Identification and molecular cytogenetic characterization of a novel complex Y chromosome rearrangement in a boy with disorder of sexual development

Ambiguous genitalia or disorder of the sexual development is a birth defect where the external genitals do not have the typical appearance of either a male or female. Here we report a boy with ambiguous genitalia and short stature. The cytogenetic analysis by G-banding revealed a small Y chromosome and an additional material on the 15p arm. Further, molecular cytogenetic analysis by Fluorescence in situ hybridization (FISH) using whole chromosome paint probes showed the presence of Y sequences on the 15p arm, confirming that it is a Y;15 translocation. Subsequent, FISH with centromere probe Y showed two signals depicting the presence of two centromeres and differing with a balanced translocation. The dicentric nature of the derivative 15 chromosome was confirmed by FISH with both 15 and Y centromeric probes. Further, the delineation of the Y chromosomal DNA was also done by quantitative real time PCR. Additional Y-short tandem repeat typing was performed to find out the extent of deletion on small Y chromosome. Fine mapping was carried out with 8 Y specific BAC clones which helped in defining the breakpoint regions. MLPA was performed to check the presence or absence of subtelomeric regions and SHOX regions on Y. Finally array CGH helped us in confirming the breakpoint regions. In our study we identified and characterized a novel complex Y chromosomal rearrangement with a complete deletion of the Yq region and duplication of the Yp region with one copy being translocated onto the15p arm. This is the first report of novel and unique Y complex rearrangement showing a deletion, duplication and a translocation in the same patient. The possible mechanism of the rearrangement and the phenotype–genotype correlation are discussed.     

Schistosoma mansoni: SmLIMPETin, a member of a novel family of invertebrate-only regulatory proteins

Eukaryotic LIM domain proteins contain zinc finger forming motifs rich in cysteine and histidine that enable them to interact with other proteins. A cDNA clone isolated from an adult schistosome cDNA library revealed a sequence that coded for a novel class of proteins bearing 6 LIM domains and an N-terminal PET domain, SmLIMPETin. Phylogeny reconstruction of SmLIMPETin and comparison of its sequence to invertebrate homologues and to the vertebrate four-and-a-half LIM domains protein family (FHLs), uncovered a novel LIM domain protein family, the invertebrate LIM and PET domain protein family (LIMPETin). Northern blots, RT-PCR and Western blot showed that SmLIMPETin gene was less expressed in sexually mature adult females compared to sexually immature adult females and sexually mature and immature adult males, and not expressed in schistosomula.     

Evolutionary history and climate conditions constrain the flower colours of woody plants in China

进化历史和气候条件共同影响中国木本植物花色的分布 本研究以中国木本植物为研究对象,主要探讨两个问题：(1)不同生活型物种花色组成的差异;(2)生物地理区、进化年龄和气候条件对不同花色地理分布格局的影响。研究使用7673种木本植物的物种分布数据和花色信息(分为白色、红色、黄色、黄绿色、绿色和蓝紫色),并结合属级系统进化树来比较不同生活型(包括灌木、乔木和藤本)物种花色组成的差异,分析不同生物地理区、进化年龄和现代气候对花色地理格局的影响。研究结果表明,与乔木和藤本植物相比,灌木具有更高比例 的由花青素着色的红色花和蓝紫色花物种。中国木本植物的花色地理格局受到区域效应和现代气候(尤其是降水和UVB辐射)的共同影响。倾向于蜂媒传粉的黄色花和蓝紫色花物种和由花青素着色、耐环境胁迫的红色花和蓝紫色花物种比例在中国西北部地区更高。绿色花物种的进化起源更早,但进化时间对花色地理格局的解释力很弱。这些结果说明中国木本植物花色的地理格局受到进化历史和现代环境的共同影响。     

Analyses of non-leucine-rich repeat (non-LRR) regions intervening between LRRs in proteins

Background

Many proteins have LRR (leucine-rich repeat) units interrupted by non-LRRs which we call IR (non-LRR island region).

