Search

Plantago lanceolata L. (plantain) increases herbage dry matter (DM) production and quality during warm and dry conditions due to its deep roots and drought tolerance and reduces nitrogen losses in grazing systems compared to traditional pastures. However, plantain density usually declines after the third growing season, mainly due to defoliation management. The effects of defoliation frequency and intensity on water-soluble carbohydrate (WSC) reserves and below-ground plant responses need further research to optimize grazing strategies for improved productivity and sustainability of grazing systems. Our study investigated the effects of defoliation frequencies (15, 25, and 35 cm of extended leaf length, ELL) and intensities (5 and 8 cm of residual heights) on morphological traits and WSC concentrations in plantain biomass under controlled environmental conditions. Defoliation frequency significantly influenced morphological and chemical characteristics and biomass distribution more than residual height. Less frequent defoliations promoted above-ground herbage DM production, reproductive stems, and root biomass. Root architecture showed adaptations in response to defoliation frequency, optimizing resource acquisition efficiency. Frequent defoliation reduced high molecular weight WSC concentrations in leaves, affecting regrowth capacity and DM mass. A defoliation frequency of 25 cm ELL (~15 days) balances herbage production and root development, promoting long-term pasture sustainability. [ABSTRACT FROM AUTHOR]

Agricultural soils account for about 60% of the global atmospheric emissions of the potent greenhouse gas nitrous oxide (N2O). One of the main processes producing N2O is denitrification, which occurs under oxygen-limiting conditions when carbon is readily available. On grazed pastures, urine patches create ideal conditions for denitrification, especially in soils with high organic matter content, like Andisols. This lab study looks at the effects of Urine-urea-N load on the Andisol potential to emit N2O. For this, we investigated the effects of three levels of urea-N concentrations in cow urine on emissions of N2O, N2, and CO2 under controlled conditions optimised for denitrification to occur. Results show total N2O emissions increased with increasing urine-N concentration and indicate that denitrification was the main N2O-producing process during the first 2–3 days after urine application, though it was most likely soil native N rather than urine-N being utilised at this stage. An increase in soil nitrate indicates that a second peak of N2O emissions was most likely due to the nitrification of ammonium hydrolysed from the added urine, showing that nitrification and denitrification have the potential to play a big part in N losses and greenhouse gas production from these soils. [ABSTRACT FROM AUTHOR]

Urea present in cattle urine contributes large amounts of nitrogen (N) to grazed pastures, which can be the equivalent to approximately 1000 kg N ha−1. However, there are no studies in volcanic soils of southern Chile on the effect of different concentrations of urinary N deposited in the soil, nor of the effect different wetting and drying conditions mimicking the variation in weather conditions on the nitrification process from urea to NH4+ and total oxidized nitrogen (TON) over time. In addition, the inhibition of nitrification driven by the accumulation of NH3 at high rates of N applied to Andisol has not been evaluated. Fresh cattle urine was applied at three different rates of N equivalent to 247 kg N ha−1 (Low N), 461 kg N ha−1 (Medium N), and 921 kg N ha−1 (High N), as well as deionized water as a control. Further, three moisture conditions were imposed: constant moisture (CM), drying–rewetting (DRW) cycles at 7-day intervals, and soil drying (SD). Destructive soil core samples were evaluated for top and bottom halves individually every 7 days over a 36-day period to measure changes on inorganic N and pH. There were no interaction effects for N rates and soil moisture. The main effect of the different rates of N on mineralization was significant throughout the incubation period, while the effect of the different moisture conditions was variable over time. High N was associated with elevated NH3 concentrations and could explain why total N mineralization was partially inhibited. These results suggest that the presence of different nitrifying microorganisms in soil under different chemical and physical conditions determines nitrification, and thus, the oxidation of ammonia should be studied in more detail as the first step of nitrification, specifically in volcanic soils. [ABSTRACT FROM AUTHOR]

Integrated Crop Livestock Systems (ICLSs) use productive diversification as a strategy to improve productivity and land use efficiency. Pasture Crop Rotations are a part of ICLSs and imply a pasture phase included in the sequence of crops. The main reasons to include pastures in crop systems are low productivity of natural grasslands and increased crop yield after a pasture phase. Our objective was to analyze the productivity indicators and management of four ICLSs that combine crop and livestock production, with data collected over a 3 y period (2019–2022). The experimental site was The Palo a Pique (Treinta y Tres, Uruguay) long-term experiment installed in 1995, located in the subtropical climate zone and on Oxyaquic Argiudolls soils (3% average slope). Systems evaluated were CC (continuous cropping), SR (two years idem CC, two years of pastures), LR (two years idem CC, four years of pastures) and FR (continuous pasture with Tall Fescue). Liveweight (LW) production, grain production and dry matter (DM) production were evaluated. Liveweight production was higher in CC and SR (426 and 418 kg LW/ha) than in LR (369 kg LW/ha) and FR (310 kg LW/ha). DM production was higher in FR and SR (6867 and 5763 kg DM/ha/year) than in LR (5399 kg DM/ha/year) and CC (5206 kg DM/ha/year). Grain production was 10%, 16% and 9% lower in soybean, wheat and sorghum in CC. [ABSTRACT FROM AUTHOR]

Cow urine is a rich source of mobile nutrients such as nitrate (NO3−) and potassium (K+). The aim of this experiment was to evaluate the wetting pattern distribution through soil profile of cow urine patch in an andisol. Two field experiments across two consecutive years were carried out to compare cow urine patches in relation to initial wetting pattern and volume of soil affected. Bromide (Br−) has successfully been used as an inert hydrologic tracer to indicate the movement of NO3− and K+ in soil–water systems. The distribution of Br− (used as a urine tracer) on the soil surface and down the profile was irregular in all the patches. Cow urine patches covered a surface area of 0.27 and 0.35 m2, respectively, and penetrated to a depth of 70 cm. The rapid downward movement of urine occurred through macropore flow but even so, between 27% and 40% of the applied Br− was detected in the 0–5 cm soil layer. Br− showed concentrations greater than 1500 mg kg−1 and up to 3000 mg kg−1, and as the concentration of Br− decreases, the frequency and depth of affected layers increases. Despite the differences in moisture and in the distribution of the Br− concentration in both years, the concentration frequency of 500 to 1500 mg kg−1 represented around 37% of the affected volume of soil (bulb of urine) in both years. Up to 40% of the bulb represented N equivalent rates between 187 and 975 kg N ha−1. These values can potentially be emitted in gases such as NH3, N2O, and N2. It is suggested that the presence of N in the volume of affected soil could vary due to the moisture content of the soil, and that in andisols of southern Chile under permanent grasslands there are a large number of macropores that would induce preferential flows. [ABSTRACT FROM AUTHOR]

