Singing humpback whales respond to wind noise, but not to vessel noise.

Animal communication systems evolved in the presence of noise generated by natural sources. Many species can increase the source levels of their sounds to maintain effective communication in elevated noise conditions, i.e. they have a Lombard response. Human activities generate additional noise in the environment creating further challenges for these animals. Male humpback whales are known to adjust the source levels of their songs in response to wind noise, which although variable is always present in the ocean. Our study investigated whether this Lombard response increases when singing males are exposed to additional noise generated by motor vessels. Humpback whale singers were recorded off eastern Australia using a fixed hydrophone array. The source levels of the songs produced while the singers were exposed to varying levels of wind noise and vessel noise were measured. Our results show that, even when vessel noise is dominant, singing males still adjust the source levels of their songs to compensate for the underlying wind noise, and do not further increase their source levels to compensate for the additional noise produced by the vessel. Understanding humpback whales' response to noise is important for developing mitigation policies for anthropogenic activities at sea.

Cyanotoxin Analysis and Amino Acid Profiles of Cyanobacterial Food Items from Chad.

In some parts of the world, cyanobacteria are used as a food in the human diet, due to their ready availability. Lake Chad, has long been a traditional site for the collection of Arthrospira fusiformis which is dried and processed at the lake into thin wafers called Dihé for later consumption or is transported to market for sale. However, Dihé purchased from markets in Chad has not been analyzed for known cyanobacterial toxins or assessed for total amino acid content. Since BMAA in traditional foodstuffs of the indigenous Chamorro people of Guam causes neurodegenerative illness, it is important that Dihé from Chad be analyzed for this neurotoxin. BMAA and its isomer AEG were not detected in our analyses, but a further isomer DAB was detected as both a free and bound amino acid, with an increase in the free concentration after acid hydrolysis of this fraction. Microcystins were present in 6 samples at up to 20 µg/g according to UPLC-PDA, although their presence could not be confirmed using PCR for known microcystin synthetic genes. Amino acid analysis of the cyanobacterial material from Chad showed the presence of large amounts of canonical amino acids, suggesting that this may supplement indigenous people on low protein diets, although regular monitoring of the foodstuffs for the presence of cyanotoxins should be performed.

The influence of physiological status on the reproductive behaviour of humpback whales (Megaptera novaeangliae).

For most cetacean species, there is little known about how an individual's physiology influences its behaviour. Humpback whales (Megaptera novaeangliae) are a good candidate to examine such links as they have a well-described distribution and behaviour, can be consistently sampled using remote biopsy systems, and have been the subject of several previous endocrine studies. The objective here was to examine whether a female humpback whale's social state (i.e. escorted by a male or not) is related to her endocrine condition, and whether male dominance ranking is related to testosterone levels. Skin and blubber biopsies were collected from the east and west Australian humpback whale populations in 2010-2016 (n = 252) at multiple times throughout the winter-spring breeding season. Steroid hormones were extracted from blubber and concentrations of progesterone (a marker for pregnancy), testosterone (a marker of male testicular activity) and oestradiol (a potential marker of ovarian activity) measured using enzyme-immunoassays. Principal escorts-the dominant males in mixed sex groups-had significantly higher blubber testosterone levels (mean ±â€¯SE; 1.43 ±â€¯0.20 ng/g wet weight) than subordinate, secondary escorts (0.69 ±â€¯0.06 ng/g wet weight). Females that were escorted by males typically possessed elevated blubber oestradiol levels (1.96 ±â€¯0.25 ng/g wet weight; p = 0.014); few were considered to be pregnant (p = 0.083). 'Unescorted' females displayed characteristically lower blubber oestradiol levels (0.56 ±â€¯0.06 ng/g wet weight). Together, these results are consistent with 'challenge hypothesis' theory and suggest the existence of associated reproductive patterns in humpback whales.

Evaluation of respiratory vapour and blubber samples for use in endocrine assessments of bottlenose dolphins (Tursiops spp.).

