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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.

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.

This work aims at to characterize the mechanical behavior of the mango fruits in function of the problems found during the stages of production and commercialization. Problems like physical damages are caused by the inadequate handing of the fruits during harvest, storage, processing or transport. These problems are caused by information deficit about the mechanical behavior of the fruits and the maximum strength necessary o start internal degradation or external damages, that it harms yours commercialization. Compression tests were carried out in the specimens of the mangos (Mangifera Indica) the variety “Keitt” and “Tommy Atkins”, in repose position, to determination of the elasticity modulus and maximum strength up to rupture as a function the maturation phases 1, 2 and 3. The elasticity modulus decreases with advancement of the maturation stage, reaching values for the “Keitt” variety of 2,065 MPa, 1,734 MPa and 1,381 MPa for the maturation stage 1,2 and 3 respectively. The “Tommy Atkins” variety reached an elasticity modulus of 1,698 MPa, 1,657 MPa e 1,518 MPa for the maturation stage 1,2 and 3, respectively. The maximum compressive strength, that causes rupture in the fruits, for the variety “Tommy Atkins” were higher than those for “Keitt”. This fact is associated with the different structural composition of the fruits, because the “Tommy Atkins” variety has a fiber content greater than the “Keitt” variety. [ABSTRACT FROM AUTHOR]

Assessing the impact of mining activity on the availability of environmental pollutants is crucial for informing health policies in anticipation of future production scenarios of critical minerals essential for the transition to a net-zero carbon society. However, temporal and spatial monitoring is often sparse, and measurements may not extend far enough back in time. In this study, we utilize variations of chemical elements contained in tree-rings collected in local villages from an area heavily affected by copper mining in the Atacama Desert since the early 20th century to evaluate the temporal distribution of pollutants and their relationship with local drivers. By combining time-varying data on local drivers, such as copper production and the dry tailings deposit area, we show how the surge in copper production during the 1990s, fueled by trade liberalization and increased international demand, led to a significant increment in the availability of metal(loid)s related to mining activities on indigenous lands. Our findings suggest that the environmental legislation in Chile may be underestimating the environmental impact of tailing dams in neighboring populations, affecting the well-being of Indigenous Peoples from the Atacama mining hotspot region. We argue that future changes in production rates driven by international demand could have negative repercussions on the environment and local communities. Therefore, mining emissions and the management of tailing dams should be carefully considered to anticipate their potential negative effects on human and ecosystem health., Competing Interests: Declaration of competing interest 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., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Linked to major volcanic eruptions around 536 and 540 CE, the onset of the Late Antique Little Ice Age has been described as the coldest period of the past two millennia. The exact timing and spatial extent of this exceptional cold phase are, however, still under debate because of the limited resolution and geographical distribution of the available proxy archives. Here, we use 106 wood anatomical thin sections from 23 forest sites and 20 tree species in both hemispheres to search for cell-level fingerprints of ephemeral summer cooling between 530 and 550 CE. After cross-dating and double-staining, we identified 89 Blue Rings (lack of cell wall lignification), nine Frost Rings (cell deformation and collapse), and 93 Light Rings (reduced cell wall thickening) in the Northern Hemisphere. Our network reveals evidence for the strongest temperature depression between mid-July and early-August 536 CE across North America and Eurasia, whereas more localised cold spells occurred in the summers of 532, 540-43, and 548 CE. The lack of anatomical signatures in the austral trees suggests limited incursion of stratospheric volcanic aerosol into the Southern Hemisphere extra-tropics, that any forcing was mitigated by atmosphere-ocean dynamical responses and/or concentrated outside the growing season, or a combination of factors. Our findings demonstrate the advantage of wood anatomical investigations over traditional dendrochronological measurements, provide a benchmark for Earth system models, support cross-disciplinary studies into the entanglements of climate and history, and question the relevance of global climate averages., Competing Interests: Conflict of interest The authors declare that they have no conflict of interest., (Copyright © 2022 Science China Press. Published by Elsevier B.V. All rights reserved.)

