UNASSIGNED: Hemorrhoids (HEM) are the most common perianal disease, but current observational studies have yielded inconsistent results in investigating the risk factors. Our further exploration of the risk factors will help prevent the disease.
UNASSIGNED: We conducted a two-sample bidirectional Mendelian randomization (MR) analysis using publicly available genome-wide association studies (GWAS) statistics from multiple consortia. The inverse-variance weighted (IVW) method was used for the primary analysis. We applied four complementary methods, including weighted median, weighted mode, MR-Egger regression, and Cochrane\'s Q value, to detect and correct the effects of horizontal pleiotropy.
UNASSIGNED: Genetically determined constipation (OR = 0.97, 95% CI: 0.91-1.03, P = 0.28) and diarrhea (OR = 1.00, 95% CI: 0.99-1.01, P = 0.90) did not have a causal effect on HEM but stool frequency (OR = 1.28, 95% CI: 1.05-1.55, P = 0.01), waist-to-hip ratio adjusted for BMI (OR = 1.11, 95% CI: 1.06-1.64, P = 1.59×10-5), and order Burkholderiales (OR = 1.09, 95% CI = 1.04-1.14, p = 1.63×10-4) had a causal effect on. Furthermore, we found a significant causal effect of constipation on HEM in the reverse MR analysis (OR = 1.21, 95% CI: 1.13-1.28, P = 3.72×10-9). The results of MR-Egger regression, Weighted Median, and Weighted Mode methods were consistent with those of the IVW method. Horizontal pleiotropy was unlikely to distort the causal estimates, as indicated by the sensitivity analysis.
UNASSIGNED: Our MR analysis reveals a causal association between stool frequency and waist-to-hip ratio with HEM, despite variations in results reported by observational studies. Unexpectedly, we found a relationship between the order Burkholderiales in the gut flora and HEM, although the mechanism is unclear.

In this study, ionic liquids were used for the selective extraction/isolation of hemoglobin from human serum for cotinine determination using the ELISA Kit. The suitability of hydrophobic imidazolium-based ionic liquids was tested, of which OMIM BF4 (1-methyl-3-octylimidazolium tetrafluoroborate) turned out to be the most suitable for direct extraction of hemoglobin into an ionic liquid without the use of any additional reagent at one extraction step. Hemoglobin was separated quantitatively (95% recovery) from the remaining types of proteins remaining in the aqueous phase. Quantum mechanical calculations showed that the interaction of the iron atom in the heme group and the nitrogen atom of the ionic liquid cation is responsible for the transfer of hemoglobin whereas molecular dynamics simulations demonstrated that the non-covalent interactions between heme and solvent are more favorable in the case of OMIM BF4 in comparison to water. The opposite trend was found for cotinine. Selective isolation of the heme/hemoglobin improved the ELISA test\'s accuracy, depending on the cotinine level, from 15% to 30%.

Proteins of the Wiskott-Aldrich syndrome protein (WASP) family play a central role in regulating actin cytoskeletal dynamics in a wide range of cellular processes. Genetic mutations or misregulation of these proteins are tightly associated with many diseases. The WASP-family proteins act by transmitting various upstream signals to their conserved WH2-Central-Acidic (WCA) peptide sequence at the C-terminus, which in turn binds to the Arp2/3 complex to stimulate the formation of branched actin networks at membranes. Despite this common feature, the regulatory mechanisms and cellular functions of distinct WASP-family proteins are very different. Here, we summarize and clarify our current understanding of WASP-family proteins and how disruption of their functions is related to human disease.

The functions of the hippocampus are conserved between birds and mammals; however, it is not known whether similar mechanisms are responsible for its development in these two classes. In mammals, hippocampus development is known to be regulated by the hem organizer. Here, we have identified that, in birds, Wnt7b secreted from the hem is sufficient for inducing the expression of hippocampal markers. Furthermore, we have demonstrated that a microRNA, miR-19b, which is selectively excluded from the hem region, is necessary and sufficient for restricting the expression of Wnt7b to the hem. This study suggests that the role of the Wnt signal emanating from the hem is conserved between birds and mammals, and that a microRNA-based mechanism is crucial for determining the position of the hippocampus.

