The ribosomal protein Rpl22 controls ribosome composition by directly repressing expression of its own paralog, Rpl22l1.

Most yeast ribosomal protein genes are duplicated and their characterization has led to hypotheses regarding the existence of specialized ribosomes with different subunit composition or specifically-tailored functions. In yeast, ribosomal protein genes are generally duplicated and evidence has emerged that paralogs might have specific roles. Unlike yeast, most mammalian ribosomal proteins are thought to be encoded by a single gene copy, raising the possibility that heterogenous populations of ribosomes are unique to yeast. Here, we examine the roles of the mammalian Rpl22, finding that Rpl22(-/-) mice have only subtle phenotypes with no significant translation defects. We find that in the Rpl22(-/-) mouse there is a compensatory increase in Rpl22-like1 (Rpl22l1) expression and incorporation into ribosomes. Consistent with the hypothesis that either ribosomal protein can support translation, knockdown of Rpl22l1 impairs growth of cells lacking Rpl22. Mechanistically, Rpl22 regulates Rpl22l1 directly by binding to an internal hairpin structure and repressing its expression. We propose that ribosome specificity may exist in mammals, providing evidence that one ribosomal protein can influence composition of the ribosome by regulating its own paralog.

Perception and adaptation of pastoralists to climate variability and change in Morocco's arid rangelands.

Since the late 1970s, extensive livestock production in the high plateaus of Eastern Morocco, particularly of small ruminants, has been seriously threatened by climate change (CC). Negative impacts include reduction in rangeland forage production and water availability, increased poverty and inequality, and increased degradation of rangelands. Different categories of pastoralists have adopted different combinations of adaptation strategies, but the factors influencing adoption have not to date been investigated. This paper aims to identify the perceptions of pastoralists on CC, to analyze the adaptive responses of different wealth categories, and to determine the factors affecting the adoption of adaptation measures. The Mann-Kendall, Pettitt and Buishand tests and the standardized precipitation index were used to analyze the climate data. Data on adaptation were examined using the chi-square homogeneity test, Kruskal-Wallis test and binary logistic regression. The observed climate trends perfectly corroborated pastoralists' perceptions of significant changes in their local climate since the 1970s: a considerable decrease in annual rainfall and an increase in temperature and frequency of droughts and high winds. There were significant differences (Chi square = 7.603, p = 0.022, df = 2) between small, medium and large pastoralists in the frequency adoption of adaptation strategies, especially between small and large pastoralists (U statistic = 16.000, p = 0.009). The distribution of most adaptation actions also differed significantly between these two groups. Wealthier pastoralists have adopted a greater range of strategies, while poorer pastoralists have less diverse adaptation portfolios, and are more likely to adopt less advantageous strategies such as casual labor. The adoption of adaptation practices was significantly influenced by equipment, educational level, household size, herd size, training received, CC perceptions and agroecological setting. Public interventions to improve the adaptive capacity of pastoralists in Morocco's arid rangelands should be geared towards addressing these determinants and should prioritise small-scale pastoralists.

The impact of climate change on smallholder and subsistence agriculture.

Some of the most important impacts of global climate change will be felt among the populations, predominantly in developing countries, referred to as "subsistence" or "smallholder" farmers. Their vulnerability to climate change comes both from being predominantly located in the tropics, and from various socioeconomic, demographic, and policy trends limiting their capacity to adapt to change. However, these impacts will be difficult to model or predict because of (i) the lack of standardised definitions of these sorts of farming system, and therefore of standard data above the national level, (ii) intrinsic characteristics of these systems, particularly their complexity, their location-specificity, and their integration of agricultural and nonagricultural livelihood strategies, and (iii) their vulnerability to a range of climate-related and other stressors. Some recent work relevant to these farming systems is reviewed, a conceptual framework for understanding the diverse forms of impacts in an integrated manner is proposed, and future research needs are identified.

Reduction of age-associated pathology in old mice by overexpression of catalase in mitochondria.

We describe the effects of mitochondrially targeted catalase (MCAT) expression on end-of-life pathology in mice using detailed semiquantitative histopathological evaluation. We previously reported that the median and maximum life spans of MCAT mice were extended relative to those of wild-type littermates. We now report that MCAT expression is associated with reduced malignant nonhematopoietic tumor burden, reduced cardiac lesions, and a trend toward reduced systemic inflammation, with no effect on hematopoietic neoplasia or glomerulonephropathy. Combined disease burden and comorbidity are also reduced, and MCAT expression is not associated with any detrimental clinical effects. The results suggest that oxidative damage is involved in aging of C57BL/6J mice via modulation of a subset of age-associated lesions. Antioxidant interventions targeting mitochondria may therefore be a viable strategy for prevention or postponement of some age-associated diseases. The variability of the MCAT effect across tissues, however, illustrates the importance of developing semiquantitative histopathology for assessment of comorbidity in life-span studies.

