Farmer adoption of water practices across four counties in California

Climate change is deeply impacting agriculture, including water availability, which is affecting farmers’ ability to have enough water to continue growing crops. In California, a large agricultural producer where drought frequency and intensity has increased in recent years, the state recently enacted the Sustainable Groundwater Management Act (SGMA). This study explores what influences farmers to adopt future water management practices, specifically water intensive practices, water reduction practices and water technology practices. Six hundred and ninety farmers across four California counties responded to a mail survey asking them about their perceptions on SGMA, farm characteristics, and on-farm practices in 2017 and 2019. The hypothesis of this study is that farmers who grow very water intensive crops, such as almonds and walnuts, will be the most likely to intend to implement water intensive practices and less likely to intend to implement water conservation or water technologies in the future versus farmers of crop types whose crops are less water intensive. A multivariable linear regression assessed whether farm and farmer characteristics such as age, income, acres managed, succession plan status, county location (Yolo, San Luis Obispo, Madera, and Fresno), education, and awareness of voluntary programs to see if these factors influenced farmer adoption. Unlike hypothesized, there is no effect of crop type on farmer adoption of any water practices, though other farm and farmer characteristics are significantly correlated. Furthermore, farmers are most likely to implement water technology practices overall, with less preference for water extraction and practices that use less water. These results suggest that farmers are more willing to use their water more efficiently, rather than accessing more water or using less water

Histone acetyltransferases:challenges in targeting bi-substrate enzymes

Histone acetyltransferases (HATs) are epigenetic enzymes that install acetyl groups onto lysine residues of cellular proteins such as histones, transcription factors, nuclear receptors, and enzymes. HATs have been shown to play a role in diseases ranging from cancer and inflammatory diseases to neurological disorders, both through acetylations of histone proteins and non-histone proteins. Several HAT inhibitors, like bi-substrate inhibitors, natural product derivatives, small molecules, and protein-protein interaction inhibitors, have been developed. Despite their potential, a large gap remains between the biological activity of inhibitors in in vitro studies and their potential use as therapeutic agents. To bridge this gap, new potent HAT inhibitors with improved properties need to be developed. However, several challenges have been encountered in the investigation of HATs and HAT inhibitors that hinder the development of new HAT inhibitors. HATs have been shown to function in complexes consisting of many proteins. These complexes play a role in the activity and target specificity of HATs, which limits the translation of in vitro to in vivo experiments. The current HAT inhibitors suffer from undesired properties like anti-oxidant activity, reactivity, instability, low potency, or lack of selectivity between HAT subtypes and other enzymes. A characteristic feature of HATs is that they are bi-substrate enzymes that catalyze reactions between two substrates: the cofactor acetyl coenzyme A (Ac-CoA) and a lysine-containing substrate. This has important-but frequently overlooked-consequences for the determination of the inhibitory potency of small molecule HAT inhibitors and the reproducibility of enzyme inhibition experiments. We envision that a careful characterization of molecular aspects of HATs and HAT inhibitors, such as the HAT catalytic mechanism and the enzyme kinetics of small molecule HAT inhibitors, will greatly improve the development of potent and selective HAT inhibitors and provide validated starting points for further development towards therapeutic agents.</p

The joy of gratifications: Promotion as a short-term boost or long-term success – The same for women and men?

Job satisfaction helps create a committed workforce with many positive effects, such as increased organisational citizenship behaviour and reduced absenteeism. In turn, job satisfaction can be increased through gratifications, such as wage increases and promotions. But human satisfaction is prone to being governed by the homeostatic principle and will eventually return to the individual's base level. Thus, we longitudinally examined the effects of promotions to managerial positions and pay raises on job satisfaction across a period of 27 years. Our analyses were based on a large-scale representative German panel (N = 5978 observations) that allowed us to separate the effect of a promotion from the effect of the corresponding wage increase. We found that promotions positively affected job satisfaction in the short term but diminished after 1 year. Furthermore, the influence of a promotion on job satisfaction was more pronounced for men than for women

Assessing the need for a protocol in monitoring weight loss and nutritional status in orthognathic surgery based on patients experiences