During forebrain development, a telencephalic organizer called the cortical hem is crucial for inducing hippocampal fate in adjacent cortical neuroepithelium. How the hem is restricted to its medial position is therefore a fundamental patterning issue. Here, we demonstrate that Foxg1-Lhx2 interactions are crucial for the formation of the hem. Loss of either gene causes a region of the cortical neuroepithelium to transform into hem. We show that FOXG1 regulates Lhx2 expression in the cortical primordium. In the absence of Foxg1, the presence of Lhx2 is sufficient to suppress hem fate, and hippocampal markers appear selectively in Lhx2-expressing regions. FOXG1 also restricts the temporal window in which loss of Lhx2 results in a transformation of cortical primordium into hem. Therefore, Foxg1 and Lhx2 form a genetic hierarchy in the spatiotemporal regulation of cortical hem specification and positioning, and together ensure the normal development of this hippocampal organizer.

Patterning of the telencephalic neuroepithelium is a tightly regulated process controlled by transcription factors and signalling molecules. The cortical primordium is flanked by two signalling centres, the hem medially, and the antihem laterally. The hem induces the formation of the hippocampus in adjacent neuroepithelium. Therefore, the position of the hem defines the position of the hippocampus in the brain. The antihem is positioned at the boundary between the dorsal and ventral telencephalon and proposed to provide patterning cues during development. LIM-homeodomain (LIM-HD) transcription factor LHX2 suppresses both hem and antihem fate in the cortical neuroepithelium. Upon loss of Lhx2, medial cortical neuroepithelium is transformed into hem, whereas lateral cortical neuroepithelium is transformed into antihem. Here, we show that transcription factor PAX6, known to regulate patterning of the lateral telencephalon, restricts this tissue from transforming into hem upon loss of Lhx2. When Lhx2 and Pax6 are both deleted, the cortical hem expands to occupy almost the complete extent of the cortical primordium, indicating that both factors act to suppress hem fate in the lateral telencephalon. Furthermore, the shift in the pallial-subpallial boundary and absence of the antihem, observed in the Pax6 mutant, are both restored in the Lhx2; Pax6 double mutant. Together, these results not only reveal a novel function for LHX2 in regulating dorsoventral patterning in the telencephalon, but also identify PAX6 as a fundamental regulator of where the hem can form, and therefore implicate this molecule as a determinant of hippocampal positioning.

Together with a complex variety of behavioral, physiological, morphological, and neurobiological innovations, mammals are characterized by the development of an extensive isocortex (also called neocortex) that is both laminated and radially organized, as opposed to the brain of birds and reptiles. In this article, we will advance a developmental hypothesis in which the mechanisms of evolutionary brain growth remain partly conserved across amniotes (mammals, reptiles and birds), all based on Pax6 signaling or related morphogens. Despite this conservatism, only in mammals there is an additional upregulation of dorsal and anterior signaling centers (the cortical hem and the anterior forebrain, respectively) that promoted a laminar and a columnar structure into the neocortex. It is possible that independently, some birds also developed an upregulated dorsal pallium.

Bacteria that reside in animal tissues and/or cells must acquire iron from their host. However, almost all of the host iron is sequestered in iron-containing compounds and proteins, the majority of which is found within heme molecules. Thus, likely iron sources for bacterial pathogens (and non-pathogenic symbionts) are free heme and heme-containing proteins. Furthermore, the cellular location of the bacterial within the host (intra or extracellular) influences the amount and nature of the iron containing compounds available for transport. The low level of free iron in the host, coupled with the presence of numerous different heme sources, has resulted in a wide range of high-affinity iron acquisition strategies within bacteria. However, since excess iron and heme are toxic to bacteria, expression of these acquisition systems is highly regulated. Precise expression in the correct host environment at the appropriate times enables heme iron acquisitions systems to contribute to the growth of bacterial pathogens within the host. This mini-review will highlight some of the recent findings in these areas for gram-negative pathogens.