Tree growth is generally considered to be temperature limited at upper elevation treelines, yet climate factors controlling tree growth at semiarid treelines are poorly understood. We explored the influence of climate on stem growth and stable isotopes for Polylepis tarapacana Philipi, the world's highest elevation tree species, which is found only in the South American Altiplano. We developed tree-ring width index (RWI), oxygen (δ18O) and carbon (δ13C) chronologies for the last 60 years at four P. tarapacana stands located above 4400 m in elevation, along a 500 km latitude aridity gradient. Total annual precipitation decreased from 300 to 200 mm from the northern to the southern sites. We used RWI as a proxy of wood formation (carbon sink) and isotopic tree-ring signatures as proxies of leaf-level gas exchange processes (carbon source). We found distinct climatic conditions regulating carbon sink processes along the gradient. Current growing-season temperature regulated RWI at northern-wetter sites, while prior growing-season precipitation determined RWI at arid southern sites. This suggests that the relative importance of temperature to precipitation in regulating tree growth is driven by site water availability. By contrast, warm and dry growing seasons resulted in enriched tree-ring δ13C and δ18O at all study sites, suggesting that similar climate conditions control carbon-source processes along the gradient. Site-level δ13C and δ18O chronologies were significantly and positively related at all sites, with the strongest relationships among the southern drier stands. This indicates an overall regulation of intercellular carbon dioxide via stomatal conductance for the entire P. tarapacana network, with greater stomatal control when aridity increases. This manuscript also highlights a coupling (decoupling) between physiological processes at leaf level and wood formation as a function of similarities (differences) in their climatic sensitivity. This study contributes to a better understanding and prediction of the response of high-elevation Polylepis woodlands to rapid climate changes and projected drying in the Altiplano., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

South American tropical climate is strongly related to the tropical low-pressure belt associated with the South American monsoon system. Despite its central societal role as a modulating agent of rainfall in tropical South America, its long-term dynamical variability is still poorly understood. Here we combine a new (and world's highest) tree-ring 14 C record from the Altiplano plateau in the central Andes with other 14 C records from the Southern Hemisphere during the second half of the 20th century in order to elucidate the latitudinal gradients associated with the dissemination of the bomb 14 C signal. Our tree-ring 14 C record faithfully captured the bomb signal of the 1960's with an excellent match to atmospheric 14 C measured in New Zealand but with significant differences with a recent record from Southeast Brazil located at almost equal latitude. These results imply that the spreading of the bomb signal throughout the Southern Hemisphere was a complex process that depended on atmospheric dynamics and surface topography generating reversals on the expected north-south gradient in certain years. We applied air-parcel modeling based on climate data to disentangle their different geographical provenances and their preformed (reservoir affected) radiocarbon content. We found that air parcel trajectories arriving at the Altiplano during the bomb period were sourced i) from the boundary layer in contact with the Pacific Ocean (41%), ii) from the upper troposphere (air above the boundary layer, with no contact with oceanic or continental carbon reservoirs) (38%) and iii) from the Amazon basin (21%). Based on these results we estimated the ∆ 14 C endmember values for the different carbon reservoirs affecting our record which suggest that the Amazon basin biospheric 14 C isoflux could have been reversed from negative to positive as early as the beginning of the 1970's. This would imply a much faster carbon turnover rate in the Amazon than previously modelled., Competing Interests: Declaration of competing interest 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., (Copyright © 2021 Elsevier B.V. All rights reserved.)

South American (SA) societies are highly vulnerable to droughts and pluvials, but lack of long-term climate observations severely limits our understanding of the global processes driving climatic variability in the region. The number and quality of SA climate-sensitive tree ring chronologies have significantly increased in recent decades, now providing a robust network of 286 records for characterizing hydroclimate variability since 1400 CE. We combine this network with a self-calibrated Palmer Drought Severity Index (scPDSI) dataset to derive the South American Drought Atlas (SADA) over the continent south of 12°S. The gridded annual reconstruction of austral summer scPDSI is the most spatially complete estimate of SA hydroclimate to date, and well matches past historical dry/wet events. Relating the SADA to the Australia-New Zealand Drought Atlas, sea surface temperatures and atmospheric pressure fields, we determine that the El Niño-Southern Oscillation (ENSO) and the Southern Annular Mode (SAM) are strongly associated with spatially extended droughts and pluvials over the SADA domain during the past several centuries. SADA also exhibits more extended severe droughts and extreme pluvials since the mid-20th century. Extensive droughts are consistent with the observed 20th-century trend toward positive SAM anomalies concomitant with the weakening of midlatitude Westerlies, while low-level moisture transport intensified by global warming has favored extreme rainfall across the subtropics. The SADA thus provides a long-term context for observed hydroclimatic changes and for 21st-century Intergovernmental Panel on Climate Change (IPCC) projections that suggest SA will experience more frequent/severe droughts and rainfall events as a consequence of increasing greenhouse gas emissions., Competing Interests: The authors declare no competing interest., (Copyright © 2020 the Author(s). Published by PNAS.)

