Setting critical nutrient values for ditches using the eutrophication model PCDitch

Critical nutrient loads to prevent duckweed dominance loads in polder ditches were assessed using the eutrophication model PCDitch. In this article the ecological target was set at 50% duckweed coverage. This may be very high for ditches with a nature function, but is not unreasonable for ditches in agricultural areas, with upwelling nutrient rich groundwater, run-off and drainage. Since the change from a ditch with submersed vegetation to duckweed coverage is often a sudden shift, the choice of the amount of duckweed coverage does not influence the calculated loading very much. The main topic of this paper is to present a method to calculate critical loads of nutrients when ecological targets have been set. Sediment type, residence time and water depth influenced the critical loading rates. The calculated critical phosphorus load ranged from 1.8 to 10.2 g P m⁻² year⁻¹, while the calculated critical nitrogen load stretched from 12.1 to 43.8 g N m⁻² year⁻¹. The concentration ranges that were derived from the loading rate were 0.19–0.42 mg P l⁻¹ and 1.3–3.3 mg N l⁻¹. Since PCDitch does not distinguish between Lemna spp. and Azolla spp., no definite conclusions were drawn concerning the effects of nitrogen reduction. In a model situation a pristine ditch was loaded with phosphorus, which resulted into complete duckweed coverage during summer within a few years. When reducing the phosphorus load, it took 10 years before the original situation was reached again. Dredging would accelerate the process of recovery significantly, because the water depth would increase and the phosphorus release from the sediments in summer would decrease. Received September 2003; accepted in revised form February 2005     

Hormonal Contraception and the Risk of HIV Acquisition: An Individual Participant Data Meta-analysis

BackgroundObservational studies of a putative association between hormonal contraception (HC) and HIV acquisition have produced conflicting results. We conducted an individual participant data (IPD) meta-analysis of studies from sub-Saharan Africa to compare the incidence of HIV infection in women using combined oral contraceptives (COCs) or the injectable progestins depot-medroxyprogesterone acetate (DMPA) or norethisterone enanthate (NET-EN) with women not using HC.ConclusionsThis IPD meta-analysis found no evidence that COC or NET-EN use increases women’s risk of HIV but adds to the evidence that DMPA may increase HIV risk, underscoring the need for additional safe and effective contraceptive options for women at high HIV risk. A randomized controlled trial would provide more definitive evidence about the effects of hormonal contraception, particularly DMPA, on HIV risk.     

Time course analysis of baroreflex sensitivity during postural stress

Postural stress requires immediate autonomic nervous action to maintain blood pressure. We determined time-domain cardiac baroreflex sensitivity (BRS) and time delay (tau) between systolic blood pressure and interbeat interval variations during stepwise changes in the angle of vertical body axis (alpha). The assumption was that with increasing postural stress, BRS becomes attenuated, accompanied by a shift in tau toward higher values. In 10 healthy young volunteers, alpha included 20 degrees head-down tilt (-20 degrees), supine (0 degree), 30 and 70 degrees head-up tilt (30 degrees, 70 degrees), and free standing (90 degrees). Noninvasive blood pressures were analyzed over 6-min periods before and after each change in alpha. The BRS was determined by frequency-domain analysis and with xBRS, a cross-correlation time-domain method. On average, between 28 (-20 degrees) to 45 (90 degrees) xBRS estimates per minute became available. Following a change in alpha, xBRS reached a different mean level in the first minute in 78% of the cases and in 93% after 6 min. With increasing alpha, BRS decreased: BRS = -10.1.sin(alpha) + 18.7 (r(2) = 0.99) with tight correlation between xBRS and cross-spectral gain (r(2) approximately 0.97). Delay tau shifted toward higher values. In conclusion, in healthy subjects the sensitivity of the cardiac baroreflex obtained from time domain decreases linearly with sin(alpha), and the start of baroreflex adaptation to a physiological perturbation like postural stress occurs rapidly. The decreases of BRS and reduction of short tau may be the result of reduced vagal activity with increasing alpha.     

Relationship of cryptorchidism with sex ratios and litter sizes in 12 dog breeds

The aim of this study was to identify the influence of genetic carriership for cryptorchidism on litter sizes and sex ratios in the offspring. Weaning data of 11,230 litters in 12 purebred dog breeds were evaluated. Parents were classified as cryptorchidism 'carriers' (C) when at least one of their offspring was found cryptorchid. Subsequently the effects of 'carrier' and 'non-carrier' (NC) parents on their litters were studied. In litters from C x C parents we found an increased number of males per litter in all breeds, a reduced number of females per litter in 8 breeds and an increased litter size in 11 breeds in comparison with litters from NC x NC parents. Over all breeds the effects on litter size, on number of males per litter and on sex ratio were highly significant. Mixed litters from C x NC and NC x C did not show these effects and were not significantly different from the NC x NC offspring. Our results suggest a general mechanism in the dog species which causes cryptorchidism as well as increased male/female ratios and increased litter sizes. A consequence of such a mechanism is that selection in favor of increasing reproduction output frustrates selective efforts to eliminate cryptorchidism.     

