An in vivo study of the effect of 5-HT and sympathetic nerves on transferrin and transthyretin mRNA expression in rat choroid plexus and meninges

Brain expression of transferrin (Tf) and transthyretin (TTR) mRNA has been demonstrated in different species, TTR being found only in the choroid plexus. We report here that both these mRNAs are also expressed in the meninges. In vitro studies have shown that Tf secretion by the rat choroid plexus is stimulated by 5-hydroxytryptamine (5-HT) while sympathetic nerves regulate different transport functions in the same tissue. We have used various in vivo models to study the neuroendocrine regulation of Tf and TTR mRNA expression in the choroid plexus and meninges. Destruction of the serotonergic nerves in the brain by either raphe nuclei lesion or intraventricular injections of 5,7-dihydroxytryptamine (5,7-DHT), which both decreased brain 5-HT levels significantly, did not affect Tf or TTR mRNA levels in choroid plexus and meninges, but increased TTR mRNA in liver. Intraventricular injection of 10 or 100 pmol 5-HT did not change the expression of these proteins in any of the tissues studied. Removal of the sympathetic innervation to the choroid plexus by cervical sympathectomy did not affect Tf or TTR mRNA levels in choroid plexus and liver, nor the incorporation of radioactive leucine into protein in various parts of the brain. In conclusion, our results do not support a regulatory role in vivo for neuronally derived 5-HT or sympathetic nerve activity on Tf and TTR mRNA expression in rat choroid plexus and meninges

Two-tiered Approach Identifies a Network of Cancer and Liver Disease-related Genes Regulated by miR-122*

MicroRNAs function as important regulators of gene expression and are commonly linked to development, differentiation, and diseases such as cancer. To better understand their roles in various biological processes, identification of genes targeted by microRNAs is necessary. Although prediction tools have significantly helped with this task, experimental approaches are ultimately required for extensive target search and validation. We employed two independent yet complementary high throughput approaches to map a large set of mRNAs regulated by miR-122, a liver-specific microRNA implicated in regulation of fatty acid and cholesterol metabolism, hepatitis C infection, and hepatocellular carcinoma. The combination of luciferase reporter-based screening and shotgun proteomics resulted in the identification of 260 proteins significantly down-regulated in response to miR-122 in at least one method, 113 of which contain predicted miR-122 target sites. These proteins are enriched for functions associated with the cell cycle, differentiation, proliferation, and apoptosis. Among these miR-122-sensitive proteins, we identified a large group with strong connections to liver metabolism, diseases, and hepatocellular carcinoma. Additional analyses, including examination of consensus binding motifs for both miR-122 and target sequences, provide further insight into miR-122 function

Priority research questions for the UK food system

The rise of food security up international political, societal and academic agendas has led to increasing interest in novel means of improving primary food production and reducing waste. There are however, also many ‘post-farm gate’ activities that are critical to food security, including processing, packaging, distributing, retailing, cooking and consuming. These activities all affect a range of important food security elements, notably availability, affordability and other aspects of access, nutrition and safety. Addressing the challenge of universal food security, in the context of a number of other policy goals (e.g. social, economic and environmental sustainability), is of keen interest to a range of UK stakeholders but requires an up-to-date evidence base and continuous innovation. An exercise was therefore conducted, under the auspices of the UK Global Food Security Programme, to identify priority research questions with a focus on the UK food system (though the outcomes may be broadly applicable to other developed nations). Emphasis was placed on incorporating a wide range of perspectives (‘world views’) from different stakeholder groups: policy, private sector, non-governmental organisations, advocacy groups and academia. A total of 456 individuals submitted 820 questions from which 100 were selected by a process of online voting and a three-stage workshop voting exercise. These 100 final questions were sorted into 10 themes and the ‘top’ question for each theme identified by a further voting exercise. This step also allowed four different stakeholder groups to select the top 7–8 questions from their perspectives. Results of these voting exercises are presented. It is clear from the wide range of questions prioritised in this exercise that the different stakeholder groups identified specific research needs on a range of post-farm gate activities and food security outcomes. Evidence needs related to food affordability, nutrition and food safety (all key elements of food security) featured highly in the exercise. While there were some questions relating to climate impacts on production, other important topics for food security (e.g. trade, transport, preference and cultural needs) were not viewed as strongly by the participants

