. Los problemas señalados son característicos de la falta de información sobre el máximo esfuerzo que el fruto puede soportar sin que el mismo sufra daño interno o rotura externa que comprometa su comercialización. Fueron realizados ensayos de compresión en mangos (Mangifera Indica) de las variedades “Keitt” y “Tommy Atkins”, en la posición natural de reposo, lo que posibilitó la determinación del módulo de elasticidad y la fuerza máxima soportada en función de las fases 1, 2 y 3 de maduración. El módulo de elasticidad se reduce con el avance de la fase de maduración, obteniéndose valores para la variedad “Keitt” de 2,065 MPa, 1,734 MPa y 1,381 MPa para las fases de maduración 1, 2 y 3 respectivamente, y para la variedad “Tommy Atkins” de 1,698 MPa, 1, 657 MPa y 1,518 para las mismas fases de maduración. Las medidas de las fuerzas máximas, que antecede la rotura de la fruta, soportadas por la variedad “Tommy Atkins” fueron superiores a las soportadas por la “Keitt”. Este hecho está relacionado con la diferente organización estructural de estas dos variedades, en la que la variedad “Tommy Atkins” presenta un porciento de fibra superior a la variedad “Keitt”.

The noise produced by farm machinery may cause hearing problems to its operators along the time. The objective of this study was to evaluate the sound power level emitted by agricultural tractor under static and dynamic conditions, in relation to the IEC651 and IEC61672 norms. It was conducted at the Universidade Federal do Vale do São Francisco, in Petrolina, Pernambuco State, Brazil, in 2009, by using a Valtra 785 TDA tractor without cabin and equipment to measure its sound power level. The measurements were: static (anterior, posterior, right, and left positions, in relation to the operator’s seat, for each meter along the maximum distance of 10 m, and different engine rotation speeds, with two measuring devices) and dynamic (five speeds on concrete and soil test tracks, with two devices). Two measurement devices were used to evaluate the sound power level. For the devices in accordance with the IEC651 and IEC62672 norms, the second one always presented higher sound power levels, due to the fact that the first one was equipped with a wind protector. In all positions, the sound power level was higher than allowed by law. As the engine rotation speed increases, the sound power level also increases. It was noticed that both test tracks can be used for sound power level analysis, due to their similar results. The tractor speed affected its sound power level, with higher values for longer gears.KEY-WORDS: Noise; ergonomics; agricultural mechanization.O ruído das máquinas agrícolas, com o passar do tempo, pode provocar problemas auditivos em seus operadores. O objetivo deste trabalho foi avaliar o nível de potência sonora emitido por trator agrícola, em condições estáticas e dinâmicas, comparando-o às normas IEC651 e IEC61672. O trabalho foi realizado na Universidade Federal do Vale do São Francisco, Petrolina (PE), em 2009, utilizando-se um trator Valtra, modelo 785 TDA sem cabine, e medidores do nível de potência sonora. As medições foram: estática (posições anterior, posterior, direita e esquerda do assento do operador a cada metro, até a distância máxima de 10 m, e diferentes rotações do motor, com dois equipamentos de medição) e dinâmica (cinco velocidades de deslocamento, em pista de concreto e terra batida, utilizando-se dois equipamentos de medição). Para os equipamentos que atendem às normas IEC651 e IEC61672, o segundo sempre apresentou maiores valores do nível de potência sonora, devido ao primeiro ser utilizado com protetor de vento. Em todas as condições, o nível de potência sonora foi maior do que o permitido pela legislação. À medida que se aumenta a rotação do motor, ocorre incremento no nível de potência sonora. Verificou-se que as pistas de terra batida e concreto podem ser utilizadas para análise do nível de potência sonora, devido aos resultados similares apresentados. A velocidade de deslocamento do trator influenciou no nível de potência sonora, sendo que as marchas mais longas apresentaram maiores valores. PALAVRAS-CHAVE: Ruído; ergonomia; mecanização agrícola.