One of the most polluted areas in Chile is the Ventanas Industrial Area (VIA; 32.74°S / 71.48°W), which started in 1958 and today comprises around 16 industries in an area of ca. 4 km 2 . A lack of consistent long-term instrumental records precludes assessing the history of contamination in the area and also limits the evaluation of mitigation actions taken since the late 1980s. Here, we use dendrochemistry as an environmental proxy to analyze environmental changes over several decades at the VIA. We present chemical measurements of tree rings from planted, exotic Cupressus macrocarpa growing near the VIA with 4-year resolution over a period of 52 years (1960-2011). These data provide unprecedented information on regional anthropogenic pollution and are compared with a tree-ring elemental record of 48 years (1964-2011) from the Isla Negra (INE) control site not exposed to VIA emissions. For the 48 years of overlap between both sites, higher concentrations of Zn, V, Co, Cd, Ag, Fe, Cr, and Al were especially registered after the year 2000 at VIA compared to INE for the periods under study. Concentrations of Pb, Cu, As, Fe, Mo, Cr, and Zn increased through time, particularly over the period 1980-1990. Decontamination plans activated in 1992 appear to have had a positive effect on the amount of some elements, but the chemical concentration in the tree rings suggest continued accumulation of pollutants in the environment. Only after several years of implementation of the mitigation measures have some elements tended to decrease in concentration, especially at the end of the evaluated period. Dendrochemistry is a useful tool to provide a long-term perspective of the dynamics of trace metal pollution and represents a powerful approach to monitor air quality variability to extend the instrumental records back in time., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The rivers originating in the southern Andes (18°-55°S) support numerous ecosystems and a large number of human populations and socio-economic activities in the adjacent lowlands of Chile, Argentina and Bolivia. Here we show that ca. 75% of the total variance in the streamflow records from this extensive region can be explained by only eight spatially coherent patterns of variability. Five (three) of these Andean patterns exhibit extreme dry (wet) conditions in recent years, with strong interannual variations in northern Chile; long-term drying trends between 31° and 41°S; a transitional pattern in the central Patagonian Andes; and increasing trends in northwestern Argentina and southern Bolivia, the Fueguian Andes, and the eastern portion of the South Patagonian Icefield. Multivariate regression analyses show that large-scale indices of ENSO variability can predict 20% to 45% of annual runoff variability between 28° and 46°S. The influence of Antarctic and North Pacific indices becomes more relevant south of 43°S and in northwestern Argentina and southern Bolivia, respectively, but their overall skill as predictors of Andean streamflows is weak. The analyses provide relevant new information to improve understanding of the spatial coherence, the main temporal features, and the ocean-atmospheric forcings of surface runoff across the southern Andes.

Extreme climatic events, such as late frosts in spring during leaf flush, have considerable impacts on the radial growth of temperate broadleaf trees. Albeit, all broadleaved species are potentially vulnerable, damage depends on the particularities of the local climate, the species, and its phenology. The impact of late spring frosts has been widely investigated in the Northern Hemisphere, but the potential incidence in Southern Hemisphere tree species is still poorly known. Here, we reconstruct spring frost occurrence at 30 stands of the deciduous tree Nothofagus pumilio in its northern range of distribution in the Patagonian Andes. We identified tree ring-width reductions at stand level not associated with regional or local drought events, matching unusual minimum spring temperatures during leaf unfolding. Several spring frosts were identified along the northern distribution of N. pumilio , being more frequent in the more continental Argentinean forests. Spring frost in 1980 had the largest spatial extent. The spring frosts in 1980 and 1992 also induced damages in regional orchards. Spring frost damage was associated with (i) a period of unusually warm temperatures at the beginning of leaf unfolding, followed by (ii) freezing temperatures. This study helps expand our understanding of the climatic constraints that could determine the future growth and dynamics of Andean deciduous forests and the potential use of tree-rings as archives of extreme events of spring frosts in northern Patagonia., (Copyright © 2019 Sangüesa-Barreda, Villalba, Rozas, Christie and Olano.)

