Abnormal Prothrombin (PIVKA-II) Expression in Canine Tissues as an Indicator of Anticoagulant Poisoning

PIVKA-II is an aberrant form of vitamin K that has been demonstrated to be increased in human coagulation disorders and in some neoplastic diseases. In veterinary medicine, PIVKA-II levels have been demonstrated to be useful for distinguishing anticoagulant poisoning from other coagulopathies. In forensic pathology, there is the need to distinguish malicious poisoning from other causes of death and, in some cases, identifying poisoned dogs from dogs that died as a result of other coagulative disorders can be challenging. In this study, dogs that suddenly died underwent necropsy, histological examination, and toxicological analysis to establish cause of death. PIVKA-II immunohistochemical expression was evaluated on hepatic and renal tissues, and on neoplastic lesions when present. A total of 61 dogs were analyzed and anticoagulant substances were identified in 16 of the 61. Immunolabelling for PIVKA-II was observed in 27 of 61 cases in the liver and in 24 of 61 cases in the kidneys. Among the poisoned dogs, the PIVKA-II expression was present in the liver in 15 of 16 cases and in the kidneys in 16 of 16. Neoplastic lesions represented mainly by haemangiosarcomas were negative. This study highlights how the immunohistochemical expression of PIVKA-II in hepatic and renal tissues can be useful to identify patients with coagulative disorders due to clinical condition or the ingestion of anticoagulants substances.

Early life trauma leads to violent behavior and its inheritance by impairing local thyroid hormone availability in brain

Violent behavior is an aberrant form of aggression that has detrimental impact on health and society. Early life trauma triggers adulthood violence and criminality, though molecular mechanisms remain elusive. Here, we provide brain region specific transcriptome profiles of peripubertal stress (PPS) exposed adult violent male and resilient female mice. We identify transthyretin (TTR) as a key regulator of PPS induced violent behavior and its intergenerational inheritance. TTR mediated long-term perturbation in hypothalamic thyroid hormone (TH) availability contributed to male violent behavior without affecting circulating hormone. Ttr gene ablation in hypothalamus impaired local TH signaling including levels of TH transporters (Mct8, Oatp1c1), deiodinase 2 (DIO2) and TH responsive genes (Nrgn, Trh and Hr). Violent behavior and impaired TTR-TH signaling was also inherited in F1 male progenies. Further, we deciphered Ttr promoter hyper methylation in hypothalamus of violent males across generations. Our findings reveal that trauma during puberty trigger lasting violent behavior by epigenetic programming of TTR and consequent impaired local thyroid availability in brain. TTR-TH signaling in hypothalamus can serve as potential target in reversal of violent behavior.

Enquiry and Normative Deviance

It is argued that science denialism brings about an aberrant form of enquiry that deviates in significant ways from the epistemic norms governing scientific enquiry. Science denialism doesn’t involve just a rejection of a scientific theory; it also challenges the practice of continuously and impartially testing research methods, theories, and evidential sources with the aim of improving the accuracy of our theories. This chapter provides an in-depth analysis of the epistemic mechanisms at work. It develops a fine-grained framework to model a variety of normative deviances that may take place in enquiry. Through analysing two case studies, it is argued that fake news plays two pivotal roles in shaping epistemic norms operating within science denialism. First, it discredits a variety of (institutional) sources of evidence; second, it also plays a part in building the alternative explanation of the target phenomena.

Celia’s Encephalopathy (BSCL2-Gene-Related): Current Understanding

Seipin, encoded by the BSCL2 gene, is a protein that in humans is expressed mainly in the central nervous system. Uniquely, certain variants in BSCL2 can cause both generalized congenital lipodystrophy type 2, upper and/or lower motor neuron diseases, or progressive encephalopathy, with a poor prognosis during childhood. The latter, Celia’s encephalopathy, which may or may not be associated with generalized lipodystrophy, is caused by the c.985C >T variant. This cytosine to thymine transition creates a cryptic splicing zone that leads to intronization of exon 7, resulting in an aberrant form of seipin, Celia seipin. It has been proposed that the accumulation of this protein, both in the endoplasmic reticulum and in the nucleus of neurons, might be the pathogenetic mechanism of this neurodegenerative condition. In recent years, other variants in BSCL2 associated with generalized lipodystrophy and progressive epileptic encephalopathy have been reported. Interestingly, most of these variants could also lead to the loss of exon 7. In this review, we analyzed the molecular bases of Celia’s encephalopathy and its pathogenic mechanisms, the clinical features of the different variants, and a therapeutic approach in order to slow down the progression of this fatal neurological disorder.

