Marine Cyclic Peptides: Antimicrobial Activity and Synthetic Strategies

Oceans are a rich source of structurally unique bioactive compounds from the perspective of potential therapeutic agents. Marine peptides are a particularly interesting group of secondary metabolites because of their chemistry and wide range of biological activities. Among them, cyclic peptides exhibit a broad spectrum of antimicrobial activities, including against bacteria, protozoa, fungi, and viruses. Moreover, there are several examples of marine cyclic peptides revealing interesting antimicrobial activities against numerous drug-resistant bacteria and fungi, making these compounds a very promising resource in the search for novel antimicrobial agents to revert multidrug-resistance. This review summarizes 174 marine cyclic peptides with antibacterial, antifungal, antiparasitic, or antiviral properties. These natural products were categorized according to their sources—sponges, mollusks, crustaceans, crabs, marine bacteria, and fungi—and chemical structure—cyclic peptides and depsipeptides. The antimicrobial activities, including against drug-resistant microorganisms, unusual structural characteristics, and hits more advanced in (pre)clinical studies, are highlighted. Nocathiacins I–III (91–93), unnarmicins A (114) and C (115), sclerotides A (160) and B (161), and plitidepsin (174) can be highlighted considering not only their high antimicrobial potency in vitro, but also for their promising in vivo results. Marine cyclic peptides are also interesting models for molecular modifications and/or total synthesis to obtain more potent compounds, with improved properties and in higher quantity. Solid-phase Fmoc- and Boc-protection chemistry is the major synthetic strategy to obtain marine cyclic peptides with antimicrobial properties, and key examples are presented guiding microbiologist and medicinal chemists to the discovery of new antimicrobial drug candidates from marine sources.     

The ‘pole-hooking’ method: A novel and economical technique for in situ tagging small to medium-sized fishes

We describe a new manual procedure for catching and tagging fish underwater, the ‘pole-hooking’ method, and demonstrate and discuss its advantages over standard tagging techniques (i.e. hook-and-line fishing). The new technique was designed for tagging Acanthistius brasilianus [Cuvier, M., Valenciennes, L.B., 1828. Histoire Naturelle des Poissons. Museau de Histoire Naturelle, Paris], a small to medium-sized fish inhabiting rocky reefs of the Argentine coast. The pole-hooking method minimizes injuries, avoids fast depressurization of fish and allows registration of the precise location of capture and release. In addition, the equipment needed is very simple and economical. The mean number of fish tagged per minute using this methodology on shallow rocky reefs (up to 25-m depth) was similar to that obtained during hook-and-line fishing sessions (ca. one tagged fish every 3 min), given similar densities of A. brasilianus in the fished reefs.     

Differences in swimbladder volume between Baltic and Norwegian spring-spawning herring: Consequences for mean target strength

Fish swimbladders, where present, contribute most to the scattering of sound by fish, as measured by the target strength (TS). The volumes of the swimbladders of two different European stocks of Atlantic herring were compared to consider the effect on estimates of TS. Swimbladder volumes of Baltic and Norwegian spring-spawning herring (Clupea harengus) were measured, together with individual herring fat content. Swimbladder volumes were found to differ significantly between the two herring stocks. Baltic herring have a larger swimbladder volume, which is suggested to be associated with the fish's low fat content, which in turn may be linked to its specific energy budget and the low salinity of the Baltic Sea. A buoyancy model that considered the different salinity conditions and fat proportions was used to evaluate the observed differences in swimbladder volume. The swimbladder volume data were subsequently used to model the mean target strength as a function of depth and growth pattern. Backscattering of the swimbladder was modelled using the modal-series-based deformed-cylinder model (MSB-DCM), describing the swimbladder as a gas-filled, elongated prolate spheroid. The fish body component was modelled as a fluid-filled ellipsoid using the distorted wave Born approximation (DWBA). Modelling results support a different TS-to-size relationship for Baltic herring, with a stronger echo, due to the larger swimbladder. Depth- and length-dependent TS relationships based on the model results are suggested.     

