Abnormal Animal Behavior Research Articles

Abstract 1883: A MUC1 antibody-conjugated with a tubulysin B analog, DXC005, demonstrates excellent synergistic effect in combination with gemcitabine for treatment of pancreatic tumors

Abstract Pancreatic cancer is a malignant tumor with high incidence and mortality. It is difficult to diagnose and detect in the early stage, with low surgical resection rate and high recurrence and metastasis rate after surgery. At present, the clinical therapeutic strategy is extremely limited. The first-line Standard of Care (SOC) for unresectable pancreatic cancer is chemotherapy. The preferred regimen includes gemcitabine combined with albumin paclitaxel or FOLFIRINOX (5-FU+Oxaliplatin+Irinotecan). Due to the limited long-term benefits and toxic side effects of chemotherapy, targeted therapy combined with chemotherapy has become a new therapeutic strategy. MUC1 is a highly glycosylated transmembrane mucin located on the lumen surface of epithelial cells. It can protect cells from extreme factors and plays an important role in tumor cell metabolism, apoptosis, epithelial-mesenchymal transition (EMT) and metastasis. Previous studies have confirmed that MUC1 is highly expressed in a variety of tumors, including pancreatic cancer, and is closely related to poor prognosis. DXC005 is a novel MUC1-targeting antibody-drug conjugate (ADC), generated by conjugating a Tubulysin B analogue to a recombinant humanized anti-Muc1 monoclonal antibody. DXC005 is the first MUC1-ADC IND in China, and is currently in phase I clinical trials. Preclinical studies have confirmed the efficacy of DXC005 monotherapy (2.5 mg/kg, 5 mg/kg, 10 mg/kg in one administration) in the HuPrime ® pancreatic cancer PDX model (PA1194). The tumor growth inhibition (TGI) was 42.53 %, 70.77 %, and 95.58 %, respectively. We want to further clarify whether DXC005 combined with chemotherapeutic drug Gemcitabine can ensure or even improve the efficacy while reducing the dosage of Gemcitabine. In PA1194 xenograft model, DXC005 (3 mg/kg or 6 mg/kg) in combination with Gemcitabine (10 mg/kg) showed significant anti-tumor efficacy with 58.77% and 93.17% TGIs, respectively. In contrast, the treatment with 10 mg/kg of Gemcitabine alone exhibited much less TGI. Furthermore, complete response (CR) was observed in some animals after treatment with DXC005 (6 mg/kg) plus Gemcitabine (10 mg/kg). All groups of treatment are tolerated well, no abnormal animal behavior and body weight loss were observed in the study. The above results concluded that DXC005 combined with Gemcitabine can achieve synergistic effect even with reduced dose of Gemcitabine, which will serve as a support for synergistic application in clinical studies. Citation Format: Xiaobo Cai, Min Cao, Huihui Guo, Qingliang Yang, Yongxiang Chen, Xiangfei Kong, Yong Du, Zhicang Ye, Zhixiang Guo, Lingli Zhang, Lu Bai, Junxiang Jia, Yunxia Zheng, Wei Zheng, Jun Zheng, Wenjun Li, Yuanyuan Huang, Zhongliang Fan, Binbin Chen, Yanlei Yang, Meng Dai, Robert Y. Zhao. A MUC1 antibody-conjugated with a tubulysin B analog, DXC005, demonstrates excellent synergistic effect in combination with gemcitabine for treatment of pancreatic tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1883.

