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شهادة الأحافير : علم الحفريات بين الحقائق والخرافات
في هذا الكتاب تري عجبا مما أخفاه اتباع الداروينية الحديثة أو جهلوا به شاهرين أمام الناس أحفورة أو أحفورتين زاعمين أنها هي الحلقات المفقودة أو من أهم الحلقات المفقوده مع اعتراف علماء التطور أنفسهم بان الأمر يزداد سوءا فيما يخص شجرة الحياة وتحديد أسلاف الكائنات في هذه الشجرة المفقودة لا يعرف العلم عنها شيئا كما وثق ذلك المصنف في الفصل السابع في هذا الكتاب فصول لايعرف كثير من اتباع الداروينية الحديثة من المتأثرين ببرنامج العلوم الشعبية Popular science والأحرى بها أن توصف ببرنامج العلوم المزيفة pseudoscience فصول لا يعرفون بوجودها وتأثيرها بالسلب أوالإيجاب علي قبول نظريتهم التي أصبحت عقيدة ودين ! مثل دراسة ظهور الإنسان المعقدة حيث حفظت جيدا وبكثرة وقد ظهرت مبكرا دون اى دلالة علي تطوها فضلا عن معرفة تفاصيل تطورها وكذلك الريش بانواعة المختلفة ! وتطور الحشرات وتطور مايسمي بالتحول في كثير من الحشرات وغيرها مثل الضفادع وظهور الاجنحة في الحشرات والطيور والتحول من الخياشيم الي الرئه والتنفس خارج الماء واسلاف الديناصورات المجهولة الي غير ذلك مما يحسن الاطلاع عليه داخل الكتاب.
BOOK
Comparative Evaluation of DNA Extraction Methods from Feces of Multiple Host Species for Downstream Next-Generation Sequencing
The gastrointestinal tract contains a vast community of microbes that to this day remain largely unculturable, making studies in this area challenging. With the newly affordable advanced sequencing technology, important breakthroughs in this exciting field are now possible. However, standardized methods of sample collection, handling, and DNA extraction have yet to be determined. To help address this, we investigated the use of 5 common DNA extraction methods on fecal samples from 5 different species. Our data show that the method of DNA extraction impacts DNA concentration and purity, successful NGS amplification, and influences microbial communities seen in NGS output dependent on the species of fecal sample and the DNA extraction method used. These data highlight the importance of careful consideration of DNA extraction method used when designing and interpreting data from cross species studies.
Journal Article
Local vibrational coherences drive the primary photochemistry of vision
The role of vibrational coherence—concerted vibrational motion on the excited-state potential energy surface—in the isomerization of retinal in the protein rhodopsin remains elusive, despite considerable experimental and theoretical efforts. We revisited this problem with resonant ultrafast heterodyne-detected transient-grating spectroscopy. The enhanced sensitivity that this technique provides allows us to probe directly the primary photochemical reaction of vision with sufficient temporal and spectral resolution to resolve all the relevant nuclear dynamics of the retinal chromophore during isomerization. We observed coherent photoproduct formation on a sub-50 fs timescale, and recovered a host of vibrational modes of the retinal chromophore that modulate the transient-grating signal during the isomerization reaction. Through Fourier filtering and subsequent time-domain analysis of the transient vibrational dynamics, the excited-state nuclear motions that drive the isomerization reaction were identified, and comprise stretching, torsional and out-of-plane wagging motions about the local C
11
=C
12
isomerization coordinate.
The isomerization of the retinal chromophore of rhodopsin is the photochemical process that initiates the sense of vision. Now, heterodyne-detected transient grating spectroscopy has been used to resolve coherent vibrational dynamics during this process, helping to identify strictly local vibrational motions as the origin of the coherent surface crossing, which occurs on a sub-50-fs timescale.
