Gill Na(+)/K(+)-ATPase (NKA) in teleost fishes is involved in ion regulation in both freshwater and seawater. We have developed and validated rabbit polyclonal antibodies specific to the NKA alpha1a ...and alpha1b protein isoforms of Atlantic salmon (Salmo salar Linnaeus), and used western blots and immunohistochemistry to characterize their size, abundance and localization. The relative molecular mass of NKA alpha1a is slightly less than that for NKA beta1b. The abundance of gill NKA alpha1a was high in freshwater and became nearly undetectable after seawater acclimation. NKA alpha1b was present in small amounts in freshwater and increased 13-fold after seawater acclimation. Both NKA isoforms were detected only in chloride cells. NKA alpha1a was located in both filamental and lamellar chloride cells in freshwater, whereas in seawater it was present only as a faint background in filamental chloride cells. In freshwater, NKA alpha1b was found in a small number of filamental chloride cells, and after seawater acclimation it was found in all chloride cells on the filament and lamellae. Double simultaneous immunofluorescence indicated that NKA alpha1a and alpha1b are located in different chloride cells in freshwater. In many chloride cells in seawater, NKA alpha1b was present in greater amounts in the subapical region than elsewhere in the cell. The combined patterns in abundance and immunolocalization of these two isoforms can explain the salinity-related changes in total NKA and chloride cell abundance. The results indicate that there is a freshwater and a seawater isoform of NKA alpha-subunit in the gills of Atlantic salmon and that they are present in distinct chloride cells.
When allocating scarce resources such as organs or public housing units, the policy maker needs to carefully balance two conflicting objectives: maximizing the reward from matching and minimizing ...inequity across different types of candidates. We consider an implementable class of policies that ranks the candidates by the sum of their waiting score and matching score. Similar policies had been proposed for allocating deceased-donor kidneys to patients on the transplant waitlist. This article provides a modeling framework to characterize the waitlist system under this type of ranking policy. This framework allows the policy maker to predict and compare the allocation outcome under different ranking policies. When the efficiency and fairness measurements take certain forms, we derive a closed-form scoring formula that optimizes the outcome of the system in the long run.
We consider a one-sided bipartite matching queueing system (OBMQ) with customers and resources of multiple types, where different customer-resource combinations can generate different rewards. Each resource is allocated on arrival to the customer with the highest score (or index), which is the sum of the customer’s waiting score and matching score, so we call it an M+W index. We assume that the waiting score is an increasing function of a customer’s waiting time and that the matching score is a function of both the customer’s and the resource’s types. Unmatched customers wait in the queue until being matched or will abandon the waitlist after a random duration. We study the fluid sample path in such a system, which provides an approximate to the system dynamics. We show that a fluid sample path can be computed over any finite horizon. We propose an efficient algorithm to check whether a steady state of the fluid sample path exists or not. When a steady state exists, the algorithm also computes one efficiently. We prove that there can be at most one steady state and that the fluid sample path will be attracted to the unique steady state under mild conditions. These results enable a policy designer to predict the behavior of an OBMQ when using an M+W index and to choose an indexing formula that optimizes a given set of performance metrics. We derive a closed-form index that optimizes the steady-state performance according to some well-known efficiency and fairness metrics.