Preface Special Issue: Developments in Earthquake Precursors Studies

This Special Issue of Annals of Geophysics is dedicated to present recent developments in the field of earthquake (EQ) precursors. Due to their potentially catastrophic nature, EQs have early attracted the attention of humans. During the last decades, a considerable amount of scientific effort has been devoted to the study of EQ precursors, aiming at EQ forecast. Prediction of large EQs, especially in the short-term, is of outmost importance for our society, since it could prevent, or at least restrict, their disastrous consequences, both in terms of infrastructure / material damages and in terms of casualties. It is clear that EQ preparation processes are complex and multifaceted, which call for a multidisciplinary approach. Many possible precursors have been reported and studied during the last decades, which include (just to mention some): foreshock activity, pre-slip effect, surface deformation, seismic electric signals (SES), ultra-low frequency (ULF) magnetic field anomalies, fracture-induced electromagnetic emissions (FEME) (fracture-induced electromagnetic radiation, FEMR), ULF/ELF (extremely low frequency) atmospheric electromagnetic radiation, atmospheric anomalies (such as SLHF, OLR etc.) and ionospheric (lower and upper regions) anomalies, lithosphere-atmosphere-ionosphere (LAI) coupling, even abnormal animal behavior.

Interhemispheric connectivity dynamics of brain activity indused by cortical spreading depolarization in rats

Growing experimental and clinical evidence indicates the crucial role of network dysfunction in neurological disorders’ pathogenesis, including migraine, one of the most prevalent chronic brain diseases. Episodic headache attacks, frequently unilateral, accompanied by an aura, are associated with migraine. Migraine aura is a neurological condition characterized by the temporary development of unilateral sensory, motor, and/or speech disturbances. The symptoms are thought to indicate transient cerebral dysfunction in the cerebral cortex resulting from cortical spreading depolarization (SD), a wave of strong cellular depolarization that gradually spreads through the cortex at a rate of 3–5 mm/min. Electrophysiologically, the cortical SD wave is revealed by a high-amplitude slow negative shift in the extracellular potential and temporary suppression of the electrical activity of the cortex (EEG depression). The change in extracellular potential is associated with strong neuroglial depolarization and disruption of local ion homeostasis, which lasts for 1–2 min in healthy neuronal tissue. The SD results in a momentary suppression of the spontaneous electrical activity within the cortex, which is preceded by a brief excitation of the neurons. The neurological symptoms of the aura suggest a unilateral impairment of interhemispheric interactions during the early phase of a migraine attack. Our study investigated the effect of unilateral SD (a probable pathophysiological mechanism of migraine aura) on interhemispheric functional communication in freely behaving rats using local field potentials of the visual and motor cortex. Two methods were used to examine connectivity: mutual information function, computed using the method proposed in [1], and phase synchronization, calculated through the method [2], for four frequency bands: delta (1–4 Hz), theta (4–10 Hz), beta (10–25 Hz), and gamma (25–50 Hz). This was done by performing calculations on non-overlapping twenty-second intervals. Functional connectivity evolution was analyzed using local field potential records collected from homotopic points of the motor and visual cortex of two hemispheres in freely moving rats after inducing a single unilateral cortical SD in the somatosensory cortex. Cortical SD caused a significant wide-band decline (3–4 times) in interhemispheric functional connectivity in both the visual and motor cortex areas. Following the depolarization wave, the functional decoupling of the hemispheres began and progressively intensified, concluding by 5 min after the induction of the cortical SD wave. The network impairment displayed region- and frequency-specific features, with greater prominence observed in the visual cortex than in the motor cortex. The decline in functional connectivity was concurrent with abnormal animal behavior and aberrant activity in the ipsilateral cortex that appeared after the SD wave had ended. The study indicated that unilateral SD leads to a reversible decline in the functional interhemispheric connectivity in the awake animal cortex. Given the crucial role of synchronizing cortical oscillations for processing sensory information and integrating sensorimotor functions, the intracortical functional interactions disruption resulting from a unilateral SD wave, which we discovered in our present study, could contribute to the neuropathological mechanisms of migraine aura and sensory processing dysfunction during a migraine attack.

An Ethogram of the Reproductive Behaviour of the American Mink (Neovison vison) in Farmed Conditions.