The original version of this Article contained an error in the Data Availability section, which incorrectly read 'All data will be freely available via https://www.ams.ethz.ch/research.html .' The correct version states ' http://www.ams.ethz.ch/research/published-data.html ' in place of ' https://www.ams.ethz.ch/research.html '. This has been corrected in both the PDF and HTML versions of the Article.

Though tree-ring chronologies are annually resolved, their dating has never been independently validated at the global scale. Moreover, it is unknown if atmospheric radiocarbon enrichment events of cosmogenic origin leave spatiotemporally consistent fingerprints. Here we measure the 14 C content in 484 individual tree rings formed in the periods 770-780 and 990-1000 CE. Distinct 14 C excursions starting in the boreal summer of 774 and the boreal spring of 993 ensure the precise dating of 44 tree-ring records from five continents. We also identify a meridional decline of 11-year mean atmospheric radiocarbon concentrations across both hemispheres. Corroborated by historical eye-witness accounts of red auroras, our results suggest a global exposure to strong solar proton radiation. To improve understanding of the return frequency and intensity of past cosmic events, which is particularly important for assessing the potential threat of space weather on our society, further annually resolved 14 C measurements are needed.

Socio-economic and environmental changes are well known causes of demographic collapse of agrarian cultures. The collapse of human societies is a complex phenomenon where historical and cultural dimensions play a key role, and they may interact with the environmental context. However, the importance of the interaction between socio-economic and climatic factors in explaining possible breakdowns in Native American societies has been poorly explored. The aim of this study is to test the role of socio-economic causes and rainfall variability in the collapse suffered by the Aymara people of the semiarid Andean region of Tarapacá during the period 1820-1970. Our motivation is to demonstrate that simple population dynamic models can be helpful in understanding the causes and relative importance of population changes in Andean agro-pastoral societies in responses to socio-environmental variability. Simple logistic models that combine the effects of external socio-economic causes and past rainfall variability (inferred from Gross Domestic Product [GDP] and tree-rings, respectively) were quite accurate in predicting the sustained population decline of the Aymara people. Our results suggest that the depopulation in the semiarid Tarapacá province was caused by the interaction among external socio-economic pressures given by the economic growth of the lowlands and demands for labor coupled with a persistent decline in rainfall. This study constitutes an example of how applied ecological knowledge, in particular the application of the logistic equation and theories pertaining to nonlinear population dynamics and exogenous perturbations, can be used to better understand major demographic changes in human societies., Competing Interests: The authors have declared that no competing interests exist.

Plant growth at extremely high elevations is constrained by high daily thermal amplitude, strong solar radiation and water scarcity. These conditions are particularly harsh in the tropics, where the highest elevation treelines occur. In this environment, the maintenance of a positive carbon balance involves protecting the photosynthetic apparatus and taking advantage of any climatically favourable periods. To characterize photoprotective mechanisms at such high elevations, and particularly to address the question of whether these mechanisms are the same as those previously described in woody plants along extratropical treelines, we have studied photosynthetic responses in Polylepis tarapacana Philippi in the central Andes (18°S) along an elevational gradient from 4300 to 4900 m. For comparative purposes, this gradient has been complemented with a lower elevation site (3700 m) where another Polylepis species (P. rugulosa Bitter) occurs. During the daily cycle, two periods of photosynthetic activity were observed: one during the morning when, despite low temperatures, assimilation was high; and the second starting at noon when the stomata closed because of a rise in the vapour pressure deficit and thermal dissipation is prevalent over photosynthesis. From dawn to noon there was a decrease in the content of antenna pigments (chlorophyll b and neoxanthin), together with an increase in the content of xanthophyll cycle carotenoids. These results could be caused by a reduction in the antenna size along with an increase in photoprotection. Additionally, photoprotection was enhanced by a partial overnight retention of de-epoxized xanthophylls. The unique combination of all of these mechanisms made possible the efficient use of the favourable conditions during the morning while still providing enough protection for the rest of the day. This strategy differs completely from that of extratropical mountain trees, which uncouple light-harvesting and energy-use during long periods of unfavourable, winter conditions., (Published by Oxford University Press on behalf of the Annals of Botany Company.)

