Machine Learning-Driven Classification of Urease Inhibitors Leveraging Physicochemical Properties as Effective Filter Criteria.

Urease, a pivotal enzyme in nitrogen metabolism, plays a crucial role in various microorganisms, including the pathogenic Helicobacter pylori. Inhibiting urease activity offers a promising approach to combating infections and associated ailments, such as chronic kidney diseases and gastric cancer. However, identifying potent urease inhibitors remains challenging due to resistance issues that hinder traditional approaches. Recently, machine learning (ML)-based models have demonstrated the ability to predict the bioactivity of molecules rapidly and effectively. In this study, we present ML models designed to predict urease inhibitors by leveraging essential physicochemical properties. The methodological approach involved constructing a dataset of urease inhibitors through an extensive literature search. Subsequently, these inhibitors were characterized based on physicochemical properties calculations. An exploratory data analysis was then conducted to identify and analyze critical features. Ultimately, 252 classification models were trained, utilizing a combination of seven ML algorithms, three attribute selection methods, and six different strategies for categorizing inhibitory activity. The investigation unveiled discernible trends distinguishing urease inhibitors from non-inhibitors. This differentiation enabled the identification of essential features that are crucial for precise classification. Through a comprehensive comparison of ML algorithms, tree-based methods like random forest, decision tree, and XGBoost exhibited superior performance. Additionally, incorporating the "chemical family type" attribute significantly enhanced model accuracy. Strategies involving a gray-zone categorization demonstrated marked improvements in predictive precision. This research underscores the transformative potential of ML in predicting urease inhibitors. The meticulous methodology outlined herein offers actionable insights for developing robust predictive models within biochemical systems.

Influence of successive heat waves on the thermoregulatory responses of pregnant and non-pregnant ewes.

The frequency of heat waves has increased over the last years, with an impact on animal production and health, including the death of animals. Therefore, the aim of this study was to evaluate the dynamics of thermoregulation and hormonal responses in non-pregnant and pregnant ewes exposed to successive heat waves. Twenty-four non-pregnant and 18 pregnant Santa Ines ewes with black coat color (live weight: 55 ± 9.03 kg; age: 60 months) were used. Weather variables such air temperature, relative humidity, and solar radiation were continuously recorded. The rectal and tympanic temperatures and respiratory rate were measured daily. Serum triiodothyronine (T3) and prolactin were evaluated during the heat wave and thermoneutral periods. The physiological variables were higher under the heat wave conditions and were related to the activation of the thermoregulatory system for maintaining homeothermy (P < 0.05). The core body temperature was higher during successive heat waves (P < 0.05), as was the tympanic temperature, which are both affected by changes in air temperature (P < 0.05). T3 and prolactin levels were not influenced by successive heat waves (P < 0.05) and rectal temperature and respiratory rate were highest in non-pregnant ewes (P < 0.05). Prolactin was not affected by temperature. The results indicate that the Santa Ines breed overcomes the thermal challenge during a heat wave without showing severe signs of thermal stress regardless of being pregnant or not.

The Effects Of Slow Breathing Exercise On Heart Rate Dynamics And Cardiorespiratory Coherence In Preschool Children: A Prospective Clinical Study.

BACKGROUND: Slow breathing has been used to improve psychophysiological regulation due to positive action on the autonomic nervous system. PRIMARY STUDY OBJECTIVE: We evaluated the effects of slow breathing on heart rate autonomic control in preschool-aged children. METHODS/DESIGN: Prospective clinical study. SETTING: Campinas, Brazil. PARTICIPANTS: We included 42 children in the experimental group (age 5.7 ± 0.3) and 33 children in the control group (age 6.2 ± 0.3). INTERVENTION: Children received a daily training of eight weeks duration for practicing a slow breathing technique. Primary Outcome Measures • We analyzed heart rate variability (HRV) and cardiorespiratory coherence at rest under spontaneous breathing and during respiratory sinus arrhythmia (RSA) at the end of the 1st, 4th, and 8th weeks of training. RESULTS: The percentage of high coherence ratio increased (P < .0001), HRV reduced (SDNN, P = .0066; RMSSD, P = .0015; pNN50, P < .0001; SD1, P = .0015; SD2, P = .0166) and the complexity of HRV increased (ApEn, P = .0004; MSE area, P < .0001; DFAαl, P = .0001; ShanEnt, P = .0106; Lmean, P = .0066) during RSA compared to spontaneous breathing after slow breathing training period. CONCLUSION: Slow breathing training exercise induced increased cardiorespiratory coherence and increased nonlinear behavior of heart rate dynamics suggesting improvements in health status. Increased cardiorespiratory coherence reinforces the importance of including respiratory exercises in strategies that aim to promote physical health and self-regulation skills in educational settings.

