Sequential activation of different pathway networks in ischemia-affected and non-affected myocardium, inducing intrinsic remote conditioning to prevent left ventricular remodeling

We have analyzed the pathway networks of ischemia-affected and remote myocardial areas after repetitive ischemia/reperfusion (r-I/R) injury without ensuing myocardial infarction (MI) to elaborate a spatial- and chronologic model of cardioprotective gene networks to prevent left ventricular (LV) adverse remodeling. Domestic pigs underwent three cycles of 10/10 min r-I/R by percutaneous intracoronary balloon inflation/deflation in the mid left anterior descending artery, without consecutive MI. Sham interventions (n = 8) served as controls. Hearts were explanted at 5 h (n = 6) and 24 h (n = 6), and transcriptomic profiling of the distal (ischemia-affected) and proximal (non-affected) anterior myocardial regions were analyzed by next generation sequencing (NGS) and post-processing with signaling pathway impact and pathway network analyses. In ischemic region, r-I/R induced early activation of Ca-, adipocytokine and insulin signaling pathways with key regulator STAT3, which was also upregulated in the remote areas together with clusterin (CLU) and TNF-alpha. During the late phase of cardioprotection, antigen immunomodulatory pathways were activated with upregulation of STAT1 and CASP3 and downregulation of neprilysin in both zones, suggesting r-I/R induced intrinsic remote conditioning. The temporo-spatially differently activated pathways revealed a global myocardial response, and neprilysin and the STAT family as key regulators of intrinsic remote conditioning for prevention of adverse remodeling

The prognosis of streptococcal prosthetic bone and joint infections depends on surgical management-A multicenter retrospective study

BACKGROUND: The optimal treatment of streptococcal prosthetic joint infections (PJIs) is unclear. METHODS: A cohort of streptococcal PJIs was reviewed retrospectively in seven reference centers for the management of complex bone and joint infections, covering the period January 1, 2010 to December 31, 2012. RESULTS: Seventy patients with monomicrobial infections were included: 47 had infections of total hip arthroplasty and 23 had infections of total knee arthroplasty. The median age was 77 years (interquartile range (IQR) 69-83 years), the median Charlson comorbidity score was 4 (IQR 3-6), and 15.6% (n=11) had diabetes. The most commonly identified streptococcal species were Streptococcus agalactiae and Streptococcus dysgalactiae (38.6% (n=27) and 17.1% (n=12), respectively). Debridement, antibiotics and implant retention (DAIR) was performed after a median time of 7 days (IQR 3-8 days), with polyethylene exchange (PE) in 21% of cases. After a minimum follow-up of 2 years, 27% of patients had relapsed, corresponding to 51.4% of DAIR treatment cases and 0% of one-stage (n=15) or two-stage (n=17) exchange strategy cases. Rifampicin or levofloxacin in combination therapy was not associated with a better outcome (adjusted p= 0.99). S. agalactiae species and DAIR treatment were associated with a higher risk of failure. On multivariate analysis, only DAIR treatment and S. agalactiae were independent factors of relapse. Compared to DAIR without PE, DAIR with PE was only associated with a trend towards a benefit (odds ratio 0.33, 95% confidence interval 0.06-1.96; adjusted p= 0.44). CONCLUSIONS: Streptococcal PJIs managed with DAIR have a poor prognosis and S. agalactiae seems to be an independent factor of treatment failure

Niche divergence facilitated by fine-scale ecological partitioning in a recent cichlid fish adaptive radiation

Ecomorphological differentiation is a key feature of adaptive radiations, with a general trend for specialization and niche expansion following divergence. Ecological opportunity afforded by invasion of a new habitat is thought to act as an ecological release, facilitating divergence, and speciation. Here, we investigate trophic adaptive morphology and ecology of an endemic clade of oreochromine cichlid fishes (Alcolapia) that radiated along a herbivorous trophic axis following colonization of an isolated lacustrine environment, and demonstrate phenotype-environment correlation. Ecological and morphological divergence of the Alcolapia species flock are examined in a phylogenomic context, to infer ecological niche occupation within the radiation. Species divergence is observed in both ecology and morphology, supporting the importance of ecological speciation within the radiation. Comparison with an outgroup taxon reveals large-scale ecomorphological divergence but shallow genomic differentiation within the Alcolapia adaptive radiation. Ancestral morphological reconstruction suggests lake colonization by a generalist oreochromine phenotype that diverged in Lake Natron to varied herbivorous morphologies akin to specialist herbivores in Lakes Tanganyika and Malawi

