Nucleus accumbens volume is related to obesity measures in an age‐dependent fashion

Motivation theories of obesity suggest that one of the brain mechanisms underlying pathological eating and weight gain is the dysregulation of dopaminergic circuits. While these dysregulations occur likely at the microscopic level, studies on gray matter volume reported macroscopic differences associated with obesity. One region suggested to play a key role in the pathophysiology of obesity is the nucleus accumbens (NAcc). We performed a meta‐analysis of findings regarding NAcc volume and overweight/obesity. We additionally examined whether gray matter volume in the NAcc and other mesolimbic areas depends on the longitudinal trajectory of obesity, using the UK Biobank dataset. To this end, we analysed the data using a latent growth model, which identifies whether certain variables of interest (e.g. NAcc volume) is related to another variable's (BMI) initial values or longitudinal trajectories. Our meta‐analysis showed that, overall, NAcc volume is positively related to BMI. However, further analyses revealed that the relationship between NAcc volume and BMI is dependent on age. For younger individuals such relationship is positive, while for older adults it is negative. This was corroborated by our analysis in the UK Biobank dataset, which includes older adults, where we found that higher BMI was associated with lower NAcc and thalamus volume. Overall, our study suggests that increased NAcc volume in young age might be a vulnerability factor for obesity, while in the older age decreased NAcc volume with increased BMI might be an effect of prolonged influences of neuroinflammation on the brain

The Constructability of the Cheops Pyramid

Abstract The aim of this paper is to forecast the methodology by which Cheops Pyramid as a historic building was built, based on notions of modular patterns discovered within the following planar illustrations, starting at the apex and descending to its grand base. Some of Cheops’ heritage in terms of form and function has existed for millennia, as its mark was recapped with a front line that was constructed thousands of years before. Such a voyage through the missing captures of the building techniques wouldn’t have occurred without the incidental outcome that resulted from overlaying the various pixelated plans of block arrangements on the floor maps of Cheops. This building is believed to exhibit norms similar to those governing the balance between matter and void in the universe. By assessing this historical masonry structure of Giza, we have come to find some regulatory approaches concerning how to asses the construction of such a building by predicting their interiors, spatial definitions, customs, and layouts. As there are no major records of their plans, the best practice anticipated in this paper is to modularize the figurative appearance of such buildings, by imitating themes of the repetitive patterns of past regional Egyptian architecture seen as pixels. This led to the fundamental solution to such a dilemma in building construction. Keywords: Cheops, Pyramid, Balance, Historical Building

Tamm-Horsfall Protein Regulates Mononuclear Phagocytes in the Kidney

Tamm-Horsfall protein (THP), also known as uromodulin, is a kidney-specific protein produced by cells of the thick ascending limb of the loop of Henle. Although predominantly secreted apically into the urine, where it becomes highly polymerized, THP is also released basolaterally, toward the interstitium and circulation, to inhibit tubular inflammatory signaling. Whether, through this latter route, THP can also regulate the function of renal interstitial mononuclear phagocytes (MPCs) remains unclear, however. Here, we show that THP is primarily in a monomeric form in human serum. Compared with wild-type mice, THP-/- mice had markedly fewer MPCs in the kidney. A nonpolymerizing, truncated form of THP stimulated the proliferation of human macrophage cells in culture and partially restored the number of kidney MPCs when administered to THP-/- mice. Furthermore, resident renal MPCs had impaired phagocytic activity in the absence of THP. After ischemia-reperfusion injury, THP-/- mice, compared with wild-type mice, exhibited aggravated injury and an impaired transition of renal macrophages toward an M2 healing phenotype. However, treatment of THP-/- mice with truncated THP after ischemia-reperfusion injury mitigated the worsening of AKI. Taken together, our data suggest that interstitial THP positively regulates mononuclear phagocyte number, plasticity, and phagocytic activity. In addition to the effect of THP on the epithelium and granulopoiesis, this new immunomodulatory role could explain the protection conferred by THP during AKI

Nucleus accumbens volume is related to obesity measures in an age‐dependent fashion

Motivation theories of obesity suggest that one of the brain mechanisms underlying pathological eating and weight gain is the dysregulation of dopaminergic circuits. While these dysregulations occur likely at the microscopic level, studies on gray matter volume reported macroscopic differences associated with obesity. One region suggested to play a key role in the pathophysiology of obesity is the nucleus accumbens (NAcc). We performed a meta‐analysis of findings regarding NAcc volume and overweight/obesity. We additionally examined whether gray matter volume in the NAcc and other mesolimbic areas depends on the longitudinal trajectory of obesity, using the UK Biobank dataset. To this end, we analysed the data using a latent growth model, which identifies whether certain variables of interest (e.g. NAcc volume) is related to another variable's (BMI) initial values or longitudinal trajectories. Our meta‐analysis showed that, overall, NAcc volume is positively related to BMI. However, further analyses revealed that the relationship between NAcc volume and BMI is dependent on age. For younger individuals such relationship is positive, while for older adults it is negative. This was corroborated by our analysis in the UK Biobank dataset, which includes older adults, where we found that higher BMI was associated with lower NAcc and thalamus volume. Overall, our study suggests that increased NAcc volume in young age might be a vulnerability factor for obesity, while in the older age decreased NAcc volume with increased BMI might be an effect of prolonged influences of neuroinflammation on the brain

Multivariate analysis reveals shared genetic architecture of brain morphology and human behavior.