Reference forecasts for CO2 emissions from fossil-fuel combustion and cement production in Portugal.

We provide reference forecasts for CO2 emissions from burning fuel fossil and cement production in Portugal based on an ARFIMA model approach and using annual data from 1950 to 2017. Our reference projections suggest a pattern of decarbonization that will cause the reduction of 3.3 Mt until 2030 and 5.1 Mt between 2030 and 2050. This scenario allows us to assess effort required by the new IPCC goals to ensure carbon neutrality by 2050. For this objective to be achieved it is necessary for emissions to be reduced by 39.9 Mt by 2050. Our results suggest that of these, only 8.4 Mt will result from the inertia of the national emissions system. The remaining reduction on emissions of 31.5 Mt of CO2 will require additional policy efforts. Accordingly, our results suggest that about 65.5% of the reductions necessary to achieve IPCC goals require deliberate policy efforts. Finally, the presence in the data of long memory with mean reversion suggests that policies must be persistent to ensure that these reductions in emissions are also permanent.

Heat loss efficiency and HSPs gene expression of Nellore cows in tropical climate conditions.

Adaptation is a relevant characteristic to be understood in livestock animals in order to maintain and raise productivity. In Brazil, the Nellore beef cattle are widely disseminated and well-adapted breed that present good thermoregulatory characteristics for tropical environment conditions. Conversely, the physiological and cellular mechanisms required for thermoregulation and thermotolerance in this breed are still limited. The aim of this study was to comprehend the heat loss efficiency at the whole animal level and heat shock response at the cellular level of Nellore cows in tropical climate conditions. Healthy purebred Nellore cows were classified according to their capacity to lose body heat as Efficient or Inefficient based on vaginal temperature which was continuously monitored by data-loggers. Rectal, tail, and ocular temperatures, sweating rate, and respiratory frequency were collected to assess other thermoregulatory responses. Peripheral mononuclear cells were used for gene expression of heat shock proteins 60, 70, and 90 induced by in vitro heat treatments at 38, 40, and 42 °C. In our findings, the Efficient cows presented higher sweating rates compared to Inefficient cows that presented higher rectal temperature with greater amplitude of vaginal temperature profile. Transcription of the HSP genes was stable at 38 and 40 °C and decreased for all HSP genes at 42 °C. In conclusion, the Nellore efficiency to lose heat was mainly associated with their sweating capacity and cellular thermotolerance confirmed by the maintenance of heat shock proteins transcripts under heat stress. Taken together, this knowledge contributes as a future key for genetic selection of adapted animals.

Extra-intestinal detection of canine kobuvirus in a puppy from Southern Brazil.

This study presents the pathological, immunohistochemical, and molecular findings associated with the extra-intestinal detection of canine kobuvirus (CaKV) in a 5-month-old Chihuahua puppy, that had a clinical history of bloody-tinged feces. Principal pathological findings were interstitial pneumonia, necrotizing bronchitis, and parvovirus-induced enteritis. Molecular diagnostic methods identified CaKV within the cerebellum, cerebrum, lung, tonsil, and liver. CaKV and rotavirus were not identified within the feces and intestine. Immunohistochemistry (IHC) assays detected antigens of CDV and CAdV-1 in the lungs. These results confirmed the extra-intestinal detection of CaKV in this puppy and represent the first extra-intestinal detection of CaKV in a dog.

Astroglial hydro-ionic waves guided by the extracellular matrix: An exploratory model.