Ethograms can serve as benchmarks against which abnormal animal behaviour can be identified, and then normal behaviour can be restored by appropriately modifying the environment in which an individual resides. The aim of the present study was to create an ethogram of the reproductive behaviour of American mink kept in farmed conditions. The research material consisted of 12 one-year-old male American mink, pearl coloured, selected randomly from among the varieties of coloured mink on the farm, and 60 two-year-old females. The animals participating in the study were grouped into two breeding sets, each consisting of 30 females and 6 males. Reproductive rituals included chasing the female, grasping her neck with the teeth, marking the local area, mounting the partner, and sniffing the neck, anal and genital areas. The copulation times recorded in this study varied greatly, ranging from several minutes to over two hours. The obtained results indicate that the American mink can express some natural reproductive behaviour in breeding conditions, which may also be an indicator of the welfare of these animals.

LPS-Induced Systemic Inflammation Caused mPOA-FSH/LH Disturbance and Impaired Testicular Function

Male reproductive function is key to the continuation of species and is under sophisticated regulation, challenged by various stressors including inflammation. In the lipopolysaccharide (LPS) intraperitoneal injection-induced acute systemic inflammation, male fecundity was compromised with decreased testosterone level, damaged spermatogenesis, and downregulations of testicular gene expression levels involved in steroidogenesis regulation and blood–testis barrier. It is also noteworthy that the testis is more sensitive to acute stress caused by LPS-induced systemic inflammation. LPS treatment resulted in lower testicular gene expression levels of steroidogenic acute regulatory protein, cholesterol side-chain cleavage enzyme, and cytochrome P450 family 11 subfamily B member 1 after LPS treatment, while no such decrease was found in the adrenal gland. In parallel to the significant decreases in testicular intercellular adhesion molecule 1, tight junction protein 1, and gap junction alpha-1 protein gene expression with LPS treatment, no decrease was found in the epididymis. In the brain, LPS treatment caused higher medial preoptic area (mPOA) activation in the hypothalamus, which is accompanied by elevated blood follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels, suggesting a disturbed hypothalamic–pituitary–gonad axis function. Besides mPOA, brain c-fos mapping and quantitative analysis demonstrated a broad activation of brain nuclei by LPS, including the anterior cingulate cortex, lateral septum, paraventricular nucleus of the hypothalamus, basolateral amygdala, ventral tegmental area, lateral habenular nucleus, locus coeruleus, Barrington’s nucleus, and the nucleus of the solitary tract, accompanied by abnormal animal behavior. Our data showed that LPS-induced inflammation caused not only local testicular damage but also a systemic disturbance at the brain–testis axis level.

Effects of N Ethyl N′ nitrosourea in mice brain in time fashion

Antioxidant enzyme plays a pivotal role in preventing oxidative stress. Chemical toxicants often exert adverse effects in the biological system by breaking the antioxidant response system leading to severe oxidative stress. N-Ethyl-N-Nitrosourea (ENU) is a DNA alkylating agent and is carcinogenic and neurotoxic in animals. ENU in the nervous system cause persistent alkylation of DNA within the neurons altering the normal functional activities of the brain. Prenatal exposure to ENU in rodents that generate malignant gliomas in the brain induces functional changes and apoptotic death in neuronal progenitors in the brain's subventricular zone (SVZ). However, as chemical toxicants, their role in the induction of oxidative stress in brain tissue and subsequent change in the brain were less studied. In this study, we have investigated the response antioxidant system and induction of oxidative stress in the Balb/c mice brain at various time points after ENU exposure. Exposures to ENU were found to raise the oxidative stress and lipid peroxidation in the brain of mice with subsequent reduction in antioxidant enzyme activity. A significant increase in lactate dehydrogenase activity in the serum and brain homogenate was recorded at 16th weeks after ENU injection, which indicates metabolic alteration due to damage in the brain and has been validated by histological damage in the cerebral cortex and abnormal neurologic behavior in animals administered with ENU.

Animal Welfare and Pig Factory Farming in Ontario, Canada (1950s – Present)

This article explores the inception and development of pig factory farming in Ontario, Canada, since the 1950s to date, focusing on animal welfare dimensions. The study showed that although the term “animal welfare” was not well-known until the 1980s, discussions on cruelty and abnormal animal behaviour begun in the early days of factory farms. The article also delves into tensions between the humane movement and the agribusiness sector in Ontario. The article further sheds light on the social context that eventually led to an alliance in support of a conservative, incomplete notion of animal welfare between these former opponents. The article posits that as opposed to supporting the abolition of factory farming, the concept of animal welfare became central to implementing limited reforms in factory farming to convince the public and to marginalize discordant voices while concurrently expanding pig and other animal production worldwide.

