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•Haemosporidians are blood parasites of great medical importance.•The relationships among haemosporidian clades are poorly understood.•By PCR we obtained nuclear genes from most major ...haemosporidian lineages.•Phylogenetic analyses show that Leucocytozoon is the most basal taxon.•A sister group relationship of Polychromophilus and Plasmodium is supported.
The apicomplexan order Haemosporida is a clade of unicellular blood parasites that infect a variety of reptilian, avian and mammalian hosts. Among them are the agents of human malaria, parasites of the genus Plasmodium, which pose a major threat to human health. Illuminating the evolutionary history of Haemosporida may help us in understanding their enormous biological diversity, as well as tracing the multiple host switches and associated acquisitions of novel life-history traits. However, the deep-level phylogenetic relationships among major haemosporidian clades have remained enigmatic because the datasets employed in phylogenetic analyses were severely limited in either gene coverage or taxon sampling. Using a PCR-based approach that employs a novel set of primers, we sequenced fragments of 21 nuclear genes from seven haemosporidian parasites of the genera Leucocytozoon, Haemoproteus, Parahaemoproteus, Polychromophilus and Plasmodium. After addition of genomic data from 25 apicomplexan species, the unreduced alignment comprised 20,580bp from 32 species. Phylogenetic analyses were performed based on nucleotide, codon and amino acid data employing Bayesian inference, maximum likelihood and maximum parsimony. All analyses resulted in highly congruent topologies. We found consistent support for a basal position of Leucocytozoon within Haemosporida. In contrast to all previous studies, we recovered a sister group relationship between the genera Polychromophilus and Plasmodium. Within Plasmodium, the sauropsid and mammal-infecting lineages were recovered as sister clades. Support for these relationships was high in nearly all trees, revealing a novel phylogeny of Haemosporida, which is robust to the choice of the outgroup and the method of tree inference.
The basement membrane (BM) is an extracellular matrix that plays important roles in animal development. A spatial heterogeneity in composition and structural properties of the BM provide cells with ...vital cues for morphogenetic processes such as cell migration or cell polarization. Here, using the Drosophila egg chamber as a model system, we show that the BM becomes heterogeneous during development, with a reduction in Collagen IV density at the posterior pole and differences in the micropattern of aligned fiber-like structures. We identified two AdamTS matrix proteases required for the proper elongated shape of the egg chamber, yet the molecular mechanisms by which they act are different. Stall is required to establish BM heterogeneity by locally limiting Collagen IV protein density, whereas AdamTS-A alters the micropattern of fiber-like structures within the BM at the posterior pole. Our results suggest that AdamTS proteases control BM heterogeneity required for organ shape.
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•Matrix proteases AdamTS-A and Stall are required for proper organ shape•AdamTS-A controls micropattern of fiber-like structures in basement membrane (BM)•Stall locally limits Collagen IV protein density•BM remodeling by AdamTS-A and Stall influences BM stiffness and cell shape
Töpfer et al. demonstrate that AdamTS proteases mediate local remodeling of the basement membrane of Drosophila egg chambers. Basement membrane remodeling establishes heterogeneity in the distribution of Collagen IV and in the micropattern of fiber-like structures that is important for proper egg chamber shape.
Abstract Dementia patients suffering from behavioral and psychological symptoms (BPSD) are often treated with antipsychotics. Trial results document an increased risk for serious adverse events and ...mortality in dementia patients taking these agents. Furthermore, the efficacy of treating BPSD with antipsychotics seems to be only modest. Using data of a German statutory health insurance company, we examined prescription trends of antipsychotics in prevalent dementia patients in the context of official warnings. The study period is 2004–2009. We studied trends in demographics, age and sex, as well as need of care and the intake of typical and atypical antipsychotics. Seeking for linear trends adjusted for age, sex and level of care between 2004 and 2009, we obtained p -values from a multivariate logistic regression. Prescription volumes were calculated by number of packages as well as defined daily doses (DDDs) using multiple linear regressions for trends in prescriptions amount. We included 3460–8042 patients per year (mean age 80 years). The prescription prevalence of antipsychotics decreased from 35.5% in 2004 to 32.5% in 2009 (multivariate analysis for linear trend: p =0.1645). Overall prescriptions for typical antipsychotics decreased (from 27.2% in 2004 to 23.0% in 2009, p <0.0001) and prescriptions for atypical antipsychotics increased from 17.1% to 18.9% ( p <0.0001). The mean DDD per treated patient increased from 80.5 to 91.2 (2004–2009; p =0.0047). Our findings imply that warnings of international drug authorities and manufacturers against adverse drug events in dementia patients receiving antipsychotics did not impact overall prescription behavior.
Summary
The pathogenicity of Plasmodium falciparum is partly due to parasite‐induced host cell modifications. These modifications are facilitated by exported P. falciparum proteins, collectively ...referred to as the exportome. Export of several hundred proteins is mediated by the PEXEL/HT, a protease cleavage site. The PEXEL/HT is usually comprised of five amino acids, of which R at position 1, L at position 3 and E, D or Q at position 5 are conserved and important for export. Non‐canonical PEXEL/HTs with K or H at position 1 and/or I at position 3 are presently considered non‐functional. Here, we show that non‐canonical PEXEL/HT proteins are overrepresented in P. falciparum and other Plasmodium species. Furthermore, we show that non‐canonical PEXEL/HTs can be cleaved and can promote export in both a REX3 and a GBP reporter, but not in a KAHRP reporter, indicating that non‐canonical PEXEL/HTs are functional in concert with a supportive sequence environment. We then selected P. falciparum proteins with a non‐canonical PEXEL/HT and show that some of these proteins are exported and that their export depends on non‐canonical PEXEL/HTs. We conclude that PEXEL/HT plasticity is higher than appreciated and that non‐canonical PEXEL/HT proteins cannot categorically be excluded from Plasmodium exportome predictions.
