Odd-paired controls frequency doubling in Drosophila segmentation by altering the pair-rule gene regulatory network

The Drosophila embryo transiently exhibits a double-segment periodicity, defined by the expression of seven 'pair-rule' genes, each in a pattern of seven stripes. At gastrulation, interactions between the pair-rule genes lead to frequency doubling and the patterning of 14 parasegment boundaries. In contrast to earlier stages of Drosophila anteroposterior patterning, this transition is not well understood. By carefully analysing the spatiotemporal dynamics of pair-rule gene expression, we demonstrate that frequency-doubling is precipitated by multiple coordinated changes to the network of regulatory interactions between the pair-rule genes. We identify the broadly expressed but temporally patterned transcription factor, Odd-paired (Opa/Zic), as the cause of these changes, and show that the patterning of the even-numbered parasegment boundaries relies on Opa-dependent regulatory interactions. Our findings indicate that the pair-rule gene regulatory network has a temporally modulated topology, permitting the pair-rule genes to play stage-specific patterning roles.This work was supported by a BBSRC PhD studentship to Erik Clark

Inference of Temporally Varying Bayesian Networks

When analysing gene expression time series data an often overlooked but crucial aspect of the model is that the regulatory network structure may change over time. Whilst some approaches have addressed this problem previously in the literature, many are not well suited to the sequential nature of the data. Here we present a method that allows us to infer regulatory network structures that may vary between time points, utilising a set of hidden states that describe the network structure at a given time point. To model the distribution of the hidden states we have applied the Hierarchical Dirichlet Process Hideen Markov Model, a nonparametric extension of the traditional Hidden Markov Model, that does not require us to fix the number of hidden states in advance. We apply our method to exisiting microarray expression data as well as demonstrating is efficacy on simulated test data