Central Effect of Components of Cannabis: Utility and Risk

Cannabis contains over 700 known cannabinoids, terpenoids, flavonoids, and so on; however, the roles and importance of these components have yet to be fully understood. Δ9-Tetrahydrocannabinol (THC) is believed the most psychoactive component in cannabis, whereas cannabidiol (CBD), cannabinol, and cannabigerol are the most well-known non-psychoactive components. THC, but not CBD, has been shown to produce abnormal behavior in animals; these effects are caused, at least in part, by binding to cannabinoid receptor type 1 (CB1) in the brain. Regarding the risks associated with cannabis use, acute effects of THC, such as a "high", cognitive deficits, and irritability, are considered more important than potential dependence. On the other hand, CBD has shown anticonvulsant, anti-inflammatory, immunosuppressive, analgesic, and anticancer effects. However, CBD has very low affinity (in the micromolar range) for the CB1 receptor, as well as for the CB2 receptor, and its underlying mechanism remains obscure. In this review, we demonstrate that THC induces abnormal behavior such as catalepsy-like immobilization, spatial memory impairment, and high and low sensitivity to ultrasonic vocalization after an aversive air-puff stimulus. Moreover, we demonstrate that THC and CBD improve brain injury in middle cerebral artery occlusion in a mouse model through different mechanisms. These findings suggest the need to discuss the recent development of "THC and CBD pharmacology" in animal studies, as well as the utility and risk of various cannabis components in humans.

Prioritization of Farm Animal Welfare Issues Using Expert Consensus

Prioritization of animal welfare issues can help identify which areas most require research funding and raise awareness of best practices. A modified Delphi method was used to obtain expert opinion on the highest priority welfare issues for UK farmed livestock. Fifty-eight UK-based experts were recruited onto the study, with a minimum of 3 years experience of working with either cattle, pigs, poultry, or small ruminants (12–16 experts per group). Experts were chosen to represent a broad range of opinions. Two rounds of surveys were conducted online using Online Survey, and the final round was an in-person workshop with 21 experts. In the first survey, experts were provided with a comprehensive list of species-specific welfare issues derived from the literature. Participants were asked to score each welfare issue, for (i) severity, (ii) duration, and (iii) prevalence on a 6-point Likert scale. The results of the first survey were reviewed and the welfare issues which scored a neutral-to-high response (scores 3–6) were carried forward. In round 2, participants were asked whether they agreed or disagreed with the rankings that were made from the results of round 1. The final stage of the process was a workshop, which consisted of a combination of group exercises and discussions, to reach the final consensus. Welfare priority lists were divided into two categories: severity/duration, and prevalence, to identify the priority welfare issues affecting individual animals and the population, respectively. Across all farmed species common concerns were inadequate or inappropriate nutrition, inability of stockpeople to recognize or treat welfare issues (such as pain or behavioral problems), lameness, chronic or endemic health issues, euthanasia and mortality and morbidity of neonates. Specific concerns related to behavioral restriction and damaging or abnormal behavior in pigs, poultry and dairy animals, inadequate housing for pigs and poultry, consequences of breeding decisions in pigs and poultry, and lack of access to veterinary care in sheep and beef. This Delphi process resulted in consensus on the most significant welfare challenges faced by UK livestock species and can help to guide future research and education priority decisions.