Journal Article
Watching the release of a photopharmacological drug from tubulin using time-resolved serial crystallography
The binding and release of ligands from their protein targets is central to fundamental biological processes as well as to drug discovery. Photopharmacology introduces chemical triggers that allow the changing of ligand affinities and thus biological activity by light. Insight into the molecular mechanisms of photopharmacology is largely missing because the relevant transitions during the light-triggered reaction cannot be resolved by conventional structural biology. Using time-resolved serial crystallography at a synchrotron and X-ray free-electron laser, we capture the release of the anti-cancer compound azo-combretastatin A4 and the resulting conformational changes in tubulin. Nine structural snapshots from 1 ns to 100 ms complemented by simulations show how
cis
-to-
trans
isomerization of the azobenzene bond leads to a switch in ligand affinity, opening of an exit channel, and collapse of the binding pocket upon ligand release. The resulting global backbone rearrangements are related to the action mechanism of microtubule-destabilizing drugs.
Photopharmacology manipulates the biological activity of small molecules by light. Using an X-ray laser, the authors follow the release of the drug azo-combretastatin A4 from tubulin and the concomitant structural changes over nine orders of magnitude in time.
Journal Article
Liquid jet capabilities for ultrafast chemistry at the SwissFEL Alvra instrument
The Alvra experimental station at the Swiss X‐ray free‐electron laser, SwissFEL, investigates ultrafast dynamics in chemical and biological systems using X‐ray scattering and spectroscopy techniques. A key feature of Alvra is its unique capability to perform time‐resolved X‐ray emission and resonant inelastic X‐ray scattering in the tender X‐ray regime, currently not available at other XFEL endstations, combined with simultaneous access to X‐ray absorption spectroscopy and X‐ray solution scattering. Together with sub‐35 fs time resolution enabled by advanced timing diagnostics, this positions Alvra as a versatile instrument for ultrafast chemical dynamics in the liquid phase. Here we cover the various technical aspects of the beamline and experimental station, and present some examples of experimental results measured during the first years of SwissFEL commissioning and user operation. The technical aspects of the Alvra endstation are outlined and its scientific capabilities are demonstrated with commissioning results obtained during the early years of SwissFEL's operation.
Journal Article
Structural effects of high laser power densities on an early bacteriorhodopsin photocycle intermediate
Time-resolved serial crystallography at X-ray Free Electron Lasers offers the opportunity to observe ultrafast photochemical reactions at the atomic level. The technique has yielded exciting molecular insights into various biological processes including light sensing and photochemical energy conversion. However, to achieve sufficient levels of activation within an optically dense crystal, high laser power densities are often used, which has led to an ongoing debate to which extent photodamage may compromise interpretation of the results. Here we compare time-resolved serial crystallographic data of the bacteriorhodopsin K-intermediate collected at laser power densities ranging from 0.04 to 2493 GW/cm
2
and follow energy dissipation of the absorbed photons logarithmically from picoseconds to milliseconds. Although the effects of high laser power densities on the overall structure are small, in the upper excitation range we observe significant changes in retinal conformation and increased heating of the functionally critical counterion cluster. We compare light-activation within crystals to that in solution and discuss the impact of the observed changes on bacteriorhodopsin biology.
Time-resolved serial crystallography at XFELs reveals ultrafast photochemical reactions, but high laser densities can cause photodamage to biological samples. Here, the authors study the early K-intermediate in bacteriorhodopsin at high power, showing overall conformation remains robust over a wide range.
Journal Article
A multi-reservoir extruder for time-resolved serial protein crystallography and compound screening at X-ray free-electron lasers
Serial crystallography at X-ray free-electron lasers (XFELs) permits the determination of radiation-damage free static as well as time-resolved protein structures at room temperature. Efficient sample delivery is a key factor for such experiments. Here, we describe a multi-reservoir, high viscosity extruder as a step towards automation of sample delivery at XFELs. Compared to a standard single extruder, sample exchange time was halved and the workload of users was greatly reduced. In-built temperature control of samples facilitated optimal extrusion and supported sample stability. After commissioning the device with lysozyme crystals, we collected time-resolved data using crystals of a membrane-bound, light-driven sodium pump. Static data were also collected from the soluble protein tubulin that was soaked with a series of small molecule drugs. Using these data, we identify low occupancy (as little as 30%) ligands using a minimal amount of data from a serial crystallography experiment, a result that could be exploited for structure-based drug design.