The inclusion of fresh forages into dairy cows' diets during the winter can represent economic and nutritional benefits but can affect cows' metabolic function. The study aimed to evaluate the effect of using fresh berseem clover/oat (MIX), fresh lucerne (LEG) and hay/silage (CON) as forage basis for total mixed ration during the winter period on dairy cows' rumen characteristics and N metabolism. Three non-lactating rumen-cannulated cows were allocated to each diet for a 14-day period in a 3 × 3 Latin Square design. Sample collection occurred on the last 3 days of each period. Rumen fluid samples were analysed for pH, volatile fatty acids and N-ammonium contents. In situ forage nutrients degradability were evaluated by ruminal incubation. Serum, urine and faecal samples were collected and analysed for N content. Cows had similar feed intakes. No major changes were observed in rumen characteristics, but LEG led to greater ruminal N-ammonium and ammonium ureic N contents. Fresh pasture diets reduced the daily urine ureic N. The fresh forages improved the ruminal kinetics of dry matter and crude protein. The forage nutrients' effective degradability was greater for the fresh pasture diets than for CON. Overall, inclusion of fresh forages had minor effects on ruminal parameters, but the use of the MIX diet represents a suitable option in terms of N use efficiency. [ABSTRACT FROM AUTHOR]

The Maraichine breed of cattle originates from the Loire region of France and has been under a conservation programme since 1986. This programme links the conservation of the breed with the conservation of its traditional environment of wet grasslands. In this case report, we describe the different steps of this programme, each of which had its own successes and challenges. We also describe how, throughout this process, researchers have been involved in the generation and dissemination of information covering areas such as stakeholder perspectives, animal performance, and socio-economics. Under the conservation programme, the Maraichine population has expanded in both size and scale. Simultaneously, stakeholder perspectives have also developed, continually shifting the balance between the productivity, conservation, and maintenance of heritage traits. The conservation programme also provided the opportunity to utilise the breed's desirable traits, such as easy calving and disease resistance. Whilst the carcasses are not necessarily as valuable as those of other breeds, farmers have implemented novel economic practices to capitalise on market opportunities. Today, Maraichine cattle and Maraichine breeders offer researchers the opportunity to deepen and enrich our knowledge on sustainable ruminant livestock farming systems. [ABSTRACT FROM AUTHOR]

Background In 2012, 11 standards describing best supportive care (bsc) in clinical trials in advanced cancer were defined through consensus statements. The consensus included 15 key components. Our objective was to analyze whether clinical trials that involved patients with advanced cancer and that included bsc in at least 1 arm met the standards and contained the key components. Methods We reviewed clinical trials registered in ClinicalTrials.gov, the isrctn (International Standard Randomised Controlled Trial Number) registry, the EU Clinical Trials Register, and the International Clinical Trials Registry Platform for 2012-2018. We selected only phase iii studies in patients with advanced cancer that included bsc in at least 1 arm. We describe the characteristics of the trials, together with the definition and components of bsc. We analyzed how the trials met the standards and adopted the key components of bsc. Results Of 193 trials retrieved, only 64 met the inclusion criteria; 36 of those trials (56%) had no definition of bsc. Less than 7% of the trials included even 3 of the 8 bsc standards that were defined to be included in the design of trials. Furthermore, trials mentioned only 5 of the 15 key components that the consensus defined to be fundamental, with symptom management appearing in 22% of trials and the other 4 components appearing in less than 8%. Summary Most clinical trials registered during 2012-2018 that involved patients with cancer and an arm with bsc did not define the bsc concept. Hence, the design of those trials does not meet the consensus recommendations. [ABSTRACT FROM AUTHOR]

The objective of this study was to assess N dynamics in the soil, and the response in regard to dry matter yield (DM yield; kg·DM·ha−1), N yield (g·N·m−2) and N concentration (g·N·kg−1 DM) under urine patches and dung pats and in the affected zone of the grassland soil over 304 days. The amount of N under the urine and dung patches increased until day 10 and then started to decrease until the end of the experiment, reaching control treatment levels. The DM yield in the urine patch zone and the 0–10 cm zone around the dung pat was higher than in the control treatment throughout the evaluated period, while in the 0–30 cm zone around the urine patch and the 10–20 cm zone around the dung pat the DM yield was negatively affected by the application of excreta. The maximum accumulated N yield was up to two times higher than the control in the 0–10 cm zone of the dung pat, while the mean concentration of N throughout the period was 42% higher than the control for the "urine patch" zone and 47% higher in the 0–10 cm area around the dung pat. The total absorbed N was 19% and 15% for urine and dung excreta, respectively. Further research is needed to explain the variables that might affect the results obtained, and it is necessary to evaluate the botanical composition as a factor that contributes to this effect. [ABSTRACT FROM AUTHOR]

The case for grazing dairy cows at pasture is reviewed in six categories: (i) optimal land use for food production; (ii) soil carbon sequestration; (iii) carbon footprint; (iv) animal health and welfare; (v) effects on human health of milk produced from grazed pasture; and (vi) consumer demand for milk from grazed cows. Land best-suited to grazing is uncultivatable peaty soil receiving relatively low levels of fertilisation. With soil carbon sequestration, carbon footprint is lower for grazing than for other systems of milk production. Some indices of animal health and welfare (e.g., lameness, status of hock integument) are influenced positively by extent of grazing. Benefits to human health may accrue from higher levels of essential amino acids, carotenoids, omega-3 fatty acids and conjugated linoleic acid in milk from cows given pasture compared to diets based on silage and concentrates. Milk producers, processors and supermarkets are responding to consumer demand for milk and milk products from cows given access to pasture during the grazing season. The major constraint to milk production from grazing is energy intake. Research opportunities to address this constraint include application of remote sensing and artificial intelligence to grazing management. [ABSTRACT FROM AUTHOR]

Increasing demands for land is necessitating the optimisation of grazing land used for livestock production. Hormonal growth promoter implants (HGPI) are widely used to improve cattle performance and thus land-use efficiency. However, there is limited information on their efficacy in grazing systems. Forty grazing steers, 10 of each breed (Angus, Hereford, Holstein, Overo Colorado), had growth rates monitored for 85 days after which half received HGPI and half continued as a control. Growth rates were monitored for an additional 61 days and performance between the groups compared. Implants had a significant impact on liveweight gain (LWG; p = 0.013), and whilst breed did not (p = 0.65), there was an interaction effect of breed × treatment (p = 0.029). For three of the four breeds, the LWG was greater in the implant group (mean +14.3%). The exception was for Holstein steers which did not respond to the implant. In general, HGPI were found to be effective in increasing LWG of grazing cattle and thus has the potential to increase yield densities and relieve pressures of land use and competition. The efficacy may be affected by breed and other extraneous factors not covered in this study. Furthermore, the use of HGPI must be carefully considered in a wider context since its use might have secondary impacts. [ABSTRACT FROM AUTHOR]