Crystal structure of a bacterial homolog to human lysosomal transporter, spinster

Lysosomes break down various biomolecules and spinster is one of the major efflux carriers removing degradation products from lysosomal lumen to keep it in healthy size and proper function. Although it is well established that a dysfunctional spinster will cause enlarged lysosomes and in turn lead to developmental defects and abnormal behavior in animals, little was known about the transportation mechanism and substrate specificity of spinster. Here, we report a crystal structure of spinster homolog from Hyphomonas neptunium, HnSPNS, in its inward-facing conformation with and without substrate bound. HnSPNS is crystallized in a monomer and a substrate-binding cavity was formed in the center of its transmembrane helices. A blob of electron density corresponding to its substrate was found in the cavity near a conserved residue, R42, which is locked in position by the interactions with conserved residues E129 and R122. Our results suggest that human spinster serves as a transporter translocating negatively-charged lipophilic small molecules and E129 might serve as a switch to control the conformational change via its protonation-deprotonation cycle.

PINK1 deficiency is associated with increased deficits of adult hippocampal neurogenesis and lowers the threshold for stress-induced depression in mice

Parkinson’s disease (PD) is characterized by motor impairments and several non-motor features, including frequent depression and anxiety. Stress-induced deficits of adult hippocampal neurogenesis (AHN) have been linked with abnormal affective behavior in animals. It has been speculated that AHN defects may contribute to affective symptoms in PD, but this hypothesis remains insufficiently tested in animal models. Mice that lack the PD-linked kinase PINK1 show impaired differentiation of adult-born neurons in the hippocampus. Here, we examined the relationship between AHN deficits and affective behavior in PINK1−/− mice under basal (no stress) conditions and after exposure to chronic stress. PINK1 loss and corticosterone negatively and jointly affected AHN, leading to lower numbers of neural stem cells and newborn neurons in the dentate gyrus of corticosterone-treated PINK1−/− mice. Despite increased basal AHN deficits, PINK1-deficient mice showed normal affective behavior. However, lack of PINK1 sensitized mice to corticosterone-induced behavioral despair in the tail suspension test at a dose where wildtype mice were unaffected. Moreover, after two weeks of chronic restraint stress male PINK1−/− mice displayed increased immobility in the forced swim test, and protein expression of the glucocorticoid receptor in the hippocampus was reduced. Thus, while impaired AHN as such is insufficient to cause affective dysfunction in this PD model, PINK1 deficiency may lower the threshold for chronic stress-induced depression in PD. Finally, PINK1-deficient mice displayed reduced basal voluntary wheel running but normal rotarod performance, a finding whose mechanisms remain to be determined.

Foraging and homing behavior of honey bees (Apis mellifera) during a total solar eclipse.

Exceptional natural phenomena, such as those that occur during a total solar eclipse, provide unique opportunities to study animal behavior outside the naturally evolved context, which can be informative in more general terms. Circumstantial descriptions of abnormal animal behavior during solar eclipses abound, although scientific studies conducted during an eclipse are relatively rare due to inherent logistical difficulties. Here, honey bee foraging and homing behavior were studied during the total solar eclipse of August 21, 2017. In the first experiment, we studied foraging behavior of honey bees during the progression of the solar eclipse and found that the foraging activity drastically decreased but did not completely cease during the totality of the eclipse, in contrast to previous reports of complete cessation. The data indicate that the level of ambient light can largely overrule the internal circadian rhythm of foraging honey bees. Furthermore, colonies with a higher need for foraging decreased their foraging activity less than satiated colonies, consistent with the hypothesis that individual foraging decisions may be influenced by colony state, which affects cost-benefit analyses. In a second experiment, the temporal dynamics of homing of released workers and drones was compared in periods before, during, and after the solar eclipse. During the totality of the eclipse, very few bees arrived back at their hive, while homing before the total eclipse was accelerated, particularly in drones. The results suggest that, while the homing abilities of honey bees are not compromised until the sun is completely eclipsed, they may still interpret the diminishing light as an indicator of deteriorating flight conditions. Our unique study provides some insight into the control of honey bee foraging behavior when external cues and internal circadian rhythms are at odds, lent support to the notion that food deprivation can lead to riskier foraging, and indicated that homing in honey bees is possible even with very small amounts of sunlight.

