Morphologically defined sub-stages of C. elegans vulval development in the fourth larval stage

Background: During the fourth larval (L4) stage, vulval cells of C. elegans undergo extensive morphogenesis accompanied by changes in gene expression. This phase of vulval development, occurring after the well-studied induction of vulval cells, is not well understood but is potentially a useful context in which to study how a complex temporal sequence of events is regulated during development. However, a system for precisely describing different phases of vulval development in the L4 stage has been lacking. Results: We defined ten sub-stages of L4 based on morphological criteria as observed using Nomarski microscopy (L4.0 ~ L4.9). Precise timing of each sub-stage at 20 °C was determined. We also re-examined the timing of expression for several gene expression markers, and correlated the sub-stages with the timing of other developmental events in the vulva and the uterus. Conclusions: This scheme allows the developmental timing of an L4 individual to be determined at approximately one-hour resolution without the need to resort to time course experiments. These well-defined developmental stages will enable more precise description of gene expression and other developmental events

Is gastro-oesophageal reflux a factor in exercise-induced asthma?

AbstractExercise-induced bronchoconstriction (EIB) occurs in the majority of patients with asthma. The relationship between asthma and gastro-oesophageal reflux (GER) is well defined, and the reports of exertional gastro-oesophageal acid reflux in healthy subjects, prompted us to study the relationship between EIB and GER.Following an overnight fast and medication withholding, 15 asthmatics and 15 normal subjects were placed on continuous monitoring of oesophageal pH and ECG. After baseline monitoring of oesophageal pH, at rest, for 30 min, spirometry was performed. Thereafter, the subjects underwent rigorous treadmill exercise for 8 min followed by spirometry, 10 min after running.Twelve out of 15 asthmatics and none in the control group demonstrated significant fall in FEV1 in response to exercise. However, only six out of 15 normal subjects and three in the asthmatic group had evidence of GER during or following exercise.We concluded that there is no significant correlation between EIB and GER in patients with asthma

Non-abelian Harmonic Oscillators and Chiral Theories

We show that a large class of physical theories which has been under intensive investigation recently, share the same geometric features in their Hamiltonian formulation. These dynamical systems range from harmonic oscillations to WZW-like models and to the KdV dynamics on $Diff_oS^1$. To the same class belong also the Hamiltonian systems on groups of maps. The common feature of these models are the 'chiral' equations of motion allowing for so-called chiral decomposition of the phase space.Comment: 1

LINKIN, a new transmembrane protein necessary for cell adhesion

In epithelial collective migration, leader and follower cells migrate while maintaining cell-cell adhesion and tissue polarity. We have identified a conserved protein and interactors required for maintaining cell adhesion during a simple collective migration in the developing C. elegans male gonad. LINKIN is a previously uncharacterized, transmembrane protein conserved throughout Metazoa. We identified seven atypical FG-GAP domains in the extracellular domain, which potentially folds into a β-propeller structure resembling the α-integrin ligand-binding domain. C. elegans LNKN-1 localizes to the plasma membrane of all gonadal cells, with apical and lateral bias. We identified the LINKIN interactors RUVBL1, RUVBL2, and α-tubulin by using SILAC mass spectrometry on human HEK 293T cells and testing candidates for lnkn-1-like function in C. elegans male gonad. We propose that LINKIN promotes adhesion between neighboring cells through its extracellular domain and regulates microtubule dynamics through RUVBL proteins at its intracellular domain

Exterior Differentials in Superspace and Poisson Brackets

It is shown that two definitions for an exterior differential in superspace, giving the same exterior calculus, yet lead to different results when applied to the Poisson bracket. A prescription for the transition with the help of these exterior differentials from the given Poisson bracket of definite Grassmann parity to another bracket is introduced. It is also indicated that the resulting bracket leads to generalization of the Schouten-Nijenhuis bracket for the cases of superspace and brackets of diverse Grassmann parities. It is shown that in the case of the Grassmann-odd exterior differential the resulting bracket is the bracket given on exterior forms. The above-mentioned transition with the use of the odd exterior differential applied to the linear even/odd Poisson brackets, that correspond to semi-simple Lie groups, results, respectively, in also linear odd/even brackets which are naturally connected with the Lie superalgebra. The latter contains the BRST and anti-BRST charges and can be used for calculation of the BRST operator cohomology.Comment: 12 pages, LATEX 2e, JHEP format. Correction of misprints. The titles for some references are adde