Fusarium head blight (FHB) is a global cereal disease caused by a complex of Fusarium species. In Europe, the main species responsible for FHB are F. graminearum, F. culmorum and F. poae. However, ...members of the F. tricinctum species complex (FTSC) have become increasingly important. FTSC fusaria can synthesize mycotoxins such as moniliformin (MON), enniatins (ENNs) and several other biologically active secondary metabolites that could compromise food quality. In this study, FTSC isolates primarily from Italian durum wheat and barley, together with individual strains from four non-graminaceous hosts, were collected to assess their genetic diversity and determine their potential to produce mycotoxins in vitro on rice cultures. A multilocus DNA sequence dataset (TEF1, RPB1 and RPB2) was constructed for 117 isolates from Italy and 6 from Iran to evaluate FTSC species diversity and their evolutionary relationships. Phylogenetic analyses revealed wide genetic diversity among Italian FTSC isolates. Among previously described FTSC species, F. avenaceum (FTSC 4) was the most common species in Italy (56/117 = 47.9%) while F. tricinctum (FTSC 3), and F. acuminatum (FTSC 2) accounted for 11.1% (13/117) and the 8.5% (10/117), respectively. The second most detected species was a new and unnamed Fusarium sp. (FTSC 12; 32/117 = 19%) resolved as the sister group of F. tricinctum. Collectively, these four phylospecies accounted for 111/117 = 94.9% of the Italian FTSC collection. However, we identified five other FTSC species at low frequencies, including F. iranicum (FTSC 6) and three newly discovered species (Fusarium spp. FTSC 13, 14, 15). Of the 59 FTSC isolates tested for mycotoxin production on rice cultures, 54 and 55 strains, respectively, were able to produce detectable levels of ENNs and MON. In addition, we confirmed that the ability to produce bioactive secondary metabolites such as chlamydosporol, acuminatopyrone, longiborneol, fungerin and butanolide is widespread across the FTSC.
•Fusarium tricinctum species complex (FTSC) are important cereal pathogens worldwide.•Phylogenetic analyses revealed Italian FTSC isolates are genetically diverse.•Four of the nine FTSC species recovered in Italy represent novel phylospecies.•Fusarium avenaceum (FTSC 4) was the predominant species on Italian cereals.•FTSC isolates produced significant levels of moniliformin and enniatin mycotoxins.
Trichothecenes are sesquiterpene toxins produced by diverse but relatively few fungal species in at least three classes of
Ascomycetes
:
Dothideomycetes
,
Eurotiomycetes
, and
Sordariomycetes
. ...Approximately 200 structurally distinct trichothecene analogs have been described, but a given fungal species typically produces only a small subset of analogs. All trichothecenes share a core structure consisting of a four-ring nucleus known as 12,13-epoxytrichothec-9-ene. This structure can be substituted at various positions with hydroxyl, acyl, or keto groups to give rise to the diversity of trichothecene structures that has been described. Over the last 30 years, the genetic and biochemical pathways required for trichothecene biosynthesis in several species of the fungi
Fusarium
and
Trichoderma
have been elucidated. In addition, phylogenetic and functional analyses of trichothecene biosynthetic (
TRI
) genes from fungi in multiple genera have provided insights into how acquisition, loss, and changes in functions of
TRI
genes have given rise to the diversity of trichothecene structures. These analyses also suggest both divergence and convergence of
TRI
gene function during the evolutionary history of trichothecene biosynthesis. What has driven trichothecene structural diversification remains an unanswered question. However, insight into the role of trichothecenes in plant pathogenesis of
Fusarium
species and into plant glucosyltransferases that detoxify the toxins by glycosylating them point to a possible driver. Because the glucosyltransferases can have substrate specificity, changes in trichothecene structures produced by a fungus could allow it to evade detoxification by the plant enzymes. Thus, it is possible that advantages conferred by evading detoxification have contributed to trichothecene structural diversification.
Key Points
• TRI genes have evolved by diverse processes: loss, acquisition and changes in function.
• Some TRI genes have acquired the same function by convergent evolution.
• Some other TRI genes have evolved divergently to have different functions.
• Some TRI genes were acquired or resulted from diversification in function of other genes.
• Substrate specificity of plant glucosyltransferases could drive trichothecene diversity.
This paper establishes the local-in-time existence and uniqueness of solutions to the viscous, non-resistive magnetohydrodynamics (MHD) equations in
R
d
, where
d
= 2, 3, with initial data
B
0
∈
H
s
...(
R
d
)
and
u
0
∈
H
s
-
1
+
ϵ
(
R
d
)
for
s
>
d
/
2
and any
0
<
ϵ
<
1
. The proof relies on maximal regularity estimates for the Stokes equation. The obstruction to taking
ϵ
=
0
is explained by the failure of solutions of the heat equation with initial data
u
0
∈
H
s
-
1
to satisfy
u
∈
L
1
(
0
,
T
;
H
s
+
1
)
; we provide an explicit example of this phenomenon.