Safety of Endoscopic-Ultrasound-Guided Portal Injection Chemotherapy using Drug-Eluting Microbeads in a Porcine Model

Background and Aims: Patients with diffuse liver metastases have systemic chemotherapy as their only treatment option. We developed Endoscopic Ultrasound (EUS)-guided portal injection chemotherapy (EPIC) to increase drug levels in hepatic tissue as a novel new liver directed therapy. Methods: Sixteen anesthetized pigs were treated with 50 mg of irinotecan (n=8) or doxorubicin (n=8). Half (n=4) of the animals in each drug group were treated with EPIC-injected microbeads or EUS-guided chemotherapy without beads into the inferior vena cava (control). Animals were observed twice daily for 7 days for signs of clinical toxicities. Tissue samples were harvested for histology and drug levels. Blood counts and chemistries were determined pre-treatment and at 7 days. Results: No toxicities as evidenced by abnormal animal behavior were observed. No significant changes occurred in blood chemistry or blood counts in the irinotecan groups. For doxorubicin, systemic injection significantly decreased albumin, hemoglobin, and white blood cell count (P<.05), with no changes after EPIC. Hepatic histology showed mild foreign body reactions around the beads. No significant histologic changes were seen in other tissue sites. Neither irinotecan nor SN-38 was detectable at 7 days. For doxorubicin, no drug was detected in the plasma or bone marrow. The mean (SD) doxorubicin hepatic levels were non-significantly increased with EPIC vs control (181 [241] vs 151 [67] ng/g). Cardiac doxorubicin levels were significantly lower with EPIC (15 [4] vs 138 [48] ng/g; P=.02). Conclusions: EPIC using drug-eluting microbeads was safe in this animal model. For doxorubicin, EPIC may be safer than systemic injection.

Can animals predict earthquakes?: Bio-sentinels as seismic sensors in communist China and beyond

This paper examines the international research on abnormal animal behavior prior to earthquakes, with a focus on Chinese seismology during the Cultural Revolution. China experienced a series of powerful earthquakes in the 1960s and 1970s; in response, its scientists developed approaches to earthquake prediction, including the use of bio-sentinels. The paper demonstrates that Chinese seismology did not treat an earthquake simply as a geophysical event, but rather as an amalgam of environmental phenomena, including sensory experiences. Hence, distributive experience and sensory networks of humans and bio-sentinels constituted an important component of studying the environment. This historical case suggests insights into bio-monitoring of the global environment.

Review: Can Animals Predict Earthquakes?

