Coupling of growth rate and developmental tempo reduces body size heterogeneity in C. elegans.

Animals increase by orders of magnitude in volume during development. Therefore, small variations in growth rates among individuals could amplify to a large heterogeneity in size. By live imaging of C. elegans, we show that amplification of size heterogeneity is prevented by an inverse coupling of the volume growth rate to the duration of larval stages and does not involve strict size thresholds for larval moulting. We perturb this coupling by changing the developmental tempo through manipulation of a transcriptional oscillator that controls the duration of larval development. As predicted by a mathematical model, this perturbation alters the body volume. Model analysis shows that an inverse relation between the period length and the growth rate is an intrinsic property of genetic oscillators and can occur independently of additional complex regulation. This property of genetic oscillators suggests a parsimonious mechanism that counteracts the amplification of size differences among individuals during development

Fauna of monogenean trematodes-parasites of some cyprinid fishes from lake Prespa, Macedonia

During parasitological investigations six species of monogenean trematodes were found on the gills of three cyprinid fish species from Lake Prespa (Macedonia), as follows: Dactylogyrus prostae and Dactylogyrus sphyrna in Leuciscus cephalus albus, Dactylogyrus erhardovae, Dactylogyrus sphyrna and Paradiplozoon zeller in Rutilus rubilio prespensis and Dactylogyrus elegantis and Dactylogyrus vistulae in Chondrostoma nasus prespensis. The prevalence in Leuciscus cephalus albus was 62.22%, in Rutilus rubilio prespensis 59.87% while in Chondrostoma nasus prespensis it was the lowest and amounted to 41.59%. The overall, prevalence of monogeneans in the investigated cyprinid fishes from Lake Prespa was 53.65%, and the mean intensity of infestation was 6.08. Among the monogenean species the highest prevalence occurred with Dactylogyrus sphyrna (25.08%), and the greatest intensity of infestation was evident in the cases of infestation with Dactylogyrus erhardovae (12.87). The greatest pathological effect was associated with the monogeneans Dactylogyrus vistulae and Paradiplozoon zeller. All monogenean species found represented the first record for such parasite fauna of fishes in Macedonia.U toku parazitoloških istraživanja ciprinidnih riba iz Prespanskog jezera (Makedonija), kod 3 vrste riba na škrgama pronađeno je 6 vrsta monogenih trematoda, i to: kod Leuciscus cephalus albus su nađeni Dactylogyrus prostae i Dactylogyrus sphyrna, kod Rutilus rubilio prespensis su pronađeni Dactylogyrus erhardovae, Dactylogyrus sphyrna i Paradiplozoon zeller, kod Chondrostoma nasus prespensis su pronađeni Dactylogyrus elegantis i Dactylogyrus vistulae. Ekstenzitet infestacije kod Leuciscus cephalus albus iznosio je 62,22%, kod Rutilus rubilio prespensis 59,87%, a kod Chondrostoma nasus prespensis je bio najniži i iznosio je 41,59%. Ukupno, ekstenzitet infestacije sa monogeneama kod ispitivanih ciprinidnih riba Prespanskog jezera iznosio je 53,65%, a intenzitet infestacije 6,08. Pojedinačno, po vrstama monogenea, najviši ekstenzitet infestacije je bio sa Dactylogyrus sphyrna (25,08%), a najviši intenzitet infestacije je utvrđen u slučajevima infestacije sa Dactylogyrus erhardovae (12,87). Najveći patogeni uticaj su imale monogene trematode Dactylogyrus vistulae i Paradiplozoon zeller. Sve pronađene vrste monogenea predstavljaju prvi nalaz za parazitofaunu riba Makedonije.nul

Neuronal mTORC1 inhibition promotes longevity without suppressing anabolic growth and reproduction in C. elegans.

mTORC1 (mechanistic target of rapamycin complex 1) is a metabolic sensor that promotes growth when nutrients are abundant. Ubiquitous inhibition of mTORC1 extends lifespan in multiple organisms but also disrupts several anabolic processes resulting in stunted growth, slowed development, reduced fertility, and disrupted metabolism. However, it is unclear if these pleotropic effects of mTORC1 inhibition can be uncoupled from longevity. Here, we utilize the auxin-inducible degradation (AID) system to restrict mTORC1 inhibition to C. elegans neurons. We find that neuron-specific degradation of RAGA-1, an upstream activator of mTORC1, or LET-363, the ortholog of mammalian mTOR, is sufficient to extend lifespan in C. elegans. Unlike raga-1 loss of function genetic mutations or somatic AID of RAGA-1, neuronal AID of RAGA-1 robustly extends lifespan without impairing body size, developmental rate, brood size, or neuronal function. Moreover, while degradation of RAGA-1 in all somatic tissues alters the expression of thousands of genes, demonstrating the widespread effects of mTORC1 inhibition, degradation of RAGA-1 in neurons only results in around 200 differentially expressed genes with a specific enrichment in metabolism and stress response. Notably, our work demonstrates that targeting mTORC1 specifically in the nervous system in C. elegans uncouples longevity from growth and reproductive impairments, and that many canonical effects of low mTORC1 activity are not required to promote healthy aging. These data challenge previously held ideas about the mechanisms of mTORC1 lifespan extension and underscore the potential of promoting longevity by neuron-specific mTORC1 modulation