Calcium waves are generated from the astrocyte endoplasmatic reticulum, in response to neuronal electrochemical stimulation. The waves feed back on neurons, modulating (reinforcing or depressing) their activity and the resulting behavior. How do these waves propagate from the astrocyte endoplasmatic reticulum to the synaptic space and reach neuron membrane channels? An exploratory model is elaborated, on the basis of complex interactions of ions, water negative exclusion zones and charged sites of proteins. The mechanism includes a role for the extracellular matrix to guide the hydro-ionic wave towards regions of the neuronal membrane where they are functional. The function of the waves is explored, suggesting that their dynamic patterns compose an adequate substrate for feelings (from basic feelings as hunger and thirst, pain and pleasure, to more complex ones, such as joy and sadness, love and hate).

Patterns of calcium signaling: A link between chronic emotions and cancer.

Intra and inter-cellular calcium signaling is present in all types of cells and body tissues. In the human brain, calcium currents and waves are related to mental activities, including emotions. We present a theoretical interpretation of these phenomena suggesting their involvement in chronic emotional patterns and in the pathology of cancer. Recent developments on biophysics, translational biology and psychoneuroendocrinoimmunology (PNEI) can support explanatory hypotheses about the link between emotional stresses and the origin and development of different types of tumor cells. Chronic stresses may cause perturbations of rhythms of the PNEI system, excessive activation of HPA axis and abnormal activation of calcium signals in somatic tissues, with deleterious effects on different parts of the body. The increasing of calcium signaling inside cells may lead to a deregulation of different pathways and epigenetic systems that promote the production of genomic mutations in a second phase. In particular, the hyperactivation of the transcription nuclear factor kappaB (NF-κB), if is not counterbalanced by the following activation of the nuclear factor (erythroid-derived 2)-like 2 (NFE2L2 or Nrf2), increases the production of oxidative catabolites, as the advanced glycation end products (AGE), which play a key role in the progression of different types of cancer and other degenerative diseases. Cortisol binding to glucocorticoid receptor (GR) reduces the activity of both NF-κB and Nrf2 inside the cells but inhibits the cellular immunity and the anabolic processes of tissue regeneration. The tissue atrophy and the defective anti-ageing mechanisms promotes the tumoral cells growth and their escape from the immune-surveillance.

Detection of 70 kDa heat shock protein in the saliva of dairy cows.

This Research Communication describes, for the first time, the detection of HSP70 in saliva of dairy cows. Thermal stress is a major environmental stress that limits animal growth, metabolism, and productivity. The cellular response to heat stress involves the synthesis of heat shock proteins (HSPs), presumably to protect the functional stability of cells at increasing temperatures. HSP70 has been found to be present in cattle blood serum and may also be present in other secretory fluids, such as saliva, as already observed in humans. The aim of this study was to detect heat shock protein HSP70 in bovine saliva. Saliva samples were taken from higher- (n = 5) and lower milk producing (n = 5) Holstein-Friesian cows in summer and in winter for the detection of HSP70. HSP70 concentrations were assayed using the ELISA technique. Salivary HSP70 concentrations ranged from 0·524 to 12·174 ng/ml in cows. Higher salivary HSP70 concentrations were significantly associated with higher milk production and higher environmental temperature, but not with rectal temperature.

Elastomeric enriched biodegradable polyurethane sponges for critical bone defects: a successful case study reducing donor site morbidity.

Bone substitutes have been a critical issue as the natural source can seldom provide enough bone to support full healing. No bone substitute complies with all necessary functions and characteristics that an autograft does. Polyurethane sponges have been used as a surgical alternative to cancellous bone grafts for critical bone defect donor sites. Critical bone defects were created on the tibial tuberosity and iliac crest using an ovine model. In group I (control-untreated), no bone regeneration was observed in any animal. In group II (defects left empty but covered with a microporous polymeric membrane), the new bone bridged the top ends in all animals. In groups III and IV, bone defects were implanted with polyurethane scaffolds modified with biologically active compounds, and bone regeneration was more efficient than in group II. In groups III and IV there were higher values of bone regeneration specific parameters used for evaluation (P < 0.05) although the comparison between these groups was not possible. The results obtained in this study suggest that biodegradable polyurethane substitutes modified with biologically active substances may offer an alternative to bone graft, reducing donor site morbidity associated with autogenous cancellous bone harvesting.