Managing Spoilers in a Hybrid War: The Democratic Republic of Congo (1996-2010)

Scholarship on the management of spoilers in a hybrid type of conflict is almost non-existent. Through an examination of the recent Congolese wars and peace efforts (1996–2010), we develop an understanding of how spoilers are managed in a conflict characterised by both interstate and intrastate dynamics. Certainly, more strategies of dealing with spoiler behaviours in this type of conflict are likely to emerge as similar cases are investigated, but our discussion recommends these non-related, but strongly interacting principles: the practice of inclusivity, usually preferred in the management of spoilers, is more complex, and in fact ineffective, particularly when concerned groups’ internal politics and supportive alliances are unconventional. Because holding elections is often deemed indispensable in peacemaking efforts, it is vital that total spoilers be prevented from winning or disrupting them. The toughest challenge is the protection of civilians, especially when the state lacks a monopoly on the use of violence and governance remains partitioned across the country

Rational Design of a Plasmid Origin That Replicates Efficiently in Both Gram-Positive and Gram-Negative Bacteria

Background: Most plasmids replicate only within a particular genus or family

Widespread colonisation of Tanzanian catchments by introduced Oreochromis tilapia fishes: the legacy from decades of deliberate introduction

From the 1950s onwards, programmes to promote aquaculture and improve capture fisheries in East Africa have relied heavily on the promise held by introduced species. In Tanzania these introductions have been poorly documented. Here we report the findings of surveys of inland water bodies across Tanzania between 2011 and 2017 that clarify distributions of tilapiine cichlids of the genus Oreochromis. We identified Oreochromis from 123 sampling locations, including 14 taxa restricted to their native range and three species that have established populations beyond their native range. Of these three species, the only exotic species found was blue-spotted tilapia (Oreochromis leucostictus), while Nile tilapia (Oreochromis niloticus) and Singida tilapia (Oreochromis esculentus), which are both naturally found within the country of Tanzania, have been translocated beyond their native range. Using our records, we developed models of suitable habitat for the introduced species based on recent (1960–1990) and projected (2050, 2070) East African climate. These models indicated that presence of suitable habitat for these introduced species will persist and potentially expand across the region. The clarification of distributions provided here can help inform the monitoring and management of biodiversity, and inform policy related to the future role of introduced species in fisheries and aquaculture

Phytoplankton composition from sPACE: Requirements, opportunities, and challenges

Ocean color satellites have provided a synoptic view of global phytoplankton for over 25 years through near surface measurements of the concentration of chlorophyll a. While remote sensing of ocean color has revolutionized our understanding of phytoplankton and their role in the oceanic and freshwater ecosystems, it is important to consider both total phytoplankton biomass and changes in phytoplankton community composition in order to fully understand the dynamics of the aquatic ecosystems. With the upcoming launch of NASA\u27s Plankton, Aerosol, Clouds, ocean Ecosystem (PACE) mission, we will be entering into a new era of global hyperspectral data, and with it, increased capabilities to monitor phytoplankton diversity from space. In this paper, we analyze the needs of the user community, review existing approaches for detecting phytoplankton community composition in situ and from space, and highlight the benefits that the PACE mission will bring. Using this three-pronged approach, we highlight the challenges and gaps to be addressed by the community going forward, while offering a vision of what global phytoplankton community composition will look like through the “eyes” of PACE

Promiscuous drugs compared to selective drugs (promiscuity can be a virtue)