Protein serial crystallography at X-ray free-electron lasers (XFELs) is a powerful technique for structure determination. Here, authors present a device for sample delivery designed to abate challenges to non-specialists allowing for compound screening.
Journal Article
Spin cascade and doming in ferric hemes
The structure–function relationship is at the heart of biology, and major protein deformations are correlated to specific functions. For ferrous heme proteins, doming is associated with the respiratory function in hemoglobin and myoglobins. Cytochrome c (Cyt c) has evolved to become an important electron-transfer protein in humans. In its ferrous form, it undergoes ligand release and doming upon photoexcitation, but its ferric form does not release the distal ligand, while the return to the ground state has been attributed to thermal relaxation. Here, by combining femtosecond Fe Kα and Kβ X-ray emission spectroscopy (XES) with Fe K-edge X-ray absorption near-edge structure (XANES), we demonstrate that the photocycle of ferric Cyt c is entirely due to a cascade among excited spin states of the iron ion, causing the ferric heme to undergo doming, which we identify. We also argue that this pattern is common to a wide diversity of ferric heme proteins, raising the question of the biological relevance of doming in such proteins.
Journal Article
Tracking polar solvation dynamics of a photoexcited organic chromophore with ultrafast X-ray scattering
Solvation plays a key role in many photochemical and biological processes. Yet, direct atomic-scale observation of solvent reorganization around photoexcited molecules containing only light atoms has so far remained elusive. Here, we use time-resolved X-ray scattering at an X-ray free-electron laser to track with a ~ 120 fs time resolution the photoinduced ultrafast rearrangement of polar acetonitrile solvent molecules around an organic hemithioindigo chromophore. The experiments reveal that the solvation shell reorganizes with a ~ 0.3 ps time constant driven by photoinduced charge transfer in the chromophore, and then reequilibrates over ~ 3 ps as the excited state population returns to the ground state. These results demonstrate the viability of using ultrashort X-ray pulses to directly visualize the motion of light atoms in solution, paving the way for atomic-scale understanding and control of photoinduced processes in biological and synthetic photoactive organic molecules.
Solvation dynamics shape many light-driven reactions but are challenging to observe. Time-resolved Xray scattering reveals the atomic-scale ultrafast reorganization of a polar solvent driven by charge transfer in a photoexcited organic molecule.
Journal Article
Evaluation of the aMAP score for hepatocellular carcinoma surveillance: a realistic opportunity to risk stratify
Background and aimsThe aMAP score is a model that predicts risk of hepatocellular carcinoma (HCC) development in patients with chronic hepatitis. Its performance in a ‘real world’ surveillance setting has not yet been ascertained.Patients and methodsWe had access to a cohort of 3473 individuals enrolled in a rigorously implemented and prospectively accrued surveillance programme (patients undergoing regular ultrasound and biomarker examination between 1998 and 2021). During this period 445 had HCC detected. Of these, 77.8% had early stage disease (within Milan criteria), permitting potentially curative therapy to be implemented in nearly 70% of cases. We applied the recently developed aMAP score to classify patients according to their initial aMAP score in to low, medium and high-risk groups as proposed in the original publication. The performance of the aMAP score was assessed according to the concordance-index and calibration (i.e. agreement between observed and predicted risk). Allowance was made for competing causes of death.ResultsThe aMAP score achieved an overall C-index of 0.81 (95% CI: 0.79–0.82) consistent with the initial report and was unaffected by allowance for competing causes of death. Sub-group analysis showed that the results did not change significantly according to gender, or aetiology. However, aMAP discrimination was greater for younger individuals (versus older individuals), and also for individuals without cirrhosis. The HCC incidence rate was 0.98, 7.05 and 29.1 events per 1000 person-years in the low-, moderate- and high-risk aMAP groups, respectively.ConclusionsThe results from this ‘real-world’ cohort demonstrate that risk stratification is a realistic prospect and that identification of a subgroup of chronic liver disease patients who have a very low risk of HCC is feasible.
Journal Article