Simple Summary: An understanding of the way that animals respond to heat stress is key to the development of adaptation and mitigation strategies for a changing climate. The response of mammals to heat exposure involves changes at every level of organization from molecular and cellular to systemic and behavioral. The concert of events involves many genes and gene products. The Na+/K+ ATPase ∝1 (ATP1A1), a product of the ATP1A1 gene, is important for the response to heat because it determines the activity of the Na+/K+ pump that is ubiquitous in cell membranes. It was shown recently that ATP1A1 is important in combating the oxidative stress that a cell faces and that it modulates the Src signaling pathway that is involved in the response to many stressors. Vechur cattle (dwarf Bos taurus indicus) are well known for their adaptability to the tropical heat and humidity that persists in their native state of Kerala, India. We here analyze the comparative expression profile of the ATP1A1 gene in heat-tolerant Vechur and Kasaragod (another dwarf B. t. indicus) cattle and a heat-intolerant crossbreed (B. t. taurus × B. t. indicus) and characterize the sequence of ATP1A1 mRNA in the Vechur genotype. Environmental stress and heat tolerance were measured. Expression profiling indicated that ATP1A1 was differentially expressed in the phenotypically disparate cattle breeds. A molecular evolutionary genetic analysis revealed that the divergent origin of dwarf cattle was adaptive in response to heat stress and suggests the potential use of ATP1A1 as a marker for heat tolerance. Climate change is an imminent threat to livestock production. One adaptation strategy is selection for heat tolerance. While it is established that the ATP1A1 gene and its product play an important role in the response to many stressors, there has been no attempt to characterize the sequence or to perform expression profiling of the gene in production animals. We undertook a field experiment to compare the expression profiles of ATP1A1 in heat-tolerant Vechur and Kasaragod cattle (Bos taurus indicus) with the profile of a heat-susceptible crossbreed (B. t. taurus × B. t. indicus). The cattle were exposed to heat stress while on pasture in the hot summer season. The environmental stress was quantified using the temperature humidity index (THI), while the heat tolerance of each breed was assessed using a heat tolerance coefficient (HTC). The ATP1A1 mRNA of Vechur cattle was amplified from cDNA and sequenced. The HTC varied significantly between the breeds and with time-of-day (p < 0.01). The breed–time-of-day interaction was also significant (p < 0.01). The relative expression of ATP1A1 differed between heat-tolerant and heat-susceptible breeds (p = 0.02). The expression of ATP1A1 at 08:00, 10:00 and 12:00, and the breed–time-of-day interaction, were not significant. The nucleotide sequence of Vechur ATP1A1 showed 99% homology with the B. t. taurus sequence. The protein sequence showed 98% homology with B. t. taurus cattle and with B. grunniens (yak) and 97.7% homology with Ovis aries (sheep). A molecular clock analysis revealed evidence of divergent adaptive evolution of the ATP1A1 gene favoring climate resilience in Vechur cattle. These findings further our knowledge of the relationship between the ATP1A1 gene and heat tolerance in phenotypically incongruent animals. We propose that ATP1A1 could be used in marker assisted selection (MAS) for heat tolerance. [ABSTRACT FROM AUTHOR]

Understanding the behaviour of grazing animals at pasture is crucial in order to develop management strategies that will increase the potential productivity of grazing systems and simultaneously decrease the negative impact on the environment. The objective of this review was to summarize and analyse the scientific literature that has addressed the site use preference of grazing cattle using global positioning systems (GPS) collars in the past 21 years (2000–2020) to aid the development of more sustainable grazing livestock systems. The 84 studies identified were undertaken in several regions of the world, in diverse production systems, under different climate conditions and with varied methodologies and animal types. This work presents the information in categories according to the main findings reviewed, covering management, external and animal factors driving animal movement patterns. The results showed that some variables, such as stocking rate, water and shade location, weather conditions and pasture (terrain and vegetation) characteristics, have a significant impact on the behaviour of grazing cattle. Other types of bio-loggers can be deployed in grazing ruminants to gain insights into their metabolism and its relationship with the landscape they utilise. Changing management practices based on these findings could improve the use of grasslands towards more sustainable and productive livestock systems. [ABSTRACT FROM AUTHOR]

Simple Summary: Energy supplements such as high moisture maize or cracked wheat increase total dry matter intake (DMI) and dairy cow performance compared to pasture-only diets. However, the effectiveness of such a feeding strategy depends upon the level of herbage allowance (HA). In this study, increasing HA from 20 to 30 kg DM/cow had no effect on milk production but increased the concentration of urea in milk and plasma regardless of the type of energy supplement offered to grazing dairy cows. These results demonstrate that in high-quality pasture, low HA is appropriate to improve milk production performance per cow and per hectare. The aim was to determine the effect of the herbage allowance (HA) and supplement type (ST) on dry matter intake (DMI), milk production and composition, grazing behavior, rumen function, and blood metabolites of grazing dairy cows in the spring season. Experiment I: 64 Holstein Friesian dairy cows were distributed in a factorial design that tested two levels of daily HA (20 and 30 kg of dry matter (DM) per cow) and two ST (high moisture maize (HMM) and cracked wheat (CW)) distributed in two daily rations (3.5 kg DM/cow/day). Experiment II: four mid-lactation rumen cannulated cows, supplemented with either HMM or CW and managed with the two HAs, were distributed in a Latin square design of 4 × 4, for four 14-d periods to assess ruminal fermentation parameters. HA had no effect on milk production (averaging 23.6 kg/day) or milk fat and protein production (823 g/day and 800 g/day, respectively). Cows supplemented with CW had greater protein concentration (+1.2 g/kg). Herbage DMI averaged 14.17 kg DM/cow.day and total DMI averaged 17.67 kg DM/cow.day and did not differ between treatments. Grazing behavior activities (grazing, rumination, and idling times) and body condition score (BCS) were not affected by HA or ST. Milk and plasma urea concentration increased under the high HA (+0.68 mmol/L and +0.90 mmol/L, respectively). Cows supplemented with HMM had lower milk and plasma urea concentrations (0.72 mmol/L and 0.76 mmol/L less, respectively) and tended (p = 0.054) to have higher plasma β-hydroxybutyrate. Ruminal parameters did not differ between treatments. [ABSTRACT FROM AUTHOR]