Kynurenine pathway inhibition reduces central nervous system inflammation in a model of human African trypanosomiasis

Human African trypanosomiasis, or sleeping sickness, is caused by the protozoan parasites <i>Trypanosoma brucei rhodesiense</i> or <i>Trypanosoma brucei gambiense</i>, and is a major cause of systemic and neurological disability throughout sub-Saharan Africa. Following early-stage disease, the trypanosomes cross the blood-brain barrier to invade the central nervous system leading to the encephalitic, or late stage, infection. Treatment of human African trypanosomiasis currently relies on a limited number of highly toxic drugs, but untreated, is invariably fatal. Melarsoprol, a trivalent arsenical, is the only drug that can be used to cure both forms of the infection once the central nervous system has become involved, but unfortunately, this drug induces an extremely severe post-treatment reactive encephalopathy (PTRE) in up to 10% of treated patients, half of whom die from this complication. Since it is unlikely that any new and less toxic drug will be developed for treatment of human African trypanosomiasis in the near future, increasing attention is now being focussed on the potential use of existing compounds, either alone or in combination chemotherapy, for improved efficacy and safety. The kynurenine pathway is the major pathway in the metabolism of tryptophan. A number of the catabolites produced along this pathway show neurotoxic or neuroprotective activities, and their role in the generation of central nervous system inflammation is well documented. In the current study, Ro-61-8048, a high affinity kynurenine-3-monooxygenase inhibitor, was used to determine the effect of manipulating the kynurenine pathway in a highly reproducible mouse model of human African trypanosomiasis. It was found that Ro-61-8048 treatment had no significant effect (P = 0.4445) on the severity of the neuroinflammatory pathology in mice during the early central nervous system stage of the disease when only a low level of inflammation was present. However, a significant (P = 0.0284) reduction in the severity of the neuroinflammatory response was detected when the inhibitor was administered in animals exhibiting the more severe, late central nervous system stage, of the infection. <i>In vitro</i> assays showed that Ro-61-8048 had no direct effect on trypanosome proliferation suggesting that the anti-inflammatory action is due to a direct effect of the inhibitor on the host cells and not a secondary response to parasite destruction. These findings demonstrate that kynurenine pathway catabolites are involved in the generation of the more severe inflammatory reaction associated with the late central nervous system stages of the disease and suggest that Ro-61-8048 or a similar drug may prove to be beneficial in preventing or ameliorating the PTRE when administered as an adjunct to conventional trypanocidal chemotherap

Bundle Theory of Improper Spin Transformations

{\it We first give a geometrical description of the action of the parity operator ($\hat{P}$) on non relativistic spin ${{1}\over{2}}$ Pauli spinors in terms of bundle theory. The relevant bundle, $SU(2)\odot \Z_2\to O(3)$, is a non trivial extension of the universal covering group $SU(2)\to SO(3)$. $\hat{P}$ is the non relativistic limit of the corresponding Dirac matrix operator ${\cal P}=i\gamma_0$ and obeys $\hat{P}^2=-1$. Then, from the direct product of O(3) by $\Z_2$, naturally induced by the structure of the galilean group, we identify, in its double cover, the time reversal operator ($\hat{T}$) acting on spinors, and its product with $\hat{P}$. Both, $\hat{P}$ and $\hat{T}$, generate the group $\Z_4 \times \Z_2$. As in the case of parity, $\hat{T}$ is the non relativistic limit of the corresponding Dirac matrix operator ${\cal T}=\gamma^3 \gamma^1$, and obeys $\hat{T}^2=-1$.}Comment: 8 pages, Plaintex; titled changed, minor text modifications, one reference complete