The role of Adipocytokines, Vitamin D, and C in Colorectal Cancer

يعد سرطان القولون و المستقيم ثالث أكثر الأورام الخبيثة انتشارًا في العالم ورابع أكثر أنواع السرطانات شيوعًا في العراق. اللبتين و الأديبونكتين هما نوعان من السيتوكينات الشحمية الرئيسية التي تنتجها الخلايا الدهنية التي لها تأثيرات معاكسة على تكوين أورام القولون والمستقيم. اللبتين يحفز نمو الورم وانتشاره، بينما الأديبونكتين يمنع نمو الورم. ١،٢٥- ديهيدروكسي فيتامين د يتحكم ويحد من تكاثر الخلايا السرطانية والتمايز والبقاء على قيد الحياة. من ناحية أخرى، تم اكتشاف نقص فيتامين سي بانتظام في الأنسجة السرطانية وله خصائص قوية مضادة للسرطان. الغرض من هذه الدراسة هو تقييم التأثير الكيميائي الحيوي لمستويات أديبوسيتوكينات (اللبتين والأديبونكتين) في الدورة الدموية، وكذلك التأثيرات المضادة للسرطان لفيتامينات د وسي في مرضى سرطان القولون و المستقيم العراقيين. يركز البحث على الحالات المؤكدة المصابة بسرطان القولون والمستقيم الذين شوهدوا في مستشفى ناناكالي لأمراض الدم والسرطان في أربيل قبل جلسات العلاج. تم تشخيص ٣٥ مريضا المؤكد إصابتهم بسرطان القولون و المستقيم و ٣٦ شخصا من الاصحاء كمجموعة ضابطة المتطابقين من العمر والجنس و مؤشر كتلة الجسم. تم استخدام تقنية إليزأ لقياس مستويات اللبتين، الأديبونكتين، فيتامين د وفيتامين سي في المصل. أظهرت النتائج زيادة معنوية (ف القيمة<0,001) في مستوى الأديبونكتين (١،٥٩±١٢،٠٦) في دم المصابين بسرطان القولون و المستقيم بالنسبة إلى مستوياته في مجموعة ضابطة (٩٦، ٠± ٠٥، ٢). على العكس من ذلك، كان مستوى اللبتين في المصل أقل بشكل ملحوظ(ف القيمة<0,098) في مرضى سرطان القولون والمستقيم (٢،٩٢±٢٤،٠٩)مقارنة بمجموعة الضوابط (٥٤ ،١±٨٤ ،٥٣). علاوة على ذلك، كانت مستويات فيتامين د في الدم (١٣،١٤ ± ١،٢١) و فيتامين سي (١،٠٣ ± ٠،١)  في مرضى سرطان القولون و المستقيم أقل بشكل ملحوظ (ف القيمة<0,001) مقارنة بمجموعة الضوابط (٢٤،٤٩ ± ١،٤٧ & ٥،٧٨ ± ٢،١٦)، على التوالي. وتشير نتائج الدراسة الحالية إلى دور كيميائي حيوي الحتمي لـأديبوسيتوكينات (اللبتين و الأديبونكتين) و خلل الأنسجة الدهنية في التسبب في مرضى سرطان القولون و المستقيم. إلى جانب ذلك، فإن انخفاض مستويات فيتامين د و سي في المصل يضعف آثارهما القوية المضادة للأورام ويسمح بالبقاء على قيد الحياة وتطور الأورام الخبيثة في القولون والمستقيم. وكما أن نتائج الدراسة الحالية تظهر أن (اللبتين والأديبونكتين) عوامل تنبؤية وخطورة قوية لمرض سرطان القولون والمستقيم. بالإضافة إلى أن نقص فيتامين د وفيتامين سي يعتبر من عوامل الخطر الرئيسية بين مرضى سرطان القولون والمستقيم العراقيين.Colorectal cancer is the world's 3rd most frequent malignant neoplasm and the 4th most common cancer in Iraq. Leptin and Adiponectin are two major Adipocytokines produced by adipose cells that have opposite effects on the formation of colorectal tumors. Leptin induces tumor growth and metastasis, whereas Adiponectin inhibits it. 1,25-Dihydroxyvitamin D controls and limits cancer cell proliferation, differentiation, and survival. Vitamin C deficiency, on the other hand, has been regularly detected in cancer tissues and has potent anti-cancer properties. The purpose of this study was to look at the biochemical role of circulatory Adipocytokine levels (Adiponectin and Leptin) as well as the anti-cancer potentials of Vitamin D and C in CRC patients from Iraq. The research looked at confirmed cases of CRC who were seen at Nanakali Hospital for Blood diseases and Cancer in Erbil before their treatment sessions. A total of 35 patients with confirmed CRC cases and 36 healthy participants who were age, gender, and BMI matched were recruited. ELISA technique was used to quantify serum levels of Adiponectin, Leptin, Vitamin D, & C. The results showed a significant increase (P<0.0001) of serum Adiponectin levels (12.06±1.59) in CRC patients relative to the controls (2.05±0.96). On the contrary, the serum Leptin levels (24.09±2.92) were non-significantly lower (P=0.098) in CRC patients in comparison to controls (53.84±1.54). Furthermore, serum Vitamin D (13.14±1.21) and Vitamin C (1.03±0.10) levels in CRC patients were significantly lower (P<0.0001) when compared to controls (24.49±1.47, 5.78±2.16), respectively. The findings in the current study suggest an imperative biochemical role of Adipocytokines (Adiponectin and Leptin) and Adipose tissue dysfunction in the pathogenesis of CRC patients. Furthermore, decreased serum levels of Vitamin D and C reduce their effective anti-cancer effects, allowing Colorectal malignant neoplasms to survive and develop. Thus, the present study findings suggest Adiponectin and Leptin as potent prognostic and risk factors of CRCs. Also, Vitamin D and C deficiencies are the major risk factors among Iraqi CRC patients

Gene circuit analysis of the terminal gap gene <i>huckebein</i>

The early embryo of Drosophila melanogaster provides a powerful model system to study the role of genes in pattern formation. The gap gene network constitutes the first zygotic regulatory tier in the hierarchy of the segmentation genes involved in specifying the position of body segments. Here, we use an integrative, systems-level approach to investigate the regulatory effect of the terminal gap gene huckebein (hkb) on gap gene expression. We present quantitative expression data for the Hkb protein, which enable us to include hkb in gap gene circuit models. Gap gene circuits are mathematical models of gene networks used as computational tools to extract regulatory information from spatial expression data. This is achieved by fitting the model to gap gene expression patterns, in order to obtain estimates for regulatory parameters which predict a specific network topology. We show how considering variability in the data combined with analysis of parameter determinability significantly improves the biological relevance and consistency of the approach. Our models are in agreement with earlier results, which they extend in two important respects: First, we show that Hkb is involved in the regulation of the posterior hunchback (hb) domain, but does not have any other essential function. Specifically, Hkb is required for the anterior shift in the posterior border of this domain, which is now reproduced correctly in our models. Second, gap gene circuits presented here are able to reproduce mutants of terminal gap genes, while previously published models were unable to reproduce any null mutants correctly. As a consequence, our models now capture the expression dynamics of all posterior gap genes and some variational properties of the system correctly. This is an important step towards a better, quantitative understanding of the developmental and evolutionary dynamics of the gap gene network

Does visual flicker phase at gamma frequency modulate neural signal propagation and stimulus selection?