Simple Summary: Globally, the livestock sector is responsible for 37% of total anthropogenic methane emissions, most of which are produced from enteric fermentation of ruminants. Livestock is also responsible for 65% anthropogenic nitrous oxide and 64% of anthropogenic ammonia emissions. The literature reports several dietary management options to reduce greenhouse gas emissions from ruminants, and potentially improve productivity. However, strategies that aim to reduce the emissions of one specific greenhouse gas can have side effects (increase) on other pollutant gases. In this study, we evaluated the effect of two types of perennial ryegrass (PRG) pastures differing in their concentration of water-soluble carbohydrates (WSC, high (HS) and low (LS)) on the in vitro nitrogen use efficiency in the rumen and on methane emissions. The greater WSC and lower crude protein (CP) concentrations of high sugar pastures modified in vitro rumen fermentation, tending to increase total volatile fatty acids (VFA) production, reduce acetate:propionate ratio and methane (CH4) concentration, and improve nitrogen (N) use efficiency through lower rumen ammonia-N (NH3-N) concentrations. In vivo studies with cattle are required to confirm the potential of these measures to increase the sustainability and reduce the environmental impact of grazing livestock production systems. The objective of this study was to determine the effect of perennial ryegrass (PRG) forages differing in their concentration of water-soluble carbohydrates (WSC) and crude protein (CP), and collected in spring and autumn, on in vitro rumen fermentation variables, nitrogen (N) metabolism indicators and methane (CH4) output, using a batch culture system. Two contrasting PRG pastures, sampled both in autumn and spring, were used: high (HS) and low (LS) sugar pastures with WSC concentrations of 322 and 343 g/kg for HS (autumn and spring), and 224 and 293 g/kg for LS in autumn and spring, respectively. Duplicates were incubated for 24 h with rumen inocula in three different days (blocks). Headspace gas pressure was measured at 2, 3, 4, 5, 6, 8, 10, 12, 18, and 24 h, and CH4 concentration was determined. The supernatants were analysed for individual volatile fatty acids (VFA) concentrations, and NH3-N. The solid residue was analysed for total N and neutral detergent insoluble N. Another set of duplicates was incubated for 4 h for VFA and NH3-N determination. The HS produced more gas (218 vs. 204 mL/g OM), tended to increase total VFA production (52.0 mM vs. 49.5 mM at 24 h), reduced the acetate:propionate ratio (2.52 vs. 3.20 at 4 h and 2.85 vs. 3.19 at 24 h) and CH4 production relative to total gas production (15.6 vs. 16.8 mL/100 mL) and, improved N use efficiency (22.1 vs. 20.9). The contrasting chemical composition modified in vitro rumen fermentation tending to increase total VFA production, reduce the acetate:propionate ratio and CH4 concentration, and improve N use efficiency through lower rumen NH3-N. [ABSTRACT FROM AUTHOR]

Mixed crop–livestock long-term experiments (LTE) are critical to increase the understanding of sustainability in complex agroecosystems. One example is the 'Palo a Pique' LTE which has been running for 25 years in Uruguay (from 1995 to present), evaluating four pasture–crop rotations under livestock grazing with no-till technology in soils with severe limitations. The results demonstrate that cropping systems reduced soil organic carbon (SOC) compared with permanent pastures, and that perennial pastures rotating with crops were critical to mitigate SOC losses. Data from the 'Palo a Pique' LTE has contributed to the establishment of new national policies to secure the sustainability of agricultural-based systems. Although the original purpose of the LTE was oriented to crops and soils, a demand for sustainable livestock intensification has gathered momentum over recent years. As a result, the current approach of the 'Palo a Pique' LTE matches each pasture–crop rotation with the most suitable livestock strategy with the common goal of producing 400 kg liveweight/ha per year. General approaches to the pursuit of sustainable livestock intensification include shortening the cycle of production, diversifying animal categories, increasing liveweight gain and final animal liveweight, and strategic livestock supplementation. Prediction of trade-offs between environmental, economic, and production indicators can be addressed through monitoring and modeling, enabling the timely anticipation of adverse sustainability issues on commercial farms. The 'Palo a Pique' LTE serves as a framework to address contemporary and future questions dealing with the role of ruminants on climate change, competition for land, nutrient dynamics, and food security. [ABSTRACT FROM AUTHOR]

Simple Summary: The livestock sector is a significant contributor to global greenhouse gas emissions, with cattle representing 62% of CO2 emissions. Genetic selection is a tool that has the potential to reduce emissions from rumen fermentation and can be adopted in grazing and feedlot systems. Therefore, the purpose of this study was to evaluate steers from a new line of the Canchim breed (5/8 Charolais, 3/8 Zebu) derived by genetic selection improvement, and formed and maintained as a closed herd since 1998, in regards to performance, carcass dressing, and enteric methane emissions, when compared with the old line formed and maintained as a closed herd since 1960. Animals from the new line of the Canchim breed should be used for rearing on pasture to obtain greater liveweight gain. However, genetic improvement in Canchim breed does not guarantee animals with lower methane emissions under grazing conditions. For the finishing feedlot phase, increased liveweight gain, improved feed conversion, and a better carcass dressing percentage are obtained using animals from the new line of Canchim breed. The new line also leads to higher daily feed intake and higher daily liveweight gain, but with the same methane emissions per kg of animal liveweight than the other lines. The present study aimed to investigate whether different lines of a composite breed (5/8 Charolais × 3/8 Zebu), formed at different times, and genetically improved, would result in differences in animal performance, enteric methane emissions, and carcass traits. Forty-six Canchim steers (15 months, 280 ± 33 kg liveweight) from three different lines were used: old, new, and their cross. These three breed lines were considered the treatments (arranged in four randomized blocks based on initial liveweight) and were evaluated under grazing and feedlot conditions in relation to the performance and emission of enteric methane. During the grazing period, the new line was found to be superior to the old only in relation to the average daily liveweight gain (0.692 vs. 0.547 kg/day), and with no differences in relation to the cross line (0.692 vs. 0.620). In the feedlot finishing phase, only the average daily liveweight gain was significantly higher in the new line compared to the cross and old line (1.44 vs. 1.32 and 1.23 kg/day). The new and cross lines demonstrated higher dry matter intake when compared to the old line (10.25 and 10.42 vs. 9.11 kg/day), with the crossline animals demonstrating the best feed conversion. The new line showed higher enteric methane emissions compared to the old line (178 vs. 156 g/day). The line had an effect on the carcass dressing of the animals, with greater fat thickness in carcasses from the new and cross lines than the old line (4.4 and 3.8 vs. 3.2 mm). Canchim cattle selected for improved productive performance characteristics does not guarantee animals with lower methane emissions under grazing conditions; while in feedlots, can lead to increased daily feed consumption, and hence, to higher emissions of methane. [ABSTRACT FROM AUTHOR]