In this paper we investigate non-linear matroid optimization problems with polynomial objective functions where the monomials satisfy certain monotonicity properties. Indeed, we study problems where ...the set of non-linear monomials consists of all non-linear monomials that can be built from a given subset of the variables. Linearizing all non-linear monomials we study the respective polytope. We present a complete description of this polytope. Apart from linearization constraints one needs appropriately strengthened rank inequalities. The separation problem for these inequalities reduces to a submodular function minimization problem. These polyhedral results give rise to a new hierarchy for the solution of matroid optimization problems with polynomial objectives. This hierarchy allows to strengthen the relaxations of arbitrary linearized combinatorial optimization problems with polynomial objective functions and matroidal substructures. Finally, we give suggestions for future work.
Human beta-defensins (hBDs, -1, 2, 3) are a family of epithelial cell derived antimicrobial peptides (AMPs) that protect mucosal membranes from microbial challenges. In addition to their ...antimicrobial activities, they possess other functions; e.g., cell activation, proliferation, regulation of cytokine/chemokine production, migration, differentiation, angiogenesis, and wound healing processes. It has also become apparent that defensin levels change with the development of neoplasia. However, inconsistent observations published by various laboratories make it difficult to reach a consensus as to the direction of the dysregulation and role the hBDs may play in various cancers. This is particularly evident in studies focusing on oral squamous cell carcinoma (OSCC). By segregating each hBD by cancer type, interrogating methodologies, and scrutinizing the subject cohorts used in the studies, we have endeavored to identify the "take home message" for each one of the three hBDs. We discovered that (1) consensus-driven findings indicate that hBD-1 and-2 are down- while hBD-3 is up-regulated in OSCC; (2) hBD dysregulation is cancer-type specific; (3) the inhibition/activation effect an hBD has on cancer cell lines is related to the direction of the hBD dysregulation (up or down) in the cancer from which the cell lines derive. Therefore, studies addressing hBD dysregulation in various cancers are not generalizable and comparisons should be avoided. Systematic delineation of the fate and role of the hBDs in a specific cancer type may lead to innovative ways to use defensins as prospective biomarkers for diagnostic/prognostic purposes and/or in novel therapeutic modalities.
IL-17C is a functionally distinct member of the IL-17 family that binds IL-17 receptor E/A to promote innate defense in epithelial cells and regulate Th17 cell differentiation. We demonstrate that ...IL-17C (not IL-17A) is the most abundant IL-17 isoform in lesional psoriasis skin (1058 versus 8 pg/ml; p < 0.006) and localizes to keratinocytes (KCs), endothelial cells (ECs), and leukocytes. ECs stimulated with IL-17C produce increased TNF-α and KCs stimulated with IL-17C/TNF-α produce similar inflammatory gene response patterns as those elicited by IL-17A/TNF-α, including increases in IL-17C, TNF-α, IL-8, IL-1α/β, IL-1F5, IL-1F9, IL-6, IL-19, CCL20, S100A7/A8/A9, DEFB4, lipocalin 2, and peptidase inhibitor 3 (p < 0.05), indicating a positive proinflammatory feedback loop between the epidermis and ECs. Psoriasis patients treated with etanercept rapidly decrease cutaneous IL-17C levels, suggesting IL-17C/TNF-α-mediated inflammatory signaling is critical for psoriasis pathogenesis. Mice genetically engineered to overexpress IL-17C in KCs develop well-demarcated areas of erythematous, flakey involved skin adjacent to areas of normal-appearing uninvolved skin despite increased IL-17C expression in both areas (p < 0.05). Uninvolved skin displays increased angiogenesis and elevated S100A8/A9 expression (p < 0.05) but no epidermal hyperplasia, whereas involved skin exhibits robust epidermal hyperplasia, increased angiogenesis and leukocyte infiltration, and upregulated TNF-α, IL-1α/β, IL-17A/F, IL-23p19, vascular endothelial growth factor, IL-6, and CCL20 (p < 0.05), suggesting that IL-17C, when coupled with other proinflammatory signals, initiates the development of psoriasiform dermatitis. This skin phenotype was significantly improved following 8 wk of TNF-α inhibition. These findings identify a role for IL-17C in skin inflammation and suggest a pathogenic function for the elevated IL-17C observed in lesional psoriasis skin.
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