The Plastic Glial-Synaptic Dynamics within the Neuropil: A Self-Organizing System Composed of Polyelectrolytes in Phase Transition.

Several explanations have been proposed to account for the mechanisms of neuroglial interactions involved in neural plasticity. We review experimental results addressing plastic nonlinear interactions between glial membranes and synaptic terminals. These results indicate the necessity of elaborating on a model based on the dynamics of hydroionic waves within the neuropil. These waves have been detected in a small scale experimental model of the central nervous system, the in vitro retina. We suggest that the brain, as the heart and kidney, is a system for which the state of water is functional. The use of nonlinear thermodynamics supports experiments at convenient biological spatiotemporal scales, while an understanding of the properties of ions and their interactions with water requires explanations based on quantum theories. In our approach, neural plasticity is seen as part of a larger process that encompasses higher brain functions; in this regard, hydroionic waves within the neuropil are considered to carry both physiological and cognitive functions.

Some views are better than others: evidence for a visual bias in object views self-generated by toddlers.

How objects are held determines how they are seen, and may thereby play an important developmental role in building visual object representations. Previous research suggests that toddlers, like adults, show themselves a disproportionate number of planar object views - that is, views in which the objects' axes of elongation are perpendicular or parallel to the line of sight. Here, three experiments address three explanations of this bias: (1) that the locations of interesting features of objects determine how they are held and thus how they are viewed; (2) that ease of holding determines object views; and (3) that there is a visual bias for planar views that exists independently of holding and of interesting surface properties. Children 18 to 24 months of age manually and visually explored novel objects (1) with interesting features centered in planar or ¾ views; (2) positioned inside Plexiglas boxes so that holding biased either planar or non-planar views; and (3) positioned inside Plexiglas spheres, so that no object properties directly influenced holding. Results indicate a visual bias for planar views that is influenced by interesting surface properties and ease of holding, but that continues to exist even when these factors push for alternative views.

Triple-aspect monism: physiological, mental unconscious and conscious aspects of brain activity.

Brain activity contains three fundamental aspects: (a) The physiological aspect, covering all kinds of processes that involve matter and/or energy; (b) the mental unconscious aspect, consisting of dynamical patterns (i.e., frequency, amplitude and phase-modulated waves) embodied in neural activity. These patterns are variously operated (transmitted, stored, combined, matched, amplified, erased, etc), forming cognitive and emotional unconscious processes and (c) the mental conscious aspect, consisting of feelings experienced in the first-person perspective and cognitive functions grounded in feelings, as memory formation, selection of the focus of attention, voluntary behavior, aesthetical appraisal and ethical judgment. Triple-aspect monism (TAM) is a philosophical theory that provides a model of the relation of the three aspects. Spatially distributed neuronal dendritic potentials generate amplitude-modulated waveforms transmitted to the extracellular medium and adjacent astrocytes, prompting the formation of large waves in the astrocyte network, which are claimed to both integrate distributed information and instantiate feelings. According to the valence of the feeling, the large wave feeds back on neuronal synapses, modulating (reinforcing or depressing) cognitive and behavioral functions.

Evaporative heat loss in Bos taurus: do different cattle breeds cope with heat stress in the same way?