Rainfall variability and drought characteristics in two agro-climatic zones: An assessment of climate change challenges in Africa.

This paper examines drought characteristics as an evidence of climate change in two agro-climatic zones of Nigeria and farmers' climate change perceptions of impacts and adaptation strategies. The results show high spatial and temporal rainfall variability for the stations. Consequently, there are several anomalies in rainfall in recent years but much more in the locations around the Guinea savanna. The inter-station and seasonality statistics reveal less variable and wetter early growing seasons and late growing seasons in the Rainforest zone, and more variable and drier growing seasons in other stations. The probability (p) of dry spells exceeding 3, 5 and 10 consecutive days is very high with 0.62≤p≥0.8 in all the stations, though, the p-values for 10day spells drop below 0.6 in Ibadan and Osogbo. The results further show that rainfall is much more reliable from the month of May until July with the coefficient of variance for rainy days <0.30, but less reliable in the months of March, August and October (CV-RD>0.30), though CV-RD appears higher in the month of August for all the stations. It is apparent that farmers' perceptions of drought fundamentally mirror climatic patterns from historical weather data. The study concludes that the adaptation facilities and equipment, hybrids of crops and animals are to be provided to farmers, at a subsidized price by the government, for them to cope with the current condition of climate change.

Hepatic S6K1 Partially Regulates Lifespan of Mice with Mitochondrial Complex I Deficiency.

The inactivation of ribosomal protein S6 kinase 1 (S6K1) recapitulates aspects of caloric restriction and mTORC1 inhibition to achieve prolonged longevity in invertebrate and mouse models. In addition to delaying normative aging, inhibition of mTORC1 extends the shortened lifespan of yeast, fly, and mouse models with severe mitochondrial disease. Here we tested whether disruption of S6K1 can recapitulate the beneficial effects of mTORC1 inhibition in the Ndufs4 knockout (NKO) mouse model of Leigh Syndrome caused by Complex I deficiency. These NKO mice develop profound neurodegeneration resulting in brain lesions and death around 50-60 days of age. Our results show that liver-specific, as well as whole body, S6K1 deletion modestly prolongs survival and delays onset of neurological symptoms in NKO mice. In contrast, we observed no survival benefit in NKO mice specifically disrupted for S6K1 in neurons or adipocytes. Body weight was reduced in WT mice upon disruption of S6K1 in adipocytes or whole body, but not altered when S6K1 was disrupted only in neurons or liver. Taken together, these data indicate that decreased S6K1 activity in liver is sufficient to delay the neurological and survival defects caused by deficiency of Complex I and suggest that mTOR signaling can modulate mitochondrial disease and metabolism via cell non-autonomous mechanisms.

Corrigendum: Hepatic S6K1 Partially Regulates Lifespan of Mice with Mitochondrial Complex I Deficiency.

[This corrects the article on p. 113 in vol. 8, PMID: 28919908.].

Pancreatic beta-cell failure and diabetes in mice with a deletion mutation of the endoplasmic reticulum molecular chaperone gene P58IPK.

The endoplasmic reticulum (ER) transmits apoptotic signals in the pancreas during ER stress, implicating ER stress-mediated apoptosis in the development of diabetes. P58(IPK) (DNAJC3) is induced during ER stress and functions as a negative feedback component to inhibit eIF-2alpha signaling and attenuate the later phases of the ER stress response. To gain insight into a more comprehensive role of P58(IPK) function, we generated deletion mutant mice that showed a gradual onset of glucosuria and hyperglycemia associated with increasing apoptosis of pancreatic islet cells. Lack of P58(IPK) had no apparent effect on the functional integrity of viable beta-cells. A set of genes associated with apoptosis showed altered expression in pancreatic islets from P58(IPK)-null mice, further substantiating the apoptosis phenotype. The data provide in vivo evidence to support the concept that P58(IPK) functions as a signal for the downregulation of ER-associated proteins involved in the initial ER stress response, thus preventing excessive cell loss by degradation pathways. Insulin deficiency associated with the absence of P58(IPK) mimics beta-cell failure associated with type 1 and late-stage type 2 diabetes. P58(IPK) function and activity may therefore provide a novel area of investigation into ER-mediated mechanistic and therapeutic approaches for diabetes.