Small-scale field evaluation of PermaNet® Dual (a long-lasting net coated with a mixture of chlorfenapyr and deltamethrin) against pyrethroid-resistant Anopheles gambiae mosquitoes from Tiassalé, Côte d'Ivoire

BACKGROUND: Due to the rapid expansion of pyrethroid-resistance in malaria vectors in Africa, Global Plan for Insecticide Resistance Management (GPIRM) has recommended the development of long-lasting insecticidal nets (LLINs), containing insecticide mixtures of active ingredients with different modes of action to mitigate resistance and improve LLIN efficacy. This good laboratory practice (GLP) study evaluated the efficacy of the chlorfenapyr and deltamethrin-coated PermaNet((R)) Dual, in comparison with the deltamethrin and synergist piperonyl butoxide (PBO)-treated PermaNet((R)) 3.0 and the deltamethrin-coated PermaNet((R)) 2.0, against wild free-flying pyrethroid-resistant Anopheles gambiae sensu lato (s.l.), in experimental huts in Tiassale, Cote d'Ivoire (West Africa). METHODS: PermaNet((R)) Dual, PermaNet((R)) 3.0 and PermaNet((R)) 2.0, unwashed and washed (20 washes), were tested against free-flying pyrethroid-resistant An. gambiae s.l. in the experimental huts in Tiassale, Cote d'Ivoire from March to August 2020. Complementary laboratory cone bioassays (daytime and 3-min exposure) and tunnel tests (nightly and 15-h exposure) were performed against pyrethroid-susceptible An. gambiae sensu stricto (s.s.) (Kisumu strain) and pyrethroid-resistant An. gambiae s.l. (Tiassale strain). RESULTS: PermaNet((R)) Dual demonstrated significantly improved efficacy, compared to PermaNet((R)) 3.0 and PermaNet((R)) 2.0, against the pyrethroid-resistant An. gambiae s.l. Indeed, the experimental hut trial data showed that the mortality and blood-feeding inhibition in the wild pyrethroid-resistant An. gambiae s.l. were overall significantly higher with PermaNet((R)) Dual compared with PermaNet((R)) 3.0 and PermaNet((R)) 2.0, for both unwashed and washed samples. The mortality with unwashed and washed samples were 93.6 +/- 0.2% and 83.2 +/- 0.9% for PermaNet((R)) Dual, 37.5 +/- 2.9% and 14.4 +/- 3.9% for PermaNet((R)) 3.0, and 7.4 +/- 5.1% and 11.7 +/- 3.4% for PermaNet((R)) 2.0, respectively. Moreover, unwashed and washed samples produced the respective percentage blood-feeding inhibition of 41.4 +/- 6.9% and 43.7 +/- 4.8% with PermaNet((R)) Dual, 51.0 +/- 5.7% and 9.8 +/- 3.6% with PermaNet((R)) 3.0, and 12.8 +/- 4.3% and - 13.0 +/- 3.6% with PermaNet((R)) 2.0. Overall, PermaNet((R)) Dual also induced higher or similar deterrence, exophily and personal protection when compared with the standard PermaNet((R)) 3.0 and PermaNet((R)) 2.0 reference nets, with both unwashed and washed net samples. In contrast to cone bioassays, tunnel tests predicted the efficacy of PermaNet((R)) Dual seen in the current experimental hut trial. CONCLUSION: The deltamethrin-chlorfenapyr-coated PermaNet((R)) Dual induced a high efficacy and performed better than the deltamethrin-PBO PermaNet((R)) 3.0 and the deltamethrin-only PermaNet((R)) 2.0, testing both unwashed and 20 times washed samples against the pyrethroid-susceptible and resistant strains of An. gambiae s.l. The inclusion of chlorfenapyr with deltamethrin in PermaNet((R)) Dual net greatly improved protection and control of pyrethroid-resistant An. gambiae populations. PermaNet((R)) Dual thus represents a promising tool, with a high potential to reduce malaria transmission and provide community protection in areas compromised by mosquito vector resistance to pyrethroids