Blubber and respiratory vapour ('blow') are now commonly used for endocrine studies on cetaceans, primarily because they can be obtained using minimally invasive methods. For many species, these samples have yet to be validated for these purposes. The objective of this study was to examine the performance of blow and blubber hormone monitoring, relative to serum hormone monitoring, for evaluating the reproductive and adrenal condition of captive bottlenose dolphins (Tursiops spp.). Eighteen bottlenose dolphins were sampled five times for serum and blow and twice for blubber throughout a one-year period. Concentrations of progesterone, testosterone, oestradiol and cortisol were measured in each sample type. Hormone levels were examined in relation to dolphin age, sex, reproductive status, season, time of sample collection (morning/afternoon) and collection type (in- or out-of-water sampling). Patterns in hormone levels were similar for serum and blubber. For instance, in both sample types, progesterone levels were significantly higher in pregnant (serum: 34.10 ±â€¯8.64 ng/mL; blubber: 13.01 ±â€¯0.72 ng/g) than in non-pregnant females (serum: 0.32 ±â€¯0.09 ng/mL; blubber: 1.17 ±â€¯0.10 ng/g). This pattern was not detected in blow, primarily because seawater contamination, nylon sampling materials and variable sample volumes influenced measured concentrations. In addition, the respiratory water content of a blow sample is known to affect measured hormone levels. Two methods were trialled to control for variability in sample volumes and dilution: (1) normalising blow hormone concentrations relative to urea nitrogen levels (a potential endogenous standard), and (2) measuring the relative proportions (i.e. ratios) of blow hormones. These correction measures had little influence on blow hormone results. Further refinement of blow hormone monitoring methods is required before they can be used for reproductive or adrenal assessments of bottlenose dolphins. Blubber, on the other hand, should be a suitable proxy for serum when attempting to classify pregnancy status and male maturity in these species.

L-Serine: a Naturally-Occurring Amino Acid with Therapeutic Potential.

In human neuroblastoma cell cultures, non-human primates and human beings, L-serine is neuroprotective, acting through a variety of biochemical and molecular mechanisms. Although L-serine is generally classified as a non-essential amino acid, it is probably more appropriate to term it as a "conditional non-essential amino acid" since, under certain circumstances, vertebrates cannot synthesize it in sufficient quantities to meet necessary cellular demands. L-serine is biosynthesized in the mammalian central nervous system from 3-phosphoglycerate and serves as a precursor for the synthesis of the amino acids glycine and cysteine. Physiologically, it has a variety of roles, perhaps most importantly as a phosphorylation site in proteins. Mutations in the metabolic enzymes that synthesize L-serine have been implicated in various human diseases. Dosing of animals with L-serine and human clinical trials investigating the therapeutic effects of L-serine support the FDA's determination that L-serine is generally regarded as safe (GRAS); it also appears to be neuroprotective. We here consider the role of L-serine in neurological disorders and its potential as a therapeutic agent.

Mechanisms of L-Serine Neuroprotection in vitro Include ER Proteostasis Regulation.

ß-N-methylamino-L-alanine (L-BMAA) is a neurotoxic non-protein amino acid produced by cyanobacteria. Recently, chronic dietary exposure to L-BMAA was shown to trigger neuropathology in nonhuman primates consistent with Guamanian ALS/PDC, a paralytic disease that afflicts Chamorro villagers who consume traditional food items contaminated with L-BMAA. However, the addition of the naturally occurring amino acid L-serine to the diet of the nonhuman primates resulted in a significant reduction in ALS/PDC neuropathology. L-serine is a dietary amino acid that plays a crucial role in central nervous system development, neuronal signaling, and synaptic plasticity and has been shown to impart neuroprotection from L-BMAA-induced neurotoxicity both in vitro and in vivo. We have previously shown that L-serine prevents the formation of autofluorescent aggregates and death by apoptosis in human cell lines and primary cells. These effects are likely imparted by L-serine blocking incorporation of L-BMAA into proteins hence preventing proteotoxic stress. However, there are likely other mechanisms for L-serine-mediated neuroprotection. Here, we explore the molecular mechanisms of L-serine neuroprotection using a human unfolded protein response real-time PCR array with genes from the ER stress and UPR pathways, and western blotting. We report that L-serine caused the differential expression of many of the same genes as L-BMAA, even though concentrations of L-serine in the culture medium were ten times lower than that of L-BMAA. We propose that L-serine may be functioning as a small proteostasis regulator, in effect altering the cells to quickly respond to a possible oxidative insult, thus favoring a return to homeostasis.