Oscillatory synchronization of neuronal populations has been proposed to play a role in perceptual integration and attentional processing. However, some conflicting evidence has been found with respect to its causal relevance for sensory processing, particularly when using flickering visual stimuli with the aim of driving oscillations. We tested psychophysically whether the relative phase of gamma frequency flicker (60 Hz) between stimuli modulates well-known facilitatory lateral interactions between collinear Gabor patches (Experiment 1) or crowding of a peripheral target by irrelevant distractors (Experiment 2). Experiment 1 assessed the impact of suprathreshold Gabor flankers on detection of a near-threshold central Gabor target (“Lateral interactions paradigm”). The flanking stimuli could flicker either in phase or in anti-phase with each other. The typical facilitation of target detection was found with collinear flankers, but this was unaffected by flicker phase. Experiment 2 employed a “crowding” paradigm, where orientation discrimination of a peripheral target Gabor patch is disrupted when surrounded by irrelevant distractors. We found the usual crowding effect, which declined with spatial separation, but this was unaffected by relative flicker phase between target and distractors at all separations. These results imply that externally driven manipulations of gamma frequency phase cannot modulate perceptual integration in vision

Preparation and Characterization of Organic Nanoparticles of Oxadiazole Derivative in Aqueous Media

A novel  oxadiazole derivative, 2,5-disubstituted-1,3,4-oxadiazole (Z)-4-((1-(5-(4-hydroxyphenyl)-1,3,4-oxadiazol-2-yl)prop-1-en-2-yl)amino)-1,5-dimethyl-2-phenyl-1H-pyrazol-3(2H)-one (HOPA) was synthesized from reaction of (Z)-3-[(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)amino]but-2-enehydrazide, with 4-hydroxybenzaldehyde in the presence of iodine as catalyst .The structure of HOPA was characterized by using IR,1H-NMR and mass spectroscopy. Nanoparticles of the prepared compound HOPA have been fabricated in aqueous media using re-precipitation method. Characterizations of the organic nanoparticles (ONPs) have been performed by using UV-Vis spectrophotometry, and scanning electron microscope (SEM). The HOPA NPs were approximately monodisperse even without using capping agent or surfactant. The size of the nanoparticles were around 150-200 nm as indicated by SEM. The maximum of absorption spectrum of the dispersed nanoparticles is red shifted by 5 nm from the molecular absorption spectra of the HOPA in the solution, which indicate head to head alignment (J aggregate) of the molecules of HOPA during the aggregation. The well dispersed organic nanoparticles in aqueous media holds potential application in future to be used as a tag for biomedical imagining. Keywords: Nanoscience, Organic Nanoparticle, Reprecipitation, Oxdiazoles

Evolution of a Novel Appendage Ground Plan in Water Striders Is Driven by Changes in the Hox Gene Ultrabithorax

Water striders, a group of semi-aquatic bugs adapted to life on the water surface, have evolved mid-legs (L2) that are long relative to their hind-legs (L3). This novel appendage ground plan is a derived feature among insects, where L2 function as oars and L3 as rudders. The Hox gene Ultrabithorax (Ubx) is known to increase appendage size in a variety of insects. Using gene expression and RNAi analysis, we discovered that Ubx is expressed in both L2 and L3, but Ubx functions to elongate L2 and to shorten L3 in the water strider Gerris buenoi. Therefore, within hemimetabolous insects, Ubx has evolved a new expression domain but maintained its ancestral elongating function in L2, whereas Ubx has maintained its ancestral expression domain but evolved a new shortening function in L3. These changes in Ubx expression and function may have been a key event in the evolution of the distinct appendage ground plan in water striders

Propagation of activity through the cortical hierarchy and perception are determined by neural variability

Brains are composed of anatomically and functionally distinct regions performing specialized tasks, but regions do not operate in isolation. Orchestration of complex behaviors requires communication between brain regions, but how neural dynamics are organized to facilitate reliable transmission is not well understood. Here we studied this process directly by generating neural activity that propagates between brain regions and drives behavior, assessing how neural populations in sensory cortex cooperate to transmit information. We achieved this by imaging two densely interconnected regions—the primary and secondary somatosensory cortex (S1 and S2)—in mice while performing two-photon photostimulation of S1 neurons and assigning behavioral salience to the photostimulation. We found that the probability of perception is determined not only by the strength of the photostimulation but also by the variability of S1 neural activity. Therefore, maximizing the signal-to-noise ratio of the stimulus representation in cortex relative to the noise or variability is critical to facilitate activity propagation and perception