Iñupiaq Knowledge of Polar Bears (Ursus maritimus) in the Southern Beaufort Sea, Alaska

Successful wildlife management depends upon coordination and consultation with local communities. However, much of the research used to inform management is often derived solely from data collected directly from wildlife. Indigenous people living in the Arctic have a close connection to their environment, which provides unique opportunities to observe their environment and the ecology of Arctic species. Further, most northern Arctic communities occur within the range of polar bears (nanuq, Ursus maritimus) and have experienced significant climatic changes. Here, we used semi-structured interviews from 2017 to 2019 to document Iñupiaq knowledge of polar bears observed over four decades in four Alaskan communities in the range of the Southern Beaufort Sea polar bear subpopulation: Wainwright, Utqiaġvik, Nuiqsut, and Kaktovik. All but one of 47 participants described directional and notable changes in sea ice, including earlier ice breakup, later ice return, thinner ice, and less multiyear pack ice. These changes corresponded with observations of bears spending more time on land during the late summer and early fall in recent decades—observations consistent with scientific and Indigenous knowledge studies in Alaska, Canada, and Greenland. Participants noted that polar bear and seal body condition and local abundance either varied geographically or exhibited no patterns. However, participants described a recent phenomenon of bears being exhausted and lethargic when arriving on shore in the summer and fall after extensive swims from the pack ice. Further, several participants suggested that maternal denning is occurring more often on land than sea ice. Participants indicated that village and regional governments are increasingly challenged to obtain resources needed to keep their communities safe as polar bears spend more time on land, an issue that is likely to be exacerbated both in this region and elsewhere as sea ice loss continues. La gestion réussie de la faune dépend des efforts de coordination et de consultation avec les collectivités locales. Toutefois, il arrive souvent qu’une grande partie de la recherche utilisée pour éclairer la gestion dérive uniquement des données recueillies directement de la faune. Les peuples autochtones qui vivent dans l’Arctique entretiennent des liens étroits avec leur environnement, ce qui crée des occasions uniques d’observer l’environnement et l’écologie des espèces de l’Arctique. Il y a également lieu de remarquer que la plupart des collectivités du nord de l’Arctique se trouvent dans l’aire de répartition des ours polaires (nanuq, Ursus) et connaissent d’importants changements climatiques. Dans le cadre de cette étude, nous nous sommes appuyés sur des entrevues semi-structurées réalisées entre 2017 et 2019 pour documenter les connaissances des Iñupiaq au sujet des ours polaires découlant d’observations échelonnées sur quatre décennies dans quatre collectivités de l’Alaska situées dans l’aire de répartition de la sous-population d’ours polaires du sud de la mer de Beaufort : Wainwright, Utqiaġvik, Nuiqsut et Kaktovik. Les 47 participants, sauf un, ont décrit des changements directionnels et remarquables en ce qui a trait à la glace de mer, dont des débâcles plus hâtives, le retour plus tardif de la glace, de la glace plus mince et moins de banquises pluriannuelles. Ces changements correspondent aux observations d’ours qui passent plus de temps sur la terre ferme en fin d’été et en début d’automne au cours des dernières décennies. Ces observations coïncident avec les études sur les connaissances scientifiques et autochtones réalisées en Alaska, au Canada et au Groenland. Les participants ont fait remarquer que la condition corporelle des ours polaires et des phoques ainsi que leur abondance à l’échelle locale variaient d’une région à l’autre ou n’affichaient aucune tendance. Cependant, les participants ont décrit un phénomène récent selon lequel les ours sont épuisés et léthargiques lorsqu’ils arrivent sur la rive à l’été et à l’automne, après avoir parcouru de longues distances à la nage depuis les banquises. Aussi, plusieurs participants ont laissé entendre que les aires de mise bas se retrouvent plus souvent sur la terre ferme que sur la glace de mer. Les participants ont indiqué que le gouvernement des villages et les gouvernements régionaux ont de plus en plus de difficulté à obtenir les ressources nécessaires pour assurer la sécurité de leurs collectivités, car les ours polaires passent plus de temps sur la terre ferme, un enjeu qui risque de s’aggraver, tant dans cette région qu’ailleurs, à mesure que la glace de mer continuera de perdre de l’ampleur.

Mouse nuclear myosin I knock-out shows interchangeability and redundancy of myosin isoforms in the cell nucleus.