Homozygosity Mapping Reveals PDE6C Mutations in Patients with Early-Onset Cone Photoreceptor Disorders

Cone photoreceptor disorders form a clinical spectrum of diseases that include progressive cone dystrophy (CD) and complete and incomplete achromatopsia (ACHM). The underlying disease mechanisms of autosomal recessive (ar)CD are largely unknown. Our aim was to identify causative genes for these disorders by genome-wide homozygosity mapping. We investigated 75 ACHM, 97 arCD, and 20 early-onset arCD probands and excluded the involvement of known genes for ACHM and arCD. Subsequently, we performed high-resolution SNP analysis and identified large homozygous regions spanning the PDE6C gene in one sibling pair with early-onset arCD and one sibling pair with incomplete ACHM. The PDE6C gene encodes the cone α subunit of cyclic guanosine monophosphate (cGMP) phosphodiesterase, which converts cGMP to 5′-GMP, and thereby plays an essential role in cone phototransduction. Sequence analysis of the coding region of PDE6C revealed homozygous missense mutations (p.R29W, p.Y323N) in both sibling pairs. Sequence analysis of 104 probands with arCD and 10 probands with ACHM revealed compound heterozygous PDE6C mutations in three complete ACHM patients from two families. One patient had a frameshift mutation and a splice defect; the other two had a splice defect and a missense variant (p.M455V). Cross-sectional retinal imaging via optical coherence tomography revealed a more pronounced absence of cone photoreceptors in patients with ACHM compared to patients with early-onset arCD. Our findings identify PDE6C as a gene for cone photoreceptor disorders and show that arCD and ACHM constitute genetically and clinically overlapping phenotypes.     

The APC/C recruits cyclin B1–Cdk1–Cks in prometaphase before D box recognition to control mitotic exit

The ubiquitin ligase anaphase-promoting complex/cyclosome (APC/C) is activated at prometaphase by mitotic phosphorylation and binding of its activator, Cdc20. This initiates cyclin A degradation, whereas cyclin B1 is stabilized by the spindle checkpoint. Upon checkpoint release, the RXXL destruction box (D box) was proposed to direct cyclin B1 to core APC/C or Cdc20. In this study, we report that endogenous cyclin B1–Cdk1 is recruited to checkpoint-inhibited, phosphorylated APC/C in prometaphase independently of Cdc20 or the cyclin B1 D box. Like cyclin A, cyclin B1 binds the APC/C by the Cdk cofactor Cks and the APC3 subunit. Prior binding to APC/C^Cdc20 makes cyclin B1 a better APC/C substrate in metaphase, driving mitotic exit and cytokinesis. We conclude that in prometaphase, the phosphorylated APC/C can recruit both cyclin A and cyclin B1 in a Cks-dependent manner. This suggests that the spindle checkpoint blocks D box recognition of APC/C-bound cyclin B1, whereas distinctive complexes between the N terminus of cyclin A and Cdc20 evade checkpoint control.     

Binding of low density lipoprotein to platelet apolipoprotein E receptor 2' results in phosphorylation of p38MAPK

Binding of low density lipoprotein (LDL) to platelets enhances platelet responsiveness to various aggregation-inducing agents. However, the identity of the platelet surface receptor for LDL is unknown. We have previously reported that binding of the LDL component apolipoprotein B100 to platelets induces rapid phosphorylation of p38 mitogen-activated protein kinase (p38MAPK). Here, we show that LDL-dependent activation of this kinase is inhibited by receptor-associated protein (RAP), an inhibitor of members of the LDL receptor family. Confocal microscopy revealed a high degree of co-localization of LDL and a splice variant of the LDL receptor family member apolipoprotein E receptor-2 (apoER2') at the platelet surface, suggesting that apoER2' may contribute to LDL-induced platelet signaling. Indeed, LDL was unable to induce p38MAPK activation in platelets of apoER2-deficient mice. Furthermore, LDL bound efficiently to soluble apoER2', and the transient LDL-induced activation of p38MAPK was mimicked by an anti-apoER2 antibody. Association of LDL to platelets resulted in tyrosine phosphorylation of apoER2', a process that was inhibited in the presence of PP1, an inhibitor of Src-like tyrosine kinases. Moreover, phosphorylated but not native apoER2' co-precipitated with the Src family member Fgr. This suggests that exposure of platelets to LDL induces association of apoER2' to Fgr, a kinase that is able to activate p38MAPK. In conclusion, our data indicate that apoER2' contributes to LDL-dependent sensitization of platelets.     

Strong and symmetric halogen bonding in coordination compounds of carboxylic acid derivatives; the crystal structure of (3,6-dithiaoctanedioato-S,S′-(3,6-dithiaoctanedioic acid-S,S′)-copper(I) redetermined at 173 K

3,6-dithianoctanedioic acid forms a Cu(I) compound in which electrical neutrality is achieved by elaborate hydrogen bonding and sharing on protons. The title compund crystallizes in the monoclinic space group P2/n with Z = 2. Unit-cell parameters are a = 11.625(2), b = 7.664(1), c = 9.874(2) Å, β = 95.16°, D_m = 1.80(2), D_c = 1.83 g cm^?3. The structure was solved by means of standard direct methods and refined with full-matrix least-squares techniques to an R-value of 0.026 (R_w = 0.042). The Cu(I) ion is tetrahedrally coordinated by four thioether S-atoms (CuS = 2.29–2.33 Å). The molecules are linked by very strong hydrogen bonds between non-coordinating carboxylate groups in such a way that the average number of acidic hydrogens per molecule is three. One of these hydrogens lies on a twofold axis and forms a short symmetrical hydrogen bond, with a OO distance of 2.441(2) Å. Unusual features in the infrared spectrum of this compund can be interpreted on the basis of the observed crystal structure.