Reconstruction of a Posterior Tracheal Wall Defect With a Myocutaneous Pectoralis Major Flap After Salvage Cervical Exenteration for a Squamous Carcinoma of the Upper Third of the Esophagus.

In this article, we describe the case of a 59-year-old patient suffering from a squamous cell carcinoma affecting the upper third of the esophagus, treated with a cervical exenteration with extended resection of the posterior wall of the trachea, which was reconstructed with a gastric tube transposition and a myocutaneous pectoralis major flap for coverage of the gastropharyngeal anastomosis and stabilization of the posterior tracheal wall. Also, a review of literature regarding posterior tracheal wall reconstruction is performed.

Variable Pacing Is Associated with Performance during the OCC® Ultra-Trail du Mont-Blanc® (2017-2021).

The current evidence suggests that pacing may not be affected by performance level or sex in trail-running races as may occur in road running races. However, the previous studies included races of >100 km. Therefore, we aimed to verify the influence of performance level and sex on pacing in the last four (2017, 2018, 2019, and 2021) editions of a shorter (56.3 km) ultra-trail running race (i.e., Orsières-Champex-Chamonix; OCC®) that maintained the same race profile. The mean finishing time for the 5656 participants was 10 h 20 min 33 s ± 2 h 01 min 19 s. Pacing variability (CV%) was higher in high-level participants, thus showing a greater ability to adapt their pace to the race profile than low-level runners. Males also had a higher pacing variability than females although the effect sizes were small. Based on the current findings, we may recommend for non-elite OCC® participants to adapt their pace to the race profile with a slower pace during uphills and a faster pace during downhills. Further studies including participants' experience are necessary to confirm the effectiveness of this suggestion in trail-running races of variable distances.

How Drosophila change their combs: the Hox gene Sex combs reduced and sex comb variation among Sophophora species.

Identification of the events responsible for rapid morphological variation during evolution can help understand how developmental processes are changed by genetic modifications and thus produce diverse body features and shapes. Sex combs, a sexually dimorphic structure, show considerable variation in morphology and numbers among males from related species of Sophophora, a subgenus of Drosophila. To address which evolutionary changes in developmental processes underlie this diversity, we first analyzed the genetic network that controls morphogenesis of a single sex comb in the model D. melanogaster. We show that it depends on positive and negative regulatory inputs from proximo-distal identity specifying genes, including dachshund, bric à brac, and sex combs distal. All contribute to spatial regulation of the Hox gene Sex combs reduced (Scr), which is crucial for comb formation. We next analyzed the expression of these genes in sexually dimorphic species with different comb numbers. Only Scr shows considerable expression plasticity, which is correlated with comb number variation in these species. We suggest that differences in comb numbers reflect changes of Scr expression in tarsus primordia, and discuss how initial comb formation could have occurred in an ancestral Sophophora fly following regulatory modifications of developmental programs both parallel to and downstream of Scr.

Regulation of larval hematopoiesis in Drosophila melanogaster: a role for the multi sex combs gene.

Drosophila larval hematopoietic organs produce circulating hemocytes that ensure the cellular host defense by recognizing and neutralizing non-self or noxious objects through phagocytosis or encapsulation and melanization. Hematopoietic lineage specification as well as blood cell proliferation and differentiation are tightly controlled. Mutations in genes that regulate lymph gland cell proliferation and hemocyte numbers in the body cavity cause hematopoietic organ overgrowth and hemocyte overproliferation. Occasionally, mutant hemocytes invade self-tissues, behaving like neoplastic malignant cells. Two alleles of the Polycomb group (PcG) gene multi sex combs (mxc) were previously isolated as such lethal malignant blood neoplasm mutations. PcG genes regulate Hox gene expression in vertebrates and invertebrates and participate in mammalian hematopoiesis control. Hence we investigated the need for mxc in Drosophila hematopoietic organs and circulating hemocytes. We show that mxc-induced hematopoietic hyperplasia is cell autonomous and that mxc mainly controls plasmatocyte lineage proliferation and differentiation in lymph glands and circulating hemocytes. Loss of the Toll pathway, which plays a similar role in hematopoiesis, counteracted mxc hemocyte proliferation but not mxc hemocyte differentiation. Several PcG genes tested in trans had no effects on mxc hematopoietic phenotypes, whereas the trithorax group gene brahma is important for normal and mutant hematopoiesis control. We propose that mxc provides one of the regulatory inputs in larval hematopoiesis that control normal rates of plasmatocyte and crystal lineage proliferation as well as normal rates and timing of hemocyte differentiation.

Getting new bronchodilator compounds from molecular topology.

Molecular topology has been used to select new lead bronchodilator compounds. The main advantage of this method, as compared to others frequently used, is that it does not require a previous explicit knowledge of the mechanism of action (MOA) of the compounds analyzed. A large database (12,000 chemicals) has been examined in this study to find less than 5% compounds with bronchodilator activity. After removing those compounds already described as bronchodilators, we present here the results for 20 among these compounds, some of them showing other pharmacological activities. Some of the compounds selected in this study showed higher relaxation and higher potency than theophylline, which is the reference drug used in the bronchodilator assay performed. For instance, tetrahydro-papaveroline showed significantly higher values than theophylline (93.9% versus 77.0% and pD2=7.30 versus pD2=4.69, respectively). Other compounds, although eliciting small or no relaxation at 0.1mM, produced larger relaxation at higher concentrations (1mM). In conclusion, the molecular topology based approach used in this work has demonstrated to be effective in the search of new bronchodilators.