Simple Summary: Daily herbage allowance (defined as herbage mass × daily offered area) is recognized as the main grazing management factor to improve pasture utilization and milk output per hectare. Daily herbage allowances should balance the dual objectives of high milk output per hectare while maintaining the quality of the pasture to optimize the profitability of grazing-based dairy production systems. We tested two contrasting herbage allowances (17 and 25 kg dry matter (DM)/cow.day) and two levels of maize silage supplementation (4.5 and 9 kg DM/cow.day) in grazing dairy cows and measured a set of variables related to pasture management, sward characteristics, dynamic of herbage depletion throughout the grazing sessions, and cows grazing behavior, among others. Our results suggest that a more intensive grazing regime of 17 kg DM/cow per day of daily herbage allowance rather than a high level of supplementation with maize silage is appropriate to improve milk production and solids yield per hectare without affecting pasture quality or sward characteristics over the short-term. The aim of this study was to evaluate the short-term effects of daily herbage allowance (DHA, defined as the product of pre-grazing herbage mass and offered area per animal) on pasture conditions and milk production of Holstein-Friesian dairy cows. Forty-four early lactation dairy cows were randomly assigned to one of four treatments in a 2 × 2 factorial design that tested two levels of DHA (17 and 25 kg DM/cow.day) and two levels of maize silage supplementation (MSS, 4.5 and 9 kg DM/cow.day) over a 77-day period. Low DHA decreased the post-grazing herbage mass from 1546 to 1430 kg DM/ha and the compressed sward height from 5 to 4.4 cm, while the grazing efficiency remained unaffected. Low DHA induced a faster herbage mass reduction, while the sward-height and pasture characteristics did not differ from the high DHA regime. Low DHA decreased the tiller production rates and daily lamina growth, while the leaf-production rate was not affected by the DHA. Daily increases of herbage mass were greater in the high DHA than in the low DHA treatments. Individual milk production and milk protein concentration decreased at a low DHA compared to high DHA, while the milk fat concentration was greater and the milk output per hectare increased by 1510 kg. Neither the MSS level nor the interaction DHA by the MSS level had any effect on the sward characteristics or the productivity of the cows. From these results, it is suggested that, in a high-quality pasture, using 17 kg DM/cow.day was appropriate for improving both herbage utilization and milk production per hectare while maintaining the short-term conditions of a pasture grazed by dairy cows in the autumn. [ABSTRACT FROM AUTHOR]

Simple Summary: Improving the performance of grazing systems and reducing their environmental impact are crucial in the current and future world contexts. In temperate grazing dairy systems, perennial ryegrass is widely used. Its nutritional composition can by modified via cultivar selection and management. We tested two swards: (1) a high-sugar cultivar submitted to fertilisation and defoliation regimes aimed at increasing sugar content and sugar-to-protein ratio and (2) a standard cultivar submitted to fertilisation and defoliation regimes aimed at decreasing sugar content and sugar-to-protein ratio. We tested these two swards with mid-lactation dairy cows grazing in daily strips for nine days in autumn and measured the amount of forage offered and consumed, the milk production and composition, and the grazing behaviour between morning and afternoon milkings. We found that the amount of residual herbage was greater in the standard cultivar sward, but the herbage consumed per cow was similar. Cows spent less time grazing in the high-sugar sward, but no difference was observed in the rumination time. Milk production and composition were similar between the two groups. This could imply that good-quality pastures would require a greater difference in nutritional composition to have an impact on animal performance. Grazing ruminant systems can be sustainably intensified by improving efficiency while reducing their environmental impact. The objective of the present study was to examine the potential of pastures differing in water-soluble carbohydrates (WSC) and crude protein (CP) contents to affect milk production and composition as well as the behaviour of cows grazing perennial ryegrass (PRG) swards. By modifying the nitrogen (N) fertilisation rate (83 and 250 kg/ha per year) and the defoliation frequency (two or three leaves per tiller) in combination with cultivar selection (high-sugar vs. standard cultivars), we obtained two swards differing in WSC and CP contents. The two contrasting swards were each grazed by six dairy cows in nine daily strips in autumn. Pasture samples were collected to determine herbage mass and quality. Cow behaviour was recorded by direct observation. Herbage offered and apparently consumed were similar between swards (averaging 37.3 and 18.2 kg/cow, respectively), although the residual was lower in the high-sugar sward (1735 vs. 2143 kg/ha). Cows spent less time grazing in the high-sugar sward (66.9% v. 71.6%), but the rumination times was similar (14.6%). Milk production and composition were similar between groups, suggesting that high-quality pastures would require a greater difference in nutritional composition to affect animal performance. [ABSTRACT FROM AUTHOR]

Simple Summary: Outdoor-reared European wild boar (Sus Scrofa L.) is regarded as a delicacy by consumers due to its favourable meat properties and an association with high welfare standards. The rearing of wild boar on pasture has the potential to minimise input costs relative to conventional production systems. However, some pasture production systems have been found to perform poorly due to low growth rates. This review collates the available scientific evidence on pasture-based production of wild boar and domestic pigs, to identify factors that influence feed intake, performance, and behaviour. Factors explored include season/weather, dietary supplementation, grazing management, forage availability, herbage quality, and sward type. For example, the additional feed availability associated with pasture grazing has been shown to be a significant factor that positively correlates with dry matter intake of wild boar. This has been demonstrated to result in better feed conversion efficiency and reduced feed costs without reductions in growth rates compared to animals without access to pasture. Furthermore, the increased availability of favoured species in pasture may also promote dry matter intake. The long-term sustainability of wild boar production is dependent on the economic, social, and environmental viability of the systems. Pasture-based production systems may be one way by which this can be achieved, but only if implemented correctly. Due to its distinct properties, wild boar meat is considered a highly desirable consumer product, in a market that is expanding. Outdoor production is also favoured by consumers who value animal welfare and environmental sustainability when choosing meat products. There is evidence that farms that include pasture for grazing typically have reduced feeding costs. Such production systems can also be more environmentally sustainable as the input (pasture) is inedible to humans, compared to conventional indoor systems, which use human-edible feeds (e.g., soya). However, some wild boar farms have performed poorly compared to those rearing other swine such as hybrid wild boar and domestic pigs. Diet is central to all livestock production and is likely a significant influencing factor of wild boar performance, both in terms of forage consumption and nutritional composition. Other factors may also influence performance, such as weather, behaviour and grazing management. Wild boar production systems hold their own intrinsic value in a growing marketplace. However, information gathered through the study of wild boar has external applications in informing outdoor domestic pig production systems to encourage the use of pasture as part of the habitat of domestic pigs. [ABSTRACT FROM AUTHOR]