Human variation in brain morphology and behavior are related and highly heritable. Yet, it is largely unknown to what extent specific features of brain morphology and behavior are genetically related. Here, we introduce a computationally efficient approach for multivariate genomic-relatedness-based restricted maximum likelihood (MGREML) to estimate the genetic correlation between a large number of phenotypes simultaneously. Using individual-level data (N = 20,190) from the UK Biobank, we provide estimates of the heritability of gray-matter volume in 74 regions of interest (ROIs) in the brain and we map genetic correlations between these ROIs and health-relevant behavioral outcomes, including intelligence. We find four genetically distinct clusters in the brain that are aligned with standard anatomical subdivision in neuroscience. Behavioral traits have distinct genetic correlations with brain morphology which suggests trait-specific relevance of ROIs. These empirical results illustrate how MGREML can be used to estimate internally consistent and high-dimensional genetic correlation matrices in large datasets

Submucosal Tunnel Endoscopic Resection of Gastric Lesion Before Obesity Surgery: a Case Series

Background: Submucosal tumors (SMTs) of the gastrointestinal tract are a rare pathological entity comprising a wide variety of neoplastic and non-neoplastic lesions. Even if most SMTs are benign tumors (e.g., leiomyomas), a smaller portion may have a malignant potential (e.g., gastrointestinal stromal tumor (GIST)). Preoperative diagnosis of SMT in bariatric patients may arise challenging clinical dilemmas. Long-term surveillance may be difficult after bariatric surgery. Moreover, according to SMT location, its presence may interfere with planned surgery. Submucosal tunneling endoscopic resection (STER) has emerged as an effective approach for minimally invasive en bloc excision of SMTs. This is the first case series of STER for SMTs before bariatric surgery. Methods: Seven female patients underwent STER for removal of SMTs before bariatric surgery. All lesions were incidentally diagnosed at preoperative endoscopy. STER procedural steps comprised mucosal incision, submucosal tunneling, lesion enucleation, and closure of mucosal defect. Results: En bloc removal of SMT was achieved in all cases. Mean procedural time was of 45 min (SD 18.6). No adverse event occurred. Mean size of the lesions was 20.6 mm (SD 5.8). Histological diagnoses were 5 leyomiomas, 1 lipoma, and 1 low grade GIST. Bariatric procedure was performed after a mean period of 4.1 months (SD 1.6) from endoscopic resection. Conclusion: STER is a safe and effective treatment for the management of SMT even in bariatric patients awaiting surgery. Preoperative endoscopic resection of SMTs has the advantages of reducing the need for surveillance and removing lesions that could interfere with planned surgery. STER did not altered accomplishment of bariatric procedures

Genome-wide footprints in the carob tree (Ceratonia siliqua) unveil a new domestication pattern of a fruit tree in the Mediterranean

Intense research efforts over the last two decades have renewed our understanding of plant phylogeography and domestication in the Mediterranean basin. Here we aim to investigate the evolutionary history and the origin of domestication of the carob tree (Ceratonia siliqua), which has been cultivated for millennia for food and fodder. We used >1000 microsatellite genotypes to delimit seven carob evolutionary units (CEUs). We investigated genome-wide diversity and evolutionary patterns of the CEUs with 3557 single nucleotide polymorphisms generated by restriction-site associated DNA sequencing (RADseq). To address the complex wild vs. cultivated status of sampled trees, we classified 56 sampled populations across the Mediterranean basin as wild, seminatural or cultivated. Nuclear and cytoplasmic loci were identified from RADseq data and separated for analyses. Phylogenetic analyses of these genomic-wide data allowed us to resolve west-to-east expansions from a single long-term refugium probably located in the foothills of the High Atlas Mountains near the Atlantic coast. Our findings support multiple origins of domestication with a low impact on the genetic diversity at range-wide level. The carob was mostly domesticated from locally selected wild genotypes and scattered long-distance westward dispersals of domesticated varieties by humans, concomitant with major historical migrations by Romans, Greeks and Arabs. Ex situ efforts to preserve carob genetic resources should prioritize accessions from both western and eastern populations, with emphasis on the most differentiated CEUs situated in southwest Morocco, south Spain and eastern Mediterranean. Our study highlights the relevance of wild and seminatural habitats in the conservation of genetic resources for cultivated trees

Francisella tularensis Transmission by Solid Organ Transplantation, 20171.

In July 2017, fever and sepsis developed in 3 recipients of solid organs (1 heart and 2 kidneys) from a common donor in the United States; 1 of the kidney recipients died. Tularemia was suspected only after blood cultures from the surviving kidney recipient grew Francisella species. The organ donor, a middle-aged man from the southwestern United States, had been hospitalized for acute alcohol withdrawal syndrome, pneumonia, and multiorgan failure. F. tularensis subsp. tularensis (clade A2) was cultured from archived spleen tissue from the donor and blood from both kidney recipients. Whole-genome multilocus sequence typing indicated that the isolated strains were indistinguishable. The heart recipient remained seronegative with negative blood cultures but had been receiving antimicrobial drugs for a medical device infection before transplant. Two lagomorph carcasses collected near the donor's residence were positive by PCR for F. tularensis subsp. tularensis (clade A2). This investigation documents F. tularensis transmission by solid organ transplantation