The aim of this study was to compare two Portuguese (Alentejana and Mertolenga) and two exotic (Frisian and Limousine) cattle breeds in terms of the relationship between the increase in ambient temperature and the responses of the evaporative heat loss pathways and the effects on homeothermy. In the experiment, six heifers of the Alentejana, Frisian, and Mertolenga breeds and four heifers of the Limousine breed were used. The animals were placed in four temperature levels, the first one under thermoneutral conditions and the other ones with increase levels of thermal stress. When submitted to severe heat stress, the Frisian developed high thermal tachypnea (125 mov/min) and moderate sweating rates (117 gm(-2) h(-1)), which did not prevent an increase in the rectal temperature (from 38.4 °C to 40.0 °C). Moderate increases in rectal temperature were observed in the Alentejana (from 38.8 °C to 39.4 °C) and Limousine (from 38.6 °C to 39.4 °C), especially in the period of highest heat stress. The Limousine showed moderate levels of tachypnea (101 mov/min) while showing the lowest sweating rates. The Alentejana showed significant increases in sweating rate (156 gm(-2)h(-1)) that played a major role in homeothermy. The Mertolenga showed a superior stability of body temperature, even in the period of highest heat stress (from 38.5 °C to 39.1 °C). Uncommonly, the maintenance of homeothermy during moderate heat stress was achieved primarily by intense tachypnea (122 mov/min). The sweating rate remained abnormally low under conditions of moderate heat stress, rising significantly (110 gm(-2)h(-1)) without evidence of stabilization, only when tendency for heat storage occurred. This unusual response of the evaporative heat loss pathways infers a different thermoregulatory strategy, suggesting a different adaptation to semi-arid environment and strong association with water metabolism.

A Comprehensive Review of Bovine Colostrum Components and Selected Aspects Regarding Their Impact on Neonatal Calf Physiology.

Colostrum contains macro- and micronutrients necessary to meet the nutritional and energy requirements of the neonatal calf, bioactive components that intervene in several physiological aspects, and cells and microorganisms that modulate the calf's immune system and gut microbiome. Colostrum is sometimes mistaken as transition milk, which, although more nutritive than whole milk, has a distinct biochemical composition. Furthermore, most research about colostrum quality and colostrum management focuses on the transfer of maternal IgG to the newborn calf. The remaining components of colostrum and transition milk have not received the same attention, despite their importance to the newborn animal. In this narrative review, a large body of literature on the components of bovine colostrum was reviewed. The variability of these components was summarized, emphasizing specific components that warrant deeper exploration. In addition, the effects of each component present in colostrum and transition milk on several key physiological aspects of the newborn calf are discussed.

Predicting Body Weight in Pre-Weaned Holstein-Friesian Calves Using Morphometric Measurements.

Regularly weighing calves helps to assess the efficiency of the rearing period and contributes to animal welfare by allowing more precise feeding and medication application in dairy farming, but many farmers do not weigh their calves regularly. Improving the feasibility of this process is, therefore, important. The use of morphometric measurements has been used to estimate the weight of cattle. However, many studies have focused on adult animals or used a wide age range. As calves experience allometric tissue growth, specific models for certain ranges might be more accurate. Therefore, the aim of this work was to develop a weight estimation model specific for pre-weaned Holstein-Friesian calves using morphometric measurements and to compare the model with another equation previously validated for the same breed with young and adult animals. From four dairy farms, 237 measurements of body weight, heart girth, abdominal girth, hip height, withers height, and body length were taken from Holstein-Friesian male and female calves. Linear and non-linear regression analysis was used to test the relationship between body weight and morphometric measurements, with age, sex, and farm as possible explanatory variables. Selected models were compared with goodness of fit and agreement tests. The final model was able to accurately predict body weight (R2 = 0.96) with a mean difference of -1.4 ± 3.24 kg. Differences in the relationship between body weight and morphometric traits were observed between farms, but not between males and females. The genetics of the animal population at farm level may be responsible for this variability and further studies are needed to understand this variability and improve weight prediction models. The developed model was able to perform better in the agreement tests than the previously validated model for Holstein-Friesian animals, suggesting that different equations should be used depending on the growth phase the animal is in. In addition, a web application has been developed to facilitate the use of the developed model by farmers. This avoids the use of calibrated weight bands, which are usually calibrated for a broader age range or for beef cattle.

Utilization of Infrared Thermography in Assessing Thermal Responses of Farm Animals under Heat Stress.

Heat stress is a condition that can affect the health, performance, and welfare of farm animals. The perception of thermal stress leads to the activation of the autonomic nervous system to start a series of physiological and behavioral mechanisms to restore thermostability. One of these mechanisms is vasodilation of peripheral blood vessels to increase heat loss through the skin. Due to this aspect, infrared thermography has been suggested as a method to assess the thermal state of animals and predict rectal temperature values noninvasively. However, it is important to consider that predicting rectal temperature is challenging, and its association with IRT is not always a direct linear relationship. The present review aims to analyze the neurobiological response associated with heat stress and how thermal imaging in different thermal windows can be used to recognize heat stress in farmed ungulates.