Nuclear myosin I (NM1) is a nuclear isoform of the well-known "cytoplasmic" Myosin 1c protein (Myo1c). Located on the 11(th) chromosome in mice, NM1 results from an alternative start of transcription of the Myo1c gene adding an extra 16 amino acids at the N-terminus. Previous studies revealed its roles in RNA Polymerase I and RNA Polymerase II transcription, chromatin remodeling, and chromosomal movements. Its nuclear localization signal is localized in the middle of the molecule and therefore directs both Myosin 1c isoforms to the nucleus. In order to trace specific functions of the NM1 isoform, we generated mice lacking the NM1 start codon without affecting the cytoplasmic Myo1c protein. Mutant mice were analyzed in a comprehensive phenotypic screen in cooperation with the German Mouse Clinic. Strikingly, no obvious phenotype related to previously described functions has been observed. However, we found minor changes in bone mineral density and the number and size of red blood cells in knock-out mice, which are most probably not related to previously described functions of NM1 in the nucleus. In Myo1c/NM1 depleted U2OS cells, the level of Pol I transcription was restored by overexpression of shRNA-resistant mouse Myo1c. Moreover, we found Myo1c interacting with Pol II. The ratio between Myo1c and NM1 proteins were similar in the nucleus and deletion of NM1 did not cause any compensatory overexpression of Myo1c protein. We observed that Myo1c can replace NM1 in its nuclear functions. Amount of both proteins is nearly equal and NM1 knock-out does not cause any compensatory overexpression of Myo1c. We therefore suggest that both isoforms can substitute each other in nuclear processes

Nitrosative stress treatment of E. coli targets distinct set of thiol-containing proteins

Reactive nitrogen species (RNS) function as powerful antimicrobials in host defence, but so far little is known about their bacterial targets. In this study, we set out to identify Escherichia coli proteins with RNS-sensitive cysteines. We found that only a very select set of proteins contain cysteines that undergo reversible thiol modifications upon nitric oxide (NO) treatment in vivo . Of the 10 proteins that we identified, six (AtpA, AceF, FabB, GapA, IlvC, TufA) have been shown to harbour functionally important thiol groups and are encoded by genes that are considered essential under our growth conditions. Media supplementation studies suggested that inactivation of AceF and IlvC is, in part, responsible for the observed NO-induced growth inhibition, indicating that RNS-mediated modifications play important physiological roles. Interestingly, the majority of RNS-sensitive E. coli proteins differ from E. coli proteins that harbour H 2 O 2 -sensitive thiol groups, implying that reactive oxygen and nitrogen species affect distinct physiological processes in bacteria. We confirmed this specificity by analysing the activity of one of our target proteins, the small subunit of glutamate synthase. In vivo and in vitro activity studies confirmed that glutamate synthase rapidly inactivates upon NO treatment but is resistant towards other oxidative stressors.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72397/1/j.1365-2958.2007.05964.x.pd

Ethylene supports colonization of plant roots by the mutualistic fungus Piriformospora indica

The mutualistic basidiomycete Piriformospora indica colonizes roots of mono- and dicotyledonous plants, and thereby improves plant health and yield. Given the capability of P. indica to colonize a broad range of hosts, it must be anticipated that the fungus has evolved efficient strategies to overcome plant immunity and to establish a proper environment for nutrient acquisition and reproduction. Global gene expression studies in barley identified various ethylene synthesis and signaling components that were differentially regulated in P. indica-colonized roots. Based on these findings we examined the impact of ethylene in the symbiotic association. The data presented here suggest that P. indica induces ethylene synthesis in barley and Arabidopsis roots during colonization. Moreover, impaired ethylene signaling resulted in reduced root colonization, Arabidopsis mutants exhibiting constitutive ethylene signaling, -synthesis or ethylene-related defense were hyper-susceptible to P. indica. Our data suggest that ethylene signaling is required for symbiotic root colonization by P. indica

Post-stroke inhibition of induced NADPH oxidase type 4 prevents oxidative stress and neurodegeneration

Ischemic stroke is the second leading cause of death worldwide. Only one moderately effective therapy exists, albeit with contraindications that exclude 90% of the patients. This medical need contrasts with a high failure rate of more than 1,000 pre-clinical drug candidates for stroke therapies. Thus, there is a need for translatable mechanisms of neuroprotection and more rigid thresholds of relevance in pre-clinical stroke models. One such candidate mechanism is oxidative stress. However, antioxidant approaches have failed in clinical trials, and the significant sources of oxidative stress in stroke are unknown. We here identify NADPH oxidase type 4 (NOX4) as a major source of oxidative stress and an effective therapeutic target in acute stroke. Upon ischemia, NOX4 was induced in human and mouse brain. Mice deficient in NOX4 (Nox4(-/-)) of either sex, but not those deficient for NOX1 or NOX2, were largely protected from oxidative stress, blood-brain-barrier leakage, and neuronal apoptosis, after both transient and permanent cerebral ischemia. This effect was independent of age, as elderly mice were equally protected. Restoration of oxidative stress reversed the stroke-protective phenotype in Nox4(-/-) mice. Application of the only validated low-molecular-weight pharmacological NADPH oxidase inhibitor, VAS2870, several hours after ischemia was as protective as deleting NOX4. The extent of neuroprotection was exceptional, resulting in significantly improved long-term neurological functions and reduced mortality. NOX4 therefore represents a major source of oxidative stress and novel class of drug target for stroke therapy