Methods

We identified proteins containing LRR@IRs (LRRs having IR) by using a new method and then analyzed their natures and distributions.

Results

LRR@IR proteins were found in over two hundred proteins from prokaryotes and from eukaryotes. These are divided into twenty-one different protein families. The IRs occur one to four times in LRR regions and range in length from 5 to 11,265 residues. The IR lengths in Fungi adenylate cyclases (acys) range from 5 to 116 residues; there are 22 LRR repeats. The IRs in Leishmania proteophosphoglycans (ppgs) vary from 105 to 11,265 residues. These results indicate that the IRs evolved rapidly. A group of LRR@IR proteins—LRRC17, chondroadherin-like protein, ppgs, and four Pseudomonas proteins—have a super motif consisting of an LRR block and its adjacent LRR@IR region. This indicates that the entire super motif experienced duplication. The sequence analysis of IRs offers functional similarity in some LRR@IR protein families.

General significance

This study suggests that various IRs and super motifs provide a great variety of structures and functions for LRRs.     

Binding and Functional Folding (BFF): A Physiological Framework for Studying Biomolecular Interactions and Allostery

EF-hand Ca²⁺-binding proteins (CBPs), such as S100 proteins (S100s) and calmodulin (CaM), are signaling proteins that undergo conformational changes upon increasing intracellular Ca²⁺. Upon binding Ca²⁺, S100 proteins and CaM interact with protein targets and induce important biological responses. The Ca²⁺-binding affinity of CaM and most S100s in the absence of target is weak (^CaK_D > 1 μM). However, upon effector protein binding, the Ca²⁺ affinity of these proteins increases via heterotropic allostery (^CaK_D < 1 μM). Because of the high number and micromolar concentrations of EF-hand CBPs in a cell, at any given time, allostery is required physiologically, allowing for (i) proper Ca²⁺ homeostasis and (ii) strict maintenance of Ca²⁺-signaling within a narrow dynamic range of free Ca²⁺ ion concentrations, [Ca²⁺]^free. In this review, mechanisms of allostery are coalesced into an empirical “binding and functional folding (BFF)” physiological framework. At the molecular level, folding (F), binding and folding (BF), and BFF events include all atoms in the biomolecular complex under study. The BFF framework is introduced with two straightforward BFF types for proteins (type 1, concerted; type 2, stepwise) and considers how homologous and nonhomologous amino acid residues of CBPs and their effector protein(s) evolved to provide allosteric tightening of Ca²⁺ and simultaneously determine how specific and relatively promiscuous CBP-target complexes form as both are needed for proper cellular function.     

Oplopane Sesquiterpenes from Ligularia knorringiana and Their Anti‐Complementary Activity

Three new oplopane sesquiterpenes, knorringianalarins D – F ( 1 – 3 , respectively), and five known analogues ( 4 – 8 , respectively), were isolated from the roots and rhizomes of Ligularia knorringiana. The structures of three new compounds were identified as 4‐acetoxy‐11α,12‐epoxy‐2β‐hydroxy‐3β‐(2‐methylbutyryloxy)‐9α‐(4‐methylsenecioyloxy)oplop‐10(14)‐ene ( 1 ), 3β,4‐diacetoxy‐9α‐(4‐acetoxy‐4‐methylsenecioyloxy)‐11α,12‐epoxy‐8α‐(2‐methylbutyryloxy)oplop‐10(14)‐ene ( 2 ), and (1R,5R,6R,7R,9R)‐5,9,11‐trihydroxy‐4,15‐dinoroplop‐10(14)‐en‐3‐one ( 3 ) based on spectroscopic methods including 1D‐ and 2D‐NMR, mass spectrometry, and CD spectroscopy techniques. All compounds were evaluated for their anti‐complementary activity on the classical pathway of the complement system in vitro. Among which, three oplopane sesquiterpenes ( 3 , 7 , and 8 ) exhibited better anti‐complementary effects with CH₅₀ values ranging from 0.33 to 0.89 mm , which are plausible candidates for developing potent anti‐complementary agents.