Advances in our understanding of the mechanisms that bring about the resolution of acute inflammation have uncovered a new genus of pro-resolving lipid mediators that include the lipoxin, resolvin, protectin and maresin families, collectively called specialized pro-resolving mediators. Synthetic versions of these mediators have potent bioactions when administered in vivo. In animal experiments, the mediators evoke anti-inflammatory and novel pro-resolving mechanisms, and enhance microbial clearance. Although they have been identified in inflammation resolution, specialized pro-resolving mediators are conserved structures that also function in host defence, pain, organ protection and tissue remodelling. This Review covers the mechanisms of specialized pro-resolving mediators and omega-3 essential fatty acid pathways that could help us to understand their physiological functions.

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Pro-resolving lipid mediators are leads for resolution physiology

ION, GENERAL CONCEPTIONS, SELF-CONSCIOUSNESS, MENTAL INDIVIDUALITY. It would be very difficult for any one with even much more knowledge than I possess, to determine how far animals exhibit any traces of these high mental powers. This difficulty arises from the impossibility of judging what passes through the mind of an animal; and again, the fact that writers differ to a great extent in the meaning which they attribute to the above terms, causes a further difficulty. If one may judge from various articles which have been published lately, the greatest stress seems to be laid on the supposed entire absence in animals of the power of abstraction, or of forming general concepts. But when a dog sees another dog at a distance, it is often clear that he perceives that it is a dog in the abstract; for when he gets nearer his whole manner suddenly changes, if the other dog be a friend. A recent writer remarks, that in all such cases it is a pure assumption to assert that the mental act is not essentially of the same nature in the animal as in man. If either refers what he perceives with his senses to a mental concept, then so do both. (44. Mr. Hookham, in a letter to Prof. Max Muller, in the 'Birmingham News,' May, 1873.) When I say to my terrier, in an eager voice (and I have made the trial many times), "Hi, hi, where is it?" she at once takes it as a sign that something is to be hunted, and generally first looks quickly all around, and then rushes into the nearest thicket, to scent for any game, but finding nothing, she looks up into any neighbouring tree for a squirrel. Now do not these actions clearly shew that she had in her mind a general idea or concept that some animal is to be discovered and hunted? It may be freely admitted that no animal is self-conscious, if by this term it is implied, that he reflects on such points, as whence he comes or whither he will go, or what is life and death, and so forth. But how can we feel sure that an old dog with an excellent memory and some power of imagination, as shewn by his dreams, never reflects on his past pleasures or pains in the chase? And this would be a form of self-consciousness. On the other hand, as Buchner (45. 'Conferences sur la Theorie Darwinienne,' French translat. 1869, p. 132.) has remarked, how little can the hardworked wife of a degraded Australian savage, who uses very few abstract words, and cannot count above four, exert her self-consciousness, or reflect on the nature of her own existence. It is generally admitted, that the higher animals possess memory, attention, association, and even some imagination and reason. If these powers, which differ much in different animals, are capable of improvement, there seems no great improbability in more complex faculties, such as the higher forms of abstraction, and selfconsciousness, etc., having been evolved through the development and combination of the simpler ones. It has been urged against the views here maintained that it is impossible to say at what point in the ascending scale animals become capable of abstraction, etc.; but who can say at what age this occurs in our young children? We see at least that such powers

https://www.jstage.jst.go.jp/article/ase1887/22/257/22_257_458/_pdf

The descent of man and selection in relation to sex

Short protocols in molecular biology

Caspases are proteases with a well-defined role in apoptosis. However, increasing evidence indicates multiple functions of caspases outside apoptosis. Caspase-1 and caspase-11 have roles in inflammation and mediating inflammatory cell death by pyroptosis. Similarly, caspase-8 has dual role in cell death, mediating both receptor-mediated apoptosis and in its absence, necroptosis. Caspase-8 also functions in maintenance and homeostasis of the adult T-cell population. Caspase-3 has important roles in tissue differentiation, regeneration and neural development in ways that are distinct and do not involve any apoptotic activity. Several other caspases have demonstrated anti-tumor roles. Notable among them are caspase-2, -8 and -14. However, increased caspase-2 and -8 expression in certain types of tumor has also been linked to promoting tumorigenesis. Increased levels of caspase-3 in tumor cells causes apoptosis and secretion of paracrine factors that promotes compensatory proliferation in surrounding normal tissues, tumor cell repopulation and presents a barrier for effective therapeutic strategies. Besides this caspase-2 has emerged as a unique caspase with potential roles in maintaining genomic stability, metabolism, autophagy and aging. The present review focuses on some of these less studied and emerging functions of mammalian caspases.

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Old, new and emerging functions of caspases.

Until recently, the Y chromosome seemed to fulfil the role of juvenile delinquent among human chromosomes — rich in junk, poor in useful attributes, reluctant to socialize with its neighbours and with an inescapable tendency to degenerate. The availability of the near-complete chromosome sequence, plus many new polymorphisms, a highly resolved phylogeny and insights into its mutation processes, now provide new avenues for investigating human evolution. Y-chromosome research is growing up.