On the causes of sterility in some interspecific hybrids from theMelanogaster subgroup ofDrosophila.

The females produced in the crossesD. melanogaster×D. simulans andD. melanogaster×D. mauritiana are sterile and have reduced ovaries.Normal and fertile ovaries were produced when genetically marked pole cells ofD. melanogaster were transplanted into eggs which gave rise to the hybrid females.These results eliminate the possibility that the sterility of these hybrids is due to the somatic component, i.e. the follicular cells of the ovaries, or to other physiological causes. The results also suggest that the control of gonadal morphogenesis is dependent mainly on the germ line.

Developmental analysis of two wing scalloping mutantsct 6 andBx J ofDrosophila melanogaster.

The mutantscut 6 (ct6) andBeadex of Jollos (Bx J) show nicks in the wing margins as well as other malformations in different regions of the body. Clonal analysis of the wing disk's development in these mutants indicates that massive cell loss occurs during the third larval instar. Morphogenetic mosaics, originating from mitotic recombination, reveal a non-autonomous behaviour of both mutant and wild-type cells. X-rays applied during the third larval instar produce phenocopies of these mutants. A clonal and a genetic analysis of these phenocopies has been carried out.The hypothesis that scalloping mutants such asct 6, BxJ and others, as well as X-rays, affect properties of cellular interaction, such as cell adhesivity or cohesion, is discussed. Morphogenetic mosaics in the wing margin suggest that the differentiation of the marginal cuticular elements requires the interaction of the cells of the ventral and dorsal surfaces of the wing.

Pattern triplications following genetic ablation on the wing ofDrosophila : Effect of eliminating thepolyhomeotic gene.

The effects ofpolyhomeotic (ph) mutants in imaginal cells have been studied in a clonal analysis. Clones of cells, homozygous forph, sort-out after a few divisions, probably as a consequence of modified cell affinities. The dorso-ventral margin of the wing has special characteristics that retard this phenomenon. The formation and exclusion of a clone of 8-16 cells affect the polarity of the wild-type neighbour cells and can provoke pattern triplications. The results suggest that a defect in intercellular communication prevents the wild-type cells from maintaining coordinated positional information. The cells react by regenerative growth, and reorganize into a new pattern. The pleiotropic phenotypes ofph mutants are explained according to a common hypothesis aboutph + function.

Maternal and zygotic requirement for thepolyhomeotic complex genetic locus inDrosophila.

The complex genetic locuspolyhomeotic (ph) is a member of thePolycomb (Pc)-group of genes and as such is required for the normal expression of ANT-C and BX-C genes. It also has probably other functions since amorphicph alleles display a cell death phenotype in the ventral epidermis of 12-h-old embryos. Here it is shown that lethal alleles ofph (amorph and strong hypomorph) show transformation of most of their segments towards AB8. Theph + product is required autonomously in imaginal cells. The total lack ofph + function prevents viability of the cuticular derivatives of these cells.ph has a strong maternal effect on segmental identity and epidermal development that can not be rescued by one paternally supplied dose ofph + in the zygote. These phenotypes differ substantially from those of previously describedPc-group genes. AmongPc-group genes,ph seems to be the only one that is strongly required both maternally and zygotically for normal embryonic development.

The multi sex combs gene of Drosophila melanogaster is required for proliferation of the germline.

We present a genetic analysis showing that the Drosophila melanogaster gene multi sex combs (mxc; Santamaria and Randsholt 1995) is needed for proliferation of the germline. Fertility is the feature most easily affected by weak hypomorphic mutations of this very pleiotropic locus. Pole cell formation and early steps of gonadogenesis conform to the wild-type in embryos devoid of zygotic mxc + product. mxc mutant gonad phenotypes and homozygous mxc germline clones suggest a role for mxc + in control of germ cell proliferation during the larval stages. mxc + requirement is germ cell autonomous and specific in females, whilst in males mxc + product is also needed in somatic cells of the gonads. Although mxc can be classified among the Polycomb group (Pc-G) of genes, negative trans-regulators of the ANT-C and BX-C gene complexes, germline requirement for mxc appears independent of a need for other Pc-C gene products, and mxc gonad phenotypes are different from those induced by mutations in BX-C genes. We discuss the possible functions of the mxc + product which helps to maintain homeotic genes repressed and prevents premature larval haemocyte differentiation and neoplasic overgrowth, but promotes growth and differentiation of male and female gonads.

Differential requirements for the neurogenic gene almondex during Drosophila melanogaster development.

During early development, the neurogenic genes of Drosophila melanogaster are involved in the control of cell fates in the neurectoderm; almondex (amx) belongs to this category of genes. We have identified the amx locus and rescued the amx embryonic neurogenic phenotype with a 1.5 kb DNA fragment. Using a small deficiency, we generated a new amx mutant background called amx(m), which is a null allele. Besides the characteristic neurogenic maternal effect caused by loss of amx, amx(m) flies display a new imaginal phenotype resembling loss of function of Notch. We describe amx-induced misregulation of the Notch pathway target E(spl) m7 in embryos and genetic interactions between amx and Notch pathway mutants in adult flies. These data show that wildtype amx acts as a novel positive regulator of the Notch pathway and is required at different levels during development.