α-Synuclein oligomers mediate the aberrant form of spike-induced calcium release from IP3 receptor

Emerging evidence implicates α-synuclein oligomers as potential culprits in the pathogenesis of Lewy body disease (LBD). Soluble oligomeric α-synuclein accumulation in cytoplasm is believed to modify neuronal activities and intraneural Ca2+ dynamics, which augment the metabolic burden in central neurons vulnerable to LBD, although this hypothesis remains to be fully tested. We evaluated how intracellular α-synuclein oligomers affect the neuronal excitabilities and Ca2+ dynamics of pyramidal neurons in neocortical slices from mice. Intracellular application of α-synuclein containing stable higher-order oligomers (αSNo) significantly reduced spike frequency during current injection, elongated the duration of spike afterhyperpolarization (AHP), and enlarged AHP current charge in comparison with that of α-synuclein without higher-order oligomers. This αSNo-mediated alteration was triggered by spike-induced Ca2+ release from inositol trisphosphate receptors (IP3R) functionally coupled with L-type Ca2+ channels and SK-type K+ channels. Further electrophysiological and immunochemical observations revealed that α-synuclein oligomers greater than 100 kDa were directly associated with calcium-binding protein 1, which is responsible for regulating IP3R gating. They also block Ca2+-dependent inactivation of IP3R, and trigger Ca2+-induced Ca2+ release from IP3R during multiple spikes. This aberrant machinery may result in intraneural Ca2+ dyshomeostasis and may be the molecular basis for the vulnerability of neurons in LBD brains.

A new species of black fly with a yellow thorax in the genus Prosimulium (Diptera: Simuliidae) in Japan

A new species of black fly, Prosimulium kazukii, is described based on female, male and pupal specimens collected from central Honshu, Japan. It is placed in the Prosimulium magnum species-group, and is characterized in the female and male by yellow thoraces, and in the pupa by the frons and dorsal surface of the thorax without distinct tubercles. By these characters, it is distinguished from all four related species (P. apoina Ono, P. kalibaense Ono, P. sarurense Ono, and P. yezoense Shiraki) of the same species-group in Japan. The female of this new species was previously known as an aberrant form of P. yezoense.

Nevada’s Regulated Brothels

This chapter examines how brothels are regulated in Nevada. More specifically, it looks at how local municipalities in Nevada—the only US state that has legalized prostitution—regulate prostitution markets. It begins with an overview of Nevada’s legal indoor prostitution, the history and development of legal brothels, and brothel laws and regulations. It then considers how sex workers in Nevada brothels are regulated, the present state of brothel organization and market, and rural and suburban brothels. It also discusses how the legal system functions to regulate worker health and safety in Nevada brothels. The chapter argues that Nevada’s brothels are not some aberrant form of organized deviance but rather are part and parcel of today’s neoliberal consumer economy. The political climate that has allowed and sustains legal brothels in Nevada reflects contemporary neoliberal politics and a “morality” in which personal consumer choice is elevated to a moral right.

Description of the family Padaungiellidae and morphological variability of Padaungiella lageniformis (Amoebozoides: Arcellinida) from the Vlasina Lake area, Serbia

Based on theoretical conclusions, a new family of testate amoebae, Padaungiellidae, is described. It includes three genera: Alocodera, Apodera and Padaungiella. The most striking characteristic of the members of this family is an elongated neck, and absence of sets of teeth and septa along the oral-aboral axis on the inner side of the neck. The most common species of this family is Padaungiella lageniformis. Morphometrically, this species is not analyzed yet, so the qualitative and quantitative characters of a sphagnicolous population of P. lageniformis from the Vlasina Lake area (Serbia) are reported here. Quantitative characters were analyzed by univariate statistical methods. Coefficients of variation were moderately low for all the measured characters (range from 4.37 to 10.71%). Frequency distribution of only seven of sixteen variables showed approximately zero level of kurtosis, which indicated that specimens with average measurements were not predominant in the studied population. This paper provides evidence of the presence of an aberrant form of P. lageniformis.