A 3-year assessment of nitrous oxide emission factors for urine and dung of grazing sheep in a subtropical ecosystem

Purpose

Grazing livestock has strong impact on global nitrous oxide (N₂O) emissions by providing N sources through excreta. The scarcity of information on factors influencing N₂O emissions from sheep excreta in subtropical ecosystems such as those of Southern Brazil led us to conduct field trials in three different winter pasture seasons on an integrated crop–livestock system (ICL) in order to assess N₂O emission factors (EF-N₂O) in response to variable rates of urine and dung.

Materials and methods

The equivalent urine-N loading rates for the three winter seasons (2009, 2010, and 2013) ranged from 96 to 478 kg ha^?1, and the dung-N rates applied in 2009 and 2010 were 81 and 76 kg ha^?1, respectively. Air was sampled from closed static chambers (0.20 m in diameter) for approximately 40 days after excreta application and analyzed for N₂O by gas chromatography.

Results and discussion

Soil N₂O-N fluxes spanned the ranges 4 to 353 μg m^?2 h^?1 in 2009, ??47 to 976 μg m^?2 h^?1 in 2010, and 46 to 339 μg m^?2 h^?1 in 2013. Urine addition resulted in N₂O-N peaks within for up to 20–30 days after application in the 3 years, and the strength of the peaks was linearly related to the N rate used. Emission factors of N₂O (EF-N₂O, % of N applied that is emitted as N₂O) of urine ranged from 0.06 to 0.34% and were essentially independent of N rate applied. By considering a ratio of N excreted by urine and dung of 60:40, a single combined excretal EF-N₂O of 0.14% was estimated.

Conclusions

Our findings showed higher mean EF-N₂O for sheep urine than that for dung (0.21% vs 0.03%), irrespective of the occurrence or not of urine patches overlap. This value is much lower than default value of 1% of IPCC’s Tier 1 and reinforces the needs of its revision.

     

Short-wave solar radiation level willingly tolerated by lactating Holstein cows in an equatorial semi-arid environment

The amount of short-wave solar radiation willingly tolerated by lactating Holstein cows on pasture was determined in an equatorial semi-arid environment. The study was carried out on a dairy farm located in Limoeiro do Norte, CE, northeastern Brazil. The observed behaviours were as follows: grazing, under the sun, under the shade, standing, lying, ruminating, idling and wallowing in the water. The behaviours were recorded using instantaneous scan sampling at regular intervals of 15 min from 0600 to 1800 hours over 5 days. On all sampling days, the meteorological variables, including local short-wave solar radiation (R _S-W, W m^?2), were recorded. The R _S-W data were divided into five levels. The sun exposure was more frequent under low (100 %) and moderately low (97 %) levels, when R _S-W remained below 500 W m^?2. The grazing was more intense under low (100 %) and moderately low (93 %) levels. Above 500 W m^?2, the grazing time significantly decreased (11 %). The cows avoided grazing under high (0 %) and very high (0 %) levels, when R _S-W exceeded 700 W m^?2. The ruminating behaviour was more frequent under high (33 %) and very high (37 %) levels, in which the highest averages of R _S-W were recorded (815 and 958 W m^?2, respectively). The standing posture was more frequent under low (100 %) and moderately low (97 %) levels. Therefore, the critical R _S-W level that motivates cows to stop grazing and seek shade was in the interval between 500 and 700 W m^?2.     

Genetic‐Quantitative Study of the First‐Service Pregnancy Probability of Murrah Heifers

Because of the importance of reproduction in stock breeding systems, it is necessary to find selection criteria that increase reproductive efficiency. The aim of this study was to estimate genetic parameters for the probability of conception on first service (PROB) in Murrah heifers, and its association with other traits of economic interest [age at first calving (AFC), service period, calving interval and milk yield at 270 days], with the purpose of evaluating their use as selection criteria. Reproductive information and first lactation records of 1200 Murrah heifers were used to perform two‐trait analyses between PROB and the other characteristics. Bayesian inference was used to estimate the variance components, considering PROB as threshold and the other as linear factors. The results demonstrate that this trait has heritability of 0.15, indicating the possibility of a genetic gain by using it for selection. With respect to the genetic correlation estimates, the only high‐magnitude association was with AFC (?0.899), which is the current criterion indicating sexual precocity of females. In the light of the parameters estimated, the first‐service pregnancy rate is an alternative for indication of sexual precocity, although presenting a smaller genetic gain than the current standard AFC. Nevertheless, additional research should be conducted regarding this trait to assess the economic importance of its use in dairy buffalo production systems.     