Review Article| April 17, 2018 Review: Can Animals Predict Earthquakes? Heiko Woith; Heiko Woith aGFZ German Research Centre for Geosciences, Helmholtzstraße 7, 14467 Potsdam, Germany, heiko.woith@gfz-potsdam.de Search for other works by this author on: GSW Google Scholar Gesa M. Petersen; Gesa M. Petersen aGFZ German Research Centre for Geosciences, Helmholtzstraße 7, 14467 Potsdam, Germany, heiko.woith@gfz-potsdam.debAlso at Institute of Earth and Environmental Sciences, University of Potsdam, Golm, Germany. Search for other works by this author on: GSW Google Scholar Sebastian Hainzl; Sebastian Hainzl aGFZ German Research Centre for Geosciences, Helmholtzstraße 7, 14467 Potsdam, Germany, heiko.woith@gfz-potsdam.de Search for other works by this author on: GSW Google Scholar Torsten Dahm Torsten Dahm aGFZ German Research Centre for Geosciences, Helmholtzstraße 7, 14467 Potsdam, Germany, heiko.woith@gfz-potsdam.debAlso at Institute of Earth and Environmental Sciences, University of Potsdam, Golm, Germany. Search for other works by this author on: GSW Google Scholar Bulletin of the Seismological Society of America (2018) 108 (3A): 1031–1045. https://doi.org/10.1785/0120170313 Article history first online: 17 Apr 2018 Cite View This Citation Add to Citation Manager Share Icon Share Facebook Twitter LinkedIn MailTo Tools Icon Tools Get Permissions Search Site Citation Heiko Woith, Gesa M. Petersen, Sebastian Hainzl, Torsten Dahm; Review: Can Animals Predict Earthquakes?. Bulletin of the Seismological Society of America 2018;; 108 (3A): 1031–1045. doi: https://doi.org/10.1785/0120170313 Download citation file: Ris (Zotero) Refmanager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentBy SocietyBulletin of the Seismological Society of America Search Advanced Search Abstract In public perception, abnormal animal behavior is widely assumed to be a potential earthquake precursor, in strong contrast to the viewpoint in natural sciences. Proponents of earthquake prediction via animals claim that animals feel and react abnormally to small changes in environmental and physico‐chemical parameters related to the earthquake preparation process. In seismology, however, observational evidence for changes of physical parameters before earthquakes is very weak.In this study, we reviewed 180 publications regarding abnormal animal behavior before earthquakes and analyze and discuss them with respect to (1) magnitude–distance relations, (2) foreshock activity, and (3) the quality and length of the published observations. More than 700 records of claimed animal precursors related to 160 earthquakes are reviewed with unusual behavior of more than 130 species. The precursor time ranges from months to seconds prior to the earthquakes, and the distances from a few to hundreds of kilometers. However, only 14 time series were published, whereas all other records are single observations. The time series are often short (the longest is 1 yr), or only small excerpts of the full data set are shown. The probability density of foreshocks and the occurrence of animal precursors are strikingly similar, suggesting that at least parts of the reported animal precursors are in fact related to foreshocks. Another major difficulty for a systematic and statistical analysis is the high diversity of data, which are often only anecdotal and retrospective. The study clearly demonstrates strong weaknesses or even deficits in many of the published reports on possible abnormal animal behavior. To improve the research on precursors, we suggest a scheme of yes and no questions to be assessed to ensure the quality of such claims. You do not have access to this content, please speak to your institutional administrator if you feel you should have access.

IN0523 (Urs-12-ene-3α,24β-diol) a plant based derivative of boswellic acid protect Cisplatin induced urogenital toxicity

The limiting factor for the use of Cisplatin in the treatment of different type of cancers is its toxicity and more specifically urogenital toxicity. Oxidative stress is a well-known phenomenon associated with Cisplatin toxicity. However, in Cisplatin treated group, abnormal animal behavior, decreased body weight, cellular and sub-cellular changes in the kidney and sperm abnormality were observed. Our investigation revealed that Cisplatin when administered in combination with a natural product derivative (Urs-12-ene-3α,24β-diol, labeled as IN0523) resulted in significant restoration of body weight and protection against the pathological alteration caused by Cisplatin to kidney and testis. Sperm count and motility were significantly restored near to normal. Cisplatin caused depletion of defense system i.e. glutathione peroxidase, catalase and superoxide dismutase, which were restored close to normal by treatment of IN0523. Reduction in excessive lipid peroxidation induced by Cisplatin was also found by treatment with IN0523. The result suggests that IN0523 is a potential candidate for ameliorating Cisplatin induced toxicity in the kidney and testes at a dose of 100mg/kg p.o. via inhibiting the oxidative stress/redox status imbalance and may be improving the efflux mechanism.

Influence of feed type and its effect on repressing wool-biting behavior in housed sheep.

Sheep sometimes develop an abnormal behavior termed as wool-biting when kept in an indoor system; however, little is known about this behavior. As the provided feed type may affect the foraging behavior and repress abnormal behavior in animals, we tested the effect of feed type on repressing wool-biting behavior in this study. We used hay prepared in three forms, that is hay bales, rolls and cubes. The wool-biting frequency associated with hay bales was significantly higher than that associated with rolls (P < 0.05) and cubes (P < 0.05); however, there was no significant difference between rolls and cubes. For hay rolls, wool-biting significantly decreased after feeding (P < 0.05), suggesting that rolls may provide sheep with appropriate oral stimulation; thus, decreasing the post-feeding oral abnormal behavior. An individual difference of wool-biting behavior between sheep was also detected, and an unexpected bed-eating behavior was found in the hay cube treatment. We suggest that sheep performing movements that are similar to their natural foraging behavior while grazing would repress wool-biting behavior, which happened in hay roll and hay cube treatments. Considering sanitation and animal welfare, providing sheep with hay rolls may provide an easier method to control wool-biting behavior in housed sheep.

