Explore the vast range of titles available.

ينبري مؤلفو هذا الكتاب لبعض المزاعم منها : \"زعم البعض أن من الأعراق أو الأجناس ما هو أحط من غيرها، مع محاولة إثبات أن هذا له دليل علمي يرجع إلى التكوين الوراثي الذي تحمله الجينات، مما لا يقبل التغيير\" فيفندونها في دحض كامل لنظرية الحتمية البيولوجية وما تدعيه من تعريفها لطبيعة الإنسان المحتومة وراثيا، ويتم ذلك من خلال دراسة نقدية علمية مسهبة وشيقة عن طبيعة الوراثة والبيئة في عدة موضوعات مهمة من بينها نظرية معامل الذكاء، وما تدعي من وجود فروق أساسية بين الأعراق وبين الجنسين، ومشاكل علاج الأمراض العقلية، وتحويل أصول المشاكل الاجتماعية إلى مسببات طبية وراثية، وغير ذلك من نظريات البيولوجيين الاجتماعيين التي ترد سلوك الإنسان في تبسيط مخل إلى عامل أساسي واحد هو الوراثة. وفي هذا كله يوضح المؤلفون في تحليل علمي متمكن، ومن خلال منظور تاريخي التأثير المتبادل بين الأيديولوجيا والعلم.

Conditional gene targeting has been extensively used for in vivo analysis of gene function in adipocyte cell biology but often with debate over the tissue specificity and the efficacy of inactivation. To directly compare the specificity and efficacy of different Cre lines in mediating adipocyte specific recombination, transgenic Cre lines driven by the adipocyte protein 2 (aP2) and adiponectin (Adipoq) gene promoters, as well as a tamoxifen-inducible Cre driven by the aP2 gene promoter (iaP2), were bred to the Rosa26R (R26R) reporter. All three Cre lines demonstrated recombination in the brown and white fat pads. Using different floxed loci, the individual Cre lines displayed a range of efficacy to Cre-mediated recombination that ranged from no observable recombination to complete recombination within the fat. The Adipoq-Cre exhibited no observable recombination in any other tissues examined, whereas both aP2-Cre lines resulted in recombination in endothelial cells of the heart and nonendothelial, nonmyocyte cells in the skeletal muscle. In addition, the aP2-Cre line can lead to germline recombination of floxed alleles in ∼2% of spermatozoa. Thus, different “adipocyte-specific” Cre lines display different degrees of efficiency and specificity, illustrating important differences that must be taken into account in their use for studying adipose biology.

All life on Earth requires nitrogen to survive. About 78% of the atmosphere alone is nitrogen, yet humans cannot use it directly. Instead, we obtain the nitrogen we need for our survival through the food we eat. For more than 100 years, a substantial portion of agricultural productivity has relied on industrial methods for nitrogen fertilizer synthesis, which consumes significant amounts of nonrenewable energy resources and exacerbates environmental degradation and human-induced climate change. Promising alternatives to these industrial methods rely on engineering the only biological pathway for generating bioaccessible nitrogen: microbial nitrogen fixation. Bioengineering strategies require an extensive understanding of underlying genetics in nitrogen-fixing microbes, but genetic tools for this critical goal remain lacking. The CRISPRi gene silencing system that we report, developed in the broadly utilized nitrogen-fixing bacterial model, Azotobacter vinelandii , is an important step toward elucidating the complexity of nitrogen fixation genetics and enabling their manipulation.

Human expansion into the solar system is currently at the forefront of space research. For our astronauts to survive, they will need to be fed a healthy and nutritious diet on a consistent basis. Right now, our current method of feeding astronauts consists of resupplied prepackaged food from Earth, which is unsustainable for long-term missions. Using planetary resources via in situ resource utilization to grow crops is the next step toward sustainability in space. Asteroids are an abundant space resource and should not be overlooked when considering crewed missions. In particular, the primordial CI carbonaceous asteroids are of interest because the regolith is suggested to contain soluble elemental nutrients, such as phosphorous and potassium, that crops can use for growth and development. We present a study on the ability of CI carbonaceous asteroid regolith simulant to sustain plant growth of lettuce (Latuca sativa), radishes (Raphanus sativus), and peppers (Capsicum annuum). We tested growing the selected crops in increasing mixtures of simulant and peat moss. The results showed that each species reacted differently to each treatment and that the radishes were more affected by the treatments. Subsequent analysis showed that the simulant contains small amounts of plant-usable nutrients, despite its high pH, low cation exchange capacity, and classification as a silt-based soil. Our results indicate that the simulant is prone to compaction and crusting, leading to drought stress on the crops. Further investigations are needed to determine mitigation strategies to make CI asteroid regolith a more conducive soil.