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The human Y chromosome: an evolutionary marker comes of age

Male infertility represents one of the clearest examples of a complex disease with a substantial genetic basis. Numerous male mouse models, mutation screening and association studies reported over the last few years reveal the high prevalence of genetic causes of spermatogenic impairment, accounting for 10-15% of severe male infertility, including chromosomal aberrations and single gene mutations. Natural selection prevents the transmission of mutations causing infertility, but this protective mechanism may be overcome by assisted reproduction techniques. Consequently, the identification of genetic factors is important for appropriate management of the infertile couple. However, a large proportion of infertile males are diagnosed as idiopathic, reflecting poor understanding of the basic mechanisms regulating spermatogenesis and sperm function. Furthermore, the molecular mechanisms underlying spermatogenic damage in cases of genetic infertility (for example Yq microdeletions) are not known. These problems can be addressed only by large scale association studies and testicular or spermatozoal expression studies in well-defined alterations of spermatogenesis. It is conceivable that these studies will have important diagnostic and therapeutic implications in the future. This review discusses the genetic causes of male infertility known to date, the genetic polymorphisms possibly associated with male infertility, and reports novel results of global gene expression profiling of normal human testis by microarray technology.

https://www.rbmojournal.com/article/S1472-6483(10)60677-3/pdf

Male infertility: role of genetic background

Multiplex Ligation-dependent Probe Amplification (MLPA) assay is a recently developed technique able to evidence variations in the copy number of several human genes. Due to this ability, MLPA can be used in the molecular diagnosis of several genetic diseases whose pathogenesis is related to the presence of deletions or duplications of specific genes. Moreover, MLPA assay can also be used in the molecular diagnosis of genetic diseases characterized by the presence of abnormal DNA methylation. Due to the large number of genes that can be analyzed by a single technique, MLPA assay represents the gold standard for molecular analysis of all pathologies derived from the presence of gene copy number variation. In this review, the main applications of the MLPA technique for the molecular diagnosis of human diseases are described.

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Use of the MLPA Assay in the Molecular Diagnosis of Gene Copy Number Alterations in Human Genetic Diseases

Valproic acid (VPA), an established antiepileptic and antimanic drug, has recently emerged as a promising neuroprotective agent. Among its many cellular targets, VPA has been recently demonstrated to be an effective inhibitor of histone deacetylases. Accordingly, we have adopted a schedule of dietary administration (2% VPA added to the chow) that results in a significant inhibition of histone deacetylase activity and in an increase of histone H3 acetylation in brain tissues of 4 weeks-treated rats. We have tested this schedule of VPA treatment in an animal model of Parkinson’s disease (PD), in which degeneration of nigro-striatal dopaminergic neurons is obtained through sub-chronic administration of the mitochondrial toxin, rotenone, via osmotic mini pumps implanted to rats. The decrease of the dopaminergic marker tyrosine hydroxylase in substantia nigra and striatum caused by 7 days toxin administration was prevented in VPA-fed rats. VPA treatment also significantly counteracted the death of nigral neurons and the 50% drop of striatal dopamine levels caused by rotenone administration. The PD-marker protein α-synuclein decreased, in its native form, in substantia nigra and striatum of rotenone-treated rats, while monoubiquitinated α-synuclein increased in the same regions. VPA treatment counteracted both these α-synuclein alterations. Furthermore, monoubiquitinated α-synuclein increased its localization in nuclei isolated from substantia nigra of rotenone-treated rats, an effect also prevented by VPA treatment. Nuclear localization of α-synuclein has been recently described in some models of PD and its neurodegenerative effect has been ascribed to histone acetylation inhibition. Thus, the ability of VPA to increase histone acetylation is a novel candidate mechanism for its neuroprotective action.

Valproic acid is neuroprotective in the rotenone rat model of Parkinson's disease: involvement of alpha-synuclein.

The correlation between epigenetics and human reproduction represents a very interesting field of study, mainly due to the possible transgenerational effects related to epigenetic modifications of male and female gametes. In the present review, we focused our attention to the role played by epigenetics on male reproduction, evidencing at least four different levels at which sperm epigenetic modifications could affect reproduction: (1) spermatogenesis failure; (2) embryo development; (3) outcome of assisted reproduction technique (ART) protocols, mainly as concerning genomic imprinting; and (4) long-term effects during the offspring lifetime. The environmental agents responsible for epigenetic modifications are also examined, suggesting that the control of paternal lifestyle prior to conception could represent in the next future a novel hot topic in the management of human reproduction.

/pdf/epigenetics-and-male-reproduction-the-consequences-of-5dwmgrueww.pdf

Epigenetics and male reproduction: the consequences of paternal lifestyle on fertility, embryo development, and children lifetime health

Naturally occurring antioxidants are extensively studied for their capacity to protect organisms and cells from damage induced by oxygen reactive species. In fact, oxidative stress is considered a cause of aging, degenerative disease and cancer. We have focused our attention on two agents, ascorbic acid and β-carotene, commonly considered to be antioxidants, but whose protective activity against cancer is insufficiently known. This paper reports on the ability of these agents to act against damage induced by H 2 O 2 and bleomycin, in Chinese hamster ovary cells cultivated in vitro. Cytogenetic and cytofluorimetric analyses were performed. Both vitamins proved effective in reducing H 2 O 2 .induced sister chromatid exchanges, but increased H 2 O 2 . and bleomycin-induced chromosomal aberrations. Cytofluorimetric data, in contrast, showed that ascorbic acid and β-carotene act as scavengers of endogeneous and H 2 O 2 -induced oxygen species.

https://www.nanotechnologystore.com/(10)Ascorbic-acid-and-B-carotene-as-modulators-of-oxidative-damage-1.pdf

Valentina Gatta

Papers

Male infertility: role of genetic background

Use of the MLPA Assay in the Molecular Diagnosis of Gene Copy Number Alterations in Human Genetic Diseases

Valproic acid is neuroprotective in the rotenone rat model of Parkinson's disease: involvement of alpha-synuclein.

Epigenetics and male reproduction: the consequences of paternal lifestyle on fertility, embryo development, and children lifetime health

Ascorbic acid and beta-carotene as modulators of oxidative damage.