BACKGROUND: The word selectivity describes a drug's ability to affect a particular cell population in preference to others. As part of the current state of art in the search for new therapeutic agents, the property of selectivity is a mode of action thought to have a high degree of desirability. Consequently there is a growing activity in this area of research. Selectivity is generally a worthy property in a drug because a drug having high selectivity may have a dramatic effect when there is a single agent that can be targeted against the appropriate molecular-driver involved in the pathogenesis of a disease. An example is chronic myeloid leukemia (CML). CML has a specific chromosomal abnormality, the Philadelphia chromosome, that results in a single gene that produces an abnormal protein DISCUSSION: There is a burgeoning understanding of the cellular mechanisms that control the etiology and pathogeneses of diseases. This understanding both enables and motivates the development of drugs that induce a specific action in a selected cell population; i.e., a targeted treatment. Consequently, drugs that can target distinct molecular targets involved in pathologic/pathogenetic processes, or signal-transduction pathways, are being developed. However, in most cases, diseases involve multiple abnormalities. A disease may be associated with more than one dysfunctional protein and these may be out-of-balance with each other. Likewise a drug might strongly target a protein that shares a similar active domain with other proteins. A drug may also target pleiotropic cytokines, or other proteins that have multi-physiological functions. In this way multiple normal cellular pathways can be simultaneously influenced. Long term experience with drugs supposedly designed for only a single target, but which unavoidably involve other functional effects, is uncovering the fact that molecular targeting is not medically flawless. SUMMARY: We contend that an ideal drug may be one whose efficacy is based not on the inhibition of a single target, but rather on the rebalancing of the several proteins or events, that contribute to the etiology, pathogeneses, and progression of diseases, i.e., in effect a promiscuous drug. Ideally, if this could be done at minimum drug concentration, side effects could be minimized. Corollaries to this argument are that the growing fervor for researching truly selective drugs may be imprudent when considering the totality of responses; and that the expensive screening techniques used to discover these, may be both medically and financially inefficient

The nonlinear effect of somatic cell count on milk composition, coagulation properties, curd firmness modeling, cheese yield, and curd nutrient recovery

The aim of this study was to investigate the relationships between somatic cell count (SCC) in milk and several milk technological traits at the individual cow level. In particular, we determined the effects of very low to very high SCC on traits related to (1) milk yield and composition; (2) coagulation properties, including the traditional milk coagulation properties (MCP) and the new curd firming model parameters; and (3) cheese yield and recovery of milk nutrients in the curd (or loss in the whey). Milk samples from 1,271 Brown Swiss cows from 85 herds were used. Nine coagulation traits were measured: 3 traditional MCP [rennet coagulation time (RCT, min), curd firming rate (k20, min), and curd firmness after 30 min (a30, mm)] and 6 new curd firming and syneresis traits [potential asymptotic curd firmness at infinite time (CFP, mm), curd firming instant rate constant (kCF, % 7 min-1), syneresis instant rate constant (kSR, % 7 min-1), rennet coagulation time estimated using the equation (RCTeq, min), maximum curd firmness achieved within 45 min (CFmax, mm), and time at achievement of CFmax (tmax, min)]. The observed cheese-making traits included 3 cheese yield traits (%CYCURD, %CYSOLIDS, and %CYWATER, which represented the weights of curd, total solids, and water, respectively, as a percentage of the weight of the processed milk) and 4 nutrient recoveries in the curd (RECFAT, RECPROTEIN, RECSOLIDS, and RECENERGY, which each represented the percentage ratio between the nutrient in the curd and milk). Data were analyzed using a linear mixed model with the fixed effects of days in milk, parity, and somatic cell score (SCS), and the random effect of herd-date. Somatic cell score had strong influences on casein number and lactose, and also affected pH; these were traits characterized by a quadratic pattern of the data. The results also showed a negative linear relationship between SCS and milk yield. Somatic cell score influenced almost all of the tested coagulation traits (both traditional and modeled), with the exceptions of k20, CFP, and kSR. Gelation was delayed when the SCS decreased (slightly) and when it increased (strongly) with respect to a value of 2, as confirmed by the quadratic patterns observed for both RCT and RCTeq. The SCS effect on a30 showed a quadratic pattern almost opposite to that observed for RCT. With respect to the CFt parameters, kCF decreased linearly as SCS increased, resulting in a linear decrease of CFmax and a quadratic pattern for tmax. Milk SCS attained significance for %CYCURD, %CYWATER, and RECPROTEIN. As the SCS increased beyond 3, we observed a progressive quadratic decrease of the water retained in the curd (%CYWATER), which caused a parallel decrease in %CYCURD. With respect to RECPROTEIN, the negative effect of SCS was almost linear. Recovery of fat and (consequently) RECENERGY was characterized by a more evident quadratic trend, with the most favorable values associated with an intermediate SCS. Together, our results confirmed that high SCS has a negative effect on milk composition and technological traits, highlighting the nonlinear trends of some traits across the different classes of SCS. Moreover, we report that a very low SCS has a negative effect on some technological traits of mil