L-Serine-Mediated Neuroprotection Includes the Upregulation of the ER Stress Chaperone Protein Disulfide Isomerase (PDI).

The unfolded protein response (UPR) is a highly evolutionarily conserved response to endoplasmic reticulum (ER) stress, which functions to return cells to homeostasis or send them into apoptosis, depending on the degree of cellular damage. ß-N-methylamino-L-alanine (L-BMAA) has been shown to induce ER stress in a variety of models and has been linked to several types of neurodegenerative disease including Guamanian amyotrophic lateral sclerosis/Parkinsonism dementia complex (ALS/PDC). L-Serine, an amino acid critical for cellular metabolism and neurological signaling, has been shown to be protective against L-BMAA-induced neurotoxicity in both animal and cell culture models. While the mechanisms of L-BMAA neurotoxicity have been well characterized, less is known about L-serine neuroprotection. We recently reported that L-serine and L-BMAA generate similar differential expression profiles in a human ER stress/UPR array, despite L-serine being neuroprotective and L-BMAA being linked to neurodegenerative disease. Here, we further investigate the mechanism(s) of L-serine-induced UPR dysregulation by examining key genes and proteins in the ER stress/UPR pathways. We report that L-serine selectively increased protein disulfide isomerase (PDI) protein translation, an ER chaperone involved in refolding misfolded proteins, suggesting it may be modulating the UPR to favor recovery from ER stress. This constitutes a new mechanism for L-serine-mediated neuroprotection and has implications for its use as a therapy for neurodegenerative illnesses.

Kavalactones Yangonin and Methysticin induce apoptosis in human hepatocytes (HepG2) in vitro.

While cases of severe kava hepatotoxicity have been reported, studies examining the toxicity of individual kavalactones are limited. The present study examined the in vitro hepatotoxicity of kavain, methysticin and yangonin on human hepatocytes (HepG2) and the possible mechanism(s) involved. Cytotoxicity was assessed using lactate dehydrogenase (LDH) and ethidium bromide (EB) assays. The mode of cell death was analysed with acridine orange/ethidium bromide dual staining with fluorescence microscopy. Glutathione oxidation was measured using the ortho-phthalaldehyde (OPT) fluorescence assay. Kavain had minimal cytotoxicity, methysticin showed moderate concentration-dependent toxicity and yangonin displayed marked toxicity with ~ 40% reduction in viability in the EB assay. Acridine orange/ethidium bromide staining showed the predominant mode of cell death was apoptosis rather than necrosis. No significant changes were observed in glutathione levels, excluding this as the primary mechanism of cell death in this model. Further studies may elucidate the precise apoptotic pathways responsible and whether toxic kavalactone metabolites are involved.

Token economy, pimozide and chronic schizophrenia.

Response to a token economy was assessed in male chronic schizophrenic in-patients who were given, in a double-blind cross-over trial, pimozide (up to 20 mg daily) or chlorpromazine )up to 1,000 mg daily), each for three months. After six months there was little change in the patients' mental state, but general ward behaviour and token-rewarded "target" behaviours improved significantly. There were no statistically significant between-drug differences, but the trend was that general ward behaviour, but not token-rewarded behaviour, improved more on pimozide. The patients who showed initiative and cooperated best with staff were those whose token-rewarded behaviour was most satisfactory.