Insights into energy balance dysregulation from a mouse model of methylmalonic aciduria

Inherited disorders of mitochondrial metabolism, including isolated methylmalonic aciduria, present unique challenges to energetic homeostasis by disrupting energy-producing pathways. To better understand global responses to energy shortage, we investigated a hemizygous mouse model of methylmalonyl-CoA mutase (Mmut)–type methylmalonic aciduria. We found Mmut mutant mice to have reduced appetite, energy expenditure and body mass compared with littermate controls, along with a relative reduction in lean mass but increase in fat mass. Brown adipose tissue showed a process of whitening, in line with lower body surface temperature and lesser ability to cope with cold challenge. Mutant mice had dysregulated plasma glucose, delayed glucose clearance and a lesser ability to regulate energy sources when switching from the fed to fasted state, while liver investigations indicated metabolite accumulation and altered expression of peroxisome proliferator–activated receptor and Fgf21-controlled pathways. Together, these shed light on the mechanisms and adaptations behind energy imbalance in methylmalonic aciduria and provide insight into metabolic responses to chronic energy shortage, which may have important implications for disease understanding and patient management

Neurobeachin, a Regulator of Synaptic Protein Targeting, Is Associated with Body Fat Mass and Feeding Behavior in Mice and Body-Mass Index in Humans

Neurobeachin (Nbea) regulates neuronal membrane protein trafficking and is required for the development and functioning of central and neuromuscular synapses. In homozygous knockout (KO) mice, Nbea deficiency causes perinatal death. Here, we report that heterozygous KO mice haploinsufficient for Nbea have higher body weight due to increased adipose tissue mass. In several feeding paradigms, heterozygous KO mice consumed more food than wild-type (WT) controls, and this consumption was primarily driven by calories rather than palatability. Expression analysis of feeding-related genes in the hypothalamus and brainstem with real-time PCR showed differential expression of a subset of neuropeptide or neuropeptide receptor mRNAs between WT and Nbea+/− mice in the sated state and in response to food deprivation, but not to feeding reward. In humans, we identified two intronic NBEA single-nucleotide polymorphisms (SNPs) that are significantly associated with body-mass index (BMI) in adult and juvenile cohorts. Overall, data obtained in mice and humans suggest that variation of Nbea abundance or activity critically affects body weight, presumably by influencing the activity of feeding-related neural circuits. Our study emphasizes the importance of neural mechanisms in body weight control and points out NBEA as a potential risk gene in human obesity

Optimal timing for managed relocation of species faced with climate change

Managed relocation is a controversial climate-adaptation strategy to combat negative climate change impacts on biodiversity. While the scientific community debates the merits of managed relocation(1-12), species are already being moved to new areas predicted to be more suitable under climate change(13,14). To inform these moves, we construct a quantitative decision framework to evaluate the timing of relocation in the face of climate change. We find that the optimal timing depends on many factors, including the size of the population, the demographic costs of translocation and the expected carrying capacities over time in the source and destination habitats. In some settings, such as when a small population would benefit from time to grow before risking translocation losses, haste is ill advised. We also find that active adaptive management(15,16) is valuable when the effect of climate change on source habitat is uncertain, and leads to delayed movement

A large scale hearing loss screen reveals an extensive unexplored genetic landscape for auditory dysfunction

The developmental and physiological complexity of the auditory system is likely reflected in the underlying set of genes involved in auditory function. In humans, over 150 non-syndromic loci have been identified, and there are more than 400 human genetic syndromes with a hearing loss component. Over 100 non-syndromic hearing loss genes have been identified in mouse and human, but we remain ignorant of the full extent of the genetic landscape involved in auditory dysfunction. As part of the International Mouse Phenotyping Consortium, we undertook a hearing loss screen in a cohort of 3006 mouse knockout strains. In total, we identify 67 candidate hearing loss genes. We detect known hearing loss genes, but the vast majority, 52, of the candidate genes were novel. Our analysis reveals a large and unexplored genetic landscape involved with auditory function