Deletion of genes encoding the E26 transformation-specific transcription factors PU.1 and Spi-B in B cells (CD19-CreΔPB mice) leads to impaired B cell development, followed by B cell acute lymphoblastic leukemia at 100% incidence and with a median survival of 21 wk. However, little is known about the target genes that explain leukemogenesis in these mice. In this study we found that immature B cells were altered in frequency in the bone marrow of preleukemic CD19-CreΔPB mice. Enriched pro-B cells from CD19-CreΔPB mice induced disease upon transplantation, suggesting that these were leukemia-initiating cells. Bone marrow cells from preleukemic CD19-CreΔPB mice had increased responsiveness to IL-7 and could proliferate indefinitely in response to this cytokine. Bruton tyrosine kinase (BTK), a negative regulator of IL-7 signaling, was reduced in preleukemic and leukemic CD19-CreΔPB cells compared with controls. Induction of PU.1 expression in cultured CD19-CreΔPB pro-B cell lines induced Btk expression, followed by reduced STAT5 phosphorylation and early apoptosis. PU.1 and Spi-B regulated Btk directly as shown by chromatin immunoprecipitation analysis. Ectopic expression of BTK was sufficient to induce apoptosis in cultured pro-B cells. In summary, these results suggest that PU.1 and Spi-B activate Btk to oppose IL-7 responsiveness in developing B cells., (Copyright © 2015 by The American Association of Immunologists, Inc.)

Stomatin-like protein 2 (SLP-2) is a mostly mitochondrial protein that regulates mitochondrial biogenesis and function and modulates T cell activation. To determine the mechanism of action of SLP-2, we generated T cell-specific SLP-2-deficient mice. These mice had normal numbers of thymocytes and T cells in the periphery. However, conventional SLP-2-deficient T cells had a posttranscriptional defect in IL-2 production in response to TCR ligation, and this translated into reduced CD4(+) T cell responses. SLP-2 deficiency was associated with impaired cardiolipin compartmentalization in mitochondrial membranes, decreased levels of the NADH dehydrogenase (ubiquinone) iron-sulfur protein 3, NADH dehydrogenase (ubiquinone) 1β subcomplex subunit 8, and NADH dehydrogenase (ubiquinone) 1α subcomplex subunit 9 of respiratory complex I, and decreased activity of this complex as well as of complex II plus III of the respiratory chain. In addition, SLP-2-deficient T cells showed a significant increase in uncoupled mitochondrial respiration and a greater reliance on glycolysis. Based on these results, we propose that SLP-2 organizes the mitochondrial membrane compartmentalization of cardiolipin, which is required for optimal assembly and function of respiratory chain complexes. This function, in T cells, helps to ensure proper metabolic response during activation.

B cell acute lymphoblastic leukemia (B-ALL) is frequently associated with mutations or chromosomal translocations of genes encoding transcription factors. Conditional deletion of genes encoding the E26-transformation-specific transcription factors, PU.1 and Spi-B, in B cells (ΔPB mice) leads to B-ALL in mice at 100% incidence rate and with a median survival of 21 wk. We hypothesized that PU.1 and Spi-B may redundantly activate transcription of genes encoding tumor suppressors in the B cell lineage. Characterization of aging ΔPB mice showed that leukemia cells expressing IL-7R were found in enlarged thymuses. IL-7R-expressing B-ALL cells grew in culture in response to IL-7 and could be maintained as cell lines. Cultured ΔPB cells expressed reduced levels of B cell linker protein (BLNK), a known tumor suppressor gene, compared with controls. The Blnk promoter contained a predicted PU.1 and/or Spi-B binding site that was required for promoter activity and occupied by PU.1 and/or Spi-B as determined by chromatin immunoprecipitation. Restoration of BLNK expression in cultured ΔPB cells opposed IL-7-dependent proliferation and induced early apoptosis. We conclude that the tumor suppressor BLNK is a target of transcriptional activation by PU.1 and Spi-B in the B cell lineage.