Exported Plasmodium proteins are responsible for pathogenicity‐related modifications of the infected red blood cell. Here, we show that the plasticity of the Plasmodium export element (PEXEL/HT) is higher than presently anticipated and that the exportome of P. falciparum, the most malignant agent of human malaria, contains proteins with a non‐canonical PEXEL/HT.
Background:
Tube feeding is a common form of long-term nutritional support, especially for nursing home residents, of whom many have dementia.
Objective:
Estimating the incidence of feeding tube ...placement in nursing home residents with and without dementia.
Methods:
Using claims data, we studied a cohort of newly admitted nursing home residents aged 65 years and older between 2004 and 2009. Analyses were stratified by dementia. We estimated incidence rates and performed multivariate Cox regression analyses.
Results:
The study cohort included 7174 nursing home residents. Over a mean follow-up of 1.3 years, 273 people received a feeding tube. The incidence per 1000 person-years was 28.4, with higher estimates for patients with dementia. When adjusting for age, sex, and level of care as a time-dependent covariate, influence of dementia decreased to a nonsignificant hazard ratio.
Conclusion:
It seems that not dementia itself but the overall clinical condition might be a predictor of tube feeding placement.
Background
Dementia is a main reason for nursing home admission. Information on institutionalization is often based on studies of limited methodological quality. We aimed to analyze time until ...nursing home admission since first coding of dementia diagnosis and factors associated with institutionalization in incident dementia patients compared to non-demented controls.
Methods
We analyzed claims data of a German Health insurance company including a cohort of 1,440 patients with a first diagnosis of dementia and 6,988 age- and sex-matched controls aged 65 years and older. The follow-up was up to 5 years. We used Kaplan–Meier analysis for examining time until nursing home admission and cox regression for estimating crude and adjusted Hazard ratios.
Results
Dementia patients and controls were on average 78 years and about 55 % were males. The mean time to nursing home admission was 4.0 years in patients with dementia and 4.6 years for controls. After the 5-years observation-period 62.7 % (95 % CI 59.0–66.1) of dementia patients still lived in the community in comparison to 86.2 % (95 % CI 85.2–87.2) of controls. Cox regression models show that the risk for institutionalization is 3.45 (95 % CI 3.05–3.90) times higher in dementia patients in comparison to controls when adjusted for sex, age, and comorbidity.
Conclusions
Our analysis shows a significant influence of dementia on institutionalization in comparison to age- and sex-matched controls, especially in the youngest age groups. Hence, the results add substantial information on the disease progression of dementia and are, therefore, of great importance for health-care as well as long-term care planning.
Summary
The pathogenicity of
P
lasmodium falciparum
is partly due to parasite‐induced host cell modifications. These modifications are facilitated by exported
P
. falciparum
proteins, collectively ...referred to as the exportome. Export of several hundred proteins is mediated by the
PEXEL
/
HT
, a protease cleavage site. The
PEXEL
/
HT
is usually comprised of five amino acids, of which
R
at position 1,
L
at position 3 and
E
,
D
or
Q
at position 5 are conserved and important for export. Non‐canonical
PEXEL
/
HT
s with
K
or
H
at position 1 and/or
I
at position 3 are presently considered non‐functional. Here, we show that non‐canonical
PEXEL
/
HT
proteins are overrepresented in
P
. falciparum
and other
P
lasmodium
species. Furthermore, we show that non‐canonical
PEXEL
/
HT
s can be cleaved and can promote export in both a
REX
3 and a
GBP
reporter, but not in a
KAHRP
reporter, indicating that non‐canonical
PEXEL
/
HT
s are functional in concert with a supportive sequence environment. We then selected
P
. falciparum
proteins with a non‐canonical
PEXEL
/
HT
and show that some of these proteins are exported and that their export depends on non‐canonical
PEXEL
/
HT
s. We conclude that
PEXEL
/
HT
plasticity is higher than appreciated and that non‐canonical
PEXEL
/
HT
proteins cannot categorically be excluded from
P
lasmodium
exportome predictions.
identified unequivocally. Putative microbial pathogens (fungi and bacteria) were studied in dieback affected sissoo trees collected from Bangladesh, using plant pathological techniques combined with ...molecular tools. DNA based characteri-zation showed the presence of heterogeneous patterns of various fungi (mostly saprophytic). It did not support the hypothesis of Fusarium solani being the cause of sissoo dieback. In contrast, isolation and molecular characterisation of bacteria from dieback affected sissoo revealed the presence of Pseudomonas in 83% of the samples. Sequencing the gene of 16S ribosomal RNA, the rpoD-gene, the gacA-gene and the rnpB-gene strongly suggested that these isolates belong most probably to a still unassigned Pseudomonas species. Hypersensitivity response assays and infection studies using sissoo seedlings demonstrated their pathogenic potential. Key words: Sissoo, dieback, Pseudomonas, fungal pathogens D.O.I. 10.3329/ptcb.v21i2.10214 Plant Tissue Cult. & Biotech. 21(2): 101-113, 2011 (December)
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