In two studies, a wearable, automated, bihormonal, “bionic” pancreas used in adults and adolescents with type 1 diabetes mellitus in unrestricted outpatient settings improved mean glycemic control, with fewer hypoglycemic episodes, as compared with usual care. Maintaining glycemic values as close to the nondiabetic range as possible is effective in preventing or delaying long-term complications of type 1 diabetes mellitus, 1 – 3 but achieving near normoglycemia is challenging. Most patients are unable to meet glycemic targets 4 – 6 and have frequent episodes of hypoglycemia, which can be life-threatening. 7 – 11 The availability of accurate continuous glucose monitoring has made feasible the development of bionic endocrine pancreatic systems that are designed to improve glycemic control and reduce the burden on patients. Tests of glycemic regulation lasting 1 day or more with the use of such systems have been limited to . . .

Key Points Mutations in single genes can increase the lifespans of lower metazoan organisms (worms and flies) and mammals. Many of these mutations affect genes that are involved in endocrine signalling pathways. Attenuation of signalling through the insulin/insulin-like growth factor-1 (IGF1) pathways prolongs the lifespans of worms and flies. Decreased IGF1 signalling also prolongs lifespan in mammals; however, diminished insulin signalling has been shown to prolong lifespan in mammals only when limited to adipocytes. The regulation of ageing by some hormone-receptor pathways is cell non-autonomous; genetic changes in a small group of cells can alter the lifespan of the whole organism. For example, worms that carry mutations in the insulin/IGF1 pathway in only a few cells are long-lived, and mice with a fat-specific insulin-receptor deficiency are also long-lived. Lipophilic hormones, including steroids, also modulate ageing in worms and flies. Related lipophilic hormones are present in mammals; however, the role of lipophilic hormones in regulating mammalian ageing has not yet been defined. A protein encoded by the Klotho gene can circulate in the blood and might function as a hormone. Overexpression of Klotho prolongs lifespan, possibly by altering insulin signalling. The regulation of lifespan by cell non-autonomous endocrine pathways might allow exploitation of the inherent specificity of hormone–receptor interactions to alter the ageing process. Mutations in genes that regulate endocrine signalling pathways can increase the lifespans of worms, flies and mammals. Endocrine pathways might therefore serve as targets for the manipulation of the ageing process and prevention of age-related diseases. Over the past 15 years it has become clear that mutations in genes that regulate endocrine signalling pathways can prolong lifespan. Lifespan can be increased by altered endocrine signalling in a group of cells or a single tissue, which indicates that crosstalk between tissues functions to coordinate ageing of the organism. These endocrine pathways might serve as targets for the manipulation of the ageing process and prevention of age-related diseases.

Aims/hypothesis Continuous glucose monitoring (CGM) improves glycaemic outcomes in the outpatient setting; however, there are limited data regarding CGM accuracy in hospital. Methods We conducted a prospective, observational study comparing CGM data from blinded Dexcom G6 Pro sensors with reference point of care and laboratory glucose measurements during participants’ hospitalisations. Key accuracy metrics included the proportion of CGM values within ±20% of reference glucose values >5.6 mmol/l or within ±1.1 mmol/l of reference glucose values ≤5.6 mmol/l (%20/20), the mean and median absolute relative difference between CGM and reference value (MARD and median ARD, respectively) and Clarke error grid analysis (CEGA). A retrospective calibration scheme was used to determine whether calibration improved sensor accuracy. Multivariable regression models and subgroup analyses were used to determine the impact of clinical characteristics on accuracy assessments. Results A total of 326 adults hospitalised on 19 medical or surgical non-intensive care hospital floors were enrolled, providing 6648 matched glucose pairs. The %20/20 was 59.5%, the MARD was 19.2% and the median ARD was 16.8%. CEGA showed that 98.2% of values were in zone A (clinically accurate) and zone B (benign). Subgroups with lower accuracy metrics included those with severe anaemia, renal dysfunction and oedema. Application of a once-daily morning calibration schedule improved accuracy (MARD 11.4%). Conclusions/interpretation The CGM accuracy when used in hospital may be lower than that reported in the outpatient setting, but this may be improved with appropriate patient selection and daily calibration. Further research is needed to understand the role of CGM in inpatient settings. Graphical Abstract