Integrated control of vector-borne diseases of livestock--pyrethroids: panacea or poison?

Tick- and tsetse-borne diseases cost Africa approximately US$4-5 billion per year in livestock production-associated losses. The use of pyrethroid-treated cattle to control ticks and tsetse promises to be an increasingly important tool to counter this loss. However, uncontrolled use of this technology might lead to environmental damage, acaricide resistance in tick populations and a possible exacerbation of tick-borne diseases. Recent research to identify, quantify and to develop strategies to avoid these effects are highlighted.

Attenuation of age-related metabolic dysfunction in mice with a targeted disruption of the Cbeta subunit of protein kinase A.

The cyclic adenosine monophosphate-dependent protein kinase A (PKA) pathway helps regulate both cell growth and division, and triglyceride storage and metabolism in response to nutrient status. Studies in yeast show that disruption of this pathway promotes longevity in a manner similar to caloric restriction. Because PKA is highly conserved, it can be studied in mammalian systems. This report describes the metabolic phenotype of mice lacking the PKA catalytic subunit Cbeta. We confirmed that Cbeta has high levels of expression in the brain but also showed moderate levels in liver. Cbeta-null animals had reduced basal PKA activity while appearing overtly normal when fed standard rodent chow. However, the absence of Cbeta protected mice from diet-induced obesity, steatosis, dyslipoproteinemia, and insulin resistance, without any differences in caloric intake or locomotor activity. These findings have relevant pharmacological implications because aging in mammals is characterized by metabolic decline associated with obesity, altered body fat distribution, and insulin resistance.

Disruption of protein kinase A in mice enhances healthy aging.

Mutations that cause a reduction in protein kinase A (PKA) activity have been shown to extend lifespan in yeast. Loss of function of mammalian RIIbeta, a regulatory subunit of PKA expressed in brain and adipose tissue, results in mice that are lean and insulin sensitive. It was therefore hypothesized that RIIB null (RIIbeta(-/-)) mice would express anti-aging phenotypes. We conducted lifespan studies using 40 mutant and 40 wild type (WT) littermates of equal gender numbers and found that both the median and maximum lifespans were significantly increased in mutant males compared to WT littermates. The median lifespan was increased from 884 days to 1005 days (p = 0.006 as determined by the log rank test) and the 80% lifespan (defined here as 80% deaths) was increased from 941 days to 1073 days (p = 0.004 as determined by the Wang-Allison test). There was no difference in either median or 80% lifespan in female genotypes. WT mice of both genders became increasingly obese with age, while mutant mice maintained their lean phenotype into old age. Adiposity was found to correlate with lifespan for males only. 50% of male mice between 30 and 35 g, corresponding to about 5% body fat, for either genotype lived over 1000 days. No male mouse outside of this weight range achieved this lifespan. During their last month of life, WT mice began losing weight (a total of 8% and 15% of body weight was lost for males and females, respectively), but RIIbeta(-/-) male mice maintained their lean body mass to end of life. This attenuation of decline was not seen in female mutant mice. Old male mutant mice were insulin sensitive throughout their life. Both genders showed modestly lower blood glucose levels in old mutants compared to WT. Male mutants were also resistant to age-induced fatty liver. Pathological assessment of tissues from end of life male mutant mice showed a decrease in tumor incidence, decreased severity of renal lesions, and a trend towards a decrease in age-related cardiac pathology. These findings help establish the highly conserved nature of PKA and suggest that disruption of PKA affects physiological mechanisms known to be associated with healthy aging.

Utility of a C57BL/6 ES line versus 129 ES lines for targeted mutations in mice.

Inbred ES lines, though useful for generating targeted mutations in mice, are used infrequently. To appreciate the relative efficiency of inbred ES lines, a C57BL/6 ES line was compared with 129 strain ES lines for effectiveness in chimera formation leading to the establishment of targeted mutations in mice. Data from a transgenic facility spanning 7 years were collected. C57BL/6 ES cells injected into Balb/c embryos results in lower coat color chimerism than do 129 ES cells injected into C57BL/6 embryos. Combined data indicate that five independent targeted C57BL/6 clones should be injected as compared to three independent 129 clones to generate enough chimeras to effectively test for germ-line transmission. Thus, although less efficient than 129 ES lines, the C57BL/6 ES line is a relatively competent line and useful for the routine generation of targeted mutations in mice on a defined genetic background.