A Study on the Correlation of Milk Yield of Cows with Seismicity and ULF Magnetic Field Variations

A statistical study on the basis of one-year data of 2014 has been performed in order to find whether abnormal animal behavior is related with seismic activity and also whether the ULF (Ultra Low Frequency) electromagnetic radiation might be a possible sensory mechanism of abnormal animal behavior. Abnormal animal behavior has been studied with the use of digitally recorded milk yield of cows at Ibaraki Prefecture Livestock Station, and the ULF magnetic field changes have been studied with the data at a magnetic observatory of Kakioka. As the result of correlation analyses, clear responses are observed for both the milk yield of cows and ULF magnetic field changes (both ULF radiation (ULF emissions from the lithosphere) and ULF depression (as an indicator of lower ionospheric perturbations)) for most powerful and not distant earthquakes (EQs) with magnitude > 6, that is, the milk yield of cows is found to exhibit a conspicuous depletion about 17 - 18 days before an EQ, though the correlation coefficient is not so big. Another important objective in this paper is to identify that ULF radiation is the main agent of abnormal behavior so that we have compared the temporal evolutions of milk yield of cows, ULF radiation and ULF depression for three major EQs. As a result, it is found that ULF radiation happens, at least, during the periods of abnormal depletion of milk yield of cows.

On the Precursory Abnormal Animal Behavior and Electromagnetic Effects for the Kobe Earthquake (M~6) on April 12, 2013

After the 2011 Tohoku earthquake (EQ), there have been numerous aftershocks in the eastern and Pacific Ocean of Japan, but EQs are still rare in the western part of Japan. In this situation a relatively large (magnitude (M) ~6) EQ happened on April 12 (UT), 2013 at a place close to the former 1995 Kobe EQ (M~7), so we have tried to find whether there existed any precursors to this EQ, especially abnormal animal behavior (milk yield of cows), observed at Kagawa, Shikoku, near the EQ epicenter. The milk yield of cows has been continuously monitored at Kagawa, and it is found that the milk yield exhibited an abnormal depletion about 10 days before the EQ. This behavior has been extensively compared with the former electromagnetic precursors (ULF radiation, ionos-pheric perturbation). This leads to the discussion on the sensory mechanism of unusual behavior of mild yield of cows, and it may be suggested that ULF radiation among different electromagnetic precursors is a mostly likely driver, at least, for this EQ.

Is It Possible to Predict Strong Earthquakes?

The possibility of earthquake prediction is one of the key open questions in modern geophysics. We propose an approach based on the analysis of common short-term candidate precursors (2 weeks to 3 months prior to strong earthquake) with the subsequent processing of brain activity signals generated in specific types of rats (kept in laboratory settings) who reportedly sense an impending earthquake few days prior to the event. We illustrate the identification of short-term precursors using the groundwater sodium-ion concentration data in the time frame from 2010 to 2014 (a major earthquake occurred on February 28, 2013), recorded at two different sites in the south-eastern part of the Kamchatka peninsula, Russia. The candidate precursors are observed as synchronized peaks in the nonstationarity factors, introduced within the flicker-noise spectroscopy framework for signal processing, for the high-frequency component of both time series. These peaks correspond to the local reorganizations of the underlying geophysical system that are believed to precede strong earthquakes. The rodent brain activity signals are selected as potential "immediate" (up to 2 weeks) deterministic precursors due to the recent scientific reports confirming that rodents sense imminent earthquakes and the population-genetic model of Kirshvink (2000) showing how a reliable genetic seismic escape response system may have developed over the period of several hundred million years in certain animals. The use of brain activity signals, such as electroencephalograms, in contrast to conventional abnormal animal behavior observations, enables one to apply the standard "input-sensor-response" approach to determine what input signals trigger specific seismic escape brain activity responses