Hypertrophic gastropathy associated with gastric sarcoma in a dog

A 14-y-old spayed female Labrador Retriever was presented with an 8-mo history of chronic vomiting. Abdominal ultrasound and gastrointestinal endoscopy revealed a mass protruding into the gastric lumen, with cytologic features suggestive of sarcoma. A partial gastrectomy was performed; the gastric body and antrum were thickened, with a cerebriform appearance of the mucosal surface. Histologic examination revealed a submucosal neoplastic proliferation of fusiform cells variably arranged in irregular bundles and scattered whorls. Fusiform cells strongly reacted to antibodies against vimentin, S100, and neuron-specific enolase; glial fibrillary acidic protein was moderately and multifocally expressed. Pancytokeratin, KIT, α–smooth muscle actin, and desmin were nonreactive. Histologic and immunohistochemical findings suggested a diagnosis of gastric sarcoma with features referable to a non-GIST (gastrointestinal stromal tumor), non–smooth muscle NIMT (non-angiogenic, non-lymphogenic intestinal mesenchymal tumor). The overlying gastric mucosa was thickened by elongated and dilated gastric glands, predominantly lined by intensely periodic acid-Schiff–stained mucous cells. This altered mucosal architecture was suggestive of Ménétrier-like disease. Although this disease has been hypothesized to predispose to gastric adenocarcinoma in dogs, an association with gastric sarcoma has not been documented previously in the veterinary literature, to our knowledge.     

Energy and protein requirements for maintenance and growth of Boer crossbred kids

Meat production by goats has become an important livestock enterprise in several parts of the world. Nonetheless, energy and protein requirements of meat goats have not been defined thoroughly. The objective of this study was to determine the energy and protein requirements for maintenance and growth of 34 (3/4) Boer x (1/4) Saanen crossbred, intact male kids (20.5 +/- 0.24 kg of initial BW). The baseline group was 7 randomly selected kids, averaging 21.2 +/- 0.36 kg of BW. An intermediate group consisted of 6 randomly selected kids, fed for ad libitum intake, that were slaughtered when they reached an average BW of 28.2 +/- 0.39 kg. The remaining kids (n = 21) were allocated randomly on d 0 to 3 levels of DMI (treatments were ad libitum or restricted to 70 or 40% of the ad libitum intake) within 7 slaughter groups. A slaughter group contained 1 kid from each treatment, and kids were slaughtered when the ad libitum treatment kid reached 35 kg of BW. Individual body components (head plus feet, hide, internal organs plus blood, and carcass) were weighed, ground, mixed, and subsampled for chemical analyses. Initial body composition was determined using equations developed from the composition of the baseline kids. The calculated daily maintenance requirement for NE was 77.3 +/- 1.05 kcal/kg(0.75) of empty BW (EBW) or 67.4 +/- 1.04 kcal/kg(0.75) of shrunk BW. The daily ME requirement for maintenance (118.1 kcal/kg(0.75) of EBW or 103.0 kcal/kg(0.75) of shrunk BW) was calculated by iteration, assuming that the heat produced was equal to the ME intake at maintenance. The partial efficiency of use of ME for NE below maintenance was 0.65. A value of 2.44 +/- 0.4 g of net protein/kg(0.75) of EBW for daily maintenance was determined. Net energy requirements for growth ranged from 2.55 to 3.0 Mcal/kg of EBW gain at 20 and 35 kg of BW, and net protein requirements for growth ranged from 178.8 to 185.2 g/kg of EBW gain. These results suggest that NE and net protein requirements for growing meat goats exceed the requirements previously published for dairy goats. Moreover, results from this study suggest that the N requirement for maintenance for growing goats is greater than the established recommendations.