The objective of this study was to assess the joint effect of perennial ryegrass cultivars and drying methods on concentrations of water-soluble carbohydrates (WSC) and crude protein (CP) and WSC/CP ratio. AberMagic AR1 and Expo AR1 forage were collected in December 2016, March, June, September and November 2017 and either oven-dried at 60 °C for 48 h (OD_60), at 80 °C for 16 h (OD_80), frozen at −80 °C for 48 h then freeze-dried (−80_FD), or flash-frozen with liquid N then freeze-dried (LN_FD). Data were analyzed by ANOVA in a factorial design with cultivar and drying method as factors. AberMagic AR1 had between 9.0 to 31.5% higher WSC concentration than Expo AR1 in the four samplings. Freeze-drying preserved more WSC than oven-drying treatments (+22.7%), particularly in June. The CP concentration of Expo AR1 was higher only in December (+6.8%), and was 22.9 and 10.9% higher in OD_60 samples compared to LN_FD samples in December and November, respectively. The WSC/CP ratio varied in June, being greater in AberMagic AR1 (+36.1%). Drying method affected WSC/CP ratio in December, June and November where freeze-drying produced greater ratios. Drying techniques generated differences in WSC, CP and WSC/CP ratio, which may affect the accuracy of the estimated impacts of forages on productivity and N use efficiency. [ABSTRACT FROM AUTHOR]

Simple Summary: Increasing soluble sugars in pasture species can lead to an improved nutrient use efficiency in the rumen and a greater digestibility of forage, which in turn might increase pasture intake. However, this improvement in nutritional value must not be at the expense of pasture productivity; the amount of nutrients harvested is a relevant factor in ruminant grazing systems' efficiency. Therefore, we tested four different cultivars of perennial ryegrass (two selected for greater soluble sugar content and two standard cultivars) submitted to two contrasting managements (one aimed at improving sugar content and one with the opposite intended effect) for their effects on pasture productivity (by cutting herbage every time the plots reached the target number of leaves per tiller, i.e., two or three) and the grazing preference of dairy cows (six cows grazed for up to 5 hours, in an experimental area with three plots for each of the eight treatments) in spring, summer and autumn. We found that high sugar grasses had lower annual dry matter productivity and no preference was shown by cows, although the agronomic management aimed at reducing sugar concentration enhanced crude protein concentration and increased the herbage harvested (greater preference) in the three seasons, and the time spent grazing in autumn. The objective of this study was to evaluate the pasture performance of different cultivars of perennial ryegrass, two "high sugar" and two standard cultivars, under two contrasting agronomic managements (aimed at either decreasing or increasing water soluble carbohydrates concentration), and their effects on the grazing preference of dairy cows. Eight treatments arising from the factorial combination of four cultivars and two managements were randomly applied to 31-m2 plots in three blocks. Pasture dry matter production and growth rate were measured for one year. Three grazing assessments were performed to establish the grazing preferences of six dairy cows in spring, summer and autumn. High sugar cultivars produced less dry matter per hectare than the standard cultivars. Cows consumed more grass and harvested a greater proportion of the pasture under the agronomic management aimed at decreasing sugar concentration, i.e., with a greater nitrogen fertilization rate and under a more frequent defoliation regime, which could be explained by the greater crude protein concentration achieved under this management. The results suggest that the genetic selection for greater levels of sugars was at the expense of herbage yield, and that cows preferred to graze herbage with a greater crude protein level instead of a greater sugar concentration. [ABSTRACT FROM AUTHOR]

Here we describe the livestock performance and baseline productivity over a two-year period, following the establishment of the infrastructure on the North Wyke Farm Platform across its three farmlets (small farms). Lowland permanent pastures were continuously stocked with yearling beef cattle and ewes and their twin lambs for two years in three farmlets. The cattle came into the farmlets as suckler-reared weaned calves at 195 ± 32.6 days old weighing 309 ± 45.0 kg, were housed indoors for 170 days then turned out to graze weighing 391 ± 54.2 kg for 177 days. Therefore, it is suggested for predominantly grass-based systems with minimal supplementary feeding that target live weight gains should be 0.5 kg/day in the first winter, 0.9 kg/day for summer grazing and 0.8 kg/day for cattle housed and finished on silage in a second winter. The sheep performance suggested that lambs weaned at 100 days and weighing 35 kg should finish at 200 days weighing 44 to 45 kg live weight with a killing out percentage of 44%. Good levels of livestock production are possible with grass and forage-based systems using little or no additional supplementary concentrate feeds. [ABSTRACT FROM AUTHOR]

Markers that allow for the selection of tailored treatments for individual patients with inflammatory bowel diseases (IBD) are yet to be identified. Our aim was to describe trends in real-life treatment usage. For this purpose, patients from the ENEIDA registry who received their first targeted IBD treatment (biologics or tofacitinib) between 2015 and 2021 were included. A subsequent analysis with Machine Learning models was performed. The study included 10,009 patients [71% with Crohn's disease (CD) and 29% with ulcerative colitis (UC)]. In CD, anti-TNF (predominantly adalimumab) were the main agents in the 1st line of treatment (LoT), although their use declined over time. In UC, anti-TNF (mainly infliximab) use was predominant in 1st LoT, remaining stable over time. Ustekinumab and vedolizumab were the most prescribed drugs in 2nd and 3rd LoT in CD and UC, respectively. Overall, the use of biosimilars increased over time. Machine Learning failed to identify a model capable of predicting treatment patterns. In conclusion, drug positioning is different in CD and UC. Anti-TNF were the most used drugs in IBD 1st LoT, being adalimumab predominant in CD and infliximab in UC. Ustekinumab and vedolizumab have gained importance in CD and UC, respectively. The approval of biosimilars had a significant impact on treatment.

Enzymes reliant on pyridoxal 5'-phosphate (PLP), the metabolically active form of vitamin B 6 , hold significant importance in both biology and medicine. They facilitate various biochemical reactions, particularly in amino acid and neurotransmitter metabolisms. Vitamin B 6 is absorbed by organisms in its non-phosphorylated form and phosphorylated within cells via pyridoxal kinase (PLK) and pyridox-(am)-ine 5'-phosphate oxidase (PNPOx). The flavin mononucleotide-dependent PNPOx enzyme converts pyridoxine 5'-phosphate and pyridoxamine 5'-phosphate into PLP. PNPOx is vital for both biosynthesis and salvage pathways in organisms producing B 6 vitamers. However, for those depending on vitamin B 6 as a nutrient, PNPOx participates only in the salvage pathway. Transferring the PLP produced via PNPOx to client apo-enzymes is indispensable for their catalytic function, proper folding and targeting of specific organelles. PNPOx activity deficiencies due to inborn errors lead to severe neurological pathologies, particularly neonatal epileptic encephalopathy. PNPOx maintains PLP homeostasis through highly regulated mechanisms, including structural alterations throughout the catalytic cycle and allosteric PLP binding, influencing substrate transformation at the active site. Elucidation at the molecular level of the mechanisms underlying PNPOx activity deficiencies is a requirement to develop personalized approaches to treat related disorders. Finally, despite shared features, the few PNPOx enzymes molecularly and functionally studied show species-specific regulatory properties that open the possibility of targeting it in pathogenic organisms.