Adaptive integumentary features of beef cattle raised on afforested or non-shaded tropical pastures.

We aimed to analyze the seasonal acclimatization process of Nelore and Canchim cattle raised on two production systems (non-shaded, NS, and integrated crop-livestock-forest, ICLF), based on the dynamics of the morphological and functional attributes of the hair coat and skin during winter and summer. The study was conducted in Brazil, in a low-altitude tropical climate region. A completely randomized 2 × 2 factorial design was adopted as follows: two production systems (NS and ICLF), two breeds (Nelore and Canchim) in a longitudinal structure, with measurements repeated over time through two stations (winter and summer). The experimental animals consisted of 32 Nelore (Bos indicus) and 32 Canchim (5/8 Bos taurus × 3/8 Bos indicus) bulls. The animals were equally distributed between two intensive rotational grazing systems. In both breeds, the hair coat was significantly thicker in winter but longer in summer, which increased epidermal protection. The Nelore bulls had shorter, wider, and thicker hairs, which are attributes that promote heat loss via conduction. The Canchim bulls showed significantly lower hair density and higher epithelium distance to sweat glands, which resulted in higher core temperature and respiratory rate. In turn, Nelore bulls had higher serum concentrations of triiodothyronine and lower serum concentrations of cortisol. However, Canchim bulls more frequently and intensely activated their thermoregulatory system and markedly adjusted their hair coat and hair features to reduce heat gain, especially in summer. Therefore, the anatomical plasticity and functional integumentary characteristics of Nelore and Canchim bulls reflect their acclimatization to tropical conditions.

Effects of an evaporative cooling system on plasma cortisol, IGF-I, and milk production in dairy cows in a tropical environment.

Access to an evaporative cooling system can increase production in dairy cows because of improved thermal comfort. This study aimed to evaluate the impact of ambient temperature on thermoregulation, plasma cortisol, insulin-like growth factor 1 (IGF-I), and productive status, and to determine the efficiency of an evaporative cooling system on physiological responses under different weather patterns. A total of 28 Holstein cows were divided into two groups, one with and the other without access to a cooling system with fans and mist in the free stall. The parameters were analyzed during morning (0700 hours) and afternoon milking (1430 hours) under five different weather patterns throughout the year (fall, winter, spring, dry summer, and rainy summer). Rectal temperature (RT), body surface temperature (BS), base of tail temperature (TT), and respiratory frequency (RF) were lower in the morning (P < 0.01). The cooling system did not affect RT, and both the groups had values below 38.56 over the year (P = 0.11). Cortisol and IGF-I may have been influenced by the seasons, in opposite ways. Cortisol concentrations were higher in winter (P < 0.05) and IGF-I was higher during spring-summer (P < 0.05). The air temperature and the temperature humidity index showed positive moderate correlations to RT, BS, TT, and RF (P < 0.001). The ambient temperature was found to have a positive correlation with the physiological variables, independent of the cooling system, but cooled animals exhibited higher milk production during spring and summer (P < 0.01).

How does sensitivity influence early executive function? A critical review on hot and cool processes.

There is compelling evidence that the quality of caregiver-child interactions during toddlerhood and the preschool years supports the development of executive function (EF) (Bernier et al., 2010; 2015; 2016; Fay-Stammbach et al., 2014; Geeraerts et al., 2021). Based on such findings, we make the case herein that sensitivity may be one of the most important dimensions of parenting contributing to early EF. In the present article, we will review empirical evidence, integrating findings from a wide range of scientific disciplines - cognitive psychology, neuroscience, and developmental psychopathology - and present theoretical ideas about how two contexts of sensitive caregiving - i.e. sensitivity to distress and non-distress cues - may be contributing differently to hot and cool EF development. Implications for future investigations on the environmental contributors of early EF, and its mechanisms, are discussed.