Stomatin-like protein 2 (SLP-2) is a member of the stomatin-prohibitin-flotillin-HflC/K (SPFH) superfamily. Recent evidence indicates that SLP-2 is involved in the organization of cardiolipin-enriched microdomains in mitochondrial membranes and the regulation of mitochondrial biogenesis and function. In T cells, this role translates into enhanced T cell activation. Although the major pool of SLP-2 is associated with mitochondria, we show here that there is an additional pool of SLP-2 associated with the plasma membrane of T cells. Both plasma membrane-associated and mitochondria-associated pools of SLP-2 coalesce at the immunological synapse (IS) upon T cell activation. SLP-2 is not required for formation of IS nor for the re-localization of mitochondria to the IS because SLP-2-deficient T cells showed normal re-localization of these organelles in response to T cell activation. Interestingly, upon T cell activation, we found the surface pool of SLP-2 mostly excluded from the central supramolecular activation complex, and enriched in the peripheral area of the IS where signalling TCR microclusters are located. Based on these results, we propose that SLP-2 facilitates the compartmentalization not only of mitochondrial membranes but also of the plasma membrane into functional microdomains. In this latter location, SLP-2 may facilitate the optimal assembly of TCR signalosome components. Our data also suggest that there may be a net exchange of membrane material between mitochondria and plasma membrane, explaining the presence of some mitochondrial proteins in the plasma membrane.

Stomatin-like protein 2 (SLP-2) is a widely expressed mitochondrial inner membrane protein of unknown function. Here we show that human SLP-2 interacts with prohibitin-1 and -2 and binds to the mitochondrial membrane phospholipid cardiolipin. Upregulation of SLP-2 expression increases cardiolipin content and the formation of metabolically active mitochondrial membranes and induces mitochondrial biogenesis. In human T lymphocytes, these events correlate with increased complex I and II activities, increased intracellular ATP stores, and increased resistance to apoptosis through the intrinsic pathway, ultimately enhancing cellular responses. We propose that the function of SLP-2 is to recruit prohibitins to cardiolipin to form cardiolipin-enriched microdomains in which electron transport complexes are optimally assembled. Likely through the prohibitin functional interactome, SLP-2 then regulates mitochondrial biogenesis and function.

Objective: To assess the role of T cells in the mouse model of citrullinated human fibrinogen-induced rheumatoid arthritis (RA) using CTLA-4Ig, an agent that blocks T cell costimulation, which is required for T cell activation., Methods: Humanized HLA-DRβ1*0401-transgenic (DR4-Tg) mice were immunized with Cit-human fibrinogen to induce arthritis. Prior to, and at the onset or peak of, arthritis, the DR4-Tg mice were treated with CTLA-4Ig or control human IgG1 or were left untreated. Arthritis development and progression were monitored by measuring ankle swelling with calipers and by assessing histopathologic changes. The immune responses to the citrullinated antigens and the corresponding unmodified antigens, as well as the arthritogenicity of lymphocytes from these mice, were examined. The latter was performed using lymphocyte transfers from CTLA-4Ig-treated or control mice via intraperitoneal injection into naive DR4-Tg mice. Recipient mice also received an intraarticular injection of Cit-human fibrinogen, unmodified human fibrinogen, or vehicle., Results: CTLA-4Ig-treated, but not human IgG1-treated, arthritic mice had significantly reduced ankle swelling and pathologic joint damage. Treatment with CTLA-4Ig, but not human IgG1, suppressed Cit-human fibrinogen-induced T cell activation, including citrulline-specific T cell activation, when given prior to disease onset. Transfer of splenic lymphocytes from untreated or human IgG1-treated arthritic mice caused arthritis in recipients, and this occurred when Cit-human fibrinogen, but not unmodified fibrinogen, was deposited into the joint. Splenocytes from CTLA-4Ig-treated mice were unable to transfer arthritis., Conclusion: Activated citrulline-specific T cells play a direct role in the development and progression of arthritis in this model of Cit-human fibrinogen-induced RA.

13C-NMR has been applied to the study of the metabolism of [1-13C]glucose by macrofilariae of Dipetalonema viteae under conditions of restricted glucose supply. In a medium buffered with 13C-labelled bicarbonate, succinate labelled in the carboxyl position is formed in good yield. Quinolinic acid, a known inhibitor of phosphoenol pyruvate carboxykinase (PEPCK) has been shown to suppress the formation of labelled succinate from [1-13C]glucose. Both sets of experiments support the formation of succinate through the PEPCK-mediated carboxylation of phosphoenol pyruvate, followed by the operation of a partial tricarboxylic acid cycle.