Transplantation of immature dopaminergic neurons or neural precursors derived from embryonic stem cells (ESCs) into the substantia nigra pars compacta (SNpc) is a potential therapeutic approach for functional restitution of the nigrostriatal pathway in Parkinson's disease (PD). However, further studies are needed to understand the effects of the local microenvironment on the transplanted cells to improve survival and specific differentiation in situ. We have previously reported that the adult SNpc sustains a neurogenic microenvironment. Non-neuralized embryoid body cells (EBCs) from mouse ESCs (mESCs) overexpressing the dopaminergic transcription factor Lmx1a gave rise to many tyrosine hydroxylase (Th + ) cells in the intact and damaged adult SNpc, although only for a short-term period. Here, we extended our study by transplanting EBCs from genetically engineered naive human ESC (hESC), overexpressing the dopaminergic transcription factors LMX1A , FOXA2 , and OTX2 (hESC-LFO), in the SNpc. Unexpectedly, no graft survival was observed in wild-type hESC EBCs transplants, whereas hESC-LFO EBCs showed viability in the SNpc. Interestingly, neural rosettes, a developmental hallmark of neuroepithelial tissue, emerged at 7- and 15-days post-transplantation (dpt) from the hESC-LFO EBCs. Neural rosettes expressed specification dopaminergic markers (Lmx1a, Otx2), which gave rise to several Th + cells at 30 dpt. Our results suggest that the SNpc enables the robust initiation of neural differentiation of transplanted human EBCs prompted to differentiate toward the midbrain dopaminergic phenotype.

Metallocarboxypeptidases are zinc-dependent peptide-hydrolysing enzymes involved in several important physiological and pathological processes. They have been a target of growing interest in the search for natural or synthetic compound binders with biomedical and drug discovery purposes, i.e., with potential as antimicrobials or antiparasitics. Given that marine resources are an extraordinary source of bioactive molecules, we screened marine invertebrates for new inhibitory compounds with such capabilities. In this work, we report the isolation and molecular and functional characterization of NpCI, a novel strong metallocarboxypeptidase inhibitor from the marine snail Nerita peloronta . NpCI was purified until homogeneity using a combination of affinity chromatography and RP-HPLC. It appeared as a 5921.557 Da protein with 53 residues and six disulphide-linked cysteines, displaying a high sequence similarity with NvCI, a carboxypeptidase inhibitor isolated from Nerita versicolor , a mollusc of the same genus. The purified inhibitor was determined to be a slow- and tight-binding inhibitor of bovine CPA (Ki = 1.1·× 10 -8 mol/L) and porcine CPB (Ki = 8.15·× 10 -8 mol/L) and was not able to inhibit proteases from other mechanistic classes. Importantly, this inhibitor showed antiplasmodial activity against Plasmodium falciparum in an in vitro culture (IC 50 = 5.5 μmol/L), reducing parasitaemia mainly by inhibiting the later stages of the parasite's intraerythrocytic cycle whilst having no cytotoxic effects on human fibroblasts. Interestingly, initial attempts with other related proteinaceous carboxypeptidase inhibitors also displayed similar antiplasmodial effects. Coincidentally, in recent years, a metallocarboxypeptidase named PfNna1, which is expressed in the schizont phase during the late intraerythrocytic stage of the parasite's life cycle, has been described. Given that NpCI showed a specific parasiticidal effect on P. falciparum, eliciting pyknotic/dead parasites, our results suggest that this and related inhibitors could be promising starting agents or lead compounds for antimalarial drug discovery strategies.

An increased risk of lymphoma has been described in patients with inflammatory bowel disease (IBD). The aims of our study were to determine the clinical presentation, the previous exposure to immunosuppressive and biologic therapies, and the evolution of lymphomas in patients with IBD. IBD patients with diagnosis of lymphoma from October 2006 to June 2021 were identified from the prospectively maintained ENEIDA registry of GETECCU. We identified 52 patients (2.4 cases of lymphoma/1000 patients with IBD; 95% CI 1.8-3.1). Thirty-five were men (67%), 52% had ulcerative colitis, 60% received thiopurines, and 38% an anti-TNF drug before lymphoma diagnosis. Age at lymphoma was lower in those patients treated with thiopurines (53 ± 17 years old) and anti-TNF drugs (47 ± 17) than in those patients not treated with these drugs (63 ± 12; p < 0.05). Five cases had relapse of lymphoma (1.7 cases/100 patient-years). Nine patients (17%) died after 19 months (IQR 0-48 months). Relapse and mortality were not related with the type of IBD or lymphoma, nor with thiopurines or biologic therapies. In conclusion, most IBD patients had been treated with thiopurines and/or anti-TNF agents before lymphoma diagnosis, and these patients were younger at diagnosis of lymphoma than those not treated with these drugs. Relapse and mortality of lymphoma were not related with these therapies.

This study analyses the aortic wall structure in nine cetacean species with deep diving habits belonging to four Odontoceti families: Ziphiidae, Kogiidae, Physteridae, and Delphinidae. Samples of ascending, thoracic and abdominal aorta were processed for histological and morphometric studies. The elastic component was higher in the proximal aortic segments, and the muscular elements increased distally in all cases. Morphometric analyses showed that all families presented a decrease in the thickness of the arterial wall and the tunica media along the aorta. The reduction was dramatic between ascending and thoracic aorta in the Physeteridae specimens; meanwhile, the other three families showed a more uniform decrease between the ascending, thoracic and abdominal aorta. The decline was not correlated with a reduced elastic or lamellar unit thickness but with a loss of lamellar units. The organization of the elements in the aortic wall did not show essential modifications between the four families, resembling the structure described previously in the shallow and intermediate diving dolphins. Our findings support that the difference in the morphometric characteristics of the different segments in the aortic wall is likely related to the diving habit more than the absolutes values of any other parameter.