The safety and effectiveness of a continuous, day-and-night automated glycaemic control system using insulin and glucagon has not been shown in a free-living, home-use setting. We aimed to assess whether bihormonal bionic pancreas initialised only with body mass can safely reduce mean glycaemia and hypoglycaemia in adults with type 1 diabetes who were living at home and participating in their normal daily routines without restrictions on diet or physical activity. We did a random-order crossover study in volunteers at least 18 years old who had type 1 diabetes and lived within a 30 min drive of four sites in the USA. Participants were randomly assigned (1:1) in blocks of two using sequentially numbered sealed envelopes to glycaemic regulation with a bihormonal bionic pancreas or usual care (conventional or sensor-augmented insulin pump therapy) first, followed by the opposite intervention. Both study periods were 11 days in length, during which time participants continued all normal activities, including athletics and driving. The bionic pancreas was initialised with only the participant's body mass. Autonomously adaptive dosing algorithms used data from a continuous glucose monitor to control subcutaneous delivery of insulin and glucagon. The coprimary outcomes were the mean glucose concentration and time with continuous glucose monitoring (CGM) glucose concentration less than 3·3 mmol/L, analysed over days 2–11 in participants who completed both periods of the study. This trial is registered with ClinicalTrials.gov, number NCT02092220. We randomly assigned 43 participants between May 6, 2014, and July 3, 2015, 39 of whom completed the study: 20 who were assigned to bionic pancreas first and 19 who were assigned to the comparator first. The mean CGM glucose concentration was 7·8 mmol/L (SD 0·6) in the bionic pancreas period versus 9·0 mmol/L (1·6) in the comparator period (difference 1·1 mmol/L, 95% CI 0·7–1·6; p<0·0001), and the mean time with CGM glucose concentration less than 3·3 mmol/L was 0·6% (0·6) in the bionic pancreas period versus 1·9% (1·7) in the comparator period (difference 1·3%, 95% CI 0·8–1·8; p<0·0001). The mean nausea score on the Visual Analogue Scale (score 0–10) was greater during the bionic pancreas period (0·52 [SD 0·83]) than in the comparator period (0·05 [0·17]; difference 0·47, 95% CI 0·21–0·73; p=0·0024). Body mass and laboratory parameters did not differ between periods. There were no serious or unexpected adverse events in the bionic pancreas period of the study. Relative to conventional and sensor-augmented insulin pump therapy, the bihormonal bionic pancreas, initialised only with participant weight, was able to achieve superior glycaemic regulation without the need for carbohydrate counting. Larger and longer studies are needed to establish the long-term benefits and risks of automated glycaemic management with a bihormonal bionic pancreas. National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health, and National Center for Advancing Translational Sciences.

To test whether safe and effective glycemic control could be achieved in type 1 diabetes using a bihormonal bionic endocrine pancreas driven by a continuous glucose monitor in experiments lasting more than two days and including six high-carbohydrate meals and exercise as challenges to glycemic control. Six subjects with type 1 diabetes and no endogenous insulin secretion participated in two 51-h experiments. Blood glucose was managed with a bionic endocrine pancreas controlling subcutaneous delivery of insulin and glucagon with insulin pumps. A partial meal-priming bolus of insulin (0.035 units/kg/meal, then 0.05 units/kg/meal in repeat experiments) was administered at the beginning of each meal (on average 78 ± 12 g of carbohydrates per meal were consumed). Plasma glucose (PG) control was evaluated with a reference quality measurement on venous blood every 15 min. The overall mean PG was 158 mg/dL, with 68% of PG values in the range of 70-180 mg/dL. There were no significant differences in mean PG between larger and smaller meal-priming bolus experiments. Hypoglycemia (PG <70 mg/dL) was rare, with eight incidents during 576 h of closed-loop control (0.7% of total time). During 192 h of nighttime control, mean PG was 123 mg/dL, with 93% of PG values in the range of 70-180 mg/dL and only one episode of mild hypoglycemia (minimum PG 62 mg/dL). A bihormonal bionic endocrine pancreas achieved excellent glycemic control with minimal hypoglycemia over the course of two days of continuous use despite high-carbohydrate meals and exercise. A trial testing a wearable version of the system under free-living conditions is justified.