Global Climate

In 2021, both social and economic activities began to return towards the levels preceding the COVID-19 pandemic for some parts of the globe, with others still experiencing restrictions. Meanwhile, the climate has continued to respond to the ongoing increase in greenhouse gases and resulting warming. La Niña, a phenomenon which tends to depress global temperatures while changing rainfall patterns in many regions, prevailed for all but two months of the year. Despite this, 2021 was one of the six-warmest years on record as measured by global mean surface temperature with an anomaly of between +0.21° and +0.28°C above the 1991–2020 climatology. Lake surface temperatures were their highest on record during 2021. The number of warm days over land also reached a new record high. Exceptional heat waves struck the Pacific Coast of North America, leading to a new Canadian maximum temperature of 49.6°C at Lytton, British Columbia, on 29 June, breaking the previous national record by over 4°C. In Death Valley, California, the peak temperature reached 54.4°C on 9 July, equaling the temperature measured in 2020, and the highest temperature recorded anywhere on the globe since at least the 1930s. Over the Mediterranean, a provisional new European record of 48.8°C was set in Sicily on 11 August. In the atmosphere, the annual mean tropospheric temperature was among the 10 highest on record, while the stratosphere continued to cool. While La Niña was present except for June and July, likely influencing Australia’s coolest year since 2012 and wettest since 2016, other modes of variability played important roles. A negative Indian Ocean dipole event became established during July, associated with a warmer east and cooler west Indian Ocean. Northern Hemisphere winters were affected by a negative phase of the North Atlantic Oscillation at both the beginning and end of 2021. In the Southern Hemisphere, a very strong positive Southern Annular Mode (also known as the Antarctic Oscillation) contributed to New Zealand’s record warm year and to very cold temperatures over Antarctica. Land surface winds continued a slow reversal from the multi-decadal stilling, and over the ocean wind speeds were at their highest in almost a decade. La Niña conditions had a clear influence on the regional patterns of many hydrological variables. Surface specific humidity and total column water vapor over land and ocean were higher than average in almost all datasets. Relative humidity over land reached record or near-record low saturation depending on the dataset, but with mixed signals over the ocean. Satellite measurements showed that 2021 was the third cloudiest in the 19-year record. The story for precipitation was mixed, with just below-average mean precipitation falling over land and below-average mean precipitation falling over the ocean, while extreme precipitation was generally more frequent, but less intense, than average. Differences between means and extremes can be due to several factors, including using different indices, observing periods, climatological base reference periods, and levels of spatial completeness. The sharp increase in global drought area that began in mid-2019 continued in 2021, reaching a peak in August with 32% of global land area experiencing moderate or worse drought, and declining slightly thereafter. Arctic permafrost temperatures continued to rise, reaching record values at many sites, and the thickness of the layer which seasonally thaws and freezes also increased over 2020 values in a number of regions. It was the 34th-consecutive year of mass balance loss for alpine glaciers in mountainous regions, with glaciers on average 25 m thinner than in the late 1970s. And the duration of lake ice in the Northern Hemisphere was the fourth lowest in situ record dating back to 1991. The atmospheric concentrations of the major long-lived greenhouse gases, CO2, CH4, and N2O, all reached levels not seen in at least the last million years and grew at near-record rates in 2021. La Niña conditions did not appear to have any appreciable impact on their growth rates. The growth rate for CH4, of 17 ppb yr−1, was similar to that for 2020 and set yet another record, although the causes for this post-2019 acceleration are unknown presently. Overall, CO2 growth continues to dominate the increase in global radiative forcing, which increased from 3.19 to 3.23 W m−2 (watts per square meter) during the year. In 2021, stratospheric ozone did not exhibit large negative anomalies, especially near the poles, unlike 2020, where large ozone depletions appeared, mainly from dynamical effects. The positive impact of reductions in emissions of ozone depleting substances can be seen most clearly in the upper stratosphere, where such dynamical effects are less pronounced. It was the fourth-lowest fire year since global records began in 2003, though extreme regional fire activity was again seen in North America and also in Siberia; as in 2020, the effects of wildfires in these two regions led to locally large regional positive anomalies in tropospheric aerosol and carbon monoxide abundance. Vegetation is responding to the higher global mean temperatures, with the satellite-derived measures for the Northern Hemisphere for 2021 rated among the earliest starts of the growing season and the latest end of the season on record. The first bloom date for cherry trees in Kyoto, Japan, broke a 600-year record set in 1409. This year we welcome a sidebar on the global distribution of lightning, which has been recently declared an essential climate variable (ECV) by the Global Climate Observing System (GCOS). Time series and anomaly maps from many of the variables described in this chapter can be found in Plates 1.1 and 2.1. As with other chapters, many of the sections have moved from the previous 1981–2010 to the new 1991–2020 climatological reference period, in line with WMO recommendations (see Chapter 1). This is not possible for all datasets, as it is dependent on their length of record or legacy processing methods. While anomalies from the new climatology period are not so easily comparable with previous editions of this report, they more clearly highlight deviations from more recent conditions