Cetacean brain sampling may be an arduous task due to the difficulty of collecting and histologically preparing such rare and large specimens. Thus, one of the main challenges of working with cetaceans' brains is to establish a valid methodology for an optimal manipulation and fixation of the brain tissue, which allows the samples to be viable for neuroanatomical and neuropathological studies. With this in view, we validated a methodology in order to preserve the quality of such large brains (neuroanatomy/neuropathology) and at the same time to obtain fresh brain samples for toxicological, virological, and microbiological analysis (neuropathology). A fixation protocol adapted to brains, of equal or even three times the size of human brains, was studied and tested. Finally, we investigated the usefulness of a panel of 20 antibodies (neuromarkers) associated with the normal structure and function of the brain, pathogens, age-related, and/or functional variations. The sampling protocol and some of the 20 neuromarkers have been thought to explore neurodegenerative diseases in these long-lived animals. To conclude, many of the typical measures used to evaluate neuropathological changes do not tell us if meaningful cellular changes have occurred. Having a wide panel of antibodies and histochemical techniques available allows for delving into the specific behavior of the neuronal population of the brain nuclei and to get a "fingerprint" of their real status.

The development of switching converters to perform with the power processing of photovoltaic (PV) applications has been a topic receiving growing interest in recent years. This work presents a nonisolated buck-boost converter with a quadratic voltage conversion gain based on the I-IIA noncascading structure. The converter has a reduced component count and it is formed by a pair of L - C networks and two active switches, which are operated synchronously to achieve a wide conversion ratio and a quadratic dependence with the duty ratio. Additionally, the analysis using different sources and loads demonstrates the differences in the behavior of the converter, as well as the pertinence of including PV devices (current sources) into the analysis of new switching converter topologies for PV applications. In this work, the voltage conversion ratio, steady-state operating conditions and semiconductor stresses of the proposed converter are discussed in the context of PV applications. The operation of the converter in a PV scenario is verified by experimental results., Competing Interests: The authors declare no conflicts of interest.

Colorectal cancer (CRC) is the third most common cancer worldwide. The standard treatment in locally advanced rectal cancer is preoperative radiation alone or in combination with chemotherapy, followed by adjuvant chemotherapy. Rectal cancer is highly lethal, with only 20% of patients showing a complete remission (by RECIST) after standard treatment, although they commonly show local or systemic relapse likely due to its late detection and high chemotherapy resistance, among other reasons. Here, we explored the role of PAI1 (Serpin E1) in rectal cancer through the analyses of public patient databases, our own cohort of locally advanced rectal cancer patients and a panel of CRC cell lines. We showed that PAI1 expression is upregulated in rectal tumors, which is associated with decreased overall survival and increased metastasis and invasion in advanced rectal tumors. Accordingly, PAI1 expression is correlated with the expression of (Epithelial-to-Mesenchymal Transition) EMT-associated genes and genes encoding drug targets, including the tyrosine kinases PDGFRb, PDGFRa and FYN, the serine/threonine kinase PIM1 and BRAF. In addition, we demonstrate that cells expressing PAI1 protein are more sensitive to the PIM inhibitor AZD1208, suggesting that PAI1 could be used to predict response to treatment with PIM inhibitors and to complement radiotherapy in rectal tumors., Competing Interests: The authors declare no conflicts of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Background: In 2012, 11 standards describing best supportive care (bsc) in clinical trials in advanced cancer were defined through consensus statements. The consensus included 15 key components. Our objective was to analyze whether clinical trials that involved patients with advanced cancer and that included bsc in at least 1 arm met the standards and contained the key components., Methods: We reviewed clinical trials registered in ClinicalTrials.gov, the isrctn (International Standard Randomised Controlled Trial Number) registry, the EU Clinical Trials Register, and the International Clinical Trials Registry Platform for 2012-2018. We selected only phase iii studies in patients with advanced cancer that included bsc in at least 1 arm. We describe the characteristics of the trials, together with the definition and components of bsc. We analyzed how the trials met the standards and adopted the key components of bsc., Results: Of 193 trials retrieved, only 64 met the inclusion criteria; 36 of those trials (56%) had no definition of bsc. Less than 7% of the trials included even 3 of the 8 bsc standards that were defined to be included in the design of trials. Furthermore, trials mentioned only 5 of the 15 key components that the consensus defined to be fundamental, with symptom management appearing in 22% of trials and the other 4 components appearing in less than 8%., Summary: Most clinical trials registered during 2012-2018 that involved patients with cancer and an arm with bsc did not define the bsc concept. Hence, the design of those trials does not meet the consensus recommendations., Competing Interests: CONFLICT OF INTEREST DISCLOSURES We have read and understood Current Oncology’s policy on disclosing conflicts of interest, and we declare that we have none., (2020 Multimed Inc.)

Thioredoxin fold proteins (TFPs) form a family of diverse proteins involved in thiol/disulfide exchange in cells from all domains of life. Leptospirillum spp. are bioleaching bacteria naturally exposed to extreme conditions like acidic pH and high concentrations of metals that can contribute to the generation of reactive oxygen species (ROS) and consequently the induction of thiol oxidative damage. Bioinformatic studies have predicted 13 genes that encode for TFP proteins in Leptospirillum spp. We analyzed the participation of individual tfp genes from Leptospirillum sp. CF-1 in the response to oxidative conditions. Genomic context analysis predicted the involvement of these genes in the general thiol-reducing system, cofactor biosynthesis, carbon fixation, cytochrome c biogenesis, signal transduction, and pilus and fimbria assembly. All tfp genes identified were transcriptionally active, although they responded differentially to ferric sulfate and diamide stress. Some of these genes confer oxidative protection to a thioredoxin-deficient Escherichia coli strain by restoring the wild-type phenotype under oxidative stress conditions. These findings contribute to our understanding of the diversity and complexity of thiol/disulfide systems, and of adaptations that emerge in acidophilic microorganisms that allow them to thrive in highly oxidative environments. These findings also give new insights into the physiology of these microorganisms during industrial bioleaching operations.

A very powerful proteinaceous inhibitor of metallocarboxypeptidases has been isolated from the marine snail Nerita versicolor and characterized in depth. The most abundant of four, very similar isoforms, NvCla, was taken as reference and N-terminally sequenced to obtain a 372-nucleotide band coding for the protein cDNA. The mature protein contains 53 residues and three disulphide bonds. NvCIa and the other isoforms show an exceptionally high inhibitory capacity of around 1.8 pM for human Carboxypeptidase A1 (hCPA1) and for other A-like members of the M14 CPA subfamily, whereas a twofold decrease in inhibitory potency is observed for carboxypeptidase B-like members as hCPB and hTAFIa. A recombinant form, rNvCI, was produced in high yield and HPLC, mass spectrometry and spectroscopic analyses by CD and NMR indicated its homogeneous, compact and thermally resistant nature. Using antibodies raised with rNvCI and histochemical analyses, a preferential distribution of the inhibitor in the surface regions of the animal body was observed, particularly nearby the open entrance of the shell and gut, suggesting its involvement in biological defense mechanisms. The properties of this strong, small and stable inhibitor of metallocarboxypeptidases envisage potentialities for its direct applicability, as well as leading or minimized forms, in biotechnological/biomedical uses.