Mechanoenzymatic reactions for the hydrolysis of PET

Recent advances in the enzymatic degradation of poly(ethylene terphthalate) (PET) have led to a number of PET hydrolytic enzymes and mutants being developed. With the amount of PET building up in the natural world, there is a pressing need to develop scalable methods of breaking down the polymer into its monomers for recycling or other uses. Mechanoenzymatic reactions have gained traction recently as a green and efficient alternative to traditional biocatalytic reactions. For the first time we report increased yields of PET degradation by whole cell PETase enzymes by up to 27-fold by utilising ball milling cycles of reactive aging, when compared with typical solution-based reactions. This methodology leads to up to a 2600-fold decrease in the solvent required when compared with other leading degradation reactions in the field and a 30-fold decrease in comparison to reported industrial scale PET hydrolysis reactions

Occurence of Anguillicola crassus, ematoda: Dracunculoidea, in eels of lake Ohrid, Macedonia

The first record of the eel parasite Anguillicola crassus Kuwahara (Niimietltagaki, 1974) from Lake Ohrid and the Republic of Macedonia is reported here. Parasitological examinations comprised 68 specimens of the eel Anguilla anguilla Linnaeus, 1758 of which 39.71% were infected with Anguillicola crassus. The prevalence varied depending on the season, with the highest value occuring during the autumn (47.06%). Average intensity of infection was 10.33. Anguillicola crassus was probably introduced into the lake by the artificial stocking with eel young, imported from abroad. It has found convenient conditions for development and multiplication in the lake due to the presence of transitional and paratenic hosts.U periodu od aprila 1995. do marta 1996. godine, na makedonskom delu Ohridskog jezera, parazitološkompretragomobuhvaćenoje68primerakajegulja (Anguilla anguilla Linnaeus, 1758), od kojih je 27 bilo inficirano nematodom Anguillicola crassus (ekstenzitet infekcije je iznosio 39,71%). Ekstenzitet infekcije je varirap u zavisnosti od sezone. Najveći je bio u toku jeseni. Intenzitet infekcije je iznosio između 1-90, a prosecan intenzitet infekcije je iznosio 10,33. Anguillicola crassus je najverovatnije uneta u jezero veštačkim poribljavanjem podmlatkom jegulja, uvezenim iz inostranstva. U jezeru je ovaj parazit našao povoljne uslove za razvoj i razmnožavanje prisustvo prelaznih i parateničnih domaćina. Anguillicola crassus je po prvi put spomenuta u ihtioparazitofauni Ohridskog jezera i Makedonije.nul

Fauna of monogenean trematodes-parasites of some cyprinid fishes from lake Prespa, Macedonia

During parasitological investigations six species of monogenean trematodes were found on the gills of three cyprinid fish species from Lake Prespa (Macedonia), as follows: Dactylogyrus prostae and Dactylogyrus sphyrna in Leuciscus cephalus albus, Dactylogyrus erhardovae, Dactylogyrus sphyrna and Paradiplozoon zeller in Rutilus rubilio prespensis and Dactylogyrus elegantis and Dactylogyrus vistulae in Chondrostoma nasus prespensis. The prevalence in Leuciscus cephalus albus was 62.22%, in Rutilus rubilio prespensis 59.87% while in Chondrostoma nasus prespensis it was the lowest and amounted to 41.59%. The overall, prevalence of monogeneans in the investigated cyprinid fishes from Lake Prespa was 53.65%, and the mean intensity of infestation was 6.08. Among the monogenean species the highest prevalence occurred with Dactylogyrus sphyrna (25.08%), and the greatest intensity of infestation was evident in the cases of infestation with Dactylogyrus erhardovae (12.87). The greatest pathological effect was associated with the monogeneans Dactylogyrus vistulae and Paradiplozoon zeller. All monogenean species found represented the first record for such parasite fauna of fishes in Macedonia.U toku parazitoloških istraživanja ciprinidnih riba iz Prespanskog jezera (Makedonija), kod 3 vrste riba na škrgama pronađeno je 6 vrsta monogenih trematoda, i to: kod Leuciscus cephalus albus su nađeni Dactylogyrus prostae i Dactylogyrus sphyrna, kod Rutilus rubilio prespensis su pronađeni Dactylogyrus erhardovae, Dactylogyrus sphyrna i Paradiplozoon zeller, kod Chondrostoma nasus prespensis su pronađeni Dactylogyrus elegantis i Dactylogyrus vistulae. Ekstenzitet infestacije kod Leuciscus cephalus albus iznosio je 62,22%, kod Rutilus rubilio prespensis 59,87%, a kod Chondrostoma nasus prespensis je bio najniži i iznosio je 41,59%. Ukupno, ekstenzitet infestacije sa monogeneama kod ispitivanih ciprinidnih riba Prespanskog jezera iznosio je 53,65%, a intenzitet infestacije 6,08. Pojedinačno, po vrstama monogenea, najviši ekstenzitet infestacije je bio sa Dactylogyrus sphyrna (25,08%), a najviši intenzitet infestacije je utvrđen u slučajevima infestacije sa Dactylogyrus erhardovae (12,87). Najveći patogeni uticaj su imale monogene trematode Dactylogyrus vistulae i Paradiplozoon zeller. Sve pronađene vrste monogenea predstavljaju prvi nalaz za parazitofaunu riba Makedonije.nul

Discovery and Optimisation of a Compound Series active against Trypanosoma cruzi, the causative agent of Chagas’ Disease

Chagas disease is caused by the protozoan parasite; Trypanosoma cruzi; . It is endemic in South and Central America and recently has been found in other parts of the world, due to migration of chronically infected patients. The current treatment for Chagas disease is not satisfactory, and there is a need for new treatments. In this work, we describe the optimization of a hit compound resulting from the phenotypic screen of a library of compounds against; T. cruzi; . The compound series was optimized to the level where it had satisfactory pharmacokinetics to allow an efficacy study in a mouse model of Chagas disease. We were able to demonstrate efficacy in this model, although further work is required to improve the potency and selectivity of this series