To investigate retrospectively the orthognathic surgery (OGS) patients experience in weight loss and the influence of gender, age, duration of the surgical procedure, length of hospital stay, location of surgery and use of intermaxillary fixation (IMF) or without IMF on postoperative weight loss. A total of 4487 patients treated by OGS where all patients visited the outpatient clinic one, three and six weeks after the surgical procedure. After six weeks, patients filled out a questionnaire in which weight loss was addressed. The patients were asked to give an estimate of their experiences weight loss. The population was first divided in two groups weight loss and no weight loss. In the weight loss group there is no significant difference in weight loss between patients with IMF and patients without IMF. In the weight loss group there were significantly more females then males. Further, in the subgroup IMF the operation time was significantly longer compared with the subgroup without IMF. The other parameters including age and hospital stay were not different in the groups. IMF in orthognathic treatment does not result in a difference self-reported loss of body weight compared to patients without IMF. Treatment protocols should include pre- and post-operative dietician consultations and possible indications for medical nutrition and vitamins

WHO guidelines for antimicrobial treatment in children admitted to hospital in an area of intense Plasmodium falciparum transmission: prospective study

Objectives To assess the performance of WHO’s “Guidelines for care at the first-referral level in developing countries” in an area of intense malaria transmission and identify bacterial infections in children with and without malaria

Enzyme kinetics and inhibition of histone acetyltransferase KAT8

Lysine acetyltransferase 8 (KAT8) is a histone acetyltransferase (HAT) responsible for acetylating lysine 16 on histone H4 (H4K16) and plays a role in cell cycle progression as well as acetylation of the tumor suppressor protein p53. Further studies on its biological function and drug discovery initiatives will benefit from the development of small molecule inhibitors for this enzyme. As a first step towards this aim we investigated the enzyme kinetics of this bi-substrate enzyme. The kinetic experiments indicate a ping-pong mechanism in which the enzyme binds Ac-CoA first, followed by binding of the histone substrate. This mechanism is supported by affinity measurements of both substrates using isothermal titration calorimetry (ITC). Using this information, the KAT8 inhibition of a focused compound collection around the non-selective HAT inhibitor anacardic acid has been investigated. Kinetic studies with anacardic acid were performed, based on which a model for the catalytic activity of KAT8 and the inhibitory action of anacardic acid (AA) was proposed. This enabled the calculation of the inhibition constant Ki of anacardic acid derivatives using an adaptation of the Cheng-Prusoff equation. The results described in this study give insight into the catalytic mechanism of KAT8 and present the first well-characterized small-molecule inhibitors for this HAT

Discovery of chromenes as inhibitors of macrophage migration inhibitory factor

Macrophage migration inhibitory factor (MIF) is an essential signaling cytokine with a key role in the immune system. Binding of MIF to its molecular targets such as, among others, the cluster of differentiation 74 (CD74) receptor plays a key role in inflammatory diseases and cancer. Therefore, the identification of MIF binding compounds gained importance in drug discovery. In this study, we aim to discover novel MIF binding compounds by screening of a focused compound collection for inhibition of its tau- tomerase enzyme activity. Inspired by the known chromen-4-one inhibitor Orita-13, a focused collection of compounds with a chromene scaffold was screened for MIF binding. The library was synthesized using versatile cyanoacetamide chemistry to provide diversely substituted chromenes. The screening provided inhibitors with IC50’s in the low micromolar range. Kinetic evaluation suggested that the inhibitors were reversible and did not bind in the binding pocket of the substrate. Thus, we discovered novel inhibitors of the MIF tautomerase activity, which may ultimately support the development of novel therapeutic agents against diseases in which MIF is involved

Levonorgestrel-releasing intrauterine system versus endometrial ablation for heavy menstrual bleeding

Acknowledgments: We thank all the women who participated in this trial; the participating general practitioners, gynecologists, and hospitals; the research nurses; and the staff of the Dutch Consortium for Studies in Women’s Health and Reproduction.Peer reviewedPublisher PD

Duodenal Adenomas and Cancer in MUTYH-associated Polyposis: An International Cohort Study

Although duodenal adenomas and cancer appear to occur significantly less frequently in autosomal recessive MUTYH-associated polyposis (MAP) than in autosomal dominant familial adenomatous polyposis (FAP),1 current guidelines recommend similar endoscopic surveillance for both disorders.2-4 This involves gastro-duodenoscopy starting at 25 to 35 years of age and repeated at intervals determined by Spigelman staging based on the number, size, histological type and degree of dysplasia of adenomas, and by ampullary staging. Case reports of duodenal cancers in MAP suggest that they may develop in the absence of advanced Spigelman stage benign disease and even without coexisting adenomas.1 Recent molecular analyses suggest thatMAPduodenal adenomashave a higher mutational burden than FAP adenomas and are more likely to harbor oncogenic drivermutations, such as those in KRAS.5 These apparent differences in the biology and natural history of duodenal polyposis in FAP and MAP challenge the assumption that the same surveillance should be applied in both conditions